Ole Hammerich (Editor) - Bernd Speiser (Editor) - Organic Electrochemistry - Revised and Expanded-CRC Press (2015)

Organic Chemistry Hammerich
Speiser
“Outstanding praise for previous editions…the single best general reference

FIFTH EDITION
ORGANIC
for the organic chemist.”
—Journal of the Electrochemical Society
“The cast of editors and authors is excellent, the text is, in general, easily
ELECTROCHEMISTRY
readable and understandable, well documented, and well indexed…those
who purchase the book will be satisfied with their acquisition.”
—Journal of Polymer Science
“…an excellent starting point for anyone wishing to explore the application
of electrochemical technique to organic chemistry and…a comprehensive
up-to-date review for researchers in the field.”
R E V I S E D A N D E X PA N D E D
—Journal of the American Chemical Society
Highlights from the Fifth Edition:
• Coverage of the electrochemistry of buckminsterfullerene and related

compounds, electroenzymatic synthesis, conducting polymers, and
electrochemical fluorination
• Systematic examination of electrochemical transformations of organic
compounds, organized according to the type of starting materials
• In-depth discussions of carbonyl compounds, anodic oxidation
of oxygen-containing compounds, electrosynthesis of bioactive
materials, and electrolyte reductive coupling
• Features 16 entirely new chapters, with contributions from
several new authors who also contribute to extensive revisions
throughout the rest of the chapters
Completely revised and updated, Organic Electrochemistry, Fifth

Edition explains distinguishing fundamental characteristics that separate
organic electrochemistry from classical organic chemistry. It includes
descriptions of the most important variants of electron transfers and
emphasizes the importance of electron transfers in initiating various
electrochemical reactions. The sweeping changes and lengthy additions
in the fifth edition testify to the field’s continued and rapid growth in
research, practice, and application, and make it a valuable addition to
your collection.
EDITED BY
Ole Hammerich
84011
ISBN: 978-1-4200-8401-6
90000
F I F TH E D ITI O N
Bernd Speiser
9 781420 084016
FIFTH EDITION
ORGANIC
ELECTROCHEMISTRY
FIFTH EDITION
ORGANIC
ELECTROCHEMISTRY
EDITED BY
Ole Hammerich
University of Copenhagen, C o p e n h a g e n , D e n m a r k
Bernd Speiser
Universität Tübingen, Tü b i n g e n , G e r m a n y
Boca Raton London New York
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Contents
Preface...............................................................................................................................................ix
Acknowledgments .......................................................................................................................... xiii
Editors .............................................................................................................................................. xv
Contributors ...................................................................................................................................xvii
SECTION I Fundamentals and Methods
Chapter 1 Basic Concepts ............................................................................................................. 3

Christian Amatore
Chapter 2 Techniques for Studies of Electrochemical Reactions in Solution.............................97

Ole Hammerich and Bernd Speiser
Chapter 3 In Situ Spectroelectrochemistry of Organic Compounds ........................................ 169

Peter Rapta, Evgenia Dmitrieva, Alexey A. Popov, and Lothar Dunsch
Chapter 4 Surface Techniques .................................................................................................. 191

Mohamed M. Chehimi and Jean Pinson
Chapter 5 Application of Digital Simulation ............................................................................ 205

Bernd Speiser
Chapter 6 Theoretical Calculation of Reduction Potentials...................................................... 229

Junming Ho, Michelle L. Coote, Christopher J. Cramer, and Donald G. Truhlar
SECTION II General Preparative Aspects
Chapter 7 Preparative Electrolysis on the Laboratory Scale .................................................... 263

Jakob Jörissen and Bernd Speiser
Chapter 8 Application of Ionic Liquids, Emulsions, Sonication, and Microwave Assistance ..... 331
John D. Watkins and Frank Marken
v
vi Contents
Chapter 9 Combinatorial Electrochemistry and Miniaturization ............................................. 345

Kevin D. Moeller
Chapter 10 Relations between Micro- and Macrophenomena.................................................... 371

Christian Amatore
SECTION III Electron Transfers and Concerted Processes
Chapter 11 Influence of Molecular and Medium Effects on Two-Electron Processes ............... 395
Kevin Lam and William E. Geiger
Chapter 12 Electrochemically Driven Supramolecular Devices ................................................ 433

Paola Ceroni, Alberto Credi, and Margherita Venturi
Chapter 13 Proton-Coupled Electron Transfers .......................................................................... 481

Cyrille Costentin, Marc Robert, and Jean-Michel Savéant
Chapter 14 Dissociative Electron Transfers ................................................................................ 511

Chapter 15 Electron Transfer–Catalyzed Reactions ................................................................... 531

Kazuhiro Chiba and Yohei Okada
SECTION IV Organic Electrochemical Reaction Types
Chapter 16 Cleavages and Deprotections ................................................................................... 559

Ole Hammerich
Chapter 17 Reductive Coupling .................................................................................................. 621

James H.P. Utley, R. Daniel Little, and Merete Folmer Nielsen
Chapter 18 Oxidative Coupling .................................................................................................. 705

Hans J. Schäfer
Chapter 19 Oxidative Substitution and Addition Reactions ....................................................... 775

Ole Hammerich and James H.P. Utley
Chapter 20 Fluorination ..............................................................................................................807

Toshio Fuchigami and Shinsuke Inagi
Contents vii
SECTION V Electrochemical Conversions of Organic Compounds

Chapter 21 Electrochemistry of Fullerenes, Derivatives, and Related Compounds................... 829
Frederic Melin, Lourdes E. Echegoyen, and Luis Echegoyen
Chapter 22 Aliphatic and Aromatic Hydrocarbons: Reduction .................................................. 861

Jürgen Heinze
Chapter 23 Oxidation of Hydrocarbons ...................................................................................... 891

Ole Hammerich
Chapter 24 Activation of the Carbon–Halogen Bond ................................................................. 917

Armando Gennaro, Abdirisak Ahmed Isse, and Patrizia Romana Mussini
Chapter 25 Aliphatic and Aromatic Halides: Conversions ......................................................... 941

Dennis G. Peters
Chapter 26 Oxygen-Containing Compounds: Alcohols, Ethers, and Phenols ........................... 981

Robert Francke, Thomas Quell, Anton Wiebe, and Siegfried R. Waldvogel
Chapter 27 Sulfur-, Selenium-, and Tellurium-Containing Compounds .................................. 1035

Richard S. Glass
Chapter 28 Aliphatic Nitrogen–Containing Compounds: Amines, Amino Alcohols,

and Amino Acids.................................................................................................... 1103
Osamu Onomura
Chapter 29 Aromatic Nitrogen–Containing Compounds ..........................................................1121

Jan S. Jaworski
Chapter 30 Reduction of Nitro Compounds and Related Substrates .........................................1149

Ole Hammerich
Chapter 31 Reduction of Aldehydes, Ketones, and Azomethines ............................................ 1201

Jiří Ludvík
Chapter 32 Reductions of Carboxylic Acids and Derivatives................................................... 1249

Rolf Breinbauer and Martin Peters
Chapter 33 Oxidation of Carboxylic Acids and Derivatives .................................................... 1267

Hideo Tanaka, Manabu Kuroboshi, and Sigeru Torii
viii Contents
Chapter 34 Heterocyclic Compounds ....................................................................................... 1309

Fructuoso Barba and Belen Batanero
Chapter 35 Organoelemental Compounds ................................................................................ 1357

Jun-ichi Yoshida, Toshiki Nokami, and Seiji Suga
Chapter 36 Organometallic Compounds as Tools in Organic Electrosynthesis ....................... 1393

Anny Jutand
SECTION VI Stereochemical and Biological Aspects

Chapter 37 Electrosynthesis of Bioactive Materials ................................................................. 1435
Randi K. Gbur and R. Daniel Little
Chapter 38 Stereochemistry of Organic Electrode Processes .................................................. 1461

Chapter 39 Electroenzymatic Synthesis ....................................................................................1511

Christina Kohlmann and Stephan Lütz
Chapter 40 Electrochemical Modeling of Biological Processes ............................................... 1543

Richard D. Webster
SECTION VII Surface Confined Systems

Chapter 41 Electrochemistry of Conducting Polymers ............................................................ 1571
Jürgen Heinze
Chapter 42 Surface-Bound and Immobilized Molecules ......................................................... 1605

Jean Pinson
SECTION VIII Special Applications

Chapter 43 Electrogenerated Bases and Nucleophiles.............................................................. 1625
James H.P. Utley, Merete Folmer Nielsen, and Peter B. Wyatt
Chapter 44 Electrocatalytic Hydrogenation .............................................................................. 1657

Jean Lessard
Index ............................................................................................................................................ 1673

Preface
Organic electrochemistry is concerned with the reduction and oxidation of organic molecules at
electrodes. Although it is now more than 200 years ago that the so-called Volta pile was discov-
ered, it was not until 1830–1850 that investigations of organic electrochemical processes, pioneered
by Faraday and Kolbe, were established as a research area in their own right. Toward the end of
the nineteenth century, investigators such as Tafel and Haber made significant contributions to the
present knowledge of organic electrode processes. Haber, for instance, in his now famous paper
on the reduction of nitrobenzene (F. Haber, Z. Elektrochem. 1898, 4, 506) recognized the signifi-
cance of the electrode potential in the following words: “Oxydations- und Reduktionsprozesse hän-
gen in erster Linie von dem Potential der Elektrode ab, an welcher sie ablaufen, und Stromdichte,
Stromdauer und Elektrodenmaterial sind nur insofern bedeutsam, als sie das Elektrodenpotential
und seine Änderungen im Gang der Elektrolyse bestimmen.” (“Oxidation and reduction processes
primarily depend on the potential of the electrode at which they proceed, and current density, cur-
rent duration, and electrode material are only important insofar as they determine the electrode
potential and its changes during the electrolysis.”) The application of electrolysis as a means of
preparing organic compounds continued in the first half of the twentieth century. This development
took place along with the development of new electrochemical techniques for the study of electrode
processes, for instance, polarography at the dropping mercury electrode introduced by Heyrovsky
in the early 1920s. Other important contributions were due to Lingane, Kolthoff, Laitinen, and
Delahay. Later, Hickling’s potentiostat (A. Hickling, Trans. Faraday Soc. 1942, 38, 27) as an exper-
imental tool to control experiments led into the computerization era.
Most of the work reported before World War II was carried out in aqueous electrolyte solu-
tions. This situation changed after the war, and since the mid-1950s, the attention has been focused
mostly on the application of nonaqueous solvents. This has allowed for the detection of the primary
intermediates, typically radical anions and radical cations, and for the study of their reactions. The
theoretical foundations for the analysis of kinetics and mechanisms by, for instance, cyclic voltam-
metry and related techniques were mostly published in the 1960s and 1970s. The application of such
techniques has resulted in a steadily increasing understanding of the kinetics and mechanisms of
organic electrochemical processes.
Facing the fact that thousands of organic electrochemical processes are now known, it is striking
that most often the only electrochemical reaction to be mentioned in a typical organic chemistry
textbook is the oxidation of an organic carboxylic acid R-COOH to the corresponding dimeric
alkane R-R reported by Kolbe as early as 1849. Also, it is often overlooked that reductions by met-
als involving radical anions as intermediates are intimately related to cathodic reductions. And
most frequently, radical cations are not mentioned at all, except, of course, in the context of mass
spectrometry! This problem, that organic electrochemistry has had difficulties in penetrating into
the organic chemistry curriculum, was pointed out already in the preface to the first edition of this
book. Unfortunately, not much has changed in the more than 40 years that have elapsed between
that edition and this fifth edition.
The knowledge of organic electrochemistry had in the 1960s and the early 1970s matured to the
point where the time was ripe for the first edition of Organic Electrochemistry (M.M. Baizer, ed.,
Organic Electrochemistry, Marcel Dekker: New York, 1973). The editor was Manual M. Baizer,
well known for his contributions to preparative organic electrochemistry, first of all the develop-
ment of the electrohydrodimerization of acrylonitrile into a highly successful industrial process for
the manufacture of adiponitrile. Baizer set the standards for the book that was organized to include
chapters both on the electrochemical reduction and oxidation of specific classes of compounds and
ix
x Preface
on specific types of electrode processes. This approach obviously led to some overlap, a problem that
Baizer touched upon in the following words: “It has become routine, at least for reviewers, to point
out that in a multi-authored book there is overlap of material, non-uniformity of style, repetition etc.
This book was not hastily assembled, and there was adequate time to achieve uniformity if that had
been desired. But the material was deliberately organized so that a given segment might appear in
two or more contexts and, further, where unanimity of opinion does not exist, more than one current
viewpoint might be expressed.” The same basic philosophy was followed in the organization of the
second (Baizer, M.M., Lund, H., eds., Organic Electrochemistry, Marcel Dekker: New York, 1983),
third (Lund, H., Baizer, M.M., eds., Organic Electrochemistry, Marcel Dekker: New York, 1991),
fourth (Lund, H., Hammerich, O., eds., Organic Electrochemistry, Marcel Dekker: New York, 2001)
editions, and now for this fifth edition. Owing to this intentional overlap between chapters, the reader
is encouraged to use the index to find details, in addition to those found in a given chapter, of the
electrochemistry of a specific compound or a class of compounds. Also, some formal variations that
reflect common usage by different authors have not been brought into line, for example, the use of “e”
or “e −” for the electron or the nomenclature of electrochemical mechanisms (“ECE” vs. “eCe,” etc.).
The progress in organic electrochemistry that has taken place since the appearance of the fourth
edition is reflected by the organization of this edition. Organic electrochemical reactions are rather
complex with electron transfers and transport processes interwoven with bond breaking and forming
reaction steps. As a consequence, different perspectives have developed over the years and organic
electrochemistry may be discussed following different lines of thought. Moreover, organic electro-
chemical reactions are often integrated into more complicated synthetic strategies and advanced
chemical reasoning or are applied to complex materials and structures. Consequently, it was decided
to present the field as follows. After an introduction of some basic and technical aspects, the reac-
tion step that distinguishes organic electrochemistry from classical organic reactions, the electron
transfer to and from organic molecules, is described and its most important variants are presented.
Second, the importance of electron transfers for the initiation of various organic electrochemical
reaction types (follow-up reactions) is emphasized. Third, the electrochemical transformations of
organic compounds are systematically presented according to the type of starting materials. Finally,
cases where organic electrochemistry forms an integral part in a wider context of chemical research
(e.g., in biological or materials science) are discussed.
In comparison with the fourth edition, the following major changes have been made to this
edition:
Sixteen new chapters have been included. These are:
• Chapter 3: In Situ Spectroelectrochemistry of Organic Compounds by Peter Rapta, Evgenia

Dmitrieva, Alexey A. Popov, and Lothar Dunsch
• Chapter 4: Surface Techniques by Mohamed M. Chehimi, and Jean Pinson
• Chapter 5: The Application of Digital Simulation by Bernd Speiser
• Chapter 6: Theoretical Calculation of Reduction Potentials by Junming Ho, Michelle L.
Coote, Christopher J. Cramer, and Donald G. Truhlar
• Chapter 8: The Application of Ionic Liquids, Emulsions, Sonication, and Microwave
Assistance by John D. Watkins and Frank Marken
• Chapter 9: Combinatorial Electrochemistry and Miniaturization by Kevin D. Moeller
• Chapter 11: Influence of Molecular and Medium Effects on Two-Electron Processes by
• Chapter 12: Electrochemically Driven Supramolecular Devices by Paola Ceroni, Alberto
Credi, and Margherita Venturi
• Chapter 13 and 14: Proton-Coupled Electron Transfers and Dissociative Electron Transfers
by Cyrille Costentin, Marc Robert, and Jean-Michel Savéant
• Chapter 15: Electron Transfer Catalyzed Reactions by Kazuhiro Chiba and Yohei Okada
Preface xi
• Chapter 24: Activation of the Carbon-Halogen Bond by Armando Gennaro, Abdirisak

Ahmed Isse, and Patrizia Romana Mussini
• Chapter 36: Organometallic Compounds as Tools in Organic Electrosynthesis by Anny
Jutand
• Chapter 40: Electrochemical Modeling of Biological Processes by Richard D. Webster
• Chapter 42: Surface-Bound and Immobilized Molecules by Jean Pinson
• Chapter 44: Electrocatalytic Hydrogenation by Jean Lessard
Approximately one-fourth of the previous chapters have been rewritten by new authors:
• Chapter 7: Preparative Electrolysis on the Laboratory Scale by Jakob Jörissen and Bernd
Speiser
• Chapter 16: Cleavages and Deprotections by Ole Hammerich
• Chapter 26: Oxygen Containing Compounds: Alcohols, Ethers, and Phenols by Robert
Francke, Thomas Quell, Anton Wiebe, and Siegfried R. Waldvogel
• Chapter 27: Sulfur, Selenium, and Tellurium Containing Compounds by Richard S. Glass
• Chapter 30: Reduction of Nitro Compounds and Related Substrates by Ole Hammerich
• Chapter 31: Reduction of Aldehydes, Ketones, and Azomethines by Jiri Ludvik
• Chapter 32: Reduction of Carboxylic Acids and Derivatives by Rolf Breinbauer and Martin
Peters
• Chapter 34: Heterocyclic Compounds by Fructuoso Barba and Belen Batanero
• Chapter 39: Electroenzymatic Synthesis by Christina Kohlmann and Stephan Lütz
All other chapters have been thoroughly revised or updated where needed, in some cases in coop-
eration with new coauthors.
The following four chapters have been omitted:
• Old Chapter 4: Comparison Between Electrochemical Reactions and Chemical Oxidations

and Reductions
• Old Chapter 28: Amalgam and Related Reductions
• Old Chapter 29: Electrogenerated Reagents
• Old Chapter 31: Industrial Electroorganic Chemistry
Thus, in a sense, this is a new book and not just a conservative update to the previous edition.
Altogether this book encompasses 44 chapters written by 66 authors.
In most cases, we have encouraged authors to avoid back references to the fourth edition.
However, this was not always possible, nor desirable. The text of some chapters in the fourth edition
is still authoritative and not much could be added (see, e.g., the appendices on solvents and support-
ing electrolytes in Chapter 7).
Many of the authors of the fourth and previous editions have now retired. Fortunately, new
authors have willingly accepted to carry the torch on to this new edition. Sadly, one of these new
authors, Lothar Dunsch, passed away in late 2013. This was a great loss to the electrochemical com-
munity, and he will be remembered as one of the leading figures in the development and application
of spectroelectrochemistry.
Ole Hammerich
Bernd Speiser
Acknowledgments
The editors thank all the authors for the enthusiasm with which they have undertaken the enormous
task of making this fifth edition possible. We have strived to maintain the basic philosophy and
not least the high standards of the previous editions to make this a worthy fifth edition of the well-
known “Baizer.” Hopefully, we have succeeded.
We acknowledge the help of several people who have contributed “behind the scenes” in
some way or the other. Klaus-Michael Mangold (Frankfurt/Main, Germany), Susanne Hempel
(Tübingen, Germany), and Tatiana V. Magdesieva (Moscow, Russia) helped with locating or citing
some unusual references. Practically, each and every manuscript file (often in a multitude of ver-
sions) went through the hands (and across the fingertips) of Britta Rochier (Tübingen, Germany),
who almost always found a way to cope with the astonishingly variable word processing software
in use around the world.
Finally, we thank the staff at Taylor & Francis Group, Barbara Glunn, Kari A. Budyk, and
Jennifer Derima, for their patience with our inquiries while we were collecting the manuscripts
from the authors.
xiii
Editors
Ole Hammerich is an associate professor in the Department of Chemistry, University of
Copenhagen, Denmark, where he has taught since 1975. Dr. Hammerich’s research interests include
kinetics and mechanisms of organic radical ion reactions, charge-transfer complexes, and elec-
tropolymerization. He is author or coauthor of more than 110 articles, papers, and book chapters
and was, together with Henning Lund, the editor of the fourth edition of Organic Electrochemistry.
Together with Jens Ulstrup, he was the editor of Bioinorganic Electrochemistry. Dr. Hammerich
has served as the national secretary for Denmark and as the chairman of the molecular electrochem-
istry division in the International Society of Electrochemistry and he is a member of the Danish
Electrochemical Society and the Electrochemical Society. He earned his PhD (1974) from the
University of Copenhagen, Denmark.
Bernd Speiser is an außerplanmäßiger professor in the Institut für Organische Chemie, Universität
Tübingen, Germany. He received his doctoral degree in Tübingen in 1981 and finished his habili-
tation in 1990. He was a Heisenberg fellow of the Deutsche Forschungsgemeinschaft in the years
1992–1996. He teaches courses in organic chemistry and molecular electrochemistry. His research
is focused on the elucidation of reaction mechanisms of organic, organometallic, and inorganic
compounds with experimental methods and computer simulation. This includes the study of multi-
electron transfers, transport properties, redox-active nanoparticles, and combinatorial electro-
chemistry. He has published more than 140 full papers, communications, and book chapters. He
was the founding chair of Division 6 (molecular electrochemistry) in the International Society of
Electrochemistry and is a member of the Electrochemical Society, the International Society of
Electrochemistry, the Society of Electroanalytical Chemistry, the Gesellschaft Deutscher Chemiker
(GDCh), and DECHEMA Gesellschaft für chemische Technik und Biotechnologie.
xv
Contributors
Christian Amatore Michelle L. Coote
Ecole Normale Supérieure ARC Centre of Excellence for
Department of Chemistry Electromaterials Science
(ENS-CNRS-UPMC) Research School of Chemistry
PSL Research Univerisity Australian National University
Sorbonne Universités Canberra, Australian Capital Territory,
Paris, France Australia
Fructuoso Barba Cyrille Costentin

Department of Organic Chemistry Laboratoire d’Electrochimie Moléculaire,
University of Alcala UMR CNRS 7591
Madrid, Spain Université Paris Diderot
Sorbonne Paris Cité
Paris, France
Belen Batanero
Department of Organic Chemistry Christopher J. Cramer
University of Alcala Department of Chemistry, Chemical Theory
Madrid, Spain Center, and Supercomputing Institute
University of Minnesota
Rolf Breinbauer Minneapolis, Minnesota
Institute of Organic Chemistry
Graz University of Technology Alberto Credi
Graz, Austria Dipartimento di Chimica “G. Ciamician”
Alma Mater Studiorum
Paola Ceroni Università di Bologna
Dipartimento di Chimica “G. Ciamician” Bologna, Italy
Alma Mater Studiorum
Università di Bologna Evgenia Dmitrieva
Bologna, Italy Department of Electrochemistry and
Conducting Polymers
Center of Spectroelectrochemistry
Mohamed M. Chehimi Leibniz Institute for Solid State and Materials
Université Paris Diderot Research
Sorbonne Paris Cité, ITODYS, UMR 7086 Dresden, Germany
CNRS
Paris, France Lothar Dunsch (deceased)
Department of Electrochemistry and
Kazuhiro Chiba Conducting Polymers
Department of Applied Biological Chemistry Center of Spectroelectrochemistry
Tokyo University of Agriculture and Leibniz Institute for Solid State and Materials
Technology Research
Tokyo, Japan Dresden, Germany
xvii
xviii Contributors
Lourdes E. Echegoyen Junming Ho

Department of Chemistry Institute of High Performance Computing
University of Texas at El Paso Singapore
El Paso, Texas
Shinsuke Inagi
Luis Echegoyen Department of Electronic Chemistry
Department of Chemistry Tokyo Institute of Technology
University of Texas at El Paso Yokohama, Japan
El Paso, Texas
Abdirisak Ahmed Isse
Robert Francke Dipartimento di Scienze Chimiche
Department of Chemistry Università degli Studi di Padova
University of Rostock Padova, Italy
Rostock, Germany
Jan S. Jaworski
Toshio Fuchigami Faculty of Chemistry
Department of Electronic Chemistry University of Warsaw
Tokyo Institute of Technology Warszawa, Poland
Yokohama, Japan
Jakob Jörissen
Randi K. Gbur Lehrstuhl für Technische Chemie (Chemische
Department of Chemistry and Biochemistry Prozessentwicklung)
University of California, Santa Barbara Technische Universität Dortmund
Santa Barbara, California Dortmund, Germany
William E. Geiger Anny Jutand

University of Vermont Département de Chimie
Burlington, Vermont Ecole Normale Supérieure
Paris, France
Armando Gennaro
Christina Kohlmann
Dipartimento di Scienze Chimiche
BASF Personal Care and Nutrition GmbH
Università degli Studi di Padova
Düsseldorf, Germany
Padova, Italy
Manabu Kuroboshi
Richard S. Glass School of Natural Science and Technology
Department of Chemistry and Biochemistry Okayama University
The University of Arizona Okayama, Japan
Tucson, Arizona
Kevin Lam
Ole Hammerich School of Science and Technology
Department of Chemistry Nazarbayev University
University of Copenhagen Astana, Kazakhstan
Copenhagen, Denmark
Jean Lessard
Jürgen Heinze Laboratoire de Chimie et Électrochmie
Institut für Physikalische Chemie Organiques
Freiburger Materialforschungszentrum Département de Chimie
Universität Freiburg Université de Sherbrooke
Freiburg, Germany Sherbrooke, Québec, Canada
Contributors xix
R. Daniel Little Osamu Onomura

Department of Chemistry and Biochemistry Nagasaki University
University of California, Santa Barbara Nagasaki, Japan
Santa Barbara, California
Jiří Ludvík Dennis G. Peters

Department of Molecular Electrochemistry Department of Chemistry
J. Heyrovský Institute of Physical Chemistry Indiana University
Academy of Sciences of the Czech Republic Bloomington, Indiana
Prague, Czech Republic
Martin Peters
Stephan Lütz Institute of Organic Chemistry
Global Discovery Chemistry Graz University of Technology
Novartis Pharma AG Graz, Austria
Basel, Switzerland
Frank Marken Jean Pinson

Department of Chemistry Université Paris Diderot
University of Bath Sorbonne Paris Cité, ITODYS, UMR 7086
Bath, United Kingdom CNRS
Paris, France
Frederic Melin
Laboratoire de Bioélectrochimie
et Spectroscopie Alexey A. Popov
Université de Strasbourg Department of Electrochemistry and
Strasbourg, France Conducting Polymers
Center of Spectroelectrochemistry
Kevin D. Moeller Leibniz Institute for Solid State and Materials
Department of Chemistry Research
Washington University in St. Louis Dresden, Germany
St. Louis, Missouri
Thomas Quell
Patrizia Romana Mussini
Department of Organic Chemistry
Dipartimento di Chimica
Johannes Gutenberg University
Università degli Studi di Milano
Mainz, Germany
Milan, Italy
Merete Folmer Nielsen Peter Rapta

The Danish Emergency Management Agency Institute of Physical Chemistry and Chemical
Birkerød, Denmark Physics
Slovak University of Technology Bratislava
Toshiki Nokami Bratislava, Slovak Republic
Department of Chemistry and Biotechnology
Tottori University
Tottori, Japan Marc Robert
Laboratoire d’Electrochimie Moléculaire,
Yohei Okada UMR CNRS 7591
Graduate School of Biomedical Sciences Université Paris Diderot
Tokyo University of Agriculture and Technology Sorbonne Paris Cité
Tokyo, Japan Paris, France
xx Contributors
Jean-Michel Savéant Margherita Venturi

Laboratoire d’Electrochimie Moléculaire, Dipartimento di Chimica “G. Ciamician”
UMR CNRS 7591 Alma Mater Studiorum
Université Paris Diderot Università di Bologna
Sorbonne Paris Cité Bologna, Italy
Paris, France
Siegfried R. Waldvogel
Hans J. Schäfer Department of Organic Chemistry
Organisch-Chemisches Institut Johannes Gutenberg University
Westfälische Wilhelms-Universität Mainz, Germany
Münster, Germany
John D. Watkins
Bernd Speiser
Department of Chemistry
Institut für Organische Chemie
University of Bath
Universität Tübingen
Bath, United Kingdom
Tübingen, Germany
Seiji Suga Richard D. Webster

Division of Applied Chemistry Division of Chemistry and Biological
Graduate School of Natural Science and Chemistry
Technology School of Physical and Mathematical
Okayama University Sciences
Okayama, Japan Nanyang Technological University
Singapore, Singapore
Hideo Tanaka
School of Natural Science and Technology Anton Wiebe
Okayama University Department of Organic Chemistry
Okayama, Japan Johannes Gutenberg University
Mainz, Germany
Sigeru Torii
The Institute of Creative Chemistry Co., Ltd.
Peter B. Wyatt
Okayama-City, Japan
School of Biological and Chemical
Donald G. Truhlar Sciences
Department of Chemistry, Chemical Theory Queen Mary University of London
Center, and Supercomputing Institute London, United Kingdom
University of Minnesota
Minneapolis, Minnesota Jun-ichi Yoshida
Department of Synthetic Chemistry and
James H.P. Utley Biological Chemistry
School of Biological and Chemical Sciences Graduate School of Engineering
Queen Mary University of London Kyoto University
London, United Kingdom Kyoto, Japan
Section I
Fundamentals and Methods
1 Basic Concepts
Christian Amatore
CONTENTS
I. Introduction .............................................................................................................................. 4
II. Fundamental Aspects of Electron Transfer Reactions ............................................................. 6
A. Oxidation–Reduction Reactions versus Electron Transfer Reactions in Organic
Chemistry and Electrochemistry��6
1. Oxidation–Reduction versus Electron Transfer Reactions ........................................ 6
2. Outer Sphere and Inner Sphere Electron Transfers ................................................... 8
B. Standard Potentials: What They Mean and What They Do Not Mean .......................... 11
1. Standard Potentials .................................................................................................. 11
2. Reference Electrodes and Liquid Junction Potentials .............................................. 12
3. Standard Reduction Potentials versus Ionization Potentials or Electron
Affinities ................................................................................................................14
4. Comparison or Extrapolation between Solvents ...................................................... 16
5. Formal Reduction Potentials.................................................................................... 17
6. Relationships between Thermodynamic Driving Force ΔE 0 and Feasibility
of an Electron Transfer Reaction��20
C. Mechanism and Theory of Outer Sphere Electron Transfer Reactions .......................... 22
1. Diffusion Limitation in Electron Transfer Reactions .............................................. 22
2. Basic Features of Electron Transfer in Solution ......................................................26
3. Role of the Solvent: The Outer Shell Reorganization Energy ................................. 31
4. Physical Meaning of the Reorganization Energy and of Energy Diagrams ............ 33
5. Energies and Free Energies in Electron Transfer Theories ..................................... 35
6. Quadratic Free Energy Relationships ...................................................................... 36
7. Cross-Relationships: Evaluation of Rate Constants from Isotopic Rate Constants .....38
8. Experimental Illustrations ....................................................................................... 39
III. Fundamental Aspects of Electrode Phenomena ..................................................................... 42
A. Monitoring a Half-Reaction: The Electrochemical Cell................................................. 42
1. Monitoring a Half-Reaction ..................................................................................... 42
2. Electrochemical Cell................................................................................................44
3. Resistive Effects and Ohmic Drop: The Supporting Electrolyte–Solvent
System ...................................................................................................................... 45
4. Electrode/Solution Interfacial Region......................................................................46
B. General Overview of an Electrode Reaction .................................................................. 47
C. Kinetics of Heterogeneous Electron Transfers ............................................................... 48
1. Mechanism and Theory of Outer Sphere Electron Transfers at Electrodes ............ 48
2. Transfer Coefficient α............................................................................................... 52
3. Reversible and Irreversible Electron Transfers: Their Role in the Meaning
of Oxidation or Reduction Potentials�� 53
D. Adsorption Phenomena ................................................................................................... 55
3
4 Organic Electrochemistry
E. Coupled Chemical Reactions .......................................................................................... 55

1. Electrochemical versus Homogeneous Chemical Reactivities ................................ 55
2. Chemical Reversibility and Irreversibility: Their Role in the Meaning
of Oxidation or Reduction Potentials�� 57
3. Classification of Coupled Chemical Reactions ........................................................ 59
4. Electrochemical Reaction Mechanisms and the Principle of Microscopic
Reversibility .............................................................................................................64
IV. Mass Transfer in Electrochemistry ......................................................................................... 65
A. Fundamental Aspects of Mass Transfer Processes ......................................................... 65
1. Physical Processes of Mass Transfer: Fick’s First Law ...........................................66
2. Relationships between the Electrochemical Current and Mass Transfers............... 68
3. Microscopic Origin of the Diffusion Coefficient: Mass Transfer Rates and
Diffusion Layer Thickness....................................................................................... 70
4. Electrochemical Homogeneous Kinetics: Fick’s Second Law................................. 72
5. Dimensionless Formulation of Electrochemical Equations..................................... 74
B. Steady-State Electrochemical Methods: Half-Wave Potential E1/2 ................................. 78
1. Pure Electron Transfer Mechanisms........................................................................ 78
2. Mechanism Involving a Follow-Up Reaction: EC Mechanisms .............................. 81
3. Chemical Kinetics from Half-Wave Potentials: Determination of Rate
Constants and Reaction Orders��84
C. Transient Electrochemical Methods ............................................................................... 87
1. Introduction: Time Hysteresis in Current Reversal Techniques .............................. 87
2. Transient Electrochemical Methods and Chemical Kinetics...................................90
Acknowledgments............................................................................................................................92
References ........................................................................................................................................92
A te convien tenere altro viaggio …

Chè questa bestia, per la qual tu gride,
Non lascia altrui pasar per la sua via,
Ma tanto lo impedisce, che l’uccide…
Dante
Divina Commedia
I. INTRODUcTiON
Our objective in this chapter is to familiarize organic chemists with fundamental electrochemical
concepts that support several aspects of organic electrochemistry elaborated in this book, as well as
many important features of electron transfer reactions. In fact, although the term electrochemistry
evokes for most readers the idea of chemistry at electrodes, in our opinion, electron transfer chem-
istry constitutes a better definition when organic or organometallic electrochemistry is concerned.
This is particularly obvious when one thinks of an electrode as a macrosized molecule whose abil-
ity to provide or accept electrons is virtually infinite (versus a one-shot molecular redox species)
and may be precisely adjusted by fine-tuning of the electrode potential. Similarly, electrochemical
reactions involving specific interactions with the electrode material are no more than the analogs
of inner sphere, ion-pairing, or complexation reactions. Thus, in many respects, electrochemical
reactions do not differ basically from their homogeneous counterparts except for the topology: an
electrode is a 2D structure placed in a 3D volume, while molecular redox species are generally dis-
persed in the solution. This similarity is even more true insofar as it concerns the chemical reactiv-
ity of electrogenerated intermediates, since they evolve under conditions that a priori do not differ
from those considered in homogeneous chemistry. Indeed, the extraordinarily large electric fields
(of magnitude comparable to those at the origin of storm lightning) drop to negligible values within
Basic Concepts 5
a few angstroms of the electrode surface, in contradiction to generally held ideas. Thus, as soon as
molecules have moved over a few molecular diameters from the electrode surface, they probe no
special electrical effects associated with their electrochemical origin. This is an important point,
although not well recognized or publicized, since it permits an easy transposition of electrochemical
results to homogeneous situations or vice versa.
Yet there are specific particularities of chemistry at electrodes. They arise from the fact that
electrodes both supply and accept electrons to and from molecules dissolved in a solution. This
has two important consequences dealing with mass transfer (i.e., transfer of the reagents from the
homogeneous volumic space and to the heterogeneous 2D surface) and with current transport across
the solution.
Transport of the current through the solution requires that rather conductive media be used, at
least when high currents are considered. The ensuing necessity for an inert electrolyte is an obvi-
ous disadvantage of electrochemical methods, although in our opinion, it is fully compensated by
the extraordinary advantage of a precise adjustment of the driving force via the electrode potential.
Mass transfer from a volumic homogeneous region, the bulk solution, to a 2D surface results in
a spatial structuring of solutions in the close vicinity of the electrode surface. Although such effects
are not specific to electrochemistry,* they may be thought of, at first, as additional difficulties to
cope with in electrochemistry. However, these spatial structurings may be used with considerable
advantage to control the chemical route followed by a given intermediate and force it into a pathway
that would never be followed under homogeneous conditions. Indeed, this is used in most electro-
chemical reactions, especially in indirect reductions or oxidations, in which the proper choice of the
electron transfer mediator or of the electrogenerated reagent precursor is crucial to the success of a
particular reaction.
From our experience, the largest difficulty (or intellectual activation barrier) that homogeneous
chemists encounter in trying to deal with the electrochemical literature is directly related to elec-
trochemical jargon rather than to fundamental concepts. Although electrochemistry was born as a
synthetic method (by Kolbe, Haber, and Fichter, among others), most electrochemical textbooks use
an analytic approach to these fundamental concepts. As a result, mathematical formulations and
jargon invade most of the presentations, which often results in an effect similar to the caveat at the
entrance of Dante’s Inferno:
Per me si va nella città dolente,

Per me si va nell’ eterno dolore
Per me si va tra la perduta gente …
Lasciate ogni speranza, voi ch’ entrate.
Dante Alighieri
Divina Commedia
Our point is not to criticize these necessary and worthwhile approaches that give to electrochem-
istry its ability to interpret and rationalize on a quantitative basis a large number of experimental
facts that extend far beyond strictly electrochemical domains. Most of our published work (as well
as the later sections of this chapter) advocates our belief in the usefulness of these physicomath-
ematical approaches, yet we regret that they may be perceived by nonanalytic chemists as impor-
tant obstacles in approaching molecular electrochemistry. For this reason, in this chapter, we take
advantage of the fact that most of these precise approaches are extremely well exposed in popular
electrochemical textbooks [1] to try to present most of the necessary electrochemical basis in
* They intervene as soon as heterogeneous reactants or phase boundaries are involved in the reaction medium, for example,
as in phase-transfer catalysis. In fact, the conscious (or even subconscious) use of spatial structuring of solutions is not
a privilege of electrochemists: nature uses the same phenomenon in most of its reactions, as in the proton transfer pump
crucial to ATP synthesis or in the photosynthetic chain.
words and concepts using as much as possible references (or antireferences) to analogous concepts
of homogeneous chemistry. Thus, we hope that this chapter may constitute both a whole and a
guide to further and more specialized readings in electrochemistry. Yet there are three excep-
tions, each dealing with kinetic aspects, in which we had to break our resolution. The first two
concern electron transfer theories, and the third relates to electrochemical kinetics in the presence
of follow-up chemical reactions. Although these three points, and their pertinent derivations, are
in our opinion very important for a fine understanding of electrochemical processes and capabili-
ties, we suggest that the reader not interested in the mathematical body may skip the equations but
nevertheless follow the corresponding text.
This chapter is divided into three parts. In the first, basic definitions and their consequences for
homogeneous chemistry are presented. The second deals with the fundamental aspects of elec-
trode phenomena, whereas the third discusses the problem of mass transfer at electrodes and its
consequences for electrochemical kinetics. The particular problems and concepts associated with
preparative-scale electrolysis are presented in a separate chapter (Chapter 10).
II. FUNDAMENTAL ASPEcTS Of ELEcTRON TRANSfER REAcTiONS

A. XIDaTIoN–REDUCTIoN REaCTIoNS VErSUS ELECTroN TraNSFEr
O
REaCTIoNS IN OrGaNIC CHEMISTrY aND ELECTroCHEMISTrY
1. Oxidation–Reduction versus Electron Transfer Reactions
In homogeneous chemistry, pure electron transfer reactions are seldom encountered. Indeed, with
the exception of a few examples, electron transfers are often associated with atom or group trans-
fers. This usually results in a confused notion of the nature of oxidation–reduction reactions. For
example, the reaction of a ketone with sodium in alcohol to afford the corresponding alcohol, via
the sequence in the following [2] (see also Chapters 13 and 14),
Na – ROH Na ROH
C O C O C OH CH O– CH OH (1.1)

is termed a reduction. The same term is used for the Meerwein–Ponndorf–Verley reaction, which is
supposed to involve a concerted cyclic transition state [3,4]:
AI AI
O O O O OH
CH3 CH3
(1.2)
C C C C C
H CH3 H CH3 H

Similarly, reactions of metallic hydrides of aluminum or boron, in which the hydride is transferred
to the carbon (Equation 1.3 [5], or 1.4 [6,7]), are also considered reductions [7]):
Solv Solv
H H H
–Solv
C + C AIH–2 C AIH–2 C
+ Li , AIH–4
O Solv Solv O H O H OH (1.3)

Li+ Li+
Solv Solv Solv Solv

Solv Solv
Basic Concepts 7
O O
C H C H
ROH
C O + BH4– H O H O (1.4)
– –
B R B R
H H H H
H H
Although the preceding four reactions all obey the same stoichiometry for the carbonyl–alcohol
transformation and thus involve the same variation in the oxidation state of the carbon atom, they
are obviously different. Sodium reduction, in Equation 1.1, supposedly involves single electron [8]
and proton transfers in a succession of separate steps; conversely, in reactions (1.2) through (1.4),
groups or atoms are transferred.
The same confused notions also exist for oxidation reactions, the problem being even more sub-
tle. For example, permanganate is presented in most introductory textbooks as a typical oxidant
corresponding to the half-reaction in Equation 1.5:
MnO 4 − + 5e + 8H + Mn 2+ + 4H 2O (1.5)
This, associated with the classic one-electron oxidation of ferrous to ferric salts by permanganate,
for example, may lead to the implicit notion that permanganate actually sequentially accepts elec-
trons in a similar way as the carbonyl group in Equation 1.1. The fact that this is not always the case
in practice is clearly evidenced by the mechanism of alcohol or aldehyde oxidation by permanganate
to ketones or carboxylic acids. Indeed, it is generally accepted that the mechanism of acidic oxida-
tion of aldehydes by permanganate involves no electron transfer steps but rather atom transfers as
in the sequence of Equations 1.6 through 1.8 (where B− is one of the bases present in the reaction
medium) to afford the carboxylic acid and an unstable manganese (V) moiety, which rapidly evolves
into MnO2 or Mn2+ according to the pH of the solution [9].
R R
C O + H3O+ C O+ – H + H2O (1.6)
H H
H H
–
R C O R C O
(1.7)
O+ MnO3 O MnO3
H H
H
C O
B– R
BH + R – CO2H + MnO–3 (1.8)
HO MnO3
Similarly, a reaction proceeding through a sequence of one-electron transfers and chemical steps,
such as pinacol formation from a ketone (Equations 1.9 and 1.10),
R R R
Na/Ng +BH
C O C O– C OH (1.9)
+B–
R΄ R΄ R΄
R R
R R
R R R΄ R΄
BH
C OH + C O– C C R΄ C C R΄ (1.10)
R΄ R΄
O O– OH OH
H
can be reversed via a totally different sequence of steps involving atom transfers as in the classic
glycol oxidation to ketones by lead tetraacetate as follows [10]:
C OH C O Pb(OAc)3
+ Pb(OAc)4 + AcOH (1.11)
C OH C OH

C OH Pb(OAc)3 C O
Slow
Pb(OAc)2 + AcOH (1.12)
C OH C O

C O C O
Pb(OAc)2 + Pb(OAc)2 (1.13)
C O C O
2. Outer Sphere and Inner Sphere Electron Transfers

The preceding examples, which were purposely restricted to well-known reactions of carbonyl
and related functions, illustrate the large ambiguities associated with oxidation–reduction notions
in organic chemistry. As suggested earlier, these ambiguities certainly stem from the fact that
more attention is given to the overall transformation of one of the reactants (the substrate of
interest) than to the other(s) (the reagents). Indeed, in the ketone-to-alcohol reductions described,
more interest is devoted to the ketone than to the coreactant [Na, Al(OR)3, Li + AlH4−, or BH4−].
When the complete stoichiometrics are considered, it appears more clearly that all four reactions
(Equations 1.1 through 1.4) are totally different though substrate and product of interest are for-
mally the same.
On the other hand, when one thinks in terms of electrochemical reductions or oxidations, special
attention is devoted to the coreactant, that is, to the electrode that provides or accepts electrons.
Thus, in order to discuss or compare electrochemical reactions with their organic analogs, it is
of the utmost importance to use more precise terms than the so inaccurate reduction or oxidation
notions. A similar problem has been addressed in the inorganic and organometallic fields. Indeed, it
was early recognized that oxidation–reduction reactions at metal centers must be classified accord-
ing to two types: outer sphere and inner sphere reactions.* A typical example of the inner/outer
sphere dichotomy is given in Equations 1.14 and 1.15, which relate to chromium(II) oxidations by
cobalt(III) complexes.
* Another complementary concept, named concerted electron transfer, which bridges the gap between homogeneous and
electrochemical electron transfers was introduced by Savéant [2d] (see also Chapter 13).
Basic Concepts 9
Outer sphere (electron transfer) reaction [11]:
Cr 2+ + Co( III ) (NH 3 )63+ → Cr 3+ + Co( II ) (NH 3 )6 2+ (1.14)
Inner sphere (ligand transfer) reaction [11,12]:
Cr 2+ + Co( III ) (NH 3 )5 Cl 2+ → Cr ( III )Cl 2+ + Co( II ) (NH 3 )52+ (1.15)
Besides their relatively close stoichiometrics, the fact that the fundamental nature of the reactions
differs is evidenced by the acceleration by a factor of approximately 6 × 109 in the rate constant
when a chlorine ligand is involved in the transition state of the process.
Outer sphere electron transfers correspond to situations in which an electron is transferred with-
out the necessity of bond formation or bond cleavage between or within the reactants. The electron
is then transferred when the partners are sufficiently close to allow orbitals of suitable geometries
to overlap. The energetic stabilization required is of the order of 1 kcal/mol, which is considerably
smaller than that corresponding to any bond formation. The ketone reduction by sodium metal in
Equation 1.1 is considered to belong to this class of electron transfer. Similarly, owing to the usual
poor ability of electrodes in establishing bonds with the electroactive molecules, most of the elec-
trochemical electron transfers pertain to this group.* Interestingly, theories have been developed for
outer sphere electron transfers that allow reasonable predictions of their rate constants and activa-
tion energies (see Sections II.C and III.C).
Note that this definition does not imply that the products obtained upon electron transfer must be
stable, but only that the electron transfer activation process does not imply any important molecular
rearrangement. Indeed, one or both of the products may chemically evolve through fast follow-up
reactions as in the reaction sequences (1.1) or (1.9) and (1.10). Under some specific circumstances,
the electron transfer step may be strongly coupled with the chemical reaction expected to follow
would a pure outer sphere mechanism be taking place. This is termed concerted (outer sphere)
electron transfer [2d].
Inner sphere reduction or oxidation is normally restricted to bond formation between the reac-
tants in the transition state. For example, the chromium (II) oxidation in Equation 1.15 has been
shown to involve a chloride bridge between the chromium and cobalt centers as depicted in the fol-
lowing activated complex structure [12]:
#
Cr 2+ Cl Co( III ) (NH3 )5  (1.16)
 
The organic chemical reduction–oxidations presented in the reaction sequences (1.2), (1.3), (1.4),
(1.7), or (1.11) through (1.13) belong to this class. Obviously, because an electrode is considered
able only to supply or accept electrons, this class of reduction–oxidation reactions should not be
observed in electrochemistry. However, this is not a clear-cut problem. Indeed, crucial interactions
with the electrode surface (e.g., organometallic partial bonding, chemisorption, physisorption) may
be crucially involved in the overall electron transfer process although the electrochemical kinetic
signature remains characteristic of a classical outer sphere case [13].
In our opinion, a third class of reduction–oxidation reactions exists, which is not clearly encom-
passed by one of the two just mentioned. It corresponds to the cases in which there really is an
electron transfer (i.e., not a group or atom transfer), but the latter is concerted with bond breaking or
formation within one of the reactants. It was proposed that the phrase concerted electron transfer
* This is not completely true, and a weak chemical interaction with the substrate undergoing the electron transfer step may
be crucial. This is always the case in electrocatalysis (e.g., proton reduction, fuel cells) but is hard to observe for organic
or organometallic cases. However, there are several perfectly documented examples in the recent literature [13b and
references therein].
be used to refer to such situations [2d, 14–16]. A characteristic example of this class is given by the
reduction of alkyl halides, represented as follows:
RR′R′′C − X + e → RR′R′′C• + X − (1.17)
Indeed, it is now considered that carbon–halide bond cleavage is concerted with electron uptake
(see References 2d,14,15
−
as well as Chapter 24), that is, there is no intermediacy of an anion radical,
such as [ RR′R′′C − X],• during the electron transfer [15]. These cases must be contrasted with those,
such as the following aryl halide reduction:
Cl + e – Cl + Cl–, etc (1.18)

in which the electron is taken up (or lost) without drastic molecular rearrangement [14,16], to afford
an anion radical (or a cation radical in oxidations), although the latter may be extremely short-lived.
Formally, the carbonyl reduction in Equation 1.l should fall in this class of reaction, since it is usu-
ally considered that the π-carbonyl bond is broken (1.2) upon electron transfer to yield a ketyl anion
radical (Equation 1.20) that is better described as a tautomer of the delocalized one in Equation 1.19
than by a simple mesomeric form due to the ion pairing by the alkaline cation:
C O–
C O+e (1.19 and 1.20)
C O–

Yet the nature of the bond cleaved, especially when the latter is involved in extended delocalizations
as in aromatic ketones, and the fact that the skeleton of the molecule remains intact, may explain
why these reductions are generally considered as belonging to the outer sphere class.
From Table 1.1, which summarizes this discussion, it is seen that outer sphere and inner sphere
electron transfers have their exact analogs in both fields of organic chemistry and electrochemistry.
TABLE 1.1
Chemical and Electrochemical Reductions or Oxidations in Organic Chemistry
Bond Breaking or Follow-Up Examples
Formation in the Chemical
Designation Transition State Reaction Chemical Electrochemical
Outer sphere No No Na
Anthracene → Anthracene •
Anthracene + e Anthracene •
electron transfer
No Yes ArCH3 + Fe(III) ⇌ ArCH3 • + + Fe(II) ArCH3−e ⇌ ArCH3• +
ArCH3 • + + base → ArCH2•,… ArCH3 • + + base → ArCH2•,…
Concerted No No ? RX + e→R• + X−
(outer sphere)
electron transfer
Ag
Inner sphere Within reactants Yes Wurtz reaction PhCH 2 Cl + e  →…
electron transfer (see Reference 13b)
Group or atom Between reactants Frequent Meerwein–Ponndorf reaction Invoked to interpret the effect of
transfer additives or electrode surface
states (as in the Kolbe reaction)
Basic Concepts 11
The third class, that is, concerted (outer sphere) electron transfer, is not easily recognized in organic
chemistry, at least to the best of our knowledge. The fourth class, that is, inner sphere group trans-
fers, deals with the peculiar properties of special reactants in organic chemistry or with those of
special electrode materials in electrochemistry.
At this point, it should be emphasized that there is a large body of outer sphere or inner
sphere electron transfer reactions identified and used in electrochemistry, whereas this class
of reactions is less developed in organic chemistry. Conversely, there is an extensive variety
of chemicals designed for specific group or atom transfer in reduction–oxidation reactions in
organic chemistry, but this is an area that is not very developed in molecular electrochemistry.
This certainly originates from the obvious fact that the reductive or oxidative strength of an
electrode can be varied over a wide range and adjusted with considerable precision because
of the easy control of the electrode potential. This advantage is not matched in homogeneous
organic chemistry owing to the discrete number of electron transfer reagents, particularly for
reductions. On the contrary, surface modifications and reactivities, especially under the condi-
tions of the large electrical fields encountered in electrochemistry (see Section III.4), are not
easy to design and control within the present state of the art, whereas owing to the extensive
development of organic [7], inorganic, and organometallic [17] chemistry, a large variety of
specific agents is made available. However, the apparent disadvantage of electrochemistry in the
latter area exists only when the electrode is considered as the only reactant affecting the sought
reaction. Indeed, specific chemicals (catalytic or stoichiometric reactants) that affect a desired
transformation on a substrate of interest may easily be electrochemically generated or recycled
as discussed in this book [18].
B. STaNDarD PoTENTIaLS: WHaT THEY MEaN aND WHaT THEY Do NoT MEaN
1. Standard Potentials
When considering a reaction between a possible electron donor and a possible electron acceptor, it is
important to decide a priori whether it will take place or not. This is usually answered by compari-
son of the standard (reduction) potentials E0 pertinent to each reactant. Indeed, when one considers
the possible reaction in the following,
− +
A + D A• + D • (1.21)
the corresponding equilibrium constant K is related to the difference between the standard
0 0 • −
(reduction) potentials E A/A − and E D+ /D of the A/A and D• + /D couples, respectively. It follows
from the expression of K (F is the Faraday, R is the perfect gas constant and T the absolute
temperature)
0
F ( EA / A−
− E0 + )/ RT
K =e
D /D

0 0
that at equilibrium, Equation 1.21 should be displaced toward the right-hand side when EA/A − ED +/D
and to the left-hand side when the converse is true (however, see Section II.B.6). When the dif-
ference between the values of the two standard reduction potentials is small, the reactant(s) and
product(s) equilibrium concentrations obviously depend not only on the potential difference but also
greatly on the initial composition of the solution. −
According to its definition, the standard (reduction)
−•
potential of the A/A • couple is the standard
electromotive force of a cell in which an A/A electrode is opposed to a normal hydrogen electrode
(NHE) whose potential is assigned to zero by convention.
−
A+ e A• (E 0 ) (1.22)

Thus, a standard reduction

−•
potential E 0 is ascribed to the half-reaction in Equation 1.22.* The
potential of the A/A electrode is then given by the Nernst equation [20]:
RT (A)
E = E0 + ln −• (1.23a)
F (A )

where (X) represents the activity of species X. Note that in this discussion, a simple or elementary
electron transfer is considered. In actual practice, the definition of E0 may be extended to more
complex situations (see Section II.B.5) in which the half-reaction includes a series of pre- or post-
equilibria and at least one electron transfer step. If the pertinent half-reaction is written
α1O1 + α 2O2 + + ne β1R1 + β2 R 2 +

the potential of the corresponding electrode is given by the Nernst equation:
RT ( O1 ) ( O2 ) …
α1 α2
E=E + 0
ln (1.23b)
nF ( R1 )β1 ( R 2 )β2 …

In practice, there are several limitations to such measurement. Obviously, it implies that both
members of the half-reaction are sufficiently stable for a cell to be constructed. This is a seri-
ous difficulty in organic chemistry owing to usual great reactivities of the species formed upon
electron transfers. For the most frequent cases, it is then impossible to rely on reversible ther-
modynamic transformations to determine experimental values of standard reduction potentials.
However, these important figures, or at least very precisely approximated values, can be obtained
from current intensity potential curves or transient electrochemical methods as is discussed in
Section III.E.
2. Reference Electrodes and Liquid Junction Potentials

Potentials are not measurable on an absolute scale, yet relative scales are easily constructed from
measurements of potential differences. This is a fortiori true for electrode potentials. Thus, as
explained earlier, electrode potentials are given, by convention, as their potential difference versus
the NHE. Yet there are several difficulties associated with the use of the NHE especially under
organic conditions. The most obvious is that, although it may be approximated via extrapolations,
a real NHE cannot be constructed according to the stipulations included in its definition. The other
limitations directly follow from the fact that approximated NHEs are almost impossible to use
under situations of organic and organometallic interest. Thus, many other reference electrodes have
been proposed and constructed [21]. Each of these electrodes is used by electrochemists according
to historical or sentimental reasons or because a given reference electrode is more adequate for a
given experimental situation owing to geometric factors or to limit possible pollution of the solution
under study.
* Because of thermodynamic and electrochemical conventions, standard potentials are defined in the direction of reduc-
tion, independently of the respective chemical stabilities of the molecules involved. Thus, for the oxidation of toluene to
its cation radical, E 0 refers to the reduction of the highly unstable cation radical into highly stable toluene. To overcome
such a priori chemical nonsense, for example, E 0 is frequently designated as the standard oxidation potential of toluene.
However, such a term should not be accepted according to canonical rules because it formally implies that the cell now
operates in a driven mode, that is, it is connected to an external power supply [19]. Thus, in this chapter, we prefer to use
the denomination standard reduction potentials, rather than the usual term standard potential as a reminder of the E 0
definition, although such an expression is basically a pleonasm.
Basic Concepts 13
TABLE 1.2
Potentials of Some Reference Electrodes
0
Reference Electrode ERef , V versus NHEa
Half-Cellb Name 25°C 20°C
Hg/HgO, NaOH (1 N) 0.14c
Ag/AgCl, KC1 (s) 0.20c
Ag/AgCl, KC1 (1 M) 0.22c 0.22c
Hg/Hg2Cl2, NaCl (s) SSCE 0.236d
Hg/Hg2Cl2, KC1 (s) SCE 0.241d 0.245d
Hg/Hg2Cl2, KC1 (1 M) NCE 0.280d 0.281d
Hg/Hg2Cl2, KCl (0.1 M) 0.334d
Hg/Hg2SO4, K2SO4 (s) 0.64c
Hg/HgO, NaOH (0.1 M) 0.93d
a For any O/R couple, E 0 ( versus NHE ) = E 0 ( versus Ref ) + ERef

0
.
b In aqueous solutions, (s) indicates saturation.
c From Reference 21c.
d From Reference 21a,b.
To be considered a suitable reference electrode, an electrode must have a known and reproduc-
ible potential versus the NHE. This potential must be nearly an invariant of the current flowing
through the electrode, which implies that the electrode reaction is extremely fast and the electrode
reactants are extremely concentrated (see Sections III.C.3 and IV.B.2). It should also have a small
temperature coefficient and should be easily constructed in a reproducible way. A large variety of
electrodes meeting these requirements to different degrees have been devised; Table 1.2 presents a
few of the most frequently used.
Inspection of Table 1.2 shows that the solution composition of the electrode half-cell is criti-
cal. These solutions may differ considerably (nature of the solvent, nature and concentrations of
the electrolytes or ionic members of the half-reaction, and so on) from those used in organic or
organometallic electrochemistry. The two solutions, that of the experimental system under study
and that in the inner reference electrode compartment, then tend to equilibrate across their inter-
face (the liquid junction) to reach a final state in which both solutions are identical. Reaching such
mixing equilibrium would lead to pollution of the organic solution on the one hand (i.e., alteration
0
of the reactions of interest) and drift of ERef on the other hand. In practice, to slow down pollution
of both solutions significantly, another solution is usually interposed, which acts as a buffer. This
bridge then results in the creation of two liquid junctions. At each of these junctions, the physical
process of equilibration is controlled by the diffusion of the various components, that is, depends
on their mobilities, which may be extremely different [22]. In the process of equilibration, there is
then a trend to break the electroneutrality on both sides of the junction. Indeed, the center of posi-
tive charges tends to separate from the center of negative charges because of intrinsic differences
in the mobilities of the cations and anions. This results in the creation of an electrostatic potential
difference Ej across the junction, which opposes the charge separation. The system reaches then
a steady-state equilibrium so that the electrostatic energy exactly matches that resulting from
differences in chemical composition across the liquid junction. For identical solvents on both
sides of the junction, models have been developed to estimate the resulting junction potentials Ej,
which may reach several tens of millivolts in practice [23]. Yet in most organic or organometallic
experiments, different solvents are used on both sides of the liquid junctions. Other phenomena
(e.g., solvent mixing, different abilities in wetting the physical interface, usually a sintered glass
frit or a glass crack, and interfacial and capillary tensions [24]) are then involved. This makes
the corresponding analysis intractable or totally irrelevant to real conditions, especially when one
considers the difficult reproducibility of most of these phenomena from one experimental setup
to another.
In practice, it is advisable to use reference electrodes or at least bridges involving, when possible,
a solvent identical to that used in the electrochemical cell. Yet this is not always possible, since, for
example, other problems may arise from solubilities or temperature dependence. In any case, when
potential determinations are crucial, a way to overcome these difficulties is to calibrate the potential
scale by measuring the potential of a reference compound (usually ferrocene since solvation of the
two redox forms is not expected to vary importantly; see Section II.B.3 and Chapter 7) in the same
solution, that is, introducing it in the investigated solution at the end of the experiment. Under such
conditions, and provided that the solution composition remains invariant in the course of the experi-
ment, a floating reference electrode may also be used. A silver wire of large surface area or a mer-
cury pool, for example, constitutes such a floating reference electrode. Indeed, it keeps a constant,
but unknown potential difference vis-à-vis the solution. Yet the resulting potential scales obtained
from run to run need to be reconciled, via the calibration procedure explained earlier, since the
floating reference potential is unknown and prone to vary as a function of the exact composition of
the solution.
3. Standard Reduction Potentials versus Ionization Potentials or Electron Affinities

When one of the members of a given half-reaction is too unstable for the measurement of the
pertinent standard reduction potential, one frequently relies on the values of ionization potentials
or affinities since these can be measured for a wide variety of species. However, one should be
extremely cautious in the use of such data obtained from gas phase when applying them to reactions
in solution [25].
Let us consider a simple half-reaction O + e⇌R, with a standard reduction potential E 0. It must
be realized that E0 corresponds to (1) stable solvation states for O and R and (2) stable nuclear con-
figurations for O and R. On the other hand, ionization potentials Ip or affinities Aff correspond to
nonsolvated O and R and radiative transitions (see Section II.C), that is, to unstable nuclear configu-
rations R* or O*, respectively, for O (affinities) or R (ionization potentials). The ensuing thermody-
namic relationships between the three numbers E0, Ip, and Aff are then derived from thermodynamic
considerations based on the cycles in Scheme 1.1.*
Thus, it follows that
(∆GO,solv
0
− ∆GR,solv
0
) − ∆GR*,rel
0
E 0 = − Aff + + Cst (1.24)
F
and
(∆GO,solv
0
− ∆GR,solv
0
) − ∆GO*,rel
0
E0 = Ip + + Cst (1.25)
F
where E 0, Aff, and Ip are expressed in volts, whereas ΔG 0 is in joules and relative to molar quanti-
ties. From Equations 1.24 and 1.25, it is seen that E0 and Ip (or E 0 and Aff ) should correlate linearly,
* Note that no explicit attention to NHE or metal phases [26] has been given in the cycles, since these factors introduce a
constant term Cst in Equation 1.24 or 1.25, independent of the O/R couple. In Scheme 1.1, rel stands for structural relax-
ation and met1 and met2 for metal 1 and metal 2 to emphasize that generally different metals are used in the different
measurements.
Basic Concepts 15
NA Aff R*gas ∆G 0R*, rel
Ogas+ emet 2 Rgas
–∆G 0O, solv ∆G 0R, solv
∆G0rad = FE 0
Osolv + emet 1 Rsol
–∆G 0O, solv ∆G 0R, solv
Ogas + emet 2 Rgas
∆G 0O*, rel O*gas + emet 2

–NA IP
SchEME 1.1 Thermodynamic relationships between ionization potentials, affinities and standard reduction
potentials.
with a slope of unity for an extended series of O/R couples, only when the terms in the additional
term are reasonably constant within the series. In practice, this condition is almost impossible to
fulfill accurately but is approximated for large delocalized molecules belonging to an identical class
[27,28]. Indeed, for such molecules, the gain or loss of an electron introduces only small distur-
bances in the molecules. Similarly, there are nearly no specific solvation effects, the charge being
largely delocalized, hence easily screened. Then, provided the equivalent solvation radii are large
or remain close within the series, the solvation differences are small [27]. Figure 1.1 shows that
when these conditions are fulfilled, good correlations with slopes close to the unity are observed.
2
Affinities, eV
–1.5 –0.5
Reduction potentials, V
FiGURE 1.1 Correlation between affinities and reduction potentials for an extended series of polycyclic
aromatic hydrocarbons. (Data from Dewar, M.J.S. et al., J. Am. Chem. Soc., 92, 5555, 1970.)
2.5
E 0, V vs NHE
2.0
0.6 V
1.5 8.0 8.5 9.0
Ionization potential, eV
FiGURE 1.2 Correlation between ionization potentials and standard reduction potentials of the correspond-
ing cation radicals for a series of alkylbenzenes. Two dotted lines, with slopes of unity, are positioned at each
end of the series to emphasize the deviations vis-à-vis the data in Figure 1.1. (Data from Howell, J.O. et al.,
J. Am. Chem. Soc., 106, 3968, 1984.)
Thus, determination of E0 for some of the compounds of the series allows good estimates of E 0 to
be obtained from Ip or Aff measurements. Yet it must be emphasized at this point that there should
be virtually no special difficulties in the direct measurements of the unknown E 0 values for the O/R
couples meeting all the requirements discussed here. Indeed, these conditions restrict the validity
of the method to chemically reversible outer sphere electron transfers, that is, to those systems for
which direct E0 determination does not represent any serious problem (except may be for solubility).
From this statement, it is seen that the real practical interest of the method deals with redox
couples that involve one too chemically unstable member for experimental E 0 to be determined eas-
ily. An example of such a case is given by the series of alkylbenzenes [29] presented in Figure 1.2.
Indeed, owing to the rather small size of the benzene π system compared with the large aromatics in
Figure 1.1, as well as to the considerable variations in size with the number and nature of the alkyl
substituent(s), it seems obvious that the difference in solvation energies in Equation 1.25 has to vary
within the series.

( ∆G
0
O,solv − ∆GR,solv
0
)
− ∆GO*,rel
0
≈ −0.3FE 0
Interestingly, a good linear correlation (i.e., with data dispersion similar to that in Figure 1.1) is
nevertheless observed in Figure 1.2, yet with a slope of 0.7, instead of unity as in Figure 1.1. From
Equation 1.25, it follows that Ip also correlates with E 0, a reasonable conclusion owing to the homo-
geneity in the series of substituents. Yet the correlation in Figure 1.2 clearly shows the danger of the
blind use of such correlations, that is, of the use of Ip or Aff values instead of E0. Indeed, a difference
larger than 0.5 V is introduced when extrapolating E 0 from Ip values relative to either ends of the
series while assuming a unity slope as in Figure 1.1.
4. Comparison or Extrapolation between Solvents

Owing to the extremely large variety of solvents used in organic or organometallic chemistry, it is
unlikely that all the pertinent electrochemical data can be found for a particular system and a par-
ticular solvent [30]. Thus, the problem of the transposition of data obtained for one solvent to another
frequently arises. As discussed for Ip or Aff, this should not be done without extreme precautions.
Basic Concepts 17
Indeed, by subtraction of the two equations, akin to Equation 1.25, pertinent to each solvent, one
obtains readily for any O/R redox system placed in two different solvents
E solv1 − E solv2
0 0
=
( ∆G0
O,solv1 − ∆GO,solv2
0
)− (∆GR,solv1
0
− ∆GR,so
0
lv2 )
+ C′
F
where C′ is a constant term independent of the O/R couple. However, the numerator of the frac-
tion in the right-hand side, which may include specific solvation terms for each solvent, may vary
considerably from one redox couple to the other. Thus, on an absolute basis, extrapolations between
solvents are meaningless; however, they may be used with great caution. Evidently, the same is a
fortiori true for the use of HOMO or LUMO energies [31] or Hammett–Taft and related extrather-
modynamic relationships [32].
5. Formal Reduction Potentials

It is usually difficult to determine or impose activities, since activation coefficients are nearly always
unknown for the redox systems investigated in organic or organometallic chemistry. Thus, formal
reduction potentials E 0′ are measured, when feasible, rather than E0. E 0′ corresponds to the electrode
potential versus NHE when the concentration ratio CO/CR is made unity, rather than the ratio of the
activities, as in the definition of E 0 [33]. Thus, from Equation 1.23, it follows that
RT (O) RT f C
E = E0 + ln = E0 + ln O O
F (R) F f RC R
that is,
RT f
E 0′ = E 0 + ln O (1.26)
F fR
where f J is the activity coefficient of species J. The latter being affected by ionic strength and con-
centrations, for example, it is predicted that E 0′ values should vary from medium to medium. This is
important to remember when E 0′ values, determined under the conditions of low concentration and
large ionic strength usually met in electrochemistry, need to be transposed under the conditions of
low ionic strength and high concentration frequently used in organic chemistry [34].
Formal potential may also include some constant or selected components of the medium that
participate in the overall redox reaction. Thus, pH and concentrations of complexing reagents, for
example, are often included in E 0′ [35] when the O and R molecules are not interconnected by a
simple electron transfer. To explicate this point, let us discuss a typical example related to aldehyde
oxidation. The stoichiometry of the reaction in the following involves an overall transfer of two
electrons and one oxygen atom:

RCHO + 3H 2O RCO2H + 2e + 2H 3O + (E )
0
1 (1.27)
Yet the acid may exist under two equivalent forms, the acid per se or its conjugated base. Thus,
when the pH is such that the carboxylate anion is the stable form, Equation 1.27 is better rewritten
as follows:

RCHO + 4H 2O RCO2 − + 2e + 3H3O + (E )
0
2 (1.28)
From a preparative point of view, both reactions are nearly identical, since the acid and its conju-
gated base are two forms of the same chemical entity. From a thermodynamic point of view, how-
ever, they differ because of the involvement of the acid dissociation in the following:
RCO2H + H 2O RCO2 − + H3O + (Ka ) (1.29)

which thus corresponds to the definition of a second standard reduction potential E20 in Equation
1.28. Yet E10 and E20 are related because of the necessity of a unique potential for the solution. Indeed,
from Equation 1.27, the potential is obtained as in Equation 1.30, whereas it is expressed as in
Equation 1.31 from 1.28 (note that activity of the water solvent is taken as unity):
RT (RCO2H)(H 3O + )2
E = E10 + ln (1.30)
2F (RCHO)
RT (RCO2 − )(H 3O + )3
E = E20 + ln (1.31)
2F (RCHO)
Identification of both equations readily gives the relationship between E10 and E20 in Equation 1.32,
which shows that provided that Ka is known, knowledge of either one of E10 or E20 is sufficient.
RT
E20 = E10 − ln K a (1.32)
2F
On the other hand, owing to the involvement of proton activities in Equation 1.30 or 1.31, it is expected
that the acid–aldehyde reduction potential is extremely dependent on the pH. Thus, it is more conve-
nient to separate the pH-dependent terms from those featuring the degree of conversion. Similarly,
it is more realistic to consider the sum of the acid and its conjugated base activities to represent the
carboxylic product. Thus, taking that into account, Equation 1.30 is rewritten as follows:
RT (H 3O + )3 RT [acid]
E = E10 + ln + ln (1.33)
2 F H 3O + + K a 2 F [aldehyde]
where the term [acid] represents the sum of the concentrations of its two forms, so that
RT [acid]
E = E 0′ + ln (1.34)
2F [aldehyde]
This allows finally the rewriting of Equation 1.33 under the form in Equation 1.34, which directly
gives the conversion ratio as a function of the potential and of the pH-dependent formal potential E 0′
in Equation 1.35, where K a′ = K a ( fRCO2H /fRCO2− ) and E10 ′ = E10 + ( RT / 2 F ) ln( fRCO2H /fRCO2− ) whenever
activities significantly differ from concentrations (h stands for (H3O+)):
RT  h3 
E 0′ = E10 + ln   (1.35)
2 F  h + K a′ 

It is seen from Equation 1.34 that although the significance of E 0′ is not established on definitions as
solid as those of E 0, E 0′ nevertheless is of great practical interest since it is the reference parameter
that controls the actual conversion ratio in a given situation. Indeed, at any pH or ionic strength,
Basic Concepts 19
E > E 0′ requires that the acid is the major component in the system, whereas it is the aldehyde for
E < E 0′ . At E = E 0′ , 50% of the aldehyde is oxidized. To decide which potential is needed at a given
pH, or vice versa, it is then important to know the variations of E 0′ with pH. These variations are
conveniently represented in the form of a potential–pH diagram and are derived from Equation
1.35. Indeed, from the latter, it is easily seen that E 0′ varies linearly with the pH as soon as the latter
differs slightly from pK a′ , that is (at room temperature),
pH < pK a′ E 0′ ≈ E10′ − 0.06pH
pH = pK ′ E 0′ ≈ E10′ − 0.01 − 0.06 pK a′

pH > pK a′ E 0 ′ ≈ E10 ′ + 0.03pK a′ − 0.09pH

Such a diagram is represented in Figure 1.3. The acid predominance zone corresponds to the upper
part of the diagram, that is, to pH and potential conditions so that the point representing the system
is above the E 0′ versus pH curve. Conversely, the aldehyde predominates when the point figuring
the system is located under this boundary. To illustrate the practical interest of these diagrams, let
us refer to the classic test of the silver mirror, which corresponds to aldehyde oxidation by the silver
nitrate–ammonia reagent.
The standard reduction potential for Ag + /Ag is 0.80 V versus NHE. Comparison with the dia-
gram in Figure 1.3 shows that the silver ion is not able to oxidize aldehydes except under basic
conditions. Yet under such conditions, silver oxides are formed and precipitated.
Ag + + 2NH 3 Ag(NH 3 )+ + NH 3 Ag(NH 3 )2 + (1.36)

Thus, a particular base, ammonia, which gives stable complexes with Ag + in Equation 1.36, is used
to bring about the basic pH. However, because of the formation of complexes in Equation 1.36,
Acid
–1
E
Aldehyde
–1.5
5 10
pH
FiGURE 1.3 Potential–pH diagram for the aldehyde–acid transformation (solid line). The dashed line gives
that for Ag/Ag+ (0.1 M) when the pH is imposed by NH3. The hatched zone corresponds to the only region
where the silver mirror test can be performed.
the free Ag+ concentration decreases, which tends to lower the oxidative strength of the solution
+
( E = EAg
0
+ + 0.06 ln( Ag )). This implies that the ammonia concentration must be adjusted precisely:
sufficient for the pH to be in the required range, but not too high in order to retain a sufficient oxidiz-
ing power of the silver ion solution. In practice, the best concentration is that corresponding to the
titration point of the silver ion, which explains the great caution used in the preparation of the mirror
test reagent, [ Ag(NH 3 )2 + ,NO3− ], a fact that is often puzzling for freshman chemists.
6. Relationships between Thermodynamic Driving Force ΔE0

and Feasibility of an Electron Transfer Reaction
According to thermodynamics, the feasibility of an electron transfer reaction depends on the free
energy change ΔG associated with it.
α1O1 + β2 R 2 β1R1 + α 2O2 (1.37)

For the electron transfer in Equation 1.37, which involves the two half-reactions in Equations 1.37a,b,

α1O1 + ne β1R1 (E )
0
1 (1.37a)

α 2O2 + ne β2 R 2 (E )
0
2 (1.37b)
the initial Gibbs energy driving strength ΔGin. is given from basic thermodynamics by*
 (R )β1 (O )α2 
∆Gin. = ∆G 0 + RT ln  1 α1 2 β2  (1.38)
 (O1 ) (R 2 )  in.
where
∆G 0 = nF ( E20 − E10 )
the subscript “in.” means that the activities to be used in the bracketed term are those corre-
sponding to the initial state of the system.
Provided ΔGin. is negative or positive, a reaction proceeds up to when an equilibrium point is reached
where ΔG = 0; therefore, at equilibrium, the activities are such as given in Equation 1.39, where the
subscript “eq.” indicates equilibrium:
 (R1 )β1 (O2 )α2  0 0
 α1 β2 
= e( nF /RT )( E1 − E2 ) (1.39)
 (O1 ) (R 2 )  eq.

From Equation 1.39, it is deduced that for the forward electron transfer in Equation 1.37 to be real-
ized to some extent, it is necessary that the term on the left-hand side of Equation 1.39 is consider-
ably larger than unity, which is supposed to translate into E10 > E20. Conversely, E10 < E20 is often
leading to the conclusion that the reaction in Equation 1.37 is not possible. This conclusion may not
be true, however, depending on the respective concentrations of the various species considered in
Equation 1.37 due to the logarithmic term in Equation 1.38. This is in particular the case when some
of the species involved are unstable so that their steady concentrations are always extremely low.
* Starting here, we will note (X) the activity of species X. Concentrations, noted [X], may be substituted in all equations
for experimental convenience provided the caveats disclosed earlier are duly remembered.
Basic Concepts 21
When all reactants and products are stable, these conclusions are valid. However, when one
or both products are not stable, Equation 1.37 is continuously displaced to the right, even when
thermodynamics would predict that the equilibrium should lie to the left-hand side. This is a
situation akin to that usually considered in equilibrium displacements by physical removal (e.g.,
distillation, precipitation, and complexation) of one of the products. Thus, one may have E10 < E20
and nevertheless observe an efficient redox reaction between O1 and R2. Characteristic examples
of such situations are given elsewhere in this book, particularly in Chapters 15, 43, and 44, since
this phenomenon is the basis of redox catalysis. In such a situation, the validity of Equations 1.38
and 1.39 is not altered, provided the equilibrium remains established. Yet whenever (R1) or (O2)
approaches zero, because of the follow-up chemical reaction(s), the bracketed term on the right-
hand side of Equation 1.38 remains considerably smaller than unity, opposing the intuitive conclu-
sion based on E10 < E20 .
α1O1 + β2 R 2 β1R1 + α 2O2 → (1.40)

It is thus seen that a direct relationship exists between the thermodynamic driving force ΔE0 and the
feasibility of an electron transfer reaction only for those special cases in which all the products and
reactants are stable within the time scale considered. Yet it must be pointed out that this is seldom
encountered in usual practice owing to the generally high reactivities of the species formed upon
electron transfers.
This discussion may lead to the extreme conclusion that when the products of an electron
transfer reaction are unstable, as in Equation 1.40, thermodynamic figures, such as ΔE 0, are
irrelevant. From a simple point of view, this is true. Yet in practice, kinetic notions are implicitly
involved in the discussion of the feasibility of any chemical reaction. Indeed, a possible reaction
whose completion would require infinite time is not considered feasible. Amazingly, it is because
of kinetics that thermodynamic figures recover an interest for situations like that featured in
Equation 1.40. To state this point exactly, let us present and discuss the case of the oxidation
of methylbenzenes by tris-(l,10-phenanthroline)–iron(III) complexes (FeL33+) in the presence of
pyridine bases [36].
From their standard reduction potentials, in the range of 1.35 V versus NHE [37], FeL33+ com-
plexes should not be able to oxidize methylbenzenes, the standard potentials of which exceed 1.75 V
versus NHE [29]. The reaction, however, proceeds smoothly in the presence of a pyridine base,
according to the following stoichiometry:
ArCH3 + 2FeL 33+ + 2py → ArCH 2 − py + + pyH + + 2FeL 32+

and was shown [36,38,39] to initiate through an electron transfer between the iron and the arene
centers, as outlined in Scheme 1.2. Two limiting kinetic situations are observed according to
ArCH3 + Fe(III) ArCH3+ + Fe(II) (kf, zb)

(1.41)
ArCH3+ + py ArCH2 + pyH+z (kH) (1.42)
ArCH2 + Fe(III) ArCH2+ + Fe(II) (Fast) (1.43)
ArCH2+ + py ArCH2 – py+ (Fast) (1.43)
SchEME 1.2 Mechanistic outline of the oxidation of methylbenzenes by iron(III) phenanthroline complexes.
the respective rates of the proton transfer (Equation 1.42) or of the backward electron transfer in
Equation 1.41. When the latter is larger, the electron transfer in Equation 1.41 acts as a rapid equi-
librium, the proton transfer being the rate-determining step (RDS). Thus, an apparent rate constant
is determined, as follows:
kf
k ap = kH (1.45)
kb
where kf and k b are the forward and backward rate constants of the reaction in Equation 1.41.
Conversely, when the proton transfer rate is considerably faster than the backward electron transfer,
the RDS is the forward electron transfer, and the observed rate constant is then kf, as given here:
k ap = kf (1.46)
It is thus seen that, in the first situation, although the thermodynamic interdiction has been over-
ruled, thermodynamic figures control the apparent rate constant observed. Indeed, Equation 1.45
may be rewritten as follows:
0 0
( F /RT )( EFe − EArCH )
k ap = kH e 3
(1.47)
Thus, owing to the large magnitude of k H (103–106 M–1 s–1 [36b,c,38,40]), the apparent rate constant
in Equation 1.47 remains appreciable even for largely endergonic electron transfers (for 1,2,4,5-
tetramethylbenzene, EFe 0
− EArCH
0
3
< −0.6 V). Yet if the electron transfer is too endergonic, kap becomes
too small for the reaction to proceed at a significant rate; hence, there is still a thermodynamic limit
for the sequence in Equations 1.41 and 1.42, but this limit may be considerably less stringent than a
strict application of thermodynamics to Equation 1.41 would predict.
The involvement of thermodynamic figures when the forward electron transfer is the RDS is
more subtle and arises because of linear or quadratic [41] relationships between activation free ener-
gies and thermodynamic driving force, which applies for outer sphere electron transfers like that in
Equation 1.41 (see Section II.C.6).
C. MECHaNISM aND THEorY oF OUTEr SpHErE ELECTroN TraNSFEr REaCTIoNS

Owing to the aim and scope of the present chapter, it is impossible to discuss here all the subtleties
and refinements of electron transfer theories. Yet our purpose is to give a general overview of the
different concepts on which these theories are elaborated. As such, this text may constitute per se a
presentation of the basic features essential to a thoughtful experimental use of outer sphere electron
transfer mechanisms. On the other hand, we hope it may constitute an introduction to more special-
ized readings [42].
In the following, we tried to rely, for the sake of simplicity, on simple physicochemical pictures
that often were not involved in the original works [41,43,44]. As a consequence, this text short-
circuits some extremely important but more specialized theoretical aspects of the original theories.
1. Diffusion Limitation in Electron Transfer Reactions

A very common characteristic of electron transfer reactions is that they frequently involve acti-
vation energies lower than other chemical reactions that relate to group or atom transfers. As a
consequence, the activated processes may be extremely fast compared with the physical process of
bringing the two reactants close together (or separating the products) so that they can react. In such
cases, the overall rate constant determined does not reflect activation parameters but rather transport
properties. Note that occurrence of this phenomenon is also implicitly recognized in homogeneous
Basic Concepts 23
kf
Overall (measured) A+D A–+ D+
kb
k #f k#b
r
Diffusion (physical) k dif kpdif
k act
f
Activation (chemical) [A, D] [A–, D+]
kbact
SchEME 1.3 Debye-Smoluchowski microscopic representation of a homogeneous electron transfer indicating

its diffusional and activation-driven components.
chemistry. Indeed, the diffusion limit rate constant, of the order of 109–1010 M–1 s–1, corresponds to
reactions that are limited by encounters of the reactants, whereas the limit related to product separa-
tion is intuitively included within the fuzzy notion invoked in cage separation.
Thus, in a general situation, an electron transfer between a donor D and an acceptor A must be
considered in terms of, at least, the three successive elementary steps outlined in Scheme 1.3. This
representation may be even more segmented when, for example, different ion pairs are involved, such
− + − +
as [A • , solvent, D •] or [A • , (solvent)n, D •]. Yet it is sufficient here to consider the simplest situation
represented in Scheme 1.3 [45]. The formation or dissociation of cages in Scheme 1.3, each a physical
process, is normally handled on physicochemical grounds. Yet following a notation by Debye, their
r
effects may be represented under the form of pseudo-chemical rate constants: kdif (reactant pair) and
p
kdif (product pair).* Using this notation, it follows [46] that the overall forward kf and backward k b
rate constants are given by Equations 1.48 and 1.49 as a function of the activation rate constants kfact
and kbact relative to the reacting pairs:
f 0
1 e ∆Gr /RT 1 e ∆G /RT
= + + (1.48)
kf kfact r
kdif p
kdif
f 0
1 e ∆Gp /RT 1 e − ∆G /RT
= act
+ p + r
(1.49)
kb kb kdif kdif
− ), while ∆Gr or ∆Gp represents the Gibbs energies

f
In Equations 1.48 and 1.49, ∆G 0 = F ( ED0 + /D − EA/A
0 f
necessary to form the pairs in Scheme 1.3 for the reactants and products, respectively. The so-called
diffusion rate constants are given by Equations 1.50 and 1.51 [45], where r is the distance between
the pair of reacting centers and Dr or Dp the sum of the diffusion coefficients of the reactants or
products, respectively.
4πN A Dr
r
kdif = ∞
(1.50)
∫ x −2e r ( ) dx
W x / RT
* Note that this abusive usage (even if correct in terms of physicochemical formulations of rates, but not of rate constants,
as recognized by Debye [45]) leads to the fuzzy notions of diffusion and cage separation rate constants.
4πN A Dp (1.51)
p
kdif = ∞
∫ x −2e p ( ) dx
W x / RT
Both pseudo-rate constants may then be evaluated from a suitable description of the work terms
Wr(x) and Wp(x) necessary to bring the reactant centers or those of the products, respectively, from
infinity to a distance x. When the work terms are negligible, straightforward integration of Equations
1.50 and 1.51 yields
r
kdif = 4πN A Drr and kdif
p
= 4πN A Dpr

which corresponds to the usual diffusion limit rate constants of the order of 109–10l0 M–1 s–1 first
proposed by Smoluchowski [45b]. When the work terms are not negligible compared to RT (due to,
e.g., specific steric interactions, electrostatic interactions between charged ions, or any other specific
ion pairs interactions), the diffusion limit rate constant may differ appreciably from these values
[36], being larger when the work terms are negative (attractive pairs) or considerably smaller when
the work terms are positive (repulsive pairs).
Because of the symmetry in Equations 1.48 and 1.49, we restrict the following discussion to the
forward process. It is also noted that kf and k b fulfill the thermodynamic condition in Equation 1.52:
0
kf = kbe ∆G /RT
(1.52)
0′
kfact = kbact e − ∆G /RT

(1.53)
Indeed, kfact and kbact, being true chemical rate constants, must obey Equation 1.53, where ΔG 0′ is the
Gibbs free energy change between the reacting pairs. When there is no other entropic contribution
in the formation of the pairs besides those corresponding to the formation of rigid pairs, one has
∆Grf − ∆Gpf ≈ Wr − Wp and then ∆G 0′ = ∆G 0 − Wr + Wp

From Equation 1.48, it is seen that the observed rate constant is always smaller than or equal to
kfdif , defined by considering only the transport limitations in kf expression, that is, by the following
equation*:
0
1 1 e ∆G /RT
dif
= r + p
(1.54a)
kf kdif kdif
When ∆G 0 RT ln(kdif p r
/kdif ), the first term in Equation 1.54a predominates, which means that in
the corresponding range, one obtains kfdif ≈ kdif r
. This corresponds to the traditional diffusion limit,
that is, to the case of extremely exergonic reactions. Conversely, for highly endergonic reactions,
p −∆G 0 /RT
Equation 1.54a yields kfdif ≈ kdif e . In the latter case, it might be surprising that a diffusion
control may be observed, yet this apparent paradox corresponds simply to the fulfillment of the ther-
modynamic conditions in Equations 1.52 and 1.54b, the highly exergonic backward reaction being
diffusion controlled. In fact, this later formulation valid for ΔG 0 > 0 provides a formal support for
the fuzzy notion of case separation rate constant.
* Note that, similarly, a transport limit is defined for the backward electron transfer. Based on Scheme 1.3 and Equations
1.48 and 1.49, kbdif is given as in Equation 1.54b:
0
kbdif = kfdif e ∆G / RT
(1.54b)

Basic Concepts 25
log k dif
f
r
k dif
f ~ k dif
p
k dif 0
f ~ k dif exp(–ΔG /RT)
0 –ΔG 0
FiGURE 1.4 Variations in kfdif , as given in Equation 1.54, with the driving force. The shaded area corre-
sponds to the zone where an activation control is not achievable, the overall kinetics being under diffusion
control.
Thus, under any circumstances, the overall observed rate constant kf cannot exceed the limit of
kfdif given in Equation 1.54a. This limit is represented in the form of a log kfdif versus ΔG 0 plot in
Figure 1.4. It must be noticed that since no special considerations have been given to the intrinsic
nature of the overall reaction up to this point, these results are valid for any kind of bimolecular
chemical reaction. Yet for reactions involving group or atom transfers, Wr(r) and Wp(r) may reach high
values (precursor complexes) compared with electron transfer reactions [47]. As a result, the values of
r p
kdif or kdif may be considerably smaller than the usual figures observed in the 109–1010 M–1 s–1 range
for electron transfers.
Activation control of the reaction is observed when kf kfdif , the latter being given in Equation
1.54a. Indeed, formation of the precursor or successor complexes is then considerably faster than the
chemical activation process, which therefore limits the overall reaction. This ensues from Equations
1.48 and 1.49 that kf ≈ kf# and kb ≈ kb#,
f f
kf# = kfact e − ∆Gr /RT and kb# = kbact e − ∆Gp /RT (1.55)

where the rate constants kf# and kb# defined in Equation 1.55 correspond to the usual measurements
of activation rate constants. Indeed, they refer to the activated process “seen” through the diffu-
− +
sional stages, the initial states being the dissociated A, D or A • , D • pairs, respectively (compare
Scheme 1.3). Owing to this formulation, Equations 1.48 and 1.49 are usually rewritten under their
equivalent forms as follows:
1 1 1 1 1 1
= # + dif and = # + dif (1.56a)
kf kf kf kb kb kb
kf 0
= e ∆G /RT (1.56b)
kb
where kf# , kb#, kfdif and kbdif are defined in Equations 1.54a and b and 1.55. Note that these rate con-
stants have exact physicochemical meanings, while kf and k b are operational global values. Though,
in general, only kf and k b values are of interest to synthetic chemists. Finally, when using such
elegant but compact formulations, it is important to recall that kfdif and kbdif are not the usual diffu-
sion limit rate constants defined in Equations 1.50 and 1.51 but may be considerably smaller when
considering endergonic reactions (compare Figure 1.4 and Equation 1.54).
In the following, we focus the presentation on the activation contributions, that is, on kf# or kfact, to
the macroscopic overall rate constant kf. First, we discuss the nature of an electron transfer reaction.
Later, models for the evaluation of the activation energy ∆Gf# are presented.
2. Basic Features of Electron Transfer in Solution

The fundamental role of the surrounding medium in an electron transfer reaction was early recog-
nized by Libby [48]. Indeed, because of the large number of molecular collisions in solution, mole-
cules are thermalized, in contrast to what occurs in gas phase, though most chemical textbooks rely
on gas phase reactions to establish kinetic laws, which are then bluntly applied to solution chemis-
try. Radiative electron transfers (i.e., analogous to photochemical excitation; see Section II.C.4) do
not take place in condensed phases. In other words, an electron cannot be transferred between two
systems in which its energy is different, as shown schematically in Figure 1.5a. In the following,+
−
a system designates a couple of molecules exchanging an electron, that is, A and D or A • and D •
e
B C
e
B
D D
A A qP
qR qP qR
C' D'
qelectron B' qelectron

A'
(a) (b)
Electron coordinate
A' B'
C' D'
qReq q# qPeq
(c) Nuclear coordinates
FiGURE 1.5 Schematic variation in the electron potential energy as a function of the nuclear coordi-
nates (qR and q P for the reactant and product systems, respectively) and of the electron coordinate (qelectron).
(a) Forbidden electron transfer; (b) allowed electron transfer; (c) projection of the system trajectory on the
electron coordinate–nuclear coordinates plane. qReq and qPeq are the values of the nuclear coordinate at the equi-
librium for the reactant or product systems, respectively, and q# that at the transition state. Solid lines, varia-
tions of the nuclear coordinates; (wavy arrow) electron tunneling. Note that, for simplicity, only one nuclear
coordinate is represented (see Figure 1.16 and the associated text for a more realistic situation).
Basic Concepts 27
together with the surrounding solvent. Thus, the initial system corresponds to the reactants and
the surrounding medium, in any nuclear configuration, which may greatly differ from its equi-
librium state. Similarly, the final system is associated with the products. Because of the intrinsic
difference in mass between the nuclei and the transferred electron, the Franck–Condon principle
applies during the very act of electron transfer. In other words, nuclear motions (10 –12 s) are then
frozen vis-à-vis those of the transferring electron (10 –15 s). Thus, for any nuclear configuration of
the initial (or final) system, a potential energy, termed the energy of the initial (or final) system, is
associated with the electron, which probes the field of the nuclei (and other electrons), as shown
− +
schematically in Figure 1.5. Each initial (viz., [A, D]) and final (viz., [ A • , D • ] energy well has a
minimum corresponding to the more stable configuration, so that energy increases when the initial
and final nuclear configurations depart from these equilibrium positions. Eventually, a point can
− +
be reached so that [A, D] and [ A • , D • ] have the same nuclear configurations and the same energy.
− +
At this point only the electron may be transferred, thus converting [A, D] into [ A • , D • ] or recipro-
cally, thus shifting the system from the initial to the final state, which may then relax to its stable
nuclear configuration.
However, even when this point is reached (q = q# in Figure 1.5b and c) transfer of the electron
(i.e., shifting from the initial to the final energy well) experiences an energetic blockage. Indeed,
− − +
it is formally stable only “in” D within the [A, D]# state or in A • within the [ A • , D • ]# one. In the
physical process of being transferred, the electron must then tunnel through a potential barrier
corresponding to the virtual states in which the electron would be between A and D. The height
of this barrier is inversely related to the degree of overlapping of the A and D orbitals affecting
the electron transfer, that is, of the coupling between the initial and final states at q = q#, which is
a point of degeneracy. The intensity of this coupling greatly influences Pe, the probability that the
electron tunnels during the time interval in which the initial and final systems have identical ener-
gies (compare Figure 1.5b). This time interval, a function of nuclear motions, is in the range of pico-
seconds, nearly independent of the acceptor and the donor, so that Pe depends mainly on the height
of the barrier. As soon as the energy stabilization Vi arising from overlapping orbitals is larger than
approximately 1 kcal/mol, Pe is close to unity, and the electron transfer is termed adiabatic. In the
converse situation, the electron transfer is called nonadiabatic, and Pe is considerably smaller than
unity (see Section II.C.4).
From this presentation, it is seen that the overall probability P of electron transfer is tentatively
approximated by P = Pn·Pe, where Pn is the probability that the nuclei achieve the q = q# configura-
tion so that the electron energy is identical for the initial and final systems (Figure 1.5b). In usual
kinetic terms, this means that the rate constant kfact is given by kfact = κ(kfact )ad, where κ is the trans-
mission coefficient (κ = 1 for an adiabatic electron transfer; κ ≪ 1 for nonadiabatic transfers) and
(kfact )ad is the rate constant observed for an adiabatic electron transfer. The latter then depends only
on nuclear motions that affect the potential energy of the electron in the initial and final states. In
usual chemical terms, (kfact )ad is then directly related to the height of the activation barrier, that is, to
the energetic separation ∆Efact between the state where the electron may tunnel and that correspond-
ing to the initial system at equilibrium (compare Figure 1.5b):

( k ) = κ kTh e
act
f
− ∆Efact /RT
(1.57)
From absolute rate theory [49], kfact is then given by Equation 1.57, where ∆Efact is the activation
energy barrier defined usually and expressed for molar quantities. From Equation 1.55, it follows
that under such conditions,
kT − ∆Grf /RT − ∆Efact /RT

kf# = κ e e
h
Note that the same presentation applies to kb# and thus
kT − ∆Gpf /RT − ∆Ebact /RT

kb# = κ e e
h
It is usually more convenient to introduce explicitly the internal energy (Wr and Wp, respectively) and
the entropic components of the free energies ∆Grf and ∆Gpf . When the formation of pairs involves no
specific interaction, their entropy of formation is identical to that of a rigid rotator (ΔSrot) that yields
∆Grf = Wr − T∆Srot and ∆Gpf = Wp − T∆Srot
and thus
 kT ∆Srot /R −Wr /RT − ∆Efact /RT 

kf# = κ  e e e 
 h 
and
 kT ∆Srot /R −Wp /RT − ∆Ebact /RT 

kb# = κ  e e e 
 h 
From classic statistical thermodynamics [50], the product
kT ∆Srot /RT
e
h
is shown to be equal to the collision frequency Z [51], which is usually of the order 1011 M–1 s–1*:
 8πRT ( mA + mD ) 
1/ 2
Z = 10 −3 N A   r2
 mA mD 

One then finally obtains [43,44]
− ∆Efact /RT
kf# = κZe −Wr /RT e (1.58)
and
− ∆Ebact /RT
kb# = κZe −Wp /RT e (1.59)
0′
where kf# = kb# e ∆G /RT because ∆G 0′ = ∆G 0 − Wr + Wp ≈ ∆Efact − ∆Ebact .
An absolute expression for κ is nearly impossible to derive in a general case owing to its close
dependence on the orbital system of a specific A and D couple [52]. Thus, general theories consider
only adiabatic electron transfers, that is, those corresponding to κ = 1. In practice, owing to the very
small (less than 1 kcal/mol) interaction required, this is not a strong limitation for most electron
transfers in organic chemistry [40].
* In this expression, mA and m D are the molar masses of A and D, and r, the distance between the molecule centers in the
precursor complexes, is expressed in angstroms, Z being in M−1 s−1. However, the very physical concept of the collision
frequency, Z, is strictly related to gas phase events and has no physicochemical meaning in solution chemistry where
molecular trajectories are constantly randomized by shocks with solvent molecules. The expression of Z is nevertheless
introduced in condensed phase because ΔSrot value is independent of the way leading to the rigid rotator configuration.
Basic Concepts 29
The theoretical predictions of kf# then amount to evaluating the magnitude of ∆Efact in Equation
1.58. Various models have been proposed for this determination, and most of them rely on harmonic
approximations in modeling the variations of energy of the initial or final systems with nuclear defor-
mation. The basis of the harmonic assumption is that, for outer sphere electron transfers, (1) only small
perturbations in bond length or bond angle are involved and (2) a large number of nuclear coordinates
participate in the activation process. Owing to these two considerations, it is understood that although
the accumulated energies may be important (from several kilocalories per mole to a few tens of kilo-
calories per mole), each of the nuclear coordinates may remain close to its equilibrium value, where
harmonic descriptions of the corresponding energy variations are roughly accurate. Note in this con-
text that since for inner sphere electron transfers (see Section II.A.2 and Table 1.1) bonds are broken
or created in the activation process, the harmonic assumption fails. Indeed, in such electron transfers,
the activation energy is concentrated within one given bond, which needs more detailed description
of the potential energy reaction coordinate surfaces [54].* Similarly, the geometric requirements for κ
to be unity are certainly more important than for outer sphere electron transfers, owing to the extreme
localization of the orbitals concerned in the electron exchange. Thus, in the following, we limit our
presentation to the harmonic model approximation.
Let us denote by qi the ith nuclear coordinate (i = 1, N), qiin and qifin, its equilibrium values
in the initial and final systems, respectively, and Ω i, the corresponding reduced force constant
(i.e., Ωi = 2Ωiin Ωifin /(Ωiin + Ωifin ), where Ωiin and Ωifin are the force constants in the initial and final
systems, respectively [43]). With these notations, the energy of the initial and final systems are
given in Equations 1.60 and 1.61:
1
E in = Eeqin + ∑ Ωi (qi − qiin )2 (1.60)
2
1
E fin = Eeq
fin
+ ∑ Ωi (qi − qifin )2 (1.61)
2
fin
where Eeqin and Eeq are the respective equilibrium values, such as
fin
Eeq − Eeqin = ∆G 0′ = ∆G 0 − Wr + Wp (1.62)

The energy E# of the transition state must be such as E # = Ein = Efin. Then, by subtraction of
Equations 1.60 and 1.61 and denoting the value of qi at the transition state by qi#, one obtains
∑Ω ( q ) − (q )
1
− qifin 
2 2
0 = ∆G 0′ − #
− qiin #
(1.63)

i i i
2
Equation 1.63 describes a hypersurface of N − 1 dimensions, which corresponds to all the possible
transition states (compare Figure 1.6 when N = 2). Yet the transition state through which the system
reacts is that of lower energy. This is obtained by derivation of Equation 1.63 versus qi#. From the
resulting equation and Equation 1.63, one shows readily by the Lagrange multiplier method that
∆Efact is given in the following equation:
2
λ  ∆G 0′ 
∆Efact = E # − Eeqin = 1 +  (1.64)
4 λ 

* Note however that despite this intuitive view, Savéant’s treatment of concerted electron transfers [2c,14–16] (see also
Chapter 13) shows that even when extremely nonharmonic contributions are involved, the general formulation derived by
Marcus retains its structure.
q1
q2
FiGURE 1.6 Schematic representation of the reaction pathway (…), for two nuclear coordinates (N = 2). The
dashed line represents the location of all possible transition states corresponding to the intersection of the two
energy wells.
where
1
( )
2
λ= ∑ Ωi qifin − qiin (1.65)
2
is the reorganization energy of the system. Because λ is a sum, one may separate the terms relative
to bond length or bond angle variations in the A and D molecules (i = 1, M) from those relative to
the surrounding medium (i = M + 1,N). Thus, λ is usually written as the sum of two contributions:
λ = λi + λo (1.66)
with
1
( )
2
λi = ∑ Ωi qifin − qiin for i = 1, M (1.67)
2
being the inner shell reorganization energy and
1
( )
2
λo = ∑ Ωi qifin − qiin for i = M + 1, N (1.68)
2
the outer shell reorganization energy. Note, however, that albeit the homonymy, these terms must
not be confused with the inner sphere or outer sphere nature of an electron transfer (see Section
II.A.2 and Table 1.1).
λi may be evaluated from x-ray and infrared (IR) data or from theoretical calculations. However,
for most organic outer sphere electron transfers, this contribution is usually much smaller than λo
because electron transfers involve often very delocalized molecules. In our opinion, one of the
Basic Concepts 31
greatest merits of the Marcus [43] and Levich–Dogonadze [44] theories is that they allow rather
correct predictions of λo through simple equations. Thus, for most outer sphere electron transfers,
reasonably accurate values of the rate constants can be predicted.
3. Role of the Solvent: The Outer Shell Reorganization Energy

Owing to the usually small energetic interactions between a solvent molecule and the solutes, ran-
dom fluctuations of the medium surrounding the reactants or the products constantly take place.*
Figure 1.7 gives a schematic representation of such solvent fluctuations. During these fluctuations,
the solvent nuclei have out-of-equilibrium positions, which then induce nonequilibrium values
for the electrostatic field probed by the electron to be transferred. Yet the electrons of the solvent
instantly adjust to the local field. This then results in equilibrium values for the electronic compo-
nents of the electrostatic field probed by the electron exchanged. This dichotomy between the nuclei
(vibrational–orientational–translational) and the electronic polarizations arises because of large dif-
ferences in motion frequencies (10 –12 s for atoms and 10 –15 s for electrons).
To determine the resulting energetic variations, the solvent is treated as a dielectric continuum
surrounding the reactants or the products. Since we need to consider only virtual charges, the reac-
tant pair (or the product one) is represented by a pair of two metallized spheres† of initial charges
ZA = 0 and ZD = 0 (i.e., before the exchange of one electron) for the reactants, or ZA − 1 and ZD + 1
for the products (i.e., after the exchange of one electron). Electron transfer is supposed to proceed
through a continuous sequence of virtual states in which only a fractional electron change δ has
been transferred, corresponding to virtual charges ZA − δ and ZD + δ for the reactant or product
pairs. The metallized sphere radii (respectively, aA and aD in each pair) are supposed constant dur-
ing the electron transfer, and their centers are separated by a constant distance r.
Within this model, the energy associated with a nonequilibrium polarization state is determined
by considering that [57] (1) for the solvent nuclei, the polarization corresponds to an equilibrium
state in which a virtual fractional charge δe has been transferred, whereas (2) the solvent electronic
polarization still corresponds to the real charges. In practice, for the initial system, for example, this
is equivalent to determining the variation in the overall electrostatic energy, that is, that associated
with the static dielectric constant εs of the solvent when the reactant charges vary from (ZA,Z D) to
(ZA − δ, Z D + δ), and to correcting it from the electronic contribution, which is associated with εop,
the optical dielectric constant of the solvent (εop = nop
2
, nop being the refractive index of the solvent).
From the corresponding energetic cycle represented in Scheme 1.4, it is easily deduced that the
ε
free energy required to produce an appropriate nonequilibrium polarization is Wδnoneq = Wδεs − Wδ op .
e e e e
(a) (b) (c) (d)
FiGURE 1.7 Schematic representation of the solvent fluctuations inducing the electron transfer. (a, d)
Equilibrium states for the reactants and products, respectively. (b, c) Out-of-equilibrium states for the reac-
tants and the products at the transition state.
* Note that the tightly bound solvent molecules are then considered as belonging to the inner shell subsystem, and their
contributions to the activation energy are then included in λi.
† Note that more sophisticated models have been proposed to take into account the nonspherical nature of reactant and
products, the eventual distribution of charges on different centers within the molecule [55], the eventual coupling between
the inner and solvent fluctuation modes, and other factors [56]. Yet the simplest model described here is sufficient for our
purposes, since it includes most of the essential features of electron transfer reactions.
Nuclei probe: ZA, ZD W δnoneq Nuclei probe: ZA – δ, ZD + δ

Electron probe: ZA, ZD Electron probe: ZA, ZD
Equilibrium state Nonequilibrium state
W δεs –W δεop
Nuclei probe: ZA – δ, ZD + δ
Electron probe: ZA – δ, ZD + δ
Equilibrium state
SchEME 1.4 Thermodynamic cycle representing the relationships between “equilibrium” and “non-
equilibrium” states as inferred from Rudolph Marcus concept.
This difference is readily evaluated from simple electrostatics, as in the Born solvation model [27].
ε
Thus, both Wδεs and Wδ op are obtained, using εs or εop, respectively, by the sum of the three electro-
static contributions: (1) charge of the A sphere from ZA to ZA − δ, (2) charge of the D sphere from
Z D to Z D + δ, and (3) variation of the electrostatic interaction between the two metallized spheres
A and D at distance r. Thus, one obtains for ZA = Z D = 0*
ε  N (δe)2   1 1 2
Wδεs or Wδ op = −  A  + − 
 8πε   aA aD r 
where
ε = εs or εop accordingly
e is the charge of the electron
It is thus seen that for a given δ value, the outer shell component of the energy of the out-of-equilibrium
state of the initial system is given by Equation 1.69:
 N e2   1 1  1 1 2 2
( )
( E in )δ = Eeqin −  A   −  + − δ (1.69)
 8π   εs εop   aA aD r 
A similar expression would be obtained along the same lines for the final system, yet with δ being
replaced by 1 − δ. Comparison of Equations 1.60 and 1.69 shows that the outer shell (solvent) contri-
butions are equivalent to a single harmonic oscillator of force constant Ωo, given as follows:
 N e2  1 1   1 1 2
Ωo = −  A  −   + −  (1.70)
 4π  εs εop    aA aD r 
where the virtual charge transferred δ represents the elongation. It then results from Equation 1.68 that
1 1
λo = Ωo (δfin − δin )2 = Ωo (1.71)
2 2
* When ZA and/or Z D are not null, the establishment of λ o is more complex, but overall, the formulations in Equations 1.69
through 1.72 are retained.
Basic Concepts 33
since δin = 0 and δfin = 1 for one electron transferred. The outer shell reorganization energy λo is thus
finally obtained under the formulation [57] in Equation 1.72:
 N e2  1 1   1 1 2
λo =  A  −   + −  (1.72)
 8 π ε
 op ε a
 A
s  a D r

The latter equation, involving easily accessible data, allows suitable predictions of λo for most situ-
ations of interest. Note that because of the involvement of a squared term in Equation 1.71, the reor-
ganization energy for a simultaneous transfer of n electrons is n2 times larger than that for a single
electron transfer since δfin−δin = n for n electrons transferred. This evidences that in most general
situations, electrons are transferred individually and not as multiples.
4. Physical Meaning of the Reorganization Energy and of Energy Diagrams

From the preceding discussion, it is understood that although the real phenomenon of electron
transfer affects a large number of nuclear coordinates involving the redox centers and a com-
paratively immense number of solvent molecules, the overall effect is akin to what would be
observed for a single generalized coordinate q. This is particularly true for the external medium
contribution as established earlier. For simplification of the following discussion, let us assume
that only one coordinate q is involved, which varies from qin at the initial system equilibrium to
qfin at the final system equilibrium. Let us then introduce the normalized coordinate x = (q−qin)/
(qfin−qin). It is seen from Equation 1.60 or Equations 1.61 and 1.65 that Ein and E fin are given as a
function of x by
E in = Eeqin + λx 2 (1.73)

E fin = Eeq
fin
+ λ(1 − x )2 (1.74)

with x = 0 corresponding to the initial system equilibrium point, whereas x = 1 corresponds to the
final system equilibrium point. Note that the following harmonic model can be adapted to encom-
pass a larger variety of nonharmonic situations that are amenable to harmonic ones simply by
using a suitable change of space variable. For example, a simple logarithmic change of variable
y = −(ln x)/β, that is, x = exp(−βy), transforms any associative/dissociative Morse potential curve,
which represents an energy well in the real space y, into a parabola that represents the same well in
the transformed space x. Thus, Equations 1.73 and 1.74 apply in the transformed space, although the
real energy well is strongly nonharmonic.* For this reason and for the sake of simplicity, we thus
proceed assuming fully harmonic energy wells. Figure 1.8a represents the resulting variations in
the two energies with x according to Equations 1.73 and 1.74. It is seen from this figure that, if the
electron transfer were to occur radiatively from the initial system equilibrium point, as in the gas
phase (e.g., in Ip determinations), then the final system curve would be reached at the point x = 0,
that is, from Equation 1.74, at E = Eeqfin
+ λ. The system would then relax to its equilibrium, that is,
x = 1 and E = Eeq , thus radiating an energy λ during its reorganization. Such comparison is at the
fin
origin of the term reorganization energy for λ though in a real solution system, this path does not
occur under thermal activation.
A second usual interpretation of the reorganization energy is related to the activation process
rather than to a comparison between the gas and the condensed phases. The activation barrier for
* In fact, this is the very fact why harmonic approximations, viz., Equation 1.77 keeps its general structure even when
electron transfer are concerted with a bond-making or a bond-breaking event, that is, when a fully nonharmonic strong
contribution is involved (see concerted electron transfers in References 2c,14,16, see also Chapter 13).
E E
Excited
Fundamental
λ
2Vi
ΔG #
ΔG 0΄
x x
# #
0 x 1 0 x 1
(a) (b)
FiGURE 1.8 Potential energy–normalized reaction coordinate diagrams, without (a) or with (b) interaction
between the initial and final subsystems (see text).
the forward reaction is given by equating Ein and Efin in Equations 1.73 and 1.74. Thus, it follows that
x#, the normalized coordinate at the transition state, is given by the resolution of
E # = Eeqin + λ( x # )2 = Eeq
fin
+ λ(1 − x # )2

which easily yields Equation 1.75 when taking into account that ∆G 0′ = Eeq
fin
− Eeqin.
1  ∆G 0′ 
x# =  + 1 (1.75)
2 λ 

2
λ  ∆G 0′ 
∆Efact = E # − Eeqin = λ( x # )2 = 1 +  (1.76)
4 λ 

Introduction of this value into Equation 1.73 affords the expression of the activation energy in Equation
1.76 for the forward reaction.* Thus, it is seen from the latter equation that λ/4 is equal to the intrinsic
activation barrier ∆Go#, that is, to the activation energy that would be obtained for ΔG 0′ = 0. Thus,
if a series of electron transfers with virtually identical λ is considered, interpolation of the activation
barrier versus ΔG 0′ quadratic law at ΔG 0′ = 0 gives direct access to the experimental value of λ.
Proponents of this second interpretation then prefer to reformulate Equations 1.64 or 1.76 under the
equivalent form
2
 ∆G 0′ 
∆Efact = ∆Go#  1 + # 
(1.77)
 4∆Go 
To conclude, we wish to elaborate more deeply about the energetic diagrams like that presented in
Figure 1.8a. As noted previously, the A and D orbitals must interact in order that the electron may be
transferred. This simply means that an electronic coupling must occur between the initial and final
systems. This results in the mixing of the two systems, which amounts to separating the degenerate
* Note that Equation 1.76 is identical to Equation 1.64.

Basic Concepts 35
potential energy curves in Figure 1.8a into a lower (or fundamental) state and an upper (or excited)
state, as represented in Figure 1.8b. Because the potential energies of the electron tend to be identi-
cal for the initial and final systems when the transition state is approached, the degree of mixing in
this region is higher than near the bottom of each potential well. Thus, the maximal effect is reached
at the transition state, where a splitting of magnitude 2Vi is observed [58].
In practice, as soon as 2Vi > RT, that is, Vi > 0.25 kcal/mol at room temperature, when the system
crosses the transition point, it has not enough kinetic energy to jump from the fundamental state
to the excited one. As a consequence, the system remains on the lower curve and then ultimately
reaches the final system equilibrium. This corresponds to a probability of 1 for electron transfer each
time the system crosses the barrier (provided its momentum is in the right direction), that is, κ = 1.
When 2Vi ≈ RT, when reaching the transition point, the system may jump onto the upper curve.
If so, when it goes backward, it falls onto the lower curve, with a large probability (because of the
direction of its momentum) of advancing toward the initial potential well. In such a case, the elec-
tron has not been transferred and then κ < 1.
When 2Vi ≪ RT, this phenomenon occurs almost every time the system crosses the transition
point, which means that κ ≈ 0, and no electron transfer occurs.
From these considerations, it is understood that Equations 1.64, 1.76, and 1.77, derived without
considering electronic coupling, give activation energies overestimated by a term Vi and should
normally be corrected. However, as noted for κ, Vi is predictable with difficulty from simple con-
siderations and is usually not included in the activation energy. However, the resulting error is often
negligible because λ is not known with a sufficient accuracy [40] (compare the above threshold
value of 0.25 kcal/mol for Vi).
5. Energies and Free Energies in Electron Transfer Theories

In the preceding description of electron transfer theories, energies were used rather than free ener-
gies. For a reaction in liquid phase, ΔE is nearly identical with ΔH, so that the results obtained earlier
are valid as soon as entropic variations are negligible,* and thus ΔE ≈ ΔH ≈ ΔG, so that the distinc-
tion between ΔG and ΔE may be dismissed. Since outer sphere electron transfers involve small bond
lengths or angle variations, this is acceptable for inner shell components of activation free energies.
Concerning outer shell components, the approximation is considered not drastic and is equivalent
[59] to those made for solvation models (Born) or according to the Debye–Hückel theory [la,c]. Thus,
within these approximations and that previously discussed dealing with Vi, it is considered that the
activation rate constant of outer sphere electron transfers is given by (from Equation 1.58)
− ∆Gf# /RT
kf# = κZe (1.78)
with
2
λ  ∆G 0′ 
∆Gf# = Wr + 1 +  (1.79)
4 λ 

where ΔG 0′ is the free energy change between the precursor and successor complexes:

(
∆G 0′ = F ED0 + /D − EA/A
0
)
− − Wr + Wp (1.80)
and λ is given in Equations 1.66, 1.67, and 1.72.
* Note that for the transition state, the entropy corresponding to the formation of pairs is included in the models through
the free energies of formation of the precursor or successor complexes using a rigid rotator approximation (see Sections
II.C.1 and II.C.2).
6. Quadratic Free Energy Relationships

When one considers a series of related electron transfers, that is, involving acceptors (and donors)
of reasonably close chemical electronic structures and radii, the reorganization energy λ should
remain constant for the series. Thus, it is seen from Equation 1.79 that the activation energy varies
as a quadratic function of the driving force, in contrast to the usual observation of linear free energy
relationships in organic chemistry (Brönsted correlations between log(k) and log(K), where k and K
are the rate and equilibrium constants of the reactions). As a result, the Brönsted coefficient β var-
ies linearly with the driving force, with a value of 0.5 at ΔG 0 = 0. Indeed, from Equation 1.78 and a
derivation of Equation 1.79, one obtains
 ∂ ln kf#  1 ∆G 0′
β = − RT  = + (1.81)
 ∂∆G 2λ
0
 2
When |ΔG 0′| < λ, the predictions of such an equation are in agreement with the deductions of the
Hammond postulate. Indeed, for exergonic reactions, β tends to zero when ΔG 0′ → −λ, which cor-
responds to an activationless reaction. Conversely, for endergonic reactions, β tends to unity when
ΔG 0′ → λ, which features a barrierless reaction.
However, when |ΔG 0′| > λ, β reaches negative values in the exergonic domain and is greater than
unity in the endergonic case, according to Equation 1.81. To recall these facts, the region such as
|ΔG 0′| > λ is usually called the abnormal or inverted region, the second term referring to the unusual
decrease in rate constant with larger exergonicity of the reaction. In actual practice, there is a large
debate about the experimental existence of this inverted region. Moreover, more elaborate models
have been proposed involving the possible participation of excited vibronic states, which show that
for most organic electron transfers, one should observe a normal behavior, that is [60],
∆G # ≈ Wr , or β = 0 for ∆G 0′ < −λ (1.82)

∆G # ≈ Wr + ∆G 0′ , or β = 1 for ∆G 0′ > λ (1.83)

although ΔG #, given in Equation 1.79, remains valid for |ΔG 0′| > λ. Since under electrochemical
circumstances, when a conductor electrode is used, the electronic levels in the electrode form a con-
tinuum, Efrima et al. considerations [60] fully apply. Hence, no inverted region should be observ-
able, a prediction that is in total agreement with experiments to the best of this author’s knowledge.
Similarly, other models, such as the Marcus–Levine–Agmon [61] one, have been developed that
also predict the nonexistence of the inverted region. The latter model leads to the ΔG # variations
with ΔG 0′ and λ in the following:
λ 0′
∆G # = ∆G 0′ + ln(1 + e − ∆G 4 ln 2 /λ ) (1.84)
4 ln 2
Particularly interesting is that Equation 1.84 respects the limits in Equations 1.82 and 1.83. For
intermediate values of the driving force, the calculated activation barrier from Equation 1.84 is
very close to that obtained in the classic harmonic model developed in this section (Equation 1.79).
Thus, from an experimental point of view, distinction between the two models is rather difficult or
impossible [36a], although seemingly different mathematical expressions for ΔG # variations with
ΔG 0′ and λ are obtained.
Basic Concepts 37
To conclude, we discuss the experimental use of Equation 1.81. Indeed, in experimental practice,
one has access to overall rate constants kf or k b in Scheme 1.3 and Equations 1.56. Thus, the experi-
mental Brönsted coefficient βexp is determined as follows:
 ∂ ln kf 
βexp = − RT  0 
(1.85)
 ∂∆G 
The latter becomes identical to that in Equation 1.81 only when kf ≈ kf# , that is, when kf# kfdif in
Equation 1.54a. However, when diffusion of the reactants or products becomes the rate-determin-
ing factor, kf ≈ kfdif , as discussed earlier. Owing to the discreteness of homogeneous experimental
data, the shift from an activation control to a diffusion control of the reaction is usually difficult
to appreciate, particularly in the endergonic region. The perversity of the problem is even larger
when one realizes that application of Equation 1.85 to a diffusion-controlled reaction yields βexp = 0
for exergonic situations and βexp = 1 for endergonic, owing to the two components in the overall
pseudo-rate constant kfdif in Equation 1.54a. The difficulty is greater as the reorganization energy λ
decreases, as evidenced by Figure 1.9. This caveat [36] is conveniently represented in Figure 1.10,
5
10
10
20
5
log kf
30
–5 10 0 –10
ΔG 0΄, kcal/mol
FiGURE 1.9 Variations in the observed rate constant kf as a function of the driving force for various values
of the reorganization energy (numbers on the curves in kcal/mol). The solid curves correspond to an activation
control. The hatched zone corresponds to a diffusion control (compare Figure 1.4).
20
I
ΔG 0΄, kcal/mol
II
109
5 . 109 0 Activation
1010 10 control
5 . 10
–20
∞, 1011
0 20 λ, kcal/mol 0 20 λ, kcal/mol
FiGURE 1.10 Relationship between the driving force and the reorganization energy for the reaction to be
under activation control or diffusion control (hatched zone). The boundaries between the two zones are given for
v arious values of krdif = kpdif . The boxes correspond to the location of the experimental systems in Figure 1.11 (I)
or 1.12 (II) (see Section II.C.1).
which summarizes the various conclusions reached here in the form of a plot of ΔG 0′ versus λ.
Indeed, it is seen from this diagram that according to the location of a given system, the physical
meaning of experimental activation energies obtained by strict application of the following equation
(deduced from Equation 1.78, assuming κ = 1) may greatly differ [36a]:
kf
∆Gexp
#
= − RT ln (1.86)
Z
7. Cross-Relationships: Evaluation of Rate Constants from Isotopic Rate Constants

An interesting consequence of the additive formulation in Equations 1.66, 1.67 and 1.68 of the reor-
ganization energy λAD for an A/D electron transfer is that it may be broken in three components:
λ oAD , the outer shell reorganization, and λ iA and λ iD, which involve the inner shell contributions
related specifically to bond length and bond angle variations in the acceptor (and the donor) center:
λ AD = λ oAD + λ Ai + λ Di (1.87)
On the other hand, for the isotopic electron transfer (i.e., J* is the same species as J except that it is
an isotope),
− − + +
A* + A • A*• + A (or D* + D • D∗ • + D)

the inner shell component for the reorganization energy becomes
λ AA
i = 2λ Ai
since two A centers are involved; similarly, λ DD

i = 2λ Di for the isotopic electron transfer relative to
the donor. Thus, it follows that Equation 1.87 may be rewritten under the following form:

λ AD = λ oAD +
2
(
1 AA
λ i + λ DD
i ) (1.88)
Formally, λ oAD cannot be split into two (A and D) components because of the presence of r ≈ aA + aD
in Equation 1.72, which acts as a coupling term. Yet a tedious but elementary algebraic transforma-
tion allows Equation 1.72 to be rewritten as
 − aD )2 
λ oAD =
2
(
1 AA
λ o + λ oDD ) 1 + ((aa A
2
A + aD ) 
(1.89)

In Equation 1.89, λ oAA and λ oDD are the outer shell reorganization energies for the respective isotopic
electron transfers, defined similarly as λ oAD in Equation 1.72. Thus, as soon as the equivalent radii
for the acceptor and the donor do not differ by a factor larger than 2, one gets within about 10%
precision, that is, perfectly acceptable owing to the crudeness of Equation 1.72:

λ oAD =
2
(
1 AA
λ o + λ oDD )
Basic Concepts 39
Introduction of this latter result into Equation 1.88 allows one to formulate λAD as the sum of two
components relative to the individual isotopic reactions in Equation 1.90:

λ AD =
2
(
1  AA
λ o + λ AA
i ) (
+ λ oDD + λ DD
i
 2 ) ( )
 = 1 λ AA + λ DD (1.90)
The operative interest of such a cross-relationship is extreme, since when associated with Equations
1.78 through 1.80, it allows an a priori estimation of the rate constant of any outer sphere electron
transfer reaction provided the corresponding standard reduction potentials and isotopic rate con-
stants are known. For kinetics, this is the equivalent of E 0 for thermodynamics, since knowledge of
a series of half-cell potentials (E 0) allows the voltage of any battery formed by combination of two
such half-cell to be evaluated. Yet a caveat in this approach is that it should be ensured that κ = 1 for
all reactions, that is, there is always sufficient overlap between the orbitals [62].
8. Experimental Illustrations
The purpose of this section is not to present a compendium or a discussion of the numerous experi-
mental illustrations of the validity of electron transfer theories, but rather to select two typical
examples that illustrate the main features of these theories in organic chemistry [63].
a. Validity of QFER over a Wide Domain of Free Energies

The main difficulty in discussing the dependence of rate constants with driving force over a wide
domain stems from the fact that, to be significant, the series must involve electron transfers with
nearly constant reorganization energies. However, it is easily understood that the two requirements
(ΔG 0 variations over a range of several tens of kilocalories per mole but λ invariant) are difficult to
satisfy simultaneously.
Such a series, which extends over nearly 70 kcal/mol in ΔG 0, has been presented by Rehm and
Weller [64]. The series corresponds to electron transfer between an excited acceptor and a donor
acting as a quencher or between an excited donor and an acceptor quencher. Thus, rate constants,
ranging from 106 to 2 × 1010 M–1 s–1, have been determined for more than 60 different donor–accep-
tor pairs in acetonitrile. Examination of the corresponding results, presented in Figure 1.11, clearly
shows that three domains may be defined: (1) ΔG 0 < −10 kcal/mol, where kf is independent of
the driving force, that is, where βexp = 0; (2) −10 kcal/mol < ΔG 0 < 10 kcal/mol, where βexp var-
ies from zero to unity; (3) ΔG 0 > 10 kcal/mol, where β = 1. These data were corrected for diffu-
sion components, so they correspond to an activation control of the electron transfer reactions.
10
log kf
0 –10 –20 –30 –40 –50
ΔG 0, kcal/mol
FiGURE 1.11 Linear energy relationship over an extended domain of driving force. (Experimental data
from Rehm, D. and Weller, A., Isr. J. Chem., 8, 259, 1970.)
They qualitatively agree with the predictions of Equations 1.78 and 1.79 for |ΔG 0| < 10 kcal/mol but
show that Equation 1.79 is not valid outside this range, Equations 1.82 and 1.83 being more ade-
quate. As such, they have been considered a convincing experimental argument for the nonexistence
of the inverted region [65].* Yet, owing to the large scatter of the data, a precise determination of the
validity of Equation 1.79 in the intermediate (|ΔG 0| < 10 kcal/mol) free energy range is impossible.
b. Validity of the QFER for Low-Endergonicities or Exergonicities

In order to test the experimental validity of the quadratic relationship between ΔG # and ΔG 0′, a
rather small free energy domain needs to be investigated. As a consequence, even small variations
in λ result in too large a scatter of the data for significant quantitative conclusions to be drawn
(compare the data in Figure 1.11 for |ΔG 0| < 10 kcal/mol). Thus, a series of very closely related
redox couples must be investigated.† A series meeting these requirements is given by the endergonic
oxidation in acetonitrile of methylbenzenes by tris-(5X-phenantroline)-iron(III), X = H, Cl, NO2,
already discussed [36a,c]. Indeed, for such a series, the inner shell contributions are minimal owing
to the delocalization and close identity of the iron(II/III) complexes [66] and the small distortions
of the arene cation radical vis-à-vis the neutral (for C6H6 + •, the inner shell reorganization energy
from a nuclear configuration corresponding to benzene involves a Jahn–Teller distortion [67] and
has been evaluated to be approximately 3 kcal/mol by Salem [67c]). Thus, the outer shell reorganiza-
tion energy predicted according to Equation 1.72 is (λ o in kcal/mol: aAr, aFe, and r = aAr + aFe in Å)
 1 1  1 1 2
λ o = 1.67 × 102  −  + − 
ε
 op ε a
s   Ar a Fe r

* However, it should not be concluded that the inverted region does not exist. A visible proof of its existence when the
density of rovibronic states is scarce is given by photosynthesis. In plants, the inverted region process impedes the
recombination of the electron/hole pair created by photochemical process, so that a much less favorable process (thermo-
dynamically speaking) can occur (e.g., reduction of quinone carriers). In fact, the inverted region simply shows up when
a too large amount of energy (generated by an extremely downhill electron transfer) is dissipated for a few picoseconds.
When the molecules engaged in this process are too rigid to absorb this large Gibbs energy release within the required
time range, the system cannot proceed. This is reflected by an increasing activation barrier when ΔG 0 is made more and
more negative beyond ΔG 0 = −λ. However, if ΔG 0 is negative enough that rovibronically excited states of the final system
can be met, then the reaction proceeds through such states.
Inverted region Non inverted region: ECL

(fundamental-fundamental) (fundamental-vibronic-fundamental)
R P R P* P
#
#
hv
These can in turn relax to the fundamental final system state either by the release of a visible photon (which is the basis
of electrochemiluminescence or ECL) or a cascade of infrared photons generating heat. In Rehm and Weller work [64],
system pairs possessed large densities of rovibronic excited states so that the inverted region could not be observed [60].
† Note that the corresponding condition is more easily satisfied for electron transfer at electrodes, owing to the easy varia-
tion of the driving force, by adjustment of the electrode potential without modification of the redox couple.
Basic Concepts 41
5 0.25 ΔG #/λ
log kf
0.50
0
0.75
ΔG 0, kcal/mol ΔG 0/λ
–5
20 10 0 0.75 0.50 0.25 0
(a) (b)
FiGURE 1.12 Quadratic free energy relationship (QFER) in the low endergonic region for the oxidation of
methylbenzenes by Fe(phen)33+ . (a) Experimental variation of the observed rate constant compared with the
theoretical variations (solid curve): (- - -) activation or (−⋅−⋅−) diffusion controls, (b) experimental relationship
between the activation free energy and the driving force compared with the theoretical variations for λ = 27
kcal/mol in the solid curve: (- - -) polynomial regression in Equation 1.92 [36a,c]. (Data from Schlesener, C.J.,
J. Am. Chem. Soc., 106, 3567, 1984; Schlesener, C.J. et al., J. Am. Chem. Soc., 106, 7472, 1984; Schlesener,
C.J. et al., J. Phys. Chem., 90, 3747, 1986.)
that is, λo ≈ 21 kcal/mol for aAr ≈ 3.5 Å, aFe ≈ 7 Å [68], and εs = 37.5, and εop = nop 2
= (1.34)2 for
acetonitrile. The resulting predicted value of the global reorganization energy is then predicted to
be ca. 24 kcal/mol for each couple in the series.
Figure 1.12a indicates how the measured rate constant kf for the endergonic electron transfer
oxidation of methylbenzene by (phen)3-iron(III) complexes varies with the driving force. It is seen
from these data that, provided that ΔG 0′ < 10 kcal/mol, a very good fit is obtained with the rate con-
stant predicted from Equations 1.78 through 1.80 on the basis of an activation control of the overall
reaction when using κ = 1, Z = 1011 M–1 s–1, and λ = 24 kcal/mol, determined earlier. However, for
larger positive values of ΔG 0′, the diffusion cage processes contribute significantly to the experi-
mental rate constant. Yet the activation rate constant kf# may be extracted from the experimental kf
data through the use of Equation 1.56a. The real activation free energy ∆Gf# is then derived through
Equation 1.78 and plotted as a function of ΔG 0′ = ΔG 0 + Wp in Figure 1.12b. Quadratic regression
analysis of these data allowed their fit by a second-order polynomial expression in Equation 1.91
[36a,c] (represented as the dashed line in Figure 1.12b):
∆Gf# = 6.7 + 0.50∆G 0′ + 8.7 × 10 −3 (∆G 0′ )2 (1.91)
which is in good agreement with the predicted variations in Equation 1.79 for λ = 27 kcal/mol.
Indeed, development of Equation 1.79 with λ = 27 kcal/mol yields
∆Gf# = 6.7 + 0.50∆G 0′ + 9.3 × 10 −3 (∆G 0′ )2 (1.92)
Another way to appreciate the correctness of Equation 1.79 in the prediction of the experimental
barrier consists in the evaluation of λ for each individual couple as presented in Table 1.3. Indeed,
from Equation 1.79, λ is obtained through the solution of the second-order equation

( )
λ 2 + 2 ∆G 0′ − 2∆Gf# λ + (∆G 0′ )2 = 0 (1.93a)
TABLE 1.3
Experimental Evaluation of the Reorganization Energy λ for the Oxidation
of Methylbenzenes by Tris-(5X-phenantroline)–Iron(III) Complexes [36a]
Methylbenzene X ΔG0’a ∆Gf#a λa λava,b
H 11.2 13.4 26.4 28.2 (1.8)

Cl 8.86 12.6 30.1
NO2 6.55 10.7 28.2
H 14.2 15.6 26.4 26.3 (0.4)

Cl 11.9 13.9 26.4
NO2 9.55 12.4 27.1
H 16.0 16.8 24.9 25.1 (0.2)
C1 13.7 13.4 —c
NO2 11.4 13.3 25.2
H 15.8 18.0 32.8 27.3 (6.7)
Cl 13.5 14.0 19.8
NO2 11.2 14.0 29.3
a In kcal/mol.
b Average value for a given arene, standard deviation indicated in parentheses. For all couples, λav = 27.0 ( ± 3.3) kcal/mol.
c Not determinable since ΔGf > ΔG0′.
Z
∆Gf# = RT ln (1.93b)
kf#
where ΔG 0′ and the experimental activation free energy ∆Gf# from Equation 1.93 are known. Thus,
a value of 27.0 kcal/mol (standard deviation 3.3 kcal/mol, 11 data) is obtained for the average reor-
ganization energy, which is in very close agreement with that predicted (24 kcal/mol).
III. FUNDAMENTAL ASPEcTS Of ELEcTRODE PhENOMENA

A. MoNITorING a HaLF-REaCTIoN: THE ELECTroCHEMICaL CELL
1. Monitoring a Half-Reaction
In homogeneous chemistry, an electron transfer reaction involves two reactants, an acceptor A and
a donor D. Thus, formally, an electron transfer reaction consists of the superimposition of two ele-
mentary chemical acts: the reduction of the acceptor and the oxidation of the donor. Yet as discussed
in the first part of this chapter, since more attention is given to one of these elemental reactions, the
overall reaction is termed a reduction when the acceptor is the compound of interest or an oxidation
when chemical transformation of the donor is favored.
In electrochemistry, the same phenomenon (essentially related to charge conservation) occurs,
yet the reduction of the acceptor A occurs at one electrode (the cathode in electrolytic cells) and
the oxidation of the donor D at the other (anode). Thus, the kinetics of the overall cell reaction*
depends on both half-reactions, in a similar way as the kinetics of a homogeneous electron trans-
fer depends on the acceptor and the donor. However, because the two half-reactions occur at dif-
ferent locations, it is technologically possible to break the coupling between the two electrodes.
* That is, the current flowing through the cell, since it corresponds to an identical number of electrons consumed at each
electrode per unit of time.
Basic Concepts 43
I W E + R0i Ref A
Zcat Zan
φan R R
Z cat E 0Ref Zn
Ri R0 R – R0
Ccat Can Ccat Can
φcat
Ccat Can
(a) (b) (c) (d)
E
Potentiostat Potential
E + R0i E' generator
Ref
W A
(e)
FiGURE 1.13 Representation of the potential variation in the electrochemical cell and associated electronic
schemes (a–d). (Φcell = Φcat + Ri + Φan; see text). W, working electrode; Ref, reference electrode; A, auxiliary
electrode. (e) Schematic description of the electrochemical cell with a potentiostat.
This is done via two different approaches, based on the same principle, that take advantage of
the potential distribution in an electrochemical cell, shown in Figure 1.13a. From this schematic
representation, it is seen that the potential difference Φ between the two electrodes is the sum
of three components: two of them, Φcat and Φan, are related to each electrode, and the third, Ri,
arises because of the ohmic drop due to the current intensity, i, flowing through the cell solution
resistance. The potential variations Φcat and Φan are localized within an extremely thin layer
(<100 Å) of solution adjacent to the electrode (see Section III.A.4), which means that the overall
cell behaves like an electrical circuit composed of two capacitors and a resistance as sketched in
Figure 1.13b. However, such a simple circuit is not sufficient since it does not allow any constant
current to flow through the cell because of the capacitors. In practice, two additional impedances,
Z cat and Z an (Z cat and Z an are called faradaic impedances because of their origin) are connected in
parallel with each capacitor, which correspond to the electrochemical reactions taking place at
the electrodes. The latter are necessarily in parallel with the capacitors, as shown in Figure 1.13c,
since they use the potential difference between the electrode and the local solution as their driv-
ing force and act as derivations allowing the faradaic currents to flow. Thus, it is easily under-
stood that when a given potential difference is imposed between the two electrodes, the three
individual potential drops Φcat, Φan, and Ri must adjust in order that the currents flowing through
each electrode and through the solution are equal; this results in coupling the processes occurring
at each electrode and in the solution by distributing the cell potential Φcell across all components
Φcell = Φcat + Φan + Ri.
Thus, to individualize one of the electrodes, it is necessary to control, that is, to measure or to
impose, its individual potential difference versus the solution (Φcat or Φan). This is done via the
introduction of a third electrode, the reference electrode Ref, placed in the solution near the elec-
trode of interest (hereafter named the working electrode W, the other electrode being called the
auxiliary electrode A). Because of its characteristics (see Section III.C.3), the reference electrode
maintains a potential difference Φ Ref ≈ ERef 0
vis-à-vis the point of the solution where it is located.
ΦRef may include various components related to the redox half-reaction or junction potentials,
for example, but is independent of the very small current allowed to flow through the reference
electrode. Such a three-electrode system, sketched in Figure 1.13d, formally allows the physical
individualization of the working electrode. Indeed, one may impose an arbitrary potential differ-
ence Φcell = ΦW − ΦA, for example, between the working and auxiliary electrodes, measure the
resulting Φ W − ΦRef potential difference, and compare it to the desired value E to be imposed.
If Φ W − ΦRef is too small, ΦW − ΦA is increased; if ΦW − ΦRef is too large, ΦW − ΦA is decreased.
Thus, ΦW − ΦRef is progressively adjusted to the selected value E (note then that ΦRef − ΦA is also
imposed as a result of the procedure, but its exact value is a priori of no interest). Then, the cur-
rent i flowing through the cell may be measured and related to the potential E. Repetition of the
whole procedure allows the current–potential characteristic, that is, the (i,E) relationship, of the
half-reaction taking place at the working electrode to be determined. Yet, although possible, if
the whole procedure were performed manually, it would take several hours to record precisely
an (i,E) characteristic. Thus, pertinent electronic apparatus, called potentiostats [69], have been
designed to perform the whole procedure within microseconds or less [70]. Besides their conve-
nience, potentiostats allow the recording of transient electrochemical kinetics, which would not
have been possible manually.
The second approach, although used first in electrochemistry, derives from that corresponding
to three electrodes and potentiostat. It consists of using a reference electrode as the auxiliary elec-
trode. This is indeed possible, provided the size of the reference electrode is sufficiently large for
the current density flowing through it to be infinitely small, although the current may be large. The
potential difference between the reference–auxiliary electrodes (called a counter electrode, CE, in
a two-electrode device) and the solution in its near proximity is thus constant (see Section III.C.3).
The potential difference ΦW associated with the working electrode is then given by
Φ W = Φ cell − Φ CE − Ri (1.94)
which shows that, provided that Φcell ≫ Ri, ΦW is measured (or imposed) within a constant term ΦCE
when the overall potential difference Φcell is measured (or imposed).
This second approach has been discarded vis-à-vis the three-electrode potentiostat approach
because in organic electrochemistry, the solution resistance is usually large so that the ohmic drop
term Ri is not negligible under the usual conditions.* Thus, the relationship between ΦW and Φcell
depends on the current flowing through the cell. Note that a similar problem is also involved for the
three-electrode approach, since the working and reference electrodes are separated physically by
part of the solution, which introduces an ohmic drop component in the potential difference between
the working electrode and the reference electrode. Yet, this effect is usually smaller because the
resistance R0 involved is smaller and is eventually corrected via additional electronic circuitry in
the potentiostat [70b].†
2. Electrochemical Cell
From this presentation, it is seen that electrochemical data that pertain to a single half-reaction tak-
ing place at the working electrode can be experimentally obtained. In our opinion, this is one of the
greatest advantages of electrochemistry, although not really identified and recognized in other fields
of chemistry. Indeed, whatever the homogeneous chemical technique used, the chemistry associ-
ated with a donor–acceptor couple necessarily depends on both members.
Another important advantage, less apparent in this presentation, is that because of the involve-
ment of an external electrical driving force, electrochemistry allows overall endergonic reactions to
be performed at a considerable rate. Indeed, let us consider the a priori endergonic electron transfer
reaction in Equation 1.95:
−
A + D A • + D +• (1.95)
* However, it regains interest with the development of ultramicroelectrodes. Indeed, because of their micrometer (or
smaller) sizes, the currents are of the order of nanoamperes or below. Thus, even with R of several kiloohms, the ohmic
drop term is totally negligible.
† In the latter case, the current is measured, and an R i term is reinjected via a feedback loop so that the potentiostat actu-
0
ally imposes the potential difference E + R0 i between the working electrode and the reference electrode; this results in
canceling the ohmic drop (Figure 1.13e) [70b].
Basic Concepts 45
Thus, under electrochemical conditions, A can be reduced and D oxidized provided that sufficient
− +
cathodic and anodic potentials are applied. Yet upon preparative-scale electrolysis, A • and D • would
then necessarily recombine into A and D, except if they react chemically at faster rates:
−
Cathode: A + e A • →
Anode: D − e D• + →
Thus, in the absence of chemical reaction or when undesired reactions between the follow-up
product(s) may arise, it is necessary to avoid the unwanted reaction. Taking advantage of the dif-
ferent physical locations of the two electrodes, this is done by separating the bulk solution into two
parts (catholyte and anolyte, respectively) using a glass frit or a membrane so that the electrical
connection (via ionic transport; see Section IV.A.2) is not interrupted [71].
3. Resistive Effects and Ohmic Drop: The Supporting Electrolyte–Solvent System

In the preceding part of this section, we focused our attention on the electrodes, where the real
electrochemical events occur. Yet as already explained, the current exchanged at the electrodes
must flow through the cell, that is, through the solution between the working and counter or
auxiliary electrodes. For this reason, the solution must be conducting; otherwise, no current
flows, even when the electrode processes are extremely easy. Indeed, if the resistance of the
solution is R and i the current flowing through the cell, Ohm’s law indicates that the potential
lost for conducting purposes is Ri.* In practice, ohmic drop can be overcome by increasing the
potential difference between the working and auxiliary electrodes by the amount required. Yet
this is not an acceptable solution because of the electrical power required and the need to evacu-
ate the thermal energy dissipated. Indeed, Ri is associated with an electrical power Ri2 that is
dissipated thermally in the solution and needs to be supplied by the potentiostat or the external
power supply connected to the cell. To roughly quantify these effects, let us consider a laboratory
electrolysis cell in which i = 1 A is required. Let us assume that R = 100 Ω, a common figure for
most organic solutions. Thus, Ri = 100 V and Ri 2 = 0.1 kW. For an average thermal capacitance of
1 cal/K per mL and a cell of 100 mL, for example, this amounts to a temperature increase in the
cell of approximately 0.25°C/s when it does not exchange energy with the external atmosphere.
Thus, in an actual experiment, the cell must be cooled so that its temperature is maintained
within reasonable limits. In other words, this means that an additional 0.1 kW power must be
lost to cool the cell.
At the laboratory scale, these energetic losses are easily controlled; thus, the main problem
relates to the potentiostat, or potential supply, power limitation, since most of the usual equipment
affords between 70 and 100 W of usable electrical power. At the industrial scale, since the current
intensities are considerably larger, serious problems arise from lost energy and temperature control
of the cell.
To conclude this introductory section concerning ohmic drop effects, let us consider the case
of transient electrochemical techniques. In this case, the currents are of the order of few milliam-
peres or less, and thus all these effects should cancel. Unfortunately, this is not the case because
of the size of the working electrodes. Indeed, these are often of millimetric dimensions, which
amounts to a considerable narrowing of the field lines near the tip of the working electrode.† As
a result, the resistance increases, and most of it is concentrated near the very tip of the work-
ing electrode, even when a Luggin–Haber capillary probe is used [72]. Resistances of several
kiloohms are frequently involved, which introduces important difficulties for an exact control of
* Ri is usually said to be the ohmic drop to recall that this potential is not used for purely electrochemical purposes.
† The auxiliary electrode is usually of considerably larger dimensions (1 to several cm 2). Thus, the equivalent conductor
should be thought of as a cone rather than as a cylinder as for preparative cells.

the potential of the working electrode (compare Equation 1.94). Obviously, when one does not
care about such control, this should not be perceived as a limitation, and rather resistive solutions
may be used. Note also in this respect that when the working electrode is a disk of radius r 0, the
resistance R varies as 1/r 0 provided the auxiliary electrode is of considerably larger dimensions.
On the other hand, the current flowing through the electrode is proportional to its surface area
(see Section III.B), provided the electrode is not under diffusional steady state. Thus, the ohmic
drop is proportional to r 0 and decreases when the latter decreases. This explains one of the advan-
tages of ultramicroelectrodes, at which ohmic drop effects naturally cancel since r 0 is of the order
of a few micrometers or below [73].
This discussion and presentation of ohmic drop problems should lead to the conclusion that, with
maybe an exception of ultramicroelectrodes, the resistivity of electrochemical solutions must be
decreased as much as possible.
In solutions, the current is necessarily carried by dissociated ionic species. Theories of this
phenomenon are well developed and presented in most introductory electrochemistry textbooks.
Yet it is sufficient for our purpose here to recall that the resistance is then inversely proportional
to the concentration of the dissociated electrolyte (see Section IV.A.2) for the usual case of a 1:1
electrolyte (e.g., NBu4 + BF4− and NEt4 + BF4−). Thus, a normal means to decrease ohmic drop is
to add an inert* electrolyte in large concentration. Yet as mentioned earlier, only the dissociated
ions participate in the current transport since electrically neutral ion pairs play no role. Thus, it is
important that most of the supporting electrolyte be dissociated. Such a condition, together with
the large concentrations required (approximately 0.1 M), implies that a rather dissociating solvent
is used. This is the reason that, in organic electrochemistry, the preference is for solvents with
rather large dielectric constants (εs > 10) and supporting electrolytes with rather large ions (e.g.,
NBu4 + BF4−). Considering these conditions and that the solvent should be able to dissolve organic
molecules explains why most electrochemical experiments involve a narrow class of solvents, such
as acetonitrile (εs = 37.5), dimethylformamide (40), dimethyl sulfoxide (46.7), and propylene car-
bonate (36.7) [71].
4. Electrode/Solution Interfacial Region

To simplify the following discussion, we restrict it to the case of a cathode. Obviously, the results
and phenomena directly apply to anodes, cations being replaced by anions, and vice versa.
Experimentally, it was early recognized that an electrode/solution interphase behaves as a capac-
itor† [74]. This is because the negatively charged surface of the cathode generates a very strong
electrical field that tends to attract positive ions from the solution, as sketched in Figure 1.14a. The
positive layer thus formed exerts, on the solution side, an electrical field of opposite direction that
attracts negative ions from the solution.
However, since this latter field is partly compensated by that resulting from the negative charges
in the electrode, the charge density of the anionic layer is smaller than that of the cationic one.
Repetition of this phenomenon results in alternating layers of positive and negative charges, with
a charge density in each layer decreasing with the electrode distance, as pictured in Figure 1.14b.
Because of the decrease in electrical field with distance, the successive layers are less and less
bound. Then, owing to thermal agitation, these layers cannot be as rigid as might be deduced from
the preceding presentation and interpenetrate each other except for the first, which is tightly bound
* Inert means that the electrolyte is not involved in the electrochemical transformation occurring at the electrodes. The elec-
trolyte is usually also called the supporting electrolyte after its function of supporting the current flow through the cell.
† Note that this property is used in electronics in the so-called electrochemical capacitors, which are no more than electro-
chemical cells without faradaic reactions within their potential range of use. That is why these capacitors have a polarity
and a voltage limit; they must then be used with non-alternative voltages to avoid their explosion due to undue Faradaic
production of gazes.
Basic Concepts 47
OHP
φM
x
φsol
0 xOHP x0
(a) (b) (c) (d)
FiGURE 1.14 Schematic representation of the electrode–solution interfacial region. (a) Helmholtz model;
(b) structured layer model; (c) thermally disorganized layers; and (d) resulting potential variations with dis-
tance from the electrode; ΦM, electrode potential; Φsol, solution potential; OHP, outer Helmholtz plane (few Å);
x0, extremity of the diffuse layer (few tens of Å); x < xOHP, compact layer; xOHP < x < x0, diffuse layer.
onto the electrode or onto a tightly bound strong dipolar layer of solvent [75]. This phenomenon
is indicated by the corresponding names compact layer for the first layer and diffuse layer for
the remaining part; both of them constitute the double layer and act as two capacitors in series.
The capacitance (usually 20–50 μF/cm2) and dimensions (a few angstroms for the compact layer
and a few tens of angstroms for the diffuse layer) may be evaluated via the Gouy–Chapman–Stern
theory [76], which is developed in most electrochemical textbooks. The main conclusions of this
model, which are in general agreement with experimental observations, are the following: (1)
because of the compact layer, a large potential drop arises within a few angstroms of the electrode
surface (compare Figure 1.14d); thus, most of the potential difference between the electrode and
the solution is lost at the end of the compact layer (i.e., at the outer Helmholtz plane, OHP); (2) the
potential difference between the OHP and the solution results in an electrical field considerably
lower than that between the electrode and the OHP, which nearly exponentially decays with dis-
tance; (3) beyond several tens of angstroms from the electrode, the potential is identical to that in
the bulk of the solution, except for eventual ohmic drop effects, as discussed earlier (compare Figure
1.13a); (4) as a result of the third conclusion, beyond a few tens of angstroms, the electrode exerts
no electrostatic attraction or repulsion on any ionic species, which explains why an anion may be
reduced or a cation oxidized at electrodes.
B. GENEraL OVErVIEw oF aN ELECTroDE REaCTIoN

When thinking of any electrochemical reaction, it is important to remember that the very act
of electron transfer takes place at a surface, whereas the material to be reduced or oxidized is
dispersed in a volumetric phase. Thus, mass transfer from the bulk of the solution (or to the bulk
solution, for the products) plays a central role in electrochemical processes. As such, the physi-
cal processes of mass transfer (diffusion, migration, and convection) have received considerable
attention in the electrochemical literature and are discussed separately in Section IV.A.1. For our
purpose here, it is sufficient to know that mass transfer results in the creation of concentration
profiles as a function of the distance from the electrode, as illustrated in Figure 1.15. For most of
the usual electrochemical situations, these profiles extend over a few to a few tens of micrometers
from the electrode surface. Beyond this region, called the diffusion layer, where mass transfer
processes are effective, the solution is homogeneous (except for microscopic convective effects as
in homogeneous chemistry).
Thus, a simple electrode reaction involves successively the following three steps: (1) mass
transfer of the reactant from the bulk solution to the electrode, (2) electron transfer at the electrode
CR
CR
CP CP
x x
0 δ δconv 0 δconv
(a) (b)
FiGURE 1.15 Concentration profiles for the reactant and the product as a function of the electrode distance
x in (a) transient or (b) steady-state electrochemical techniques: δ and δconv, diffusion layer and stagnant layer
thicknesses.
surface, and (3) mass transfer of the product of the reaction from the electrode surface to the bulk
solution. These three elementary steps may be perturbed by earlier or later chemical steps and
by adsorption or desorption phenomena at the electrode surface. Each of these processes may
become the RDS or may interfere significantly in the overall kinetics. At first glance, the situ-
ation then seems much more complicated than in homogeneous chemistry. Yet this is only an
illusion because most of these steps have their exact counterparts in homogeneous chemistry.
Mass transfer, though occurring here over macroscopic dimensions, corresponds to the diffusion
control of a chemical reaction as described. Earlier or later chemical steps are involved in most
homogeneous electron transfer reactions. Adsorption and desorption are analogous to the forma-
tion of stable precursor or successor complexes. Electron transfer to or from an adsorbed species
is very reminiscent of inner sphere reductions or oxidations. These analogies are not fortuitous;
indeed, an electrode may be viewed as a gigantic molecule with an infinite supply of reducing or
oxidizing power adjustable at will.
C. KINETICS oF HETEroGENEoUS ELECTroN TraNSFErS

1. Mechanism and Theory of Outer Sphere Electron Transfers at Electrodes
In the following, we consider an outer sphere electron transfer reaction involving the exchange of n
electrons (n > 0 for a reduction; n < 0 for an oxidation), taking place at an electrode whose potential
is E*:
R + ne P (E 0 ) (1.96)
The electrode is supposed to have no particular interaction with R or P. Its surface area is hereafter
designated by A.
Because in electrochemical reactions electron transfers occur near the electrode/solution inter-
face, that is, at a 2D surface, it is more suitable to refer to the number of moles converted per unit
of time and unit of electrode surface area, dNR /dt and dNP/dt, rather than using concentrations as
in homogeneous kinetics. Since there is no stable interaction with the electrode, dNR /dt = −dNP/dt.
* From the discussion in Section III.A.1, E = ΦW − ΦRef. Yet when E 0 is given vis-à-vis the same reference, the contribution
of the reference cancels in the difference E − E 0. Thus, in the following, E is considered the electrode potential vis-à-vis
that of the solution.
Basic Concepts 49
kf
Overall: R0 + ne P0 (E0,ΔG0)
kb
Diffusion/migration:
k act
f
Activation: RΦ + ne PΦ (E0 + Φs, ΔG0')
k act
b
SchEME 1.5 Debye-Smoluchowski microscopic representation of a heterogeneous electron transfer indi-

cating its diffusional and activation-driven components (compare to Scheme 1.3 for a homogenous situation).
On the other hand, each mole of the reactant R electrolyzed corresponds to a charge nF transferred
that affords the charge consumed per unit of time, that is, the current:
dN R dN
i = −nFA = nFA P (1.97)
dt dt
Since the definition of E 0 in Equation 1.96 refers to standard conditions, that is, conditions in which
no external electrical field applies on the reactant or the product, it is more convenient to consider
the act of electron transfer as a succession of three individual steps as outlined in Scheme 1.5,
which is reminiscent of that in Scheme 1.3 established for the homogeneous analogous situation
(see Section II.C.1). In Scheme 1.5, R0 or P0 relates to R or P in the closest plane to the electrode
where no electrical potential applies, that is, at the end of the diffuse layer,* denoted x0 in Figure
1.14d. RΦ and PΦ relate to R and P at the site of electron transfer xΦ, usually considered close to or
slightly within the OHP, where an electrical potential Φs (i.e., the electrical potential at the electron
transfer site) applies.
Let (R)0 and (P)0 be the activities of R and P at x0 and (R)Φ and (P)Φ those at x = xΦ (the electron
activity is not considered because it is implicitly included in the potentials). For all the electron trans-
fer reactions investigated up to now, the rates of the diffusion–migration steps in Scheme 1.5 do not
limit the overall process. Although this may be of importance for the prediction of the maximal rate
of electron transfer at an electrode, we do not consider the possible kinetic limitation by either of
these physical processes (compare the diffusion control of a homogeneous electron transfer discussed
earlier). Thus, within this restriction, the existence of the diffusion–migration processes reflects only
thermodynamic contributions. Thus, the overall rate constants in Scheme 1.5, defined in Equation 1.98,
i −dN R dN P
= = = kf (R )0 − kb (P )0 (1.98)
nFA dt dt
are related to the true activation constants via the relationship in Equations 1.99 and 1.100, where
∆GΦR and ∆GΦP are the respective free energy changes for R and P between the end of the diffuse
layer and the electron transfer site.
kf = kfact e −∆GΦ / RT (1.99)
* Note that this limit must not be confused with that of the diffusion layer/bulk solution interface, owing to the extreme
differences in size: some tens of angstroms for the double layer and some tens of micrometers for the diffusion layer.
kb = kbact e −∆GΦ / RT (1.100)
Note that because of their definitions in Equation 1.98, the heterogeneous rate constants are
expressed in units of length per units of time (usually in cm/s in the electrochemical literature).
As for the homogeneous case, it is more convenient to separate the terms arising from electrical
potential from those, ΔSpair, of entropic nature, due to the formation of a pair electrode/molecule.
Thus, ∆GΦR = Z R FΦ s − T∆Spair and ∆GΦP = Z P FΦ s − T∆Spair, where Z R and Z P are the respective ionic
charges of R and P (note that Z P = Z R − n owing to the charge balance). On the other hand, kfact and
kbact are obtained from the absolute rate constant theory as
kT −( ∆Gfact /RT )
kfact = e
h
kT −( ∆Gbact /RT )
kbact = e
h
This allows one finally to write the experimentally observed rate constants as follows:
− ∆Gfact /RT
kf = Z ele − Z R FΦ /RT e (1.101)
− ∆Gbact /RT
kb = Z ele − Z P FΦ /RT e (1.102)
where Z el = (kT/h)e∆S / R is shown from classic statistic thermodynamics to be related to the collision
pair
frequency of a molecule on a wall [50], that is,

1/ 2
 RT 
Z el =   (1.103)
 2πm 
in which m is the molar mass of R or P. For most organic molecules, Z el is of the order of approxi-
mately 2 × 103 cm/s. Note, however, that no transmission coefficient (compare the κ terms in the
homogeneous analog rate constants in Equations 1.58 and 1.59) is included in Equations 1.101 and
1.102. Indeed, the orbital variety at an electrode surface is sufficiently wide for convenient overlap
to occur with most organic molecules prone to outer sphere electron transfer, so that the adiabatic
requirement is generally fulfilled. Moreover, Hale [77] estimated that electron transfers at an elec-
trode are adiabatic as soon as the electron transfer site is within 15 Å of the electrode surface, for
most organic molecules.
Thus, determination of the rate constants in Equation 1.101 or 1.102 requires only that of ∆Gfact
since ∆Gbact = ∆Gfact − ∆G 0′ , ΔG 0′ being the free energy of the electron transfer between RΦ and PΦ
(compare Scheme 1.5):

(
∆G 0′ = ∆G 0 − Z R FΦ s + Z P FΦ s = nF E − E 0 − nFΦ s )
that is,

(
∆G 0′ = nF E − E 0 − Φ s ) (1.104)
The forward activation free energy is determined along the same lines as presented for homoge-
neous electron transfer since both problems are strictly equivalent [43,44,78,79]. Thus, ∆Gfact is given
Basic Concepts 51
as a function of the local driving force (ΔG 0′ in Equation 1.104) and of the associated reorganization
energy λ el by the expression in Equation 1.105, which derives from Equation 1.64.
2
λ el  ∆G 0′ 
∆Gfact =  1 + el  (1.105)
4  λ 

Again, λ el involves two contributions, of inner shell λ eli and outer shell λ elo nature, but these con-
tributions relate only to the R/P couple since the electrode is not affected by the electron transfer.
λ eli may be evaluated from bond length and bond angle variations, as is its homogeneous analog in
Equation 1.67.
For the evaluation of λ elo , the same model as in the homogeneous case is used, yet the electrode is
replaced by the electrical image of reactant for the initial system (or that of the product for the final
system) through the electrode, which acts as an electrostatic mirror. However, since these images
are imaginary, only the real contributions are considered for the final evaluation of λ elo , given as
follows:
e2  1 1  1 1 2
λ elo = N A  −  − n (1.106)
8π  εop εs   aR rΦ 

where
aR is the equivalent radius of R (or P)
rΦ is the distance between the centers of the R (or P) molecule and its electrical image when R
(or P) is at the electron transfer site
In practice, Marcus approximates rΦ by 2aR, assuming that the molecule is in contact with the
electrode surface when at the electron transfer site. Thus, it follows that λ elo is given in Equation
1.107 [43a,b]:
e2  1 1 1 2
(λ )
el
o
Marcus
= NA  − 
8π  εop εs  2aR
n (1.107)

Hush [78c] disagrees with the formulation in Equation 1.106, considering that the solvent polariza-
tion does not affect the potential in the double layer, the compact layer acting as an electrostatic
Faraday cage. Thus, the incidental solvent fluctuations energetically affect only R or P, without con-
sideration of their images (note that this amounts to considering rΦ, as infinite in Equation 1.106).
Thus, Hush proposed the expression in Equation 1.108 for the outer shell reorganization energy:
e2  1 1 1
(λ ) el
o
Hush
= NA  −  n2
8π  εop εs  aR
(1.108)

Interestingly, the Marcus heterogeneous reorganization energy (λ elo )Marcus in Equation 1.107 is exactly
half that, λ oRR, of the homogeneous isotopic electron transfer:
R* + P P* + R
whereas that proposed by Hush is identical to λ oRR. Based on this analogy, an elegant series of
experiments by Kojima and Bard [80] led to the conclusion that Hush’s reorganization energy is
more adequate [81].
Introduction of λ el = λ elo + λ eli in Equation 1.105, when taking into account Equations 1.98, 1.101,
1.102, and 1.104, allows the expression of the current to be predicted as in Equation 1.109, where
k(E) is the apparent rate constant for an electrode potential E. k(E) is given in Equation 1.110 under
a formulation modeled on that of the empirical Volmer and Butler law [82], where the transfer coef-
ficient α is given in Equation 1.111.
0
i = nFAk ( E )[(R )0 − (P )0 e nF ( E − E ) /RT
] (1.109)

k ( E ) = kt0e( αn− Z R ) FΦs /RT e − αnF ( E − E ) /RT

(1.110)
1 F (E − E 0 − Φs )
α= + (1.111)
2 4λ el
The true standard heterogeneous rate constant kt0 is expressed in Equation 1.112 as a function of λel.
Yet note that usually an intrinsic standard heterogeneous rate constant k0 in Equation 1.113 is defined
and used rather than kt0.
el
kt0 = Z ele −λ / 4 RT
(1.112)
k 0 = kt0e( αn− Z R ) FΦs /RT (1.113)
Provided the exponential term in Equation 1.113, called the Frumkin correction, is invariant with
E, that is, when Φs does not depend on the electrode potential, both are constant and characterize
the R/P electron transfer independently of the electrode potential. Otherwise, kt0 is preferred. In the
following, we nevertheless use k0 for simplicity in the formulations.
2. Transfer Coefficient α
The formulation in Equation 1.110 shows that the apparent heterogeneous rate constant k(E) depends
on the potential. This dependence has been observed experimentally since the earliest times of elec-
trode kinetics and is at the origin of the so-called Tafel plots [83]. Indeed, when the potential E is
sufficiently different from E0, for example, nF(E − E0) ≪ 0, the term relative to (P)0 in Equation
1.109 vanishes, and the current is given by the following:
i = nFAk ( E )(R )0 = nFAk 0e − αnF ( E − E ) /RT

( R )0 (1.114)
When (R)0 is maintained constant, then a plot of the logarithm of the current versus the potential yields
a straight line of slope αnF/RT, provided that α is constant. Thus, such observations led Butler and
Volmer, two pioneers in this area, to propose an empirical law [82], named after them, in the form of
Equation 1.109, with α being in their case an adjustable constant parameter. α is called the transfer coef-
ficient after the following observation: when the driving force, that is, −nF(E − E 0) in Equation 1.114,
is increased, only a fraction α of the additional energy is used to increase the apparent rate constant.
Thus, α is the fraction of the driving force transferred for kinetic purposes and plays a role identical to
that of the Brönsted coefficient in organic chemistry (see Section II.C.6).
From Equation 1.111, it is seen that, provided that λ el term is large enough, α remains constant
with the potential and is close to 0.5. This is generally in agreement with observations dealing
with reactions with low values of kt0 (compare the λ el term in Equation 1.112). However, for organic
molecules with small inner shell contributions and rather large radii, λ el (≈ λ elo ) is not expected to be
Basic Concepts 53
0.5
log k(E)
–2 α
–4 0.2
–6 0.25 –0.25 0.5 0.25 –0.25 –0.5

(E – E0), V (E – E0), V
(a) (b)
FiGURE 1.16 (a) Variations of the apparent heterogeneous rate constant k(E) in Equation 1.110 with the elec-
trode potential for the reduction of (CH 3 )3 CNO2 in DMF at the hanging mercury drop. A dashed line with
slope 0.5 is positioned at E = E 0 to emphasize the curvature. (b) Resulting variations in the transfer coefficient
α in Equation 1.111. (Experimental data from Savéant, J.-M. and Tessier, D., J. Phys. Chem., 81, 2192, 1977.)
extremely large, and therefore variations of α with the potential should be observed. This is indeed
the case in practice [84], as illustrated by the curvature of the logarithmic plot of k(E) with the
potential in Figure 1.16 for the reduction of 2-methyl-2-nitropropane, in DMF at the HMDE [84].
−
(CH 3 )3 CNO2 + e (CH 3 )3 CNO•2 (1.115)

Moreover, the plot of the corresponding α(E) variations in Figure 1.16b shows that α depends lin-
early on the potential with a slope (0.249 V–1), in close agreement with that predicted (0.210 V–1)
from the Marcus reorganization energy (29 kcal/mol) determined from Equation 1.107.
3. Reversible and Irreversible Electron Transfers: Their Role

in the Meaning of Oxidation or Reduction Potentials
From the current expression in Equation 1.109, it is seen that when k0 is extremely large, the brack-
eted term on the far right must tend to zero in order that the current remains finite. Thus, in these
conditions,*
0
(R ) x =0 ≈ (P ) x =0 e nF ( E − E )/ RT

which may be written under the form of the classic Nernst law in Equation 1.116. Thus, provided
the heterogeneous rate constant is large (>0.1 cm/s), the electron transfer is controlled entirely by
thermodynamics, and the relative activities of the oxidant and the reductant at the electrode surface
obey the Nernst law in Equation 1.116. The electron transfer is thus termed reversible or nernstian.
RT (R ) x =0
E = E0 + ln (1.116)
nF (P ) x =0
In other words, when (J)x = 0 = (J)bulk, with J = R and P, because of a large excess of material at the
electrode surface, for example, the electrode potential is given in Equation 1.116 independently of
the current flow. Such an electrode is then suitable for use as a reference electrode (large k0, large
surface area A, and excess of material).
* Hereafter, (R)0 and (P)0 are considered to be the activities at the electrode surface and denoted (R)x = 0 and (P)x = 0 to recall
this definition, x being the distance from the electrode. Yet, this usual notation is somewhat abusive since x = 0 does
not imply a close contact but rather that R and P are located at the end of the diffuse layer (compare Scheme 1.5 and the
associated discussion).
Conversely, when k0 is extremely small, the current flow is negligible in the potential range
around E0. Thus, in order that a measurable current may flow, the value of E − E0 must be sig-
nificantly increased (compare k(E) in Equation 1.110). For example, in order that a cathodic cur-
rent (n > 0) be observed, E must be considerably more negative than E 0. Thus, in Equation 1.109,
0
e nF ( E − E ) /RT → 0 in the potential range where the wave is observed, and Equation 1.109 can be rewrit-
ten as in Equation 1.117:
i = nFAk 0e − αnF ( E − E ) /RT

( R ) x =0 (1.117)
Similarly, the observation of an anodic current requires that E is considerably positive to E 0. Then, in
0
the potential range where the reverse anodic current is observed (n > 0 in this case), e nF ( E − E ) /RT → ∞,
and Equation 1.109 becomes
i = −nFAk 0e(1−α ) nF ( E − E ) /RT

( P ) x =0 (1.118)
In these situations, the current flow is entirely controlled by the kinetics of the heterogeneous
electron transfer, which is then said to be slow or irreversible. The current–potential characteris-
tic of the redox couple under study then reflects thermodynamic (E 0) and kinetic (k 0) properties.
Indeed, the driving force E − E 0 is used to overcome not only thermodynamic but also kinetic
limitations.
In this presentation, we discussed the reversible or irreversible nature of the electron transfer on
an absolute basis. Yet, in practice, the notion of measurable current flow is obviously related to a
given scale. In electrochemistry, the usual scale referred to is based on the mass transfer rate. Thus,
for a given mass transfer rate, a given current density is expected to flow through the electrode. This
limit is defined by the current density that would be observed if the electron transfer under investi-
gation is nernstian. Within this context, it is easily understood that any electron transfer is nernstian
at sufficiently small mass transfer rates. Similarly, it should become slow or irreversible for large
mass transfer rates, because then, the current scale is made very high. In practice, the largest mass
transfer rates routinely achievable with standard equipment are such that if k0 > 0.1 cm/s, the elec-
tron transfer may be considered intrinsically nernstian.
A second point not considered in the discussion is related to the possible involvement of chemical
reactions. For the sake of simplicity, let us restrict the presentation to the most common situation in
which the product P formed upon electron transfer is consumed by a fast chemical step, as outlined
in Scheme 1.6.
It is easily seen from this simple representation that as soon as the rate of the chemical removal of
P is larger than that of the back electron transfer, the RDS of the overall process is the forward elec-
tron transfer. Thus, independent of the intrinsic value of k0, the Butler–Volmer law in Equation 1.109
simplifies to that in Equation 1.117, because (P)x = 0 is made negligible. As a result, the R/P electron
transfer presents all the kinetic characteristics of a slow electron transfer [85]. However, since this
behavior is not related to the intrinsic value of k0, the current–potential curve may be observed in the
close vicinity of E0 or even positive to E0 for a reduction (negative to E 0 for an oxidation) [81]. This is
an important notion to recall when trying to relate this position of an irreversible wave to thermody-
namics. In absence of additional knowledge E 0 may be located on either side of the observed wave.
kf
R + ne P
kb
SchEME 1.6 Competition between forward and backward electron transfer reactions and follow-up reac-
tion at the level of the electron transfer intermediate product P.
Basic Concepts 55
D. ADSorpTIoN PHENoMENa
Many solutes or follow-up products of electrochemical reactions may have a large tendency to
adsorb on electrode surfaces [86]. This may be related to long-range electrostatic interactions, such
as those discussed in the presentation of the double layer; there is then no specificity of the ions
attached, particularly as concerns their chemical properties. In such cases, the phenomenon is said
to be nonspecific and is akin to nonspecific salt effects or ion pairing in organic chemistry. On the
other hand, because of particular chemical affinities between the electrode surface and a substrate,
specific adsorption occurs, which involves generally strong interactions and may result in the cre-
ation of organic layers at the electrode surface. Analogies of the latter are given by complexation
reactions or specific salt effects (e.g., Li + with an enolate ion or Bu− Li + solutions) in organic chem-
istry or chemisorption and physisorption in heterogeneous catalysis.
Both classes are distinct because of the nature of the electrode–adsorbed species interactions.
Yet from a phenomenological point of view, a better classification seems to be that based on the pos-
sible electroactivity or conductive properties of the adsorbed material.
When adsorbed, electroinactive species may give rise to partial or total blocking of the electrode
surface, which may then not be able to transfer electrons to or from other electroactive molecules. Thus,
depending on the nature of the electrode coverage, various phenomena may be observed, ranging from
an apparent decrease in the electrode surface (large and separated islands of adsorbed species) to an
apparent decrease in the electron transfer rate but with the appearance of unchanged electrode surface
area (micrometric islands at micrometric distances from each other) [87]. Related also to this class is
the natural blocking of electrodes by oxide layers or functional groups at carbon electrodes [88].
Conducting (via electrons or via permeation of electroactive species) adsorbed species usually
introduce small disturbances in electrochemical behavior compared with the former class. Yet obvi-
ously, the diffuse layer is extremely affected vis-à-vis the bare electrode. Thus, the rate constants k0
may be modified to a high degree because of large changes in the Frumkin correction.* Such effects
may easily explain, at least on a qualitative basis, the well-known dependence of k0 on the size of
the supporting electrolyte cation (reductions) or anion (oxidations), as well as on ionic additives [89].
The third class involves electroactive adsorbed species, yet it also encompasses the case in
which, although originally inactive, the species is activated or modified in the adsorption process
to give rise to the formation of electroactive adsorbed molecules. Obviously, all these effects dis-
cussed for the two previous classes are observed for this class, but additional effects are observed
for the adsorbed species itself. Indeed, adsorption modifies (1) the concentration of the species at
the electrode surface vis-à-vis that predicted from its bulk concentration, and (2) the energetics of
the electron transfer reaction. The latter point arises because of additional thermodynamic contri-
butions to be considered in the R0/RΦ or P0/PΦ equilibria in Scheme 1.5 and also from changes in
the reorganization energies. The former point leads to a variety of behaviors, since it is obviously
a function of the kinetics of adsorption–desorption phenomena [90]. A third additional effect of
electroactive adsorbed species arises from their possible ability to act as electron transfer media-
tors for other species that are reduced or oxidized with more difficulty. This special class (the term
electrode modification is then more adequate) is at present a very active area of research.
E. CoUpLED CHEMICaL REaCTIoNS

1. Electrochemical versus Homogeneous Chemical Reactivities
In the preceding sections of this chapter, much attention was devoted to the essential act of electron
transfer. Yet although being, for fundamental or analytic purposes, the subject of a large body of the
electrochemical literature, pure electron transfer reactions generally are of less interest in terms of
* Note that for n = 1, an increase by 0.2 V in ΦS results in the multiplication of k0 by approximately 50 when α = 0.5, and
by approximately 350 when α = 0.75, as determined from Equation 1.113.
preparative electrochemistry. In the opinion of this author, electron transfer at an electrode must be
considered as a particular class of activation of molecules to enhance their chemical reactivity. As
such, electrode kinetics must be understood (as for other methods of chemical activation) in order to
control and eventually direct the overall process to the selected target (compare Chapter 10).
From the preceding discussion, it should appear that electrochemistry affords a very facile and
precise way to generate highly energetic intermediates via control of the electrode potential. Note in
this respect that one electron exchanged over a potential difference of 1 V amounts to injecting 1 eV in
a molecule, that is, approximately 23 kcal/mol. Owing to the possibility of performing electrochem-
istry over potential differences of several volts, it is easily seen that the method may involve energies
comparable to those of most chemical bonds and largely beyond most activation energies. Thus, highly
energetic intermediates may be generated under mild and precisely controlled conditions. Another use-
ful aspect of electrochemical generation of chemical intermediates is related to the current flow through
the cell. Indeed, the current is a direct measure of the production rate of the intermediate. It ensures
that the production rate, an important parameter in product selectivity, is easily controlled and adjusted.
At this point, two questions must be addressed: Are these intermediates identical to those
obtained under usual chemical conditions? Do they react under conditions matching those of homo-
geneous experiments?
The answer to the first question is obviously positive. Indeed, since the substrates are generally
neutral, the primary electron transfer affords paramagnetic intermediates (anion or cation radicals)
that may undergo selected cascades of reactions to afford most of the well-identified intermedi-
ates of organic chemistry: radicals, carbocations, carbanions, carbenes, and so on. Neutral radicals
may also be generated by reduction or oxidation of stable cations or anions, respectively. It is thus
seen that all the basic intermediates of organic chemistry may be electrochemically generated, pro-
vided an electroactive precursor exists. Yet this is not always a serious limitation, since the sought
intermediates may be eventually formed indirectly, that is, through an electroactive proreagent, as
discussed elsewhere in this book (Chapters 15, 43, and 44).
The second question is more difficult to answer. Indeed, since the electrical perturbation extends
only over a few angstroms from the electrode surface, the medium in which the electrogenerated
intermediates react is identical to the bulk of the solution, which favors a positive answer. On the
other hand, they react under essentially nonisotropic conditions because of the existence of concen-
tration profiles, that is, of concentration changes with distance from the electrode (see Figure 1.15).
Yet this is a situation identical to that encountered when heterogeneous reagents or polyphasic
conditions are used in usual homogeneous chemistry. A more serious difference is related to the
nature of the media often used under electrochemical conditions. As explained in Section III.A.3,
electrochemical solutions must generally be rather conducting, a requirement met by using sol-
vents with rather high dielectric constants and an excess of inert electrolyte (see Chapter 7). Thus,
although solvents, such as liquid ammonia, or media with smaller dielectric constants, such as
methylene chloride, THF, DME, or even arenes and alkanes, can be used [91,92], the preference of
most organic electrochemists is for convenience or by tradition, to such solvents as acetonitrile and
dimethylformamide. The latter are prone to intervene in the reaction paths of the electrogenerated
intermediates via their nucleophilic or acidobasic properties, for example, as well as via hydrogen
atom transfers to radicals [93]. The same is true for the so-called inert electrolytes, frequently qua-
ternary ammonium salts, known for their acidic (Hofmann reaction) abilities, as well as for being
relatively good hydrogen atom donors. Thus, the usual electrochemical media may induce reaction
paths that are quite different from those observed with identical intermediates under conventional
organic conditions. We want to emphasize, however, that this is not to be viewed as a limitation of
the method. Indeed, these induced reaction paths may be used with great profit, as in organic chem-
istry when methanol is used as the solvent to incorporate methoxy groups. Several examples of this
strategy are given in various places in this book. On the other hand, as mentioned earlier, a large
variety of solvent–electrolyte systems may be used in electrochemistry [71,91], although the general
body of reported data pertains to a limited class of media.
Basic Concepts 57
2. hemical Reversibility and Irreversibility: Their Role

C
in the Meaning of Oxidation or Reduction Potentials
When considering a simple electron transfer reaction at an electrode, as in Equation 1.119, one can
conceive easily that there are, a priori, four limiting situations in which chemical reactivity may
affect the electrochemical measurements: R may be consumed or produced, and P may be con-
sumed or produced.
R + ne P (E 0 ) (1.119)

In practice, all four possibilities may be combined, which leads to a large variety of electrochemi-
cal mechanisms. Thus, our purpose in this section cannot be exhaustive if we wish to keep some
generality. We want, however, to describe qualitatively the role and the effect of chemical reactions
on the overall electrode kinetics. Thus, for the sake of simplicity, we discuss the case of simple EC
(electrochemical–chemical steps; see Section III.E.3) sequence, in Equations 1.120 and 1.121 as a
typical example:
R + ne P( E 0 , k 0 , α) (1.120)
P → (k ) (1.121)
The chemical step in Equation 1.121 is homogeneous and thus intervenes while P, which is formed
at the electrode, is transported to the bulk of the solution via the mass transfer mechanisms dis-
cussed earlier. From this simple consideration, it is easily understood that an important factor is the
relative magnitude of the rate constant of the chemical reaction vis-à-vis that of mass transfer, as
outlined in Scheme 1.7.
Obviously, when the mass transfer rate is much larger than that of the chemical steps, the transfer
of P from the electrode surface to the bulk solution is not affected by the presence of kinetics. Thus,
the electrochemical behavior of the EC sequence in Equations 1.120 and 1.121 is identical to that of
a simple electron transfer mechanism. The R/P electron transfer is then said to be chemically revers-
ible but may be nernstian or slow, according to the magnitude of k0 in Equation 1.120.*
In the converse situation, three limiting cases may be observed. In the first case, the electron
transfer is intrinsically slow. The RDS of the overall process is then the forward electron transfer,
and the redox system is said to be slow and chemically irreversible. The electrochemical wave is
then observed at potentials sufficiently different from E 0 for n(E − E 0) ≪ 0 (see Section III.C.3). The
two other situations are encountered when k0 is large enough for the electron transfer to be nernstian
in the absence of the follow-up chemical step.
Mass transfer
kf
Rx = 0 + ne Px = 0
kb
k
Chemical sequence
SchEME 1.7 Competition between forward and backward electron transfer reactions, diffusion, and follow-
up reaction at the level of the electron transfer intermediate product P.
* To avoid possible confusion with the reversible or irreversible nature of the electron transfer step per se, we suggest that
reversibility or irreversibility be reserved to the chemical part and the electron transfer be designated by nernstian or
slow, according to its rate versus the mass transfer one. In the following, we use this terminology.
When the chemical reaction is slow compared with the backward electron transfer, the reduction
or oxidation in Equation 1.120 remains at equilibrium. The electrode potential is then given by the
Nernst law:
RT (R ) x =0
E = E0 + ln (1.122)
nF (P ) x =0
Yet because of the chemical reaction, the activity of P at the electrode surface is considerably
decreased when the chemical rate exceeds that of the mass transfer. From Equation 1.122, it is
seen that the electrode potential is then positive (for a reduction; negative for an oxidation) to that
observed for the same current density, but in the absence of the follow-up reaction. As a result, the
current–potential characteristic is observed in a potential range positive to E 0 for a reduction and
negative to E 0 for an oxidation. The system is then said to be nernstian and chemically irreversible.
In the last situation, the rate of back electron transfer, although intrinsically fast, is slower than
that of the chemical step. Thus, as in the first situation, the RDS is the forward electron transfer,
and the redox system is said to be slow and chemically irreversible. Yet since k0 is large, the electro-
chemical wave is observed before E 0 [81,85].
From this description, it is seen that, depending on the exact degree of competition between the
four rates in Scheme 1.7, the electrochemical wave is observed in potential ranges that may be posi-
tive or negative to E0, as summarized in Table 1.4. Without a quantitative treatment of the pertinent
electrochemical data, it is almost impossible to decide the position of E0 vis-à-vis the potential
location EW, where the wave is observed. This is an important caveat to remember when using
published potential values, such as peak potentials or half-wave potentials, instead of E0 values.
The experimental difficulty is even more severe in practice. Indeed, when one considers a series of
related chemicals, there are great chances that E 0, k0, and k vary uniformly with respect to each other
because they relate intimately to the orbital energy and characteristics of the acquired (LUMO) or
lost (HOMO) electron [16,29]. Thus, the potential EW at which the electrochemical wave is observed
may correlate with E0, since it depends on the three figures. Such a case is presented in Figure 1.17
for the series of alkylbenzenes [29] already mentioned in this chapter, in which the peak potentials of
the chemically irreversible voltammograms (at 0.1 V/s) correlate with E0 with a slope close to unity.
To conclude this section, we discuss the special case of follow-up equilibria, that is, when the
chemical step in Equation 1.121 is reversible [93].
R + ne P Z ( E 0 , k ( E ); kf , kb )
TABLE 1.4
Nature and Locationa of the Electrochemical Wave Observed for an EC Sequenceb
as a Function of the Mass Transfer Rate
k0 versus Mass Transfer Rate
k versus Mass Transfer Rate Small Large
Small Slow reversible,c Nernstian, reversible,c
n(EW − E0) < 0 EW ≈ E0
Large Slow irreversible,c Nernstian or slow irreversible,c
n(EW − E0) < 0 n(EW − E0) > 0
a EW, any characteristic potential of the wave: E1/2, Ep, Ep/2,…, E0, standard reduction potential of the electron transfer step,
involving an exchange of n electrons (n > 0 for a reduction; n < 0 for an oxidation).
b k0, intrinsic standard heterogeneous rate constant; k, rate constant of the homogeneous follow-up chemical reaction.
c Chemically reversible or irreversible.
Basic Concepts 59
2.5
E 0 , V vs NHE
2.0
2.0 2.5
Ep , V vs NHE
FiGURE 1.17 Correlation between E 0 and anodic peak potentials Ep of the chemically irreversible cyclic
voltammograms at v = 0.1 V/s determined for an extended series of alkylbenzenes. (Data from Howell, J.O.
et al., J. Am. Chem. Soc., 106, 3968, 1984.)
Obviously, when K = kf/k b ≪ 1, the equilibrium lies toward P and does not affect the R/P electron
transfer. In the converse situation, and when kf and k b are larger than the mass transfer rate, a rapid
equilibrium displaced toward Z establishes, and (P)x = 0 ≈ (Z)x = 0/K. Introduction of this relation in
the current rate law Equation 1.109 then yields Equation 1.123, which is identical in its formulation
to a Butler–Volmer law but for a hypothetical electron transfer R + ne ⇌ Z whose formal potential
is E 0′ = E 0 + ( RT /nF ) ln K , as evidenced by the formulation in Equation 1.124.
 0
e nF ( E − E ) /RT 
i = nFAk ( E ) (R ) x =0 − ( Z) x =0  (1.123)
 K 

0′
i = nFAk ( E )[(R ) x =0 − ( Z) x =0 e nF ( E − E )/ RT
] (1.124)
This constitutes the basis of the operational significance of formal potentials introduced in Section
II.B.5. Yet the formal analogy between Equations 1.109 and 1.124 should not mask the fact that k(E),
that is, α, kt0, or k0 in Equation 1.124, remains related to the real electron transfer R + ne ⇌ P, that
is, to E 0, not to E 0′ (compare Equations 1.110 through 1.113).
3. Classification of Coupled Chemical Reactions

From this discussion, it is seen that the electrochemical behavior of a given electron transfer reaction
may be extremely perturbed by the intervention of coupled chemical steps. The resulting modifica-
tions obviously depend on the exact nature of the chemical sequence associated with the electron
transfer step. It is thus convenient to classify the different possible reaction schemes that may arise.
Yet as in organic chemistry, for the basic mechanisms (e.g., SN1, SN2, E1, and E2), such a classifica-
tion needs to be viewed only as a general frame to which real mechanisms are referred. Indeed, the
latter may often be more subtle (compare, e.g., SNi or E1cb vis-à-vis the earlier mechanisms) or involve
cooperative or competitive combinations of the elementary schemes presented later. A second
similarity with the organic basic schemes is that there is no unity in the denominations of the various
sequences of electron transfers and chemical steps. Indeed, each school or laboratory has proposed
its own nomenclature, which has received a different audience and may have evolved with time. In
the following, we use as much as possible the most frequent designations, and when not possible, we
refer to the nomenclature used in Savéant’s group, owing to its large contributions to this area [94].
The following classification is based upon the fact that electrochemical behavior depends on
the location of the electron transfer step in the overall sequence. Also, electron transfer steps are
considered to involve the exchange of a single electron, that is, n = ±1 (n = 1 for a reduction and
n = −1 for an oxidation), a normal situation in organic electrochemistry. Indeed, although overall
stoichiometrics involving the net exchange of many electrons are frequently observed, the energetic
and activation requirements for a direct polyelectron transfer are too high for any to exist concur-
rently with a rapid succession of single-electron transfer and chemical steps.
Within this frame, the most frequently encountered situations are the following.*
a. Preceding Chemical Reaction: CE Mechanism
 k  (C)
Z A  kf , kb , K = f 
 k b 
A + ne B ( E 0 ) (E)

The electroactive species A is generated by a reaction, generally an equilibrium displaced toward Z,

that precedes the electron transfer step. Z is the reactant introduced in the cell or the predominant
form of the reactant in the reaction medium. These reaction schemes were introduced to rational-
ize the various electrochemical phenomena observed during the reduction of certain aldehydes in
aqueous solutions. Indeed, in water, formaldehyde, π-electron-poor heterocyclic aldehydes, and a
few aldehydes with strongly electron-attracting groups exist as their nonreducible hydrated form in
rapid equilibrium with the reducible carbonyl (Scheme 1.8).
When the rate of the Z ⇌ A interconversion is slow vis-à-vis the rate of mass transfer,† it acts
as the RDS for the overall sequence. The currents observed are then abnormally low for the mass
transfer rate and reactant concentration considered and are said to be kinetic currents.
Conversely, when both rates are fast, the preceding chemical reaction acts as a rapid pre-
equilibrium, and (A) = K(Z). The electrochemical data are then formally identical to that of the
virtual Z + ne ⇌ B electron transfer, with a formal potential
RT K
E 0′ = E 0 − ln
nF K + 1
OH
RCH RCHO + H2O
OH
R
RCHO + e C O–
H
SchEME 1.8 Reduction mechanism of a hydrated carbonyl species (CE mechanism).
* Hereafter, we use the following notations: E stands for heterogeneous electron transfer, C for a chemical step. In chemical
reactions, A, B, C, and so on designate the electroactive molecules or their reaction product(s), whereas Y, Z, and so on
indicate coreagents or nonelectroactive species.
† In the following, rapid, fast, and slow always refer to a comparison to the rate of mass transfer.
Basic Concepts 61
A + ne B ( n = ±1) (E)
B+Z A+Y etc (C')
SchEME 1.9 Schematic representation of redox catalysis (ECʹ mechanism).
b. Redox Catalysis or Mediated Electron Transfer: EC′ Mechanism

In this sequence, the A/B couple acts as an electron transfer mediator, which allows the reduction
or the oxidation of the electroinactive (at the A/B wave potential) Z species (Scheme 1.9). The elec-
troactive species A is regenerated via the homogeneous electron transfer step C′, which results in a
considerable enhancement of the current observed for the A/B wave as soon as the C′ step is rapid.
Various subclassifications exist according to the exact nature of the chemical step, which may
eventually be a succession of elementary steps with formation of intermediate products. As explained
earlier for the displacement of endergonic electron transfer steps, the C′ step occurs because it is
continuously pulled to the right by the further chemical reaction of the Y species. Note that most of
this book is devoted to this class of mechanisms.
c. Consecutive Reaction: EC Mechanism

A + ne B (n = ±1) (E)

B→C (C)
This sequence is one of the most ubiquitous in organic or organometallic chemistry and has already
been discussed in preceding parts of this section. The chemical step may involve reactions (or a
succession of chemical reactions) of high-order modularities, not only first-order reactions as sug-
gested by the notation. Classic examples are given by activated olefin electrohydrodimerization
mechanisms (Scheme 1.10)*.
d. Multielectron Reactions: ECE and Related Mechanisms

As explained earlier, a direct exchange of many electrons at the same redox center appears to
be extremely difficult because of energetic and activation requirements. From the formulation in
Equation 1.106, it is indeed noted that the exchange of 2e involves a reorganization energy λ elo four
times larger than that for a single-electron exchange at the same center. For this reason and because
of the free energy relationship in Equation 1.105, a two-electron step without formation of an inter-
mediate should correspond to a slower process than the corresponding EE sequence as follows:
−
A + 2e A • + e A 2 − (1.125)
H H
–
CH2 C +e CH2 C
Z Z
H H H
– – – 2H+
2 CH2 C C (CH2)2 C Z (CH2)4 Z
Z Z Z
SchEME 1.10 Radical anion–radical anion coupling sequence during the electrodimerization of activated
olefins.
* We use here only one example called radical–radical coupling though many other coupling steps may occur [94].
On the other hand, in the second step of this sequence, the electron is transferred to a molecule with
an additional negative charge compared with A. Thus, at least a coulombic repulsion term must be
overcome, which implies that the second electron transfer is necessarily performed at a more nega-
tive potential than the first (by at least 0.250 V for an equivalent radius of 2 Å for the redox centers
and, e.g., ε ≈ 37.5 for acetonitrile as the solvent). As a result, an overall EE sequence should not be
observed at the potential of the A reduction but should occur in two separate waves (see Chapter 11).
However, there are two ways in which this conclusion may be invalid, and both need the relay of
a chemical reaction.
The first possibility is that the reorganization energy associated with the first electron transfer is
considerably larger than that of the second. Such a difference is obviously not related to the outer
shell components, which are necessarily close, as evidenced by Equation 1.106. Thus, the origin
for the differences must be sought in the inner shell reorganization energy, which implies that a
profound molecular reorganization must be involved during the first electron transfer. Examples of
this situation are given by the numerous cases in which two redox centers are electronically coupled
in the same molecule, as in O2 N −(CH 2 )n − NO2. Similarly, for inner sphere electron transfers, the
molecular moiety bearing the negative charge may be lost, leaving a neutral and easily reducible
species. This is so in the non-concerted reduction of alkyl halides to alkanes:
RX + e → R • + X (E1)
R• + e → R − (E 2)

R − + H + → RH (C)
in which the first electron transfer leads to the carbon–halogen bond cleavage and affords an easily
reducible neutral radical [95].
However, for most organic electroactive molecules, such large reorganization energies cannot
be invoked, owing to the extended delocalization of the orbitals participating in electron transfers.
Yet the interposition of a chemical step (possibly a simple conformational change) between the two
electron transfers results in the same effect, as soon as the chemical reaction gives rise to a species
more easily reducible (or oxidizable, in oxidations) than the starting reactant.
A + ne B E10 (E)

B→C (C)

C + ne D (E ;n(E
0
2
0
2 ) )
− E10 > 0 (E)
The intermediate formed is then reduced (or oxidized) at the electrode or in the solution owing to
the large exergonicity of the resulting reaction:

B+C → A + D ( ∆G 0
( )
= −nF E20 − E10 0 ) (DISP)
In the former case (second electron transfer at the electrode), the overall sequence is termed ECE;
it is designated a DISP (rather than an ECDisp) mechanism in the second case because the homo-
geneous electron transfer step is akin a disproportionation reaction. Indeed, the latter involves an
electron transfer between two chemically related molecules with the same oxidation numbers. In
practice, the distinction between the two mechanisms is nearly impossible on experimental grounds
[96] because their RDS, the B → C reaction, is identical.
Basic Concepts 63
A typical example of this sequence is given by the non-concerted reduction of aromatic halides:
−
ArX + e ArX •
−
ArX • → Ar • + X −
−
Ar • + e → Ar − and/or Ar • + ArX • → Ar − + ArX

Ar − + H + → ArH
As in the EC electrochemical sequence, a large variety of mechanisms belong to the general ECE–
DISP frame and differ according to the exact molecularity of the interposed chemical step, which
may also be a succession of elementary steps. Similarly, cascades of ECECE… sequences are pos-
sible, as in the classic reduction of nitro derivatives to hydroxylamines, which involves four elec-
trons and four protons [97]:
ArNO2 + 4e + 4ROH → ArNHOH + 4RO − + H 2O (1.126)

e. Zero-Electron Reactions: Electron Transfer Catalysis of Chemical Reactions

In the preceding ECE sequence, both electron transfers are of the same kind, that is, both reductions
or oxidations, and thus their combination gives an increase in the absolute value of the number of
electrons exchanged. Yet when the second electron transfer is of a nature opposite to the first, the
overall number of electrons consumed is zero. Thus, the sequence amounts to an electron transfer
catalysis of a nonredox chemical reaction [98], as outlined in the following sequence:
A + ne B (E)
B→C (C)
C − ne → D and/or C + A → D + B
(E)
Naturally, such mechanisms are observed only when the overall A→D reaction is exergonic but is
considerably slower than that occurring at the level of the reduced or oxidized states B and C. These
processes have been shown to be general and to encompass a large variety of chemical reactions.
Among the most documented is the SRN1 reaction, which amounts to an aromatic nucleophilic sub-
stitution. Although initially postulated by Bunnett [99a], the confirmation and the subtleties of its
mechanism have been established on electrochemical grounds [100]:
−
ArX + e → ArX •
−
ArX • → Ar • + X −
−
Ar • + Nu − → ArNu•
− − −
ArNu• − e → ArNu and/or ArNu• + ArX → ArNu + ArX •

Overall
ArX + Nu − → ArNu + X −
4. Electrochemical Reaction Mechanisms and the Principle of Microscopic Reversibility

As understood from the large variety of possible reaction sequences outlined in Section III.E.3,
a large number of reaction paths may be invoked a priori to explain the same overall electrochemical
transformation. Yet owing to the great capabilities of electrochemical techniques for the identifica-
tion of reaction mechanisms, the problem of their distinction frequently arises. For example, let us
consider the very common two-electron two-proton electrochemical sequence as follows:
A + 2e + 2H + AH 2 (1.127)
The latter is involved, for example, in the reduction of aromatics to their dihydro derivatives, of qui-
nones to hydroquinones, carbonyls to alcohols. A priori, there are six plausible different possibilities of
transferring two electrons and two protons, depending on the exact order of the steps. These six paths
− − +
involve the participation of seven different intermediates: A • , A2−, AH • , AH • , AH + , AH 2+ •
2 , and AH 2 .
It is thus seen that the discussion of the possible mechanism(s) may rapidly become an overwhelm-
ing task, particularly when more steps are involved, as in the 4e + 4H + sequence in Equation 1.126.
Thus, in order to discuss the exact route followed, a convenient representation of the different possible
schemes is highly desirable. Such a representation of all possible paths is given by square-schemes dia-
grams [101], such as that shown in Scheme 1.11 for the A/AH2 reduction. The horizontal transforma-
tions correspond to electron exchanges, whereas the vertical transformations involve a proton transfer.
Based on chemical grounds, several routes may be ruled out in Scheme 1.11. For example, starting
from an aromatic hydrocarbon A, routes δ, ε, and φ may be excluded, except in a superacidic medium. +
This is also certainly true for the γ route, which involves a difficult protonation of AH • to AH 2• . Thus,
only two routes, α and β, appear chemically reasonable under usual electrochemical conditions. In prac-
tice, both may be followed, path α prevailing under weakly acidic media and low cathodic potentials, and
path β predominating in less acidic conditions and at more negative values of the potential. Note, how-
ever, that additional complications, not considered in Scheme 1.11, involve the possible role of homoge- −
neous electron exchanges. Thus, AH • may be reduced at the electrode but also by the strong reductant A • .
The reverse transformation may also be considered, as in the oxidation of aromatic dihydro
derivatives to their parent hydrocarbon. Then, one starts from AH2, and routes α, β, and δ must be
eliminated,
−
except in very basic media. This is also certainly true for route γ, since the anion radi-
cals A • usually have a marked basic character. Thus, under usual electrochemical conditions, only
“Square-scheme”: Possible mechanisms

–
A A– A2 A A A
AH+ AH AH– AH2

(α) AH2 (β) AH2 (γ)
A A A
+
AH2+
2 AH2 AH2
AH2 AH2
AH2
(δ) (ε) (φ)
SchEME 1.11 Square-scheme mechanism detailing all possible sequential electron transfer and chemical
steps that may be involved in the two-electron reduction of species such as quinones. Left: global square-
scheme; Right: representation of all individual possible pathways that may occur depending on the exact
experimental conditions.
Basic Concepts 65
routes ε and φ must be retained. Path ε predominates at less positive potentials and weakly basic
conditions, whereas path φ should be observed at more positive potentials.
Consider now a given Ar ⇌ ArH2 reaction under rather neutral conditions. It is inferred from the
preceding discussion that route α is followed for the reduction, whereas the oxidation goes through
path ε. At first glance, such a result seems to have to be rejected since it apparently contradicts the
principle of microreversibility, which claims that both reactions should follow the same mechanism.
However, both transformations do not occur at the same electrode potentials: the reduction
Ar → ArH2 needs rather negative values, whereas the oxidation ArH2 → Ar is performed at rather
positive values. Thus, the two reactions occur under driving forces of opposite direction, with an
energetic difference of approximately 100–130 kcal/mol. Thus, invoking the principle of microrev-
ersibility under such conditions is no more reasonable than invoking it when comparing the Birch
reduction to the oxidation of aromatic dihydro derivatives by a strong oxidant.
IV. MASS TRANSfER iN ELEcTROchEMiSTRY

A. FUNDaMENTaL ASpECTS oF MaSS TraNSFEr ProCESSES
As mentioned in the preceding sections, mass transfer plays a crucial role in electrochemistry. The
ubiquity of this phenomenon evidently arises because the electrons are exchanged at 2D surface
boundary, but the reactants and products are dispersed in a 3D solution. Thus, in the absence of
mass transfer, only a small layer (of a few molecular radii thicknesses) would exchange electrons
with each electrode, as is the case, for example, when the electroactive material is adsorbed at the
electrode (see Section III.D). As such, mass transfer is essential in controlling the success and rate
of most electrochemical reaction.
Another important feature of mass transfer processes is related to the very physical nature of the
phenomenon. As such, it is easily quantifiable and predictable. Thus, the rate of mass transfer to and
from an electrode may be determined a priori for a given electrochemical system. As a result, this
rate may be used as natural built-in clock by which the rate of other electrochemical processes may
be measured. Such a property was apparent in our earlier discussions related to electrode kinetics
(electron transfer and coupled chemical reactions). Basically, it proceeds from the same idea as that
frequently used in organic chemistry for relative rate constant determinations, when opposing a
chemical reaction of known (or taken as the reference in a series of experiments) rate constant against
a chemical reaction whose rate constant (or relative rate constant) is to be determined. Many such
examples exist in the organic literature, among which are the famous radical-clocks (Scheme 1.12).
However, because of the intrinsic specificity of such chemical clocks, they cannot have a
general use outside a given class of chemistry. Thus, a better analogy with the electrochemical
approach involving mass transfer rates would be that in which a reaction rate constant is matched
to the diffusion limit rate constant that represents the physical process of bringing two reactants
to distances such that they can interact chemically (see Section II.C.1). Obviously, such methods
k( )
Z
Z I
(I)/[(II) ( )] = k/kclock
Z
kclock
II
SchEME 1.12 Principle of using a product ratio I/II for evaluating the relative rates of two pathways involv-
ing a radical clock.
are not frequently used in homogeneous chemistry, principally because most chemical reactions,
with maybe a few exceptions, among which are electron transfer or radical reactions, proceed
with rates considerably slower than that of the diffusion limit. Another limitation to the develop-
ment of such an approach is also related to the fact that diffusion limit is a rate of mass transfer
(analogous to that involved in electrochemical experiments) but relates to mass transfer over
atomic distances and is thus not prone to be adjusted at will.
In this respect, electrochemical mass transfer is particularly convenient. As mentioned earlier, its
physical nature and its necessary involvement in any electrochemical experiment confer on it one of
the characteristics of the internal clock just described. On the other hand, that it is active in the vicin-
ity of a macroscopic object, the electrode allows its precise control. In practice, mass transfer rates at
electrodes are continuously adjustable from equivalent times of a few seconds to a few nanoseconds
[102]. When this is coupled to the use of a diffusion limit in the nanosecond or less time scale, it
explains why electrochemical transient techniques allow kinetic information to be obtained and rate
constants determined for reactions whose lifetimes range from seconds to tens of picoseconds [103].
1. Physical Processes of Mass Transfer: Fick’s First Law

There are three physical processes involved in the transport of molecules in solutions: convection,
migration, and diffusion.
Convection may be the most intuitive and is present in all areas of chemistry; it corresponds to forced
displacements of small volumic parts of the solution. The molecule is then carried within the fluid
elements in which it is dissolved. The flux of particles Jconv through an elementary surface, that is, the
number of moles of particles crossing a unit surface area per unit of time, is then simply expressed as
J conv = Cv( x ) (1.128)
where
v(x) is the velocity of the fluid normal to the surface
C is the concentration of the particle in the fluid element
It then follows that the mass transfer contribution is independent of the particle but is only a func-
tion of the local hydrodynamics (natural or thermal convection, forced convection, eddies, and
so on). A large amount of work has already been devoted to quantifying the hydrodynamics of
a solution [104]. Yet for our purposes here, it is sufficient to recall two conclusions that apply in
most electrochemical situations. (1) Because of shocks and interpenetration of the fluid elements
in motion, concentrations are nearly identical at any point of a solution far from any wall. (2) Near
any wall or solid surface, solid–liquid frictions and bouncing phenomena result in the creation of an
immobile solution layer in which no convective effects occur.* Obviously, the thickness δconv of this
layer depends on the fluid velocity in the vicinity of the wall. Yet the resulting variation is small:
in nonviscous solvents, thermal agitation and average vibrations result in δconv ≈ 100 μm, whereas
magnetic stirring at maximum agitation results in δconv ≈ 10−20 μm.
From an electrochemical point of view, it is easily inferred that the solution in a cell near an elec-
trode is separable into two parts [105]: a stagnant layer adjacent to the electrode in which no con-
vective motions occur and the remainder of the solution, which is homogeneous (bulk solution). Yet
this is not a particularity of electrochemical methods since the same phenomena occur at any solid/
liquid interface, as when metal particles (e.g., reductions by Zn or Na) or any heterogeneous reagent
is used in organic homogeneous chemistry, as well as in phase-transfer catalysis or related methods.
* Note that the separation of the solution into two parts near a wall, that is, the immobile layer and the agitated homoge-
neous solution, is really simplistic since there is a continuous variation in the fluid velocity from the wall to the bulk
[105]. Yet this dichotomous approximation is sufficient for most purposes and allows great simplifications in physico-
mathematical treatments of the transport problem.
Basic Concepts 67
The other two contributions to mass transfer arise from forces exerted on the molecule consid-
ered. When the molecule or particle is charged and an external electrical field is applied, electro-
static forces are effective, and a positive molecule descends the electrical potential gradient, that
is, goes in the direction of lower potentials, whereas a negative ion climbs the potential gradient.
Because of frequent shocks and bouncing against solvent molecules, the molecule reaches a limiting
velocity proportional to the potential gradient times its charge z, the proportionality coefficient γ
depending on the molecules shape and size, as well as on the viscosity of the medium. This phenom-
enon, designated migration, then corresponds to a flux Jmigr given in the following:
∂Φ
J migr = − γzF C (1.129)
∂x
where
x is the coordinate normal to the elementary surface crossed
∂Φ/∂x is the electrical potential gradient along the x axis
C is the local molecule concentration
Φ can have an external origin as in electrophoresis or can be the result of local changes in the dis-
tribution of other charges. In the presence of a sufficient excess of supporting electrolyte, the latter
contribution is shown to be extremely small [106].
The third contribution is called diffusion, but a better name, although not used, would be
“spreading.” Indeed, it corresponds to the natural tendency of nonrigid objects to spread so that
the object’s constituents are leveled. This is well known in any field of chemistry and particularly
disturbing in chromatography, since it is responsible for the enlarging of peaks with retention times.
The physical origin of this phenomenon is easily understood when considering the chemical poten-
tial μ of a solute (for simplicity, concentrations and activities are assumed equal) given in Equation
1.130, where μ0 is the standard value. Thus, when C is not uniformly distributed along the x axis,
one obtains the chemical potential gradient in Equation 1.131:
µ = µ0 + RT ln C (1.130)

∂µ ∂ ln C RT ∂C
= RT = (1.131)
∂x ∂x C ∂x
This potential gradient can be considered as a force that acts on the molecule, as occurs for a
charged species submitted to an electrical potential gradient. Again this gives the molecule a limit-
ing velocity oriented in the direction opposite to the gradient, that is, toward the lesser values of
μ, and proportional to the force −∂μ/∂x. Because of the same collisions and bouncing effects as in
the migration case, the proportionality coefficient is γ, identical to that in Equation 1.129. Thus, the
diffusion flux Jdif is given as follows:
∂µ ∂C
J dif = − γ C = − γRT (1.132a)
∂x ∂x
In practice, one prefers to reformulate Equations 1.129 and 1.132a by introducing the diffusion coef-
ficient D = γRT of the molecule in the medium considered, that is,
∂C
J dif = − D (1.132b)
∂x
which is commonly designated as Fick’s first law.

In the most general situation, all three mass transfer modes cooperate algebraically; thus, the
number of moles crossing a surface of unit area per unit of time is given as follows, which consti-
tutes an extension of the Fick’s first law:
zF ∂Φ ∂C
J ( x ) = J conv + J migr + J dif = Cv( x ) − CD −D (1.133)
RT ∂x ∂x
2. Relationships between the Electrochemical Current and Mass Transfers

On the basis of the dichotomous representation of the solution near the electrode surface, Equation
1.133 simplifies in the two domains [105]. Within the stagnant layer and in the presence of an
excess of supporting electrolyte, the two first terms are negligible, and one obtains Equation 1.134.
Conversely, when x > δconv, the solution is macroscopically homogeneous; the diffusional contribu-
tion then vanishes, and the flux is given in Equation 1.135.
∂C
0 < x < δconv : J ( x ) = − D (1.134)
∂x
 zF ∂Φ 
x > δconv : J ( x ) = C  v( x ) − D (1.135)
 RT ∂x 
Equation 1.135 allows one to discuss more specifically the problem of ohmic drop. Indeed, the cur-
rent density through any surface area A located at any point in the bulk solution is given by addition
of the fluxes of all ionic species times their charge:
∑ z J ( x) = −v( x)∑ z C + RT ∂x ∑ z C D
i F ∂Φ
=− j j j j
2
j j j
FA
Because of electroneutrality, the first summation term on the right-hand side of this equation van-
ishes, which yields
RT dx
dΦ = i (1.136)
∑ (z F C j D j ) A
2
j
2
This gives the potential drop dΦ associated with the current i through a space element of cross sec-
tion A and thickness dx. By comparison with Ohm’s law and the definition of the resistivity, it is
seen that the resistivity ρ of the solution is given by Equation 1.137. The ensuing resistance RΩ for a
solution of cross section A and length is obtained in Equation 1.138.
1
ρ= (1.137)

∑( )  z 2 F 2 C D /RT 
 j j j

ρ
RΩ = (1.138)
A
Basic Concepts 69
Such an expression justifies a posteriori the previous discussion about ohmic drop effect in electro-
chemical cells (see Section III.A.3). Indeed, for a given resistance of the solution in Equation 1.138, the
ohmic drop across the cell is expressed as
Φ Ω = RΩi (1.139)
Thus, the larger the concentration of dissociated ions, the smaller the ohmic drop. This in turn
depends on the nature and affinity of the solvent/supporting electrolyte system, as discussed earlier
and in Chapter 7.
Let us now discuss more precisely the relationship between current and mass transfer at the elec-
trode surface. From Equation 1.134, it is seen that the flux of electroactive species at the electrode
surface (x = 0) is given, in the absence of migration (viz., in the presence of an excess of supporting
electrolyte [106]), by Equation 1.140:
 ∂C 
J x =0 = − D   (1.140)
 ∂x  x = 0
 ∂C 
i = −nFAJ x = 0 = −nFAD   (1.141)
 ∂x  x = 0
When there is no accumulation of material at the electrode surface, this flux corresponds to an
exchange of n electrons per molecule, that is, to a current given in Equation 1.141.* Thus, for the
electrochemical reaction in Equation 1.142, the reactant flux is associated with an identical, but with
an opposite sign, product flux, that is,
R + ne P
 ∂[ R ]   ∂[ P ] 
i = nFADR   = −nFADP   (1.142)
 ∂x  x =0  ∂x  x =0
Both fluxes must also correspond to the rate of electron exchange at the electrode surface. Since
this latter has already been shown to be given by the Butler–Volmer rate law in Equation 1.109, the
current must fulfill simultaneously the set of the following three equations:

i = nFAk 0e − αnF [ E − E
0
] /RT
([ R ] x =0 − [ P ]x =0 e nF ( E − E
0
)/ RT
) (1.143)
 ∂[ R ] 
i = nFADR   (1.144)
 ∂x  x =0
 ∂[ P ] 
i = −nFADP   (1.145)
 ∂x  x =0
* Note that we use the polarographic convention generally used in organic electrochemistry due to historical reasons. In
this convention, a reduction current is counted positive and an oxidation one negative. The IUPAC convention is opposite,
so all analytical formulations given here correspond to −i when using the IUPAC rules.
Comparison of Equations 1.143 and 1.144, for example, allows us to discuss more quantitatively the
relationship between mass transfer rate and reversibility or irreversibility of an electron transfer step
(see Table 1.4). Indeed, by equalizing both equations, one readily obtains the following for E = E 0:
[ P ]x =0 DR (∂[ R ]/∂x ) x =0
1− = (1.146)
[ R ]x =0 k 0 [ R ]x = 0
From this simple equation, it is seen that when k0 is much larger than the flux at the electrode, the
right-hand side tends to be zero, and thus [P]x = 0 ≈ [R]x = 0, which corresponds to the fulfillment of
a Nernst equation at the electrode surface for E = E 0. Conversely, when k0 is much smaller than the
demanded flux, one obtains [P]x = 0 > [R]x = 0 or [P]x = 0 < [R]x = 0, according to the flux sign. Thus, to
obtain [P]x = 0 ≈ [R]x = 0, one must impose an electrode potential E, such as
0 0 DR (∂[ R ]/∂x ) x =0
(1 − e nF [ E − E ] /RT
)e − αnF ( E − E ) /RT
= (1.147)
k 0 [ R ]x =0
that is, such that n(E − E 0) ≪ 0, which is highly cathodic with respect to E0 for a reduction and
highly anodic versus E0 for an oxidation.
3. Microscopic Origin of the Diffusion Coefficient: Mass

Transfer Rates and Diffusion Layer Thickness
Before concluding this section devoted to Fick’s first law, we discuss the microscopic origin of the
ubiquitous diffusion coefficient D (compare Equations 1.133 through 1.137, 1.140 through 1.142, and
1.144 through 1.147). In the preceding presentation, D was introduced as D = γRT, where γ is the
proportionality constant between the velocity of the molecule and the forces acting on it, based on
semimacroscopic considerations.
In the absence of any applied force, a molecule is nevertheless moving because of thermal agita-
tion. Yet owing to frequent collisions with the surrounding molecules, free motions occur only over
atomic distances. The overall molecular movement then resembles a random succession of linear
segments of approximately identical length and duration τ. Over a time period t = mτ, the average
2 2
square displacement ∆ is determined via statistical equations to be ∆ = m 2 = ( 2 /τ)t [107]. Let us
now suppose that a force is applied to the particle arising, for example, from a concentration gradi-
ent along the x axis. Consider a plane perpendicular to the x axis at x = 0, as shown in Figure 1.18a.
2
During a time interval of t seconds, a random-walking molecule covers a mean distance L = (∆ )1/ 2 .
Thus, those molecules from the negative axis region that may cross the plane at x = 0 during the
time duration t originate from a volume element, adjacent to the plane, of thickness L. Let C(−L/2)
be the average concentration of molecules within this element. Similarly, those that may also cross
the plane but originate from the positive axis pertain to an identical volume element of thickness L
in which the average concentration is C(+L/2). Since movements in a positive or negative direction
x J(x–dx) J(x+dx)
–L 0 +L x–dx x x+dx
(a) (b)
FiGURE 1.18 Symbolic representations of (a) the mass fluxes through one unit area surface, and (b) the
entering and outgoing mass fluxes in an elementary volume of solution of unit area cross section (see text).
Basic Concepts 71
are equally probable, one half of the molecules contained in each of these elements of solution cross
the plane. Thus, a unit surface area of the plane at x = 0 is crossed by (1/2)LC(−L/2) molecules
moving toward positive values of x and (1/2)LC(L/2) molecules moving toward negative values. The
flux of molecules, that is, the balanced number of molecules that have crossed the unit surface area
of the plane at x = 0 per unit of time and are lost (algebraically) from the layer on the negative axis
side, is then
(1/ 2)LC (− L / 2) − (1/ 2)LC ( L / 2)

J x=0 =
t
Noting that [C(L/2) − C(−L/2)]/L is the concentration gradient at x = 0, which is (dC/dx)x = 0, this

equation is rewritten as
L2  dC 
J x =0 = −
2t  dx  x =0

which, owing to the definition of L, yields finally
2  dC 
J x =0 = −
2τ  dx  x =0

and thus
2
D= (1.148)
2τ
Comparison of this equation with Equation 1.132b or 1.134 provides a microscopic meaning to the
diffusion coefficient D in Equation 1.148, where is the average free motion length and τ is the
average time duration between two collisions. Besides its intrinsic value, such a result allows one to
estimate how far a molecule has moved over an average period of time t. Indeed, from the expres-
sions of L and D, one readily obtains
L = (2 Dt )1/ 2 (1.149)
First, this equation provides a very convenient means to estimate, for example, the average distance
covered by a molecule during a time interval t. In other words, a molecule generated at time zero at
an electrode reaches a distance of approximately δ = (2Dt)1/2 after a time t has elapsed, provided its
movements are controlled only by diffusion. For this reason, δ is usually called the diffusion layer
thickness. This figure has an extreme importance in evaluating the nature of mass transfer at an elec-
trode. Indeed, as discussed earlier, transport is governed by diffusion–migration only when δ < δconv
and by convection when δ > δconv. This limit corresponds to a maximum time tmax = δ2conv / 2 D beyond
which convection dominates. For t < tmax, mass transfer processes at the electrode are then governed
by diffusion (and possibly, at low excesses of supporting electrolyte, by migration). Conversely, when
t > tmax, only an extremely small part of the molecular trajectories is controlled by diffusion, convec-
tion being the main means of mass transfer. As is elaborated in the following, this simple notion is
extremely important in discriminating transient electrochemical techniques (t ≤ tmax) from steady-
state techniques (t > tmax), that is, diffusion-controlled from convection-controlled mass transfer.
The second important property of Equation 1.149 is that it provides an estimate of the rate, in
terms of a characteristic time θ, associated with mass transfer. Indeed, this is the time θ needed for
a molecule to reach the electrode, that is, to cover the space interval in which the molecular con-
centration differs from that in the bulk. In transient methods, this time is identical to that elapsed
since the beginning of the experiment, provided that it is lower than tmax = δ2conv /2 D. For steady-state
methods, the length to be covered is δconv, and thus from Equation 1.149, it follows that θ = δ2conv /2D.
The rate of mass transfer can be defined as 1/θ, since it is obviously equivalent to a first-order
process (see Chapter 10 for a demonstration of this point). Yet in light of the previous discussion,
it is preferable to think in terms of a characteristic time θ associated with a given electrochemical
method rather than in terms of mass transfer rate, although this intuitive latter notion was extremely
worthwhile up to this point.*
4. Electrochemical Homogeneous Kinetics: Fick’s Second Law

Fick’s second law is based upon mass conservation at any point in time and space. To formulate this
point more precisely, let us consider that the spatial distribution of the concentration C of the spe-
cies of interest depends on a single direction x.† Consider now a cylindrical space element of length
2 dx and cross-sectional area A, centered at x, and let us designate C(x,t) the average concentration
at time t within this element, as shown in Figure 1.18b.
During time interval dt, an algebraic flux J[x−dx,t] enters the volume element through its
boundary at x−dx.‡ Similarly, an algebraic flux J[x + dx,t] leaves the element through. During the
same time interval, k p dt moles of the species have been produced, via chemical reactions within
the volume element, where k p and k c represent the kinetic rates of production and consumption
of the species considered. Thus, the number of moles of the species varied by dN during the time
duration dt:
dN = J ( x − dx, t ) Adt − J ( x + dx, t ) Adt + k p dt − k c dt (1.150)

Dividing the dN expression by the volume of element, 2A dx, gives the concentration variation, that is,
∂C J [ x − dx, t ] − J [ x + dx, t ] kp kc
=− + −
∂t 2dx 2 Adx 2 Adx
The first term on the right-hand side is the derivative of the flux vis-à-vis x, whereas k p /2 Adx and
k c /2 Adx relate to the concentration variations from chemical origin, denoted (∂C/∂t)chem.
∂C ∂J  ∂C 
= − + (1.151)
∂t ∂x  ∂t chem

Then, Equation 1.151 simply relates the overall time dependence of the concentration to the alge-
braically additive mass transfer and chemical components. In this respect, it is important to point
out that the chemical term is identical to that obtained under homogeneous conditions for the same
chemical sequence and identical composition. Thus, Equation 1.151 constitutes a generalization of
the usual kinetic rate laws to conditions in which concentrations are not homogeneous. Although
* Note also that all the preceding discussions immediately transpose when comparing the half-lifetimes t1/2 associated with
chemical reactions to θ. In our opinion, this is more satisfactory since it avoids the necessity of defining a rate constant
associated with mass transfer processes, which are essentially of a physical, not a chemical, nature.
† Note that, as for Fick’s first law, all the demonstrations easily adapt to a 3D space. Yet since for most electrochemical
methods the linear space approximation, that is, depending only on the normal distance from the electrode, is adequate,
we restrict ourselves to this simpler case in this presentation.
‡ Note that the terms enter and leave are used with respect to the volume shown in Figure 1.18 because fluxes are oriented
with respect to the x axis. Thus, J > 0 through a surface corresponds to a flux oriented toward positive x values, and the
converse is also true.
Basic Concepts 73
developed here in the context of electrochemical techniques, it is valid in any kind of chemical
situation in which concentrations are not uniform, as nearly any heterogeneous reactant or phase-
transfer boundaries.
Under electrochemical conditions, that is, near an electrode surface, two limiting formulations
are obtained for Equation 1.151. For distances from the electrode larger than δconv, the solution is
macroscopically homogeneous [108]. Thus, ∂J/∂x = 0, and Equation 1.151 simplifies to the usual
kinetic rate law in Equation 1.152:
∂C  ∂C 
x > δconv : = (1.152)
∂t  ∂t chem

∂C ∂ 2C  ∂C 
0 < x < δconv : = D 2 +  (1.153)
∂t ∂x  ∂t chem

Conversely, within the stagnant layer and in the presence of a sufficient excess of supporting elec-
trolyte, the flux is given in Equation 1.134. Introduction of this latter figure in Equation 1.151 yields
finally Equation 1.153, which is also commonly designated as Fick’s second law for diffusion reaction.
In the derivation of Equation 1.152, we neglected the quantity of the species produced or con-
sumed at the electrode. In practice, this is true for microscale electrochemical experiments but is
necessarily inexact for macroscale or exhaustive electrolysis. To derive the general equation, let us
consider the total equation for the bulk solution. The chemical contribution is given in Equation 1.152.
On the other hand, a flux of the species at the convection layer limit δ conv must be considered. This
flux corresponds to an algebraic number dNelec of moles of the species produced, given as follows:*
−
dN elec = J ( x = δconv , t ) Adt (1.154)
where A is the electrode surface area. Dividing both members of Equation 1.154 by the volume V of
the bulk solution allows the reformulation of Equation 1.154 as
 ∂C  DA  ∂C 
 ∂t  = − V  ∂x  − (1.155)
 elec   x =δconv
Thus, the overall concentration rate law in the solution is finally expressed as follows in a general
case:
∂C DA  ∂C   ∂C 
x > δconv : =−   +  (1.156)
∂t V  ∂x  x =δconv
−  ∂t chem

The absolute value of the first term on the right-hand side of Equation 1.156 is at maximum equal to
(DA/V)C0/δconv, where C0 is the bulk concentration of the electroactive reactant (see Section IV.B).
The electrode consumption or production is then equivalent to pseudo-first-order kinetics whose
apparent rate constant is at maximum equal to
DA
kelec = (1.157)
Vδconv
−
* The minus superscript in δconv means that the flux is that within the diffusion layer, that is, the limit of J(x), when x tends
toward δ conv from lower values.
To evaluate kelec, let us consider the following average figures: D = 10−5 cm2/s, δconv = 10 μm =
10−3 cm, and cell volume V = 100 cm3. Then, kelec = 10−4 A, when expressed in s−1 and A is expressed
in cm2. For microscale electrochemical experiments, A is of the order of few square millimeters at
most, that is, a few hundredths of a square centimeter; thus, kelec ≈ 10−6 s−1. This means that several
hours of continuous electrolysis are needed to significantly perturb (>1%) the bulk solution. This
is the reason why this term is neglected in practice, Equation 1.152 being used instead of the more
rigorous Equation 1.156. Obviously, when preparative-scale electrolysis is considered, one wants to
increase kelec in Equation 1.157, that is, use large A/V ratios and small δconv by increasing the elec-
trode surface area and convection within the cell.
Owing to the organization of this book, preparative-scale electrolysis is discussed separately in
Chapter 10. Thus, in the following, we restrict to analytic conditions, viz., we assume that Equation
1.152 represents the dependence on time of the concentration. In other words, the electrochemical
behavior, in the absence of migrational contributions, is given by a set of equations analogous to
that in Equation 1.158, with boundary conditions at x = 0, depending on the electrode potential and
kinetics (compare Equations 1.143 through 1.145), and at x = δconv, C = Cb, where the bulk concentra-
tion Cb is given as a function of time by Equation 1.159*:
∂C ∂ 2C  ∂C 
0 < x < δconv : = D 2 +  (1.158)
∂t ∂x  ∂t chem

dC b  dC b 
x > δconv : C = C b such as =  (1.159)
dt  dt chem

5. Dimensionless Formulation of Electrochemical Equations

The dimensionless analysis of equations is an analytic mathematical technique of frequent use in
engineering. Indeed, this technique allows one to “concentrate” all the a priori independent param-
eters resulting in an identical effect into a single dimensionless parameter. To illustrate the principle
and operational interest of the method, let us consider a general second-order homogeneous reac-
tion, such as that in the following, the reactant concentration being C0 at the beginning (t = 0) of the
experiment:
2R → P (k ) (1.160)
Strict application of homogeneous chemical kinetics readily yields the rate law in Equation 1.161,
which governs the reactant concentration, as a function of time. Integration of this rate law gives
the classic expression in Equation 1.162 for an experiment of duration θ. Yet Equation 1.162 may be
rewritten under the equivalent form in Equation 1.163.
d[ R ]
= −2k[ R ]2 (1.161)
dt
1 1
= 0 + 2kθ (1.162)
[R] C
* Note that when a figure C depends on several independent variables x and t, its variations vis-à-vis one of these variables
are given by its partial derivative ∂C/∂x with respect to the variable. When C depends on a single variable, the usual
derivation is used: dC/dx. The intrinsic difference between the two kinds of derivations is indicated by the symbolic use
of ∂ or d in the derivative notations.
Basic Concepts 75
[R] 1
= (1.163)
C 0 1 + 2kC 0θ
In many respects, the formulation in Equation 1.163 is more interesting than that in Equation 1.162.
Indeed, its left-hand side gives the instantaneous fraction of the reactant not converted to the prod-
uct at any time θ. Chemically, this is usually more significant than the actual concentration. Its right-
hand side shows that this fraction depends on a single factor (or parameter) 2kC0 θ, which includes
the effect of the a priori three independent factors: an intrinsic factor k and two experimental param-
eters C0 and θ. Just at a glance it shows that doubling the concentration, for example, results in the
same effect as keeping the same concentration and doubling the duration of the experiment, or
increasing the temperature, so that k is doubled.
In this example, the dimensionless reactant fraction r = [R]/C0 and dimensionless rate parameter
λ = 2kC0 θ were introduced by reformulating the integrated rate law in Equation 1.162. However,
this could have been done directly on the rate law in Equation 1.161 by introducing a dimensionless
time τ = t/θ (i.e., the elapsed fraction of the overall experiment duration θ) and the reactant fraction
r defined earlier. Then, Equation 1.161 reformulates as in Equation 1.164a and is associated with the
initial condition in Equation 1.164b. Integration of Equation 1.164a, owing to the initial condition,
yields readily Equation 1.165, which is identical to Equation 1.163.
dr
τ>0: = − λ dτ (1.164a)
r2
τ = 0 : r =1 (1.164b)

1
τ = 1: r = (1.165)
1+ λ
The interest of this second approach, that is, dimensionless analysis of the rate law itself, becomes
obvious for cases in which the integration of the rate law is not achievable analytically and must
be performed numerically. Indeed, the set of Equations 1.164 shows that the variable of interest,
r = [R]/C 0, depends only on λ = 2kC0 θ. Thus, would an analytic derivation be impossible to achieve,
numerical integration must be performed only for a selected number of λ values to obtain a single
curve giving r as a function of λ, that is, a function of all factors k, C0, and θ affecting the conversion
yield. If one says that 10 different values of λ, for example, are needed to determine the curve with the
required accuracy, the process needs 10 calculations. Yet without dimensionless analysis, the same
information with the same accuracy would be contained in at least 1000 curves, that is, [R] as a func-
tion of 10 values of θ, for 10 selected values of C0 and for each 10 values of k. Besides the intrinsic
interest of having all the information contained in a single curve, the method is essentially time sav-
ing. For example, consider that a numerical integration requires 30 s; the whole dimensionless curve
needs about 5 min calculation time, whereas the normal or direct method requires at least 8.33 h!
As explained in the previous parts of this section, two figures tightly control electrochemical
kinetics: a spatial one δ, the thickness of the diffusion layer, and a temporal one θ, the time elapsed
since the beginning of the electrochemical perturbation. Thus, in most situations, these figures
constitute adequate and suitable references for the definitions of the dimensionless space y = x/δ and
time τ = t/θ. Similarly, in most electrochemical kinetic experiments, the bulk concentration C0 of
the starting material remains constant (see, however, Chapter 10 for preparative electrochemistry).
It follows that s = [S]/C0 constitutes a meaningful dimensionless concentration for any species S
whose real concentration is [S]. Another obvious dimensionless parameter concerns the potential
figures. Indeed, in nearly all electrochemical circumstances, the electrode potential per se is not
important but influences the electrochemical behavior through its difference from E 0 times nF/RT.
(Compare, e.g., the Nernst equation or the Volmer–Butler rate law in Equation 1.143.) Thus, defini-
tion of the dimensionless potentials as ξ = (nF/RT)(E − E 0) appears suitable. y, τ, s, and ξ constitute
the master dimensionless parameters from which the definition of all others ensues, as is shown in
the following.
Let us consider first the electrode boundary conditions in Equation 1.144 or 1.145. Introduction
of r = [R]/C0 and y = x/δ in Equation 1.144, for example, directly affords
nFADC 0  ∂r 
i=   (1.166)
δ  ∂y 0

where the subscript 0 is used to indicate at y = 0, which shows that a convenient dimensionless defi-
nition for the current is ψ = i/(nFADC0/δ), which yields Equation 1.167:
 ∂r 
ψ=  (1.167)
 ∂y 0
k 0δ αξ
ψ= e (r0 − p0e − ξ ) (1.168)
D
ψ = Λeαξ (r0 − p0e − ξ ) (1.169)

Introduction of r, p = [P]/C0, ξ = (nF/RT)(E − E0), and ψ in the Volmer–Butler rate law (Equation
1.143) readily yields Equation 1.168. The latter shows that a convenient dimensionless rate of elec-
tron transfer is Λ = k0 δ/D, since it compares the intrinsic value of the rate constant to that of the
mass transfer process. Thus, Equation 1.168 reformulates as Equation 1.169. Let us now examine
the time- and space-dependent partial derivative equation of the kind demonstrated by Equation
1.158, which describes variations in the concentration profiles in the stagnant layer adjacent to the
electrode. For any species S, introducing τ, y, and s leads to reformulation of Equation 1.158 as in
follows:
δconv C 0 ∂s DC 0 ∂ 2 s  ∂[S] 
0<y< : = 2 + (1.170)
δ θ ∂τ δ ∂y 2  ∂t chem

To proceed further, it is necessary to define the nature of the chemical production or consumption
terms in (∂[S]/∂t)chem. For that, let us consider the general kinetic term, k j , in Equation 1.171:

 ∂[S] 
 ∂t 
 chem
= ∑k j with k j = ± k j [S]αj ∏[ Z ]
1
β1
(1.171)
C0D C0D

k j = ± λ j  s αj
 ∏ z1β1  2 = λ
 δ j
δ2
(1.172)
where the + or − sign corresponds to an S production or consumption, respectively. Thus,

j are defined as
k j reformulates as in Equation 1.172, where dimensionless rate constants λ
Basic Concepts 77
j = k j (δ2 /D)(C 0 )αj −1+Σβ1 .* Introduction of these expressions in Equation 1.170 yields, after multipli-
λ
cation of both members by δ2/DC0,
∑ λ
δconv δ2 ∂s ∂ 2 s
0<y< : = + j (1.173)
δ Dθ ∂τ ∂y 2
The formulation in Equation 1.173 shows that the dimensionless parameter δ2/Dθ plays a crucial
role in the time dependence of the S concentration profile. This parameter compares the diffusion
layer thickness δ to (Dθ)1/2. On the other hand, we have discussed the dependence of δ on the dura-
tion of the experiment. Thus, from Equation 1.149, δ ≈ (Dθ)1/2, provided that δ ≪ δconv, that is, that
θ δ2conv /D. Then, the diffusion layer extends within a small fraction of the stagnant layer, and
Equation 1.173 reformulates as follows:
∑ λ
δconv ∂s ∂ 2 s
0<y< ≈∞: = + j (1.174)
( Dθ) 1/ 2
∂τ ∂y 2
which shows that the concentration profile of S depends on the space as well as on the time. For
this reason, the corresponding electrochemical methods are said to be transient. Note also that
j = k j θ(C 0 )αj −1+Σβ1 or
since θ = δ2/D under these conditions, the dimensionless rate constant is then λ
0 αj −1
λ j = k j θ(C ) .
ap
Conversely, when θ δ2conv /D, the diffusion layer would extend well beyond the stagnant layer,
which is physically impossible. Thus, one has δ = δconv, and δ2/Dθ ≈ 0. On the other hand, ∂s/∂τ
cannot assume infinite values, except maybe at temporal discontinuities related to the exact electro-
chemical perturbation considered. Thus, with the exception of these discontinuities, the left-hand
side member of Equation 1.173 tends to zero. Thus, Equation 1.173 reformulates as follows:
∑ λ
∂ 2s
0 < y < 1: 0 = + j (1.175)
∂y 2
which shows that a steady-state concentration profile is observed. For this reason, the correspond-
ing electrochemical methods are said to be steady-state methods. Note that the expression of the
dimensionless rate constants reformulates as
j = k j δconv (C 0 )αj −1+Σβ1 or λ δconv

2 2
λ j = k ap
j (C 0 )αj −1
D D
It is thus seen that dimensionless analysis of electrochemical equations allows a very straightfor-
ward classification of the electrochemical methods into two limiting classes. Transient methods
(including linear sweep voltammetry, cyclic voltammetry, chronoamperometries, and chronocou-
lometries; see Section IV.C and Chapter 2) correspond to the shortest perturbation times (usually
less than 10 s) and the widest convection-free layers (usually = 100 µm, as imposed by natu-
ral convection and vibrations). On the other hand, steady-state methods (e.g., polarography and
* Note that an alternative formulation, when the [Z1] concentrations in Equation 1.171 are kept constant, consists of includ-
j = kj
ing their contribution into the rate constant, which amounts to defining a pseudo-rate constant k ap ∏
[ Z1 ]β1 . Thus,
Equation 1.171 is rewritten as
αj
k j = ± k ap
j [S]
= k ap (δ2 /D)(C 0 )αj −1. Obviously, any intermediate attitude is possible as a function of
which results in the definition of λ j j
the particular experiment dealt with.
TABLE 1.5
Dimensionless Variables for Electrochemical Kinetics
Variable Variable
Real Dimensionless Real Dimensionless
t
Time t a
τ= Rate constants k:
θ
x kδ2
Distance xb y= First order λ=
δ D
C 0 δ2
Second order λ=k
D
[S] δ2
Concentration or activity [S] s= ρth order λ = k (C 0 )(ρ−1)
C0 D
nF k 0δ
Potential Ec ξ=− (E − E 0 ) Heterogeneous k0 Λ=
RT D
δ K
Current ib ψ=i Equilibrium constantd K κ= 0 m
nFADC 0 (C )
a Cyclic voltammetry: θ = RT/nFv; v, scan rate. Staircase methods: θ = duration of the forward pulse.
b Steady-state methods: δ = δconv. Transient methods, δ = (Dθ)1/2.
c E0, standard reduction potential; n, number of electrons exchanged; n > 0 for reductions, n < 0 for oxidations.
d The dimensions of K are considered molm L–m.
rotating disk electrodes; see Section IV.B and Chapter 2) need δ conv to be as small as possible
(usually = 10–50 µm, as imposed by forced convection) and the experiment to be of long enough
duration.
The preceding presentation encompassed the widest class of electrochemical methods. As such,
the reference figures used in the definition of the dimensionless parameters used were not specifi-
cally related to a particular method. Yet when a specific electrochemical method is considered,
other equivalent definitions may be used for greater convenience. For example, in cyclic voltam-
metry, θ is frequently defined as the time elapsed, θ = ΔE/v, between two waves separated by a
potential difference ΔE at a scan rate v (in V/s). Yet in linear sweep voltammetry, θ is usually
defined as θ = RT/nFv, that is, approximately the time needed to describe the rising branch of a
nernstian voltammogram (see Chapter 2). Table 1.5 presents the most widely used dimensionless
formulations.
B. STEaDY-STaTE ELECTroCHEMICaL METHoDS: HaLF-WaVE PoTENTIaL E1/2

1. Pure Electron Transfer Mechanisms
In the following, we consider a simple electron transfer mechanism in order to discuss quantitatively
the variations in the potential location of the steady-state voltammogram of the system according
to the kinetics of the heterogeneous electron transfer. In the derivation of the kinetics, we con-
sider that the solution contains only the reactant at concentration C0 before the electrochemical
experiment. Let E 0, k0, and α be the standard reduction potential, the standard heterogeneous rate
constant, and the transfer coefficient of the electron transfer in the following:
R + ne P ( E 0 , k 0 , α) (1.176)

For most organic electroactive molecules, the variations in shape and solvation upon electron trans-
fer are minimal, owing to the usually large delocalization. It follows that the diffusion coefficients
Basic Concepts 79
relative to R and P are generally very close to their average value D, which is then used to introduce
a simplification in the following derivations.
From the general equation (1.175), the concentration profiles of R and P are solutions of the fol-
lowing differential equations in dimensionless variables (see Table 1.5):
d 2r 
2
= 0
dy 
 0 < y <1 (1.177 and 1.178)
d2 p
= 0
dy 2 

These equations are associated with the boundary conditions
 dr   dp  
ψ =   = −  
 dy 0  dy 0  electrode (y = 0) (1.179 and 1.180)

ψ = Λe (r0 − p0e− ξ ) 
αξ

r =1
 convection layer boundary ( y = 1) (1.181 and 1.182)
p = 0

Integration of Equations 1.177 and 1.178, when taking Equation 1.179 into account, readily yields
r = r0 + ψy and p = p0 − ψy

Introduction of conditions (1.181) and (1.182) into these linear concentration profiles gives the rela-
tionships between r 0, p 0, and ψ in Equation 1.183. Incorporation of these latter figures into Equation
1.180 and reorganization of the latter as a function of the dimensionless current ψ yields the equa-
tion of the dimensionless voltammogram in Equation 1.184.
r0 = 1 − ψ and p0 = ψ (1.183)

1
ψ= (1.184)
1 + e − ξ + (1/Λ)e − αξ
The latter shows that the current reaches two limiting values for ξ → −∞ (i.e., for n(E − E 0) ≪ 0)
and ξ → +∞ (i.e., for n(E−E 0) ≫ 0). Indeed, from Equation 1.184, it ensues easily that ψ → 0 for
ξ→−∞ and ψ → 1 for ξ → +∞, which shows that no current is observed when the potential is much
less cathodic than E 0 (for a reduction, n > 0) or anodic than E 0 (for an oxidation, n < 0). Conversely,
at sufficient cathodic (n > 0) or anodic (n < 0) values of the electrode potential, the current tends to
a plateau value (ψ → 1) given in the following:
nFADC 0
i lim = (1.185)
δconv
Of interest is the proportionality of ilim to the bulk concentration of the reactant. Indeed, Equation
1.185 demonstrates that the electrochemical current can be used to monitor the bulk concentration
of any chemical species, provided the latter is electroactive. This is the basis of a large variety of
chemical or biochemical sensors, as well as that of electrochemical detectors in high-performance

liquid chromatography. From Equation 1.183, it is seen that the observance of the current plateau
corresponds to the fact that the reactant concentration has been completely depleted (r0 = 0) at the
electrode, so that increasing ξ results in no further change in the concentration profiles and therefore
of the current. Similarly, the limit at ψ = 0 corresponds to p 0 = 0, thus decreasing the dimensionless
potential results in no further change. The observation of the two limits thus corresponds to the fact
that the concentrations of R and P at the electrode are limited by 0 and C0. This is independent of
the electrode kinetics, which explains that the limiting current ilim does not depend on the kinetics of
the electron exchange. However, the location of the voltammogram depends on the rate of electron
transfer.
When Λ ≫ 1, that is, when k0 ≫ D/δ,* the third term in the denominator in Equation 1.184 van-
ishes, and the voltammogram equation simplifies to the following:
i 1
=ψ= (1.186)
i lim
1 + e−ξ
which is independent of the electron transfer rate. Moreover, introduction of r0 and p 0, as given by
Equation 1.183, into Equation 1.186 shows that
r0 = p0e −ξ (1.187)

that is, in real variables,
RT [ R ]x =0
E = E0 + ln
nF [ P ]x =0
which demonstrates that the electrode potential obeys the Nernst equation. Thus, the electron trans-
fer is sufficiently fast to be controlled thermodynamically. It is then said to be fast or nernstian. At
E = E0, [R]x = 0 = [P]x = 0, that is, from Equation 1.183, i/ilim = 0.5. Thus, E0 may be determined as the
potential for which i/ilim = 0.5. This potential, the half-wave potential E1/2, thus bears an important
thermodynamic significance since it allows the determination of E 0. Indeed, most E 0 values deter-
mined for organic redox couples have been measured through this or related techniques. Yet it must
be emphasized that E1/2 involves contributions other than E 0. In a real situation, the activity and
diffusion coefficients of R and P may differ, which yields [109]
RT  fR  DP  
1/ 2
E1/ 2 = E 0 + ln   
nF  fP  DR  
 
However, most of the time, the corrective term to E 0 is unfortunately unknown and beyond the error
associated with potential measurements on an absolute (NHE) scale, mainly because of junction
potential and reference electrode potential drifts. Thus, in actual experiments, E1/2 and E0 (or E 0′)
are generally considered identical for Nernstian reactions [94].
Let us now consider the converse situation, that in which Λ ≪ 1 (i.e., k0 ≪ D/δ). Then, Equation
1.184 simplifies to the following form:
i 1
ψ= = (1.188)
i lim 1 + (1 / Λ)e − αξ
* In practice, D ≈ 5 × 10−6 cm 2/s and δ ≈ 10 μm = 10−3 cm may be considered as typical values; thus, the inequality is
generally satisfied for k0 ≫ 0.01 cm/s.
Basic Concepts 81
1.
∞ 10–3 10–4 10–5
α = 0.2 0.30.4 0.5 0.6 0.7 0.8
n (E 0–E 1/2)
i/(nFADC 0/δ)
.2
.5
.1
0 0
0 0.2 0.4 0.6 2 1 0 –1 –2 –3
n (E – E 0), V log (k 0δ/D)

(a) (b)
FiGURE 1.19 (a) Steady-state voltammograms of a simple redox system as a function of its intrinsic het-
erogeneous rate constant (number on the curves: k0 in cm/s) for δ2/D = 0.1s. (b) Variations in the half-wave
potential E1/2 as a function of the dimensionless rate constant Λ = k0 δ/D for different values of the transfer
coefficient α.
The half-wave potential, that is, E1/2 at which i/ilim = 0.5, is then such that
RT RT k 0δ
E1/ 2 = E 0 + ln Λ = E 0 + ln (1.189)
αnF αnF D
Since k0 δ ≪ 1, the logarithmic term in Equation 1.189 is negative, and n(E1/2 − E 0) ≪ 0. The wave
is thus located in a potential range well cathodic of E 0 for a reduction process (n > 0) or anodic of
E 0 for an oxidation process. The E1/2 represents both thermodynamic (E0) and kinetic contributions
(lnk0 δ/D) and must not be used as a substitute for E 0.
Figure 1.19a presents the variations in the steady-state voltammograms for the R/P redox system
as a function of Λ = k0 δ/D for α constant and equal to 0.5. The variations in E1/2 with the same
parameter k0 δ/D are presented in Figure 1.19b for selected constant values of α. Therefore, in an
actual experiment, variations in E1/2 with δ (note that k0 and D are intrinsic figures for a given couple
R/P and a given medium) are indicative of kinetic complications and should warn against the use
of E1/2 as an estimate of E 0.
2. Mechanism Involving a Follow-Up Reaction: EC Mechanisms

Let us first consider the case in which the initial electron transfer in Equation 1.190 is sufficiently
rapid to be nernstian (i.e., Λ = k0 δ/D ≫ 1) but is followed by an irreversible pseudo-first-order
chemical reaction (i.e., k may include the concentrations of other reagents, when constant).
R + ne P ( E 0 , k 0 , α) (1.190)

P → (k ) (1.191)
The dimensionless equations governing the R and P concentration profiles are obtained from Table
1.5, as in Equations 1.192 and 1.193:
d 2r 
2
=0 
dy 
2  0 < y <1 (1.192 and 1.193)
d p 
= λ p
dy 2 

For a Nernstian heterogeneous electron transfer, the boundary conditions at the electrode formulate
as in Equations 1.194 and 1.195:
 dr   dp  
ψ =   = −  
 dy 0  dy 0  y=0 (1.194 and 1.195)
−ξ 
r0 = p0e 

(Compare Equation 1.187). For a bulk solution containing only R, the boundary condition at the
extremity of the convection layer is then
y = 1 : r = 1, p = 0 (1.196)

Integration of Equation 1.192, taking into account Equations 1.194 and 1.196, yields
r = r0 + ψy, with r0 = 1 − ψ, (1.197)

From this simple equation, it is seen that, as for the preceding situations, the voltammogram has
two limiting values. When r0 ≈ 1, ψ ≈ 0, which corresponds to large negative values of ξ according
to Equation 1.195. Conversely, ψ ≈ 1 when r0 ≈ 0, which is observed for large positive values of ξ
as seen from Equation 1.195. Thus, the overall qualitative shape of the steady-state voltammogram
remains identical to that observed in the absence of a chemical follow-up reaction. Yet they differ
considerably on a quantitative basis, as shown by the following analysis.
Integration of Equation 1.193 yields the dimensionless concentration profile of P:
1/ 2 1/ 2
p = Ae( λ y)
+ B e( − λ y)
(1.198)

where A and B are two constants. These constants are determined according to the boundary
conditions (1.194) and (1.196). Indeed, Equation 1.194 yields by derivation (and setting y = 0) of
Equation 1.198:
ψ = −λ1/ 2 A + λ1/ 2 B (1.199)

1/ 2 1/ 2
0 = Ae( λ )
+ B e( − λ )
(1.200)

whereas Equation 1.196 affords Equation 1.200 by setting y = 1 in Equation 1.198. The system of
two linear Equations 1.199 and 1.200 with two unknowns (A and B) allows A and B to be determined
as a function of ψ and λ. Thus,
ψ / λ1/ 2 1/ 2
A= and B = − Ae( 2 λ )
( 2 λ1/ 2 )
1+ e
ψ tanh λ1/ 2
p0 = A + B = (1.201)
λ1/ 2
Basic Concepts 83
Determination of p 0 = A + B from Equation 1.198 is thus readily obtained as in Equation 1.201.

Incorporation of this latter value, as well as r0 = 1 − ψ from Equation 1.197, into the Nernst equation
(1.195), gives access to the equation of the steady-state voltammogram in Equation 1.202:
i 1
=ψ= (1.202)
i lim 1 + e( − ξ*)
1
ξ* = ξ + ln λ − ln tanh λ1/ 2 (1.203)
2
Equation 1.202 is identical with that obtained for a nernstian system (compare Equation 1.186)
but one in which the potential axis has been translated by a constant term (for a constant value
of λ = kδ 2/D), as evidenced by Equation 1.203. Its half-wave potential then corresponds to
ξ* = 0 instead of ξ = 0. From Equation 1.203 and the definition of ξ in Table 1.5, one obtains
the expression in Equation 1.204. Since one always has λ1/2 > tanh λ1/2, the corrective term to
E 0 in Equation 1.204 always has the sign of n. Thus, the wave is observed in a potential range
E W such that n(E W − E 0) > 0, that is, anodic to E 0 for a reduction (n > 0) and cathodic to E 0 for
an oxidation (n < 0).
RT RT
E1/ 2 = E 0 + ln λ − ln tanh λ1/ 2 (1.204)
2nF nF
When λ → 0, that is, k ≪ D/δ2, one obtains E1/2 ≈ E 0, since then tanh λ1/2 ≈ λ1/2, resulting in a
negligible corrective term in Equation 1.204. This means that the chemical reaction in Equation
1.191 is too slow vis-à-vis the mass transfer rate to significantly affect the voltammogram. The
system is then said to be nernstian and chemically reversible. Conversely, when k ≫ D/δ2, that is,
when the chemical reaction is faster than the mass transfer at the electrode, λ → ∞. Then, because
tanh λ1/2 → 1 for λ1/2 → ∞, Equation 1.204 simplifies to the following:
RT kδ2
E1/ 2 = E 0 + ln (1.205)
2nF D
From the latter, it is seen that for n = 1 and room temperature, for example, E1/2 shifts anodically by
approximately 30 mV per unit of logkδ2/D. As for the slow electron transfer case, E1/2 is therefore
not an acceptable substitute for E0 since it incorporates kinetic contributions that then arise from the
follow-up chemical reaction.
The variations in E1/2 with λ = kδ2/D result from the fact that when λ increases, the P concentra-
tion at the electrode surface decreases, as is apparent in Equation 1.201 and Figure 1.20.* Thus, at
any driving force imposed by the value of ξ, one obtains from Equation 1.195 for large λ values:
ψ ( −ξ) ψ
r0 = e = e( − ξ ) (1.206)
λ1/ 2
(kδ /D)1/ 2
2
which shows that the reactant concentration is considerably less than that, r0 = ψe(−ξ), obtained at the
same potential in the absence of a fast follow-up chemical step. Thus, the heterogeneous electron
* Indeed from Equation 1.201, one obtains p 0 ≈ ψ/λ1/2 when λ > 7, with an accuracy better than 1%.
1 1
.01
.1 [P]/C 0 [P0]/C 0
100 10
0 0
1000 0.5 1.0 0 2 4
2
x/δ log (kδ /D)
(a) (b)
FiGURE 1.20 Steady-state electrochemical method. (a) Concentration profiles of the product obtained upon
electron transfer in the EC sequence in Equations 1.190 and 1.191 as a function of the dimensionless chemical
rate constant kδ2/D (numbers on the solid curves). The reactant concentration is shown for comparison as the
dashed line. (b) Variations in the product electrode concentration as a function of kδ2/D. The dashed curve
corresponds to the approximation in Equation 1.206.
transfer is continuously displaced by P removal in a way similar to that already observed for the
corresponding homogeneous situation in Equations 1.207 and 1.208. Yet in the latter case, as elabo-
rated in Section II.B (see Equations 1.45 and 1.47), the follow-up chemical step affects the overall
kinetics by a factor involving k with a unity exponent, whereas an exponent of one-half is involved
in the heterogeneous equivalent case:
M + ne N
N + R M + P (K ) (1.207)

P → (1.208)
(Compare the half-factor in Equation 1.205 or the half-exponent in Equation 1.206.) This effect,
which arises from the heterogeneous nature of the electrochemical process (i.e., a surface reac-
tion vis-à-vis a volume reaction in homogeneous phases), is the basis of the efficiency of redox
catalysis or mediated electron transfer (see Section III.E.3). Thus, for a given redox system, as in
the sequence in Equations 1.190 and 1.191, the use of a redox mediator M in Equation 1.207 allows
the reduction of R to be performed at potentials less cathodic than E1/2 in Equation 1.205 (or the R
oxidation at potentials less anodic than E1/2) for the same electrochemical setup (i.e., an identical
mass transfer rate).
3. C hemical Kinetics from Half-Wave Potentials: Determination

of Rate Constants and Reaction Orders
The preceding two examples were presented to illustrate the simplicity of electrochemical analysis
under steady-state conditions. Indeed, the kinetic derivations are very similar to those encountered
in the homogeneous chemical situation, except for the replacement of the usual derivative dC/dt by
a second-order derivative vis-à-vis the space variable d2C/dt2 as apparent, for example, in Equation
1.193. The existence of a second-order differentiation introduces unusual dependencies on reac-
tion orders when compared with those observed in homogeneous kinetics. Thus, if one considers
the rate constant k in the chemical reaction (1.191) to be a pseudo-first-order rate constant, that is,
k = k0[Z], where Z is a coreagent, the concentration of which is maintained constant, a dependency
Basic Concepts 85
on [Z]1/2 is observed (because of the involvement of k with a power of one-half in Equation 1.198)
for electrochemical experiments rather than the dependency on [Z] that would be observed under
homogeneous experiments. Let us consider a general case in which the product formed upon elec-
tron transfer reacts via a chemical reaction of the ρth order in P and involving other coreagents
A, B, …, in excess, as featured in the reaction sequences (1.209) and (1.210):
R + ne P (E 0 ) (1.209)

ρP + αA + βB + … → … (k0 ) (1.210)

One obtains the pseudo-rate constant k = k0[A]α[B]β…. Thus, dimensionless analysis affords the
differential equation in Equation 1.211, which describes the concentration profile of the P species
when λ is given as in Equation 1.212:
d2 p
= ρλpρ (1.211)
dy 2
δ2
λ = k (C 0 )(ρ−1) , k = k0 [ A]α [ B]β …, (1.212)
D
When λ is extremely large and the usual situation in which the bulk solution contains no P is con-
sidered, integration of Equation 1.211 is performed as follows. Multiplication of both members by
2(dp/dy) dy yields
dp d 2 p
2 dy = 2ρλpρdp (1.213)
dy dy 2
The left-hand term in Equation 1.213 is the derivation of (dp/dy)2 vis-à-vis y. The right-hand side is
the derivation of [2ρλ/(ρ + 1)]p(ρ + 1) versus p. Thus, integration of Equation 1.213 yields
2
 dp  2ρλ ρ+1
  = p + cst (1.214)
dy
  ρ +1

The integration constant in Equation 1.214 is determined by the condition p 0 ≈ 0 when y ≈ 1. When
λ is large, this is also equivalent to saying that dp/dy ≈ 0 when y ≈ 1, since P exists only in a thin
layer (called the kinetic layer) adjacent to the electrode (compare, e.g., Figure 1.20a). The integration
constant in Equation 1.214 is then zero, and one obtains at the electrode surface, for y = 0,
2ρλ (ρ+1)  dp 
ψ2 = p0 since ψ = −   (1.215)
ρ +1  dy 0

On the other hand, since R is not involved in chemical reactions, one obtains as in Equation 1.183,
r0 = 1 − ψ. Thus, for the nernstian electron transfer in Equation 1.209, one obtains Equation 1.216
when taking Equation 1.215 into account.
r0 = p0e( − ξ)

1/( ρ+1)
 ρ +1 
1 − ψ = ψ 2 /(ρ+1)   e( − ξ ) (1.216)
 2λρ 
λ being a constant term, it may be included in the exponential factor, which yields the final equation
of the steady-state voltammogram in Equation 1.217. From this equation, it is seen that the current
depends only on the apparent dimensionless potential ξ* given in Equation 1.218.
ψ + ψ 2 /(ρ +1)e( − ξ* ) = 1 (1.217)

1 2λρ nF 0 1 2λρ
ξ* = ξ + ln = (E − E ) + ln (1.218)
ρ + 1 ρ + 1 RT ρ +1 ρ +1
From the equation ψ = 1 − r 0, the limiting plateau current corresponds to ψ = 1. Thus, the half-wave
potential E1/2 is obtained by replacing ψ by 1/2 in Equation 1.217, which yields
RT 1 − ρ RT /nF 2ρ
E1/ 2 = E 0 + ln 2 + ln
nF 1 + ρ ρ +1 ρ +1

 RT 1   δ2 
+  ln k0 [ A]α [ B]β …(C 0 )(ρ −1)  (1.219)
 nF (ρ + 1)   D
Because of the expression of the last term, it is seen that at room temperature, for example, where
RT/F ln10 ≈ 60 mV, E1/2 varies by [60α(ρ + 1)/n], [60β(ρ + 1)/n], and [60(ρ−1)(ρ + 1)/n] mV per unit
of log[A], log[B], and logC0, respectively. These variations then allow an easy determination of the
various reaction orders of any follow-up chemical reactions, provided the initial electron transfer is
fast enough and the number n of electrons exchanged is known.
Another approach consists of varying a reactant concentration and modifying the mass transfer
rate δ in order that E1/2 remains constant. The term in braces in Equation 1.219 must then be kept
constant; this is achieved when δ is equal to δ1/2, as follows:
1/ 2
k 
δ1/ 2 = constant [ A]α / 2 [ B]β / 2 (C 0 )(ρ−1)/ 2  0  (1.220)
D
Expression (1.220) shows that the slope of logδ1/2 versus log[A] is α/2. Similarly, β/2 and (ρ − 1)/2
are the slopes observed for the variations with log[B] or logC0, which is a convenient way to deter-
mine the reaction orders. Note that although developed here for E1/2, this procedure may be used
with any chosen potential E ε such that i/ilim has a fixed value ε. Similarly, variations in k0/D with
the temperature (i.e., activation energy determinations) can be obtained through this procedure,
provided care is taken of the RT/F factors, which need to be corrected (compare Equation 1.219)
(see, e.g., Chapter 2 for extensions of this method).
All these methods stem from the fact that for a given reaction sequence, such as that in Equations
1.209 and 1.210, which involve a single RDS, all the kinetics and thus the shape and location of
the voltammogram depend only on the dimensionless rate constant parameter λ in Equation 1.212.
As a result, any modification of the experimental conditions that keep λ constant does not modify
the dimensionless voltammogram.* Thus, quantitative information on the chemical mechanism
* Yet any variation(s) associated with the temperature may result in additional effects because of the temperature involve-
ment in Equation 1.219.
Basic Concepts 87
(Equation 1.210 may be a succession of chemical steps) is obtained without mathematical deriva-
tion, but only from dimensionless analysis (compare Chapter 2).
However, determination of the intrinsic rate constant k0 or of the apparent ρth order rate constant
k requires that the precise mathematical dependence of E1/2, for example, on the dimensionless rate
constant be determined as in Equation 1.219. Indeed, the principle of all methods for determining
k0 or k consists of increasing the mass transfer rate (i.e., here upon decreasing δ) up to a range such
that kδ2/D ≈ 0, that is, E1/2 ≈ E 0.
These methods constitute the frame on which any particular method can be elaborated. Yet in
practice, the experimental difficulty is that with standard apparatus, δ2/D cannot be varied over an
extremely wide range. For example, with the rotating disk electrode, which is the most convenient
steady-state method (with the exception of ultramicroelectrodes [110]), δ depends on the rotation fre-
quency ω of the electrode (see Chapter 2). Yet to maintain correct hydrodynamic conditions, ω cannot
be varied, with standard apparatus, outside the range of 10 rotations per second (rps) to 1000 rps,
which limits access to fast kinetics.
Transient electrochemical techniques [102,111] allow this range of investigation to be widely
extended (from 1 s to approximately 10 ns). Indeed, the same method may be used in a time domain
extending over approximately eight orders of magnitude. Besides this very important point, tran-
sient electrochemical techniques provide current–time and current–potential patterns that are easily
recognizable, for example, in cyclic voltammetry. Thus, with minimal eye training, a large amount
of qualitative or nearly quantitative data may be obtained just by inspection of a transient voltam-
mogram. This is in many respects an important advantage for diagnosis of kinetics, analogous with
that of IR, ultraviolet, or nuclear magnetic resonance spectroscopies for structural information. In
our opinion, this is one of the main reasons why transient electrochemical methods have progres-
sively supplanted steady-state methods. Indeed, as illustrated by the preceding examples, steady-
state voltammograms have generally sigmoidal shapes that are difficult to relate to a particular
mechanism without quantitative analysis.
C. TraNSIENT ELECTroCHEMICaL METHoDS

1. Introduction: Time Hysteresis in Current Reversal Techniques
As explained earlier, in transient electrochemical methods, an electrical perturbation (potential,
current, charge, and so on) is imposed at the working electrode during a time period θ (usually less
than 10 s) short enough for the diffusion layer δ ≈ (2Dθ)1/2 to be smaller than the convection layer
δconv imposed by natural convection. Thus, the electrochemical response of the system investigated
depends on the exact perturbation as well as on the elapsed time. This duality is apparent when one
considers a double-pulse potentiostatic perturbation applied to the electrode as in the double-step
chronoamperometric method.
R + ne P ( E 0 ) (n > 0) (1.221)

Let us consider, for example, the simple nernstian reduction (n > 0) reaction in Equation 1.221 and
a solution containing initially only the reactant R. Before any electrochemical perturbation, the
electrode rest potential E1 is made largely positive to E 0. At time zero, the potential is stepped to a
value E2, sufficiently negative to E 0, so that the concentration of R is close to zero at the electrode
surface. After a time θ, the electrode potential is stepped back to E1, so that the concentration of
P at the electrode surface becomes zero. When this potentiostatic perturbation, represented in
Figure 1.21a, is applied in a steady-state method, the R and P concentration profiles are linear and
depend only on the electrode potential but not on time, as shown in Figure 1.20a (for k ≈ 0). Yet
when the same perturbation is applied in transient methods, the concentration profiles are curved
and time dependent, as evidenced in Figure 1.21b. Thus, it is seen from this figure that a return
1
0
1 5 10 ms
Current
E2
C/C0
E2
E0 0
∞ 1
20 0
15
C/C0
E1 11
E1 E1
0
Time 0 20 Time
0 θ x, μm 0 θ
(a) (b) (c)
FiGURE 1.21 Transient potentiostatic electrochemical perturbation of a simple electron transfer reaction:
(a) imposed potential; (b) resulting concentration profiles for the reactant (solid curves) or the product (dashed
curves) for a step duration θ = 10 ms at various times from the beginning of the pulse; (c) resulting variations
in the current.
step duration at E1 much longer than the step duration θ at E2 is needed for the initial concentra-
tion profiles to be restored. This hysteresis corresponds to the propagation of the diffusion per-
turbation within the solution, which then keeps a “memory” of the past perturbation [108b]. This
information is stored via the structuring of the concentrations in the space near the electrode as a
function of the elapsed time.
The current flowing through the electrode is proportional to the gradient of the R (or the P)
concentration profile at the electrode surface. Thus, the progressive smoothing of the concentra-
tion profiles with the time elapsed after each discontinuity of the perturbation results in a constant
decrease in the current with time, as represented in Figure 1.21c.
Let us now assume that the product P formed upon the electron transfer in Equation 1.221 may
react chemically with a half-life t1/2. When θ ≪ t1/2, almost no P has time to disappear during the
time duration of the experiment. The P concentration profile then remains identical to that shown in
Figure 1.21b, and the current observed for t > θ, which corresponds to P reoxidation, is identical to
that in Figure 1.21c. Conversely, when θ ≫ t1/2, nearly all P molecules produced at the electrode are
consumed, and the P concentration profile is flat and close to zero, except in the close vicinity of the
electrode. As a result, almost no oxidation current is observed for t > θ, that is, during the period in
which the electrode potential is stepped back to E1 (see Figure 1.21a). In the intermediate range, that
is, when θ and t1/2 are of similar orders of magnitude (generally 0.1 t1/2 < θ < 10 t1/2), intermediate
values of the oxidation current are observed as shown in Figure 1.22. Determination of these varia-
tions allows the precise identification of the chemical follow-up sequence in which P is involved, as
well as of the pertinent rate constants (see Chapter 2).
However, this large sensitivity for mechanistic analysis is earned at the expense of two important
factors. First, owing to the large potential variations, the fine dependence of the system on the elec-
trode potential around E 0 is not seen. Second, and maybe more important, the current versus time
variations have no important visual characteristics. Indeed, as seen from Figure 1.22, for example,
all the curves are very similar, and only their juxtaposition on the same figure allows their shapes
to be compared.
For these two reasons, cyclic voltammetry has progressively supplanted potentiostatic or gal-
vanostatic methods in electrochemical kinetic investigations. A more complete description of this
method is given in Chapter 2, yet for our purposes, here we present the method briefly. It basically
consists of applying a linear variation of the electrode potential E with time from a potential E i,
where the reactant R is not electroactive, to a potential Ef sufficient for the reactant concentra-
tion to be zero at the electrode surface. At Ef, the potential is linearly scanned back to Ei, usually
Basic Concepts 89
iθ1/2/(FSC 0D1/2)
2
∞
10 0
1
0
–1
0 .5 1 1.5 2
Time, t/θ
FiGURE 1.22 Variations in the current trace in a potentiostatic experiment for an EC sequence for different
values of the dimensionless chemical rate constant kθ (numbers on the curves).
with an identical slope with respect to the time. The latter, v, is designated as the scan rate (in
volts per second). Figure 1.23a presents such a potential–time dependence, together with the cor-
responding i−E curve* (Figure 1.23b) obtained for the reduction process in Equation 1.221. Eye
inspection of the cyclic voltammogram in Figure 1.23b shows the presence of two current peaks,
in contrast to the monotonous variations of the current in Figure 1.21c. These peaks result from
the existence of two opposite effects that successively control the magnitude of the current. For
example, for the cathodic scan in Figure 1.23, the gradual decrease in R concentration at the elec-
trode surface, when the potential is made more and more cathodic, tends to increase the current
Ef
Epc
E0 E0
v
Ei
i
Ef
R
0 Time P
(a) Ei
Ei
i
Epa
Ei E0 Ef
Ei Ef
(c) (b)
FiGURE 1.23 Cyclic voltammetry. (a) Imposed potential versus time variations. (b) Resulting transient cur-
rent–potential curve for a simple electron transfer. The concentration profiles of the reactant R and product
P are indicated at various characteristic potentials of the voltammogram. Epc and Epa, cathodic and anodic
peak potentials. (c) Schematic change of the cyclic voltammogram as a function of the chemical stability of
the product.
* Note that in voltammetry (Figure 1.23), one presents usually the current as a function of the electrode potential rather
than displaying it as a function of time as one does in chronoamperometry (Figure 1.22). Thus, in Figure 1.23b, the upper
trace corresponds to the forward cathodic scan, whereas the lower trace corresponds to the backward anodic scan.
by making the R concentration profile steeper. Yet the propagation of the perturbation into the
solution, as shown in Figure 1.21b, tends to flatten the concentration profile, which results in a
progressive decay of the current. In practice, it is easily understood that the large variations in
the surface concentrations for potentials in the vicinity of E 0 overwhelm the diffusion effect, the
current then tending to rise. Yet when [R]x = 0 is close to zero, the potential variations affect the
current magnitude less than the diffusion propagation in the solution, which explains why the cur-
rent progressively decays. For the backward scan, the same phenomenology applies to the prod-
uct concentration [P]x = 0, which then results in the appearance of an inverted peak on the lower
trace in Figure 1.23b. When P reacts chemically, the magnitude of the reverse peak gradually
decreases (Figure 1.23c) because there is less and less P present in the solution. Again, this allows
determination of mechanisms and their pertinent rate constants, as explained for the double-step
chronoamperometric method.
From this brief presentation, it is seen that an important aspect of cyclic voltammetry is that
the shapes of cyclic voltammograms are extremely indicative of the chemical processes occurring
at the electrode or in the solution. As such, it is an extremely useful tool for kinetic diagnosis. Yet
the much more complicated shapes, when compared with those in Figure 1.22, for example, makes
quantitative information on the current difficult to obtain.
2. Transient Electrochemical Methods and Chemical Kinetics

From the preceding presentation, it is seen that the current variations with time or potential–time
are intimately related to the concentration profiles of the species engaged in heterogeneous electron
transfers at the electrode surface [110]. Thus, any kinetic or thermodynamic perturbation of these
concentration profiles results in a variation of the current/time or current/potential–time transient
characteristics as outlined in Figures 1.22 or 1.23c. As was also apparent in the preceding discus-
sion, as well as in several other places in this chapter, the degree to which these perturbations
affect the concentration profiles is a function of their relative effect vis-à-vis the mass transfer
rate. Dimensionless analysis again proves to be a very convenient way to appreciate this degree of
interference through the dimensionless rate constants λ, equilibrium constants κ, or heterogeneous
rate constants Λ in Table 1.5. Thus, any experimental variation resulting in an overall constancy of
these dimensionless parameters does not change the dimensionless current ψ versus τ or ψ versus ξ
curve, that is, the dimensionless voltammogram. This is a situation identical to that developed more
extensively for the steady-state methods and is the basis of most electrochemical methods for the
determination of reaction orders and rate constants.
Yet when applied to current reversal techniques, such as double-step chronoamperometry or
cyclic voltammetry, these methods require that an appreciable current be observed during the back-
ward perturbation, that is, for t > θ, in potentiostatic methods or after the potential scan inversion in
cyclic voltammetry. This requires that the characteristic time θ of the method is adjusted to match
the half-life t1/2 of the electrogenerated intermediate. Today, owing to the recent development of
ultramicroelectrodes, θ can be routinely varied from a few seconds to a few nanoseconds [102]. Yet
with basic standard electrochemical equipment, θ is usually restricted from the second to the low
millisecond range. Thus, for experimental situations involving faster chemical reactions, current
reversal techniques are of little use. Yet, as is the case for steady-state methods, much kinetic infor-
mation allowing mechanistic discriminations and reaction order determinations may be gathered
from characteristic potential changes. Obviously, staircase methods, such as chronoamperometries,
which are blind to these variations, are not convenient, but such methods as cyclic voltammetry or
its descendants (Chapter 2) are extremely precise and adequate through peak potential or half-peak
potential analysis.
Indeed, in cyclic voltammetry, peak potentials Ep play a role identical to that of half-wave poten-
tials E1/2 in steady-state methods. As for the latter methods, peak potentials vary linearly with the
logarithm of dimensionless kinetic parameters λ or Λ in Table 1.5, provided these latter have values
Basic Concepts 91
sufficiently large when compared to unity [94]. These linear variations, which may be used for the
determination of reaction orders, stem from the same mathematical reasons as explained in the case
of E1/2. Yet, the physical reason is quite different as evidenced by the case of the simple EC sequence
in the following:
R + ne P (E 0 ) (1.222)

P → (k ) (1.223)

From Equation 1.174, the partial derivative equation describing the concentration profile of P is
written in dimensionless terms (compare Table 1.5):
∂p ∂ 2 p
0< y: = − λp (1.224)
∂τ ∂y 2
When λ = kθ ≫ 1, the kinetic term in Equation 1.224 tends to be extremely large. On the other
hand, ∂p/∂τ cannot be infinite, for obvious physical reasons (except at possible discontinuities in the
potential variations). Thus, the diffusion term ∂2p/∂τ2 must compensate for the kinetic term in order
that ∂p/∂τ remain finite.* In other words, a quasi-steady state is reached by mutual compensation of
kinetics and diffusion. As a result, ∂p/∂τ ≪ ∂2p/∂y2 and λp. Equation 1.224 thus becomes equivalent
to Equation 1.225, at least as concerns the derivation of the concentration profile of P.
∂2 p
0< y: 0≈ − λp (1.225)
∂y 2
Comparison of Equation 1.225 and Equation 1.193 or 1.211 shows that the problem is identical to
that presented for steady-state methods. Thus, the same mathematical derivations show that any
characteristic potential figure (Ep or half-peak potential Ep/2, and so on) varies linearly with the
logarithm of λ = kθ. Indeed, one obtains by simple transposition in Equation 1.219
 RT 
Ep = E 0 +  { α β 0 ( ρ−1)
 ln k0 [ A] [ B] (C ) θ + cst
 nF (ρ + 1) 
} (1.226)

for the peak potential variations relative to the EC sequence in the following:
R + ne P ( E 0 ) (1.227)

ρP + αA + βB + → … (k0 ; k = k0 [ A]α [ B]β …) (1.228)

In Equation 1.226, θ is usually defined as θ = RT/Fvn, v being the scan rate, yet any dimensionless
parameter, such as θ = ΔE/v, where ΔE is an adequate difference of potential, is equally convenient.
Then, even when k0 cannot be determined, its temperature variations, that is, ΔH#, as well as the
different reaction orders ρ, α, β,…, may be determined through the same experimental procedures
already discussed for the analogous case of E1/2 in steady-state methods.
* Note that this may be established on firm mathematical grounds, but it is beyond the scope of this presentation [94].
Extension of these approaches to much more sophisticated kinetic situations, which involve, for
example, two or three routes for a key intermediate, has been developed (Reference 94 and refer-
ences therein). Relative rate constants (or relations between rate constants) may then be obtained
that allow, by reference to a known value, the absolute determination of all the series. For example,
rate constants for the cleavage of aromatic halide anion radicals, corresponding to a half-life from
about a second to a few picoseconds, have been determined using these procedures [103].
AckNOwLEDGMENTS
This work was supported by ENS, CNRS, and UPMC (UMR 8640 PASTEUR). The author wishes
to acknowledge several discussions with Prof. Irina Svir and Dr. Alexander Oleinick and their
useful comments and suggestions.
REfERENcES
1. Most of the concepts developed in this chapter are presented in detailed analytical form in: (a) Bard,
A. J.; Faulkner, L. R. Electrochemical Methods: Fundamentals & Applications, 2nd edn.; John
Wiley & Sons: New York, 2001. (b) Kissinger, P. T.; Heineman, W. R., eds. Laboratory Techniques in
Electroanalytical Chemistry; Marcel Dekker: New York, 1984. (c) Bockris, J. O’M.; Reddy, A. K. N.
Modern Electrochemistry; Plenum: New York, 1977, Vols. 1, 2.
2. (a) Huffman, J. W. Acc. Chem. Res. 1983, 16, 399–405. (b) Rautenstrauch, V.; Geoffroy, M. J. Am.
Chem. Soc. 1976, 98, 5035–5037. (c) Rautenstrauch, V.; Geoffroy, M. J. Am. Chem. Soc. 1977, 99,
6280–6286. (d) for a recent analogy in electrochemistry (termed “concerted electron transfer”) see,
e.g.: Costentin, C.; Hajj, V.; Louault, C.; Robert, M.; Savéant, J.-M. J. Am. Chem. Soc. 2011, 133,
19160–19167.
3. See, e.g., (a) Shiner, V. J., Jr.; Whittaker, D. J. Am. Chem. Soc. 1963, 85, 2337–2338. (b) Warnhoff, E. W.;
Reynolds-Warnhoff, P.; Wong, M. Y. H. J. Am. Chem. Soc. 1980, 102, 5956–5957.
4. See however, Ashby, E. C.; Goel, A. B.; Argyropoulos, J. N. Tetrahedron Lett. 1982, 23, 2273–2276 for
the possible occurrence of paramagnetic intermediates (SET mechanisms [5]) in the reduction with metal
alkoxides.
5. Ashby, E. C.; Boone, J. R. J. Am. Chem. Soc. 1976, 98, 5524–5531.
6. Wigfield, D. C.; Gowland, F. W. J. Org. Chem. 1977, 42, 1108–1109.
7. March, J. Advanced Organic Chemistry, 3rd edn.; John Wiley & Sons: New York, 1985, pp. 811–814.
8. For an extensive review on single electron transfer (SET) mechanisms, see Chanon, M; Tobe, M. L.
Angew. Chem. 1982, 21, 1–23.
9. See Freeman, F.; Lin, D. K.; Moore, G. R. J. Org. Chem. 1982, 47, 56–59.
10. (a) Criegee, R.; Kraft, L.; Rank, B. Liebigs Ann. Chem. 1933, 507, 159–197. (b) Waters, W. A. Mechanisms
of Oxidation of Organic Compounds; Wiley: New York, 1964, pp. 97–106. (c) See, however, Kochi, J. K.
Organometallic Mechanisms and Catalysis; Academic Press: New York, 1978, p. 108, for the possible
involvement of one-electron transfer steps, with, e.g., Vv/Viv.
11. Reference 10c, pp. 11–13.
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this book.
2 Techniques for Studies
of Electrochemical
Reactions in Solution
Ole Hammerich and Bernd Speiser
CONTENTS
I. Introduction ............................................................................................................................ 98
II. Linear Sweep Voltammetry and Cyclic Voltammetry ........................................................... 98
A. Introduction ..................................................................................................................... 98
B. Experimental Setup....................................................................................................... 100
1. The Electrochemical Cell ...................................................................................... 100
2. The Solvent-Supporting Electrolyte System .......................................................... 101
3. The Electronic Equipment ..................................................................................... 102
C. Simple Electron Transfer Reactions.............................................................................. 102
1. Reversible Electron Transfer .................................................................................. 103
2. Quasireversible Electron Transfer.......................................................................... 106
3. Irreversible Electron Transfer ................................................................................ 107
4. Concluding Remarks and Examples ...................................................................... 108
D. Electron Transfer Reactions Followed by Chemical Reactions in Solution ................. 110
1. Typical Irreversible Follow-Up Reactions ............................................................. 110
2. Kinetic Classification of Simple Irreversible Follow-Up Reactions ...................... 111
3. Irreversible Follow-Up Reactions, Mixed Diffusion, and Kinetic Control
(CV and DCV)�� 113
4. Irreversible Follow-Up Reactions, Purely Kinetic Control (LSV) ........................ 117
5. Reversible Follow-Up Reactions ............................................................................ 119
6. Irreversible Follow-Up Reactions, the Prepeak Method ........................................ 124
7. Irreversible Follow-Up Reactions, Redox Catalysis .............................................. 125
8. Chemical Reactions Following Quasireversible or Irreversible
Electron Transfer Reactions�� 128
9. General Remarks and Conclusions ........................................................................ 128
E. Limiting Experimental Factors ..................................................................................... 128
1. The Cell and the Working Electrode ..................................................................... 129
2. Uncompensated Solution Resistance, Ru................................................................ 130
3. Importance of Precision in Potential Measurements ............................................. 132
4. Background Currents ............................................................................................. 132
F. Computer-Based Methods for Analysis of Voltammetric Data .................................... 132
1. Semi-Integration and Convolution Techniques ...................................................... 133
2. Fitting Simulated to Experimental Voltammograms ............................................. 133
97
III. Ultramicroelectrodes and Scanning Electrochemical Microscopy ...................................... 134

A. Ultramicroelectrodes .................................................................................................... 134
1. Determination of Eo′ for the A/B Redox Couple When B Is Highly Reactive...... 136
2. Determination of Heterogeneous Electron Transfer Rate Constant ...................... 138
3. Kinetics of Rapid Follow-Up Reactions ................................................................ 138
4. Voltammetry in Electrolytes with Low Conductivity............................................ 139
B. Application of Scanning Electrochemical Microscopy for Studies
of Reaction Kinetics�� 139
IV. Potential-Step and Current-Step Methods ............................................................................ 141
A. Chronoamperometry and Double Potential-Step Chronoamperometry ....................... 141
B. Chronocoulometry and Double Potential-Step Chronocoulometry ............................. 144
C. Chronopotentiometry and Current-Reversal Chronopotentiometry ............................. 144
V. Polarography ......................................................................................................................... 146
VI. Methods Based on Forced Convection ................................................................................. 150
A. General Considerations .................................................................................................150
B. The Rotating Disk Electrode.........................................................................................150
C. The Rotating Ring-Disk Electrode ............................................................................... 154
VII. Methods for Determination of the Number of Electrons Transferred per
Molecule of Substrate ........................................................................................................... 157
VIII. Methods for Determining the Diffusion Coefficient of Electroactive Molecules ................ 159
References ...................................................................................................................................... 160
I. INTRODUcTiON
Electrochemical methods are widely used to gain information about the kinetics and mechanisms
of chemical reactions associated with the electron transfer at an electrode. A unique feature of these
methods is that the electrode serves both as the means of generating a reactive intermediate, for
instance, a radical ion, and as the means to monitor its reactions to products.
This chapter is meant to serve both as a guide for the beginner and as an overview for the non-
electrochemist with a need to know some of the methods available. Approximately half of the
chapter is concerned with various aspects of linear sweep and cyclic voltammetry in view of the
importance and widespread use of these techniques. Some general aspects of the heterogeneous
electron transfer process, and the chemical reactions associated with it, are introduced in this part.
The reader is strongly encouraged to consult Chapter 1 in which basic electrochemical concepts are
discussed in detail and monographs on the topic [1,2].
In most cases, electrons are transferred one by one [3]. Depending on the ordering of potentials
of individual steps in multi-electron reactions, more complicated behavior may be observed (see,
e.g., Reference 4, and the discussion in Section II.C in Chapter 11). In order to preserve the formal-
ism used in electrochemistry, the number of electrons n, that is, transferred is maintained in most
formulas although its value equals one in practically all cases.
The general discussion of electrochemical reactions is, for the sake of consistency, restricted
to cover reductions only. The transposition to oxidations should not present any problem, but the
reader should be aware that the plus or minus sign in some equations has to be changed.
II. LiNEAR SwEEP VOLTAMMETRY AND CYcLic VOLTAMMETRY

A. INTroDUCTIoN
Voltammetry in an unstirred solution where the predominant mode of mass transport is limited to
diffusion is one of the most useful techniques for the study of electrochemical reactions [1,2,5,6]
(however, see the critical remarks in Reference 7). Most often, a triangular potential–time waveform
Techniques for Studies of Electrochemical Reactions in Solution 99
–1.0
–1.2
Potential, E (V)
–1.4
–1.6
–1.8
–2.0
0 5 10 15 20
(a) Time, t (s)
1.2 Ep = –1.57 V
1.0
Ep/2
0.8
0.6
ip
i (mA)
0.4
0.2 Ep = –1.22 V ip/2
0.0
–0.2
–0.4
–1.0 –1.2 –1.4 –1.6 –1.8 –2.0
(b) E (V)
FiGURE 2.1 (a) Potential–time waveform for a triangular voltage sweep between −1 and −2 V at a sweep
rate (ν) of 0.1 V s−1 and (b) a simulated (DigiSim®) voltammogram for a substrate that is reduced at Ep = −1.57 V
to a product or intermediate, the oxidation of which is observed at Ep = −1.22 V.
with equal positive and negative slopes is used with v = dE/dt being the sweep or scan rate. Usually,
the initial potential (Einitial) and final potential (Efinal) are the same as illustrated in Figure 2.1a. This
has given rise to the term cyclic voltammetry (CV). However, sometimes the voltage sweep is con-
tinued to include one or more additional E–t half-cycles or includes more complicated sawtooth-like
waveforms to meet special needs.
An example of a current–potential curve, a so-called voltammogram, resulting from a simple
triangular sweep is shown in Figure 2.1b. There are two conventions to draw cyclic voltammograms:
according to the American or polarographic convention, more negative potentials are plotted to
the right (Figure 2.1b), while according to IUPAC (European Convention), positive potentials are
shown in that direction [8]. The experiment should preferably start from an equilibrium situation,
that is, close to the rest potential of the working electrode in the electrolyte, with a current i = 0.
The graphical display of the currents is adjusted so that the voltammogram evolves in a clock-
wise direction. Thus, the two conventions are also different in the sign of the current (reductive/
cathodic or oxidative/anodic currents denoted by positive values, respectively; the former is used
in Figure 2.1b).
A characteristic feature is the presence of peaks, in this case two, identified by the peak potential Ep.
The particular voltammogram shown in Figure 2.1b results from a process in which a substrate during
the forward, negatively going voltage sweep is reduced at Ep = −1.57 V to a product or intermediate,
the oxidation of which is observed at a peak potential Ep = −1.22 V during the backward (or reverse),
positively going sweep. In addition to Ep, a voltammogram is usually characterized by the peak
current ip and often also by the half-peak width Ep − Ep/2, where Ep/2 is the half-peak potential, that
is, the value of E at which i = ip/2 (see Figure 2.1b). Analysis of how Ep, Ep − Ep/2, and ip vary with, for
instance, changes in the voltage sweep rate, ν, and the bulk concentrations of the substrate, CA* ,
and a reagent, CX* , may provide information about the thermodynamics and kinetics of the follow-
up reaction. This type of analysis is discussed in some detail in Sections II.C and II.D. If only the
voltammogram corresponding to the first half-cycle is used for data analysis, the technique is usu-
ally referred to as linear sweep voltammetry (LSV). Multicycle experiments finally lead to what
has been termed ultimate cyclic voltammograms [9] that represent a steady-state-like behavior with
curves of subsequent cycles being superimposed.
The method dates back to experiments by Randles [10a,b] and Ševčík [10c]. Significant theoreti-
cal contributions to this type of voltammetry were published in 1955 by Matsuda and Ayabe [11]
and in 1964 by Nicholson and Shain [12]. The years to follow were a period of intense activity in
the calculation of the electrode response for many different mechanisms. Most notable of the large
volume of papers published are those of Nicholson and coworkers [13–16] and of the Savéant group
[2,17–25]. Efforts initiated by Parker and coworkers [26–37] have been directed toward the devel-
opment of LSV and CV as practical tools for quantitative studies of electrode processes. Nowadays,
CV is probably the most popular electrochemical technique in organic electrochemistry [4–6,38–41].
One key element for this success may be the strong interaction between experimental and theoreti-
cal development, leading to user-friendly commercial simulation software (DigiSim from BAS),
which is now available and has been used in this chapter for illustration purposes. The reader
interested in simulation may obtain additional information about the simulation of cyclic voltam-
mograms from Chapter 5.
B. EXpErIMENTaL SETUp
1. The Electrochemical Cell
An example of the instrumentation for LSV and CV is shown in Figure 2.2.
The cell is a simple and convenient design consisting of a 30 mL tube fitted with a B19/26
ground-glass joint. The electrode holder is made of Teflon and has holes for the three electrodes [1].
In addition, there is an inlet for an inert gas, usually nitrogen or argon, by which the voltammetry
solution is purged before the measurements are made. This serves to remove dissolved oxygen,
which, during the study of reduction processes, may itself be reduced or may react with intermedi-
ates such as radical anions produced at the cathode. Oxygen may react also with radical cations
generated at the anode. Therefore, even for oxidations, it is recommended that measurements are
carried out in the absence of oxygen. The fixed arrangement of the electrodes is desirable to avoid
changes in the geometry when an electrode is taken out of the electrolyte and then replaced.
The working electrode usually is a circular disk made of platinum, gold, or glassy carbon,
which together with the electrical connection is fitted into a nonconducting material and polished
to mirror quality. For reductions, mercury (film) electrodes are frequently used also owing to
their microscopic smoothness and because of the large overpotential for hydrogen evolution char-
acteristic for this electrode material. The latter makes possible the study of difficultly reduced
substrates in water and other hydroxylic solvents. The oxidation of mercury at a low potential
(0.3–0.4 V vs. SCE) to mercury salts or organomercurials prevents the use of these electrodes for
oxidations.
Reference electrodes are frequently commercial aqueous calomel electrodes or similar.
However, the use of these types of electrodes may cause unnecessary complications, such as the
need to separate the reference and working compartments of the cell in order to avoid exchange
of dissolved species or solvents if the electrochemical process is studied under nonaqueous con-
ditions (see, e.g., Chapter 7). In the latter case, it is often more convenient to use nonaqueous
Computer
i
E
Function
generator Potentiostat Current–voltage converter
E
W R C
t
N2
Teflon stopper
Test tube
FiGURE 2.2 Experimental setup for linear sweep and cyclic voltammetry. W, working electrode; R, reference
electrode; C, counter electrode.
reference electrodes most simply consisting of a silver wire immersed in the same solvent-
supporting electrolyte solution as that in the working compartment [42]. A disadvantage of the
latter type of reference electrode is that the potential usually cannot be accurately predicted.
Thus, it is necessary to calibrate the electrode, for instance, by recording the voltammogram
of a standard redox couple, if the measured potentials are to be used in comparison with pub-
lished values. A commonly used standard is the ferrocene/ferrocenium (Fc/Fc+) redox couple [43]
(see also Chapter 7).
The counter electrode usually consists of a platinum wire or a small platinum foil.
Without any further refinement, the cell shown in Figure 2.2 is suitable for measurements at
voltage sweep rates from about 0.1 to 500 V s−1 using working electrodes with surface diameters
ranging from about 2 to 0.1 mm. Higher sweep rates will need more sophisticated instrumentation
(see Section II.B.3).
2. The Solvent-Supporting Electrolyte System

For routine work, solvents and supporting electrolytes of the highest commercial quality may
usually be used without further purification. It is, however, often necessary to have solvent-
supporting electrolyte solutions that are essentially free of reactive impurities in order to study
the voltammetric behavior of highly reactive intermediates. Elaborate vacuum line apparatus has
been described for this purpose [5,44–47]. Sometimes, it is more convenient instead to conduct
the voltammetric experiments over neutral alumina [48]. The method is simply to add active
neutral alumina directly to the voltammetric cell, for example, of the type shown in Figure 2.2,
and to mix vigorously for a few minutes before the measurements are made. The method is
very effective in removing the electrophilic and nucleophilic impurities normally present in trace
amounts even in the most carefully purified solvent-supporting electrolyte solutions. However,
one should be aware that also the substrate may be adsorbed at the alumina, and therefore this
approach should in general be used only in qualitative work where the main goal is to suppress
unwanted follow-up reactions.
3. The Electronic Equipment

A discussion of the instrumental aspects of voltammetry and leading references to the original liter-
ature can be found in some of the monographs already cited in Section I [1,2,5,6]. The essential units
are the potentiostat, a triangular waveform generator, and a recording device, nowadays most often
a digital computer. Commercial equipment with the units combined into one instrument controlled
by a PC is available from a number of manufactures. Also home-built instrumentation has found
use in many cases, for instance, in studies in which so-called ultramicroelectrodes (see Section III)
have been used for CV at sweep rates exceeding 10,000 V s−1.
Sweep rates up to 10 MV s−1 have been achieved with improved electronic circuitry aimed at
minimizing artifacts in the nanosecond time scale [49]. Thus, extremely fast processes can be
observed with a simultaneous extremely high spatial resolution and with diffusion layer thicknesses
approaching those of the electric double layer.
C. SIMpLE ELECTroN TraNSFEr REaCTIoNS

In this section, we examine the relationship between current and potential in the case where the
primary product of the electrode reaction is nonreactive, that is, there are no chemical reactions
coupled to the electron transfer reaction at the time scale of the experiment.
An electron transfer reaction, Equation 2.1, is characterized thermodynamically by the standard
potential Eo, that is, the value of E at which the activities of the oxidized form A and the reduced
form B of the redox couple are the same. Thus, the second term in the Nernst equation, Equation 2.2,
cancels. Here, R is the molar gas constant (8.314 J K−1 mol−1), T is the temperature (K), n is the number
of electrons, and F is Faraday’s constant (96,485 C). Parentheses are used for activities, brackets for
concentrations, and fA and f B are the activity coefficients. However, what may be measured directly
is the formal potential Eo′ defined in Equation 2.3. It follows that the relation between Eo and Eo′
is given by Equation 2.4. In this chapter, we shall assume that activity coefficients are unity and
therefore that Eo′ = Eo:
k
A + ne −

k
s,f
o
B (E ) (2.1)
s,b
RT ( A) RT f [ A]
E = Eo + ln = Eo + ln A (2.2)
nF (B) nF fB [ B]
RT [ A]
E = E o′ + ln (2.3)
nF [ B]
RT f
E o′ = E o + ln A (2.4)
nF fB
The kinetics of the electron transfer reaction, Equation 2.1, are described by the heterogeneous elec-
tron transfer rate constants ks,f and ks,b (in units of cm s−1), where the subscript s indicates a surface
process. The values of ks,f and ks,b depend exponentially on the potential E as seen in Equations
2.5 and 2.6, in which ko is the standard heterogeneous electron transfer rate constant and α is the
electrochemical transfer coefficient [50] (see Chapter 1). It is seen from Equations 2.5 and 2.6 that
ks,f = ks,b = ko at E = Eo. The relation between ks,f and ks,b, and the current, i, is given by the Butler–
Volmer equation, Equation 2.7, where A is the electrode area (cm2) and [A]s and [B]s are the surface
concentrations of A and B:
 −αnF ( E − E o ) 
ks,f = k oexp   (2.5)
 RT 

 (1 − α)nF ( E − E o ) 
ks,b = k oexp   (2.6)
 RT 

i = nFA ( ks,f [ A]s − ks,b [ B]s )

  −αnF ( E − E o )   (1− α)nF ( E − E o )  
= nFAk o [ A]s exp   − [ B ]s exp   (2.7)
  RT   RT  

In electrochemistry, electron transfer reactions are classified as reversible, quasireversible, or
irreversible depending on the ability of the reaction to respond to changes in E. In voltammetry,
the relevant kinetic parameters are ko, α, and ν. The mutual influence of ko and ν is conveniently
expressed through the magnitude of the dimensionless parameter, Λ, defined in Equation 2.8 [11],
where DA and D B are the diffusion coefficients for A and B, respectively. Usually, these are assumed
to be identical, DA = D B = D.
α /2
D 
k  A
o
 DB  ko
Λ= 1/ 2
= 1/ 2
for DA = DB = D (2.8)
 DAνnF   DνnF 
 RT   RT 
   
1. Reversible Electron Transfer

A reversible electron transfer is, strictly speaking, the limiting case where A and B are in ther-
modynamic equilibrium at the electrode surface, that is, the electron transfer reaction responds
instantaneously to a change in E. Thus, the ratio between [A]s and [B]s depends only on E − Eo, the
relationship being given by the rearranged Nernst equation:
[ A]s  nF ( E − E o ) 
= exp   (2.9)
[ B]s  RT 

The equilibrium condition implies an infinitely large value of Λ that may result from an infinitely
large value of ko and/or an infinitely small value of ν. Under these conditions, the overall process is
controlled by the diffusion of A and B to and from the electrode. In practical work, an electron trans-
fer process is called reversible if the deviations from this limiting case are too small to be detected
experimentally. This happens typically when Λ is larger than approximately 12 (see Section II.C.4). It
also follows from the earlier discussion that the shape and the position of the voltammogram, defined,
for instance, by the values of Ep, Ep − Ep/2, and ip, are independent of the parameters ko and α.
A cyclic voltammogram for a reversible one-electron reduction is shown in Figure 2.3.
1.0 red Epred

Ep/2
0.8
0.6
0.4 ipred
ipred/2
0.2
i (mA) 0.0
–0.2 ipox
–0.4
–0.6
–0.8 Epox
–1.0 –1.2 –1.4 –1.6 –1.8 –2.0
E (V)
FiGURE 2.3 Simulated (DigiSim®) cyclic voltammogram for a reversible one-electron reduction with
Eo = −1.5 V. The other simulation parameters are ko = 104 cm s−1, α = 0.5, T = 298.2 K, C A* = 1 mM, and
A = 1 cm2. These are the same for the other simulations included in this section unless otherwise stated.
The simulations do not include effects caused by uncompensated solution resistance (see Section II.E.2) and
double-layer charging (see Chapter 1) or other background contributions.
Ideally, the part of the voltammogram recorded during the forward scan satisfies the following
three criteria [11], where the values given in mV refer to T = 298 K:
1. The value of Ep − Eo is given by Equation 2.10 and is independent of ν. This is often

expressed as in Equation 2.11:
RT 28.5
Ep − E o = −1.11 V=− mV (2.10)
nF n
dEp
=0 (2.11)
d log ν
2. The value of Ep − Ep/2 is given as follows:
RT 56.5
Ep − Ep/2 = −2.20 V=− mV (2.12)
nF n
3. The value of ip is given by Equation 2.13, sometimes called the Randles–Ševčík equation.
It is seen that ip increases linearly with ν1/2:
1/ 2
 nF 
ip = 0.4463nFACA* DA1/ 2ν1/ 2   (2.13)
 RT 
If also the part of the voltammogram recorded during the backward sweep is included, we
have the following:
4. The peak current ratio −ipox /ipred is unity and independent of ν. For a simple electron transfer
process, measurements of the peak current ratio serve to control the assumption that B
does not react on the time scale of the experiment.
5. The peak separation, ∆Ep = Epox − Epred, is equal to approximately 57 mV, the exact value
being dependent on the potential, Eswitch, at which the voltage sweep is reversed. The fol-
lowing equation refers to the limiting case Eo − Eswitch = ∞, where ΔEp for obvious reasons
is twice the value of Ep − Eo:
RT 57.0
∆Ep = Epox − Epred = 2 ⋅ 1.11 V= mV (2.14)
nF n
6. The average of Epox and Epred is often referred to as the midpoint potential E, which is
approximately equal to Eo (Equation 2.15). Again, this equation is only strictly valid for
Eo − Eswitch = ∞, but the error at, for instance, Eo − Eswitch = 0.3 V is negligible in most
practical works:
Eo ≈ E =
(E ox
p +Epred ) (2.15)
2
A difficulty arises in determining −ipox /ipred in that it is not obvious how the baseline for ipox should be
determined. Indeed, experimental voltammograms are often less well-behaved than the simulated
one shown in Figure 2.3. The most reliable procedure appears to be a graphical method [51], which,
however, should be used with care [52].
It is often possible to observe a second electron transfer reaction, Equation 2.16, within the poten-
tial window defined by the discharge of the solvent-supporting electrolyte solution. An example of a
voltammogram for two consecutive one-electron reductions is shown in Figure 2.4.
B + ne − C (2.16)
When the two electron transfer reactions are as well separated as those shown in Figure 2.4,
the difference between the peak potentials for the first and second electron transfers is a good
approximation to the difference in the standard potentials, E2o − E1o. When the two electron transfer
reactions are closely spaced, this difference may be determined from the half-peak width of the
overlapping waves [53]. However, depending on the exact value of E2o − E1o , a variety of shapes of
1.5
1.0
0.5
i (mA)
0.0
–0.5
–1.0
–1.0 –1.2 –1.4 –1.6 –1.8 –2.0
E (V)
FiGURE 2.4 Simulated (DigiSim®) cyclic voltammogram for two consecutive reversible one-electron reduc-
tions with E1o = −1.3 V and E2o = −1.7 V. For other simulation parameters, see Figure 2.3.
the voltammograms is observed (see Chapter 11, and Reference 305.). When E2o − E1o is known, the
equilibrium constant for disproportionation, Kdispr, Equation 2.17, may be calculated from Equation
2.18. Introduction of the Eo values used in the simulation for Figure 2.4, that is, E1o = −1.3 V and
E2o = −1.7 V, together with n = 1 results in Kdispr = 1.7·10 –7. The value of Kdispr is dependent on solvent
and is, as a rule, found to decrease with decreasing polarity of the solvent [48]. The formation of
more highly charged species may be observed in special cases such as, for example, the reduction
of C60 and its derivatives (see Chapter 21):
2B A + C ( K dispr ) (2.17)

K dispr = exp 
( )
 E2o − E1o nF 
 (2.18)
 RT 
 
2. Quasireversible Electron Transfer

In the general case, named quasireversible, the electron transfer reaction, Equation 2.1, does not
respond instantaneously to changes in E. In other words, [A]s and [B]s are determined not only by
the value of E − Eo, but also, via Equations 2.5 and 2.6, by the magnitudes of ko and α. There is a
mixed control by diffusion and electron transfer kinetics.
Typical voltammograms for quasireversible electron transfers are shown in Figure 2.5.
In comparison with the voltammogram for the reversible case (Figure 2.3), it is seen that the
reduction peak has moved in the negative direction and the oxidation peak in the positive direction
resulting in a peak separation ΔEp larger than ~57 mV. It appears from Equations 2.5 and 2.6 that
decreasing values of α cause ks,f to decrease and ks,b to increase, and as a consequence, Epred and Epox
both move in the negative direction (Figure 2.5). Conversely, increasing values of α cause Epred and
Epox to move in the positive direction (Figure 2.5). The overall result is that the effect of the magni-
tude of α on ΔEp is small as long as α does not deviate too much from 0.5 [13,54]. In that case, ko
may conveniently be determined from values of ΔEp recorded at different values of ν. It is important
to notice, however, that the mere observation of ΔEp larger than ~57 mV (at T = 298 K) is not in itself
a sufficient criterion for the classification of an electron transfer reaction as quasireversible. Many
0.8
0.6
0.4
0.2
i (mA)
0.0
–0.2
–0.4
–0.6
–1.0 –1.2 –1.4 –1.6 –1.8 –2.0
E (V)
FiGURE 2.5 Simulated (DigiSim®) cyclic voltammograms at ν = 1 V s−1 for quasireversible one-electron
reductions with Eo = −1.5 V, ko = 3·10 −3 cm s−1, and α = 0.3 (dot), α = 0.5 (full), and α = 0.7 (dash). For other
simulation parameters, see Figure 2.3.
other factors, such as adsorption phenomena and insufficient electronic compensation of the voltage
drop caused by the solution resistance (see Section II.E), may cause voltammograms to have peak
separations larger than ~57 mV.
The expressions for Ep − Eo, Ep − Ep/2, and ip for the quasireversible case are given in Equations
2.19 through 2.21, where Ξ(Λ, α), Δ(Λ, α), and Κ(Λ, α) are nonlinear functions of Λ and α. These
are available as graphical representations in the paper by Matsuda and Ayabe [11]. Alternatively,
the reader may find expressions for Ep − Eo, Ep − Ep/2, and ip in dimensionless notation in a paper by
Nadjo and Savéant [19].
RT
Ep − E o = −Ξ(Λ, α) (2.19)
nF
RT
Ep − Ep/2 = −∆(Λ, α) (2.20)
nF
1/ 2
 nF 
ip = 0.4463Κ (Λ, α)nFACA* DA1/ 2ν1/ 2   (2.21)
 RT 
3. Irreversible Electron Transfer

When Λ becomes progressively smaller, the shape of the voltammogram continues to change.
Experimentally, a constant shape is reached when Λ is smaller than approximately 0.2 (see Section
II.C.4). The value of E required to obtain an appreciable rate of reduction of A is now so much on
the negative side of Eo that the second term in Equation 2.7 may be neglected. In other words, the
electron transfer has become irreversible. By the same type of argument, it is clear that the oxida-
tion of B back to A during the backward sweep proceeds irreversibly as well. Sometimes this is
called electrochemically irreversible to make a distinction to chemically irreversible (irreversible
follow-up reaction).
Typical voltammograms for irreversible electron transfers are shown in Figure 2.6.
In comparison with the voltammograms for the quasireversible case (Figure 2.5), it is seen that
the reduction peak has moved even more in the negative direction and the oxidation peak even more
in the positive direction, now to the point that there is a potential region between the two peaks in
0.8
0.6
0.4
i (mA)
0.2
0.0
–0.2
–0.4
–0.5 –1.0 –1.5 –2.0 –2.5
E (V)
FiGURE 2.6 Simulated (DigiSim®) cyclic voltammogram at ν = 1 V s−1 for irreversible one-electron reduc-
tions with Eo = −1.5 V, ko = 10 −5 cm s−1, and α = 0.3 (dot), α = 0.5 (full), and α = 0.7 (dash). For other simulation
parameters, see Figure 2.3.
which essentially no current flows. The extension of this region depends on the magnitude of Λ.
Also, the effect of α is more pronounced than for the quasireversible case.
Ideally, the voltammogram for the irreversible case satisfies the following three criteria [11],
where, as before, the values given in mV refer to T = 298 K:
1. The value of Ep − Eo is given by Equation 2.22 and depends on α, ko, DA, and ν. It follows
that Ep changes with ν as given in Equation 2.23:
 ko 1 ανnF  RT
Ep − E o =  −0.783 + ln 1/ 2 − ln  (2.22)
 DA 2 RT  αnF

dEp 1 RT 29.6
=− ln 10 = − mV (2.23)
d log ν 2 αnF αn
2. The value of Ep − Ep/2 is given in the following equation, which for α = 0.5 results in Ep − Ep/2
equal to −95.4 mV:
RT 47.7
Ep − Ep/2 = −1.857 V=− mV (2.24)
αnF αn
3. The value of ip is given by Equation 2.25. It is seen that ip increases linearly with ν1/2. By
comparing Equations 2.13 and 2.25, it is seen that ip for the irreversible case is 1.11α1/2
(= 0.78 for α = 0.5) times ip for the reversible case.
1/ 2
 αnF 
ip = 0.4958nFACA* DA1/ 2ν1/ 2   (2.25)
 RT 
4. Concluding Remarks and Examples

The borderlines between reversible, quasireversible, and irreversible behavior were originally defined
by Matsuda and Ayabe [11] on the basis of mathematical reasoning. However, in practical work, it
is more convenient to define borderlines reflecting where deviations from the two limiting cases,
reversible and irreversible, may be observed experimentally. Using the conservative estimate (see
Section II.E.3) that the error in peak potential measurements is typically ±2 mV, Nadjo and Savéant
[19] arrived at the borderlines given by Equations 2.26 through 2.28 for α = 0.5. The handy expres-
sions for ko refer to n = 1, T = 298 K, and D = 1·10 −5 cm2 s−1, and assume that ν is measured in V s−1:
Reversible: Λ ≥ 11.5 or k o ≥ 0.23ν1/ 2 cm s−1 (2.26)

Quasi-reversible:11.5 ≥ Λ ≥ 0.2 or 0.23ν1/ 2 cm s−1 ≥ k o ≥ 0.004ν1/ 2 cm s−1 (2.27)

Irreversible: Λ < 0.2 or k o < 0.004ν1/ 2 cm s−1 (2.28)

It follows from the earlier discussion that an electron transfer reaction that appears reversible at one
(low) sweep rate may change to a quasireversible or even an irreversible process at higher sweep
rates. This should be kept in mind since the application of LSV and CV in kinetics and mechanism
studies, detailed in Section II.D, includes the recording of voltammograms at a number of different
sweep rates, and the data analysis is usually based on the assumption that the electron transfer is
reversible.
Radical ions and radicals are usually highly reactive and react further on the time scale of
voltammetric experiments at low ν. Exceptions are many heterocyclic compounds and substrates
carrying a substituent that is able to stabilize a negative or positive charge and/or an unpaired elec-
tron. Examples include the reduction of nitro compounds (Chapter 30), quinones (Chapter 26), and
compounds such as viologens containing two reducible functional groups [55] or the oxidation of
thianthrene (Chapter 27), tetrathiafulvalenes (Chapter 27), and a number of methoxy-substituted
aromatic hydrocarbons (Chapter 18). Numerous other examples may be found throughout this book.
In many of the examples mentioned, it is possible to observe also the second electron transfer
leading to the dianion or dication. In a special case, reversible or quasireversible electron transfers
leading ultimately to the formation of an octaanion have been observed [56].
The determination of Eo for the oxidation or reduction of a substrate provides a direct measure
of the free energy of formation of the resulting intermediate, a radical ion or radical. Values of
Eo are important quantities in thermochemical calculations of, for instance, bond energies [57].
The temperature dependence of Eo that gives insight into ΔS for the electron transfer reaction
has been investigated in a number of cases, in particular for the reduction of aromatic nitro com-
pounds [58]. Values of −ΔS273.2 are typically in the range 5–20 cal K−1 mol−1. Pressure-dependent
CV revealed the activation volume of electrode processes [59] and led to the conclusion that the
electron transfer for the decamethyl ferrocene/ferricinum redox couple is controlled by solvent
dynamics.
Electron transfer reactions that are accompanied by large structural changes may give rise to
the unusual observation that the second electron is easier to add or remove than the first, so-called
potential inversion [4,60–62] (see also Chapter 11).
Examples of the application of CV for the study of the kinetics of the heterogeneous electron
transfer reaction include the reduction of quinones [63,64] and nitroalkanes [64–66]. For radical
anions, the effect of the nature of the counterion, that is, the cation of the supporting electrolyte, has
been investigated [64,67], and the general trend is that the value of ko decreases when the length of
the carbon chain in R4N+ increases (see also Section II.D.5 for other counterion effects). Attention
should be paid also to the fact that ko is sometimes observed to depend on the electrode material and
thus is not a true standard value [68].
Subtle details of electron transfer reactions can be revealed, such as the difference between
inner- and outer-sphere electrode reactions [69] or the type of kinetic relationship (Butler–Volmer
versus Marcus–Hush) [70]. In addition to CV, methods based on AC voltammetry are useful for
studies of heterogeneous electron transfer kinetics [71].
This technique where a sinusoidal waveform is superimposed on the classical cyclic voltammet-
ric triangle can be viewed as a special case of voltammetries with any periodic potential applied
to an electrode [72a,b]. The experimental current variation with time is advantageously analyzed
by applying a Fourier transformation (FT-CV), resulting in a power spectrum in the frequency
domain. Selection of particular frequency bands and inverse Fourier transformation generates not
only the classical (DC) voltammogram but also fundamental, second-, third-, and higher harmonic
signals. The full potential of the technique is revealed by comparison to simulated curves [72c,d]
and reveals particular patterns depending on the prevalent electrode reaction mechanisms [72e].
The analysis was extended to coupled chemical reactions [72f,g] and electron transfer of surface-
confined proteins [72h,i]. As an additional feature, separation of faradaic and background contribu-
tions to the currents was achieved [72j]. The FT technique was also applied to experiments at the
rotating disk electrode [72k] (RDE; see Section VI.B), allowing separation of transport modes in
the harmonic analysis, thus providing a full characterization of electron transfers. Although FT-CV
might not be readily available in most electrochemical research labs, it might become a valuable
tool in the future owing to the wealth of information provided. Recent examples are the observation
of dianions derived from trans-stilbenes [73], the study of tetrathiafulvalene oxidation electrode
kinetics [74], and the analysis of the redox behavior of flavin adenine dinucleotide in the redox
center of glucose oxidase [75].
D. ELECTroN TraNSFEr REaCTIoNS FoLLowED bY CHEMICaL REaCTIoNS IN SoLUTIoN

Some of the most successful applications of LSV and CV are concerned with the study of the kinet-
ics and mechanisms of the reactions of electrode-generated intermediates, and a large share of the
classical electrochemical literature in this field deals with this aspect of voltammetry [12–37,76–78].
The majority of electrochemical reactions include radical ions as the primary intermediates, and the
reaction schemes describing the conversion of a substrate A to products are typically composed of
one or two one-electron transfers and one or two chemical steps. Examples include hydrogenations,
(+2e−, +2H+) (see Chapters 22 and 44) and hydrodimerizations (+e−, +H+) (see Chapter 17), and
anodic additions (−2e−, +2Nu−) (see Chapter 19), dehydrodimerizations (−e−, −H+) (see Chapter 18),
and substitutions (−2e−, +Nu−, −H+), where Nu− is a nucleophile (see Chapter 19).
The electrochemical literature abounds with symbols and abbreviations that are not always
strictly logical. Therefore, a few comments about the abbreviations used in the following to des-
ignate basic electrode mechanisms are necessary. The notation is based on that due to Testa and
Reinmuth [79], where the letter e indicates an electron transfer process and the letter c indicates a
chemical reaction. It is helpful to distinguish between reversible (fast) and rate-determining (slow)
steps by using lowercase letters for reversible and capital letters for rate-determining steps. Since
the second electron transfer reaction can take place either at an electrode (heterogeneous electron
transfer) or in solution (homogeneous electron transfer, that is, in the diffusion layer or in the bulk
solution), those taking place in solution are given the subscript h. The use of this and other abbrevia-
tions frequently met in the literature is illustrated in the following. The presentation is restricted to
cover only chemical reactions that follow a reversible electron transfer. Reaction schemes includ-
ing quasireversible electron transfer or dissociative electron transfer reactions [80,81], for instance,
observed for the reduction of alkyl halides (Scheme 2.1), are mentioned only briefly (see Chapters
14, 24, and 25 for details).
1. Typical Irreversible Follow-Up Reactions

Examples of mechanisms resulting in first-order rate laws are summarized in Scheme 2.2, where the
right-hand part of (ii) refers to the situation where the reaction of B is with a reagent X. In that case,
R-X + e– R + X–
SchEME 2.1 Dissociative electron transfer reaction.
A + e– B (i)
kii kii'
B C or B+X C (ii)
C + e– D (iii)
B+C A+D (iv)
D+X E (v)
Mechanism abbreviation Observed rate law kobs (CX* /CA* >>1)
(i)–(ii): eC –d[B]/dt = kobs[B] kii or kii'CX* (vi)

(i)–(ii)–(iii): eCe –d[B]/dt = kobs[B] kii or kii'CX* (vii)
(i)–(ii)–(iv): eCeh –d[B]/dt = kobs[B] 2kii or 2kii'CX* (viii)
SchEME 2.2 Mechanisms resulting in first-order rate laws.

A + e– B (i)
kii
2B C (ii)
kiii
A+B I (iii)
B+I A+C (iv)
C+X D (v)
Mechanism abbreviation Observed rate law kobs
(i)–(ii): eC(dim) or RR –d[B]/dt = kobs[B]2 2kii (vi)
(i)–(iii)–(iv): RS –d[B]/dt = kobs[A][B] 2kiii (vii)
SchEME 2.3 Mechanisms resulting in second-order rate laws.
the kinetics are often studied under pseudo-first-order conditions, that is, at CX∗ /CA∗ 1. Often, the
product C is more easily reduced than A [82] resulting in a second electron transfer. This may take
place either at the electrode (iii) or in solution (iv) [83] resulting in an eCe or an eCeh mechanism,
the latter sometimes being referred to as a DISP1 mechanism [84,85]. The intermediate D finally
reacts with, for example, the reagent X, to the product E. The observed rate laws (vi) through (viii)
for all these cases are the same if step (ii) is rate determining.
Another important set of reactions are the dimerizations, which are usually discussed within the
frames of the two mechanisms shown in Scheme 2.3. If the formation of C results from the cou-
pling of two radicals or radical ions (ii), the reaction is referred to as a radical–radical (RR) process.
Another route to C, the radical–substrate (RS) process, includes the coupling between A and B (iii)
resulting in the formation of an intermediate I that is further reduced to C by reaction with B (iv).
The direct reduction of I to C at the electrode is usually without importance. Finally, the intermedi-
ate C reacts with a reagent X to the product D. These dimerization mechanisms belong to a more
general scheme to be discussed in some detail later (Section II.D.5).
2. Kinetic Classification of Simple Irreversible Follow-Up Reactions

Let us now consider the voltammetric response for a reversible one-electron reduction followed by
an irreversible chemical reaction, for instance, the eC mechanism with the rate constant k (= kii in
Scheme 2.2). The voltammograms resulting from different values of k at ν = 1 V s−1 are shown in
Figure 2.7.
Given the value of ν, it is seen that both the shape and the position of the voltammogram depend
on the magnitude of k. On the other hand, given the value of k, it is intuitively understood that the
effect of the chemical reaction will gradually diminish if the sweep rate is allowed to increase. In
the limit, the experiment time is so short that the chemical reaction does not have the time to mani-
fest itself, and consequently, the voltammogram observed is just that for the one-electron transfer
reaction, Equation 2.1.
The effect of the relative magnitudes of k and ν on the position and shape of a voltammogram is
conveniently discussed in terms of the dimensionless parameter λ, defined by Equation 2.29 for a
reaction following a first-order rate law and by Equation 2.30 for a reaction following a second-order
rate law [17–19].
kRT
λ= (firstorder rate law) (2.29)
νnF
1.0
0.8
0.6
0.4
0.2
i (mA) 0.0
–0.2
–0.4
–0.6
–0.8
–1.0 –1.2 –1.4 –1.6 –1.8 –2.0
E (V)
FiGURE 2.7 Simulated (DigiSim®) cyclic voltammogram at ν = 1 V s−1 for an eC mechanism with Eo = −1.5 V
and k = 2 s−1 (dash), 10 s−1 (dot), 102 s−1 (dash-dot), 10 4 s−1 (dash-dot-dot), 10 6 s−1 (short dash), and 108 s−1
(short dot) corresponding to λ = 0.0513, 0.257, 2.57, 2.57·102, 2.57·104, and 2.57·106, respectively. The full line
corresponds to the simple electron transfer reaction shown in Figure 2.3, where also other simulation param-
eters are given.
kCA* RT
λ= (secondorder rate law) (2.30)
νnF
It is convenient to classify the electrochemical reactions with regard to the nature of the response.
Given the value of ν, it is seen from Equations 2.29 and 2.30 that increasing values of k correspond
to increasing values of λ. Beginning with λ = 0, the effect of increasing values of λ is initially that
the current associated with the oxidation of B during the backward sweep gradually disappears
(see, e.g., Figure 2.7). The peak potential is, so far, only little affected. The region of λ values, from
the point where the effect of the chemical reaction becomes experimentally detectable, to the point
where the current for the oxidation of B has totally disappeared is given by Equation 2.31 for the eC
mechanism (first-order rate law) and Equation 2.32 for the RR dimerization (second-order rate law)
[19]. Again, the handy expressions correspond to n = 1 and T = 298 K. In this region, the system is
under mixed diffusion and kinetic control. Limits for λ relating to other mechanisms, including the
eCe, eCeh, and more complex reaction schemes, have been reported in the literature [17–19]:
eC mechanism: 0.11 < λ < 1.89 or 4.3ν s−1 < k < 73.5ν s−1 (2.31)

RR dimerization: 0.37 < λ < 1.35 or 14.5ν s−1 < kCA* < 52.5ν s−1 (2.32)

At λ values higher than those given, for instance, by the upper limits in Equations 2.31 and 2.32,
the shape of the voltammogram is essentially independent of λ, and an increase in λ only results
in a displacement of the voltammogram in the positive direction. This is illustrated by the voltam-
mograms corresponding to k = 104, 106, and 108 s−1 in Figure 2.7. A stationary state has now been
established in solution by mutual compensation of the chemical reaction of B and the diffusion pro-
cess, and the system is said to be under purely kinetic control. The limits given by Equation 2.31 or
2.32 define zones of particularly controlled regimes. Note that for more complex mechanisms, such
an approach yields 2D or 3D zone diagrams [2] (see also Chapters 5 and 10).
The peak current in the first sweep is only slightly affected by the value of λ, with an increase at
small λ to a somewhat larger value as compared with the reversible case.
3. Irreversible Follow-Up Reactions, Mixed Diffusion, and Kinetic Control (CV and DCV)
As mentioned earlier, the characteristic features of processes in this category are that Ep is close to
that for the no-reaction case, Equation 2.1, and that the peak current ratio −ipox /ipred varies from approxi-
mately unity to zero. The observation of oxidation current for B during the backward sweep shows that
the material conversion is low. By comparison of the voltammograms for the eC and the eCeh mecha-
nisms in Figure 2.8, it is seen that the second electron transfer reaction in the eCeh mechanism gives
rise to only little additional current illustrating that only a small fraction of B has been converted to C.
Although the value of E p in this kinetic region is only slightly affected by the magnitude of λ,
a careful investigation of the sweep rate dependence of Ep may, nevertheless, have diagnostic
value, for instance, in the distinction between the RR- and RS-dimerization mechanisms. This
is illustrated in Figure 2.9, which shows the theoretical curves, the so-called working curves, for
1.2
1.0
0.8
0.6
i (mA)
0.4
0.2
0.0
–0.2
–0.4
–1.0 –1.2 –1.4 –1.6 –1.8 –2.0
E (V)
FiGURE 2.8 Simulated (DigiSim®) cyclic voltammograms for the eC mechanism (full line) and the eCeh
mechanism (dot) at ν = 1 V s−1 with Eo = −1.5 V and k = 4 s−1 (corresponding to λ = 0.103). For other simulation
parameters, see Figure 2.3.
0
a
Ep– E o (mV)
20
40
–3 –1 1
log(λ)
FiGURE 2.9 Working curves for RR- (full line) and RS-dimerization (dotted line) mechanisms showing
the predicted variation of Ep − Eo with log λ together with data obtained by LSV for the dimerization of the
7,12-diphenylbenzo[k]fluoranthene radical cation in benzene/MeCN (1/1); CA* = 0.44 mM (◊),CA* = 1.04 mM
(Δ), and CA* = 2.00 mM ( ). (Reprinted with permission from Debad, J.D., Morris, J.C., Magnus, P., and
Bard, A.J., J. Org. Chem., 62, 530–537. Copyright (1997) American Chemical Society.)
Ep − Eo for the two mechanisms together with experimental data obtained for the dimerization of
7,12-diphenylbenzo[k]fluoranthene radical cation [86]. The data clearly indicate that the dimeriza-
tion is of the RR type.
A common procedure for studying the kinetics of follow-up reactions by CV is to compare values
of −ipox /ipred recorded at different sweep rates to the working curve for the proposed mechanism [12].
However, a problem with this approach is the difficulty already mentioned in evaluating the baseline
for the backward sweep, and therefore, CV suffers from some limitations when used in quantitative
work. Simulation (see Chapter 5) is a common helpful approach nowadays, but originally, deriva-
tive cyclic voltammetry (DCV) was developed to solve this problem [37,77,87]. The latter has been
applied to settle many mechanistic questions and has various advantages (see later in this section).
The application of the first derivative of the CV curve was investigated during the 1960s by
Perone and coworkers [88,89], but due to difficulties in performing differentiation using analog
electronic equipment, the method was not recommended for the measurement of electrode poten-
tials. Digital differentiation may now be carried out by using Fast Fourier Transform methods [90],
and differentiation algorithms are included in modern software.
The voltammogram shown in Figure 2.3 is redrawn in Figure 2.10a, now showing the current
i as a function of the time t. The problem of defining a baseline for the measurement of ipox is illus-
trated by the two broken lines, a problem that becomes more serious as Eswitch comes closer to Eo.
The differentiated curve, di/dt versus t, is shown in Figure 2.10b. The peaks labeled if′ and ib′ , cor-
responding to the maximum steepness of the voltammogram during the forward and backward
1.0
0.8
0.6
0.4
0.2
i (mA)
0.0
–0.2
–0.4
–0.6
–0.8
0.0 0.5 1.0 1.5 2.0
(a) t (s)
0.06
0.04
i΄f
0.02
0.00
di/dt
–0.02
i΄b
–0.04
–0.06
0.0 0.5 1.0 1.5 2.0
(b) t (s)
FiGURE 2.10 The cyclic voltammogram in Figure 2.3 shown as (a) the current–time curve and (b) the
differentiated current–time curve.
sweeps, respectively, reflect the CV peak heights. Both if′ and ib′ are easily being measured relative
to the zero line. Since the slope of the baseline for ipox, that is the extension of the reduction wave, is
not far from zero where the measurement is made, it follows that the magnitude of ib′ is essentially
baseline independent. Another advantage of recording the derivative signal is that the effect of the
background current is strongly diminished.
The ratio RI′ = −ib′ /if′ plays the same role in DCV as the ratio −ipox /ipred in CV. It should be noticed,
however, that −ib′ /if′, in contrast to −ipox /ipred, does not approach zero for increasing values of λ, but a
value close to 0.1. This is related to the fact that the derivative curve during the backward sweep is
not zero, even when the peak owing to B has completely vanished.
The kinetic analysis of a follow-up reaction by DCV involves the recording of RI′ at different ν,
and the rate constant k (or kobs) is then obtained by fitting the working curve for the appropriate rate
law, usually in the form of RI′ versus log λ, to these data. An example is shown in Figure 2.11, where
the working curve for the RR-dimerization mechanism is fitted to the experimental data for the
dimerization of (−)-bornyl cinnamate radical anions [91]. The rate constant is obtained by matching
the two scales; in the present case, this results in k = 5.6·102 M−1 s−1.
The approach works equally well for reactions taking place after the second electron transfer, for
instance, at the dication [92] or dianion [93] oxidation state.
The rate law necessary for making a mechanism suggestion is conveniently determined by DCV.
The procedure, sometimes referred to as the reaction order approach, is based on measurements of
the sweep rate necessary to maintain a certain constant conversion of B as a function of CA∗ , and CX∗ if
relevant. Usually, the sweep rate necessary to keep RI′ equal to 0.5 is used. This sweep rate is referred
to as ν1/2 or ν0.5. The reciprocal value, 1/ν1/2, is conceptually related to the half-life time t1/2 in conven-
tional kinetics. If the generalized rate law for the reaction to be investigated is written as Equation
2.33, where kobs is defined, for instance, as in Schemes 2.2 and 2.3, the relations between ν1/2 and the
reaction orders a, b, and x are given by Equations 2.34 and 2.35, where RA/B is equal to a + b and
RX is equal to x. It is seen that RA (= a) and RB (= b) are not directly separable, a common feature of
all reversal techniques, where A and B are in thermodynamic equilibrium at the electrode surface.
a b x
Rate = kobs  A   B   X  (2.33)

log ν (V s–1)
–1 0 1 2
1
0.8
0.6
RI
0.4
0.2
0
–1 0 1 2 3
–log(kCRT/nFv)
FiGURE 2.11 DCV working curve for the RR-dimerization mechanism (bottom scale) together with experi-
mental data obtained for the dimerization of (−)-bornyl cinnamate radical anion in DMF (top scale). (From
Amatore, C. and Savéant, J.M., J. Electroanal. Chem., 85, 27, 1977.)
2.4
1.6
log (ν1/2/Vs–1)
0.8
0.0 Slope: 1.06
0.6 1.0 1.4 1.8 2.2 2.6

log (C oHB/mM)
FiGURE 2.12 Data for log ν1/2 as a function of log(CXo /mM) obtained by DCV for the protonation of the
anthracene radical anion by phenol (HB) in DMSO. (From Nielsen, M.F. and Hammerich, O., Acta Chem.
Scand., 43, 269, 1989. With permission.)
d log ν1/ 2
RA/B = 1 + (2.34)
d log CA*
d log ν1/ 2
RX = (2.35)
d log CX*
Usually, the data treatment includes that values of log ν1/2 are plotted against log CA* or log CX* ,
which, for a simple rate law such as Equation 2.33, results in a straight line with the slope RA/B − 1 or
RX. Data obtained for the protonation of the anthracene radical anion by phenol in DMSO [94] are
shown in Figure 2.12 as an example. The slope of the regression line in this case is 1.06 indicating
that the rate law is first order in the concentration of phenol.
Once the rate law is known, the value of k (or kobs) may in principle be obtained directly from ν1/2
as illustrated by the relations given in Equation 2.36 for the eC mechanism (first-order rate law) and
Equation 2.37 for the RR dimerization (second-order rate law), in both cases for Eo − Eswitch = 0.3 V [95].
Relations for other mechanisms may be found in the literature [95].
ν1/ 2 nF
eC mechanism: k = 0.078 (2.36)
RT
ν1/ 2 nF
RR dimerization: k = 0.117 (2.37)
CA* RT
However, in general, it is recommended that the full working curve is used for the determination
of the rate constant in view of the larger number of data points included. This approach also offers
the additional benefit that the validity of the mechanism hypothesis is tested by the goodness of
the fit for each determination. This is particularly important in cases such as those where changes
in the substrate substitution pattern or in the experimental conditions may result in a change in
the mechanism or, for complex reaction schemes, a change in the rate-determining step (see also
Section II.D.5).
The kinetic window for CV and DCV may be derived from the limits for λ given, for example,
in Equations 2.31 and 2.32. Assuming that the applicable range of useful ν values is 0.1–500 V s−1,
the limits translate approximately as follows:
eC mechanism: 0.4 s−1 < k < 4 ⋅ 10 4 s−1 (2.38)

RR dimerization: 1.5 s−1 < kCA* < 3 ⋅ 10 4 s−1 (2.39)

Typical examples of the application of DCV for kinetic and mechanistic studies include the cleavage
of the carbon–halogen bond in the radical anions of aromatic halides [96], the protonation of radical
anions [94,97–99], and the dimerization of radical ions [91].
4. Irreversible Follow-Up Reactions, Purely Kinetic Control (LSV)

The characteristic feature of the voltammogram in this region of λ values is the absence of a peak
during the backward sweep, which for the same reason is not included in the data analysis (LSV).
The position of the voltammogram, as measured by Ep, is displaced in the positive direction relative
to that for the no-reaction case, Equation 2.1, and depends markedly on the value of λ. In contrast,
the shape of the voltammogram, as measured by Ep − Ep/2, is nearly constant and independent of λ.
However, Ep − Ep/2 depends on the mechanism, which is of diagnostic value (see later in this section).
It is appropriate to mention at this place that processes belonging to this category are often referred
to as irreversible. This may be confusing, since the term irreversible in this case refers to the effect
of an irreversible chemical reaction on the total process and not just to the electron transfer reac-
tion. Common to the two types of irreversible processes is, however, the absence of an oxidation
peak owing to B in the potential region where the reduction of A takes place. Sometimes the term
c hemically irreversible is used for the case discussed here. A slightly different meaning is adopted
for this in Section III.E.2 in Chapter 1.
The lack of an oxidation peak for B indicates a high material conversion, which can also be seen
by comparison of the voltammograms for the eC and eCeh mechanisms in Figure 2.13. In contrast
to the voltammograms in Figure 2.8, it is seen that ip for the eCeh mechanism is now close to being
twice that for the eC mechanism illustrating that the conversion of B to C has proceeded almost to
completion.
2.0
1.6
1.2
i (mA)
0.8
0.4
0.0
–1.0 –1.2 –1.4 –1.6 –1.8 –2.0

E (V)
FiGURE 2.13 Simulated (DigiSim®) cyclic voltammograms for the eC mechanism (full line) and the eCeh
mechanism (dot) at ν = 1 V s−1 with Eo = −1.5 V and k = 106 s−1 (corresponding to λ = 2.57·104). For other
simulation parameters, see Figure 2.3.
LSV is a powerful tool for the study of processes under purely kinetic control. Theoretical analy-
ses of the response for various mechanisms have been carried out [12,14–25], and a series of papers
[35,78,87,100] has been devoted to assimilating the theoretical results in a form useful to the experi-
mentalist. For the general rate law, Equation 2.33, the dependence of Ep on changes in log ν, log CA* ,
and log CX* , respectively, is linear with the slopes given by Equations 2.40 through 2.42, where a, b,
and x are the reaction orders:
dEp 1 RT
=− ln 10 (2.40)
d log ν b + 1 nF
dEp a + b − 1 RT
= ln 10 (2.41)
d log CA* b + 1 nF
dEp x RT
= ln 10 (2.42)
d log CX* b + 1 nF
Introduction of the reaction orders for, for instance, the eC mechanism under pseudo-first-order
conditions (a = 0, b = 1, and x = 1) results in dEp/d logν = −29.6 mV, dEp / log CA* = 0 mV , and
dEp / log CX* = 29.6 mV at n = 1 and T = 298 K.
Important is also the shape of the voltammogram represented by the value of Ep − Ep/2. The
limiting values for the eC and RR-dimerization mechanisms are given in Equations 2.43 and 2.44,
where, again, the values given in mV refer to T = 298 K. Values of Ep − Ep/2 for other mechanisms
are available in the literature [17–19].
RT 47.8
eC mechanism: Ep − Ep/2 = −1.86 V=− mV (2.43)
nF n
RT 38.8
RR dimerization: Ep − Ep/2 = −1.51 V=− mV (2.44)
nF n
When Eo for the initial electron transfer reaction is known, the measurements of Ep directly gives
access to the rate constant k. Examples of the relationship between Ep − Eo and k are given by
Equations 2.45 and 2.46 [19], where Equation 2.46 refers to rate law (vi) in Scheme 2.3, that is, the
stoichiometric coefficient 2 is not included in the rate constant.
 1 kRT   RT 
eC mechanism: Ep − E o =  −0.783 + ln ⋅  (2.45)
 2 νnF   nF 
 1 4kCA* RT   RT 
RR dimerization: Ep − E o =  −0.902 + ln ⋅  (2.46)
 3 3νnF   nF 

It is easily seen that the application of equations such as Equations 2.45 and 2.46 requires data for
Ep − Eo of high precision. For example, for the RR-dimerization mechanism, a change in k by a
factor of 10 corresponds only to a change in Ep of 19.7 mV (at T = 298 K). Taking into account that
both the precision and the accuracy of literature values for Eo may not be better than ±10 mV, it is
strongly recommended that the value of Eo to be used is the result of a measurement made in con-
junction with the Ep measurements. Since, by definition, the value of λ is rather large for Equations
2.45 and 2.46 to apply, it follows that large sweep rates are required to outrun the chemical reaction.
This is conveniently achieved by using ultramicroelectrodes for the measurements [101,102] (see
Section III). Reliable Eo data may also be predicted within a series of compounds from correlations
to data obtained by NMR spectroscopy [103].
Although LSV is experimentally easy to use, the technique should be used with care. The major
concern is to make sure that the electron transfer reaction is reversible and that the process under
investigation is indeed under purely kinetic control in the range of ν and concentrations employed. If
increasing sweep rates bring the electron transfer into the quasireversible region (see Section II.D.8),
the values of, for instance, dEp/d log ν, will be larger than predicted for the reversible case [19,104],
and if the follow-up reaction is brought into the region of mixed kinetic and diffusion control,
dEp/d log ν will be smaller than predicted [19,105]. This may lead to a wrong mechanism assign-
ment. However, in both cases, the Ep − Ep/2 will be larger than predicted and therefore serves as an
excellent diagnostic tool for probing whether the reaction being studied does indeed confine to the
purely kinetic conditions as defined earlier.
Another problem may arise in the study of processes of the type where B reacts with an added
reagent X. In that case, the kinetic measurements are often carried out under pseudo-first-order
conditions, that is, at CX* /CA* 1, and values of dEp / log CX* are obtained by carrying out a series
of E p measurements at increasing values of CX* . If now the ratio CX* /CA* at the lowest concentra-
tion of CX* is not sufficiently large, the consumption of X cannot be neglected, and accordingly,
the rate of the chemical reaction is too low. The problem gradually disappears with increasing
values of CX* , and the overall effect is that the increase in the reaction rate with increasing CX*
becomes too large, and accordingly, the resulting value of dEp / log CX* becomes too large as
well [105]. This may lead to the erroneous interpretation that the reaction order in X is larger
than one.
Illustrations of the application of LSV for studies of reactions under purely kinetic
c onditions include the oxidation of 9-substituted fluorenide ions [106] and the reduction of
2,6-diphenylpyrylium ions [49a], in both cases leading to the neutral radical that dimerizes in an
RR-type reaction, the oxidation of 1,4-dithiafulvenes into tetrathiafulvalenes [107], the oxidative
ring opening of arylcyclopropanes [108], the reduction of fluoroalkoxyarenes in liquid ammonia
[109], and the competition between protonation and dimerization during the reduction of cin-
namic acid esters in MeOH [110].
5. Reversible Follow-Up Reactions
Let us now consider a reversible electron transfer reaction followed by a reversible chemical reac-
tion. Typical examples, including the reaction of B with a reagent X (ii), here with p equivalents, and
the reversible dimerization (iii), are shown in Scheme 2.4.
If the chemical reaction responds instantaneously to changes in the concentration of B or C,
it is adequately described by the magnitude of the equilibrium constant K, which means that the
total system is reversible. For reaction (ii), the resulting voltammogram, shown in Figure 2.14a
for p = 1 and CX* /CA* = 100, has the same shape as that in Figure 2.3, but is displaced on the volt-
age axis according to Equation 2.47, where K corresponds to K ii in Scheme 2.4. It is seen that E p
changes by 59.1 mV (at T = 298 K) in the positive direction for a 10-fold increase in K for K ≫ 1.
(See, e.g., the voltammograms shown in Figure 2.14a for K = 100 and 1000.) It follows from
A + e– B (E 0) (i)
[C]
B + pX C Kii = (ii)
[B][X]p
[C]
2B C Kiii = (iii)
[B]2
SchEME 2.4 Mechanisms including reversible follow-up reactions.

1.0
0.8
0.6
0.4
0.2
i (mA)
0.0
–0.2
–0.4
–0.6
–0.8
–1.0 –1.2 –1.4 –1.6 –1.8 –2.0
(a) E (V)
3e–5
e a e d c b a
2e–5
1e–5
0e+0
a = DMOBQ
–1e–5 b = 0.06 M EtOH
c = 0.2 M EtOH
–2e–5 d = 0.47 M EtOH
e = 0.9 M EtOH
–3e–5
0.0 –0.2 –0.4 –0.6 –0.8 –1.0 –1.2 –1.4 –1.6 –1.8 –2.0
(b) Potential (V vs. SCE)
FiGURE 2.14 (a) Simulated (DigiSim®) cyclic voltammograms for a reversible one-electron reduc-
tion followed by a reversible chemical reaction (Scheme 2.4) with Eo = −1.5 V, C A* = 1 mM, CX* = 100 mM,
and K = 10 (dash), 100 (dot), and 1000 (dash-dot). The full line corresponds to the simple electron transfer
reaction shown in Figure 2.3, where also other simulation parameters are given. (b) Experimental cyclic
voltammograms for the reduction of 2,5-dimethoxy-1,4-benzoquinone (DMOBQ) in benzonitrile containing
Bu4NPF6 (0.1 M) and different concentrations of ethanol. (Reprinted with permission from Gupta, N. and
Linschitz, H., J. Am. Chem. Soc., 119, 6384–6391. Copyright (1997) American Chemical Society.)
Equations 2.10 and 2.47 that the difference in peak potentials ΔEp for (i) and (ii), and (i) is given
by Equation 2.48 [111]. The relation between Ep − Eo and Kiii for the dimerization reaction (iii) is
more complex owing to the presence of the second-order term [B]2 in the expression for Kiii. The
reader is referred to the original literature [112] for details, which also contains a zone diagram
for this mechanism.
RT RT 
( ) 
p
Ep − E o = −1.11 + ln 1 + K CX* (2.47)
nF nF  
RT 
( ) 
p
∆Ep = ln 1 + K CX* (2.48)
nF  
Reversible reactions of type (ii) in Scheme 2.4 are typically observed for radical anions with X
being a cation (formation of ion pairs) [114] or a hydroxylic compound such as water or an alcohol
A + ne– + mH+ B
SchEME 2.5 Electron transfer reaction including reversible proton transfer.
(formation of hydrogen bond complexes) [113,114]. An example of the latter is shown in Figure
2.14b, where also the (larger) effect on the second redox couple is shown. Usually, the product
K (CX* ) p is much larger than unity, and consequently a plot of Ep versus logCX* should yield a straight
line from the slope of which the stoichiometric number p may be obtained. Deviations from the
linear dependence of Ep on logCX* are observed in some cases at high concentrations of X, which
may be attributed to the formation of higher associates. Attention should also be brought to a series
of papers in which reduction processes including reversible proton transfer reactions (Scheme 2.5)
are thoroughly discussed [115] (see also Chapter 13).
Reversible dimerizations are observed less frequently, since often the reactions are not fast
enough to be treated as thermodynamic equilibria. Examples are the dimerizations of the radical
cations of thianthrenes [116] and thiophene derivatives [117].
Let us now reexamine the dimerization mechanisms shown in Scheme 2.3 in a little more detail.
The rate-determining steps, (ii) and (iii), in that scheme are both formulated as being irreversible.
This, however, is not meant to imply that the dimerization of B, or the coupling of A and B, is an
irreversible process by nature. In fact, the only well-documented example of an inherently irrevers-
ible reaction of this type is (ii) when B is a neutral free radical. More often, for instance, when B is a
radical ion, the chemical reactions (ii) and (iii) in which the intermediates C and I are produced are
reversible, and the observed irreversibility is a kinetic phenomenon caused by the further reactions
of C and I. Thus, a more natural starting point for the discussion would be the general situation in
which both the forward and the backward reactions are considered for all steps except the last one.
This is shown in Scheme 2.6.
It is convenient first to examine briefly the RS-dimerization mechanism. Usually, the intermedi-
ate I is more easy to reduce than A (or to oxidize, when B is a radical cation), which means that
the equilibrium constant Kiv for the eCeh step (iv) is large. Also, the rate constant for this type of
process is usually large. This allows for the application of the steady-state approximation for the
A + e– B (i)
kii
2B C (Kii = kii/k–ii) (ii)
k–ii
kiii
A+B I (Kiii = kiii/k–iii) (iii)
k–iii
kiv
B+I A+C (Kiv = kiv/k–iv) (iv)
k–iv
kv
C+X D (v)
Mechanism Assumption Observed rate law kobs
RR kv[X] >> k–ii –d[B]/dt = kobs[B]2 2kii (vi)
RR k–ii >> kv[X] –d[B]/dt = kobs[B]2[X] 2Kiikv (vii)
RS kiv[B] >> k–iii –d[B]/dt = kobs[A][B] 2kiii (viii)
RS k–iii >> kiv[B] –d[B]/dt = kobs[A][B]2 2Kiiikiv (ix)
SchEME 2.6 Mechanisms including reversible dimerization.

intermediate I, that is, it is assumed that d[I]/dt = 0. The general rate law resulting for B degener-
ates to either of two limiting cases depending on the relative magnitudes of k−iii and kiv [B]. When
kiv [B] ≫ k−iii, the intermediate I reacts almost exclusively by reaction (iv), and forward reaction (iii)
becomes rate determining. The resulting rate law (viii) is the same as rate law (vii) in Scheme 2.3.
On the other hand, when k−iii ≫ kiv [B], reaction (iii) behaves as a true equilibrium prior to the rate-
determining reaction (iv) resulting in rate law (ix). It is seen that under conditions where rate law
(viii) applies, the reaction order RA/B is equal to 2, whereas rate law (ix) corresponds to RA/B equal to 3.
Thus, ideally, it would be possible to distinguish between the two limiting cases by a DCV reaction
order analysis carried out as described earlier.
Next, let us examine the situation where the reversible RR dimerization (ii) results in a dimer
C that is stable on the time scale of the voltammetric experiment. The voltammograms that ide-
ally may be obtained in different kinetic regimes are shown in Figure 2.15a. At low sweep rates
(full line), reaction (ii) behaves like a thermodynamic equilibrium, and the response observed
1.0
0.8
0.6
iν–1/2 (mA V–1/2 s1/2)
0.4
0.2
0.0
–0.2
–0.4
–0.6
–0.8
–1.0 –1.2 –1.4 –1.6 –1.8 –2.0
(a) E (V)
1.1
1.0
0.9
0.5
0.8
1.0
0.7
ipc/ipa
2.0
0.6
5.0
7.0
0.5 10
15
20
0.4 40
50
100
0.3 400 300
200
0.2
–6 –4 –2 0 2 4
(b) –log (RT/nF kf c/v)
FiGURE 2.15 (a) Simulated (DigiSim®) cyclic voltammograms for a reversible one-electron reduction fol-
lowed by a reversible RR-dimerization reaction (Scheme 2.5) with Eo = −1.5 V, C A* = 1 mM, Kii = 104 M−1,
kii = 106 M−1 s−1, and ν = 0.1 (full line), 30 (dash), and 10,000 (dot) V s−1. For other simulation parame-
ters, see Figure 2.3. Note that units of iν−1/2 are used at the y-axis to facilitate the comparison of voltammo-
grams obtained at different sweep rates. (b) Working curves for the reversible RR-dimerization mechanism
(full line) and experimental values (■) of −ipred /ipox for the dimerization of the all-trans 1,10-diphenyl-
3,8-dimethyldecapentaene radical cations and related compounds. The numbers on the curves refer to the
value of K iiC A* (see Scheme 2.5). (With kind permission from Springer Science+Business Media: J. Solid State
Electrochem., 2, 1998, 102, Heinze, J., Tschuncky, P., and Smie, A.)
is close to that shown in Figure 2.14a. At intermediate sweep rates, the dissociation of C is too
slow to allow for the observation of oxidation current for B, and at high sweep rates, it is possible
even to outrun forward reaction (ii), and the response is essentially that for a reversible electron
transfer process.
For radical cations, this situation is typically observed when deprotonation of the dimer dication
is slow, and for radical anions under conditions that are free from electrophiles, for example,
acids that otherwise would react with the dimer dianion. Most often, this type of process has been
observed for radical anions derived from aromatic hydrocarbons carrying a substituent that is
strongly electron withdrawing, most notably and well documented for 9-substituted anthracenes
[119,120] (see also Chapter 17). Examples from the radical cation chemistry include the dimeriza-
tion of the 1,5-dithiacyclooctane radical cations [121] and of the radical cations derived from a
number of conjugated polyenes [118,122].
The kinetics (kii and k−ii) and thermodynamics (Kii) of such reactions are conveniently studied by
CV or DCV. Working curves for CV are shown in Figure 2.15b for different values of Kii together
with the experimental points obtained for the oxidation of conjugated polyenes, such as the all-
trans 1,10-diphenyl-3,8-dimethyldecapentaene [118]. In going from right to left, corresponding to
increasing values of λ, it is seen that the value of −ipred /ipox initially decreases until a minimum is
reached. In this kinetic region, the reaction is essentially controlled by the rate of the dimerization.
The rising part of the working curve observed after the minimum illustrates the increasing kinetic
importance of the dissociation of C to B. In the limit λ = ∞, corresponding to an infinitely large
value of kii or concentration and/or an infinitely small value of ν, the chemical reaction responds as
a true equilibrium.
We now introduce the situation where the dimer C undergoes a subsequent chemical reaction (v).
The corresponding working curves, in this case for DCV, are shown in Figure 2.16 for two values of
K iiCA* (1 and 10) and different values of kvCX* /k− ii (shown in the figure).
The detailed discussion [123] of the curves is beyond the scope of this chapter, but it is seen that
the effect of increasing values of kvCX* /k− ii, as intuitively expected, is a gradual transition from the
reversible case (kvCX* /k− ii = 0, labeled rev on Figures 2.16a and b) to the totally irreversible case
(kvCX* /k− ii = ∞, labeled irr on Figures 2.16a and b). In other words, the reaction of C gradually
changes from dissociation to irreversible conversion to D. The latter situation corresponds to the
limiting case in which the dimerization is kinetically irreversible as described by rate law (vi) in
Scheme 2.6 (=rate law (vi) in Scheme 2.3).
1.0 1.0
K5C(A)° = 1 K5C(A)° = 10
rev
0.8 0.8
rev
0.6 0.6
Ri
Ri
0.4 irr 1 0.1 0.01 0.4 0.01

irr 1 0.1
0.2 0.2
0.0 0.0
–3 –2 –1 0 1 2 3 –3 –2 –1 0 1 2 3
(a) log(k5C(A)°/a) (b) log(k5C(A)°/a)
FiGURE 2.16 DCV working curves for a reversible dimerization followed by an irreversible reaction for
(a) K iiC A* = 1 and (b) K iiC A* = 10 (K iiC A* = K5C(A)o in the figures). The labels 1, 0.1, and 0.01 at the working
curves refer to the values of kvCX* /k− ii. The rate constant k5 in the figure corresponds to kii in Scheme 2.5, and
the constant a is equal to νnF/(RT). (From Hammerich, O. and Nielsen, M.F., Acta Chem. Scand., 52, 831,
1998. With permission.)
An important consequence of the different shapes of the working curves in Figure 2.16 is that
a reaction order analysis based on Equation 2.34 may lead to a value of R A/B that is not related
to rate law (2.33) and, hence, cannot easily be used for mechanism assignment. An example
serves to illustrate this point. Let it be assumed that the reaction being studied is described by
K iiCA* = 1 and kvCX* /k− ii = 0.1 corresponding to the working curve labeled 0.1 in Figure 2.16a.
It is seen that RI′ = 0.5 in this case requires that log[ kiiCA* RT /(νnF )] is equal to approximately
0.2. If now the concentration of substrate is increased by a factor of 10, the appropriate work-
ing curve is the one labeled 0.1 in Figure 2.16b, and it is seen that RI′ = 0.5 now requires that
log[ kiiCA* RT /(νnF )] is equal to approximately −0.8. The two-point value of d log ν1/ 2 /d log CA*
calculated from these data is 2.0, which gives R A/B equal to 3.0 using Equation 2.34. This would
seem to be in good agreement with rate law (ix) for the RS-mechanism with the electron transfer
(iv) being rate determining, but not with the RR-mechanism with irreversible dimerization (ii),
for which RA/B is equal to 2. The major origin of the problem is of course that RI′ = 0.5 at the
low substrate concentration (Figure 2.16a) corresponds to the part of the working curve that is
essentially defined by rate law (vii), whereas RI′ = 0.5 at the high concentration (Figure 2.16b)
corresponds to the part essentially defined by rate law (vi). The same type of analysis carried out
for kvCX* /k− ii = 0.01 and 1 results in R A/B = 4.1 and 2.2, respectively. It is seen that R A/B increases
with decreasing values of kvCX* /k− ii and that therefore virtually any value larger than 2 may result
when the analysis is based on Equation 2.34. Problems of this kind may be difficult to detect
experimentally. For example, for the reaction following the working curves 0.1, it is seen that
the shape of the working curve at low concentration (Figure 2.16a) is similar to that for irr as
long as RI′ is lower than 0.7, and at the high concentration (Figure 2.16b), the same is true
as long as RI′ is higher than 0.4. Thus, if the data for RI′ recorded during a preliminary DCV
investigation were all between 0.4 and 0.7, the results would seem to indicate that the kinetics
would be adequately described by a simple rate law such as that in Equation 2.33. The only
solution to problems of this kind is to record the full working curves in all cases and to supply
the data obtained by DCV (or DPSCA, see Section IV.A) with data from LSV. An example of
the latter approach is the study of the dimerization of the radical cations derived from a series
of 2,5-diaryl-1,4-dithiins [124]. As a general rule, it is recommended to use as many individual
data as possible for mechanistic analyses of this kind, recorded at widely different conditions
(concentration, sweep rates, temperature).
6. Irreversible Follow-Up Reactions, the Prepeak Method

Reactions between B and X may conveniently be studied also under conditions where CX* /CA* < 1.
In that case, the reagent X is consumed during the early parts of the voltammetric wave giving rise
to a prepeak (at Ep,pre) in front of the main peak (at Ep,main) for the reduction of A, now in a solution
that close to the electrode is essentially free from X [119]. An example of such a voltammogram is
shown in Figure 2.17a.
The rate constant may be obtained from the potential difference Ep,pre − Ep,main, which has been
tabulated for a number of reaction mechanisms [126]. This method has been used extensively in
kinetic studies of reactions between radical cations and nucleophiles [126–129].
Alternatively, the determination of k may be based on measurements of Ep/4 − Ep,main, where the
quarter-peak potential Ep/4 is the value of E at i = ip,main/4 [125] (see Figure 2.17a). The advantage of
this approach is that measurements can be made even in cases where the prepeak appears only as
a shoulder on the main peak and where Ep,pre therefore cannot be determined. The working curve
for the eC mechanism is shown in Figure 2.17b together with experimental data obtained for the
protonation of the anthracene radical anion by benzoic acid. The rate constant resulting from these
data is 2.7·106 M−1 s−1 [125].
The prepeak method may be used for reactions with second-order rate constants ranging from
approximately 105 M−1 s−1 to that for a diffusion-controlled reaction.
0.8
Ep,main
0.6 Ep,pre
0.4 Ep/4
ip,main
0.2
i (mA)
ip,main/4
0.0
–0.2
–0.4
–1.0 –1.2 –1.4 –1.6 –1.8 –2.0
(a) E (V)
log (ν/Vs–1)
–2.0 –1.0 0.0 1.0 2.0 3.0
150
(Ep/4 – Ep) (mV)
125
100
75
0.0 1.0 2.0 3.0 4.0 5.0
(b) log(k4C oHB RT/(vnF ))
FiGURE 2.17 (a) Simulated (DigiSim®) cyclic voltammogram at ν = 1 V s−1 for an eC mechanism with Eo =
−1.5 V, C A* = 1 mM, CX* /C A* = 0.5, and k = 109 M−1 s−1. For other simulation parameters, see Figure 2.3. (b) Working
curve for the quarter-peak width Ep/4 − Ep,main (bottom scale) together with experimental points (top scale) for the
protonation of anthracene radical anion (C A* = 2 mM) with benzoic acid (CHB *
= 1 mM) in DMSO (rate constant k4).
(From Nielsen, M.F. and Hammerich, O., Acta Chem. Scand., B41, 668, 1987. With permission.)
7. Irreversible Follow-Up Reactions, Redox Catalysis

Common to all the methods discussed earlier is that B is generated at the electrode surface, that
is, by a direct electron exchange between the electrode and the substrate A. This approach is, how-
ever, sometimes hampered by the limitations imposed by the heterogeneous nature of the electron
transfer reaction. For instance, studies of the kinetics of fast follow-up reactions may be difficult or
even impossible owing to interference from the rate of the heterogeneous electron transfer process.
In such cases, the kinetics of the follow-up reactions may be studied instead by an indirect method,
generally known as redox catalysis [2,130–132]. Another application of redox catalysis is the study
of dissociative electron transfer reactions (Scheme 2.1, see also Chapter 14) [80,81,133,134].
The principle is illustrated in Scheme 2.7 for a reaction that in a direct process follows the eC
mechanism.
The direct process includes the reduction of A to B (i) followed by the irreversible reaction of
B to a product C (iv). If now a compound P, a so-called mediator, that is easier to reduce than A is
A + e– B E oAB (i)
P + e– Q E oPQ (ii)
kiii
Q+A P+B Kiii (iii)
k–iii
kiv
B C (iv)
SchEME 2.7 Mechanism including redox catalysis.
added to the solution, the direct reduction of A is replaced by the reaction sequence (ii) and (iii).
During the electron transfer process (iii), the oxidized form P of the mediator is regenerated. In
other words, the reduction of A to B is catalyzed by the redox couple P/Q. Cyclic voltammograms
typical for the catalyzed process are shown in Figure 2.18. The effect of increasing values of kiii
is shown in Figure 2.18a, and the effect of an increasing concentration ratio CA* /CP* is shown in
Figure 2.18b.
3
ip,revγ
2
i (mA)
ip,cat
1
ip,rev
0
–1
–1.0 –1.2 –1.4 –1.6 –1.8
(a) E (V)
25
20
15
i (mA)
10
–5
–1.2 –1.3 –1.4 –1.5 –1.6 –1.7 –1.8
(b) E (V)
FiGURE 2.18 Simulated (DigiSim®) cyclic voltammograms at ν = 1 V s−1 for the catalytic reaction shown
in Scheme 2.7 with EPQ o
= −1.5 V, CP* = 1 mM, Kiii = 5·10 −7, and (a) k iv = 108 M−1 s−1, C A* /CP* = 4 , and k iii = 0
(full line), 10 (dash), 10 (dot), 10 6 (dash-dot), and 108 (dash-dot-dot) M−1 s−1, and (b) k iii = 10 6 M−1 s−1, k iv =
4 5
108 M−1 s−1, and C A* /CP* = 1 (full line), 2 (dash), 5 (dot), 10 (dash-dot), 20 (dash-dot-dot), and 50 (short dash).
For other simulation parameters, see Figure 2.3. The magnitude of ip,cat is shown for k iii = 105 M−1 s−1.
The description of the kinetics is simplified considerably by the fact that often the three rate con-
stants, kiii, k−iii, and kiv, are all large allowing for the application of the steady-state approximation
for the concentration of B, that is, −d[B]/dt = 0 [124]. The system is conveniently discussed by the
introduction of three dimensionless parameters: (1) the kinetic parameter λ, Equation 2.49; (2) the
competition parameter σ, Equation 2.50; and (3) the concentration excess factor γ, Equation 2.51. In
addition, it is convenient to introduce the catalytic efficiency CAT, Equation 2.52, where ip,cat is the
peak current during LSV observed for the catalytic system and ip,rev is the peak current observed for
P in the absence of A (see Figure 2.18a). The product ip,revγ then is the maximum possible catalytic
current.
kiiiCP* RT
λ iii = (2.49)
νF
kiv
σ= (2.50)
k− iiiCP*
CA*
γ= (2.51)
CP*
ip,cat
CAT = (2.52)
ip,rev γ

Two limiting cases result depending on the magnitude of σ. For σ ≫ 1, the kinetics are controlled
by kiii, that is, by the rate of the solution electron transfer reaction, and for σ ≪ 1 by Kiiikiv, that is,
the case where the electron transfer reaction may be considered as a true equilibrium prior to the
reaction of B. The transition is shown by the voltammograms in Figure 2.18a for σ varying between
5·102 (lower curve for kiii = 102 M−1 s−1) and 5·10 –4 (upper curve for kiii = 108 M−1 s−1). Under condi-
tions where σ ≫ 1, the value of kiii may be obtained by fitting the appropriate working curve for
a certain CAT(λiii, γ) [130] to the experimental data. In this kinetic region, the value of CAT is
proportional with CP* . On the other hand, for σ ≪ 1, the value of Kiiikiv may be obtained by fitting
the working curve for CAT(λiii, σ, γ) [130]. In this region, the value of CAT is independent of CP* .
For the complete characterization of the system, the value of k−iii is needed. This may be obtained
under conditions where the system is under mixed control of reactions (iii) and (iv), again by fitting
the appropriate working curve to the experimental data. Once Kiii is known, it is possible also to
o
determine EAB as follows:
RT
o
EAB = EPQ
o
+ ln K iii (2.53)
nF
Numerous examples of the application of redox catalysis to studies of the kinetics of the cleavage
of the carbon–halogen bond in the radical anions of aromatic halides have been reported [131,135]
(see also Chapter 24). Other examples include the fragmentation of tert-butyl radicals from the radi-
cal cations of NADH model compounds [136], the reduction of CO2 [137], and the cleavage of the
carbon–nitrogen bond in the radical anions of 1,1-dinitroalkanes [138].
Another application of redox catalysis is the study of dissociative electron transfer reactions
(Scheme 2.8). The resulting free radical R· may undergo either of two reactions, coupling with the
mediator radical anion (iii) or reduction to R− (iv) [134]. The coupling reaction is usually considered
as unwanted since the mediator is irreversibly consumed in this step. The reaction is, however, syn-
thetically useful [134].
A + e– A – (EoA/A –) (i)
kii
A –+ R – X A + R + X– (ii)
kiii A – R– (iii)
–+ R
A
kiv A + R– (iv)
SchEME 2.8 Reduction of alkyl halides by redox catalysis.
The competition between reactions (iii) and (iv) is usually described by the magnitude of the
parameter q given as follows, which may be determined, for instance, by LSV [139,140]:
kiv
q= (2.54)
kiii + kiv
It is seen that q = 0 for a clean coupling reaction and that q = 1 for a clean electron transfer reaction.
The value of kiii is close to that for a diffusion-controlled process, whereas the value of kiv increases
o
when EA/ A•−
moves in the negative direction. Accordingly, a plot of q versus EAo /A• − will give rise
q
to an S-shaped curve from which the potential E1/2 corresponding to q = 0.5 may be determined.
q
Once the value of E1/2 is known, the standard potential for the reduction of R· may be determined by
application of the Marcus theory [134].
8. hemical Reactions Following Quasireversible

C
or Irreversible Electron Transfer Reactions
Although processes of this kind are often met in practical work, the presentation of the theoretical
data associated with these reactions is beyond the scope of this chapter. The reader is referred to
the original literature for details [19,141]. When studied under purely kinetic conditions as defined
earlier, processes belonging to this category are usually observed to result in values of Ep − Ep/2
larger than those given, for instance, in Equations 2.43 and 2.44. The analysis of the experimental
data typically includes the simulation of working curves that take into account also the effect of ko
and α. In spite of the fact that the description of the system now involves ko and α in addition to the
usual kinetic parameters, it is often possible to gain information about all the parameters by a stra-
tegic variation of ν, CA* , and CX* . An illustrative example is the dimerization of 2,5-diaryl-1,4-dithiin
radical cations [124].
9. General Remarks and Conclusions

The applications of LSV and CV to the study of chemical processes following an electron
transfer reaction are so numerous that a review of the subject is clearly beyond the scope of
this chapter. The examples were selected to demonstrate the application of the techniques in
practical work. Although obvious, it should be emphasized that electrochemical reactions are
not different from any other chemical reaction and, therefore, that the whole arsenal of methods
of attack known from conventional kinetics may be used in the characterization of the process.
This includes, not least, the effect of temperature [100,127,142–144] and studies of kinetic iso-
tope effects [144,145].
E. LIMITING EXpErIMENTaL FaCTorS

The shape and position of the voltammogram depends not only on the kinetics and thermodynamics
of the electrochemical reaction, but is affected also by the design of the voltammetry cell and the
potentiostat. Closely related to this is the question of measurement precision.
1. The Cell and the Working Electrode

Two problems may arise at low ν. The first of these is related to the assumption that mass transport is
caused by diffusion only. If we approach, during a voltage sweep, potentials that cause conversion of A,
a diffusion layer starts to develop. At a planar electrode, assuming linear diffusion, its thickness δ
increases with time t as given in the following:
δ = πDAt (2.55)

This Nernstian definition of δ assumes a linear approximation of the concentration profile with its
slope equal to that found at the electrode surface [146]. Other formulations are possible [146], and
one of them is used in Section IV.A.3 in Chapter 1, Equation 1.149.
When δ becomes larger than a few tenths of a millimeter, natural convection begins to inter-
fere, and the assumption of diffusion as the only means of mass transport is no longer valid. For
typical values of DA (10 –5 cm2 s−1), this happens when t is of the order of 10 s, corresponding to
ν = 0.2 V s−1 for a CV sweep with Einitial − Eswitch = 1 V. At times larger than approximately 1 min,
or ν approximately less than 0.025 V s−1, the deviations from pure diffusion are so pronounced and
unpredictable that the measured current cannot be related to a practical theoretical model. Only
recently, the effect of natural convection on CV was modeled by a stagnant convection layer [147].
This influence of natural convection at low ν may be reduced by using properly shielded working
electrodes [148] (Figure 2.19), which are, however, difficult to handle in practical work. In particu-
lar, the replacement of electrolyte in the diffusion layer after recording a cyclic voltammogram
proves impractical.
Another problem at low ν is the so-called edge-effect observed when the thickness of the diffu-
sion layer at an unshielded working electrode is comparable to its diameter [149,150]. At the edges,
the diffusion of material to and from the electrode is not limited to being linear as illustrated in
Figure 2.20, and it is seen that the deviations become progressively larger when the diameter of the
electrode becomes smaller until, in the limit, the transport may be described as hemispherical dif-
fusion. This applies for the so-called ultramicroelectrodes, and it is advantageously used with such
devices to improve diffusional transport to the electroactive surface (see Section III). By inspec-
tion of Figure 2.20, it is easily understood that mass transport close to the edges is more effective
than at the central part of a circular electrode, and accordingly, the current density (e.g., in units of
mA cm−2) increases when the diameter of the electrode decreases.
The effect of this change in the diffusion pattern on the voltammogram for a reversible electron
transfer reaction, Equation 2.1, is shown in Figure 2.21. It is seen that the gradual change of the dif-
fusion pattern has a profound influence not only on the magnitude of the current density but also on
the appearance of the voltammogram, which gradually changes to the S-shaped curve characteristic
FiGURE 2.19 Schematic of a shielded working electrode. The arrows illustrate the diffusion pattern below
the electrode.
FiGURE 2.20 Schematic of the diffusion pattern below electrodes with decreasing diameters of the electrode
surface (from left to right).
for hemispherical diffusion [150]. In the latter case, the diffusion of material away from the elec-
trode is so effective that a reverse current for the reoxidation of B to A cannot be observed even, as
in this case, when B is perfectly stable in the solution.
At high ν, the relative positions of the three electrodes need to be optimized and the size of the
working electrode to be reduced in order to minimize resistance and capacitance problems [151].
The quality of the potentiostat, usually reflected by the rise time, also becomes critical at high ν.
The two factors are actually not separable since the electrochemical cell is inherently a part of the
total electronic circuit.
2. Uncompensated Solution Resistance, Ru

The Ru problem in LSV and CV has received considerable attention [152–159]. The electrode poten-
tial during LSV for a sweep in the negative direction is described by Equation 2.56, where i is the
current flowing at the time t.
Emeasured = Einitial − νt + iRu (2.56)
This equation suggests that the real electrode potential Ereal can be determined only under condi-
tions where the last term (the iR-drop) vanishes.
A first countermeasure is to reduce Ru by minimizing the distance between working electrode
and reference electrode tip, while avoiding diffusion shielding and increasing the conductivity of
the electrolyte. Then, the concentration of the electroactive species may be decreased, to decrease i.
In many situations, especially in organic electrolytes, still an appreciable iRu remains. Thus, the
problem is to correct Emeasured for the contribution of iRu. This is normally accomplished by a positive
feedback circuit incorporated into the potentiostat, which adds a fraction of the current follower out-
put to the voltage provided by the function generator. If the feedback resistance Rf is exactly equal
to Ru, the iRu term in Equation 2.56 is compensated for and Emeasured is equal to Ereal. The problem
then is the selection of the value of Rf. Although this can be accomplished by direct measurement of
Ru and other techniques [152,153], a simpler procedure is desirable for the level of sophistication of
most electrochemical studies. Such a simple and convenient method is to adjust the feedback circuit
until the output of the current follower goes into oscillation and then to back off slightly [159]. This
method is quite effective for electrodes with diameters less than 2 mm as long as ν is not larger than
about 100 V s−1. For high sweep rate experiments, specialized iRu-drop correction techniques have
been employed [49b,d,e].
Unfortunately, the iRu effect in CV affects the shape of the current/potential curves in a way
similar to the effect of quasireversibility (increase in ΔEp; see Section II.D.8). How, then, can we
prove the absence of iRu for quasireversible voltammograms?
Since iRu increases for a given electrolyte and a fixed positioning of the electrodes with i, any such
artifact linearly increases with the substrate concentration C*A. Within a series of voltammograms
0.8
0.6
0.4
iA–1 (mA cm–2)

0.2
0.0
–0.2
–0.4
–0.6
–1.0 –1.2 –1.4 –1.6 –1.8 –2.0
(a) E (V)
1.0
0.8
0.6
iA–1 (mA cm–2)
0.4
0.2
0.0
–0.2
–0.4
–0.6
–1.0 –1.2 –1.4 –1.6 –1.8 –2.0
(b) E (V)
3.0
2.5
2.0
iA–1 (mA cm–2)
1.5
1.0
0.5
0.0
–0.5
–1.0
–1.0 –1.2 –1.4 –1.6 –1.8 –2.0
(c) E (V)
24
20
16
iA–1 (mA cm–2)
12
8
4
0
–4
–1.0 –1.2 –1.4 –1.6 –1.8 –2.0
(d) E (V)
FiGURE 2.21 Simulated (DigiSim®) cyclic voltammograms for a reversible one-electron reduction with
Eo = −1.5 V at electrodes with (a) r = 0.7 mm, (b) r = 0.05 mm, (c) r = 0.01 mm, (d) r = 0.001 mm. Note that
the y-axis displays the current density (in mA cm−2) in order to facilitate the comparison of voltammograms
obtained at different surface radii. For other simulation parameters, see Figure 2.3.
recorded at different C*A , ΔEp should be constant if any iRu drop is absent. On the other hand, a
concentration dependence of ΔEp indicates that iRu significantly contributes to the experimental
outcome. Note that this approach is no longer valid if reactions with second- or higher-order kinetics
are coupled to the electron transfer.
The concentration dependence of iRu has further been used to correct ΔEp values recorded as a
function of v and C*A [160].
3. Importance of Precision in Potential Measurements

The precision of Ep required for comparison with literature values is of the order of ±5 mV. This can
easily be accomplished by commercial computer software.
In other cases, including LSV analysis (see Section II.D.4) and studies of the effect of small
structural changes such as deuterium isotope effects, the required precision is ±0.5–1 mV or better.
This can easily be appreciated by considering that the theoretical values of, for instance, dEp/dlogν
in LSV, Equation 2.40, differ by only 10 mV for the first- and second-order follow-up reactions.
Similarly, it has been found that 2,7-d2-pyrene is only 1.5 ± 0.2 mV more difficult to reduce than
pyrene itself [161]. Such a high precision requires highly stable reference electrodes and advanced
data treatment including averaging of measurements, baseline corrections, and sophisticated peak
fitting routines.
Another approach involves the application of derivative LSV or DCV (Figure 2.10b). These tech-
niques allow a precision of the order of ±0.2 mV to be realized during peak potential measurements
[28–30,35]. The feature giving the high precision is that the peak potential is measured at the point
where the steeply descending first derivative crosses zero.
4. Background Currents
The faradaic current, which is usually of interest in the analysis of cyclic voltammograms with
respect to electron transfer–coupled organic reactions, is only one contribution of the total current
through the electrode. Other components are related to double-layer charging [158] and impurities.
Conventionally, these unwanted currents are designated as background current.
For precise current data, as well as an adequate analysis of the shape of a cyclic voltammogram,
the background current must be subtracted from the raw current/potential curve. Most commercial
instruments have simple procedures for this. However, the respective background curve must be
recorded under identical or at least as similar as possible conditions as the substrate curve. This
can be achieved by recording the background first and then adding the substrate to the electrolyte
in the cell (possibly in several portions to generate solutions of increasing concentration after each
addition) without changing the cell geometry. Still, particularly for signals close to the limits of the
accessible potential window (low signal-to-background ratio), artifacts may be introduced by sub-
traction. Detrimental effects can also be observed if the substrate slightly changes the double layer,
for example, by adsorption phenomena.
F. CoMpUTEr-BaSED METHoDS For ANaLYSIS oF VoLTaMMETrIC DaTa

Although relevant information can be extracted from voltammograms by the techniques described
in Sections II.C and II.D already, the analysis of CV data is traditionally linked to computer applica-
tion. This supports data acquisition, signal processing, and the determination of kinetic and thermo-
dynamic parameters of interest. It is particularly true for cases where the relation between data and
information is nonlinear, the chemistry is described by several parameters (e.g., rate constants), and
these are possibly correlated. Then, the task at hand (sometimes called the inverse problem) may
need extensive computation. Some aspects with respect to simulation of electrochemical processes
are discussed in Section III.D in Chapter 5. Here, we restrict the treatment to practical comments
and the case of CV.
Several approaches were already developed several decades ago and include, for instance, pat-
tern recognition [162], the recording of current–time profiles of the form Δlni/Δlnt versus t for
mechanistic classification [163], as well as nonlinear regression techniques [164–167]. Efforts have
also been made to use knowledge-based systems for the elucidation of reaction mechanisms [168].
More recently, artificial neural networks [169] and wavelet transformation [170] were applied, but
often, such work is devoted mainly to analytical electrochemistry. The application of support vector
machines showed that analysis of full voltammograms rather than only selected prominent points
(peaks) provides better estimation of diffusion coefficients [171].
As examples for more widely used advanced techniques, we discuss convolution and fitting
approaches.
1. Semi-Integration and Convolution Techniques

The essential feature of these methods is that semi-integration [172–177] or calculation of the con-
volution integrals, Equation 2.57 [156,178–184], results in the transformation of the voltammogram
into what has been called a neopolarogram. Experimentally, the convolution integral may be evalu-
ated by using the Riemann–Liouville algorithm, Equation 2.58 (see also Reference 1). The resulting
curve is given by Equation 2.59, where Il is defined in Equation 2.60.
t
1 i(u)
I (t ) = 1/ 2
π ∫ (t − u )
1/ 2
du (2.57)
0
1/ 2 t / ∆
∆  t 
1/ 2
t
1/ 2
 
I (t ) =  
π ∑ j =1
(i( j∆) + i( j∆ − ∆))   − j + 1  −  −
 ∆
  ∆
j




(2.58)

RT I l − I (t )
E = E1/2 + ln (2.59)
nF I (t )
I l = nFADA1/ 2CA* (2.60)
Logarithmic analyses can be carried out on the neopolarogram in much the same way as with
classical polarography (see Section V). Examples that illustrate the application of the convolution
technique include not only simple quasireversible electron transfers [185] but also more complex
cases such as the reversible dimerization of radical cations [121], the study of dissociative electron
transfer reactions [186,187], and investigations of the possible potential dependence of the transfer
coefficient α [184,188,189].
2. Fitting Simulated to Experimental Voltammograms

The advances in computer technology have, in more general terms, stimulated the development of
techniques that use more than just a few data points, such as Ep, Ep/2, and ip, along the voltammet-
ric wave. Thus, after selection of a proper mechanistic hypothesis, a voltammogram is calculated
(predicted; see Chapter 5) and, by means of variation of the kinetic, thermodynamic, and transport
parameters provided to the simulation, fitted to the respective experimental curve. This would at
first glance seem to be an advantage. However, it should be brought in mind that the problems
originating from, for instance, background currents and nonproper adjustments of the electronic
equipment remain and it becomes even more crucial to avoid these artifacts. For less ideal experi-
mental data, some skill is required to incorporate parameters, for instance, for the uncompensated
electrical solution resistance (see Section II.E.2) and the double-layer capacity (see Chapter 1) in the
data treatment. Furthermore, this approach can be dangerous if too many unknown parameters are
35
30
25
20
i (μA)
15
10
–5
0.0 0.2 0.4 0.6 0.8 1.0
+
E (V vs. Ag/Ag )
FiGURE 2.22 Cyclic voltammetry data (solid line) for the oxidation of 2,4-dimethyl-3-ethylpyrrole in
MeCN at ν = 0.2 V s−1 and the simulated curve corresponding to the mechanism shown in Scheme 2.9.
(Reprinted from Hansen, G.H. et al., Electrochim. Acta, 50, 4936, 2005.)
subject to (possibly automated) variation, and overfitting may pretend good coincidence between
experimental and fitted curves while the parameter values are not reliable (see also recommenda-
tions in Section III.D in Chapter 5).
The opinion of the authors of this chapter is that trends in the kinetic data and their origin are
often easier to locate when a more classical approach to the data analysis is taken. Still, with appro-
priate care, fitting voltammograms can be a valuable tool. It should be mentioned here also that
the commercial software package DigiSim® offers the possibility to fit simulated voltammograms
directly to experimental ones. A particular problem is that voltammograms, even for very differ-
ent mechanisms, are very similar, and for that reason, the method should also be used with care.
Also in this case, it is recommended that voltammograms obtained with different scan rates and a
variety of substrate and reagent concentrations are included in the fitting procedure. In our opinion,
the method works best when the voltammogram presents structural features that are unique for
the mechanism in question. An example, the oxidation of 2,4-dimethyl-3-ethylpyrrole, is shown in
Figure 2.22.
The additional structural feature in this case is the trace crossing observed at 0.6 and 0.15 V,
respectively, which is caused by slow proton transfer from the initially formed dimer to the unoxi-
dized substrate. The overall reaction scheme is summarized in Scheme 2.9.
The values of the rate and equilibrium constants for the proton transfer reactions resulting from
the curve fitting were k2+,m = 6∙103 M−1 s−1, K2+,m = 7 and k+,m = 4∙103 M−1 s−1, K+,m = 0.15, and it is
seen that k2+,m and K2+,m are both found to be larger than k+,m and K+,m, respectively, as intuitively
expected. The values of the two proton transfer rate constants compare favorably with those already
reported for alkylpyrroles [191,192].
III. ULTRAMicROELEcTRODES AND ScANNiNG

ELEcTROchEMicAL MicROScOPY
A. ULTraMICroELECTroDES
The discussion in the Section II is mainly concerned with electroorganic reactions at macroscopic
electrodes with sizes in the mm range. Then, linear diffusion with flux of material perpendicular to
+
Et Me Et Me
–
–2e
2 2
Me 2e– Me
N N
H H
PyrH PyrH+
+ Et Me
Et Me H
H
kdim
Me N + Me
2
Me
N +N H
H
H Me Et
PyrH+ +PyrH-HPyr+
Et Me Et Me
H Et Me H Et Me
H k2+,m; K2+,m
Me N + Me + Me N + Me + H
+N Me
N
H Me
H N N+ H
H H
Me Et H Me Et H
+
PyrH-HPyr+ PyrH Pyr–HPyr+ PyrH2+
Et Me Et Me
H Et Me H Et Me
k+,m and K+,m
Me N + Me + Me N Me +
N N H
H Me Me
H N H N+ H
Me Et H Me Et H
+
Pyr-HPyr PyrH Pyr-Pyr PyrH2+
Et Me Et Me + Et Me
H H H
–e– –e–
Me N Me Me N Me Me N + Me
N e– N e– +N
H H H
Me Et Me Et Me Et
Pyr-Pyr Pyr-Pyr+ +Pyr-Pyr+
Et Me
H
kp
N+ Products
Me Me
+N
H
Me Et
+Pyr-Pyr+
SchEME 2.9 The initial steps for the oxidation of 2,4-dimethyl-3-ethylpyrrole (kryptopyrrole). (Adapted
from Hansen, G.H. et al., Electrochim. Acta, 50, 4936, 2005.)
the electrode surface is ensured. If the electrode size becomes smaller (Figure 2.20) and reaches,
within the time scale of the experiment, the thickness of the diffusion layer (see Equation 2.55),
linear diffusion can no longer be assumed, and the term ultramicroelectrode is used. Some aspects
of these devices are covered in Chapters 1 and 10. Nowadays, even electrodes with low nanometric
dimensions (nanoelectrodes) are prepared and used in electrochemical studies [193].
The definition of an ultramicroelectrode is somewhat arbitrary and, with reference to the com-
mon disk geometry, is currently meant to describe electrodes with diameters of about 10–20 μm or
less [131,150,151,194,195]. The electrochemical response at ultramicroelectrodes can be classified
into two categories depending on the value of ν, and a rational definition of ultramicroelectrode
behavior may be based on these [196].
At low ν, the transport to and from an ultramicroelectrode is best described as hemispherical
diffusion; this results in a faradaic current that greatly exceeds that expected for linear diffu-
sion [150,197] (see Section II.E.1 and Figure 2.21). An important feature of the voltammogram
shown in Figure 2.21d is the absence of a peak. Instead, the current reaches a plateau indicat-
ing that a steady-state has been obtained. The steady-state current for an ultramicroelectrode
inserted in a large insulating shaft (Figure 2.20c) is given by Equation 2.61, where r is the radius
of the electrode surface [198]. The effective transport resulting from hemispherical diffusion
also results in an electrode system that is under certain conditions relatively insensitive to natu-
ral convection [196]:
i = 4nFrDACA* (2.61)
The second category of electrode response for an ultramicroelectrode occurs at high ν. Under these
conditions, linear diffusion is operative, and the response does not differ from that of conven-
tional electrodes with surface diameters in the 0.1–2 mm range. However, the effects of double-layer
charging (see Chapter 1) and solution resistance are considerably reduced owing to the small size
of the electrode. The transition from low to high ν is shown in Figure 2.23 for an electrode with
r = 1 μm at ν = 0.03, 10, 500, and 100,000 V s−1, respectively.
Although the use of ultramicroelectrodes is not restricted to any specific measurement tech-
nique [131,151,194,199], only applications in the context of CV at high sweep rates will be con-
sidered here (see also Section IV). For the studies of reaction kinetics using ultramicroelectrodes
under steady-state conditions, the reader is referred to the original literature [150,195,200] and
Section III.B.
1. Determination of Eo′ for the A/B Redox Couple When B Is Highly Reactive
The perspective in using very high voltage sweep rates during CV has been demonstrated by several
authors [131,151,201–205]. Historically, it is of interest to notice that Perone already in 1966 used
sweep rates up to 50,000 V s−1 [201] in studies of the electron transfer rates for inorganic redox
couples, the 1,000,000 V s−1 mark was passed in 1988 [204,205], and 10 MV s−1 have been reached
recently (see Section II.B.3). Cyclic voltammograms for the reduction of anthracene in MeCN at
sweep rates up to 100,000 V s−1 [203] are illustrated in Figure 2.24. It is seen that the contribu-
tion from the double-layer charging current increases relative to the contribution from the faradaic
current with increasing sweep rate. This is because the double-layer charging current is directly
proportional to the sweep rate, whereas the faradaic current increases only with the square root of
the sweep rate (Equation 2.13). Subtraction of a background curve obtained in the absence of the
substrate may eliminate the problem [206].
An obvious application of high sweep rates is the determination of Eo values for A/B couples
where B undergoes a chemical reaction so fast that it cannot be outrun by the sweep rates applicable
to conventional electrodes [49a,101,207]. Once Eo is known, the rate constant may be determined
from LSV relations of the type already given (Equations 2.45 and 2.46).
iν–1/2 (nA V–1/2s1/2)

2
–1
–1.0 –1.2 –1.4 –1.6 –1.8 –2.0
(a) E (V)
0.3
0.2
iν–1/2 (nA V–1/2s1/2)
0.1
0.0
–0.1
–1.0 –1.2 –1.4 –1.6 –1.8 –2.0
(b) E (V)
0.100
0.075
iν–1/2 (nA V–1/2s1/2)
0.050
0.025
0.000
–0.025
–0.050
–1.0 –1.2 –1.4 –1.6 –1.8 –2.0
(c) E (V)
0.075
0.050
iν–1/2 (nA V–1/2 s1/2)
0.025
0.000
–0.025
–0.050
–1.0 –1.2 –1.4 –1.6 –1.8 –2.0
(d) E (V)
FiGURE 2.23 Simulated (DigiSim) cyclic voltammograms for a reversible one-electron reduction with
E o = −1.5 V at an electrode with r = 0.001 mm and (a) ν = 0.03, (b) ν = 10, (c) ν = 500, (d) ν = 100,000 V s−1.
For other simulation parameters, see Figure 2.3. Note that units of iν−1/2 are used at the y-axis to facilitate the
comparison of voltammograms obtained at different sweep rates.
(a–d)
200 nA
–2.0 –2.5
E (V) vs Ag/AgClO4
(e) (f ) (g)
500 nA 900 nA 1600 nA

–2.0 –2.5 –2.0 –2.5 –2.0 –2.5
E (V) Ag/AgClO4
FiGURE 2.24 Cyclic voltammograms for the reduction of anthracene (2.22 mM) in MeCN containing
Et4NClO4 (0.6 M) at a gold electrode with r = 6.5 μm and (a) ν = 1,000, (b) ν = 2,000, (c) ν = 5,000, (d) ν =
10,000, (e) ν = 20,000, (f) ν = 50,000, and (g) ν = 100,000 V s−1. (Reprinted with permission from Howell, J.O.
and Wightman, R.M., Anal. Chem., 56, 524–529. Copyright (1984) American Chemical Society.)
2. Determination of Heterogeneous Electron Transfer Rate Constant

It follows from the discussion of electron transfer reactions in Section II.C that a reversible pro-
cess when studied by CV inevitably passes into the quasireversible regime at some value of ν
when ν is allowed to increase. For ko = 3 cm s−1, a value typical for many aromatic hydrocarbons,
for example [71], it is seen from Equation 2.27 that this happens at approximately ν = 170 V s−1.
Thus, studies of electron transfer rates in this region require voltage sweep rates in the range
200–1000 V s−1. Ultramicroelectrodes are superb for this purpose as demonstrated, for example,
in a study of the oxidation of ferrocene [208]. Peak potential separations recorded at sweep rates
between 500 and 3000 V s−1 at an electrode with a surface diameter of 10 μm over a range of
substrate concentrations resulted in k o equal to 1.10, 1.13, and 1.13 cm s−1 (see, however, a criti-
cal review that compares such values determined under various conditions [209]). A more recent
example is the oxidation of selenanthrene and related compounds [210].
3. Kinetics of Rapid Follow-Up Reactions

Ultramicroelectrodes are excellent tools also for the study of the kinetics of fast follow-up reac-
tions provided that the high sweep rates needed do not bring the electron transfer process into the
quasireversible region. Thus, a reaction that, during a study with conventional electrodes, is under
purely kinetic conditions may at high sweep rates be studied under mixed diffusion and kinetic
control using the approach described in Section II.D.3.
An early example of this approach is the study of the interconversion of the A and B forms of
bianthrone [211]. The stable isomer at ambient temperature is the yellow A form, which is equili-
brated with the green B form as the temperature is increased. Reduction of A produces A• −, which
rapidly undergoes a conformational change to the B-like radical anion. The formal potentials for the
two forms differ by about 230 mV for the isomers of 1,1′-dimethylbianthrone in DMF at 361 K. The
rate constant for the conversion of B to A could be determined to be equal to 500 s−1 under these
conditions by comparing experimental cyclic voltammograms obtained at 200, 500, 1,000, and
5,000 V s−1, using 5 μm Pt disk electrodes, to theoretical voltammograms obtained by digital simu-
lation. Other examples include studies of the cleavage of the carbon–halogen bond in the radical
anions of aromatic halides [205,212] and the RR-dimerizations of the N,N-dimethylaniline radical
cation [213] and diphenylamine radical cation [214].
4. Voltammetry in Electrolytes with Low Conductivity

Already early experiments with ultramicroelectrodes proved the usability in situations of extremely
low conductivity: thus, electrochemistry in the gas phase was accomplished [215]. The low absolute
currents through these devices can be sustained without the use of a supporting electrolyte. In addi-
tion, the iRu drop at a disk ultramicroelectrode is proportional to the radius [215b] and very low for
small sizes, even if the uncompensated resistance Ru is large. Thus, voltammetry in solutions with
low concentrations of supporting electrolytes is based on diffusional and migrational transport and
has been used to study the effects of the ionic concentration and of ion pairing on organic electrode
reactions [216] and their mechanisms (e.g., aryl halide bond cleavage [216c] or anthraquinone radi-
cal anion disproportionation [216b]).
B. AppLICaTIoN oF SCaNNING ELECTroCHEMICaL MICroSCopY

For STUDIES oF REaCTIoN KINETICS
Scanning electrochemical microscopy (SECM) [217] is a member of the growing family of scan-
ning probe techniques. In SECM, the tip serves as an ultramicroelectrode at which, for instance, a
radical ion may be generated at very short distances from the counter electrode under steady-state
conditions. The use of SECM for the study of the kinetics of chemical reactions following the elec-
tron transfer at an electrode [217] involves the SECM in the so-called feedback mode [218], where
the counter electrode serves to collect the primary electrode intermediate generated at the ultrami-
croelectrode (Figure 2.25).
At sufficiently small distances between the ultramicroelectrode tip and the counter electrode,
the time of diffusion from the tip to the counter electrode is of the same order as the lifetime of
the intermediate, which makes possible the detection of the intermediate at the counter electrode.
The upper limit for first-order rate constants is close to 105 s−1 and for second-order rate constants
108–109 M−1 s−1 [219]. The relationship between the distance and the kinetics of the follow-up reaction
is expressed by the dimensionless parameter K, as follows, where k is the rate constant of the chemi-
cal reaction, r is the radius of the tip, and d is the distance between the tip and the counter electrode:
kd 3
K= (first-order rate law) (2.62)
rDA
kCA* d 3
K= (second-order rate law) (2.63)
rDA
Tip of ultramicroelectrode
e–
k
A B Products
e–
Counter electrode
FiGURE 2.25 The principle of the application of scanning electrochemical microscopy for studies of reac-
tion kinetics.
At very short distances, depending on the rate of the chemical reaction, essentially all B gener-
ated at the tip is detected by the counter electrode. When the distance gradually is made larger,
an increasing fraction of B reacts to products until, in the limit, no B is detected at the counter
electrode. By plotting the ratio between the current at the counter electrode ic and the tip cur-
rent it, −ic/it, as a function of the distance, information about the kinetics of the follow-up reac-
tion may be obtained by fitting the data to the appropriate working curve −ic/it versus log K
(Figure 2.26). Thus, the parameter −ic/it plays a role equivalent to that, for instance, of the collec-
tion efficiency in rotating ring-disk electrode (RRDE) voltammetry (Section VI.C). The distance
between the tip and the counter electrode is determined by a calibration procedure including
the recording of −ic/it for a reversible redox couple for which B is stable and fitting the data to a
working curve [220].
An advantage of SECM is that it is a steady-state technique that does not require the measure-
ments of transient currents. The technique also offers the same advantage as, for instance, double
potential-step chronoamperometry (DPSCA) (Section IV.A) in that the potential of the tip electrode
can be made sufficiently negative that the heterogeneous electron transfer process proceeds at the
diffusion-controlled rate.
An example of the application is the oxidation of trans-anethole [trans-1-(4-methoxyphenyl)
propene], the radical cation of which by LSV was found to undergo rapid RR-dimerization
(through C-2). The rate constant measured by SECM is as high as 4·108 M−1 s−1 [221]. The fit of the
experimental data to the working curve is shown in Figure 2.26. The SECM technique has also
been used to determine the rate constant for the dimerization of the radical anions of acrylonitrile,
the prototype example of electrohydrodimerization (Chapter 17). The value of k was found to be
6·107 M−1 s−1 [222].
SECM-like methodology was used to map concentration profiles in front of a larger electrode
[223]. Recently, an extensive compilation of SECM modes and their application to determine reac-
tion rates with lateral resolution across a surface has been provided [224], including those of mono-
layers, polymers, bioactive materials, membranes and tissues, enzymes, and individual cells.
0.9
0.8
0.7
0.6
Is/IT
0.5
0.4
0.3
0.2
0.1
0
–1 –0.5 0 0.5 1 1.5 2 2.5 3 3.5 4
log(K)
FiGURE 2.26 SECM working curve for the RR-dimerization mechanism together with experimental points
obtained for the oxidation of trans-anethole. The ratio IS/IT at the figure corresponds to −ic/it in the text, and
K is defined in Equation 2.63. (From Demaille, C. and Bard, A.J., Acta Chem. Scand., 53, 842, 1999. With
permission.)
IV. POTENTiAL-STEP AND CURRENT-STEP METhODS

A. CHroNoaMpEroMETrY aND DoUbLE PoTENTIaL-STEp CHroNoaMpEroMETrY
When the potential of a planar electrode is suddenly shifted from a value at which no current flows
to a value where the electron transfer, Equation 2.1, proceeds at the diffusion controlled rate, the
current–time behavior is given as follows, where ic is the double-layer charging current [1,152]:
nFACA* DA1/ 2
i= + ic (2.64)
(πt )1/ 2
When conventional electrodes with diameters between 0.1 and 2 mm are used, the latter quantity
has usually decayed to zero after 0.5 ms or less and may be neglected in experiments lasting 1 ms
or more. This decay time is reduced to the microsecond time regime when ultramicroelectrodes
are used [101,131,225]. According to Equation 2.64, which for ic = 0 is known as the Cottrell equa-
tion, the current approaches zero when the time approaches infinity. However, undisturbed linear
diffusion can be maintained only over rather short time intervals unless special precautions are
taken (see Section II.E.1), and the measurements of current–time curves, called chronoamperom-
etry (CA), are often complicated by additional modes of transport. Therefore, the use of prop-
erly shielded electrodes [148] should be considered in chronoamperometric experiments exceeding
approximately 1 s. The mathematical formalism for CA has been developed also for the application
of ultramicroelectrodes [226] including the transition from nonstationary (increasing diffusion layer
thickness) to steady-state transport [198a,227].
The application of CA for monitoring the progress of chemical reactions following the hetero-
geneous electron transfer is limited by the nature of the process. As it appears from Equation 2.64,
the only parameter that may be affected by a follow-up reaction is n. Thus, important mechanisms
such as the eC (Scheme 2.2) and eC(dim) (Scheme 2.3) cannot be characterized by this type of
experiment. However, it has been demonstrated that if the potential is shifted to values insufficient
for diffusion-controlled electron transfer, rate constants, for instance, for the eC mechanism, may be
determined [228]. Working curves have been calculated relating the apparent number of electrons
exchanged napp/n to the dimensionless parameter log(kt), where k is the first-order or pseudo-
first-order rate constant for the chemical step:
napp it 1/2
= 1/2actual (2.65)
n itdiff.control

An example of the application of the technique is a study of the kinetics of the benzidine rearrange-
ment, which follows the reduction of azobenzene in acidic aqueous ethanol [229]. The approach has
been further developed and extended to encompass the automatic recording of three-dimensional
i–E–t curves [230]. However, experiments of this kind may be hard to perform with high precision
because of difficulties in the accurate control of the potential in the region close to Eo.
If, during the chemical step, a product is formed that undergoes further electron transfer at the
applied potential, as, for example, in the eCe- and eCeh-type mechanisms (Scheme 2.2), or if the
electroactive substrate is regenerated in a catalytic process (Scheme 2.7), the value of napp/n depends
on k even under conditions in which the heterogeneous electron transfer is diffusion controlled
[66,139]. It is easily understood that napp/n approaches unity when k decreases toward zero, and a
higher value, depending on the mechanism, when k increases.
The competition between heterogeneous electron transfer (eCe) and electron transfer in solution
(eCeh) in the second e step (Scheme 2.2) and the possibility of distinguishing between these two
pathways have been analyzed in detail [85,231]. It was concluded that the eCeh pathway dominates
over the eCe pathway unless the measurement time is kept below approximately 10 –7 s. The appli-
cation of CA to determine the rate constants in more complicated reaction schemes, such as, for
example, the eCeCe-type mechanism, has been addressed as well [232].
An important extension of CA, double potential step chronoamperometry (DPSCA), involves a
second potential step to a potential at which B is converted back to A at the diffusion-controlled
rate [1,152,233,234]. The potential–time program and the current–time curve are illustrated in
Figure 2.27.
The current is measured twice, the first time at t = tf(if ) and the second time usually at t = 2tf(ib).
For a simple electron transfer reaction, the ratio −ib/if is independent of tf and has the value 0.2928.
1.5
1.0 tf 2tf
i (arbitrary units)
0.5
if
E (V)
0.0 ib
–0.5
–1.0
–1.5
0 5 10 15 20 25
t (arbitrary units)
FiGURE 2.27 Double potential-step chronoamperometry; potential–time program for a potential step from
0 to −1 V (dotted line and left-hand scale) and current–time curve (full line and right-hand scale).
–2 –1 0
R log λ
1.0
0.5
0.0
log(θ[PhOH])
–5 –4
FiGURE 2.28 Double potential-step chronoamperometry working curve (top scale) for the eCeh mechanism
(full line) and experimental data (bottom scale) for the protonation of the anthracene radical anion by phenol in
DMF (0.1 M Bu4NBF4). C A* = 1 mM and C *PhOH (mM) = 9.95 (+), 18.2 (•), 40.0 (o), 78.8 (x), 100 (◻), and 200 (*).
R at the figure corresponds to RI in this chapter and λ = ktf CPhOH
*
. (Reprinted from J. Electroanal. Chem., 147,
Amatore, C., Gareil, M., and Savéant, J.M., 1–38, Copyright (1983), with permission from Elsevier.)
However, if a chemical reaction is associated with the electron transfer reaction, the ratio −ib/if
depends on tf. Working curves based on analytical solutions of the diffusion–kinetics equations have
been presented for simple mechanisms [235]. More generally, the working curves may be calculated
by digital simulation and are usually presented as the normalized current ratio RI = −ib/(if·0.2928)
as a function of log(ktf ) (first-order rate law) or log(kCA* tf ) (second-order rate law; Figure 2.28). The
value of k (or kobs) may be determined by fitting the working curve to the experimental data as dem-
onstrated in Figure 2.28 for the protonation of anthracene radical anion by phenol.
Alternatively, the rate constant may also be determined directly from the measured value of t1/2,
that is, the value of t required to obtain RI = 0.5, in a fashion analogous to that described for DCV
earlier (see Equations 2.36 and 2.37) as follows:
0.406 −1
eC mechanism: kobs = s (2.66)
t1/2
0.830 −1 −1
RR dimerization: kobs = M s (2.67)
t1/2CA*
The approximate kinetic window of DPSCA at electrodes with a diameter in the 0.1–2 mm range is
given by Equation 2.68, where k is a first-order or pseudo-first-order rate constant. With the applica-
tion of ultramicroelectrodes, the upper limit can be extended considerably [225]:
0.3 s−1 < k < 300 s−1 (2.68)

DPSCA offers two attractive features, at least. First, since the method includes potential steps to
E values at which the heterogeneous electron transfer reaction is diffusion controlled, experiments
may be performed with the iR-compensation circuit of the potentiostat switched off. Second, the
perturbation of the reaction layer is very small, which means that even a small excess of reagent
relative to substrate ensures pseudo-first-order conditions [97]. A disadvantage is that DPSCA is a
blind technique, and current caused by, for example, long-lived intermediates may erroneously be
attributed to regeneration of substrate. In such cases, it may be advantageous to use triple potential-
step CA [237] in which the current flowing after the third potential step reflects whether starting
material has indeed been formed after the second step. In general, potential-step techniques should
be used only together with a potential-sweep technique, such as CV.
Examples illustrating the application of DPSCA include the cleavage of the carbon–halogen
bond in radical anions derived from aromatic compounds [238]; the protonation of radical anions
derived from aromatic hydrocarbons [97,236,239]; the dimerization of radical anions [119,120,240],
radical cations [241], and neutral radicals [101]; and the conversion of the B form to the A form for
10,10′-dimethyl-9,9′-biacridylidene [242].
B. CHroNoCoULoMETrY aND DoUbLE PoTENTIaL-STEp CHroNoCoULoMETrY

A method analogous to CA is chronocoulometry, by which the charge Q instead of the current is
monitored as a function of time [1,152,243]. The method has found less widespread use than CA in
organic electrochemistry but offers certain advantages when, for instance, an electroactive reactant
is adsorbed at the electrode surface [243–247]. Integration of Equation 2.64 with respect to time
results in Equation 2.69, which illustrates that a plot of Q versus t1/2 results in a straight line with the
intercept Qc, that is, the charge flowing into the interfacial capacitance as a result of the potential
step. This quantity contains information about the degree of substrate adsorption at the electrode
surface.
2nFACA* ( DAt )1/ 2

Q= + Qc (2.69)
π1/ 2
The application of chronocoulometry for mechanism analysis and evaluation of kinetic parameters
is similar to the application of CA and is often based on visual comparison of experimental data
with working curves.
Double potential-step chronocoulometry [1,152,243] may be used similarly to DPSCA. The
working curves now include the charge ratio −Q b/Qf, which takes the value 0.414 for a simple
electron transfer reaction. The reductive cyclization of ethyl cinnamate (see Chapter 17) illustrates
the use of the technique [248,249].
C. CHroNopoTENTIoMETrY aND CUrrENT-REVErSaL CHroNopoTENTIoMETrY

Chronopotentiometry in its most simple form involves the measurement of the potential of the
working electrode as a function of time after the onset of a constant current, i [1,152]. Because
of the decrease in concentration of A close to the electrode, the potential changes with time, and
when the concentration is sufficiently small, a rapid potential shift is observed to the value of
another redox system or to the value for discharge of the solvent-supporting electrolyte solution
(Figure 2.29).
The time at which this rapid potential shift is observed, called the transition time τ, can, for
reversible electron transfer, be calculated from the Sand equation:
π1/ 2 nFADA1/ 2CA*

τ1/ 2 = (2.70)
2i
E1/4
τ/4 τ Time
FiGURE 2.29 Chronopotentiometry; potential–time relationship after application of a constant current.

E1/4 is the potential acquired by the electrode at time τ/4.
The complete chronopotentiometric wave is described by Equation 2.71. If t = τ/4, the third term
cancels, and Equation 2.71 reduces to Equation 2.72, which defines the quarter-wave potential E1/4
and which is equal to Eo for DA = D B:
RT D RT τ1/ 2 − t 1/ 2
E = Eo + ln B + ln (2.71)
2nF DA nF t 1/ 2
RT D
E1/4 = E o + ln B (2.72)
2nF DA
Thus, the quarter-wave potential plays the same role in chronopotentiometry [250] as the half-wave
potential E1/2 in polarography (see Section V). The mathematical formalism for chronopotentiom-
etry has been developed also for the application of ultramicroelectrodes [251].
Chronopotentiometry has found only little use in mechanistic organic electrochemistry. This is
primarily due to experimental difficulties in the accurate evaluation of the transition time. A solu-
tion to this problem includes the application of a convolution procedure [252]. Another extension
includes the application of exponential and other current–time functions, and theoretical data for
this method are now available for a number of mechanisms [253,254].
When applied to the analysis of kinetic data, chronopotentiometry is most often used in the cur-
rent-reversal mode, in which the direction of the current is changed after some time tf (Figure 2.30).
When only the direction but not the magnitude of the current is changed, the reverse transition time
τr is given as follows [255]:
tf
τr = tf ≤ τ (2.73)
3
Diagnostic criteria for a number of mechanisms have been summarized [256]. The analysis of
experimental data is most conveniently carried out with the aid of a working curve (Figure 2.31)
relating the parameters tf, τr, and the rate constant k (or kobs).
An example of the application of chronopotentiometry is the oxidation of tropylidene [258,259]
and thioxanthene [259].
E1/4
τ/4 tf tf +τr Time
FiGURE 2.30 Current-reversal chronopotentiometry; current–time program and potential–time curve.
0.33
0.30
0.20
Tr/tf
0.10
0.00
0 1 2 3 4 5
kta
FiGURE 2.31 Current-reversal chronopotentiometry working curve for the catalytic eC mechanism. The
parameter ta on the figure corresponds to tf in the text. (Reprinted with permission from Testa, A.C. and
Reinmuth, W.H., Anal. Chem., 32, 1512–1514. Copyright (1960) American Chemical Society.)
V. POLAROGRAPhY
Polarography is the term used for voltammetry with the dropping mercury electrode (DME). The tech-
nique has been discussed extensively in several textbooks and reviews [1,152,260–265] to which the
reader is referred for details concerning both theoretical problems and practical applications. The elec-
trode (Figure 2.32) was developed early in the twentieth century by Heyrovsky and was the dominating
tool in electroanalytical chemistry for several decades. Because of the low oxidation potential of mercury
(0.3–0.4 V versus SCE), the DME has been used almost exclusively for the study of reduction processes.
Compared with mercury film electrodes, the DME offers the advantage that the electrode surface is
continuously renewed. This property reduces undesirable surface effects caused by adsorption.
(–)
(+)
FiGURE 2.32 Schematic of a dropping mercury electrode.
A typical current–voltage curve, a so-called polarogram, obtained at the DME as a result of a

slow (1–10 mV s−1) linear potential sweep in the negative direction is shown in Figure 2.33.
The shape of the polarogram illustrates clearly the expansion of the electrode surface during the
lifetime of the individual mercury drops. Two parameters are generally used to characterize the
polarogram, the half-wave potential E1/2 and the limiting current ilim. For a simple electron transfer
reaction, the height of the current plateau, measured as the mean current during the drop lifetime id,
is given by the Ilkovic equation:
id = 607nm 2/3t 1/6 DA1/2CA* (2.74)
i i
E1/2
ilim
1i
2 lim
(+) (+)
0 0
(–) (–)
0 (V vs. Ref ) E
FiGURE 2.33 Polarogram obtained at the dropping mercury electrode.

The subscript d indicates that the surface concentration of substrate is dependent only on the
diffusion of material to the electrode, m is the mass (mg) of mercury flowing out of the capillary
per second, and t is the drop lifetime (s). Polarographic current data are frequently normalized
with respect to CA* , m2/3, and t1/6 to eliminate the parameters associated with a particular experiment.
The current normalized as in the following equation is called the diffusion current constant I:
id
I= = 607nDA1/2 (2.75)
C m 2/3t 1/6
*
A
If the electron transfer, Equation 2.1, is reversible, the complete polarographic wave may be
described by a modified Nernst equation [260,261]:
RT f DB1/2 RT id − i
E = Eo + ln A 1/2 + ln (2.76)
nF fB DA nF i
If i = 0.5 id, the third term in Equation 2.76 cancels, and the expression reduces to the following
equation that defines the half-wave potential E1/2:
RT f DB1/2
E = E1/2 = E o + ln A 1/2 (2.77)
nF fB DA
When fA = f B and DA = D B, E1/2 equals Eo. It is seen also that E1/2 is independent of the substrate
concentration. Introduction of E1/2 into Equation 2.76 results in the more convenient form, where the
constant 0.0591 refers to T = 298 K, as follows:
RT id − i 0.0591 i −i
E = E1/2 + ln = E1/2 + log d (2.78)
nF i n i
The reversibility of the electron transfer reaction may be tested via this equation, which pre-
dicts that a plot of E versus log(( id − i ) / i ) results in a straight line with the slope 0.0591/n V
(at T = 298 K) for a reversible redox system. Slopes smaller than 0.0591/n V are observed when
the electrode process is quasireversible or irreversible. In the latter case, E and i are related
through the following [261,264]:
RT 1.349k ot 1/ 2 RT i −i
E= ln + 0.9163 ln d for i ≥ id /10 (2.79)
αnF DA1/ 2 αnF i
It should be noted that when Equation 2.79 is used, it is the current at the end of the drop life rather
than the mean current that should be measured. In analogy to the reversible case, the half-wave
potential can be introduced, Equation 2.80, resulting, finally, in Equation 2.81:
RT 1.349k ot 1/ 2
E = E1/ 2 = ln (2.80)
αnF DA1/ 2
RT i −i 0.0542 i −i
E = E1/ 2 + 0.9163 ln d = E1/ 2 + log d (2.81)
αnF i αn i
The transfer coefficient α may be obtained from a plot of E versus log((id − i)/i), which should be
linear with a slope of 0.0542/(αn) V.
Both m and t in the Ilkovic equation (Equation 2.74) depend on the height of the mercury
reservoir h, and since m is equal to c′h and t is equal to c″/h, where c′ and c″ are constants, we
have the relationship between id and h given by Equation 2.82. Thus, the magnitude of a purely
diffusion-controlled polarographic wave is proportional to the square root of the height of the
mercury reservoir:
1/6
 c′′ 
id = 607n(c′h)2/3   DA1/2CA* = (const) ⋅ h1/2 (2.82)
h
Polarography has been used to characterize the electrochemical reduction of numerous substrates
under aqueous conditions [260–265]. Both E1/2 and ilim may be affected by the proton activity. The
polarograms resulting from reduction of anthracene in solvent systems of increasing proton activity
illustrate a general trend observed during this type of experiment (Figure 2.34). Under essentially
nonaqueous conditions, two reversible one-electron polarographic waves are observed correspond-
ing to the successive formation of the radical anion and the dianion (Figure 2.34, curve a). When the
water content increases, the first wave grows at the expense of the second wave, the sum of the two
remaining almost constant, until finally at high proton activities, the two waves have merged into
one two-electron wave (Figure 2.34, curve e). This behavior can be rationalized in terms of the eCeh
mechanism in Scheme 2.2 with X representing a water molecule. The increase in the height of the
first wave is related to the increasing importance of the first proton transfer step (ii).
In comparison with CV, curve a in Figure 2.34 would correspond to Figure 2.4, whereas curve e
in Figure 2.34 would correspond to Figure 2.13 (dotted curve).
In purely aqueous solution, the half-wave potential E1/2 for the general reversible reaction shown
in Scheme 2.5 is given (at T = 298 K) as follows:
pH = 0 m
E1/2 = E1/2 − 0.0591 pH (2.83)
n
2
i (μA)
1
e d c b a
0.5 V
Potential
FiGURE 2.34 Effect of increasing proton activity (a through e) on the polarogram of anthracene. For the
sake of clarity, the five polarograms have been shifted horizontally. Note also that the oscillations caused
by the growth and fall of the mercury drops are not shown. (Hoytink, G.J., in: Delahay, P., ed.: Advances in
Electrochemistry and Electrochemical Engineering. Vol. 7. pp. 221–281. 1970. Copyright Wiley-VCH Verlag
GmbH & Co. KGaA. Reproduced with permission.)
Thus, for two reaction schemes commonly met in organic electrochemistry, m = n = 1 and m = n = 2,
a plot of E1/2 versus pH should yield a straight line with the slope 59 mV/pH. Numerous examples of
the variation of E1/2 with changing pH have been reported [266–268].
Although polarography to some extent has lost importance relative to new powerful techniques,
the method deserves not to be forgotten [265]. Polarography is still in many cases a competitive
method for the examination of, for example, electron transfer reactions preceded or followed by
slow chemical steps or electrochemical reactions associated with adsorption phenomena.
VI. METhODS BASED ON FORcED CONvEcTiON

A. GENEraL CoNSIDEraTIoNS
It is characteristic for the methods described so far that the measurements are carried out in a quiet
solution and that the transport of material to and from the working electrode is assumed to be governed
by diffusion only (except in solution with very low concentration of supporting electrolytes). It has been
mentioned also that undisturbed diffusion cannot be maintained over longer periods of time unless the
working electrode is properly shielded. Another way to suppress the effects caused by natural convec-
tion is to use a rotating disk electrode (RDE). Owing to the rotation of the electrode, a strong convective
force is imposed on the solution (see Section VI.B.), and in comparison, other forces that may influence
the solution transport are small and can be neglected. Furthermore, the diffusion layer thickness for a
rotating electrode is stagnant and small compared to that of a stationary electrode, and taken together,
these characteristics result in an experimental setup that is relatively insensitive to the nature of the
surroundings. However, this advantage has to be paid for by the drawback that the RDE, when used in
organic electrochemistry, often suffers from electrode fouling presumably caused by the deposition of
insulating films, a problem related to the high material conversion at the electrode surface.
Thorough discussions of the applications of RDEs and the associated mathematics are found in
several texts [1,269–272].
B. THE RoTaTING DISk ELECTroDE

The electrode tip of an RDE system may consist of a cylindrical piece of conducting material (usu-
ally Pt, Au, or glassy carbon), which together with a wire or a steel rod for electrical contact is
sealed into an insulating shaft (Figure 2.35).
When the electrode is rotated, an adjacent thin layer of the solution dragged by the electrode surface
acquires the tangential velocity of the electrode. Because of the centrifugal force, this is superimposed by
a radial velocity, resulting in an overall flow pattern at the electrode surface, as illustrated in Figure 2.36.
The liquid thrown out horizontally is replaced through an upward vertical flow (Figure 2.35).
The mathematical treatment on which the equations given in this section are based is valid only
as long as the fluid flow is laminar. At very high rotation rates, the flow becomes turbulent, and
at very low rotation rates, natural convection begins to play an unwanted role. The two extremes
can be given in terms of the Reynolds number Re, which for the RDE is defined in Equation 2.84,
where r is the radius (cm) of the RDE, including the insulating shaft (!), ω is the angular rotation
rate (rad s−1), and ν k is the kinematic viscosity coefficient (cm2 s−1). Laminar flow can be maintained
for Re values between 10 and 104, both values being approximate. For a typical commercial RDE,
these extremes limit the useful range of rotation rate to values roughly between 0.2 and 200 rev s−1.
Re = r 2 ων −k1 (2.84)
The tangential and radial velocities decrease with increasing distance from the electrode surface,
and at some critical distance δo, it is sufficiently accurate to consider the laminar upward motion as
the only mode of transport. The liquid layer in which it is necessary to take into account both the
Electrical
contact
Insulating
shaft
Conducting
material
FiGURE 2.35 Schematic of a rotating disk electrode. The streamlines indicate the flow below the disk.
FiGURE 2.36 Streamlines at the electrode surface of a rotating disk electrode.
tangential and radial velocities is called the hydrodynamic boundary layer, and its thickness is given
approximately by Equation 2.85. Thus, the value of δo varies between 2.7 and 0.08 mm for rotation
rates in the range 0.2 and 200 rev s−1 assuming the value 0.01 cm2 s−1 for νk.
δo = 3ν1k/ 2ω−1/ 2 (2.85)
When an electrochemical process takes place at the electrode surface, a concentration gradient
develops near the surface, resulting in diffusion as an additional mode of mass transport. The liquid
layer in which the transport by diffusion is comparable to the convectional motion is called the dif-
fusion boundary layer, and its approximate thickness δ is given by Equation 2.86, corresponding to
approximately 5% of δo with viscosity and diffusion coefficient in typical ranges.
δ = 1.61DA1/3ν1k/6ω−1/ 2 (2.86)
A B C
2
ilim
1
0
E0 E
FiGURE 2.37 Current–voltage curves for a rotating disk electrode: (1) without and (2) with substrate added.
The regions indicated are as follows: (A) control by electron transfer; (B) mixed control by electron and mass
transfer; (C) control by mass transfer.
Both δo and δ have the same value over the entire electrode surface, which has given rise to the
description of the electrode as a uniformly accessible surface. The concepts of a hydrodynamic and
a diffusion boundary layer have no theoretical significance as such but serve mainly to provide a
suitable model for the hydrodynamic conditions related to the rotating electrode.
At constant rotation speed, the current–voltage curve (Figure 2.37) for a simple reversible elec-
tron transfer reaction, Equation 2.1, is similar to a polarographic wave, and the half-wave potential
E1/2 for the current–voltage curve obtained by an RDE is defined in the same way as in polarography
(Section V).
The curve can be considered as consisting of three regions, a, b, and c, depending on the value of
the applied potential compared to Eo. For the general case where the process is under the mixed con-
trol of mass and electron transfer (region b in Figure 2.37), the current is given as follows [273,274]:
nFACA* DA nFACA* DA
i= −1/ 2
= (2.87)
1.61D ν ω + ( DA /ks,f ) δ + ( DA /ks,f )
1/ 3 1/ 6
A k

For a typical value of δ ≈ 10 −3 cm, the term DA /ks,f can be neglected if ks,f > 10 −1 cm s−1. The current
is now controlled solely by the mass transfer to the electrode (region c in Figure 2.37), and the equa-
tion reduces to the so-called Levich equation, Equation 2.88, which may be used together with the
Cottrell equation, Equation 2.64, in the experimental determination of δ [275]:
nFAC A* DA
ilim = 0.62nFACA* DA2 /3ν −k1/6ω1/ 2 = (2.88)
δ
An important consequence of this equation is the prediction that ilim varies linearly with ω1/2, a cru-
cial test of the quality of the RDE. On the other hand, if ks,f < 10 −4 cm s−1, the term DA /ks,f is large
compared to δ, and for this situation, in which the current is controlled by the rate of the electro-
chemical process (region a in Figure 2.37), Equation 2.89 is valid:
i = nFACA* ks,f (2.89)

These relations have been discussed and experimentally tested [273]. Values of ko up to approxi-
mately 0.1 cm s−1 may be measured using the RDE.
By inspection of Equations 2.87 through 2.89, it is seen that measurement of the rotating disk cur-
rent may provide information about either n, CA* , DA, νk, or ks,f when the remaining parameters are
known. Accuracy in determination of n values depends mainly on how accurately the value of DA for
the compound in question is known. For the majority of organic compounds, diffusion coefficients in
the common organic solvents have not been measured, but comparison with a suitable compound of
similar structure for which both n and D are known can often solve the problem (assuming the same
value of D for the two substrates; see also Section VIII for methods to determine D). Since DA appears
only to the power of 2/3 in Equation 2.88, the resulting n value is only moderately dependent on the
uncertainty of the DA estimate. The measurement of diffusion coefficients by means of the RDE tech-
nique has been the subject of a number of papers [271,276] and need not be treated further at this place.
A major field of application of the RDE in organic electrochemistry is elucidation of the mecha-
nistic details for reactions following the heterogeneous electron transfer reaction. One way of using
the RDE in kinetic work is based on the relationship between ilim and ω. In the absence of kinetic
complications, a plot of ilim versus ω1/2 should be a straight line (Equation 2.88). However, if the
electron transfer reaction is followed by a chemical step, the linear dependence of ilim on ω1/2 may
change to a curved relationship. For the eCe mechanism (Scheme 2.2), the relationship between the
apparent number of electrons, napp, ilim, and ω is given by Equation 2.90 [277], where n and ilim 1
are
the number of electrons and the current observed for the first electron transfer step only, that is, in
the absence of the chemical reaction. Other mechanisms have been treated as well [271,278,279].
napp ilim ( −0.834 ν1k/3k /( D1A/3ω))

= 1 = 2−e (2.90)
n ilim
It is easily seen that for relatively fast chemical steps where k ≫ ω, the exponential term is close to
zero, and the current corresponds to the exchange of two electrons. On the other hand, if k = 0, the cur-
rent will correspond to a one-electron process. Consequently, for intermediate values of k, the appar-
ent number of electrons varies between 1 and 2. Equation 2.90 predicts that napp tends toward smaller
values with increasing ω. The working curve showing the relationship between napp and ω (ω1/2) can be
calculated from Equation 2.90 for any value of k provided that the remaining parameters are known.
Working curves at different k values for the eCeh mechanism (Scheme 2.2) are shown in Figure 2.38.
The range of measurable first-order rate constants is given as follows:
0.1 s−1 < k < 103 s−1 (2.91)

Typical studies, in which the RDE has been used, include the dimerization of the triphenylamine
radical cation [280] and the cyclization of the tetraphenylethylene dication [281].
Another approach includes measurements of E1/2 relative to that for the simple electron transfer reac-
tion [282–284]. For instance, for the eCeh mechanism, ΔE1/2 is given by Equation 2.92, and it is seen
that a plot of ΔE1/2 versus log ω is predicted to be linear with the slope −2.303RT/(2nF) (= −29.5 mV
at n = 1 and T = 298 K). The value of k can easily be determined from this plot.
2.303RT  D  1/ 6
ω 
∆E1/ 2 = − log  A   + log 2 (2.92)
nF  ν k  0.643 k 

An example is shown in Figure 2.39 for the reduction of fluorescein in aqueous solution at
pH 9.5–9.7 [282].
1.9
1000 s–1
1.8
300 s–1
1.7
1.6 100 s–1

nobs
1.5
1.4
30 s–1
1.3
1.2 10 s–1
1.1 3 s–1
1.0
5 10 15 20
ω1/2
FiGURE 2.38 Rotating disk electrode working curves for the eCeh mechanism at different values of the rate
constant k for the chemical step.
The applications of the RDE presented so far all relate to operation under steady-state conditions.
However, it has been shown that the possibility to discriminate between closely related mechanisms,
such as the eCe and the eCeh, may be improved considerably by using a potential-step technique
together with the RDE. The reader interested in such details is referred to the original literature
[279,285,286].
C. THE RoTaTING RING-DISk ELECTroDE

At the RDE, the electrode products are thrown horizontally away from the electrode surface and
thus escape further detection. A solution to the need for additional information in RDE experiments
is the rotating ring-disk electrode (RRDE) [287]. The electrode consists of a conducting disk and a
conducting ring in a concentric arrangement separated by insulating material (Figure 2.40).
By proper adjustment of the ring potential, initial electrode products or products from follow-
up reactions may be monitored as a function of the angular rotation rate. The parameter most
frequently used in RRDE experiments is the collection efficiency N, which relates the ring current
ir to the disk current id as follows:
ir
N= (2.93)
id
–1.150
E1/2 (V) vs. SCE

–1.140
–1.120
–1.110
–0.4 –0.2 0 0.2 0.4

log10 (ω/Hz)
FiGURE 2.39 Variation of the half-wave potential for the reduction of fluorescein with the rotation speed for
the current–voltage curves obtained at pH 9.68 (⬩) and 9.51 (x). (Compton, R.G., Harland, R.G., Unwin, P.R.,
and Waller, A.M., J. Chem. Soc., Faraday Trans. 1, 83, 1261–1268, 1987. Reproduced by permission of The
Royal Society of Chemistry.)
r3
r1 r2
FiGURE 2.40 Schematic of a rotating ring-disk electrode.
These observables usually have opposite signs and should be measured at potentials where mass
transport is rate determining. The value of N is less than unity, even for a simple electron transfer
reaction, because only a fraction of the molecules generated at the disk electrode reaches the ring
owing to diffusion away from the electrode. The theoretical value of N depends on the geometry of
the electrode system. Of special importance is the size of the gap between the two electrodes r 2 − r1
(see Figure 2.40). The value of N typically varies between 0.45 and 0.2 [288] and is independent of
ω for a simple electron transfer reaction.
If the initial electrode product B undergoes a chemical reaction, the observed ring current, and
therefore N, drops to a lower value. The fraction of the B molecules that escape detection at the ring
depends on two factors, the rate of the chemical step and the time interval between the generation
and detection of B, that is, on ω. Consequently, it can be expected that for a given chemical reaction,
the value of N increases with increasing ω and in the limit approaches the value for the simple elec-
tron transfer reaction. Working curves for the determination of rate constants can be constructed by
analogy to those already described for the RDE, this time relating N to ω or an expression contain-
ing this parameter. Because of the complexity of the mathematics associated with the calculation,
digital simulation has been extensively used for this purpose [288–290]. Comparison of analytical
and numerical solutions for a number of cases demonstrated satisfactory agreement between the two
approaches [291]. If the mechanism is known, the rate constant can be obtained from the appropri-
ate working curve, which for the RRDE usually relates the collection efficiency to one of the two
parameters given in the following [288]:
XKT = (0.51)−2 /3 kω−1ν1k/3 DA1/3 (first order rate law) (2.94)

XKTC = (0.51)−2 /3 kCA* ω−1ν1k/3 DA1/3 (second order rate law) (2.95)

However, for a specific case, it may be more convenient to use a set of working curves, similar to
those shown for the RDE, that relates N to ω1/2 (Figure 2.41).
Application of the RRDE as a diagnostic tool to explore the mechanism of an unknown
reaction pathway relies, as most methods do, on the differences between the different working
curves. For the RDE, the working curves for different mechanisms in many cases do not devi-
ate sufficiently to allow a distinction between two possible pathways [282]. The presence of the
ring electrode provides extra information, and thus the RRDE is a more sensitive instrument for
mechanism analysis. An example is the distinction between the RR- and the RS-dimerization
mechanisms for CS2 radical anion [292]. It has been pointed out, however, that even with this
electrode setup, the working curves do not allow the unequivocal discrimination between, for
example, eCe-type (Scheme 2.2) and catalytic mechanisms (Scheme 2.7) [288] or the different
dimerization mechanisms (Scheme 2.3) [289]. A solution to this problem has been found, which
0.2 s–1 0.5 s–1 1 s–1

2 s–1
5 s–1
0.15
10 s–1
0.10 20 s–1
N
0.00 50 s–1
0
2.5 5.0 7.5 10.0 12.5 15.0 17.5 20.0 22.5 25.0 27.5 30.0
ω1/2
FiGURE 2.41 Rotating ring-disk electrode working curves for the eCe mechanism at different values of
the first-order rate constant k for the chemical step. The value of N corresponding to k = 0 is 0.184 for this
particular electrode.
takes advantage of the possibility of varying the relative fluxes of A and B from the disk via the
current density [289,293–295].
The RRDE technique can provide quantitative information for reactions having rate constants
in the ranges given by Equations 2.96 and 2.97. The limits are dependent on the dimensions of the
RRDE, in particular the size of the gap between the ring and the disk.
10 −1 s−1 < k < 103 s−1 (first-order rate law) (2.96)

10 M −1 s−1 < k < 108 M −1 s−1 (second-order rate law) (2.97)

VII. METhODS fOR DETERMiNATiON Of ThE NUMBER Of

ELEcTRONS TRANSfERRED PER MOLEcULE Of SUBSTRATE
An important parameter in all kinds of electrochemical work, including mechanism analysis, is the
number of electrons n transferred per molecule during the electrochemical reaction.
Values of n may be obtained by almost any electrochemical technique provided that a number
of other parameters are known as illustrated, for example, by the relations between n and i given in
Equations 2.13, 2.61, 2.64, 2.74, and 2.88. However, it is the exception rather than the rule that all the
necessary parameters are known for a particular experiment. This applies especially to the effective
electrode area A and diffusion coefficient DA, which is known only for few substances in the solvent
systems commonly used in electrochemical studies (see also Section VIII). A simple solution to this
kind of problem is based on the quantitative comparison of, for instance, LSV and CA [296]. From
Equations 2.13 and 2.64, it is easily seen that the ratio R = (ip/ν1/2)/(it1/2) is given by the following
simple expression, since all other parameters cancel:
(ip / ν1/ 2 )
R= = 4.92n1/ 2 (2.98)
it 1/ 2
Thus, it is possible to estimate n values without the prior knowledge of DA and A, provided the same
working electrode is used for both experiments. The experimental values of R for systems with known
n were found to agree with the theoretical values (4.92 for n = 1 and 6.96 for n = 2) within 6%. This
approach for the determination of n has later been discussed in more detail elsewhere [297].
A different way of determining n values is based on the measurement of the amount of charge
necessary for the exhaustive electrolysis of a known amount of substrate. This type of experiment,
traditionally called coulometry, may be carried out either at constant potential or at constant current.
During coulometry at constant potential, the amount of charge is obtained by integration of the
current–time curve (Figure 2.42).
The advantage of potential control during the coulometry experiment has to be paid for by a
rather long electrolysis time. The end point, i = 0, is in principle not reached until infinite time
has elapsed. In practice, however, the electrolysis is stopped when the current has decayed to a
few percent of the initial value. The error introduced in this way can be neglected for all practical
purposes.
Coulometry at constant current is often considered as being less attractive than coulometry at
constant potential. Control of the current rather than the potential has, however, a number of advan-
tages. First, the charge consumed during the reaction is directly proportional to the electrolysis
time, and second, simpler electronic equipment may be used. It has been demonstrated [299] that
when the current density is low, the potential of the working electrode stays almost constant until
90% of the substrate is consumed. The total conversion of, for example, 0.1 mmol of substrate at
25 mA requires an electrolysis time of 6.44 min for n = 1. The change in concentration during elec-
trolysis is conveniently followed by LSV or CV. Cyclic voltammograms of a solution containing
Time
FiGURE 2.42 The current i as a function of the time t in constant potential electrolysis. The current is
given by i = it=0·10 −kt, where k is a constant depending on the construction of the electrochemical cell. (From
Lingane, J.J., J. Am. Chem. Soc., 67, 1916, 1945.)
0.1 mmol 3,4-diphenyl-1,2-dithiolylium ion [300], after constant current (25 mA) reduction in 0, 1,
2, 3, 4, 5, and 6 min, respectively, are shown in Figure 2.43. Extrapolation of the current to ip = 0
gives time for complete conversion, which in the present case was very close to the time, 6.44 min,
predicted for n = 1.
Under conditions where the primary electrode product undergoes a slow chemical reaction,
that is, t1/2 is of the order of seconds, the value of n determined by a relatively fast technique like
LSV may differ from that obtained by a slow experiment like coulometry. This type of behavior
was observed in the anodic oxidation of 2,3,5,6-tetraphenyl-1,4-dithiin in MeCN [301]. During
CV, the reversible oxidation to the radical cation is observed. However, when constant-current
I I
(+) (+)
0 0
(–) (–)
0 1 2 3 4 5 6
Ph
S S 2e– S S
2 + H Ph
Ph Ph H
S S
Ph Ph
FiGURE 2.43 Constant-current coulometry (i = 25 mA) of 3,4-diphenyl-1,2-dithiolylium ion (0.1 mmol). Cyclic
voltammograms, horizontally displaced, are shown after reduction for 0, 1, 2, 3, 4, 5, and 6 min, respectively.
(+) (+)
0 0
(–) (–)
0 1 2 3 4 5 6
Electrolysis time (min)
Ph S Ph
Ph Ph
S
FiGURE 2.44 Constant-current coulometry (i = 50 mA) of 2,3,5,6-tetraphenyl-1,4-dithiin (0.1 mmol). Cyclic

voltammograms, horizontally displaced, are shown after oxidation for 0, 1, 2, 3, 4, 5, and 6 min, respectively.
coulometry was carried out as described earlier, this time at i = 50 mA, 6.44 min was required
to oxidize completely 0.1 mmol of the substrate to a product electroinactive in the potential
region of interest, indicating an overall two-electron process (Figure 2.44). Thus, apparently
contradictory results may be obtained due to the difference in time scale between the two types
of experiment.
The equipment necessary for the determination of n by coulometry as described earlier does in
principle not differ from that used for a microscale preparative electrolysis. Therefore, in addition to
the determination of n, it is possible also to investigate the voltammetric properties of the product
and, for example, whether the starting material may be regenerated by electrolysis after the direc-
tion of the current has been changed.
VIII. METhODS fOR DETERMiNiNG ThE DiffUSiON

COEfficiENT Of ELEcTROAcTivE MOLEcULES
Similar to the determination of n (Section VII), diffusion coefficients may be estimated from vari-
ous electrochemical methods discussed in this chapter, provided some other parameters, in par-
ticular the electroactive area of the electrode A, the bulk concentration of the compound C *, and n,
are known. Thus, for example, Equation 2.13 can be used for the determination of D from cyclic
voltammetric peak currents. As mentioned already, however, not always all of these data are avail-
able. While A is accessible from calibrating experiments with compounds of known n, D, and C *
(often ferrocene can be used for this purpose, with n = 1 and D having been reported in a number
of commonly used nonaqueous solvents [302]), it is often necessary that n and D have both to be
determined for a given system.
One alternative is to use a combination of macro- and ultramicroelectrode data. In the former
case, Equation 2.13 is valid, while in the latter, Equation 2.61 applies. Since n and D are related
by different mathematical functions in these equations, both parameters can simultaneously be

determined. It has been shown that combining steady-state (ultramicroelectrode) data with CA (see
below) may result in minimum uncertainties [297]. In some cases, D and the electrode radii (or
electroactive areas) [302,303], or D and C * [304] were estimated. A simultaneous determination of
D and A [302] minimizes calibration errors in electrode size.
An additional problem with CV data is encountered resulting from the fact that the numerical
constant 0.4463 in the Randles–Ševčík equation (2.13) is strictly valid only for reversible electrode
processes without any complication by coupled kinetics. Furthermore, if we consider a reaction
with two consecutive one-electron steps, Equation 2.16, with overlapping waves, this constant criti-
cally depends on E2o − E1o. Only at the extreme cases of fully separated waves (Figure 2.4; two times
n = 1) or strong potential inversion [60,305] (Chapter 11; n = 2) Equation 2.13 can be applied. For
E2o − E1o = 35 mV, the voltammogram corresponds to two superimposed nonseparable, one-electron
curves, with ip = 2·ip (n = 1), and consequently, D is also accessible. Intermediate cases, however,
do not allow easy interpretation with respect to D. This is an intrinsic problem of the fact that CV
uses a potential sweep.
Thus, CA has been a common method for such experiments, because the step is usually per-
formed into the limiting current region of the potential [303,306]. The planar (Cottrell; Equation
2.64) and hemispherical diffusion conditions could be realized in chronoamperograms at short
and long times, respectively [307]. Several papers deal with the CA-based estimation of D with-
out the knowledge of the exact concentration [297,303b,306–308]. Convolution voltammetry
(see Section II.F.1) also proved to be advantageous in respect even in room-temperature ionic
liquids where diffusion is inherently slow owing to the high electrolyte viscosity [309].
In still other cases, D was determined by non-electrochemical techniques, for example, pulse
gradient spin-echo nuclear magnetic resonance experiments [302,310]. Thus, D follows from a non-
electrochemical method, and any errors in the current data and their interpretation can be avoided.
The technique was also used in ionic liquids of higher viscosity than common typical organic
solvents with corresponding lower D [311]. Estimation by comparison with similar molecules [312]
(see however, the cautious remarks in Reference 313) was also used. Diffusion coefficients have also
been estimated from molecule sizes [314].
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3 In Situ
Spectroelectrochemistry
of Organic Compounds
Peter Rapta, Evgenia Dmitrieva,
Alexey A. Popov, and Lothar Dunsch
CONTENTS
I. Development and the recent state of In Situ spectroelectrochemistry ............................... 169
A. Scope of Spectroelectrochemistry.................................................................................169
B. In Situ Spectroscopic Methods Used with Electrochemistry ........................................170
C. Triple In Situ UV–Vis–NIR/ESR Spectroelectrochemistry ......................................... 172
1. Method ...................................................................................................................173
2. LIGA Electrodes in Voltammetric and Spectroelectrochemical Studies ...............174
3. In Situ UV–Vis–NIR/ESR Spectroelectrochemistry of Conducting Polymers......176
4. In Situ UV–Vis–NIR/ESR Spectroelectrochemistry at Variable Temperatures ... 177
II. Spectroelectrochemistry of Organic Compounds in Solution or as Solid Layers on the
Electrode Surface.................................................................................................................. 179
A. Empty Fullerenes ..........................................................................................................179
B. Derivatives of Fullerenes ..............................................................................................179
C. Endohedral Fullerenes ..................................................................................................181
D. Dimerization Reactions ................................................................................................ 183
E. Conducting Polymers .................................................................................................... 186
References ...................................................................................................................................... 187
I. DEvELOPMENT AND ThE REcENT STATE Of

IN SITU SPEcTROELEcTROchEMiSTRY
A. SCopE oF SpECTroELECTroCHEMISTrY
Although a large variety of electrochemical methods is nowadays available [1–6] (see also Chapter 2),
there is no way to get any structural information about species formed on the electrode upon redox
events. Modern electrochemistry is intensively focused on electrode reaction mechanisms, and
spectroelectrochemistry helps us to get a detailed picture about the intermediates and products
formed as a result of the heterogeneous electron transfer reaction [7–11]. Organic compounds that
can be easily and reversibly oxidized and/or reduced received a lot of interest in recent times. The
redox processes of such redox-active compounds can lead to different redox states where each of
these species exhibits different chemical and spectroscopic properties, which are very meaningful
for the application purposes of certain structures. Additional information from various spectro-
scopic methods, which give direct evidence for the chemical species in the complex redox reactions
pathway, frequently helps to find a plausible reaction mechanism for redox processes accompanied
by electron transfers [12].
169
Spectroelectrochemistry deals with the theory and application of spectroscopic methods in

electrochemistry as a bridge between electrochemistry and spectroscopy. In general, spectro-
scopic methods are applied in electrochemical systems under the condition that the electromag-
netic radiation does not change the electrochemical reaction and the equilibrium at the electrode.
Electrochemistry is focused on processes at interphases, while spectroscopic methods are often
dealing with bulk properties of different materials. Modern research in spectroelectrochemistry is
characterized by a combination of different spectroscopic methods for a detailed study of electrode
reaction mechanisms or complex electrode systems. In situ spectroelectrochemistry includes all
spectroscopic measurements at a working electrode under electron transfer. Spectroscopic meth-
ods can be applied both to the solid and to the liquid phases at the electrode–electrolyte interface.
Although a huge variety of methods arose in the last decades concerning spectroscopic methods
applied in electrochemistry, there are some spectroscopic methods that are preferred in their use in
spectroelectrochemistry.
B. IN SiTU SpECTroSCopIC METHoDS USED wITH ELECTroCHEMISTrY

The simultaneous use of ultraviolet (UV)–visible, infrared (IR), electron spin resonance (ESR),
and electrochemical methods is now widely accepted and is well developed as a powerful tool
in the identification of paramagnetic intermediates or other reaction products [13], and there
have been published already several monographs in the field. UV–vis–near IR (NIR) spectros-
copy is the most applied method in spectroelectrochemistry [14–21]. The electronic structure
of molecules and the changes induced by charge transfer reactions are studied by absorption
spectroscopy in the range from NIR through visible to the UV region with photon energies
from below 1 up to 6.5 eV. This completely covers the field of electronic transitions in mole-
cules and crystal lattices. For instrumental reasons, these three energy ranges are often applied
in the same apparatus and are also considered in a combined treatment of the spectroscopic
data. These electronic and vibronic transitions are preferably measured in the absorption mode,
while the emission of light from excited single molecules and solids is monitored by lumines-
cence spectroscopy [22–30].
An increased understanding of redox processes and various complex reactions in all kinds of
organic systems associated with paramagnetic intermediates has been strongly promoted by the
application of in situ ESR spectroelectrochemical techniques [31,32]. ESR spectroscopy is both
very sensitive and delivers detailed structural information on paramagnetic species. A variety of
ESR spectroelectrochemical cells having different design and construction have been developed
concerning both qualitative and quantitative works as well as for measurements at different tem-
peratures as illustrated for several basic cell designs in Figure 3.1 [33–48].
In the electrochemical formation of radicals occurring in one-electron transfer processes of
organic species, in situ ESR spectroscopy has been applied successfully in the elucidation of reac-
tion mechanisms. If the electrode reaction product is diamagnetic, in situ UV–vis–NIR spectros-
copy is widely recognized as the most valuable spectroscopic method. This method, which can be
used both in reflection and in transmission, has been applied to mechanistic studies, although the
structural information so obtained is not as detailed as that in ESR spectroscopy.
The field of spectroelectrochemistry was broadened by the introduction of optically transparent
electrodes (OTEs) for absorption spectroscopy in transmission [49], the introduction of the attenu-
ated total reflection (ATR) technique [50], and the use of thin-layer cells for IR spectroelectrochem-
istry [51]. OTEs mostly consist of a transparent material (glass, quartz) covered with a thin noble
metal film (Pt, Au) or oxides of Sn and In. Alternatively, the minigrid electrodes made from a wire
mesh can be used as OTE where the transparency is due to the holes in the metal grid. An optically
transparent thin-layer electrode within the thin-layer cells is already widely used due to a small vol-
ume of the electrolyte solution needed and due to the fast conversion of the redox system in solution
under thin-layer conditions [52–57].
In Situ Spectroelectrochemistry of Organic Compounds 171
RE AE RE RE
WE
WE WE WE
WE
AE
AE AE RE
(a) (a1) (a2) (a3) (a4) (a5)
WE
WE
WE
AE
(b) (c) (c1) (c2)
AE RE
WE AE
WE
WE WE
AE
(d) (d1) (d2) (d3) (d4)
RE RE AE WE
AE
WE
WE WE WE
(e) (e1) (e2) (e3) (e4) (f)
FiGURE 3.1 Illustrative overview of some basic ESR spectroelectrochemical cells. (a) Flat cells: (a1 and a2)
from Reference 33, (a3) from Reference 34, (a4) from Reference 35, (a5) from Reference 36. (b) Flow-through
channel flat cell from Reference 37. (c) Tubular flow-through cells: (c1) from Reference 38 and (c2) from Reference
39. (d) Stationary tubular cells: (d1) from Reference 40, (d2) from Reference 41, (d3) from References 42 and 43,
(d4) from Reference 43. (e) Flow-through tubular cells: (e1) from Reference 44, (e2) from Reference 45, (e3) from
Reference 46, (e4) from Reference 47. (f) Column cell from Reference 48.
Vibrational spectroscopy is nowadays widely used as a spectroelectrochemical technique

resulting in detailed information on molecular structures [58–61]. Raman spectroscopy provides
complementary data regarding non-IR active vibrational modes. A breakthrough in Raman spec-
troelectrochemistry was the discovery of surface-enhanced Raman patterns at silver electrodes [62].
Together with the availability of the laser Raman technique, this vibrational spectroscopy was since
then a standard method in in situ spectroelectrochemistry. In situ Raman spectroelectrochemistry
was proven as a powerful tool in the study of redox processes of carbon nanostructures [63].
Nuclear magnetic resonance (NMR) spectroelectrochemistry of molecular structures was made
accessible in 1975 by a spinning cell construction to get well-resolved NMR spectra, but it took
three more decades to develop a more suitable in situ NMR cell with high sensitivity for a broad
range of in situ NMR spectroelectrochemical studies [64–70]. Use of an electrochemical cell within
the detection area of an NMR spectrometer enables the structural identification of electrochemi-
cally generated species. Static in situ NMR spectroelectrochemical cells require a low solution
volume, and several working electrode designs have been already published including Sb–SnO2
deposited on the inner surface of the NMR tube [65], NMR tubes coated with gold [67,69], or work-
ing electrodes based on carbon fibers operating under a large variety of frequencies [68,70].
In general, absorption spectroscopy in the UV–vis–NIR range remains the main spectroscopic
method for the characterization of the electronic structure, and the changes occurring from charge
transfer reactions are monitored by electrochemistry using in situ methods. Although each spec-
troscopic technique is considered with respect to its advantages in electrochemical research, it is
obvious that both vibrational (IR and Raman) and optical absorption spectroscopies are preferred
in electrochemistry due to their valuable chemical information. Fourier transform infrared (FTIR)
spectroscopy is the most widespread method and is based on effective cell constructions. On the
other hand, NMR spectroelectrochemistry delivers useful structural details of molecules and solids
present within the electrochemical system.
The advantage of these methods in spectroelectrochemistry is their applicability in the study of
an electrochemical system, as both the solid and liquid phases are accessible to a detailed spectro-
scopic study. However, due to the variety of the investigated systems as well as of the experimental
conditions used (e.g., nonaqueous and aqueous solutions, homogeneous and heterogeneous systems
and polymers, and nontransparent and optically transparent electrodes), it was necessary to con-
struct special spectroelectrochemical cells for each system individually.
In in situ spectroelectrochemical methods, the measurement within an electrochemical experi-
ment at the same electrode system is realized. Advantages of in situ methods in electrochemical
studies include mainly a direct access to kinetic data of electrode reactions and qualitative and
quantitative information on the state of the interface at electrochemical conditions. Simultaneous
acquisition of data from different methods in one single experiment and separation of the faradaic
and non-faradaic parts of an electrochemical reaction by a quantitative identification of the reaction
products at the electrode also contribute to the power of these methods. However, there are also
some disadvantages of in situ methods in electrochemical studies such as the low concentration of
the reaction products at the phase boundary and the high time consumption with respect to the prep-
aration of the experimental setup, the simultaneous data acquisition, and the evaluation of all data.
Special cells are required, the type and size of which are adjusted to the requirements of the spec-
troscopic method, which might contradict the requirements of the electrochemical method in terms
of electrode geometry, electrolyte composition, and volume. The selection of solvents, supporting
electrolytes, and the electrode materials is limited by the requirements of the spectroscopic method.
C. TrIpLE IN SiTU UV–VIS–NIR/ESR SpECTroELECTroCHEMISTrY

In combination with ESR and UV–vis–NIR spectroscopy, cyclic voltammetry (CV) is an important
analytic method for estimating the ability of organic compounds to lose or to accept electrons and
to elucidate the chemical structure and the electronic nature of the reduced or oxidized species
generated in course of the corresponding electron transfer processes. The development of an optical
ESR cavity opened the route to a simultaneous application of both ESR and UV–vis–NIR spec-
troscopy in a single in situ spectroelectrochemical technique (triple method) for studies at the same
working electrode [71]. In this way, both the paramagnetic and diamagnetic structures can be fol-
lowed in electrode reactions at the same working electrode. Additional information from optical
spectroscopic methods (UV–vis–NIR), which directly refers to both the diamagnetic and para-
magnetic chemical species in complex redox reaction pathways, support the search for a plausible
reaction mechanism.
1. Method
In order to obtain structural information on both the paramagnetic and diamagnetic species in an
electrode reaction, it is required to combine the spectroscopic methods mentioned earlier, that is,
to measure both in situ UV–vis–NIR and ESR spectra simultaneously during the electrochemical
experiment (Figure 3.2).
Simultaneous in situ measurements by both ESR and UV–vis spectroscopy have been car-
ried out for the first time in 1996 by Petr et al. during a single cyclic voltammetric experiment
with the methyl-substituted p-phenylenediamine [71]. The experimental technique, including a
special optical ESR cavity and an electrochemical cell for both ESR and UV–vis spectroscopy
in transmission mode, was used. An improvement of UV–vis measurements was reached by the
application of diode array spectrometers or spectrometers with CCD arrays in which a larger
number of spectra can be recorded in the timescale of a single electrochemical experiment. The
standard ESR optical transmission cavity was modified with respect to the construction of two
optical openings. The front optical opening was adapted for the light guide of the continuous light
source.
The correct choice of the working electrode for studies of different kinds of compounds plays
a crucial role. The use of a flat cell provides good conditions for sensitive ESR measurements but
requires flat electrodes within the cell. The use of OTE electrodes in the flat cell compartment is
often difficult and reduces the available potential range. Microstructured electrodes fulfill most
requirements for a stable and sensitive behavior of the working electrode, but the penetration depth
of the microwave field is too small for ESR measurements. It was found that a Pt-mesh electrode
is the best experimental solution for doing first measurements of UV–vis–NIR spectra within the
ESR cavity. Increasing the mesh size makes the ESR measurements more sensitive but leads to a
broadening of the peaks in the cyclic voltammograms. An increase in the size of the holes in the
Optical ESR cavity

ESR spectrometer
Potentiostat
CE RE WE
ESR
console
Trigger signal
Trigger signal
Halogen UV–vis detector

lamp Light guides NIR detector
Deuterium
lamp
FiGURE 3.2 Simplified scheme of the triple in situ UV–vis–NIR/ESR spectroelectrochemical setup.
platinum mesh or of the wire diameter was found to lead to a decrease in sensitivity and a delayed
response of the UV measurements.
A new kind of OTE based on very fine galvanically deposited metal meshes (1500 wires/in.),
mechanically stabilized by insulating the edge and the connection wire by thermal laminating foil,
was described for use in electrochemistry with common solvents by Neudeck and Kress [72]. The
extremely fine mesh (with the extension of the diffusion layer exceeding the range of wire distance)
with the well-insulated border enables a description of the voltammetric as well as the spectroscopic
behavior with the simple model of finite planar diffusion. However, to get a signal proportional to
the generated amount of product at the electrode, only very thin capillary slit cells with fast conver-
sion times should be used. For conversion times in the range of several hundreds of milliseconds,
the linearity is achieved after several seconds up to minutes, which allows to follow the decay of
electrochemically generated radicals [72].
The electrochemical oxidation or reduction of molecules to more highly charged ions leads to
the formation of differently charged compounds that can undergo comproportionation/dispropor-
tionation reactions in the bulk solution giving rise to products with different charges and spins. To
overcome difficulties of the formation of several charged states in bulk at a distinct electrode poten-
tial, spectroelectrochemical measurements in thin-layer cells are recommended. It should be noted
that even at thin-layer conditions, disproportionation of radical ions still takes place. At mesh elec-
trodes, convection and edge effects can be observed for long electrolysis times, and an additional
divergence appears at short times when the diffusion layers at each wire do not yet overlap. One
can obtain an ESR signal proportional to the number of spins only if either spins are generated only
inside the sensitive range of the cavity or the generation rate inside and outside the sensitive range
is equal. By fixing these micromeshes in the center of a flat cell or a capillary slit cell, the electro-
chemical behavior can be simulated on the basis of planar finite diffusion and from the integration
of concentration profiles the spectroscopic time dependence is available [72]. For in situ thin-layer
UV–vis–NIR/ESR spectroelectrochemistry, a three-electrode arrangement with a laminated work-
ing electrode with a gold-μ-mesh, a platinum wire as a counter electrode, and a silver wire as a
pseudoreference electrode was used [73]. To reach the thin-layer conditions, the electrolyte volume
was reduced by inert foil sheets inserted into the flat cell as illustrated schematically in Figure 3.3.
Commercially available thermal lamination foils of different thicknesses have been shown to
be resistant against solvents such as acetonitrile, dimethyl sulfoxide, dimethylformamide, and
others that are frequently used for electrochemical investigations. The lamination technique is
applied to give micromeshes a sufficient mechanical stability. In this state, they can be handled
as optical transparent electrodes with insulated edges. By thermal lamination of the micromesh
between two laminating foils with holes for the active electrode surface, such meshes can be
mechanically stabilized, insulated, and connected with a wire to have an insulated electrical
contact to the working electrode.
But the absorption spectra of diamagnetic structures are overlapping in mixtures of intermedi-
ates and/or products, and UV–vis–NIR spectroscopy generally suffers from fairly low resolution.
Therefore, other spectroscopic methods resulting in more detailed structural information have to be
applied, including FT-IR and NMR spectroelectrochemistry.
In many cases in the electrochemical generation of radicals and their detection using ESR, it is
often necessary to distinguish between paramagnetic species that are formed by an electron transfer
process and those produced in a side or follow-up reaction, particularly in rapidly reacting redox
systems. This problem could be solved by application of the phase-selective second harmonic AC
voltammetry [74–76]. In the case of spectroelectrochemistry, only the absorbance of the primary
intermediates varies in the same way as the perturbation signal.
2. LIGA Electrodes in Voltammetric and Spectroelectrochemical Studies

The honeycomb lithographic-galvanic (LIGA) structures can be understood as a system of tubes
that permit a fast electrochemical conversion time by using the structures in a capillary slit with a
0 3 0
5 5 3 9
3
1
7
2 7
6 6
10
11
4
8 8
(a) (b) (c)
FiGURE 3.3 Scheme of (a) spectroelectrochemical cell, (b) detail of the central part of standard spectroelec-
trochemical cell (front and profile views), and (c) detail of the central part of thin-layer spectroelectrochemical
cell (front and profile views): (1, quartz ESR flat cell; 2, laminated working electrode; 3, Ag wire; 4, Pt-wire
counter electrode; 5, gold foil; 6, gold-μ-mesh; 7, laminating foil; 8, electroactive surface, not laminated;
9, inert and optically transparent foil sheets; 10, electrolyte volume in standard ESR spectroelectrochemical
cell; 11, electrolyte volume in a thin-layer cell). (Adapted with permission from Matis, M. et al., J. Phys. Chem. B,
114, 4451. Copyright 2010 American Chemical Society.)
5 mm
5 mm Gold-LIGA PPy-LIGA
3 mm
50 μm
25 μm 50 μm
25 μm
Detail
Detail
110 μm 110 μm
Epoxy glue
PPy-microstructure
1 μm gold layer PPy-layer on gold
(a) (b)
FiGURE 3.4 Schematic diagrams of gold-LIGA electrode (a) and polypyrrole-LIGA electrode (b).
(Reproduced with permission from Springer Science + Business Media: J. Anal. Chem., 367, 2000, 314–319,
Dunsch, L., Neudeck, A., and Rapta, P., Copyright (2000) Springer.)
slit width of less than 25 µm (Figure 3.4a). But until now, these structures are rather expensive and
not commercially available, and for their use in in situ ESR spectroelectrochemistry, we need a
special cell design. The advantages of LIGA fabricated microstructured honeycomb electrodes were
demonstrated for spectroelectrochemical cells with respect to the response time (the time neces-
sary to generate the product in a sufficient layer thickness close to the electrode to be detectable by
UV–vis–NIR spectroscopy) and to the conversion of the redox system in solution under thin-layer
conditions [77]. Transmission UV–vis–NIR spectroscopy for several electrochemical applications

can be performed in a special spectroelectrochemical cell based on the LIGA electrode and the
two quartz rods, forming the walls of the cell and conducting the light beam through the cell. They
are limiting the diffusion layer at the structured part of the working LIGA electrode. These micro-
structured LIGA electrodes can be used as well-defined models of porous electrodes at which redox
processes occur under finite diffusion conditions. Such electrodes have been successfully used in
the voltammetric and spectroelectrochemical study of various redox systems in both aqueous and
nonaqueous solutions [77–80].
Additionally, the possibility to fabricate the well-defined microstructures from various organic
conducting polymers was demonstrated by the electrochemical deposition of polypyrrole in molded
LIGA forms at high current densities in aqueous solutions [81] (Figure 3.4b).
The studies were done in a spectroelectrochemical cell based on microstructured gold produced
by the LIGA technique or on microstructured conducting polypyrrole layers as working electrode
materials. These electrodes with well-defined hexagonal holes exhibit a large number of applications
in the field of thin-layer CV and spectroelectrochemistry. Besides their application in voltammetric
studies, they can be used as a new kind of OTEs with an aspect ratio, that is, the quotient of the
width of the walls surrounding a honeycomb (or hexagonal hole) and the height (or thickness) of
the structure of up to 20. The response behavior is advantageous without decreasing the active opti-
cal length as the small size of the honeycombs limits the diffusion layer thickness and results in a
very fast conversion of the starting redox component into the product inside the hexagonal holes.
The structure height of several hundreds of micrometers permits an extended optical length of the
light beam passing the honeycomb holes where the electrochemical reaction takes place. Therefore,
the response and the conversion time can be realized by using structures with a high aspect ratio
under constant sensitivity of the spectroscopic measurement. The complete conversion of the redox
system during the electrochemical experiment in the range of hundreds of milliseconds enables the
study of complex redox reactions accompanied by follow-up reactions in the millisecond range.
Additionally, the preparation of such microstructured electrodes using conducting polymers opens
new ways to study the redox processes on the conducting polymer surface employing spectroelec-
trochemical techniques.
3. In Situ UV–Vis–NIR/ESR Spectroelectrochemistry of Conducting Polymers

The use of several in situ spectroelectrochemical techniques results in the direct detection of both
the paramagnetic and diamagnetic species formed during electrochemical doping of organic poly-
mers. The simultaneous use of ESR and optical spectroscopies does allow us to differentiate the
nature of the charge carriers electrogenerated during p-doping and n-doping to get the individual
spectrum of each intermediate. A UV–vis–NIR/ESR spectroelectrochemical cell equipped with a
laminated indium-tin oxide (ITO) working electrode [82] was used in the investigation of various
organic substrates that are potential electron- or hole-transporting materials. The two ITO-coated
glass plates were thermally laminated with solvent-resistant nonconductive lamination foil with two
openings, 3 mm in diameter, to obtain the small electrochemically active surface with an insulated
electrical contact (Figure 3.5).
The nonelectrically contacted ITO piece enables the simple measurement of reference spectra.
By changing the position of the electrode up and down in the ESR cell, the reference or probe spec-
tra were measured without any changes in the spectrometer setup. To control the exact position for
the reference and probe openings, a black mask with a hole smaller than the active electrode surface
was fixed onto the ESR cell. To avoid oscillations of the cell voltage, two counter electrodes can be
used where the second counter electrode, connected by a resistor with the potentiostat, is situated
above the flat part of the cell [71].
The measurement of the reference UV–vis–NIR spectra direct in the ESR cavity was possible
using a specially constructed noncontacted ITO plate in the spectroelectrochemical cell. The
simultaneous in situ UV–vis–NIR/ESR spectroelectrochemical technique enables the monitoring
CE1
RE
3
Cu wire WE
Laminating foil
4
Gold foil
Mn(II)
2 standard
ESR cavity
Centre
Black mask 4
3 2
Polymer ITO
1
1
Reference
CE2
(a) (b) (c)
FiGURE 3.5 Schematic diagrams of UV–vis–NIR/ESR spectroelectrochemical cell equipped with a

laminated indium-tin oxide (ITO) working electrode. (a) Laminated ITO electrode with the nonelectrically
contacted ITO piece enabling the simple measurement of reference spectra. (b) Position of the cell for the
measurement of reference (left) and polymer (right) optical spectra (WE, working electrode, RE, reference
electrode, CE1 and CE2, counter electrodes). (c) Real view of the polymer deposited on laminated ITO posi-
tioned in the ESR flat cell. (1, polymer deposited on electroactive part of the ITO electrode; 2, laminated ITO
plate with a gold foil contact; 3, Ag wire pseudo-reference electrode; 4, ESR flat quartz cell.)
of both ESR silent and paramagnetic species present in the investigated system during redox
cycling. The obtained sets of spectral and electrochemical data can help to find a plausible redox
mechanism of the investigated solid redox-active substrates on the electrode as well as to sepa-
rate the superimposed UV–vis–NIR spectra. Using the calibrated manganese ESR standard, the
quantitative time dependences of the three oxidation states in the polymer layer were obtained
during redox cycling. The quantitative cyclic voltammetric and ESR data can be used to separate
the superimposed UV–vis–NIR spectra into those of the individual redox states using the least-
squares method [83].
4. In Situ UV–Vis–NIR/ESR Spectroelectrochemistry at Variable Temperatures

The triple in situ experimental technique for the simultaneous measurement of UV–vis–NIR
and ESR spectra in electrochemical experiments at different temperatures, including a spe-
cial optical ESR cavity and Bruker temperature control system, was published by Rapta and
Dunsch [84]. With the possibility of recording spectra at several temperatures and concen-
trations during oxidation or reduction, it was possible to favor the formation of the radical
ion or the corresponding dimer. The quantitative in situ UV–vis/ESR spectroelectrochemical
technique was extended to the NIR region to enlarge the spectroscopic characterization of
reaction products. The spectroelectrochemical cell was modified for measurements at differ-
ent temperatures in a standard ESR Dewar insert positioned in an optical ESR cavity. For the
spectroelectrochemical ESR flat cell applied in the in situ UV–vis–NIR/ESR cyclic voltam-
metric experiments at different temperatures, a laminated platinum-mesh electrode was used
as a working electrode (Figure 3.6a).
WE 1081 nm
RE 0.15
CE
Absorbance
0.75
0.00
400 600 800 1000 1200 1400 1600

(b) Wavelength, nm
Mn
0.030 1020 nm
1081
* *
Absorbance
0.015
T
0.000
400 600 800 1000 1200 1400 1600
(a) (c) Wavelength, nm
FiGURE 3.6 (a) Scheme of the low-temperature spectroelectrochemical cell: WE—laminated platinum-
mesh working electrode; RE—silver wire pseudo-reference electrode; CE—platinum wire counter electrode;
T—flexible teflon tube; Mn—glass capillary filled with magnesium oxide containing traces of Mn2+. (b) Vis–
NIR spectra observed during cyclic voltammetry of fullerene C120 in o-DCB + 0.1 M TBABF4 at 298 K and
(c) at 260 K (inset: schematic structure of C120 monoanion and representative ESR spectrum simultaneously
measured during the cyclic voltammetric scan at first reduction peak; *two ESR lines of Mn(II)-ESR standard
sample). (Reprinted from J. Electroanal. Chem., 507, Rapta, P. and Dunsch, L., 287–292, Copyright (2001),
with permission from Elsevier.)
A silver wire served as a pseudo-reference electrode and a platinum wire as a counter electrode.
A flexible Teflon tube positioned on the bottom of the cell enabled all bubbles to escape from the
cell before the measurement. During the triple in situ experiment, the spectroelectrochemical cell
was positioned in a standard insert Dewar located inside the ESR optical resonator. The standard
variable temperature setup was used to control the cell temperature. The triple in situ spectroelec-
trochemical measurements were controlled by triggering the UV–vis–NIR and ESR spectrometers.
As an example of the valuable use of such a setup, it was shown that the stability of the C120 dimer
is much lower as compared to C120O as the C120 molecule readily undergoes dissociation upon a
one-electron reduction. In the spectroelectrochemical response of C120 at room temperature, the
C60 − • anion radicals dominate as the reaction product as illustrated in Figure 3.6b. Thus, the char-
acteristic NIR band of negatively charged C120 − • at 1020 nm during the cathodic reduction at 260 K
was observed (Figure 3.6c). The presence of a narrow ESR line points to very similar ESR charac-
teristics of both C120 and C120O dimers and corresponds to the single ESR line of R2C60 − • fullerides.
II. SPEcTROELEcTROchEMiSTRY Of ORGANic COMPOUNDS iN

SOLUTiON OR AS SOLiD LAYERS ON ThE ELEcTRODE SURfAcE
More illustrative examples for spectrochemical methods discussed earlier are given in the next
p aragraphs with examples of electrode reactions both in solution and in the solid state.
A. EMpTY FULLErENES
Fullerenes are good electron acceptors and undergo multiple reversible single-electron reductions
in solution. For instance, electrochemical studies of C60 showed that it is able to accept up to six
electrons [85], and similar behavior is also found for other fullerenes (see also Chapter 21). Many
spectroelectrochemical studies of the reduction process were reported since the early 1990s [86].
The anionic states of fullerenes exhibit characteristic absorptions in the NIR range originating
from LUMO → LUMO+N excitations (here LUMO is the lowest-unoccupied molecular orbital of
the pristine fullerene, which is populated upon reduction) [87]. Such excitations are absent in the
pristine fullerene, which makes absorption spectroscopy an especially convenient tool for spectro-
electrochemical studies. In the ESR spectra, anion radicals of fullerenes exhibit single-line signals
whose line width may be rather large due to the Jahn–Teller effect when the degenerate LUMO is
partially filled. For example, the ESR line width of C60 − • at room temperature is approximately
40 Gauss (G) [88]. For fullerenes with lower symmetry, the typical line width is less than 1 G (e.g.,
0.15 G for C82− • and 0.2–1.0 G for isomers of C84− •) [89–92]. For anion radicals with sharp ESR sig-
nals, a 13C satellite structure can also be observed and gives information on the spin density distribu-
tion. The g-factor of monoanion radicals of fullerenes, g = 2.001–2.002, is close to the free-electron
value (2.0023). A special exception is C60 − •, whose g-factor, 1.999–2.000, is noticeably smaller than
in all other fullerenes because of the unquenched orbital momentum [88]. The g-factors of the trian-
ions are usually shifted by approximately 0.001 to larger values than in corresponding monoanions.
Especially beneficial can be a combination of ESR and absorption spectroscopies in spectroelec-
trochemical studies as shown in the studies of C60 [93], C82 [90,92], and four isomers of C84 [89].
A spectroelectrochemical study of C60 revealed the problem of a spike signal of unknown origin
often observed in the ESR study of C60 − • anion radicals [86]. The in situ UV–vis–NIR/ESR study
showed that only the broad signal of C60 − • is found if the fullerene is reduced solely at the first
reduction step. However, if the potential range in the voltammetric study is extended further into
the cathodic range (to the second reduction or beyond), the sharp ESR signal appears during the
second voltammetric scan already in the region of the first reduction peak upon C60 reduction
in o-dichlorobenzene, which is the most common solvent used in electrochemical studies of
fullerenes. Thus, the ESR spectroelectrochemical study emphasized the high reactivity of the dian-
ion (and higher charged anionic states of C60) and showed that a reaction with the solvent can take
place already at the second reduction step. Note that the integrated intensity of the sharp signal was
less than 1% of the main C60 − • signal, and hence the extent of the reaction at the timescale of the CV
experiment is not sufficient to be detected by electrochemical methods.
B. DErIVaTIVES oF FULLErENES
The 13C hyperfine structure in the ESR spectra of the charged radicals of non-derivatized fullerenes
is usually not sufficiently informative for a detailed analysis of the spin density distribution because
of the low natural abundance of the 13C isotope. The situation can be changed when fullerene is
exohedrally functionalized with substituents carrying magnetic nuclei such as 1H or 19F. Besides,
derivatization also changes the π-system of a fullerene via saturation of some C-sp2, and hence the
NIR absorption features of the anion can also be affected substantially. The vis–NIR/ESR spectro-
electrochemical studies of alkyl [94–97] and perfluoroalkyl [98–101] derivatives of fullerenes showed
a resolved hyperfine structure in many anion radicals and changes in their NIR absorption patterns.
E vs. C700/–, V IESR E vs. C700/–, V IESR

0.0 0.4 0.8 –0.4 0.0 0.4 0.8 1.2
1.1 V 1.1 V
0.1 V –0.3 V
E vs. C700/– E vs. C70 0/–
(a) 1.1 V (b) 1.1 V
Sim.
Exp.
2G 61 70
6 71 72 69
60
(c)
1000
C70 C70(CF3)2
–3
1090
q=0
ΔA
q = –1
q = –2 –4
E, eV
–5
–6
400 600 800 1000 1200 1400 1600

(d) λ, nm (e)
FiGURE 3.7 (See color insert.) (a) ESR spectra (only positive part is shown) measured in situ during cyclic
voltammetry of C70(CF3)2 at the first reduction; (b) the same at the first and the second reduction peaks. The
insets in (a) and (b) show cycling voltammograms measured in the same experiments (scan rate 10 mV s−1,
0.1 M TBABF4 in CH2Cl2 supporting electrolyte; Pt-mesh working electrode). (c) ESR spectrum of the
C70(CF3)2− • radical anion. Insets: spin density distribution in C70(CF3)2− •, enhancement of the 13C satellite
features and their simulation, and a fragment of the Schlegel diagram. In all simulations, the a(13C) values for
C71, C72, C61, C70, C69, C6, and C60 (see Schlegel diagram for numbering) are 6.40, 4.46, 3.78, −3.66, 3.37,
2.83, and −2.67 G, respectively, which gave the best fit to the experimental spectrum. (d) Difference vis–NIR
spectra measured in situ during electrochemical reduction of C70(CF3)2 at the first and second reduction peaks.
(e) MO levels in C70 and C70(CF3)2, black arrows denote HOMO–LUMO gaps, gray arrows show schemati-
cally the excitations corresponding to the strong NIR bands in the absorption spectra of the anions and dian-
ions. (Popov, A.A., Shustova, N.B., Boltalina, O.V., Strauss, S.H., and Dunsch, L.: ChemPhysChem. 2008. 9.
431–438. Copyright Wiley-VCH Verlag GmbH & Co. KGaA. Reproduced with permission.)
To illustrate a typical spectroelectrochemical study of a fullerene derivative, Figure 3.7a,b shows

ESR spectra measured during CV of C70(CF3)2 at the first reduction step [99].
The ESR spectrum of C70(CF3)2− • (Figure 3.7c) exhibited (1) a prominent 1:3:3:1 quartet with a
hyperfine coupling constant (a(19F)) of 0.323 ± 0.004 G and (2) 13C satellites. This quartet structure
indicates that only one of the CF3 groups is strongly coupled to the unpaired electron (i.e., only three
equivalent F atoms are measurably coupled to the unpaired electron). DFT calculations performed
to interpret the ESR spectra showed that the hfc constant of the CF3 group with the C71 carbon atom
(see Figure 3.7c) is indeed several times larger than the value predicted for the second CF3 group
(with carbon atom C72), and hence the latter cannot be seen in the experimental spectrum. The
well-resolved 13C hyperfine structure with a(13C) values up to 6.4 G was also interpreted based
on the calculations and showed that the largest values correspond to the 13C atom in CF3 groups
f ollowed by several carbon atoms of the fullerene cage.
The evolution of the difference vis–NIR spectrum of C70(CF3)2 measured in situ during CV
at the first and second reduction peaks is shown in Figure 3.7d. At the first reduction step, an
absorption maximum at 1090 nm (1.138 eV) has appeared, while the new intense band at
1000 nm (1.240 eV) has developed at the second reduction step. The main NIR bands of C70(CF3)2
anions are blue-shifted vs. the analogous transitions in C70 anions, 1370 nm (0.905 eV) in C70 − • and
1170 nm (1.060 eV) in C702− [86]. The blue-shift vs. C70 − • NIR band was also observed by Kadish
et al. [97] for the C70(C6H5CH2)2− • anion radical, which exhibited two NIR absorption bands at
1062 and 1250 nm. In agreement with experimental data, time-dependent DFT computations of the
electronic excitations of C70(CF3)2− • and C70(CF3)22 predicted one intense NIR excitation at 1.065 eV
(oscillator strength f = 0.013) for the monoanion, which is blue-shifted to higher energy in the dian-
ion (1.153 eV, f = 0.022). Analogous transitions in C70 − • and C702 are predicted at 0.872 ( f = 0.017)

and 1.018 eV ( f = 0.036), respectively. On the basis of these computations, intense NIR bands in
C70(CF3)2− • and C70 − • are assigned to SOMO → LUMO+3 and SOMO → LUMO+4 excitations,
respectively (Figure 3.7e), which become HOMO → LUMO+2 and HOMO → LUMO+3 excitations
in the respective dianions.
C. ENDoHEDraL FULLErENES
Endohedral fullerenes (see also Chapter 21) encapsulate ions, molecules, or clusters in the interior
space of the carbon cage [102], which results in a more complex redox behavior in comparison
to empty fullerenes [103]. Whereas the carbon cage is the only redox-active center in the latter,
both fullerene cage and endohedral species can exhibit redox activity in endohedral fullerenes.
Electrochemical methods alone can hardly distinguish cage- or cluster-based redox processes, but
this problem can be efficiently addressed by ESR spectroelectrochemistry if encapsulated species
have nuclei with a nonzero spin (such as Sc with nuclear spin I = 7/2). The hyperfine structure in
the ESR spectra can reveal if the spin density in the cation or anion radicals is localized on the
endohedral cluster (large coupling constants and a pronounced shift of the g-factor from the free-
electron value will then be observed) or on the carbon cage. Besides, unlike empty fullerenes,
many endohedral cluster fullerenes exhibit electrochemically irreversible but chemically revers-
ible reductions [104]. The nature of the follow-up chemical process is still not well understood,
and in situ spectroelectrochemical studies can deliver valuable information on the reasons of such
redox behavior.
Thorough in situ UV–vis–NIR and ESR spectroelectrochemical studies were performed for
Sc3N@C68, an endohedral fullerene with the scandium nitride cluster Sc3N encapsulated in the
C68 carbon cage [105,106]. A CV study showed that at room temperature in o-dichlorobenzene
solution, Sc3N@C68 has two reversible oxidation and two irreversible reductions. Figure 3.8a
shows the CV curve measured at the first reduction step, whereas Figure 3.8b demonstrates the
time dependence of the ESR and NIR absorption signals detected in situ during the measurement
of the CV.
c
0.8
g
0.6 d
b e
Absorbance at 1226 nm
f
Intensity of ESR signal

0.4
0.2 a
I, μA
0.0
–0.2
–0.4
–0.6 3 mV s–1
Forward scan Back scan
–0.2 0.0 0.2 0.4 0.6 0.8 –0.23 V 0.77 V –0.23 V
(a) E, V vs. Fc/Fc+ (b)
10 G
a(45Sc) = 1.28 G
(c) (d)
g
f
Absorbance
e
d
c
b SOMO
HOMO(–1)
a
HOMO(–2)
HOMO(–3)
400 600 800 1000 1200 1400 1600
(e) λ, nm (f )
FiGURE 3.8 (See color insert.) (a) Cyclic voltammogram of Sc3N@C68 at the first oxidation step; the letters
denote times when ESR and absorption spectra were measured. (b) Normalized intensity of ESR and NIR
absorption at 1226 nm. (c) ESR spectrum of Sc3N@C68+ •; (d) DFT-computed spin density in Sc3N@C68+ •;
(e) Vis–NIR absorption spectra measured during oxidation of Sc3N@C68. (f) MO energy levels in Sc3N@
C68 and intense NIR excitations in the cation (gray arrows). (Yang, S.F., Rapta, P., and Dunsch, L., Chem.
Commun., 189, 2007. Reproduced by permission from The Royal Society of Chemistry. Copyright 2006.)
Figure 3.8c shows the ESR spectrum measured during electrochemical oxidation of Sc3N@C68
at the first oxidation step. The hyperfine structure of the ESR signal comprising 22 equidistant lines
is consistent with three equivalent Sc atoms. The small value of the hfc constant, 1.28 G, shows
that the Sc atoms are weakly coupled to the unpaired spin in the cation radical. In good agree-
ment with the experimental data, DFT calculations showed that the spin density in Sc3N@C68+ • is
predominantly localized on the carbon cage (Figure 3.8d). Vis–NIR absorption spectra measured
simultaneously with ESR showed that formation of the cation radical is accompanied by the two
NIR absorption bands at 1097 and 1220 nm (Figure 3.8e). With the help of TD-DFT calculations,
these absorptions were assigned to the HOMO–2 → SOMO and HOMO−3 → SOMO excitations,
respectively (Figure 3.8f). Coincidence of the normalized ESR and absorption intensity time pro-
files obtained in the spectroelectrochemical measurements (Figure 3.8b) proved that the paramag-
netic Sc3N@C68+ • cation radical is the only product of the electrochemical process.
Formation of the paramagnetic anion radical with a 45Sc hfc value of 1.75 G was also detected by
ESR at the first reduction step [105]. However, the integral intensity of the signal was approximately
1 order of magnitude lower than that of the cation measured under the same conditions. This result
clearly shows that the main product of the electrochemical reduction is diamagnetic, which can be
tentatively explained by the reversible formation of the diamagnetic single-bonded dianionic dimer:
2 Sc3N@C68− • ⇌ (Sc3N@C68)2−.
Whereas Sc3N@C68 is an example of the endohedral metallofullerene with cage-based redox
activity, Sc3N@C80 (which has the same endohedral cluster encapsulated in a different fuller-
ene cage) is an example of an endohedral metallofullerene with cluster-based reduction as illus-
trated by ESR spectroscopic studies of its anion radical. The 45Sc hfc constant of Sc3N@C80 − • is
55.6 G (compared to 1.28 G in Sc3N@C68− •), and its g-factor is shifted to approximately 1.999
[107]. ESR spectroelectrochemical studies of exohedrally functionalized Sc3N@C80 derivatives,
such as its monopyrrolidino-adduct and Sc3N@C80(CF3)2, showed that cluster-based reduction is
still observed; however, hfc constants are smaller than in the anion radical of pristine Sc3N@C80
[108,109]. That is, the spin density in the anion radicals is partially transferred to the carbon cage,
and the extent of this transfer is strongly controlled by the exohedral addition pattern. For Sc3N@
C80(CF3)2, ESR spectra were measured both at the first and third reduction steps and revealed
substantially different hyperfine structure in monoanion (a(45Sc) = 2 × 9.34, 10.7 G) and trianion
(a(45Sc) = 2 × 10.8, 49.2 G) [105].
The most pronounced effect of the spin density distribution in the electrochemically generated
ion radicals was found in the recently studied Sc4O2@C80 with a mixed-valence state of the Sc atoms
(Figure 3.9a) [110]. The compound exhibited two reversible redox steps in both the cathodic and
anodic ranges, and DFT calculations showed that the HOMO and the LUMO are localized on the
Sc4O2 cluster (Figure 3.9a,b). ESR spectra measured during the first reduction and oxidation steps
of Sc4O2@C80 exhibited rich hyperfine structure corresponding to two pairs of nonequivalent Sc
atoms (Figure 3.9c and d). Spin density is primarily localized on the Sc atoms either in anion or cat-
ion radicals, but the magnitude of the hfc constants is dramatically different. Whereas in the anion
radical the a(45Sc) constants, 2 × 2.6 G and 2 × 27.4 G, are rather moderate, the cation exhibited
very high hfc constants for one of the two pairs of Sc atoms: a(45Sc) = 2 × 19.0 G and 2 × 150.4 G.
Such a large value was explained by the nature of the HOMO of Sc4O2@C80 having Sc–Sc bonding
character with large 4s contributions (note that the isotropic hfc constant is proportional to the spin
density at the nuclei and is therefore determined by the spin contribution from the s orbital since
orbitals with higher angular momenta have nodes at nuclei). Thus, the ESR spectroelectrochemical
study of Sc4O2@C80 not only proved the redox activity of the endohedral cluster but also provided
information on metal–metal bonding in the molecule.
D. DIMErIZaTIoN REaCTIoNS
Our strong interest in the past was focused also to investigate the driving force of dimerization in
monomer/oligomer structures. Monodisperse organic compounds with low molecular weight such
as naphthalene diimides, thianthrenes, bipyrrols, bithiophenes, and extended conjugated oligomers,
for example, oligothiophenes, oligophenylenes, and oligopyrroles were used for such studies (see
Reference 111 and cited therein). For structural studies of the dimerization reaction products at elec-
trode surfaces, the in situ UV–vis–NIR/ESR technique was applied [84,112–114].
ScIII
O
HOMO ScII LUMO
–2.5 –2.0 –1.5 –1.0 –0.5 0.0 0.5 1.0

(a) (b) E, V vs. Fe(Cp)20/+
Exp. Exp.
500 G 50 G
Sim. Sim.
2000 2400 2800 3200 3600 4000 4400 4800 3300 3400 3500 3600 3700
Magnetic field, G Magnetic field, G
(c) (d)
FiGURE 3.9 (a) Frontier orbitals of the Sc4O2@C80 molecule and enlarged view on the Sc4O2 cluster show-
ing two types of Sc. (b) Cyclic and square-wave voltammograms of Sc4O2@C80. (c) ESR spectrum of the
Sc4O2@C80+ • cation; (d) ESR spectrum of the Sc4O2@C80 − • anion. An asterisk in (d) denotes an ESR signal of
an unidentified impurity; intensity of the impurity signal is less than 1% of the total ESR intensity. (Reprinted
with permission from Popov, A.A., Chen, N., Pinzón, J.R., Stevenson, S., Echegoyen, L.A., and Dunsch, L.,
Am. Chem. Soc., 134, 19607–19618. Copyright (2012) American Chemical Society.)
Oligothiophenes represent an attractive material for organic electronics as the type, number,
and position of substituents, and the number of monomers in oligothiophenes can influence both
the stabilization of charged states and the solubility of oligomers. The influence of the molecular
structure on the stabilization of charged states was studied in detail by in situ UV–vis–NIR/ESR
spectroelectrochemistry at a novel α,ω-dicyano substituted β,β′-dibutylquaterthiophene (DCNDBQT,
Figure 3.10a) [115]. In this compound, the alkyl side chains result in sufficient solubility in organic
solvents, while the electron acceptor cyano groups promote reduction processes.
The CV of DCNDBQT points to a two-step oxidation (the first one is reversible, whereas the
second one is irreversible at moderate scan rates) and a single reduction step (Figure 3.10b) [116].
The first oxidation and reduction processes should result in radical ions that are to be followed by
in situ UV–vis–NIR/ESR spectroelectrochemical analysis. Direct evidence for the radical species
of DCNDBQT was supplied by ESR spectroelectrochemistry (Figure 3.10c and d). The g-factor of
the cation radical (g = 2.0025) is close to that of the free electron. The ESR spectrum with hyper-
fine structure indicates the predominant contribution of carbon atom orbitals to the SOMO of the
cation radical with a slight contribution of nitrogen atoms. The higher g-factor of the anion radical
(g = 2.0042) points to a higher portion of the sulfur atoms to the SOMO as compared to the cation
radical.
5 μA
Oxidation
CH3
Reduction
S S CN
NC S
S
H3C –2.0 –1.6 –1.2 –0.8 –0.4 0.0 0.4 0.8 1.2 1.6 2.0
(a) (b) E, V vs. DmFc/DmFc+
Experiment
Experiment
Simulation
Simulation
0.5 mT
0.5 mT
(c) (d)
0.5 0.3
+
0.4
0.2
0.3 –
Rel. absorbance
Rel. absorbance
0.2 +
0.1 –
0.1
0.0 0.0
–0.1
–0.1
–0.2
400 600 800 1000 1200 1400 1600 400 600 800 1000 1200 1400 1600
(e) Wavelength, nm (f ) Wavelength, nm
FiGURE 3.10 Structure of DCNDBQT (a), cyclic voltammetry (b), ESR spectra of cation (c) and anion
(d) radical, and UV–vis–NIR spectra of DCNDBQT recorded during the first oxidation (e) and reduction
(f) steps. (Reprinted with permission from Haubner, K., Jaehne, E., Tarabek, J., Lukeš, V., and Dunsch, L.,
J. Phys. Chem. A, 114, 11545–11551. Copyright (2010) American Chemical Society.)
The quantitative ESR analysis of the first cathodic and anodic steps was done. Referring
the charge transferred to the spin number of the cation radical of DCNDBQT, a ratio charge/
spin of 2.1 is found. That is, less than 50% of the charge units are used in the formation of a
stable radical, while the higher percentage is forming a diamagnetic structure presumably by
dimerization. The reversible formation of a diamagnetic π-dimer from two cation radicals was
proven by in situ UV–vis–NIR and temperature-dependent in situ NMR spectroelectrochemi-
cal measurements [117].
Figure 3.10e and f shows the UV–vis–NIR spectra during the first electron transfer in the
anodic and cathodic ranges. The experimental absorption maxima together with the calculated
ones (by TD-DFT method) at the first anodic step prove the presence of a cation and an anion
radical. The two bands at 646 and 1050 nm for DCNDBQT + • are assigned to SOMO → LUMO
and HOMO → SOMO transitions, respectively, while for DCNDBQT − •, the bands at 752 and
1506 nm can be assigned to HOMO → SOMO and SOMO → LUMO transitions, respectively.
The additional optical bands (554, 906, and 1294 nm for the cation radical and 492, 908, and
1260 nm for the anion radical) can be attributed to the formation of corresponding dimer struc-
tures. The optical spectra of the π-dimer present two optical π–π* transitions blue-shifted in rela-
tion to the optical bands of the corresponding radical ions and a third band at longer wavelengths
(1294 and 1260 nm for the cation and anion radicals, respectively) assigned to charge transfer
between the rings of the dimer.
The reduction peak of DCNDBQT in the cathodic range results in even lower extent of an anion
radical. The quantitative ESR spectroelectrochemistry showed that for the anion radical, the ratio
charge/spin is as high as 3.0. The anion radical is therefore less stable at the experimental conditions
used and transformed into dimeric and trimeric structures or even polymers as shown by ex situ
MALDI-TOF mass spectrometry and indicated by in situ NMR spectroelectrochemistry [117]. The
quantitative ESR spectroelectrochemistry supports the existence of follow-up reactions with the
formation of diamagnetic structures for both the cation and anion radicals.
E. CoNDUCTING PoLYMErS
The spectroelectrochemistry of solid structures at electrodes can be advantageously studied by
in situ UV–vis–NIR/ESR spectroelectrochemistry to follow the influence of the chemical structure
on the redox reactions of the polymer [118,119]. The chemical structure of polyaniline (PANI) is
often given as a linear model with a linear arrangement of the monomers (Figure 3.11a). As the lin-
ear form of PANI is often applied in studies of charge transfer reactions, it is to be clarified whether
NH NH N NH R
R NH NH N NH NH
HSO4–
(a)
Reduced state
ESR maximum Absorption at 460 nm
After the first peak in CV ESR
After the second peak in CV Current
1310
620
0.2
Normalized absorption/current/
1.0
single integrated ESR signal
Absorbance
460
0.1 0.5
0.0
0.0
400 600 800 1000 1200 1400 1600 1800 –0.6 –0.4 –0.2 0.0 0.2 0.4 0.6
(b) Wavelength, nm (c) Potential, V
FiGURE 3.11 Structure of PANI with phenazine branches (a), UV–vis–NIR spectra of the polymer recorded
during its oxidation (b), and potential dependence of the current, ESR intensity, and absorption at 460 nm (c).
(Reprinted with permission from Dmitrieva, E., Harima, Y., and Dunsch, L., J. Phys. Chem. B, 113, 16131–
16141. Copyright (2009) American Chemical Society.)
only linear chains are existent in such structures of so-called “linear” PANI and whether their real
structure has any influence on the stabilization of charged states in such kind of polymer. Especially
the role of phenazine structures in the stabilization of charged states in PANI is of interest for the
use of differently prepared PANI.
The IR and ESR studies on “linear” PANI and in several copolymers of aniline and a phenazine
derivative have provided evidence on the existence of phenazine units in the polymer structure
[120]. However, the branching structure caused by the presence of the phenazine units in the poly-
mer chains stabilizes different charged states in the polymer upon p-doping as shown by the combi-
nation of in situ UV–vis–NIR/ESR and ATR–FTIR spectroelectrochemistry.
The detailed study of charged states in conducting polymers is of high importance because the
existence of a polaron pair and that of a polaron can be differentiated by in situ UV–vis–NIR/
ESR spectroelectrochemistry, and their electrode potential–dependent formation is available now
to give new insights into the formation of these charged states in electrochemically prepared PANI.
The ESR spectrum of PANI in the doped state has a narrow ESR signal with a line width of 0.5 G,
while a polymer containing phenazine only gives no ESR signal upon oxidation or reduction [121].
Obviously, some extent of a linear chain is required to stabilize a polaron near the phenazine-like
units.
The potential dependence of the polaron formation in PANI points to a potential difference
between the half-peak current and the ESR intensity (as the signal of the polaron) to be 70 mV
(Figure 3.11b and c). Therefore, the formation of the polaron is potential-delayed. It is the rare case
for PANI that the polaron is not the primarily formed charged state at the polymer chain, but at
first, the polaron pair is formed by a two-electron transfer, which can dissociate into two polarons
at higher potentials. The absorption band at 460 nm increases together with charge injection into
the polymer and can be attributed to the polaron pair. The absorption peaks of the polaron might be
hidden by the absorption of the polaron pairs, but the existence of the polaron can be clearly proven
by the simultaneous ESR measurements. Due to the shift of the maximum of the polaron forma-
tion from the peak current, it is concluded that the polaron can be formed both by oxidation of the
neutral polymer at higher potentials and by dissociation of the polaron pair at the lower potential
range. The mechanism for the formation of the charged states in PANI upon oxidation includes an
early step in the charge injection as the polaron pair formation.
By in situ UV–vis–NIR/ESR spectroelectrochemistry, the formation of charged states in proton-
ated and unprotonated structures of emeraldines was followed [122]. The initial stage of oxidation in
emeraldine salt is preferably the polaron structure, while π-dimers and polaron pairs are formed by
oxidation of emeraldine base. By quantitative in situ ESR measurements, the spin concentration for
commercially available PANI structures was determined. The number of monomer units per spin
was calculated to be 1 spin/100 aniline units in emeraldine salt. To conclude, the combination of dif-
ferent in situ spectroelectrochemical methods allows to establish the complete reaction mechanism
of the formation of charged states in PANI upon oxidation.
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4 Surface Techniques
Mohamed M. Chehimi and Jean Pinson
CONTENTS
I. Electrochemistry ................................................................................................................... 192
II. Infrared and Raman Spectroscopy ....................................................................................... 194
III. X-Ray Photoelectron Spectroscopy ...................................................................................... 197
IV. Time-of-Flight Secondary Ion Mass Spectroscopy .............................................................. 198
V. Atomic Force Microscopy ....................................................................................................200
VI. Miscellaneous ....................................................................................................................... 201
VII. Conclusion ............................................................................................................................202
References ......................................................................................................................................203
Chapter 42 describes the formation of surface-bound films by electrochemistry. In most cases, these
films are nanometer thick, and their detection and characterization is by no way straightforward as
it requests the use of high-performance surface-sensitive analytical tools. This chapter highlights a
large set of methods that permit to interrogate the said thin films in terms of the following important
characteristics: (1) the thickness of the film, (2) the chemical structure (Which chemical groups are
present? What is the length of the oligomers?), (3) the compacity of the film (presence or absence of
pinholes in the film; How many groups are bonded to the surface per cm2, Γsurf? How many groups
are there in the whole thickness of the layer, Γvol?), (4) the presence of a chemical bond between
the surface and the film, and (5) the final properties of the film (hydrophilic/hydrophobic surface,
possible attachment of biomolecules, possible analytical measurements, permeability to molecular
probes, etc.).
During the design of experiments dealing with the modification of surfaces and the necessary
ensuing analysis, some important points should be taken into account.
In order to obtain a good characterization of the film, it is interesting to prepare the film with a
functional group or a unique elemental marker that can be easily identified by one or several of the
techniques described in the following; for example, nitroaromatic groups can be identified through
their reversible system in aprotic medium (~−1.2 V vs. SCE), through their asymmetric and sym-
metric infrared (IR) bands (~1520 and 1340 cm−1), and through a characteristic x-ray photoelectron
spectroscopy (XPS) signal at 406 eV clearly separated from other nitrogen signals; this is why this
group has been widely used. Fluoro and perfluoro groups and long alkyl chains can also be easily
characterized.
Electrografting reactions, but also chemical or spontaneous grafting, often yield, besides the film
on the surface, products in solution that can physisorb on the surface. Therefore, the surface must be
carefully cleaned to be certain that only the grafted products are examined. This is generally done
by rinsing the surface under sonication or in a Soxhlet extractor in good solvents of the expected
side products.
When examining thin films using different physicochemical techniques, one should be aware that
depending on the method, different parts of the film are observed. For example, electrochemistry
should, in principle, reflect the presence of all the electroactive groups in the film, but we will see in
Section I, that this is not always the case. An IR beam penetrates the film on a distance of the order 1
191
wavelength that is on a distance of the order of 1 µm, which for thin films amounts to the whole thick-
ness of the film. In XPS, photoelectrons escape elastically from a depth of 5–10 nm, which means that
for relatively thick films, only the outermost layers will be examined. In contrast, inelastically scat-
tered electrons escape from very well-buried layers (up to 30 nm or more) and contribute to the shape
and intensity of the survey spectral background. With time-of-flight secondary ion mass spectroscopy
(ToF-SIMS), only the extreme surface of the film (<1 nm) is observed; therefore, if one looks for a sig-
nature of the bond between the surface and the film, very thin layers should be prepared.
This chapter does not intend to describe the backgrounds of the different analytical techniques
used for the characterization of thin films [1], but rather emphasizes their usefulness in investigating
the physicochemical properties of the latter.
I. ELEcTROchEMiSTRY
Electrochemistry (for a general description of electrochemical methods, see Chapter 1 and [2]) is
very useful to prepare thin films as shown in Chapter 42; in this section, we will show that it is also
very useful for the characterization of the films particularly when the films contain electroactive
groups. This is shown [3] in Figure 4.1, which presents the cyclic voltammetry of a poly(4-nitrophen-
ylene) film (10.7 nm) on glassy carbon (GC) obtained by reduction of 4-nitrobenzenediazonium.
The reversible system is located at the same potential as nitrobenzene under the same conditions.
This system decreases upon cycling due to the slow protonation of the radial anion by the residual
water in the solvent. From the integration of such voltammograms, it is possible to deduce the con-
centration of the aryl groups on the surface; however, such measurements are not valid for films
thicker than approximately 4 nm as not all of the nitro groups do respond electrochemically (see
Section V).
The use of redox probes is also very useful for the detection of films on surfaces: an electro-
chemical couple (redox probe, e.g., Fe(CN)63/4− in solution) that gives a reversible system on a bare
electrode is observed on the modified electrode. If the reversible system becomes slower or even
vanishes, this is a good indication of the presence of a film on the surface as shown in Figure 4.2.
A detailed interpretation of the voltammograms is however difficult. It depends on a number of fac-
tors such as electrostatic interactions between the probe and the film on the surface (e.g., between
–C6H4 –COO − and Fe(CN)63−/4−; Figure 4.2), the compacity of the film and the presence of pinholes,
and the possibility of transferring electrons through the film.
The presence of a film on the surface can also be detected by electrochemical impedance
spectroscopy, for example, the capacity and the charge transfer resistance can be obtained from
F GC-Ph΄-NP NO2
NO2
C NO2
Increasing cycle no.

(2–13)
–2.0 –1.5 –1.0 –0.5 0.0
E(V) vs. SCE
FiGURE 4.1 Cyclic voltammogram of a poly(4-nitrophenylene) film grafted on GC in ACN + 0.1 M Bu4NBF4.
(Reprinted with permission from Ceccato, M., Nielsen, L.T., Iruthayaraj, J., Hinge, M., Pedersen, S.U., and
Daasbjerg, K., Langmuir, 26, 10812–10821. Copyright (2010) American Chemical Society.)
Surface Techniques 193
120
80
C –(C6H4NO2)n
40 C6H4NO2
I (μA)
Fe(CN)63–/4–
0 C6H4COOH In solution
–40
C –(C6H4COOH)n
–80
–120
–0.2 0.0 0.2 0.4 0.6
E (V vs. Ag/AgCl)
FiGURE 4.2 Cyclic voltammogram recorded in aqueous (0.1 M KCl, pH = 7) 5 mM Fe(CN)63−/4−

solution; v = 50 mV s−1 for a bare carbon electrode (---) and 4-nitrophenyl- and 4-carboxyphenyl-modified
GC electrodes (—). Modification by reduction of the corresponding diazonium salt. (Reprinted with permis-
sion from Baranton, S. and Bélanger, D., J. Phys. Chem. B, 109, 24401–24410. Copyright (2005) American
Chemical Society.)
a Nyquist diagram as shown in Figure 4.3. One observes that the charge transfer resistance Rct
depends on the grafted film (including the thickness of the film) [5]. The highest resistance is
obtained for dodecylphenyl groups, which also lead to the lowest capacity.
In scanning electrochemical microscopy (SECM) [6], the species formed at the microelectrode
in the solution, in front of a surface, can react on this surface. This method also permits to observe
the modification of the surface, for example, the response observed at the SECM microelectrode
is different whether the surface is conductive or not [7]. This is exemplified in Figure 4.4: a nitro-
benzene derivative is reduced to aniline at the SECM tip, this amine is diazotized as it diffuses to
the surface, and the resulting diazonium attaches to the surface to produce a micropattern on the
surface. This pattern can be imaged by the SECM; the current at the SECM microelectrode due
to the oxidation of K4[Fe(CN)6] decreases over the aryl-modified pattern as the insulating organic
layer passivates the surface and prevents the regeneration of the reduced species. This method also
permits to detect and characterize pinholes in the film [8].
High frequency
21,000
1/C
14,000
–Zim (Ω)
C C12 H25
7,000
n
c d Rct
0 a b
0 10,000 20,000 30,000
Zre (Ω)
–7,000
FiGURE 4.3 Impedance spectra of an iron electrode in a 0.01 M aqueous solution. (a) Bare, (b–d) modified
by (b) phenyl, (c) 4-bromophenyl, (c) 4-dodecylphenyl groups by reduction of the corresponding diazonium
salt. (Reprinted with permission from Chaussé, A., Chehimi, M.M., Karsi, N., Pinson, J., Podvorica, F., and
Vautrin-Ul, C., Chem. Mater., 14, 392–400. Copyright (2002) American Chemical Society.)
8.3
8.2
1
O 2N R H 2N R
I (μA)
8.1
Diazotization
+
–– R 8.0
R N –N
2
7.9
0 20 40 60 80 100
(a) (b) x (μm)
FiGURE 4.4 (a) Electrografting of a GC surface with aryl groups by use of a SECM and (b) characterization
of the micropattern by the SECM tip. (Adapted from Cougnon, C. et al., Angew. Chem. Int. Ed., 48, 4006, 2009.
With permission.)
II. INfRARED AND RAMAN SPEcTROScOPY

The reader is referred to textbooks for the basics of IR and Raman spectroscopy [9]. Most surfaces
cannot be examined by transmission, but several methods can be used to obtain IR spectra from
modified surfaces. Infrared reflection–absorption spectrometry (IRRAS also known as RAIRS),
polarization-modulated IRRAS (PMIRRAS), attenuated total reflection (ATR), and multiple inter-
nal reflection Fourier transform infrared spectroscopy (MIRFTIRS) have been mostly used to
investigate electrografted surfaces. Using very sensitive mercury cadmium telluride semiconduct-
ing detectors at the temperature of liquid nitrogen and a Fourier transform spectrometer, it is
possible to record spectra down to or below organic monolayers. With Raman spectroscopy, a
very high sensitivity can be reached by using surface-enhanced Raman spectroscopy (SERS) on
rough surfaces or on nanoparticles. This enhancement factor can reach 1010 over normal Raman
spectroscopy. From these spectra, one can not only determine the type of chemical groups on the
surface (mostly chemical groups with very characteristic IR spectra are included in the structure
such as –NO2, –CF3, and alkyl) [9c,d] and the orientation of ordered molecules on the surface but
also observe the chemical bond between the surface and the organic film. We now show some
characteristic examples of these vibrational spectroscopies for the characterization of thin films
attached to various surfaces.
IRRAS spectra are obtained by measuring the light reflected by the surface at near grazing
incidence (e.g., 85° to the normal of the surface); due to surface selection rules, only vibra-
tions with a component perpendicular to the surface will be active [10]. Figure 4.5 displays the
spectrum of poly(p-phenylene) on a gold surface [11]. This surface was obtained by attaching
a near-monolayer of phenyl groups on a gold surface by electrochemical reduction of benzene-
diazonium salt. Then the growth of this layer on top of the primary layer was achieved by oxi-
dation of biphenyl; both reactions were performed in one pot in the [BMIm][PF 6] ionic liquid.
The vibrations in the in- or out-of-plane region (1001, 812, 763, 695 cm −1) are characteristic of
a para substitution.
101.546
100
1001 Au + N N+
Echem red Au
1398 BF4– [BMIm] [P6F]
695 ACN
95 Bu
N N
CH3
%T
= [BMIm] [PF ]
PF – 6
6
1482 763
Echem Ox
Au
biphenyl
90 [BMIm] [P6F]
812
n
87.0145
1571.16 1400 1200 1000 800 650
Wavenumber (cm–1)
FiGURE 4.5 IRRAS spectrum of a poly(para-phenylene) layer attached on a gold substrate. (Adapted from
Descroix, S. et al., Echim Act., 106, 172, 2013.)
PMIRRAS spectra are obtained by modulating the polarization of the incipient beam with a polar-
izer and gating the response of the detector accordingly, which results in an enhanced sensitivity.
ATR spectra are obtained by pressing the modified surface to be analyzed against a prism (dia-
mond, germanium); the incident light enters the prism at such an angle that total reflection (single or
multiple) occurs at the prism–sample interface. The evanescent wave penetrates the sample and decays
exponentially; a spectrum of the modifying film can be recorded. Figure 4.6b presents the ATR spec-
trum (obtained on a Ge prism at 65° incidence) of a near-monolayer (1.9 nm) of 4-[2-(4-nitrophenyl)
diazenyl]-phenyl groups (NAB monolayer) grafted on an atomically flat type of carbon (PPF) by
1344
1521
690
860
1588
774
0.1
NAB solid
(a) NO2
0.001 NAB (1.9) monolayer N

N
Absorbance
(b)
C
0.001 NAB physisorbed
(c)
600 900 1200 1500 1800

Wavenumber (cm–1)
FiGURE 4.6 ATR spectra of (a) solid NAB, (b) the corresponding grafted monolayer, and (c) a physisorbed layer
of NAB; (b) and (c) recorded on a PPF surface. (Reprinted with permission from Anariba, F., Viswanathan, U.,
Bocian, D.F., and McCreery, R.L., Anal. Chem., 78, 3104–3112. Copyright (2006) American Chemical Society.)
reduction of the corresponding diazonium salt [12]. This example is interesting as it shows that both
the structure of the grafted group and its orientation on the surface can be ascertained.
The spectrum of nitroazobenzene (NAB) can be calculated in order to assign the different bands
of the spectrum corresponding to the ring vibration (1588 cm−1): the very characteristic bands of
the nitro group (1521 and 1344 cm−1 asymmetric and symmetric vibrations), in-plane ring breath-
ing vibration coupled to an in-plane phenyl–NO2 bend at 860 cm−1, and out-of-plane C–H vibrations
at 774 and 690 cm−1. It is interesting to compare the spectra of solid NAB (NABsolid, Figure 4.6a)
and physisorbed NAB (NABphysisorbed, Figure 4.6c), with that of the monolayer. In solid NAB, the
molecules are randomly oriented, and both in-plane and out-of-plane vibrations are observed; in
NABphysisorbed, the symmetric vibration of the NO2 groups (1344 cm−1) has nearly disappeared and the
asymmetric one (1521 cm−1) has decreased, while the out-of-plane vibrations have a significant inten-
sity. These features are consistent with a molecule lying flat on the surface of carbon. On the contrary,
the out-of-plane bands of NABmonolayer are very weak indicating that the groups stand upright on the
surface. It is possible to calculate that the molecule is tilted by approximately 30° by reference to the
surface normal. In addition, the absence of the –+N≡N vibration in the 2100–2130 cm−1 region indi-
cates that the dediazonation has occurred during the electrochemical reduction of the diazonium salt.
MIRFTIRS spectra on Si have been obtained by using a Si wafer polished on both faces and
beveled on the two opposite sides; the IR that enters one side undergoes several reflections before
reaching the detector. One side of the prism is used for modification. It is thus possible to follow the
course of the electrografting reaction by recording spectra as a function of time. Figure 4.7 presents
the electrografting of a hydrogenated silicon surface (Si–H) modified by oxidation of phenylmag-
nesium bromide that provides a polyphenylene layer (see Chapter 42) [13]. The spectra recorded
as a function of the number of electrochemical pulses show the disappearance of the νSi–H band,
which is a good indication of the formation of covalent bonds between the film and the Si surface
that gives interfacial Si–C bonds (note that the Si–H band is negative and becomes larger with the
number of pulses: the background spectrum is recorded with a Si–H surface; therefore, Si–H vibra-
tions do not appear at the start of the experiment; as these Si–H groups disappear, they give rise to
a negative band on the spectrum). The presence of νC–H bands in the 2800–3000 cm−1 region is
related to the incorporation of solvent fragments into the film. The bands in the 1400–1600 cm−1
region are related to the aromatic ring vibrations; they increase nearly linearly with the charge used
for the modification, indicating the growth of the polymer. The negative νC–H aliphatic bands and
the increase of the νC–H aromatic bands in the 3000 cm−1 region correspond to the exclusion of the
solvent tetrahydrofuran from the surface due to the growth of the polymer.
νSiH νCH
Aromatic
Aliphatic
Absorbance per reflection
n = 80
0.1 n = 70
n = 60
n = 50 H –Ar–Ar–Ar
n = 40 Si H + ArMgCl – 1e– Si –Ar–Ar–Ar
0.05 n = 30 H –Ar–Ar–Ar
n = 20
n = 10
n=0
0 n=0
1000 2000 3000 4000
Wavenumber (cm–1)
FiGURE 4.7 In situ IR spectra during the electrochemical modification of the Si–H surface in phenylmag-
nesium bromide; n is the number of current pulses applied before recording the spectrum. (Reprinted with
permission from Fellah, S., Ozanam, F., Chazalviel, J.-N., Vigneron, J., Etcheberry, A., Stchakovsky, M.,
J. Phys. Chem. B, 110, 1665–1672. Copyright (2006) American Chemical Society.)
1,358
4,000 counts
1,577
1,073
1,130 1,107
50,000 counts
860
635 dNB on AuNPs
1,010
1,545
dNB
powder R
(a)
1,344
1,282
R
1,110
1,589
1,201
–N2
40 nm + ?
852
1,080 AuNP
1,005
dNB on
412
AuNPs N2+
300 500 700 900 1,100 1,300 1,500 1,700 350 375 400 425 450 475
(b) Raman shift (cm–1) (c) Raman shift (cm–1)
FiGURE 4.8 Raman spectra of (a) 4-nitrobenzenediazonium, (b) Au nanoparticles spontaneously grafted
with a film of 4-nitrophenyl groups, and (c) the 412 cm−1 band corresponding to the Au-aryl bond. (Reprinted
with permission from Laurentius, L., Stoyanov, S.R., Gusarov, S., Kovalenko, A., Du, R., Lopinski, G.P., and
McDermott M.T., ACS Nano, 5, 4219–4227. Copyright (2011) American Chemical Society.)
SERS has been used to demonstrate the existence of a bond between gold nanoparticles and a film of
4-nitrophenyl groups obtained by spontaneous grafting of 4-nitrobenzenediazonium in ACN [14]. The
spectrum (dNB on AuNPs; Figure 4.8) shows the NO2 symmetric stretching vibration at 1344 cm−1 and
the ring vibration at 1589 cm−1, but the most interesting feature is a small band at 412 cm−1 that corresponds
to the Au–aryl bond as shown by comparison with density functional theory (DFT) calculations. These
results were further confirmed by high-resolution electron energy loss spectroscopy (measures the energy
loss of electrons inelastically scattered by adsorbed molecules); the Au–C bond appears at 420 cm−1.
III. X-RAY PhOTOELEcTRON SPEcTROScOPY

In this technique [15], an x-ray beam is shone on a surface with sufficient energy to extract core
electrons (e.g., C1s, N1s, and O1s of the organic films). The kinetic energy of this electron is
measured by a spectrometer as well as the number of electrons emitted at a given energy. The
basic equation is given by KE = hν − BE, where KE is the kinetic energy of the electron, hν is the
energy of the x-ray beam, and BE is the binding energy of the core electron, which is characteris-
tic of the emitting element (C1s, O1s, Au4f 7/2 at 285, 530, and 84 eV, respectively). This bonding
(between the electron and the nucleus) is somewhat sensitive to the chemical environment of the
atom. Therefore, it is possible to distinguish the chemical environment of each element, for exam-
ple, the BE of C1s from C–H, C=O, and C–F2 is 285, ~288, and ~292 eV, respectively). This so-
called chemical shift is the cornerstone of XPS. Databases are available that provide the energy of
a number of elements in different compounds [15b]. Besides, the peak area is proportional to the
concentration of the emitting element, hence the possibility to compute a raw formula of the film
on the surface. The thickness of the film can be obtained by measuring the attenuation of the peak
corresponding to the substrate or that of the top layer via the well-known Beer–Lambert equation,
or by peak shape analysis (e.g., quantitative analysis of surfaces by electron spectroscopy) [16].
Figure 4.9 shows the XPS spectrum of a gold surface electrografted by butylamine: Au–NH–Bu
[17]. One observes the Au4f 7/2–Au4f5/2 doublet at 84.0–87.7 eV, C1s centered at 285 eV (part of
the signal corresponds to surface contamination), and N1s centered at 400 eV and O1s at 532 eV
(surface oxide and contamination). Observation of the gold substrate indicates that the layer is thin-
ner than the analysis depth (~10 nm). Interestingly, the peak-fitted N1s peak indicates the presence
of a signal at 398.1 eV that can be assigned to the Au–NH– bond.
Figure 4.10 presents the XPS spectra of bromophenyl groups electrografted from the corresponding
diazonium salt and then submitted to positive and negative potentials [18]. These spectra indicate that
at quite high potential, most of the film is removed, but that part of it remains attached to the surface.
50,000 Au 41,500
Au –NH–Bu
40,000 41,000
Intensity (cps)
Intensity (cps)
N
30,000
40,500
C
20,000
40,000
10,000
39,500
0
0 200 400 600 395 400 405
(a) Binding energy (eV) (b) Binding energy (eV)
FiGURE 4.9 XPS spectrum of a gold surface electrografted by oxidation of butylamine: Au–NH–Bu.
(a) Survey spectrum and (b) N1s peak. (Reprinted with permission from Adenier, A., Chehimi, M.M., Gallardo,
I., Pinson, J., and Vilà, N., Langmuir, 20, 8243–8253. Copyright (2004) American Chemical Society.)
18
4-bromophenyl
16
2.6 V
14 Br
12
Counts (kCPS)
2.2 V
10
8
6
4 as-deposited C
2 –2.6 V –1.6 V
0
75 70 65
–Binding energy (eV)
FiGURE 4.10 XPS spectrum (Br3d5/2–Br3d3/2 doublet) of a bromophenyl layer submitted to positive or nega-
tive potentials. (Reprinted with permission from D’Amours, M. and Bélanger, D., J. Phys. Chem. B, 107,
4811–4817. Copyright (2003) American Chemical Society.)
IV. TiME-Of-FLiGhT SEcONDARY ION MASS SPEcTROScOPY

A pulsed ion beam (Au+, Bi+, etc.) is used to bombard the surface, fragments are emitted from the
surface, and most of them are neutral, but some ions are produced that can be analyzed by mass
spectroscopy [19]. Organic fragments can be identified through their exact mass. This permits to
obtain a detailed analysis of the surface. Figure 4.11 presents a demonstrative ToF-SIMS spectrum
of a Ru complex electrografted from the corresponding diazonium salt [20]; the observation of
many fragments containing Ru and bipy and particularly C6H4-bipyRu(bipy)2+ leaves no doubt about
the presence of the complex on the surface.
Bonding between the substrate and the film can also be demonstrated by ToF-SIMS. A cop-
per surface electrografted by reduction of n-C6H13-I has been analyzed by ToF-SIMS [21]. One
can observe not only (CH 2)1–4 –CH3+ that testifies for the presence of an alkyl chain on the sur-
face but also Cu(CH 2)2–4+ that demonstrates that this layer is attached to the copper surface via
a Cu–C bond.
In dynamic SIMS, the film is much more eroded by sputtering high doses of ions (O2+, Cs+, etc.) on
the surface while recording the intensity of characteristic secondary ions at a given mass. With this
×105 ×6
Intensity
1.5
bpy+
1.0
0.5
40 60 80 100 120 140 160 180 bipy bipy
Ru
×104
×2
(ph-bpy-N2 )+ Ru(ph-bpy)+
Intensity
1.5 (ph-bpy)+ bipy

1.0 Ru(bpy)2+
0.5
250 300 350 400
×103 Ru(bpy)(ph-bpy)+ C
Intensity
0.6 ×2 Ru(bpy)2 (ph-bpy)+

0.4
0.2
450 500 550 600 650 m/z
FiGURE 4.11 ToF-SIMS spectrum of a carbon surface electrografted by a Ru complex. bipy = 2,2′-bipyri-
dine. (Reprinted with permission from Piper, D.J.E., Barbante, G.J., Brack, N., Pigram, P.J., Hogan, C.F.,
Langmuir, 27, 474–480. Copyright (2011) American Chemical Society.)
100 PBMA
90
80
70 NPPBMA–NPPBMA–NPPBMA–NPPBMA–NP–NP–NP–
Normalized intensity
NP–NP–NP
60 NPPBMA–NPPBMA–NPPBMA–NPPBMA–NP–NP–NP– Au
50 NPPBMA–NPPBMA–NPPBMA–NPPBMA–NP–NP–NP–
40 Au
30
NP Fragments Attribution m/z
20 C2H PBMA 25.01
C4H5O2 PBMA 85.04
10 CNO PNP 42.00
Au Substrate 196.97
0
0 100 200 300 400 500 600 700 800 900 1000
Time (s)
FiGURE 4.12 (See color insert.) Dynamic SIMS of an organic layer electrografted by simultaneous reduc-
tion of 4-nitrobenzenediazonium and butyl methacrylate in an aqueous miniemulsion. NP, nitrophenyl frag-
ment; NP–NP–NP, poly(para-nitrophenylene); PBMA, fragments from polybutyl methacrylate. (Reprinted
with permission from Tessier, L., Deniau, G., Charleux, B., and Palacin, S., Chem. Mater., 21, 4261–4274.
Copyright (2009) American Chemical Society.)
technique, increasing times correspond to analyzing very-well-buried layers in the film. Figure 4.12
presents the dynamic SIMS analysis of a gold surface modified by electrografting simultaneously
butyl methacrylate and 4-nitrobenzenediazonium in an aqueous emulsion [22]. The film includes
a primary layer of poly(4-nitrophenylene) bonded to the surface and an external layer bonded to
the first one composed of poly(n-butyl methacrylate), PBMA, chains terminated by a nitrophenyl
group (see Chapter 42, Scheme 42.6). This is clearly evidenced on the profile of Figure 4.12: at short
etching times, fragments of nitrophenyl-terminated PBMA are observed (PBMA and NP groups in
Figure 4.12). As the analysis time increases, the primary beam penetrates deeper and deeper in the
film; the intensity of secondary NPPBMA fragments decrease, while poly(4-nitrophenylene) frag-
ments (NP–NP–NP) increase; and finally the gold surface is reached as shown by the appearance
of the Au+ ion. This experiment indicates that, as presented in Figure 4.12, the film consists in a
primary layer of poly(p-nitrophenylene) attached to the gold surface and to a secondary layer of a
copolymer poly(MBA-co-NP).
V. ATOMic FORcE MicROScOPY

Atomic force microscopy (AFM) [23] has been used to image films obtained by electrografting;
Figure 4.13 presents a film obtained by electrografting 4-nitrobenzenediazonium on a H-terminated
boron-doped diamond surface, reducing the nitro group to an amino group and attaching DNA
oligonucleotides [24]. A fine structure corrugation is observed with an amplitude of 0.8 nm.
AFM has also been used to image the surface during the electrografting process, for example, on
highly oriented pyrolytic graphite (HOPG), electrografting of 4-diethylaminophenylbenzenediazo-
nium takes place initially at step edges and then on defects, before covering the surface from these
defects (Figure 4.14) [25].
AFM is also a very useful technique for measuring the thickness of the films. For this purpose,
one must use a very flat and rather hard surface such as PPF or diamond, attach the organic film,
scratch the film with an AFM tip (without scratching the surface), and measure the height of the
step by recording a profile with a second tip. An example of this method [26a] is presented in
Figure 4.15. A methylphenyl film is electrografted on a PPF surface by reduction of the correspond-
ing diazonium salt; it is then locally removed by scratching with an AFM tip. The profile indicates
that the film is 2.3 nm thick. Such measurements have permitted [26b] to demonstrate that integra-
tion of voltammograms does not provide reliable surface concentration (Γvol) for films thicker than
approximately 4 nm as shown in Figure 4.15b, where the integration gives constant values while the
AFM thickness of the film increases.
AFM also permits to measure the strength of the substrate–film bond [27]. For this purpose, a
gold AFM tip was modified with 2-aminoethanethiol Au–SH–(CH2)2–NH2, and a gold electrode DNA*
DNA
Relative height (nm)
O N O
CH2
3
C=O
2 HN
1
Diamond
0
Z range 3 nm H 10 nm 0 100 200 300
(a) (b) Lateral distance (nm)
FiGURE 4.13 (See color insert.) AFM surface morphology of a diamond surface modified with DNA oli-
gonucleotides: (a) morphology and (b) profile after filtering. (Reprinted with permission from Rezek, B.,
Shin, D., and Nebel, C., Langmuir, 23, 7626–7633. Copyright (2007) American Chemical Society.)
(a) (b)
Et Et
N
(c) (d)
HOPG
(e) 1 μm (f ) 1 μm
FiGURE 4.14 AFM images of an HOPG surface during its modification by reduction of 4-diethylamino
benzenediazonium. (a) bare surface; (b–f) increasing number of voltammetric cycles. (Reprinted with per-
mission from Kariuki, J.K. and McDermott, M.T., Langmuir, 15, 6534–6540. Copyright (1999) American
Chemical Society.)
was electrografted by poly(N-succinimidyl acrylate) (Au–(CH2–CH)nC(=O)–N–Suc). An interac-

tion of 0.3 nN is measured when the unmodified gold tip is brought into contact with the polymer
and then retracted; this strength corresponds to the physisorption of poly(N-succinimidyl acrylate)
on gold. However, an interaction of 1.3 nN is measured when the tip is modified. This is due to the
reaction of the amino groups on the tip with the succinimidyl groups on the electrode leading to
the formation of an amide bond. A force of 1.3 nN is indicative of the rupture of a chemical bond,
indicating a chain of covalent bonds between the tip and the gold electrode. This demonstrates the
existence of a bond between the gold electrode and the vinylic polymer (Figure 4.16).
VI. MiScELLANEOUS
Other methods are available such as contact angle measurements (that measure the surface
energy and evidences, e.g., the hydrophilicity/hydrophobicity of a film) [28]; Rutherford back-
scattering (that gives an absolute value of the surface concentration Γvol) [29]; IR spectroscopic
ellipsometry (that permits to obtain at the same time the film thickness and the dielectric func-
tion in the IR range) [1b]; and quartz crystal microbalance (that permits to follow the mass
deposited on the gold-coated crystal during the grafting) [30].
CH3
PPF
12
(10–10 mol cm–2)

10
4.0 8
Height (nm)
measured
0 4
2.3 nm
NO2
2
–4.0
0
0 2.5 5.0 7.5 0 1 2 3 4 5 6 7
(a) μm (b) Film thickness, δ (nm)
FiGURE 4.15 (See color insert.) (a) AFM measurement of the thickness of a poly(4-methylphenyl) film.
(b) Correlation of the surface concentration measured by electrochemistry ΓNO2 and the AFM thickness of the
film. (Reprinted with permission from Brooksby, P.A. and Downard, A.J., Langmuir, 21, 1672–1675; J. Phys.
Chem. B, 109, 8791–8798. Copyright (2005) American Chemical Society.)
NH
CO
1.3 nN
0.3 nN
Au
FiGURE 4.16 AFM demonstration of the bonding between an aminated tip and a gold substrate electro-
grafted with a polyacrylate film. (Adapted from Cuenot, S. et al., Macromol. Chem. Phys., 206, 1216, 2005.
With permission.)
VII. CONcLUSiON
This chapter gathers some examples of the methods available for the characterization of electro-
grafted or spontaneously grafted thin films and monolayers from a range of organic compounds.
Provided one can access and compile results from a set of these techniques, a very detailed char-
acterization of a film can be obtained. In addition, surface modeling by theoretical methods (such
as DFT) provides a lot of information that can be compared with the experimental results. For
example, the following characteristics can be deduced from calculations: the type of bonding of
a molecule (attached to one or two atoms on the surface), the energy of the bond and therefore its
stability, and the stereochemistry of the attachment (the molecules are tilted, lying flat, or upright
on the surface) [31].
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5 Application of Digital
Simulation
Bernd Speiser
CONTENTS
I. Introduction .......................................................................................................................... 205
II. Basics and Theory ................................................................................................................206
A. Definition ......................................................................................................................206
B. Modeling .......................................................................................................................207
1. Physicochemical Modeling ....................................................................................207
2. Mathematical Modeling .........................................................................................208
C. Algorithms ....................................................................................................................209
1. (Semi)Analytical Solution......................................................................................209
2. Basic Numerical Algorithms ................................................................................. 210
3. Problem Situations ................................................................................................. 210
4. Adaptive Algorithms.............................................................................................. 212
D. Simulators ..................................................................................................................... 214
III. Application............................................................................................................................ 216
A. Solution Quality ............................................................................................................ 216
B. Exploration and Prediction ........................................................................................... 216
C. Presentation of Simulated Results ................................................................................ 217
D. Qualitative and Quantitative Analysis of Mechanisms ................................................ 217
IV. Conclusion ............................................................................................................................ 222
References ...................................................................................................................................... 222
Simulation … is the generation by models of a real without origin or reality: a hyperreal.

Baudrillard [1]
I. INTRODUcTiON
The term simulation has made a surprising career over the last few decades. Despite the rather pes-
simistic view taken by postmodern French philosopher Jean Baudrillard [1], who sees our society as a
precession of simulacra—artifacts produced by the simulation of something not real—simulation has
proven itself as a rather helpful tool in scientific research. Starting out even before the advent of elec-
tronic equipment with calculations in fluid dynamics (see [2], p. 2), through human computing groups
with mechanical calculators for ballistic computation during World War II and John von Neumann’s
first uses of programmable machines [3], simulation is nowadays indispensable in very-large-scale
scientific endeavors such a astronomy, weather, or climate modeling [4]. Already in 1981, Douglas R.
Hofstadter [5] used the example of simulating a storm to point out that a simulation is indeed (only)
a simulation, but not reality, and as such is an entity by itself. Most recently, the methodological and
epistemological implications of simulation research have begun to be addressed by historians, sociolo-
gists, and philosophers of science [4,6]. In this context, simulation was described as a new, third means
205
of generating scientific knowledge, besides experimentation and theoretical reasoning [4,7]. Such in
silico experiments (see [6], p. 1) might well fundamentally transform the way we are doing science [6].
On a much smaller spatial and temporal scale of the pertinent phenomena as compared to climate
and earth science simulation, organic electrochemistry has benefitted from simulation already when
chemists started to understand organic electrochemical reactions from a physical–organic point of
view [8], that is, in terms of kinetics, thermodynamics, and mechanisms. Britz (see [2], p. 2) mentions
that simulations (by “pencil and paper”) were performed in electrochemistry as early as 1948 [9].
This chapter provides a discussion of the basics of simulations in organic electrochemistry, the
methods used, and how such techniques are advantageously applied to both, elucidate organic elec-
trode reactions and characterize organic compounds with respect to their redox properties. Only a
selection of pertinent papers can be mentioned. See earlier reviews and books on the use of simulation
techniques in the electrochemical context [2,8,10–12] for additional information and more details.
II. BASicS AND ThEORY

A. DEFINITIoN
A model is—for the purpose of this discussion—the description of an electrochemical experiment
including the chemical reactions associated with it. By necessity, this description will be a simpli-
fication of the complex reality, making (sometimes far-reaching) assumptions about certain details
and their (un-)importance. It is formulated as a set of mathematical equations. Both the process of
solving the model equations and the result of such a calculation are called simulation. Note, that in
the literature, the terms modeling and simulation are sometimes used as synonyms [13].
Despite the simplifications, in general, the model equations cannot be solved in a closed form,
that is, by presenting a mathematically exact relationship based on elementary functions between
some parameters describing the experiment on one hand and the observables that are accessible to
the experimenter on the other. Rather, a form of approximation is introduced, often to express an
integral, a differential quotient, or a continuous variable by a discrete finite value (discretization).
In the majority of cases, the approximated equations are solved by numerical calculations on a
digital computer, and consequently, the terms numerical simulation and digital simulation are both
popular. Numerical artifacts incurred during solution comprise another potential source of errors in
addition to simplifications and approximations. Analog simulation has been mentioned [14,15] but
has remained much less important, except in impedance work, which is not considered here.
Modeling of electrochemical experiments is also possible “without digital simulation” [16], using
semianalytical formulas as a more recent variation of rather early numerical modeling approaches
[17] (see Section II.C.1). Still, however, certain discretization (and numerical summation) steps are
involved [16].
Computational electrochemistry is in use for simulation in the field of electrochemistry
[11,18,19], although this is sometimes reserved for quantum chemical models (see, e.g., Chapter 6).
Such calculations on an atomistic level result in energies and, consequently, redox potentials [20]
or mechanistic details [21,22], but a first-principle approach has also been applied to cyclic voltam-
metric simulation [23].
The level of transport, electron transfer, and chemical reaction processes, that is, elementary
reaction steps, that will be treated in this chapter is characterized by the task to solve reaction–
diffusion (partial differential) equations. Such simulations are probably most often performed to
model cyclic voltammetry [24–26]. However, many other types of electrochemical experiments,
including chronoamperometry [24,27–30], bulk electrolysis [31], as well as those conducted with the
scanning electrochemical microscope [32,33], channel electrodes [27,34], or in multiphase systems
[35] were also modeled by simulations.
Even more complex are simulations of complete electrochemical cell systems including their
environments from a technological point of view [36,37]. Multiscale simulations that link numerical
Application of Digital Simulation 207
Comparison to
experimental data
Solver
algorithm
Concentration/space
Physico chemical Mathematical and/or
model model current/potential/time
results
Extraction of
features
FiGURE 5.1 Stages of (electrochemical) modeling studies.
results of several levels of complexity have also been reported [23,38]. In organic electrochemistry,
usually the intermediate elementary reaction level is applied, and the simulation generally com-
prises the following steps (Figure 5.1): In the beginning, we define a physicochemical model of the
processes and the reaction steps that are involved and assumed to be relevant to describe the real
situation. The laws of physics and chemistry then lead to a mathematical formulation in the form
of differential equations that are solved by means of a selected numerical algorithm. The resulting
data describe the concentrations of all pertinent chemical species at certain space points and/or the
development of current and electrode potential with time. Such data are either directly compared to
experimental data for qualitative or quantitative analysis of the experiment or analyzed with respect
to characteristic features of the numerical solution results for further use.
B. MoDELING
1. Physicochemical Modeling
Many elements of the underlying physicochemical models have been discussed in Chapters 1 and 2
of this book. They will be briefly reviewed.
The processes investigated in organic electrochemistry proceed at the surface and in the vicinity
(diffusion layer, bulk electrolyte) of the working electrode, and include the following:
• Transport to and from the charged interface, typically diffusion, resulting in a diffusion
layer close to the electrode
• The transfer of electrons through the phase boundary between electrode and electrolyte
• Coupled preceding or follow-up chemical reactions in the diffusion layer and possibly in
the bulk electrolyte
• Adsorption of starting compounds, intermediates, or products at the electrode surface,
their redox, and chemical reactions
We call the network of these processes and reaction steps the electrode reaction.
General formulations of the ensuing physicochemical equations either become rather abstract
[29] or yield unwieldy expressions. Consequently, we will concentrate on the case of a simplified
system that can be described by a single space coordinate x. In 2D or 3D cases (for some examples,
see [32,39–43]), coordinates y and z have also to be taken into account. Further complications that
have been treated in simulations include the effects of uncompensated resistance and double-layer
capacitance [44,45], current distribution problems [46], as well as transport by convection [47–49]
and migration [47,48,50–52].
2. Mathematical Modeling
Diffusional transport is characterized by Fick’s laws, and Equations 5.1 and 5.2 describe the mass
flux J and the temporal (time t) variation of a concentration c by the diffusion coefficient D and the
first or second space derivative of c, respectively. The exact form of the term describing the second
space derivative depends on the geometry of the experimental setup and is given here for planar
conditions (for other geometries, see, e.g., [2], p. 7, and [45]). The left-hand side of Equation 5.2
becomes zero for stationary (steady-state) processes, where c ≠ f(t), but is nonzero for nonstation-
ary processes with time-dependent c. Both cases are treated by simulation:
∂c
J = −D (5.1)
∂x
∂c ∂ 2c
= − D 2 + K(c) (5.2)
∂t ∂x
Equation 5.2 is conventionally designated as a parabolic partial differential equation for

∂c/∂t ≠ 0 [43] (see also [2], p. 1), while it is an elliptic partial differential equation for ∂c/∂t = 0. It is
formulated for each species involved in the electrode reaction. The respective kinetic term K(c) is
composed of rate laws that describe all relevant homogeneous chemical reaction steps contributing
to the production or loss of a particular species. This term accounts for the almost infinite variety
of electrode reactions and the opportunities of organic electrosynthesis and is defined by the (hypo-
thetical) electrode reaction mechanism.
The resulting system of partial differential equations is solved subject to initial and boundary
conditions. The initial conditions describe the concentrations at the beginning of the time period
investigated in the simulation, t = 0, that is, c(0, x). Typically, we assume the system to be in equi-
librium at t = 0, defined by a homogeneous electrolyte composition throughout the bulk and the
diffusion layer.
The boundary conditions define concentrations for certain points in space, in particular at x = 0
(the working electrode surface, but possibly other electrodes as well, Equation 5.3). Such conditions
include the potential dependence of concentrations imposed by the potential E, fluxes according
to Equation 5.1, electron transfer rate laws (Butler–Volmer [8,25,53,54], Marcus–Hush [54–56], or
equilibrium [30,57,58] relationships), and/or adsorption kinetics and thermodynamics (defined by
isotherms, such as Langmuir [59,60] or Frumkin [61] type). Kinetics of surface reactions has been
included as well [60].
Other boundary conditions are formulated in the bulk of the solution (Equation 5.4), where we
often assume that nothing happens during the simulation (i.e., the c remain at their starting val-
ues) or at the wall of a thin-layer cell (either again an electrode or an inert wall, Equations 5.3 and
5.5, respectively). Since ∂c/∂x defines a flux according to Equation 5.1, it must vanish at an inert
boundary:
∂c
Electrode: = f (E ) (5.3)
∂x xelectrode

Bulk: c(t,∞) = const. (5.4)

∂c
Inert wall: =0 (5.5)
∂x xwall

Additional boundary conditions refer to flux continuity conditions. The current through an electrode
is related to the flux of the redox-active species. In the most simple case
∂c
i = nFAD (5.6)
∂x xelectrode

applies (with n as the number of transferred electrons, F as the Faraday constant, and A as the
electroactive area of the electrode). Together with Equation 5.3, Equation 5.6 can be evaluated for i
(given E and the calculated flux—potential-controlled techniques) or E (given i or the respective
flux—current-controlled techniques [13]).
C. ALGorITHMS
The set of elliptic or parabolic differential equations, defined in Section II.B.2, is solved starting
from the initial and subject to the boundary conditions by integration along the space and time coor-
dinates, under the assumption that values for all parameters such as D, rate constants, and formal
potentials are known. The solution supplies values of the unknown concentrations (concentration
profiles) c = f(x, t) (for nonstationary) or c = f(x) (for stationary problems) and—sometimes simulta-
neously [29]—the current through the electrode(s) or (for galvanostatic experiments) the potential(s)
of the electrode(s). This type of calculation is called the forward problem, while the inverse problem
is defined as the determination of the parameters from comparison of experimental data and simula-
tions [62,63] (see also Section III.D).
The solution of partial differential equation systems describing an electrode reaction as dis-
cussed here does typically not rely on limiting case assumptions (such as used in Chapter 1), which
on the other hand are important tools for the benchmarking (see Section III.A) of the simulation
algorithms described in the following.
1. (Semi)Analytical Solution
If the integration leads to a closed-form (so-called analytical) solution, the simulation results can be
calculated directly. This is, however, impossible in the majority of cases interesting to organic elec-
trochemists. A notable exception is the recent application of transient diffusion equivalent capaci-
tance [64] to electrochemical experiments at arbitrary electrode geometry, which however uses a
linearization of the concentration profiles and only treats diffusion and electron transfer steps. For
more complex electrode reactions and without linearizing assumptions, still, in favorable cases,
judiciously chosen transformations, for example, Laplace transformation [65], lead to expressions
that can be evaluated with only a minimal numerical effort and, possibly, to an assured accuracy
[66] (semianalytical solution). Already the probably most-cited paper for cyclic voltammetric curve
calculation, Nicholson and Shain’s seminal work [17], used such a technique, where either a numeri-
cal (integration by conversion into a set of algebraic equations), an analytical (Abel integral equa-
tion with an exact solution in terms of another integral that is solved approximately), or a series
solution (conversion into a summation) was provided. In particular, the Abel approach has been
revived recently [67–69]. An extensive series of examples that apply the so-called Huber method
has been published by Bieniasz [67–70]. In a similar way, Oldham’s extended work on semi-integral
modeling of electrochemical experiments is based on transformation and subsequent evaluation of
summation expressions [66,71].
Another notable technique that provides approximate analytical solutions to electrochemical
problems is the homotopy perturbation method (described by He [72] and used in electrochemical
contexts by Rajendran and coworkers [73]).
2. Basic Numerical Algorithms

Despite their efficiency, however, semianalytical solutions (see Section II.C.1) cannot guarantee
general applicability. On the other hand, simulation algorithms strive to implement some generality
over a certain class of problems to be solved (see also Section II.D). Several more general numerical
approaches are used widely in electrochemical simulations.
Finite difference approximations of the partial differential equations are probably the most popu-
lar discretization technique in electrochemistry [2,8,12]. In general, the space and time axes are
subdivided into intervals (defined by nodes), and these are either characterized as boxes (see [2],
p. 145ff.) or points (see [2], p. 2). Taking into account the concentration changes between the nodes,
each continuous partial differential equation is converted into a system of ordinary (or algebraic)
equations, effectively substituting the differentials by differences. Britz [2] discusses a large number
of schemes applicable to electrochemical problems. The solution process proceeds through time
steps Δt, calculating new concentrations at the various space nodes for each t. The smooth, exact but
unknown concentration profile at a certain t is substituted by steps or linear segments. By decreas-
ing the interval size, the differentials and the concentration profiles can be approximated more
closely, but the numerical effort increases.
Orthogonal collocation substitutes the concentration profiles by polynomials of appropriate
order. The polynomial is determined by forcing exact fulfillment of the differential equation locally,
at certain points (usually, the zeroes of the polynomials) [2,10,74]. The procedure converts each par-
tial differential equation into a set of ordinary differential equations (ODEs) [75,76], which is then
solved by standard numerical methods [77,78].
The finite element method imposes global constraints over finite domains on the solution. The
domains (elements) define the discretization along the space coordinate [79–82]. The integrated
residual between the approximate result and the true solution of the partial differential equation
over the element is forced to zero, subject to a weighting function. This space discretization is
coupled to another algorithm that propagates the solution along the time axis (often a so-called
Rosenbrock method). This may take the form that time discretization leads to elliptic partial dif-
ferential equations first, which are then solved for c = f(x) at each t step [83–85]. The method is also
well suited for the simulation of hydrodynamic experiments in electrochemistry [18,86,87].
Of all these basic algorithms, numerous variants exist. The reader is referred to the reviews
mentioned in Section I for further details. In addition, simulation algorithms based on other math-
ematical concepts have been proposed. For example, stochastic, random-walk, or Monte Carlo sim-
ulations provided numerical models for nonstandard diffusion processes [88], electrocrystallization
[89], or redox polymer behavior [90,91]. Most recently, also cellular automata methodology has
been applied [92].
3. Problem Situations
The basic numerical algorithms discussed in Section II.C.2 have all been successfully used for a
large variety of electrochemical simulations. However, there are also situations that are problematic
for such relatively simple calculation procedures. Many of these situations are related to abrupt or
intense changes of the concentration of one of the species involved in the electrode reaction with t
or x. This causes numerical difficulties, inaccuracies, or at least inefficiencies.
The list of problematic situations includes the following:
1. If the experiment is characterized by an abrupt change of a boundary condition, the

simulation has to accommodate the respective change in concentrations at, for exam-
ple, the electrode, immediately. For example, such a situation is characteristic for
chronoamperometry where, at t = 0, the potential is stepped from the rest potential of
the electrode in the surrounding electrolyte to a value in the limiting current region
with concomitant changes in the concentrations of the redox-active species at x = 0
(see Section IV in Chapter 2). This is particularly dramatic in double- (or multi-) poten-

tial-step chronoamperometry, where the discontinuity of the temporal development of
c(x = 0) occurs at every step. The evolution of error oscillations caused by such an initial
singularity has been discussed for the finite difference solution with the Crank–Nicolson
technique in detail [93]. A similar abrupt change of concentrations is found if the ini-
tial potential is not far enough from the formal potential E 0′ of the redox-active species
(more cathodic for an oxidation, more anodic for a reduction) and the general formula-
tion of the initial conditions is inadequate. Usually, one assumes that the electroactive
educt species is homogeneously distributed in the entire electrolyte at t = 0 with some
concentration c 0 and that products of the electron transfer and other steps of the electrode
reactions are absent (c 0 = 0). As soon as we impose a potential E on the electrode (begin-
ning of the experiment), the concentrations at x = 0 change to adapt to E, similar to the
earlier stepping situation. Of course, initial potentials too close to E 0′ should be avoided.
If this is impossible, however, the situation is dealt with in different ways: Feldberg and
coworkers routinely assume that the solution is homogeneous, but the concentrations
are changed into those dictated by E in the entire electrolyte [94]. Some versions of the
DigiSim software (see Section II.D) allow to switch off this feature [95]. It is indeed
probably more realistic to only change c(x = 0) at t = 0 and then observe relaxation of
the concentration profiles from this situation [30]. Even closer to the actual experimental
situation might be to model the development of a stagnant diffusion layer limited by
natural convection and use the resulting concentration profile as a starting point for the
simulation [49].
2. During an experiment, the diffusion layer that extends from x = 0 into the electro-
lyte increases in thickness, roughly with t1/2. Quite naturally, one would expect that
the algorithm should adapt the discretization to the actual situation at each time step
and react by improving the accuracy of the solution at the problematic points in time
(short Δt) and possibly space (close to the electrode, or in some mechanistic cases,
inside the diffusion layer [10,96–98]). Such adaptive algorithms will be discussed in
Section II.C.4.
3. Fast chemical reactions are described by large chemical rate constants in the K(c) term of
Equation 5.2. This leads to stiff partial differential equation systems (see, e.g., [99], p. 301),
which require specialized solver algorithms [77,100–103].
4. An additional problem can be envisaged by assuming that large K(c) terms cause very thin
reaction layers located within the diffusion layer. If the space discretization is too coarse,
only few or even no node remain(s) within the reaction layer, and the effect of the chemical
step may go undetected.
5. Reactions with an order other than unity or some boundary terms (e.g., related to
adsorption isotherms) introduce nonlinearities into the partial differential equation set.
In general, a differential-algebraic equation system [104] results that again may require
special treatment.
Apart from such situations that cause problems with the numerical solution of the model equations,
the combination of many physical phenomena in some experiments makes electrochemical simula-
tions difficult. For example, electrochemiluminescence includes nonelectrochemical concepts and
entities such as a photon. This situation has been treated by assuming the photon to be a fictitious
chemical compound, being consumed at the electrode at a virtual potential outside the potential
scan region and having a very large virtual diffusion coefficient [105], which is a kind of “trick”
(see [2], p. 278), although an obviously successful one. Recently, in a more elegant approach, mul-
tiphysics software was applied to electrochemical simulation problems at complex microelectrode
array geometries [106]. In order to receive meaningful results, great care, however, has to be taken
to correctly define the discretization properties and boundary conditions for such algorithms that
are not intrinsically aware of electrochemistry [106,107].
Finally, problems may be encountered if electrochemical experiments with unusual experimen-
tal setups are to be simulated. This can be attempted to be solved by writing very specialized
programs for only these situations or, more generally, with flexible programming techniques
(see Section II.D).
4. Adaptive Algorithms
As mentioned in Section II.C.3 some of the problem situations in electrochemical simulation can be
alleviated by using adaptive solution algorithms. In such numerical schemes, the nodes defining the
discretization in space and/or time coordinates are adjusted according to the details of the concen-
tration profiles. Thus, the box size, point distance, or element extension is dynamically forced to be
small in regions where the concentrations change strongly, while being larger in regions of almost
constant c. Likewise, time steps are arranged to be small as long as concentrations change quickly,
and become more relaxed if the temporal development slows down, or vice versa. An example is
presented in Figure 5.2.
Such adjustments of the discretization were already successfully used in simple ways for early
finite difference simulations [108,109] (exponentially expanding spatial grids, more recently: with
unequal intervals [110–112]; see also [2], p. 103ff.). This accounts for the spatial development of con-
centration gradients in a very general sense (high gradients close to the electrode, decreasing toward
the bulk). In a similar way, orthogonal collocation simulations were improved by spline functions
[113,114], taking into account the occurrence of thin reaction layers close to x = 0, as well as nonlinear
space transformations [115,116] with increased accuracy for reactions of an order higher than unity.
These approaches are, however, static and the grid is predefined at the beginning of the simulation.
Time-dependent transformations [117,118], on the other hand, are dynamic, although they still
rely on a fixed temporal development during the calculation (e.g., given by the typical t1/2 increase in
diffusion layer thickness). They were used to ensure that all nodes in orthogonal collocation simula-
tions remain located within the diffusion layer at all times, further improving accuracy. Time step
selection was used in solvers for (preferably, stiff) ODE systems [102,103,119,120].
The full power of adaptivity, however, requires redefinition of the entire discretization scheme
while the simulation proceeds, based on the previously developed numerical solution, and to account
for any problematic behavior of the concentration profiles. Such dynamically adaptive grids advan-
tageously use an objective function (error estimator) that tries to predict the solution evolution dur-
ing the next time step and to keep errors within predefined limits by readjusting the node locations.
Possibly, intricate balancing between space and time step sizes is used [60,84].
For example, in the context of finite element simulations, the gradient of the concentration pro-
files on neighboring elements was compared [121], and for strong changes, the grid was locally
improved by further subdivision (addition of nodes, so-called h-refinement). This was also applied
to 2D models [122] and various hydrodynamic complications [123,124], but does not directly control
the error of the solution components (unknowns) of interest. A dual problem approach with high
demand of mathematical derivation and computing resources was applied to control the error of
the final simulation result, the electric current [125–128] for steady-state (and transient [126]; see,
however, the discussion in [85]) problems.
For the simulation of transient experiments, an efficient adaptive multilevel solver [84] with only
local refinements proved successful to keep errors of concentrations (as the central solution compo-
nents in an electrochemical simulation) within predefined boundaries [85]. This was later extended
to the combined control of concentrations (in solution and, if necessary, in the adsorbed state) as well
as the current through the electrode (for potential-controlled situations) [29] or the electrode potential
for current-controlled experiments [13]. The algorithm allowed very accurate simulations of multi-
step chronoamperometry (Figure 5.2a and b: current/time curves). The Rosenbrock algorithm defines
increasing time steps while a chronoamperometric potential-step proceeds, and these are automatically
30 30
20 20
10 10
0 0
–10 –10
–20 –20
–30 –30
0 0.5 1 1.5 2 0 0.5 1 1.5 2 2.5 3
(a) Time (s) (b) Time (s)
1 1
0.8 0.8
0.6 0.6
δ
0.4 0.4
0.2 0.2
0 0
0 0.5 1 1.5 2 0 0.5 1 1.5 2 2.5 3
(c) Time (s) (d) Time (s)
0.12 0.06
0.1 0.05
0.08 0.04
Step size
Step size
0.06 0.03
0.04 0.02
0.02 0.01
0 0
0 0.5 1 1.5 2 0 0.5 1 1.5 2 2.5 3
(e) Time (s) (f ) Time (s)
FiGURE 5.2 Adaptive grid finite element simulation of chronoamperometric data, reversible electron trans-
fer: (a, c, e) double-step and (b, d, f) multistep chronoamperometry; (a, b) current–time curves, full lines:
analytical solutions, symbols: simulated data; (c, d) evolution of spatial grids; (e, f) development of time step
length; data generated by EChem++ (see Section II.D); for details, see [29]. (Reprinted from J. Electroanal.
Chem., 608, Ludwig, K. and Speiser, B., 91–101, Copyright (2007), with permission from Elsevier.)
reduced to a very small value when E is changed to another constant value (Figure 5.2c through f).
Moreover, the element size is adapted in several ways: while the extension of the diffusion layer is
small shortly after t = 0 (Figure 5.2c and d; left part of time axis) and only few nodes are located at
δ > 0.2 (δ is a dimensionless distance from the electrode), more nodes are inserted when the layer
relaxes into the solution (h-refinement). At the same time, the nodes move out from δ = 0 (bottom) into
the solution (top). Furthermore, if the prescribed accuracy can be reached with fewer points, the grid is
dynamically coarsened to improve efficiency of the solution process by deleting some nodes.
Adaptive techniques were also applied in finite difference schemes [51,96,129,130] for a variety
of problems with complex concentration profiles. Rosenbrock time stepping is applied and control
is exerted over the solution itself and its gradient [129].
Recently, Amatore and coworkers [97,98] (see also the discussion in [131]) have proposed to use
the rates (not rate constants!) of homogeneous chemical reactions as control criterion. This work
has been extended to 2D simulations as well, including appropriate conformal mapping coordinate
transformations [132].
These adaptive approaches are more complex than the basic algorithms described in Section
II.C.2; however, they provide a flexible way to generate accurate simulation results even in problem-
atic situations as discussed in Section II.C.3.
D. SIMULaTorS
The full advantage of electrochemical simulation comes with its general applicability to a wide
variety of experiments and electrode reactions. Apart from writing program code that solves a par-
ticular, specialized set of model equations, it was always a goal of workers in this field to provide
general tools for the use by not necessarily mathematically skilled or interested electrochemists.
Such tools have been termed problem-solving environments [11,133,134], electrochemical simula-
tors [10], or simulation packages [2].
Recent such programs try to achieve among others the following goals:
• A large (virtually infinite) number of electrode reactions can be simulated, advantageously

by providing a chemical notation to be supplied to the program. This requires automatic
translation or compilation of the chemical equations describing the electrode reaction into
the partial differential equation system with initial and boundary conditions and a suffi-
ciently general solver algorithm.
• The user of the program is required to invest only a minimum mathematical effort to
generate the solution. Thus, application- rather than theory-oriented electrochemists are
enabled to use simulation in their work. Automatic selection of algorithmic parameters that
control the solution accuracy, however, is not always a simple task.
• User input of model parameters such as rate constants should be tested for consistency.
For example, in complex reaction networks, some rate or equilibrium parameters are cor-
related. This leads to thermodynamically superfluous reactions [60,135–137], and several
electrochemical simulators do provide facilities to detect such a situation. However, stoi-
chiometric consistency can also be checked [60,136], as well as charge consistency [60] if
the chemical notation includes the specification of species charges.
• A graphical user interface should provide choices to the user in a readily comprehensible
format.
The following, necessarily incomplete, list of electrochemical simulators (for other compilations,
see [2,10,11]) does also show the historical development:
• cvsim [24,138] was a FORTRAN-based program for cyclic voltammetric simulation in

the EASI (electroanalytical simulation) package, which also included casim for chrono-
amperometric simulations) and gesim [31] (galvanostatic electrolysis simulation, includ-
ing exhaustive and other variants). The programs only provided a limited set of electrode
reaction mechanisms that were simulated with the orthogonal collocation technique. The
user interface was text based. It should be noted that another program by the same name,
but on the basis of finite differences, was propagated [139].
• DigiSim [25] became the first commercialized electrochemical simulator

[94,95,140,141]. It features a graphical user interface with display of the calculated
curve, a mechanistic translator, semi-infinite and finite diffusion spaces, as well as
hydrodynamic conditions. The temporal development of concentration profiles can be
visualized (“the movie”), providing an impressive demonstration of the events occurring
within the diffusion layer. Some limitations are: no adsorption processes and possibly
inconsistent initial conditions (see Section II.C.3, item 3). DigiSim is based on finite
difference algorithms.
• DigiElch (presently in version 7 [142]) is also commercialized [143] and has been devel-
oped by one of the original DigiSim writers. It additionally includes—as compared to
DigiSim—adsorption, more specific electron transfer laws, and concerted electron trans-
fer steps (concerted proton–electron transfer, see Chapter 13). A limited trial version is
available for test purposes.
• ELSIM [133,134,144,145] has grown through various versions [146] and has a decidedly
more complex user interface that, although requiring some mathematical background of
the user, provides even higher flexibility. An extension of this system in the form of a
“semiautomatic model builder for electroanalytical chemistry” (SAMBEAC) has been
presented [147].
• ES-1 and ES-2 provide a simulation and visualization tool for assisted learning in the
electrochemical context, in particular, finite diffusion conditions. The JAVA programs are
integrated with HTML technology to form a dynamic textbook [148].
• EChem++ [13,29,30,60,85,149] uses still another approach different from the other simula-
tors mentioned. It is an open-source project, providing free access [150] to the code base
written in C++ [151]. In contrast to most of the other programs, it is developed on the Linux
operating system. The design is based on object-oriented paradigms [149], which result
in a rather flexible use of the program code. Besides having an electrochemical compiler
[60] for the translation of chemical reaction sequences, EChem++ is characterized by a
graphical user interface that flexibly allows the definition of some experimental details for
both potential- and current-controlled experiments. For example, the user selects how the
excitation of the electrode occurs, and complex combinations of steps, ramps, and other
temporal functions of E (or i) are possible. Thus, based on the same core solver (adaptive
finite elements), cyclic voltammetric [29,30,85], chronoamperometric (including multistep)
[29,30], constant and programmed current chronopotentiometric [13], and other experi-
ments can be simulated. Moreover, besides diffusional transport, electron transfer, and
homogeneous kinetics (with separate definition of the reaction order and stoichiometry),
adsorption, surface (heterogeneous) chemical reactions, and multielectrode arrangements
(e.g., thin-layer, parallel-plane electrolysis) can be treated. Electron transfer modeled by
Nernst conditions (equilibrium at x = 0 is attained at all times) and Butler–Volmer kinetics
are available [30].
• KISSA-1D and KISSA-2D are based on the reaction rate control approach men-
tioned in Section II.C.4 [97,98,132,152]. (Hemi)spherical and (hemi)cylindrical
geometries provide access to ultramicroelectrode simulation for general mecha-
nisms. KISSA-1D was extended to the simulation of electrochemiluminescence
experiments [153].
• Online services for electrochemical simulation were listed earlier (see [2], p. 279). However,
at the time of this writing, only one of them [154] for a specific adsorption model was still
available on the net.
Electrochemical simulators are increasingly used in the electroorganic literature, and some exam-
ples of simulation results are also found in other chapters of this book (see, e.g., Figures 11.1, 11.4,
and 11.5).
III. APPLicATiON
While Section II demonstrates the current state of simulation techniques, we will now discuss by
means of examples what we can learn from applying such an approach in organic electrochemistry
and how this can be done.
A. SoLUTIoN QUaLITY
We first describe how we judge the quality of simulation results. Is it possible to show that a particu-
lar simulation is true (verification, from Latin verus) or at least valid (validation; often by compari-
son to experimental data [155,156])? This is not a problem unique to electrochemical simulation, and
at least from an epistemological point of view, the question has been answered no [155]. The best
we can do is to make it highly probable that the model and the resulting simulation provide a good
means to reproduce (calculated or experimental) data (confirmation [155]). Often, for electrochemi-
cal simulations, this is done by showing that solutions obtained at certain extreme parameter values
replicate analytical results or other already accepted numerical values (limiting cases). For example,
such benchmarking [155] was applied to spline orthogonal collocation simulations of cyclic voltam-
metric models based on reaction mechanisms with fast preceding or follow-up chemical equilibria
coupled to an electron transfer [113]. The intrinsic problem of such a procedure is undoubtedly that
the most interesting situations, where the model will have to be used later, are those that cannot be
treated by limiting assumptions. However, an increasing number of such successful tests will add
increasing credibility to the model.
Some additional tests are as follows: confirming the correct operation of isolated algorithms
within the simulation programs; refining the mesh formed by the nodes for discretization and check-
ing convergence of the resulting simulation data (see the discussion in [2], p. 247ff., which also deals
with consistency of the solution); analyzing the stability of the solution. Stability describes how an
error at time t propagates while the solution develops further. This problem was already apparent
in early finite difference simulations (Crank–Nicolson algorithm, leading to oscillatory behavior
[93]) and has since been treated for a variety of related solution techniques [50,157–160]. Stability of
electrochemical models has also been analyzed in strict mathematical terms (see, e.g., [161]). Owing
to the inherent error control in adaptive schemes (see Section II.C.4), this seems to have become less
important for such techniques.
B. EXpLoraTIoN aND PrEDICTIoN

Simulations in organic electrochemistry are useful to explore the behavior of model reactions or
experimental conditions that have not yet been (or even cannot at all be) applied to a real system.
It can be quite instructive to predict, for example, the expected changes in observable i when add-
ing or removing steps of the electrode reaction, varying rate and equilibrium constants, or using an
unusual setup such as unsymmetrical potential–time triangles in cyclic voltammetry. Literature on
this subject is extensive, and we discuss here only two selected recent examples.
Fourier transform voltammetry, where a sinusoidal waveform is superimposed on the potential
scan, has been advocated as an attractive alternative to classical (dc-) cyclic voltammetry [162]. The
advantages of the technique were early demonstrated by simulation studies, and further “experi-
mental strategies…based on knowledge gained from a perfectly general numerical simulation treat-
ment…” were developed [163]. Behavioral patterns were observed in simulated data and expand
the possibilities of dc voltammograms [164]. In particular, the fundamental, second, and higher
harmonics [165] of the current response as well as its power spectrum (frequency dependence)
were analyzed. Moreover, simulation studies provided estimates of experimental error effects, both
random and systematic [166], as well as predictions of differences between Butler–Volmer and
Marcus–Hush electron transfer kinetic models [167].
Recently, a simulation study was performed to investigate systems in which the electrolyte
is not or cannot be stirred between experiments. The calculations allow to estimate the effect of
recovery of the initial diffusion layer during some waiting time in chronoamperometry [168],
which would not easily be accessible by experiments. In a similar way, the development of con-
centrations close to the electrode during an initial period, where the electrode is held at its rest
potential in the electrolyte, was simulated among others under natural convection conditions [49].
Again, these studies explore the behavior of a system that is barely subject to simple experimental
investigation.
C. PrESENTaTIoN oF SIMULaTED RESULTS

With the simplicity to quickly generate results of model calculations, it is no problem to pro-
duce large numbers of simulation data sets by systematically changing one or more param-
eters (see Section IV.A.5 in Chapter 1). For example, within a certain reaction mechanism, a
particular rate constant k could be varied and the cyclic voltammetric response be calculated
for each value of k. Often such work is done in the framework of dimensionless parameters.
Given simple and fast simulation, it rather becomes difficult to deal with the quantity of
numerical data.
Working curves are a classical method to visualize simulation results, where we select a par-
ticular striking feature in the voltammogram (Figure 5.1), for example, the peak potential, and plot
its value as a function of the dimensionless parameter characteristic for the electrode reaction (see,
e.g., Figure 5.3a). Early examples of this technique historically mark the onset of cyclic voltam-
metric success [17,53,169]. While the curve is often presented only graphically, also mathematical
functions may be provided [170–174].
The working curve approach has been extended to cases where two parameters determine the
feature value, for example, the dependence of the peak potential difference ΔEp in cyclic voltam-
mograms on rate constant and transfer coefficient of a quasireversible electron transfer [172,173] or
the peak potential in an ECE mechanism variant (Figure 5.3b) on rate constants. Of course, here,
the mathematical descriptions are highly advantageous.
If more than two parameters are important, their combination into dimensionless quantities
(see, e.g., Section IV.A.5 in Chapter 1) might be an effective way to reduce the complexity. This
is particularly popular in the case of zone diagrams that are also a compact representation of the
information content of a large number of simulations. Section III.B in Chapter 10 depicts some
examples, as does Reference 175. A recent monograph [176] makes extensive use of such graphical
representations. In a zone diagram (Figure 5.3c), we show the behavior of the simulation results in
terms of limiting cases. Within a zone, a particular feature, based, for example, on voltammetric
peak current, varies only within an experimentally achievable limit of, for example, 5% and is
assumed to change only insignificantly [177], or follows a characteristic dependency. Each zone
then defines characteristic behavior. In addition, these diagrams help to assess effects exerted if a
reaction or experimental parameter changes.
Recently, a mapping technique (high-dimensional model representation) has been established
[179], where a set of voltammetric curves and its dependencies on parameters are described by an
expansion into functions that have fewer variables. Then, in particular, data storage needs are drasti-
cally decreased, while full voltammograms can be quickly regenerated.
D. QUaLITaTIVE aND QUaNTITaTIVE ANaLYSIS oF MECHaNISMS

Simulations support the elucidation of electroorganic reaction mechanisms in a qualitative way. In
general, a mechanistic hypothesis can be made likely by rejecting alternatives if the behavior of the
latter does not comply with the experimental data (qualitative analysis) [180]. On the other hand,
it is impossible to prove a certain mechanism to be unique as an explanation for given experimental
40
20
40
0
E p–E (mV)
EIp–E 0 (mV)
–20
0
–40
I
–60
–80 –160
6 6
–100 log k
–1 log k 1
–6 –4 –2 0 2 4 6 –6 –6
(a) log k1 (b)
log ρ c0
Disp
1
Cl k1
0 DMSO k2 δ
–1
Br
ECE
DMSO I
–2
DMSO
–3 Cl CN ACN
H-atom DMSO
Br CN ACN
Cl
–4 I CN ACN
DMSO
Br DMSO log σ
–5 –4 –3 –2 –1 C 1 2 3
(c)
FiGURE 5.3 Data presentation by working curves and zone diagrams: (a) electrochemically initiated dimer-
ization, 2D working curve for one parameter, half-peak potential Ep/2 (referred to formal potential E 0) as a
function of model rate constant κ1 = k1c 0/τ with k1 = dimerization rate constant, c 0 = initial concentration of
electroactive substrate, and τ = timescale parameter of experiment (=F/RTv for cyclic voltammetry); (b) ECE
mechanism with reversible chemical step, 3D working surface for two parameters, peak potential of first peak
EpI (referred to formal potential of first electron transfer E 0) as a function of model rate constants κ1 = k1/τ and
κ−1 = k−1/τ (k1 and k−1 being the rate constants of the forward and reverse chemical reactions); and (c) zone dia-
gram for concurrent reactions initiated by electrochemical reductive cleavage of aromatic halides in terms of
competition parameters ρ and σ (logarithmic scales), the hatched zone defines mixed control. (Reprinted with
permission from M’Halla, F., Pinson, J., and Savéant, J.M., J. Am. Chem. Soc., 102, 4120–4127. Copyright
(1980) American Chemical Society.)
data, because there might be additional alternatives that have not been considered in comparison,
but reproduce the data with similar or even better quality.
A systematic procedure to add necessary reaction steps to a mechanism (model expansion) or to
delete superfluous steps to comply with the principle of Ockham’s razor (see [181], but also note the
critical remarks in [155]; model reduction) based on sensitivity analysis has been proposed in the
electrochemical context [182].
The quantitative use of simulation is based on a likely reaction mechanism (i.e., a model of
the electrode reaction): the main goal is then to determined kinetic, thermodynamic, and transport
parameters pertinent to the real system. This is often called an inverse problem (already mentioned
in Section II.C), because we intend to find the parameters that—used in the simulation—give a best
fit to the experimental data. The inverse problem in the electrochemical context is complicated by
the fact that in general we deal with a multiparameter problem, where we need to estimate several
parameters simultaneously, the relation between experimental data and parameters is often nonlinear
(see, e.g., the working curves in Figure 5.3), the parameters might be strongly correlated (e.g., rate
and equilibrium constants), and a suitable mechanistic hypothesis must be available.
As a basis, experimental data must be used that are free of artifacts. In particular, iR-drop (uncompen-
sated resistance, see Section II.E.2 in Chapter 2) must be avoided, and background currents must have
been subtracted.
Comparison of experimental and simulated curves is done in various ways:
• Data transformation, often linearization, for example, by semi-integration [183]. In a simi-

lar way, global analysis has been applied [184].
• Feature analysis, which relies on working curves or surfaces as discussed in Section III.C
and concentrates on particularly noticeable points in the data. As a particular application, a
multiparameter estimation approach based on mathematically described working surfaces
has been discussed [172,173,185,186]. Nonlinear optimization techniques determine those
parameter values that provide a best representation of the features’ changes as a function
of experimental conditions.
• Analysis of full curves [25,187]: This is sometimes termed fitting [140] and is often directly
coupled to simulation (e.g., in DigiSim [140] or the “professional” version of DigiElch
[142]). The difference between experimental and simulated curves, expressed as a sum of
squared residuals of data points R, is guiding the estimation of optimal parameters, starting
from an initial guess. Unfortunately, most optimization algorithms are subject to be caught
in local minima of R, while the best fit will be provided by a unique global minimum of this
quantity. The use of various starting parameter combinations [140] is mandatory and the
results must be critically compared. It is also important to check that the results are physi-
cally meaningful [95], for example, rate constants must not be negative.
The data must cover a large range of experimental parameters (concentration c, scan rate v, addi-
tives and reagents in the electrolyte). For example, a single voltammogram can often be simulated
easily with good agreement. However, the same set of reaction parameters should be used for the
simulation of a large number of current/potential curves recorded at several c and v to increase the
credibility of the results (see the following example).
Thus, fitting to a set of data rather than to a single curve is highly recommended. If the data
values in such a set differ by a large factor (e.g., currents in cyclic voltammograms recorded at
various v), a suitable scaling procedure must be employed to avoid incorrect weighting of residuals.
Indeed, such algorithms are customary in simulators such as DigiSim (see Section II.D).
The curves in Figure 5.4 are the results of fitting simulated to experimental data according to
these ideas. Figure 5.4b shows a selection of curves for the oxidation of anisaldehyde phenylhydra-
zone [188,189] at various v and c that are compared to simulations with a single set of rate constants.
The experimental cyclic voltammograms are background corrected and iR-drop compensation by
positive feedback was used. The simulations were generated under the assumption of the reaction
mechanism shown in Figure 5.4a and the reaction parameters given in the figure legend. The radical
cation produced in the primary electron transfer dimerizes (second-order kinetics) and/or is depro-
tonated by another hydrazone molecule, and the neutral radical resulting from the second reaction
is further oxidized (ECE sequence with two additional side reactions). The proton transfer between
radical cation and neutral starting hydrazone was formulated in the model mechanism as a sequence
of two equilibrium steps (first-order deprotonation of radical cation and second-order protonation of
hydrazone). Several alternative mechanisms were tested and unable to even qualitatively reproduce
the experimental curves: both radical cation dimerization and self-protonation steps are essential
parts of the overall reaction.
220
R1 N N C R2
H H
+e– –e–
+
R1 NH N CH R2
+ Dimerization
R1 N N C R2 and other products
H H
R1 NH N CH R2
+
B
B = R1 N N C R2
H H
HB+
R1 N N C R2
H
+e– –e–
+
R1 N N C R2 Products
H
(a)
Organic Electrochemistry
FiGURE 5.4 Anodic oxidation of anisaldehyde phenylhydrazone (R1 = H, R2 = OCH3) in dichloromethane/0.1 M NBu4PF6: (a) reaction mechanism. (Continued)
2.1 10 40
8 30
1.6
6 20
1.1 10
4
0.6 0
2
–10
0
Current, i · 106 (V)

0.1
–20
–2
–0.4 –30
0.15 0.20 0.25 0.30 0.35 0.40 0.45 0.50 0.55 0.60 0.15 0.20 0.25 0.30 0.35 0.40 0.45 0.50 0.55 0.60 0.15 0.20 0.25 0.30 0.35 0.40 0.45 0.50 0.55 0.60
–3.6 16
–3.1 14 60
12
–2.6 40
Application of Digital Simulation
10
–2.1 8
20
–1.6 6
–1.1 4 0
2

–0.6
0 –20
–0.1 –2
–0.4 –4 –40
0.15 0.20 0.25 0.30 0.35 0.40 0.45 0.50 0.55 0.60 0.15 0.20 0.25 0.30 0.35 0.40 0.45 0.50 0.55 0.60 0.15 0.20 0.25 0.30 0.35 0.40 0.45 0.50 0.55 0.60
7 31 130
6 110
26
90
5
21 70
4 50
16
3 30
11 10
2
6 –10
1

–30
0 1
–50
–1 –4 –70
0.15 0.20 0.25 0.30 0.35 0.40 0.45 0.50 0.55 0.60 0.15 0.20 0.25 0.30 0.35 0.40 0.45 0.50 0.55 0.60 0.15 0.20 0.25 0.30 0.35 0.40 0.45 0.50 0.55 0.60
(b) Potential, E (V) Potential, E (V) Potential, E (V)
FiGURE 5.4 (Continued) Anodic oxidation of anisaldehyde phenylhydrazone (R1 = H, R2 = OCH3) in dichloromethane/0.1 M NBu4PF6: (b) experimental (symbols)
and simulated (lines) cyclic voltammograms in the potential range of first oxidation: top row, c = 0.12 mM; middle row, c = 0.22 mM; bottom row, c = 0.41 mM; left column,
v = 0.05 V s−1; middle column, v = 1 V s−1; right column, v = 20 V s−1. Potentials vs. ferrocene reference. Optimal parameters [188]: formal potential of hydrazone oxidation
E0′ = +0.39 V, electron transfer rate constant of hydrazone oxidation ks = 0.4 cm s−1, dimerization rate constant kdim = 2.4 × 104 L mol−1 s−1, rate constant of radical cation
deprotonation k deprot = 6.6 s−1, deprotonation equilibrium constant Kdeprot = 4.6 × 10 −8, rate constant of hydrazone protonation kprot = 1.1 × 108 L mol−1 s−1, protonation
equilibrium constant Kprot = 5.2 × 105; values of the dimerization equilibrium constant (1010), the formal potential (0 V) and electron transfer rate constant (1 cm s−1) of neutral
221
radical oxidation, as well as the transfer coefficients (α = 0.5) for both electron transfers were assumed as constants for fitting purposes.
The experimental scan rate and the concentration were varied by factors of 400 and approxi-
mately 3.5, respectively. Still, all experimental curves are reproduced in shape and intensity of for-
ward and reverse peaks by the simulations with a single set of rate and equilibrium constants [188].
The fit is not perfect. In particular, experimental currents between the oxidation peak and the
switching potential are sometimes larger, while some experimental peak currents are slightly
smaller than the prediction. However, the example provides an estimate of the fitting quality that
can be obtained in the real world. An additional note of caution concerns the fact that cyclic voltam-
mograms commonly do show relatively little structure (as compared to, e.g., NMR or IR spectra).
Then, relevant information is rather contained in the full ensemble of curves that have been recorded
under varying experimental conditions. Consequently, the example demonstrates that it is much
more important to be able to fit all curves satisfyingly, rather than a single curve perfectly. This also
minimizes the danger of using an inappropriate mechanistic hypothesis: Single voltammograms
can often be reproduced by several mechanisms (with certain kinetic and transport parameters) and
the determination of mechanism and parameters does not give a unique solution. This is much less
likely if a large ensemble of curves can be fitted using the same set of parameters.
If a reasonable fit between experiments and simulation is found only in some of the voltammograms,
for example, only for high scan rates, this might indicate that the mechanism is inappropriate, for
example, missing a chemical reaction that becomes important at slow scan rates.
IV. CONcLUSiON
Simulation provides a widely used and valuable tool for the study of electroorganic reactions.
A large variety of numerical algorithms is discussed in the literature, and comprehensive computer
programs are available for the organic electrochemist. These programs allow the exploration of
experimental conditions and reaction mechanisms and their effect on electrochemical measure-
ments. On the basis of artifact-free experimental data, simulations support the estimation of kinetic,
thermodynamic, and transport parameters. Thus, redox-active organic compounds are character-
ized and basic information for the planning of organic electrosyntheses is provided.
Note added in proof: While this Chapter was in the proof reading state, a comprehensive work on
the use of integral equations (see, Section II.C.1) was published [190].
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6 Theoretical Calculation
of Reduction Potentials
Junming Ho, Michelle L. Coote,
Christopher J. Cramer, and Donald G. Truhlar
CONTENTS
I. Introduction .......................................................................................................................... 229
II. Formal Definitions, Electrochemical Concepts, and Basic Considerations ......................... 231
A. Ionization Potentials and Electron Affinities ................................................................ 231
B. Standard versus Formal Potentials ............................................................................... 232
C. Cyclic Voltammetry ......................................................................................................233
D. Effects of Protonation ................................................................................................... 234
E. Reversible and Irreversible Redox Processes................................................................ 235
F. Liquid Junction Potentials............................................................................................. 235
G. Reference Electrodes .................................................................................................... 236
III. Computation of Reduction Potentials ................................................................................... 236
A. Gas-Phase Free Energies of Reaction ........................................................................... 237
1. Gibbs Free Energy and the Treatment of Nuclear Motion..................................... 237
2. Electronic Energies of Atoms and Molecules ........................................................ 240
3. Standard State of the Electron ............................................................................... 241
B. Free Energies of Solvation ............................................................................................ 242
1. Absolute Potential of the Aqueous SHE ................................................................ 243
2. Nonaqueous Systems .............................................................................................244
C. Standard States ............................................................................................................. 245
D. Rates of Electron Transfer ............................................................................................ 247
IV. Examples............................................................................................................................... 247
A. Aqueous Standard One-Electron Reduction Potentials of Nitroxides and Quinones... 247
B. Chemically Irreversible Processes—Reductive Dechlorination .................................. 250
C. Constructing a Pourbaix Diagram for the Two-Electron Reduction of o-Chloranil .... 252
V. Concluding Remarks ............................................................................................................ 255
Acknowledgments.......................................................................................................................... 255
References ...................................................................................................................................... 255
I. INTRODUcTiON
The reduction potential is a direct measure of the thermodynamic feasibility of an oxidation–
reduction half reaction; and it is fundamentally important in many aspects of organic, bioin-
organic, and environmental chemistry, as well as in biology and materials science. The design
of rational strategies for tuning the redox properties of compounds depends on understanding
the key molecular features that dictate the reduction potential. As an example, in environmen-
tal chemistry, chlorinated aliphatic compounds are common environmental contaminants due
to their widespread use as solvents and degreasers and are known to degrade via a reductive
229
dehalogenation [1,2]; the environmental persistence of these compounds has been found to cor-
relate with their relative reduction potentials, and the computation and measurement of these
quantities is therefore valuable for understanding structure–activity trends and the design of
environmentally friendly derivatives of these compounds [1,3–8]. Similarly, in biochemistry,
nitroxides are a class of kinetically stable free radicals that have been widely studied as potential
antioxidants against reactive oxygen species, which can lead to tissue injury and even cell death;
both oxidation and reduction processes involving nitroxides are biologically relevant [9–12],
and the ability to predict the redox potentials of nitroxides with various substituents and those
embedded in rings can help prioritize synthetic targets for potentially biologically relevant anti-
oxidants [13,14].
Reduction potentials are most straightforwardly defined when associated with readily reversible
equilibria; in such instances, they contain equivalent information to equilibrium constants or free
energy changes for electrochemical half reactions. In practice, the high reactivity of many species
(e.g., organic radicals) participating in electrochemical reactions or the irreversibility or mechanistic
complexity of redox reactions can make the direct experimental measurement of a corresponding
reduction potential difficult. For this reason, computational chemistry offers a valuable alternative
to experiment for the characterization of redox reactions. The theoretical calculation of any ther-
mochemical quantity, including free energies and therefore including reduction potentials, usually
takes advantage of the Born–Oppenheimer separation of electronic and nuclear motion, which ulti-
mately reduces the problem to three steps: (1) the calculation of molecular potential energy surfaces
by electronic structure calculations; (2) the treatment of nuclear motion, for example, vibrations; and
(3) statistical mechanical averaging over relevant configurations, conformations, or solvent struc-
tures. Step (3) is often carried out by classical statistical mechanics and step (2) by quasiharmonic
methods, whereas step (1) generally requires more expensive quantum mechanical (QM) calcula-
tions, which can limit the accuracy of predictions if sufficiently large systems make the application
of accurate QM models impractical. However, the relatively recent development of efficient quan-
tum chemical algorithms and powerful computer architectures has facilitated the quantitatively
useful study of many reactions. Because most redox processes of practical interest occur in con-
densed phases, the development of reliable solvation models has also been critical to progress, and
both implicit and explicit solvent models are now available such that well-chosen combinations of
theoretical models have the potential to be used to make quantitative predictions of electrochemical
quantities like reduction potentials.
Although this chapter is concerned with thermodynamics, the reader should keep in mind that
reactivity and biological activity also depend on kinetics. While kinetics is often correlated with
thermodynamic descriptors such as reduction potentials, it also includes other factors whose com-
plete discussion is beyond the scope of this chapter. Nevertheless, we will mention kinetic effects in
some places because they are relevant to interpreting measurements.
There are several approaches to calculating a condensed-phase reduction potential, ranging
from phenomenological or theoretically guided linear free energy relationships (LFERs) correlat-
ing reduction potentials with other computed (or experimental) observables to direct calculations
of reduction potentials. When using LFERs, computed properties are again often obtained by QM
electronic structure calculations. Calculated or measured properties that may be correlated with
reduction potentials include ionization energies and electron affinities in the gas phase, as well
as energies of the frontier molecular orbitals (e.g., the highest occupied molecular orbital), and
these quantities may be regressed on solution-phase reduction potentials in order to develop a pre-
dictive equation [15–28]. LFERs are appealing because they allow for very rapid evaluation of
reduction potentials, which is especially important, for example, in high-throughput screening of
large databases of drug candidates. The implicit assumption of such an approach is that the errors
associated with neglecting contributions to the reduction potential that do not correlate with the
chosen independent variables are negligible, as are errors associated with the level of theory used to
compute these variables. In practice, LFERs may work well if the compounds under consideration
Theoretical Calculation of Reduction Potentials 231
are sufficiently similar to those used in the regression. The semiempirical nature of this approach
means that it may be difficult to estimate the errors associated with these models, particularly when
they are applied on compounds outside of the training set.
When one attempts to calculate the reduction potentials directly, without linear regression against
simpler quantities, typically only the most active portion of the system, for example, the solute and
perhaps the first-solvent shell, is treated explicitly by quantum mechanics. The rest of the system
is treated by molecular mechanics (MM), classical electrostatics, or both (although occasionally
the whole system is treated by explicit quantum mechanics). Combining quantum mechanics for a
primary subsystem with MM for the rest of the system is labeled QM/MM, and if the MM subsys-
tem is the solvent, it is an example of an explicit solvent method that requires molecular dynamics
(MD) or Monte Carlo (MC) methods to ensemble average the solvent. MD and MC free energy
simulations permit examination of solvent structure and reorganization [29–32]. Methods based on
classical electrostatics usually replace the discrete solvent molecules by a dielectric continuum, so
that the solvent and the ensemble average over solvent configurations both become implicit. QM/
MM and implicit-solvent treatments are the methods of choice for the study of redox potentials
in condensed-phase and biological systems because treating the entire system quantum mechani-
cally raises the cost so much that one is usually forced to use less reliable methods or to skimp on
ensemble averaging.
In this chapter, we will focus exclusively on methods based on thermodynamic cycles where
solution-phase reduction Gibbs free energies are computed by combining gas-phase energetics with
solvation free energies of the products and reactants. Such methods are also used extensively in
solution-phase pKa predictions [33–35] as well as in studies of other condensed-phase reactions such
as free-radical polymerization [36,37].
In the following, Section II presents some formal concepts in equilibrium electrochemical ther-
modynamics. The Section III is concerned with the implementation of the computational protocols.
The Section IV presents some worked examples.
II. FORMAL DEfiNiTiONS, ELEcTROchEMicAL CONcEPTS,

AND BASic CONSiDERATiONS
This section introduces some formal concepts in equilibrium electrochemical thermodynamics that
are important for calculating solution-phase reduction potentials.
A. IoNIZaTIoN PoTENTIaLS aND ELECTroN AFFINITIES

The adiabatic ionization energy, usually called the ionization potential, is the energy required to
form a molecular or atomic cation in its ground state via the loss of an electron from the ground
state of the neutral system in the gas phase. The vertical ionization energy applies to the change in
electronic energy upon removal of an electron from the equilibrium structure of the neutral without
change in geometry, again in the gas phase. For this reason, the two quantities are identical for an
atom, and for a molecule the vertical ionization energy is almost always higher than its adiabatic
counterpart. The electron affinity (EA) is defined similarly to the adiabatic ionization energy, and
the vertical electron attachment energy is similar to the vertical ionization energy, but these quan-
tities refer to minus the change in energy when a neutral system gains an electron. The adiabatic
quantities correspond to enthalpy changes at 0 K:
M(g) → M + (g) + e − , ∆H 0 = IP
(6.1)
M(g) + e − → M − (g), ∆H 0 = −EA
where the subscript denotes the temperature in units of kelvin.

B. STaNDarD VErSUS ForMaL PoTENTIaLS

At the heart of electrochemical thermodynamics is the chemical potential (μ), which equals the
molar Gibbs energy (G) for a pure substance and the partial molar Gibbs free energy for a compo-
nent of a solution. For a species A in a solution,
 γC 
µ A = µA° + RT ln   = µ°A + RT ln(a) (6.2)
C 
where
C is the concentration
a small circle in a superscript denotes the value of a quantity in the standard state
a and γ are the activity and activity coefficient, respectively
The usual standard states in the gas phase are an ideal gas at a pressure of 1 atm or 1 bar (0.987 atm),
and the usual standard states for solutes in liquid-phase solutions are ideal solutions at a concentra-
tion of 1 M (1 mol/L of solution) or 1 molal (1 mol of solute/kg of solvent). Notice that we have
introduced the dimensionless activity coefficients γi defined by [38]
ci
ai = γ i (6.2a)
c°i
If we apply Equation 6.2 to the reaction
Ox + e − → Red (6.3)
where
Ox is the oxidant
Red is the reductant
the free molar energy of reaction is given by
a 
∆G = ∆G° + RT ln Q = ∆G° + RT ln  Red  (6.4)
 aOx 
where Q is the dimensionless reaction quotient. The relation between free energy and the maximum elec-
trical work that can be performed, as expressed in terms of the electrode potential E of a half-cell [39], is
∆G = −nFE (6.5)
where
F is the Faraday constant (96,485 C mol−1)
n is the number of electrons in the half reaction
Combining this with Equation 6.4 yields the following Nernst equation [40]:
RT  aOx 
E = E° + ln  (6.6)
F  aRed 

where E° is the standard electrode potential, also called the standard-state potential or the half-cell
potential.
Notice that E equals E° when the activities of all species are 1. However, such standard-state
conditions are often difficult to achieve in practice, and standard-state potentials are often replaced
by formal potentials, E°′. Formal potentials are sometimes called conditional potentials to denote
that they apply under specified conditions rather than under standard conditions [38]. Specifically,
this quantity is the measured potential of the half-cell when the ratio of the total concentrations of
oxidized and reduced species is unity and other specified substances (e.g., proton) are present at
designated concentrations. For example, they can be defined to correspond to the half-cell potentials
when the concentration quotients (Qc) in the Nernst equation equal 1:
RT RT  COx 
E = E °′ + ln Qc = E °′ + ln  (6.7)
F F  CRed 

Then the formal potential (E°′) is related to the standard reduction potential (E°) as follows:
RT  γ Ox 
E °′ = E ° + ln   (6.8)

F  γ Red 
For example, the absolute potential of the normal hydrogen electrode is based on a concentration
of the proton equal to 1 mol L−1 and is therefore a formal potential. This may be corrected to give
the absolute potential of the standard hydrogen electrode (SHE) by taking into account the activity
coefficient for a 1 mol L −1 solution of [H + ] in water, which has been estimated to be 0.8 [41]:
RT
E °SHE = ENHE − ln ( γ H+ ) = ENHE + 0.006 V (6.9)
F
In this particular instance, activity effects account for only a small change (6 mV) in the potential [42].
As an example of a more extreme case, the formal potential of the Fe3+ /Fe2+ couple varies from 0.53 to
0.7 V in 10 and 1 mol L−1 HCl solutions, respectively [43].
Typically, experimental standard reduction potentials are obtained by assuming a functional
form that models the dependence of the potential on ionic strength. A series of formal potential
measurements is then carried out at different values of ionic strength, and they are extrapolated to
zero ionic strength where the activity coefficients approach unity [43].
C. CYCLIC VoLTaMMETrY
Cyclic voltammetry is commonly used in the determination of formal potentials, which may be
extracted directly from a fully reversible cyclic voltammogram as the average (midpoint) of the
anodic and cathodic peak potentials, Epa and Epc, or from the half-wave potential of a sigmoid curve
in steady-state voltammetry [43], to give a half-wave or midpoint potential, E1/2. Because the mea-
sured half-wave potential is affected by diffusion (a nonthermodynamic effect), it is related to the
formal potential by
Epc + Epa RT  DRed 

E1/ 2 = = E °′ + ln  (6.10)
2 2nF  DOx 

where D Ox is the diffusion coefficient of Ox. When the diffusion coefficients of the oxidized and
reduced species are very similar, the half-wave potential provides a good approximation to the
formal potential.
D. EFFECTS oF ProToNaTIoN
In aqueous solution, thermodynamically favored proton transfer is usually rapid, and electrochemi-
cal measurements usually give reduction potentials for half reactions that include any thermody-
namically favorable proton addition or loss. As such, an n-electron, m-proton half reaction can be
represented in two possible ways:
Ox + ne − → Ox n− (6.11a)
Ox + ne − + mH + → H m Ox ( n−m )− (6.11b)
with corresponding standard reduction potentials denoted E°(Ox/Ox n−) and E°(Ox, mH+/
H mOx(n−m)−), respectively. The potential for the latter equation is directly dependent on pH and is
equal to the formal potential E°′(Ox, mH+/H mOx(n−m)−) when the concentrations of all species are
1 mol L −1:
RT [Ox][H + ]m RT [Ox] RT m

E = E °′ + ln = E °′ + ln − 2.303  n  pH (6.11c)
nF [H m Ox] nF [H m Ox] F  
By monitoring how this cell potential varies with pH, it is possible to determine the electron–
proton stoichiometry (m/n) of the electrochemical measurement. For example, consider quinones
and their derivatives, which are electroactive organic compounds that play a vital role in a number
of biochemical processes. These compounds can undergo either a two-electron reduction (Ox/Ox2−),
a two-electron–one-proton reduction (Ox, H+/HOx−), or a two-electron–two-proton reduction
(Ox, 2H+/H2Ox), depending on the pH of the solution [44]. In Section IV.C, we illustrate how one
constructs an E versus pH diagram, which is called a Pourbaix diagram [45–47] and is analogous to
a chemical speciation plot or predominance zone diagram determined by pH.
A measured formal potential is a good approximation to the standard reduction potential only
when activity and kinetic effects associated with chemical reaction(s) are relatively minor. Where
this is not the case, explicit treatment of these effects should be included in the calculations, or com-
parisons should be made with other experimental potentials that correspond more closely to infinite
dilution and to thermodynamic control.
Consider the reduction of nitroxide radicals in aqueous solution in Figure 6.1.
E(Ox/Ox–) –
N O + e– N O
– 1/K2
N O + H+ N OH
1/K1 + OH
N OH + H+ N
H
E(Ox, 2H+/H2Ox) + OH
N
Net reaction N O + 2H + e–
+
H
FiGURE 6.1 The microspecies present in the one-electron reduction of a nitroxide radical in aqueous
solution.
The measured half-wave potential E1/2 is related to the formal potential for the one-electron–two-
proton (1e, 2H+) transfer reaction as follows [48,49]:

(
E1/ 2 = E °′ Ox, 2H + H 2Ox + + ) RT
F
(
ln K1K 2 + K1[H + ] + [H + ]2 ) (6.12)
where K1 and K2 are the equilibrium constants associated with the protonation steps. In previous
work, it was found that explicit consideration of the prototropic equilibria was necessary to obtain
good agreement with the experimental half-wave potentials [14]. In some cases, the experimental
potential corresponds to that for a one-electron (1e) transfer E°′(Ox/Ox−), and this is related to the
formal potential of the (1e, 2H+) reduction potential E°′(Ox, 2H+/H2Ox+) by

( ) (
E °′ Ox Ox − = E °′ Ox, 2H + H 2Ox + + ) RT
F
ln( K1K 2 ) (6.13)
E. REVErSIbLE aND IrrEVErSIbLE REDoX ProCESSES

Occasionally, half-wave potentials are also reported for quasi-reversible cyclic voltammetry experi-
ments with a back wave partially present; however, the reader should note that these are usually
estimated values and therefore may not be well suited for quantitative comparisons. It is impossible
to extract E1/2 from completely irreversible processes (no back wave) because of kinetic control of
the current such that the Nernst equilibrium is established less quickly than the change in potential
or because there are fast follow-up (side) reactions consuming the pertinent species.
There are instances where the transfer of an electron to or from a neutral precursor leaves the
resulting radical ion in an electronic ground state that is dissociative [1,50]. (The former process is
called dissociative attachment [51], and the latter is called dissociative ionization [52].) Following
the electron-transfer event, which is rapid on the time scale of nuclear motion, the ion relaxes along
the dissociative coordinate, leading to the scission of one or more bonds. Typically, the energetics
associated with this fragmentation are such that the electron-transfer event is effectively irrevers-
ible. Depending on whether the ion lives long enough to be reoxidized/rereduced on the return
sweep, the back wave may be only partially present or completely absent in a cyclic voltammogram,
in which case it is not possible to extract a half-wave potential. An example of such a chemically
irreversible process is the reductive dehalogenation of haloalkanes. For such processes, the equi-
librium potential may alternatively be defined as the Gibbs free energy associated with the overall
process, which in this case is
Cl Cl Cl Cl
Cl + 2e– + H+ Cl + Cl– (6.14)
Cl Cl
Cl Cl Cl H
F. LIqUID JUNCTIoN PoTENTIaLS

The liquid junction potential arises whenever solutions with two different compositions come into
contact. Its magnitude depends on the relative concentrations of the various ions at the boundary
and on their relative mobilities. These potentials may be significant in cases where the solvent sys-
tem changes across a junction (e.g., from acetonitrile or dimethyl formamide [DMF] on one side
to aqueous on the other). The liquid junction potentials of a number of dissimilar solvent junctions
have been determined to range from 10 to 200 mV, depending on the junction [53].
G. REFErENCE ELECTroDES
The conventional reference electrode for aqueous systems is the SHE, which has been assigned a
potential of zero in experimental measurements. In theoretical calculations, the absolute (rather
than relative) reduction potentials are often computed, and knowledge of the absolute potential of
the SHE is essential for comparing computations with experiment. A schematic of a cell with the
aqueous SHE as reference and an Ox/Red couple in solvent S is as follows:
Pt | H + (aq) (aH+ = 1); H 2 (g) (pH2 = 1 atm) | Ox(S)(aOx ); Red(aRed ) | Pt (6.15)

In this equation, the SHE is the anode (where oxidation takes place, on the left), and the Ox/Red
couple is the cathode (where reduction takes place, on the right). The vertical lines indicate phase
boundaries. The cell voltage (ECathode − EAnode) is given by Equation 6.16 where EOx/Red

is the standard
potential of the Ox/Red couple (see Equation 6.6) and Ej is the liquid junction potential between the
aqueous SHE and the solvent/electrolyte containing Ox and Red:
RT  aOx 
Ecell = EOx/Red − ESHE + E j = EOx/Red − ESHE + ln  + Ej (6.16)
F  aRed 

If all species are in their respective standard states, with the activity (or concentration, as an estimate
for activity) equal to 1 mol L−1 for solutions and fugacity (or pressure, as an estimate for fugacity)
equal to 1 bar for gases, then Equation 6.16 simplifies into

Ecell = EOx/Red − ESHE + Ej (6.17)

Since the physical setup of an SHE is somewhat cumbersome, reduction potentials are often
referenced to other electrodes. In laboratory measurements, a secondary reference electrode
whose potential versus the SHE(aq) is well known is usually used. Examples include the (KCl)
saturated calomel electrode (SCE) and the saturated silver/silver chloride electrode; the pres-
ence of saturated KCl in these electrodes leads to sharply reduced values of Ej. As such, in
comparing with experiment, it is also important to examine the details of the experimental
measurement to ascertain whether a correction for Ej is necessary in theoretical calculations.
The conversion constants between different electrodes in aqueous solvents have been measured
[54], and these may be used to convert reduction potentials that are referenced to SHE to other
reference electrodes. For example, the potential of the SCE is 0.244 V relative to the SHE at
298 K in aqueous solution. Therefore, to convert values based on SHE to SCE, one needs to
subtract 0.244 V.
III. COMPUTATiON Of REDUcTiON POTENTiALS

As indicated in Equations 6.4 and 6.5, the standard-state Gibbs free energy change for a half reac-
tion is the quantity required for computing a standard reduction potential. Since experimental
reduction potentials are not measured in isolation but are instead measured relative to the potential
of a reference electrode, theoretical calculations of reduction potentials are typically carried out
either for a half-cell reaction (Figure 6.2, cycle A) with the subtraction of the reduction potential of
the reference electrode (e.g., SHE) or on a full-cell reaction (Figure 6.2, cycle B). In Figure 6.2 we
have introduced the general notation ∆GS for a standard-state free energy of solvation, which is the
free energy change upon transfer from the gas phase (sometimes called air in the transfer literature)
to the liquid solution.
Cycle A ΔGrxn
M(aq) + e–(g) M–(aq)
–ΔGso(M) ΔG = 0 ΔGso(M–)
o
ΔG gas
M(g) + e–(g) M–(g)
Cycle B ΔG rxn
M(aq) + 1/2H2(g) M–(aq) + H+(aq)
–ΔGso(M) ΔG = 0 ΔGso(M–) ΔGso(H+)
ΔG ogas
M(g) + 1/2H2(g) M–(g) + H+(g)
FiGURE 6.2 Thermodynamic cycles for calculating an absolute and relative reduction potential.
The corresponding reduction potentials are
−∆Grxn (A)
Ecell = − ESHE (cycle A) (6.18)
nF
and
−∆Grxn (B)
Ecell = (cycle B) (6.19)
nF
In principle, both cycles yield the same result. However, cycle B effectively uses calculated values
of ESHE and ∆GS (H + ), whereas cycle A effectively uses empirical (accurate) values. Thus, cycle A
is simpler, and in this cycle, the key ingredients for the calculation of a reduction potential are the
gas-phase Gibbs free energy of reaction and the free energies of solvation of the reagents, that is, of
the reactants and products.
A. GaS-PHaSE FrEE ENErGIES oF REaCTIoN

1. Gibbs Free Energy and the Treatment of Nuclear Motion
The Gibbs energy change of the gas-phase reaction shown in cycle A is simply the EA of M, EA(M),
plus the thermal contribution to the Gibbs free energy (ΔG therm) of M− less that of M:

∆Ggas = G (M − ) − G (M)
= U e (M − ) + ZPE(M − ) + ∆Gtherm (M − )  − U e (M) + ZPE(M) + ∆Gtherm (M) 
= −EA(M) +  ∆Gtherm (M − ) − ∆Gtherm (M)  = −EA(M) + ∆∆Gtherm (6.20)

where
Ue denotes the Born–Oppenheimer equilibrium potential energy
ZPE denotes the vibrational zero point energy
ΔG therm denotes the thermal contribution to the free energy, that is, the part that vanishes at 0 K
The thermal contribution includes the free energy due to multiple conformations (if present), rota-
tions, and vibrational and electronic excitation. Note that the change in ZPE is included in the EA.
We have neglected nuclear spin considerations, since the effect of nuclear spin cancels out in almost
all cases, the main exception being the H2 molecule.
It is useful to introduce the enthalpy at 0 K, which is labeled H0. Then
H 0 = U e + ZPE (6.21a)
and Equation 6.20 becomes

∆Ggas = H 0 (M − ) + ∆Gtherm (M − ) − H 0 (M) − ∆Gtherm (M) (6.21b)

If the conformations, geometries, and vibrational frequencies of the charged molecule are very similar to
those of the neutral and neither has low-lying electronically excited states, then the thermal correction to

the Gibbs energy of M− and M is likely to be similar and one could roughly estimate ∆Ggas as approxi-
mately equal to EA(M). In some cases however, the gain (or loss) of an electron can result in significant
changes to the electronic structure of a molecule (e.g., quinones acquire an aromatic ring structure upon
the gain of two electrons), and this approximation becomes unreliable. In such situations, the thermal
corrections are sometimes calculated by assuming ideal gas behavior and the rigid-rotor harmonic oscil-
lator approximation, to arrive at analytic expressions for the molecular partition function (Q), from
which one can calculate the entropy (S), and the thermal contributions to the enthalpy (ΔHtherm) and the
Gibbs free energy (ΔGtherm), which are evaluated from the following expressions:
 
+ T  ∂ ln Q  
S = R  ln Q
  ∂T V 

 ∂ ln Q
∆H therm = RT 2   + RT (6.22)
 ∂T V
∆Gtherm = ∆H therm − TS
where Q is the molecular partition function with zero of energy at the ground state and the equiva-
is
lent expression for the Gibbs free energy in terms of Q

G = U e + ZPE + PV − RT ln Q (6.23)

Furthermore, if one assumes that there is only one conformation and negligible coupling between
electronic excitation, vibrations, and rotations, the molecular partition function can be separated
into a product of partition functions associated with the translational, rotational, vibrational, and
electronic motions:
= qtransqrot qvibqelec
Q (6.24)

If we assume separability, the electronic partition function is

∞
∑ ω exp  k T 
 −ε i 
qelec = ω1 + i (6.25)
i =2 B

where
εi is the electronic energy (including nuclear repulsion but not vibrational energy) of level i
ωi is the degeneracy of that level
When the first electronic excitation is thermally inaccessible at room temperature, the electronic
partition is well approximated by the degeneracy associated with the electronic ground state:
qelec = ω1 (6.26)

For monatomic species, if the total electronic angular momentum associated with electronic state
i is Ji, we have ωi = 2Ji + 1. For example, the ground state of a halogen atom is 2 P3/ 2 with J1 = 3/2, so
ω1 = 4, and the first excited state is 2 P1/ 2 with J2 = 1/2 and ω2 = 2. Based on Equation 6.25 and the
excitation energy of 0.109 eV of the first electronically excited state, the electronic partition function
for chlorine atom at 298 K is therefore
qelec = 4 + 2e −4.2 = 4.03 (6.27a)

Higher excited states make a negligible contribution in this case.

The vibrational partition function is usually treated by the harmonic oscillator approximation or
by a quasiharmonic approximation in which one uses the harmonic oscillator formulas but scales
the frequencies [55–57] to account for anharmonicity (and for systematic deficiencies of the elec-
tronic structure method used to calculate the frequencies).
The rotational partition function is usually treated classically.
For molecules where there are multiple conformers that are close in energy to the lowest-energy
structure, the conformational flexibility contributes to the G therm. If we again make a separable
approximation, we can include this by putting another factor in Equation 6.24, yielding
= qtransqrot qvibqelecqconf
Q (6.27b)

N conf
 −∆U j 
qconf = ∑ exp 
j =1
kBT 

(6.27c)

where ΔUj is the potential energy difference of conformation j from the lowest one and the confor-
mational partition function is summed over all the conformational space of the molecule, which is
equivalent to performing a Boltzmann average over the Gibbs free energies of all the conformers.
A much better approximation is to use Equation 6.24—or a more accurate analog with less sepa-
rability approximations—to calculate a free energy Gj for each conformer. Then the free energy
including all conformers is
 −G j 
G = − RT ln ∑ exp  k T 
j B
(6.27d)

One should only include distinguishable conformers. However, even the number of distinguish-
able conformers grows rapidly with molecule size for chain molecules. For example, n-heptane
has 59 distinguishable conformations [58]. Glucose has 2916 potential conformations [59]. Even
the approximation of Equation 6.27d is far from realistic, though, if the barriers separating the
conformers are not all high compared to k BT, both because the contributions of any one conformer
are no longer independent and because the individual contributions differ from their harmonic
values. If the barriers are low, the system must be treated as having one or more internal rota-
tions. A theoretical formalism, based on internal coordinates and including intermode coupling,
is available [60].
In practice, a full conformational search typically involves at least 3N geometry optimizations

where N is the number of rotatable bonds in the molecule that yield distinguishable structures (e.g., the
C-3 to C-4 torsion in 1-butanol does not yield distinguishable structures). Additional considerations
apply if one must consider ring isomerism as well as torsional isomerism. Therefore, a full conforma-
tional search is usually restricted to molecules with N ≤ 5. It is worth noting that a rough approximate
upper bound on the effect of considering higher conformers is given by the case where there are Nconf
conformers with energies, structures, and frequencies identical to those of the lowest-energy struc-
ture; then the error associated with not including the conformational partition function is RT ln(Nconf ).
A variety of methods such as simulated annealing [61], MC methods [62], and an energy-directed
tree search algorithm [63] have been developed for locating the lowest-energy conformer without
having to sample the entire conformational space of the molecule. In principle, one should rank the
conformers in terms of their Gibbs free energies as in Equation 6.23; however, this entails relatively
expensive Hessian calculations, and in practice, the conformers are usually ranked in terms of their
electronic energies (Ue). As a precaution, one could, at the end of the search, perform Hessian calcu-
lations only on conformers that are within some energy difference from the lowest-energy structure
and rerank the conformers in terms of their Gibbs energies.
The expressions for the partition functions as derived from the ideal gas, rigid-rotor harmonic
oscillator approximation can be found in standard textbooks [64] and will not be presented here.
A discussion of the potential sources of error in the application of these partition functions (e.g.,
breakdown of the harmonic oscillator approximation) and the errors that could arise from the
assumptions used to derive them has been discussed elsewhere [65,66]. These treatments assume
that the torsions are separable and may be identified with specific normal modes. When this is not
the case, one must use the internal-coordinate nonseparable treatment mentioned earlier [60].
Having laid out the key ingredients for calculating a gas-phase Gibbs free energy, we now discuss
possible levels of theory for calculating geometries, Born–Oppenheimer (electronic) energies, and
free energies.
Geometries are often calculated at lower levels of theory such as density functional theory (DFT)
with a small basis set that can predict equilibrium geometries and vibrational frequencies (when
scaled by appropriate scale factors [56,57,60]) reasonably well but is not usually sufficiently accu-
rate for reaction energies. However, it is also usually possible to calculate geometries at the same
level as reasonably reliable energies if one uses DFT with a modern density functional and a good
basis set.
2. Electronic Energies of Atoms and Molecules

Chemically accurate (errors of 5 kJ mol−1 or less) electronic energies of reaction can usually be
achieved for small- and moderate-sized systems provided that electronic energies are calculated at
high levels of theory, for example, CCSD(T) or QCISD(T), with very large one-electron basis sets
incorporating high angular momentum basis functions. Here CC denotes coupled cluster theory,
QCI denotes quadratic configuration interaction, SD denotes the inclusion of single and double exci-
tations, and (T) denotes a quasiperturbative treatment of connected triple excitations [67]. One diffi-
culty with electronic wave function theory (WFT) methods of this sort is the very slow convergence
of the energies with respect to the size of the one-electron basis set. Furthermore, a CCSD(T) calcu-
lation formally scales as the seventh power of the number of atoms in the system [67] and is therefore
restricted to relatively small molecular systems. Popular alternatives to large-basis-set CCSD(T)
calculations are composite methods that have been designed to approximate high-level-correlated
calculations using a series of lower cost calculations in conjunction with additivity and/or extrapola-
tion routines. The Gaussian-n (e.g., G4 [68], G3 [69], G3(MP2) [70], and G3(MP2)-RAD [71,72])
methods with high-level corrections, multicoefficient correlation methods [73–82], the correlation-
consistent composite approach [83,84], and CBS-X (e.g., where X is QB3 [85]) are examples of such
methods. These methods involve some degree of empirical parameterization and are practical for
medium-sized systems. By comparison, the Wn (n = 1–4) methods [86–89] have been designed to
compute thermochemical properties with even higher accuracy (ca. 1 kJ mol−1), without empirical
parameterization, but are also considerably more expensive and therefore limited to relatively small
systems. For larger systems where even composite methods become computationally expensive,
one could employ an ONIOM approximation [90,91] where the chemical system is partitioned into
layers. The innermost layer is usually defined by the reaction center and its nearby substituents so
that the chemistry of the reaction is modeled accurately. This layer is treated at the highest level
of theory. The subsequent layer(s) are then treated at lower levels of theories. As an example, this
approach has been successfully used to approximate the G3(MP2)-RAD calculations for a test set of
112 different radical reactions with a mean absolute deviation of 1.2 kJ mol−1 [92]. There are a large
number of other shortcuts and “tricks of the trade,” for example, basis-set extrapolation [93–96] to
ameliorate the aforementioned slow convergence, but these are too numerous to mention.
3 4
An important alternative to WFT is DFT. Here the computational work scales as N atom or N atom
7
rather than N atom, where Natom is the number of atoms in the system, but the accuracy depends on the
quality of the exchange–correlation functional [97]. This quality is improving rapidly [98].
We next address relativistic effects, which begin to be energetically important at the level
of chemical accuracy near the end of the first transition-metal series. There are two kinds of
relativistic effects: (1) scalar relativistic effects and (2) spin–orbit coupling [99]. Scalar relativis-
tic effects are most simply handled by replacing the core electrons with appropriate effective
core potentials [100–105]; however, the accuracy can be low [106]. If all electrons are to be
treated, the most rigorous approach makes use of the four-component Dirac spinor operator.
More efficient approaches are based on two-component spinors; such methods can be derived
from the four-component formulation through various transformations that lead either to the
Douglas–Kroll–Hess Hamiltonian [107–109] or the zero-order-regular approximation [110].
Additional reduction to a one-component formulation yields the spin–orbit operator in its usual
form and also a spin–spin interaction term [111].
Spin–orbit effects, associated with the coupling of spin and orbital angular momenta in a relativ-
istic framework, are sometimes neglected in electronic structure calculations that make use of basis
sets including relativistic pseudopotentials [99]. Rather, only scalar relativistic effects are included
and computed energies represent averages over spin–orbit states, if they exist. Spin–orbit effects
can be included through either perturbation theory or variational methods without sacrificing the
simplicity of one-component computational models. When the relevant transition-metal compounds
may be viewed as substantially ionic in character, a particularly simple approach is to estimate
spin–orbit effects on standard reduction potentials by assuming the same spin–orbit coupling in the
complexes as that for the bare ions, where the latter are usually available from experiment.
3. Standard State of the Electron

In calculating ionization energies and electron attachment energies at nonzero temperatures or
when calculating the free energy of reaction of processes like Equation 6.3, one needs to take into
account the Gibbs free energy of the electron. There are two thermochemical conventions concern-
ing the thermodynamics of the electron: (1) the electron convention (EC) and (2) the ion convention
(IC). There are various literature reports giving slightly different calculated reduction potentials
depending on which thermochemical convention of the electron is used. However, this should not be
the case, and it originates from confusion regarding the definition of the zero of energy in the two
conventions. An important point is that the Gibbs free energy obtained from a particular convention
must be compatible with the quantum chemical calculation, that is, they need to have the same zero
of energy. In quantum chemistry, it is convenient to define a zero of energy, at least temporarily, as
corresponding to all nuclei and electrons being infinitely separated and at rest. With regard to the
zero of energy for the free electron, the two conventions primarily differ in their definition of the
formation enthalpy of the electron. The EC treats the reference state for electrons in the same way as
for elements, that is, the enthalpy of formation is defined to be zero at all temperatures, ∆ f H T (e − ) = 0.
On the other hand, the IC defines the standard enthalpy of formation of the electron to be equal to
TABLE 6.1
Thermodynamics of the Electron under the Various Thermochemical Conventionsa
EC–B IC (Bartmess) IC–B EC/IC–FD
∆ f H °298 0 0 6.197 0
∆ f G°298 0 (0)b 0 0
S °298 20.979 (0)b 20.979 22.734
[ H °298 − H °0 ] 6.197 0 6.197 3.146
G°298 −0.058 (0)b −0.058 −3.632
EC, electron convention; IC, ion convention; B, Boltzmann statistics; FD, Fermi–Dirac statistics.
a Enthalpies and free energies in kJ mol−1, entropies in J mol−1 K−1.
b Defined values [114].
its integrated heat capacity at all temperatures [112,113]. Accordingly, under the two conventions,
the enthalpy of formation of ions differs by the integrated heat capacity of the electron; the actual
value depends on the statistical formalism used to treat the electron. Using Boltzmann statistics and
the ideal gas model, the Gibbs energy of the electron is 0 kJ mol−1 at 298 K. However, since elec-
trons are fermions, Fermi–Dirac statistics are more appropriate, and this yields a Gibbs energy of
−3.6 kJ mol−1 at 298 K. Contrary to the earlier report by Bartmess [114], these values are the same
under both conventions and the thermochemistry of the electron is summarized in Table 6.1. In the
calculation of reduction potentials, it makes no difference which formalism or convention is used as
long as these are used consistently for both the half-cell and the reference electrode.
B. FrEE ENErGIES oF SoLVaTIoN

Continuum solvation models [115–118] have been designed to make accurate predictions of free
energies of solvation. Free energies of solvation can then be combined with the gas-phase Gibbs
energies in Equations 6.20 and 6.21 to obtain the Gibbs free energy of reaction in solution.
In continuum solvation models, the solute is encapsulated in a molecular-shaped cavity embed-
ded in a dielectric continuum. The solute is acted on by a reaction field, which is the field exerted
on the solute by the polarized dielectric continuum, and the polarization of the solute by this field is
calculated via the Poisson equation for a nonhomogeneous dielectric medium (the nonhomogeneous
formulation [119] is required because ε is unity inside the cavity—because polarization is treated
explicitly—but not unity outside the cavity where it is given the value of the solvent’s bulk dielec-
tric constant). The reaction field is used to calculate the bulk-electrostatic contribution, which is then
combined with the non-bulk-electrostatic terms to yield the solvation free energy. There are two con-
tributions to the non–bulk electrostatics. One is the deviation of the true electrostatics from the elec-
trostatics calculated using the bulk dielectric constant. The other is the nonelectrostatic portion of
the solvation free energy. Some continuum solvent models such as the polarized continuum models
(PCM, e.g., [IEF]-PCM [120] (IEF = integral equation formalism) and CPCM [121,122]) model the
non-bulk-electrostatic and bulk-electrostatic terms independently; such models are called [123] type 3
models. Such models are less accurate than type 4 models [49,118,123–131], which are models in which
the non-bulk-electrostatic terms are adjusted to be consistent with a particular choice of the cavity
boundary. This adjustment is necessary because that boundary is intrinsically arbitrary, but the bulk-
electrostatic contribution is very sensitive to it. The most accurate of the type 4 continuum solvation
models are SM8 [129], SM8AD [128], and solvation model based on density (SMD) [127]. (These are
sometimes called SMx models where x specifies which one.) The conductor-like screening model for
real solvents (COSMO-RS) [132,133] adopts a different strategy in which a conductor-like screening
calculation is performed on a molecule to generate a set of screening charges on the molecular cavity.
The distribution of these charges forms a unique electrostatic fingerprint (called the σ-profile) that is
characteristic of that molecule. The solvation free energy is then evaluated from a statistical mechani-
cal procedure involving the interaction of the screening charges of the solute and those of the solvent.
The COSMO-RS model has good accuracy (similar to the SMx models), at least for neutral solutes.
The coupling of the solute to the solvent is directly related to Gibbs free energy change associ-
ated with the transfer of a particle in the gas phase to the solvent in a process in which the concentra-
tion in moles per liter does not change [134]. Therefore, it is sometimes convenient to use a standard
state where the solute concentration in both phases is 1 mol L−1, and this standard state is denoted
by “*” in ∆GS* , to distinguish it from ∆GS, which corresponds to a gas-phase partial pressure of the
solute of 1 atm or 1 bar.
We note that when metal complexes have open coordination sites, it is generally inaccurate to
assume that a continuum solvation approach will accurately reflect the interactions of the metal with the
“missing” first solvation shell. In principle, first-shell solvent molecules could be regarded as ligands
that are explicitly included in the atomistic model. Indeed, for small, highly charged ions, it may be
necessary for highest accuracy to include explicitly not only the first solvation shell but also the second
[135,136]. However, inclusion of even the first shell raises questions about conformational averaging,
and the best practical way to address these questions has not yet been convincingly demonstrated.
The option of adding explicit solvent is more general than just filling open coordination sites. It
has been concluded that continuum solvent models become quantitatively inaccurate near highly
concentrated regions of charge [33,130]. Therefore, it was recommended that one should add a
single explicit water molecule to any anion containing three or fewer atoms, to any anion with one
or more oxygen atoms bearing a more negative partial atomic charge than the partial atomic charge
on oxygen in water, and to any (substituted or unsubstituted) ammonium or oxonium ion [130].
Next, we comment on the issue of molecular geometry. Many solvation calculations use the
gas-phase geometry in both phases. This is often reasonable because the difference in solvation
energies calculated with gas-phase geometries and liquid-phase geometries is often less than other
uncertainties in the calculations. However, it is safer to optimize the geometry separately in each
phase. In cases where the conformational or other structural change associated with solvation is
large, one can include this contribution to the solvation free energy computed on the solution-phase
optimized geometry as follows:
∆GS ≅ ∆GS (soln geom) + Egas (soln geom) − Egas (gas geom) (6.28)

Discussions of the use of gas-phase and solution-phase frequencies are given elsewhere [137,138].
1. Absolute Potential of the Aqueous SHE

In calculating free energies of solvation of ionic species (with charge ±z), a distinction is made
between the absolute or intrinsic free energy of solvation and the real free energy of solvation, where
the latter includes the contribution associated with the surface potential (χ) of the solvent [139]. The
surface potential of water is controversial, and a rather large scatter of values, differing by more than
1 eV, has been reported [139–143]. The choice of χ directly affects the real solvation free energy of
the proton and therefore also the value of ESHE, which is determined by the cycle in Figure 6.3:
−∆Grxn
ESHE = (6.29a)
F

−∆Grxn = ∆Gion
+ ∆Gatom + ∆GS (H + ) = ∆ f G (H + ) + ∆GS (H + ) (6.29b)
At present, the ESHE values of 4.28 and 4.42 V are most commonly used; these are derived from
values of ∆GS* (H + ) of −1112.5 [144,145] and −1098.9 kJ mol−1 [140], respectively, in conjunction
ΔGrxn
H+(aq) + e–(g) 1/2H2(g)
–ΔGso(H+) ΔG = 0 –ΔGoatom
-ΔGoion
H+(g) + e–(g) H (g)
FiGURE 6.3 Thermodynamic cycle for the SHE.
with a value of ΔfG°(H+) of 1517.0 kJ mol−1. The reader should note that the values of the two terms
in Equation 6.29b depend on the choice of statistical formalism used to treat the electron, and the
preceding values are based on Boltzmann statistics. The corresponding ∆GS* (H +) and ΔfG°(H+)
values based on Fermi–Dirac statistics are −1108.9 [42], −1095.3, and 1513.3 kJ mol−1 [114]. The
quantity ∆GS* (H +) is positively shifted by 3.6 kJ mol−1, and ΔfG°(H+) is negatively shifted by the
same amount; therefore, the value of ESHE is independent of convention.
The ESHE value of 4.42 V includes an estimate of the contribution due to the surface potential of
water. More recent experimental estimates of ESHE (4.05, 4.11, and 4.21 V) [146–148] derived from
nanocalorimetric measurements have been reported; however, the uncertainty associated with this
technique is still relatively large. Because the total charge is conserved in a reaction, the contribu-
tion due to the surface potential cancels out in a chemically balanced chemical reaction that occurs
in a single phase. As such, where calculation of equilibrium reduction potentials involving a single
phase is concerned, it should not matter whether the contribution from surface potential is included
in the solvation free energy, as long as this is done consistently for all reacting species and prod-
ucts. This raises the question as to whether continuum solvent models are designed to predict real
or absolute solvation free energies. Continuum solvent models generally contain parameters (e.g.,
atomic radii used to construct the molecular cavity) that have been optimized to reproduce experi-
mental solvation free energies. However, the experimental solvation free energies of ionic solutes
are indirectly obtained via thermochemical cycles involving, for example, the solvation free energy
of the proton, aqueous pKa values, and gas-phase reaction energies. Accordingly, the ESHE values
that should be used with a continuum model are those that are based on a consistent ΔG S(H+).
Table 6.2 provides an overview of several continuum solvent models typically used in aqueous cal-
culations, the ΔGS(H + ) upon which they are based, and examples of the levels of theory for which they
have been most extensively benchmarked. As shown, some continuum solvent models such as the (C)
PCM-UAHF and (C)PCM-UAKS models, where UAHF denotes the use of united-atom parameters
optimized for Hartree-Fock calculations, and UAKS denotes the use of united-atom parameters opti-
mized for Kohn-Sham calculations, are based on ∆GS* (H + ) values that are slightly different from those
used to derive the ESHE values of 4.28 and 4.42 V. In such cases, where the difference is significant, one
could adjust the value of the ESHE to make it compatible with the continuum solvent model as shown in
Table 6.2. The COSMO-RS model was parameterized using solvation free energies (and related data)
of neutral solutes [133], and therefore its compatibility with a particular ESHE is unclear.
2. Nonaqueous Systems
In nonaqueous solution, there is no primary reference electrode equivalent to the aqueous SHE or
SCE. Nonaqueous silver electrodes using silver nitrate or perchlorate are reliable reference elec-
trodes for nonaqueous solutions; however, details on the actual Ag+ concentration or salt anion
in the Ag+/Ag are often not reported, making it difficult to directly compare potentials obtained
from different studies [54]. Although aqueous reference electrodes are often used for nonaqueous
systems, the liquid junction potential between the aqueous and nonaqueous solutions can affect the
measurements. For these reasons, the IUPAC Commission on Electrochemistry has recommended
TABLE 6.2
Examples of Commonly Used Solvent Models and the Levels of Theory at Which
They Are Applied
Solvent Model ∆GS* (H+ ) (kJ mol−1) Level of Theory ESHE (V)
(C)-PCM-UAHF [149] −1093.7 HF/6-31G(d) for neutrals and HF/6-31+G(d) for ions 4.47
(C)-PCM-UAKS −1093.7a B3LYP or PBE0/6-31+G(d) 4.47
SM6 [130] −1105.8 MPW25/MIDI!6D or 6-31G(d) or 6-31+G(d) 4.34
B3LYP/6-31+G(d,p)
B3PW91/6-31+G(d,p) and any DFT method that can
deliver a reasonably accurate electronic density for
the solute of interest
SMD [127] −1112.5 Any electronic structure model delivering a 4.28
reasonable continuous density distribution
SM8 [129] and SM8AD [128] −1112.5 HF theory and many local and hybrid density 4.28
functionals with basis sets of up to minimally
augmented polarized valence double-zeta quality
COSMO-RS [133] — BP/TZP —
The value of the solvation free energy of the proton upon which the model is based and corresponding aqueous ESHE values
are also shown.
a Assumed value.
that the ferrocenium/ferrocene (Fc+/Fc) couple be used as an internal reference for reporting elec-
trode potentials in nonaqueous solutions [150], and knowledge of its absolute potential is therefore
essential for calculations to be referenced to this electrode.
The absolute potential of the Fc+/Fc couple in a nonaqueous solvent can be quite simply obtained
from ESHE and the conversion constant between aqueous SHE and (Fc+/Fc) in a nonaqueous solvent.
Pavlishchuk and Addison determined the conversion constants between various reference electrodes,
including the Fc+/Fc couple in acetonitrile and aqueous SCE (and SHE) [54]. Thus, using ESHE values
of 4.28 and 4.42 V in conjunction with the conversion constant of 0.624 V leads to Fc+/Fc potentials of
4.90 and 5.04 V, respectively. More recent calculations using the SMD and COSMO-RS solvent models
(in conjunction with gas-phase free energies calculated at G3(MP2)-RAD-Full-TZ and Fermi–Dirac
statistics for the electron) provided estimates of 4.96 and 4.99 V for the Fc+/Fc potential in acetonitrile,
respectively [151]. These values are generally in good agreement with the two “experimental” values
of the Fc+/Fc potential (within a 100 mV). The choice of Fc+/Fc potential for continuum-solvent-based
predictions is less obvious, and one could instead adopt an approach analogous to cycle B in Figure 6.2
where both half-cells are treated using the same continuum solvent model.
Related to this point, the reader should note that not all solvent models have been designed to
predict solvation free energies in nonaqueous solvents. Examples of models that have been designed
to treat nonaqueous solutions are the SMD [127] and the COSMO-RS models [132,133]. The PCM-
UAKS and PCM-UAHF models were designed specifically for predicting aqueous free energies
of solvation [149], although there have been attempts [152] to extend these models to nonaqueous
solvents through the manipulation of other parameters within the solvent model such as the scaling
factor (α) that relates to the solvent-inaccessible cavity.
C. STaNDarD STaTES
When calculating solution-phase reaction energies using a thermodynamic cycle that combines
quantities obtained from different sources and/or calculations, it is important to pay attention to the
standard state of these quantities. The literature on calculating solvation free energies by quantum
mechanics usually uses a solute standard-state concentration of 1 mol L−1, whereas 1 molal is more
common in some other subfields of chemical thermodynamics. The approximation of molality by
molarity is reasonable for aqueous solutions since the density of water is approximately 1 kg L−1 for
quite a large range of temperatures. This is not necessarily true for solutions involving organic sol-
vents since the density of these solvents is typically much lower.
As noted earlier, the quantity yielded directly by continuum solvation models without a con-
centration term is the Gibbs free energy change associated with the transfer of a particle in the gas
phase to the solvent, where the molarity of the solute is the same in both phases. On the other hand,
gas-phase thermodynamic quantities are conventionally calculated using a standard state of 1 atm.
The conversion between free energies of solvation in the two conventions is straightforward when
we recall the standard states are actually ideal gases and ideal solutions. Thus, the standard-state
quantities correspond to measurements at infinite dilution followed by extrapolation to unit activity
as if the activity coefficient were unity (ideal behavior). Therefore,
∆GS = ∆GS* + ∆Gconc

(6.30)
where
 RT 
∆Gconc = RT ln   (6.30a)
P 
where
R is the gas constant
P° is the standard-state pressure

At 298 K, we get ∆Gconc = 7.96 kJ/mol for P° = 1 bar and ∆Gconc = 7.93 kJ/mol for P° = 1 atm.
A separate issue relating to standard states is that experimental measurements are not usually
made at either an activity of one or a molarity of one. For example, they may be made in systems
buffered to keep particular reactant and/or product concentrations at some convenient concentra-
tion. For example, reductive chlorination potentials are nearly always measured with the chloride
ion concentration at about 10−3 M—these are conditional potentials, but they are not standard or
formal potentials; however, they can be converted to standard concentrations. Similarly, to use
thermodynamic data in applications, one must convert from tabulated standard-state quantities to
quantities pertaining to real experimental conditions. To facilitate the comparison between standard
free energies and those pertaining to nonstandard conditions, we note that the Gibbs free energies of
reaction at nonstandard concentrations and those at standard concentrations are related by
Q 
∆G = ∆G + RT ln   (6.31)
Q 
where
Q is the reaction quotient
ΔG and Q are for nonstandard concentrations
ΔG° and Q° are for standard states
At equilibrium, ΔG = 0 and Q becomes the equilibrium constant K, so this yields
 K 
∆G = − RT ln   (6.31a)
Q 
D. RaTES oF ELECTroN TraNSFEr

The focus of this chapter is on the prediction of standard reduction potentials, and not on kinetics,
but we note here that the sum of two standard half reactions defines the standard driving force ΔG°
for an electron-transfer reaction between a donor D and an acceptor A. For convenience of notation,
we will here write D and A as neutral species and the post-electron-transfer products D + and A− as
singly positively and negatively charged species, respectively, but there is no restriction on the initial
and final charge states beyond the obvious one that after a single electron-transfer D will be one unit
more positively charged and A one unit more negatively charged.
In the Marcus theory, the driving force is a key variable for the prediction of free energies of activation
associated with electron-transfer reactions. This free energy of activation can be used in a transition-state
theory equation or a diabatic collision theory approach to compute rate constants for electron-transfer
reactions. In particular, the Marcus theory [153] takes the free energy of activation to be
( λ + ∆G )
2

∆G ‡
= (6.32)
4λ
where we have omitted some work terms necessary to bring the reagents together and where λ is
the reorganization energy associated with the electron-transfer reaction. The reorganization energy
may be taken as the sum of two components: an outer-sphere and an inner-sphere reorganiza-
tion energy. The former is associated with the change in solvation free energy that occurs when a
generalized bulk solvent coordinate equilibrated with the pre-electron-transfer state is confronted
instantaneously with the post-electron-transfer state. Such changes in solvation free energy may be
computed using two-time-scale continuum solvation models [154–156] that permit the fast (optical)
component of the solvent reaction field to be equilibrated to the post-electron-transfer state while
the slow (bulk) component remains frozen as it was equilibrated to the pre-electron-transfer state.
The free energy of solvation of the charge-transfer (CT) state interacting with the nonequilibrium
two-time-scale reaction field minus the free energy of solvation of the pre-CT state interacting with
its fully equilibrated reaction field defines the outer-sphere reorganization energy. The inner-sphere
reorganization energy, on the other hand, is associated with changes in the donor and acceptor struc-
tures (including possibly their first solvation shells) as they relax following the electron transfer.
From a computational standpoint, these various quantities are readily computed. Thus, for
instance, by computing the energy change as D+ relaxes from the geometry of D to that of D+
(which in some instances may involve including the first solvation shell of D/D+), one may compute
the contribution of the donor molecule to the inner-sphere reorganization energy. Since kinetics is
a digression from our main subject, we will not develop this topic further, but we emphasize that
the computational techniques outlined here to compute electron-transfer driving forces, combined
with approaches to compute reorganization energies, offer a practical avenue to addressing electron-
transfer rate questions.
IV. ExAMPLES
This section contains examples of calculations of reduction potential. All calculations were per-
formed using Gaussian 09 [157] or MOLPRO 2009 [158].
A. AqUEoUS STaNDarD ONE-ELECTroN REDUCTIoN PoTENTIaLS

oF NITroXIDES aNDQUINoNES
In this example, we calculate the standard potentials of the aqueous one-electron reduction half
reactions shown in Figure 6.4.
expt E o (V) vs SHE

COOH COOH
+ + e– 0.81
4-COOH-TEMPO N N
–
–
–
O O
CONH2 CONH2
+ 0.96
3-CONH2-TCPO + e–
N N
–
–
–
O O
–
O O
+ e– 0.10
benzoquinone
O O
–
O O
2,3-dimethylnaphthoquinone + e– –0.24
O O
FiGURE 6.4 Species studied with their experimental reduction potentials (see Table 6.3 for details).
The relevant computational data are shown in Table 6.3. The gas-phase Gibbs free energies were
computed at the G3(MP2)-RAD(+) level of theory, which is a modification of the G3(MP2)-RAD [71]
method. The (+) signifies that calculations originally defined to involve the 6-31G(d) basis set have
been carried with the 6-31+G(d) basis set so as to allow for an improved description of anionic species.

The aqueous-phase Gibbs free energy of reaction, ∆Gsoln , is calculated using cycle A in Figure 6.2:

∆Gsoln = Ggas (Red) − Ggas (Ox) − Ggas (e) + ∆GS (Red) − ∆GS (Ox) (6.33)

By substituting the appropriate values into this expression, one obtains the ∆Gsoln in Table 6.3 and
the corresponding standard reduction potentials. The values of 4.47 and 4.28 V for ESHE were used
in conjunction with calculations employing the CPCM-UAHF and SMD solvent models as outlined
in Table 6.2.
The table shows that while the approach performs reasonably well for nitroxides, its performance
is much less satisfactory for the quinones where the magnitude of the errors is 380 mV or larger for
both solvent models. This example illustrates the difficulty associated with the direct calculation
of absolute reduction potentials where performance depends heavily on the accuracies of absolute
solvation free energies of the reactants and products. In particular, all half reactions generate or
consume a charged species, and because the uncertainty in the solvation free energies associated
of these species are significantly higher, this directly impacts the accuracy of absolute potentials.
The present example also illustrates that the good performance of directly calculated reduction
potentials by a given method for a particular class of compounds does not necessarily extend to
other types of compounds. An interesting observation for the four cases in Table 6.3 is that in every
instance, the reduced product would be expected to be a much stronger hydrogen bond acceptor than
the oxidized precursor. Thus, first-solvent shell water molecules are very important.
An alternative approach is to calculate relative reduction potentials, which can be more accurate
by systematic error cancellation. For example, the data in Table 6.3 reveal that calculations based on
the CPCM-UAHF model underestimate the standard potentials for quinones by about 600 mV. Such
a systematic error will largely cancel out for the reaction shown in Figure 6.5.
The potential associated with this reaction is readily obtained from the data in Table 6.2 as
the reduction potential of 2,3-dimethylnaphthoquinone less that of benzoquinone. Using the
TABLE 6.3
Computational Data for the Calculation of Standard Reduction Potentials at 298 K and Relative to SHEa
4-COOH-TEMPOg 3-CONH2-TCPOg Benzoquinone 2,3-Dimethylnapthoquinone
Ox Red Ox Red Ox Red Ox Red
H0 (kJ mol−1) −1,761,669.5 −1,762,348.8 −1,603,319.8 −1,604,000.7 −1,000,069.2 −1,000,250.1 −1,608,881.0 −1,609,042.0
ΔGtherm (kJ mol−1) −108.5 −110.2 −105.6 −107.6 −78.5 −79.1 −102.5 −101.0
G°gas (kJ mol−1)b −1,761,778.0 −1,762,459.0 −1,603,425.4 −1,604,108.3 −1,000,147.8 −1,000,329.2 −1,608,983.5 −1,609,143.0
∆G°S (UAHF; kJ mol−1)c −233.2 −42.2 −212.3 −39.9 −28.1 −243.3 −13.5 −209.9
∆G°S (SMD; kJ mol−1)c −242.6 −44.7 −241.9 −52.5 −24.9 −233.0 −19.7 −215.6
∆G°soln (UAHF; kJ mol−1)d −486.3 −506.9 −393.1 −352.2
Theoretical Calculation of Reduction Potentials
∆G°soln (SMD; kJ mol−1)d −479.5 −489.9 −386.0 −351.8

E° (UAHF) rel. SHEe (V) 0.57 (−0.24) 0.78 (−0.18) −0.40 (−0.50) −0.82 (−0.58)
E° (SMD) rel. SHEf (V) 0.69 (−0.12) 0.80 (−0.16) −0.28 (−0.38) −0.63 (−0.39)
E° (expt) 0.81 [159] 0.96 [159] 0.10 [160] −0.24 [160]
Signed errors are shown in parentheses.

a The gas-phase energies were computed at the G3(MP2)-RAD(+) level. Solvation calculations using the CPCM-UAHF and SMD models were performed by the HF/6-31+G(d) and
B3LYP/6-31+G(d) methods on the respective solution-phase optimized geometries. CPCM-UAHF solvation free energies were performed at the ROHF/6-31+G(d) level on UHF/6-31+G(d)
solution optimized geometries for open-shell species.
b G o = H + ∆G
gas 0 therm .
c Solvation free energies printed in Gaussian 09 correspond to ∆G * and Equation 6.30 is used to obtain ∆G °.
S S
d
∆G°soln calculated from Equation 6.32.
e E
SHE = 4.47 V.
f E
SHE = 4.28 V.
g 4-COOH-TEMPO = 2,2,6,6-tetramethylpiperidinoxyl; 3-CONH -TCPO = 2,2,5,5-tetramethyl-3-carbamido-3-pyrroline-1-oxyl.
2
249
– –
O O O O
+ +
O O O O
FiGURE 6.5 An isodesmic CT reaction.
– ΔGCT –
A (soln) + Ref (soln) A (soln) + Ref (soln)
–
ΔGso(Ref )
–
–ΔGso(A) –ΔGso (Ref ) ΔGso (A )
– ΔGogas –
A(g) + Ref (g) A ( g) + Ref (g)
FiGURE 6.6 Thermodynamic cycle for a CT reaction.
CPCM-UAHF model, this CT potential is −0.42 V. Thus, by using benzoquinone as a reference

molecule for which the experimental standard potential is known (0.10 V), one can estimate the
standard potential of 2,3-dimethylnaphthoquinone by adding the CT potential to E°(benzoquinone)
to give E°(2,3-dimethylnaphthoquinone) = −0.32 V. This approach brings the error down from
580 to 80 mV. More generally, for the CT reaction between A and a reference molecule (Ref) with
known E°, the standard potential E°(A/A−) may be obtained from the thermodynamic cycle in
Figure 6.6 and Equation 6.34a:

∆GCT = ∆Ggas + ∆GS (A• − ) + ∆GS (Ref ) − ∆GS (A) − ∆GS (Ref • − ) (6.34)

∆GCT
(
E A A• − = ) 96.5 C mol −1

+ Eexpt (
Ref Ref • − ) (6.34a)

An added advantage of this approach is that ESHE is no longer needed, thereby eliminating a source of
uncertainty. However, since the method relies on systematic error cancellation, it is expected to work
best when the reference molecule is structurally similar to A. The major limitation of this approach is
that a structurally similar reference with accurately known E° may not always be available.
B. CHEMICaLLY IrrEVErSIbLE ProCESSES—REDUCTIVE DECHLorINaTIoN

Next, we show how the reduction potentials corresponding to the dissociative electron-transfer reac-
tions of some alkyl halides in aqueous and nonaqueous solutions (Figure 6.7) are calculated. The
relevant computational data and results are presented in Tables 6.4 and 6.5, respectively.
Since the potentials of reactions 1, 3, and 4 are measured in DMF and are referenced to the aque-
ous SCE, a 0.172 V [53] correction for a liquid junction potential was applied to the calculations.
Accordingly, using the reductive cleavage of carbon tetrachloride (reaction 3) as example, its reduc-
tion potential was calculated as follows:
∆Gsoln = − 361.4 kJ mol −1

−∆Gsoln
E =
− ESHE − E ( SCE SHE ) − E j
96.5
= 3.75 − 4.28 − 0.241 + 0.172 = −0.60 V (6.35)
where the calculations are referenced to the aqueous SCE and E°(SCE/SHE) is its potential relative
to aqueous SHE (0.241 V) [42].
E (expt)
–
Cl(soln) + e –
Cl (soln) E°aq = 2.59 vs SHE; E°DMF = 2.12 vs SCEaq
CCl4(soln) + e– CCl3(soln) + Cl–(soln) E°DMF = –0.58 vs SCEaq
CHCl3(soln) + e– CHCl2(soln) + Cl–(soln) E°DMF = –0.84 vs SCEaq
Cl Cl Cl Cl
Cl (soln) + e– Cl (soln) + Cl–(soln) Eaq = 0.11 vs SHE; [Cl–] = 10–3 M
Cl Cl
Cl Cl Cl
Cl Cl Cl Cl
Cl (soln) + 2e
–
(soln) + 2Cl–(soln) Eaq = 1.15 vs SHE; [Cl–] = 10–3 M
Cl
Cl Cl Cl Cl
Cl Cl Cl Cl
Cl (soln) + H+(soln) + 2e– Cl (soln) + Cl–(soln) Eaq = 0.67 vs SHE; [Cl–] = 10–3 M, [H+] = 10–7 M
Cl Cl
Cl Cl Cl H
FiGURE 6.7 Species studied with their experimental reduction potentials in V (see Table 6.5 for details).
TABLE 6.4
Calculated Gas-Phase Gibbs Free Energies and Solvation Free Energies at 298 Ka
Cl• Cl−/Cl−⋅H2O CCl4 CCl•3 CHCl3 CHCl•2

G°gas (kJ mol−1)a −1,206,953.9c −1,207,306.1/−1,407,825.0 −4,928,225.9 −3,721,026.3 −3,722,725.7 −2,515,500.8
∆GS° (SMD) H2Ob 8.4 —/−260.3 — — — —
∆GS° (SMD) 1.8 −264.8/— −4.2 2.1 −12.9 −0.8
DMFb
C2Cl6 C2Cl5• C2HCl5 C2Cl4 H+ H2O
° (kJ mol )
Ggas −1 a
−7,442,299.2 −6,235,086.3 −6,236,794.9 −5,028,088.6 −26.3 −200,483.0
∆GS° (SMD) H2Ob 13.2 13.9 3.0 15.7 −1,104.6 —
a Computed at the G3(MP2)-RAD(+) level of theory.

b Calculations (in kJ mol−1) performed by the B3LYP/6-31+G(d) method on solution-phase optimized geometries.
c Includes spin–orbit correction (−1.34 millihartrees).
As mentioned in Section III.B, first-solvent shell interactions are likely to be very important for species
with regions of concentrated charge such that a continuum model is likely to be inadequate. The reader
should therefore note that the SMD, SM6, and SM8 solvent models are to be used as mixed discrete-
continuum models in such cases; in particular, they have been parameterized to reproduce the experimen-
tal aqueous solvation free energy of the Cl−⋅H2O cluster and (H 2O)2 dimer, not the solvation free energy
of bare Cl− or H2O [33,127,129,130]. As such, for the aqueous reactions that involve a bare chloride ion,
that is, reactions 2 and 5 to 7, the calculations were carried out with the addition of a water of hydration,

as shown in Table 6.5. Using the last reaction as example, the calculated ∆Gsoln was obtained as follows:

∆Gsoln
= ∆Ggas + ∆∆GS = − 961.5 kJ mol −1 (6.36)

where
∆∆GS = ∆GS (Cl ⋅ H 2O − ) + ∆GS (C2HCl 5 ) − ∆GS (H + ) − ∆GS (C2Cl6 ) − ∆GS (H 2O)

= 842.6 kJ mol −1 (6.37)
TABLE 6.5
Calculated Reduction Potentials and Experimental Valuesa
E/ V (calc) E/ V (expt)
1 Cl•(dmf) + e− → Cl−(dmf) 2.03 2.12 [161]
2 Cl•(aq) + H2O(l) + e− → [Cl(H2O)]−(aq) 2.40c 2.59 [161]
3 CCl 4 (dmf ) + e − → CCl3• (dmf ) + Cl − (dmf ) −0.60 −0.58 [162]
4 CHCl3 (dmf ) + e − → CHCl•2 (dmf ) + Cl − (dmf ) −0.93 −0.84 [162]
5 C2 Cl6 (aq) + H 2 O(l) + e − (g) → C2 Cl•5 (aq) + [Cl(H 2 O)]− (aq) −0.20b,c 0.11b [1]
6 C2Cl6(aq) + 2H2O(l) + 2e−(g)→C2Cl4(aq) + 2[Cl(H2O)]−(aq) 0.91b,c 1.15b [1]
7 C2Cl6(aq) + H2O(l) + H + (aq) + 2e−(g)→C2HCl5(aq) + [Cl(H2O)]−(aq) 0.58b,c 0.67b [1]
a Reactions in DMF and aqueous solution are referenced to SCE(aq) and SHE(aq), respectively.
b These potentials correspond to the experimental conditions [Cl−] = 10−3 mol L−1 and pH = 7.
c Calculations that include an explicit water of hydration. The experimental solvation free energy of the water (−8.6 kJ mol−1)
that corresponds to a standard state of [H2O] = 55 mol L−1 (i.e., pure water) and 1 atm in the liquid and gas phase was used
in these calculations.
Note that in these calculations, we have used the experimental value for the solvation free energy
for water (−8.6 kJ mol−1) [163] under the conventional standard state for pure liquids, that is, mole
fraction of 1 in the liquid phase and 1 atm in the gas phase. In these reactions, the experimental
potentials for the reductive cleavage of hexachloroethane were referenced to SHE, and therefore
no correction for Ej was applied. However, the potentials corresponded to nonstandard conditions
of [Cl−] = 10−3 mol L−1 and pH 7, and a correction using Equation 6.31 was applied to arrive at the
values in Table 6.5:

∆Gsoln = ∆Gsoln + RT ln 
(
 [1 M C2HCl 5 ][10 −3 M Cl − ] / [1 M C2Cl6 ][10 −7 M H + ] ) 

 (
[1 M C2HCl 5 ][1 M Cl − ] / [1 M C2Cl6 ][1 M H + ] ) 


= ∆Gsoln + RT ln(10 4 ) = −938.7 kJ mol −1 (6.38)
Accordingly, the potential for this two-electron reduction is
−938.7
E=− − 4.28 = 0.58 V (6.39)
2 × 96.5
C. CoNSTrUCTING a PoUrbaIX DIaGraM For THE Two-ELECTroN

REDUCTIoN oF O-CHLoraNIL
Consider the two-electron reduction of o-chloranil (OCA) in aqueous solution [164]. Depending
on the pH of the solution, the reduction process can be represented in one of the following ways as
shown in Figure 6.8.
The corresponding standard reduction potentials are denoted E°(OCA/OCA2−), E°(OCA,H+/
OCAH−), and E°(OCA,2H+/OCAH2), and these are related to each other as follows:

( ) (
E OCA OCA 2 − = E OCA, H + OCAH − + ) RT
2F
ln K 2 (6.40)
Cl Cl
Cl O Cl O –
+ 2e–
Cl O Cl O –
Cl Cl
Cl Cl
Cl O Cl OH
+ 2e– + H+
Cl O Cl O –
Cl Cl
Cl Cl
Cl O Cl OH
+
+ 2e– + 2H
Cl O Cl OH
Cl Cl
FiGURE 6.8 The microspecies present in the two-electron reduction of OCA in aqueous solution.

( ) (
E OCA OCA 2 − = E OCA, 2H + OCAH 2 + ) RT
2F
ln K1K 2 (6.41)
where K1 and K2 are the first and second acid dissociation constants of OCAH2. From Equation 6.11,
the potential for the E(OCA,2H+/OCAH2) is
RT [OCA 2 − ][H + ]2
(
E = E °′ OCA, 2H + OCAH 2 + ) 2F
ln
[OCAH 2 ]
(6.42)

Equation 6.42 can alternatively be expressed in terms of the acid dissociation constants (K1 and K2)
of the conjugate acid of the reduced product (H2A):
(
E = E °′ OCA, 2H + OCA 2 − + ) RT
2F
(
ln K1K 2 + K1[H + ] + [H + ]2 +
RT S
)
ln Ox
2 F SRed
(6.43)

SOx = [OCA] (6.43a)
SRed = [OCA 2− ] + [OCAH − ] + [OCAH 2 ] (6.43b)
Using techniques such as cyclic voltammetry, one can measure a half-wave potential (E1/2) where
the concentrations of the reductant are approximately equal to the oxidant, that is, SOx = SRed, and
Equation 6.43 becomes

(
E1/ 2 = E °′ OCA, 2H + OCA 2 − + ) RT
2F
(
ln K1K 2 + K1[H + ] + [H + ]2 ) (6.44)
TABLE 6.6
Calculateda Reduction Potentials in V and pKa Values
E°(OCA,2H + /OCAH2) 0.83 (0.79) [164]
E°(OCA,H + /OCAH−) 0.63 (0.67) [164]
E°(OCA/OCA2−) 0.41b
pK1 (5) [164]
pK2 9.2c
Experimental values, where available, are shown in parentheses.

a Calculations are based on the G3(MP2)-RAD(+) gas-phase energies with SMD solvation
energies obtained at the B3LYP/6-31+G(d) level and ESHE of 4.28 V.

b Calculated from Equation 6.40 using the data in this table.
c Calculated using a proton-exchange method [34,35] using orthoquinone (expt pK = 13.4)

a
[165] as the reference.
From the calculated reduction potentials in Equations 6.40 and 6.41 as well as the acid dissociation
constants (K1 and K2) of the diprotic acid, OCAH2, a chemical speciation plot denoting the dominant
microspecies in a particular pH range can be obtained. The data needed for such a plot are shown
in Table 6.6.
From Equation 6.43, three distinct linear pH ranges can readily be identified. In the range where
pH < pK1, [H+] ≫ K1 ≫ K2, the molecule OCAH2 is the predominant form of the reduced product,
and the midpoint potential has a pH dependence based on Equation 6.44:

(
E1/ 2 = E °′ OCA, 2H + OCAH 2 + ) RT
2F
ln[H + ]2 (6.45)
In the other two linear segments at pK1 < pH < pK2 and pH > pK2, the reduced product exists pre-
dominantly as OCAH− and OCA2−, respectively, and the corresponding half-wave potentials have
pH dependence following equations:

(
E1/ 2 = E °′ OCA, 2H + OCAH 2 + ) RT
2F
ln( K1[H + ]) (6.46)

(
E1/ 2 = E °′ OCA, 2H + OCAH 2 + ) RT
2F
ln( K1K 2 ) (6.47)
Extrapolation of the three linear segments (with theoretical slopes −2.303mRT/2F, where m is the
number of protons involved in the reaction) to pH 0 yields the formal potential E°′(OCA,2H + /OCAH2),
E°′(OCA,H+/OCAH−), and E°′(OCA/OCA2−), respectively. Collectively, this information can be
used to construct a E versus pH (Pourbaix diagram) as shown in Figure 6.9. The vertical lines cor-
respond to the pKas of the diprotic OCAH2 acid.
The reader should note that the formal potential E°′ is pH invariant since the condition
[H+] = 1 mol L −1 applies. However, half-wave potentials are strongly pH dependent, and these
are quite often reported instead of standard or formal reduction potentials. Thus, in comparing
with experiment, it is also important to examine the details of the experimental measurement to
ascertain whether the calculation corresponds to the same quantity as the one reported.
pH < pK1 pK1 < pH < pK2 pH > pK2

0.9
E°(OCA, 2H+/OCAH2)
0.8
Half-wave potential (V) versus SHE
0.7
E°(OCA, H+/OCAH–)
0.6
0.5
0.4 E°(OCA/OCA2–)
0.3
OCA/OCAH2 OCA/OCAH– OCA/OCA2–
0.2
0.1
0
0 2 4 6 8 10 12 14
pH
FiGURE 6.9 An E versus pH diagram (Pourbaix diagram) for OCA. The vertical dotted lines correspond to
the pKas of OCAH2 and indicate the pH regions in which various stable species predominate.
V. CONcLUDiNG REMARkS
We have presented an introductory guide to carrying out QM continuum solvent prediction of solu-
tion-phase reduction potentials. We stress that reduction potentials are equilibrium thermochemical
parameters. We discussed issues pertaining to thermochemical conventions for the electron, the
choice of standard electrode, and the advantages and limitations of methods based on thermody-
namic cycles for calculating reduction potentials. Just as in experimental work, a key consider-
ation for predicting chemically accurate reduction potentials is the difficulty of obtaining accurate
estimates of the solvation free energies of ionic species. Careful work often involves including (or
expanding) a first solvation shell, particularly in solvents donating or accepting strong hydrogen
bonds. Relative reduction potential calculations can partly remedy this problem by exploiting sys-
tematic error cancellation in the solvation calculations.
AckNOwLEDGMENTS
We gratefully acknowledge support from the Australian Research Council under their Centres of
Excellence program and the generous allocation of computing time on the National Facility of the
National Computational Infrastructure. MLC also acknowledges an ARC Future Fellowship. This
work was supported in part by the U.S. Army Research Lab under Grant No. W911NF09-1-0377
and the U.S. National Science Foundation under Grant No. CHE09-56776.
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885–892.
Section II
General Preparative Aspects
7 Preparative Electrolysis on
the Laboratory Scale
Jakob Jörissen and Bernd Speiser
CONTENTS
I. Principles of Electroorganic Cell Operation ........................................................................ 265
A. Introduction ................................................................................................................... 265
B. Basic Requirements and Theoretical Definitions .........................................................266
1. Precondition of Any Electrolysis: A Closed Electric Circuit ................................266
2. Types of Electrochemical Reactions ...................................................................... 266
3. Cell Current ........................................................................................................... 266
4. Electrode Potential ................................................................................................. 267
5. Cell Voltage............................................................................................................ 270
6. Basic Definitions for Chemical Reactions, Also Valid for Electroorganic Electrolysis .....271
7. Operation Modes of (Electrochemical) Reactors .................................................. 271
8. Control of Electrochemical Reactions ................................................................... 272
II. Components of Electroorganic Reaction Systems ................................................................ 275
A. Electrodes...................................................................................................................... 275
1. General Requirements for Electrode Materials ..................................................... 275
2. Special Requirements for Cathode Materials ........................................................ 276
3. Special Requirements for Anode Materials ........................................................... 276
B. Examples of Electrode Materials .................................................................................. 277
1. Platinum, Platinum Metals, Other Noble Metals, and Their Alloys ..................... 277
2. Nickel ..................................................................................................................... 277
3. Iron (Mild Steel), Stainless Steel ........................................................................... 278
4. Lead ....................................................................................................................... 278
5. Mercury.................................................................................................................. 278
6. Carbon.................................................................................................................... 279
7. Conductive Ceramic, for Example, Ebonex ........................................................... 279
8. Electrocatalytic Coatings on Carrier Materials .....................................................280
9. Boron-Doped Diamond Coating ............................................................................280
C. Examples of Electrode Types and Their Special Properties ........................................ 281
1. Porous vs. Smooth Electrodes................................................................................ 281
2. Gas-Evolving Electrodes........................................................................................ 281
3. Sacrificial Anodes .................................................................................................. 281
4. Gas Diffusion Electrodes ....................................................................................... 282
D. Electrolytes ................................................................................................................... 282
1. Solvents .................................................................................................................. 282
2. Supporting Electrolytes ......................................................................................... 282
3. Solid Polymer Electrolyte Technology .................................................................. 283
E. Cell Separators .............................................................................................................. 283
1. Porous Materials .................................................................................................... 283
2. Ion Exchange Membranes ......................................................................................284
263
F. Electrochemical Cells ................................................................................................... 285

1. Homogeneous Current Density .............................................................................. 285
2. Electrode Potential Measurement ..........................................................................287
3. Uniform Mixing and Mass Transport .................................................................... 289
4. Temperature Control .............................................................................................. 289
5. Cell Construction Materials ................................................................................... 290
6. Procedure of Electrolysis Experiments, Mass Balancing and Charge Balancing...... 292
G. Examples of Electrochemical Cells .............................................................................. 294
1. H-Cell..................................................................................................................... 294
2. Beaker Glass Cells .................................................................................................294
3. Flow-Through Cells ............................................................................................... 296
4. Innovative Cell Constructions................................................................................ 298
References ...................................................................................................................................... 298
III Appendices ...........................................................................................................................300
III.A Appendix A: Solvents for Electrolysis .................................................................................300
III.A.1 General Considerations .........................................................................................300
III.A.1.a Proton Activity .....................................................................................300
III.A.1.b Usable Potential Range ........................................................................303
III.A.1.c Dielectric Constant...............................................................................303
III.A.1.d Dissolving Power .................................................................................303
III.A.1.e Temperature Range and Other Factors.................................................305
III.A.1.f Purification...........................................................................................306
III.A.2 Protic Solvents .......................................................................................................306
III.A.2.a Acid Solvents .......................................................................................306
III.A.2.b Neutral Solvents ...................................................................................308
III.A.2.c l,l,l,3,3,3-Hexafluoropropan-2-ol .........................................................309
III.A.2.d Basic Solvents ......................................................................................309
III.A.3 Aprotic Solvents .................................................................................................... 311
III.A.3.a Acetonitrile ..........................................................................................312
III.A.3.b Dimethylformamide .............................................................................313
III.A.3.c N-Methylpyrrolidone ...........................................................................314
III.A.3.d 3-Methyl-2-Oxazolidinone (3M2O) ..................................................... 314
III.A.3.e Hexamethylphosphoramide (HMPA) .................................................. 314
III.A.3.f Pyridine ................................................................................................315
III.A.3.g Dimethyl Sulfoxide (DMSO) ...............................................................315
III.A.3.h Sulfolane ..............................................................................................316
III.A.3.i Propylene Glycol Sulfite ......................................................................316
III.A.3.j Nitromethane........................................................................................316
III.A.3.k Nitrobenzene ........................................................................................317
III.A.3.l Propylene Carbonate (PC) ...................................................................317
III.A.3.m Benzene and Chlorobenzene ................................................................317
III.A.3.n Ethers ...................................................................................................317
III.A.3.o Methylene Chloride and 1,1,2,2-Tetrachloroethane.............................318
III.A.3.p Sulfur Dioxide...................................................................................... 318
III.A.4 Salts ....................................................................................................................... 318
III.A.5 Supercritical Fluids ............................................................................................... 319
References for Appendix A ............................................................................................................ 320
III.B Appendix B: Electrolytes...................................................................................................... 325
III.B.1 Anions ................................................................................................................... 325
III.B.1.a Perchlorate ...........................................................................................325
III.B.1.b Tetrafluoroborate .................................................................................. 325
Preparative Electrolysis on the Laboratory Scale 265
III.B.1.c Hexafluorophosphate, Hexafluoroarsenate ..........................................326

III.B.1.d Trifluoromethanesulfonate ...................................................................326
III.B.1.e Nitrate ..................................................................................................326
III.B.1.f Aromatic Sulfonates.............................................................................326
III.B.1.g Carboxylate Ion....................................................................................326
III.B.1.h Tetramethylaluminate and Tetraphenylborate ..................................... 327
III.B.2 Cations ................................................................................................................... 327
III.B.2.a Lithium Ions .........................................................................................327
III.B.2.b Sodium Ions .........................................................................................327
III.B.2.c Magnesium Ions ...................................................................................327
III.B.2.d Tetraalkylammonium Ions ...................................................................327
III.B.2.e Sulfonium Salts ....................................................................................328
III.B.2.f Cryptates ..............................................................................................328
III.B.2.g Polyelectrolytes .................................................................................... 328
III.B.3 Buffers ................................................................................................................... 328
III.B.3.a Acids ....................................................................................................328
III.B.3.b Bases ....................................................................................................329
III.B.3.c Buffer Systems ..................................................................................... 329
References for Appendix B ............................................................................................................ 329
I. PRiNciPLES Of ELEcTROORGANic CELL OPERATiON

A. INTroDUCTIoN
Any electrolysis process needs a careful selection of optimal operation conditions as well as of an appro-
priate electrochemical cell. These decisions will be responsible for the result. The variety of possibili-
ties is very broad and precise planning and usually also experiments are indispensable. The theoretical
background of electroorganic reactions is comprehensively elucidated in Chapter 1. Nevertheless, as
basis for the following discussion of practical requirements, some fundamental features and defini-
tions of electrolysis will be recapitulated here, sometimes knowingly in a simplified form.
If electrochemical knowledge, which is included in this book, has to be transferred into applica-
tion as a preparative electrolysis in laboratory—or even into industrial electrochemistry—numerous
practical aspects have to be considered. Selected issues are briefly discussed in this chapter: vari-
ous alternatives for electrochemical cell operation, including recommendations for procedure and
measurements in electrolysis experiments, an overview of relevant properties of electrode materi-
als, electrolyte components and cell separators, as well as examples of cell constructions using
different materials. More detailed information is available in the previous (fourth) edition of this
book [1].
The best basis for planning of a preparative electroorganic synthesis is to collect previous infor-
mation about the desired electrochemical reaction as much as possible. It will be advantageous
to know the influence of temperature, solvent, pH value, stirring rate, and so on. Additional to
such parameters, which are generally important for chemical reactions, typical electrochemical
information, especially the dependence of the processes on the electrode potential, is needed.
Electroanalytical standard methods to acquire these data are discussed in Chapter 2. In particular,
cyclic voltammetry and coulometry—when necessary combined with other methods—are useful
tools for this task. If no special information about the intended reaction is available at the beginning
of investigations, also literature data about comparable reactions will be helpful. A comprehensive
overview of published electroorganic reactions is given in this book.
The desired amount of products determines the scale of the electrolysis cell and the demand of chem-
icals. Limiting cases may be on the one hand only to prove analytically the formation of compounds
or on the other hand to generate a product quantity that is sufficient for application tests. To achieve
reliable information about an electrolysis process, experiments are suitable on a scale large enough to
enable a balancing of reactants, products, and consumed electrical charge (see Section II.F.6).
B. BaSIC REqUIrEMENTS aND THEorETICaL DEFINITIoNS

The following characteristics of electrochemistry (and reaction engineering) should be considered for the
design of a suitable preparative-scale electrolysis (see also Chapter 1 and literature as, e.g., Reference 2–7).
1. Precondition of Any Electrolysis: A Closed Electric Circuit

The electrochemical cell is part of a closed electric circuit. As a consequence, always at least two elec-
trodes have to be used. It is the principle of electrochemistry to replace the direct electron transfer
between atoms and molecules in conventional redox reactions by the separated electron release (oxida-
tion) at the anode and the electron consumption (reduction) at the cathode (both processes described
with respect to the chemical species in the electrolyte). Nevertheless, in most cases, only one of these
reactions may be intended (at the working electrode), but inevitably, the other one has to be carried out
(at the counter electrode). Only sometimes useful reactions are possible at both electrodes (so-called
paired electrolysis). Even though no valuable product may be achievable at the counter electrode, the
reaction there has to proceed at a sufficient rate, and at least any detrimental effect on the desired reac-
tion has to be avoided. Therefore, it is essential to select an optimized combination of electrode materials
and a suitable cell: if possible, undivided or divided by a separator if otherwise undesired electrochemi-
cal and/or chemical reactions cannot be circumvented (see Section II.E).
The transfer of ions between the electrodes is indispensable to realize a closed electric circuit if
the electrodes are connected to an electrical power supply, which acts as an electron pump. Thus,
an electrolyte of sufficient ion conductivity is needed. Usually, this is a solution containing at least
a minimal concentration of an acid, a base, or a salt as supporting electrolyte, which normally has
to be separated after the reaction.
2. Types of Electrochemical Reactions

Different types of electrochemical reactions within electrolysis processes may be available and
the most suitable should be chosen. The practical consequences for cell construction and operation
conditions have to be considered (benefits and handicaps of these alternatives are discussed for
numerous examples in this book, including industrial applications):
• Direct electroorganic electrolysis at an inert or at an electrocatalytically active electrode

surface. If this operation mode is possible, the essential properties of electrochemistry are
completely applied and no additional agent in the electrolyte is needed.
• Indirect electrolysis, using a conventional chemical reaction with an oxidizing or reducing
agent that is regenerated electrochemically in a separate electrolysis cell.
• Utilization of a redox agent as a mediator, that is, a chemical reaction takes place like in
indirect electrolysis, but the mediator is immediately regenerated in situ at the electrode so
that it is continuously present like a homogeneous catalyst in the electrolysis cell.
3. Cell Current
The cell current within the closed electric circuit (called i in Chapter 1 of this book, usually mea-
sured in [mA] or [A]) represents the overall reaction rate of an electrolysis. It induces the charge
transfer and the product formation simultaneously at both electrodes, theoretically according to
Faraday’s law. The following definitions apply:
• Required charge transfer: 1 mol of product needs theoretically 96,485 A s ≈ 26.8 A h (this
is the Faraday constant F = charge of 1 mol electrons), multiplied by the stoichiometric
number of transferred electrons.
• Current efficiency (current yield) is a characteristic value of an electrolysis process,

being the fraction of the electrical cell current—or (integrated over the time) the fraction
of the transferred charge—which is consumed to generate the specified product (sepa-
rately for anode and cathode). It has to be considered which products result additionally
if the current efficiency is less than 100%, for instance, a problematic by-product or a
harmless gas.
• In order to calculate the required charge for the formation of a product in practical electrol-
ysis, the theoretical value from Faraday’s law has to be divided by the current efficiency.
• Current density, called j in this chapter, is the cell current divided by the geometrical
electrode area and usually given in [mA cm−2], possibly different for anode and cath-
ode. It represents the local reaction rate of an electrochemical reaction—independent
of the size of the entire electrolysis cell—and is a decisive factor for electrochemi-
cal reactions due to its close correlation to the electrode potential (see Section I.B.4).
Therefore, an even current density distribution on the electrode area is an important
demand of cell design.
Frequently, a low current density favors the intended electroorganic reaction. However, a higher
current density is advantageous considering economic aspects of a sufficient production rate in the
electrolysis cell (high space time yield). A compromise has to be found.
4. Electrode Potential
The electrode potential—defined in Chapter 1 of this book separately for anode, Φan, and cathode,
Φcat—is correlated with the energy conversion during electrochemical reactions, and therefore it is
the decisive parameter for thermodynamics as well as for kinetics of any electrolysis. It is defined
as the potential difference between the electrode (electron conductor) and the electrolyte (ion con-
ductor) in front of the electrode, which are separated by the electrochemical double layer (see
Chapter 1, Section III.A.4). It can be measured in [V] using a reference electrode combined with a
(Haber) Luggin capillary (see Section II.F.2 and Chapter 1, Sections II.B.2 and III.A.3). The follow-
ing elements of the electrode potential have to be considered.
a. Equilibrium Potential

Reversible electrochemical reactions will spontaneously proceed at an electrode in contact with
reactants and electrolyte until the dynamic equilibrium is reached: that is, cathodic reduction and
anodic oxidation are running at the same rate and no external current is detectable (the internal
bidirectional current flow is called exchange current density = j0). Under these conditions, the elec-
trode will be charged to the characteristic equilibrium potential E, resulting from the charge transfer
during the electrochemical reactions.
Any electrolysis includes the two equilibrium potentials of the cathode Ecat and the anode Ean.
The difference Ecat − Ean is called open-circuit voltage (OCV [V]). It is related to the energy that is
at least necessary to perform this electrochemical cell reaction. Multiplied with the correlated trans-
ferred charge, the free enthalpy ΔG (Gibbs energy [J mol−1]) of the combined overall cell reaction
results. It stands for the thermodynamics of the reaction:
∆G = −OCV ⋅ n ⋅ F (7.1)
where
n is the number of transferred electrons
F is the Faraday constant; notice the definition of positive and negative signs
The equilibrium potential of the reference reaction
H 2 2H + + 2e − (7.2)
at standard conditions is set, by definition, to E 0 = ±0 V (NHE = normal hydrogen electrode).

The equilibrium potentials E0 of all electrode reactions at standard conditions can be arranged in
relation to this value in the electrochemical series. The Nernst equation (see Equation 1.23b)
R ⋅T a
E = E0 + ⋅ ln ox (7.3)
n⋅F ared
enables to calculate the equilibrium potential E at real conditions (R = gas constant = 8.314 J K−1 mol−1,
T = absolute temperature [K] = [°C] + 273.15, aox, ared = activities of the oxidized and reduced spe-
cies of the reactants; frequently—mainly at low concentrations—in place of activities approximately
concentrations can be used).
b. Overpotentials
At the equilibrium potential E, by definition, no cell current is flowing. In order to cause a cell
current and to start product formation in the electrolysis cell, additionally, overpotentials η have to
be applied at both electrodes: A positive overpotential at the anode η = Φan − E > 0 enhances the
anodic oxidation and retards the cathodic reduction, and a negative overpotential at the cathode
η = Φcat − E < 0 has the inverse effect. Therefore, the overpotentials represent the kinetics of an
electrochemical reaction and are the deciding parameters to adjust the reaction rate and generally
the performance of an electrolysis.
c. Charge Transfer Overpotential (Activation Overpotential)

This overpotential is required to overcome the kinetic hindrance of the charge transfer reaction. Its
effect has much similarity to the temperature dependency of the reaction rate constant k for chemi-
cal reactions, which can be expressed using the empirical Arrhenius equation:
 E 
k = A ⋅ exp  − A  (7.4)
 R ⋅T 
Two fitting parameters are included: A = preexponential factor, theoretically the maximum reaction
rate constant at indefinitely high temperature, and EA = activation energy. Only colliding reactants
with sufficient thermal energy—according to the Maxwell–Boltzmann distribution—can overcome
the activation energy and will react. In the same manner, this model is valid for the charge transfer
of electrochemical reactions. However, in electrochemistry—additionally to the thermal energy—
electrical energy from the overpotential can be applied for overcoming the activation energy. Thus,
in principle, with a sufficiently high electrode potential, each electrochemical reaction could be
enforced, even at low temperature (provided that reactions, which can proceed at a lower energy
level, are excluded).
The empirical Butler–Volmer equation describes—in analogy to the Arrhenius equation—the
dependency of the current density j, which represents the electrochemical reaction rate, on the
charge transfer overpotential ηCT:
  η ⋅α ⋅ n⋅ F   −ηCT ⋅ α cat ⋅ n ⋅ F  
j = j0 ⋅ exp  CT an  − exp   (7.5)
  R ⋅ T   R⋅T  

Two exponential terms with opposite signs consider the anodic and cathodic reactions. The electrical
energy, given by ηCT · n · F, is used—dependent on the sign—to decrease or increase the activation
energy and in consequence to enhance or retard the anodic or cathodic reactions, respectively. The
charge transfer coefficient (symmetry factor) α is the fraction of this electrical energy that influ-
ences the respective reaction (αan for the anodic, αcat for the cathodic reaction; for simple reversible
reactions, α is in the range of 0.5 and αan + αcat = 1). The exchange current density j0 is dependent
on the reaction conditions, for example, temperature and concentrations. However, first of all, it
is related to the activation energy and hence with the electrocatalytic activity of the electrode for
the specified reaction: a low activation energy results in a high exchange current density j0, and in
consequence, already a small charge transfer overpotential ηCT is sufficient to generate a major cell
current density j (at a high activation energy, the inverse effect occurs). The parameters j0 and α are
used for fitting the Butler–Volmer model equation to measured potential current density curves.
At elevated positive or negative charge transfer overpotentials ηCT, the term of the respective
reverse reaction in the Butler–Volmer equation can be neglected. Then it is possible to take the loga-
rithm (neglecting the identical measurement units of j and j0) and the Tafel equation results (here
for a positive overpotential ηCT):
ηCT ⋅ α ⋅ n ⋅ F
ln ( j ) = ln ( j0 ) + (7.6)
R ⋅T
ηCT ⋅ α ⋅ n ⋅ F
log ( j ) = log ( j0 ) + [ln (10) ≈ 2.3] (7.6a)
ln (10) ⋅ R ⋅ T
This is a linear equation of log (j) as a function of ηCT; thus, the current density j increases exponen-
tially with increasing charge transfer overpotential ηCT, for anodic as well as for cathodic reactions
(or vice versa, the charge transfer overpotential ηCT increases logarithmically with increasing cur-
rent density j). The intercept at ηCT = 0, that is, at the equilibrium potential, is log (j0), corresponding
to the exchange current density j0. The slope is dependent on the number of transferred electrons n
and the charge transfer coefficient α, separately for anode and cathode. A typical value is ≈120 mV
additional overpotential per decade of current density (for one electron in the charge transfer step,
α = 0.5 and room temperature).
d. Concentration Overpotential (Concentration Polarization)

In the state of equilibrium, all concentrations at the electrode surface are equal to the concentrations
in the electrolyte bulk phase. However, as soon as a cell current is flowing, reactants are consumed at
the electrode surface and their concentrations will decrease if their supply is retarded. Analogously,
the concentrations of products will increase. The correlating overpotentials result from the Nernst
equation as the difference between the equilibrium potential and the potential at the changed con-
centrations. Typically, two types of concentration overpotential—based on different effects—will
occur in electroorganic chemistry:
i. Diffusion Overpotential (Diffusion Polarization): Generally, electrochemical reactions take

place heterogeneously at the electrode surfaces and mass transfer has a major influence on
electrode reactions. Even in a well-mixed electrolyte, there is a stagnant diffusion layer
without convection directly adjacent to the electrode, where mass transport of uncharged
species is exclusively possible by diffusion. According to Fick’s first law, a concentration
difference results, which is proportional to the mass transport and hence to the current
density. If this difference is small compared with the entire concentration, the resulting
diffusion overpotential, given by the Nernst equation, has only a marginal effect. But with
increasing current density, the remaining reactant concentration at the electrode becomes
smaller and smaller, resulting in a significant diffusion overpotential. The mass transport
of ions (migration) is—in addition to diffusion—enhanced or hindered by the electrical
field, dependent on the charge of the ions. The resulting correlation between concentrations
and current density can be described in the same way analogously to Fick’s first law. In
consequence, all effects of mass transport hindrance result in the diffusion overpotential.
Finally, if the current density is increased up to the limiting current density, the reactant
concentration at the electrode tends to zero. Thus, the maximum possible driving concen-
tration difference is reached, and diffusion cannot be further enhanced. Then, the diffu-
sion overpotential would increase to indefinitely high values. However, in practice, usually
a concurrence reaction, like decomposition of the solvent, will start at a high electrode
potential (see Section I.B.8).
ii. Reaction Overpotential (Reaction Polarization): Decreased reactant concentrations and/or
increased product concentrations at the electrode could also be caused by slow chemical
reaction steps that are required before or after the electrochemical reaction. In this case—
again given by the Nernst equation—a reaction overpotential occurs.
5. Cell Voltage
Figure 7.1 elucidates the composition of the cell voltage in an electrolysis cell. Elements are the
equilibrium potentials and the overpotentials at the electrodes as described before.
Additionally, the ohmic voltage drop (resistance polarization) has to be considered. It is caused
by the resistance in the electrodes (electron conductors) and in the electrolytes (ion conductors),
including the electrolyte in a cell separator (if applied). The ohmic voltage drop does not directly
influence the electrochemical reactions like the electrode potentials. However, it can be a significant
part of the cell voltage and influences the following cell characteristics:
• Energy demand: Given as the product of cell voltage and cell current.
• Heat dissipation: All introduced electrical energy, which exceeds the heat of reaction.
ΔH = ΔG + T · ΔS (ΔS = reaction entropy) is lost as heat. Mainly, this is caused by the
overpotentials and the ohmic voltage drop. It has to be considered in the context of the tem-
perature control of the electrolysis cell. Local overheating may be possible, for example,
in the cell separator.
+
anode current feeder ohmic voltage drop
anode (electron conductors)
potential
anode
anodic equilibrium potential

charge transfer
reaction diffusion overvoltage anode
anolyte
cell voltage
(possibly increased by gas bubbles)

ohmic voltage drop
cell separator (ion conductors)
catholyte
(possibly increased by gas bubbles)
charge transfer
reaction diffusion overvoltage cathode
potential
cathode
cathodic equilibrium potential

cathode ohmic voltage drop
cathode current feeder (electron conductors)
–
FiGURE 7.1 Scheme of the composition of the voltage in an electrolysis cell. (From Jörissen, J., in Bard,
A.J., Stratmann, M., Eds., Encyclopedia of Electrochemistry, Vol. 8, Ch. 2, p. 35, 2004. Copyright Wiley-VCH
Verlag GmbH & Co. KGaA. Reproduced with permission.)
6. Basic Definitions for Chemical Reactions, Also Valid for Electroorganic Electrolysis
• Yield, being the fraction of the entire supplied reactant, which has formed the product.
• Selectivity, being the fraction only of the converted reactant, which has been used to gen-
erate the product. It is a typical criterion to evaluate an (electro-) chemical reaction, espe-
cially considering the quality of an (electro-) catalyst. Insufficient selectivity causes losses
of reactants and presumably problems in separation of by-products.
• Conversion (degree of conversion), being the fraction of a reactant that has been consumed
by the reaction. Since the concentrations of reactants are decreased and those of products
increased with rising conversion, the selectivity of the desired reaction mostly declines at
higher conversion due to diminution of the intended reaction of the reactants and enhance-
ment of consecutive reactions of the products. Typically, a compromise has to be found
between increased effort for separation of unutilized reactants at low conversion and inten-
sified by-product formation at high conversion.
7. Operation Modes of (Electrochemical) Reactors

Any electrolysis cell—even in a small laboratory scale—is a chemical reactor, and the principles of
reaction engineering have to be observed because their influence on the results can be significant.
Fundamental differences characterize the two reactor operation modes:
• Batch operation, where the electrolysis cell (if necessary anode and cathode com-
partment separated) is filled with the reactants and operated during a certain time.
Subsequently, the products are separated from the solutions. This is the well-known
operation mode in chemistry and electrochemistry. Ideally, the entire volume is mixed
without any concentration difference (backmix reactor, stirred tank reactor). The con-
version and consequently most other conditions in the cell are changing with time.
Much information about the electrolysis process is available by analytical monitoring,
for example, of concentrations and electrode potentials, during the reaction time (see
Section II.F.6).
If the reaction conditions change during time—typical for batch operation—it is essential
to differentiate between the following:
• The actual values of, for example, yield, selectivity, conversion, cell current, current
d ensity, charge transfer, and current efficiency.
• The summarized (integrated) values from the start to the end of the reaction.
• Continuous operation (flow-through cell), where a continuous stream is fed into the cell (if
necessary, separated into anode and cathode compartments) and, after partial conversion,
exits the cell. Constant operation conditions (stationary state) are reached after a run-in
period. Continuous operation is especially interesting for long-time stability tests of cell
compounds like electrodes and membranes.
For continuous operation, the mixing behavior within the flow-through electrolysis cell
is of decisive importance. Two idealized limiting cases can be discriminated:
• Backmix reactor with ideal mixing (see item “batch operation”). It is important to con-
sider that the solution in the entire volume is equal to the cell outlet with consequences
especially at high conversion (see item “conversion”).
• Plug flow reactor, where the flow moves through the cell along the electrode surfaces
(theoretically ideal tubular reactor, which means hypothetically no backmixing
within the reactor volume but perfect local mixing). Conversion and other operation
c onditions do not change with time (stationary state) but with location between input
and output of the cell.
• A real flow-through electrolysis cell will be more or less similar to one of these alterna-
tives, dependent on its construction. However, usually the mixing behavior may not be
clearly defined, and theoretically calculated results of electrolysis possibly cannot be
practically achieved (see cell constructions in Section II.G.3).
8. Control of Electrochemical Reactions

The possibility to control the reaction by electrical parameters, which can easily be adjusted—
especially using the direct equivalence of cell current and reaction rate—is a typical advantage of
electrochemistry in comparison to conventional chemical reactions. Knowledge about the correla-
tion between the potential at the working electrode and the current density is necessary to find a
suitable operation mode.
Figure 7.2 shows a simplified example for an anodic oxidation reaction, simulated using the ele-
ments of the electrode potential that are discussed before. Practically, such a diagram is available,
for instance, by cyclic voltammetry or rotating disk experiments with a very low scan rate.
The thin line demonstrates the anodic oxidation of the electrolyte (solvent and/or supporting
electrolyte) without reactants at an elevated potential, here if the equilibrium potential of this
“background” reaction at 0.8 V is exceeded. The current density rises exponentially with increas-
ing charge transfer overpotential. This reaction is undesired at the working electrode and can be
neglected here below 0.8 V (for selection of the electrolyte, see Section II.D). This represents the
upper limit of the potential window where organic oxidation reactions are possible without decom-
position of the electrolyte.
If a reactant 1 is added, it can be oxidized according to the thick compact lines. The equilibrium
potential is about 0 V, and a significant current density for this desired reaction starts above 0.2 V.
However, at increasing potential, soon a limiting current density is attained, which is proportional
to the concentration of reactant 1 (indicated for C1 and two-thirds and one-third of it). Even applying
a high potential (that means at a high diffusion overpotential), the current density cannot be further
100
Reactant 2
90 Constant
Concentration C2
80
C2
Current density/mA cm–2
70
C2
60
Reactant 1 C2
tion
50 Changing
decomposi
Concentration C1
40
C1
30
2/3 C1
Electrolyte
20
1/3 C1
10
0
0 0.2 0.4 0.6 0.8 1 1.2
Electrode potential/V versus NHE
FiGURE 7.2 Current density–potential curves for the anodic oxidation of two different reactants and
finally of the electrolyte. The electrode potentials are related here to the NHE as reference electrode. (From
Jörissen, J., in Bard, A.J., Stratmann, M., Eds., Encyclopedia of Electrochemistry, Vol. 8, Ch. 2, p. 35, 2004.
Copyright Wiley-VCH Verlag GmbH & Co. KGaA. Reproduced with permission.)
enhanced and the oxidation runs selectively at the shown constant rate (constant current density)
until the potential of electrolyte decomposition is reached.
The situation changes if an additional reactant 2 is present that can be oxidized above 0.4 V
(thick dotted lines). In this example, a constant concentration C2 is assumed. The limiting current
density for the oxidation of reactant 2 is achieved at about 0.8 V and is significantly higher than for
the oxidation of reactant 1.
Under the conditions of Figure 7.2, a selective oxidation of reactant 1 will be possible at 0.3 V.
Reactant 2 can be oxidized only simultaneously with reactant 1 and the respective selectivities are
dependent on the concentrations.
Analogous correlations have to be considered for the counter electrode (here the cathode).
A suitable reaction has to be performed at the counter electrode, but undesired reactions should
be avoided, if necessary using a divided cell with a separator (see Section II.E).
Different control modes of electrolysis cells are possible as follows.
a. Potentiostatic Operation (Operation at Constant Electrode Potential)

As discussed before, the selective oxidation of reactant 1 in the example of Figure 7.2 will be opti-
mally realized at a constant potential of 0.3 V of the working electrode (here the anode). Then, the
maximum possible current density (reaction rate) is automatically adjusted, independent of other
parameters. This is especially important for batch operation with changing reactant concentrations.
Thus, potentiostatic operation in principle is the optimal control mode from the electrochemical
point of view, even though problems are possible (see Section I.B.8.d). A suitable electrode poten-
tial–measuring equipment in the cell and a potentiostat as shown in Figure 7.3 are required. Special
practical aspects of potential measurement are discussed in Section II.F.2. Potentiostatic operation
is relatively expensive, especially in larger-scale cells, which need high power (the required quality
and in consequence the costs of the potentiostat should be carefully reflected). For charge balanc-
ing, an integrator of the changing cell current is necessary (in case of data recording, this is possible
using software).
b. Galvanostatic Operation (Operation at Constant Cell Current)

Operation of an electrochemical cell at constant cell current is uncomplicated, using an inexpensive
power supply (also a potentiostat normally can work in galvanostatic operation), and charge balanc-
ing is easy. However, suitable results require selection of a current density where a clear potential
difference between desired and undesired reactions exists, for example, less than 30 mA cm−2 for
the oxidation of reactant 1 in Figure 7.2. This is realizable especially for continuous operation of
flow-through cells (steady state) and is typically applied in industrial electrolysis. For batch opera-
tion with changing concentrations, a constant cell current is appropriate only if exclusively harmless
side reactions can occur. Otherwise, potentiostatic operation will be preferred.
c. Operation at Constant Cell Voltage

This may be the simplest electrolysis operation, using a cheap power supply. Nevertheless, the target
remains generally to apply the optimal potential at the working electrode. This is difficult to realize
at constant cell voltage due to the large number of different parts of the cell voltage that are depen-
dent on various parameters (see Figure 7.1). Therefore, operation at constant cell voltage is unusual.
d. Challenges in Controlling of Electroorganic Reactions

The discussed correlations between cell current and electrode potentials (overpotentials) are appli-
cable without problems in case of reversible electrochemical reactions (see also Chapter 1). However,
particularly in case of organic electrochemistry, the reaction mechanism may be a complex chain of
electrochemical and chemical reactions, including energy-rich intermediates and irreversible reac-
tion steps. Then it will be impossible to measure an equilibrium potential.
Potentiostat
Direct
current
mA source
Control input
mV
Reference electrode
Working electrode
Counter electrode
RE
Diaphragm
Luggin
capillary
FiGURE 7.3 Scheme of an electrolysis in potentiostatic operation. The potentiostat ensures a constant poten-
tial at the working electrode. The control circuit of the potentiostat determines this potential using a Luggin
capillary, which is connected to a reference electrode (RE, see Section II.F.2.a). It adjusts this potential to
the voltage at the control input by regulating the cell current between working and counter electrodes. (From
Jörissen, J., in Bard, A.J., Stratmann, M., Eds., Encyclopedia of Electrochemistry, Vol. 8, Ch. 2, p. 35, 2004.
Copyright Wiley-VCH Verlag GmbH & Co. KGaA. Reproduced with permission.)
Also a theoretical calculation using thermodynamic data in Equation 7.1 may be scarcely useful
for application, because the Gibbs energies ΔG are similar for many organic reactions. Thus, there
are only little differences in the theoretical equilibrium potentials, different from Figure 7.2, where
significant potential differences are available. In consequence, concurrent reactions and only a poor
selectivity of the electrode reactions may be possible.
Additionally, an effect similar to a large activation energy is caused if the reaction mechanism
includes species that need a high energy, for example, energy-rich radical ions. Then, a major charge
transfer overpotential—up to 1 V or more—can be observed, and the small differences in the equi-
librium electrode potential become irrelevant.
Furthermore, complicated and only partially understood influences may be found, for instance,
of the electrode material (possibly including its history) or of the electrolyte composition, includ-
ing unknown impurities. In consequence, sometimes it can be difficult to reproduce electrolysis
results.
Nevertheless, usually an electroorganic electrolysis can be successfully operated on the base of
empirical and experimental knowledge. However, particularly in this case, the discussed challenges
necessitate the careful selection of optimal operation conditions as well as of an appropriate elec-
trochemical cell.
II. COMPONENTS Of ELEcTROORGANic REAcTiON SYSTEMS

An impression of some usual or innovative cell components and materials is given in the following;
a more detailed overview is available, for example, in References 1,8,9.
A. ELECTroDES
The characteristic and most important components of any electrochemical cell are the electrodes—
particularly the working electrode. In most cases, they are decisive for the success of an electroorganic
synthesis. Electrode materials require a sufficient electronic conductivity and corrosion stability as
well as, ideally, a selective electrocatalytic activity that favors the desired reaction due to a low over-
potential. Simultaneously, the overpotentials for undesired reactions should be high. Different require-
ments have to be considered for the working and counter electrodes, respectively. For example, anodic
oxygen or cathodic hydrogen evolution, respectively, by decomposition of water as solvent is undesired
at the working electrode, and high overpotentials for these reactions are favorable. At the counter elec-
trode, such reactions may be intended, and a low overpotential is beneficial.
Typically, the electrode reaction includes several steps, such as adsorption and desorption, a sin-
gle or multiple electron transfer(s), and preceding and/or subsequent chemical reactions. All these
steps, and as a consequence the selectivity of the reactions, will be dependent on the properties of
the electrode surface. Typical examples are chemical composition, morphology, and porosity. These
all may be additionally influenced by the electrode history, for example, removing of a surface con-
tamination or roughening due to corrosion. Moreover, there will be considerable interdependencies
between the electrode properties and the electrolyte composition of reactants, products, solvents,
and supporting electrolytes, possibly including impurities. As a consequence of such influencing
factors, a more or less long-lasting run-in period may be necessary until reproducible results are
achievable.
Special problems can be caused due to passivation of the working or counter electrode surfaces
by insulating layers. Examples are tight oxide films on metals, formed at a high anodic potential,
or polymer deposits, generated by anodic oxidation of olefinic or aromatic compounds. Then, the
activity of the electrode is reduced, because the surface is partially blocked, and a decrease in the
cell current may be necessary. Examples of remedies are as follows:
• Periodical changing of the polarity of the electrodes (a symmetrical construction of the cell
should be provided)
• Additives for an increased polymer solubility in the electrolyte
Rarely, in disadvantageous cases, it may be difficult to observe reproducible results of an organic

electrolysis due to unforeseeable circumstances at the electrodes.
1. General Requirements for Electrode Materials

Electrodes can be made of the following:
• A homogeneous material that is electrocatalytically active itself

• A homogeneous material that forms in situ an active layer on the surface
• A carrier material with an active coating
Additionally to these decisive electrochemical properties, experimental requirements for successful

investigations have to be considered:
• Leak-proof installation of electrodes in the cell body

• Proper connection with low ohmic resistance to the current feeder
• Appropriate assembling of the cell
Moreover, the selection criteria for electrode materials include mechanical and practical properties
as follows:
• Stability, rigidity, elasticity, brittleness, etc.

• Ability to be converted to sheets, wires, grids, expanded metal sheets, and porous plates,
such as sintered or foamed material and felt
• Possibilities of machining, cutting, welding, or soldering
• Corrosion resistance
• A possible contamination of electrolyte and products has to be considered.
• Especially important in case of toxic materials.
• Corrosion determines the electrode lifetime (possibly important expense factor).
• Price, which may be deciding, particularly in case of commercial use
In Sections II.B and II.C, typical electrode materials for application as anode and/or as cathode,
and then electrode designs of practical interest are discussed. A comprehensive overview about
electrodes is given, for example, in References 8 and 9.
2. Special Requirements for Cathode Materials

A typical requirement for a cathode material, used as working electrode in aqueous media, is a high
hydrogen overpotential ηH as condition for a strong reduction power. Different materials include a
large range of overpotentials (here at 1 mA cm−2, 25°C, in acidic solution [3,7,10]):
• Very low ηH < 0.1 V Pt, platinum metals (also active hydrogenation catalysts), Au
• Low ηH ≈ 0.2 V Ni (also active hydrogenation catalyst)
• Medium ηH 0.2−0.6 V Fe, Cr, Ag, Al, Ti, Mo, W, Bi, graphite stainless steels (Cr–Ni–Fe),
brass (Cu–Zn), Monel® (Cu–Ni)
• High ηH ≈ 1.0 V Sn, Zn, Cd, Pb, Hg
• Very high glassy carbon, Ebonex® (TinO2n−1, n ≈ 4), Boron-doped diamond
(BDD) (very low electrocatalytic activity)
In nonaqueous media, the hydrogen overpotential is less important.

A specific problem can be that a pure cathode material has a sufficiently high hydrogen overpo-
tential, which, however, may be decreased even by very small amounts of other metals (poisoning),
and hydrogen evolution occurs. Possible sources of such metals can be impurities in the electrode
metal itself and in all applied chemicals, but frequently also corrosion of an (noble metal) anode.
For the selection of the anode material, this effect should be considered.
Hydrogenation is another typical electroorganic cathode reaction that requires the choice of a
cathode material with specific catalytic activity (see Chapter 44).
At the cathode as counter electrode, usually hydrogen is evolved. An undivided cell is applicable,
if the hydrogen overpotential and the hydrogenation activity of the cathode material are adequately
low in order to avoid undesired reduction and/or hydrogenation reactions.
3. Special Requirements for Anode Materials

A high positive potential at the anode favors corrosion so that corrosion resistance is an important
property of anode materials (unless metal dissolution is intended using a sacrificial anode, see
Section II.C.3.). The stability of an anode material is strongly influenced by the operation condi-
tions and by the anolyte composition, for example, temperature, aqueous or nonaqueous medium,
pH value, and presence of halides. In most cases, the electrochemical behavior of anode materials
in aqueous electrolytes is dependent on in situ formed surface oxides. Also adsorbed compounds,
which are formed by oxidation from reactants—a well-known example is carbon monoxide—may
be of decisive influence.
The oxygen overpotential is a significant attribute of an anode material for use in aqueous elec-
trolytes. It should be high for the anode as working electrode, especially if a strong oxidation power
is required, in order to minimize concurrent oxygen generation.
During oxygen evolution at the anode as counter electrode, undesired oxidation reactions are
hardly avoidable at the high oxygen potential, including the oxygen overpotential. A low-oxygen
overpotential would be helpful; however, this property is not available using known materials.
Therefore, frequently, a divided cell is required where the anode as counter electrode operates in
a separate compartment (a sacrificial or gas depolarized anode could be an alternative, see Sections
II.C.3 and II.C.4).
B. EXaMpLES oF ELECTroDE MaTErIaLS

1. Platinum, Platinum Metals, Other Noble Metals, and Their Alloys
These metals are classical electrode materials that are very often applied in the literature. The main
reasons are the high electrochemically as well as chemically catalytic activity and the resistance to
corrosion in nearly all solutions. These properties show significant differences between the various
metals and alloys of this group so that a careful selection is necessary. A considerable influence of
the orientation of single crystals is observable; nevertheless, only polycrystalline materials will be
appropriate for synthesis applications. It can be economically interesting to use these very expensive
metals as a thin coating on a carrier (see Section II.B.8).
a. Cathode
Platinum and palladium—and comparably the other platinum metals—operate with the lowest
known overpotentials for hydrogen. Simultaneously, they are the most effective catalysts for hydro-
genation reactions [11].
b. Anode
The anodic behavior of these metals is strongly influenced by surface oxides and/or adsorbed com-
pounds (this can be demonstrated by cyclic voltammetry, see Chapter 2). For example, the anodic
activity of platinum is intensely declined by adsorbed carbon monoxide, while the oxidation of
carbon monoxide to carbon dioxide is enhanced using a mixed ruthenium platinum catalyst (this is
important, e.g., in the direct methanol fuel cell [DMFC] [12]).
Usually, corrosion is no significant problem for platinum metals under most conditions and ano-
lyte compositions (probably, it has to be considered economically for commercial applications).
Nevertheless, as previously mentioned, even traces of anode corrosion can cause a decrease in the
necessary high hydrogen overpotential at the cathode. Anodic corrosion of this group of metals is
very dependent on the anolyte pH value, particularly in case of the less noble metals.
2. Nickel
a. Cathode
Nickel has a relatively low hydrogen overpotential as well as a high hydrogenation activity and may
be an inexpensive alternative for platinum metals, as working and also as counter electrode. Its cor-
rosion resistance as a nonnoble metal has to be checked for the actual conditions. Typically, nickel
is suitable for aqueous alkaline solutions. Very fine dispersed Raney nickel offers an increased
activity. It is prepared from a layer of a nickel alloy with aluminum or zinc on the cathode surface.
Prior to use, the alloy metal is dissolved in alkaline solution (see, e.g., Reference 13. Caution: Raney
nickel is attacked by oxygen and self-ignition in air is possible).
b. Anode (Active Surface: NiOOH)

A layer of NiOOH is formed on the surface of a nickel anode in aqueous alkaline solution.
This is intensively studied [14] because it is used in nickel cadmium and nickel metal hydride
accumulators. In electroorganic chemistry, selective oxidation reactions are possible [15].

Additionally, it can be used as oxygen-evolving counter electrode.
3. Iron (Mild Steel), Stainless Steel

a. Cathode
Iron has a relatively low hydrogen overpotential. Nevertheless, selective cathodic reactions are pub-
lished, for example, Reference 16. Due to its very low price, it is favored for commercial applica-
tions, mainly as counter electrode. Corrosion can occur when the cell current is switched off. An
alternative, particularly for laboratory cells, may be stainless steel with much better corrosion resis-
tance and only marginally increased hydrogen overpotential.
4. Lead
The classical electrode material lead is largely used in lead–acid batteries. Therefore, it has been
comprehensively investigated in the literature, for example, Reference 17. The mechanical stability
of the very soft pure lead is insufficient for application. Alternatives are lead-coated carrier elec-
trodes or tougher alloys (typically with antimony: type metal).
a. Cathode
Lead cathodes achieve a strong reduction activity in aqueous solutions due to the very high hydro-
gen overpotential. However, this requires very pure lead and a clean procedure. If the cathode
reaction has to operate at the limit of hydrogen evolution, the presence of other metals with a lower
hydrogen overpotential is detrimental (poisoning). Sources, which have to be carefully excluded,
may be impurities or alloying metals in the lead, contaminations of the electrolyte and the reactants,
and possibly corrosion of the anode [3].
b. Anode (Active Surface: PbO2)

The surface of lead as anode material is oxidized at high anodic potentials in acidic aqueous solu-
tions to lead dioxide (e.g., Reference 18). The continuous growing of this layer destroys the lead base
metal during longer operation. The overpotential for oxygen evolution on PbO2 in acidic aqueous
solutions (frequently sulfuric acid) is very high so that a high anodic potential and a strong oxidation
activity are enabled. However, PbO2 simultaneously is a powerful chemical oxidation agent, and the
electrode may be damaged by a spontaneous reaction with a reactant.
Basically, the stability of pure PbO2 anodes is relatively poor. Reasons can be dissolution in
the electrolyte and frequent mechanical erosion. Considering the toxicity of lead, this can be a
problem.
Meanwhile, high stability has been achieved by the development of PbO2 coatings on suitable
carrier materials (see Section II.B.8) with sophisticated additives (comprehensive review [19]).
PbO2-coated titanium anodes are commercially available (e.g., from References 20 and 21).
5. Mercury
a. Cathode
Mercury is traditionally the most used cathode metal for electroorganic reduction reactions. In
aqueous solutions, it has the highest hydrogen overpotential of all metals. Another property is its
liquid state, which has to be considered for cell constructions (see Section II.G.2). This enables—
simply using a (magnetic) stirrer—a continuous renewing and cleaning of the cathode surface. At
very negative potentials, all present metal cations can be reduced, possibly even alkali metals of a
supporting electrolyte. However, these metals are dissolved as amalgam and the risk of decreasing
the hydrogen overpotential (poisoning) is less than at a solid metal surface.
Dependent on the application, an amalgamated electrode of copper or another metal may be
appropriate for easier handling.
The application of mercury is limited due to its toxicity, and careful safety precautions are
required. The hazard of mercury contamination restricts its use for commercial syntheses.
6. Carbon
Carbon has several advantages as less expensive electrode material that is available in very differ-
ent variations (e.g., References 22 and 23). Usually, its electrocatalytic activity is relatively low. It
is used in large amounts for inorganic and organic industrial electrolysis as well as for batteries.
Appropriate constructions of electrodes and current feeders enable the application of carbon despite
its low conductivity (about one-hundredth of most metals).
Traditional carbon materials for electrode applications differ in the content of crystalline graph-
ite, conductivity, and mechanical and chemical stability. Usually, they are impregnated with chemi-
cally resistant resins in order to reduce the originally high porosity and become leak-proof against
gases and fluids. Such materials are brittle, their solidity is limited, and their machinability is good.
Flexible sheets of graphite are produced as sealing material (e.g., SIGRAFLEX®, SGL Group). It
is easy to handle as a corrosion-resistant electrode or current feeder; however, during gas evolution,
swelling and erosion can occur.
Fiber materials of carbon or graphite are offered, for example, as tissue, felt, or paper. Typically, they
are used as conductive diffusion zones in fuel cells. Additionally, they are interesting electrode materials
of very high porosity (free space volume up to 80%, 3D electrodes) and with remarkably good elasticity.
Glassy carbon (vitreous carbon) is another carbon modification (ceramic-like, based on micro-
structures of fullerene instead of graphite [24]). It is an interesting electrode material, if very high
corrosion resistance is required. Additionally, its electrocatalytically activity is low; thus, a large
potential window in aqueous solution is accessible. Methods of surface modification and doping
are reviewed in Reference 25. Glassy carbon is rigid, smooth, and tight against gases and liquids.
The price is relatively high but lower than for noble metals. It is available in simple shapes and as
a foamed material (reticulated vitreous carbon for 3D electrodes [26,27]). Due to its hardness,
machining is restricted (only with diamond tools).
Further carbon-based electrode materials are carbon-filled polymers or a carbon paste with
paraffin, which is interesting for laboratory investigations, because a surface layer can easily be
removed for regeneration.
a. Cathode
Carbon has a relatively high hydrogen overpotential so that manifold reduction reactions are pos-
sible, if the cathode is the working electrode. Additionally, the catalytic activity for hydrogenation
reactions is low. This is beneficial, if a carbon cathode is the counter electrode: besides the intended
hydrogen evolution, undesired cathodic hydrogenation reactions are prevented (such reactions, in
the worst case, could attack the products of the anode).
b. Anode
Carbon anodes are destroyed by oxidation to carbon dioxide, if oxygen is evolved in aqueous media.
This is enhanced with increasing porosity, while glassy carbon is relatively stable. The oxygen evo-
lution can be hindered at a lower pH value; however, generally, carbon anodes may not be optimal
in aqueous solutions. Moreover, intercalation of anions can decrease the stability of carbon anodes.
Carbon (graphite) is a typical anode material in nonaqueous media. For example, it is suitable
for methoxylation reactions, even in an industrial scale, especially due to its increased overpotential
for the oxidation of methanol.
7. Conductive Ceramic, for Example, Ebonex

As an alternative for glassy carbon (see Section II.B.6), Ebonex can be an interesting electrode mate-
rial, if high corrosion resistance, coupled with low electrocatalytic activity and high overpotentials
for oxygen and hydrogen, is required [28]. Furthermore, it is a suitable carrier material for electrode
coatings (see Section II.B.8). Ebonex is made of Magneli phases, substoichiometric titanium oxides
with reduced oxygen content TinO2n–1 (3 < n < 10, mainly n ≈ 4), which are sufficiently electrically
conductive. As a ceramic material, it is hard and brittle with limited possibilities of machining
(diamond tools).
8. Electrocatalytic Coatings on Carrier Materials

Thin layers of noble metals on a less expensive carrier material are frequently used as cost-efficient
alternative for compact noble metals. Additionally, there are several interesting electrode materials
published in the literature that can be applied only as a coating. For example, some transition metal
oxides enable a considerably high reaction selectivity. However, their relevance in electroorganic
synthesis until now is low due to their insufficient stability (no detailed discussion is provided here).
An up-to-date exception is the BDD electrode, whose development meanwhile achieved excellent
durability (see Section II.B.9).
If a corrosion-resistant and electrochemically less active carrier material is used—for example,
glassy carbon or Ebonex—even very thin layers of a coating will be sufficient for laboratory small-
scale experiments with low current densities. Then, the electrochemical properties of the electrode
are correlated only with the coating but not with the carrier (e.g., Reference 29).
Titanium metal is a typical carrier metal for larger electrodes up to an industrial scale, especially
for inorganic electrolysis. In aqueous electrolytes under oxidizing conditions (even in the presence
of chlorine), it is excellently corrosion resistant due to a stable, self-healing TiO2 passivation layer.
However, under reducing—and especially acidic—conditions, titanium is unstable, intensified in
the presence of organic acids or fluorides. Usually, for nonaqueous organic media, it is inapplicable.
The oxide layer on titanium is semiconducting and inhibits an electron transfer in anodic direc-
tion (valve metal). In principle, an application as cathode may be possible, but if hydrogen is evolved,
titanium is destroyed by the formation of titanium hydride.
Platinum-coated titanium electrodes as replacement for pure platinum are commercially avail-
able (e.g., from References 20,21 and 30). For sufficient stability, the platinum layer has to be pore-
free tight. Lead dioxide–coated titanium electrodes are mentioned in Section II.B.4.
Dimensionally stable anodes (DSA®) are the most used anodes in industry [31]. Here, the TiO2
passivation layer on the titanium is replaced by a conductive coating, based on titanium and ruthe-
nium oxides, with optimal electrocatalytic activity for chlorine evolution from aqueous chloride
solutions. Comparable coatings, mainly based on iridium and tantalum oxides, are available for oxy-
gen and for simultaneous chlorine and oxygen evolution. Such titanium anodes also may be interest-
ing for electroorganic syntheses, for example, as oxygen-evolving counter electrode and probably as
working electrode (possible suppliers are, e.g., References 20,21 and 30, which is focused on special
anodes). However, previously, the stability of such electrodes in the presence of the applied organic
compounds has to be checked.
9. Boron-Doped Diamond Coating

A relative new electrode material with outstanding properties and excellent chemical durabil-
ity is diamond, which obtains electrical conductivity by doping with boron (e.g., Reference 32).
It is coated onto various high melting carriers—for example, silicon, carbon, tantalum, niobium,
titanium, conductive ceramics—by chemical vapor deposition. Its catalytic activity is low, and in
aqueous solution, it achieves the highest known overpotential for oxygen and also a high one for
hydrogen evolution. Thus, it offers an extraordinarily high potential range and electrochemical
power for oxidation as well as for reduction.
These properties of BDD electrodes appeared useful for mechanistic studies [33–35], spectro-
electrochemistry [36], as well as preparative applications up to industrial scale [37], which have
recently been reviewed [38]. The high accessible positive potentials allow “incineration” [38] and
destructive detoxification by extremely reactive radical species [38], which may, on the other hand,
turn out to be problematic for the selectivity of syntheses.
C. EXaMpLES oF ELECTroDE TYpES aND THEIr SpECIaL PropErTIES

1. Porous vs. Smooth Electrodes
The active area of a porous electrode can be much larger—up to about three orders of
agnitude—compared with the geometrical area that is active at a smooth electrode. Thus, the
m
effective current density is substantially reduced with significant influence on the electrochemi-
cal behavior at a decreased sum of overpotentials. However, there is a diffusion overpotential
included due to mass-transfer effects, which are dependent on the porosity and also on the
shape, dimension, and structure of the pores within the electrode material (a wide range of
variations is possible).
Classical examples for increased electrode surface are platinized platinum (electrochemically
deposited, e.g., Reference 39) and Raney nickel (see Section II.B.2). Here, reactions are enabled that
are impossible at smooth electrodes of the same metal. The electrode activity can also be enhanced
by a simple roughening of the surface, for example, mechanically or by etching.
Three-dimensional electrodes are a direct way to expand the effective electrode area. Typical
examples are carbon fiber felt, sintered, foamed, or reticulated materials, or a packed bed of par-
ticles. Special attention is required to include a significant depth into the working area, as part of
the porous electrode thickness, more than a small layer at the surface (the conductivity ratio of the
electrode material and the electrolyte is important; see, e.g., References 40 and 41).
2. Gas-Evolving Electrodes
Frequently, gases are evolved—at the working as well as at the counter electrode—either during
the main reaction or as an undesired by-product (e.g., carbon dioxide, hydrogen, oxygen, chlorine).
Caution: safety precautions (at least a splinter shield) are indispensable, if explosive gas mixtures
and an ignition by a shortcut of the electrodes are possible.
Usually, the movement of gas bubbles is advantageous because it enhances the desired mass
transport at the electrode surface. However, gas bubbles increase the voltage drop between the
electrodes, and a suitable electrode design is necessary to remove gases quickly from the front to
the backside of the electrode, for example, using a mesh or an expanded metal sheet. An additional
problem of (big) gas bubbles is a deformation of the even current density distribution at the elec-
trodes and, in consequence, a possible degradation of the reaction selectivity (see Section II.F.1).
In the worst case, the electrode surface could be partially disabled. Thus, if there is an intense gas
evolution, the removal of gas from the gap between the electrodes and out of the electrolysis cell is
a significant cell design attribute (see Section II.G, theoretical discussion in Reference 42).
3. Sacrificial Anodes
Usually, a sufficient corrosion resistance is required for electrodes, especially for anodes. However,
in case of a sacrificial anode, its disintegration is the desired reaction. It is a special type of depo-
larized electrode where a reactant is delivered—here the anode material itself—for an additional
electrode reaction [43]. The sacrificial anode will be the working electrode, if the synthesis of an
organometallic compound of the anode material is intended (see Chapter 35). Another example is
polysulfides, which are producible from sulfur as anode material, which is mixed with carbon pow-
der for adequate conductivity [44].
Typically, sacrificial anodes are applied as counter electrodes. Using a strongly electronega-
tive metal—for example, zinc, aluminum, magnesium—no anodic oxidation is possible at the
very negative potential, and an undivided cell is utilizable. This technique can be operated also
in nonaqueous media ([43], industrial example [45]). Anions have to be available as counterions
for the produced metal cations (generated either by the cathodic reaction at the working electrode
or added as an acid whose H+ ions are consumed there). It will be useful, if the produced salt is
soluble enough for sufficient conductivity of the electrolyte, but its excess should precipitate for
easy separation.
4. Gas Diffusion Electrodes

Depolarized electrodes of another type apply a gas as additional reactant. However, the electro-
chemical conversion of a gas is much more complicated than gas evolution. Gas diffusion elec-
trodes (GDEs) are necessary: the gas, the electrolyte, and the catalyst—electrically connected with
the current feeder—have to be in optimal contact at a maximized electrode surface (three phase
zones within a highly porous electrode structure). GDEs are well known for fuel cells and object
of intensive research (overview, e.g., References 46 and 47). GDEs may be interesting also for elec-
troorganic synthesis (until now, only for aqueous electrolytes), though actually there are merely
a few results published (e.g., References 48 and 49). Nevertheless, a DMFC—in principle—is an
electroorganic reactor for the oxidation of methanol in aqueous solution in combination with an
oxygen-depolarized cathode (ODC) [12,50].
GDEs could be advantageous especially as counter electrodes. The potential of an oxygen-
consuming cathode (= ODC) is significantly more positive than a hydrogen-evolving cathode under
the same conditions (theoretically shifted by 1.23 V, practically by up to 1 V). Thus, undesired
reduction reactions are nearly impossible. Vice versa, a comparable shift in negative direction is
achieved by a hydrogen-consuming anode (possible alternative for a metallic sacrificial anode, see
Section II.C.3). Here, unwanted oxidation reactions are excluded (e.g., no chlorine evolution in the
presence of chloride ions).
D. ELECTroLYTES
The typical liquid reaction medium for organic electrolyses consists of a solvent and a supporting
electrolyte. This solution is commonly called the electrolyte. It does not only provide the environ-
ment for the electrochemical reaction but also ensures the ionic charge transport in the cell between
the working and counter electrodes.
1. Solvents
An excellent review of solvents used in organic electrochemistry forms part of Lund’s chapter
on Practical Problems in Electrolysis in the fourth edition of this monograph [1]. The respective
s ection is reproduced as Appendix A. Izutsu [51] provides another collection.
2. Supporting Electrolytes
Similar to Section II.D.1, the commonly used supporting electrolytes for electroorganic applications
have been described extensively by Lund [1]. The section dealing with this topic is reproduced as
Appendix B. Again, Izutsu’s monograph [51] gives additional information.
A noteworthy development, which has not yet been foreseeable in the fourth edition, is the
increasingly popular use of ionic liquids in organic electrochemistry. Chapter 8 of the present edi-
tion is devoted to this evolving field, as well as to electrochemistry in emulsion-based and supercriti-
cal fluid (SCF) electrolytes. Here, we discuss some additional aspects of supporting electrolytes.
Electrolytes on the basis of weakly coordinating anions have recently been described as very
useful for mechanistic investigations [52–57], in particular with respect to the separation of formal
potentials in multielectron transfer reactions (see Chapter 11). Such anions are often highly fluori-
nated [52,53] or derivatives of closo-borates [57] and are characterized by a large volume over which
the negative charge is distributed [53]. As a result, a low tendency toward ion pairing with cations
is observed and shielding of the positive charge is decreased [54]. Furthermore, the nucleophilicity
of such anions is weak [53], minimizing side reactions of electrochemically generated electrophiles.
Another advantage of such electrolytes is a more extended potential window in the positive potential
range [52].
The popular quaternary ammonium cations of supporting electrolytes are well known to undergo
Hofmann elimination upon reduction (see Appendix B, Section III.B.2.d). Recently, another side
reaction during oxidation was identified that produces alcohols, ketones, and amides [58].
The need to separate the supporting electrolyte after electrolysis causes additional workup
efforts. Electrosyntheses in the absence of such salts would simplify the overall processes. Apart
from solid–polymer–electrolyte (SPE) technology (see Section II.D.3), electrochemical experi-
ments in organic solvents in the absence of supporting electrolytes have been reported as early
as 1984 [59]. Such conditions were used mainly in mechanistic work at ultramicroelectrodes [60],
which is then complicated by migration effects [61]. However, recently, electrosynthesis in organic
solvents without supporting electrolyte was also described in miniaturized environments (see
Chapter 9) [62].
3. Solid Polymer Electrolyte Technology

Generally, an ion exchange membrane is working as an ion conductor if it is used as a cell separator
(see Section II.E.2). Thus, it is also able to function directly as an electrolyte even in the absence of
an ion-conducting solution. This SPE technology is established in fuel cells (proton exchange mem-
brane fuel cell [PEMFC] and DMFC) [12,46,47,50]. Analogously, electroorganic syntheses without
any supporting electrolyte are possible in comparable electrolysis cells if a sufficient conductivity
of the membrane can be achieved in the reaction system (see Section II.E.2). In this case, operation
is easy, and expenses for separating and recycling a supporting electrolyte are economized [63].
For various reactions applying cation and anion exchange membranes, combined with different
electrode materials in aqueous and even in nonaqueous media, possible advantages of the SPE tech-
nology have been demonstrated [64–66].
E. CELL SEparaTorS
The easy construction and operation of undivided electrochemical cells is generally advantageous
(see Section I.B.1). However, if the success of the electrolysis is impeded by an unavoidable reaction
at the counter electrode, resulting, for example, in significant deficits of yield and/or contamination
of the products, a separator between anode and cathode will be necessary. No ideal separator is
available; always a compromise of several properties has to be found.
On the one hand, the characteristic of a cell separator is to prevent a direct mixing of anolyte and
catholyte and to decrease diffusion in both directions; on the other hand, the voltage drop during
the obligatory migration of ions has to be minimized. A possible overheating as a consequence of
an excessively high voltage drop should be considered.
With increasing differences in the properties of anolyte and catholyte, the functioning of the
separator becomes more and more difficult. Diffusion is intensified by increasing concentration gra-
dients. A less porous and/or thicker separator will diminish diffusion but increase the voltage drop.
Precipitation of a compound at the surface or within the separator in case of different solubilities in
both electrolytes can be a problem and must be prevented.
A nearly optimal separation of anolyte and catholyte is possible using two separators in series, if
in laboratory experiments a high voltage is acceptable. Additionally, the volume between the sepa-
rators can be rinsed with a suitable solution in order to remove compounds that enter through the
separators but are not tolerable in the opposite cell compartment.
1. Porous Materials
Characteristics of a porous separator (diaphragm) are pore diameter, porosity, and thickness.
Additional aspects are essential for practical application such as mechanical strength (brittle or
flexible), chemical stability, and constant dimensions (possible swelling in the solvent).
The classical porous separator in laboratory cells is sintered (fritted) glass (frit). A glassblower
easily can mount it by melting into the walls of glass cells (leak-proof). Types of different proper-
ties are available and also similar sintered ceramic materials are used (e.g., alumina, unglazed
porcelain, or pottery). Glass and certain ceramic materials will be attacked by strongly alkaline and
acidic fluoride-containing media. In principle, separators of glass or ceramic materials are rigid and
brittle and need an increased thickness for sufficient mechanical stability in larger dimensions, thus
causing a high voltage drop.
Glass or ceramic surfaces adsorb OH− ions in aqueous solutions. Therefore, they are nega-
tively polarized and a positive charge appears in a thin layer of the solution close to the surface
(ζ-potential). As a consequence, this solution can be moved in the electric field toward the
cathode. This so-called electroosmotic transport occurs especially in separators with small
pores and therefore large surface. It can produce significant undesired transportation through
the separator.
Flexible porous diaphragms (down to thin foils) can be manufactured from fibrous materials,
for example, as paper, felt, or woven fabric, and are applicable up to large dimensions. Even simple
materials such as filter paper, regenerated cellulose film (cellophane), or an agar–agar plug may be
useful in case of nonaggressive solutions. Diaphragms made of asbestos exhibit very good technical
properties; however, its application as carcinogenic substance today is obsolete.
Several polymers are used as base materials for porous diaphragms (e.g., as separators in batter-
ies). Organic solvents can attack polymers, typically by swelling that may clog a diaphragm. The
stability of a polymer is strongly influenced by all compounds in the electrolyte mixture. Therefore,
a careful selection of the diaphragm in combination with the electrolyte is required, especially in
case of long-term applications. Polyethylene and polypropylene are inexpensive and stable at vari-
ous conditions. Nearly universal stability is assured with porous (expanded) polytetrafluoroethylene
(PTFE, e.g., Teflon®, a traditional trade name of expanded PTFE is GORE-TEX®). The hydro-
phobic properties of such polymers inhibit an immediate application in aqueous media. However,
after initial wetting with a completely water-miscible alcohol (e.g., 2-propanol), aqueous electrolytes
become applicable.
2. Ion Exchange Membranes

While porous separators are permeable for all compounds and ions, there is a transport selectivity
for either cations or anions in ion exchange membranes. A large variety is commercially available,
especially for utilization in electrodialysis. Thus, their application as cell separator can be interest-
ing, but special properties have to be considered [67].
Ion exchangers and ion exchange membranes consist of a base polymer (typically polystyrene)
with covalently bonded fixed ions, typically sulfonate anions or (quaternary) ammonium cations,
respectively. For electrical neutrality, counter ions of the opposite charge have to be present. These
are cations in a cation exchange membrane (e.g., H+, Na+) or anions in an anion exchange membrane
(e.g., Cl−), respectively. They become mobile and exchangeable as charge carrier if the membrane
is swollen in a suitably polar solvent, and the fixed and counter ions are sufficiently dissociated and
separately solvated. The charge carrier ion in the ion exchange membrane has to be present also in
the cell electrolytes.
The typical solvent is water that enables a high ion conductivity of ion exchange membranes.
Other solvents with adequately high polarity or solvents in mixtures may be possible (experimental
checking will be necessary). The material of the ion exchange membrane has to be durable in the
cell electrolytes, both chemically and resistant against excessive swelling. A well-known cation
exchange membrane of nearly universal chemical stability is Nafion® (Dupont, perfluorinated poly-
mer with sulfonic acid groups). However, it is expensive and its swelling in organic solvents can be
prohibitive. A suitable membrane—cation or anion exchange membrane—for a planned application
should be selected in contact with the technical support of suppliers.
Usually, the transport selectivity of ions will be satisfactory. However, dependent on the condi-
tions—especially due to significant concentration differences—also permeation of ions with the
opposite charge and diffusion of other compounds are possible.
A characteristic, unavoidable transport mechanism of ion exchange membranes is electroosmo-
sis (enhanced in comparison with porous glass or ceramic; see Section II.E.1). It is generated by the
solvation shells of the charge carrier ions, because predominantly ions of only one type—cations
or anions, respectively—are migrating in a definite direction through the membrane. Unselectively,
all solvents, reactants, and products are included in the electroosmotic flow. The magnitude of this
effect is influenced by the membrane type and by the composition and concentration of the elec-
trolyte solutions. Up to several molecules per migrating ion can be involved, resulting in a sizable
flow. Therefore, this effect has to be considered if an ion exchange membrane will be used as a cell
separator.
F. ELECTroCHEMICaL CELLS
Optimized electrochemical cells are needed to execute electroorganic electrolysis, considering—as
far as possible—all aspects discussed in this chapter. The requirements of the following checklist
commonly will be essential; however—dependent on the reaction system and on the goal of the
planned research—their significance may be different:
• General properties
• Suitable materials of electrodes and cell components
−− Chemically and mechanically stable and not corroding
−− Optimal electrocatalytic enhancement of the desired reaction and suppres-
sion of undesired side reactions (for electrode materials, see Sections II.A
and II.B)
−− Uncomplicated and inexpensive manufacturing (for cell construction materials,
see Section II.F.5)
• Homogeneous current density on the entire area of the working electrode, that is, equal
current distribution at uniform electrode potential
• Reliable electrode potential measurement
• Constant mixing for steady mass transfer
• Well-defined temperature
• Effective handling during experiments
• Easy and leak-proof mounting
• Accurate sampling
• Reliable mass and charge balancing
• Requirements in special cases may be, for example,
• Inert gas atmosphere
• Reflux condenser to prevent a loss of solvent (in case of gas evolution, an additional
low-temperature cold trap may be necessary)
• Balancing of gas evolution
1. Homogeneous Current Density

The close interdependence between current density and electrode potential and in consequence
the influence on the electrode reactions and their selectivity has been discussed in Section
I.B.8. Hence, usually an even current density on the entire electrode area is essential for authen-
tic results. This requires for every point of the electrode area a sufficiently constant overall
cell resistance: of the electrodes, of the electrolytes, and—where used—of the cell separator.
Satisfactory conductivities of the electrode materials and adequately dimensioned, symmetri-
cal current feeders are required. Only parallel mounted electrodes in a matched cell volume
enable a constant resistance of the electrolyte, and in addition, locally invariable concentrations
by sufficient mixing are necessary. This is demonstrated in Figure 7.4(a), where the parallel and
equidistant lines illustrate the homogeneous current density distribution.
C W C W RE
C W L
i i i i i i
1
(a)
(b) (c)
RE RE RE
C L W C L W C L W
i i i i i i
∆U = i · R d
2d
(d)
2/3d (f)
(e)
C W
RE RE
C L W C W
L
i i
i i i i
RE
(g) (h) (i)
FiGURE 7.4 Scheme of current density distribution and Luggin capillary positions in electrolysis cells.
W, working electrode; C, counter electrode; i, cell current; L, (Haber) Luggin capillary; RE, reference electrode;
ΔU, resistive voltage drop; R, Ohmic electrolyte resistance.
Inhomogeneity occurs if the cell volume is bigger than necessary for the electrodes, as in the
example of Figure 7.4(b). The cell current will use also the electrolyte outside of the electrode shape,
where the resistance altogether is smaller and the current density is enhanced at the electrode edges.
Inhomogeneity is increased if electrolyte also is present behind the electrodes (Figure 7.4(c)) and
some current can flow to the back sides of the electrodes. Additionally, the current distribution will
be deformed in case of unsymmetrical cell constructions.
The preconditions for homogeneous current density distribution according to Figure 7.4(a)
become more and more important in case of increasing current density, decreasing electrolyte
conductivity, and reduced electrode distance.
Examples of cell constructions, which enable a homogeneous current density, will be dis-
cussed in Section II.G. A special case of disturbed current density distribution can be caused
by gas evolution, in particular in the upper part of a cell with vertical electrodes. Therefore, a
fast displacement of gases from the electrolyte between the electrodes or between the separator
and the electrodes has to be provided by electrode and cell construction. If required, the current
density has to be limited so that the gases can be released without problems.
2. Electrode Potential Measurement

A precondition of electrolysis at an appropriate potential of the working electrode is a sufficiently
reliable potential measurement. It is indispensable for potentiostatic operation (see Section I.B.8).
Although it may not be necessary for galvanostatic operation also, in this case it provides important
information about the reaction.
Generally, potential measurement requires a (Haber) Luggin capillary (see Section II.F.2.c),
which connects the electrolyte in front of the working electrode with the electrolyte in the refer-
ence electrode. The Luggin capillary functions as a salt bridge that is filled with a fitting electro-
lyte; a typical example is saturated aqueous potassium chloride solution. The reference electrode
has to guarantee a well-defined and well-known potential between its electrolyte and its electrical
connector.
Exact electrode potential measurement is complicated, especially in case of organic electrochem-
istry (see also Section I.B.8.d). Possible errors can be minimized only using highly sophisticated
methods (see, e.g., Reference 68). However, practical preparative organic electrolysis does not need
necessarily the knowledge of exact electrode potentials. Adequately reproducible current density/
potential curves (see Figure 7.2), which are available by electroanalytical methods (see Chapter 2)
and should be sufficiently valid equally in electrolysis cells, will be satisfactory. A constant devia-
tion from the exact value in both measurements causes no detrimental effect. Nevertheless, the fol-
lowing practical recommendations should be considered in order to avoid systematic errors, which
could have a negative influence on the results of electrolysis experiments.
a. Reference Electrodes

The reference electrode [69] defines the zero of the potential scale in the electrolysis experiment.
For aqueous electrolytes, a variety of (even commercially available) reference electrodes of the
second kind (i.e., the potential-determining ion concentration is fixed by the presence of a sparingly
soluble salt, e.g., calomel or Ag/AgCl electrodes) is in common use [69a,b] (see also Chapter 1,
Section II.B.2). The situation is much more complex in nonaqueous solvents [51,69c]. The common
aqueous reference electrodes are often unstable in such environments [70], for example, owing to
disproportionation [71].
Separating the aqueous reference electrode from the nonaqueous electrolyte by a diaphragm
(e.g., frit, agar–agar stopper) and a salt bridge induces liquid junction potentials [72]. For
porous glass plugs, electrostatic ion transfer screening [73] has been described, which is sample
dependent and leads to errors of several tens of mV in the reference potential. In addition, con-
tamination in both directions, for example, transport of water into the cell electrolyte, might
be a problem.
As a consequence, nonaqueous Ag/Ag+ electrodes (silver wire in a solution of a silver salt soluble
in the respective solvent, often AgClO4, with a specified concentration and separated from the
electrolyte by a frit and a salt bridge) are popular [69c]. Although being reference electrodes of the
first kind, for practical purposes, they appear to be stable enough with respect to reproducibility.
Their use has been commented critically [74a]. A miniaturized construction for application in ionic
liquids has been described [74b].
It is not uncommon, especially in miniaturized cells, to employ chloridized Ag wires [75] or even
Pt wires [76] as pseudo-reference electrodes [69c]. The potential of such an electrode, however, may
strongly depend on the composition of the electrolyte surrounding the wire and possibly changes in
an unpredictable way during experiments. This might be particularly dangerous in solvents contain-
ing traces of halide ions (e.g., dichloromethane).
Owing to the often high resistance in organic electrolytes, the construction of reference
electrodes has received attention with respect to the minimization of ohmic drop and oscillatory
artifacts caused, for example, by the reference electrodes’ internal resistance [77a] (see also Section
II.F.2.c). Dual reference electrodes have been recommended [77].
b. Reference Redox Systems in Organic Electrolytes

To overcome some of the problems described in Section II.F.2.a, reference redox systems are used.
0
These are redox couples with a more or less reproducible formal potential Eref , which defines the
zero of the potential scale.
An IUPAC recommendation is the use of the ferrocene/ferricenium (fc/fc+) or bis(biphenyl)chro-
mium (0/I) redox couples [78a]. It has been argued that these redox systems do even present a
0
solvent-independent Eref , as far as possible (extrathermodynamic assumption [78b], see, however,
[78c]). Thus, E 0(fc/fc+) can easily be obtained in the respective electrolyte from cyclic voltammetric
peak potentials Epox and Epred (see Chapter 2) as the mean (Epox + Epred ) / 2. This value is given vs. a cer-
tain reference electrode, for example, a frit-separated Ag/Ag+ electrode with silver ions in a defined
concentration, typically 0.01 M, in CH3CN. Note that the resulting value is not necessarily indepen-
dent of the electrolyte composition owing to, among others, diffusion potentials developing in the
frit. It can, however, be used as a reference for any other potential measured in the same electrolyte
vs. the same reference electrode:

( ) ( ) (
E vs. fc/fc + = E vs. Ag/Ag + − E 0 fc/fc + vs. Ag/Ag + )
The resulting E (vs. fc/fc+) are then comparable. This has been used for the characterization of solvent
exchange equilibria coupled to an electron transfer by analysis of E0 shift data in solvent mixtures of
a broad composition [79] in order to eliminate artifacts introduced by the solvent variation.
When reporting such potential results, it is essential to clearly state the conditions of the refer-
ence experiment and how the conversion of the potential values is being made [74].
Another problem encountered with a reference redox system is caused by the fact that often
the redox system is added to the electrolyte under investigation in the presence of the substrate
(e.g., addition of fc to the solution at the end of a cyclic voltammetric experiment, recording of
additional voltammograms, and determination of the fc redox potential from the resulting curves).
It has recently been warned that such a procedure might introduce artifacts if redox cross-reactions
occur [80]. Either the internal reference redox system must be chosen such that cross-reactions
0
are avoided [80] or careful external determination of Eref has to be performed and checked for
reproducibility.
The use of fc as a reference redox system has also been extended to ionic liquids [81]. Apart
from the redox couples mentioned earlier, decamethylferrocene [82] and cobaltocene [81c,d,83]
have been suggested as reference redox systems.
c. (Haber) Luggin Capillary

The position of the Luggin capillary has a decisive influence on the measured potential. It includes
an unavoidable resistive voltage drop ΔU within the cell electrolyte (see Figure 7.4(d)), dependent
on the cell current i and the distance from the electrode surface. If ΔU represents a significant
part of the measured potential, it becomes difficult to evaluate the real electrode potential. Also
the application for controlling the potentiostat is complicated. Only in case of very low current
densities—for example, in cyclic voltammetry at ultramicroelectrodes—ΔU may be negligible. In
preparative electrolysis, ΔU can be estimated, for example, by calculations using the conductivity
of the electrolyte or by measurements at different distances from the electrode surface. Then, a
compensation in the electrical circuit of the potentiostat is possible (see manufacturer’s manuals for
individual procedures). Furthermore, the fraction of all resistive voltage drops within the electrode
potential is detectable by fast current interruption measurements (shutdown within about 1 µs). Any
resistive voltage drop disappears immediately, while all other potentials and overpotentials stay at
least some microseconds nearly unchanged. Comfortable potentiostats can correct the electrode
potential automatically based on this method. Another method, compensation by positive feedback
techniques [84], is common in commercial instruments since many years.
The discussed interdependence between current density and electrode potential implicates vice
versa that an exact measurement is possible only at a location in front of the working electrode
with a well-defined current density. However, usually the Luggin capillary itself disturbs the local
current density. A classical standard for the Luggin capillary dimension and position with minimal
influence on the local current density is elucidated in Figure 7.4(e) (d ≈ 0.5–1 mm) [3]. It may be dif-
ficult to adjust the distance. A minimum distance like that in Figure 7.4(f) causes inaccurate results.
The design in Figure 7.4(g) is helpful for a well-defined position and to prevent that gas bubbles
from gas evolution at the electrode can enter the orifice. A blocking of the Luggin capillary by gas
bubbles will be detrimental because in this case the control of the potentiostat is interrupted and its
voltage and current limits may be reached, probably causing a damage in the cell. The position in
Figure 7.4(h) is possible if a borehole can be applied into the electrode (however, also here the local
current density is changed).
A nearly optimal position demonstrates Figure 7.4(i), if it is correctly realized as, for example, in
the FlexCell® of Gaskatel GmbH [85]. Here, the Luggin capillary is a fine borehole in the cell wall
and ends in the cell electrolyte close to the electrode surface. No perturbation of the current den-
sity distribution is caused (a complete isolation from the electrode is necessary for reliable results).
A Luggin capillary position behind the working electrode as in Figure 7.4(e) is incorrect because the
potential is related to a too small current density (also in case of perforated or grid electrodes, the
current density on the backside is smaller than that in the front of the electrode).
The potential measurement needs a high-impedance input (measurement current typically
<1 nA) in order to minimize ohmic drop and to avoid damage (polarization) of the reference elec-
trode. Nevertheless, the resistance of the Luggin capillary/reference electrode combination should
be adequately low, especially for undisturbed potentiostatic operation. A noncorroding wire, for
example, of platinum or carbon fiber within the Luggin capillary is useful to reduce its resistance
(a direct contact to any electrode has to be prevented). If this wire is in addition led through outside
the capillary and connected to the reference electrode output using a highly insulated capacitor, it
does not change the stationary behavior of the potential, but it increases the high-frequency stability
of the potentiostat and helps to avoid oscillations [77,86]. Moreover, such a wire is advantageous to
inhibit a blocking of the Luggin capillary by gas bubbles. In this configuration, even a PTFE tube
instead of glass is possible as material of the capillary.
3. Uniform Mixing and Mass Transport

In principle, electrode reactions proceed heterogeneously. Therefore, they can be significantly
influenced by mass transport, especially in case of low reactant concentrations (see discussion of
diffusion overpotential in Section I.B.4). As a consequence, a uniform mixing of the cell electrolyte
is desired in order to avoid local concentration inhomogeneity. Possibly, gas evolution at the elec-
trode may be sufficient for mixing. Also a (magnetic) stirrer, particularly in cells for batch opera-
tion, can be useful (see Section II.G.2).
In flow-through cells, a special design for optimal fluid distribution may be suitable (see Section
II.G.3). Additionally, more enhanced mixing is attained using a turbulence promoter, for example,
a coarse woven mesh of polymer wires. The permanent shift of direction during the flow through
the cell chamber within the plane of this mesh results in a strong agitation. Additionally, this mesh
acts as mechanical support for fixing the distance, for example, between an electrode and a mem-
brane. However, gases may be a problem for turbulence promoters as gas bubbles can adhere to
the mesh.
4. Temperature Control
The reaction rate of electrochemical reactions is given by the cell current. Therefore, in princi-
ple, it can be adjusted independently of the temperature (in galvanostatic operation). However, the
required overpotentials decrease with increasing temperature. As a consequence, the rates of elec-
trochemical and chemical reactions are similarly dependent on the temperature (see Section I.B.4).
In addition, most electroorganic conversions include chemical reaction steps so that the temperature
influence—particularly on reaction kinetics and selectivity—is comparable with that of pure chemi-
cal reactions. Consequently, a constant temperature is an important prerequisite to achieve clearly
defined conditions for electroorganic investigations.
Characteristic for electrochemical systems is the increasing conductivity of electrolytes and
the reduced cell voltage at elevated temperature. Hence, a higher temperature may be advanta-
geous, as high as the chemistry of the reaction system allows. A further limit is the boiling tem-
perature of the electrolyte. If vapor bubbles occur, resistance and voltage drop of the electrolyte
are increased, additional heat will be evolved, and the temperature will be further elevated. Thus,
an unstable situation, a local overheating (hot spot), would emerge. Such effects especially may be
expected at locations of lower conductivity, for example, within a diaphragm. The result is a loss
of yield and selectivity and probably a damage of cell components. This has to be prevented by
temperature controlling in combination with electrolyte mixing and by choosing suitable opera-
tion conditions.
The evolved heat during the current flow in the electrolysis cell (see Section I.B.5) is the conse-
quence of the overpotentials and of the ohmic voltage drop (Joule heating). While little cells usu-
ally need a heating for application at elevated temperature, for larger cells and high cell currents, a
sufficient heat dissipation by cooling is required.
For small-sized cells, the easiest temperature-controlling method is a jacket round the cell, which
is connected to the fluid circulation of a thermostat (see Section II.G.2). Flow-through cells, espe-
cially for batch operation with circulation through a reactant reservoir, should use a heat exchanger
(e.g., of glass) in the cell liquid loop. It can be advantageous to use the backsides of the electrodes as
heat-exchanger areas for temperature controlling, for example, in a cell as shown in Section II.G.3.
Caution: without additional protection, for example, by insulating, it is interdicted to bring the back-
sides of both electrodes in contact with a noninsulating temperature control medium, like water!
The potential difference between the electrodes will initiate severe damage by (pitting) corrosion,
additionally even in a thermostat that is electrically connected to earth. Advanced temperature-
controlling methods, for example, using temperature sensors in the cell, electronic controllers, and
electrical quartz heaters, are well proven in practice.
5. Cell Construction Materials

The typical material for small cells is glass (see Section II.G.1). It is electrically insulating, durable
in most electrolytes (except strongly alkaline and acidic fluoride-containing media), and applicable
up to high temperatures. The possibility to observe reactions immediately is very useful, for exam-
ple, shifting of liquid level, color changes, gas evolution, precipitation of solids, or formation of
two liquid phases. The problem of glass, its breakability, especially in case of larger cells, has to be
considered. A glassblower can realize even a complex construction and adjust it to special require-
ments. Various devices for coupling and easy handling are available in different diameters like
ground-glass equipment, flanged joints, and screw cap connections. Glass is perfectly tight, and any
diffusion—for example, of oxygen or solvent vapor—into and out of the cell is precluded. If neces-
sary, for example, in case of extremely oxygen-sensitive compounds, the glassblower can substitute
coupling devices by direct connections.
Metals, for example, different chromium–nickel steels or titanium, are mechanically robust and
tight materials. Application in electrochemical cells is restricted because they are conductive and
may corrode due to potential differences. Corrosion can be substantially influenced if the metal is
insulated or connected to one of the electrodes.
Polymers are interesting insulating materials of easy machinability, for example, polypropylene,
polymethylmethacrylate (Plexiglas®, clear-transparent), or polyvinylidenfluoride. However, their
chemical stability, especially against organic solvents, has to be verified in each case.
PTFE (e.g., Teflon) has nearly universal chemical stability, but it is relatively weak and expen-
sive. Cold flow can be a problem, that is, PTFE is slowly deformed under the mechanical stress
of the pressure onto the gasket seals, and a leakage of the cell is possible (this effect is reduced
for PTFE compounds, e.g., with glass powder or graphite, and for alternative perfluorinated
polymers).
It is necessary to consider that polymers—unlike glass and metals—in principle are more or less
permeable for gases and vapors (especially in thin layers, e.g., films or tube walls). PTFE, which
cannot be molten but only sintered, generally is appreciably porous. If this is inacceptable, fusible,
and less permeable but more expensive, perfluorinated polymers can be used, like perfluoroalkylvi-
nylether (PFA) or fluorinated ethylene propylene (FEP). A thin FEP film, for example, is applicable
for shielding and/or insulating metal surfaces.
Gasket materials require chemical stability and should be elastic in order to reduce the necessary
force for sealing. Typically, O-rings, which need a groove for fixing, or flat gaskets, which can be
cut from sheet material, are utilized. However, common elastomers, also, for example, ethylene-
propylene-diene copolymer or silicone rubber, are affected by many organic solvents (swelling) and
have to be checked in each case in detail. Fluorinated elastomers, for example, Viton® or Kalrez®,
may be applicable in many cases but are expensive. Probably, O-rings with a resistant FEP jacket
round an elastic core (e.g., silicone rubber) can be an alternative. A paste of pure PTFE that can be
used like joint grease for sealing is available.
A sealing material for all purposes—but expensive and only usable once—is expanded PTFE
(e.g., GORE-TEX). It is available as a cord of various diameters ≥1 mm or as sheet material. Initially,
it is very soft and can be adapted to each surface. For example, even a metal mesh can be mounted
as electrode tightly between (glass) flanges, connecting its edges outside with a current feeder. The
cord is formed to a closed loop (inclined cutting and overlapping). To fix it for assembling, an inte-
grated adhesive stripe or the earlier mentioned PTFE paste is useful.
During mounting, this gasket will be strongly compacted. Using a small pressing force, a leak-
proof sealing for aqueous solutions is enabled by the hydrophobic properties of PTFE. Increased
force is required to tighten also against organic solvents, gases, and vapors. It is even applicable in
high-pressure cells by strong pressing, up to a translucent appearance. No could flow is observed,
as in case of common PTFE. If delicate materials, like a membrane or mesh, have to be installed,
preforming of the gaskets is recommended (preliminary fixing of the cell at reduced force with a
plastic film instead of the vulnerable material).
Always a sufficiently strong and constant pressure on the gaskets seals is required. However, it
must be limited to avoid any damage of sensitive cell parts such as gaskets, membranes, or compo-
nents made of glass or PTFE. An adequately elastic construction is necessary. Probably, it can be
fulfilled by inherently elastic and thick gaskets. Another method may be a (silicone) rubber sheet
(some millimeters thick) between cell and fixing plate. Also, cup springs as washers at the screwing
of the cell are practically proven.
Various connectors, valves, and other equipment of fluoropolymers are available from laboratory
suppliers (at a high price). The principle of a quick, inexpensive, and simple technique for connec-
tions of electrochemical cells using PTFE tubes is shown in Figure 7.5.
A PTFE tube (1) is cut some centimeters longer than finally needed. In this example, an outer
diameter of 3 mm and an inner diameter of 2 mm is given (tubes from 0.5 mm up to 6 mm outer
diameter have been successfully applied with this method, even in a pressure electrolysis cell at
5 bar). The end of the tube is heated to approximately 250°C for approximately 2–3 cm with a hot
air blower (2) until it becomes clearly transparent. Then the end of the tube is quickly stretched, and
the diameter becomes smaller than the bore (3). The squeezed end is cut off (4).
A capillary is cut to approximately 2 cm (5). Any material (e.g., glass, polymers like PTFE,
metals) is suitable. Alternatively, a cylindrical bore of sufficient length (at least about three times
the diameter) can be used, even included in larger devices of these materials. For the chosen tube
of this example, the bore diameter should be 2.4 mm. Any burr or sharp edge, which could damage
the tube, has to be removed (see enlarged picture (5); in case of glass, this is possible using a file or
hard-metal tool or by melting).
1 PTFE tube
2 Heating
3
Elongate
4 Cutoff
5
Capillary Removing of any burr
(e.g., of glass) and sharp edge
8
Cutoff
9 Heating
10 Cutoff
FiGURE 7.5 Leak-proof fixing of PTFE tube in a bore, here in a glass capillary, that can be linked to a
common screw cap connection (bore diameter about 20% lesser than the original outer diameter of the tube,
length of the bore at least three times the diameter). (From Jörissen, J., in Bard, A.J., Stratmann, M., Eds.,
Encyclopedia of Electrochemistry, Vol. 8, Ch. 2, p. 35, 2004. Copyright Wiley-VCH Verlag GmbH & Co.
KGaA. Reproduced with permission.)
The elongated end of the tube is drawn through the bore (6) and fixed in a bench vise. Then, the
capillary—or the device with the bore—is slowly moved on the tube to the desired position (7). If a
significantly strong and constant force during this movement is required, a leak-proof connection of
the tube can be expected. Again the squeezed end is cut off (8). The part of the tube, which has been
drawn through the bore, is largely elongated. Heating to clear transparency reestablishes its original
length and diameter (9, a heating of the material at the bore itself should be avoided). To cut off the
tube at about 2 mm (10) is a protection against pulling out. If an additional connection is needed,
the process can be repeated with the reestablished PTFE tube.
6. Procedure of Electrolysis Experiments, Mass Balancing and Charge Balancing

The items in the following checklist of important practical aspects should be considered for elec-
troorganic experiments:
• Data recording during electrolysis

• Cost-efficiently realizable using a computer with data acquisition system.
−− Caution: maximally allowed voltage differences have to be observed!
−− If necessary, electrical potential separation has to be applied!
• Continuous recording of all important data during electrolysis is recommended.
• At least cell current and cell voltage data should be recorded.
−− Additional recording as far as possible: temperatures, electrode potentials
−− Interesting in case of continuous operation: weights, perhaps flow rates, and others
• Generally, such data are a valuable help for analyzing the progress of the experiment:
−− In case of batch operation: watching of the changing conditions
−− In case of continuous operation: validation of stationary conditions
−− In case of a failure: assistance for diagnosis of the reason (e.g., identification of the
initial dysfunction)
• Sampling during electrolysis (also needed for calculation discussed in item “Balancing”)
• Multiple measurements and analyses are recommended, using a well-organized sam-
pling plan (reliable results should be based not on single data only, as far as possible).
• In case of batch operation
−− At least weighing of the reactants before start-up and weighing plus analysis of the
products after the experiment.
−− Weighing and analysis of additional intermediate samples yield supplementary
information (e.g., a consistent trend of the concentrations with time demonstrates
the authenticity of the experiment).
−− The decrease of the amount of chemicals and of the reaction volume in the elec-
trolysis cell due to the withdrawal of intermediate samples has to be considered in
all calculations discussed in item “Balancing”
• In case of continuous operation
−− Flow rates should be checked continuously or at least by difference weighing of the
reactant tank as well as of outlet samples.
−− Usually, evaluable results are possible only in a stationary state that is proven by
constant concentrations and electrical data.
−− If there is any trend in the data detectable, a suitable interpretation will be impos-
sible or very difficult (for new measurements, waiting is recommended until the
run-in period is finished).
• Techniques of sampling
• Sampling of cell fluid
−− Typically, using cheap disposable medical syringes.
−− An easy way is to mount a screw cap with a septum at a suitable place of the cell,
possibly in combination with a connection according to Figure 7.5.
−− A permanent contact of the fluid with the septum and a loss from the gas phase
through a perforated septum should be avoided.
• Sampling of gas
−− Information about the produced gas volume and composition may be necessary in
order to clarify an electrochemical process.
−− Typically, gases—even small volumes—are sampled by replacing a liquid that is
enclosed in a vessel (a connection according to Figure 7.5 may be suitable).
−− The solubility of the gas in the liquid should be low.
−− An equipment for measuring a gas volume and the possibility for subsequent
analysis by gas chromatography are described in Reference 2, p. 60.
−− Caution: explosive gas mixtures can be formed in electrochemical cells (e.g., includ-
ing hydrogen)—a splinter shield has to be arranged!
• Balancing
• In addition to the detection and quantification of the products, important information is
available by using the discussed data for calculating the following balances:
• Total mass balance
−− That is, the sum of inputs has to be equal to the sum of outputs.
−− This is necessary to detect a possible leakage (otherwise, it is nearly impossible to
recognize a loss of gases and/or vaporized liquids).
−− It will be particularly interesting for long-term and generally for continuously
operated experiments.
• Partial balances of selected compounds (if possible, of all compounds)

−− That is, the individually converted reactants have to be found in their products,
considering stoichiometry.
−− This will be helpful to detect the reason if there is a loss of single compounds (also
as a consequence of unknown side reactions).
• Charge (current) balance and calculation of the current efficiency (see Section I.B.3)
−− That is, the electrochemical products on both electrodes, including product gases,
have to be equivalent to the consumed electrical charge.
−− Charge balance is enabled in case of potentiostatic operation using an electronic
integrator or by software integration of the recorded changing cell current.
−− Charge balance can detect a partial electrical shortcut or—more probably—an
electrochemical shortcut, that is, the consumption of a product of one electrode
at the other one (e.g., anodic oxidation of hydrogen that has been evolved at the
cathode in an undivided cell).
• Detection of incorrect data
−− Improper data will be indicated by inconsistent results of at least two independent
values or balances.
−− If contradictory results are found, frequently an error of measurement, analysis, or
simply of calculation or writing can be identified and corrected.
• The efforts to carry out all these balances may be high. However, the reliability of the
entire results of electrolysis experiments is significantly increased.
G. EXaMpLES oF ELECTroCHEMICaL CELLS

Electrochemical cells, which have been used for published investigations, may—in the majority of
cases—be made by the facilities in the institutes of the authors (research cells are also commercially
available, e.g., from the suppliers of electronic equipment for electrochemistry). The goal of the
f ollowing few examples is to show some ideas for own constructions.
1. H-Cell
The traditional cell for the demonstration of electrochemical experiments has a shape similar to
the letter “H” (Figure 7.6). It is very easy to mount the electrodes in the vertical containers. The
horizontal electrolyte connection between anode and cathode compartments is separated by a glass
frit as diaphragm. As discussed before, the current density at the electrodes will be very unbalanced
and a high cell voltage will cause a large energy loss. Nevertheless, there are many classical exam-
ples of the successful application of comparable cells in literature, even using a mercury cathode
(e.g., References 87 and 88). In a similar cell design—but with flat, solid, or perforated electrodes,
mounted parallel nearby the diaphragm—the earlier mentioned problems are avoided and the elec-
trolysis can work with optimal current distribution [1,89].
2. Beaker Glass Cells

Beaker glass cells as shown in Figure 7.7 are usually applied for investigations in batch operation.
They are easy to operate and the reactions are directly observable in the small volume. In this exam-
ple, a mercury cathode and a platinum mesh anode (with a current feeder, made of a platinum wire
ring) are used. Electrolyte mixing and continuous renewing of the mercury surface are provided by
a magnetic stirrer. A nearly homogeneous current density distribution is enabled due to the parallel
mounting of the electrodes. The diameters of cathode, anode, and electrolyte volume should be as
similar as possible, and the influence of the moving stirrer on the current density distribution will be
negligible. No gas is generated at the cathode, and a gas evolution at the horizontal anode will not
cause a problem because the gas is easily released upward. If a divided cell is necessary (Figure 7.7b),
FiGURE 7.6 Scheme of the classical H-cell.
TI +
– + RE – RE
PTFE RC PTFE RC
Th Th
An
An Dia
Stir Stir
Hg Hg
Th Th
(a) (b)
FiGURE 7.7 Schemes of beaker glass cells: (a) Undivided and (b) divided. An, anode; Dia, diaphragm (glass
frit); Hg, mercury cathode; PTFE, PTFE stoppers; RC, reflux condenser; RE, reference electrode with Luggin
capillary; Stir, magnetic stirrer; Th, connection to thermostat; TI, temperature indication; + and −, insulated
current feeders.
the anode can be enclosed in a glass tube with a diaphragm (e.g., glass frit). A reference electrode
with an integrated Luggin capillary can be added. Heating or cooling is done by a jacket that is con-
nected to a thermostat.
If gas is evolved also at the lower electrode—here, for example, by using another cathode
aterial—this could be acceptable in an undivided cell according to Figure 7.7a, if no undesired
m
reactions occur (caution in case of explosive gas mixtures). However, under these conditions, a
divided cell according to Figure 7.7b with horizontal electrodes is impossible. Two gas-producing
electrodes in a divided cell require usually an arrangement of parallel, vertical electrodes (also a
concentric combination of electrodes and cell separator is realizable).
3. Flow-Through Cells
The typical application of flow-through cells is a continuous operation at stationary concentra-
tions with well-defined flow conditions (see Section I.B.7). Relatively large amounts of reactants
will be converted and have to be available. Also batch operation is possible if a flow-through cell
is connected with a reactant reservoir by a circular flow.
Numerous cell constructions are published in the literature, including small laboratory realiza-
tions of cell types that are used for industrial applications. Special examples are a 800 cm2 coaxial
design [1,90] or a cyclone cell with strongly enforced mixing [91].
Frequently, at inlet and outlet of the cell, special flow distribution devices are included.
A commonly used cell type—in laboratory as well as in industry—is the plate and frame design
(also called filter press type). A possible commercial supplier is, for example, Reference 21
(dimensions from laboratory to industrial scale with a large variety of available electrodes, cell
separators, etc.).
In Figure 7.8, a simple laboratory plate and frame cell, based on the PTFE tube technique in
Figure 7.5, is presented. It is relatively easy to realize and no highly sophisticated facilities will be
necessary.
The rectangular frame (Figure 7.8a) enables strong mixing in the cell chamber (at a high pump-
ing rate). The number of the PTFE tubes should be adjusted to the mixing requirements. It can be
suitable to use more tubes for outlet than for inlet in order to avoid an excess pressure within the cell
compartment due to the pressure drop in the tubes. Turbulence promoters can be added for enhanced
mixing (see Section II.F.3). If mixing is less important, also ring-shaped frames (Figure 7.8b) are
suitable. Such easy-to-produce parts are available from turning machines or simply can be cut from
thick-walled tubes, including glass.
A cell design like the one in Figure 7.8 is very flexible concerning material, shape, dimensions,
thickness, and required connections of the cell compartments. Different electrodes can be applied,
including materials that are available only as foils or sheets or are not machinable, for example,
graphite felt or metal foam. The desired electrodes and separators as well as the necessary cell
chambers between—possibly including heating/cooling chambers—can simply be combined and
mounted together with sealing gaskets by fixing plates and screws. Electrode plates or foils can be
applied without any machining—even of larger dimensions than necessary for the frames—like the
cathode in Figure 7.8b, using the edges as current feeders.
The electrode distance from the membrane usually is given by frame plus sealing gaskets thick-
ness. If a reduced electrode distance for low cell voltage is required, a perforated electrode of
a suitable material can be connected in an adequate distance in front of a current feeder plate
(preelectrode), like the anode A in Figure 7.8b.
This design will be also advantageous in case of gas evolution in order to route the gas from the
front to the backside of the electrode. Otherwise, the current density will decrease upward and anal-
ogously increase downward due to accumulation of gas in the electrolyte (= reduced conductivity)
with possible consequences for the reaction selectivity (see Section II.F.1). A collection of gas in
+ –
A G G M G G C
AC CC
(a) (b)
FiGURE 7.8 Examples of parallel-plate and frame designs for laboratory flow-through cells. (a) Rectangular
cell chamber for strong mixing. (b) Various parts of a cylindrical cell. A, anode (with preelectrode); G, sealing
gaskets; AC, anode compartment (glass ring, reduced mixing requirements); M, separator (e.g., membrane,
diaphragm); CC, cathode compartment (three tubes for satisfactory gas outlet, sufficient mixing within the
chamber by gas evolution); C, cathode (current feeders outside the cell at the four corners). (From Jörissen, J.,
in Bard, A.J., Stratmann, M., Eds., Encyclopedia of Electrochemistry, Vol. 8, Ch. 2, p. 35, 2004. Copyright
Wiley-VCH Verlag GmbH & Co. KGaA. Reproduced with permission.)
the upper part of the cell with local blocking of the electrode has to be avoided by sufficient gas
discharge, for example, using additional tubes (see cathode compartment CC in Figure 7.8b).
An essential precondition for correct operation of a flow-through cell is the selection of appropri-
ate pumps. Just as for electrochemical cells, suitable materials are required. Ideally, the flow should
be pulsation free. This is achieved using centrifugal pumps (leak-free with a magnetic coupled
drive); however, the flow rate is strongly dependent on pressure, and such pumps are suitable only
for electrolyte circulation.
In most cases, dosing (metering) pumps are required. Membrane pumps (as leak-free alterna-
tive for piston pumps) are reliable, relatively inexpensive, available in different materials including
PTFE, and therefore, nearly universally applicable. However, they work with strong pulsations
(different types of dampers and electronically controlled pumps can reduce pulsations). Peristaltic
pumps are a low-cost alternative with relatively low pulsations if flexible tubes, which are consistent
with the electrolyte, are available. There are many additional constructions, for example, with low
pulsation, but expensive: magnetically coupled toothed wheel pumps (very sensitive against par-
ticles in the liquid) or syringe pumps.
The cell design in Figure 7.8 enables batch operation without flow-through too, for example, for
easy testing of electrode or separator materials. In this case, the frame thickness has to be adjusted for
the required cell compartment volume (for a thickness ≥15 mm, also a magnetic stirrer is applicable).
4. Innovative Cell Constructions

There is a large number of innovative cell constructions described in the literature that may also
be suitable for electroorganic syntheses, from laboratory up to industrial scale. Examples are rotat-
ing electrodes, application of ultrasound, and packed or fluidized particle bed 3D electrodes for
increasing the active electrode area and enhancing the mass transport. Some examples are shown
in References 5 and 6.
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III APPENDicES
III.A APPENDix A*: SOLvENTS fOR ELEcTROLYSiS
III.A.1 GENEraL CoNSIDEraTIoNS
Electrolysis can occur only at the boundary between an electrode and a medium that conducts the
electric current, and the nature of the solvent is important for the course of electrolytic reactions.
Such factors as proton activity, usable potential range, dielectric constant, ability to dissolve
electrolytes and substrates, ion pair formation, accessible temperature range, vapor pressure,
viscosity, toxicity, and price must be taken into consideration when the choice of solvent is made.
III.A.1.a Proton Activity

The availability of protons is one of the most important properties of a medium by which it can
influence an electrolytic reaction, especially a reduction. Anodic reactions are generally less sus-
ceptible to the proton activity, but both the stability of cation radicals and the reactivity of some
nucleophiles in anodic substitution reactions depend on proton activity.
At high proton activity, a protonation of the substrate may occur prior to the charge transfer
step. A protonated molecule is reduced at a less negative potential than an unprotonated one.
* The following text is taken from Lund H., in Lund H. and Hammerich O., Organic ElectroChemistry, 4th edn., Marcel
Dekker, New York, 2001, pp. 251–272; references and sections have been renumbered, cross-references have been
adapted, and refer to chapters of the present, fifth edition, except where otherwise noted; some obvious (typographical)
errors in the original have been corrected and formatting has been adapted. Table 7.1 was referenced in the original
outside the text which is reproduced. It is included here for completeness, and contains important information about
available reference electrodes in various solvents.
TABLE 7.1
Reference Electrodes in Different Solvents
SCE Li(Hg)/ Na(Hg)/ Zn(Hg)/ Cd(Hg)/ Pb(Hg)/ Cu/ Electrons
(Aqueous) Hg/Hg2X2 Ag/AgCl Ag/Ag+ Li+ Na+ Tl(Hg)/Tl+ Zn2+ Cd2+ Pb2+ CuF H2(Pt)/H+ Chloranil I3−/I− (Solvated) PVFa
CH3CN +[A3,A4]b − (−)[A5] +[A4,A6] −[A7] +[A8] +[A9]
DMF + (+) (+)[A10] +[A11] +[A10] +[A10,A12] (+)[A10] −[A9]
NH3 − (+)[A3] − − +[A13] +[A14] +[A10]
(H2NCH2)2 + (+)[A15] +[A16]
C5H5N + +[A16,A17] −[A18]
((CH3)2N)3PO + +[A11]
DMSO + − (+)[A10,A19] +[A20] +[A10,A21] −[A22]
CH3OH + + + +
CH3COOH +[A23] +[A24] −[A25] +[A26]
(CH3CO)2O +[A27] +[A28]
Preparative Electrolysis on the Laboratory Scale
H2SO4 +[A29]
FSO3H +[A30] +[A31]c +[A32]
PC + +[A33] (+)[A10] −[A10] (−)[A10] +[A34]
CH3NO2 +[A35] +[A35]
THF +[A36] +[A37] +[A38]
HFP +[A39]
CH2Cl2 +
THAB +[A40]
HF +[A41,A42] +[A43] +[A44,A45]
Symbols: +, stable reference electrode; (+), usable comparison electrode; (−), dubious comparison electrode; −, unsuitable electrode.
DMF, dimethylformamide; DMSO, dimethyl sulfoxide; PC, propylene carbonate, THF, tetrahydrofuran; HFP, 1,1,1,3,3,3-hexafluoro-2-propanol; THAB, tetrahexylammonium benzoate;
TBAPF6, tetrabutylammonium hexafluorophosphate.
a Poly(vinylferrocene) electrode.
b Reference numbers.
c Au/Au3+.
301
At medium proton activity, the unprotonated molecule is reduced to a radical anion; this is rapidly
protonated to a radical, which generally is more easily reduced than the unreduced substrate. In
aprotic media the radical anion formed in the charge transfer step may be so long-lived that it can
be regarded as the product. The radical anion is normally more difficult to reduce than the unre-
duced substrate. The substrate itself may act as a proton donor (“father/son reaction”) [A1,A2].
A high proton activity generally makes an oxidation occur at more positive potentials; it also
diminishes the tendency to lose protons from cation radicals, which thus may have reasonable
stability under strongly acidic conditions.
In aqueous solution, (1) a change in pH may alter the sequence of reducibility of different “elec-
trophores”; (2) the degree of reaction of an “electrophore” may be different in acid and alkaline
solutions; (3) a branching of a reaction may be influenced by the availability of protons; and (4) the
stereochemistry of the product may be pH dependent. As examples can be given, (1) the reduction
of isonicotinic amide in which the carboxamide group is reduced in acid solution, whereas the pyri-
dine ring suffers reduction at high pH (Chapter 18)*; (2) the reduction of aromatic nitro compounds,
which at low pH at a suitable potential yields an amine and, in alkaline solution, a phenylhydroxyl-
amine (and its condensation products; Chapter 30); (3) the reduction of acrylonitrile that may yield
the two-electron reduction product, propionitrile, or the one-electron reaction product, adiponitrile,
depending on the availability of protons (Chapter 17); and (4) the stereochemistry of the product
mixture of pinacols formed on electrolysis of aromatic ketones that is pH dependent (Chapters
31 and 38).
When considering an aprotic solvent, it must be recalled that it is difficult to obtain a strictly
anhydrous medium. Especially in voltammetric experiments in which the concentration of the sub-
strate is low, the residual water nearly always present in a “dry” solution may influence the results
obtained. It must also be considered that the anodic limiting reaction of some anions, such as per-
chlorates [A46–A48], results in the formation of water. Protons may also be supplied by abstraction
by an electrogenerated base from the nonaqueous solvent or from tetraalkylammonium ions, in the
latter case by a Hofmann elimination. A convenient way to remove the major part of acidic impuri-
ties from “aprotic” solvents is to add active anhydrous alumina to the solution [A49,A50] or let the
solution pass through a column of anhydrous alumina.
Acidity and basicity scales in polar solvents have been discussed [A51], and it has been concluded
that the most appropriate scales are the acceptor number, AN, or donor number, DN, introduced
by Gutmann [A52–A54], although it does not directly allow one to estimate the basicity of a protic
solvent.
A determination of water in a “dry” solution is thus often of interest. A gas chromatographic
method has been employed [A55] for the determination of water in certain cyclic esters, but injec-
tion of electrolyte solutions causes accumulation of salts in the injection chamber and sometimes
erratic results due to thermal decomposition of electrolytes. Analytical use of the 1.9-µm water band
in the near-infrared [A56] may be practical for certain solvents, such as propylene carbonate, but not
for many of the commonly used solvents. A method has been described [A57] in which the water
reacts with lead tetraacetate in benzene; the lead dioxide thus formed is determined spectrophoto-
metrically at about 400 nm. As little as 2.5 ppm in a 2-ml sample can be measured. The method
was found to be applicable to a wide range of solvents and to certain solutions commonly employed
in electrochemistry.
The two one-electron reduction waves of 2,5-diphenyl-1,3,4-oxadiazole have been used as a
c riterion for estimating the degree of drying of aprotic solvents [A58]. When c H2O < 3 − 5 × 10−3 M,
the two waves had equal height and E1/2 −1.96 and −2.33 V (SCE), respectively, whereas in insuffi-
ciently purified solvents, the heights of the two one-electron waves were not equal and ΔE1/2 decreased.
The Karl Fischer method may be used in many cases. An extremely sensitive method using
tritiated water as tracer for the determination of solvent water content has been developed [A59]
* This chapter reference refers to the fourth edition.

in which drying efficiency is determined by the addition of a specified amount of tritium-labeled

water to a rigorously dried solvent and subsequent determination of the decrease in the activity of
the solvent after treatment with the drying agent.
Besides the ability to donate protons, the properties of the medium (solvent, supporting
e lectrolyte) as hydrogen atom donor are of importance. Hence, the strength of the available bonds
to hydrogen must be considered. The ability as a hydrogen atom donor is H2O < NH3 < MeCN ~
DMSO < DMF < THF.
III.A.1.b Usable Potential Range

The useful potential range that can be obtained in a given system depends on the electrode material,
the supporting electrolyte, the temperature [A60], and the solvent; only the solvent is discussed here.
Approximate values for the anodic and cathodic limits of some commonly used solvents are given
in Table 7.2. The numbers can be taken only as a crude indication of the usable potential range, as
the latter depends on the criteria used.
Many solvents are available that are so difficult to reduce that it is the discharge of the sup-
porting electrolyte that sets the cathodic limit for the potential; on the other hand, only few polar
solvents are resistant to anodic oxidation. The reason is that most polar groups have loosely bound
nonbonding electrons on oxygen or nitrogen that are easily lost at the anode. The solvents useful
for anodic reactions at high potentials contain electron-attracting groups, such as nitrile, carboxy,
sulfone, or nitro groups. For more easily oxidized substrates, sulfoxides or dialkylamides may be
used, whereas water, alcohols, and aliphatic amines have a very limited useful potential range for
anodic reactions.
III.A.1.c Dielectric Constant

The dielectric constant is of interest primarily because it influences the ohmic resistance of the
medium. Solvents with high dielectric constant are preferable because salts dissociate better in
such media. The dielectric constants for some solvents commonly used for electrolysis are listed in
Table 7.2. These solvents can be divided roughly into three main groups: those with high dielectric
constant (D > 60), those with medium dielectric constant (20 < D < 50), and those with low dielec-
tric constant (D < 13). In the first group are solvents like water, formamide, N-methylamides, and
PC; the second one comprises compounds like acetonitrile, dimethylformamide (DMF), dimethyl
sulfoxide (DMSO), methanol, nitromethane, and ammonia; whereas in the last group belong sol-
vents like acetic acid, ethylenediamine (EDA), methylamine, tetrahydrofuran (THF), dioxane, and
methylene chloride. The solvents in the last group require a higher concentration of supporting
electrolyte in order to acquire a reasonable conductivity.
For acetonitrile, propylene carbonate, 4-butyrolactone, DMSO, DMF, and similar amides, the
maximum conductance for fully ionized salts occur at approximately 1 M concentration and is
about 10 −2 Ω−1 cm−1, comparable to an aqueous salt solution of 0.5–1 M.
The rate constant for the heterogeneous electron transfer to aromatic compounds is usually some-
what higher in MeCN than in DMF, which indicates that not only the dielectric but also the dynamic
properties of the solvents influence the rate of radical anion formation [A70].
III.A.1.d Dissolving Power

The choice of solvent is often a result of a series of compromises. Very few solvents have good
d issolving power for both organic substrates and inorganic salts. The good electrochemical properties
of water are marred by the lack of its ability to dissolve many organic systems. This ability may be
raised by using water in a mixture with an organic solvent like ethanol, acetonitrile, DMF, or dioxane,
or by using a “hydrotropic” supporting electrolyte [A71] like tetraalkylammonium p-toluenesulfonate.
Tetraalkylammonium salts are soluble in most polar solvents and even in less polar liquids, such as
chloroform and methylene chloride. Some polar solvents, such as acetonitrile, DMSO, and DMF,
combine good dissolving power for both organic compounds and a variety of salts.
304
TABLE 7.2
Dielectric Constants and Accessible Potential Range for Some Solvents
Dielectric Working Reference Supporting Anodic Working Reference Supporting Cathodic
Constant Electrode Electrode Electrolyte Limit (V) Electrode Electrode Electrolyte Limit (V)
Water 80 Pt SCE HCIO4 1.5 Hg SCE TBAP −2.
Methanol 33 Hg Hg pool TEAB −2.
H2SO4 (96–99%) >84 Hg Hg pool None −0.7 [A29]
CH3COOH 6.2 Pt SCE NaOAc 2.0 [A61]a Hg SCE TEAP −1.7
CH3CN 37.5 Pt Ag/Ag+ LiClO4 2.4 [A62] Pt Ag/Ag+ LiClO4 −3.5 [A62]
DMF 36.7 Pt Hg pool LiClO4 1.5 [A63] Hg Hg pool TEAP −3.5 [A63]
NMP 32 Pt Hg pool LiClO4 1.4 [A63] Hg Hg pool TEAP −3.3 [A63]
HMPA 30 Pt Ag/Ag+ LiCO4 0.8 [A62] Hg Ag/Ag+ LiClO4 −3.6 [A64]
NH3 23 Hg,Pt Hg pool TBAI −2.3 [A3]
(H2NCH2)2 12.5 C SCE TEAP 0.1 [A23] Hg SCE TEAP −2.65 [A23]
Pyridine 13 Graphite Ag/Ag+ LiClO4 1.4 [A65] Hg Hg pool LiClO4 −1.7 [A65]
DMSO 46.7 Pt SCE NaClO4 0.7 [A66] Hg SCE TEAP −2.8 [A66]
Sulfolane 44 Pt SCE NaClO4 2.3 [A67] Pt SCE NaClO4 −4 [A67]
PC 69 Pt SCE TEAP 1.7 [A68] Hg SCE TEAP −2.5 [A68]
CH3NO2 36.7 Pt SCE LiClO4 2.7 [A35] Hg SCE LiClO4 −1.2 [A35]
THF 7.4 Pt Ag/Ag+ LiClO4 1.8 [A39] Pt Ag/Ag+ LiClO4 −3.6
HFP 16.6 Pt Ag/AgCl TBAPF6 2.1 [A39] Pt Ag/AgCl TBAPF6 +0.4 [A39]
CH2C12 8.9 Pt SCE TBAP 1.8 [A69] Pt SCE TBAP −1.7 [A69]
The limit for the accessible potential for a solvent depends on many factors, such as supporting electrolyte, electrode material, and magnitude of permissible cur-
rent density, and the numbers given are cited as illustrative values only.
DMF, dimethylformamide; NMP, N-methylpyrrolidone; HMPA, hexamethylphosphotriamide; DMSO, dimethyl sulfoxide; sulfolane, tetramethylene sulfone; PC,
propylene carbonate; THF, tetrahydrofuran; HFP, hexafluoro-2-propanol; TBAP, TBAI, tetrabutylammonium perchlorate or iodide, respectively; TEAP, TEAB,
tetraethylammonium perchlorate or bromide, respectively; TBAPF6, tetrabutylammonium hexafluorophosphate.
a Reference numbers.
Besides the dissolving power of a solvent toward substrate and supporting electrolyte, the
ability to solvate intermediate cations and anions is also important. The chemical properties of
charged species are dependent on whether there are formed tight ion pairs, solvent-separated ion
pairs, or symmetrically solvated ions. Redox potentials of ions are thus dependent on solvent (see,
e.g., Reference A72). A knowledge of the donor and acceptor values [A53,A54] of a solvent is thus
helpful in predicting its properties as medium. Also, the autoprotolytic constant of a solvent is of
interest in this respect.
A combination of the good conductivity of water and the dissolving power of an organic sol-
vent may be exploited by using an emulsion [A73–A84]. A simple emulsion is useful only if the
substrate has a reasonable solubility in water and thus only a limited advantage compared with a
suspension of the substrate. For reactions in which the product is much more soluble in an organic
phase than the reactants, an emulsion may continuously extract the product and protect it against
further reaction. Emulsions are made from an aqueous phase, an organic phase, and a surfactant;
they may be “water in oil”, “oil in water”, or a bicontinuous microemulsion. The first two types have
one continuous phase, whereas the bicontinuous microemulsion has both the aqueous and organic
phases as continuous phases; it consists of a dynamic intertwined network of the two phases with
a surfactant monolayer at the interphase [A80–A82]. Bicontinuous microemulsions are nontoxic
and have a large interfacial area facilitating an intimate mixing of polar and nonpolar reactants,
good solubilization of polar and nonpolar compounds, and high conductivity. Bicontinuous micro-
emulsions could thus be useful for electrochemical synthesis as an alternative to the use of organic
solvents [A80–A82].
Utilization of a mediator and a phase transfer catalyst may enhance the reaction rate consider-
ably; in a bimolecular reaction, the rate may be enhanced by preconcentration of a mediator by
adsorption to the electrode in a microemulsion [A81,A82]. When a desired bimolecular reaction
involves ions (including radical ions), the nature of the surfactant (cationic, anionic, neutral) may
play a role in the product distribution [A83].
Ultrasound-assisted electrolytic reduction of emulsions of activated unsaturated systems pro-
vides a method for hydrogenation of water-insoluble materials in an aqueous environment [A85].
The effect of ultrasound on electrochemical reactions in emulsions may vary depending on the
reaction; in some cases, solubilization of an insoluble reaction product is furthered, whereas in other
cases, the heterogeneous rate constant is influenced [A84].
When cells with solid polymer electrolytes (SPE) are used, no electrolytes need to be dissolved in
the medium, and solvents, which usually cannot be employed in electrolysis, may be used [A85–A90].
III.A.1.e Temperature Range and Other Factors

It is desirable that the solvent be a liquid in a convenient temperature interval and that the vapor
pressure be not too high at the working temperature to avoid excessive loss of solvent. This is not
an important point since the electrolysis is often carried out in a closed system anyway. The vapor
pressure may also sometimes be lowered considerably by working with a high salt concentration.
Too low a vapor pressure of the solvent is inconvenient, as it may be difficult to remove the solvent
during the workup.
The viscosity of the medium influences not only the mass transfer but also the rate constant of
the heterogeneous electron transfer [A91]. A low viscosity is preferable both from the point of view
of diffusion and from considerations of pumping in flow cells. For some kind of electroanalytical
work, however, a high viscosity is preferable. Diffusion coefficients in some solvents useful for
electrolysis have been published [A92].
The toxicity and odor of the solvent warrant consideration. Proper design of the apparatus and
careful handling of the solvent make these properties less objectionable.
The chirality of a solvent, S,S-(+)2,3-dimethoxy-l,4-bis(dimethylamino)-butane, has been used
to induce chirality in reduction products [A93].
III.A.1.f Purification
Few, if any, organic solvents are obtained commercially pure enough for electrochemical work.
However, when selecting a method for purification of a chosen solvent, one should realize that it is
seldom necessary to lower the concentration of all impurities. An aprotic solvent used for a reduc-
tion should especially be purified for electrophiles, whereas nucleophiles (bases) should be removed
from a solvent for oxidations.
Solvents obtained from different sources may have different impurities, and even in solvents
from the same source, the kind and concentration of impurities may change from batch to batch.
Water is always an impurity in an organic aprotic solvent. The influence of a given water con-
centration depends on the stability of the complexes between water and the solvent; water is, for
example, less firmly bound to MeCN than to DMF or DMSO.
When one wants to remove a given impurity, there is always a danger that the reagent or method
introduces other impurities or decomposition products; some solvents, such as DMF, decompose
somewhat on distillation at ambient pressure.
The storage of a solvent is important, and ideally, one should use the solvent immediately after
purification. Some solvents are decomposed by light, and most solvents absorb some water if given
the chance.
Methods for purification of some aprotic solvents and tests for impurity recommended by IUPAC
have been published [A94].
III.A.2 ProTIC SoLVENTS

It is practical to divide solvents into two groups, protic and aprotic solvents. Protic solvents are
those that have protons bonded to heteroatoms and include acids, neutral solvents, and some bases.
A review of solvents useful for electrochemistry has appeared [A69]. Electrochemical reactions in
nonaqueous systems [A95] and the chemistry of nonaqueous solvents [A96] have been treated in
monographs.
III.A.2.a Acid Solvents

The electrochemistry of a protonated organic compound differs in many cases from that of the
neutral molecule, and the strength of the acid necessary for protonation of the substrate must be
considered. Sulfuric acid and acetic acid, often containing some water, have generally been used.
When high acidities are desired, fluorosulfonic acid may be used.
III.A.2.a.i Sulfuric Acid

Concentrated or slightly diluted sulfuric acid is in many respects an excellent medium for electroly-
sis. It dissolves many organic compounds, and it is sufficiently dissociated to make the addition of
foreign electrolytes unnecessary.
Sulfuric acid can protonate even very weak bases, such as aromatic ethers or some aromatic
hydrocarbons; it may promote the formation of carbocations either by dehydration of hydroxyl com-
pounds or by addition of a proton to a double bond. These properties are still more strongly devel-
oped in the “superacids”.
Sulfuric acid has certain disadvantages: It cannot be removed by distillation during the workup.
It is, therefore, often most practical to dilute the medium with water and extract the product. If neu-
tralization is necessary, concentrated ammonia is preferable. Another disadvantage is that sulfuric
acid may oxidize or sulfonate the substrate.
Most of the electrolyses in sulfuric acid have been performed without control of the potential. In
polarographic work, the mercury pool has been used for anodic and cathodic reactions: as anode,
platinum, or lead dioxide has been employed and as cathode, lead, mercury, or platinum.
A 1:1 mixture of sulfuric acid and ethanol was a very popular medium for electrolytic reductions
around 1900. The mixture dissolves many organic compounds, but the leveling effect of the alcohol
lowers its protonating ability considerably.
III.A.2.a.ii Fluorosulfonic Acid

This solvent is a very strong acid and may be used when stabilization of cationic species is required
[A31,A97–A103]. It has above all been used as medium for the oxidation of alkanes. It is rather
resistant toward anodic oxidation, the oxidation product being peroxydisulfuryldifluoride [A101].
Fluorosulfonic acid is not a conducting medium, and it is necessary to add a supporting electro-
lyte, such as NaSO3F or KSO3F, or an ionizable organic compound, such as acetic acid, which acts
as a strong base and forms CH3CO+. Antimony pentafluoride acts as an acid in FSO3H.
In fluorosulfonic acid containing sulfuric acid, anodic dissolution of platinum is reported to take
place; in anhydrous FSO3H, an oxide layer is formed, which protects the platinum electrode [A103].
As reference electrode, the hydrogen electrode [A32], the Au(s)/Au+3 electrode [A31], and
HgSO4/Hg in HSO3F [A30] have been used, but an internal reference system, such as perylene+/
perylene2+, has been recommended [A59] to avoid unknown liquid junction potentials.
Perfluorosulfonic acids may be used similarly [A104]. They may be purified by distillation
and treatment with H 2O2 [A105]. Trifluoromethanesulfonic acid has been used as a solvent for
CV with sodium trifluoromethanesulfonate as supporting electrolyte, glassy carbon as indica-
tor electrode, platinum as counter electrode, and a silver wire as pseudo-reference electrode. At
v = 100 mV s−1, the accessible potential window was from +0.4 to +3.0 V vs. NHE (calibrated
against Ru(bpy)33+/2+) [A106].
III.A.2.a.iii Hydrogen Fluoride

Hydrogen fluoride has been used for electrochemical fluorination of organic compounds [A107–
A110] and is a promising solvent for electrochemical studies. It has a high dielectric constant (80 at
0°C), is less viscous than water, is transparent for UV light to 165 nm, and is difficult to oxidize. It
dissolves many metal fluorides, giving highly conducting solutions; it also dissolves many organic
substances. The main disadvantages are its poisonous effect, its ability to attack glass, and its rela-
tively low boiling point, 19.5°C. The low boiling point gives it a tendency to form bubbles, which
must be taken into account in the construction of cells. This and other practical problems have been
discussed [A111].
Hydrogen fluoride can be handled in an apparatus of suitable metals (copper, nickel, magne-
sium, or aluminum, which all form a protective fluoride coating, or platinum) or plastic materials
[especially polypropylene, Teflon, and polyvinylidene fluoride (Viton)]; polychlorotrifluoroethyl-
ene (Kel-F) can be made into transparent windows. A capillary for a dropping mercury electrode
may be made from Teflon [A112]. Hydrogen fluoride is obtained commercially in steel cylinders
in a purity of 99.5%. The impurities may be removed by distillation [A113] or electrolysis [A114].
During the electrolytic removal of water, the explosive F 2O is formed, which must be taken into
consideration [A110].
The useful potential range in the cathodic direction is rather limited owing to the evolution of
hydrogen, whereas the anodic limit is about 2.6 V (SCE). Sodium or potassium fluoride as support-
ing electrolyte may be used; the addition of these salts lowers the protonating power of the solvent.
The solubility of NaF is about 30 g NaF per 100 g HF; other fluorides, such as LiF, KF, CsF, NH4F,
AgF, and TlF, are very soluble in liquid HF. The acidity of HF may be enhanced by the addition of
BF3 or SbF5.
The addition of amines to hydrogen fluoride makes the fluoride ion a better nucleophile and
reduces the acidity of HF; Et3N/3HF and pyridine/HF are commercially available. Et3N/3HF may
be used as such or mixed with MeCN as a medium for electrochemical fluorination (Chapter 20)
[A115,A116].
Several types of reference electrodes may be used. The hydrogen electrode has been shown to
behave reversibly in HF [A44,A45] and has been employed as a reference electrode both in elec-
troanalytical and in preparative work [A45], and mercury fluoride [A41,A117] and copper fluoride
[A43,A111] have also been used as such. A comparison of these reference electrodes pointed to the
hydrogen electrode (H2/Pd) as the most convenient [A118].
III.A.2.a.iv Trifluoroacetic Acid

Trifluoroacetic acid (TFA) has mainly been used as a medium for oxidations [A119]. It has a dielec-
tric constant of 8.4 [A120,A121] and a boiling point at 72.5°C; although it has a low conductivity,
it is possible to conduct electrolysis in it without using a supporting electrolyte [A122]. Its main
advantage is that many cation radicals show considerable stability in this medium. Sometimes it is
used in a mixture with its anhydride and methylene chloride [A49].
III.A.2.a.v Acetic Acid

Acetic acid is a good solvent for many organic compounds and some inorganic salts. It has a rather
low dielectric constant, which makes it necessary to have a considerable electrolyte concentration
(≥0.5 M) to obtain a reasonable conductance.
Acetic acid may be considered as solvent for acetoxylations [A61,A123,A124] and for reactions
that require an acidic medium other than sulfuric acid. The acidity may be enhanced by adding
perchloric acid to acetic acid containing a suitable amount of acetic anhydride, which reacts with
the introduced water.
Usable supporting electrolytes include NaOAc, NH4OAc, LiCl, HCl, H2SO4, HClO4, NaClO4,
Bu4NClO4, and Bu4NBF4. The choice of supporting electrolyte may influence the product distribu-
tion. Thus, anodic acetoxylation gives different results in NaOAc/HOAc and in Bu4NBF4/HOAc.
Several types of reference electrodes work well in acetic acid. The chloranil electrode [A26] behaves
reversibly in this medium and so does the analog of SCE [A65] [Hg/Hg2Cl2(s), LiCl(s), HOAc]; the
mercury pool [A125] and the Ag/AgCl electrode [A24] can also be used.
The cathodic limit is about −1.7 V (SCE), and the limiting reaction is evolution of hydrogen. The
anodic range ends at about 2.0 V (SCE) when NaOAc is the electrolyte [A61]. The limiting reaction
is probably the discharge of acetate ions.
Acetic acid may be purified by partial freezing [A61] or by distilling it from CrO3 [A65,A125]
in the presence of acetic anhydride. CrO3 oxidizes impurities and acts as an acid catalyst for the
reaction between water and acetic anhydride. An excess of acetic anhydride is necessary to force
the equilibrium 2AcOH ⇌ Ac2O + H2O sufficiently to the left [A126]. Modifications of the method
have been described [A23,A125].
III.A.2.a.vi Other Acids

Methanesulfonic acid [A127] and formic acid have also been used as solvent for electrolysis; super-
acids offer possibilities for unusual electrode reactions.
III.A.2.b Neutral Solvents

This group comprises water, mono- and polyvalent alcohols, and monoethers of polyvalent alcohols.
Often mixtures of water and alcohols are used. Such mixed solvents retain the favorable characteristics
of water to some degree but raise its ability to dissolve organic substrates.
III.A.2.b.i Water
Water is the solvent of choice for electrolysis, unless some of its properties are undesired or
inadequate. An aprotic solvent is sometimes preferable to water since a reaction mechanism of
an electrode reaction in an aprotic, organic solvent is often simpler to elucidate than in water.
Adsorption phenomena are often a complicating factor in aqueous solution, but much less so
in many organic solvents. The usable potential range of water in the anodic direction is quite
limited, and the most important factor, the solubility of many organic compounds in water, is
quite unsatisfactory. The use of “hydrotropic” salts (Appendix B, Section III.B.1) may enhance
the solubility of organic compounds in an aqueous medium. Another way of combining the
good conductivity of aqueous solutions with the better dissolving power for organic substrates
is the use of emulsions [A73–A84], preferentially with a mediator and a phase transfer reagent.
III.A.2.b.ii Methanol
The electrochemical behavior of methanol is rather similar to that of water. Methanol is well suited
for anodic reactions of the Kolbe type and for methoxylations; for reductions, it may be used when
the solubility of the substrate in water is too low. The dielectric constant of methanol is fairly high
(ε = 33); its liquid range (−98 to 64°C) is convenient, and it is easy to remove during the workup.
Quite a few electrolytes are soluble in methanol, such as NH4Cl, LiCl, HCl, KOH, KOMe, NaClO4,
and tetraalkylammonium salts. For reductions, a solution of HCl in MeOH is convenient as it has
a high conductance and both components are easy to get rid of during the isolation of the product.
Reference electrodes that can be used in water work in most cases also in MeOH; thus the
Hg/Hg(I) and Ag/Ag(I) electrodes may be used. The useful potential range for large-scale elec-
trolysis is about the same as for water, but methanol is less satisfactory for electroanalytical work.
Methanol can in general be used as received; it can be dried by treatment with magnesium [A128].
It has been reported that methanol oxidized at the anode may diffuse to the catholyte and react
with nucleophiles or EGB [A129].
III.A.2.b.iii Other Alcohols

Ethanol and the higher alcohols have lower dielectric constants and poorer ability to dissolve elec-
trolytes. They have been used mostly in mixture with water or sulfuric acid. 2,2,2-Trifluoroethanol
is more acidic than ethanol and can be used when strong bases are undesired [A128].
III.A.2.c 1,1,1,3,3,3-Hexafluoropropan-2-ol
1,1,1,3,3,3-Hexafluoropropan-2-ol (HFP) is a solvent [A39] with unusually low nucleophilicity; it has a
high ionizing power, a high hydrogen bonding strength, and a low hydrogen bonding acceptor strength,
which makes it a good solvent for investigations of cation radicals. It may be useful for electropolymer-
ization. It dissolves many polar compounds, but is less good in dissolving nonpolar substrates.
It has a liquid range from −5 to 58.6°C, a dielectricity constant of 16.7, pKA in water 9.30,
and pK A in DMSO 18.2. It is rather volatile and should be handled in a well-ventilated hood.
Tetrabutylammonium hexafluorophosphate or tetrafluoroborate has a sufficient solubility in HFP
to give a good conductivity. Aqueous Ag/AgCl or SCE has been used in connection with a suitable
low-leaking salt bridge. The reversible potential ferrocenium/ferrocene couple in HFP was found
[A39] to be 0.05 V vs. Ag/AgCl, to be compared with that in CH2C12, 0.43 V vs. Ag/AgCl. The
potentials in HFP generally differ appreciably from those in, for example, MeCN.
HFP of highest quality may be used as received; it is rather expensive as a solvent for electro-
chemistry and regeneration of the solvent could be attractive, but as HF might be formed during
regeneration, the procedure should be carefully considered. However, in the author’s laboratory,
solvents from CV (HFP/TBABF4), depending on the substrates, have been regenerated by distilla-
tion at 30°C/½ atm after use with a loss of 10–15%.
III.A.2.d Basic Solvents

Basic, protic solvents include ammonia and primary and secondary amines. These solvents are
primarily of interest for an organic electrochemist because of their ability to solvate electrons, and
solvated electrons have special reducing properties (Chapter 29).* They also permit reductions in a
protic medium in the presence of a very strong base, the conjugate base of the solvent.

III.A.2.d.i Ammonia
The use of ammonia as a solvent for electrochemical reactions presents some problems due to
its inconvenient liquid range (−77.7 to −33.4°C); this difficulty can be coped with in different
ways. The electrolysis may be made in a suitable low-temperature thermostat [A131], the cell
can be equipped with an efficient reflux condenser [A132], a high-pressure apparatus can be used
[A133] (ammonia has even been used in its supercritical phase as a medium for electrochemical
investigations [A134]), or strong solutions (5–10 M) of various salts, such as NH4SCN, NH4I,
LiNO3, LiClO4, NaSCN, and NaI, can be used [A135] as they form a medium in which the vapor
pressure of ammonia at ambient temperature is below 1 atm. The easy purification and low price
of ammonia compared with the alternative amines favor the choice of ammonia for large-scale
preparations.
When using a divided cell, a tube must connect the anode and cathode compartments for equili-
bration of the pressure.
Ammonia has a medium–high dielectric constant (23.7 at −36°C) and good dissolving power
toward inorganic salts but less for nonpolar organic compounds. It can act as both an acid and a
base; the strongest possible acid in ammonia is ammonium ion and the strongest base the amide ion.
The pK values of some weak acids have been determined in NH3 at −60°C [A136].
The combination of low proton availability together with the low temperature usually employed
makes ammonia a suitable medium for electrochemical investigations of strongly basic species,
such as dianions [A137,A138]. The low tendency to donate hydrogen atoms, due to the strength of
an N–H bond, is important for many investigations [A139–A141].
Besides the electrolytes mentioned earlier, such salts as NH4Cl, NH4NO3, KNO3, and NaClO 4
may be used as supporting electrolyte; the tetraalkylammonium salts are generally rather
sparingly soluble in ammonia. Most electrolyses in ammonia, except in voltammetric studies,
have been performed without a reference electrode; as such, a Zn(Hg)/ZnCl2 [A13] or Pb/Pb2+
electrode [A3,A131,A142] may be used. In polarography, the mercury pool electrode has been
applied [A3].
Ammonia has been employed mostly for cathodic reactions, but some oxidations [A132,A135]
have been carried out in this medium, although the potential range in the anodic direction is quite
small. The anodically limiting reaction is oxidation to nitrogen and protons [A143]; the cathodically
limiting reaction is the transfer of electrons to the solvent, which occurs at about −2.3 V (vs. Hg pool
electrode) in a saturated solution of TBAI. In the electrolytic generation of solvated electrons, the
potential is determined by the surface concentration of electrons and no external reference electrode
is needed.
Ammonia is purified by distilling it after treatment with sodium; the distillation from sodium
may have to be repeated.
The threshold limit value (TLV) is 25 ppm.
III.A.2.d.ii Methylamine
Methylamine behaves electrochemically much like ammonia but has a somewhat more convenient
liquid range (−93.45 to −6.3°C), although its odor and low boiling point require special consider-
ations. Its dielectric constant is rather low (11.4 at −10°C), but sufficient conductivity for large-scale
electrolysis can be obtained using LiCl as supporting electrolyte. Like ammonia, it is both an acid
and a base.
Methylamine has mainly been used in large-scale electrolysis [A144,A145], and no reference
electrodes have been employed so far. Reference electrodes such as the Zn(Hg)/Zn2+ electrode, which
work both in ammonia and in EDA, would be assumed to be applicable to methylamine solutions.
Methylamine has been employed only for reductions, especially as solvent for electrolytic gen-
eration of solvated electrons. It would be of very limited use for anodic reactions. It may be purified
by distillation from sodium. Its TLV is 10 ppm.
III.A.2.d.iii Ethylenediamine
Ethylenediamine (EDA) is a primary amine with a more convenient liquid range (11–117°C) than
methylamine. Its dielectric constant (ε = 12) is about the same as that of methylamine. It dissolves
many inorganic salts and is a better solvent than ammonia for many organic substrates.
LiCl, NaNO3, and tetraalkylammonium salts can be used as supporting electrolytes. For the elec-
trolytic generation of solvated electrons, mainly LiCl has been employed [A146,A147]. A reversible
reference electrode in EDA is the Zn(Hg)/Zn2+ electrode [A148], but the Hg pool [A15] or the aque-
ous calomel electrode, fitted with a suitable salt bridge, is also applicable.
EDA is oxidized rather easily anodically but is resistant to reduction; the cathodic limiting
current is the discharge of cations or the donation of electrons to the solvent. EDA may be purified
by repeated refluxing and distillation from sodium [A149]. It is extremely hygroscopic. The TLV is
10 ppm.
Other primary or secondary, aliphatic or cyclic amines may be used with similar results.
III.A.3 AproTIC SoLVENTS

The use of aprotic solvents is of interest in many cases in which aqueous solutions lack desired
or have undesired properties. The scarcity of protons makes it generally simpler to elucidate the
mechanism of an electrode reaction for several reasons. The intermediates (e.g., radical anions) are
more stable in the absence of protons, and the reaction scheme becomes simpler.
The scarcity of protons in aprotic solvents also makes it possible for added reagents (e.g., electro-
philes) to compete successfully with protons for the intermediates.
“Dry” aprotic solvents usually contain some water, which is especially of importance in
v oltammetric studies in which the concentrations of water and substrate are about equal. The influ-
ence of a certain molar concentration of water depends on the solvent, the supporting electrolyte, and
the substrate.
In certain solvents, such as DMF and DMSO, water is a rather poor proton donor [A150], and
other impurities may be responsible for the protonation of the basic intermediates (radical anions,
anions, and dianions). During preparative experiments, the impurities may be reprotonated by water
or, in case tetraalkylammonium salts (except tetramethylammonium salts), are used as supporting
electrolyte, by attack on the cations (Hofmann elimination). Treatment of the medium with active
alumina may lower the concentration of such protonating impurities [A51,A151].
When choosing a drying agent, one must take into account that its affinity to water is different
in vacuum and in a solvent, so the activity of a drying agent may be different in various solvents.
When deuterium oxide is added to an aprotic solvent containing tetraalkylammonium salts
to promote incorporation of deuterium in the product, the base-promoted Hofmann elimination
may become a problem, as the deuterium oxide becomes diluted with water. This can largely be
avoided by running the reduction in the presence of a suspension of dry silica, which prevents the
medium from being basic enough for the elimination to occur; the deuterium oxide adsorbed on
the silica is in most cases sufficiently acidic to prevent Hofmann elimination. However, when the
parasitic reaction is hydrogen abstraction from the solvent or supporting electrolyte, silica has no
effect.
Controlled addition of a suitable proton donor or electrophile (reductions) or nucleophile (oxi-
dations) is often useful in determining a reaction mechanism. The strength of a proton donor may
vary from perchloric acid through acetic acid and a phenol to an alcohol; C acids, such as malo-
nic ester, or N acids, such as urea, may also be used. Used as bases may be pyridine, carboxylate
ions, alkoxides, or salts of malonic ester. Sometimes it is of interest to determine whether it is the
basic or the nucleophilic properties of the compound that are important. The use of two bases with
approximately the same pK values but widely differing in nucleophilicity, such as pyridine and a
2,6-dialkylpyridine, might answer the question.
In the absence of proton donors, the “aprotic” solvent may act as a proton donor; the conjugate
base of the solvent may act as a nucleophile toward substrate or intermediates.
Electrochemical phenomena may also be simplified in organic solvents, compared with aqueous
solutions, because of the less important role adsorption plays in organic solvents.
III.A.3.a Acetonitrile
Acetonitrile (MeCN) is one of the most used polar aprotic solvents for both anodic and cathodic
reactions. It is an excellent solvent for many organic substrates and quite a few organic and inor-
ganic salts; it is miscible with water. Salt solutions show a reasonably high conductivity due to its
rather high dielectric constant (ε = 37). MeCN is somewhat toxic, with a recommended maximum
air concentration of 20 ppm.
Besides having good electrochemical properties, acetonitrile is an unusually good solvent for
UV spectroscopy, being transparent until about 190 nm. It is furthermore a convenient solvent for
electron spin resonance spectroscopy, which is valuable for the investigation of radicals produced
during electrolysis. For use in preparative electrochemistry, its liquid range (−45 to 82°C) is suf-
ficient for most purposes and its relatively low boiling point makes the removal of the solvent easy.
On gas–liquid chromatography, tailing may occur, unless a suitable polar column is used.
Acetonitrile has a wide, usable potential range in both the anodic and cathodic directions. The
limit is set by the electrode reaction of the supporting electrolyte in both directions. In the pres-
ence of sodium or lithium ions, their discharge sets the limit; the sodium subsequently reacts with
acetonitrile, whereas lithium does not. Quaternary ammonium ions are reduced with dealkylation.
Perchlorate ions, a widely used supporting electrolyte, are discharged to perchlorate radicals, which
probably rapidly form oxygen and chlorodioxide radicals [A50]. Transfer of protons in acetonitrile
is a rather slow process. Its autoprotolysis constant is 33.2. In DMSO, MeCN has pK A = 31.3 [A152].
MeCN is less apt to donate hydrogen atoms than DMF. Anhydrous perchloric acid in MeCN has
been prepared by oxidation of H2 to H+ at a platinized platinum electrode in a solution of TBA+ClO4−
in MeCN [A153].
Useful supporting electrolytes in acetonitrile are NaClO4, LiClO4, tetrabutylammonium salts, as
well as other tetraalkylammonium salts. AgNO3 and AgClO4 are very soluble in acetonitrile; AgCl
is somewhat soluble, especially in the presence of an excess of chloride ions. It is possible to make
CV in MeCN with TEACF3SO3 or CF3SO3Na as supporting electrolyte near the supercritical condi-
tions, but the resistance is too high for preparative reactions [A154].
The Ag/Ag+ electrode [A155,A156], which is reversible in acetonitrile, may be used as refer-
ence electrode. Quite often, an aqueous calomel electrode with a suitable liquid junction is used
[A3]; a comparison of different reference electrodes has been made [A4]. The Hg/Hg(I) is not
stable in acetonitrile, as Hg(I) decomposes [A157]. A platinum electrode coated with a film of
poly(vinylferrocene) is a stable reference electrode in MeCN [A158].
Commercial acetonitrile usually contains impurities, such as acrylonitrile, acetic acid, alde-
hydes, amines, and water. Several methods of purification [A159–A161] have been proposed: one
is to distill it several times from P2O5 followed by fractionation from K2CO3 [A162]; a pure prod-
uct may be obtained, but the procedure is time consuming and wasteful due to polymerization of
MeCN; polymerization may be avoided by using B2O3 instead of P2O5 [A163].
CaH2 treatment of MeCN has been recommended [A141], but it does not remove traces of aro-
matic hydrocarbons and is a surprisingly ineffective drying agent in MeCN [A163]. For removal of
acrylonitrile, which boils 4°C lower than MeCN, treatment with NaH [A164] or azeotropic distilla-
tion with ethanol [A165] has been recommended.
Removal of impurities by reaction in turn with benzoyl chloride and KMnO4 followed by care-
ful distillation gives a product suitable for both electrochemical and spectroscopic work [A166].
Alternatively, acetonitrile is treated with N2O4, then with CaH2, fractionated under N2 from
CaH2, and the product further purified by letting it run through a column of activated alumina
[A51,A165,A167].
Water may be removed from commercial MeCN by azeotropic distillation [A62,A168] or by

treatment with molecular sieves 3A; 3A is much more efficient than 4A for drying MeCN [A163].
The procedures recommended by IUPAC for purification are described in Reference A169.
As is the case for other relatively inert solvents, it is unlikely that an all-purpose purification
procedure can be devised that will give optimum results in all possible applications. Consequently,
purification should be tailored to the intended use of the solvent.
Pure acetonitrile is not particularly hygroscopic. The product obtained by these procedures can
be stored for several months without deterioration; the water content is approximately 1 mM. It is
advisable to use the same glass apparatus repeatedly for the purification and storing of acetonitrile.
Electrolysis in MeCN, in the absence of added proton donor may produce the anion of MeCN
(CH2CN)−, which may act as a nucleophile toward electrophilic centers [A170].
At a Pt anode, the solvent system MeCN/TBABF4 breaks down to an adduct, CH3CNBF3,
whereas the cathodic breakdown mainly gives the anion of 3-amino crotonitrile; in the presence of
water, the anion of acetamide is also formed and the breakdown commences at much less negative
potentials [A171].
Other nitriles, aliphatic and aromatic, have been investigated as solvents for electrolysis.
Butyronitrile has been suggested as the solvent of choice for low-temperature electrochemistry
[A172], and propionitrile has in some cases been employed, as it is less hygroscopic than MeCN
[A173]. Benzonitrile might be considered when hydrogen atom abstraction from the solvent is
undesirable.
III.A.3.b Dimethylformamide
Dimethylformamide (DMF) is a polar solvent with a dielectric constant (ε = 37) comparable to
that of acetonitrile. It is a good solvent for most organic compounds and also for many organic and
inorganic perchlorates and organic fluoroborates. Owing to these properties, DMF has been widely
used in electrochemical work. DMF is, however, susceptible to hydrolysis, which yields the easily
oxidizable dimethylamine and the reducing agent formic acid.
DMF has an acceptable liquid range (−61 to 153°C), although the boiling point is near the upper
limit for its convenient removal by distillation during the workup. DMF is inferior to acetonitrile as
a solvent for UV spectroscopy. Contact with the skin and vapor concentrations over 10 ppm should
be avoided.
For reductions, DMF has a usable potential range comparable to that of acetonitrile, but it is
inferior for oxidations. In the presence of inorganic ions, their discharge is the cathodic limiting
reaction, whereas it is more uncertain whether it is the solvent or the cation that is reduced in solu-
tions of tetraalkylammonium ions. The anodic limiting reaction at a Pt electrode is an oxidation of
DMF, which involves the removal of an electron from the amide nitrogen. Its autoprotolysis constant
is 29.4. DMF is a better hydrogen atom donor than MeCN and DMSO.
As supporting electrolyte, tetraalkylammonium perchlorates or fluoroborates are mostly used,
but LiCl or NaClO4 may also be employed. The reference electrode may be a modified Ag/AgCl
electrode [A10,A12], a Cd(Hg)/Cd2+ electrode [A10,A12], Na(Hg)/Na+ electrode [A11], or silver/
silver cryptate electrode [A174].
For many purposes, the commercial reagent-grade DMF, dried with molecular sieves, can
be used; DMF decomposes on distillation at atmospheric pressure. The most convenient way to
purify DMF is probably to let it pass through a column [A165] of alumina (e.g., ICN Alumina
N-Super I). Other methods involve drying (CuSO4 [A167], which also removes amines), azeo-
tropic distillation with benzene, or percolation through molecular sieves [A176] followed by frac-
tional distillation at a reduced pressure. DMF is difficult to obtain in an anhydrous form, but for
most purposes, a small water content is not critical. An impurity of N-methylformamide may
act as a proton donor or otherwise interfere in the follow-up reactions [A177]. DMF should be
stored in the dark under nitrogen. The different purification methods have been compared and
discussed [A178].
III.A.3.c N-Methylpyrrolidone
DMF has certain disadvantages that can be traced to its hygroscopic properties and rather easy
hydrolysis; N-methylpyrrolidone (NMP), which is an N-disubstituted amide just like DMF, is less
apt to hydrolyze owing to its cyclic structure. Furthermore, the product of hydrolysis is not a reduc-
ing agent as is formic acid formed from DMF. Although only a limited number of experiments in
NMP have been done [A63,A179], it seems probable that NMP will replace DMF in a number of
cases because of its higher stability [A180]. Vapor concentrations over 100 ppm should be avoided.
Like DMF, NMP is of limited value for oxidations but useful for cathodic reactions. Its dielectric
constant is 32, and it is able to dissolve the same types of salts and organic compounds as DMF.
NMP has a liquid range of from −24 to 205°C; the useful potential range is approximately the same
as for DMF. Mercury in contact with its oxidation products has been used as reference electrode; it
is more stable than the Ag/Ag+ electrode [A63,A179].
Other organic amides, such as formamide, N-methylformamide, N-methylacetamide, and tet-
ramethylurea (TMU), have been investigated as solvents for electrochemical use primarily due to
their high dielectric constant; none of them, however, seem to offer distinct advantages over DMF
or NMP, and in some respects, they are inferior. N,N-Dimethylacetamide may be purified by distil-
lation in vacuum [A181].
III.A.3.d 3-Methyl-2-Oxazolidinone (3M2O)

3M2O is a colorless, nonvolatile (kp, 87–90°C) solvent with a high dielectric constant (77.5). It may
be purified by vacuum distillation over BaO. With tetrabutylammonium perchlorate (TBAP) as
electrolyte, the cathodic limit is −2.9 V (aqueous SCE); the anodic limit at a Pt anode is +1.3 V. The
suitability of 3M2O for voltammetry has been investigated [A180].
III.A.3.e Hexamethylphosphoramide (HMPA)

HMPA is a polar solvent that is remarkable for its ability to solvate electrons. Even in a mixture
with ethanol (67 mol% ethanol and 33 mol% HMPA), reductions via solvated electrons may take
place [A180–A184]. It has been suggested that HMPA is selectively adsorbed at the electrode, thus
providing a layer of low proton activity near the electrode.
The liquid range of HMPA is 7.2–235°C; its dielectric constant is 30 (20°C). HMPA solvates
cations strongly, whereas anions are less solvated. Unlike carboxamides, such as DMF, it is not
attacked by aqueous alkali at t < 80°C, and it is very resistant toward nucleophilic attack [A184] but
forms peroxides under the influence of light and oxygen [A183].
HMPA is completely miscible with water; it can be extracted from water by chloroform, which
forms a complex with HMPA [A185], K(CHCl3/H2O) = 5.5 [A186]; HMPA is somewhat more basic
than DMF. HMPA dissolves such salts as LiCl, LiClO4, NaClO4, and R4NClO4; the Ag/Ag+ may be
used as reference electrode [A64]. The solvation effect of the cation of the supporting electrolyte in
HMPA has been investigated [A187]. Using R4NClO4, the accessible potential range is from +0.14
to −3.35 V (Ag/Ag+) at a mercury electrode [A183]. HMPA can be purified by fractionation under
vacuum, boiling point 88–92°C (3 mm), 68–70°C (1 mm).
Reflux over BaO, followed by fractionation under vacuum, reflux over sodium, and finally
vacuum distillation have been recommended for purification [A187]. Alternatively, fractional dis-
tillation over CaH2, followed by purification through a column of activated alumina and standing
over pyrene and sodium, produced a product that after distillation on a vacuum line contained
only a negligible amount of impurities [A188]. The purification of HMPA has been critically
discussed [A189].
Just like DMF, HMPA is not suitable for anodic reactions, since the amide nitrogen loses an
electron easily. For cathodic reactions, the useful potential range extends, in the presence of LiCl,
to the value at which electrons are given off to the solution. HMPA has not been used widely in
electrochemical experiments, and although its special properties are useful in electrochemistry, it
should be used only when sufficient precautions have been taken with regard to its carcinogenic
and other toxic properties [A66]. Tetramethylurea (TMU) may in some cases be used as a nontoxic
replacement for HMPA [A190]. TMU may be purified by distillation from CaH2.
III.A.3.f Pyridine
Pyridine is a reasonably strong base and a good nucleophile. Although its dielectric constant is
rather low (ε = 12), many salts are soluble in pyridine and the solutions have good conductivity. In
contradistinction to most bases, pyridine, which is a π-electron-deficient heteroaromatic compound,
is rather resistant toward oxidation.
Pyridine has a liquid range from −41 to 115°C; it is miscible with water and a good solvent for
many organic compounds. Such salts as LiNO3, LiCl, LiClO4, NaI, KSCN, and tetraalkylammo-
nium salts are soluble in pyridine. As a reference electrode, the Ag/Ag+ [A17] or the Hg pool elec-
trode can be employed. Solute–solvent interactions have been discussed [A65].
The useful potential range is from about −2.3 V [A17] (versus Ag/Ag+ electrode, DME, Bu4NI)
to +1.4 V vs. Ag/Ag+, graphite electrode/LiClO4 [A65]. The cathodic limiting reaction might be
the discharge of the cation, whereas an electron abstraction from pyridine is the anodic limiting
reaction, in which probably 2-pyridylpyridinium ion is formed.
Besides being used as a solvent, pyridine has been employed as a nucleophile that is oxidiz-
able with difficulty [A156]. Reagent pyridine is satisfactory for most purposes; it may be dried
with molecular sieves, type 5A. A recommended procedure for obtaining pure pyridine has been
published [A191]. The TLV is 5 ppm.
III.A.3.g Dimethyl Sulfoxide (DMSO)

DMSO is an excellent solvent for many inorganic salts and organic compounds. It is difficult to
reduce and fairly resistant to electrolytic oxidation. Its dielectric constant is high (ε = 47). It thus
has many of the qualities desirable for a solvent for electrolysis, and it shows promise of being
one of the most important electrochemical media [A192]. The liquid range is from 18°C to 189°C,
which makes it somewhat inconvenient to get rid of DMSO in the workup. When used as solvent for
electrolysis, it must be considered that DMSO is not always inert but has a fair reactivity in certain
reactions. DMSO is unfit for UV spectroscopy. Its autoprotolysis constant is 31.8.
DMSO has low toxicity; it is, however, transported through the skin very rapidly. Thus, minutes
after applying a drop of DMSO to the palm of the hand, its sweetish taste can be detected in the
mouth. It may carry with it dissolved toxic materials that otherwise would be unable to penetrate
the skin.
Many salts are soluble in DMSO, so the choice of supporting electrolyte is less restricted than
in most other nonaqueous solvents. In general, perchlorates, even KClO4, nitrates, and halides, are
soluble, whereas fluorides, cyanides, sulfates, and carbonates are not; thus, not only NaClO4, LiCl,
NaNO3, and tetraalkylammonium salts can be used but also such salts as NH4PF6 and NH4SCN. The
ability of DMSO to solvate ions is also of importance in the indirect electrolytic hydrodimerization
of, for example, acrylonitrile using Na(Hg) [A193].
The equilibrium constant of the self-ionization of DMSO is 5 × 10 −8 (25°C); the conjugate base
(CH3SOCH2)−, which is formed when DMSO acts as a proton donor during a reduction, is a rather
strong base and a fairly good nucleophile, which may attack electrophilic centers or radicals [A194].
The potential range of DMSO in the cathodic direction is at an Hg electrode limited by the
discharge of the cation. Potassium and sodium react with DMSO, whereas lithium does not; tet-
raalkylammonium ions are reduced to about −2.8 V (SCE) [A195]. The anodic limiting reaction at
a Pt electrode is the oxidation of DMSO; probably one of the nonbonding electrons is lost, but the
limiting reaction has not been investigated yet.
As reference electrode [A10] for polarographic work, an aqueous or methanolic calomel elec-
trode, connected to the DMSO solution with a suitable salt bridge to avoid contamination, has been
used. The most stable reference electrodes in DMSO seem to be the amalgam electrodes, such as
Tl(Hg)/TlCl [A21] or Li(Hg)/LiCl [A196].
DMSO is somewhat hygroscopic, and the main impurity in a good commercial grade of DMSO
is water; the odor is due to dimethyl sulfide. For many purposes, DMSO can be used as received or
after drying either by shaking with CaO–MgO or by passing through a column of molecular sieves.
For further purification, fractional distillation or crystallization may be used. It has been recom-
mended [A197] that a fractional crystallization be done followed by two fractional distillations in
vacuo, one through a column packed with activated carbon and one through a spinning band col-
umn. The pure DMSO must be handled without contact with humidity.
The different purification procedures have been discussed [A198].
III.A.3.h Sulfolane
Among sulfones, sulfolane (tetrahydrothiophen-1,1-dioxide, tetramethylene sulfone) shows promise
for electrochemical use. It has a wide liquid range (28.6–285°C); on dissolving 0.1 M salts in sulfo-
lane, its melting point is depressed below 25°C. Sulfolane has a relatively high dielectric constant
(43 at 20°C), it is chemically stable toward both reducing and oxidizing agents, and it has a fair dis-
solving power for inorganic salts. One of its drawbacks is that it is rather hygroscopic.
The accessible potential range is large in both the anodic and cathodic directions. The limiting
cathodic reaction seems to be the discharge of the supporting electrolyte, whereas the limiting
anodic reaction probably is the oxidation of the solvent. With NaClO 4 as supporting electrolyte,
the anodic limit at a Pt electrode is about 2.3 V and the cathodic limit about −4 (versus Ag/Ag+
electrode) [A67].
As a supporting electrolyte, NaClO4, LiClO4, NH4PF6, and quaternary ammonium compounds
can be used. The Ag/Ag+ [A67,A199] or Ag/AgCl [A200] electrode or an aqueous SCE [A201] with
a suitable salt bridge can be used as the reference electrode.
Sulfolane may be purified by fractional crystallization followed by fractional distillations at
reduced pressure [A201]; alternatively, treatment with aqueous hydrogen peroxide, followed by
extraction with CH2C12 and fractional distillation, may be employed [A67]. The purification proce-
dures have been discussed [A202].
Sulfolane is an alternative to acetonitrile or nitromethane as a solvent for anodic reactions; in
reductions, it generally offers no advantages over such solvents as MeCN, DMF, or DMSO, but for
anodic fluorination, sulfolane might be better than MeCN, as a competing acetamidation is avoided
(Chapter 20).
Among other sulfones, dimethyl sulfone has been used as electrochemical medium [A203,A204];
its high melting point, 109°C, makes it less suitable for organic compounds.
III.A.3.i Propylene Glycol Sulfite

A series of other sulfur-containing solvents has been investigated for electrolytic use. Of these,
propylene glycol sulfite [A205], a derivative of 1,3,2-dioxthiol, was found most suitable. It has a
dielectric constant of 33, forms solutions with good conductivity with such salts as LiClO4, and does
not react with lithium. It has not yet been used for organic electrolysis.
III.A.3.j Nitromethane
Nitromethane is one of the few solvents useful for anodic reactions, among them anodic coupling of
aromatic hydrocarbons. Its application for cathodic reactions is limited, but in some cases in which
its unreactivity toward certain active halogen compounds is valuable, it may be used. The liquid
range of nitromethane is −29 to 101°C; its dielectric constant is 37, but the dissociation of salts is not
as high as could be expected.
Nitromethane dissolves rather few inorganic salts; LiClO4 [A206], Mg(ClO4)2, and tetrabutyl-
ammonium salts can be used as supporting electrolyte. The Ag/Ag+ or Ag/AgCl electrode can be
employed as the reference electrode [A35].
At a platinum electrode, potentials of about 3 V (vs. Ag/AgCl) can be reached, and the limiting
reaction is the discharge of the supporting electrolyte. The useful range in cathodic direction is very
dependent on the water content.
Nitromethane has been purified by repeated washings with bicarbonate, sulfuric acid, and
water, followed by drying and fractional distillation; the water content of the product is 5–8 mM.
Alternatively, fractional distillation at reduced pressure followed by repeated fractional freezing
may be employed [A207]. The TLV is 100 ppm.
III.A.3.k Nitrobenzene
Nitrobenzene has been used for electrolysis [A208]; it was found that certain radicals were rather
stable in this solvent. Nitrobenzene has a liquid range from 5.7 to 210.9°C; Bu4NClO4 may be used
as supporting electrolyte. An aqueous SCE separated from the solution by a suitable bridge with
porous glass has been used as reference electrode. Nitrobenzene may be purified by passing it
through a column of alumina followed by a distillation in vacuo.
III.A.3.l Propylene Carbonate (PC)

PC is of potential use in organic electrochemistry [A68,A209,A210]. It has a high dielectric constant
(ε = 69) and a wide liquid range (−49 to 242°C), but it is more reactive than acetonitrile, and the
potential limit for anodic reactions is lower than for acetonitrile. It has so far been used mostly for
electrochemical generation of cation radicals [A68].
The cathodic limiting reaction of PC containing LiClO4 has been shown [A211–A214] to be a
reduction to propene and carbonate. This reductive elimination is analogous to the reduction of
vicinal halogen compounds to alkenes. The anodic reaction is an oxidation to CO2 [A213,A214].
PC decomposes slowly on standing to allyl alcohol and CO2; after standing for a year, small
amounts of allyl alcohol could be detected. Protons increase the rate of decomposition [A215].
With LiAsF6, the oxidation limit of PC is 4.0 V vs. Li+/Li [A216].
As a reference electrode, an Li/LiCl electrode, which in the presence of excess tetrabutylam-
monium chloride is an electrode of the second kind, may be used [A217]. An Ag/AgClO4 refer-
ence electrode with an NaClO4 salt bridge has been used [A33]; AgCl/Ag [A218] and TlX/Tl
[A219] reference electrodes have also been employed. The purification of PC has been discussed
[A220].
III.A.3.m Benzene and Chlorobenzene

It has been possible to use these nonpolar solvents for electroanalytical measurements by employing
a minute working electrode [A221], an ultramicroelectrode, or using a benzene solution containing
a crown ether (15-crown-5) and sodium tetraphenylborate [A222].
Tetrahexylammonium perchlorate (THAB) and tetrabutylammonium tetrafluoroborate have
been used as supporting electrolyte in benzene and chlorobenzene, respectively. The latter was
suggested [A221] to be an excellent solvent for the study of reversible oxidations and reductions of
aromatic compounds. The TLV for chlorobenzene is 75 ppm.
Benzene and even aliphatic hydrocarbons [A85] have been used as solvents in SPE cells.
III.A.3.n Ethers
Ethers, such as THF and 1,2-dimethoxyethane, have low dielectric constants (7.4 and 7.2, respec-
tively), and the choice of supporting electrolyte is very limited. The ethers are difficult to reduce
and are inert toward many metalorganic reagents [A36] that are soluble in the ethers. Ethers
are thus suitable as a medium for the anodic addition of Grignard reagents to olefins [A223].
Dimethoxyethane and polyethylene glycol dimethyl ethers have the ability to solvate electrons
[A224]. Dissociation constants for some acids and the relative strength of some bases in THF have
been determined [A225].
As a supporting electrolyte, NaClO4 or LiClO4 may be used in both solvents; TBAI in THF and
TBAP in dimethoxyethane have also been employed. As a reference electrode, the Ag/Ag+ electrode
functions satisfactorily [A36]. Ferrocene and bis(biphenyl)chromium have also been used as refer-
ence electrodes in THF [A226].
The ethers form peroxides. These can be removed by distillation from LiAlH4. They must be
stored under nitrogen or distilled from LiAlH4 or Na directly into the electrolytic cell. If the water
content of DME or THF is not negligible, the cathode may be passivated by a layer of a hydroxide
formed during electrolysis, when an alkali metal salt is used as the supporting electrolyte [A227].
Purification of THF using sodium dianions of benzophenone and anthracene has been described
[A228]. Protons and Lewis acids (EGA) can induce polymerization of THF; this may cause prob-
lems at the anode. The TLV for THF is 200 ppm.
III.A.3.o Methylene Chloride and 1,1,2,2-Tetrachloroethane

Electrolysis may be carried out in methylene chloride. It dielectric constant is low (ε = 9), and only
the larger tetraalkylammonium salts are soluble in methylene chloride.
Methylene chloride has been used for both anodic and cathodic reactions. The major advantages
of using methylene chloride seem to be that certain cation radicals are more stable in methylene
chloride than in the solvents usually employed in electrochemistry [A229,A230]. A disadvantage
is that chloride ions produced at the cathode may diffuse to the anode compartment and interfere
with the anodic reactions. This can partially be avoided by the addition of small amounts of acetic
acid to the catholyte whereby the cathodic reaction becomes an evolution of hydrogen rather than
formation of chloride ions.
In electrosynthesis in systems of two immiscible liquids and a phase transfer catalyst, methylene
chloride is in many cases preferred as the organic solvent.
The addition of TFA and its anhydride (TFAn) to CH2Cl2 enhances the stability of cation radi-
cals in the solution. A mixture of CH2Cl2–TFA–TFAn of 45:1:5 has been recommended [A49]. TLV
is 100 ppm.
1,1,2,2-Tetrachloroethane has been found to be a good solvent for anodic investigations of
fullerenes (Chapter 21). It may be purified by refluxing over CaH 2 and dried over P2O5 under high
vacuum [A231].
III.A.3.p Sulfur Dioxide

Sulfur dioxide is a solvent of low nucleophilicity and may be used when nucleophilic trapping by
solvent is to be avoided. Its liquid range is somewhat inconvenient (−75 to −10°C), but its dielectric
constant is reasonably high (17.6 at −20°C).
The SO2 may be purified by washing with concentrated sulfuric acid, percolated through P2O5,
and finally treated through a column of basic alumina [A232,A233].
As a supporting electrolyte, Bu4NClO4 or Pr4NPF6 may be used [A234–A236]; at 0.2 M solution
of these salts, it has a conductivity of about 9 × 10 −3 Ω−l cm−1 at −22°C. CsAsF6 gives a potential win-
dow to about 5 V vs. SCE, enough to oxidize methane; however, the solubility (and thus conductivity)
of CsAsF6 in SO2 is too low to allow a preparative oxidation [A232]; however, Bu4NBF4 has been
used for preparative methylthiation [A237]. As a reference electrode, Ag/0.1 M AgNO3 in acetoni-
trile has been used. The anodic range of perchlorates or hexafluorophosphates in sulfur dioxide is
large. AlCl3 may also be used as a supporting electrolyte [A238]; cation radicals are considerably
stabilized in this medium.
III.A.4 SaLTS
In certain electrolytic media, the concentration of salts is so high that the medium could be
regarded as consisting of a solvated salt. This is thus the case in the strong solutions (10 M) of
many salts in ammonia in which the vapor pressure of ammonia at ambient temperature is less
than 1 atm. It also applies to the strong solutions of tetraalkylammonium p-toluenesulfonates in

water, used sometimes in organic electrochemistry.
A genuine liquid salt is tetrahexylammonium benzoate (THAB) [A40], which is a viscous liquid
capable of acting as both solvent and supporting electrolyte; it has, however, a rather high resistance.
Although it is a fairly polar solvent, THAB is miscible with benzene, toluene, and carbon tetrachlo-
ride; a mixture of THAB–toluene (75:25) has a rather low specific resistance of 3.8 kΩ and a much
lower viscosity than pure THAB, which is about as viscous as glycerol. Relatively little water is
miscible with THAB; addition of 1% by volume of water to THAB results in a two-phase system.
THAB is soluble in acetone.
THAB is useful for reductions; the cathodic limit at an Hg electrode is about −2.6 V versus
Ag/AgCl; at a platinum electrode, the anodic limit is at about 0.3 V.
THAB has been prepared by neutralizing tetrahexylammonium hydroxide, obtained from the
iodide by treatment with Ag2O, with benzoic acid and evaporation of the water. The analysis of the
dried product corresponds to a hemihydrate. The material is somewhat hygroscopic but can be dried
by brief heating to 90°C.
Voltammetry has also been made in (toluene)3tetrabutylammonium tetrafluoroborate; the resis-
tance of the solution is between that of DMF and THF [A239] but closer to that of DMF. On addition
of proton donors, a low “buffer capacity” of the solvent is observed.
Aluminum chloride in mixture with an alkylpyridinium chloride, preferentially butylpyridinium
chloride, has certain possibilities as a medium for studying electrochemically generated cation radi-
cals. The 0.8:1 AlCl3–BuPy+Cl− mixture is molten at room temperature but has generally been used
at 40°C [A240].
A mixture of l-methyl-3-ethylimidazolium chloride with aluminum chloride also gives an
ionic liquid that may be used as electrolytic medium [A241]. The medium is not quite inert;
for example, quinone reacts with an excess of chloride to 2-chlorohydroquinone in an acid-
catalyzed Michael addition [A242]. As a reference electrode, an aluminum wire was used.
l-Methyl-3-ethylimidazolium chloride is in MeCN reduced at −2.35 versus Ag in 0.1 M TBAP
[A243].
At higher temperature, certain quaternary ammonium salts (40–150°C) [A244] may be used as
media for electrolysis.
III.A.5 SUpErCrITICaL FLUIDS

SCFs have been used mainly for selective extraction of compounds; the solubility of a compound
in a given solvent is in many cases vastly different under ambient and supercritical conditions.
Thus, supercritical water dissolves both polar and nonpolar compounds, which may be explored
in electrochemistry. When temperature and pressure approach the critical values, the internal
structure of the solvent is loosened and the viscosity, the dielectric constant, and the density
diminish; the dielectricity constant ε of water thus diminishes from 80 at 25°C to 5.2 at 647°C
at 221 bar [A245].
Cyclic voltammetry in supercritical water-0.2 M NaHSO4 [A246] and ammonia-0.14 M CF3SO3K
[A134,A246] of some organic compounds shows that this electroanalytical technique was appli-
cable under these conditions. The behavior of phenazine in NH3 at −40°C and under supercritical
conditions, for example, was analogous; two reversible reductions were found in both cases [A246].
Dimethyl carbonate has been prepared from CO and MeOH on anodic oxidation in a supercritical
mixture of CO2 and MeOH [A247].
Supercritical carbon dioxide (scCO2) has a dielectric constant ε = 1.6 (cyclohexane ε = 2.0), and
even though tetrakis(decyl)ammonium tetraphenylborate has some solubility in scCO2, the conduc-
tivity is too low for practical electrochemistry [A248]. 1,1,1,2-Tetrafluoroethane (HFC 134a) has a
higher polarity in the supercritical state, and well-behaved CV may be obtained; with TBAClO4,
a potential “window” of about 9 V has been obtained [A249].
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III.B APPENDix B*: ELEcTROLYTES

The passage of electric current through a nonmetallic liquid is dependent on ions. The choice of
electrolyte depends on such properties as its solubility, dissociation constant, mobility, discharge
potential, and protic activity. It is desirable to employ a salt with high solubility, complete dissocia-
tion, high mobility of the ions, and a numerically high discharge potential. The role of adsorption
of ions at the electrode is discussed elsewhere. The electrolyte may influence the rate constant for
electron transfer from an electrode to a substrate.
III.B.1 ANIoNS
The choice of anion is of most importance in anodic reactions in which the choice may influence the prod-
uct distribution. Unless the oxidized anion is desired in an indirect electrolytic oxidation (Chapter 29)†,
an anion that is oxidizable with difficulty, such as perchlorate, tetrafluoroborate, hexafluorophosphate,
or nitrate, is chosen. In aqueous solution, the choice of anion is less critical than in nonaqueous solvents.
In cathodic reactions, the choice of cation has highest priority, and the anion is generally selected on the
basis of solubility of the salt or the ability of the anion to assist in dissolving the substrate.
III.B.1.a Perchlorate
The perchlorate ion has a high anodic discharge potential, and only in a few solvents, such as aceto-
nitrile or nitromethane, is the perchlorate ion oxidized in preference to the solvent. When oxidized,
the primarily formed perchlorate radical decomposes into oxygen and chlorodioxide radical [B1].
Caution must be exercised when handling perchlorates. Silver perchlorate is explosive; grinding it in
a mortar should be avoided. For use in reference electrodes, it may be prepared by anodic dissolution of
silver in a perchlorate medium [B2]. Evaporation of solutions of organic perchlorates is discouraged but,
if necessary, must occur in vacuo and at moderate temperatures. Even sodium perchlorate, which can be
dried at 100°C without undue risk, may cause explosions when heated with an organic solvent.
Sodium perchlorate is soluble in many organic solvents. It is hygroscopic but can be dried at
110°C. Drying NaClO4, H2O often results in a sintered mass that must be broken and dried. By
recrystallization of NaClO4 at temperatures about 80°C, the anhydrous salt can be obtained, which
can be dried without difficulty. Lithium perchlorate is very hygroscopic.
Tetraalkylammonium perchlorates are less hygroscopic, and some of them may be recrystallized
from water; they are useful for voltammetric studies in organic solvents.
III.B.1.b Tetrafluoroborate
The discharge potential of the tetrafluoroborate ion is slightly more positive [B3] than that of the
perchlorate ion. Tetrafluoroborates do not have a tendency to explode, and they are recommended
instead of perchlorates for use in preparative work when the solvent must be removed during the
workup.
It has been reported that BF4− as anion in a supporting electrolyte in DMF gives in CV an anodic
peak around 0.8 V versus SCE at a glassy carbon electrode [B4].
* The following text is taken from Lund H., in Lund H. and Hammerich O., Organic Electrochemistry, 4th edn., Marcel
Dekker, New York, 2001, pp. 272–277; references have been renumbered, cross-references have been adapted, and refer
to chapters of the present, fifth edition if not otherwise noted; some obvious (typographical) errors in the original have
been corrected.
† This chapter reference refers to the forth edition.
Tetrabutylammonium tetrafluoroborate is only slightly soluble in water but is soluble in organic

solvents. It is prepared by mixing solutions of NaBF4 with a soluble tetrabutylammonium salt. Its
solubility properties are convenient for its use in preparative electrolysis. During the workup, the
organic solvent may be diluted with water, whereby the salt precipitates are recovered for future use.
It may be recrystallized from toluene; the solution is dried by azeotropic distillation (or by molecu-
lar sieves A4); the compound crystallizes slowly on cooling [B5].
III.B.1.c Hexafluorophosphate, Hexafluoroarsenate

Hexafluorophosphates are slightly more resistant toward anodic oxidation than tetrafluoroborates and
perchlorates [B3]; in a 0.1 M solution of these salts in acetonitrile, the potentials (versus Ag/0.l M Ag+
electrode) at a platinum disk electrode (0.12 cm2) at 1 mA were for perchlorate, 2.48 V; for tetrafluo-
roborate, 2.91 V; and for hexafluorophosphate, 3.02 V [B3]. Hexafluoroarsenates have been used in
liquid SO2 [B6,B7].
III.B.1.d Trifluoromethanesulfonate
The trifluoromethanesulfonates have certain advantages over perchlorates (nonexplosive)
and tetrafluoroborates (even less reactive toward oxidizing agents) [B8]. The tetraalkylam-
monium trifluoromethanesulfonates are just as soluble or more soluble in the commonly
used organic solvents than the corresponding perchlorates or fluoroborates. They can be
prepared either by metathesis or by alkylation of a tertiary amine by an ester of trifluoro-
methanesulfonic acid.
III.B.1.e Nitrate
Nitrate ion is not as resistant to oxidation as perchlorate or tetrafluoroborate; in nitromethane [B9]
solution, it is oxidized anodically to NO2+ and oxygen, and the NO2+ reacts either with the water
always present in “dry” organic solvents to form nitric acid or with nitrate ion to form N2O5. Nitrates,
to a higher degree than perchlorates [B10], form ion pairs in some solvents. Tetrabutylammonium
nitrate can be prepared conveniently by mixing an aqueous solution of NaNO3 with the commer-
cially available tetrabutylammonium hydrogen sulfate. The salt is then extracted into methylene
chloride, giving an almost quantitative yield of Bu4NNO3.
III.B.1.f Aromatic Sulfonates

The use of aromatic sulfonates stems from their ability to assist the solution of organic substrates in
an aqueous medium. This “hydrotropic” effect [B11–B13] is accentuated if a quaternary ammonium
sulfonate, rather than an alkali metal sulfonate, is used.
The aromatic sulfonates have been employed mostly for reductions, but they would be expected
to be reasonably stable toward oxidation. To obtain a reasonable hydrotropic effect, rather high
concentrations are used; in the original hydrodimerization reaction of acrylonitrile, the medium
may be regarded as either a solution of tetraalkylammonium p-toluenesulfonate in water or the salt
containing some water.
III.B.1.g Carboxylate Ion

In the Kolbe reaction and in anodic carboxylation reactions, salts of carboxylic acids function as
both substrate and electrolyte. Usually the presence of other anions diminishes the yield of the
Kolbe reaction, whereas the presence of anions that are oxidizable with difficulty, like bicarbonate
or perchlorate ions, favors the related Hofer–Moest reaction.
For reductions in aprotic media, tetraalkylammonium salts of derivatives of oxalic and formic
acid may be employed; in many cases, the reaction may then be performed in an undivided cell, as
the reaction at the counter electrode (oxidation of the anion to carbon dioxide) generally does not
interfere with the cathodic reaction [B14].
III.B.1.h Tetramethylaluminate and Tetraphenylborate

The sodium salts of these anions are soluble in THF and have been found suitable as supporting
electrolyte in this solvent [B15,B16].
III.B.2 CaTIoNS
The discharge potential of a cation determines whether it is useful; so in practice, only alkali and
alkali earth metal ions together with ammonium and tetraalkylammonium ions are used. The non-
discharge of a cation is a sine qua non, but in addition, a choice of cation must take into consideration
ion pair formation, solvation, and adsorption of particular species (see, e.g., References B17–B19).
III.B.2.a Lithium Ions

Many lithium salts, such as lithium perchlorate and the halides, are soluble in nonaqueous solvents.
The reduction potential of Li+ depends on the electrode and the solvent. At a mercury cathode,
amalgam formation takes place, whereas formation of lithium metal occurs at platinum in aprotic
media. Lithium metal is less reactive than sodium, and in some solvents, sodium attacks the solvent,
whereas lithium is unreactive. A small water content in an aprotic solvent may react with lithium
(or Li+ may react with hydroxyl ions formed at the cathode) to form lithium hydroxide, which may
cover the electrode with an insoluble, insulating layer.
III.B.2.b Sodium Ions

In aqueous buffers, sodium ion is a common cation, but in nonaqueous solvents, practically only
NaClO4 is useful. Even NaBF4 is not suitable in most aprotic solvents.
III.B.2.c Magnesium Ions

Magnesium ions interact with radical ions in aprotic media, which may influence the course of
the reaction; in some cases, Mg+ also stabilizes the product and thereby helps avoiding unwanted
further reactions [B20,B21].
III.B.2.d Tetraalkylammonium Ions

The most commonly used quaternary ammonium salts are tetrabutylammoniumperchlorate
(TBAP), tetrafluoroborate (TBAT), the halides (TBACl, TBAB, and TBAI), and the corresponding
tetraethylammonium salts, such as the perchlorate (TEAP), but also the tetramethyl- or tetrapro-
pylammonium salts have been employed; the former cannot undergo a base-promoted Hofmann
elimination. However, evidence has been found for the formation of trimethylammonium methylide
[B22]. In nonpolar solvents, it may be necessary to employ tetrahexyl- or tetraoctylammonium salts.
The tetraalkylammonium ions are soluble in many nonaqueous media, and they may be extracted
from an aqueous solution by means of chloroform or methylene chloride [B23,B24], and tetraalkyl-
ammonium salts may thus be prepared by ion extraction [B24]. Tetrakis(decyl)ammonium tetrap-
henylborate is soluble even in hexane [B25,B26].
Reduction of R4N+ at a glassy carbon electrode in DMF yields an alkyl carbanion, which
deprotonates residual water or R4N+ in a Hofmann elimination with formation of an alkene and a
trialkylamine. Tetraethylammonium is attacked more easily than tetrabutylammonium [B27].
The discharge potential becomes slightly more negative with increasing size of the ion, but in
practice, there is not much gain by going beyond tetrabutylammonium ions [B28]. The reduction
route of these ions is discussed elsewhere (Chapter 16).
In aqueous solution, the tetraalkylammonium ions are adsorbed at the electrode, where they
form a layer with a low proton activity. This property is used in the commercial production of
a diponitrile from acrylonitrile (Chapter 31)*. The adsorption of the ions depends on the potential
of the electrode, the electrode material, the composition of the medium, and the size of the cation.
The rate constant for electron transfer from an electrode to a substrate decreases with the size of
the cation; for instance, the rate constants for electron transfer at a mercury electrode in MeCN to a
substrate were always smaller when tetra-n-heptylammonium perchlorate was the electrolyte than
when tetraethylammonium perchlorate was used [B29].
Quaternary ammonium salts are readily accessible; some are commercially available, and their
preparation presents no problems [B23,B24]. Reducible impurities may be removed by electroly-
sis at a sufficiently negative potential. The production of tetraalkylammonium hydroxide using an
anion [B30] or cation [B31] exchange membrane has been reported.
III.B.2.e Sulfonium Salts

Tris(dimethylamino)sulfonium tetrafluoroborate (TASBF4) has been investigated as a supporting
electrolyte in MeCN and CH2C12. Compared with TBABF4, the conductance of TASBF4 in CH2C12
is slightly higher, suggesting a higher degree of dissociation of the latter [B32].
III.B.2.f Cryptates
Crown ethers and other cryptates form stable complexes with several metal cations, which gener-
ally are soluble in nonaqueous media, even in rather nonpolar solvents [B33]. In some cases, such
complexes may be considered supporting electrolytes, especially when some of the special proper-
ties of a given cryptate are desirable also in other contexts. By complexing Ag+ with a cryptate, the
Ag/AgCryp+ electrode becomes stable in DMF [B34].
III.B.2.g Polyelectrolytes
Polyelectrolytes having ion exchange properties may be coated on one or both electrodes [B35–B40],
which makes it possible to use virtually nonconducting liquids. This was discussed in Section II.D.3.
A copolymer of 4-vinylpyridine or styrene with a diaryl-4-(l-trifluoromethylvinyl)-aryl amine
has sufficiently solubility and conductivity to serve as both supporting electrolyte and redox media-
tor; after use, it can be recovered by ultrafiltration [B41].
III.B.3 BUFFErS
Control of an electrolytic reaction often requires that the proton activity remains within acceptable
limits during the electrolysis. For small-scale electrolytic preparations (less than about 10 g/liter
of substrate), a sufficiently high initial concentration of buffer, acid, or base is adequate in aque-
ous solution; for large-scale electrolysis, a controlled addition of protons during a reduction must
be provided. This addition may be controlled by a pH-stat or coupled to the current integrator. In
aprotic media, a proton donor, electrophile, or nucleophile may play a similar role as buffers in
aqueous media.
III.B.3.a Acids
Hydrochloric acid is a convenient acid for laboratory-scale electrolysis; it is easy to remove during
the workup by evaporation. The oxygen-containing acids, such as sulfuric or perchloric acid, must
be neutralized before basic products can be extracted. Sulfuric acid is most conveniently neutralized
by concentrated ammonia rather than by sodium hydroxide, whereby the precipitation of sodium
sulfate is avoided.
Even in acetic acid, perchloric acid is a strong acid. Anhydrous solutions are made by adding
acetic anhydride equivalent to the water present in the acetic acid and introduced together with the
perchloric acid. An excess of acetic anhydride should be avoided as this solution is a very strong

acylating agent, and it forms yellow condensation products on standing. Anhydrous perchloric acid
in MeCN has been prepared by oxidation of H2 to H+ at a platinized platinum electrode in a solution
of TBA+ClO4− in MeCN [B42].
In aprotic media, the addition of proton donors may be important. If the proton donor is too
strong, protons may be reduced in preference to the substrate and a too weak proton donor may not
furnish sufficient protons. Often a phenol is an acceptable compromise.
Extreme acidic conditions may be obtained in superacids, such as SbF5 or BF3 in HF or SbF5 in
FSO3H.
III.B.3.b Bases
Reductions in aqueous alkaline solution do not present many problems; the choice of cation was
discussed earlier. In nonaqueous solvents, bases may be generated electrolytically (Chapter 43)
[B43,B44] or formed by reaction of the solvent with an alkali metal. The conjugate base of the sol-
vent is the strongest base obtainable in any medium.
During oxidation in a nonaqueous solvent, the removal of a proton or an attack of a nucleo-
phile on the oxidized substrate may be a chemical step in an ECE reaction. To explore which
reaction is operating, one can, in parallel voltammetric experiments, use two compounds that
are equal in base strength but differ widely in nucleophilicity; such a pair is pyridine and
2,6-dimethylpyridine.
III.B.3.c Buffer Systems

The use of buffers in electrolysis to maintain a desired pH warrants some consideration. During a
reduction, protons are consumed at the cathode surface, and unless they are replenished rapidly, the
pH in the reaction layer is considerably higher than in the bulk of the solution. A high concentration
of a buffer system, which exchanges protons rapidly, is required to maintain a desired pH.
In aqueous solution, phosphate, borate, and carboxylate buffers are applicable, but in mixed
solvents, the solubility of phosphate and borate buffers is low; in such mixtures, carboxylate buf-
fers may be used in slightly acid medium and amine buffers in slightly alkaline medium. To avoid
excessive buffer concentrations, it is advisable to maintain pH in the bulk of the solution constant
by means of a pH-stat.
Buffering in an aprotic medium is sometimes a problem. Proton donors, such as a suitable phenol,
malonic ester, or amine salt, together with the corresponding base, may be an acceptable solution.
Guanidine perchlorate [B45] has been proposed as an efficient proton donor (and supporting elec-
trolyte) in aprotic solvents, as it brings the protons into the Helmholtz double layer.
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A Djurhuus, K Gustavii, U Junggren, B Lamm, B Samuelsson. Acta Chem Scand 23:2202, 1969;
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New York: Elsevier, 1987, p. 467.
B32. JY Becker, T Berzins, BE Smart, T Fukunaga. J Electroanal Chem 248:363, 1988.
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8 Application of Ionic Liquids,
Emulsions, Sonication, and
Microwave Assistance
John D. Watkins and Frank Marken
CONTENTS
I. Introduction: The Need for Special Conditions in Organic Electrosynthesis ...................... 331
II. Ionic Liquids in Organic Electrosynthesis ........................................................................... 332
III. Supercritical Conditions in Organic Electrosynthesis .......................................................... 335
IV. Emulsions and Biphasic Conditions in Organic Electrosynthesis ........................................ 336
V. Ultrasound in Organic Electrosynthesis ............................................................................... 339
VI. Microwaves in Organic Electrosynthesis .............................................................................340
VII. Special Conditions in Specific Applications ........................................................................ 341
References ...................................................................................................................................... 341
I. I NTRODUcTiON: ThE NEED fOR SPEciAL CONDiTiONS

iN ORGANic ELEcTROSYNThESiS
Electrochemical processes are predominantly heterogeneous in nature requiring mass transport
and in some cases thermal reaction control. The need for special conditions in electrosynthesis is
therefore intertwined with the control of the mechanism and linked either to the enhancement of
reaction selectivity, conversion rate, or product yield. Increasingly however, it is also the search
for green conditions that drives the exploration of special conditions [1]. For example, the use of
excess solvents has long been regarded as detrimental to the environment, with an onus to reduce
their quantity or replace them with less hazardous alternatives. It is for this reason that supercritical
fluids and various types of room temperature ionic liquids (RTILs) are receiving much attention in
standard organic preparations as well as electrosynthesis.
Electrosynthesis often allows access to molecules inaccessible by standard synthetic procedures
[2], but the need for special electrosynthesis equipment often limits its use to niche applications.
Product separation from electrolytes can be time consuming and adds an extra separation step not
usually required in organic synthesis, so either the electrochemical approach must be of sufficient
benefit to outweigh this drawback or new methods to avoid this problem are required. For example,
emulsion-based synthesis [3] or biphasic methods [4] have been proposed to eliminate the separa-
tion step by keeping electrolytes and reagents separated from products. The additional problem of
beneficially using the often-ignored counterelectrode process can be approached, for example, by
paired electrosynthesis conditions [5] or by the choice of a very small counterelectrode in a single-
compartment reactor to push the counterelectrode process potential into the solvent decomposition
region with minimal loss of product [6].
Generally, new methods for improving the rate, selectivity, and yield in organic electrochemis-
try are desirable. It is for this reason that sonication [7] and microwave [8] techniques are some-
times considered. These techniques are readily focused on the working electrode surface to create
331
synthesis conditions that are more effective than conventional stirring and heating techniques. In
combination with the application of special reaction media, for example, ionic liquids or emulsions,
entirely new processes may in future be possible. The following sections summarize some of the
recent progress for methods that could be of benefit in electroorganic synthesis.
II. IONic LiqUiDS iN ORGANic ELEcTROSYNThESiS

Ionic liquids are of special interest to the electrochemist due to their inherent ionic conductivity,
tunable physical properties, low volatility, huge range of structural diversity, and potential for reuse
[9–12]. RTILs (see Table 8.1) are most widely studied and are defined as an ion pair material that is
sufficiently disordered at, or near to, room temperature so as to exist as a liquid [13–15]. To create
TABLE 8.1
Examples for RTIL Molecular Structures. (a) RTIL cations, (b) RTIL anions,
and (c) Distillable Ionic Liquids
+
+ N +
R N CH3 N N
R CH3
R
1-alkyl-3-methylimidazolium 1-alkylpyridimium 1-alkyl-1-methylpyrrolidinium
[CnC1im]+ [Cnpyr]+ [CnC1pyrr]+
R4N+ R4P+ R3S+

Tetraalkylammonium Tetraalkylphosphonium Trialkylsulfonium
[C4N]+ [C4P]+ [C3S]+
(a)
O O O–
–
F3C S N S CF3 F3C S O RSO4–
O O O
Bis(trifluoromethylsufonyl)imide Trifluoromethanesulfonate Alkylsulfate
[NTf2]– triflate, [OTf ]– [CnSO4]–
F– F–
NC – CN F F
N P B
F F F
F F
F
Dicyanamide Hexafluorophosphate Tetrafluoroborate
[N(CN)2]– [PF6]– [BF4]–
(b)
CO2 + R1R2NH R1R2NH – COOH
R1R2NH – COOH + R1R2NH [R1R2NH2] +[R1R2NH – COO]–
(c)
Source: Hallett, J.P. and Welton, T., Chem. Rev., 111, 3508, 2011.
Application of Ionic Liquids, Emulsions, Sonication, and Microwave Assistance 333
this state, mismatched ion pairs of low symmetry are often used. Generally, this is achieved by
bulky asymmetric organic cations accompanied by almost any anion. Small halide-based anions
generally lead to higher-temperature ionic liquids than inorganic complex anions such as PF6 −.
Furthermore, the tunability of physical properties allows parameters such as organic molecule solu-
bility and water miscibility to be controlled. The physical properties of RTILs as well as their
reactivity for electrochemistry have been extensively reviewed [16,17], and a new classification of
solvation properties has been developed [18]. Pioneering early work in 1980 by Osteryoung and
coworkers focused on electrochemistry in alkyl-pyridinium aluminates [19], and special cases have
been reported such as N,N-dialkyl-ammonium-N′,N′-dialkylcarbamate distillable ionic liquids [20]
and purely natural ionic liquids (or deep Eutectic mixtures) based on choline chloride [21]. In this
chapter, some key electrochemical processes will be discussed with an emphasis on electrosynthetic
transformations as well as some useful publications concerned with the general use of ionic liquids
Although ionic liquids are known to be inherently ion conducting, due to their ionic structure,
it is often their higher viscosity that limits their use as an effective medium for electrosynthesis.
This higher viscosity is linked to poor mass transport and limited ionic conductivities compared to
conventional organic solvent media [22,23]. Like most physical properties of RTILs, the viscosity
can be finely tuned by the choice of the cation and anion, with long-chain alkyl groups on the cat-
ion giving an increased viscosity. To counter this problem, cosolvents have been employed [24] as
well as the inclusion of dissolved gasses, which have been shown to significantly affect the rate of
diffusion [25]. Initial studies have often been focused on electropolymerization processes [26–29].
However, many electrosynthetic transformations have now been reported in RTIL media, including
Michael addition [30], oxidation [31–33], reduction [34–36], aromatic substitution [37], cyclization
[38], fluorination [39–41], dehalogenation [42], and coupling reactions [36,43–45].
The Michael addition, reported by Palombi [30] (see Figure 8.1), uses a divided flow cell and a
paired electrosynthetic approach where both the anodic and cathodic compartments contribute to
the process. The Michael product at the cathode is derived from enolate formation, and the process
at the anode is catalyzed by BF3 Lewis acid formed in situ from the ionic liquid. With a paired con-
vergent process strategy, it was possible to improve the current efficiency.
O O
BF–4
1a Xc
Pt cathode
Pt anode
1 mmol
EMImBF4 EMImBF4
O– O
BF3
Xc
O O O O
O
X c’
Xc= O N 1 mmol
Bn O O
Cathodic current yield Anodic current yield

7.3 mol of 2a 6.8 mol of 2a
per mol of charge O Xc per mol of charge
2a
Overall isolated yield 71%
FiGURE 8.1 Schematic of the proposed mechanism for a divided cell paired electrolysis method for a Michael
addition in 1-ethyl-3-methyl-imidazolium tetrafluoroborate. (From Palombi, L., Electrochim. Acta, 56, 7442,
2011.) The same, approximately 70% diastereoisomeric ratio, was observed for anodic and cathodic cells.
The Shono oxidation in ionic liquid media with the inclusion of methanol was investigated
by Bornemann and Handy [24], and good result and recovery of ionic liquids in the presence
of a sufficiently high level of methanol were observed. Barhdadi et al. have demonstrated some
examples of electrolysis in RTILs including the 2,2′,6,6′-tetramethylpiperidin-N-oxyl (TEMPO)-
mediated oxidation of alcohols [31] and the nickel-catalyzed electroreductive coupling of organo-
halides [45]. In the first case, a highly efficient TEMPO-mediated alcohol oxidation was achieved
with the viscosity of RTIL overcome by the addition of appropriate amounts of alcohol and
base. The current efficiencies achieved were up to 100% with conversions also 100%, although
enolizable products were not tolerated to this degree. The second case demonstrates the first
steps toward an efficient coupling reaction of organic halides with each other or with activated
alkenes via a nickel catalyst (see Table 8.2). Experiments were conducted with a sacrificial Mg
or Al anode and a bipyridyl-NiBr 2 catalyst in 1-octyl-3-methyl-imidazolium tetrafluoroborate.
Similar nickel coupling reactions have been demonstrated by Mellah et al., who show that the
homocoupling of aryl halides can be achieved and note that upon separation the nickel catalyst
remains in the RTIL while organic materials are washed out. The same RTIL phase can be
reused for further reactions. Mellah et al. [44] have also demonstrated an oxidative aromatic cou-
pling process in RTILs. Another electroreductive coupling reaction by Duran Pachon et al. [46]
has shown another benefit of an RTIL-based synthesis in the stabilization of in situ palladium
nanoparticles. In this reaction, a counterelectrode reaction–generated Pd nanoparticle cluster was
used as a ligand-less catalyst for the Ullmann coupling reaction of aryl iodides in good yield and
functional group tolerance.
TABLE 8.2
Aryl Coupling and Addition Processes Catalyzed by Ni(0) Complexes
in 1-Octyl-3-Methyl-Imidazolium Tetrafluoroborate
RTIL, cat NiBr2bpy
2ArX + 2e– Ar – Ar + 2X–
Anode Fe or stainless steel
R–X Isolated R–R Yield (%)

C8H17Br C16H34 48
Ph–CH2Br Ph–CH2–CH2–Ph 75
Ph–CH2Cl Ph–CH2–CH2–Ph 78
Ph–CCl2–Ph Ph2C = CPh2 68
R
RTIL, cat NiBr2
Z
ArX + R–CH = CH–Z
Stainless steel anode Ar
ArBr Activated olefin Product and isolated Yield (%)

Ph—Br CH2 = CH–CO–Me Ph–CH2–CH2–CO–Me 58
Ph—Br CH2 = CH–CO2–Bu Ph–CH2–CH2–CO–Bu 61
Ph—Br MeO2C CO2Me CO2Me 41
Ph
CO2Me
3–MeO–C6H4Br Ch2= CH–CO–Me 3–MeO–C6H4–(CH2)2–CO–Me 42
Source: Barhdadi, R. et al., Chem. Commun., 1434, 2003.

O
O –2.4 V vs. Ag/AgCl
+ CO2 (1 atm) O O
R Ionic liquids, rt
R
FiGURE 8.2 Cathodic activation of epoxides to react with CO2 in ionic liquid media with a sacrificial anode
(Mg, Al) and a Cu cathode. Less than 1 mol equivalent of charge was passed.
Other uses of ionic liquids in electrosynthesis have been proposed for the in situ generation
of reactive intermediates. It has been found by Martiz et al. that in a highly fluorinated RTIL,
dioxygen is highly soluble and easily reduced to form a stable superoxide [28]. Hydrogen perox-
ide has also been successfully generated in situ by the electroreduction of oxygen in RTILs by
both Tang et al. [47] and Ho et al. [48]. The former of these publications has shown that hydrogen
peroxide was created in an RTIL water-mixed phase under basic conditions for direct epoxida-
tion of electrophilic alkenes while being reusable for multiple syntheses. Ho et al. have used a
similar oxidation system for a wider range of alkene epoxidations. This has been achieved by
using carbon dioxide with the electrogenerated HO2− to create the peroxymonocarbonate ion
(HCO4 −) intermediate. This intermediate, with a manganese (MnSO4) catalyst, was able to epoxi-
dize a much wider range of alkenes. For the reuse of the RTIL phase, the manganese had to be
extracted. The facile cathodic formation of peroxodicarbonate from O2 and CO2 in dry ionic
liquids has also been reported [49].
A fixation of carbon dioxide by epoxides based on RTIL electrochemistry has been reported by
Yang et al. [50] in which the reaction results in cyclic carbamates (see Figure 8.2). Dehalogenation
reactions carried out with a vitamin B12 catalyst are common in organic electrosynthesis, but it has been
found that these reactions are further enhanced by the polarity increase in RTILs [42,51]. In conclusion,
there is a lot more scope for beneficial applications of RTILs in electroorganic reactions [52].
III. SUPERcRiTicAL CONDiTiONS iN ORGANic ELEcTROSYNThESiS

Solvents such as ionic liquids, supercritical carbon dioxide, or water are sometimes classed as neo-
teric solvents [53]. In contrast to RTIL media, supercritical fluids provide low polarity with fast
diffusion and often require elevated temperature conditions. Applications of supercritical CO2, for
example, in heterogeneous catalysis have been highly successful [54]. Potential for supercritical
electrosynthesis [55] has been proposed in particular for CO2-based media [56,57] and for carbox-
ylation processes [58]. A supercritical fluid is a phase that is subjected to pressures and or tempera-
tures above their critical point values, thus creating a new gas–liquid fluidlike state. A commonly
used supercritical liquid is carbon dioxide (scCO2), which may be considered both environmen-
tally friendly and nonhazardous as well as useful under relatively mild conditions (TC = 31.1°C,
PC = 73.8 bar [59]). A potential problem limiting the use of scCO2 in electrosynthetic applications is
its low polarity and thus incompatibility with ionic electrolytes. This problem has been addressed by
the use of appropriate cosolvents such as acetonitrile [60]. The cosolvent approach has been used for
the electrocarboxylation of α-chloroethylbenzene with the addition of an ionic liquid (N,N-diethyl-
N-methyl-N-(2-methoxyethyl)ammonium bis-(tri-fluoromethanesulfonyl)amide) and as a function
of applied CO2 pressure [61] (see Figure 8.3). A similar approach to circumvent the problem of
electrolyte solubility in scCO2 has been demonstrated for the potentially high-yielding oxidation of
benzyl alcohol to benzaldehyde in a mixed scCO2 ionic liquid mixed system [62]. Ionic liquid was
used as an electrolyte, and scCO2 pressure was used to control the product yield. Facile product
isolation was possible in scCO2. Furthermore, the ionic liquid phase was shown to be reused over
many reactions and thus was waste-free.
Cathode reaction
Cl +2e– CO2 COO–

–
–Cl
Anode reaction
Mg Mg2+ + 2e–
Bulk reaction R-COOMgCl

R–COO– + Cl– + Mg2+ and/or
(R-COO)2Mg
H3O+
COOH
FiGURE 8.3 Overall reaction scheme proposed for the reduction of α-chloroethylbenzene in ionic liquid/
CO2 with a platinum cathode and sacrificial Mg anode. (From Hiejima, Y. et al., Phys. Chem. Chem. Phys.,
12, 1953, 2010.)
Supercritical fluids may be considered true designer solvents in a similar way as ionic liquids.
The key difference is that instead of a laborious synthetic approach to change chemical composi-
tions, temperature and pressure and cosolvent may be varied to continuously change the solvent
properties. The miscibilities of cosolvents such as ionic liquids can be varied such that the reaction
is completed in a monophasic system, and with a change in pressure, separation is carried out in
a biphasic system. The presence of a biphasic system, and in particular the presence of a separate
liquid phase deposit on the working electrode, has to be considered as a potential source of arti-
facts in electrochemical measurements in supercritical media. Films of poly(ethylene oxide) at the
electrode surface have been employed intentionally to conduct electrosynthetic transformation in
supercritical CO2 [63].
IV. EMULSiONS AND BiPhASic CONDiTiONS iN

ORGANic ELEcTROSYNThESiS
Emulsion or biphasic media are of significant importance in electrosynthesis [64,65] and have been
employed in large-scale processes such as the Monsanto production of Nylon 66 [66]. It is possible
to form emulsions from a range of phase combinations, but aqueous phase systems are most com-
monly employed. Water is an ideal green electrosynthetic solvent due to its high dielectric constant
with the only drawback being its incompatibility with some organic functional groups or reaction
intermediates. Biphasic systems allow the conductivity of a fully supported electrolytic phase to be
utilized alongside a secondary nonpolar organic phase in which a capture reagent can be used to
contain products and to allow easy separation as well as preventing overelectrolysis. An emulsion
system acts to separate electrolyte and products so as to form an in situ extraction procedure.
Direct interaction of nonpolar reactants in aqueous-based biphasic processes can be enhanced,
for example, by power ultrasound [67], microwave [68], or high-shear ULTRA-TURRAX homog-
enization [69]. However, more often, emulsion electrosynthesis requires an indirect electrosynthetic
strategy using mediators, as reviewed by Ogibin et al. [70]. The topic of electrosynthesis in micro-
emulsion has been reviewed also by Rusling et al. [3,71] in 1997 emphasizing the use of surfactants
as stabilizing groups for microemulsions with biphasic mediators. Biphasic mediators are redox
species that are able to transfer charge across a phase boundary by shuttling electrons from the
B12r
Oil — water
interface B12s
–2Br–
R
R΄ R B12s B12r
R΄
Br
Br +e–
2–10 μm
(a)
Polar Polar
O O O O
H H H H H H H H
Br Br Br
C12H25 θ
H
H CH3
H CH3 H
C12H25
Br
Nonpolar Nonpolar
(b)
FiGURE 8.4 (a) Reaction scheme for vitamin B12–mediated reductive dehalogenation of vicinal dibro-
mides at the oil–water interface for a microdroplet of oil immobilized at an electrode surface. (b) Close-up
scheme suggesting a rotational polarization of dibromides at the oil–water interface. (From Davies, T.J. et al.,
ChemPhysChem, 6, 2633, 2005.)
electrode and into another phase. A common mediator that has been used previously in single-
phase electrosynthesis is vitamin B12, which has been shown to be also an effective biphasic media-
tor. In the work by Davies et al. [72], the mechanism of the vitamin B12 biphasic mediation was
investigated, and it was shown that the reduced B12 is able to diffuse to the phase interface of an
aqueous–organic boundary and reduce vicinal dibromide species to form olefins (see Figure 8.4).
A comparison of homogeneous and heterogeneous chemical rate constants for dehalogenation of
different dibromides suggested that the liquid–liquid interface does play an active role in this pro-
cess. Periodate has also been shown to be an effective biphasic mediator system in electrosynthesis.
Khan et al. [73] applied an iodate aqueous phase to in situ create the powerful and more hydro-
phobic periodate oxidizing agent, which was able to transfer to the organic phase aided by a phase
transfer catalyst to oxidize organic species. The emulsion-mediated approach has also been applied
to the sharpless asymmetric dihydroxylation of alkenes [74]. In this case, a mixed cyclohexane–
water biphasic system was employed with a ferricyanide mediator to maintain the concentration of
an osmium(VIII) catalyst. The organic reaction is kept separate in the cyclohexane phase for ease
of work-up. The use of a chiral oxaziridinium salt as organocatalyst for epoxidation in acetonitrile–
aqueous biphasic media has been reported by Page et al. [6].
In a second review, Rusling [71] emphasizes the green impact of microemulsions and also their
ability to direct electrosynthesis toward unexpected products. Despite not using a true emulsion,
Chiba et al. [75] have used biphasic electrosynthesis to perform Diels–Alder reactions of electro-
generated quinones in the close proximity of water by employing an SDS surfactant. Under conven-
tional conditions, the quinone would be unstable in water, but it is the effect of the local hydrophobic
conditions that allows the reaction to proceed. A similar study by Chiba et al. [76] demonstrated the
application of PTFE fibers to form hydrophobic regions for reactions.
Often, emulsions are stabilized by surfactant molecules, which can cause complications in the
work-up. Alternatively, metastable emulsions can also be generated by power ultrasound [77–79] or
via ULTRA-TURRAX [69] emulsification. These emulsions are generated only during the external
application of high-shear mixing but return to separate bulk phases when the agitation is removed.
This methodology has the benefit of an emulsion during a reaction but is able to be easily separated
postreaction in its bulk phase form. Asami et al. [78,79] reported the applications of acoustically
generated emulsions in electrosynthesis. The benefits of the emulsion in this case are that the redox-
active substrate is anodically converted in an electrolytic phase, whereas the oxidation-sensitive
nucleophile is maintained in a separate organic phase without electrolyte to avoid the competing
oxidative pathway (see Figure 8.5 and Table 8.3). Furthermore, the separated electrolytic phase
was chosen as ionic liquid, 1-ethyl-3-methylimidazolium tetrafluoroborate (EMIM+BF4−), due to its
ability to dissolve the pyrrolidine substrate, remain immiscible with the acetonitrile nucleophilic
phase, and not dissolve the nucleophile. In a single-phase system, the allyltrimethylsilane nucleo-
phile would be preferentially oxidized, leading to lower yields. A further benefit of the biphasic
system is that the electrolytic phase may be recovered for reuse, and the product remains in the
acetonitrile for easy extraction.
A related methodology recently developed for biphasic electrosynthesis is the use of the
triple-phase boundary electrode–aqueous electrolyte–organic solvent [80]. This technique
Nucleophile
(without electrolyte)
+ –
Nu Acoustic
Nu P P P
Nu emulsification
Electrolysis Nu
S Nu
S
Nu S S+ S
S Nu
S Nu S
S
S Nu
Emulsion Emulsion
Electrolytic medium S = Substrate N u = Nucleophile S+= Carbocation P = Product
–2e–, –H+
+ SiMe3
N N
COOMe EMIM BF4 COOMe

0.2 mA cm–2, Pt – Pt
(1 mmol) (10 equiv)
FiGURE 8.5 Schematic description and reaction scheme for the electrolysis methodology based on in situ
emulsification of reagents and mass transport enhancement in 1-ethyl-3-methyl-imidazolium tetrafluoroborate
employing a divided cell. (From Asami, R. et al., Chem. Commun., 244, 2008.)
TABLE 8.3
Data for Electrolysis Processes Based on In Situ Emulsification of Reagents
and Mass Transport Enhancement in 1-Ethyl-3-Methyl-Imidazolium
Tetrafluoroborate Employing a Divided Cell
Entry Substrate Charge (mol equivalent) Product Yield (%)
1 2 70
N N
COOMe COOMe
2 2 43
N N
COMe COMe
3 3 50
N N
COOMe COOMe
4 N 4 N 66
COOMe COOMe
Source: Asami, R. et al., Chem. Commun., 244, 2008.
involves placing the electrode at the interface of electrolyte phase and organic solvent phase
allowing, for example, reductive electrosynthesis to be completed in an organic phase without
the need for intentionally added electrolyte [81,82].
V. ULTRASOUND iN ORGANic ELEcTROSYNThESiS

Ultrasound is defined as a sound wave with a frequency above the range of human hearing,
typically about 20 kHz and higher. The frequency and power used often play a key role in the
various applications of ultrasound. Generally, a distinction can be made between two frequency
bands of ultrasound [83]. For electrosynthesis, frequencies between 20 and 100 kHz (power
ultrasound) are generally used due to their larger mechanical, agitation, or cavitation effects
[84,85].
Ultrasound is highly beneficial for synthetic electrochemistry by providing a high degree of
mass transport, especially for slow diffusers [86], gained through two key mechanisms: (1) acous-
tic streaming, where a directed turbulent jetflow of bulk material is in effect causing fast material
transport to the electrode surface; and (2) cavitation or microstreaming, where the effect of the
ultrasonic wave causes a compression and rarefaction cycle in the bulk liquid leading to implosive
voids being created at the electrode surface [87]. Upon collapse, these voids lead to a roughening of
the electrode surface and additional localized mass transport.
Often, ultrasonic bath systems are employed, but these introduce some degree of irreproduc-
ibility, and therefore, horn emitters have been introduced to apply power ultrasound more locally to
the electrode surface. Three geometries of horn probe sonication in electrochemistry are considered
in a review by Compton et al. [7] as the face on, the side on, and sonotrode case (see Figure 8.6).
In general, for power ultrasound, the face on configuration is chosen for direct mass transport and
horn emitter
Ultrasonic
Electrode
Face on
Side on Sonotrode
Electrode
Electrode
(a) (b) (c)
FiGURE 8.6 Three ultrasonic horn emitter geometries for the application of power ultrasound (a) face-on,
(b) side-on, and (c) in sonotrode configuration to electrodes for high mass transport. (From Compton, R.G.
et al., Electroanalysis, 9, 509, 1997.)
cavitation at the electrode surface. For an effective electrolysis, it is key that the faradaic current is
kept as high as possible, and this is generally achieved by using a high degree of mass transport. This
high value of faradaic current is directly related to the diffusion layer thickness, and Marken et al.
[88] have shown that in an acoustically generated mass transport system, the mass transport–limited
diffusion layer thickness is governed by the solvent viscosity. Marken et al. have also demonstrated
a simple ultrasound-enhanced reductive synthetic approach for a range of activated alkenes to their
corresponding alkanes [89] as emulsions in water without the need for organic solvent.
Mass transport enhancement effects are not the only benefit from ultrasound in heterogeneous
electrochemical processes. Ultrasound can also induce mechanistic changes of electrochemical pro-
cesses [90,91] and stop electrode surfaces from being fouled by polymers and other solid materials
in a depassivation effect, for example, in Birch electroreduction [92]. The depassivation is mainly
achieved through the cavitation mechanism and dependent on frequency, sonication power, elec-
trode geometry, and solvent.
VI. MicROwAvES iN ORGANic ELEcTROSYNThESiS

In spite of the popularity of microwave activation in organic synthesis [93], there have been only
relatively few attempts to apply microwaves to electrosynthetic reactions. Microwave electrochemi-
cal experiments have been carried out by Compton et al. [94] predominantly at microelectrodes.
Recent reviews summarize some of the progress [8,95]. For metallic microelectrodes, a focusing
effect is observed that allows high-intensity microwave radiation to be applied directly to the dielec-
tric at the tip of the electrode [96]. However, for larger film electrodes, for example, tin-doped
indium film electrodes [97], direct heating of the electrode in a flow-through reactor dominates (see
Figure 8.7), similar to cases where carbon- or boron-doped diamond electrodes are employed [98].
Radiofrequency heating [99] of platinum film electrodes has also been proposed as a way of enhanc-
ing electrochemical processes in flow reactors.
(e) (c)
(d)
Collection Sample
vessel reservoir
(a)
(b)
(f )
Microwave
field
FiGURE 8.7 Schematic drawing of a microwave-enhanced flow electrolysis cell with (a) the port of the
microwave cavity, (b) a Teflon or glass flow cell, (c) the working electrode lead-in inserted into the cavity, (d)
the upstream reference electrode, (e) the downstream counterelectrode, and (f) the working electrode in the
flow field. (From Rassaei, L. et al., Electrochim. Acta, 54, 6680, 2009.)
VII. SPEciAL CONDiTiONS iN SPEcific APPLicATiONS

Apart from activation methods based on heat, ultrasound, and microwave, there have been some
reports exploiting new combinations such as plasma processes at the surface of ionic liquid media
[100,101]. Plasma discharge processes that are known to allow ozone generation and polymer depo-
sition could be of wider use with an ionic liquid phase to supply reagents or capture products.
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9 Combinatorial
Electrochemistry and
Miniaturization
Kevin D. Moeller
CONTENTS
I. Introduction .......................................................................................................................... 345
II. Split–Pool-Type Methods...................................................................................................... 347
A. Cation Pools .................................................................................................................. 347
B. Microflow Processing and the Cation-Flow Method .................................................... 353
III. Parallel Synthesis Methods................................................................................................... 355
A. Initial Electrochemical Efforts .....................................................................................355
B. Application to Synthesis: Bulk Methods ...................................................................... 357
C. Microflow Applications to Parallel Synthesis............................................................... 358
D. Microelectrode Array–Based Approaches....................................................................360
IV. Conclusions and a View for the Future ................................................................................. 366
References ...................................................................................................................................... 367
I. INTRODUcTiON
Efforts to discover and develop new molecules that can perform a particular function (either biologic
or catalytic) often benefit from the screening of molecular libraries. Use of the libraries enables mul-
tiple candidate structures to be rapidly screened, a process that can accelerate both the discovery of
initial lead compounds for development and the collection of data that can inform subsequent work.
Such efforts depend on the availability of synthetic tools that allow for construction of the librar-
ies. The result has been the development of combinatorial strategies for molecular synthesis. These
strategies typically fall into one of two general categories: split–pool methods (Figure 9.1) and paral-
lel synthesis methods (Figure 9.2). Split–pool applications to both biological problems [1] and cataly-
sis development [2] have been recently reviewed. Early examples of parallel synthesis methods [3]
and more recent applications [4] have also been reviewed. Both split–pool and parallel synthesis
approaches have advantages. The split–pool method is best for building larger libraries because it
exponentially increases the number of molecules synthesized with each new step, while parallel syn-
thesis methods lead to much smaller, spatially isolated libraries that can be more readily characterized.
With both types of libraries, modern methods for miniaturization have paid significant divi-
dends, especially in the area of microarray technology. Libraries of molecules are only as useful
as the methods available to screen their activity. Miniaturization aids these efforts by allowing for
automation of the screening process, simultaneous evaluation of multiple molecules that enables
higher throughput analysis, lower costs, and the use of biologically relevant amounts of material
(e.g., the screening of whole-cell extracts) [5].
As with traditional synthetic strategies, electrochemical methods offer unique opportunities to
expand the scope of combinatorial methods. For split–pool-type strategies, electrochemical methods
345
M Reaction 1 M1
Split Recombine M1 M2
M M M Reaction 2 M2
M3 M4
M M Pool
M Reaction 3 M3
Split–pool
M Reaction 4 M4 (second-iteration)
M11 M21 Reaction 1 M1 M2

M31 M41 M3 M4
Pool with Reaction 2 M1 M2

M12 M22
16 new Recombine M3 M4
compounds M32 M42
Split pool Reaction 3 M1 M2

(third-iteration) M13 M23
M33 M43 M3 M4
Reactions 1–4
Recombine
M14 M24 Reaction 4 M1 M2
M34 M44 M3 M4
Pool with 64 new compounds
FiGURE 9.1 Split–pool synthesis.
M Reaction 1 M1 Reaction 2 M12
M Reaction 2 M2 Reaction 3 M23

Four pathways
lead to four new
molecules, etc.
Reaction 3 Reaction 4 M34
M M3
Reaction 4 Reaction 1
M M4 M41
FiGURE 9.2 Parallel synthesis strategies.
are used to generate highly reactive intermediates in a manner that allows them to be subdivided
and then used to trigger a variety of synthetic transformations. Miniaturization of such efforts with
the use of microflow reactors imparts unique selectivities to these reactions. For parallel synthesis
efforts, multiple electrodes are used to guide the synthesis of library members. The result is the
generation of products that are each associated with the electrode used in their generation. In these
cases, miniaturization leads to spatially isolated, addressable libraries that can take advantage of
microarray technology to both build and monitor the libraries.
In this chapter, recent developments in combinatorial electrochemistry are highlighted along
with the potential the techniques hold for making significant contributions to the larger field of
molecular library synthesis and evaluation.
Combinatorial Electrochemistry and Miniaturization 347
II. SPLiT–POOL-TYPE METhODS

A. CaTIoN PooLS
Electrochemical strategies aimed at split–pool-type syntheses began with the development of the
cation-pool method by Suga, Yoshida, and coworkers. Reviews of both early studies [6a] and more
recent efforts [6b] have appeared. The cation-pool method first appeared in an intriguing 1999
report that demonstrated the stability of electrochemically generated N-acyliminium ions in non-
nucleophilic solvents at low temperature (Scheme 9.1) [7]. The N-acyliminium ions were gener-
ated by the anodic oxidation of an amide in dichloromethane solvent. The reactive intermediate
could then be stored as long as the temperature was kept below −50°C. Subsequent treatment of the
N-acyliminium ion with an allylsilane, enol ether, aryl, or malonate nucleophile led to the addition
products. Two points about the experiment were of particular note. First, the reaction allowed for a
one-pot oxidation—nucleophilic addition sequence involving the amide. Hence, the more cumber-
some, less sustainable two-step protocol that required the generation and isolation of a methoxylated
amide followed by a Lewis- or Bronsted-acid-catalyzed addition to a regenerated N-acyliminium
ion could be avoided. In the one-step procedure, the amide oxidation reaction was completed before
the addition of the nucleophile. Therefore, the method was still compatible with the use of electron-
rich nucleophiles with oxidation potentials lower than that of the amide. Second, formation of the
stable cation pool allowed for a split–pool approach to combinatorial synthesis. To this end, the
N-acyliminium could be subdivided into smaller pools and then each new pool treated with a dif-
ferent nucleophile in order to generate a series of derivatives from the amide starting material. In
effect, the cation-pool method allowed for a reactive intermediate to serve as the branch point for a
combinatorial synthesis effort.
This initial paper triggered a number of applications and advances of the cation-pool approach.
In 2000 [8], the work was extended to include the electrochemical generation of oxonium ions
(Scheme 9.2, Equation a). The oxonium ions were generated by the oxidative cleavage of a car-
bon–silicon bond at low temperature. Methods involving the use of electroauxiliaries have been
reviewed [9]. The oxonium ions generated decomposed above −50°C, but as in the case of the
N-acyliminium ions, at low temperature, they could be subdivided and then trapped with a number
of nucleophiles.
SiMe3
–2e– N
+
N –H+ CO2Me N
CO2Me CO2Me
Stable cation pool
87%
OCOCH3
O O
O
N
MeO2C O
O
71%
N
N
MeO2C
CO2Me
72%
88%
SchEME 9.1 The use of cation pools.

+ OMe TMS
OMe OMe
–2e–
C8H17 SiMe3 –Me3Si+ C8H17 C8H17
80%
(a) (14 examples, 54–84%)
MgBr
–2e–
N +N N
–H+ CO2Me MeO2C
CO2Me
79%
(b) (16 examples, 45–79%)
SchEME 9.2 Cation pools of electro-generated oxonium ions (a) and N-acyliminium Ions (b), and the use
of reactive nucleophiles.
The initial cation-pool work was also expanded in terms of the nucleophile used. Since the
nucleophile used in the reaction does not need to be compatible with the electrolysis, any nucleophile
can be utilized. In 2001 [10], Yoshida, Suga, and coworkers demonstrated that N-acyliminium ions
generated using the cation-pool method can be trapped with organometallic reagents (Scheme 9.2,
Equation b) (see also Chapter 35).
Cation pools can also be trapped with alkenes and acetylenes to affect a net cation carbohydrox-
ylation of the π-system (Scheme 9.3) [11]. For these reactions, the carbamate serves as a protecting
group for a primary amine. Hence, the reactions enable the synthesis of amino alcohols and amino
ketones.
Dimethylsulfoxide has also been used as a nucleophile to trap cation pools. In this case, the
reactions generate sulfoxonium ions (Scheme 9.4) [12]. Workup with a triaryl amine then affords a
chemical oxidation step that generates a ketone product.
In an another intriguing application (Scheme 9.5), a cation pool was electrochemically reduced
to form radicals [13]. The radicals can be used in order to generate homodimers, or they can be
treated with electron-poor olefins in order to generate carbon–carbon bonds (see also Chapter 17).
Cation pools have been used to not only generate radical intermediates but also trap radical
intermediates (Scheme 9.6) [14]. In this chemistry, hexabutyldistannane serves to propagate a
radical-chain process. It is involved in the initial generation of an alkyl radical that then adds to
the N-acyliminium ion in the cation pool leading to the formation of a nitrogen radical cation.
Ph Ph OH
Anodic oxidation R Ph
a) R1
N SiMe3 – “SiMe3” N R1
+ N
Bu4NBF4 R
O O O b) H2O, Et3N
O CH2Cl2 O O
Yields = (four examples, 60–85%)

a) R R1 R = H, Ph
b) H2O, Et3N R1 = SiMe3, Ph, OAc, C5H11
O
Ph
Yields = (five examples, 47–81%)
R1 R = H, Me, Ph
N
R R1 = SiMe3, Ph, C6H13
O O
SchEME 9.3 Cation pools and carbohydroxylation reactions.

Me +
S Me
O H O
Anodic oxidation
(2.1 F), 0°C Et3N, 35°C
NHTs
Bu4NBF4 N 1h N
1:2 DMSO/CH2Cl2 Ts Ts
86%
8 Cyclizations were performed using sulfonamide,

alcohol, aryl, and styrene nucleophiles. Yields
ranged from 52–90%
SchEME 9.4 Cation pools, DMSO, and the formation of ketones.
Anodic oxidation +2e–

–2e–, –H+ TfOH
CO2Me
N +N N
–72°C
CO2Me CO2Me
CO2Me CO2Me
(Nine examples, 39–84%)
+e–
75%
N N
CO2Me CO2Me
SchEME 9.5 Electrochemical reduction of cation pools.
Anodic oxidation Bu3SnSnBu3

–2e–, –H+ R–I
N –72°C +N N R
–20°C
CO2Me CO2Me CH2Cl2 CO2Me
Bu3SnSnBu3 (Three examples, 73–86%)

–20°C
CH2Cl2
N N N
CO2Me CO2Me CO2Me
81%
SchEME 9.6 Cation pools and tin-initiated radical chain reactions.
The radical cation then oxidizes the hexabutyldistannane to form a new radical cation that frag-
ments in the presence of the tetrafluoroborate electrolyte to generate fluorotributylstannane and
the tributyl tin radical. The tin radical then reacts with the starting alkylhalide to make the alkyl
radical and start the process over again. The reactions worked best with alkyliodides and the five-
membered ring N-acyliminium ion.
N-Acyliminium-based cation pools have also been used to generate new ring skeletons. In one
interesting example, the addition of nucleophiles to the sequentially generated intermediates in
a cation pool has been used to generate spirocyclic products (Scheme 9.7) [15]. The chemistry
SiMe3 Anodic oxidation Me3Si

–2e–, –SiMe+3 n n
SiMe3
N SiMe3
–78°C +N N SiMe3
CO2Me CO2Me (or a Grignard CO2Me
reagent)
72–88%
Anodic oxidation
–2e–, –SiMe3+
–78°C
Me3Si
n m
Ring closing
N n
n
m metathesis N (or a vinyl- +N
CO2Me m zinc reagent)
CO2Me CO2Me
77–92%
(3 examples, 46–67%)
SchEME 9.7 Cation pools and the synthesis of spirocyclic compounds.
R2
SiMe3 a)
Bu
Bu +N Bu R1
–2e–, –SiMe+3 R1 N
N
–78°C O O b) H2O
O O O R2
O Me
Me (11 examples, 68–88%)
SchEME 9.8 Diels-Alder reactions with pooled cations.
takes advantage of a pair of silyl groups in order to guide the regioselectivity of two successive
N-acyliminium ion formations toward the same carbon. In each case, the cation generated is trapped
with either an allylsilane or a vinyl zinc to afford a bis-olefin product that is then cyclized with
a ring-closing metathesis reaction. The chemistry was used to complete an efficient synthesis of
cephalotaxine. In a second example, cation pools have been used to accomplish Diels–Alder reac-
tions that utilize N-acyliminium ions as dienes for an electron-rich dienophile (Scheme 9.8) [16].
The use of the cation pool is essential for the success of these reactions because the electron-rich
dienophile is not compatible with the amide oxidation used to generate the N-acyliminium ion. In
one intriguing aspect of this work, the reaction yield for cycloadditions using styrene as the dieno-
phile benefited greatly from micromixing (see the following text) the olefin and the N-acyliminium
ion. This approach decreased the amount of polymer generated.
The polymer is generated from a stepwise addition of the styrene to the N-acyliminium ion lead-
ing to a benzylic cation. With poor mixing, this cation can undergo an addition to a second styrene,
an event that starts the polymerization. With micromixing, the effective concentration of styrene
is lower. This favors the intramolecular reaction that finishes the net cycloaddition reaction. The
effects of miniaturization can have a number of additional benefits for the reactions, something that
will be discussed in Section II.B.
Cation pools can also be used to generate new polymers. For example, cation pools of diphenyl-
carbenium ions have been used to synthesize dendrimer structures (Scheme 9.9) [17]. The use of
a cation pool in this manner provides an opportunity to synthesize dendrimers using a split–pool
approach.
Another variation in the cation-pool method uses the technique to generate highly reactive inter-
mediates that are then used to remotely trigger reactions (Scheme 9.10). Both the method [18] and
its application to oxonium ion formation [19] have been reviewed.
F F F F Ar Ar
Anodic
Oxidation Ar Ar
+
Cation pool SiMe3

SiMe3
Ar = p-F-C6H4–
Ar Ar Ar Ar
Anodic
Oxidation
etc. Ar Ar
SiMe3
Ar Ar
Ar Ar
+
Ar SiMe3 Ar
Cation pool
SchEME 9.9 Cation pools and the synthesis of polymers.
Substrate
Starting
R.I.+
material
I+ Product
R.I. = Reactive Intermediate
SchEME 9.10 A new approach to generation and use of reactive intermediates.
The result is a method for the generation of reactive intermediates that cannot be made with
a direct electrolysis. The method again opens up new opportunities for the use of split–pool
approaches to synthesis. In principle, either the initial reactive intermediate generated (R.I.+) or the
second intermediate generated (I+) can be used as the branching point for such an effort.
One intriguing application of this chemistry is illustrated in Scheme 9.11 [20]. In this example, an
anodic oxidation of ArSSAr is used to generate ArS(ArSSAr)+ as a reactive intermediate that in turn
triggers the formation of an oxonium ion from an alkoxy thiol acetal. The indirect oxidation was advan-
tageous over the direct oxidation to form the oxonium ion because the direct electrolysis reaction is too
slow. Hence, the oxonium cannot be accumulated prior to decomposition. This problem can be solved by
first generating and accumulating the more stable ArS(ArSSAr)+, and then using this reactive species to
rapidly generate the desired oxonium ion. The oxonium ion can then be employed in a split–pool synthe-
sis to synthesize a number of olefin addition products. The reactions provided a significant improvement
over previous efforts that had utilized the direct oxidation of silylated ethers to generate the oxonium ions
[19]. A similar mediated approach to oxonium ion formation using the ArS(ArSSAr)+ intermediate has
been used to initiate electrochemical glycosylation reactions [21].
OMe
C8H17 SPh
Anodic oxidation
Bu4NBF4/
ArSSAr ArS(ArSSAr)+BF4–
CH2Cl2 TMS
OMe OMe
+ C8H17
C8H17
(Seven examples, 42–91%)
SchEME 9.11 An indirect oxidation to form oxonium ions.

, MeOH Me
Anodic oxidation
Bu4NBR4/ OMe
ArSSAr ArS(ArSSAr)+BR4–
CH2Cl2 (R = F/Ar = p-FC6H4)
SAr
68%
Ph a) R1 R2
(R = C6F5/ R1 R2
Ar = p-MeOC6H5) b) Et3N
(R = F/Ar = p-FC6H4) ArS SAr
SAr (Four examples, 66–84%)
ArS
Ph
77% (Three other examples, 58–84%)
SchEME 9.12 Alkene substrates and the formation of sulfur substituted products.
Anodic oxidation R1 R2
Bu4NBR4/ SAr O
ArSSAr ArS(ArSSAr)+BF4–
CH2Cl2
R1 SAr
R = C 6F5/Ar = p-FC6H5 R2
(Six examples, 62–88%)
SchEME 9.13 An indirect approach to triggering cyclization reactions.
In the examples highlighted by the reaction in Scheme 9.11, a split–pool synthesis could be
accomplished by taking advantage of the oxonium ion generated. Split–pool syntheses can also
be accomplished by subdividing the initial ArS(ArSSAr)+ intermediate (Scheme 9.12) [22,23]. In
these reactions, a thiol group from the reactive species is incorporated into the product. A similar
approach was also used to generate oxonium ions and initiate cyclization reactions from a series
of substrates (Scheme 9.13) [24]. Six examples of the reaction have been accomplished with yields
ranging from 62% to 88%.
In a related application, an indirect electrolysis reaction has been utilized to oxidize furan rings
on solid supports (Scheme 9.14) [24]. The anodic oxidation was used to generate “Br +” that in turn
Anodic oxidation
nBu4NBr O
O 1:1 MeOH/1,4-dioxane O OMe
O N 3 O
N 3 O C-anode, 15 mA/cm 2
H OMe
O
H 40 F
O
Five equiv. LiOH
20/1: 1,4-dioxane/water
Source of “Br+” RT, 2 days
HO OMe
O
OMe
(Six examples, 53–63%)
SchEME 9.14 Indirect oxidation of solid phase substrates.

oxidized furans tethered to polystyrene beads. After cleavage of the product from the beads, the
reactions afforded the methoxylated furans in good yield and excellent purity.
B. MICroFLow ProCESSING aND THE CaTIoN-FLow METHoD

As illustrated for the Diels–Alder reaction in Scheme 9.8, electrochemical reactions can greatly
benefit from miniaturization and the use of a microflow reactor [25,26]. Microflow reactors
have channels that are micrometer size in scale, a situation that allows for the downsizing of
chemical reactions. Such reactions offer four potential advantages over larger, more typical
batch processes. First, they offer the opportunity for micromixing [27], the aspect of the process
that improved the earlier Diels–Alder reaction. Micromixing is accomplished by having two
solutions flow into a micromixer that is comprised of a collection of narrow channels that are
arranged in either a parallel or a series format. This increases the contact area between two solu-
tions while reducing the diffusion length necessary for complete mixing, a scenario that results
in more uniform mixing of reactive species. Second, microflow reactors offer improved tem-
perature control. This advantage steps from the greater surface-to-volume ratio of the reactors
that enables faster heat exchange between the reactor and the bulk solution. Third, microflow
reactors offer better control over reactions that take place on the interface between the catholyte
and the anolyte in an electrolysis reaction. This advantage again stems from the greater surface-
to-volume ratio in the microflow reactor that in this case leads to improved phase-boundary
conditions. Finally, microflow reactors offer control over the contact time a reactive intermedi-
ate has with the electrolysis conditions. For a sensitive intermediate, short contact times can
dramatically improve yields.
Many of the recent efforts to develop microflow electrolysis reactions began with the realization
of how the advantages offered by a microflow reactor might improve the synthetic reactions derived
from cation pools (Scheme 9.15) [25]. This work has been reviewed [26]. By taking a stable cation
pool and then introducing it into a microflow reactor, a cation flow can be generated. This cation
flow can then be treated with nucleophiles, a method that can improve mixing of the cation with the
nucleophile, allow for shorter reaction times with sensitive cations, and provide better temperature
control over the often exothermic process. The initial examples of this approach used the electroly-
sis reaction to make a pool of N-acyliminium ions that were subsequently trapped with allylsilane
and enol ether nucleophiles [25,26c,28]. In this work, Yoshida and coworkers nicely demonstrated
the utility of the method for combinatorial synthesis by utilizing a combination split–pool/parallel
synthesis approach. To this end, an iminium ion pool was subdivided and then processed in parallel
fashion with several different nucleophiles.
The nucleophilic trapping of an N-acyliminium ion in a microflow reactor benefited greatly
from the improved mixing associated with the experiment [29]. Consider the Friedel–Crafts
Substrate Cation pool
Micro
Product
mixer
Nucleophile
SchEME 9.15 Microflow techniques and the use of cation pools.

O
O + Bu
Bu Anodic MeO N
MeO N O OMe O OMe
Oxidation
SiMe3 N N
Bu Bu
MeO OMe + MeO OMe
Micromixer Bu
N O
MeO OMe OMe OMe OMe
Batch mixing 33% : 33%
OMe Micromixing 92% : 4%
SchEME 9.16 Microflow and the Friedel–Crafts alkylation reaction.
reaction shown in Scheme 9.16. In this example, the alkylation of 1,3,5-trimethoxybenzene

with an N-acyliminium ion led to the formation of a mixture of both mono- and disubstituted
products. When the reaction was accomplished in a batch reactor, roughly equal amounts of
the products were formed. However, when the reaction was conducted in a microflow reactor
equipped with a micromixer, both the yield and the selectivity of the reaction improved. Using
the microflow channel, a 92% yield of the monoalkylated product was formed along with only
4% of the dialkylated product. The observation that micromixing improved the chemoselec-
tivity of the reaction proved to be general. For example, the use of a micromixer also led to a
dramatic improvement in the yield of monosubstituted product generated from the iodination of
electron-rich aryl rings [30].
Interestingly, the same reactive N-acyliminium ion intermediate employed in the chemistry illus-
trated in Scheme 9.16 can be used to trigger polymerization reactions with enol ether monomers
[31]. The reactions again benefited from the generation of a cation pool of the substrate and then
the fast mixing associated with the microflow reactors. In this case, the combination of cation-pool
chemistry and the microflow reaction enabled better control over the monodispersity of the polymer.
The better distribution resulted from the ability to carefully generate and control the concentration
of the reactive initiating group. It was important to quench the polymerization in a uniform manner
so that the polymerization reaction ran for a uniform length of time. This was accomplished by con-
trolling the path length of the reaction in the microflow channel before introduction of a quenching
reagent (Scheme 9.17).
O
+ Bu
MeO N
Cation
pool
Variable
path length Micromixer
O OMe
Micromixer N N(i-Pr2)
Bu
n
OR OR
(i-Pr)2NH, CH2Cl2
OR
(quencher)
R = n-Bu, i-Bu, t-Bu
Cooling bath
SchEME 9.17 Microflow and the synthesis of polymers

O
+ Bu
MeO N
CO2Me
Bu N
Micromixer
O
Micromixer
N
CO2Me
O
82%
N SiMe3
CO2Me
(Other allylsilane, allyl stannane,
and ketene acetal olefins were studied)
SchEME 9.18 Microflow and the use of multicomponent reactions.
ArS(ArSSAr)+ OBn
–
B(C6F5)4 +
O
BnO
BnO OBn Micromixer OBn
Micromixer
Micromixer O OR
BnO
BnO OBn
OBn
O SAr Yield = 67–98%
BnO ROH Et3N
BnO R = Me, sugar
OBn
SchEME 9.19 Microflow and the synthesis of glycosides.
In a similar manner, the addition of a second reagent to a microflow reaction affords the oppor-
tunity to conduct multicomponent reactions (Scheme 9.18) [32]. In this case, the second coupling
component is added downstream of the initial nucleophile added to the N-acyliminium ion. The
cation-flow strategy also proved useful for the generation of reactive reagents. For example, the
use of [ArS(ArSSAr)]+ has proven particularly useful for the generation and synthetic application
of glycosyl cations (Scheme 9.19) [33]. In these experiments, the yield of the product obtained was
highly dependent on both the resident time and the temperature of the reaction.
Since the reaction benefited from low temperature and shorter retention times, it appeared that
the stability of the oxonium ion was an issue. Overall, the approach proved compatible with the gen-
eration of a variety of oxonium ions and the trapping of those oxonium ions with alcohol, allylsilane,
and enol ether nucleophiles.
III. PARALLEL SYNThESiS METhODS

A. INITIaL ELECTroCHEMICaL EFForTS
The reactions outlined earlier fall into the split–pool category because they use a single electrode to
generate a reactive intermediate that is then subdivided and used to initiate a number of subsequent
reactions. The methods are attractive because they convert a single intermediate into a variety of
products. Many of the reactions are also compatible with a parallel synthesis format that uses mul-
tiple electrodes to generate a variety of different intermediates that are then individually carried
forward. Of course, the techniques can be combined in that the intermediates generated in a parallel
process can be used to start split–pool syntheses.
Parallel approaches to electrochemistry have been frequently used in the discovery of new metal-
based catalyst systems [34]. In these efforts, electrochemistry is typically used as an analytical
technique for rapidly screening the utility of catalysts that are synthesized using traditional means.
The pioneering work in this area was reported by Smotkin and Mallouk in 1989 [35]. In this effort,
catalysts for methanol oxidation were screened by pipetting various metal salts and aqueous sodium
borohydride onto carbon paper. The carbon substrate was conductive but not catalytic for the oxi-
dation of methanol. The result was an array electrode that could be used to screen the catalysts
for activity. This was done by stepping up the potential of the array electrode in the presence of
a fluorescent indicator that was luminescent in acid. Since methanol oxidation generates acid, the
presence of the indicator showed the locations on the array electrode where methanol was oxidized
most readily. In this way, all of the catalysts could be screened in a single experiment. A very simi-
lar method was used to discover methanol-tolerant nonplatinum electrocatalysts for use in direct
methanol fuel cells [36].
More traditional parallel synthesis approaches have also been used for catalyst discovery. For
example, a series of Pd-binary catalysts for the reduction of oxygen were spotted onto a working
electrode [34b]. The electrode was then covered with a PTFE mask that had 88 holes with a diam-
eter of 5 mm and a depth of 10 mm. The holes were aligned with the catalyst on the working elec-
trode. A Pt-wire counter electrode and Ag/AgCl reference electrode were then placed into one of the
holes, and the oxygen reduction reaction activity measured for the catalyst composition at that site.
Following the electrochemical evaluation in one of the holes, the counter and reference electrodes
were moved to the next site. In this way, a series of new catalysts could be systematically prepared
and rapidly evaluated.
Speiser and coworkers have used a similar parallel approach to discover new catalysts for con-
ducting synthetic organic reactions [37]. In a recent example, a series of homogeneous ruthenium(II)
hydrogenation catalysts were explored by first dissolving them in an electrolyte solution and then
placing them in the wells of a microtiter plate [37d]. Electrode bundles were then moved using
computer control [37b] and placed into each of the wells one at a time. Cyclic voltammograms were
recorded for each catalyst. The voltammograms obtained in this manner could be correlated to the
success of the catalysts leading to a high-throughput method for identifying new catalysts.
The importance of such efforts is driving the development of a number of interesting new tech-
nologies. For example, Crooks and coworkers have reported a new method for screening oxygen
reduction catalysts using bipolar electrodes (Scheme 9.20) [38]. To this end, a bipolar indium tin
oxide (ITO) electrode is coated with a series of Ag strips on one end and a catalyst for the reduc-
tion at the other. The functionalized bipolar electrode is then placed in an electric field that creates
an anode on the end with the silver strips and a cathode at the catalytic end. If the catalyst on the
cathode can do the desired reduction of oxygen, then a current is passed that reduces the oxygen at
the cathode and oxidizes the Ag strips on the anodic side of the bipolar electrode. The potential drop
in the bipolar electrode is proportional to distance between the electrodes so the oxidation takes
place first at the Ag strip located furthest from the catalyst. When this strip is consumed, the next
strip becomes active lowering the overall potential of the system. The more active the catalyst is for
O2 H2O
Ag+
– +
Ag strips ITO Catalyst
SchEME 9.20 Bipolar electrodes and the screening of oxygen reduction catalyses.
oxygen reduction, the lower the potential that can be tolerated by the reaction leading to the con-
sumption of more Ag strips. In this way, the activity of the catalyst can be directly ascertained from
an examination of the Ag strips consumed. By placing a series of functionalize bipolar electrodes in
the electric field, a number of catalysts can be evaluated at the same time.
The bipolar electrode approach is also applicable to the synthesis and evaluation of other materi-
als. Inagi and Fuchigami have used bipolar ITO electrodes in order to synthesize gradient-doped
conducting polymer films [39]. To this end, the ITO electrodes were coated with a thin film of the
conducting polymer and then placed in an electric field. This led to a gradient potential in the bipo-
lar electrode, and hence a gradient potential being applied to the polymer. The gradient potential led
to varying levels of dopant being inserted into the polymer matrix with the amount of dopant being
dependent on the distance from the ends of the ITO electrode.
B. AppLICaTIoN To SYNTHESIS: BULk METHoDS

Parallel electrochemical methods are also useful for the synthesis of small organic molecules.
Yudin and coworkers have employed parallel electrosynthesis methods to conduct both oxidation
and reduction reactions. The work has been reviewed [40]. As an example, a strategy for the oxida-
tion of amides, carbamates, and sulfonamides is illustrated in Scheme 9.21 [41]. In the setup shown,
the electrolyses were conducted in 16 individual reaction vials (or wells in a Teflon block) that were
fitted with a Teflon cap with 16 matching openings. In between the Teflon cap and the vials was
placed a stainless steel plate with 16 stainless steel electrodes welded in position to match the vials.
These stainless steel electrodes served as the counter electrode in each of the reactions. Into each
vial was placed a working electrode using the opening in the Teflon cap. In this way, a galvanostatic
electrolysis could be conducted in each vial. The reaction setup was used to both make a small
library of alkoxy-substituted products and rapidly optimize the reaction conditions for a particular
reaction.
The same reaction setup was also employed for a reduction reaction (Scheme 9.22) [42]. In this
example, diamines were synthesized by the Pd(0)-mediated electroreductive coupling of imines.
In order to minimize the cost of the parallel electrolysis setup, a stainless steel cathode was used
along with a sacrificial aluminum anode. The sacrificial anode was employed in order to avoid
Anode
Cathode –2e– OR
N N
(stainless steel ROH
plate beneath the cap) O Ot-Bu O Ot-Bu
80–95%
SchEME 9.21 The parallel synthesis of N-acyliminium ions.
Cathode Al anode
NH2
R1
R1
Pd2+ 2/3 Al3+
NH2
NH
Pd0 2 + TFA
R1 H
SchEME 9.22 Parallel synthesis and reduction reactions.

Series format – +
– + – + – +
Cathode Anode n
Electrochemical cells
TMS RVC anode, Pt cathode

21.0 mA, 2.0 F MeO
R O
0.03 M Bu4NBF4, MeOH R O
Cbz N
N OMe Cbz N
Each substrate was oxidized N OMe
H O CH2Ph in two separate cells for a total H O CH2Ph
R = H, Me, CH2Ph six simultaneous oxidations
Cbz = PhCH2OC(O) Yields = 74–91%
SchEME 9.23 A series approach to N-acyliminium ions.
oxidation of the product amines. The reactions were superior to conventional coupling reactions
with activated metals in that they led to significantly less reduction of the imine without coupling.
Presumably, this change in the reaction occurred because of the low working potential of the cath-
ode due to the use of the sacrificial anode, a feature that affords careful control of Pd(0) generation.
The oxidation of silylated amides using both a parallel electrochemical approach and a series-
type format has also been reported (Scheme 9.23) [43]. The silyl group was added to the amides in
order to expand the scope of the substrates that can be oxidized. For example, with the use of a silyl
electroauxiliary, a single amino acid in a peptide can be oxidized. The compatibility of the chem-
istry with combinatorial synthesis was initially demonstrated using a parallel synthesis strategy
directly analogous to the method illustrated in Scheme 9.21. This approach allowed for individual
control of each electrolysis reaction. However, for these reactions, independent control of the reac-
tions was not necessary. With the electroauxiliary, the oxidation potential of the substrates did not
vary greatly, and a simple series format could be used (Scheme 9.23). In this experimental setup,
the cathode of one electrolysis reaction is hooked to the anode of the next. A single power supply is
used, and the amount of current passed through each of the cells is identical.
The series format has also proven compatible with the oxidation of carbamates without the elec-
troauxiliary [44]. In this case, both pyrrolidine- and piperidine-derived carbamates were methoxyl-
ated. The reaction took advantage of a solid-supported base [45] to generate the electrolyte for the
reaction. This change enabled a high-throughput separation of the products generated.
C. MICroFLow AppLICaTIoNS To ParaLLEL SYNTHESIS

As with the earlier split–pool syntheses, microflow channels offer a number of advantages for
parallel reactions. In one powerful development, microflow channels have been used to conduct
laminar-flow-based reactions (Scheme 9.24) [46]. This method relies on the channel being small
enough to ensure that the flow through it is both stable and laminar. The result is a stable interface
between two flows introduced into the microchannel. Substrates introduced in Flow 1 do not reach
the anode, and substrates introduced in Flow 2 do not reach the cathode. In this way, cations can
be generated at the anode and then allowed to react with nucleophiles at the interface between the
flows without exposing the nucleophiles to the oxidation. The nucleophiles can either be introduced
Flow
1 Cathode
Subs. Nuc–
Product (Nuc-E)
Subs. E+
Flow Anod e
2
SchEME 9.24 A laminar-flow approach to parallel synthesis.
in Flow 1 or generated at the cathode (see the following text). The reaction setup has a major advan-
tage in that it allows for reactions with unstable cations. In the first example of this reaction, an
N-acyliminium ion generated at the anode was quenched with an allylsilane nucleophile that was
introduced into the reaction via Flow 1 [46,47]. As an alternative, the nucleophile can be added
to the product from the electrolysis following the electrochemical reaction [25]. Once again, the
laminar flow in the channel controlled the rate of product formation. This second setup allowed
more time for the formation of the desired electrophile, an approach that can be beneficial if the
electrophile generated is stable.
The laminar-flow method has also been used to generate anions (Scheme 9.25) [48]. In the reac-
tion shown, the chemoselective reduction of either an aldehyde or an allylchloride is conducted
independent of the reduction potentials of the two groups. This was accomplished by controlling
which channel the substrates were introduced into. For example, if the aldehyde was introduced
through Inlet 1, then it was reduced to a radical anion that in turn underwent reaction with the allyl-
chloride to form A as the major product. If the allylchloride was introduced through Inlet 1, then
it was reduced to an allylanion that added to the aldehyde to predominately form B. The reaction
illustrates how laminar flow in the microreactor can be employed to control the chemoselectivity
of the reaction.
Because of the closeness of the electrodes in a microflow cell, the reactions are ideal for paired
syntheses that take advantage of both the anodic and cathodic processes of the electrolysis. A review
on this effort has appeared [49]. To this end, Atobe, Fuchigami, and coworkers used the laminar-
flow-based reaction design highlighted in Scheme 9.25 to add benzyl anions to ketones [50]. In these
transformations, the cathode was used to make the anion, while the anode was used for the oxida-
tion of a secondary alcohol.
Flow 1 O
Method A Ar H
Method B Cl
Cathode
OH OH
Subs. Nuc–
vs.
Ar Ar
A. Method A B. Method B
Anode
Flow 2
Cl
Method A
Method B O
Ar H
SchEME 9.25 Laminar-flow and the synthesis of anions.

N+
CO2Me
N SiMe3 Anode
CO2Me
Micromixer
N
Ph
Ph Cl CO2Me
Cathode
+ 70%
TMSCI Ph SiMe3
SchEME 9.26 Divided flow reactors and paired electrolyses.
Anode 80 μm
O
+ + H2
MeO O OMe
MeOH Cathode
Max. yield = 98%
SchEME 9.27 Thin-film reactors and paired electrolyses.
In a related example from the Yoshida group, a divided cell microreactor was used to generate
both an N-acyliminium ion (at the anode) and an allylsilane nucleophile (at the cathode) [28]. The
flow from each chamber was then combined to effect the net addition reaction (Scheme 9.26). An
alternative reaction design that flowed substrates as a thin film between two parallel plate elec-
trodes was forwarded by Fuchigami, Marken, and coworkers (Scheme 9.27) [51]. The reactor was
used to remove two electrons from a furan group while at the same time generating two equiva-
lents of methoxide and an equivalent of hydrogen. The combination of anodically and cathodically
generated intermediates afforded the desired methoxylated furan product. As in the laminar-flow
method, this reaction was intriguing from an environmental perspective because it did not require
the addition of an electrolyte. Instead, the combination of intermediates generated at the anode and
cathode to form the desired product avoided the buildup of charge at the electrodes. As a related
reaction design, Yoshida and coworkers used a microflow channel with a porous membrane divider
to accomplish the methoxylation of 4-methoxytoluene and N-methoxycarbonyl pyrrolidine without
the use of an electrolyte [52].
A pair of alternative microflow reactor designs has been forwarded by Kristal and coworkers
[53]. In these reactors, the electrolysis is conducted by passing the substrate through a parallel array
of bipolar electrodes [54] (one example is shown in Scheme 9.28). The result is a series of parallel
channels that each comprises a galvanostatic cell. The approach enables a parallel electrochemical
method with greatly simplified electric circuitry.
D. MICroELECTroDE ArraY–BaSED ApproaCHES

In principle, microelectrode arrays can also be used to conduct the parallel synthesis of a molecular
library. A description of the arrays cited in the following has been published [55]. With a microelec-
trode array, each electrode in the array is used to facilitate the synthesis of a molecule in the library.
The result is unique in that it builds each molecule in the library proximal to a unique, individually
addressable microelectrode in an array. The electrodes can then be used to monitor the binding
properties of the molecules. For example, consider the electrochemical impedance experiment out-
lined in Scheme 9.29. A review of such experiments as they apply to analytical sensors has appeared
[56], and the experiment works well on microelectrode arrays [57]. In the current context, an array
Out
+ –+ –+ –+ –
+ –+ –+ –+ –
Anode + –+ –+ –+ – Cathode
+ –+ –+ –+ –
+ –+ –+ –+ –
In
SchEME 9.28 Parallel synthesis using bipolar electrodes.
Fe2+
O
M1
O S
Fe3+
O
M2 Fe2+
Signal O S M2R
Fe2+
O M3
O S
Fe3+
Auxiliary
Anode
cathode
SchEME 9.29 A microelectrode array approach to molecular signaling.
functionalized with ligands for a receptor (M1, M2, and M3) is submerged in a solution containing
an iron redox couple along with a Pt counter electrode. The iron redox couple is then oxidized at
the array and reduced at the counter electrode leading to a current that can be measured at each
electrode of the array. The targeted receptor (M2R) is then added to the solution above the array.
When the receptor binds a molecule on the surface of the array, it blocks the iron redox couple from
reaching the anode below. The current drops off at that electrode leading to a signal that can be
measured. The result is a method for monitoring the binding of the molecules on the surface of the
array and the receptor as the events happen.
Of course, the challenge of setting up such an experiment is placing or building the molecules in
the molecular library proximal to individual electrodes in the array, especially when the array con-
tains upward of 12,544 electrodes/cm2. One approach to solving this problem has been forwarded
by Heller and coworkers [58]. In this work, free-field electrophoresis was used to deliver charged
reagents to specific reaction sites on an array. Each site on the array was comprised of an attach-
ment layer, a permeation layer, and an underlying direct current microelectrode. The attachment
layer was used to bind a monomer to the site, and the permeation layer was used to prevent reagents
generated at the underlying electrode from reaching the surface. Hence, all reactions at a given site
on the chip resulted from the charged reagents delivered to the site. That delivery was accomplished
by using the electrode to attract and then concentrate the charged reagent at the site. Once there,
the reagent triggered a transformation involving the molecule bound to the attachment layer. For
example, reagents were delivered to selected sites on the array in order to carry out the deprotection
of a monomer. Subsequent coupling reactions conducted on the array occurred only at sites selected
for the deprotection.
A similar method for building peptides was reported by Beyer and coworkers [59]. In this work,
activated amino acids were embedded into polar particles. Electrical fields patterned by individual
pixel electrodes were then used to deliver the particles to various sites on an array. Strong adhesive
forces then held the particles in place on the surface even when new electrical fields were applied. In
this way, multiple amino acids were delivered to multiple different sites on the array. After placement
of the particles on the array, the particles were melted leaving behind the activated amino acid sub-
strate. The ensuing coupling reactions then added new amino acids to the peptides being constructed
at each location. The method is advantageous in that the coupling reactions are all done in parallel.
This allows for the construction of a molecular library with a minimal number of coupling steps.
An alternative strategy is to use the electrodes at selected sites in an array to synthesize reagents
and catalysts for doing desired reactions at the site. Since electrodes can be used to synthesize
acids, bases, oxidants, reductants, nucleophiles, electrophiles, transition metal catalysts, etc., such
an approach would allow for a wide range of synthetic chemistry to be conducted site-selectively
on an array. Efforts along these lines began with the site-selective generation of acid and the syn-
thesis of DNA oligomers [60,61]. The chemistry started by coating the array with a sucrose surface
[62] that was then functionalized with a DNA primer. The electrodes in the array were then used
to site-selectively generate acid by the oxidation of water. Base in solution confined the acid to the
electrodes selected. The acid generated led to the removal of a dimethoxytrityl protecting group
from the 3′-hydroxy of the DNA, and then the alcohol used to add a nucleotide to the DNA oligomer.
Repeating the process allowed for the synthesis of an oligomer.
The overall strategy is not restricted to the generation of acid [62,63]. It has been shown to work
for the site-selective generation of base [57b,64], Pd(II) [65], Pd(0) [66], Cu(I) [67], Sc(III) [68], and
ceric ammonium nitrate [69]. In each case, an electrolysis reaction is used to generate the chemical
reagent or catalyst, and in each case, a solution-phase reaction is used to scavenge the reagent or
catalyst generated before it can migrate to remote sites on the array. The result is a powerful method
for the synthesis of a variety of molecules on an array.
The site-selective generation of Cu(I) on an array provides an excellent example of how the
electrodes in an array can be used as cathodes (Scheme 9.30) [67a]. All such sequences start with
coating the array with a porous reaction layer that allows for the attachment of molecules to the
surface of the array. For the chemistry outlined in Scheme 9.30, the array was coated with agarose.
A substrate was then placed onto the agarose by each electrode in the array with the use of a base-
catalyzed esterification reaction [57b]. The base was generated by the reduction of vitamin B12.
The resulting radical anion deprotonated the alcohols on the agarose leading to the formation of
an alkoxide that in turn added to an N-hydroxysuccinimide ester. The reaction was confined with
the use of excess activated ester in the solution above the array. The activated ester reacts with any
base (methoxide) that migrates away from the electrode where it was generated. Following the sur-
face functionalization, a Cu(I)-catalyzed click reaction was used to add a benzotriazepine to each
of the electrodes in the array. This reaction was conducted by treating the entire array with copper
sulfate, disodium bis(bathophenanthroline)-disulfonate ligand, and tetrabutylammonium bromide
electrolyte. The copper sulfate was then reduced to the necessary Cu(I) catalyst by setting the
electrodes in the array to a potential of −2.4 relative to the Pt-anode counter electrode. In this
case, the click reaction was run at every microelectrode in the array, although it can be confined
to selected electrodes with the use of oxygen as a confining agent [67]. Following the click reac-
tion, a second Cu(I) reaction was conducted. In this case, the Cu(I) catalyst was used to effect a
7:2:1 MeCN/DMF/H2O
Bu4NBr, CuSO4, Phen.
Vitamin B12, –2.4 V, 400 cycles
Me4NNO3 O 0.5 s on, 0.1 s off O
MeOH, DMF wholeboard pattern
OH O N3 O N NN
–2.4 V, 600 cycles
0.5 s on, 0.1 s off
3 3
O O
O N N
N N Me O
O N3
N N N
O Me
7:2:1 MeCN/DMF/H2O
Bu4NBr, CuSO4, Ph3P,
–2.4 V, 600 cycles
0.5 s on, 0.1 s off
checkerboard pattern
I
pyrene
O
O N
N N
3
N
O
pyrene N N
Me
SchEME 9.30 (See color insert.) Site-selective Cu(I)-reactions on a microelectrode array.
Heck-type reaction that added a vinylhalide across the imine in the benzotriazepine substrate. The
conditions were nearly identical to those used for the click reaction with two exceptions. First,
triphenylphosphine was used as the ligand for the reaction in analogy to the known solution-phase
reaction. Second, for this reaction, only selected electrodes (a checkerboard pattern) were used for
the reduction along with oxygen as a confining agent. The oxygen reoxidized any Cu(I) catalyst
in the solution above the array before it could migrate to remote sites on the array. The image
provided in Scheme 9.30 shows the success of this confining strategy.
The chemistry highlighted in Scheme 9.30 shows not only the utility of the microelectrodes in
the array as cathodes but also the use of Cu(I) click reactions as a method for rapidly synthesizing
mass spectrometry cleavable linkers [67b]. The array synthesized was analyzed by TOF-SIMS [70].
Under these conditions, the triazole product from the click reaction fragmented and thereby allowed
for the mass of the product to be measured. In this way, characterization data can be obtained for
molecules synthesized on an array.
The microelectrodes in an array are also useful anodes. Two examples serve as particularly
effective illustrations. In the first, the electrodes were used to generate Pd(II) in order to effect the
oxidation of the agarose polymer coating the array (Scheme 9.31) [65b]. The oxidant was confined
to selected electrodes in the array with the use of ethylvinylether as the confining agent. The eth-
ylvinylether confined the Pd(II) by means of a solution-phase Wacker oxidation that rereduced the
Pd(II) back to Pd(0). The result was an opportunity to conduct site-selective reductive amination
reactions on an array. In the image shown, a checkerboard pattern of electrodes was used for an
initial oxidation that was then used to add an amine with a red fluorescent tag to the array (via a
reductive amination). The sequence was then repeated using the opposite checkerboard pattern for
the oxidation and an amine with a green fluorescent tag for the reductive amination. In the gray
scale image shown, the green spots appear as a darker shade of gray. The lighter gray spots are red.
No crossover was observed between the electrodes used for the two patterns.
Porous hydroxylated polymer
Electrode NH2–(Red) H
OH –e– O NaCNBH3, MeOH
Electrode
on Br N N (Red)
Pd(OAc)2, off
3 12 h
Et4NOTs; (7:1) CH3CN/H2O
Electrode CH3CH2OCHCH2
Electrode
off OH 16 min OH on OH
NaO3S NH2 –e–

N O N+ Pd(OAc)2,
Br N
3
SO3– Et4NOTs; (7:1) CH3CN/H2O
NaO3S SO3Na CH3CH2OCHCH2
O SO
NHNH2 (Red) (Green) 16 min
H H
NH2–(Green)
N (Red) N (Red)
NaCNBH3, MeOH
12 h
N (Green)
O
H
SchEME 9.31 (See color insert.) Microelectrode arrays and site-selective oxidation reactions.
Similar approaches have been used to generate a range of oxidants including CAN, DDQ, and
Cu(II). But the chemistry is not restricted to the generation of stoichiometric oxidants. In the sec-
ond example of a microelectrode array being used as an anode, the microelectrodes were employed
to site-selectively generate Lewis acids on the array. In the chemistry illustrated in Scheme 9.32, the
microelectrodes in the array were used to oxidize a Sc(I) precursor. The resulting Sc(III) Lewis acid
was used to catalyze a site-selective Diels–Alder reaction [68]. The chemistry worked beautifully
O O
NHBoc NHBoc
O Sc(OTf )3 O
Me4NNO3
O CH2Cl2
O
3.5 V, 900 cycles
N 0.5 s on, 0.1 s off N
Wholeboard pattern
pyrene
O H O
N
Ph
S
H
NN
H
OH Bu4NPF6, MeOH
+ +3.0 V, 0.5 s on, 0.1 s off,
900 cycles
O Checkerboard pattern
pyrene
O
HN
n
N
SchEME 9.32 (See color insert.) The use of “safety-catch” linkers on an array.
on both 1K and 12K arrays. In each case, the Sc(I) precursor for the reaction was generated in
the solution above the array by treating a catalytic amount of Sc(OTf)3 with an excess of a 2-aryl-
benzothiazole. The benzothiazole reduced the Sc(OTf)3 and then served as a confining agent for
the ensuing microelectrode array reaction. For the reaction shown in Scheme 9.32, the dienophile
for the Diels–Alder reaction was attached to the array with a safety-catch linker [71]. This linker
possessed a masked amine that could be deprotected by the generation of acid at the associated
electrode, a scenario that was accomplished nicely by the oxidation of diphenylhydrazine [62,63].
Release of the amine triggered lactam formation and cleavage of the molecule from the surface
of the array. The result was the ability to recover the Diels–Alder product from the array, a sce-
nario that allowed for the determination of both the stereochemistry and purity of the product. The
use of the safety-catch linker strategy is particularly attractive in that it uses the same electrodes
employed to monitor the biological behavior of the molecules in the library to recover them from
the array. In this way, there is no chance for a loss of fidelity on the array between the signaling and
characterization studies.
Reactions have also been developed for the placement of more complex biological ligands onto a
microelectrode array. Initially, this chemistry focused on the use of a thiol-based Michael reaction
(Scheme 9.33) [57b]. The chemistry was confined by controlling the reaction that placed the Michael
acceptor onto the array. The image provided illustrates the level of confinement that can be obtained
on a 12K array with this strategy. The chemistry proved compatible with the placement of peptides
onto the arrays and was used to provide an initial probe of the analytical capabilities of the arrays
[57b]. However, the reactions were plagued by the reversibility of the conjugate addition. At a pH 7,
molecules placed on an array using a thiol-based Michael reaction migrate from one site to another.
The retro-Michael reaction can be stopped at pH 4, but most biological studies require neutral pH.
A different approach was needed.
To this end, site-selective Cu(I) reactions have proven ideal (Scheme 9.34) [67]. In the example
shown, a fluorescent ligand tied to biotin was placed onto an array having 12,544 microelectrodes/
cm2 [57c]. A second set of electrodes was then functionalized with just the linker. Both of the
coupling reactions involved a Cu(I)-mediated addition of an amine nucleophile to an aryl bromide
surface coating the array [67b]. The Boc-protecting group on the initial substrate was removed dur-
ing the electrolysis by acid generated at the counter electrode. The Cu(I) catalyst was generated in a
fashion identical to that discussed earlier in connection with Scheme 9.28. The rate of the addition
was dependent on the nature of the ligand used. As with solution-phase Cu(I)-coupling reactions,
the chemoselectivity of array-based coupling reactions with competing heteroatomic nucleophiles
is dependent on the nature of the ligand used for copper [67b].
O O
O
HS O
N
O O
OH O
O
Vitamin B12, Me4NNO3 Vitamin B12, MeNNO3
MeOH, DMF MeOH, DMF
–2.4 V, 300 cycles –2.4 V, 300 cycles
0.5 s on, 0.1 s off 0.5 s on, 0.1 s off
Single electrode
O O
O S O
SchEME 9.33 (See color insert.) Functionalizing electrodes with conjugate addition reactions.
HN NH
H
H
S
Diblock copolymer [72] 4 Ph
O
H N O
O
N R
Br Boc N
On OFF
CuSO4, Bu4NBr, H
N
Ph3P, CH3CN/DMF/H2O H
–1.7 V, 180 s
Br Br
Off
H On
N R1 O
Boc HN NH
CuSO4, Bu4NBr, H
Ph3P, H
CH3CN/DMF/H2O,
S
–1.7 V,
Ph
180 s 4
O
O N O
N
H
N Ph
Me H
O
O N O
N
H
N
H
SchEME 9.34 A biotin functionalized microelectrode array.
The array synthesized with the chemistry illustrated in Scheme 9.34 was used to confirm the
utility of the arrays for monitoring molecular interactions in “real time” [57]. In these experiments,
the array was submerged in solutions containing an Fe2+/Fe3+ redox couple and various concentra-
tions of streptavidin. For each concentration of streptavidin, a cyclic voltammogram for the iron
was obtained. As the concentration of streptavidin increased, the current associated with the iron
decreased at electrodes that were functionalized with the biotin. No decrease occurred at either
unfunctionalized sites on the array or sites functionalized with the linker but no biotin. The array
clearly detected the biotin–streptavidin binding event, a result that demonstrated the potential for
the approach as a method for interrogating biological receptors. Similar analytical experiments
using peptides that contain arginine–glycine–aspartic acid residues and the integrin receptors they
target have proven equally successful [72].
IV. CONcLUSiONS AND A ViEw fOR ThE FUTURE

Electrochemistry is a versatile tool for organic synthesis that provides a variety of opportunities to
solve synthetic challenges in unique ways. This statement appears especially true as the larger field of
organic chemistry pushes further into the biological arena and the synthetic challenges encountered
expand. Such efforts often require the rapid assembly and analysis of molecular libraries. The librar-
ies are assembled by using split–pool and parallel synthesis techniques. For both, electrochemistry
offers enticing opportunities. From the use of cation-flow methods that allow for the use of highly
reactive intermediates as branching points for combinatorial syntheses to the use of microelectrode
arrays that allow for the synthesis of addressable libraries, electrochemistry provides opportunities
to rapidly construct molecular libraries in ways that are simply not possible using more traditional
methods. From a medicinal chemistry standpoint, this is very important. The availability of unique
molecular libraries and unique methods for monitoring them gives rise to the potential for unique,
proprietary lead compounds and new opportunities for drug discovery. So unlike previous efforts
to apply electrochemistry to the synthesis of natural products, the success of combinatorial electro-
chemistry will not depend on its adoption by a reluctant organic synthesis community, but rather the
opportunities it offers for the application of organic chemistry to the solution of biological problems.
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10 Relations between Micro-
and Macrophenomena
Christian Amatore
CONTENTS
I. Introduction .......................................................................................................................... 371
II. Basic Principles .................................................................................................................... 372
A. Homogeneous Chemical Equivalent of Electrolysis Rates ........................................... 372
B. Coulometry: Apparent Number of Electrons Consumed..............................................375
C. Separation of Waves and Selectivity in Electrolysis ..................................................... 379
III. Competitive Reaction Schemes: Optimization of Preparative-Scale Electrolysis................ 381
A. Slow Reaction Schemes ................................................................................................ 381
B. Elementary Method for Fast Competitive Kinetics ...................................................... 383
1. Presentation of the Method .................................................................................... 383
2. Predictive Value of the Method ............................................................................. 386
3. Rationalization of a Series of Results .................................................................... 388
IV. Conclusion ............................................................................................................................ 390
References ...................................................................................................................................... 391
There is no art as difficult as the art of observation: a rational intelligent mind together with
educated experience, only attainable through practice, are indispensable: not the observer
who only visually perceives the object, but rather the observer who sees the different parts and
how these parts are connected to the whole.
Justus von Liebig
I. INTRODUcTiON
In Chapter 1, our presentation of electrochemical concepts was focused mainly on an analytical/
kinetic point of view, namely, on the specific aspects related to the electrode and to the solution in its
close vicinity. Indeed, as soon as kinetics is considered, the bulk solution may often be regarded as a
concentration buffer whose only role is to maintain constant or known reactant concentrations at the
external diffusion layer boundary. Obviously, this is not the case when preparative electrochemistry
is considered. Indeed, the goal is then to change the solution composition. Yet this composition
change is effected through the relay of the diffusion layer, which “transmits” the modifications
achieved at the electrode to the bulk solution. Since chemical reactions may take place within the
diffusion layer, as discussed in Chapter 1, the way the bulk solution is affected depends largely on
the microphenomena occurring in the thin solution layer (5–20 µm, usually) adjacent to the elec-
trode [1]. This results in an extensive coupling between micro- and macrophenomena at electrodes,
which is one of the reasons why kinetics, the study of microelectrolysis phenomena, is so developed
371
Yet these important relations should not conceal the large differences between micro- and macro-
electrolysis. These differences, which were discussed briefly in Chapter 1, have their main origin in
the necessity of passing a current through the solution between the working and auxiliary (or coun-
ter) electrodes. Obviously, the ensuing problems are quite different when one considers currents in
the microampere (or even femtoampere for ultramicroelectrodes) range or in the ampere range as in
macroscale laboratory electrolysis.* Other changes are also introduced that originate from the dif-
ferences in dilution. Under microelectrolytic conditions, very dilute (usually 0.1−10 mM) solutions
are considered. Thus, activities and diffusion coefficients, for example, are close to their values at
infinite dilution. This is not the case in macroelectrolysis since rather concentrated solutions are
used. This may introduce large changes in mass transfer rates as well as in chemical reactivity, and
also in such specific factors as migration [3]. These changes in concentration, as well as the larger
current densities and electrolysis times, may also result in an increased importance of adsorption,
coatings, or pollution phenomena at the electrodes. This is particularly true in aqueous media in
which adsorption or chemisorption may play a decisive role in the distribution and selectivity of the
products as a function of the electrode material.
As understood from this discussion, it is generally unrealistic to believe that microelectrolytic
results transpose exactly to macroelectrolytic conditions.† However, provided one keeps these dif-
ficulties in mind, microelectrolysis results and approaches constitute extremely useful guides in
tackling with macroscale electrolysis. Amazingly, data obtained at ultramicroelectrodes (i.e., of
micrometric or smaller dimensions) should transpose with the least difficulty since they may be
obtained with concentration or current density (a few amperes per square centimeter) conditions
matching those found in preparative-scale electrolysis. Moreover, they allow meaningful results to
be obtained in the presence of strong migrational contributions [4,5].
II. BASic PRiNciPLES

A. HoMoGENEoUS CHEMICaL EqUIVaLENT oF ELECTroLYSIS RaTES
As explained in Chapter 1, the bulk concentrations, C, are affected by the phenomena occurring
within the diffusion layer (which is identified, in this chapter, with the stagnant layer imposed by
hydrodynamics) through the general relationship
dC DA  ∂C   dC 
=− + (10.1)
dt V  ∂x  x =δ  dt chem
 

where
D is the diffusion coefficient
A is the working electrode surface area
V is the bulk solution volume
This equation derives from the conservation of mass fluxes at the diffusion layer/bulk solution
interface (compare Equations 1.155 and 1.156 and Figure 10.1). In Equation 10.1, dC/dt is the overall
rate of the concentration variations considered, whereas (dC/dt)chem is that arising from possible
consumption or production of the species within the bulk solution. The electrochemical rate of pro-
duction or consumption is given by the first term on the right-hand side of Equation 10.1. It depends
on the concentration gradient of the species at the end of the diffusion layer, that is, at x = δ, as well
* Note that in the following, we do not discuss the ultraspecific aspects of industrial-scale electrolysis, which generally
cannot be dissociated from a particular process [2].
† But this is not particular to electrochemistry, since most of the aforementioned difficulties (with the exception of those
related to the current) are encountered when transferring any physical organic result to preparative conditions.
Relations between Micro- and Macrophenomena 373
i or E
CR(x)
x
0 δ
C
CR(x)
Electrode
Bulk solution
Stagnant layer δ
FiGURE 10.1 Schematic representation of the electrochemical cell. First insert: concentration profile of the
reactant in the stagnant layer in the vicinity of the electrode. Second insert: mass transfer black box at the
boundary between the stagnant layer and the bulk solution (x = δ).
as on the ratio of the electrode surface area to the solution volume, A/V. The larger the absolute
value of this rate, the smaller the duration of the electrolysis, which is the reason that generally
large electrode surface areas and high stirring rates (i.e., small stagnant layer thickness) are used
for electrolysis.
Note that in Equation 10.1, a single space coordinate is considered, x, the distance normal to the
electrode. This necessarily implies that all electrode locations behave identically. In practice, this
may be approximated by using symmetrical electrode geometries, with the auxiliary electrode (or
separator in divided cells) parallel and of nearly identical size to that of the working electrode. This
results in a concentration field as uniform as possible at the electrode surface(s). Note that this field
is conveniently visualized when thinking in terms of the electrostatic field that would establish if
the electrodes were those of a large capacitor, since both fields obey analogous laws [6]. However, in
practice, ideal electrochemical geometries are difficultly compatible with other experimental con-
straints, so that the potential and current distribution at electrode surfaces may not be uniform. This
is also true for the thickness of the stagnant layer since a uniform fluid velocity is difficult to achieve
at the electrode surface. For these reasons, the first term on the right-hand side of Equation 10.1 is
merely to be considered as an average over the electrode surface; this is also true for the electrode
potential E or the electrode current density i/A. Nevertheless, to maintain some generality and sim-
plicity in the following presentation, we assume that the concentration profiles depend only on the
distance x from the electrode surface.
The problem is then to relate the concentration gradient (∂C/∂x)x = δ at the stagnant layer boundary
to that (∂C/∂x)x = 0 at the electrode surface (compare Figure 10.1). This is done via the integration of
the differential equations, such as Equation 1.175, which control the concentration profiles within
the stagnant layer. In the most simple situation, the species whose bulk concentration is given in
Equation 10.1 undergoes no chemical reaction within the stagnant layer. Then from Equation 1.175,
its concentration flux is constant within the layer, and thus (∂C/∂x)x = δ = (∂C/∂x)x = 0 = (C−Cx = 0)/δ,
where Cx = 0 is the concentration of the species at the electrode surface. Thus, Equation 10.1 is trans-
formed into
dC DA  dC 
=− (C − C x = 0 ) +   (10.2)
dt Vδ  dt chem

where the constant factor DA/Vδ has the dimensions of a first-order rate constant (s−1). Most of the
time, one is interested in exhaustive electrolysis and thus imposes an electrode potential so that
Cx = 0 = 0, which in most cases simplifies Equation 10.2 for the reactant:
dC DA  dC 
=− C +  (10.3)
dt Vδ  dt chem

Interestingly, under such circumstances, the electrochemical consumption of the species is equiva-
lent to a pseudo-first-order chemical reaction taking place in the bulk solution, with a rate constant
kelec [7]:
DA
kelec = (10.4)
Vδ
Note that it may be surprising that a chemical term is considered in Equation 10.3, whereas we
have supposed that no chemical reaction term was involved within the stagnant layer. As explained
in Chapter 1, this stems from the fact that the effect of any chemical reaction of rate vchem within
the diffusion layer depends on the relative magnitude of vchemδ2/D versus unity. For usual labora-
tory conditions, δ ≈ 10−3 cm and D ≈ 5 × 10−6 cm2 s−1 and then δ2/D is of the order of 0.2 s. Thus,
provided vchem is less than approximately 1 s–1, it has no tangible effect on the concentration profiles
of the species inside the stagnant layer, whereas it has a definite effect in the bulk solution due to
the long reaction times (usually longer or comparable to half an hour). In practice, it is important to
decide when the simplification in Equation 10.2 or 10.3 applies to a given experimental situation.
The discussion just presented affords a simple answer to the problem. Indeed, consider the electron
transfer reaction in Equation 10.5, possibly followed by a chemical step in Equation 10.6:
R + ne P ( E 0 ) (10.5)

P → P′ (vchem = k[ P ]) (10.6)

The simplification in Equations 10.2 and 10.3 is equivalent to saying that vchem is much smaller
than the mass transfer rate D/δ2, which is of the order of 5 s–1. From Chapter 1, this implies that the
R/P redox couple gives a chemically reversible cyclic voltammogram at a scan rate corresponding
to the same mass transfer rate. From a dimensionless analysis and Table 1.5, this corresponds to a
scan rate v such as Fv/RT ≈ D/δ2, that is, v of the order 0.1 V s–1. Thus, observation for identical
or close experimental conditions of a chemically reversible cyclic voltammogram at v ≈ 0.1 V s–1
for the redox couple of interest is sufficient to prove the validity of the assumptions leading to the
homogeneous equivalent rate laws in:
d[ R ]
= −kelec [ R ] (10.7)
dt
d[ P ]  d[ P ] 
= + kelec [ R ] +   = + kelec [ R ] − k[ P ] (10.8)
dt  dt chem

with kelec given in Equation 10.4 and [R] and [P] being the concentrations of R and P in the bulk
solution at time t.
In the converse situation, that is, when a totally irreversible cyclic voltammogram is observed,
Equation 10.7 still applies for R, which is not chemically affected in the sequence considered, but
kelec
Bulk Rbulk Pbulk etc.
Stagnant layer
Electrode Rx = 0 + ne Px = 0
SchEME 10.1 Macroscopic vs. microscopic description of an electrochemical reaction.
Equation 10.8 does not reflect the variations in the bulk concentration of product P [8]. Indeed, the
observation of a chemically irreversible cyclic voltammogram shows that P is too short-lived to
have any possibility of escaping that stagnant layer. However, because of mass conservation within
the stagnant layer, the outgoing flux of P′, the product of chemical reaction of P in Equation 10.6,
is identical to the incoming flux of R. Equation 10.8 is then replaced by [P] ≈ 0, and the following
equation results, which is tantamount to the steady-state approximation in homogeneous chemistry:
d[ P′]
= + kelec [ R ] (10.9)
dt
From this analysis and presentation, it is seen that when single chemical pathways are followed, that
is, when no competitive route interferes in the reaction of intermediate(s) within the diffusion layer,
the electrolysis affects the different bulk concentrations in a way similar to a first-order chemical
reaction, as outlined in Scheme 10.1. This analogy affords an extremely simple way to handle the
various problems that may arise during electrolysis. Indeed, they then become exactly identical to
those that would be observed for homogeneous chemistry, that is, as if the R/P redox reaction were
performed using a homogeneous redox reagent in excess.
B. CoULoMETrY: ApparENT NUMbEr oF ELECTroNS CoNSUMED

In Section II.A, we have presented the analogy between electrolysis and homogeneous chemistry
in terms of an equivalent rate constant kelec = DA/Vδ. Yet it may be surprising that this rate constant
does not include a term related to the current. However, the current corresponds to a number of
moles consumed per unit of time, that is, to an instantaneous rate, and therefore not to a rate con-
stant. From the description outlined in Scheme 10.1 and Equation 1.141, the current exchanged at
the electrode at any time is given in
 ∂[ R ]   ∂[ P ] 
i = nFAD   = −nFAD   (10.10)
 ∂x  x = 0  ∂x  x = 0
When R undergoes no significant chemical reaction within the diffusion layer, its concentration
profile is linear, as established previously, and Equation 10.10 is rewritten as
nFAD
i=
δ
([R]bulk − [R]x =0 ) (10.11)

Again, when one considers the most frequent situation in which the electrode potential is such as
[R]x = 0 = 0, the following is finally obtained:
nFAD
i= [ R ]bulk (10.12)
δ
Comparison to the definition of kelec (Equation 10.4) affords the following relationship between the
instantaneous current and the equivalent rate of electrolysis [7]:
i = nFVkelec [ R ]bulk (10.13)
Note that Equations 10.12 and 10.13 are independent of the eventual chemical fate of R or P in the
bulk solution but suppose only that R undergoes no chemical reaction within the stagnant layer.
The overall quantity of electricity Qt consumed after a duration t of electrolysis is given by the
integration versus time of Equation 10.13, which affords
t t
∫ ∫
Qt = i dt = nFVkelec [ R ]bulk dt (10.14)
0 0
From Equation 10.14, [R]bulk is obtained as a function of time, which follows directly from
Equation 10.3:
d[ R ]bulk  d[ R ]bulk 
= −kelec [ R ]bulk +   (10.15)
dt  dt chem

When the last term in Equation 10.15 is negligible, R is consumed only at the electrode. Thus, the
charge consumption is easily obtained by considering that each mole of R converted consumes
nF coulombs, that is, Qt is given as follows, where C0 is the initial bulk concentration of R:
Qt = nFV (C 0 − [ R ]bulk ) (10.16)
On the other hand, from Equation 10.15, [R]bulk decays exponentially with time as
[ R ]bulk = C 0e − kelec t (10.17)
At the end of electrolysis, that is, for t ≫ 1/kelec, one obtains the overall charge consumption, Q, in
Equation 10.18. In practice, Equation 10.18 allows the experimental determination of n, the number
of electrons consumed per molecule of R during the electrolysis, as in Equation 10.19:
Q = nFVC 0 (10.18)
Q
n= (10.19)
C 0 FV
But when experimentally possible, one does not proceed from Equation 10.19, because when the
R concentration becomes small, that is, near the end of electrolysis, residual currents arising from
other electroactive species may contribute significantly to the current and then alter the charge
measured. It is then preferable to rely on the plot of Q versus [R]bulk, according to Equation 10.16.
Thus, a linear plot should be obtained as in Figure 10.2a, in which extrapolation at [R]bulk = 0 allows
a more accurate value of Q to be determined. Note that the ensuing value of n should be identical to
that determined from transient or steady-state methods.
1.0 1.0
[R]bulk/C 0
II.
0.5 0.5
I.
0 Q 0 Q Qth
Charge consumed (Coulombs)
(a) (b)
FiGURE 10.2 Variations in the bulk concentration of the reactant as a function of the charge consumed:
(a) in the absence or (b) in the presence of chemical reaction(s) (I) consuming or (II) regenerating the electro-
lyzed species (initial concentration of the reactant: C 0).
However, it happens frequently that the two figures do not agree, which is a proof that the chemi-
cal term in Equation 10.15 is not negligible under preparative-scale electrolysis conditions. Indeed,
when the latter is positive, that is, corresponds to a production of R in the bulk solution, as by a
regenerating sequence as
R + ne → P stagnant layer
(10.20)
P + Z → R + bulk solution

the instant R concentration is larger than predicted by Equation 10.17. From Equation 10.14, it is
seen that Q is then larger than determined via Equation 10.18, which results in a larger number of
electrons consumed nap during the electrolysis, when compared with the net electron exchange n at
the electrode identified in microelectrolysis:
Q
nap = (10.21)
FVC 0
In fact, then nap corresponds not only to the electrolysis of R but also to the formal electrolysis of
Z in Equation 10.20. Conversely, when R is consumed in the bulk solution, Q and therefore nap are
smaller than predicted in Equations 10.18 and 10.19.
A typical example of such behavior is given by the reduction of pyrylium cations (Equations
10.22 and 10.23). Under steady-state or moderate-scan cyclic voltammetry, their reduction involves
the net consumption of one electron per molecule, which corresponds to the fast radical dimeriza-
tion in Equation 10.23.
Ph Ph
(10.22)
O +e O
Ph Ph
Ph Ph Ph
2 O O O (10.23)
Ph Ph Ph
The corresponding rate constant kdim, close to the diffusion limit, has been determined in aceto-
nitrile using ultrafast cyclic voltammetry in the low million volts per second [9a]. However, bulk
electrolysis and coulometries indicate an overall consumption of two out of three electrons. This
was shown to correspond to the involvement of the slow hydride transfer sequence outlined in the
following reactions [10]:
Ph Ph Ph Ph Ph Ph
Slow +
O O + O O O + O (10.24)
Ph Ph Ph Ph Ph Ph
Ph Ph Ph Ph
+
O O + B– O O + BH (10.25)
Ph Ph Ph Ph
Reaction (10.24) is too slow to be detected in cyclic voltammetry, yet it takes place during the elec-
trolysis to afford finally a 4H-pyran and a bipyranylidene as summarized in the following balanced
equation:
Ph Ph Ph Ph
3 O + 2 e + B– O O + O + BH (10.26)
Ph Ph Ph Ph
Thus, three pyrylium molecules are consumed for only two electrons exchanged, resulting in nap = 2/3.
In this discussion, we have considered the involvement of a slow follow-up reaction of the reac-
tant as a cause for the difference between n and nap. Yet this is not the only situation possible. In
most cases, such disagreements are due to the involvement of an ECE kind of sequence such as that
featured in Equations 10.27 through 10.29 [11]:
R + ne → P (E 0 ) (10.27)

 D
P → R′  slow versus 2  (10.28)
 δ 
R′ + n′e → P′ (E 0′ ) (10.29)

as well as to their homogeneous analogs in which the heterogeneous electron transfer is replaced
by a homogeneous electron transfer (disproportionation sequences). When the interposed chemical
step or the disproportionation is slow enough to make no contribution within the diffusion layer,
the apparent number of electrons observed in microelectrolysis is n, that is, reflects only the redox
process in Equation 10.27. However, the chemical step may be sufficiently rapid when compared
with the electrolysis duration to convert quantitatively the primary product P into R′. Thus, pro-
vided that n(E 0′ – E 0) > 0, R′ is coelectrolyzed, and the apparent number of electrons exchanged is
nap = n + n′. The absolute value of nap may then be larger than that of n when both have the same
sign, or smaller when of opposite signs. Similarly, slow disproportionation reactions pulled by a
fast protonation step, for example, may affect the nap value, as outlined in the following sequence:
R + ne → P
2P R + P′
P′ + Z →
These examples illustrate some of the difficulties that may be encountered when comparing the num-
bers of electrons exchanged in micro- or macroscale electrolysis. In a few instances, these chemical
complications may be detected by important curvatures of the Q versus [R]bulk plots as sketched in
Figure 10.2b. Such curvatures are observed when the degree of involvement of the follow-up chemical
steps increases during electrolysis. Indeed, because of concentration effects, the effective rate of the
chemical step may be slow at the beginning of the electrolysis, and thus a slope corresponding to nap = n
is observed. However, when the pertinent concentrations of intermediates increase, the rate of their
chemical reaction may become sufficient so that the intermediates reach steady-state behavior, which
results in a tendency to reach a slope corresponding to nap = n + n′ while electrolysis progresses. Yet
this supposes that the degree of participation changes during the electrolysis, which obviously is not a
general fact. Thus, the absence of curvature in the Q versus [R]bulk plots cannot be taken as evidence
of no chemical complication, that is, of the fact that n = nap. This is important to remember when using
coulometric results, that is, nap values, in the rationalization of electrochemical mechanisms.
C. SEparaTIoN oF WaVES aND SELECTIVITY IN ELECTroLYSIS

It is often alleged that the fine-tuning of electrode potential allows high selectivity in electrolysis.
This is certainly true for a wide variety of electrochemical situations but may turn out totally inex-
act in others, as is shown in the following discussion. Indeed, let us consider a system involving two
successive reduction waves* at E1 and E2 for a compound involving two reduction sites A and R:
A–R. Let us assume, in addition, that electrolysis of related molecules, but without the R center,
is known to occur at potentials lying in the same range where the first wave is observed. Thus, an
evident rationalization of the observed waves consists in ascribing them to the successive reductions
in Equations 10.30 and 10.31:
−
A − R + e → i A − R − → B − R (k1 ) first wave (10.30)

−
B − R + e → B − R i − → B − P (k2 )second wave (10.31)

When the lifetime of the anion radical formed upon the electron transfer in step (10.30) is extremely
short, the mechanism in Equations 10.30 and 10.31 is strictly valid, and the electrolysis product
obtained at E = E1 is (B – R). Yet when this is not the case, a combination of (A – P) and (B – R)
* Transposition between reductions and oxidations is obvious when discussing on formal grounds, so that the discussion
hereafter is developed only for a cathodic process for the sake of simplification of its presentation.
products may be obtained although the electrolysis is performed at the first wave [12,13]. Indeed,
−
an alternative slow route is now offered to the ( iA − R ) anion radical formed in Equation 10.30 dur-
ing the long duration of an electrolysis. This slow path involves a possible intra- or intermolecular
−
electron transfer to the R site to afford the (A − R i ) anion radical:
−i −
A − R A − R i− … → A − P (10.32)
−
If the latter is not highly unstable, a back electron transfer occurs to regenerate the ( •A − R ) anion
−
radical. In the converse situation, (A − R • ) may evolve directly to the A – P product, which cor-
responds to the overall reduction of the R moiety although the first electron transfer has occurred
at the A group. The observed phenomenon is thus tantamount to indirect electrolysis [14], where
the A group plays the role of an intramolecular electron mediator for the reduction of the R group.
Although not explicitly recognized as such, this is the case for the reduction of aromatic halides, for
example, since the initial electron is transferred to the aromatic ring and then internally transferred
to the carbon–halogen antibonding orbital, resulting finally in the overall reduction of the carbon–
halogen bond.
In such situations, the exact nature−
of the− (B – R) or (A – P) product obtained depends on the
relative chemical stabilities of the A • and R • moieties (rate constants k1 and k2 in Equations 10.30
and 10.31), as well as on the difference between the standard reduction potentials of the two groups,
as explained later. Indeed, in a general case, one must consider that the mechanism occurring at the
first reduction wave is not as in Equation 10.30 but may involve the sequence in Equations 10.33
through 10.35:
−
A−R+e → •A−R (10.33)
k1 B R (10.34)
A R
K
k2
A R A P (10.35)

When the homogeneous electron transfer is sufficiently fast to be equilibrated (with an equilibrium
−
constant K), the formation rate constant of A – P product is k2K when related to • A − R:
[B − R]yield k
= 1 (10.36)
[A − P]yield k2 K

[B − R]yield k1 (k2 + kb )
= (10.37)
[A − P]yield k2 kf

Thus, the relative yields of the (B – R) and (A – P) products are given in Equation 10.36 and, it is
noteworthy, are independent of the electrode potential. In a more general case, the forward kf and
backward k b rate constants of the homogeneous electron transfer must be considered, and the relative
yields are given in Equation 10.37* and are again independent of the electrode potential, provided
it is kept on the first wave.
* Note that in Equation 10.37, the forward and backward rate constants kf and k b of the equilibrium may include a concen-
tration term when the homogeneous electron transfer is bimolecular as in Equation 10.38:
•− −
A − R + A – R A – R + A − R• (10.38)
III. OMPETiTivE REAcTiON SchEMES: OPTiMizATiON

C
Of PREPARATivE-ScALE ELEcTROLYSiS
A. SLow REaCTIoN SCHEMES
In electrochemistry, as in other chemical methods, situations in which a single product is obtained
are seldom encountered. In most experimental cases, the target product is often accompanied by
unwanted side products formed along competitive pathways. Under such conditions, optimization
of the target product yield is obviously desirable. Frequently, this optimization is sought on the
basis of chemical intuition and of “blind tests” of supposedly critical parameters. Yet is difficult
to be certain (except when a 100% yield is obtained!) that the best yield obtained is the maximum
one. In the following, we want to show that semiquantitative predictions can be made on the basis
of very simple considerations. The goal of these approaches is not to replace the necessary tests,
but to provide useful guidelines for the selection of the parameters that affect the yield of the
target product.
From the preceding presentation, it is easily inferred that different behaviors are obtained when
the key species, that is, that at which the different chemical routes are branched, exists only within the
stagnant layer or exists in the bulk solution, as schematized in Figure 10.3. In the latter case, the com-
petition problem is analogous to the homogeneous chemical situation, owing to the equivalences
established previously. For example, let us consider a reaction sequence like that in Figure 10.3
(case a or b):
A+e B (E 0) (10.39)
B C (k1) (10.40)
P1 (k2) (10.41)
C
+e

P2 (E 0΄ > E 0) (10.42)
For a potentiostatic electrolysis on the plateau of the A/B reduction wave, the reaction sequence in
Equations 10.39 through 10.42 is equivalent to the homogeneous mechanism in Equations 10.43
through 10.46, where kelec = DA/Vδ:
A B (kelec) (10.43)
B C (k1) (10.44)
P1 (k2) (10.45)
P2 (kelec) (10.46)
A+e B C
A A
B B C
(a)
A A
B C C
0 δ 0 δ
(b)
A A
B C
(c)
A A
C X X
0 δ 0 δ
(d)
FiGURE 10.3 Schematic representation of the localization of the branching point for an ECC competitive
sequence and resulting concentration profiles for (—) A, (- - -) B, and (…) C. (a, b) Slow production of the
intermediate key species C; (c) fast production of the key species; (d) reaction in the adsorbed phase.
Thus, the yield of species P1 vis-à-vis P2 is simply expressed as
[P1 ]yield k2 k2
= = (10.47)
[P1 ]yield + [P2 ]yield k2 + kelec k2 + DA /Vδ

From Equation 10.47, it is easily seen that maximizing the yield of P1 amounts to decreasing the
ratio kelec/k2, that is, of DA/Vδk2. Thus, it obviously follows that one must decrease the electrode
surface area and the stirring rate (i.e., increase δ), increase the bulk solution volume, and, when
possible, increase k2. The opposite changes are needed when the target compound is P2. Similarly,
when B is the compound sought, one wants kelec ≫ k2, that is, a large surface area for the electrode,
small bulk solution volume, and high stirring rates (small δ).
Thus, owing to the equivalent homogeneous formulation, there are no specific particularities
associated with optimization in electrochemistry, as soon as the branching point takes place only
within the bulk solution. As explained earlier, this is generally easy to decide on the basis of cyclic
voltammograms of the system of interest.
Conversely, when the key species exists only in a thin reaction layer adjacent to the elec-
trode (case c in Figure 10.3), the degree of competition between the various routes is greatly
influenced by the local concentration profiles of the different species involved. In such cases,
general theories have been established that allow a complete and quantitative description of the
optimization procedure. However, in the following, we want to present a very simple approach
to the problem.*
B. ELEMENTarY METHoD For FaST CoMpETITIVE KINETICS

1. Presentation of the Method
All the results presented in the following discussion derive from the simple consideration† that when
a species is involved in a branched kinetic scheme, the major pathway is the fastest, that is, the main
product is that formed according to the pathway corresponding to the highest rate of consumption
of the key species.
On the other hand, when the key species is formed at a given rate, the faster its consumption, the
smaller its concentration. Taking into account these two obvious statements leads to the following
conclusion: when two or more pathways compete for the consumption of a given species, the major
pathway is that leading to the smallest concentration of this species, when each pathway is consid-
ered alone under identical experimental conditions.
When two competing mechanisms are considered, a competition parameter may thus be defined
as the ratio of the average concentration of the key species obtained when each of these mechanisms
is considered alone. Let us denote by C1 and C2 the corresponding concentrations for mechanisms
1 and 2 in Scheme 10.2, when they do not interfere. The competition parameter p = C1/C2 is then
such that p ≪ 1 favors the occurrence of mechanism 1 as the main pathway since this condition
corresponds to C1 ≪ C2, whereas mechanism 2 is observed when p ≫ 1. In a general case, the
analytical dependence of both C1 and C2 on the experimental conditions (concentrations of the reac-
tants and of the coreactants, stirring rate, and so on) and intrinsic factors (e.g., rate constants and
diffusion coefficients) may be determined, thus leading to the expression of p as a function of these
factors. The effects of these parameters on the overall product distribution are then readily given
with the direction and magnitude included in the p expression.
Table 10.1 gives the average concentrations to be used for the various intermediates involved in
the most basic schemes of electrochemical mechanisms,‡ which may allow the simple derivation of
the competition parameters p for most of the possible experimental situations.
In the preceding discussion, we have considered for simplicity that only two pathways were
possible for the key species. Thus, a single parameter p is defined. However, when more routes
are branched for the same species, the situation is a priori more difficult to handle. For three
competitive routes, for example, Table 10.1 affords three concentrations C1, C2 , and C3, and
thus three parameters p1 = C1/C2 , p 2 = C1/C3, and p 3 = C2/C3 are defined, which are all affected
by the experimental and intrinsic parameters. Thus, it is a priori difficult to appreciate the
effect resulting of the variation of one of the experimental parameters on the overall competi-
tion. Yet it is first noticed that the consideration of only two parameters suffices to describe
the competition since they are all given by ratios or products of the two others, as p3 = p 2/p1.
* Note that case d in Figure 10.3, which relates to surface reactions between adsorbed and chemisorbed species, is not
considered here because of the too specific nature of the electrode–species interactions involved.
† Yet they are based and supported by a rigorous physicomathematical analysis. See, for example, References 8a,15–21.
‡ Note that each of the reactions presented in Table 10.1 may consist of true elemental reactions or of a kinetically equiva-
lent series of elemental steps.

etc.
Mechanism 1
Mechanism 2
etc.
SchEME 10.2 Branching between two mechanisms at the level of a single intermediate.
TABLE 10.1
“Average Concentrations” of the Different Intermediates Involved in the Main
Electrochemical Mechanismsa,b
Mechanismb Scheme Average Concentrationc
EC A + ne⇌B [B] = C 0/(kθ)1/2
B k
→C [C] = C 0
ECE A + ne⇌B [B] = C 0/(kθ)1/2
B k
→C [C] = C 0/(kθ)1/2
C + ne → D [D] = C 0
DISP A + ne⇌B [B] = C 0/(2kθ)1/2
B k
→C [C] = k/kd
B + C  kd
→A + D [D] = C 0
ECC A + ne⇌B [B] = C 0/(k1θ)1/2
B k1
→C [C] = (C 0/k2)(k1/θ)1/2
C k2
→D [D] = C 0
Dim 1 A + ne⇌B [B] = C 02/3(3/4kθ)1/3
2B  k
→C [C] = C 0/2
Dim 2 (ECE) A + ne⇌B [B] = C 02/3/(kθ)1/3
B + A  k
→C [C] = C 02/3/(kθ)1/3
C + ne → D [D] = C 0/2
Dim 2 (DISP) A + ne⇌B [B] = C 02/3/(2kθ)1/3
B + A  k
→C [C] = (kC 0)2/3/(kdθ1/3)
kd
B + C → A + D [D] = C 0/2
Dim 3 (DISP) A + ne⇌B [B] = (3C 0/4kKθ)1/3
B + A⇌C [K]d [C] = C 0K[B]
B + C  kd
→A + D [D] = C 0/2
ECDim A + ne⇌B [B] = C 0/(k1θ)1/2
B k1
→C [C] = (C 0/2k2)1/2(k1/θ)1/4
2C  k2
→D [D] = C 0/2
a The concentrations are given for an electrolysis on the plateau of the A/B wave. C0, bulk concentration of A; θ = δ2/D.
b Usual names, or taken from the nomenclature developed in Savéant’s group.
c These concentrations are valid provided each resulting figure is lower than approximately C0/10 (except for the final product).
d K is the equilibrium constant of the reaction considered always equilibrated.
C0
log p1
0 CZ
2
lo CY
g
p
3
0
A
C
3
1
B
log p2
FiGURE 10.4 Kinetic zone diagram and corresponding compass card for a competition between three
hypothetical mechanisms, as discussed in the text.
Thus, a convenient presentation of the competition problem consists in the construction of a

diagram in which log p1 is the ordinate axis and log p 2 is the abscissa axis, as in Figure 10.4. In
such a diagram, kinetic zones corresponding to the predominance of one of the three possible
mechanisms may be defined in a similar way as thermodynamic stability zones corresponding
to the predominance of a species are defined, for example, as a function of the solution potential
and pH (Chapter 1). Thus, mechanism 1, which corresponds to p1 ≪ 1 and p 2 ≪ 1, is located in
the lower left corner of Figure 10.4, that is, log p1 < 0 and log p 2 < 0. Mechanism 2 is observed
for p1 ≪ 1 and p3 = p2/p1 ≪ 1, and its kinetic zone is then such that log p1 > 0 and log p1 > log p 2.
Similarly, the kinetic zone corresponding to the predominance of mechanism 3 is such that
p 3 ≫ 1 and p 2 ≫ 1, that is, log p 2 > 0 and log p 2 > log p1 Then three boundary lines delimiting
the zone of predominance of each mechanism are constructed in Figure 10.4. Near one of these
boundaries, the two delimited mechanisms compete without interference from the third. The
general competition, that is, that involving the three mechanisms, is observed near the intersec-
tion of the three boundary lines in the central region of Figure 10.4. When such a diagram has
been constructed, the effect of each experimental parameter is easily predicted by construction
of a compass card, such as that shown in the upper right corner of Figure 10.4. For example,
let us assume that p 1 ∝ C 0 δ 2/C y and p 2 ∝ C 0 Cz /δ. Thus, a multiplication of δ by 10, for example,
results in an increase of 2 in log p1 and a decrease by 1 in log p 2. A vector corresponding to
the “δ effect” can then be constructed in the diagram, which has a projection −1 in the abscissa
and +2 in the ordinate. Similarly, other vectors can be drawn for C 0, C y, and Cz to constitute
the compass card shown in the upper right corner of Figure 10.4. Such a compass provides an
easy visualization of the effect of any variation in the experimental parameters. For example,
it is seen in Figure 10.4 that when the system is at point A, an increase in δ results in a trend
to shift from mechanism 3 to 2, whereas the same variation results in a tendency to pass from
mechanism 3 to 1 when starting from location B or from mechanism 1 to 2 when starting from
point C. Such different effects induced by the same experimental variation would have been
puzzling and difficult to rationalize, whereas they are easily understood from the kinetic zone
diagram and its associated compass card. Similarly, a compass card showing the effect of each
intrinsic parameter may be constructed.
In the following discussion, we want to show how this simple method may be used in practical
situations, either to rationalize a series of results or to decide a priori the worthiness of an experi-
mental strategy. To maintain some homogeneity in the presentation, the two aspects are discussed
on the basis of examples pertaining to the electrochemistry of aryl halides.
2. Predictive Value of the Method

This aspect is developed by addressing the following question: “Is there any chance that biaryls may
be formed, via aryl radical dimerization, during the reductive electrolysis of aryl halides?” −
The nonconcerted reduction of aryl halides is known [22] to afford a frangible anion radical ArX •
(Equation 10.48), which yields a σ-aryl radical by cleaving off the halide ion in Equation 10.49:
−
ArX + e → ArX • (E 0 ) (10.48)

−
ArX • → Ar • + X − (k1 ) (10.49)

Although these σ-aryl radicals are prone to undergo a facile reduction at the electrode (Equation
10.50) or in solution as in Equation 10.51, one may think of the possibility of impeding these normal
pathways to favor their radical dimerization:
Ar • +e → Ar − ( E 0′ > E 0 ) (10.50)

−
Ar • + ArX • → Ar − + ArX (kdif ) (10.51)

Ar − + BH → ArH + B− (10.52)
2Ar • → Ar − Ar (kdim ) (10.53)

Indeed, the dimerization of these σ radicals is expected to be extremely fast and possibly close to
diffusion control. Then, intuitively, owing to its bimolecular nature, a concentration effect should
favor this step vis-à-vis the reduction at the electrode. Similarly, one could envision that increasing
the rate of the anion radical cleavage in Equation 10.49 should decrease its concentration with a con-
comitant increase in the radical concentration, both effects being in favor of the duplicating step.*
The average concentrations for the key species Ar • to be used in the following analysis are
obtained from Table 10.1, where the role of Ar • is symbolized by C in the three competing sequences:
ECE (Equations 10.48 through 10.50 and 10.52), DISP (Equations 10.48, 10.49, 10.51, and 10.52),
and ECDim (Equations 10.48, 10.49, and 10.53). This allows the three competition parameters to be
obtained as in Table 10.2, p1 = (ECDim/ECE), p2 = (ECDim/DISP), and p3 = (p1/p2) = (DISP/ECE),
from the ratios of the respective average concentrations. Following this procedure, a kinetic zone
diagram and a compass card are then constructed in Figure 10.5a. Such a diagram
−
shows that these
considerations on the effect of C0 or of the cleavage rate constant k1 of ArX • are valid only when the
point representing the system is in the ECE zone (C0 effect) or in the DISP zone (k1 effect). When
starting from an ECDim zone, however, an increase in C0 results in a tendency to shift toward the
DISP zone, and an increase in k1 favors reduction via an ECE mechanism. Both effects are counter-
intuitive but can be understood. For example, when k1 increases, Ar • is produced closer and closer to
the electrode surface and then has less and less possibility to dimerize before reaching the electrode
to be reduced. As for C0, the effect of the mass transfer rate (i.e., of θ = δ2/D in the compass card)
was almost impossible to predict on an intuitive basis.
* Note that Ar• is prone to undergo other facile reaction paths (see Section III.B.3). The concurrent routes in Equations
10.50 through 10.52 then constitute the minimal competitive sequence to be considered.
TABLE 10.2
Competition Parameters for an ECDim/ECE/DISP Competing Sequence
Average Concentration of Ar•
a
Competition Parameter Major Pathwayd
• b,c
Mechanism [Ar ] Sequence Competition Parameter pi ≪ 1 pi ≫ 1
0 1/ 2 1/ 4 • •
ECDim (C / 2kdim ) (k1 /θ) ECDim/ECE p1 = (Ar )ECDim/(Ar )ECE ECDim ECE
p1 = k13/ 4 θ1/ 4 / (2kdimC 0 )1/ 2
ECE C0/(k1θ)1/2 ECDim/DISP p2 = (Ar•)ECDim/(Ar•)DISP ECDim DISP
p2 = kd (C 0 )1/ 2 /k13/ 4 (2kdim )1/ 2 θ1/ 4
DISP k1/kd DISP/ECE p3 = (Ar•)DISP/(Ar•)ECE DISP ECE
p3 = p1/p2
a Taken from Table 10.1.

b k1, rate constant of the aromatic halide anion cleavage; kdim, dimerization rate constant of the σ-aryl radicals; kd, homoge-
neous electron transfer rate constant (usually kd = kdif, the diffusion-controlled rate constant).
c C 0, ArX bulk concentration; θ = δ2/D.
d Both pathways are observed when the value of pi is close to unity (i.e., when ~0.1 ≤ pi ≤ 10).
kd
log p2 log p2
C0
θ
kdim k1
DISP DISP
0 0
ECE ECE
ECDim
ECDim
0 log p1 0 log p1
(a) (b)
FiGURE 10.5 (a) Kinetic zone diagram for an ECDim/ECE/DISP competitive sequence (see text,
Equations 10.48 through 10.53, and Table 10.2 for definitions of p1, p2, and p3; note that in (b), kd = kdif ). The
hatched zone in (b) corresponds to the region without experimental validity.
To illustrate another useful aspect of the method, let us discuss a further experimental impor-
tance related to the ECDim zone in Figure 10.5a. Indeed, the representation in Figure 10.5a
s upposes that any values are possible for p1 and p2. Yet in an actual case, this is not true since the
product p1p2 = kdif/2kdim is necessarily larger than 1/2 because kdim cannot exceed the diffusion limit
kdif. This implies that the hatched zone in Figure 10.5b, which corresponds to p1p2 < 0.5, has no
experimental validity. Thus, no system can be located in this zone regardless of the values of the
experimental (C 0, θ, and δ) or intrinsic parameters (D, kdif, kdim, or k1); this shows that almost all the
ECDim zone has no experimental significance. Although this method does not allow the maximum
yield of biaryl to be determined, it leads to the conclusion that it is necessarily poor and requires
extremely precise conditions to be achieved. A complete and accurate analysis [18] of the problem
establishes that this maximum yield is of the order of 10–20% at best, which is in complete agree-
ment with maximum experimental yields lying in the range of 7%.
However, this does not mean that biaryls cannot be obtained via aryl halide reduction but only
that this strategy is not experimentally valid as soon as Ar • is more easily reducible than the parent
halide. Yet other approaches to the synthetic problem may be found. An obvious one consists in
suppressing the facile reductions of Ar • by using an electrophore as the leaving group X−, which is
then also the site of the initial electron uptake (Equation 10.48). Ar i may not then be reducible at the
reduction potential of the parent pseudohalide, which is shown in benzylic series [23]:
Ar2CHS NO2 + e Ar2CHS NO–2 Ar2CH Dimers (10.54)
Another approach consists, for example, in using an ArX or a coreactant Ar’X, prone to react with
Ar • via the Ullman kind of reaction [24,25]:
Ar • + ArX → [ Ar − ArX]• → … (10.55)
Naturally, each of these possible approaches, as well as many others that may be conceived, may
be tested on paper following this method to decide its possible validity and the best experimental
conditions to favor it. For example, application of this on paper strategy shows that only moderate
yields are obtained for the process in Equation 10.56 when directly reducing the aryl halide at the
electrode, whereas interesting yields (i.e., from 80% to 70%) are possible by using a redox mediator
for performing the initial ArX reduction [25c]:
Ar
–e
Ar + O– O– Ar O– (10.56)
H –H+
3. Rationalization of a Series of Results

Figure 10.6 presents the variations in the yield in monodeuterated arene obtained when an aromatic
halide is reduced in acetonitrile in the presence of 10% D2O [26]:
ArX + 2e ACN,
 10% D2 O
→ y ArD + (1 − y)ArH (10.57)

The overall stoichiometry of the reaction shown in Equation 10.57 corresponds to the formation
of ArD and ArH via two competitive pathways. ArD is obtained along the sequence presented in
Equations 10.48 through 10.51, the resulting σ-aromatic anion being deuterated by D2O, as
Ar − + D2O → ArD + DO − (10.58)
ArH is formed via a H-atom transfer from the ACN solvent to the aryl radical formed upon the
mechanism in Equations 10.48 and 10.49, as outlined in the following sequence [26]*:
Ar • + CH 3CN → ArH + • CH 2CN (kH ) (10.59)

−
•
CH 2CN(+e or ArX • ) → −CH 2CN (10.60)

−
CH 2CN + D2O CH 2 DCN + DO − (10.61)
The data in Figure 10.6 show that for the 1-halonaphthalene or 4-halobenzonitrile series, a continu-
ous variation is observed, that is, the yield in ArD increases in the series Cl < Br < I, in agreement
* The scrambling in Equation 10.61 has been shown to play a minimal role during the electrolysis on the basis of experi-
mental isotopic studies [26].
% ArD
100
x
x CN
50
x
20
20
10
5 2
20
2
2
0
Cl Br I
FiGURE 10.6 Experimental variations in the yield of monodeuterated arene ArD as obtained by reduction
of the corresponding halide in acetonitrile in the presence of 10% D2O and 0.1 M LiClO4. The number on the
curves is the initial concentration (mM) of the halide. (Data from M’Halla, F. et al., J. Am. Chem. Soc., 102,
4120, 1980.)
(at least for the monotonic variation) with usual chemical expectations. But for the 9-anthracene
series, a nonuniform variation is observed as a function of the halide. Moreover, the ArD yields
obtained for the 9-chloroanthracene are extremely dependent on the concentration or the stirring
rate, whereas the effects of these factors are minimal for the bromo derivative and totally negligible
for the iodo derivative or for the 1-halonaphthalene or 4-halobenzonitrile series. Such a priori puz-
zling experimental results may, however, be easily rationalized through the preceding method.
From Table 10.1, the two parameters corresponding to the competition between ECE (reactions
10.48 through 10.50 and 10.58) or DISP (reactions 10.48, 10.49, 10.51, and 10.58) sequences and
the H-atom transfer ECC sequence (reactions 10.48, 10.49, and 10.59 through 10.61) are obtained
as follows*:
k1
p1 = ECC/ECE (10.62)
kH
C 0 kdif
p2 = ECC/DISP (10.63)
θ1/ 2 kH k11/ 2
p1
p3 = DISP/ECE (10.64)
p2
* Note that for the H-atom transfer pathway, steps (10.60) and (10.61), which occur after the branching point Equation 10.59,
play no role in the ArD yield. Thus, the sequence of reactions (10.48), (10.49), and (10.59) through (10.61) behaves like
an ECC sequence in regard to the competition between the H• versus (+e, +D2O) routes for Ar• reduction.
log p2 % ArD
kd, C 0 100
DISP (ArD)
0 kH k1
Cl θ
X Br 20 mM
I 50 10 mM
ECE (ArD)
5 mM
X CN 2 mM
X
ECC
(ArH) 0
log (k1/kH)
(a) 0 log p1 (b) –12 –8 –4 0 4 8
FiGURE 10.7 (a) Kinetic zone diagram for the ECC/ECE/DISP competitive sequence in the ArD versus
ArH formation under the experimental conditions of Figure 10.6 (see text and Equations 10.48 through 10.51
and 10.58 through 10.61; note that for the example discussed, kd = kdif ). (b) Theoretical variations [16] in the
yield of ArD as a function of the concentration of ArX (numbers on the curves) and of the rate constants
ratio k1/k H. (Experimental data in (a) from M’Halla, F. et al., J. Am. Chem. Soc., 102, 4120, 1980.)
This allows the construction of the kinetic zone diagram in Figure 10.7a according to the previously
explained procedure. The location of the experimental systems considered in Figure 10.6 indicates
that the benzonitrile or naphthalene derivatives undergo an ECE/ECC competition without inter-
ference from the DISP route. Thus, as indicated by the compass card in Figure 10.7a or by the
formulation of p1, in Equation 10.62, C0 or θ = δ2/D has no effect on the overall ArD yield, in agree-
ment with the experimental observations. Moreover, for a given aromatic moiety, k H is constant
and does not depend on the halide, whereas k1 increases in the order Cl < Br < I. Thus, p1 = k1/k H
increases monotonically in the series, which explains the uniform variations in Figure 10.6. The
9-iodo anthracene also undergoes an ECC versus ECE competition, whereas an ECC/DISP compe-
tition is observed for the 9-chloro derivative. From the compass card in Figure 10.7a, it is then seen
that C0 or θ considerably affects the ArD yield for the 9-chloroanthracene, whereas there is no effect
of these parameters on the iodo derivative. For the bromide, an intermediate situation is observed
but is more shifted toward predominance of an ECC than for the iodide or chloride cases, which
explains the minimum observed in Figure 10.6 as well as the small variations in the ArD yield with
concentration or stirring rate changes [26]. It is thus seen that the simple approach presented here
is sufficient to rationalize qualitatively all the a priori puzzling observations in Figure 10.6. But a
correct and thorough analysis of the problem on a physicomathematical basis [16] may be achieved
and leads to a more quantitative description of these facts. The result of such an analysis is shown in
Figure 10.7b, under the form of predicted variations in the ArD yield, for the systems in Figure 10.6.
Although more quantitative information is then obtained, it is seen that all the trends observed in
Figure 10.7b have been qualitatively predicted via the aforementioned approach, which requires no
sophisticated derivations and can be handled “on the back of an envelope.”
IV. CONcLUSiON
This presentation was designed to discuss the relationships between micro- and macroscale elec-
trolysis. Besides the intrinsic factors arising from scaling-up problems (larger concentrations, larger
current densities, and longer reaction times), we have tried to show how the results of microscale
electrolysis could be used with large profit, either in devising adequate experimental conditions or
in the rationalization of product distributions. However, it is important to decide in such cases if the
branching point leading to the different products takes place in the bulk solution or occurs in the
very close vicinity of the electrode. Indeed, in the first case, the problem must be examined in terms
of its homogeneous equivalent, the electrolytic reactions being replaced by first-order reactions.
Conversely, in the second case, an electrochemical analysis taking into account the concentration
profiles in the vicinity of the electrode must be performed to solve quantitatively the distribution
problem. However, in such cases, and when only semiquantitative predictions are needed, a very
simple approach based upon competition parameters and kinetic zone diagrams proves to be con-
siderably useful.*
AckNOwLEDGMENTS
This work was supported by ENS, CNRS, and UPMC (UMR 8640 PASTEUR). The author wishes
to acknowledge Prof. Irina Svir and Dr. Alexander Oleinick for useful comments and suggestions.
REfERENcES
1. For a modern and more correct notion of the so-called Nernst-layer phenomenon see: (a) Amatore, C.,
Szunerits, S., Thouin, L., Warkocz, J.-S. J. Electroanal. Chem. 2001, 500, 62–70; (b) Amatore, C.;
Klymenko, O. V., Svir, I. Anal. Chem. 2012, 84, 2792–2798.
2. See, e.g., (a) Jansson, R. AIChE Symp. Ser. 1983, 79(229), 92–99. (b) Jansson, R. AIChE Symp. Ser.
1983, 79(229), 119–125. (c) Jansson, R. In Electrochemical Cell Design; White, R. E., ed.; Plenum Press:
New York, 1984; pp. 175–195.
3. Newman, J. S. Electrochemical Systems; Prentice Hall: Englewood Cliffs, NJ, 1973; pp. 239–253.
4. Wightman, R. M.; Wipf, D. O. In Electroanalytical Chemistry, Vol. 15; Bard, A. J., ed.; Marcel Dekker:
New York, 1989. (b) In Ultramicroelectrodes; Fleischmann, M.; Pons, S.; Rolison, D.; Schmidt, P. P.,
eds.; Datatech Systems: Morgantown, NC, 1987. (c) Wightman, R. M. Science 1988, 240, 415–420.
5. (a) Amatore, C.; Deakin, M. R.; Wightman, R. M. J. Electroanal. Chem. 1987, 225, 49–63.
(b) Montenegro, M. I.; Pletcher, D. J. Electroanal. Chem. 1988, 248, 229–232.
6. See, e.g., (a) Reference 3, pp. 340–352; (b) Bard, A. J.; Faulkner, L. R. Electrochemical Methods:
Fundamentals & Application, 2nd edn.; John Wiley & Sons: New York, 2001; pp. 421–423.
(c) Booman, G. L.; Holbrook, W. B. Anal. Chem. 1963, 35, 1793–1809. (d) Booman, G. L.; Holbrook,
W. B. Anal. Chem. 1965, 37, 795–802.
7. (a) Bard, A. J.; Santhanam, K. S. V. In Electroanalytical Chemistry, Vol. 4; Bard, A. J., ed.; Marcel
Dekker: New York, 1970, p. 220. (b) Lingane, J. J. J. Am. Chem. Soc. 1945, 67, 1916–1922.
8. (a) Amatore, C.; Savéant, J.-M. J. Electroanal. Chem. 1981, 123, 189–201. (b) Wendt, H. Angew. Chem.
1982, 21, 256–270. (c) Wendt, H.; Plzak, V. J. Electroanal. Chem. 1983, 154, 13–28. (d) Plzak, V.;
Wendt, H. J. Electroanal. Chem. 1983, 154, 29–43. (e) Plzak, V.; Wendt, H. J. Electroanal. Chem. 1984,
180, 185–204. (f) Savéant, J.-M. J. Electroanal. Chem. 1987, 236, 31–42.
9. (a) Amatore, C.; Jutand, A.; Pflüger, F. J. Electroanal. Chem. 1987, 218, 361–365. (b) Fabre, C.; Fugnitto, R.;
Strzelecka, H. C. R. Acad. Sci. Paris Ser. C 1976, 282, 175–177. (c) Pragst, F.; Ziebig, R.; Seydewitz, U.;
Driesel, G. Electrochim. Acta 1980, 25, 341–352.
10. Amatore, C; Jutand, A.; Pflüger, F.; Jallabert, C.; Strzelecka, H.; Veber, M. Tetrahedron Lett. 1989, 30,
1383–1386.
11. See, e.g., (a) Parker, V. D.; Nyberg, K.; Eberson, L. J. Electroanal. Chem. 1969, 22, 150–152. (b) Parker, V. D.;
Eberson, L. J. Chem. Soc. Chem. Commun. 1969, 340. (c) Phelps, J; Bard, A. J. J. Electroanal. Chem. 1976,
68, 313–315, for examples in aromatic oxidations; or (d) Szwarc, M. Acc. Chem. Res. 1972, 5, 169–176 for
reductions.
12. See, e.g., Simonet, J.; Lund, H. Acta Chem. Scand. 1977, 31B, 909–911 for a typical experimental
example.
13. For a discussion, see Pletcher, D. J. Electroanal. Chem. 1984, 179, 263–267.
14. See, e.g., (a) Lund, H.; Simonet, J. J. Electroanal. Chem. 1975, 65, 205–218 for an early synthetic
example.
15. Amatore, C.; Savéant, J.-M. J. Electroanal. Chem. 1981, 123, 203–217.
16. Amatore, C.; M’Halla, F.; Savéant, J.-M. J. Electroanal. Chem. 1981, 123, 219–229.
* Note that this presentation considers only one branching point, but when several are present the same analysis can be
applied at each branching point.
17. Amatore, C.; Pinson, J.; Savéant, J.-M.; Thiébault, A. J. Electroanal. Chem. 1981, 123, 231–242.
21. Amatore, C.; Savéant, J.-M. J. Am. Chem. Soc. 1981, 103, 5021–5023.
22. See, e.g., Andrieux, C. P.; Savéant, J.-M.; Zann, D. Nouv. J. Chim. 1984, 8, 107–116.
23. Farnia, G.; Severin, M. G.; Capobianco, G.; Vianello, E. J. Chem. Soc. Perkin Trans. II 1978, 1–8.
24. Grimshaw, J.; Hamilton, R.; Trocha-Grimshaw, J. J. Chem. Soc. Perkin Trans. I 1982, 229–234.
25. (a) Amatore, C.; Combellas, C.; Pinson, J.; Savéant, J.-M.; Thiébault, A. J. Chem. Soc. Chem. Commun.
1988, 7–8. (b) Alam, N.; Amatore, C.; Combellas, C.; Pinson, J.; Savéant, J.-M.; Thiébault, A.; Verpeaux,
J. N. J. Org. Chem. 1988, 53, 1496–1506. (c) Alam, N.; Amatore, C.; Combellas, C.; Thiebault, A.;
Verpeaux, J. N. Tetrahedron Lett. 1987, 28, 6171–6174.
26. M’Halla, F.; Pinson, J.; Savéant, J.-M. J. Am. Chem. Soc. 1980, 102, 4120–4127.
Section III
Electron Transfers and
Concerted Processes
11 Influence of Molecular
and Medium Effects on
Two-Electron Processes
CONTENTS
I. Introduction and Scope ......................................................................................................... 396
II. Thermodynamic Aspects ...................................................................................................... 396
A. Expression of Potentials ................................................................................................ 396
B. Normal versus Inverted Ordering of E1/2 Potentials ..................................................... 397
C. Free Energy Factors ...................................................................................................... 398
D. Intrinsic versus Extrinsic Factors Affecting ∆E1/2 Values ............................................ 399
E. CV Images for Different ∆E1/2 Values ..........................................................................400
F. Examples of Calculated EE Processes..........................................................................400
1. EE with Minimal Structure Change: Anthracene .................................................400
2. EE with Major Structure Change...........................................................................402
3. Application to Reduction of Cyclooctatetraene .....................................................404
III. Effects of Slow Heterogeneous Electron Transfer ................................................................406
IV. Experimental Aspects: Determination of E.T. Stoichiometry (One or Two Electrons?) ......408
A. Analysis by a Single Electroanalytical Method ............................................................408
B. Analysis by Combined Methods ...................................................................................409
1. Electrolysis and Voltammetry................................................................................409
2. Dual Voltammetric Analysis ................................................................................. 410
V. Applications to Two-Electron Processes .............................................................................. 410
A. Involving a Single Redox Site ....................................................................................... 411
1. Dominant Electronic and Structural Changes ....................................................... 411
2. Combined Structural and Medium Effects ............................................................ 415
3. Dominant Medium Effects .................................................................................... 419
4. Effect of Slow E.T. Kinetics: Reduction of Bis(hexamethylbenzene)ruthenium2+ ....421
B. Involving Two Identical Redox Sites ............................................................................ 422
1. Electronic Communication through the Linkage .................................................. 422
2. Medium Effects...................................................................................................... 425
VI. An Integrated Approach to Medium Effects on ΔE1/2 ......................................................... 427
References ...................................................................................................................................... 430
395
I. INTRODUcTiON AND ScOPE

Electron transfer (E.T.) reactions in which there is an overall stoichiometry of two or more electrons
are common and may be found in a number of important chemical and biological processes. Many
of these reactions occur through mechanisms in which chemical reactions (C) are coupled to the
E.T. process (E). For example, the classic quinone/hydroquinone couple follows an electrochemical
reaction–chemical reaction–electrochemical reaction–chemical reaction mechanism, combining a
pair of electron and proton transfers, displaying two-electron Nernstian behavior. This chapter restricts
itself to the simpler case of E.T. reactions of two-electron stoichiometry that are uncomplicated by cou-
pled chemical reactions. This will facilitate discussion of the three principal factors affecting the rela-
tive ordering and degree of potential separation of the successive one-electron transfers of the Electron
transfer/Electron transfer (EE) mechanism (Equation 11.1): changes in electronic and molecular struc-
ture, differences in solvation energies, and differences in ion-pairing energies, between members of
the E.T. series. Furthermore, only cases in which structure change and medium effects are thought to
+ e−
− 2− + e−

A o

A
o
A (11.1)
EA/A − E − 2−
A /A
be concomitant (i.e., concerted) with E.T. will be considered. Thus, “square schemes” [1], in which
reversible structure changes “follow” E.T., are not covered. Note also that, although the principles dis-
cussed in this chapter relate also to systems having more than two sequential E.T. reactions, “super”
multielectron transfer processes such as those involving C60 will not be systematically covered.
As will become apparent, a key experimental goal is to distinguish between obviously separated
E.T. processes and those which appear to proceed through a single two-electron reaction in the
following equation:
+2 e −
2−

A o
A (11.2)
EA/A2−

Writing the E.T. reaction with a two-electron stoichiometry naturally raises the question of whether
or not it is possible to have a truly concerted two-electron transfer, that is, a reaction that does not pro-
ceed through the one-electron intermediate A−. Whereas it seems clear that a concerted two-electron
transfer is theoretically permitted [2], there appear to be no experimentally verified examples of such
a process. In evaluating the literature on this subject, Evans concluded that a concerted two-electron
process requires that the value of EAo − /A2− be at least 0.4 V (and perhaps as much as 1V) “positive”
o
of EA/A − , making disproportionation of the putative one-electron intermediate A energetically so
−
favorable as to limit the experimental ability to differentiate between concerted and separate two-
electron processes [3]. We will treat all E.T. reactions as occurring one electron at a time.
Although thermodynamic and kinetic factors are both of obvious importance to the voltam-
metric behavior of EE reactions, we will give primary attention to the ordinarily more dominant
thermodynamic effects. After going over some of the basic thermodynamic aspects of EE reactions
and reviewing the electrochemical methods best suited to characterize them, applications are taken
from the literature of organic and organometallic redox chemistry.
II. ThERMODYNAMic ASPEcTS

A. EXprESSIoN oF PoTENTIaLS
The relationships between the three most commonly used terms for the potentials of redox couples,
namely, the standard potential (Eo), the formal potential (Eo′), and the E1/2 potential, were discussed
in Chapter 1. Referring to Equation 11.3, E1/2 is identical to the standard potential when the activity
Influence of Molecular and Medium Effects on Two-Electron Processes 397
coefficients ( f ) and diffusion coefficients (D) are equal for the two members of the redox couple.
We will employ both Eo and E1/2 in the theoretical section but refer exclusively to E1/2 values when
experimental examples are discussed. Within these conventions, we employ symbols based on the
relative ordering of the redox states of the molecule, with the starting point designated by (0). Thus,
reduction of a compound by two one-electron processes (Equation 11.4) takes the fully oxidized
o
state Ox(0) successively to the first reduced state Red(1) (at potential ERed1 ) and then to the second
o
reduced state Red(2) (at potential ERed2). A similar nomenclature is employed for successive oxida-
tions of neutral compounds, this time beginning with the neutral compound being in the least oxi-
dized (most reduced) redox state (see Equation 11.5):
RT  fOx   DRed  
1/ 2
E1/ 2 =E +
o
ln    (11.3)
nF  fRed   DOx  
 
− −
+e +e

For reductions: Ox(0) o

Red(1) o

Red(2) (11.4)
ERed1 ERed2

− e− − e−

For oxidations: Red(0) o

Ox(1)
Ox(2)
o (11.5)
EOx1 EOx 2

An important factor in this chemistry is the magnitude of the potential separations for EE processes,
ΔE1/2. So that increasingly positive values of ΔE1/2 always denote systems for which disproportion-
ation of the one-electron product (usually a radical) is increasingly disfavored, the definition of ΔE1/2
is changed for sequences of reductions (Equation 11.6) versus oxidations (Equation 11.7). Thus, a
“normal” ordering of the ET processes (i.e., second reduction [“oxidation”] more negative [“positive”]
than the first) always has a “positive” ΔE1/2 value and an “inverted” ordering [4] (first reduction
[“oxidation”] less negative [“positive”] than the second) always has a “negative” ΔE1/2 value:
For Reductions: ∆E1/ 2 = E1Red

/ 2 − E1/ 2
1 Red 2
(11.6)

For Oxidations: ∆E1/ 2 = E1Ox

/ 2 − E1/ 2
2 Ox 1
(11.7)

B. NorMaL VErSUS INVErTED OrDErING oF E1/2 PoTENTIaLS

Consider the case of a neutral compound such as anthracene, 1, being reduced to a dianion in a
sequence of two E.T. steps. Owing strictly to electrostatic considerations, the second reduction is
− /2 −
expected to be energetically more difficult than the first, accounting for the fact that E1/2 is lower
0/−
(more negative) than E1/2 . This so-called normal ordering is observed in the great majority of over-
all two-electron processes. The sign of ΔE1/2 has a profound effect on the chemistry of the E.T.
series, since it determines whether or not disproportionation of the radical (1− in the present case)
(Equation 11.8) is thermodynamically favored. Using Equation 11.9 to obtain Kdisp from ΔE1/2, per-
centages of the “actual” concentration of the radical in
[1][12− ]
2 1− 1 + 12− K disp = (11.8)
[1− ]2
 RT 
∆E1/ 2 =   ln K disp (11.9)
 F 
TABLE 11.1
Kdisp Calculated for Several ΔE1/2 Values (RT/F = 0.0257 V at 298 K; ΔE1/2 in mV)
ΔE1/2 Kdisp % Radical Remaining
+500 3.5 × 10 −9 >99.9
+236 1.0 × 10−4 98
+118 1.0 × 10−2 83
+59 0.10 61
0 1 33
−59 9.9 14
−118 99 5
−236 9.7 × 103 0.50
−500 2.8 × 108 <0.1
The final column refers to the % radical (1− in Equation 11.8) compared to the nominal radical concentration
assuming no disproportionation.
– 2–
+e– +e–
0/–
E1/2 E1/2–/2–
1 1– 12–
solutions that nominally contain only the pure radical may be calculated (Table 11.1). In terms of
influencing the analytical or reaction chemistry of a radical, disproportionation can be expected to
play a role if the ΔE1/2 value of an EE system is less than about 200 mV.
2–
Bz CO Bz CO
CO CO
OC S CO –2e– OC S CO
W W W W
S CO +2e– S CO
OC OC
CO Bz CO CO Bz CO
Spectroscopy may sometimes be employed to determine a Kdisp value and, therefore, the ΔE1/2
value when the direct voltammetric approach is difficult. An IR spectroelectrochemistry example
involving an “inverted” potential system is found in the work of Hill et al. on the oxidation of
the ditungsten complex [W2(μ-SBz)2(CO)6]2−(Bz = benzyl) [5]. A cyclic voltammetry (CV) scan
of this system indicated a single two-electron oxidation to the corresponding neutral complex
(E1/2 = − 0.57 V vs. Ag/AgCl), but a precise determination of the ΔE1/2 value was clouded by compli-
cations due to sluggish heterogeneous E.T. [9]. By making precise spectroelectrochemical measure-
ments, the authors managed to extract a carbonyl-range IR spectrum of the monooxidation product,
[W2(μ-SBz)2(CO)6]−, at an equilibrated amount of about 1% of the other members of the redox
family. Working back from the spectrally determined value of Kdisp (= 7500 ± 4000), Equation 11.9
allowed determination of the inverted ΔE1/2 value as −0.23 ± 0.02 V [6].
C. FrEE ENErGY FaCTorS

The potential of an “individual” redox couple (Eo) is related to the Gibbs free energy of the reaction
by Equation 11.10, where ΔGo is the difference in free energies between the oxidized and reduced
∆G o = −nFE o (11.10)

members of the couple (e.g., 1 and 1−). In the context of a reaction in a liquid medium, ΔGo is given
by Equation 11.11, where ∆GRed
o
( g ) and ∆GOx( g ) are the gas-phase free energies of formation of
o
∆G o = ∆GRed
o
− ∆GOx
o
= ∆GRed
o
( g ) + ∆GRed( s ) − ∆GOx( g ) − ∆GOx( s )
o o o
(11.11)

Red and Ox and ∆GRed ( s ) and ∆GOx( s ) are the respective solvation energies. Additional terms would
o o
have to be entered to account for ion-pairing energies. A straightforward extension to the two-
electron process gives Equation 11.12, which provides the ΔEo value determined by the free energies
of the three compounds, Ox, Red1, and Red2, which comprise the EE process of Equation 11.4. This
expression also contains terms for the ion-pairing energies of the charged members of the E.T. series:
− F∆E o = ∆∆G o = 2∆GRed

o
1( g ) − ∆GOx ( g ) − ∆GRed 2 ( g ) + 2 ∆GRed 1( s ) − ∆GOx ( s ) − ∆GRed 2 ( s )
o o o o o

+ ∆GRed
o
1( ip ) − ∆GRed 2 ( ip )
o
(11.12)

The two different classes of free energy effects present in Equation 11.12, namely, the “intrinsic”
factors tied to molecular and electronic structure and the “extrinsic” factors tied to medium effects
(solvent and ion pairing), form the backdrop of our treatment.
D. INTrINSIC VErSUS EXTrINSIC FaCTorS AFFECTING ΔE1/2 VaLUES

A drawing tracking the major chemical and physical factors that influence the energetic spacing
of EE reactions is given in Scheme 11.1. The top row presents a typical ordering of the gas-phase
energies for sequential addition of two electrons to Ox(0). These potentials are determined only by
the intrinsic differences in free energies between the three members of the E.T. series, each in their
coordinately relaxed structures. For example, the free energy of the first E.T. reaction of Equation
11.4 (Ox(0)/Red(1)) is ∆GRed o
1( g ) − ∆GOx( g ). The much more negative potential (by 4–5 eV) of ERe d2
o o
reflects the electrostatic effect of addition of a second electron to the molecule. For reductions, the
Ox/Red1 Red1/Red2
# Gas phase, small
structure changes
# ΔE° ca 4–5 eV (intrinsic)
# Extrinsic factors:
solvation, ion pairing
# ΔE1/2 ca 0.5 V
# Intrinsic factors: large structural or

electronic relaxation of dianion
# ΔE1/2 negative (inverted ordering).

Reduction to dianion now is Red1/Red*2
owing to structure change in the dianion
Red1/Red*2 Ox/Red*1
More positive E° or E1/2
SchEME 11.1 Qualitative influence of extrinsic and intrinsic factors on the ordering of potentials for EE
reductions of a neutral compound, with structural relaxation in second reduction. Red*1 and Red*2 are struc-
turally relaxed compared to Red1 and Red2.
gas-phase free energies can sometimes be determined experimentally by measurement of single

electron-attachment energies. Conversely, for oxidations, gas-phase ionization potentials provide
access to the intrinsic electron-removal energies.
Dropping to the middle row in Scheme 11.1 (where ΔEo is re-expressed as ΔE1/2) adds the extrin-
sic factors arising from how the different members of the redox couples interact with the medium.
Although ion-pairing effects may be a crucial factor in ordering two closely spaced redox processes
(vide infra), solvation plays the dominant role in ameliorating the large gas-phase energy differ-
ence owing to stronger solvation energies of the more highly charged species [7]. Solvation effects
lower the ΔE1/2 values for aromatic hydrocarbons by about an order of magnitude compared to the
gas-phase values, to the point where they can often be measured voltammetrically [8]. The bottom
row in Scheme 11.1 brings in another category of intrinsic effects: changes in electronic structure
(e.g., spin states) or, more commonly, structural rearrangements, which are concomitant with E.T.
In this drawing, we show a case in which there is a significant structural change in the second E.T.
step, with the accompanying structural relaxation energy moving E1/2(2) positive of E1/2(1), which
will be treated in detail in the following text. However, in the great majority of EE processes, major
structural rearrangements accompany neither redox couple, and the final ΔE1/2 value changes very
little from that shown in the middle picture. As we will see in the succeeding text, this is the situa-
tion found in the reduction of anthracene to its dianion.
Owing to contemporary computational methods, the intrinsic and extrinsic effects on the free
energies (and consequent ΔE1/2 potentials) of multielectron processes may now be more quantita-
tively understood. We will take advantage of calculations published on the stepwise EE reductions
of anthracene (AN) and cyclooctatetraene (COT) to see how the various factors may influence ΔE1/2
values. The two systems are chosen to represent overall two-electron systems that have either very
small (anthracene) or dramatically large (COT) redox-induced structure changes. Both of these
molecules are considered to be “single-site” redox systems, in contrast to multiple-site systems that
contain two or more discrete redox centers such as ferrocenyl moieties. The latter are treated in
Section V.B.
E. CV IMaGES For DIFFErENT ΔE1/2 VaLUES

The dominance of cleanly separated one-electron reactions for a ΔE1/2 of 236 mV is visually appar-
ent in the theoretical CV curve (Figure 11.1, ΔE1/2 = 236 mV). When ΔE1/2 decreases from this
value, the quantity of the monoanion at equilibrium decreases, resulting in increasingly poorly
resolved cathodic features (Figure 11.1, ΔE1/2 = 118 and 59 mV). When the ΔE1/2 value reaches zero
or an “inverted” (negative) value (i.e., E1Red2 Red1
/ 2 > E1/ 2 ), there is only one coupled cathodic/anodic fea-
ture (Figure 11.1, ΔE1/2 = 0, −59, and −118 mV). With a ΔE1/2 value lower (more negative) than −118
mV, disproportionation of Red(1) dominates and the reduction of Ox has the experimental appear-
ance of a single two-electron process in the following equation:

Ox(0) +2 e −
Red(2) E =
o
2
(
1 o
ERed1 + ERed2
o
)
(11.13)
Square wave voltammetry scans for the same ΔE1/2 values are shown on the right side of Figure 11.1.
Application of this technique will be covered in Section IV.A.
F. EXaMpLES oF CaLCULaTED EE ProCESSES

1. EE with Minimal Structure Change: Anthracene
In the case of anthracene, 1, the additional gas-phase energy for electron attachment of a second
electron is a prodigious 4.2 eV for the electrostatic reasons referred to previously. After accounting
for solvation energies calculated by a simple continuum model for a solvent with a dielectric constant
ΔE1/2
Cyclic Voltammetry Square Wave Voltammetry
(mV)
I (A)
0.0004 I (A)
0.0002 0.0004
236 0 0
–0.0002 –0.0004
–0.0004 –0.0008
–0.6 –0.8 –1 –1.2 –1.4 –1.6 –1.8 –2 –1 –1.1 –1.2 –1.3 –1.4 –1.5 –1.6 –1.7 –1.8
E (V) E (V)
I (A)
I (A)
0.0004 0.0004
0.0002
0
0
118 –0.0002 –0.0004
–0.0004 –0.0008
–0.6 –0.8 –1 –1.2 –1.4 –1.6 –1.8 –2 –1 –1.1 –1.2 –1.3 –1.4 –1.5 –1.6 –1.7 –1.8
E (V) E (V)
I (A) I (A)
0.0006 0.001
0.0004 0.0005
0.0002
0
0
59 –0.0002 –0.0005
–0.0004 –0.001
–0.0006
–0.6 –0.8 –1 –1.2 –1.4 –1.6 –1.8 –2 –1 –1.1 –1.2 –1.3 –1.4 –1.5 –1.6 –1.7 –1.8
E (V) E (V)
I (A) I (A)
0.0008
0.001
0.0004
0
0
0
–0.0004 –0.001
–0.0008 –0.002
–0.6 –0.8 –1 –1.2 –1.4 –1.6 –1.8 –2 –1 –1.1 –1.2 –1.3 –1.4 –1.5 –1.6 –1.7 –1.8
E (V) E (V)
I (A) I (A)
0.0008 0.002
0.0004 0.001
0
0
–59
–0.001
–0.0004
–0.002
–0.0008
–0.6 –0.8 –1 –1.2 –1.4 –1.6 –1.8 –2 –1 –1.1 –1.2 –1.3 –1.4 –1.5 –1.6 –1.7 –1.8
E (V) E (V)
I (A)
I (A)
0.002
0.0008
0.001
0.0004
0
–118 0
–0.001
–0.0004
–0.002
–0.0008
–0.6 –0.8 –1 –1.2 –1.4 –1.6 –1.8 –2 –1 –1.1 –1.2 –1.3 –1.4 –1.5 –1.6 –1.7 –1.8
E (V) E (V)
FiGURE 11.1 Simulated (DigiElch) cyclic and SWVs for two consecutive reversible one-electron reductions
for different ΔE1/2. Parameters for cyclic voltammograms: v = 200 mV s−1, k0 = 104 cm s−1, α = 0.5, T = 298.2 K,
CA* = 1 mM, and A = 1 cm2. For square wave, f = 100 Hz.
of 36 (mimicking CH3CN or DMF), the calculated potential separation was reduced to 0.87 eV [8]
(calculationally, we have now reached the middle of Scheme 11.1). Inclusion of estimated ion-pairing
energies (not included in Scheme 11.1) of [NMe4]+ ions with 1− and 12− further lower the calculated
potential separation to 0.83 V, reasonably close to the measured ΔE1/2 value of 0.67 V [9]. The fact
that the ΔE1/2 values decrease as the medium effects are taken into account is understood intuitively
by increases in both Born solvation energies and coulombic ion-pairing strengths with increasing
charge of the products. However, the sum of the intrinsic and extrinsic stabilization energies gained
in formation of the anthracene dianion is insufficient to bring E1Red2 Red1
/ 2 positive of E1/ 2 . Referring back
to Scheme 11.1, the intrinsic structural relaxations specified in the bottom section are small. The
reduction of anthracene therefore obeys normal potential ordering, with a positive value of ΔE1/2.
A chemical consequence of the ΔE1/2 value for the 1/1−/12− ET series is that, given the absence
of a follow-up reaction such as protonation, one-electron reduction of anthracene, whether accom-
plished strictly electrochemically or with a chemical reducing agent, gives a stable solution of its
anion radical. Specifically, the experimental ΔE1/2 value of 0.67 V [9] gives a Kdisp value of 5 × 10 −12,
and much smaller values of ΔE1/2 are necessary for there to be analytically or chemically significant
amounts of the disproportionation products 1 and 12− (see Table 11.1).
2. EE with Major Structure Change

In the great majority of systems exhibiting inverted EE behavior, a major structural change accom-
panies at least one of the E.T. reactions. It is important to reiterate the distinction between this case
and “square schemes.” The latter are, in fact, sequences of electrochemical–chemical reactions
[1,3,10]. As discussed in Section 1, we will consider only electrochemical reactions, for which struc-
ture change is considered to be concomitant with E.T.
a. Structure Change in Second ET Process

Within the EE model (Equations 11.14 and 11.15), consider the case in which the structure change
occurs in the second E.T. process. In Equation 11.15, the symbol “*” indicates that the molecule has
undergone a major structural rearrangement. Referring again to the bottom row of Scheme 11.1, the
minor versus major structural relaxation energies
+ e−

Ox(0) Ox/Red1
Red(1) E1/ 2 (11.14)

+ e−

Red(1) * Red1/Red*2
Red (2) E1/ 2 (11.15)

of the two E.T. steps cause a more positive shift in the second E.T. process compared to the first. If
the structural stabilization energy is sufficient, ΔE1/2 may be negative (i.e., inverted), and the reduc-
tion of Ox(0) follows the two-electron stoichiometry of Equation 11.16. We will treat examples of
such a system in the following text when considering the reductions of bis(hexamethylbenzene)
ruthenium (II) and arene cyclopentadienyl iridium (III) complexes:
(
1 Ox/Red1
)
−
+2 e

Ox(0)
Red (2) E1/ 2 =
*
E1/ 2 + E1Red1/Red*
/2
2
(11.16)
2
b. Structure Change in First E.T. Process

That structural change in the second E.T. step may lead to potential inversion is intellectually
straightforward, in the sense that the intrinsic and extrinsic stabilization forces (structure change
and medium effects, respectively) are conveying the same directional sign changes on ΔE1/2, each
imparting a positive shift of E1/2(2) relative to E1/2(1). Less intuitive is the fact that structure change
Ox/Red*1 > Red*1/Red*2

Large relaxation energy for
E B monoanion, ΔE1/2 positive
(normal ordering)
A B C D
Ox*/Red*1 Red*1/Red*2 Ox/Red1 Red1/Red2
Small relaxation energy for

B E monoanion, ΔE1/2 negative
(inverted ordering)
Red*1/Red*2 > Ox/Red*1
More positive E1/2
SchEME 11.2 Effects of structural relaxation in first reduction on ordering of potentials for EE reductions.
The middle section shows the medium-adjusted EE potentials for the two different “frozen” structures desig-
nated as either unmarked or with a “*.” The labels A through E are discussed in the text. Solid arrow used for
E.T. involving major structure change.
in the first E.T. step may also give rise to inverted ΔE1/2 potentials. For a reduction, this requires that
the rearranged (*) structure have dramatically better electron acceptor properties than the original
structure, so that the second reduction of putative Ox*(0) would be more facile than the first reduc-
tion of Ox(0) to Red*(1).
Consider Scheme 11.2, which begins with the assumption that account has already been taken
of the extrinsic (electrolyte) effects. The middle of the scheme pictures a pair of hypothetical EE
processes for two structurally different molecules assumed to be “locked” into their two different
isomeric structures. Their two individual E.T. series (Equations 11.17 and 11.18) are represented by
the less
+ e− + e−

Ox(0) Ox/Red1

Red(1) Red1/Red2

Red(2) (11.17)
E1/ 2 (C ) E1/ 2 (D )

+ e− + e−

Ox * (0) Ox*/Red*1

Red*(1) Red*1/Red*2

Red*(2) (11.18)
E1/ 2 (A ) E1/ 2 (B )

negative pair of lines, A and B, for Ox*(0) and the more negative pair, C and D, for Ox(0), the
latter being the true starting material. The upper and lower drawings show the possible conse-
quences of introducing a major structure change into the first reduction of Ox(0). In both cases, the
couple Ox(0)/Red(1) (C) becomes Ox(0)/Red*(1) (E), modifying the potential of the first reduction
by the amounts of the solid arrows. The potential E1Red*1/Red*2
/2 (B) remains unaffected and those of
E1Ox*/Red*1
/2 (A) and E1Red1/Red2
/2 (D) are no longer pertinent.
If the stabilization energy shifts E positive of B (top drawing), the system retains normal poten-
tial ordering, with its positive ΔE1/2 value now representing E1Ox/Red*1
/2 − E1Red*1/Red*2
/2 . If the structural
stabilization energy is small (bottom drawing), then B resides positive of E, inverting the E1/2 values
and leading to a single two-electron wave as Ox(0) goes to Red*(2) (Equation 11.16). One example
of a system that can be experimentally manipulated to exhibit either normal or inverted behavior is
the reduction of cyclooctatetraene, which we now consider.
3. Application to Reduction of Cyclooctatetraene

Reduction of tub-like COT to its planar dianion (COT2−) has been intensely studied through a
number of chemical, electrochemical, and theoretical methods [11], with general agreement that a
two-step EE mechanism is involved. Studies under dissimilar experimental conditions have shown
that this system switches between normal and inverted EE behavior, depending on the electrolyte
medium. In most electrolytes, COT undergoes two normally ordered reductions having potentials
that are closely spaced, at least relative to anthracene and other aromatic hydrocarbons. Putting
aside for the moment the effects of slow heterogeneous E.T. on the shape of the first waves, the d.c.
and a.c. polarographic scans of Figure 11.2 clearly demonstrate the normally ordered EE process,
COT/COT−/COT2−, in DMF/0.1 M [NBu4][ClO4] (ΔE1/2 = +0.24 V) [12]. However, an inverted ΔE1/2
value of −0.22 V was estimated for the same redox process in liquid ammonia (0.1 M KI) [13], in
which the CV scan (Figure 11.3) shows only a single matched pair of cathodic and anodic features
consistent with a two-electron process, COT/COT2−.
+e– +e–
0/–
– 2–
E1/2 E1/2–/2–
COT COT– COT2–
A quantitative treatment of the thermodynamics of this system was detailed by Baik et al. [14].
Scheme 11.3 demonstrates the principal energetic impacts of structural relaxation and ion pair-
ing on the potentials of the EE sequence for COT. Conceptually, there are four redox couples that
must be accounted for, based on two idealized structures, either tub (T0/−/2−) or planar (P0/−/2−).
(We are simplifying this, considering only a delocalized dianion. In fact, the calculations also take
into account the energy gained by the planar anions going from non-delocalized to delocalized
electronic structures.) The computed potentials sketched in the top row of Scheme 11.3 show that
reductions of both isomers would follow normal EE mechanisms if locked into their given tub or
4.00 1.50
3.00
1.00
μA
2.00
μA
0.50
1.00
0.00 0.00
–1.00 –1.10 –1.20 –1.30 –1.40 –1.50 –1.00 –1.10 –1.20 –1.30 –1.40
(a) Applied d.c. potential (mV) (b) Applied d.c. potential (mV)
FiGURE 11.2 Comparison of theory and experiment for the first two polarographic waves of COT. (o)
Experimental d.c. current (a) and experimental fundamental harmonic inphase a.c. polarographic current
(b). (⎯) theoretical polarograms for ks1 = 2.0 × 10 − 3 cm s−1, α1 = 0.40, ks2 = 0.15 cm s−1, α2 = 0.50, and Do = 1.4 ×
10 −5 cm2 s−1. (From Huebert, B.J. and Smith, D.E., J. Electroanal. Chem., 31, 333, 1971. With permission.)
–0.8 –1.2 –1.6

E(V) vs. Ag/Ag+
FiGURE 11.3 Simulated voltammogram of COT (- - -) versus experimental voltammogram (–). ks1 = 1.58 ×
10 −4 cm s−1, ks2 = 1.26 × 10 −2 cm s−1, (E1 − E2 ) = − 220 mV, T = 245 K. (From Smith, W.H. and Bard, A.J.,
0 0
J. Electroanal. Chem., 76, 19, 1977. With permission.)
planar forms, with ΔE1/2 values of about +0.76 V for the planar isomer and 1.05 V for the tub iso-
mer. Importantly, both E1/2 potentials of the planar form are higher (more positive) than the first
potential of the tub form. Introduction of structural relaxation into the calculations (middle sketch)
shifts the reduction of the neutral tub positively by 1.02 eV as the monoanion takes on the planar
geometry. E1/2(1) now refers to the couple T0/P−. The second reduction, E1/2(2), is necessarily that
of P−/P2−, which shifts only slightly owing to the much smaller relaxation energy (0.13 V) inherent
to formation of the planar dianion from the structurally similar monoanion. Referring back to our
earlier theoretical treatment, the COT system is now described by the top sketch of Scheme 11.2.
The calculated ΔE1/2 value of + 0.41 V does not take into account the modest ion-pairing effects of
[NBu4]+ with COT2−, which would likely reduce this value by about 0.1 V and bring it very close to
the measured value [12] of +0.24 V.
The strong ion pairing required in order to bring E1/2(2) positive of E1/2(1) was quantitatively eval-
uated by introducing a solvated ion-pair model based on potassium into the calculations (bottom
sketch of Scheme 11.3). The strong ion pairing of K2(COT) provides the final stabilizing energy
to achieve potential inversion, with the calculated ΔE1/2 of −0.25 V being remarkably close to the
experimental value [13] of −0.22 V in NH3(l)/0.1 M KI.
P0/P– P–/P2– T0/T– T–T2–
Solvated, rigid structures

0.76 V 0.73 V 1.05 V P = planar, T = tub
0.13 V
1.02 V
Introduce
structural relaxation,
T0/P– P–/P2–
ΔE1/2 = +0.41 V (normal)
P–/P2– T0/P– Introduce K+ ion-pairing

ΔE1/2 = –0.25 V (inverted)
More positive E1/2
SchEME 11.3 Sequence of calculated energies of E1/2 values of COT reductions, beginning from solvated
species having either a planar (P) or tub (T) geometry.
III. EffEcTS Of SLOw HETEROGENEOUS ELEcTRON TRANSfER

It is well known that a structure change such as the COT tub-to-planar rearrangement that occurs
concomitant with E.T. lowers the standard heterogeneous E.T. rate ko (sometimes labeled ks) owing
to an increase in the inner-shell reorganization energy λi of the reaction. The redox couple then
behaves as a quasi-reversible or electrochemically irreversible E.T. system.
Given that structural reorganization is often a key factor in inducing inverted potential ordering,
it is not surprising that sluggish E.T. kinetics are often observed with inverted two-electron systems.
Furthermore, the effects of slow E.T. on voltammetric displays are more notable than in the normally
ordered case. Figure 11.4 contains CV scans for a normally ordered EE system (ΔE1/2 = +200 mV) in
which (A) both E.T. steps are Nernstian (fast); (B) the first E.T. is quasi-reversible (slow); and (C) the
second E.T. is quasi-reversible. The “spread out” appearance of the first wave in case B has its coun-
terparts in other voltammetric methods, as seen in the dc and ac polarographic scans of Figure 11.2.
Figure 11.5 gives the same sequence of fast and slow E.T. for an inverted EE system with ΔE1/2 =
−200 mV. It is immediately obvious that, compared to the normally ordered case, sluggish E.T. for
an inverted system has a much more dramatic effect on the shapes and positions of the CV waves. In
general, the forward peak (cathodic in this case) appears close to the potential of the first E.T. step,
whereas the reverse (anodic) peak appears close to the potential of the second E.T. step. When both
E.T. steps are fast (D), the cathodic and anodic peaks appear near the average of the two E1/2 potentials.
The qualitative reason for this effect has to do with how one slow (i.e., rate determining) charge
transfer affects the concentration of the other E.T. product at given applied potentials. Consider, for
example, scans D (both E.T. fast) and E (first E.T. slow) in Figure 11.5. With the measured E1/2 of
scan D being the average of E1/2(1) and E1/2(2), (0.1 V here), the first reduction of Ox(0) begins at a
significant underpotential, that is, quite positive, of E1/2(1). However, Red(1) is produced at a signifi-
cant overpotential for its reduction to Red(2). Thus, as long as both E.T. steps have high ko values, the
system moves quickly to equilibrium, and the current/potential curve is governed by the Nernst equa-
tion and mass transfer. The resulting forward wave is Nernstian shaped. However, if the E.T. of the
first reduction is slow (scan E), it becomes rate determining and governs the current/potential plot.
2.00E–03
1.50E–03
A
1.00E–03 C
Current (mA)
5.00E–04 B
0.00E+00
–5.00E–04
ks1= 1 ks2 = 1
–1.00E–03 ks1 = 0.02 ks2 = 1
ks1 = 1 ks2 = 0.01
–1.50E–03
0.3 0.2 0.1 0 –0.1 –0.2 –0.3 –0.4 –0.5 –0.6
Potential (V)
FiGURE 11.4 Simulated (DigiSim) cyclic voltammograms for normal ordered two consecutive reversible
one-electron reductions with different heterogeneous standard heterogeneous E.T. rate constants in cm s−1.
Parameters: E1 = 0 V, E2 = −0.2 V, v = 1 V s−1, α = 0.5, T = 298.2 K, CA* = 1 mM, and A = 1 cm2.
4.00E–03
3.00E–03 F
D
2.00E–03 E
Current (mA)
1.00E–03
0.00E+00
–1.00E–03
ks1 = 1 ks2 = 1
–2.00E–03 ks1 = 0.02 ks2 = 1
ks1 = 1 ks2 = 0.01
–3.00E–03
0.6 0.5 0.4 0.3 0.2 0.1 0 –0.1 –0.2 –0.3
Potential (V)
FiGURE 11.5 Simulated (DigiSim) cyclic voltammograms for inverted two consecutive reversible one-
electron reductions with different heterogeneous standard heterogeneous E.T. rate constants in cm s−1.
Parameters: E1 = 0 V, E2 = +0.2 V, v = 1 V s−1, α = 0.5, T = 298.2 K, CA* = 1 mM, and A = 1 cm2.
Thus, when the potential reaches 0 V, a diminished current is obtained owing simply to the slow
conversion of Ox(0) to Red(1). The expected currents are not observed until the applied potential
becomes close to E1/2(1), whereupon the forward wave takes on the shape of an irreversible cathodic
process. In the alternate case in which the second reduction is rate determining (scan F), the cathodic
wave again appears near E1/2(1), but it is more “reversibly” shaped because, when significant quanti-
ties of Red(1) are produced, the applied potential is already at a high overpotential for the reduction
of Red(1) to Red(2). These arguments have been well expressed by Evans [15].
Whereas the CVs in Figures 11.4 and 11.5 were produced using transmission coefficients, α, of
0.5, it should be mentioned that the shape of a quasi-reversible wave of either one-electron or two-
electron type is quite sensitive to the α value. The fact that E.T. reactions in which α ≠ 0.5 are fairly
common in two-electron chemistry means that the normal CV diagnostics (Ep − Ep/2; ip/v1/2, Ep shifts
with v, etc.) are often not easily applied to such systems. For inverted potential systems, computer
simulations of CV curves at multiple scan rates are almost always necessary to extract anything
more than qualitative conclusions about the individual one-electron steps.
IV. ExPERiMENTAL ASPEcTS: DETERMiNATiON Of E.T.

STOichiOMETRY (ONE OR TwO ELEcTRONS?)
When ΔE1/2 values are less than about 60 mV, the fact that the voltammetry shows only a single
cathodic/anodic pair (see Figure 11.1) introduces the need for additional analysis to tell whether
the redox process has a stoichiometry of one or two electrons. Several different approaches to this
problem are given in this section. Note that the voltammetric approaches refer only to two-electron
processes involving a single-site redox system and exclude the kinds of multisite systems that might
be found in polymers, dendrimers, and molecules that are “tagged” with equivalent redox-active
groups such as ferrocenyl moieties (Section V). Also, the discussion is restricted to simple EE sys-
tems without coupled reactions.
A. ANaLYSIS bY a SINGLE ELECTroaNaLYTICaL METHoD

For a diffusion-controlled system, the voltammetric current is a function of both the n-value of
the couple and the diffusion coefficient, Do, of the analyte. The latter is often estimated by using
the known Do value of a molecule of similar shape and size in the same medium. The diffusion
coefficient for an uncharged spherical molecule is given by the Stokes–Einstein equation (Do =
RT/6NAπηr), where NA is Avogadro’s number, η is the solvent viscosity, and r is the spherical radius.
For spheres of different molecular weights, M, Do ∝ M0.33 and for linear molecules, Do ∝ M0.55
[16]. Recently, an NMR method has been introduced as a convenient, electrochemically indepen-
dent approach to the determination of Do values [17,18]. However, even if Do is known, or can be
acceptably estimated, complications arise in the use of CV peak currents to determine n values.
Consider the following: The current function, χ, is defined by Equation 11.19, where ip is the peak
current in μA, v is the scan rate in V s−1, n is the number of electrons transferred, A is the area of the
electrode in cm2, Do is the diffusion coefficient of the electroactive species in cm2 s−1, and Co is its
bulk concentration in mol cm−3 [19]. Its prediction that the scan-rate normalized peak current for a
two-electron process is 2.83 times that of a one-electron process holds only when the second one-
electron process has a much milder E1/2
ip
x= = 0.269n3 / 2 ADo1/ 2C ° (11.19)
v1/ 2
potential than the first one-electron process. Considering reductions, for example, it requires that
E1Red1/Red2
/2 be significantly more positive than E1Ox/Red1
/2 . If the two E1/2 values are closer, the cathodic
peak height becomes a sensitive function of ΔE1/2 and digital simulations are needed to solve the
question of the E.T. stoichiometry.
The shape of the CV wave is also sensitive to the E.T. stoichiometry. The most readily measured
CV parameter is the separation between cathodic and the anodic current peaks, Epc and Epa, respec-
tively, which follows the relationship in the following equation:
Epa − Epc ≈ RT l n(10)/nF (≈ 60 mV/n at room temperature) (11.20)

TABLE 11.2
Partial Listing of the Effects of Changes in ΔE1/2 on the CV ΔEp (= Epa − Epc)
Value and the DPV Width at Half Height (W1/2)
Mechanism ΔE1/2 (mV) ΔEp (mV) W1/2 (mV) (DPV)
E (single one electron) n.a. 60 ± 1 a 90
EE +118 (normal) 161 207
EE +59 (normal) 84 122
EE 0 42 66
EE −59 (inverted) 34 52
EE −118 (inverted) 30 48
Sources: Nicholson, R.S., Anal. Chem., 37, 1351, 1965; Nicholson, R.S. and Shain, I., Anal. Chem.,
36, 706, 1964.
Values for EE system are taken from Reference 22. The calculations assume Nernstian E.T. behavior and
the DPV data are based on a 10 mV pulse amplitude. DPV stands for differential pulse voltammetry.
a The ΔE value for an E mechanism is sensitive to the difference between E and the experimental
p pc
switching potential, Eλ.
Thus, a ΔEp value of significantly less than 60 mV is a clear indication of an inverted two-electron
system [16,20,21]. Conversely, if normally ordered ΔE1/2 values are small enough to preclude
resolution of sequential waves, the single forward and reverse waves are broader than those of
a Nernstian one-electron process (see ΔE1/2 = +59 mV in Figure 11.1). Digital simulation of an
experimental CV wave could be employed to obtain the ΔE1/2 value, but published tables can serve
this purpose in most cases. Particularly useful are data published by Richardson and Taube [22],
examples of which are collected in Table 11.2. Note that the CV peak separation is 42 mV when
E1/2(2) = E1/2(1) and only achieves the “true” two-electron value predicted by Equation 11.20 when
the degree of potential inversion reaches 118 mV.
The ΔE1/2 values for overlapped EE waves can also be determined by measuring the widths at
half height, W1/2, obtained using pulsed voltammetric methods. Simulations of square wave voltam-
mograms (SWVs) for EE systems are shown in Figure 11.1. Similarly shaped waves are obtained
by differential pulse voltammetry (DPV) and have the advantage of being less sensitive to slug-
gish charge-transfer kinetics. Equation 11.21 indicates that when the DPV pulse height (ΔEpulse) is
kept small, the half width is about 90 mV for a one-electron process and 45 mV for a two-electron
process. Calculated W1/2 values for representative ΔE1/2 values are given in Table 11.2, and a more
exhaustive working curve is available in Reference 22:
for ∆Epulse < 20 /n mV, W1/ 2 = 90 /n mV (11.21)

B. ANaLYSIS bY CoMbINED METHoDS

1. Electrolysis and Voltammetry
Controlled potential electrolysis, in which one measures the coulometry required for a complete
bulk redox reaction, is a powerful method for determining the n-value of an electrochemical pro-
cess. Within the present context, a few cautionary notes are in order. Primary among these is the
difference in timescale between voltammetry (usually less than 10 s) and bulk electrolysis. With
the exception of experiments carried out in thin-layer cells, bulk electrolyses typically take min-
utes to scores-of-minutes to complete, raising the possibility that the short-time and long-time E.T.
mechanisms and products might be different. Voltammetric analysis before and after exhaustive
electrolysis may minimize the chances of undetected timescale-dependent changes in mechanism,

but the micro- versus macroscale natures of the different techniques must always be kept in mind.
One should also be aware that, owing to ohmic drop, the effective potential may vary considerably
from the nominal Eappl across the surface of a large electrode when the bulk electrolysis is carried
out in a nonaqueous electrolyte solution. This can introduce a considerable problem when closely
spaced reactions are involved. A review of how coupled chemical reactions affect bulk coulometric
experiments is available [23].
2. Dual Voltammetric Analysis

Based on the preceding discussion, there is a clear need for a way to determine the E.T. stoichiometry
that is not sensitive to differences in experimental timescales and is independent of the diffusion
coefficient of the test compound. This can be accomplished by using the results of two electro-
analytical experiments, one based on a “transient” technique (e.g., CV or chronoamperometry)
and the other on a “steady-state” technique (e.g., rotating disk voltammetry or ultramicroelectrode
voltammetry). The fundamental idea, apparently first suggested by Lingane [24], involves measur-
ing technique-sensitive characteristic currents that differ in their proportionality to the diffusion
coefficient of the test compound. For example, consider that the fundamental measurable in chro-
( )
noamperometry (the it1/2 value) is proportional to nDo1/2 (Cottrell equation, it 1/ 2 = n /π1/ 2 FADo1/ 2Co ),
but those of the steady-state methods are proportional to either nDo2/3 (through the Levich equation,
ilim /ω1/ 2Co = 0.62 nFADo2 / 3ν −1/ 6, where ω = angular rotation rate and ν = kinematic viscosity of solu-
tion) or nDo (for hemispherical diffusion to ultramicroelectrode disk of radius r, ilim = 4nFDorCo).
Taking as an example the reduction of COT in liquid ammonia (Figure 11.3), one might obtain
chronoamperometric it1/2 data by pulsing from −0.7 to −1.7 V at a disk electrode of 2 mm diameter
and then obtain limiting current from a steady-state voltammogram over the same potential range
with a 10 μm ultramicroelectrode. The ratio of the two measurables allows the determination of Do,
and thereby n. Chronoamperometry has advantages over CV as the transient method, as discussed
elsewhere [25].
V. APPLicATiONS TO TwO-ELEcTRON PROcESSES

Here, we consider EE applications as involving two different categories of molecules: those hav-
ing a single redox site and those having multiple, chemically identical, redox sites. Although some
structures blur this formal separation, the grouping is pedagogically useful. Certainly, single-site
and multiple-site systems may have moieties that are capable of being E.T. sites in and of them-
selves. What will distinguish the two cases in our treatment is whether or not the “multiple sites” are
significant parts of a delocalized molecular redox orbital (i.e., highest occupied molecular orbital
[HOMO] for oxidations, lowest unoccupied molecular orbital [LUMO] for reductions). Thus, the
intrinsically delocalized molecule bis(fulvalene)dinickel, 2, is treated as a single-site system, but
bis(ferrocenyl)ethane, 3, is treated as a two-site system owing to only weak electronic communica-
tion between the two ferrocenyl redox centers.
Fe
Ni Ni
Fe
2 3
A. INVoLVING a SINGLE REDoX SITE

1. Dominant Electronic and Structural Changes
a. Reduction of [M(η5−C5Me5)(η6−C6Me6)]2+
The net two-electron reduction of the mixed sandwich complexes [MCp*(η6 −C6Me6)]2+, Cp* =
(η5−C5Me5), M = Co, Rh, Ir, provides an example of how intrinsic structural and electronic molecu-
lar properties can play a major role in determining the ΔE1/2 values of an EE system. The following
equation, which defines the E.T.
+ e− + e−
[MCp∗ (η6 − C6 Me6 )]2 +

E (1)
∗ +
[ MCp (η − C6 Me6 )]
m

E (2)
∗
MCp (η − C6 Me6 ) (11.22)
m
1/ 2 1/ 2
series for these Group 9 metals, denotes the hapticity of the hexamethylbenzene (hmb) ring as η6 for
the 18-electron dications (confirmed spectroscopically or crystallographically for all three metals),
but does not specify the hapticity of hmb in the +1 and neutral complexes. In fact, as detailed else-
where [26], the Co complex appears to retain the planar, η6-coordinated, hmb ring throughout the
E.T. series, as does the Rh complex in the first reduction to 4+ [27a]. However, arene bending occurs
in the second E.T. step of the Rh (and most likely, also Ir) complex, with the structural de-hinging
providing an η4-coordinated hmb ring and an electronically more favorable 18 e− structure to neu-
tral 4. The three different metal complexes together offer an informative view of how the intrinsic
molecular properties of a congeneric series of metal complexes may affect an EE E.T. mechanism.
2+ +
+e– +e–
Rh Rh Rh
42+ 4+ 4
Figure 11.6 gives representative CV scans of the three Group 9 complexes, in which different
directions for the shifts of E1/2(1) and E1/2(2) are apparent. In going down from first-row Co to third-
row Ir, the potential of E1/2(2) shifts markedly positive with respect to E1/2(1), reaching inverted
potential behavior for the Ir system, as described by the single two-electron reaction of the following
equation [27]:
+2 e −
[ IrCp∗ (η6 − C6 Me6 )]2 +

E =[ E (1) + E (2) ]/ 2

∗
IrCp (η − C6 Me6 )
6
(11.23)
1/ 2 1/ 2 1/ 2
The negative shift of E1/2(1) is readily ascribed to an intrinsic electronic effect, as it tracks changes
in electron affinities in going from Co to Rh to Ir. The positive shift of E1/2(2), on the other hand,
is ascribed to structural relaxation energies that are considerable owing to the planar-to-bent arene
rearrangement that accompanies only the second reduction of the Rh and Ir complexes [27].
Another example of the effect of planar-to-bent arene structure change in an EE system is that
of the ruthenium sandwich compound [Ru(hmb)2]2+/+/0. Owing to the fact that this system is compli-
cated by slow heterogeneous E.T. kinetics, we will come back to it in Section V.A.4.
b. Reductions of Dinitrobenzenes and Dinitrobutenes

Although the reductions of most dinitrobenzene derivatives exhibit a normal ordering of potentials,
dinitrodurene 5 shows a significant potential inversion (ΔE = −280 mV) [28]. This behavior has been
attributed to a major structural change, which makes the radical anion a better electron acceptor
E1/2(1) E1/2(2)
M ΔE1/2
Co +970 mV
Me6
M2+
Me5
Rh + 200 mV
Ir –310 mV
0 –0.5 –1.0 –1.5

V vs. SCE
FiGURE 11.6 Cyclic voltammograms of [M(η5−C5Me5)(η6 −C6Me6)]2+/+/0, M = Co, Rh, Ir.
than the neutral compound 5 with the oxygen atoms of the nitro groups pointing out of the plane
owing to steric factors. In the dianion, the nitro groups are sp2 hybridized and have to be in the same
plane as the ring. As a consequence, in order to reduce the steric hindrance between the nitro and
the methyl groups, the six-membered ring adopts a distorted boat conformation. Evans et al. showed
that the standard heterogeneous E.T. rate for the second reduction (0.01 cm s−1) was slower than that
of the first (0.20 cm s−1), and accounted for this fact by calculations, which showed that the major
structure change (from twisted to folded) occurred in the second reduction [28].
O O O
O N N
O O
+2e–
N N
O O
5
52–
Another example of the role of structure change in inducing two-electron behavior in dinitro com-
pounds involves the reduction of trans-2,3-dinitro-2-butene (6) (ΔE 0 = −80 mV) [29], Scheme 11.4.
The important structural parameters for the three redox states of 6 are collected in Table 11.3 [1].
Surprisingly, none of the redox states of the dinitrobutene exhibits a fully planar structure. In the
neutral form, even if the dihedral angle between C2C1C1C2 is 174.6°, the two nitro groups are sig-
nificantly tilted out of the plane. In the radical anion, the olefinic bond elongates (Scheme 11.4) and
–
+ O O O
– – +
O–N +e – O N +e
–
O–N
–
N–O N O N–O
+
O O O
+ –
–
6 6– 62–
SchEME 11.4 Reduction of trans-2,3-dinitro-2-butene. (From Evans, D.H. and Hu, K.J., Chem. Soc.,
Faraday Trans., 92, 3983, 1996.)
TABLE 11.3
Relevant Structural Parameters Calculated by DFT Method
for Three Redox States of trans-2,3-Dinitro-2-butene (6)
Dihedral Angle (°) Bond Length (Å)
Species C2C1C1C2 O1NC1C1 C1C1 NC1
Neutral (6) 174.6 129.3 1.34 1.49
Radical anion (6−) 150.5 168.2 1.40 1.41
Dianion (62−) 130.0 169.9 1.46 1.34
Source: Evans, D.H. and Busch, R.W., J. Am. Chem. Soc., 104, 5057, 1982.
θ
LUMO H
H H
H
HOMO
0° 90°
θ
FiGURE 11.7 Qualitative variation of LUMO and HOMO energies of ethylene as a function of the dihedral
angle. (From Evans, D.H. and Busch, R.W., J. Am. Chem. Soc., 104, 5057, 1982. With permission.)
twists, while the nitro groups turn into the plane. Finally, in the dianion, the nitro groups are almost
coplanar with C2C1C1, but the C1C1 bond twists radically and adopts almost single-bond length.
Computations allowed the determination of the difference in the free energy of formation for
6 − and 62−. For the radical-anion 6 −, only a marginal difference in energy is found between a model
where the radical anion adopts the same geometry as the neutral compound and a model that uses
an optimized geometry: ∆∆Gfo ( g ) = 7.6 kcal mol−1. However, for the dianion 62− the difference is
significant: ∆∆Gfo ( g ) = 57.6 kcal mol−1, implying that the major structural reorganization, and ori-
gin of the potential inversion, occurs in the second reduction.
A qualitative understanding of how the distortion of an olefin can affect its reduction potential is
obtained by considering the energy of the frontier orbitals of ethylene as a function of the dihedral
angle of the molecule (Figure 11.7). At dihedral angle of 0°, the ethylene moiety is undistorted and
the two p orbitals overlap well. Increasing the torsional angle to 90° eliminates the orbital overlap
and produces a quasi-degenerate pair. Thus, the energy of the LUMO decreases as the twisting of
the molecule increases, accounting for the greater electron affinity of the more highly twisted isomer.
c. Oxidation of Tetrathiofulvalenes

Another organic example of an inverted potential ordering is found in the oxidation of tetrathiaful-
valene (TTF) derivatives, which may be oxidized to their corresponding dications [30]. Depending
on the length of the linker between the two dithiafulvalene moieties, the oxidation process may be
either a single two-electron process or separate monoelectronic processes. Long chains favor the
(a) (b) (c)
FiGURE 11.8 Optimized geometries calculated at the B3LYP/6–31G* level of the neutral (a), radical anion
(b), dianion (c) of 8. (From Bellec, N. et al., J. Phys. Chem. A, 104, 9750, 2000. With permission.)
former while short chains favor the latter. Intuitively, the repulsion between the two electrogen-
erated positive charges is less significant when a long linker is used, a point we will return to in
Section V.B. However, in the phenyl-substituted TTF derivative 7, a single 2e − wave is observed in
certain media [31]. Thus, whereas acetonitrile favors the 2e− process, a less polar and more donating
solvent such as dichloromethane favors two independent 1e− transfers. X-ray crystallography, spec-
troelectrochemistry, and molecular modeling allow an understanding of this system as one in which
dominant structure change accompanies the first redox process (as discussed in Section II.F.2.B).
Me S
S SMe
MeS S
S Me
As seen in Figure 11.8, both 7− and 72− adopt a conformation where the TTF cores are almost
planar, in contrast to the neutral form 7, in which they are twisted. Calculations delineate the cause
of the potential inversion by showing why the radical-anion 7− is a much better electron donor than
the neutral compound 7: the energy of the singly occupied molecular orbital of the radical anion is
actually raised by the structural changes and as a result, the second reduction becomes easier than
the first [31].
d. Reduction of a Carbene-CS2 Adduct
As with TTF, a potential compression or even a potential inversion may be observed in the reduction of
some N,N′-dialkyl-4,5-dimethylimidazolium-2-dithiocarboxylates (8) (Figure 11.9) [32]. Increasing
the bulkiness of the alkyl R substituents on the nitrogens of the carbene moiety, 8, decreases
the separation between the potentials of the first and the second reduction (ΔER=Me = 170 mV,
ΔER=Et = 130 mV).
In an extreme case, when R = isopropyl, a potential inversion is observed (ΔER=iPr = −30 mV). In
this case also, X-ray and NMR data show that a major structural change occurs in the first reduction.
Models for the structural changes occurring during the redox processes are depicted in Scheme
11.5. In neutral 8, the dithiolate group is perpendicular to the imidazolium ring. However, during the
first reduction, the dithiolate moiety is partially tilted, approaching the imidazolium plane. Finally,
reduction to the dianion 82−, which can exist either in triplet state (Scheme 11.5 upper pathway) or
a singlet state, results in the formation of an exomethylene moiety (Scheme 11.5 lower pathway).
Based on computational studies, the formation of the exocyclic double bond is thermodynamically
more favorable than the formation of a biradical. Thus, the formation of the dianion most likely fol-
lows a singlet-state pathway [32].
5
IV
III
Current, i (μA)
0
–5 I
II
–2.75 –2.5 –2.25

(a)
IV
III
Current, i (μA)
–5 II
–2.75 –2.5 –2.25

(b)
II
Current, i (μA)
–5
I
–2.7 –2.6 –2.5 –2.4 –2.3 –2.2 –2.1

(c)
FiGURE 11.9 Cyclic voltammograms at 50 mV s−1 with 0.24 mM 8: (a) R = Me, (b) R = Et, (c) R = iPr
in THF/0.2 [NBu4][PF6] at a GC electrode: circles, experiment data; lines, digital simulation; potentials in
V vs. Fc/Fc+. (From Dümmling, S. et al., Acta Chem. Scand., 53, 876, 1999. With permission.)
R
N S
N S
R
8
2. Combined Structural and Medium Effects

a. Reduction of [M2Mo(η5−C5Me5)2(S2C6H4)2(CO)2] (M = Co, Rh)
The cobalt and rhodium Mo–bridged bimetallic compound 9 exhibits two-electron reductive behavior
in which both structure change and medium effects are involved in determining the ordering of the
ΔE1/2 values [33]. As indicated in the calculation-based structures of Scheme 11.6, the two semibridging
–
S
S –
–
+e – 82–
–e
–
S S
1 +e–
5 2 –
4 3 –e–
S S –
+e –
–e –
8 – R
8
–
N S
N S –
R
82–
SchEME 11.5 Structural changes during stepwise two-electron oxidation of the carbene-CS2 adduct. (From
Dümmling, S. et al., Acta Chem. Scand., 53, 876, 1999. With permission.)
Mo
Co
S S S S +2e
– S S S S
Mo0
Co Mo0 Co –
Co Co
–2e S
CC +C C + Co
X X
OO C
OO
O Na
9,Co 9,Co2–.2Na+ C
H
Two semibridging Two bridging COs
COs
(a) (b)
+
X : Bu4N+, Na+@18–crown–6
S S S S 2–
0 S S SS
S S S S +e– Co Mo Co +e– Mo0
Co Co
Co Mo0 Co C C
–e– –e– C C
CC O O
OO
OO +
+
X +
X X
9,Co 9,Co– 9,Co2–

Two semibridging One semibridging CO Two bridging COs
COs One bridging CO
(c)
SchEME 11.6 (a) Schematic diagram of the CO group coordination mode transition between 9,Co and
9,Co2− upon one-step 2e− redox reaction. (b) Optimized structure of 9,Co2−·2Na+ (triplet state) (C2 symmetry)
in the CPK model. (c) Schematic diagram of the CO group coordination mode transitions between 9,Co, 9,Co−,
and 9,Co2− upon two-step 1e− redox reactions. (From Muratsugu, S. et al., Chem. Sci., 2, 1960, 2011. With
permission.)
S S S S
M Mo M
CC
OO
M = Co
9
M = Rh
E 20' E 10'
ΔEp ΔEpa
4
Current (μA) Current (μA) Current (μA) Current (μA) Current (μA)
Current (μA)
0 ΔE 0' 0
–4 ΔE 0' = 282 mV –5
(a)
4 –10
(f ) ΔEpc ΔEp = 38 mV
0 5
Current (μA)
0
–4 ΔE 0' = 221 mV
(b) –5
4
–10 ΔEp = 88 mV
0 (g)
ΔE 0' = 110 mV 5
–4
Current (μA)
(c) 0
–8
4 –5
0 –10
–4 (h) –15 ΔEp = 106 mV
(d) –8 ΔE 0' = –10 mV
0
Current (μA)
10
5
0 –5
–5
–10 ΔE 0' = 195 mV –10 ΔEp = 304 mV
(e) –15 (i)
–2400 –2000 –1600 –1200 –800 –2400 –2000 –1600 –1200
Potential (mV vs. Fc+/Fc) Potential (mV vs. Fc+/Fc)
FiGURE 11.10 Cyclic voltammograms of (a) 9,Co, in 0.1 M [NBu4][ClO4]/MeCN/toluene (1 : 1 v/v) at 253
K; (b) 9,Co, in 0.1 M [NBu4][ClO4]/THF at 258 K; (c) 9,Co, in 0.1 M [Na][BPh4]/MeCN/toluene (1 : 1 v/v) at
258 K; (d) 9,Co, in 0.1 M [Na][BPh4]/THF at 258 K; (e) 9,Co, in 0.1 M 18-crown-6/[Na][BPh4]/THF at 298
K; (f) 9, Rh in 0.1 M [Bu4][NClO4]–MeCN/toluene (1 : 1 v/v) at 253 K; (g) 9, Rh in 0.1M [Bu4N][ClO4]–THF
at 258 K; (h) 9, Rh in 0.1M Na[BPh4]–MeCN/toluene (1 : 1 v/v) at 258 K; (i) 9, Rh in 0.1 M Na[BPh4]–THF at
258 K. (From Muratsugu, S. et al., Chem. Sci., 2, 1960, 2011. With permission.)
CO ligands of the neutral complex become traditional bridging carbonyls in the dianion. Whereas only
one two-electron wave is seen under all conditions for the Rh complex, the Co complex may go from
normal to inverted ordering if the medium is tuned. When the medium discourages ion pairing of the
product anions with electrolyte cations (Figure 11.10, scans (a) and (b)), well-resolved one-electron
processes are observed with ΔE1/2 values of 200 mV or more. This changes when sodium ions are
introduced as the cation of the supporting electrolyte, Na[B(C6H5)4]. Ion-pairing stabilization of the
dianion in tetrahydrofuran (THF) gave an inverted EE system (Figure 11.10, scan (d)), and the indi-
vidual one-electron waves returned when 18-crown-6 was present, reducing the ion-pairing strength of
Na+ (scan e). The reader is referred to the original article for discussion of the Rh analogue [33].
b. 1,1,1-(CO)3-2-Ph-closo-1,2,3,4-MnC3B7H9 (10)

A case study of the joint effects of structure change and manipulations of the
medium is found in the EE reduction of the tricarbadecaboranyl manganese compound
1,1,1-(CO)3-2-Ph-closo-1,2,3,4-MnC3B7H9, 10 [34], for which structures of all three components of

the E.T. sequence of Equation 11.24 are known. X-ray crystallography showed
+ e− − 2− + e−

10 10 10 (11.24)
E (1) E (2)
1/ 2 1/ 2
O
O C O
C C
Mn
Ph
C C
C
10
that the carborane ligand is η6-coordinated to the metal center in the neutral compound but
η4-coordinated in both the monoanion and dianion. Taking into account other ligand rearrangements,
the structural changes in this series were viewed as gradual in going from 10 to 10− and finally 102−
[34]. One might therefore expect roughly equivalent structural relaxation energies in the two E.T.
processes, so that 10 would not fit into either of the two extremes treated in Section 2.F., which con-
sidered EE reactions having one dominant structure change. In such a case, explaining and manipu-
lating the ΔE1/2 of the system comes down almost exclusively to effects of the electrolyte medium.
Figure 11.11 reproduces some of the medium effects observed for this system. Beginning with scan
(d), two separate 1e− processes are observed when the solvent is strongly donating (here, THF, [donor
ipc ipc
ipa ipa
3 μA 3 μA
0 –0.5 –1 –1.5 –2 0 –0.5 –1 –1.5 –2

(a) E (V) vs. Fc (b) E (V) vs. Fc
ipc
ipc
ipa 1 μA
ipa 1.5 μA
0 –0.5 –1 –1.5 –2 0 –0.5 –1 –1.5 –2

E (V) vs. Fc E (V) vs. Fc
(c) (d)
FiGURE 11.11 CV scans (0.1 V s−1) of 10 in different media: (a) CH2Cl2/[NEt4][B(C6H3(CF3)2)4], (b) CH2Cl2/
[NBu4][B(C6F5)4], (c) CH3CN/[NBu4][B(C6F5)4], (d) THF/[NBu4][B(C6F5)4]. (From Nafady, A. et al.,
Organometallics, 26, 4471, 2007. With permission.)
number, DN, = 20]) and the supporting electrolyte cation is weakly ion pairing (here, [NBu4]+). Both
of these properties weaken the interaction with the dianion (relative to the monoanion), thermody-
namically disfavoring the formation of the dianion and pushing E1/2(2) negative compared to E1/2(1).
The ΔE1/2 value, which is 300 mV under these conditions, can be lowered by employing less donat-
ing solvents or more strongly ion-pairing electrolyte cations. Examples of the former are acetonitrile
(DN = 14.1) [scan (c), ΔE1/2 = 110 mV] and dichloromethane (DN = 0) [scan (b), ΔE1/2 = 75 mV].
Replacing [NBu4]+ by [NEt4]+ in dichloromethane further lowers the ΔE1/2 value to 35 mV, and the CV
scan (a) begins to take on the look of a single two-electron process.
Medium-dependent tuning of ΔE1/2 in order to switch from a two-electron process to a
one-electron process is of value from both electrochemical and synthetic viewpoints. The fact
that, in the present case, the disproportionation constant for the monoanion 10 − goes from
Kdisp = 8.3 × 10 −6 in THF/[NBu4][PF6] to Kdisp = 0.26 in CH 2Cl 2/[NBu4][B(C6F 3(CF 3)2) 4] aided
design of the medium conditions that would facilitate preferential generation (and, ultimately,
isolation) of either the monoanion 10 − or the dianion 10 2−. Thus, chemical reduction of 10
by Co(η5 −C5Me5)2 , when carried out in low-donor, low-polarity solvents (dichloromethane or
toluene) gave the pure dianion 10 2−, whereas the same reducing agent in THF cleanly gave the
monoanion 10 − [34].
3. Dominant Medium Effects

The practice of inducing changes in the ΔE1/2 values of two-electron systems by alterations of
solvent and/or supporting electrolyte is widespread in electrochemical applications. The effects of
altering the alkyl chain length in tetraalkylammonium ions or employing smaller, more strongly ion
pairing, cations such as alkali metals has a long history in the study of anion-based electrochem-
istry [35]. However, an equivalent breadth of ion-pairing options for supporting electrolyte anions
was only more recently made available with the introduction of weakly coordinating anion (WCA)
based electrolytes, predominantly employing either [B(C6H3(CF3))4]− (11, BArF24) or [B(C6F5)4]−
(12, TFAB) [36]. Pertinent to the present subject is the influence of WCAs on the ΔE1/2 values of
EE reactions involving cationic products. Owing to the fact that ion-pairing interactions of any
electrolyte anion increase with increasingly positively charged electrode products, altering the ion
pairing has a larger effect on the second oxidation than the first. The scale of possible ΔE1/2 changes
was first demonstrated in the groundbreaking work of Mann et al. [36a], who determined that the
Kdisp value for a trication of a dirhodium complex fell by a factor of over 107 in going from [PF6]− to
[B(C6H3(CF3)2)4]− in CH2Cl2, corresponding to an effective increase in ΔE1/2 of over 400 mV.
F
F F
F 3C CF3
F F
F3C CF3 F F F F
B– F B– F
F 3C CF3 F F F F
F F
F3 C CF3
11 F F
F
12
a. Oxidation of Bis(fulvalene)dinickel (2)

A more comprehensive study of the effects of both solvent and supporting electrolyte anion
on anodic ΔE1/2 values was carried out on the electronically well-understood [37], single-site
E1/2(1)
E1/2(2)
[Bu4N][Cl
[Bu4N][PF6]
[Bu4N][B(C6F5)4]
0.4 0 –0.4 –0.8

V vs. Fc+/Fc
FiGURE 11.12 CV scans at 0.1 V s−1 of bis(fulvalene)dinickel 2 in CH2Cl2, 0.1 M [NBu4]Cl, [NBu4][PF6], or
[NBu4][B(C6F5)4]. (From Barrière, F. and Geiger, W.E., J. Am. Chem. Soc., 128, 3980, 2006. With permission.)
complex bis(fulvalene)dinickel, 2 [38]. As delineated in Equation 11.12, changes in ΔE1/2 may

arise from changes in both the solvation and ion-pairing characteristics of the medium. In a
selection of 45 combinations of nonaqueous solvents and supporting electrolytes [38], the ΔE1/2
values for the sequence 2/2 +/2 2+ were shown to go from a low of 212 mV (in anisole/[NBu4]
Cl) to a high of 850 mV (in CH 2Cl 2 /Na[B(C6H 3(CF 3)2) 4]), an impressive change of 638 mV (or
14.6 kcal mol−1) in destabilization of the dication compared to the monocation. Figure 11.12
shows the effect of changing only the electrolyte anion in the medium. The dramatic increase
in ΔE1/2 while going from Cl−, to [PF6]−, to [B(C6F5) 4]− (480 mV, Table 11.4) is ascribed to the
weaker ion-pairing energies of the progressively larger, more charge-delocalized, electrolyte
anions. It was noted that the traditional electrolyte anions ([PF6]−, [BF4]−, [ClO 4]−), often con-
sidered to be ion-pairing “innocent,” actually fall midway between halides and WCAs in ion-
pairing strength. These concepts have been reviewed [36(b)].
The ion-pairing effects that play a dominant role in the potential shifts in CH 2Cl 2 (ε = 8.9)
are still present in THF (ε = 7.5), but the ΔE1/2 shifts are less (361 mV for the same three
anions; see Table 11.4). This is readily explained by noting the increased donor strength of
THF, which enhances the solvation effects compared to dichloromethane, thus facilitating
the second oxidation process. Another informative set of measurements involved DMSO,
in which there is very little change in ΔE1/2 with alterations of the electrolyte anion (only
56 mV for the three anions). In this case, the ion-pairing effects are minimized owing to the
TABLE 11.4
Changes in ΔE1/2 Values for the Successive One-Electron Oxidations of 2
in Different Solvents
Solvent Solvation Ion Pairing ΔΔE1/2 (mV) ΔKdisp
Dichloromethane Weak Strong 480 1.3 × 108
Tetrahydrofuran Strong Strong 361 1.3 × 106
Dimethylsulfoxide Strong Weak 56 8.9
Source: Data taken from Barrière, F. and Geiger, W.E., J. Am. Chem. Soc., 128, 3980, 2006.
In each case, the spread of ΔE1/2 for electrolytes containing Cl−, [PF6]−, and [B(C6F5)4]− is given as ΔΔE1/2.
1000
Na BArF24
TBA TFAB
800
TBA BArF24
TBA BPh4
600
ΔE½ (mV)
TBA PF6
TBA ClO4
400
TBA triflate
TBA BF4
200
TBA Br
TBA Cl
0
CH2Cl2 THF DMSO
FiGURE 11.13 Schematic representation of the available tuning window of ΔE1/2 values for complex 2 as a
function of the supporting salt in dichloromethane, tetrahydrofuran, and dimethylformamide. (Reprinted from
Barrière, F. and Geiger, W.E., J. Am. Chem. Soc., 128, 3980, 2006. With permission. Consult this reference
for exact ΔE1/2 values.)
high dielectric constant of DMSO (ε = 47.2). Figure 11.13 is a pictorial representation of the
influence of solvent on the ΔE1/2 values in solutions of different anions. Remarkably, the
anion-based differences in Κdisp, which are 1.3 × 10 8 in CH 2Cl 2 , fall by over seven orders of
magnitude in DMSO.
4. Effect of Slow E.T. Kinetics: Reduction of Bis(hexamethylbenzene)ruthenium2+

As discussed in Section III and exemplified by the reduction of cyclooctatetraene (Section
II.F.3), two-electron processes having inverted or compressed ΔE1/2 values frequently display
at least one slow E.T. reaction owing to redox-induced structural changes. An organometallic
example is the reduction of the bis(hexamethy1benzene)ruthenium dication, [(η 6 −C6Me 6)2Ru]2+,
13 2+, which has the idealized structures shown below as it is reduced first to 13 + and then to
13 [39]. The defining structural feature is the bending of the η 6 -coordinated arene ring of the
monocation into the η4 -coordinated structure of the neutral complex. This structural rear-
rangement provides the relaxation energy to compress the ΔE1/2 value and also is the origin of
the increased inner-sphere reorganization energy required for the second E.T. The combina-
tion of structural changes and inherent electronic effects [40] leads to slow heterogeneous E.T.
kinetics for the 13 +/13 couple. Thus, the η 6/η4 structure change eases the thermodynamics but
impedes the kinetics of formation of 13.
2+ +
+e– +e–
Ru Ru Ru
132+ 13+ 13
In dichloromethane, the two one-electron processes are thermodynamically resolved (ΔE1/2 ≈

0.14 V) in slow to medium sweep rate CV scans (Figure 11.14), which also give evidence of the slow
second charge-transfer step. The stronger solvation of cations by acetonitrile lowers ΔE1/2 to the
inverted value of −0.03V and changes the CV scan dramatically, giving a single two-electron wave.
At high sweep rates, however, the electrochemically irreversible second wave partitions from the
first wave (Figure 11.15), giving a rare example of “kinetic differentiation” of the two E.T. reactions
of an EE process [39].
B. INVoLVING Two IDENTICaL REDoX SITES

A special and important case of EE processes is that involving one-electron transfer of molecularly
linked single redox sites. The structures shown below are readily recognized as precursors to mixed-
valent systems that would be obtained by one-electron reduction of 14 or by one-electron oxidation
of 15 or 16. These and a wide variety of loosely related compounds, all of which are inherently two-
electron systems, have been intensely studied since the original reports on the formally mixed-valent
species [Ru2(NH3)10(μ-pyrazine)]5+ (the “Creutz/Taube Ion”) [41] and [biferrocene][ClO4], 15+ [42].
The spectroscopic and chemical behaviors of these molecules are tied closely to the degree of elec-
tronic communication between the redox centers, as reviewed elsewhere [43].
6+
Fe
(H3N)5Ru N N Ru(NH3)5 N N
14 Fe
16
15
1. Electronic Communication through the Linkage

Our discussion of the ΔE1/2 values of this family, modeled as 17 in Scheme 11.7, is conceptually
simpler than the single-site redox case owing to the rarity of significant structural relaxation in
the E.T. processes. This allows the emphasis to be on electronic and medium effects alone. In
terms of electronic effects, a purely electrostatic model would suggest that the differences in
ΔE1/2 values for the two redox sites will decrease as the length of the linker increases and as its
ability to transmit charge, either through bonds or through space, decreases. (Note: Even if the
site-to-site electronic interaction is completely eliminated, E1/2(1) and E1/2(2) will differ owing
to a statistical effect, with ΔE1/2 = (RT/F) ln 2 (= 35 mV at 298 K) [16].) Until fairly recently,
ΔE1/2 values greater than about 400 mV were taken to indicate that the two E.T. sites were
sufficiently strongly interacting that the mixed-valent intermediate could be characterized as
having a delocalized electronic structure (delocalized 17+ in Scheme 11.7). More sophisticated
(a)
(d)
5×i
(b)
(e)
(c) (f )
–0.5 –1.0 –1.5 V vs. Fc –0.5 –1.0 –1.5 V vs. Fc
FiGURE 11.14 0.5 mM [132+][BF4] in dichloromethane: (a) 0.1, (b) 0.2, (c) 0.5, (d) 1.0, (e) 2.0, and (f) 5.0 V s−1.
(From Pierce, D.T. and Geiger, W.E., J. Am. Chem. Soc., 114, 6063, 1992. With permission.)
analyses now treat the ΔE1/2 value simply as one part of the body of physical and spectroscopic
information about the degree of site-to-site interactions in the compounds [43]. Unquestionably,
however, ΔE1/2 values play an important part in defining the analytical and synthetic proper-
ties of these systems owing to radical disproportionation effects, as discussed in Section II.
Here, we consider two factors that may often be manipulated to achieve desired ΔE1/2 values
for two-site redox systems: the length of the molecular linker (or bridge) and the makeup of the
electrolyte medium.
(a) (d)
20×i
(b) (e)
(c) (f )
–0.5 –1.0 –1.5 V vs. Fc –0.5 –1.0 –1.5V vs. Fc
FiGURE 11.15 1 mM [132+][BF4] in CH3CN: (a) 0.1, (b) 0.2, (c) 0.5, (d) 1.0, (e) 2.0, and (f) 5.0 V s−1. (From
Pierce, D.T. and Geiger, W.E., J. Am. Chem. Soc., 114, 6063, 1992. With permission.)
1+
d LM 0.5+ 0.5+ ML
lize
el oca 2+
D
–e– –e–
LM ML LM 1+ 1+ ML
–e– 1+ –e–
17 Lo 172+
cal
ize LM 1+ 0 ML
d
SchEME 11.7 Delocalized and localized charges in mixed-valent members of two-electron process.
A glance at structures 14–16 suggests the broad structural variability that has, in fact, been
utilized in molecular linkers. For an example of how the structure of the linker might affect ΔE1/2
values, consider the differences between biferrocene (15) and structures in which the two fer-
rocenyl moieties are connected by either sp3- or sp-carbon-based linkages. In going from 15 to
bis(ferrocenyl)acetylene (18) and then to bis(ferrocenyl)ethane (3), the ΔE1/2 values measured in tra-
ditional electrolyte solutions decrease progressively from 330 [44] to 130 mV [42] to approximately
40 mV [45], in concert with the decreasing electronic communication expected with the changes in
the bridge between the cyclopentadienyl ligands. Although these systems retain normal potential
ordering with positive ΔE1/2 values, the dramatically higher values of Kdisp for 18+ and 3+ mean that
nominally pure solutions of these radical cations will contain significant amounts of their neutral
and dicationic E.T. partners, of particular importance in characterizing the chemical and physical
properties of these mixed-valent species [43]. Inverted potential ordering is not normally observed
for these types of systems, unless the linker itself undergoes E.T.-induced structural changes.
Fe
Fe
18
It is interesting to contrast the aforementioned case with one in which the carbon-based linkages
are bonded directly to the metal centers of the terminal redox centers, rather than to the Cp rings.
Here, we note the results of two related studies in which the lengths of alkynyl linkages directly
connected to the metal of a half-sandwich redox center have been systematically altered. With either
rhenium-based or iron-based redox centers (structures 19 and 20, respectively), large positive ΔE1/2
values are observed even when the alkynyl linker is eight carbons long, indicative of strong elec-
tronic communication between the metal centers (Scheme 11.8) [46,47].
The electrochemistry of these EE systems is relatively straightforward owing to their large poten-
tial spacings. We will now turn attention to systems with smaller potential spacings, and the ways
in which the electrolyte medium can be manipulated to achieve chemically desired ΔE1/2 values.
2. Medium Effects
a. Multi(ferrocenyl) Complexes
Given the positive charge of the electrode products, ΔE1/2 values for the oxidation of multi(ferrocenyl)
complexes can be expected to be quite sensitive to the ion-pairing strength of the electrolyte anion.
Indeed, replacing a traditional anion such as [PF6]−, [BF4]−, or [ClO4]− with the WCA [B(C6F5)4]−
increases the ΔE1/2 value significantly, often by hundreds of mV for bis(ferrocenyl) complexes
Me5 Me5 Me5 Me5
Re C C Re Fe C C Fe
n n
PPh3 NO PPh3 P P
NO P P
19 20
Compound n ΔE1/2 (V)

19 2 0.53
20 2 0.70
19 4 0.38
20 4 0.53
19 6 0.28
20 6 0.43
SchEME 11.8 ∆E1/2 values for successive one-electron oxidations of alkynyl-linked organometallic redox
centers, data taken from Reference 46 (compound 19) and Reference 47 (compound 20), for which P—P rep-
resents bis(diphenylphosphino)ethane.
TABLE 11.5
Representative Supporting Electrolyte Anion Effects on Differences in ΔE1/2
Values for Bis(ferrocenyl) Compounds
Compound ΔE1/2 with Traditional Anion (mV) ΔE1/2 with [B(C6F5)4]− (mV)
Bis(fulvalene)diiron 590 970
Biferrocene, 15 330 530
Bis(ferrocenyl)ethane, 3 ≈40 180
“Traditional anion” refers to [PF6]−, [BF4]−, or [ClO4]−, with the solvent being either dichloromethane,
acetonitrile, or mixed dichloromethane/acetonitrile. With [B(C6F5)4]–, the solvent was dichloromethane.
See Reference 48 for details and original literature references.
(see Table 11.5) [48]. The medium-dependent sensitivity of ΔE1/2 values has been noted as a factor
to be cautiously considered when evaluating potentially mixed-valent systems [38,49,50]. Let us
use the general principles developed in this chapter to consider a potentially three-electron system
terferrocene, 22.
Fe
Fe Fe
22
b. Oxidation of Terferrocene, 22

Owing to the fact that the three ferrocenyl moieties in 22 are electronically coupled, three succes-
sive one-electron oxidations are observed for the four-member EEE E.T. series 22/22+/222+/223+.
Figure 11.16 gives representative examples of how alterations in the medium affect the voltammetry
of this system. A key change is that shown on the right side of the figure, where dichloromethane
is the solvent and the electrolyte anion is either [PF6]− (c) or [B(C6F5)4]− (d), the overall ΔE1/2 for all
three oxidations being altered by about 500 mV [48].
c. Fulvalene Dirhodium Complex 23

A final example taken from the chemistry of identical redox sites is that of the anodic EE system
of (fulvalendiyl)bis(cyclooctadiene)dirhodium, 23. In this case, changes in the medium enabled fine
tuning between compressed and inverted ΔE1/2 values [51].
Rh
Rh
23
1×10–5
I (A)
0
–1×10–5
(a) (c)
1×10–5 1×10–5
0 0
I (A)
I (A)
–1×10–5 –1×10–5
1.2 0.8 0.4 0 –0.4 1.2 0.8 0.4 0 –0.4

(b) E (V vs. Fc/Fc+) (d) E (V vs. Fc/Fc+)
FiGURE 11.16 CV scans at 0.2 V s−1 for terferrocene (22) in different nonaqueous solutions: (a) reproduc-
tion of scan from Brown, G.M. et al., Inorg. Chem. 14, 506, 1975, in 1:1 CH3CN:CH2Cl2/0.1 M [NBu4][PF6];
(b) 0.4 mM 22 in CH3CN/0.1 M [NBu4][PF6]; (c) 0.4 mM 22 in CH2Cl2/0.1 M [NBu4][PF6]; (d) 0.4 mM 22 in
CH2Cl2/0.1 M [NBu4][B(C6F5)4]. (From Camire, N. et al., J. Organometal. Chem., 637–639, 823, 2001. With
permission.)
Consider the SWVs of Figure 11.17, which begin with the maximum separation (ΔE1/2 = 280 mV)
in dichloromethane/[NBu4][B(C6H3(CF3)2) 4], scan (a). From there, addition of the [PF6]− anion [scan
(b)], and then increasing amounts of the donor solvent 1,2-dimethoxyethane [scans (d) through (f)],
all shift E1/2(2) negative with respect to E1/2(1), collapsing the voltammetric curves into the picture
of an apparent single two-electron process. In the limit of pure glyme/[NBu4][PF6], an inverted
potential ordering exists with ΔE1/2 = −50 mV [51].
VI. AN INTEGRATED APPROAch TO MEDiUM EffEcTS ON ΔE1/2
Fe Fe
S S
Ni
S S
Fe Fe
24
Our broad discussion of extrinsic effects on ΔE1/2 values aids our understanding of the voltammet-
ric behavior of a molecule having both multistep reductions and multistep oxidations, beginning
from a neutral complex. Tetrakis(ferrocenyl)nickel dithiolene (24) has two reversible one-electron
reductions located primarily on the nickel dithiolene center and four reversible one-electron oxida-
tions located at the modestly interacting ferrocenyl moieties [38]. Systematic manipulation of the
0.5 μA/M 0.5 μA/M
0.4 0.2 0 –0.2 –0.4 –0.6 0.1 0 –0.1 –0.2 –0.3 –0.4 –0.5
(a) E (V) vs. Fc (b) E (V) vs. Fc
0.5 μA/M 0.6 μA/M
0.1 0 –0.1 –0.2 –0.3 –0.4 –0.5 0.1 0 –0.1 –0.2 –0.3 –0.4 –0.5
(c) E (V) vs. Fc (d) E (V) vs. Fc
0.7 μA/M 1 μA/M
0 –0.1 –0.2 –0.3 –0.4 –0.5 0 –0.1 –0.2 –0.3 –0.4 –0.5
(e) E (V) vs. Fc (f ) E (V) vs. Fc
FiGURE 11.17 Square-wave voltammograms (frequency 10 Hz, pulse height 25 mV) of 0.6 mM 23 at
1 mm GC disk in (a) CH2Cl2/0.1 M [NBu4][TFAB], (b) CH2Cl2/0.1 M [NBu4][TFAB] + 250 equiv of [NBu4]
[PF6], (c) solvent mixture CH2Cl2/glyme (90: 10% v/v) + 0.1 M [NBu4][TFAB] and 250 equiv of [NBu4][PF6],
(d) CH2Cl2/glyme (80%:20% v/v) + 0.1 M [NBu4][TFAB] and 250 equiv of [NBu4][PF6], (e) CH2Cl2/glyme
(60%:40% v/v) + 0.1 M [NBu4][TFAB] and 250 equiv of [NBu4][PF6], (f) CH2Cl2/glyme (50%:50% v/v) +
0.1 M [NBu4][TFAB] and 250 equiv of [NBu4][PF6]. Glyme = 1,2-dimethoxyethane. (From Nafady, N. et al.,
Organometallics, 25, 1654, 2006. With permission.)
[Bu4N][PF6]
V vs. Fc+/Fc
1 0.5 0 –0.5 –1 –1.5 –2
Na[B(C6H3(CF3)2)4]
FiGURE 11.18 CV scans at 0.1 V s−1 of tetraferrocenyl(nickel dithiolene) (24) in CH2Cl2, 0.1 M [Bu4N][PF6]
and 0.02 M Na[B{C6H3(CF3)2}4] over the full potential range (oxidation and reduction). (From Barrière, F. and
Geiger, W.E., J. Am. Chem. Soc., 128, 3980, 2006. With permission.)
solvent/supporting electrolyte medium allows either the maximizing or minimizing of ΔE1/2 values
for both reductions and oxidations of 24. In terms of solvent effects, strong donor solvents (e.g.,
ethers) favor increased separation of cathodic ΔE1/2 values but compression of anodic ΔE1/2 values,
whereas the opposite effect accrues for weak donor/strong acceptor solvents such as halocarbons.
Ion-pairing interactions between the redox products and the supporting electrolyte ions also play
an important role in tuning the ΔE1/2 values, providing that the experiments are carried out in
solvents of modest to low dielectric constant (ε ≈ 10 or less). Examples are given in Figure 11.18.
Although dichloromethane is a favorable solvent for the separation of oxidation processes, the
four anodic waves arising from the E.T. sequence 24/24+/242+/243+/244+ are unresolved in CH2Cl2/
[NBu4][PF6] (upper left in figure) owing to relatively strong ion pairing of the product cations with
[PF6]−. The two cathodic waves arising from 24/24 −/242− are, however, well resolved (ΔE1/2 =
0.78 V, upper right) owing to weak ion-pairing interactions of the product anions with [NBu4]+. The
situation is reversed when the electrolyte salt is Na[B(C6H3(CF3)2]4 owing to the weak ion-pairing
ability of [B(C6H3(CF3)2]4− with 24 n+ and the strong ion pairing of Na+ with 24 n− (lower scans of
Figure 11.18). Interestingly, the reductions go from an obviously separate EE process to a single
two-electron wave with the introduction of a sodium ion-based electrolyte. Weighing the quanti-
tative details of these effects allowed formulation of a set of rules for the medium in increasing
potential separations (i.e., enlarging ΔE1/2 values) of either oxidations or reductions. For product
cations, employ (1) a lower polarity solvent of low donor number, (2) a weakly ion-pairing electro-
lyte anion, and (3) a strongly ion-pairing electrolyte counter cation. For product anions, employ
(1) a lower polarity solvent of low acceptor number, (2) a weakly ion-pairing electrolyte cation, and
(3) a strongly ion-pairing electrolyte counter anion. Given the inverse complementarity of these
effects, the authors proposed a “mirror image” model for the effects of solvent and supporting
electrolyte on ΔE1/2 values of both reductions and oxidations (see Figure 11.19) [38].
Generation Generation
of cations of anions
Intermediate Intermediate
anions in cations in
electrolyte electrolyte
+
for example: PF6
– for example: Me4N
ΔE1/2 Large anion Large cations ΔE1/2

in electrolyte in electrolyte
– +
for example: TFAB for example: Bu4N
Small anions Small cations

in electrolyte in electrolyte
for example: Cl– for example: Na+
0V 0V
Low High High Low
Solvent polarity
Zone for conversion of sequential

one-electron waves
into a single two-electron wave.
FiGURE 11.19 Mirror image model of electrolyte effects on ΔE1/2. (From Barrière, F. and Geiger, W.E.,
J. Am. Chem. Soc., 128, 3980, 2006. With permission.)
AckNOwLEDGMENTS
The authors are grateful to the National Science Foundation for support during the writing of this
chapter.
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12 Electrochemically Driven
Supramolecular Devices
Paola Ceroni, Alberto Credi, and Margherita Venturi
CONTENTS
I. Introduction .......................................................................................................................... 433
II. Electrochemical Analysis of Supramolecular Systems ........................................................ 434
A. Intermolecular Interactions ........................................................................................... 435
B. Molecular Encapsulation of Electroactive Units .......................................................... 435
C. Redox-Controlled Supramolecular Switching .............................................................. 435
D. Electroactive Species on a Solid Support ..................................................................... 436
III. Host–Guest Systems ............................................................................................................. 437
A. Hydrogen-Bonding Interactions .................................................................................... 437
B. Metal Ion Coordination................................................................................................. 438
1. Metal Ion Translocation ......................................................................................... 439
2. Anion Translocation...............................................................................................440
3. Helicate Assembly and Disassembly ..................................................................... 441
C. Hydrophobic Interactions .............................................................................................. 442
D. Charge-Transfer Interactions ........................................................................................444
E. Host-guest Systems Working on Surfaces ....................................................................449
IV. Molecular Machines ............................................................................................................. 450
A. Basic Concepts .............................................................................................................. 450
B. Systems Based on Rotaxanes ........................................................................................ 450
1. Molecular Shuttles ................................................................................................. 451
2. Ring Pirouetting Motion ........................................................................................ 456
C. Systems Based on Catenanes ........................................................................................ 456
D. Molecular Machines Working on Surfaces ..................................................................466
1. Molecular Machines Immobilized on Electrodes..................................................466
2. Solid-State Electronic Circuits ..............................................................................468
3. Electrochemically Induced Shuttling in Single Rotaxane Molecules ................... 471
4. Electrically Driven Directional Motion of a Single Molecular Machine .............. 472
V. Concluding Remarks ............................................................................................................ 473
References ...................................................................................................................................... 474
I. INTRODUcTiON
Supramolecular chemistry, according to its most popular definition, is “the chemistry beyond the
molecule, bearing on organized entities of higher complexity that result from the association of
two or more chemical species held together by intermolecular forces” [1]. The field has devel-
oped at an astonishingly fast rate during the last three decades, and it soon became evident that
a definition strictly based on the nature of the bond that links the components would be limiting.
433
Many scientists, therefore, started to distinguish between what is molecular and what is supramo-
lecular based on the degree of intercomponent interactions [2,3]. In a general sense, one can say
that with supramolecular chemistry, there has been a shift in focus from molecules to molecular
assemblies or multicomponent structures driven by the emerging of new functions.
In the frame of research on supramolecular systems, the idea began to arise in a few labora-
tories [4–6] that the concepts of device and machine could be applied at the molecular level [7].
In other words, molecules might be used as building blocks for the assembly of multicomponent
structures exhibiting novel and complex functions that arise from the cooperation of simpler
functions performed by each component. This strategy, encouraged by a better understanding
of biomolecular devices, has been implemented on a wide variety of chemical systems, lead-
ing to highly interesting results [8]. As a matter of fact, the molecular bottom-up construc-
tion of nanoscale devices and machines has become one of the most stimulating challenges of
nanoscience.
Such achievements have been made possible because of the substantial progresses obtained in
other areas of chemistry and physics—particularly concerning the synthesis and characterization
of complex chemical systems and the study of surfaces and interfaces. In this perspective, electro-
chemistry is a very powerful tool not only for characterizing a supramolecular system but also for
the device operation. Indeed, molecular devices, as their macroscopic counterparts, need energy to
operate and signals to communicate with the operator. Electrochemistry is an interesting answer
to this dual requirement: it can be used to supply the energy needed to make the system work,
and by means of the various electrochemical techniques (e.g., voltammetry), it can also be used
to read the state of the system, controlling and monitoring the operation performed by the device.
Furthermore, electrodes represent one of the best ways to interface molecular-level systems to the
macroscopic world, a feature which is important for future applications. Hence, it is not surprising
that the marriage of electrochemistry and supramolecular chemistry has produced a wealth of very
interesting devices and functions, thereby generating new scientific knowledge and raising expecta-
tions for practical applications in energy conversion, information and communication technologies,
advanced materials, diagnostics, and medicine.
Our aim with this chapter is to provide a picture of the potentialities and applications of electro-
chemical methods for both investigating and operating multicomponent chemical systems. We start
with a brief discussion of the role and potentialities of electrochemistry in the study of supramo-
lecular systems. We then illustrate examples taken from electrochemical research applied to supra-
molecular and nanoscale systems, with particular attention to properties and functions. Although
these examples cover a wide range of topics, we do not even attempt to be comprehensive, and we
apologize from the beginning with the colleagues who may feel that their work has been omitted.
Furthermore, in some cases, the selected examples are dated, but we decided to privilege those char-
acterized by a high educational value. Several books [9–14] and reviews [15–22] are available for
more thorough discussions on the fundamentals of electrochemical methods and their application
to supramolecular systems and materials.
II. ELEcTROchEMicAL ANALYSiS Of SUPRAMOLEcULAR SYSTEMS

The primary task of most electrochemical techniques is the determination of redox potentials, which
are then correlated to intrinsic electronic properties of molecules such as the energy of HOMO and
LUMO levels. Electrochemical measurements give also access to other important quantities: dif-
fusion coefficients, interfacial properties, and thermodynamic and kinetic constants of reactions
coupled with the redox process. The knowledge of these parameters is extremely useful for under-
standing the behavior of many kinds of supramolecular assemblies. In this section, we discuss a few
important issues related to the role and potentialities of electrochemistry for the study of multicom-
ponent molecular systems.
Electrochemically Driven Supramolecular Devices 435
A. INTErMoLECULar INTEraCTIoNS
The intermolecular forces that are at the basis of supramolecular chemistry, encompassing dipole–
dipole, ion–dipole, ion–ion, hydrogen bonding, π–π, and cation–π interactions, are largely electro-
static in character. Solvophobic (hydrophobic) and van der Waals effects can also be significant in
self-assembly processes, especially those responsible for the formation of monolayers.
First of all, one should be aware that the conditions usually required for electrochemical experi-
ments (solvents with reasonably high dielectric constants, large concentration of supporting elec-
trolyte) can significantly affect the extent of the intermolecular interactions. Moreover, the redox
potential measured for a given species may differ from the true value due to interactions with the
ions of the supporting electrolyte.
Second, given the nature of the forces that govern supramolecular phenomena, a change in the
oxidation state of an electroactive species can greatly influence its propensity to interact with other
molecular components. Because of such an interplay, redox potential values can give valuable infor-
mation on intermolecular interaction energies.
On the other hand, electrochemically driven changes of the oxidation state of molecular compo-
nents can be used to direct and control their supramolecular interactions. The dual utility of electro-
chemistry as a detector and as an effector tool for supramolecular systems will emerge clearly from
the examples discussed in the next sections.
B. MoLECULar ENCapSULaTIoN oF ELECTroaCTIVE UNITS

The general meaning of molecular encapsulation is the placement of a molecule inside a much larger
one. Encapsulation can be obtained by taking advantage of supramolecular interactions: if the smaller
component (referred to as the guest) is held inside the larger one (the host) for an experimentally sig-
nificant period of time, one can say that the host encapsulates the guest. Another approach to molecu-
lar encapsulation is to covalently attach large substituents (usually, polymeric structures or dendritic
branches) to the species of interest. In both cases, encapsulation may result in site isolation of the mol-
ecule, that is, the segregation or protection from the solvent and other species present in the medium.
The encapsulation of redox-active species can have a profound influence on their electrochemical
properties [17,21,23]. In general, both the thermodynamic (i.e., the redox potential values) and the
kinetic (i.e., the heterogeneous rate constants) aspects of the electron transfer process involving the
encapsulated species will be different from those characteristic of the free form. Another distinc-
tive feature of molecular encapsulation that can be evidenced by electrochemical techniques is the
decrease of the apparent diffusion coefficient of the redox-active species when it is surrounded by a
large molecular load. Moreover, in the case of noncovalent encapsulation, the dynamic nature of the
self-assembly equilibria is important in determining the electrochemical response of the system, as
the electron transfer can potentially involve both the encapsulated and free guest.
C. REDoX-CoNTroLLED SUpraMoLECULar SwITCHING

The oxidized and reduced states of an electrochemically switchable guest (or host) molecule gen-
erally exhibit a different degree of affinity for a host (or guest). Hence, the oxidation state of the
redox-active species influences the thermodynamic stability of its complex with the other molecular
component, and an electrochemically induced change in the oxidation state will cause a supramo-
lecular switching event. When the binding interaction is sufficiently strong, the electrochemical
behavior may clearly reflect the presence of two redox couples; in other words, the bound and free
species may exhibit different redox potentials.
In order for the switching to be effective, the redox-controlled species should exhibit fast electron-
transfer kinetics. Without reversible kinetics, the switching would become too slow to be useful. A sec-
ond requirement is that at least one of the redox states must interact strongly with the molecular partner.
KH∙G
G + H H∙G
+e– +e–
–e– E °'
f –e– E c°'
KH∙G–
G– + H H ∙ G–
FiGURE 12.1 Square scheme mechanism describing an electrochemically switchable host–guest system.
Horizontal and vertical processes are the chemical equilibria and the electron transfer processes, respectively.
It is easy to show that these two conditions are fulfilled for any redox-switchable system, from recep-
tor–ion complexes to molecular shuttles.
An electrochemically switchable system is usually described with a thermodynamic square
scheme (Figure 12.1) that represents two electron transfer processes coupled with two homoge-
neous chemical equilibria (electron transfer, chemical reaction, electron transfer, chemical reaction;
ECEC mechanism).
We can assume, for example, that the guest G is electroactive and its binding with the host H is
switched from low to high upon reduction. Therefore, the stability constant KH·G− is larger than KH·G;
the ratio KH·G−/KH·G is defined as the binding enhancement and its magnitude can be estimated from
the difference in the formal potentials of the free Ef°′ and complexed Ec°′ guest equation as follows:
°′ °′
F ( Ef − Ec )
K H ⋅G − −
=e RT (12.1)
K H ⋅G
Both Ef°′ and Ec°′ values are usually approximated by the half-wave potentials; the larger the dif-
ference in the half-wave potentials, the greater the value of the binding enhancement.
The magnitude of KH·G determines whether the free or complexed guest is reduced at the elec-
trode surface. When KH·G is large, the already formed H·G complex is electrochemically switched to
a higher affinity state, H·G−. In this case, the diffusion of the host species is not relevant. Conversely,
if KH·G is small, the species undergoing reduction will be the free guest G, which will subsequently
bind the host to yield H·G−. In this situation, after the reduction of G to the high binding state, the
complexation process is essentially controlled by the diffusion of the host toward the reduced guest.
In general, two separate voltammetric waves for the free and complexed guest species will not
be observed for systems with a low KH·G. In this binding regime, it may be important to consider
the value of the rate constants for complexation and decomplexation. The typical electrochemical
response will consist of a shift of the half-wave potential for the free guest species as the host is
added to the solution. A thorough discussion of these processes is beyond the scope of this chapter
and can be found elsewhere [10,14,15].
D. ELECTroaCTIVE SpECIES oN a SoLID SUpporT

The organization and deposition of molecules on surfaces are important both for fundamental stud-
ies and for the development of platforms to interface molecular systems with the macroscopic world,
thus enabling the construction of practical devices. Self-assembled monolayers (SAMs), Langmuir
monolayers, and Langmuir–Blodgett multilayer films are widely used techniques to immobilize mol-
ecules on surfaces or at interfaces [24,25]. Molecular recognition events involving systems in which
either the host or the guest component is bound to the surface of a solid electrode can be probed by
electrochemical techniques [26]. Moreover, in many cases, the assembly–disassembly process can
also be controlled by modulating the potential applied to the electrode [10,14,15,18,27,28]. Systems
of this kind are extremely attractive for the construction of responsive surfaces that can find applica-
tions in, for example, chemo(bio)sensing, materials science, and drug delivery.
III. HOST–GUEST SYSTEMS

As already mentioned in Section II in supramolecular chemistry, the term host refers to the
larger and more structurally complex of two binding partners, while the term guest refers to
the smaller, less complex binding partner. In this section, examples of host–guest systems in
which the strength of the binding interaction can be modulated electrochemically (see Figure
12.1) are reported.
A redox process can affect the host–guest interaction in two ways: either the redox couple is
directly involved in the binding with the other substrate or the charge perturbation brought about
by the redox process modifies the binding constant via an electrostatic effect or a change in the
conformation of the host or the guest. While the former approach is likely to give a stronger redox
perturbation on the binding constant, the latter enables the design of the binding site independently
from that of the redox-active moiety.
In the following discussion, host–guest systems are divided according to the nature of interaction
occurring between the host and the guest, although in several cases, interactions of different types
are responsible for the association.
A. HYDroGEN-BoNDING INTEraCTIoNS
An example in which the redox site is directly involved in the binding process is constituted by the
host–guest system [1•2] [29].
Azoflavin 1 strongly interacts with host 2, which contains two guanidinium groups providing
four H bonds for azoflavin 1, in addition to the three setup to bind the imide portion of azoflavin.
Because of these strong interactions, the system is characterized by a high association constant:
KH·G = 1.9 × 104 M−1 in 20% CH3CN/CH2Cl2.
Reduction of the azoflavin to its radical anion increases the binding strength even further, giving
a ΔE1/2 = 317 mV. This potential shift corresponds to a binding enhancement of 2.2 × 105 and a KH·G– =
4.3 × 109 M−1 (see Equation 12.1), certainly one of the largest binding constants ever reported for these
types of H-bonded complexes.
In a similar approach, flavin 3 can interact with the simple receptor 2,6-diamidopyridine
by hydrogen bond formation. This receptor unit bearing an alkyl chain terminated by a thiol
group can be placed at the surface of a gold nanoparticle (4) [30]. The host–guest interaction is
modulated by reducing the flavin in the presence of the functionalized gold nanoparticles. From
the electrochemical studies, the corresponding association constant KH·G − can be estimated: it is
about 20-fold greater than KH·G (4500 M−1 vs 196 M−1). The redox modulation process is selec-
tive as the reduction of a methylated flavin analog (methylated at the N(3) imide position to dis-
rupt hydrogen bonding) is relatively unaffected by the presence of the same functionalized gold
nanoparticles [30].
H H
N
H
+N N
H22C12 H H
N N O
1 H
N N
N N H
O N N
H H
+ H CH
N N N N N 6 13
H H
2 C6H13
N
H

An example in which the binding and redox sites are distinct is represented by the host–guest
system formed by compounds 5 and 6 [31].
3
N N O
H
N N O
N H
O N
H
N
O
S S
S 4

Host molecule 5 contains a tetrathiafulvalene (TTF) moiety that undergoes two reversible oxida-
tions [32], directly linked to an imide derivative able to bind diaminopyridines like 6.
R O
N
H
O N
S S H
N N O
H
S S N O R
5 Bu 6
Oxidation of the TTF decreases the H bonding by removing electron density from the electron-
donating imide carbonyls; indeed, a modest +30 mV E1/2 shift for the TTF0/+ couple is observed in
NBu4PF6/CH2Cl2, indicating a threefold decrease in binding strength upon oxidation.
B. METaL IoN CoorDINaTIoN

The redox process of a host–guest system can not only weaken the interaction of the two molecular
components but also cause a movement of the guest inside the host. Representative examples are
based on metal ion coordination, and involve either the translocation of a metal ion (guest) from one
coordinating site to another one within the host or the rearrangement of the ligand (host) around the
metal ion, as in the case of helicate assembly and disassembly.
The role of the redox-active unit is usually played by the metal, in particular a transition metal
ion. The requirements are (1) a fast and reversible one-electron transfer process and (2) different
electronic and/or geometrical preferences of the two oxidation states of the metal center in the com-
plex formation. Because of these essential features, most examples rely on the Fe(III)/Fe(II) and
Cu(II)/Cu(I) redox couples.
As to the coordination preferences [33], Fe(III) is a high-spin d5 cation, which cannot take advan-
tage from ligand field stabilization energy (LFSE) effects and is therefore inclined to establish
mainly electrostatic interactions, while Fe(II) is a low-spin d6 cation, which profits at most from
LFSE in an octahedral coordinative environment and, in the presence of π-acceptor ligands, can
also exert back donation.
For the copper-based couple, the Cu(II) ion (electronic configuration d9) is ready to adapt itself to
any coordination number (4, 5, 6) and geometry offered by the coordinating environment, in order
to profit at most from LFSE. Conversely, the Cu(I) ion (d10) requires a tetrahedral geometry because
of inter-ligand steric repulsions.
1. Metal Ion Translocation

A typical example of ion translocation is represented by a redox-active metal ion that moves from a
given coordination environment to another one of the same supramolecular system, as a result of an
electrochemical input (Figure 12.2).
A supramolecular system for metal ion translocation must contain two distinct binding compart-
ments differing for their coordinating properties: for example, one is a soft receptor and the other
is a hard one. The metal ion must possess two adjacent oxidation states of comparable stability: one
of soft nature (Mn+) and the other with hard character (M(n+1)+). In a solution containing equimo-
lecular amounts of the reduced metal ion Mn+ and of the two-compartment supramolecular system,
the metal ion Mn+ will occupy the soft compartment. When Mn+ is oxidized, the hard ion M(n+1)+
will move to the nearby hard compartment to increase its stabilization. Consecutive oxidation and
reduction processes would make the metal center shuttle back and forth along a defined route. The
translocation process is described by the electrochemical square scheme shown in Figure 12.1.
A Fe(III)/Fe(II)-driven translocation process is observed with ligand 7 (Figure 12.3) [34], which
consists of a 4-methylphenol platform, to which two different terdentate coordinating units have been
appended in ortho positions: one consists of a tertiary amine nitrogen atom and two phenolate oxygen
atoms and the other possesses one tertiary amine nitrogen atom and two pyridine nitrogen atoms.
Upon addition of one equivalent of Fe(ClO4)3 to a CH3CN solution of 7, in the presence of col-
lidine that guarantees deprotonation of all the phenolic groups, the Fe(III) cation is coordinated
by the left compartment by three oxygen atoms, one nitrogen atom, and two solvent molecules (S),
Hard Soft
+e–
M(n+1)+ Mn+
–e–
FiGURE 12.2 Scheme of a host system containing a soft and a hard receptor compartment for binding metal
ions Mn+ and M(n+1)+, respectively. Metal ion translocation takes place by a reversible metal-centered redox
process.
–
N O– N +e– N O N
– 3+ S N – S N
O –e– O 2+
–
O S O S
– N N
Hard Soft
7a 7b
FiGURE 12.3 Translocation motion of an iron ion within a two-compartment ligand. The left compartment
has a harder character compared to the right one, so that the former hosts Fe(III) ions, while the latter is suitable
for Fe(II) ions. Solvent molecules (S = CH3CN) complete the coordination sphere of the metal ion. The central
phenolate oxygen atom is shared by the two compartments and acts as a pivot in the translocation process.
i(A)
FeIII
–0.8 –0.4 0
E/V
FeII
FiGURE 12.4 Cyclic voltammogram of a CH3CN/NBu4ClO4 solution of 7 (4 × 10 −3 M), containing one

equivalent of Fe(ClO4)2 and collidine. Working electrode: platinum disk (5 mm diameter); scan rate: 0.1 V s−1;
reference electrode: AgNO3/Ag in CH3CN. (From Ceroni, P., Credi, A., Venturi, M., and Schalley, C.A. eds.:
Analytical Methods in Supramolecular Chemistry. pp. 371–457. 2012. Copyright Wiley-VCH Verlag GmbH
& Co. KGaA. Reproduced with permission.)
giving rise to a six-coordinated complex (7a in Figure 12.3). On the other hand, if a stoichiometric
amount of Fe(ClO4)2 is added to a solution of 7 containing collidine, the Fe(II) center is coor-
dinated by the right compartment with three nitrogen atoms, one oxygen atom of the phenolate
group, and two solvent molecules (7b in Figure 12.3). The Fe(II) ion forms again a six-coordinated
complex, but with softer ligands compared to the Fe(III) ion. Translocation was carried out elec-
trochemically and was investigated through cyclic voltammetry experiments in a CH3CN solution
containing 0.1 M NBu4ClO4.
The cyclic voltammogram recorded at 0.1 V/s (Figure 12.4) shows an anodic and a cathodic peak,
both exhibiting chemically irreversibility according to the square mechanism illustrated in Figure 12.1.
At a potential of −0.8 V, the Fe(II) ion stays in the right compartment (7b in Figure 12.3). On
increasing the potential, oxidation to Fe(III) takes place, with an anodic peak at ca. −0.2 V. No
corresponding cathodic peak is observed upon reversing the potential scan because of the coupled
structural rearrangement, that is, the movement of the Fe(III) ion to the left compartment (7a in
Figure 12.3). The corresponding Fe(III)/Fe(II) reduction is made more difficult and takes place at a
more negative potential (Epc ca. −0.7 V). After this point, Fe(II) moves back to its original compart-
ment and the system is ready for a further cycle.
CV studies at high scan rates indicated that the lifetime of the translocation is shorter than 10 ms.
The high translocation rate can be ascribed to the beneficial assistance of the central phenolate oxy-
gen atom, which keeps the iron center coordinated over the course of the direct and reverse motion,
thus reducing the energy of the transition state.
2. Anion Translocation
Not only metal cations but also anions can be translocated within ditopic systems, taking advantage
of the coordination to a redox-active metal center. An example is represented by system 8 reported
in Figure 12.5, constituted by two tetramine coordinating sites, tren [tris(2-aminoethyl)amine)] and
cyclam (1,4,8,11-tetraazacyclotetradecane). These binding moieties, separated by a 1,4-xylyl spacer,
display different coordinating tendencies toward metals [35].
Consecutive reaction of 8 (Figure 12.5) with one equivalent of Ni(ClO4)2 and one equivalent
of Cu(ClO4)2 under the proper conditions leads to the formation of a heterodimetallic complex in
which the Ni(II) ion is firmly encircled by the tetra-aza macrocycle, whereas Cu(II) is coordinated
by the tripodal tetramine. If one equivalent of tetra-alkylammonium chloride is added to a mM
solution of the dimetallic complex, the Cl− ion binds the Cu(II) center to form a five-coordinate
complex with an axially compressed trigonal bipyramidal geometry (8a in Figure 12.5).
–
Cl
H
H N
N N
N Ni2+ H Ni3+ H
H H N N
N N
– S
CI
+e–
Cu2+
Cu2+ –e– H2N NH
H2N NH NH2
NH2
N
N
8a 8b
FiGURE 12.5 Redox-driven translocation of the Cl− anion, based on the Ni(III)/Ni(II) redox couple. S rep-
resents a solvent molecule.
Spectrophotometric titration experiments enabled to determine the binding constant:

log K = 5.66 ± 0.09. Therefore, for a mM solution of 8, addition of one equivalent of anion leads to
95% of the anion bound to the Cu(tren)2+ subunit. The Ni(cyclam)2+ moiety is not competitive for
anion binding because Ni(II) prefers the square coordination provided by the cyclam macrocycle.
The Ni(II) center undergoes one-electron oxidation at a moderately positive potential [36], and the
so-formed d7 cation, in the low-spin state, displays a strong preference toward higher coordination.
Thus, upon Ni(II) oxidation, the chloride ion moves from the Cu(II) center to the Ni(III) one, while
the free coordination position on the Cu(II) ion is taken by a solvent molecule (8b in Figure 12.5).
3. Helicate Assembly and Disassembly

Metal-centered redox processes can also cause a rearrangement of the ligand, as it happens in the
case of the assembly and disassembly of metal helicates. For example, compound 9 [37] (Figure 12.6)
gives stable complexes with Cu(I) and Cu(II), both in CH3CN solution and in the solid state.
N N
N N
Cu2+
Cu+
–2e –
Cu+ +2e – +
Cu2+
FiGURE 12.6 Redox-driven assembly–disassembly of a helicate based on Cu(II)/Cu(I) redox couple.

In particular, Cu(I) gives rise to a dinuclear complex, [Cu2(9)2](CF3SO3)2, in which each Cu(I)
ion is bound to an imine and to a pyridine nitrogen atom from each strand, and shows a rather dis-
torted tetrahedral coordination geometry. On the other hand, Cu(II) complexation by ligand 9 leads
to a mononuclear complex, [Cu(9)](CF3SO3)2, that reaches tetragonal coordination through chelation
by a single molecule of 9 in order to better profit from LFSE terms. Both these complexes were ana-
lyzed by x-ray diffraction studies. In solution, assuming that the previously described geometrical
features are maintained, the Cu(II)/Cu(I) redox change would result in an assembly–disassembly
equilibrium, as pictorially illustrated in Figure 12.6.
The occurrence of the redox-driven reversible assembly–disassembly process involving copper
complexes of 9 has been verified through cyclic voltammetry experiments at a platinum electrode in
CH3CN solution. Both electrochemical processes illustrated in Figure 12.6 appear to be chemically
irreversible because of fast assembly–disassembly processes. The analysis of the electrochemical data
suggests that the transient species [Cu2(9)2]4+ and [Cu(9)]+ have a lifetime lower than 50 ms. It has been
demonstrated that the lifetime of the dicopper(II) double-strand helicate [Cu2(9)2]4+ can be signifi-
cantly increased by introducing hindering substituents on the framework of 9 [38].
C. HYDropHobIC INTEraCTIoNS
Cyclodextrins (CDs) [39] and cucurbit[n]urils (CB[n]) [40] represent two classes of host molecules
relatively soluble in water that contain a rather rigid and well-defined cavity that can encapsulate
guests mainly by hydrophobic interactions. In spite of these general similarities, there are also
important differences between them: the cavity of the CDs reminds the shape of a truncated cone,
reaching its maximum diameter at the wider opening, while that of the CB[n] has the shape of a
barrel and its maximum diameter is located at the molecular equator. Moreover, negative charge
density (from the carbonyl oxygens) accumulates on the CB[n] cavity openings, while the hydroxyl
groups on the CD portals are believed to be extensively hydrogen bonded.
The inclusion complexes of CDs are characterized by association constant up to 103–105 M−1.
The formation of highly stable CB[n] inclusion complexes is usually driven by a combination of
hydrophobic forces and ion–dipole interactions between strategically located positive charges on
the guest and the rims of carbonyl oxygens on the cavity portals [40]. As a result, CB[n] inclusion
complexes in aqueous solution may reach association constants as high as 1015 M−1 (equivalent to
that of the avidin–biotin host–guest pair [41]).
The first work in this area reported the binding interactions of ferrocenecarboxylate anions
(FcCOO −) with β-CD in aqueous media buffered at pH 7 (Figure 12.7) [42]. The formation of a
stable inclusion complex was demonstrated by electronic absorption spectroscopy. In the presence
of β-CD, the half-wave potential (E1/2) for the one-electron oxidation of FcCOO − shifts to more
positive values. FcCOO − is more stabilized by β-CD than its mono-oxidized counterpart, Fc+COO −.
An additional observation is that the current levels associated with the voltammetric wave
decrease in the presence of β-CD. This is easily explained by the larger molecular weight and size
of the [β-CD•FcCOO]− complex compared to the free guest. Therefore, inclusion complexation
tends to slow down the diffusional flow of guest to the electrode surface. This flow is driven by
the low concentration of FcCOO − near the electrode, where it is consumed (oxidized) by the elec-
tron transfer process. FcCOO − forms a stable inclusion complex with the host, while the oxidized,
zwitterionic form of the guest does not interact strongly with β-CD. The electrochemical oxida-
tion process is best rationalized by an electron transfer process preceded by a coupled chemical
reaction (host–guest complexation/decomplexation equilibrium), which is usually referred to as
a chemical–electrochemical (CE) mechanism. It is important to realize that the mechanism does
not contemplate the direct electrochemical oxidation of the inclusion complex (right process in
Figure 12.1). Evidence for this surprising finding was gathered at fast scan rates, at which the
–
COO
–
COO
Fe
+ Fe
β-CD
+e– –e–
–
COO
Fe +
FiGURE 12.7 Chemical–electrochemical (CE) mechanism for the one-electron oxidation of FcCOO − in the
presence of β-CD.
cyclic voltammetric wave for oxidation of FcCOO − is flattened [42], because the complex dis-
sociation mechanism becomes too slow to generate enough free guest to sustain the fast electro-
chemical oxidation.
The lack of electrochemical reactivity of the inclusion complex is linked to the fact that the elec-
trochemical kinetics of the inclusion complex is slower than that of the free guest (see Section II.B)
and, because the inclusion complex is short-lived, dissociation provides a bypass mechanism for the
electron transfer to take place more quickly.
Reinhoudt and coworkers have taken advantage of the multivalent interactions between den-
drimers with multiple surface ferrocene residues and SAMs containing CD-binding sites for the
development of molecular printboards (see Section III.E).
Further investigations of the electrochemical behavior of CD complexes suggest that their
labile kinetic nature allows relatively efficient electron transfer reactions to or from the free guest,
following the fast dissociation from the host. Therefore, in spite of their accessibility and simplicity
of use, these hosts do not form complexes of enough kinetic stability to allow the investigation of
the electron transfer reactions involving the encapsulated guests.
The formation of a stable inclusion complex between the organic dication N,N′-dimethyl-4,4′-
bipyridinium (methyl viologen or paraquat, MV2+ [43]) and CB7 was reported for the first time in
2002 [44]. In aqueous media, the stability constant of this complex is ca. 105 M−1, although this
value decreases as the ionic strength of the medium increases [45]. The lifetime of the complex was
estimated to be 5.3 ms. In aqueous solution, one- or two-electron reduction of MV2+ leads to less
charged or neutral species, which are more hydrophobic and have a marked tendency to precipitate
on the electrode surface. However, if the discussion is limited to the first one-electron reduction
(MV2+ → MV+), one can see that the presence of CB7 decreases the current levels and shifts the
half-wave potential to slightly more negative values (Figure 12.8).
This finding shows that CB7 differentially stabilizes the dicationic viologen form versus the cat-
ion radical, although the small magnitude of the CB7-induced, half-wave potential shift (ca. 30 mV)
suggests only a moderate stability drop in the complex after the viologen guest loses one of its posi-
tive charges. The decrease in the current levels in the presence of CB7 reflects the larger size and
lower diffusivity of the complex compared to the free guest.
2.0 × 10–5 A
(a)
–0.2 –0.4 –0.6 –0.8

(b) E (V vs Ag/AgCl)
FiGURE 12.8 Scan rate dependence of the cyclic voltammetric response on a glassy carbon electrode
(0.072 cm2) of 1.0 mM MV2+ in 0.1 M NaCl (a) in the absence and (b) in the presence of 1 equiv CB7. Scan
rates: 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.8, and 1.0 V s−1 (arrows indicate the increasing scan rates). Potential is
referred to Ag/AgCl. (From Ceroni, P., Credi, A., Venturi, M., and Schalley, C.A. eds.: Analytical Methods
in Supramolecular Chemistry. pp. 371–457. 2012. Copyright Wiley-VCH Verlag GmbH & Co. KGaA.
Reproduced with permission.)
An interesting feature of the [CB7•MV]2+ system is that, in clear contrast to CD-based species,
the voltammetric data do not contain any indication that complex dissociation must precede any
of the electron transfer processes. Moreover, the electrochemistry of the inclusion complex is as
fast—in the timescale accessible in these CV experiments—as that of the free guest. This is clearly
illustrated by the voltammograms depicted in Figure 12.8, which shows the comparative results of
a scan rate study on the MV2+/MV+ and [CB7•MV]2+/[CB7•MV]+ redox couples. In both cases, the
observed anodic and cathodic peak potentials are basically invariant as the scan rate is increased up
to 1.0 V/s, revealing the reversible character of both couples under the experimental conditions of
the study. Therefore, it was concluded that the inclusion of methyl viologen into CB7 does not affect
the electrochemical kinetics of the former in a pronounced way.
Although no crystal structure of the [CB7•MV]2+ complex is available, all the experimental and
computational data are consistent with a structure in which the two positively charged nitrogens
interact with the carbonyl rims on the cavity portals and hydrophobic interactions further stabilizing
the midsection of the complex. Obviously the guest is not fully encapsulated, as each of its N-methyl
termini protrudes through the host portals.
D. CHarGE-TraNSFEr INTEraCTIoNS
The interaction between electron-poor and electron-rich molecules, particularly those containing
π-systems, is a common driving force for the formation of host–guest systems. An interesting class
of hosts is constituted by molecular clips and tweezers [46–48], which have a well-organized, yet
relatively flexible shape that enables interactions with guests of different sizes. The recognition pro-
cess can be based on different kinds of interaction, but an example based mainly on electron donor–
acceptor interactions is reported. Molecular clip 10 is constituted by extended aromatic sidewalls
(namely, benzo[k]fluoranthene units [BkF]) connected by a dimethylene-bridged spacer contain-

ing a benzene ring that carries two acetoxy groups. The BkF moieties are strongly fluorescent
[49] polycyclic aromatic hydrocarbons with good electron donor ability [50]. The resulting clip is
soluble in organic solvents and presents a highly negative electrostatic potential on the inner van der
Waals surface of the cavity that forms a recognition site for electron-deficient guest molecules. A
highly stable host–guest complex of clip 10 with 9-dicyanomethylene-2,4,7-trinitrofluorene (TNF)
has been reported [51]: K ≈ 105 M−1, in chloroform solution, estimated by spectrophotometric and
spectrofluorimetric titrations.
R
NC CN
R
O 2N NO2
NO2
10
O TNF
R=
O
As to the electrochemical properties, clip 10 presents two one-electron transfer processes

associated with chemical reactions, corresponding to the first oxidation of each benzo[k]fluor-
anthene sidewall that occurs at distinct potential values because of electrostatic and/or elec-
tronic interactions between the two moieties. The oxidation of BkF is known to be associated
with a dimerization reaction [52]. TNF shows three reversible one-electron reduction processes:
the first process occurs at −0.02 V (vs the saturated calomel electrode [SCE]), demonstrating
the strong electron acceptor character of this compound [53]. An equimolar solution of 10 and
TNF (1.3 mM) in CH 2Cl 2/TBAPF6 shows cyclic voltammograms in which the first oxidation
process is positively shifted and the first reduction process is negatively shifted, compared to
the CVs of the two separated components. Under the experimental conditions used, the frac-
tion of [10•TNF] formed is larger than 90%. The fact that the benzo[k]fluoranthene moiety is
more difficult to oxidize and TNF is more difficult to reduce when they are associated with
one another demonstrates the charge transfer character of this complex. Moreover, lower cur-
rent intensities are observed for [10•TNF] because of the smaller diffusion coefficient of the
complex compared to the separated components. On the other hand, successive reduction and
oxidation processes occur at the same potentials of the isolated components, because one-elec-
tron oxidation or one-electron reduction causes the disruption of the complex. By successive
addition (from 0.5 to 3 equivalents) of clip 10 to a 1.2 mM solution of TNF, a progressive shift
of the first reduction process is observed (Figure 12.9): the maximum shift of the half-wave
potential compared to the free TNF is 95 mV, recorded upon addition of two equivalents of clip
per guest molecule.
The observed electrochemical behavior can be rationalized on the basis of the square scheme
reported in Figure 12.1, in which the association constant K of 10 and TNF is much larger than
that of 10 and TNF− (K′), giving a K/K′ ratio of the order of 40. Upon variation of the scan rate in
the range 0.05–20 V/s, no change in the shape of the cyclic voltammogram is observed, indicating
that both the forward and backward scans of the first reduction process are due to the redox couple
[10•TNF]/[10•TNF]−. The heterogeneous electron transfer rates are, in any case, higher than the
association and dissociation rate constants of the complex between 10 and TNF or 10 and TNF−.
A special class of host–guest systems is represented by pseudorotaxanes [54], in which the
guest has a threadlike shape and the host a ring structure, so that the extremities of the thread are
directed away from the center of the host. At least one of the extremities of the thread does not have
Fc
10
0
i (μA) –0.3 0.0 0.3 0.6
E (V vs SCE)
–10
–20
FiGURE 12.9 Cyclic voltammograms of TNF (1.2 mM) upon addition of clip 10 from 0 (thick solid line) up to
2.0 (dashed line) equivalents in CH2Cl2/TBAPF6 solution. Working electrode: glassy carbon. Scan rate: 0.05 V/s.
The reversible wave of ferrocene (Fc) used as an internal standard is also reported.
a bulky stopper group. Hence, the constituents of the assembly, like any complex, are at liberty
to dissociate into separate molecular species (i.e., in contrast to rotaxanes, see Section IV.B, there
is no attendant mechanical bond to maintain the integrity of the system). Pseudorotaxanes can be
based on different types of intermolecular forces; in this section, only systems characterized by the
presence of electron donor–acceptor interactions are described.
One of the most extensively studied receptors in the past two decades has been the cyclophane
114+, which is a very efficient host for a wide variety of π-electron-donating guests [55].
+N N+
+N N+
114+
Two bielectronic reduction processes are observed for this tetracationic cyclophane: the first cor-
responding to the uptake of the first electron by each of the equivalent bipyridinium units and the
second one to the subsequent reduction of the radical cations to neutral units [56]. When an elec-
tron donor unit is located inside the cavity of the cyclophane, the potential associated with the first
reduction process is shifted to more negative values, as a consequence of the charge-transfer inter-
actions that stabilize the complex [16]. The second reduction process at more negative potentials
of this cyclophane is very important, because it can be used to monitor the occurrence of decom-
plexation induced by the first two-electron reduction [16], as in the case of the previously described
[10•TNF] complex. For example, in the presence of excess of a threadlike compound composed of
a polyether chain, which bears a 1,4-dioxybenzene unit in the middle, the potential value for the
first bielectronic reduction of 114+ is shifted cathodically, whereas the second reduction process
is almost unaffected [56]. This observation is consistent with the formation of a pseudorotaxane
between the cyclophane and the thread, and dethreading of the pseudorotaxane upon two-electron
reduction of the 114+ host, so that the second two-electron reduction process reflects that of the
free host. The occurrence of the dethreading reaction is not surprising, because reduction of the
electron-acceptor component weakens the charge-transfer interaction that helps to hold together
the components of the supramolecular architecture. Because all these processes are reversible,
oxidation back to the tetracationic form affords the original pseudorotaxane. It should, in principle,
also be possible to obtain useful information about the occurrence of dethreading–rethreading
processes from the electrochemical behavior of the guest; the poor reversibility of the oxidation
process associated with a 1,4-dioxybenzene unit, however, prevents the use of this type of control.
More interesting are pseudorotaxanes wherein both the cyclophane and thread components are
characterized by chemically reversible redox processes; one example is the complex of TTF with
114+ [57] and related pseudorotaxanes [57a,58]. This improvement in design not only enables to
monitor the formation of the supramolecular species by studying both the reduction of the electron
acceptor component and the oxidation of the electron donor species but also provides a dual mode
(reductive and oxidative) of control on the dethreading–rethreading processes. The molecular thread
12, obtained by attaching two polyether chains to a TTF unit (Figure 12.10), forms a very stable
pseudorotaxane with 114+.
O
O OH
OH O
+ + + +
N N N N O
O S
O O Dethreading
S S S S
+
O + O +
S S S O
O
O O +N N+
O
+
N N+
HO HO O
O
+e–
–e–
O
OH O OH
+ +
N N + + O
O N N
O O O S
S S (Re)threading
O O + S S
S S
O S O
O O
N N+ +
N N+
+
HO O
HO O
[11 12]4+ O
114+
12
+2e–
–2e–
O
OH O OH
+
N N + O
O O N N
S S O O S
O Dethreading
O + S S
S S
O S
O O O
N N+ N
+
N
HO O
HO O
O
FiGURE 12.10 Redox-driven (re)threading–dethreading of a pseudorotaxane stabilized by electron donor–

acceptor interactions.
Reversible dethreading–rethreading cycles of the pseudorotaxane [11•12]4+ can be performed

either by oxidation and successive reduction of the electron-donating thread or by reduction and
successive oxidation of the electron-accepting cyclophane. Such processes are accompanied by pro-
nounced visible spectral differences that can be followed easily by the naked eye.
Interestingly, while monoelectronic oxidation of TTF to its radical cation cancels the strong
electron donor character, its two-electron oxidation renders the formed TTF2+ dication a moderate
electron acceptor [59]. This property was exploited to devise a redox-controlled three-pole switch
[60] based on a supramolecular system composed of TTF and two hosts, namely, the π-electron-
accepting cyclophane 114+ and the π-electron-donating crown ether 13 (Figure 12.11) [61].
In its role of an electron donor, TTF forms, in acetonitrile solution, a 1:1 inclusion complex with
114+ that can be dissociated–reassociated reversibly by cyclic oxidation–reduction of TTF, while
TTF2+ acts as a π-electron acceptor, giving a 1:1 inclusion complex with 13. In contrast, TTF+ is not
bound by either of the two hosts.
When the electrochemical potential applied to the solution, where TTF is complexed by 114+,
[11•TTF]4+, becomes more positive than ~ +0.4 V (relative to the SCE), TTF is oxidized to the
monocation form and the complex disassembles to give three essentially noninteracting species.
Further one-electron oxidation to TTF2+ at potentials more positive than ~ +0.7 V (relative to the
SCE) leads to the insertion of the dication into the cavity of 13, [13•TTF]2+. Because both oxidized
forms of TTF are stable, the initial state can be restored by subsequent reduction. This system can
therefore be switched reversibly between three distinct states by exercising electrochemical control
on the guest behavior of TTF (Figure 12.11).
The fact that the three states have different colors, coupled with the ease of their electrochemical
interconversion, renders this supramolecular system suitable for electrochromic applications; the
system could, moreover, form the basis for the construction of molecular devices in which energy or
electron transfer processes between selected components can be controlled [61].
It has been shown more recently [62] that the tendency for bipyridinium radical cations to
dimerize can be exploited to assemble strong complexes between the dicationic cyclophane host
112+ (obtained upon two-electron reduction of 114+) and bipyridinium radical cationic guests
(obtained upon one-electron reduction of the corresponding dications). Such a recognition
motif forms the basis of redox-switchable supramolecular species and mechanically interlocked
molecules [62–64].
+
N N+
+
N N+ +N N+
114+ S S
S S
+N N+
+N N+ +N N+
+e– S S +e–
+ + TTF+ +
–e– S S –e–
O O O O
O O
O O O O O O O
+ S
S O O
S+S
O O O O
O O O O O O O
O
O O
O
13
FiGURE 12.11 A supramolecular switch in which selection of either cyclophane 114+ or crown ether 13 hosts
is achieved by changing the oxidation state of the TTF guest.
E. HoST-GUEST SYSTEMS WorkING oN SUrFaCES

The three-pole supramolecular switch described in Section III.D (Figure 12.11) was also constructed
and operated at the solid–liquid interface of an electrode [65]. A SAM of compound 14 was obtained
on a gold electrode. Voltammetric experiments showed that, depending on the oxidation state of the
immobilized guest unit, the TTF moiety can form a complex either with cyclophane 114+ (when it is
in the neutral TTF form) or with crown ether 13 (when it is in the dicationic TTF2+ form). Hence, the
multistage redox properties of SAMs of 14 can be exploited to produce surfaces with electrochemically
controllable binding properties. Unfortunately, the reversibility associated with the sequential oxidation
of the TTF moiety of the SAM in the presence of both 114+ and 13 macrocycles was poor, which will
significantly hamper the fabrication of usable devices from this system.
O
S S O
S S S S
14
Water-soluble supramolecular assemblies of redox-active ferrocenyl-decorated dendrimers such

as 15 (Figure 12.12) and β-CD were adsorbed at molecular printboards [27] composed of SAMs
of β-CD [66]. The dendrimers form a stable monolayer at the β-CD SAM owing to multivalent
host–guest interactions. The immobilization of the dendrimers can be electrochemically controlled
Fe
Fe
O O HO OH
HN NH O
O
Fe H
N H Fe
N N N HN 7
O
O
O
N
N
O
O
N N
Fe H N N
H Fe
HO OH
HN
NH
O
O 15 O
S
Fe O
Fe
(a) HO 7
β-CD
Oxidation
+
+ +
(b)
FiGURE 12.12 (See color insert.) (a) Structures of the ferrocene-terminated dendrimer 15, β-cyclodextrin,
and the β-cyclodextrin derivative used for the preparation of the SAMs. (b) Schematic representation of the
self-assembly of the dendrimer-β-CD complex, its adsorption on the β-CD modified surface, and the electro-
chemically induced desorption.
because, while ferrocene forms stable inclusion complexes with β-CD, the ferrocinium cation does
not (Figure 12.12). The redox-dependent adsorption process was studied by voltammetric tech-
niques and electrochemical impedance spectroscopy. Detailed information was obtained on the
adsorption and desorption kinetics and mechanism, diffusion coefficients, and conformation of the
guest dendrimers adsorbed at the host surface [66].
More recently, the electrochemical modulation of host–guest interactions has been used to con-
trol the aggregation–disaggregation of nanoparticles [67].
IV. MOLEcULAR MAchiNES

A. BaSIC CoNCEpTS
The design, synthesis, and operation of molecular-scale systems that exhibit controllable motion
of their component parts is a topic of great interest in nanoscience and a fascinating challenge of
nanotechnology. The development of this kind of species constitutes the premise to the construc-
tion of molecular machines and motors, which in a not too distant future could find applications
in fields such as materials science, information technology, energy conversion, diagnostics, and
medicine [8,68].
Like the macroscopic counterparts, molecular machines can be classified according to char-
acteristics such as the type of energy supply to make them work, the kind of motion (translation,
rotation, oscillation, etc.) performed by their components, the way of monitoring their operation (the
rearrangements of the component parts should cause readable changes in some chemical or physical
property of the system), the possibility to repeat the operation in cycles, the timescale needed to
complete a cycle, and the function that can be ultimately carried out. It should be recalled, however,
that nanoscale machines cannot be simply considered as shrunk versions of the macroscopic coun-
terparts because several intrinsic properties of molecular-level entities are quite different from those
of macroscopic objects. A thorough discussion on the basic concepts of molecular machines can be
found elsewhere [8,68].
Molecular machines operate through chemical reactions and need to be fed by an energy source.
The obvious way to provide a chemical system with energy is through an exoergonic chemical
reaction. If a molecular machine has to work by inputs of chemical energy, addition of fresh reac-
tants (fuel) at any step of its working cycle is needed, with the concomitant formation of waste
products. Research in the field has shown that artificial molecular machines can also conveniently
be powered by electrical energy (through electrochemically induced redox reactions) and by light
(through photoinduced reactions such as photoisomerization and photoinduced electron transfer
processes).
In the past 25 years, the development of supramolecular chemistry has enabled the construction
of an interesting variety of artificial molecular machines. Most of them are based on the topologi-
cally intriguing chemical systems called rotaxanes and catenanes. Simple examples of molecular
machines are also pseudorotaxanes (see Section III.D) because of the possibility of controlling the
component threading/dethreading motion.
B. SYSTEMS BaSED oN RoTaXaNES

Rotaxanes [69], the name of which derives from the Latin words rota and axis for wheel and
axle, are minimally composed (Figure 12.13) of a macrocyclic compound (the ring) threaded
by a dumbbell-shaped molecule terminated by bulky groups (stoppers) that prevent disassem-
bly. Important features of these systems derive from noncovalent interactions between compo-
nents that contain complementary recognition sites.
The switch off and again on of such interactions is at the basis of the machine-like behavior of
rotaxanes as schematized in Figure 12.13a and b.
(a)
(b)
FiGURE 12.13 Schematic representation of a rotaxane structure and the simple movements that can occur
upon appropriate energy stimulation: (a) ring shuttling and (b) ring pirouetting.
1. Molecular Shuttles
When a rotaxane contains two different recognition sites in its dumbbell component, it can behave
as a controllable molecular shuttle (Figure 12.13a), and, if appropriately designed by incorporating
suitable redox units, it can perform its machine-like operation by exploiting electrochemical energy
inputs. Of course, in such cases, electrons/holes, besides supplying the energy needed to make the
machine work, can also be useful to read the state of the system by means of the various electro-
chemical techniques.
Three paradigmatic examples of rotaxanes as electrochemically driven shuttles are reported,
which differ for the nature of the interactions stabilizing their structure: electron donor–acceptor
interactions for the first system, hydrogen-bonding and π-stacking interactions for the second one,
and strong metal–ligand bonding for the third one.
Rotaxane 16 6+, specifically designed [70,71] to achieve photoinduced ring shuttling in solution
[72], behaves also as an electrochemically driven molecular shuttle (Figure 12.14).
Because of the presence of several redox-active units, the cyclic voltammogram of this rotaxane shows
a complex redox pattern. However, the comparison with the electrochemical behavior of its molecular
components and suitable model compounds (Figure 12.14) enables to obtain useful information not only
on its conformational features, but also, and most importantly, on its machine-like operation.
In dumbbell-shaped component 18 6+, all the redox processes of the incorporated units are present
at almost the same potentials as in the separated units (Figure 12.15a); this finding shows that there
are no substantial intercomponent electronic interactions. On going from the dumbbell component
to rotaxane 16 6+, some processes are affected while others are not (Figure 12.15a).
All the processes related to the Ru-based unit, namely, the metal-localized oxidation and the
ligand-localized reductions, do not show any appreciable changes. A different behavior is, however,
observed for the A12+ unit, the first reduction of which is displaced noticeably toward more nega-
tive potential values. This result indicates that it is surrounded by the electron donor macrocycle 17
(Figure 12.15b). Accordingly, the oxidation of the two dioxybenzene (DOB) units of the macrocycle
is displaced toward more positive potential values and occurs simultaneously (Figure 12.15b), as
already observed for other rotaxanes containing ring 17 [73]. The fact that the ring encircles the A12+
station, as confirmed by the NMR spectrum, is an expected result on the basis of the reduction poten-
tials of A12+ and A22+ in component 186+ (or of separated model compounds). The second process of
16 6+, which corresponds to the first reduction of the A22+ station, is also displaced toward more nega-
tive potential values (Figure 12.15b), demonstrating that, at this stage, the A22+ unit is encircled by
macrocycle 17. A further proof of the ring displacement is given by the fact that the second reduction
of the A12+ station occurs practically at the same potential of the dumbbell (Figure 12.15b).
This behavior confirms that, when the better station (A12+) of the two has been deactivated upon
reduction, the ring moves to the alternative A22+ station. Under these conditions, from the values
of the first reduction potential of A22+ and the second reduction potential of A12+ in the dumbbell
P2+ S O O R T
A22+ O O
A1 2+
N N + + O + +
O
N N N N
N Ru2+ N O O
O O
N N O O
166+
O O
O O
O 17 O
O O
O O
N N + + + +
N N N N
N Ru2+ N O O
N N
186+
+ +
H3C N N CH3 222+
N N OH
N Ru2+ N
N N + + + +
192+ N N N N
O O
204+
+
N N+
212+
FiGURE 12.14 Structure formulas of rotaxane 16 6+, its ring and dumbbell-shaped components 17 and 18 6+,
respectively, and model compounds 192+, 204+, 212+, and 222+ of the units present in the dumbbell.
component, it can be estimated that the translational isomer with the ring surrounding A22+ is much
more populated than that in which the ring encircles A1+.
When also the A22+ station has been monoreduced, the position of the ring is no longer controlled
by strong CT interactions; from the electrochemical results, it seems that it resides close to A2+. The
reversibility of the electrochemical processes involving the two stations shows that, after a two-
electron reduction of rotaxane 16 6+, one-electron oxidation relocated the ring on the A22+ station and
a successive one-electron oxidation entices it back again onto the A12+ station. The chemical and
electrochemical reversibility of these processes also indicates that the rates of the electrochemically
induced ring movements are fast.
The second example is represented by rotaxane 23 (Figure 12.16), which comprises a macrocycle
containing aromatic hydrogen–bonding amide sites, and an axle containing a hydrogen–bonding
station (a glycylglycine unit) and a fullerene stopper separated by a triethylene glycol spacer [74].
As expected, in solvents such as CH2Cl2, CHCl3, and THF, the macrocycle stays preferentially
on the peptidic station, far away from the fullerene. Instead, in solvents such as DMSO and DMF
that weaken the hydrogen bonds, the interactions between the macrocycle and the fullerene are
promoted, inducing a large positional change of the macrocycle. In the excited state absorption
measurements, nearly solvent-independent behavior was observed for the thread, while measure-
ments carried out on the rotaxane showed that the fluorescence of the fullerene is quenched by
17
×0.5
166+
186+
192+
204+
×0.5
20 μA
212+
×0.5
222+
+1.5 +1.0 +0.5 0 –0.5 –1.0 –1.5 –2.0

(a) E (V vs SCE)
17 186+
166+
+1.4 +1.2 –0.4 –0.6 –0.8 –1.0

E (V vs SCE) E (V vs SCE)
(b)
FiGURE 12.15 (a) Cyclic voltammetric patterns for rotaxane 16 6+, its ring 17, and dumbbell-shaped compo-
nent 18 6+ and model compounds 192+, 204+, 212+, and 222+ in CH3CN solution. (b) Potential shifts caused by the
donor–acceptor interaction between ring 17 and dumbbell-shaped component 18 6+ when they are assembled
in rotaxane 16 6+. Circles, squares, and triangles represent processes centered on dioxybenzene, A12+ and A22+
units, respectively. (From Ceroni, P., Credi, A., Venturi, M., and Schalley, C.A. eds.: Analytical Methods
in Supramolecular Chemistry. pp. 371–457. 2012. Copyright Wiley-VCH Verlag GmbH & Co. KGaA.
Reproduced with permission.)
the proximity of the macrocycle by 28% and 44%, respectively, in DMF and DMSO. The residual
fullerene fluorescence in DMSO is 51% of that in CH2Cl2. These experiments provided not only a
way to identify the interactions taking place between the macrocycle and the fullerene but also a
much simpler way to monitor shuttling than with transient absorption measurements.
An important feature of rotaxane 23 is that the position and the translocation of the macrocycle
can also be monitored and achieved by the reduction of the fullerene to its trianion, which is both
affected and observed by cyclic voltammetry. In DMSO, the proximity of the macrocycle to the
O O
23
N N
HH
O H
N O N
O N
H O
H H
N N
O O
CHCl3 DMSO
–3e– +3e–
O
O
HN
O H
N O N
O N
O H O
HN
FiGURE 12.16 Conformational rearrangements in rotaxane 23 induced by changing the solvent polarity and
by electrochemical reduction of the fullerene stopper.
fullerene stabilized substantially the electrogenerated trianion (ΔE1/2 = 46 mV) through π–π interac-
tions. Surprisingly, in THF where the macrocycle is preferentially positioned on the peptide station, a
similar behavior was observed (ΔE1/2 = 40 mV). Although contradictory, this result can be easily ratio-
nalized in terms of an electrochemically induced shuttling of the macrocycle from the peptide station
to a position near the fullerene where it is stabilized by the negative charge present on this stopper.
The possibility of fine-tuning electron transfer processes through molecular shuttling was finally
shown introducing ferrocene electron donors on the macrocycle (rotaxane 24) [75].
Fe
O O
O O
N N
HH
O H
N O O N N
H O
H H
N N
O O
O O
24
Fe
Steady-state and transient absorption photophysical measurements revealed through-space pho-

toinduced electron transfer between the fullerene stopper and the ferrocenes on the macrocycle.
In CH2Cl2, the radical ion pair state lifetime of 26.2 ns was measured. This value is consistent with
the larger relative separation of the electroactive units that give longer lifetimes. Indeed, the use of
a polar solvent (hexafluoroisopropanol) shortens the lifetime to 13.0 ns, a consequence imposed by
weakening the hydrogen bonds that decrease the relative spatial separation between the donor and
the acceptor, while increasing the shuttling rate.
The third example of electrochemically driven shuttles is rotaxane [25•Cu]+ (Figure 12.17) that is
stabilized by metal–ligand bonding. It contains a phenanthroline and a terpyridine unit in its dumb-
bell-shaped component; it also incorporates a Cu(I) center coordinated tetrahedrally by the phenan-
throline ligand of the dumbbell together with the phenanthroline ligand of the macrocycle [76–78].
Oxidation of the tetracoordinated Cu(I) center of [25•Cu]+ to a tetracoordinated Cu(II) ion
occurs on electrolysis (+1.0 V relative to the SCE) of a CH3CN solution of the rotaxane. In response
to the preference of Cu(II) for a pentacoordination geometry, the macrocycle shuttles away from
the bidentate phenanthroline ligand of the dumbbell and encircles the terdentate terpyridine ligand
instead.
+
O O
O O
O O
N
N N N N O
Cu
–
N N
O [25 Cu]+
O
– e–
Cu
–
Cu
–
+e–
Cu
–
[25 Cu]2+
FiGURE 12.17 Shuttling of the macrocyclic component of [25•Cu]+ along its dumbbell-shaped component
controlled electrochemically by oxidizing–reducing the metal center.
Consistently, the cyclic voltammogram shows the disappearance of the reversible wave (+0.68 V)
associated with the tetracoordinated Cu(II)/Cu(I) redox couple and the concomitant appearance of
a reversible wave (−0.03 V) corresponding to the pentacoordinated Cu(II)/Cu(I) redox couple. A
second electrolysis at −0.03 V of the acetonitrile solution of the rotaxane reduces the pentacoor-
dinated Cu(II) center back to a pentacoordinated Cu(I) ion. In response to the preference of Cu(I)
for a tetracoordination geometry, the macrocycle moves away from the terdentate terpyridine ligand
and encircles the bidentate phenanthroline ligand. The cyclic voltammogram recorded after the
second electrolysis shows the original redox wave (+0.68 V) corresponding to the tetracoordinated
Cu(II)/Cu(I) redox couple.
This system has been improved by replacing the highly shielding and hindering phenanthroline
moiety contained in the ring with a nonhindering bi-isoquinoline unit [79]. In the new rotaxane, the
electrochemically driven shuttling of the ring is, indeed, at least four orders of magnitude faster than
in the previous phenanthroline-based system.
2. Ring Pirouetting Motion

In suitably designed rotaxanes, the pirouetting-type movements of the ring around the axle (Figure
12.13b) can be electrochemically driven. Rotaxane [26•Cu]+ has a structure (Figure 12.18a) in which
Cu(I) is coordinated tetrahedrically by the phenanthroline present in the axle and the phenanthro-
line contained in the ring [80,81]. Electrochemical oxidation of the Cu(I) center leads to a transient
tetracoordinated Cu(II) species that, by the pirouetting of the ring around the axle, rearranges in
tens of seconds to a structure in which the Cu(II) center reaches its most stable environment, being
pentacoordinated by the phenanthroline of the axle and the terpyridine of the ring ([26•Cu]2+ in
Figure 12.18b). On electrochemical reduction of Cu(II), a transient pentacoordinated Cu(I) species
is obtained, which rearranges in the millisecond timescale by means of a second pirouetting of the
ring to the most stable structure with Cu(I) tetrahedrically coordinated ([26•Cu]+ in Figure 12.18b).
The obtained results underline that the rearrangement rates from the less to the most stable geom-
etries are drastically different for the two oxidation states of the metal.
In order to increase the rate of the ring pirouetting, the new rotaxane [27•Cu]+ (Figure 12.18a)
was prepared [82] in which the metal center is more accessible because of the presence of a less
hindered ligand compared to the previous related system. Ligand exchange within the coordination
sphere of the metal is thus facilitated as much as possible. The molecular axle contains indeed a thin
2,2′-bipyridine motif, which is less bulky than a 1,10-phenanthroline fragment and it is expected
to spin more readily within the cavity of the ring as a consequence of Cu oxidation/reduction.
Compared to [26•Cu]+, in this rotaxane, both the oxidation-induced and the reduction-induced ring
pirouetting movements are more than three orders of magnitude faster. Such an example shows that
subtle structural factors can have a very significant influence on the general behavior (rate of the
movement, in particular) of Cu(II/I)-based molecular machines.
Further improvement in the pirouetting rate has then been obtained by keeping the two stoppers of
[27•Cu]+ very remote from the copper center [83]. The results obtained show that in this improved sys-
tem, the ring moves very fast around the axle (milliseconds) even at low temperature. It should be noted,
however, that, as a consequence of the oxidation–reduction cycle, the ring of these rotaxanes does not
necessarily perform a 360° rotation, but can only oscillate between the two positions on the threaded
axle. To make real rotary motors, it would be necessary to introduce directionality in the system by using,
for example, a ring containing three different coordination sites and a suitably designed axle.
C. SYSTEMS BaSED oN CaTENaNES

Catenanes [69], whose name derives from the Latin word catena for chain, are made of (at least)
two interlocked macrocycles or rings (Figure 12.19a). As for rotaxanes, the important feature of
catenanes derives from the presence of weak noncovalent interactions between the components that
O
O
O O O O
N N
N N N N
N Cu N Cu
–
–
N N N N
N N
O O O O
O
O
[26 Cu]+
[27 Cu]+
(a)
–e–
–
Cu Cu
+e–
(b)
FiGURE 12.18 (a) Structure of rotaxanes [26•Cu]+ and [27•Cu]+ and (b) schematic representation of the ring
pirouetting induced by oxidation–reduction of the metal center.
contain complementary recognition sites. Because of these interactions, catenanes, like rotaxanes,
are appealing systems for the construction of molecular machines. The large-amplitude motion that
can be achieved with catenanes is the circumrotation of one ring with respect to the other, and when
suitably designed, they can be seen as simple prototypes of molecular rotors.
As already pointed out in the case of rotaxanes, also in catenanes, the dynamic processes of one
ring with respect to the other can be controlled if at least two different recognition sites are incorpo-
rated in the structure (Figure 12.19b). In particular, if redox units are incorporated in the catenane
structure, there is the possibility of controlling these processes upon electrochemical stimulation.
An example is offered by catenane 284+ (Figure 12.20a) that incorporates the previously seen
macrocycle 17 and a tetracationic cyclophane comprising one bipyridinium and one trans-1,2-bis
(4-pyridinium)ethylene unit [84,85].
(a)
+S1
+S2
(b) State 0 State 1
FiGURE 12.19 Schematic representation of (a) a catenane structure and (b) the two conformational isomers
associated with a catenane incorporating two different recognition sites within one of its two macrocyclic
components; the two isomers can be interchanged by appropriate stimuli (S1 and S2).
In the major isomer, the bipyridinium unit is located inside the cavity of the macrocyclic poly-
ether and the trans-bis(pyridinium)ethylene unit is positioned alongside, as confirmed by the
electrochemical analysis. The cyclic voltammogram of the catenane shows four monoelectronic
processes that, by a comparison with the data obtained for the free cyclophane, can be attributed as
follows: the first and fourth processes to the first and second reductions of the bipyridinium unit, and
the second and third ones to the first and second reductions of the trans-bis(pyridinium)ethylene
unit. The comparison with the tetracationic cyclophane also evidences that all these reductions are
shifted toward more negative potential values (Figure 12.20b).
O O O O O O O O O O
+N +N
N+ N+
+e–
N+ N+
+N +N
O O O O O O O O O O
4+
28
O O O O O O O O O O
+N N+ +N N+
–e–
+N N
N+ N+
O O O O O O O O O O
(a)
FiGURE 12.20 (a) The circumrotation of the tetracationic cyclophane component of catenane 284+ can be
controlled reversibly by reducing–oxidizing electrochemically its bipyridinium unit. (Continued)
Tetracationic
ring
Catenane
284+
–0.3 –0.5 –0.7 –0.9

(b) E (V vs SCE)
FiGURE 12.20 (Continued) (b) correlation between the half-wave reduction potentials of catenane 284+
and of its tetracationic ring component (circles and squares correspond to the reduction of bipyridinium
and trans-bis(pyridinium)ethylene units, respectively). (From Ceroni, P., Credi, A., and Venturi, M. eds.:
Electrochemistry of Functional Supramolecular Systems. p. 415. 2010. Copyright Wiley-VCH Verlag
GmbH & Co. KGaA. Reproduced with permission.)
The discussion can be restricted to the first and second reduction processes that are of particular
interest in this context. The shift of the bipyridinium-based process is in agreement with the catenane
conformation in which the bipyridinium unit is located inside the cavity of the macrocyclic polyether
(Figure 12.20a); because of the CT interactions established with both the electron donor units of
the macrocycle, its reduction is more difficult than in the free tetracationic cyclophane. The shift of
the trans-1,2-bis(4-pyridinium)ethylene-based reduction indicates that, once the bipyridinium unit
is reduced, the CT interactions that stabilize the initial conformation are destroyed and, thereby, the
tetracationic cyclophane circumrotates through the cavity of the macrocyclic polyether moving the
trans-bis(pyridinium)ethylene unit inside, as shown by comparison of its reduction potential with
that of a catenane model compound [84]. The original equilibrium between the two conformations
associated with catenane 284+ is restored upon oxidation of both units back to their dicationic states.
It is interesting to notice that for a machine-like performance, the presence of a desymmetrized
ring is a necessary but not a sufficient requirement. This statement is clearly demonstrated by the
behavior of catenane 294+ made by the same tetracationic cyclophane of 284+ and a macrocycle
containing two dioxynaphthalene (DON) units [84,85]. As in the case of 284+ the major isomer
is the one in which the bipyridinium unit is located inside the macrocycle. However, in contrast with
the behavior of 284+, for which the first reduction process concerns the inside bipyridinium unit,
the first reduction of 294+ involves the alongside trans-bis(pyridinium)ethylene unit (Figure 12.21).
+N O O O O O
N+
+N
N+
N+
+N
N+
+N
–0.3 –0.5 –0.7 –0.9 O O O O O
E (V vs SCE)
294+
FiGURE 12.21 Correlation between the half-wave reduction potentials of catenane 294+ and of its tetracationic
ring component (circles and squares correspond to the reduction of bipyridinium and trans-bis(pyridinium)
ethylene units, respectively). (From Ceroni, P., Credi, A., and Venturi, M. eds.: Electrochemistry of Functional
Supramolecular Systems. p. 417. 2010. Copyright Wiley-VCH Verlag GmbH & Co. KGaA. Reproduced with
permission.)
This process has been undoubtedly attributed to this unit by performing spectroelectrochemi-
cal experiments and comparing the spectrum of the monoreduced catenane with that of a model
compound containing only the trans-bis(pyridinium)ethylene unit.
The different behavior of the two catenanes, as far as the first reduction process is concerned, can
be explained on the basis of the different strength of the CT interactions: in 294+ the bipyridinium
unit is sandwiched between two DON moieties that are stronger electron donors than the DOB
moieties of the macrocyclic component of catenane 284+. Because of these stronger interactions, the
reduction of such a unit becomes so difficult that it occurs at a potential more negative than that of
the trans-bis(pyridinium)ethylene unit (Figure 12.21).
As a consequence of the fact that in 294+ the first reduction concerns the alongside unit, the CT
interactions responsible for the initial conformation are practically unaffected and no mechanical
movement occurs in the monoreduced catenane.
Catenanes 304+ and 314+ (Figure 12.22) are other examples of systems in which the conforma-
tional motion can be controlled electrochemically [58b,86]. They are made of the already seen
symmetric tetracationic cyclophane 94+ and a desymmetrized ring comprising two different electron
donor units, namely, a TTF and a DOB (304+) or a DON (314+) units. Because the TTF moiety is a
better electron donor than the dioxyarene units, as witnessed by the potential values for their oxida-
tion, the thermodynamically stable conformation of these catenanes is that in which the symmetric
ring encircles the TTF unit of the desymmetrized one (Figure 12.22a, State 0).
The cyclic voltammogram of the free macrocycle shows a reversible process attributed to the
monoelectronic oxidation of the TTF unit. In the catenanes, such a process occurs at more positive
O O O O O
+ +
N N
S S –e–
S S
+N N+
O O O O O (b)
(a) State 0
+e–
(d) (c) State 1
304+ 314+
FiGURE 12.22 Redox-controlled ring rotation in solution for catenanes 304+ and 314+, which contain the
symmetric electron acceptor cyclophane 94+ and a desymmetrized electron donor ring.
potentials, in agreement with the fact that the TTF unit is located inside the cavity of the tetraca-
tionic cyclophane and, therefore, engaged in strong CT interactions. It is also interesting to notice
that in the catenane, this oxidation process is characterized by a large separation between the
anodic and cathodic peaks, which varies as the scan rate is changed. Upon increasing the scan rate,
the anodic peak moves to more positive potentials, while the cathodic one shifts to less positive
values. These observations indicate that the oxidation–reduction of the TTF unit is accompanied
by the circumrotation of the desymmetrized ring through the cavity of the tetracationic cyclophane
and that this change is occurring on the timescale of the electrochemical experiment. Indeed, after
oxidation, the newly formed monocationic TTF unit (Figure 12.22b) loses its electron donor power;
as a consequence, it is expelled from the cavity of the tetracationic cyclophane and is replaced by
the neutral dioxyarene unit (Figure 12.22c, State 1). After reduction, the original conformation is
restored as the neutral TTF unit replaces the dioxyarene unit inside the cavity of the tetracationic
cyclophane.
Ring rotation in these catenanes can also be obtained chemically. The tendency of o-chloroanil to
stack against TTF has been indeed exploited [58b,86] to lock this unit alongside the cavity of the tet-
racationic cyclophane. On addition of a mixture of Na 2S2O5 and NH4PF6 in H2O, the adduct formed
between the TTF unit and o-chloroanil is destroyed, and the original conformation with TTF inside
the cavity of the tetracationic cyclophane is then restored. Catenane 314+ was also incorporated in a
solid-state device that could be used for random access memory (RAM) storage. Additionally, this
compound could be employed for the construction of electrochromic systems, because its various
redox states are characterized by different colors [58b,86,87].
The six electroactive catenanes 322+–372+ (Figure 12.23) [88] are formed by (1) a desymmetrized
electron acceptor ring containing two different units, namely, a 4,4′-bipyridinium dication (BPY2+)
and a neutral naphthalene di-imide (NDI) or pyromellitic di-imide (PMI) moiety, and (2) an electron
donor ring that can be symmetric for the presence of two identical DOB or DON units, or desym-
metrized by the presence of two different donors, that is, a TTF and a DON moiety. Interestingly,
the two 342+ and 372+ catenanes, containing four different donor and acceptor units, are fully desym-
metrized. In all the catenanes, the electron donor ring surrounds the better electron acceptor BPY2+
unit, and in the case of catenanes 342+ and 372+, the better electron donor TTF unit is located inside
the electron acceptor ring. Such conformations can be switched, altering the redox state of the
donors and acceptors incorporated in the structure, as evidenced by the rich and complex electro-
chemical patterns exhibited by these catenanes.
On the reduction side, the cyclic voltammogram of 322+ reveals four reversible monoelectronic
processes. Spectroelectrochemical experiments and comparison with suitable model compounds
[84,89] indicate that (1) the first process is consistent with the reduction of a BPY2+ unit engaged in
CT interactions inside the cavity of the donor ring; (2) the second reduction concerns the monore-
duced BPY+ unit, likely still inside the cavity of the donor ring; (3) the third process corresponds to
the reduction of the inside PMI unit (the translocation probably occurs upon reduction of the BPY+
unit to its neutral form); and finally, (4) the fourth reduction involves PMI−, on the position of which
relatively to the donor ring there is little information.
In catenanes 332+ and 342+, because of the stronger electron-donating power of the crown ethers
comprised in the structure, the BPY2+ unit becomes more difficult to be reduced than in catenane
322+ so that its second reduction overlaps with the first reduction of the PMI unit (Figure 12.24).
The reduction pattern of 332+ and 342+ (Figure 12.24a) consists therefore of three reversible
waves: (1) the first process concerns the monoelectronic reduction of the BPY2+ unit located inside
the donor ring as confirmed by spectroelectrochemical experiments (for 342+, Figure 12.24b); (2) the
second process, which involves the exchange of two electrons, can be unambiguously assigned to
the overlapping reduction of the inside BPY+ and the alongside PMI [90]; and (3) the third process,
which is monoelectronic, corresponds to the PMI−/2− reduction.
The conformation changes coupled with the four-electron reduction processes for the 322+–342+
PMI-containing catenanes are summarized in Figure 12.25.
O O O O O
+N
B C A 322+–372+
+N
O O O O O
A B C [2]Catenane
O O
–N N– 322+
O PMI O DOB DON
O O
–N N– 332+
O O
O O
S S
–N N– 342+
S S
O O TTF
O O
–N N– 352+
O O
NDI
O O
–N N– 362+
O O
O O
S S
–N N– 372+
S S
O O
FiGURE 12.23 General structure and component units of the desymmetrized catenanes 322+–372+.
In the case of the three 35 2+ –372+ NDI-based catenanes, the reduction pattern comprises
four reversible monoelectronic processes regardless of the nature of the donor rings. This
behavior can be explained considering that the NDI unit is easier to be reduced than PMI.
As a consequence, the processes observed can be assigned to BPY2+/+, NDI0/−, BPY+/0, and
NDI−/2−, respectively, in the order of increasing reduction potential. The proposed confor-
mational changes coupled with these four one-electron reduction processes are as follows
(Figure 12.26): (1) the electron donor ring remains around the BPY+ radical cation after the
first reduction; (2) the second reduction is indicated by spectroelectrochemical experiment to
be the NDI0/− process [90], and the potential value, more consistent with the reduction of the
NDI moiety in the alongside position, suggests that the donor ring still encircles the mono-
reduced BPY+ unit; (3) the remarkably negative potential value found for the third process,
assigned to the BPY+/0 reduction, is in agreement with the assumption that no translocation of
the donor component has occurred; and (4) the fourth process is attributed to the reduction of
5 6
1, 4
2
5 μA
–2.0 –1.5 –1.0 –0.5 +0.5 +1.0

(a) E (V vs SCE)
0.3
1 0 V vs Ag 4 0 V vs Ag
A
A 2 –0.60 V 5 +0.60 V
0.2 3 –0.90 V 6 +1.00 V
0.1
0.1
0 0
400 600 800 1000 400 600 800 1000

(b) λ (nm) (c) λ (nm)
FiGURE 12.24 Voltammetric and spectroelectrochemical response of catenane 342+ in CH3CN at room
temperature. (a) Cyclic voltammetric curve (conditions: 0.49 mM, tetraethylammonium hexafluorophos-
phate 73 mM as supporting electrolyte, 200 mV/s, glassy carbon working electrode). (b) Absorption spectra
observed before (full line) and after exhaustive reduction at −0.60 V (dashed line) and −0.90 V (dotted line)
versus an Ag quasireference electrode. (c) Absorption spectra observed before (full line) and after exhaustive
oxidation at +0.60 V (dashed line) and +1.00 V (dotted line) versus an Ag quasireference electrode. The num-
bered arrows in (a) mark the potential values at which the corresponding curves in (b) and (c) were recorded
in the spectroelectrochemical experiments. (From Ceroni, P., Credi, A., Venturi, M., and Schalley, C.A. eds.:
Analytical Methods in Supramolecular Chemistry. pp. 371–457. 2012. Copyright Wiley-VCH Verlag GmbH
& Co. KGaA. Reproduced with permission.)
the NDI− unit, on the position of which relatively to the donor ring, there is little information,
as noted previously for the PMI-based catenanes.
On the oxidation side, only the behavior of the fully desymmetrized catenanes 342+ and 372+
is discussed because they are particularly interesting from the viewpoint of molecular machines.
Their electrochemical patterns are very similar and consist of three oxidative processes (for 342+,
Figure 12.24a): the first two (Figure 12.24c) are assigned to the two consecutive monoelectronic
TTF oxidations [61], while the third one is ascribed to the oxidation of the DON unit.
BPY reduction
+ +1e– + +1e–
+ –1e– –1e–
–1e– +1e–
–2e– +2e–
PMI reduction
DOB–DOB 322+ –1e– +1e–

= DON–DON 332+
TTF–DON 342+
–
FiGURE 12.25 (See color insert.) The conformational changes associated with the four reduction processes
for catenanes 322+–342+. Horizontal and vertical processes represent the BPY-centered and PMI-centered
reductions, respectively. In the upper part of the scheme, gray arrows refer to the behavior of 322+, while black
arrows describe the behavior of 332+ and 342+. The dotted ellipses indicate that the interactions are turned off,
and there is little information about the donor ring location.
The first and second TTF oxidations exhibit the same features observed for the previously studied
catenane 314+ [58b,86] and can be interpreted as follows: after the TTF0/+ oxidation, the electron donor
ring circumrotates with respect to the electron-accepting ring, delivering the DON unit into its cavity.
This electrochemical study evidences that in the desymmetrized 322+–372+ catenanes, the inside/
alongside topological preference, dominated by the intercomponent CT interactions, can be modu-
lated reversibly upon reduction of the electron acceptors or oxidation of the electron donors in the
cases of fully desymmetrized 342+ and 372+ catenanes. Such a feature makes these catenanes appeal-
ing structures for the construction of molecular machines and, in a perspective, rotary motors.
It should also be noted that upon electrochemical stimulation in a relatively narrow and easily
accessible potential window, these interlocked molecules can be reversibly switched among several
(six and seven for 342+ and 372+, respectively) states, all characterized by distinct electronic and
optical properties. Such a possibility could open interesting routes for the development of molecular
electronic devices that go beyond binary logic.
Recently, a redox-switchable catenane composed of two interlocking 114+ macrocycles has been
reported, and the electrochemical switching between six experimentally accessible redox states
from within the total of nine states has been demonstrated [63].
A catenane composed of two identical benzylic amide macrocycles was also investigated by
cyclic voltammetry [91]. Computer simulation of the voltammetric data, together with quantum
chemical calculations, suggests that reduction of the macrocycles is followed by their irreversible
BPY reduction
+ +1e– +
+ –1e–
–1e– +1e–
NDI reduction
+ – +1e– –
–1e–
–1e– +1e–
2+
DOB–DOB 35
= DON–DON 362+
–
TTF–DON 372+
FiGURE 12.26 (See color insert.) The conformational changes associated with the four reduction processes
for catenanes 352+–372+. Horizontal and vertical processes represent the BPY-centered and NDI-centered
reductions, respectively. The dotted ellipses indicate that the interactions are turned off, and there is little
information about the donor ring location.
chemical soldering, owing to the formation of a C–C bond between two reduced carbonyl groups.
Hence, the electrochemical stimulus can be used to prevent the mutual rotation of the two rings,
although the irreversibility of the reaction limits further developments.
Other examples of electrochemically driven switching processes concern metal-based catenanes
[92–97], including heterodinuclear bis-macrocyclic transition-metal complexes [98].
A representative case is catenane [38•Cu]+ (Figure 12.27) that incorporates two identical macro-
cyclic components comprising terpyridine and phenanthroline ligands. The Cu(I) ion is coordinated
tetrahedrally by the two phenanthroline ligands, whereas the two terpyridine ligands are located
well away from each other [97].
The cyclic voltammogram of [38•Cu]+ contains a reversible wave (+0.63 V relative to the SCE)
associated with the tetracoordinated Cu(II)/Cu(I) redox couple. The visible absorption spectrum
of the catenane contains a metal-to-ligand charge-transfer band at 439 nm for the tetracoordinated
Cu(I) chromophore. On electrochemical oxidation of [38•Cu]+ or on treatment with NOBF4, the
tetracoordinated Cu(I) center is converted into a tetracoordinated Cu(II) ion that has an absorp-
tion band at 670 nm. The intensity of this band decreases with time, however. Indeed, in response
to the preference of the Cu(II) ion for a coordination number higher than four, one of the two
macrocycles circumrotates through the cavity of the other, affording a pentacoordinated Cu(II)
ion. Subsequently, the other macrocycle undergoes a similar circumrotational process, yielding a
hexacoordinated Cu(II) ion, which gives, instead, a weak absorption band at 687 nm. Electrolysis
(−1.0 V) of the acetonitrile solution of the catenane reduces the hexacoordinated Cu(II) center back
to a hexacoordinated Cu(I) ion. In response to the preference of Cu(I) for a tetracoordinated geom-
etry, the two macrocycles circumrotate through the cavity of each other in turn, affording the origi-
nal conformation quantitatively.
O +
O
N N
N N –e–
N CuI N CuII
N N
N N
O O
[38 Cu]+
CuI CuII
+e–
CuI CuII
[38 Cu]2+
FiGURE 12.27 Circumrotation of the macrocyclic components of catenane [38•Cu]+ controlled reversibly
by oxidizing–reducing the metal center.
D. MoLECULar MaCHINES WorkING oN SUrFaCES

As already noticed, the design, synthesis, and operation of multicomponent molecular systems capa-
ble of performing specific, directional mechanical movements under the action of a defined energy
input—namely, molecular machines—constitute a fascinating challenge in the field of nanoscience.
Most of these studies have been performed in solution where a huge number of molecules behave
independently from one another because they cannot be addressed individually and hence con-
trolled. Such an incoherent behavior is the major impediment to designing and realizing systems
capable of performing useful functions. It seems, therefore, reasonable that for several real applica-
tions, the molecular machines have to be interfaced with the macroscopic world by ordering them
in some way so that they can work coherently and can be addressed in space. Viable possibilities
include deposition on surfaces, incorporation into polymers, organization at interfaces, or immobi-
lization into membranes or porous materials [99–107].
1. Molecular Machines Immobilized on Electrodes

The formation of SAMs on metallic gold is an effective yet simple method to attach molecules to
surfaces [24]. Rotaxanes with suitable functionalization have been extensively employed to prepare
Fast
e–
Fe O
+N +
N NH
O
S N S
Au N N Au N N
N H H O
N N
N
+N N+
O H
394+
Trans-40
+2e– –2e– Vis UV

e–
Slow
Fe O
NH
N N+
H O
O N
Au S N Au N
N N O H
N S
N
+N N
H N
N
cis-40
(a) (b)
FiGURE 12.28 (a) The electrochemically driven ring shuttling in rotaxane 394+ incorporated into an
Au-SAM. (b) The surface-bound photoswitchable rotaxane 40 capable of transducing an optical signal into an
electronic signal by means of the photocontrolled ring shuttling.
Au-SAMs [108,109]. The first studies on mechanical shuttling in a SAM, however, were carried out
on systems in which the molecular components became mechanically interlocked as a consequence
of surface immobilization [110]. In this setting, the metal surface plays the dual role of a stopper
and an interface (electrode).
A monolayer of the rotaxane 394+ (Figure 12.28a), consisting of the electron-accepting cyclo-
phane 94+ threaded on a molecular axle, which includes an electron-donating di-iminobenzene unit
and is stoppered by an adamantane moiety, was assembled on a gold electrode [110b].
The tetracationic ring, which is originally located on the di-iminobenzene unit by virtue of elec-
tron donor–acceptor interactions, is displaced toward the electrode upon one-electron reduction of
its two bipyridinium units at −0.53 V versus the SCE, owing to disruption of the donor–acceptor
interactions and electrostatic attraction to the electrode (Figure 12.28a). Reoxidation of the reduced
cyclophane at −0.33 V versus SCE causes ring shuttling to the original di-iminobenzene site.
The position of the tetracationic and dicationic (reduced) cyclophane rings and the shuttling
rate constants (80 s−1 and 320 s−1 at 298 K for reduction- and reoxidation-induced processes,
respectively) were determined by chronoamperometry and impedance measurements. Investigation
of the temperature dependence of the shuttling rates showed [110c] that the reduction-induced
shuttling is an energetically downhill process with no measurable activation barrier, whereas
reoxidation-induced shuttling requires thermal activation. The lack of an energy barrier in the for-
mer case is in agreement with the fact that the shuttling is mainly driven by coulombic attraction
of the still positively charged cyclophane toward the negatively polarized electrode. Therefore,
ring shuttling does not need assistance by thermal energy, in contrast to the typical operation of
molecular motors.
The surface-bound rotaxane trans-40 (Figure 12.28b) consists of a ferrocene-functionalized
β-CD macrocycle threaded on a molecule containing a photoisomerizable azobenzene unity and
a long alkyl chain [110a]. A monolayer of trans-40 was self-assembled on a gold electrode. The
azobenzene unit in the trans configuration is complexed by β-CD; photoisomerization to the cis
form renders complexation sterically impossible, so that the β-CD ring is d isplaced to the alkyl
component. Back-photoisomerization restores the original trans configuration. The position of
the β-CD-tethered ferrocene unit was determined by chronoamperometry. A fast current decay
(k = 65 s−1) was observed for the trans isomer, implying that the ring component is close to the
electrode surface (Figure 12.28b). Photoisomerization of the monolayer to the cis state resulted
in a chronoamperometric transient characterized by a substantially lower electron transfer rate
(k = 15 s−1). This result indicates that in cis-40, the β-CD ring is more distant from the elec-
trode surface. Owing to the reversibility of azobenzene photoisomerization, a cyclic pattern
for the rate constant of the heterogeneous electron transfer process was observed. In this opto-
electronic system, optical information is transduced by a mechanical shuttling to an electronic
signal [110,111].
Another clever approach involves the immobilization of bistable molecular shuttles containing
a pyridine residue in the macrocyclic component onto an Au-SAM of 11-mercaptoundecanoic acid
[112]. The grafting is achieved because of the formation of hydrogen bonds between the pyridine
unit of the rotaxane molecules and the carboxylic groups at the top of the SAM. Electrochemically
driven shuttling in one of these systems was shown to occur on the millisecond timescale by chro-
noamperometry [112b].
Surface-mounted molecular rotary motors are also extremely interesting, both from a basic
viewpoint [113] and because they could find applications in a variety of molecular-size devices
and machines, for example, in the fields of nanoelectronic, nanophotonics, and nanofluidics [114].
A family of molecular rotors (e.g., compound 41 in Figure 12.29a) has been designed to perform
rotation under electrochemical stimulation [115–117].
The molecules have a piano-stool structure with a stator meant to be grafted on an oxide surface
and a rotor bearing redox-active groups, so that addressing the molecule with nanoelectrodes would
trigger rotation (Figure 12.29b). To avoid intramolecular electron transfer between two electroactive
units, which would compete with rotation, insulating spacers based on platinum acetylide units were
inserted into the structure, but several difficulties remain to be overcome.
2. Solid-State Electronic Circuits

The redox-switching behavior observed for solid-supported thin films of bistable catenanes [118]
and rotaxanes [108ab,109a] encouraged attempts to incorporate such molecules in electrically
addressable solid-state devices [119].
A Langmuir monolayer of the TTF–DNP rotaxane 424+ (Figure 12.30a) was transferred onto a
photolithographically patterned polycrystalline silicon electrode [120].
The patterning was such that the film was deposited along several parallel lines of poly-Si on
the electrode. A second set of orthogonally oriented wires was then deposited on top of the first set
such that a crossbar architecture is obtained. This second set of electrodes consisted of a 5 nm thick
layer of Ti, followed by a 100 nm thick layer of Al. By this approach, an array of junctions, each
one addressable individually, was constructed (Figure 12.30b). In the first setup, the wire electrodes
were a few micrometers wide, but the scalability of the fabrication method allowed the construction
of wires less than 100 nm in width, yielding junctions with areas of 0.005–0.01 μm2 and containing
about 5000 rotaxane molecules [119].
The mechanism for conduction is by electron tunneling through the single-molecule thick layer
between the junction electrodes. Thus, any change in the electronic characteristics of the inter-
electrode medium is expected to affect the tunneling efficiency and change the resistance of the
junction. It should be noticed that such devices are conductors, not capacitors. Experiments were
carried out by applying a series of voltage pulses (between +2.0 and −2.0 V) and reading, after each
pulse, the current through the device at a small voltage (between +0.2 and −0.2 V) that does not
Fe
Et3P–Pt–PEt3
Fe Fe
PEt3 Et3P
Pt Pt
Et3P PEt3
Et3P PEt3
Pt Pt
Fe PEt3 RuII Et3P Fe
N N
N N N
N
B
O O
O H O
O
O
(a) 41
e–
+ – + + 1 –
1
2 2
5 5
4 3 3
4
e– e–
+ + 5 – + + –
5
1 1
4 4
2 2
3 3
(b)
FiGURE 12.29 (a) Molecular rotor 41 designed to perform rotation under electrochemical stimulation in a
nanoelectrode junction. (b) Schematic representation of the proposed operation mechanism. A potential dif-
ference applied across the nanojunction results in oxidation of the ferrocene group nearest the anode, which
is then electrostatically repelled away toward the cathode. The oxidized unit close to the cathode is reduced,
while a new ferrocene unit is oxidized at the anode. Overall, the passage of each electron across the nanojunc-
tion results in the clockwise rotation of the upper part of the molecule by one-fifth of a turn. (From Balzani, V.,
Credi, A., and Venturi, M.: Molecular Devices and Machines, 2nd edn. p. 492. 2008. Copyright Wiley-VCH
Verlag GmbH & Co. KGaA. Reproduced with permission.)
424+ O O OCH3
N+
+
N O O OCH3
O O O
O O O S S
O O O
S S
DNP O O OCH3
TTF
+N N+
(a)
Ti-Al
+
Poly-Si
(b)
FiGURE 12.30 (See color insert.) Structure formula of bistable rotaxane 424+ (a) and schematic representa-
tion of solid-state junctions consisting of a monolayer of 424+ sandwiched between poly-Si and Ti-Al crossbar
electrodes (b). (From Silvi, S., Venturi, M., Credi, A., J. Mater. Chem., 19, 2279–2294, 2009. Reproduced by
permission of The Royal Society of Chemistry.)
affect switching. The current (read)–voltage (write) curve displays a highly hysteretic profile, mak-
ing the rotaxane junction device interesting for potential use in RAM storage.
The current–voltage curve was interpreted on the basis of the mechanism illustrated in Figure 12.31,
which is derived from the behavior of the same rotaxane in solution [87]. Coconformation A is the
switch open state and coconformation D the switch closed state of the device. When the TTF unit of
424+ is oxidized (+2 V, state B), a coulombic repulsion inside the tetracationic cyclophane component
is generated, which causes the displacement of the latter and formation of state C in which the ring
encircles the DNP unit (note that, in solution at +2 V vs SCE, TTF undergoes two-electron oxidation
and DNP is also oxidized [121]). When the voltage is reduced to near-zero bias, a metastable state
D is obtained, which, however, does not return to state A. The initial coconformation can in fact
be restored only via states E and F in which the bipyridinium units of the cyclophane component
are reduced (in solution, at the potential value used, −2 V, each bipyridinium unit undergoes two-
electron reduction [121]). Most likely, the reduction of the bipyridinium units weakens the charge-
transfer interaction with the DNP unit, thereby decreasing the barrier that hinders the replacement
of the cyclophane on the TTF site. An analogous mechanism was used to interpret the behavior
of solid-state devices containing other TTF-based bistable interlocked molecules [119–122]. The
metastable state corresponding to coconformation D (Figure 12.31) was in fact observed for a num-
ber of different bistable rotaxanes and catenanes in a variety of environments (solution, SAM, and
solid-state polymer matrix) [123].
More recently, by the use of the same paradigms and the same bistable rotaxane 424+ described
earlier, a molecular electronic memory with an amazingly high density of 1011 bits cm−2 was con-
structed by sandwiching a monolayer of the rotaxane between arrays of nanoelectrodes in a crossbar
arrangement [124]. The realization of this device relies on a novel method for producing ultradense,
highly aligned arrays and crossbars of metal or semiconductor nanowires with high aspect ratios
[125]. It was estimated that each junction acting as a memory element consists of approximately 100
rotaxane molecules. For practical reasons, only 128 (16 × 8 contacts) of the 160,000 memory cells
Ti-Al
–2e –2e
Poly-Si
F A B
+2e +2e
E D C
–2 0 +2
E (V)
FiGURE 12.31 (See color insert.) Operation mechanism of solid-state molecular electronic switching
devices based on bistable molecular shuttles like 424+. (From Silvi, S., Venturi, M., Credi, A., J. Mater. Chem.,
19, 2279–2294, 2009. Reproduced by permission of The Royal Society of Chemistry.)
(400 × 400 nanowires) contained in the circuit were tested [124]. The measurements showed that
25% of the tested cells displayed good and reproducible switching, whereas 35% failed because of
bad contacts or shorts, and the remaining 40% showed poor switching. This work is a compelling
demonstration that the combination of top-down and bottom-up nanofabrication methods can lead
to outstanding technological achievements. However, several aspects—such as stability, reliability,
and ease of fabrication—need to be optimized before these systems can find real industrial applica-
tions [126].
3. Electrochemically Induced Shuttling in Single Rotaxane Molecules

Experiments on individual motor protein molecules have been crucial to understand their working
mechanism [127]. The control and observation of motion of single artificial molecular machines
is indeed a very challenging and highly stimulating task. In fact, while detailed kinetic and ther-
modynamic information on the machine and its working mechanism can be determined from
ensemble experiments, the functionality as a nanoscale device can only be investigated by operat-
ing the system at the single molecule level. Although fluorescence microscopy can be useful in some
cases [128], this kind of studies requires the use of scanning probe microscopy (SPM) techniques
[129,130]. Several investigations have shown that movements of single molecules deposited on sur-
faces can be induced and observed by using an SPM tip. Among targeted systems are molecular
rotors [113,131], polyrotaxanes [132], catenanes [133], wheelbarrows [134], rack-and-pinion devices
[135], gears [136], and nanovehicles [137].
In a remarkable investigation, bistable rotaxane molecules similar to those described in
Section IV.D.2, behaving as redox-controlled molecular shuttles in solution, were anchored
laterally on gold surfaces and investigated using an electrochemical scanning tunneling micro-
scope (STM) [138]. The rotaxane molecules (43 4+ in Figure 12.32) were bound at each end to
a Au{111} surface by means of the disulfide groups attached to the stoppers on the dumbbell
termini.
+ + 434+
N N
O
O O O O
O O O O S S
O O O O O O
O S S
S
S
S +N N+
S
–e–
+ + +
+ +
+e–
FiGURE 12.32 (See color insert.) Structure of the bistable rotaxane molecule 434+ adsorbed on Au{111}
and schematic representation of its redox-induced shuttling motion investigated using electrochemical scan-
ning tunneling microscopy.
The molecules were assembled with a surface coverage of 5–6 molecules/1000 Å2 in orien-
tations conducive to direct STM measurements of their station changes. The molecules were
imaged at two different electrode potentials, +0.12 and +0.53 V versus Ag/AgCl, for which the
TTF station is in the reduced (neutral) state and in its oxidized (cationic) state, respectively.
A displacement of the tetracationic ring was observed and correlated with the redox states of the
TTF station. The displacement exhibits partial reversibility upon stepping the potential back to
+0.12 V. The trajectories of the rings determined from imaging of many such molecules suggest
that the motion of the ring relative to the dumbbell in a surface-adsorbed molecule is affected
by its local environment and the flexibility of the molecule [138]. It is envisaged that rotaxanes
with rigid dumbbell components should enable a better visualization and exhibit consistent and
reversible motion.
4. Electrically Driven Directional Motion of a Single Molecular Machine

Single molecules that can move in a controlled manner on a nonmodified surface in response to
external stimuli have to use chemical, electrical, or light energy to modulate their interaction with
the surface in a way that generates motion. This extremely challenging objective was recently
achieved with a nanocar molecule 44 (Figure 12.33a) that comprises four rotary motor units as
the wheels [139]. Such units undergo unidirectional rotation of the fluorene moieties around the
C=C double bond as a result of sequential configurational and conformational switching processes
induced by electronic (e.g., light) and vibrational (e.g., thermal) excitation, respectively [140]. The
direction of rotation of each motor unit is dictated by its chirality. As it is known that conforma-
tional and configurational switching of molecules on surfaces can be obtained by STM-induced
vibrational and electronic excitations, it was envisaged that an STM tip could bring about the rotary
motion of the motor units of 44 and, at the same time, afford single molecule imaging.
After deposition onto a Cu{111} surface by sublimation, individual 44 molecules were imaged
with an STM at 7 K. Imaging conditions are sufficiently mild that no changes are induced upon con-
tinuous scanning, whereas electronic and vibrational excitations of the molecule are induced upon
application of appropriate voltage pulses to the STM tip. A translational motion of the molecule
across the surface should be observed if the four motors all rotate in the same direction, a require-
ment that is only met by the meso-(R,S-R,S) isomer sketched in Figure 12.33a. This is indeed what
was observed in the experiments [139].
Additional support for the electrically driven directional motion comes from investigations aimed
at probing the effect of the chirality and geometry of the molecule on its motion. For example, two
R R
N N
S S
meso-(R,S-R,S)-Y
(a)
meso-(R,S-R,S) meso-(R,S-R,S) (R,R-R,R) enantiomer

''correct landing'' ''wrong landing''
(b)
FiGURE 12.33 (See color insert.) (a) Structure and cartoon representation of the meso-(R,S-R,S) isomer
of the four-wheeled molecule 44. (b) Schematics of the directionality of the motion induced by the concerted
rotation of the motor units. The arrows indicate the direction in which the rotary action of the individual motor
units propels the molecule on the surface. Two distinct landing geometries of the meso-isomer lead either to
directional movement (left) or to no movement at all (center), whereas (R,R-R,R) (right) or (S,S-S,S) enantio-
mers move randomly.
geometries must be considered for the meso-isomer because free rotation around the bis-alkyne C–C
single bond of the frame (gray arrow in Figure 12.33a; pink in the color insert) is locked upon adsorp-
tion (Figure 12.33b). When the meso-isomer is adsorbed on the surface in the proper orientation
(correct landing), conrotatory motion of the four motor units moves the molecule along. Conversely,
in the wrongly landed meso-isomer, the effects arising from the movement of the motor units cancel
out, thereby precluding translation. The individual (R,R-R,R) or (S,S-S,S) enantiomers of 44 trans-
ferred on the surface from the racemic mixture of the compound were found to spin and randomly
move across the surface [139]. This behavior can be explained considering that the motor units on
opposite sides of the molecule rotate in a disrotatory fashion, ideally causing the molecules to spin; in
a nonideal case, the molecules exhibit random translational motion in addition to the spinning motion.
These pioneering experiments demonstrate that a single molecule with intrinsic motor functions
is capable of converting an external energy input into directional motion along a surface and that
the type of movement is a direct consequence of the molecular design.
In this chapter, we showed that redox active complex systems, as the supramolecular devices here
described, can be fully characterized by using the various kinds of electrochemical techniques.
They provide indeed a fingerprint of the analyzed systems giving fundamental information on (1)
the spatial organization of the redox sites within the molecular and supramolecular structure, (2) the
entity of the interactions between such sites, and (3) the kinetic and thermodynamic stabilities of
the reduced/oxidized and charge-separated species. Electrochemistry is, therefore, a powerful tool
to read the state of the system.
A further aim of this chapter is to evidence that in suitable designed systems, electrochemis-
try can play a more important role. By causing the occurrence of endoergonic electron transfer
processes, electrochemistry can, indeed, provide the energy needed to modify the noncovalent
interactions that stabilize a certain structure promoting mechanical movements. In such cases,
electrochemistry plays the dual role of writing and reading a system: by means of electrons and/
or holes, it supplies the energy to make these systems work as molecular machines, and by means
of the various electrochemical techniques, it is used for controlling and monitoring the operation
performed by the system. In this regard, selected examples of molecular machines have been
described. They show that, although investigations in solution are fundamental to understand the
operation mechanisms of such systems, an important step for any kind of applications in technol-
ogy requires that they are interfaced with the macroscopic world and ordered in some way so
that they can behave coherently and can be addressed in space. Another important challenge is
the control and observation of the motion of single artificial machines. The recent achievements
obtained in these directions, some of which have been reviewed here, seem to indicate that use-
ful materials and devices based on artificial molecular machines will see the light in a not too
distant future.
The systems described here evidence that electrochemists have learned how to deal with increas-
ingly complex molecular and supramolecular structures. However, it must be noticed that elec-
trochemistry is only a part of the game. As the complexity of the systems studied increases, the
contribution from many disciplines in a joint and collaborative effort is needed. The goal of trans-
forming molecular devices and machines into practically useful products requires, indeed, that
people belonging to different fields, like chemistry, solid-state physics, biology, computer science,
mathematics, materials sciences, etc., work together and learn a common language.
AckNOwLEDGMENTS
Financial support from Ministero dell’Università e della Ricerca (PRIN 2010CX2TLM "InfoChem"
and FIRB 2010RBAP11C58Y "Nanosolar") and Ministero degli Affari Esteri e Cooperazione
Internazionale (Progetto Italia-USA) is gratefully acknowledged.
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13 Proton-Coupled
Electron Transfers
CONTENTS
I. Introduction ............................................................................................................................ 481
II. Modeling Electrochemical-Concerted Electron and Proton Transfer Reactions ................... 483
A. Thermodynamics ............................................................................................................ 483
B. Modeling Concerted Proton–Electron Transfer Kinetics ............................................... 485
III. Competition between Stepwise (EPT and PET) and Concerted (CPET) Pathways ............... 488
IV. Intrinsic Characteristics of CPET Processes .......................................................................... 494
A. Similarity and Differences between ET, CPET, and CDET ........................................... 494
B. Hydrogen-Bonded Systems ............................................................................................. 496
C. Water (in Water) as Proton Acceptor ..............................................................................500
V. CPET for Bond Activation ...................................................................................................... 505
A. Breaking Bonds with Protons and Electrons .................................................................. 505
B. Activation of Molecules .................................................................................................. 507
VI. Concluding Remarks .............................................................................................................. 507
References ...................................................................................................................................... 508
I. INTRODUcTiON
The coupling between electron and proton transfers has a long experimental and theoretical history
in chemistry and biochemistry. Proton-coupled electron transfer (PCET) reactions also play a criti-
cal role in a wide range of biological processes, including enzyme reactions, photosynthesis, and
respiration. PCET is employed here as a general term for reactions in which both an electron and a
proton are transferred, either in two distinct steps or in a single step [1]. We term the latter mecha-
nism concerted proton and electron transfer (CPET) [2]. Other terms have been used in the literature
to describe the same mechanism: electron transfer–proton transfer (ETPT) [3], or electron–proton
transfer (EPT) [4], or multiple site–electron proton transfer (MS–EPT) [5]. Reactions in which the
electron and proton transfers occur between the same donor and acceptor, that is, hydrogen-atom
transfer, are not considered here. We are mainly interested in electrochemical PCET reactions in
which electrons are flowing into or from an electrode, while protons are transferred between an acid
and a base.
Among the various ways of injecting or removing electrons, molecular electrochemistry, through
nondestructive techniques such as cyclic voltammetry, has proved very useful in characterizing
electron transfers (ETs) and deciphering mechanisms where chemical reactions, for example, proton
transfer, are associated with ET [6]. This approach possesses several advantages. In the context of
PCET, separation of the ET (the electrode) and proton transfer sites, required to distinguished CPET
reactions from H-atom transfers, is readily achieved. Additionally, changing the electrode potential
is an easy way of varying the driving force of the reaction and the current is an online measure of
the reaction kinetics. It is, however, important to note that other injection or removal modes of the
electron through thermal homogeneous reaction or photoinduced reaction can be used and that
481
QA
O2 13.4
P680
2H2O P680
S0
S4 S1 PheoD1
P680 P680+
P680+ P680
S3 S2
10.6 11.1
P680 P +
680 8.2
ChlD1
(a) (b) ChlD2
10.2 10.4
PD1 PD2
13.8
GIn 165 TyrZ
CP43–Arg 357 Tyrz 5.1
D1 H190
Ala 344
2.6 4.9 OEC
CP43–Glu354 Ca 2.5 Mimic
1.7 Glu 189
2.5
Asp 170 2
2.4
4
2.1
3
1.8 H
1
2.5 2.3 2.2 2.4
2.2 O N
Asp 61 But
Asp 342 His 332
Glu 333
His 337
tBu
(c) (d)
SchEME 13.1 (See color insert.) Schematic view of photosystem II. (a) Kok cycle. (b) Structure of the
reaction center of photosystem II showing the TyrZ –ChlD1(P680)–PheoD1–QA donor–chromophore–acceptor
system, electron transfer from tyrosine (TyrZ) being coupled to proton transfer from histidine D1 H190. OEC,
oxygen evolving complex. (c) One proposed schematic view of the OEC Mn4Ca Ala, alanine; Arg, arginine;
Asp, aspartate; Glu, glutamate; His, histidine. The numbers are the distances in angstroms. In the labeling
scheme, amino acids in black are in the first coordination sphere and those beyond in gray. (d) Aminophenol
mimicking the TyrZ –histidine couple.
comparison of results obtained from various methods can be useful for a complete understanding
of the PCET processes. Likewise, the electrochemical approach can be used to investigate PCET
reactions taking place in a homogeneous context. Photosystem II (PSII) is a typical example of this
approach. As shown in Scheme 13.1, oxidation of tyrosine in PSII is part of the charge transfer path-
way between the chromophore and the oxygen-evolving complex (OEC). Oxidation of the tyrosine
residue is coupled to proton transfer to a nearby histidine. To study the possible mechanistic path-
ways of such PCET, electrochemical investigation of a mimic (see Scheme 13.1) has proved useful
as detailed later on in this chapter.
As depicted in Scheme 13.2, PCET may follow either stepwise or concerted mechanisms.
Thermodynamic and kinetic characterization of these pathways is the first purpose task of this
chapter. In the discussion, it will appear that two conditions are required to favor concerted pro-
cess vs. stepwise pathways: a favorable thermodynamical situation corresponding to high-energy
intermediates in stepwise pathways and intrinsic favorable parameters corresponding mainly to the
requirement of short distances between the proton donor and acceptor. A large part of this chapter
is thus devoted to illustrating the dichotomy of the stepwise vs. concerted competition for PCET
reaction controlled by thermodynamic parameters. Then, the intrinsic parameters of concerted
pathways will be analyzed with particular emphasis on the role of hydrogen bond (H bond), H-bond
relays, and ultimately peculiar behavior of water (in water) as proton acceptor.
This chapter ends with a discussion on the implication of CPET in the activation of molecules.
Although coupling of proton transfer to ET has a long history in organic electrochemistry involving
Proton-Coupled Electron Transfers 483
EPT
–e–
XR H + B X OH + B
–e–
–
+e
CPET
–e–
R
X + HB + XO + HB+
+e+
PET
SchEME 13.2 One-electron/one-proton PCET mechanistic scheme.
in particular carbon acid–base reactions [6], the examples discussed in this chapter are related to
oxygen or nitrogen acid–base due to their involvement in biological systems [7] or small molecules
activation in the context of contemporary energy challenges [8].
II. MODELiNG ELEcTROchEMicAL-CONcERTED ELEcTRON

AND PROTON TRANSfER REAcTiONS
A. THErMoDYNaMICS
The global equation for a one-electron/one-proton PCET reaction (Scheme 13.2) reads
X R H + B X O + e − + BH +
It is thermodynamically characterized by a standard potential,
µ 0XO + µ 0BH+ − µ 0XR H − µ0B

EX0 O + BH+ /XR H+B =
F
(the μ0 are the standard chemical potentials of the subscript species) shown on the oblique straight
line of the Pourbaix diagram of Figure 13.1, which relates the equilibrium potential when [XRH] =
[XOH], or apparent standard potential, Eap0 , to the pH of the solution
RT ln 10
Eap0 = EX0 O ,H+ /XR H − pH (13.1)
F
In this representation, the nature of the acid–base couples involved does not matter insofar the reac-
tions are all at equilibrium. The standard potential involved in Equation 13.1 may thus be equated to
µ 0XO + µH0 + − µ 0XR H

EX0 O ,H+ /XR H = ,
F
which does not refer to any particular acid–base couple and in which µ 0H+ is the standard chemical
potential of the proton in the solvent under consideration whatever the structure of the solvated
proton.
Besides the oblique line, the Pourbaix diagram also shows two horizontal lines corresponding
to the standard potential of the protonated and deprotonated redox couples: Eap0 = EX0 OH/XR H and
Eap0 = EX0 O /XR , respectively.
E0ap
XOH
E0EPT
XO
E0CEPT
XRH
E0PET
XR
pH
pK pK
XOH XRH
pKHB (= 0 if HB = H2O)
FiGURE 13.1 Thermodynamics of PCET reactions (Scheme 13.2) and Pourbaix diagram.
Overall, the Pourbaix diagram (Figure 13.1) provides a map of the zones of thermodynamic
stability of the various species involved. The standard potential corresponding to a specific acid–
base couple may thus be derived from the Pourbaix diagram by formally equating the pH to the
pK of this acid–base couple, as pictured in Figure 13.1. For, for example, water, which is the proton
acceptor in a number of cases, the pertinent standard potential is the value of Eap0 at pH 0 and not a
“standard potential” that would depend on the pH of the aqueous solution.
In the earlier mentioned thermodynamic analysis, we have implicitly assumed that the activity
coefficient of all intervening species is equal to unity. If not the case, the activity coefficient, γ,
should be introduced in the standard chemical potential by replacing in the aforementioned equa-
tions, μ0 by μ0 + RT ln(γ).
With reference to Scheme 13.2 and Figure 13.1, reactions going from XRH into XO and reverse
may follow stepwise pathways (EPT for ET followed by proton transfer or PET for proton transfer
followed by ET) and thus requires the intermediacy of XOH or XR intermediates. Alternatively or
competitively, a concerted mechanism involving an acid–base couple HB/B as proton donor/accep-
tor couple, characterized by pKHB, may take place, thus skipping these intermediates.
Distinction and competition between these mechanisms rest on kinetics, but the thermodynamic
framework provided by the driving force characterizing each pathway is an essential requisite (the
driving force of a reaction is here precisely defined as the opposite of the standard free energy of
this reaction, −ΔG 0). The two stepwise reaction pathways are governed by two driving forces, one
for ET and one for proton transfer, whereas there is a single driving force for the CPET pathway:
EPT :
−∆GET
0
( )
= F E − EX0 OH/XR H , − ∆GPT
0
= RT ln 10 ( pK HB − pK XOH )
PET :
−∆GP0T = RT ln 10 ( pK HB − pK XR H ) , − ∆GET
0
(
= F E − EX0 O /XR )
CPET :
−∆GCPET
0
(
= F E − EX0 O +HB/XR H + B )
(E is the electrode potential, or for homogeneous ETs, the standard potential of the redox couple
that provides or receives the electrons to or from the system). It is important to emphasize that, for
a given proton donor/acceptor couple HB/B, the CPET driving force does not depend on pH [9–11].
Results on the oxidation of tyrosine and tryptophan in water have been interpreted as resulting
from a CPET reaction with water as the proton endowed with a pH-dependent driving force, in the
framework of a brute-force application of the Marcus theory for outer sphere ET (see Figure 13.4
XRH + B XRH ... B XO ...HB+ XO + HB+
SchEME 13.3 Hydrogen bonding in CPET pathway.
in Reference 11a and Figure 13.5 in Reference 11b). This notion of pH-dependent driving force is
nothing else than contradictory to the second law of thermodynamics.
It should also be noted that CPET reactions may involve hydrogen bonding as sketched in
Scheme 13.3. Examples will be given in Section IV.B.
Kinetic analysis of the stepwise pathways (EPT and PET) follows the classical treatments of EC
and CE reaction schemes, in, for example, cyclic voltammetry where a precise description of the
various possible cases (kinetic control by ET and/or chemical reaction) is available [6]. In contrast,
CPET processes require modeling of the kinetics, leading to the formulation of a rate law as dis-
cussed in Section II.B.
B. MoDELING CoNCErTED ProToN–ELECTroN TraNSFEr KINETICS

The following equation is a general expression of the rate law that relates the current density I to
the reductant and oxidant concentrations at the electrode surface and to the driving force F(E − E 0).
I   F ( E − E 0 )  
= k ( E ) [ Red]0 − [Ox]0 exp  −  (13.2)
F   RT  

k(E) has then to be derived in the case of a CPET elementary step. Electrochemical CPET has been
investigated theoretically by several groups [12–16]. The main item of CPET theories is a double
Born–Oppenheimer approximation, which treats the electron as a fast subsystem with respect to
the proton and treats the proton as a fast subsystem with respect to the degrees of freedom of the
medium, as in proton transfer theories [17–21].
The four diabatic states are then mixed to generate two states that are adiabatic toward proton
transfer as represented in Figure 13.2. In a CPET step, both electron and proton are transferred at the
transition state corresponding to the crossing of these generated states where reactants and products
have the same configuration. This configuration is reached through harmonic vibration of an envi-
ronment bath representing the medium and describing the long-range electrostatic interaction of the
system with a polarizable continuum and harmonic vibration of local dispersion modes, typically,
the proton donor–acceptor vibration (Q mode) coupled to additional internal vibrations. It follows
that the medium and the local mode interactions contribute to the reaction rate independently. The
medium is treated classically and appears as a reorganization energy noted λ 0 in the expression of
the reaction activation energy. At high temperatures with respect to internal vibration modes, their
contribution also appears as a reorganization energy, noted λi, in the activation energy. Thanks to
the harmonic approximation, the expression of the CPET rate constants thus coincides with the clas-
sical Marcus–Hush [22,23] formula for a simple nonadiabatic ET:
 −λ  F (E − E 0 ) 
2

k ( E ) = Z exp  1 −   (13.3)
 4 RT  λ  
 
in which Z is a preexponential factor detailed in the following text and λ = λ0 + λi is the total reor-
ganization energy. These rate constants must be averaged over the electron energy in the electrode
as in the Marcus–Hush–Levich development [24].
Potential
energy
XOH..B e– XR ..HB+
XRH..B XO ..HB+
ZPE≠ H +
H+ coordinate (q)
ΔG≠
E – E0CPET
XR ..HB+
XRH ..B XOH...B

ZPER
XO ..HB+
H+ coordinate (q) ZPEP
H+ coordinate (q)
Heavy-atom reaction
Coordinate
FiGURE 13.2 CPET pathway. Both reactant and product electronic states potential energies as function of
heavy-atoms reaction coordinate are described by parabolas. Inserts show potential energies as function of
proton coordinate.
The preexponential factor contains information regarding the coupling of the two electronic
states, characterized by a coupling constant C. If C is small, a fully nonadiabatic regime is
reached, and C = HET〈χi|χ f〉 where HET is the electron coupling constant and 〈χi|χ f〉 the overlap
between the initial and final proton vibrational wave functions. A partially adiabatic transition
takes place when the electron coupling constant HET is sufficiently large, whereas the resonance
splitting of the proton levels remains small. The rate constant remains the same, but the coupling
constant C is now described by a tunneling probability for the proton through a potential barrier:
 q
 f 
2π 

∫
2m p (V (q) − E ) dq  
≠
C (Q) = hν exp −
0
 h  
  qi  

where
Q is the distance between the donor and acceptor atoms
q is the proton coordinate
ν 0≠ is the proton well frequency
mp is the proton mass
qi and q f are the classical turning points in each well at fixed Q
It follows that the transition probability χ is a function of Q to be averaged according to

+∞
χ=
∫ −∞
χ(Q)P(Q)dQ over the Boltzmann distribution P(Q). For a fully adiabatic transfer, the trans-
mission coefficient is 1. The link between these limiting cases is given by the Landau–Zener transi-
tion probability [25,26] χ, being given by
2p
χ= (13.4)
1+ p
In Equation 13.4, p is the probability of proton tunneling and ET taking place at the transition
state as sketched in the upper insert of Figure 13.2. p is obtained from the Landau–Zener expres-
sion [27]:
  C  2
πRT 
p = 1 − exp  −π   (13.5)
  RT  λ 
 
Note that in a more refined development, electrochemical CPET rate constant expressions are
derived that interpolate between nonadiabatic limits being defined in terms of weak vibronic cou-
pling and fast solvent relaxation and solvent-controlled regimes defined in terms of strong vibronic
coupling and slow solvent relaxation. In this chapter, we ignore solvent relaxation effects. As a result
of the aforementioned derivation and (1) assuming that the electrochemical reaction takes place at a
given distance from the electrode, (2) taking into account the multiplicity of the electrons’ electronic
states in the electrode, and (3) considering the fact that the potential excursion in cyclic voltammetry
does not exceed a few hundred millivolts thus allowing linearization of the quadratic term, the rate
law (Equation 13.3) may be recast as [28]
4πλ  −λ   F (E − E 0 )   F (E − E 0 ) 
k ( E ) = χk∞het exp   exp   = k het
S,CPET exp   (13.6)

RT  4 RT   2 RT   2 RT 
RT π RT
k∞het is equaled to the collision frequency, kcoll =
het
, times a factor account-
2πM 1 + πRT /λ 4πλ
ing for the multiplicity of electronic states in the electrode [24].
π  −λ   −λ 
,CPET = χkcoll
kShet = Z CPET
het het
exp   exp   is the standard rate constant, that
1 + πRT /λ  4 RT   4 RT 
is, the rate constant at zero driving force (for the sake of simplicity, double-layer correction
is not introduced here; it will be discussed later on). We thus end up with a rate law having
the same formulation as for simple ETs. Besides the transfer coefficient α = 0.5, it is charac-
4πλ
terized by two intrinsic parameters, λ the reorganization energy and Z CPET het
= χk∞het the
RT
preexponential factor. The latter contains the kinetic characteristics of CPET relative to the
proton transfer taking place at the transition state. These characteristics are discussed in details
and illustrated by experimental examples in Section IV. Moreover, CPET pathways may be
endowed with an H/D kinetic isotope effect (KIE) because tunneling of the proton is easier
than tunneling of deuteron. However, the KIE is not an unambiguous diagnostic criterion in
mechanism discrimination as shown in the next sections.
III. OMPETiTiON BETwEEN STEPwiSE (EPT AND PET)

C
AND CONcERTED (CPET) PAThwAYS
The competition between stepwise and concerted pathway is a kinetics issue because all three path-
ways (EPT, PET, and CPET) have the same global thermodynamics characterized by EX0 O + BH+ /XR H + B
or Eap0 . The competition can be easily analyzed for reactions taking place in buffered media when
the electronic steps are rate determining and the proton transfers are unconditionally at equilibrium,
which is often the case. Then the total current density I can be related to the electrode potential E,
the apparent standard potential Eap0 , and an apparent standard rate constant kSap according to the
following equation [29]:
I (
 F E − E ap0
= kS exp 
)   Red  (
 F E − E ap0 )  
 0 −  Ox  0 exp  −
ap
 (13.7)
F  2 RT   RT 
   
The “apparent” character refers to the fact that Equation 13.7 does not represent an elementary
step but it is a combination of standard rate constants characterizing each intervening pathway and
also that it does not correspond to a rate constant at zero driving force but to the rate constant when
the electrode potential is equal to Eap0 .
Using the symbols defined in Scheme 13.4, the apparent standard rate constant may thus be
expressed (Equation 13.8) as a weighted sum of the various standard rate constants, kSX, kSXH, and
kSCPET − B, characterizing the PET, EPT, and CPET with B as proton acceptor pathways, respectively, [29]
+
kSX kSXH kSCPET − B K asO K asR [HB][B]
kSap = + + (13.8)
[H + ] [H + ] K O K R [H + ] K R
1+ 1+ 1 + X+ H 1 + X+H 1+ 1 + X+H
K XO H K XR H [H ] [H ] K XO H [H ]

where HB/B (charge not shown) can be any acid–base couple present in the media.
It thus appears that the apparent standard rate constant depends on the acidity constants, K XOH
and K XR H, of the two acid–base couples, XRH/XR for the reduced species, and XOH/XO for the oxi-
dized species.
Figure 13.3 shows in a typical case the contributions of the various pathways to the apparent
standard rate constant as a function of the pKs (considering, for the sake of simplicity, that only one
acid–base couple participates to the concerted mechanism). It is seen that the smaller the pK XOH and
the larger the pK XR H , that is, the higher in energy the reaction intermediates of the sequential routes,
E 0XOH/XRH, k SXH
XRH + B XOH + B
K Ras
XRH ... B
k CPET–B
S
KXOH, KB
KXRH, KB E 0XO,H+ / XRH
XO ... HB
O+
Kas
XR + HB XO + HB
E 0XO/XR, k XS
SchEME 13.4 PCET with equilibrated proton transfer.

1 1 1
log(kSap) log(kSap) log(kSap)
0 0 0
–1 –1 –1
–2 –2 –2
–3 –3 –3
–4 –4 –4 pH
pH pH
–5 –5 –5
–4 0 4 8 12 16 –4 0 4 8 12 16 –4 0 4 8 12 16
(a) (b) (c)
FiGURE 13.3 Variation of the apparent standard rate constant with pH as a function of the pK gap between
redox states (a) pK XRH = 9, pK XOH = 2; (b) pK XRH = 14, pK XOH = −3; (c) pK XRH = 16, pK XOH = −5). Black line:
apparent standard rate constant; light gray: stepwise pathways contribution; dotted line: concerted pathway
contribution. [B] + [HB] = 0.1 M; pKHB = 5. kSX = kSXH = 1 cm s−1; kSCPET − B K asO+ K asR = 0.01 cm s−1 M −1.
the more dominant the concerted (CPET) contribution. As can also be read both from Equation 13.8
and Scheme 13.4, the buffer plays a crucial role in the competition between stepwise and concerted
pathways. It appears from Equation 13.8 that the more concentrated the acid–base couple, the stron-
ger the contribution of the CPET (as illustrated in Figure 13.4). This effect is simply the result of the
base being a reactant in the CPET process, whereas the acid–base couple serves only as a rapidly
equilibrated pH buffer in the stepwise pathways.
How do we know in practice whether one or the other mechanism takes place? Three main crite-
ria may be used in this purpose. The first criterion derives from the variation of the apparent stan-
dard rate constant with pH and its adherence to Equation 13.8, provided that intrinsic kinetic and
thermodynamic parameters are known or could be reasonably bracketed. Successful fitting using
only contribution from stepwise pathways would be a strong indication that the reaction proceeds
in two steps. A second clue is the dependence of the apparent standard rate constant from the acid–
base couple concentration indicating the occurrence of a CPET pathway. A significant KIE would
be a further indication of a concerted mechanism since it is the only one to involve proton transfer
in the rate-determining step. It should, however, be mentioned that careful correction of possible
1 1 1
log(kSap) log(kSap) log(kSap)
0 0 0
–1 –1 –1
–2 –2 –2
pH pH pH
–3 –3 –3
–4 0 4 8 12 16 –4 0 4 8 12 16 –4 0 4 8 12 16
(a) (b) (c)
FiGURE 13.4 Variation of the apparent standard rate constant with pH as a function of the buffer con-
centration (a) [B] + [HB] = 0.5 M; (b) [B] + [HB] = 2 M; (c) [B] + [HB] = 5 M). Black line: apparent stan-
dard rate constant; light gray: stepwise pathways contribution; dotted line: concerted pathway contribution.
pK HB = 5. kSX = kSXH = 1 cm s−1; kSCPET − B K asO+ K asR = 0.01 cm s−1 M −1; pK XRH = 9, pK XOH = 2.
thermodynamic isotope effects (differences in pKs for H and D) should be carried out before reach-
ing a reliable conclusion [30]. In addition, proton transfers may not always be at equilibrium, as
assumed earlier, especially in nonaqueous media opening the possibility of a KIE for the stepwise
pathways. In this connection, it has been established that proton transfer can be considered as
equilibrium if [31]
 RT kdif  B 
pK XR H − pK XO H < 0.5 + log   (13.9)
 F v 

where
v is the scan rate
kdif is the diffusion limit rate constant
[B] is the concentration of base
The oxidative electrochemistry of a [OsII(bpy)2pyH2O]2+ complex provides a good example of a

competition between stepwise and concerted pathways [29,32]. Two successive waves are observed
in cyclic voltammetry corresponding to the passage from OsII(OH2) to OsIII(OH) and then to
OsIV(O). For the OsII(OH2)/OsIII(OH) couple, the difference between the two pK involved is too
small (pK XRH = 9.1 and pK XOH = 2) for the mechanism to be stepwise, thus confirming that a small
pK gap involves energetically inexpensive reaction intermediates and contains a negligible con-
certed contribution. Very large amounts of the buffer have to be added for the concerted pathway
to start interfering (Figure 13.5).
The acidic constants of the OsIII(OH)/OsIV(O) couple are not accessible in the experimental pH
range, and the pK gap can thus to be assumed being higher than 14 [33]. In this case, the reaction
follows a concerted (CPET) pathway as demonstrated by the variation of the apparent rate constant
with pH, the variation of the apparent rate constant with the buffer concentration, and the observa-
tion of a significant KIE (Figure 13.6). This illustrates that the concerted mechanism is favored
when intermediates of the stepwise pathways are high in energy.
Oxidation of phenol in buffered water also illustrates competition between mechanisms but for
a system that does not exhibit a reversible cyclic voltammetry wave [34], that is, a system in which
2.4
i (μA) log kSap (cm/s)
10
1.6 –1 ap
log k (cm/s)
S
–1.5
5 0.8
log[CH3COO–]
–2
0 –3 –2 –1 0 1
0
–0.8
–5
–1.6
E (V vs. NHE) pH
–10 –2.4
–0.2 0 0.2 0.4 0.6 0 2 4 6 8 10 12 14
(a) (b)
FiGURE 13.5 Cyclic voltammetry of [OsII (bpy)2 pyH 2 O]2+ in a 0.1 M Britton–Robinson buffer. (a) Typical
two-wave voltammogram at pH = 3. (b) Variation of the apparent standard rate constant with pH for OsII(OH2)/
OsIII(OH) couple. Circle: in H2O, square: in D2O. Insert: dependence of the apparent standard rate constant on
buffer concentration in an aqueous acetate buffer at pH 5.
–2.5
–3 log kSap (cm/s)
–3.5
–4
–4.5
pH
–5
3 4 5 6
FiGURE 13.6 Oxidation of [OsII (bpy)2 pyOH]2+ in a 0.1 M Britton–Robinson buffer. Variation of the appar-
ent standard rate constant with pH. Circle: in H2O, stars: in D2O. Dotted line: prediction for a stepwise mecha-
nism. Full line: prediction for a CPET pathway.
the species resulting from the e− + H+ transfer is not stable, being engaged in further reaction, viz.,
dimerization in the present case. At low scan rates, the electrochemical oxidation of phenol involves
a fast and reversible proton-coupled ET followed, whatever its mechanism, by a rate-determining
dimerization. Knowing the latter rate constant, its effect on the cyclic voltammetric responses can
be corrected for so as to establish the Pourbaix diagram as shown in Figure 13.7. Assignment of the
1.8 0
Eap
0 1.6 ArOH +
EPET
0,H O 1.4
ECPET
2
ArO
1.2
1
0 ArOH
EPET 0.8
ArO–
0.6
pH
0.4
–10 –6 –2 2 6 10 14
pKArOH + 0 pKArOH
FiGURE 13.7 Pourbaix diagram for phenol in water.

PCET mechanism and characteristic rate constants can be achieved upon raising the scan rate. An
apparent standard rate constant, kSap , is obtained from the variations of the peak potential with scan
rate and phosphate concentration.
kSap is a measure, according to Equation 13.8, of the superposition of all pathways, stepwise
and concerted, involving B = H2O, HO −, HPO42−. Equation 13.8 may be recast, noting that the
experiments are carried out at pH = 7.2, the pKa of hydrogen phosphate so as to make appear a
2−
term independent from phosphate concentration, kSindep HPO4 , and a term proportional to phosphate
concentration:
2−
2− kSCPET − HPO4
kSap = kSindep HPO4 + HPO 4 2−  (13.10)
( pK
PhOHi +
− pH ) ( pH − pK PhOH )  
1 + 10 × 1 + 10
The very fact that the apparent standard rate constant is a unity slope linear function of phosphate
concentration points to the occurrence of a CPET-HPO42− pathway (Figure 13.8a). The relative
contributions of the various pathways besides the contribution of the CPET-HPO42− pathway can be
obtained by the application of Equation 13.8 and leading to the diagrams in Figure 13.8b. The EPT
pathway contribution is very low because PhOH∙+ is high in energy (pK = −2). The PET contribution
is the most important at pH > 9 as expected from the phenol pK (= 10) but the CPET-HPO42− path-
way is dominating for pHs around hydrogen phosphate pK provided buffer concentration is high
enough.
The competition between stepwise and concerted mechanism can also be examined in nonbuf-
fered medium, taking into account the diffusion of proton and OH− ions may interfere in the kinet-
ics. Again, oxidation of phenol in unbuffered water can be used as a typical example [35,36]. The
wave in basic pHs corresponds to the oxidation of phenoxide ion. It decreases with pH, as predicted
by the PET process controlled by the diffusion of OH−, at the expense of a more positive wave,
which is under partial control of the diffusion of the protons generated by the oxidation of phenol.
1.5 1
kSap (cm/s) log kSap (cm/s)
0
–1
1 –2
–3
–4
–5
0.5
–6
–7
Phosphate buffer
–8
conc. (M)
0 pH
–9
0 0.2 0.4 0.6 0.8 1 4 5 6 7 8 9 10 11 12
(a) (b)
FiGURE 13.8 Electrochemical oxidation of phenol. (a) Apparent standard rate constant as a function of
phosphate concentration at pH 7.2; (b) Contribution of the various pathways to the apparent standard rate
constant. Dashed line: EPT; dashed–dotted line: PET; dotted line: CPET-H2O; dashed–double dotted line:
CPET-OH−; full gray line: CPET-0.25 M HPO43−; full black line: CPET-0.5 M HPO43−.
This wave corresponds to a CPET pathway rather than to an EPT pathway, which would require
going to higher oxidation potential to reach the unstable cation radical intermediate.
In nonaqueous medium, the CPET pathway is facilitated by the presence of a proton-accepting
(or donating) group forming an H-bonded structure with the substrate being oxidized or reduced.
Oxidation of phenols with attached proton acceptor is a typical example in which the CPET path-
way prevails [37]. As mentioned in the introduction, such systems mimic a PCET process taking
place in PSII in the charge transport pathway between the chromophore and the OEC. Using values
bracketing the standard potentials and equilibrium constants of each step of the stepwise pathways,
simulation of the cyclic voltammetry responses shows that stepwise pathways can be discarded. The
reason is again that the intermediates are too high in energy. The observation of a significant KIE
at scan rate high enough for the charge transfer to kinetically interfere in the process confirms the
concerted character of the process.
Formation of an H-bonded structure in the CPET process is not restricted to nonaqueous medium
as illustrated by the OsIIIOH to OsIV=O CPET oxidation in buffered water [33]. The presence of an
anion such as NO3−, able to bind with OsIIIOH, leads to the inactivation of the CPET pathway by
preventing the formation of an H-bonded structure between OsIIIOH and the buffer base component.
Conversely, formation of an H-bonded structure is not a sufficient condition for the CPET
pathway to prevail (Scheme 13.5). Oxidation of guanine (GH) in aprotic solvent in the presence
of cytosine (C) compared to its oxidation in the presence of 2,6-lutidine (L) gives an illustrative
example of this point [38]. No H-bonded structure is formed between GH and L as checked by
NMR. The oxidation pathway follows in this case an EPT pathway kinetically controlled by the
initial ET step (∂Ep/∂logv ≃ 60 mV/decade). In the presence of C, GH forms a H-bonded (GH…C)
structure (association constant of 600 M−1 measured by NMR) but, as with L, the electrochemical
reaction is kinetically controlled by the initial formation of the cation radical as attested by the
absence of displacement of the wave upon addition of C, the shape of the wave, its displacement
with scan rate, and absence of KIE.
This observation implies that the H-bond pairing does not favor the concerted pathway in this
case.
GH C
O NH2
N
NH N
N N NH2
R΄ N O
RO R˝
O RO
H H O
H H H H
O O
H H
OR H
H3C CH3 R = tert-butyldimethylsilyl R˝
R΄
GH C
L
N O H2N
N
N NH N
R΄
N N
NH2 O R˝
SchEME 13.5 H-bonded structure.

IV. INTRiNSic ChARAcTERiSTicS Of CPET PROcESSES

A. SIMILarITY aND DIFFErENCES bETwEEN ET, CPET, aND CDET
As detailed in Section II, the rate law for an electrochemical CPET has the same form as rate
laws derived for a simple outer sphere ET or concerted dissociative electron transfer (CDET, see
Chapter 14) in which a bond between two heavy atoms is broken. It is characterized by two intrinsic
parameters, λ the reorganization energy and Z CPET
het
the preexponential factor. Besides this general
similar formulation, there are, however, important differences in these intrinsic parameters as
detailed in the succeeding text.
In all three cases, the reorganization energy is the sum of two contributions, a solvent reorga-
nization energy λ 0 and an internal reorganization energy λ i. The internal reorganization is much
larger in the case of CDET as compared to the two other cases because it includes the homolytic
bond dissociation energy D (of the order of 2–3 eV) of the bond being broken as derived from
the Morse curve model (see Chapter 14). This term is responsible for the kinetic penalty of
the concerted dissociative ET pathway in competition with a stepwise pathway. The remaining
internal reorganization due to all other interatomic distances and angle changes involving heavy
atoms may be estimated quantum mechanically by calculating the energy of the product system
in the configuration of the reactant system or vice versa. It is usually in the order of 0.5–1 eV.
Regarding the solvent reorganization, its formulation based on electrostatic models is slightly
different in the case of a CPET as in the two other cases [14]. Indeed, the solvent reaction coor-
dinate for a CPET pathway is made of two ingredients, a fictitious charge number representing
solvent reorganization upon ET, as in the case of an ET or a CDET process, and a dipole variation
index representing solvent reorganization upon proton transfer. An electrostatic model sketched
in Figure 13.9 allows the delineation of two independent contributions to the solvent reorgani-
zation energy noted λ 0ET (Equation 13.11) and λ 0PT (Equation 13.12). The first is identical to the
solvent reorganization energy obtained for ET and CDET and is typically in the order of 1 eV.
The second refers to the change in dipole moments accompanying CPET. It is usually small of
the order of few tens of eV:
e2  1 1 1
λ 0ET =  −  (13.11)
4πε0  εop εS  2a

z z
zR zP
a a
θ B– θ
HB
μR μP
y y
φ φ
A AH
x x
e–
FiGURE 13.9 Modeling solvent reorganization in CPET.

1  εS − 1   εop − 1   (µ R − µ P )2
λ 0PT =  −  (13.12)
4πε0  2εS + 1   2εop + 1   a3

in which
ε0 is the vacuum permeability
εop and εS are the optical and static dielectric constants of the solvent
a is the radius of the reactant equivalent sphere
μR and μP are the dipole moments of the reactant and product, respectively
Besides the reorganization energy, the second intrinsic kinetic parameter is the preexponential factor
4πλ het π RT
het
Z CPET = χk∞het het
. k∞ is equaled to the collision frequency, kcoll , times a factor
RT 1 + πRT /λ 4πλ
accounting for the multiplicity of the electron electronic states in the electrode. This simplified model
assumes that the electrochemical reaction takes place at a given distance from the electrode. A more
refined treatment is available and will be described later on, but this simplified version can be used to
compare ET, CDET, and CPET processes. The specificity of each process is described by the factor
χ related to the probability p (Equation 13.4) for the system to jump from one electronic state to the
other, which is obtained from the Landau–Zener expression depending on the coupling constant C
between both states (Equation 13.5). For both ET and CDET, the coupling constant can be assumed
to be large enough for the probability p and hence the factor χ to be equal to unity. The situation is
different for a CPET process. Proton transfer occurs at the transition state between two vibrational
proton states as sketched in Figure 13.2. The contribution of proton excited states may be additionally
involved especially when the driving force of the reaction is large. Because the proton is much heavier
than an electron, the coupling constant between the reactant and product states may be smaller in
the case of a CPET as compared to ET and CDET. This is the kinetic penalty to pay in order to get
the proton transfer concerted with ET and thus get benefits of the full driving force of the reaction.
This a priori comparison of ET, CDET, and CPET properties indicates that (1) CDET has a
larger reorganization energy than ET and CPET and (2) CPET has a smaller preexponential factor
than ET and CDET.
The intrinsic properties of CPET processes embodied in the preexponential factor can be analyzed
by looking at the coupling constant. The coupling constant may be estimated from quantum calculation
using the approximation that C = HET〈χi|χ f〉 where HET is the electron coupling constant and 〈χi|χ f〉 the
overlap between the initial and final proton vibrational wave functions, or it can be estimated semi-
classically using the tunneling probability for the proton through a potential barrier. A simple model,
sketched in Figure 13.10, has been proposed that allows an estimation of Ceq (i.e., the coupling constant
corresponding to the equilibrium distance between the proton donor and the acceptor) as a function of
the barrier height ΔV depending on the distance Q between the proton donor and acceptor atoms [39]:
 8 2 hν 0≠  ∆V ≠ 1 
3/ 2

C (Q) = hν exp  −
≠
0  −  
 3 ∆V ≠  hν 0≠ 2  
 
with
f0≠  Q − dAH
0
− dDH
0

∆V ≠ (Q) =  
4  2 

where
f0≠ = 4π2ν 0≠ 2 mp is the force constant of the proton well
0 0
dDH and dAH are the proton equilibrium distances in the reactant and product, respectively
Potential
energy
e–
e–
ΔV≠
H+ H+
Proton coordinate
FiGURE 13.10 Modeling the proton tunneling barrier in CPET.
The actual coupling is thus a function of Q, so proton tunneling between the reactant and product states
is a function of the donor–acceptor vibration with the shorter distance yielding easier proton tunneling.
In agreement with the aforementioned model, the coupling constant can be described by the expression
C (Q) = Ceq exp  −β(Q − Qeq ) 

in which the parameter β is the attenuation factor of the exponential decay of the vibronic coupling
of the two states with Qeq and Ceq being the proton donor–acceptor equilibrium distance and the
equilibrium coupling constant at equilibrium distance, respectively. In line with the proton being
heavier than an electron, β values are in the order of 20 Å−1, whereas corresponding values are typi-
cally 1 Å−1 for ET. In a classical description, the contribution of each distance Q to proton tunneling
is obtained by weighting the transmission coefficient by the Boltzmann probability P(Q) that the
proton donor and acceptor atoms are at a distance Q from one another. In the context of a nonadia-
batic CPET, this averaging leads to the following expression of the preexponential factor [40]:
 2 RTβ2 
het
Z CPET = Z CPET
het
,eq exp  
 f 
which involves the combination of two intrinsic parameters: an equilibrium preexponential factor
het
Z CPET ,eq characterizing the coupling of electronic states in the transition state at the equilibrium
proton donor and acceptor distance and a distance-sensitivity parameter β2/f in which f is the force
constant of the harmonic oscillator of the proton donor and acceptor H-bond vibration. Full char-
acterization of intrinsic properties of CPET processes thus requires determination of three param-
eters: the reorganization energy λ, the distance-sensitivity parameter β2/f, and the equilibrium
het
preexponential factor Z CPET ,eq . These three parameters may not be easily obtained separately from
electrochemical experiments for various reasons, but combined approach of several techniques
including electrochemistry [36], photoinduced ET [41], and stopped-flow [42] allows, as shown
in the following example of phenol oxidation in water, to fully characterize a CPET process and
check the consistency of both heterogeneous and homogeneous CPET kinetics.
B. HYDroGEN-BoNDED SYSTEMS
To take advantage of their favorable thermodynamics, CPET pathways need not be too severely
penalized kinetically in order to prevail over the competing stepwise pathways. Efficient proton
R2
H H H
O N O O N
tBu tBu
R2
R1
tBu tBu
AP
R1 R2
1 CF3 CH3
2 H CH3
3 CH3 CH3
4 H H
SchEME 13.6 H-bonded amino-phenol systems (AP).
tunneling is thus required as described earlier, which implies short distances between the group gen-
erating the proton upon oxidation and the proton acceptor (and vice versa for a reduction process)—
a necessary albeit not a sufficient condition as shown in the case of guanine oxidation in aprotic
solvent. Molecules containing an oxidizable phenol moiety and an attached nitrogen base serving
as proton acceptor have been intensively investigated to get insights into the process. Measurement
of the standard rate constant at various temperatures for the aminophenol noted AP (Scheme 13.6)
allows getting both the preexponential factor and the reorganization energy from an Arrhenius plot
(provided double-layer effect and zero-point energies are being taken into due account) [43].
The reorganization energy is around 1.4 eV in agreement with an estimation of the solvent reor-
ganization energy of about 1 eV and a calculation of the intramolecular reorganization energy of
het
0.4 eV. The preexponential factor is 34,580 cm s−1, much larger than expected from the factor kcoll
thus indicating that a realistic analysis has to take into account the fact that the reaction may take
place at various distances from the electrode surface similarly to what happens with simple ET. A
complete analysis of the problem taking into account likely approximations leads to the conclusion
that the rate law remains unchanged as well as the expression of the standard rate constant. The rate
constant appears as the product of a preexponential factor and an exponential factor depending on
the reorganization energy [43]. However, the preexponential factor for proton donor and acceptor at
equilibrium distance is now
νn π  2π2Ceq
2
,0 
,eq = ln  1 +
het
Z CPET 
βe πRT  hν n 4πRTλ 
1+
λ
where
νn is the frequency vibration of the activated complex along the reaction coordinate (typically
1012 s−1)
βe is the decay constant for the coupling constant with the distance between the electrode and the
reactant (typically 1 Å−1) [44]
Ceq,0 is the CPET coupling constant for proton donor and acceptor at equilibrium distance and the
reactant system at minimal approach distance from the electrode
In the nonadiabatic limit (corresponding to the case of interest), the averaging over Q distances
leads to
1 π 2 π2  2  4 RTβ2  
het
Z CPET = Ceq,0 exp  
βe πRT h 4πRTλ   f  
1+
λ
het
Knowing the reorganization energy from the Arrhenius plot slope and Z CPET from the intercept
 2 RTβ 
2
allows to get an effective coupling constant: C0,eff = Ceq,0 exp   = 0.015 eV (0.007 eV for the
 f 
deuterated AP compound indicating a H/D KIEs in line with the concerted process). Independent
assignment of the two intrinsic parameters Ceq,0 and β2/f could not be achieved. However, compari-
son with a simple outer sphere ET, whose preexponential factor is 54,000 cm s−1 (corresponding to
an outer sphere ET coupling constant of 0.018 eV), indicates that the proton tunneling is efficient for
this heterogeneous CPET process. It is interesting to note that a similar treatment of homogeneous
results obtained with a similar aminophenol molecule leads to the conclusion that C0,eff is smaller
in the homogeneous case. This is deemed to derive from the effect of the strong electric field within
which the electrochemical reaction takes place. Nonetheless, the tight H-bonded structure is crucial
for the efficiency of the CPET process. Homogeneous studies on similar aminophenol systems have
shown a strong rate dependence on increased proton transfer distance [45]. Computational results
indicate that anharmonicity of the H-bond vibration and influence of proton vibrational excited
states may have to be considered to describe these systems, thus illustrating the complexity of CPET
processes [46]. Despite these complications, it remains that the distances over which the proton may
travel as a result of a CPET reaction appear to be limited to the rather small values of H-bond length
(ca. 2–3 Å). However, the idea according to which this distance might be substantially increased
by inserting an H-bond relay between the group being oxidized (or reduced) and the distant proton
acceptor (or donor) has been explored. A series of molecules containing an oxidizable phenol and a
pyridine group that serves as proton acceptor and an alcohol function between them (Scheme 13.6)
have allowed testing experimentally the concept of H-bond relay [47,48]. In all cases, a chemically
reversible wave is obtained. Thermodynamics arguments can be used to discard any stepwise mech-
anism, and it is concluded that the displacement of the two protons is concerted with ET in line with
the observation of a KIE. It is worth noting that x-ray data show that the structure is not folded and
that the distance between the proton donor and acceptor sites is ca. 7 Å. Similar analysis of cyclic
voltammetry data than that performed with AP indicates that the reorganization energy is almost
constant over the whole series of compounds while the standard rate constants of the four H-bond
relay molecules are much smaller than the standard rate constant of AP (Table 13.1).
Thus, as expected and confirmed by computational studies, the reason that makes CPET oxida-
tion of the H-bond relay molecules intrinsically slower than the oxidation of AP is that the tunneling
TABLE 13.1
Reorganization Energies and Standard Rate Constants for Molecules
in Scheme 13.6; see Text for the Definition of Parameters
Molecule λi (eV) kS (cm s−1)
AP 0.390 8 × 10−3
1 0.405 9 × 10−4
2 0.433 4.5 × 10−4
3 0.420 8 × 10−5
4 0.443 4.5 × 10−4
Potential e–
energy
H+
XRH1 ..RH2 ..B XO ..H1R ..H2B
≠
ZPE qH2
qH1
ΔG≠
F E – E0
XR H1 .RH2 ...B qH2

ZPER
XO ...H1R .H2B
qH1
ZPEP qH2
qH1
Heavy-atom reaction coordinate
FiGURE 13.11 Modeling CPET in H-bonded systems with an H-bond relay.
efficiency is less in the first case because two protons move concertedly with the electron as sketched
in Figure 13.11. It is thus demonstrated that a net displacement of a proton in concert with an ET
over a distance as large as 4.5 Å is achieved thanks to an H-bonded relay. The kinetic penalty
for this is that the coupling constant and hence the preexponential factor are decreased [49]. The
decrease by a factor of ca. 50 of the standard rate constant when the traveling distance of the proton
is increased by ca. 2 Å indicates that the distance-sensitivity factor β is of the order of 2 Å−1, which
is large compared to corresponding values for simple proton transfer (ca. 20–30 Å−1). Modeling of
such a 2D CPET will require further development including the influence of the H-bond-accepting
and H-bond-donating properties of the relay on the potential energy surface. The observed varia-
tions of the standard rate constant within the series (Table 13.1) are indeed likely due to the modifi-
cation of these properties by the substituent on the relay alcohol.
The illustration of the possible translocation of proton over a long distance through H-bonded
relays concertedly with ET indicates that similar process can be envisioned with proton transfer
along a water chain, as exemplified by the reduction of superoxide ion with water as proton donor
[50]. In an aprotic solvent, dioxygen exhibits a quasi-reversible cyclic voltammetry first wave fol-
lowed by a second, broad irreversible wave. This second wave corresponds to a CPET reduction of
the superoxide ion. Indeed, if a PET pathway was followed, the first wave should involve two elec-
trons and, if an EPT pathway was followed, the second wave would be sharp (with a transfer coeffi-
cient lower than 0.5). The observation of a significant KIE (KIE = 2.5) also confirms the occurrence
O O–
OH2
e–
O O– H O– O H
H O H O–
H2O H 2O
H H
O H e– O H
O O– H O– O H
H O H O–
H2O H 2O
H H
O H e– O H
O O– H O– O H
H O H H
H O
H O H –O
H2O H2O
H H
e–
O H O H
O O– H O– O H
H H O H
H O
H H O H
H O
–O
H O H
SchEME 13.7 Reduction of superoxide ion with water as proton donor.
of a CPET pathway. The large anodic shift of the second wave upon addition of water [51] has been
interpreted as resulting from a concerted transfer of one electron and one proton through short water
chains (Scheme 13.7). The main factor driving the reaction toward such a kinetically demanding
process is the thermodynamic advantage due to a decrease of the attending repulsion between HO2−
and OH−. The same behavior is observed for the reduction of the benzophenone radical anion upon
addition of water [52].
The ability of water to form H-bonded chains creates a new type of CPET pathway allowing
the transport of a proton over a long distance concertedly with ET. This may be useful for a better
understanding of biological reactions involving PCET such as in the disproportionation of superox-
ide by superoxide dismutase [53].
C. WaTEr (IN WaTEr) aS ProToN ACCEpTor

If water may serve as proton relay as demonstrated in Section IV.B, it is also an ubiquitous proton
donor and acceptor. Its role in PCET reactions as a peculiar, H-bonded and H-bonding, proton donor
and acceptor when it is used as solvent is not only an important fundamental issue but is also of con-
siderable interest for the comprehension of natural systems. Although investigated over decades, the
mechanisms of proton conduction in water are still under active experimental and theoretical scru-
tiny [54,55]. The question raised here is whether or not proton transport in water can be concerted
with ET. In other words, does the peculiar character of water induce specific intrinsic properties
of CPET with water (in water) as proton acceptor? Interesting insights have been obtained through
the investigation of phenol oxidation using several techniques, electrochemistry and also laser flash
photoinduced ET and stopped flow techniques.
12
i (μA)
10
0
E (V vs. NHE)
–2
0.5 0.6 0.7 0.8 0.9 1 1.1 1.2 1.3
FiGURE 13.12 Cyclic voltammetry of phenol in water at 0.2 V/s in unbuffered water at various pHs (from
right to left: 2, 3, 4, 5, 6, 7, 8, 8.5, 9, 9.5, 10, 11, 12).
A first kinetic characterization of phenol oxidation with water as proton acceptor can be obtained
from cyclic voltammetry in unbuffered water [35]. Once the pH is low enough so that the OH−-PET
pathway is too slow, the followed pathway is a CPET with water as proton acceptor. If the initial
proton concentration is large (pH < 3), then the wave is kinetically controlled by dimerization of the
phenoxyl radical. At pH > 3, the initial concentration of protons is perturbed by their production
from phenol oxidation (Figure 13.12).
It is thus demonstrated that the wave depends on a single dimensionless parameter p′ measuring
the competition between dimerization and CPET kinetics:
kSCPET − H2 O (C 0 /CS )1/ 2

p′ =
( DPhOH )1/ 4 ( DH+ )1/ 4 ( Fv /RT )1/ 3 (4kdimC 0 / 3)1/ 6

in which
C0 is the phenol concentration
CS is a normalizing concentration taken equal to 1 M
Raising the scan rate allows determination of the standard rate constant kSCPET− H2 O = 25 cm s−1. The
measurement of such a high standard rate constant at such moderate scan rates can be achieved
because the follow-up dimerization is fast and competes with the “termolecular” backward CPET,
PhO • + H+ + e−. Because the medium is unbuffered, protons produced by the forward CPET diffuse
away from the electrode as attested by the appearance of the proton diffusion coefficient in p′ making
the competition less in favor of an equilibrated CPET followed by a rate determining dimerization as
observed at pH < 3. Repeating the experiments in deuterated water allows measuring a KIE of 2.5, in
line with the concerted character of the reaction.
Deciphering the reasons behind such a large standard rate constant requires separating the
various intrinsic ingredients of kinetics, that is, the reorganization energy, the distance-sensitivity
parameter β2/f, and the equilibrium preexponential factor. Homogeneous techniques have appeared
to be suitable for that purpose [40]. Measurements of the CPET homogeneous rate constant for phe-
nol oxidation as a function of the driving force by varying the electron acceptor standard potential
leads to the reorganization energy (Figure 13.13).
The major part of this reorganization energy may be ascribed to solvent reorganization accom-
panying the generation of a water-solvated proton. It is noteworthy that the ensuing value of the
12
log k
10
–2
ΔG0 (eV)
–4
–1 –0.5 0 0.5
FiGURE 13.13 Forward rate constant of phenol oxidation by various electron acceptors. Black and gray
symbols: in H2O and D2O, respectively. Squares: RuIII(bpy)(4,4′-CO2Et-bpy)2; triangles: RuIII(bpy)3; circles:
RuIII(4,4′-methyl-bpy)3 ; tilted squares: IrIVCl6. Line: activation-controlled rate constant predicted for a reor-
ganization energy of 0.45 eV.
self-exchange reorganization energy, λ se

CPET,H 2 O
= 0.45 eV, is remarkably small. The proton charge is
accordingly not concentrated on a single hydrogen atom or even on a single-protonated water mol-
ecule. It spreads over a ca. 6.5 Å-radius water cluster molecules, in agreement with recent spectro-
scopic observations [56] and with the aforementioned description of the ability of the proton to move
over several H bonds in concert with ET. With the reorganization energy in hand, analysis of tem-
perature dependence of rate constants gathered from laser flash experiments leads to the values of the
distance-sensitivity parameter β2/f and the equilibrium preexponential factor in both light H2O and
D2O. As expected, the equilibrium preexponential factor is smaller with deuterium than with hydro-
gen, and the distance-sensitivity parameter is larger with deuterium than with hydrogen (Table 13.2).
These values are compatible with a Grotthus-type mechanism during the CPET process
intrinsically efficient. Indeed, comparison with other proton-accepting bases in water, hydro-
gen phosphate, and pyridine [57] (Table 13.2) shows that the distance-sensitivity parameter is
much smaller in the latter cases than with water due to a much stiffer phenol-based system and,
TABLE 13.2
Kinetic Parameters for CPET in Water with Water, Phosphate, or
Pyridine as Proton Acceptor; see Text for the Definition of Parameters
H2O HPO42− Pyridine
λCPET (eV) 0.45 0.86 0.53
β2 (K−1) 0.0125 (H) 0 (H) 0 (H)
2R
f 0.020 (D) 0.0064 (D) 0.006 (D)
ln (Zeq) 19.5 (H) 16.8 (H) 17.6 (H)
15.9 (D) 14.8 (D) 15.1 (D)
in this sense, a less efficient CPET because the proton does not travel over a large distance in
concert with ET. The third intrinsic parameter, the equilibrium preexponential factor, is also
larger in the case of water than in the case of hydrogen phosphate and pyridine, indicating
that proton translocation is more efficient in water than it is for a conventional CPET process
where the proton is more localized. These results are in qualitative agreement with the electro-
chemical data that showed that the phenol oxidation CPET standard rate constant corrected for
double-layer effect,
−B  (2 z + 1)FφS 
kSCPET
,corr = kSCPET − B exp  
 RT 
(z is the charge number of the reactant system and ϕS the potential at the reaction site vs. the solution
− H2 O
bulk potential) is much larger when water is the proton acceptor (kSCPET ,corr = 83 cm s−1) as com-
CPET− HPO 42−
pared to the case where hydrogen phosphate is the proton acceptor (kS = 0.002 M −1 cm s−1).
A more quantitative comparison between homogeneous and electrochemical kinetic characteristics
can be achieved as follows [34]. Knowing reorganization energies for CPET self-exchange reactions,
λ se
CPET
, the corresponding reorganization energies for electrochemical heterogeneous reactions are
estimated through
CPET  a
λ CPET
el = λ se 1 − d 
 
where
a is the radius of the equivalent sphere
d = 2(δH2O + a) the distance between the reaction site and its electrical image in the electrode
(Figure 13.14)
Then, the electrochemical preexponential factor is obtained from
 λ  π  λ 
kS,corr = Z het exp  −  = Z el exp  −  (13.13)
 4 RT  1 + πRT /λ  4 RT 
Application to the comparison of the electrochemical and homogeneous results for H2O vs. HPO42−
as proton acceptor indicates that the ratio of preexponential factors is substantially larger, by a
factor of ca. 10, in the electrochemical case than in the homogeneous case. This may be due to the
existence of a strong electric field at the reaction site favoring the zwitterionic form of the reactant
system (PhO −, H+, n H2O) in the transition state.
It is finally worth noting that, as expected, preexponential factors Z el for CPET reactions are
smaller than the comparable factor of a simple outer sphere ET. In the case of the CPET phenol oxi-
dation with water as proton acceptor, comparison to phenolate oxidation shows a decrease as high as
five orders of magnitude. This decrease cannot be fully understood with the present model in which
the preexponential factor is a measure of activationless reactivity of a reactant system assimilated
as a sphere; otherwise, very large KIEs would be expected. The reactant system is in fact likely to
be structured so as to adopt a precise spatial conformation allowing the formation of one or several
H bonds as required by the occurrence of the CPET reaction.
Both electrochemical and homogeneous data are thus consistent and show that water (in water)
is an intrinsically very efficient proton acceptor in CPET processes.
–
H O
O
N
H
O O
H
O
H
H H
H
HO OH
O H H
H H H
H O O
HO H
H H H O H
O O
H O H H
H H OH O
H H O H H
O H H HO
H O H H
H O
H
O H
H
e–
H O
O
H
H
O
H
H
H H
H O
O H H OH
H O H
H HO
H O H
H H
O H O H
O H +H O H H
H O H O
HO
H H H
H H
O O H O
H H
H O H
H H
O
H O
H
O
H
H
O O–
H
H N
O O
O
H
O–
H
O N
H O O
H
O O –
H
H N
O O O
H
H
O –O
H
H
H O P O
e– O
O–
H
H H
O
H O
H
O
H
O–
H
O O P O H
H
–
O
H
O H
H O
H
O
Potential
H
H O –
O
H N
H O O
O
E
H
φ2 = 125
φHPO 2– = 108
4
φH O = 53
2
0
δH O = 1.5 OHP
2
aNO– = 2.9
3
aHPO2– = 3.5
4
aH O = 6.5
2
FiGURE 13.14 Sketch of the electrode vicinity for phenol oxidation in water.
V. CPET fOR BOND AcTivATiON

A. BrEakING BoNDS wITH ProToNS aND ELECTroNS
The concerted dissociative ET theory (see Chapter 14) together with the numerous illustrating exper-
imental examples shows the way in which electrons can break heavy-atom bonds [6]. Associating
proton transfer with ET might be additionally profitable to break bonds because of the thermo-
dynamic advantage of concerted pathways over stepwise pathways. Indeed, various pathways are
c onceivable for going from reactants to products as sketched in Scheme 13.8 in the case of a reduc-
tion (transposition to oxidation is straightforward) [58].
There is a competition between a three-step stepwise pathway, two combinations of concerted
reactions with an additional step and an all-concerted pathway. The latter is the best way to make
use of the thermodynamic advantage provided this is not counterbalanced by a large kinetic penalty.
Combining the models previously developed for concerted dissociative ET and concerted proton–
electron transfer leads to a kinetic model for the all-concerted process. As in the simple CPET
case, two successive applications of the Born–Oppenheimer approximation lead to define the tran-
sition state in terms of a heavy-atom coordinate and the preexponential factor in terms of a pro-
ton displacement coordinate. Concerning the first of these applications, heavy-atom reorganization
involves the solvent molecules, the vibrations of reactant bonds not being cleaved in the reaction,
and, most importantly, the contribution of bond cleavage.
Regarding the latter, it seems appropriate to use the same approximation for the potential energy
curves as for concerted dissociative ETs with no accompanying proton transfers, that is, a Morse
curve for the reactants and a repulsive Morse curve for the products (equal to the repulsive part of
the reactant Morse curve) as shown in Figure 13.15. Consequently, the rate law of the irreversible
all-concerted reaction is
I  ∆Ghet
≠

= Z het
3 rd
exp  −  ×  Y−X  × HB
F  RT 
 
with
2
≠ λ + D  F (E − E 0 ) 
∆Ghet = het 1 + 
4  λ het + D 

Bond breaking
– X + HB Concerted electron
Y— transfer and bond Y X– + HB
breaking
Outer sphere
electron transfer
Proton transfer
Concerted bond
breaking and
proton transfer
e–, ED
Y — X + HB Y XH + B–
All in concert
e–, ED
SchEME 13.8 Mechanistic pathways for dissociative electron proton transfers.

Potential
energy
Y–XH+ ..–B
e–
Y X– ..HB H+
Y–X .. HB
Y XH ..–B
H+ coordinate (q)
ΔG≠
ΔG0
Y–XH+ .. –B Y X– ..HB
Y–X .. HB Y XH ..–B
H+ coordinate (q)
H+ coordinate (q)
Heavy-atom reaction coordinate

mostly the Y–X distance
FiGURE 13.15 Modeling concerted dissociative proton electron transfers.
[Y–X] and [HB] are the concentrations of the indicated species at the electrode surface. The reor-
ganization energy, λhet, includes the energy for solvent reorganization and internal reorganization
in the Y–X molecule, besides the cleavage of the bond, E0 is the standard potential relative to the
all-concerted reaction and E the electrode potential. As in the case of simple CPET reactions, the
preexponential factor combines the formation of the precursor complex, the degree of adiabaticity
of ET, and the effect of proton tunneling at the transition state. As for simple ET, CDET, or CPET,
all electronic states can be taken into account. Also, as in the case of a CPET, the third-order char-
acter of such reactions does not prevent their occurrence, as shown, for example, by the oxidation
of phenol with hydrogen phosphate or pyridine as the proton acceptor. In systems where the proton
donor is attached to the structure that bears the cleavable heavy-atom bond, the rate law is replaced:
I  ∆Ghet
≠

= Z het
2 nd
× exp  −  ×  Y−X, HB
F  RT 
 
An all-concerted mechanism is thus characterized by a large reorganization energy due to the con-
tribution of D and a preexponential factor affected by proton tunneling at the transition state. As
described for CPET reactions, this last feature may induce an H/D KIE. However, the large irreversibil-
ity caused by the breaking of the heavy-atom bond implies that, in a cyclic voltammetric experiment,
H
O
O O
O
SchEME 13.9 H-bonded peroxide molecule.
the driving force at the peak potential is large to overcome this high intrinsic barrier. It follows that
the transition state closely resembles the initial state. One consequence is that, in the heavy-atom
transition state, the •Y–X− moiety is much less basic than in the products’ geometry because the Y–X
bond is barely broken. The result is that the intersection of the proton energy profiles of reactants and
product electronic states in the transition state is likely to be close to the zero-point energy level. This
indicates that the overlap of proton vibronic states is large and therefore insensitive to isotope substitu-
tion. Then the H/D KIE is predicted to be negligible in spite of the concerted character of the reaction.
Moreover, the preexponential factor is not expected to be much smaller than preexponential factors of
corresponding dissociative ET not concerted with proton transfer.
B. ACTIVaTIoN oF MoLECULES
That concerting proton transfer to electron can be profitable to activate a molecule through bond
breaking has been illustrated with the cleavage of an O–O bond helped by the presence of a proxi-
mal carboxylic acid group (see Scheme 13.9) [58].
The kinetic response to the increased driving force due to the concerted proton transfer is
revealed by the fact that the cyclic voltammetric wave of the acid is located at a potential less nega-
tive by 700 mV compared to the methyl ester. That the cleavage is concerted with ET in both cases
is attested by the large width of the waves indicating a small value of the transfer coefficient. Thus,
if a two-step pathway was to be followed with a first irreversible concerted ET and bond-breaking
step followed by a downhill protonation step, then the kinetics of the reaction would not respond to
the increase of driving force offered by the follow-up protonation. The all-concerted mechanism is
thus operating and leads to a considerable acceleration of the O–O bond activation.
VI. CONcLUDiNG REMARkS

Proton-coupled ETs are omnipresent in natural and artificial chemical processes. Understanding
mechanisms and activation–driving force relationships, which underlie their practical efficiency, is
a timely task in front of contemporary challenges concerning energy conversion. Focusing on PCET
reactions in which, in contrast with hydrogen-atom transfers, proton and electron transfers involve
different centers, the reaction may go through an electron or proton transfer intermediate, giving
rise to an EPT and a PET pathway, respectively. CPET reactions, in which proton and electron trans-
fers are concerted, have the advantage of bypassing the high-energy intermediates of the stepwise
pathways, even though this thermodynamic benefit may have a kinetic cost. Kinetics-based mecha-
nism analysis is now available, making it possible to distinguish the three pathways and to uncover
the factors governing the competition between, thanks to the modeling of the concerted pathway.
Many illustrating experimental examples have been described, most of them inspired by bio-
logical systems, for example, PSII and superoxide dismutase. It has been also shown that water
is a remarkable proton acceptor endowed with very small reorganization energies. Coming from
different corners of chemistry, these examples reveal general features of PCET reactions. Further
development concerns the coupling of PCET reactions with bond-breaking/bond-forming processes
likely to be involved in the catalytic systems currently designed to activate small molecules (O2, H+,
H2O, CO2, RCl) as required by the resolution of contemporary energy challenges.
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14 Dissociative Electron Transfers
CONTENTS
I. Introduction ............................................................................................................................. 511
II. Modeling Concerted Dissociative Electron Transfers ............................................................ 513
A. Morse Curve Model ........................................................................................................ 513
B. Sticky Concerted Dissociative Electron Transfer ........................................................... 515
III. Competition between Concerted and Sequential Dissociative Electron Transfers................. 517
A. Structural, Electronic Factors and Solvent Effects Controlling the Competition ........... 517
B. Role of the Driving Force ............................................................................................... 521
C. Electrochemical versus Photoinduced Dissociative Electron Transfer ........................... 523
IV. Cleavage of Primary Radicals ................................................................................................ 524
V. Concluding Remarks............................................................................................................... 528
References ...................................................................................................................................... 529
I. INTRODUcTiON
The coupling between electron transfer and bond breaking between two heavy atoms occurs in
a large number of biochemical and chemical processes, such as cleavage of C–halogen bonds
in organic halides as well as other bonds [1–4], electron transfer activation of small molecules
involved in contemporary energy challenges (e.g., O2 and CO2), as well as enzymatic reactions
like dechlorination processes of RCl toxic derivatives within reductive dehalogenases [5]. In all
of these reactions, the bond breaking accompanying electron transfer may be triggered in various
ways, electrochemically, by homogeneous electron donors or acceptors, photochemically, or by
means of pulse radiolysis [1–3]. The fact that so many chemical reactions can follow or accompany
electron transfer is the basis of the synthetic value of electron transfer chemistry. Such processes
also irrigate more applied fields, for example, the area of sensors and biosensors, which both
involve the transduction of the presence of a molecule into an electrochemical signal. Another,
more prospective field, concerns molecular electronics, where the understanding of the structural
changes coupled to charge transfer will be central in the design and working of devices including
redox centers connected by molecular wires. The key reactivity paradigm in charge transfer–
induced bond breaking processes is the concerted/stepwise mechanistic dichotomy, as illustrated
in Scheme 14.1 [1–3].
Charge transfer and bond cleavage reaction may indeed occur concertedly according to a single
elementary step (concerted dissociative electron transfer [CDET]), or in two successive steps, the
electron transfer then leading to a frangible species that cleaves in a distinct step (sequential dis-
sociative electron transfer [SDET]), as shown in the potential energy profiles of Figure 14.1. As
we define it here, the term dissociative charge transfer thus embraces all reactions for which an
electron transfer triggers the breaking of bond between two heavy atoms, irrespective of the exact
pathway, concerted or stepwise. This is not always the case in the literature where dissociative
means concerted in a number of cases. The context will allow one to distinguish between a con-
certed dissociative reaction and a stepwise dissociative one. Concerted reactions (CDET) have the
511
Stepwise
RX + e– RX – (π anion radical)
Concerted
(R , X–) (σ anion radical)
R + X–
e–: Electrode, homogeneous donor

(ground state, excited state)
SchEME 14.1 Dissociative electron transfer mechanisms.
Potential energy
–
RX Stepwise
–E 0
RX/RX –
–E RX + e–
Concerted
R
–E +
–E 0 R , X– X–
RX/R + X– RX + e–
Reaction coordinate
FiGURE 14.1 Potential energy profiles for the concerted and stepwise pathways according to Scheme 14.1.
The E 0s are the standard potentials of the subscript couples. E is the electrode potential or the standard poten-
tial of the homogeneous donor.
thermodynamic advantage over a sequential process (SDET) of avoiding the formation of high-
energy intermediates (i.e., the anion radical in the case of the reduction of a neutral substrate as
shown in Figure 14.1), thus going directly, during the rate-determining step, to the final products.
This advantage may, however, be counterbalanced by the large intrinsic activation barrier deriving
from bond cleavage that results in a kinetic penalty as compared to a two-step process. The CDET
modeling is presented in Section II.
After the cleavage has taken place, another energy minimum is presented in Scheme 14.1 and
in the potential energy diagram of Figures 14.1 and 14.2, corresponding to an ion–radical adduct
that may or may not survive in a polar solvent, for both CDET and SDET mechanisms. When
existing, this adduct, resulting from a charge–dipole attractive interaction between the cage frag-
ments before they diffuse out, may be viewed alternatively as a σ* anion radical or as forming a
weak three-electron bond. If such interactions are expected to decrease or even to vanish in polar
liquid, experimental studies have confirmed their existence, at least when a partial positive charge
is induced on the remaining radical part, thanks to the presence of a strong electron-withdrawing
substituent. The consequences of these interactions on the dissociative electron transfer kinetics are
discussed in Section II.
The competition that exists between the CDET and SDET pathways depends upon intramo-
lecular (structural, electronic) and environmental (solvent, energy of the incoming electron) factors.
Dissociative Electron Transfers 513
Potential
energy
R + X– R + X–
(R , X–) (R , X–)
Length of the cleaving bond

(a) (b)
FiGURE 14.2 Energy as function of the intramolecular reorganization for the reduced system (RX + 1e−),
with (dotted line) and without (full line) interaction between the fragments, along a sequential with an energy
• −
minimum at short distances corresponding to a RX intermediate (left, a) and a fully concerted (right, b)
pathway.
A detailed analysis of the thermodynamic and kinetic impacts of these factors and the outcome of the
competition are presented in Section III. As illustrated in Scheme 14.1, dissociative electron trans-
fers may be triggered photochemically. In these cases, the competition between CDET and SDET
pathways hinges upon the same factors as those in electrochemical reactions, although the driving
force offered to the reaction is larger. These reactions are presented in Section III also. Sequential
cleavage of ion radicals may occur in a homolytic or heterolytic manner, and in both cases, the
cleavage amounts to an intramolecular dissociative electron transfer reaction. These aspects will be
detailed in Section IV, with emphasis put on the systems where symmetry restrictions lead to the
formation of an avoided crossing. For all of these various aspects of charge transfer–bond breaking–
induced processes, systematic analysis of reaction mechanisms as well as the factors that control the
competition between the various reaction pathways leads to structure–reactivity relationships and
therefore to predictive rules.
For all of these reactions in which electrons are used to break bonds, a rationalized descrip-
tion emerges from the analyzed experimental examples and from the mechanistic and theoretical
analyses. Dissociative electron transfer leading to the cleavage of a bond linking two heavy atoms
is also very often coupled to a proton transfer, as it is the case, for example, during the reduction of
O2 into H2O. In these cases also, the degree of concertedness between charge transfer, proton trans-
fer, and bond cleavage is essential in determining the kinetics and the efficiency of the reaction.
These processes will be briefly introduced in Section V and fully discussed in Chapter 13. They are
indeed involved in the activation of small molecules (O2, H+, H2O, CO2) for the storage of electric-
ity (originating, e.g., from solar energy) into chemical bonds, a key challenge for the twenty-first
century chemistry.
II. MODELiNG CONcERTED DiSSOciATivE ELEcTRON TRANSfERS

A. MorSE CUrVE MoDEL
Potential energy curves describing both reactant and products are modeled by Morse curves,
with the assumption that the repulsive interaction of the two fragments formed upon charge
transfer is identical to the repulsive part of the reactant Morse curve [6]. Attending solvent
reorganization is estimated from the Marcus–Hush model. These two ingredients of the model
lead to a quadratic activation (activation free energy: ΔG ≠)–driving force (minus standard free
energy: −ΔG 0) relationship as given in the following:
2
DRX + λ 0  ∆G 0 
∆G ≠ = 1 +  (14.1)
4  DRX + λ 0 

where
D RX is the homolytic bond dissociation energy
λ0 is the solvent reorganization energy
The standard free energy of the reaction leading to complete dissociation (E: elec-
trode potential, ERX/R 0
•
+X−
: standard potential of the RX/R• + X− couple) is given by
∆G = F ( E − ERX/R• +X− ) = F ( E + DRX − T∆S 0 − EX0 • /X− ), where ΔS 0 is the bond dissociation entropy
0 0
•
and EX0 • /X− the standard potential of the X /X− redox couple. When necessary, additional sources
of intramolecular reorganization may be included as an additive term to the intrinsic barrier
∆G0≠ = ( DRX + λ 0 ) / 4 . The homolytic bond dissociation energy represents the kinetic penalty for the
concerted reaction as compared to the sequential pathway. The entropic term in the driving force for
the reaction could be estimated either from known thermodynamical data or by quantum calcula-
tion and usually represents a minor contribution. The electron transfer rates may then be expressed
as in the Marcus–Hush theory [7–11]:

( )  
2
D + λ 0  F E − ERX/R
0
+ X−
k ( E ) = Z exp  − RX
•
1+
4 RT  DRX + λ 0  
   

where Z is the pre-exponential factor. If one assumes that the electron transfer takes place at a fixed
distance from the electrode and including the effect of the multiplicity of electronic states of the
electrons in the electrode leads to
( RT )2
Z = Z coll =
8 M (1 + πRT /λ)

where M is the molar mass of the reactants. One important consequence of taking all electrode
electronic states into account is the disappearance of the inverted region predicted by Equation 14.1
at large driving forces, because of the interference of the electronic states below the Fermi level that
are thermodynamically unfavorable but kinetically advantageous.
If necessary, nonadiabatic effects at the transition state could be included through modification
of Z, for example, from the Landau–Zener theory [12,13] by introducing the transition probability p,
the probability for charge transfer, being obtained from the electronic coupling energy C between
the two involved states
 2p 
Z = χZ coll =   Z coll
 (1 + p) 
  C 2 πRT 
p = 1 − exp  −π   
  RT  λ 

O e– O–
+
O O
O O
6
–2
log (khom/M–1 s–1)
log (khet/cm s–1)

4
–4
2
–6
0
–0.4 –0.8 –1.2 –1.6
ΔG° (eV)
FiGURE 14.3 Quadraticity of the activation–driving force relationship in the electrochemical (•) and homoge-
neous (○) reduction of pivaloyl peroxide. (Reprinted with permission from Antonello, S., Musumeci, M., Wayner,
D.D.M., and Maran, F., J. Am. Chem. Soc., 123, 9577–9549. Copyright (2011) American Chemical Society.)
This set of equations were successfully applied to both heterogeneous and homogeneous CDETs
(in the latter case, the electrode potential in the driving force expression should be replaced by the
standard potential of the molecular electron donor). Many examples of the application of this model to
the reduction kinetics of various families of compounds, involving C–halogen bonds (alkyl and ben-
zyl halides) [6,14–16], O–O bonds (alkyl peroxides) [17,18], but also N–halogen bonds (N-halogeno
sultams) [19], S–C bonds (sulfonium cations) [20], or S–Cl bonds in arene sulfenyl chlorides [21,22].
A remarkable example concerns the reduction of alkyl halides, for which ab initio calculations gave
good evidence for applicability of the Morse curve model [23], while kinetics analysis of the homoge-
neous reaction between electrochemically generated aromatic anion radicals and tertiary alkyl halides
leads to a very close agreement with theoretical calculated rate constants [15]. In the case of less
hindered alkyl halides (secondary and primary), predicted rate constants are below experimental ones
due to progressive competition between simple electron transfer and a SN2 pathway [24]. Another
remarkable feature of the model derives from its quadratic character, as in the Marcus–Hush model.
Large intrinsic barriers in CDET reactions lead to the fact that the curvature of the log k(E) versus ΔG0
is not easily observed. Combining homogeneous redox catalysis and direct electrochemical reduction
of a family of peroxides with weak homolytic bond dissociation energies (DO–O ≈ 1.1–1.3 eV) allowed
to investigate a large range of driving forces (about one and a half volt) and then unambiguously
probe the curvature of the log rate constant versus driving force plot, as illustrated in Figure 14.3 for
pivaloyl peroxide [25]. One additional interesting output of the CDET model is the determination of
unknown homolytic bond dissociation energies from the experimental values of the reduction peak
potentials obtained by cyclic voltammetry, providing that the concerted character of the reaction has
been assessed and the standard potential of the leaving group is known. C–halogen, N–halogen, C–S,
and O–O bond dissociation energies have thus been determined in various families of compounds.
B. STICkY CoNCErTED DISSoCIaTIVE ELECTroN TraNSFEr

During a dissociative electron transfer, an energy minimum, represented in Scheme 14.1 and in
the potential energy diagram of Figure 14.1, corresponding to an ion–radical adduct (R•, X− ) after
the cleavage has taken place, may be obtained. This adduct results from a charge–dipole attractive
interaction between the cage fragments before they diffuse out, and it may be viewed alternatively
as a σ* anion radical or as forming a weak three-electron bond. Even if these interactions strongly
decrease from the gas phase to a polar liquid, they may partly survive when a partial positive charge
is induced on the remaining radical part, thanks to the presence of a strong electron-withdrawing
substituent [26,27]. The Morse curve model has been accordingly modified in order to take into
account these effects. Potential energy curves describing both the reactant and the product systems
are modeled by Morse curves and lead to a quadratic activation (activation free energy: ΔG≠)–
driving force (standard free energy: ΔG 0) relationship as given in the following [26,27]:
( )
2
2
 
DRX − DR•, X− + λ0  ∆G − DR•, X−
0

∆G ≠ = 1 +  (14.2)
( )
2
4  DRX − DR•, X− + λ 0 
 
where D R•, X− is the interaction energy within the ion–radical pair. This last term, through its
square root, has a marked influence of the electron transfer kinetics. As an example, if the sticky
interaction amounts to ca. 1% of D RX, then a decrease of about 15% of the intrinsic barrier will
ensue, thus accelerating the reaction to an experimentally detectable amount. To assess these
sticky effects and quantify their magnitude, experiments in polar solvents have been done for
families of compounds, on one hand by keeping the remaining radical constant while changing
the leaving anion and on the other hand by keeping the leaving anion constant while changing the
nature of the remaining radical. As concerns the former strategy, the electrochemical reduction
in DMF of three haloacetonitriles (NCCH2X; X = Cl, Br, I) provides striking examples where the
in-cage interaction rapidly decreases from Cl to Br and I (from about 40 meV to an almost vanish-
ing interaction), thus showing a decreasing correlation with the halide radius [28]. Coming now
to the latter strategy, it has been shown that the intensity of the interaction decreases as the polar
character of the remaining radical decreases. Comparison within a family of polychlorometh-
anes and polychloroethanes indeed indicates the following order of cluster interaction energies
upon departure of a chloride anion, Cl3C–CCl3 (DR• ,Cl− ≈ 190 meV) > CCl4 > CHCl3, Cl2HC–CCl3
> CH2Cl2, Cl2HC–CHCl2, ClH2C–CHCl2 (DR• ,Cl− = 75 meV), in line with the expected inductive
effects [29]. Increasing the solvation ability toward the leaving anion is still another way to probe
these interactions. The 4-cyanobenzyl chloride reduction at an electrode in various solvents of
increasing polarity leads to a decrease in the interaction energy within the (• CH2PhCN, Cl−) pair
(from 135 meV in 1,2-dichloroethane to 40 meV in formamide), thus confirming the validity of the
ad hoc sticky CDET model [27]. The model may also account for subtle intramolecular effects,
for example, intramolecular hydrogen bonds, that may influence the dynamics of the cleavage
reaction. As an example, it has been shown that with the 2-chloroacetamide (Scheme 14.2), the
chloride anion interacts with the hydrogen atoms borne by the nitrogen upon reductive cleavage
(DR•, Cl− ≈ 150 meV), and more strongly than it does with N,N-dimethylacetamide radical (obtained
from 2-chloro-N,N-dimethylacetamide reductive dechlorination) in which the hydrogen atoms in
the methyl groups are much less polarized (DR•, Cl− ≈ 100 meV) [30].
R R H
H
N C Cl + e– N C , Cl–
R R H
H
O O
R = H, Me
SchEME 14.2 Sticky dissociative electron transfer to chloroacetamides.

As a final remark, one should note that the stepwise mechanism and the concerted should not
be viewed as the extremes of a mechanism spectrum, according to the strength of the interaction
between the two fragments. The stepwise and concerted pathways may enter in competition one
with the other, and thus, the classical distinction between π and σ ion radicals seems more appro-
priate in this connection. The stepwise pathway involves a π ion radical that cleaves in an exergonic
manner, thus giving rise to a σ ion radical, composed of weakly interacting fragments, finally
y ielding the separated fragments. The concerted pathway involves a σ ion radical that ultimately
produces the separated fragments.
III. COMPETiTiON BETwEEN CONcERTED AND SEqUENTiAL

DiSSOciATivE ELEcTRON TRANSfERS
A. STrUCTUraL, ELECTroNIC FaCTorS aND SoLVENT EFFECTS CoNTroLLING THE CoMpETITIoN
The quadratic activation–driving force relationship that is obtained for both outer sphere electron
transfer and CDET leads to the following expression for the transfer coefficient α:
∂∆G ≠ 1  ∆G 0  ∆G ≠
α= = 1 + = .
∂∆G 0 2  λ  λ

In contrast with outer sphere electron transfers, λ is significantly larger for CDET reactions, since it
does include the bond dissociation energy of the cleaved bond. For a given scan rate, the activation
free energy ΔG ≠ is almost the same for the two types of reactions; it thus follows that the trans-
fer coefficient is much smaller in the concerted dissociative charge transfer. Determination of the
transfer coefficient over a range of driving forces could be easily achieved through convolution tech-
niques, and it could be also determined from peak width or variation of the peak width with the scan
rate in cyclic voltammetry through linearization of the activation–driving force relationship around
the peak value, thus providing a useful tool that helps discriminating between mechanisms [31].
RT  1.857 
α peak = −  
F  Epeak − Epeak/2 
29.5
α=
(∂Epeak /∂ log v)

As illustrated by Figure 14.1, that depicts the reduction of a neutral substrate RX through a concerted
or a stepwise pathway involving a radical anion RX as a transient (transposition to the cases where
the reactant is charge positively or negatively is straightforward), the competition between the two
routes involves thermodynamic and kinetic factors (internal factors), but also depends on the solvent
and the energy of the incoming electron (external factors) as well as on electronic factors (coupling
between the diabatic states involved). The passage from the stepwise to the concerted situation is
expected to arise when the ion radical cleavage becomes faster and faster. Under these conditions,
the rate-determining step of the stepwise process tends to become the initial electron transfer. Then,
thermodynamics will favor one or the other mechanism according to the following equation:
∆Gcleav
0
(
= F − ERX/R
0
•
+X −
+ ERX/RX
0
•− )

(
= F D − EX0 • /X− + ERX/RX
0
• − − T∆S
RX →R• +X• ) (14.3)
∆Gcleav
0
is also the standard free energy of cleavage of the ion radical. Thus, one passes from the
stepwise to the concerted mechanism as the driving force for cleaving the ion radical becomes
larger and larger. It may thus be predicted that a weak bond dissociation energy (BDE) of the
0
R–X bond, a negative value of the standard potential of the transient (ERX/RX • −), and a positive
0
value of the standard potential of the leaving group (EX• /X−) will favor the concerted mechanism
and vice versa. All three factors may vary from one RX molecule to another. However, families
of compounds provide examples where the passage from one mechanism to the other is mainly
driven by one of them, the changes in the others being minimized. Many studies have been con-
ducted along these lines, and the influence of all of the factors has been identified and illustrated
by several examples [16,19,32,33]. Some of them are reported in Table 14.1.
In this context, the solvent plays an important role in the (de)stabilization of the intermedi-
ates as well as the leaving group involved in the dissociative charge transfer. For example, it
has been shown that solvation and ion-pairing effects affect the cleavage reactivity of anion
radicals containing a frangible bond, depending upon the localization of the negative charge
[34]. For the anion radicals from 3-nitro-benzylchloride and bromide, 4-chlorobenzophenone,
and N-fluoro-7-nitrosaccharin-sultam for which the negative charge is mostly concentrated on
a small portion of the molecule (on the oxygen atom of carbonyl or nitro groups), the addition
of water or ion-pairing agents (e.g., Li+ and Mg2+) slows down the cleavage of the anion radical,
in parallel with a positive shift of the standard potential for its formation, that is, a stabilization
of π ion radicals. In contrast, when the charge on the intermediate is spread out over the entire
molecular framework, for example, in 2- and 9-chloroanthracenes, the addition of lithium or
magnesium ions has no effect on the cleavage rate, while addition of water results in an accel-
erating effect at large water concentration caused by specific solvation of the leaving anion.
Beyond these stabilization–destabilization effects, the solvent itself may be responsible for the
passage from a stepwise to a concerted mechanism of the reductive cleavage reaction, that is,
the very existence of π anion radicals may hinge on interactions between the electron first resi-
dence group and the solvent [35]. In the case of the para-cyanobenzyl chloride, gas phase calcu-
lations show that only a σ-radical anion at large C–Cl distances is obtained upon reduction [35],
while reduction in water by pulse radiolysis goes through a radical anion i ntermediate, which
decomposes quickly (submicrosecond time range) [36]. Calculations on a model compound
including explicit solvent molecules (ONCH 2Cl + e− + 2H 2O) have allowed to capture the role of
solvent molecules that stand close to the charge centers of the molecule, even if the representa-
tion of the solvent by only two water molecules is too simplistic at the quantitative level. During
bond cleavage, solvent reorganization is well pictured in qualitative terms by the decrease in
the interaction between one water molecule and the oxygen of the NO group and the parallel
increase in the interaction between the second water molecule and the leaving chloride ion, as
illustrated in Figure 14.4 [35].
The qualitative idea is that in a real solvent, the interactions of the many surrounding solvent
molecules with the negative charge on the oxygen atom weaken at the benefit of the interactions
between the solvent molecules surrounding the chlorine atom with the charge borne by this atom,
the barrier for the anion radical cleavage being due to this solvent reorganization.
In complement to the solvent effects on the thermodynamic and kinetic stability of π anion
radicals and to the role of structural parameters, the electronic coupling between the diabatic
states associated with the fragmented products on one hand and the intermediate on the other
hand appears as an additional effect that may control the very existence of a transient species
along the reaction pathway. Reductive cleavage of the three cyanobenzyl chloride isomers in
N,N-dimethylformamide illustrates this idea [37]. While charge transfer is concerted with C–Cl
bond breaking and acts as the rate-determining step in the case of both the ortho and para isomers,
an anion radical is transiently formed before fragmentation for the meta isomer. In this family,
the factors invoked so far to explain the followed mechanism are similar (bond dissociation
TABLE 14.1
Molecular Factors Governing the Competition between
Stepwise and Concerted Mechanisms
Sequential Concerted
Aryl halides, except some

iodides, see text All aliphatic halides References
Examples of the prevailing role of E 0RX/RX –
O2N CH2Cl (Br) (NC) H CH2Cl (Br) [16]
N–F N–F [19]

O2N SO2 SO2
(NC) O2N C CH2Br (CH3O) H C CH2Br [32]

O O
Examples of the prevailing role of the bond dissociation energy (DRX)
CH2Cl (Br) [16]

Cl (Br) Z
Z
(except Z = NO2)
NC CH2F NC CH2Cl (Br) [16, 32]
C CH2F C CH2Cl (Br) [32, 33]

O O
N–F N–Cl (Br, I)

[19]
O2N SO2 O2N SO2
O 2N CH2Cl (Br) N–Cl (Br) [16, 19]

O2N SO2
Examples of the prevailing role of E 0X /X –
C CH2X + e– C CH2 + X– [32]

O O
X = OPh, OCH3, OC2H5,
X = Br, Cl
SPh, SC2H5, N(C2H5)2
energy, entropy of dissociation, standard potential of the leaving group, and in-cage interaction).
As already mentioned, the electron transfer activation energy at the peak potential remains the
same at a given scan rate; therefore, the potential peak shift observed between the meta isomer
and the para and ortho isomers (about 200 mV more positive in the two latter cases) is a conse-
quence of an energetic shift of the electron transfer transition state. Since it is very likely that
the shape of the reactant potential energy curve is identical for all three isomers, the location
change of the transition state is due to an energetic shift of the product electronic state curve.
The reactant energy curve will respond by translating upward so that the activation energy
1.2
Potential energy (eV)
1
0.8
0.6
0.4
0.2
0
–0.2
–0.4
–0.6
Reaction coordinate
–0.8
–0.2 0 0.2 0.4 0.6 0.8 1 1.2
(a)
H 3.30
O N 2.40
Cl
C 2.150
2.214
1.856 2.520
O
(b)
O
FiGURE 14.4 (See color insert.) Potential energy profiles (from QCISD(T)/6-31G* calculations) for
cleavage of ONCH 2Cl anion radical in the presence of two water molecules. (a) Potential energy versus
reaction coordinate. (b) Structures at each potential energy minimum (distances between atoms in Å).
(Reprinted with permission from Costentin, C., Robert, M., and Savéant, J.-M., J. Am. Chem. Soc., 126,
2004, 16834–16840. Copyright (2011) American Chemical Society.)
remains identical. This vertical translation is endowed with a peak shift, that is, a change of the
energy of the electron being transferred (see Figure 14.5a).
The fundamental reason that underlie such shift is related to the fact that the π* orbital
receiving the extra electron in the π anion radical − •RX does overlap with the σ* C–Cl orbital.
In terms of electronic states, this means that the π* and σ* diabatic states mix. This mixing is
expected to be heavily influenced by the nature and the position of substituents on the aromatic
ring: it is stronger in the case of the ortho- and para-cyanobenzyl chlorides than it is in the
case of the meta-cyanobenzyl chloride (the coupling constant in the phase space region where
the two states' cross has been estimated to be larger than 0.15 eV in the former cases, in line
with the fact that in the anion radical, the spin density is important at the para and ortho posi-
tions), so stronger that the π anion radicals no longer exist with the ortho and para compounds,
that is, live less than a vibration, as illustrated in Figure 14.5b. In other words, the mechanistic
pathway results from a balance between various effects such as intrinsic barrier for cleavage,
solvent polarity (the more polar the solvent, the more stable the π anion radical), and also elec-
tronic coupling between the π* and σ* diabatic states, this coupling being modulated by the
molecular structure. With the meta-cyanobenzyl chloride, the balance is in favor of the π anion
radical existence in polar solvents such as acetonitrile, and the mechanism is driven toward a
stepwise pathway. In the case of the para-(ortho-)cyanobenzyl chloride derivative, the balance
may be reversed since a concerted mechanism occurs in 1,2-dichloromethane, acetonitrile,
N,N-dimethylformamide, ethanol, and formamide, whereas a stepwise mechanism, with a very
fast cleavage step, is observed in water, thanks to the solvent stabilizing effects on the interme-
diate anion radical [36].
CH2Cl CH2Cl CH2Cl
CN NC
CN
Potential energy Potential energy
–
RX
–E 0RX/RX – = –Ep,meta
–
–Ep RX
RX + e–
R + X– R + X–
–E 0RX/R + X–
Reaction coordinate Reaction coordinate
(a) (b)
FiGURE 14.5 (a) Potential energy profiles for the stepwise reduction of meta-cyanobenzyl chloride (dotted
lines) and for the concerted reduction of ortho- and para-cyanobenzyl chlorides (full lines). (b) Diabatic
(dotted lines) and adiabatic (full lines) electronic states of the products in the case of strong coupling (ortho
and para derivatives).
B. RoLE oF THE DrIVING ForCE

The electrochemical reduction of sulfonium cations in acetonitrile according to Figure 14.6 offers a
0
striking example of the combined roles of ERX/RX • − and of the homolytic bond dissociation energy,
the former parameter being a measure of the energy of the π* orbital of the radical in which the
incoming electron may be accommodated [20]. As seen in Figure 14.6, a matrix-type representation
of the occurrence of the concerted and stepwise mechanism as a function of these two parameters
may be sketched. The borderline situations that appear on the diagonal allow one to uncover the role
of the driving force offered to the reaction. As mentioned earlier, an increase in the driving force
offered to the reaction makes the mechanism pass from a concerted to a stepwise mechanism. The
change is associated with a change of the activation driving force law, which remains quadratic but
with different standard potentials and intrinsic barriers.
The symmetry factors in the concerted mechanism are smaller, in absolute value, and vary less
rapidly with the driving force than for the stepwise mechanism. In practice, cyclic voltammetry is an
ideal tool to make the driving force vary, since the potential may be driven toward more negative val-
ues by increasing the scan rate or decreasing the temperature. A first experimental example of passage
from a concerted to a stepwise mechanism was found with the reductive cleavage of the borderline
sulfonium cations of Figure 14.6. An analysis of the observed variation of the transfer coefficient α
with the scan rate shows a nonlinear variation, a characteristic of the transition zone between the two
mechanisms [1,2,20]. Involvement of adsorption of the ylide formed during the reaction was shown
to be insignificant, and thus, this unusual, nonlinear dependence of α with the driving force has been
assigned to the transition between the two concerted (at small driving forces) and stepwise (at large
driving forces) mechanisms. Another example of passage from one mechanism to the other was iden-
tified in the reduction of the tert-butyl 4-cyanoperbenzoate (O – O bond cleavage), for which cyclic
voltammetry and convolution analysis have shown an “α-wave” with an almost constant symmetry
factor at low driving forces, which progressively increases and then decreases when the driving force
becomes larger and larger, the stepwise mechanism then becoming dominant [38]. Combination of
E 0RX/RX –
S+ S+ S+
CH3 CH3 CH3
S+– R + e– S–R Stepwise Stepwise Stepwise
Concerted Stepwise
S+
S+R S+
C C
H2 H2
D Borderline Borderline
S+ S+ S+
C CN C CN C CN
H2 H2 H2
Concerted Concerted Stepwise
S+ S+
C C C C
H2 H2
O O
Concerted Concerted
FiGURE 14.6 Reductive cleavage of sulfonium cations.
this cyclic voltammetry–convolution analysis also leads to the identification of a mechanism transi-
tion upon increasing the driving force in the heterogeneous dissociative reductive cleavage of S–C
bonds in the 4-methylphenyl and 4-methoxyphenyl thiocyanate [39]. The electrochemical reduction
of aryl iodides usually follows a stepwise mechanism, with a few exceptions. The mechanism shifts
from concerted to stepwise upon increasing the scan rate in experiments carried out at room tempera-
ture with both iodobenzene and 4-methyliodobenzene (Figure 14.7). The transition between the two
0.45 0.45
α α
0.4 0.4
0.35 0.35
log (v/V s–1) log (v/V s–1)

0.3 0.3
–2 –1 0 1 –2 –1 0 1 2
FiGURE 14.7 Electrochemical reduction of aryl halides in DMF. Variation of the transfer coefficient α with
the scan rate v. ●: iodobenzene, ○: bromobenzene, ▽: 1-iodonaphthalene, ◊: 4-methyliodobenzene, at 298 K, □:
iodobenzene at 329 K.
mechanisms is also obtained at higher temperatures, but the balance is, as expected, more in favor
of the concerted mechanism. As compared to phenyl bromides, the C–halogen bond dissociation is
weaker in iodide derivatives and their π* orbital less accessible than that of other aromatic substrates,
for example, naphthalene iodides, for which the mechanism is always stepwise.
Even if more difficult to detect, a mechanism crossover involving a homogeneous reaction has
been characterized in the SRN1 reaction between the 2-nitropropane ion and the 4-nitrocumyl chlo-
ride [40]. In this case, the 2-nitropropanate ion serves both as nucleophile and electron inductor and
the charge transfer from the 2-nitropropanate ion to the halo compound is faster by five orders of
magnitude than predicted on the basis of a stepwise mechanism, thus leading to the conclusion that
the concerted pathway is followed instead, due to a low driving force (+0.1 V).
The diverse and accumulating examples thus gathered of a mechanistic shift from concerted
to stepwise when increasing the driving force in the cleavage of C–Cl, C–I, C–S, and O–O bonds
firmly confirm the key role of the energy of the incoming electron.
C. ELECTroCHEMICaL VErSUS PHoToINDUCED DISSoCIaTIVE ELECTroN TraNSFEr

Besides electrochemical induction (heterogeneous or homogeneous), reductive and oxidative cleav-
age reactions may also be triggered photochemically by means of an excited state of a sensitizer, as
pictured in Figure 14.8.
An interesting way of fighting energy-wasting back-electron transfer in photoinduced electron
transfer reactions is to use a system where either the acceptor or the donor in the resulting ion pair,
or both, undergoes a fast cleavage reaction [41]. The occurrence of a concerted dissociative reaction
rather than a stepwise reaction (Figure 14.8a) thus appears as an extreme and ideal situation where
the complete quenching fragmentation, quantum yield, should be unity [41]. From a diagnosis
standpoint, the observation of a quantum yield smaller than unity would thus rule out the occur-
rence of a concerted dissociative mechanism. This intuitive notion is in fact incorrect as illustrated
in Figure 14.8, showing a section of the potential energy surfaces along the reaction coordinate.
After the photoinduced dissociative electron transfer has taken place, the system approaches the
intersection between the fragmented product energy surface and the energy surface associated
with the uphill dark dissociative electron transfer. There is thus the possibility of a partition of the
reaction pathway between these two surfaces, leading in part to the fragmented products and in
part to back-electron transfer. Figure 14.8 shows the case of an avoided crossing between the two
surfaces, but partition may also occur in the case of a conical intersection. In any case, the quantum
yield for a concerted dissociative photoinduced electron transfer may well be smaller than one [42].
(R , X , D*)
Potential
energy
D + hv D* (R , X , D)
(RX, D*)
D* + RX D + RX
hv
Stepwise (R , X–, D +)
Concerted
Reaction coordinate
R + X– + D (RX, D)
(a) (b)
FiGURE 14.8 Photoinduced dissociative electron transfer. Reaction scheme (a). Section of the zero-order (...)
and first-order (_) potential energy surfaces along the reaction coordinate, when stretching of the cleaving bond
is the main factor of nuclei reorganization (b).
CN
CN CF3
S+
CCl4
CH2
CH2 S
CH2Cl S +
+ CN
(a) C C C Borderline S S
(b) C C Borderline S S S
(C: concerted reductive cleavage, S: sequential reductive cleavage)
SchEME 14.3 Similarities and differences in the mechanisms of (a) electrochemical and (b) photoinduced
(with the excited state of 2-ethyl-9,10-dimethoxyanthracene as an electron donor) reductive cleavage of vari-
ous compounds.
For the same substrate, the driving force offered in the photoinduced case is always larger than in
the electrochemical case, making it possible for the mechanism to be stepwise or borderline in the first
case and borderline or concerted in the second [43]. As an example, the reductive cleavage of the C–S
bond in 4-cyanobenzylmethylphenyl sulfonium cation follows a concerted pathway in electrochemical
conditions, while its photoinduced reduction by the excited state of 2-ethyl-9,10-dimethoxyanthracene
appears to be a competition between the concerted and the stepwise pathways, both being equally
favored [43]. Scheme 14.3 highlights the differences and similarities between electrochemically and
photochemically induced dissociative electron transfers in a series of substrates. The factors that con-
trol the competition between the two mechanisms electrochemical and photoinduced electron transfer
are thus coherent, provided the differences in driving force are taken into account.
IV. CLEAvAGE Of PRiMARY RADicALS

Primary radicals, for example, ion radicals, issued from one electron transfer to or from a parent
molecule RX are usually fragile species that quickly decompose, more readily than their parents.
When the unpaired electron is located on the R portion of the molecule, cleavage is heterolytic and
amounts to an intramolecular electron transfer from the R to the X leaving group in the case of
an anion radical and to an intramolecular electron transfer in the reverse direction in the case of a
cation radical (Scheme 14.4). When on contrary the unpaired electron is located on the X por-
tion of the molecule, the cleavage step involves a homolytic dissociation of the fragmented bond
(Scheme 14.4).
This distinction between two modes of cleavage is also valid in the case of uncharged radicals
resulting either from the reduction of cationic substrates or to the oxidation of anion substrates,
producing a neutral secondary radical, R− •, and a neutral leaving group, X. In both the homolytic
and heterolytic case, it has been shown that the cleavage reactions could be described as an intra-
molecular dissociative electron transfer concerted with bond breaking [44,45].
– R X – + +
R X R• X R X
Heterolytic Homolytic Heterolytic Homolytic

R + X– R + X–
(a) (b)
SchEME 14.4 Heterolytic and homolytic bond cleavages in radical anions (a) and radical cations (b).
The cleavage of aromatic anion radicals, which provides an example of heterolytic cleavage, has
attracted considerable attention, with emphasis on the cases where the leaving group is a halide
ion, stimulated by the fact that this type of reaction is involved in the propagation loop of electron
transfer–catalyzed aromatic SRN1 substitutions. An extension of the theory of dissociative electron
transfer has been proposed to the intramolecular case, leading to the following quadratic activation–
driving force relationship [44,46]:
2
≠
 ∆GRX
≠
0
•−
→R• + X −

∆G = ∆G  1 +  (14.4)
RX• − →R• + X − 
0
4∆G0≠
 
where
≠
∆GRX • − →R• + X − is the free energy of activation
∆GRX
0
• −→R• + X − is the standard free energy for cleavage and is identical to Equation 14.3

∆GRX
0 0
(
• − →R• + X − = ∆Gcleav = F DRX →R• + X• − T∆SRX →R• + X• + ERX/RX• − − EX• /X −
0 0
)
where
D RX→R• + X• is the homolytic bond dissociation energy of the starting RX
ΔSRX→R• + X• is the corresponding entropy change
The E 0 are the standard potentials of the various subscript redox couples
The intrinsic barrier, ∆G0≠ , is equal to one-fourth of the sum of the homolytic bond dissociation
energy of the intermediate and of the reorganization energy upon cleavage:
DRX• − + λ 0
∆G0≠ = (14.5)
4
where DRX•− may be expressed as
DRX• − = DRX→R• + X• + ERX/RX

0
• − − ER• /[R• ]• −
0
(the two missing entropic terms, T (SRX − SRX• −) and −T(SR•−S[R•]• −), may be considered as compen-
• •
sating each other) and [R ] − represents a species obtained from the injection of one electron in the
•
π* orbital of the σ-radical R , thus leading to an excited state of the carbanion R−. λ0, the solvent
reorganization energy, corresponds to the transfer of the negative charge from the anion radical to
the leaving halide ion, and it could be expressed in the Marcus way as
e02  1 1  1 1 1 
λ0 =  −  + − 
4πε0  εop εs   2aRX• − 2aX− aRX• − + aX− 
  

where
e0 is the electron charge
ε0 is the vacuum permittivity
εop and εS are the solvent optical and static dielectric constants, respectively
The a are the radii of the equivalent spheres of the subscript species.
12 12
log k
10 10 log k
8 8
6 6
4 4
2 2
0 0
–2 0
–ERCl/RCl – –2 0
–ERBr/RBr –
–4 –4
0.8 1.2 1.6 2 2.4 2.8 0.6 1 1.4 1.8 2.2 2.6
1.2 1.2
1 ΔG≠ – – 1 ΔG≠
RCl R + Cl RBr – R + Br–
0.8 0.8
0.6 0.6
0.4 0.4
0.2 0.2
0 ΔG0
ΔG0
–
RCl R + Cl– 0
RBr – R + Br–
–0.2 –0.2
1.5 1 0.5 0 –0.5 –1 1.5 1 0.5 0 –0.5 –1
FiGURE 14.9 Correlation between the fragmentation rate constant (in s−1) and the standard potential (in
V vs. SCE) (top) and activation–driving force relationship (free enthalpies in eV) (bottom) for aryl chloride
and bromide anion radicals.
≠
The activation free energy, ∆GRX • − →R• + X − , may also be obtained from the experimental determi-
≠ RT
nation of the cleavage rate constant k: ∆GRX •− →R• + X − = ln(kBT /hk ) . Combining electrochemical
F
and photochemical techniques (e.g., pulse radiolysis) has allowed to determine cleavage rate con-
stants spanning more than 12 orders of magnitude, for both chloro and bromo aromatic compounds
0
[46]. The activation-standard potential plots (ERX/RX •−) for both aryl chlorides (23 compounds) and
aryl bromides (22 compounds) show remarkable correlation (Figure 14.9). Converting then the
0
ERX/RX •− scale into a driving force scale through the use of Equation 14.3 leads to activation–driving
force plots shown in Figure 14.9.
These plots necessitate the estimation of both EX0 • /X− , the bond dissociation energies D RX→R• + X•
of the neutral compounds (almost constant for a given halogen) and the entropic term (the quasicon-
sistency of which were checked by DFT calculations). In the two cases, the correlation straight line
is close to 0.5, thus suggesting, taking into account that the driving force range is spread out over
positive and negative values, a linearization of the quadratic activation–driving force relationship
(14.4) [46]:
≠ 1
∆GRX •−
→R• + X −
= ∆G0≠ + ∆GRX
0
•−
→R• + X −
(14.6)
2
The intrinsic barrier, ∆G0≠, may thus be estimated to 0.41 eV for the chlorides and to 0.39 eV
for the bromides. Application of Equation 14.5 leads to a predicted estimation of ∆G0≠ , 1.23 and
1.03 eV for the chloro and bromo derivatives, respectively. The large difference obtained between
the predicted and experimental values may originate from two factors that tend to decrease the
barrier to overcome for cleavage. The first one is out-of-plane bending that permits skirting round
the conical intersection encountered upon straight stretching of the C–X bond as in the model
used to derive Equation 14.4. The second one is due to the possible formation of a weak σ anion
radical after cleavage has taken place (D R•,X−), as described in Section II.B for purely concerted
processes. The previous Morse curve model was adapted to take into account these two additional
factors [46]. The first of these is assumed to follow a harmonic law, that is, the energy increase
varies as ( fb /2)θ2b , where θb is the bending angle and f b the force constant. The gain in resonance
energy is assumed to be proportional to the bending angle: H = h 0 θb. It follows that Equation 14.4
remains valid but with a different definition of the intrinsic barrier:
( ) −h
2
λ0 + DRX• − − DR• ,X− 2
∆G0≠ = 0
(14.7)
4 2 fb
h02 / 2 fb may be regarded as constant within the linearized region around the zero of driving force.
The activation–driving force relationship (14.6) is thus modified:
( ) −h
2
λ0 + DRX• − − DR• ,X− 2
≠
∆GRX • − →R• + X − =
0
4 2 fb
+ 0.5∆GRX
0
• − →R• + X − (14.8)

It thus appears that the intrinsic barrier is decreased through two terms, −h02 / 2 fb and DR• ,X− .
Values of −h02 / 2 fb comprised between 0.3 and 0.5 eV, as computed for 4-cyanochlorobenzene are
compatible with the aforementioned experimental data.
The reduction of the 2-nitro and 2,4-dinitrophenyl sulfenyl chloride provides another exam-
ple where the initially formed π radical anion upon one electron reduction cleaves heterolyti-
cally and yields a σ* radical anion before the sulfur-centered radical and the chloride anion
fall apart [22]. The model describing the heterolytic cleavage of anion radicals also proved
to be useful in deciphering regioselectivity of the cleavage, for example, for the reduction of
nitro-substituted benzyl thiocyanates (O2N–C6H4CH 2 –S–CN), for which α-cleavage (CH 2 –S
bond) is preferred over β-cleavage (S–CN bond) from both thermodynamic and kinetic points
of view [47].
Homolytic, exothermic cleavage of radicals may exhibit a sizable activation barrier, for
example, in the electrochemical reduction of the 4-nitro-tert-butylperbenzoate, whose O–O
bond is broken after the formation of a transient π* anion radical [45]. Among various examples,
this is also the case in the cleavage of anion radicals of nitrobenzyl phenyl ether (C–O bond
cleavage), as well as during the cleavage of the S–C bond in the anion radical of the nitrophe-
nyl diphenylmethyl thioether, and of the C–N bond in the anion radical of α-nitrocumyl. Such
homolytic cleavage of radicals and ion radicals implies that an electron is being transferred
from a π* orbital into the σ* orbital of the bond being broken. It has been shown, based on a
two-state description model of the potential energy surfaces, and inclusion of the bond cleavage
and formation as Morse curves in the normal-mode analysis, that the kinetics of cleavage could
be described through a quadratic activation–driving force relationship [45]. The intrinsic bar-
rier is made of two main contributions, the π* to σ* excitation energy in the transient ion radial
and the triplet excitation energy of the leaving group. The predictions of the model in terms of
fragmentation kinetics agree well with experiments in a family of 4-cyanophenyl alkyl ether
anion radicals [45].
Activation–driving force relationship based on Morse curve description of potential energies of the
various electronic states has proved their validity for both qualitative and quantitative descriptions
of dissociative electron transfers, including concerted reactions, homolytic and heterolytic cleavage
of primary radicals and ion radicals, as well as photoinduced processes, for which the electron donor
is the excited state of an aromatic molecule. Backed with experimental facts, the understanding of
the coupling of bond breaking with electron transfer has now reached a good degree of compre-
hensiveness, in terms of kinetics, mechanisms, and models. The factors that govern the dichotomy
and competition between stepwise and concerted pathways, encompassing structural and electronic
factors as well as the influence of the solvent and the energy of the incoming electron, have been
deciphered and their role analyzed. Recent improvements lead to modeling modification to take into
account the possible attractive interactions between caged fragments (sticky dissociative electron
transfer) and symmetry restrictions leading to conical intersections. A route is therefore opened to
widespread applications of the available concepts and models, with possible emphasis on biological
processes, especially redox enzyme reactions. As an example, it is worth mentioning that reductive
dehalogenases isolated from anaerobic bacteria, which couple the reductive dehalogenation of tet-
rachloroethylene (PCE), trichloroethylene (TCE), and other chlorinated hydrocarbons to energy
conservation (dehalo-respiration), open the way to biological strategies for remediation of systems
polluted by halohydrocarbons. Sulfurospirillum multivorans catalyzes the reductive dehalogenation
of PCE and TCE to (Z)-1,2-dichloroethene (DCE) with exceptionally high specific activities, using
as cofactor a corrinoid (norpseudovitamin B12) [5]. The rate constants for electron transfer from
the enzyme or from outer sphere aromatic reduced donors to PCE or TCE were derived from cyclic
voltammetric redox catalysis experiments, and were slower with aromatic donors by 12 orders of
magnitude [48]. An electron transfer mechanism is thus not consistent with the observed rates. The
actual mechanism therefore involves more intimate interactions between the electron donor and the
substrate in which the PCE (or TCE) molecule enters the cobalt coordination sphere. Beyond this
example, there are clearly a large number of other enzymatic processes in which electron transfer
and bond breaking are coupled, the understanding of which could benefit from the same kind of
electrochemical approach.
Electron transfer–/bond breaking–coupled reactions illustrate the benefits that could result from
concertedness. It results in an increase of the driving force offered to the overall process; however,
there is a price to pay, due to the increase in the intrinsic barrier paralleling the increase in the bond
strength, even if the global result is beneficial.
Coupling of electron transfer and proton transfer is another example of the virtues of concerted-
ness. Coupling between electron transfer and proton transfer indeed occurs in a huge number of nat-
ural and artificial processes, for example, in the electron transfer activation of small molecules such
as H2O, O2, and CO2, and the growing attention that these reactions focuses is likely to intensify by
the necessity to face current energy challenges. Focusing on reactions where proton and electron
transfers involve different sites, the possibility that proton and electron transfer steps are concerted
giving rise to concerted proton–electron transfer (CPET) reactions as opposed to stepwise pathways
in which proton transfer precedes (PET) or follows (EPT) electron transfer, possess the advantage
of circumventing the stepwise pathway high-energy intermediates. This thermodynamic benefit is,
however, associated with a kinetic counterpart related to an increased nonadiabaticity due to the
tunneling of both electron and proton in the transition state rather than to an increased reorganiza-
tion energy (see Chapter 13). The next step would be to see if concertedness could apply to reactions
involving not only electron transfer and proton transfer but also breaking of a bond between heavy
atoms. The impact of concertedness for such couplings would be particularly worth investigating
in the context of small molecule activation, for example, in the electrochemical reduction of CO2,
whose first step consists in the formation of CO, which implies a two-electron reduction, a C–O
bond cleavage, and a protonation of the leaving oxygen atom. Only one example of an all-concerted
reaction has been shown in the reductive cleavage of an O–O bond [49], helped by the presence of
a proximal, H-bonded carboxylic acid group, the experimental and theoretical analysis of which is
detailed in Chapter 13.
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15 Electron Transfer–Catalyzed
Reactions
Kazuhiro Chiba and Yohei Okada
CONTENTS
I. Introduction ........................................................................................................................... 531
II. Oxidative Mediators .............................................................................................................. 534
A. General Mechanism ....................................................................................................... 534
B. Triarylamines................................................................................................................. 534
C. TEMPO ......................................................................................................................... 538
D. Halide Ions ..................................................................................................................... 538
E. Iodoarenes ...................................................................................................................... 539
F. o-Aminophenols ............................................................................................................ 543
III. Reductive Mediators..............................................................................................................544
A. General Mechanism .......................................................................................................544
B. Nickel(II) Salens ............................................................................................................544
C. o-Carboranes ................................................................................................................. 545
IV. Oxidative Chain Reactions ....................................................................................................546
A. General Mechanism .......................................................................................................546
B. Radical Cation Chain Reaction ..................................................................................... 547
C. Cation Chain Reaction ................................................................................................... 547
V. Reductive Chain Reactions ................................................................................................... 549
A. General Mechanism ....................................................................................................... 549
B. Electrochemical SRN1 Reaction ..................................................................................... 550
VI. Measuring Redox Potentials.................................................................................................. 551
A. General Aspects ............................................................................................................. 551
B. Direct Measuring ........................................................................................................... 551
C. Indirect Measuring ........................................................................................................ 551
VII. Conclusions ........................................................................................................................... 552
References ...................................................................................................................................... 553
I. INTRODUcTiON
Electron transfer is one of the most fundamental and ubiquitous processes of all chemical and bio-
logical systems, and thus has been studied in detail both theoretically and practically. In organic
synthesis, electron transfer–induced reactions have been extensively utilized to achieve various
chemical transformations, constructing a wide variety of organic compounds, including natural
products, pharmaceutical products, and functional materials. In order to trigger electron transfer–
induced reactions, photochemical processes and one-electron redox reagents are widely employed.
In this context, electrochemical processes have also been utilized to regulate either one or two
electron transfers at the surface of the electrodes that afford not only various functional group
transformations but also a wide variety of carbon–carbon bond formation reactions in a hetero-
geneous manner [1–3]. Several reactive intermediates such as ions, radicals, and radical ions are
531
generated through the electron transfer to avoid consumption of additional redox reagents and the
redox potentials can be easily controlled under mild electrolytic conditions. Therefore, they are
promising methodologies from an environmental viewpoint.
Moreover, various elegant strategies have been demonstrated to modify the surface of the elec-
trodes, which might dramatically change the reaction conditions. It is well established that gold or
carbon electrodes can be covalently grafted through treatment with thiols [4–13] or aryldiazonium
salts [14–23] to functionalize their surfaces. For example, a self-assembled monolayer (SAM) was
formed enantioselectively on the surface of a gold electrode with a (111)-oriented surface using
d- or l-homocysteine (Hcy) (Scheme 15.1) [24]. The redox behavior of an electrochemically active
chiral 3,4-dihydroxyphenylalanine (DOPA) was then analyzed by cyclic voltammetry using the
Hcy-modified gold electrode to impart enantioselectivity in the redox reaction of DOPA in acidic
solution. Thus, the SAM of d-Hcy (1) was suggested to block the redox reaction of l-DOPA (2),
while the SAM of l-Hcy (3) was suggested to block that of d-DOPA (4). These modified electrodes
have found a wide variety of applications in chemistry, including analytical, biological, and physical.
In contrast, it is well known that electron transfer between two solid phases is severely limited. In
organic electrochemistry, solid phase–bound substrates are barely oxidized or reduced at the surface
of the electrodes. Based on this fact, solid phase–supported bases have been introduced into electro-
lytic systems for in situ generation of a supporting electrolyte [25–28]. For example, methanol was
NH+3 NH+3
O O
HS HS
1 OH 3 OH
NH+3 NH+3
O O
S S
OH HO OH HO
NH+3 NH+3
O O
HO HO
2 OH 2 OH
O O
NH+3 NH+3
O O
O O
NH+3 OH NH+3 OH
O O
S S
OH HO OH HO
NH+3 NH+3
O O
HO HO
4 OH 4 OH
O O
NH+3 NH+3
O O
O O
NH+3 OH NH+3 OH
O O
S S
OH OH
Gold electrode Gold electrode
SchEME 15.1 Enantioselective redox reaction of DOPA using homocysteine modified gold electrodes.
Electron Transfer–Catalyzed Reactions 533
Base
S CF3 10 mA/cm2
5 3F OMe
S CF3
MeOH CF3
S
(+)Pt-Pt(–)
OMe 5
S CF3 Solid phase Base Yield (%)
MeOH
Porous polystyrene N 92
Base
Silica gel 76
N
MeO– + H+
Silica gel 89
N
Anode NH
SchEME 15.2 Anodic methoxylation of phenyl(2,2,2-trifluoroethyl)sulfide (5) using solid-supported bases.
dissociated into methoxide anions and protons by porous polystyrene or silica gel–supported bases to
achieve electrical conductivity without additional supporting electrolytes, while solid phase–supported
bases were not oxidized at the surface of the electrodes (Scheme 15.2) [29]. The anodic methoxylation
of phenyl(2,2,2-trifluoroethyl)sulfide (5) took place effectively in the presence of solid phase–supported
bases. In addition, these solid phase–supported bases could be recovered simply by filtration, enabling
their reuse. Surface-bound and immobilized molecules are discussed in detail in Chapter 42.
As described, in general, direct heterogeneous electron transfer at the surface of electrodes induces
electrochemical transformations. Meanwhile, several reactive intermediates generated through the
electron transfer can react in a homogeneous bulk electrolyte solution. Therefore, the possibility of
organic electrochemistry can be expanded through the use of indirect homogeneous transformations.
For example, cathodic reduction of the starting material results in electrochemical reactions forming
anionic species that function as subsequent bases or nucleophiles, known as electrogenerated bases
and nucleophiles, which are discussed in detail in Chapter 43. In this chapter, indirect electrochemical
transformations using redox mediators are discussed (Scheme 15.3). The redox mediators are recog-
nized as electron carriers, which are activated through heterogeneous electron transfer at the surface
Heterogeneous Homogeneous
electron transfer electron transfer
Mediator Starting
(inactive) substrate
Mediator Reactive Chemical

(active) intermediate transformations
Electrode
SchEME 15.3 Schematic illustration of an indirect electrochemical transformation using redox mediators.
Heterogeneous Homogeneous
electron transfer electron transfer
Starting
substrate
Chemical
transformations
Reactive Reactive
intermediate intermediate
Electrode
SchEME 15.4 Schematic illustration of an electrochemical chain reaction.
of electrodes and then function as homogeneous redox reagents. One of the most salient features of
indirect electrochemical transformations using redox mediators is that they take place over the exis-
tence of thermodynamic hurdles that would seemingly preclude electron transfer between the activated
mediators and substrates in bulk electrolyte solution [30,31]. After the homogeneous electron transfer,
the redox mediators are generally reactivated at the surface of the electrodes through heterogeneous
electron transfer. Therefore, only a small amount of the redox mediators is required to complete the
chemical transformations. To date, various organic and inorganic mediators have been established to
realize the ingenious design of the reaction systems, leading to promising manufacturing techniques.
Additionally, autoactivating chemical transformations induced by direct heterogeneous electron
transfer, known as electrochemical chain reactions, are discussed in this chapter (Scheme 15.4). In
this case, the starting substrate is activated through electron transfer at the surface of the electrode,
while the resulting intermediate is responsible for the following activation in the homogeneous bulk
electrolyte solution to drive the chain cycle. Thus, only a catalytic amount of electricity is required
to complete the reaction. The aim of this chapter is to give an outline of indirect electrochemical
transformations with recent examples.
II. OxiDATivE MEDiATORS

A. GENEraL MECHaNISM
As indicated earlier, redox mediators can be defined as electron carriers that are activated through
heterogeneous electron transfer at the surface of electrodes and then function as homogeneous redox
reagents. There are two types of redox mediators: oxidative and reductive. Typically, the oxida-
tive mediators are activated through anodic oxidation and the resulting intermediates function as
subsequent oxidants (Scheme 15.5). The oxidative mediators also play critical roles in preventing
overoxidation of the products, which suppresses the formation of a polymeric film on the anode,
known as anodic passivation [32–34].
In this section, indirect electrochemical transformations using oxidative mediators, includ-
ing triarylamines, 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO), halide ions, iodoarenes, and
o-aminophenols, are discussed with their use in recent synthetic examples.
B. TrIarYLaMINES
It has been well established that the radical cations of triarylamines are highly stable; thus, they can
be utilized as one-electron oxidants in chemical transformations [35,36]. For example, trans-ane-
thole (6) was oxidized by the radical cation of tris(4-bromophenyl)amine (7), which is commercially
Anodic oxidation Bulk oxidation
Mediator Substrate
(reduced) (reduced)
–e– +e– –e–
Mediator Substrate Chemical

(oxidized) (oxidized) transformations
Anode
SchEME 15.5 Schematic illustration of an indirect anodic transformation using oxidative mediators.
MeO Br Br
MeO +SbCl–
7 6 N
MeO Br
7
Br Br
N MeO
6
Br
7 +e– –e– MeO
MeO
Br Br
+ MeO
N 6
MeO
Br
SchEME 15.6 Oxidative dimerization of trans-anethol (6) using tris(4-bromophenyl)amine (7) as an oxida-
tive mediator.
available as a tris(4-bromophenyl)aminium hexachloroantimonate, to give the corresponding radi-

cal cation, leading to dimerization (Scheme 15.6) [37]. The mechanism of the dimerization has been
discussed in detail [38–40].
Meanwhile, such radical cations of the triarylamines can also be obtained through the anodic
oxidation of the corresponding triarylamines [41]. After the bulk oxidation, the neutral triaryl-
amines are reoxidized at the surface of the anode; thus, they function as oxidative mediators. In
these cases, the oxidation potentials of the triarylamines can be modulated as a function of different
substitution patterns of the aromatic rings (Table 15.1) [42].
With these triarylamines in hand, tris(4-methyl-2-nitrophenyl)amine (8) was then employed as an
oxidative mediator to demonstrate the indirect electrochemical cleavage of electron-deficient substituted
stilbenes [43]. These stilbenes were oxidized to give the corresponding radical cations, which were then
trapped by water, leading to the electrochemical equivalent of ozonolysis to afford the corresponding
aldehydes (Scheme 15.7) [44]. Because the oxidation potentials of these stilbenes are close to that of the
solvent, direct electrochemical cleavages required a large excess of electricity to consume the starting
substrates, which also caused undesired side reactions attributed mainly to the oxidation of solvent.
In contrast, indirect electrochemical cleavage using 8 as an oxidative mediator required rela-
tively small amounts of electricity to complete the reactions (Scheme 15.8). In these cases, the
TABLE 15.1
Oxidation Potentials of Triarylamines
R1 R1
R2 R7 R6 R2 R7 R6
+
N vs Ag/AgNO3 N
R3 R5 0.1 M LiClO4 R3 R5
CH3CN
(+)C–Pt(–)
R4 R4
Substrates Oxidation potentials (vs Ag/AgNO3)
R1 = H, R2 = OMe, R3 = H, R4 = OMe, R5 = H, R6 = OMe, R7 = H E OX = 0.25 V

1 = H, R2 = Me, R3 = H, R4 =
R Me, R5 = H, R6 = Me, R7 = H E OX = 0.40 V
R1 = H, R2 = H, R3 = H, R4 = H, R5 = H, R6 = H, R7 = H E OX = 0.54 V
7 (R1 = H, R2 = Br, R3 = H, R4 = Br, R5 = H, R6 = Br, R7 = H) E OX = 0.78 V
R1 = H, R2 = Cl, R3 = H, R4 = Cl, R5 = H, R6 = Cl, R7 = H E OX = 0.79 V
R1 = H, R2 = H, R3 = NO2, R4 = H, R5 = H, R6 = H, R7 = H E OX = 0.83 V
R1 = NO 2 3 4 5 6 7
2, R = H, R = H, R = H, R = H, R = H, R = H E OX = 0.84 V
R1 = H, R2 = NO2, R3 = H, R4 = H, R5 = H, R6 = H, R7 = H E OX = 0.88 V
R1 = H, R2 = Me, R3 = NO 4 5 6 7
2, R = Me, R = NO2, R = Me, R = H E OX = 0.96 V
R1 = H, R2 = Cl, R3 = NO2, R4 = Cl, R5 = H, R6 = Cl, R7 = H E OX = 1.00 V
R1 = H, R2 = NO2, R3 = H, R4 = NO2, R5 = H, R6 = H, R7 = H E OX = 1.08V
R1 = H, R2 = NO2, R3 = H, R4 = Br, R5 = NO2, R6 = Br, R7 = H E OX = 1.17 V
R1 = H, R2 = Cl, R3 = NO2, R4 = Cl, R5 = NO2, R6 = Cl, R7 = H E OX = 1.25 V
8 (R1 = H, R2 = Me, R3 = NO 4 5 6 7
2, R = Me, R = NO2, R = Me, R = NO2) E OX = 1.28 V
R1 = H, R2 = NO2, R3 = H, R4 = Br, R5 = Br, R6 = NO2, R7 = H E OX = 1.31 V
R1 = H, R2 = NO2, R3 = H, R4 = NO2, R5 = H, R6 = NO2, R7 = H E OX = 1.33 V
R1 = H, R2 = Me, R3 = NO2, R4 = NO2, R5 = H, R6 = Me, R7 = NO2 E OX = 1.33 V
1 2 3 4 5
R = H, R = Br, R = NO2, R = Br, R = Br, R = NO2, R = H 6 7 E OX = 1.37 V
R1 = H, R2 = Cl, R3 = NO2, R4 = Cl, R5 = NO2, R6 = Cl, R7 = NO2 E OX = 1.56 V
Ar Ar Ar Ar
Ar –e– +H2O –e–
Ar + –H+ Ar Ar
Stilbenes OH OH
+
Ar Ar
+H2O Ar Ar
Ar –e– Ar –H+
–H+ OH OH +
+ OH O
OH OH
Ar Ar
Ar Ar +
–e– + + –H+
O O
OH O
Aldehydes
SchEME 15.7 Proposed mechanism of an oxidative cleavage of stilbenes.

R1
1.3 V vs Ag/AgNO3
R2 R1 R4
4–12 F
R6 8 (Cat.) R2 R5
R3 0.1 M LiClO4 +
O O
CH3CN/H2O R3 R6
R5
(+)C–Pt(–)
R4
Substrates Oxidation potentials (vs Ag/AgNO3) Yield (%)
R1 = H, R2 = CF3, R3 = H, R4 = H, R5 = CHO, R6 = H EOX = 1.46 V 96
R1 = H, R2 = CF3, R3 = H, R4 = H, R5 = CF3, R6 = H EOX = 1.50 V 96
R1 = H, R2 = CN, R3 = H, R4 = H, R5 = CN, R6 = H EOX = 1.55 V 95
R1 = CF3, R2 = H, R3 = CF3, R4 = H, R5 = CHO, R6 = H EOX = 1.59 V 95

1 = H, R2 = CN, R3 = H, R4 = CF 5 6 93
R 3, R = H, R = CF3 EOX = 1.70 V
R1 = CF3, R2 = H, R3 = CF3, R4 = CF3, R5 = H, R6 = CF3 EOX = 1.73 V 95
SchEME 15.8 Anodic cleavage of electron-deficient stilbenes using tris(4-methyl-2-nitrophenyl)amine (8)

as an oxidative mediator.
triarylamine oxidative mediators offered not only significant improvement of the current efficien-
cies but also effective inhibition of the side reactions. Several electron-deficient substituted stil-
benes could be introduced into the electrochemical equivalent of ozonolysis that afforded a single
aldehyde from symmetrical stilbenes or an equimolar mixture of two aldehydes from asymmetrical
stilbenes in excellent yields.
Based on the oxidation potentials, the mechanism of the indirect electrochemical cleavage of the
electron-deficient substituted stilbenes was proposed (Scheme 15.9). Because the oxidation potential

O2N
R1
N
R2
O 2N NO2
R6
R3
R5
8 R4
–e– +e– –e–

O2N
R5
+ R4 R6
N R1
O 2N Cleavages
NO2 R2
+
R3
Anode
SchEME 15.9 Proposed mechanism of an anodic cleavage of electron-deficient stilbenes using tris(4-
methyl-2-nitrophenyl)amine (8) as an oxidative mediator.
O O
O
Ar –e– +MeOH Ar
Ar S
Ar S Ar –H+ Ar S
S-Arylthiobenzoates + OMe
O O
+MeOH Ar
–e– + Ar S
Ar S Ar OMe +
–H+ OMe
OMe Methyl benzoates
SchEME 15.10 Proposed mechanism of an oxidative methoxydesulfurization of S-arylthioarylates.
of 8 was lower than those of the stilbenes, 8 was selectively oxidized at the surface of the anodes
even in the presence of the stilbenes to give the radical cation of 8, which then functioned as a bulk
oxidant to generate the radical cation of the stilbenes, leading to the cleavages. After the oxidation
of the stilbenes, the neutral 8 was reoxidized at the surface of the anode to catalyze the reactions.
The comparison of indirect electrochemical transformations with their direct variants has also
been reported using the electrochemical methoxydesulfurization of S-arylthioarylates as models
[45]. The oxidation of S-arylthioarylates gave the corresponding radical cations, which were then
trapped by methanol, resulting in electrochemical methoxydesulfurizations to afford the corre-
sponding methyl arylates (Scheme 15.10). When fluoride ion was used as a nucleophile instead of
methanol, electrochemical fluorodesulfurizations could also be induced [46].
The use of tris(2,4-dibromophenyl)amine (9) as an oxidative mediator produced considerable
improvement in the reactions (Scheme 15.11). Because the oxidation potential of 9 was lower than
those of the S-arylthioarylates, the anodic potentials during electrolysis decreased even under con-
stant current conditions. The S-arylthioarylates were oxidized by the radical cation of 9 in the bulk
electrolyte solution to drive the reactions, while neutral 9 was reoxidized through the anodic oxida-
tion. Thus, only a catalytic amount of 9 was required to effectively complete the reactions.
C. TEMPO
It has been well established that 2,2,6,6-tetramethylpiperidine-1-oxyl, known as TEMPO, is a typi-
cal example of a stable free radical that serves as a useful oxidant in organic synthesis and has also
been studied theoretically [47–55]. In particular, TEMPO functions as an effective cocatalyst in
combination with copper catalysts, enabling aerobic oxidation of a wide variety of alcohols to the
corresponding carbonyl compounds [56–58]. TEMPO has also been combined with palladium cata-
lysts under electrolytic conditions as an oxidative mediator [59–62]. Thus, TEMPO was anodically
oxidized to give the corresponding N-oxoammonium cation, which could regenerate reactive cat-
ionic palladium complexes through bulk oxidation, leading to various palladium-catalyzed trans-
formations (Scheme 15.12). In these cases, only catalytic amounts of both TEMPO and palladium
catalysts were required to construct TEMPO/palladium double mediatory systems.
In this context, for example, the palladium-catalyzed electrochemical cross-couplings of ter-
minal alkynes (10) and arylboronic acids (11) were demonstrated using 4-(benzyloxy)-2,2,6,6-
tetramethylpiperidin-1-oxyl (12) as an oxidative mediator (Scheme 15.13) [63]. Both ethynylarenes and
arylboronic acids could be introduced into the reaction to construct the corresponding diarylacetylenes.
D. HaLIDE IoNS
Several halide ions can also be used as simple oxidative mediators in indirect electrochemical trans-
formations [64,65]. Thus, halide ions, typically derived from supporting electrolytes, are oxidized at
the anodes to generate the corresponding halonium ions, which then function as oxidizing reagents
10 mA/cm2 Br Br Br
R1 5F R1
9 (Cat.)
S OMe N
0.2 M Bu4NBF4
Br Br
O R2 MeOH/CH2Cl2/CH3CN O
(+)Pt–Pt(–)
Substrates Yielda (%) Yieldb (%) Br

9
R1 = H, R2 = H 62 31
R1 = H, R2 = Cl 70 40
R 1 = H, R2 = OMe 80 52
1
R = Me, R = H2 56 37
R1 = OMe, R2 = H 67 36
a Yields of the indirect electrochemical transformations using 9.

b
Yields of the direct electrochemical transformations without 9.

Br Br Br
N
R1
Br Br
S
O R2
Br
9
–e– +e– –e–
Br Br Br
+ R1
N +
S Methoxy-
Br Br desulfurizations
O R2
Br
Anode
SchEME 15.11 Anodic methoxydesulfurization of S-arylthioarylates using tris(2,4-dibromophenyl)amine

(9) as an oxidative mediator.
in bulk electrolyte solutions. For example, the indirect electrochemical 2,5-dimethoxylation of

furans has been chosen as a model to demonstrate the effectiveness of the use of bromide ions as
oxidative mediators (Scheme 15.14) [66]. As described earlier, electron transfer between two solid
phases is highly restricted; thus, solid phase–bound substrates are rarely oxidized or reduced at
the surface of the electrodes in general. Meanwhile, 2,5-dimethoxylation of solid phase–supported
furans (13) took place efficiently with the use of bromide ions as oxidative mediators, which could
be easily combined with a multistep solid-phase synthesis [67]. The anodically generated bromo-
nium ions functioned as oxidizing reagents in bulk solution.
E. IoDoarENES
Hypervalent iodines have been well established as easily handled oxidants that possess unique
reactivities [68–70]. One of the most commonly used hypervalent iodines is 1,1,1-triacetoxy-1,1-
dihydro-1,2-benziodoxol-3(1H)-one, known as Dess–Martin periodinane, which can oxidize vari-
ous primary alcohols into the corresponding aldehydes [71–76].
N 1/2 Pd(0) Subtrate

O
TEMPO
–e– +e– –e– +e–
+ 1/2 Pd(II) Product

N
O
Anode
SchEME 15.12 Schematic illustration of an indirect anodic transformation using a TEMPO/palladium

double mediatory system.
50 mA/cm2 OBn
R2 4F R1
R1
Pd(OAc)2, 12 (Cat.)
+
B(OH)2 DBU N
10 11 0.2 M NaClO4 O
CH3CN/H2O R2 12
(+)Ag–Pt(–)
Substrates Yield (%)
R1 = H, R2 = tBu 99 (42)a
R1 = H, R2 = Cl 91 (84)a
R1 = H, R2 = Ac 76 (77)a
R1 = Me, R2 = Me 99
R1 = H, R2 = OPh 91
R1 = N2O, R2 = Ac 76
a In the absence of 12.

OBn
R1 R2
N 1/2 Pd(0) +
B(OH)2
O 10 11
12
–e– +e– –e– +e–
OBn R1
+ 1/2 Pd(II)
N
O
R2
Anode
SchEME 15.13 Anodic cross-coupling of terminal alkynes (10) and arylboronic acids (11) using a
4-(benzyloxy)-2,2,6,6-tetramethylpiperidin-1-oxyl (12)/palladium double mediatory system.
15 mA/cm2
40F MeO OMe
O O
O O
0.2 M Bu4NBr
O 14 MeOH/Dioxane O
(+)C–C(–)
Br– O
O
O 14
–2e– +2e–
MeO OMe
Br+ O
O
O
Anode
SchEME 15.14 Anodic 2,5-dimethoxylation of solid phase–supported furans (14) using a bromide ion as
an oxidative mediator.
5 mA/cm2 l
4F
N
15 (Cat.) N F N+ O
N
N S R Et3N-3HF
16 N S R (CF3SO2)2N–
(+)Pt–Pt(–)
15
R = COOEt 87 (31)a
R = CN 72
a Yield without 15.
SchEME 15.15 Anodic fluorination of 2-pyrimidylsulfides (16) using an ionic liquid-supported iodoben-
zene (15) as an oxidative mediator.
Meanwhile, several hypervalent iodoarenes can also be obtained through the anodic oxidation
of the corresponding iodoarenes, which can then be utilized as oxidative mediators in indirect
electrochemical transformations. In particular, the anodic oxidation of iodoarenes in the presence
of fluoride ions gave the corresponding hypervalent iodoarene difluorides, which served as oxi-
dative mediators [77]. For example, ionic liquid–supported iodobenzene (15) has been prepared
as the oxidative mediator for the indirect electrochemical fluorination of 2-pyrimidylsulfides (16)
(Scheme 15.15) [78].
A mechanism of the indirect electrochemical fluorination of the 2-pyrimidylsulfides was pro-
posed based on the oxidation potentials (Scheme 15.16). The oxidation potential of 15 was lower
than that of 16; thus, 15 was selectively oxidized at the surface of the anodes in the presence of
fluoride ions to give the corresponding hypervalent iodoarene difluoride, which then functioned as
a bulk oxidative fluorinating reagent to induce the electrochemical fluorination of 16. Through the
fluorination of the 2-pyrimidylsulfides, 15 was regenerated to catalyze the reactions.
Anodic oxidation Bulk oxidation l

l
N+ O =
N
N
(CF3SO2)2N–
N S R
15 16 15
–2e–, +2F– +2e–, –2F–
F
N F
I
F
N S R
Anode
SchEME 15.16 Proposed mechanism of an anodic fluorination of 2-pyrimidylsulfides (16) using an ionic
liquid-supported iodobenzene (15) as an oxidative mediator.
5 mA/cm2 l
S S 4F F F
17
17
0.1 M Et4NCl
Et3N-5HF
R 18 R (+)Pt–Pt(–)

R=H 42a
R=H 40b
R=H 51c
R=H 86
R=F 84
R = Cl 86
R = Me 67
R = OMe 70
a Yield without Et4NCl and 17.
b Yield without Et4NCl.
c Yield without 17.
SchEME 15.17 Anodic fluorodesulfurization of cyclic dithioacetals (18) using a solid phase–supported
iodoarene (17)/chloride ion double mediatory system.
Moreover, iodoarenes have also been effectively combined with halide ions to construct double
mediatory systems. For example, chloride ions were anodically oxidized to generate chloronium
ions, which then oxidized iodoarenes to give the corresponding hypervalent iodoarenes
(Scheme 15.17) [79]. Chloronium ions acted as homogeneous oxidizing reagents in bulk electrolyte
solution; thus, solid phase–supported iodoarenes (17) could also be oxidized to induce anodic fluo-
rodesulfurization of cyclic dithioacetals (18). In this case, the solid phase–supported hypervalent
iodoarenes could be utilized as practical oxidative fluorinating reagents.
The indirect electrochemical fluorodesulfurization of 18 occurred effectively only in the pres-
ence of both chloride ions and 17. Therefore, the chloride ions/17 double mediatory system could be
proposed (Scheme 15.18). The chloride ions derived from the supporting electrolyte were oxidized
at the anode to play the role of initial oxidative mediator. Compound 17 then served as a secondary
oxidative mediator to direct the reactions.

l S S
Cl–
17
R 18 R
– – – –
–2e +2e –2e , +2F –2e–, –2F–
F F F
+
Cl l
F
Anode
SchEME 15.18 Proposed mechanism of an anodic fluorodesulfurization of cyclic dithioacetals (18) using a
solid phase–supported iodoarenes (17)/chloride ion double mediatory system.
F. O -AMINopHENoLS
Creating biomimetic systems in indirect electrochemical transformations has proven to be an

intriguing challenge. It is well known that benzoquinone structures play critical roles in biologi-
cal electron transfer processes. The benzoquinones are reduced to give the corresponding hydro-
quinones, which can be reoxidized to benzoquinones to function as redox mediators in biological
systems. Based on this fact, several o-iminoquinones generated through the anodic oxidation of
the corresponding o-aminophenols have been utilized as oxidative mediators in indirect electro-
chemical transformations to realize exquisite reactions [80–83]. For example, the anodic oxidation
of 1-(3-amino-2,4-dihydroxyphenyl)ethanone (19) gave the corresponding o-iminoquinone, which
induced chemoselective imine formation, leading to the N-alkylation of various primary amines
through the cathodic reduction (Scheme 15.19) [84].
In this reaction, 19 functioned as an effective biomimetic oxidative mediator (Scheme 15.20). The
anodically generated o-iminoquinone, which catalyzed the formation of the corresponding imine
of the substituted benzylamine, was quantitatively re-reduced to 19 after the reaction, driving the
reaction cycle. Thus, only a catalytic amount of 19 was required to consume the starting substituted
benzylamine.
0.6 V vs SCE OH O
3h H2N
NH2 NH2 19 (Cat.) N
+
0.1 M LiClO4 HO
R R
MeOH 19
(+)Pt–Pt(–)
–1.6 V vs SCE
1h N
H
0.1 M LiClO4 R
MeOH
(+)Pt–Hg(–)
R=F 68
R = Me 62
R = OMe 65
SchEME 15.19 Anodic N-alkylation of primary amines using 1-(3-amino-2,4-dihydroxyphenyl)ethanone

(19) as a biomimetic oxidative mediator.
OH O
H 2N
NH2 NH2
+
HO R
19
–2e–, –2H+ +2e–, +2H+
OH O
HN N
R
O
Anode
SchEME 15.20 Proposed mechanism of an anodic N-alkylation of primary amines using 1-(3-amino-2,4-
dihydroxyphenyl)ethanone (19) as a biomimetic oxidative mediator.
III. REDUcTivE MEDiATORS

In contrast to oxidative mediators, reductive mediators are activated through cathodic reduction
and the resulting intermediates function as subsequent reductants (Scheme 15.21). While several
oxidative mediators have been established to expand the possibility of anodic oxidation processes,
reductive mediators have been more limited.
In this section, indirect electrochemical transformations using reductive mediators, including
nickel(II) salens and carboranes, are discussed with their use in recent synthetic examples.
B. NICkEL(II) SaLENS
Cathodic reductive cyclizations have been studied extensively to build a wide variety of ring systems
in unique ways [85–87]. Cathodic reduction of electron-deficient olefins tethered to electrophiles,
such as aldehydes or ketones, gave the corresponding intramolecular cyclized products through
carbon–carbon bond formations. Such reductive cyclizations could also be induced using one-
electron reductants, including tributyltin hydrides and samarium diiodides. Meanwhile, the use of
nickel(II) salens as reductive mediators has been extensively studied both synthetically and mecha-
nistically [88–91]. For example, the cathodic reduction of electron-deficient olefins in the presence of
Cathodic reduction Bulk reduction
Mediator Substrate
(oxidized) (oxidized)
+e– –e– +e–

Mediator Substrate Chemical
(reduced) (reduced) transformations
Cathode
SchEME 15.21 Schematic illustration of indirect cathodic transformation using reductive mediators.
–2.10 V vs Ag/AgNO3
2F N N
O OH
20 (Cat.) Ni
R1
0.1 M Bu4NBr O O
R1 R2 R2
CH3CN
(+)Pt–RVC(–) 20

R1 2
= Me, R = COOMe 70
R1 = H, R2 = CN 73
N N O
Ni
1
O O R R2
20
+e– –e–
•–
N N OH
Ni R1
O O R2
Cathode
SchEME 15.22 Cathodic intramolecular cyclization of electron-deficient olefins using nickel(II) salen (20)
as a reductive mediator.
nickel(II) salen (20) gave the corresponding intramolecular cyclized products even under a constant
potential condition at significantly lower potentials than the reduction potentials of the substrates
(Scheme 15.22) [92].
C. O -CarboraNES
Carboranes are polyhedral clusters composed of boron and carbon atoms. In particular, icosahedral
carboranes [93,94], known as o-carboranes, have high thermal and chemical stabilities, and thus
have been studied intensively in many fields of chemistry, including medicinal [95,96], material
[97–99], and physical [100–103]. The redox properties of the o-carboranes have also been found to
produce both stable radical anions and dianions, which enable their use as reductive mediators in
indirect electrochemical transformations. Although polyaromatic hydrocarbons, such as fullerenes
[104] and transition metal ions, can also be used as reductive mediators, their low solubilities in
typical organic solvents limit their use in indirect electrochemical transformations. Meanwhile,
several substituents can be introduced into the two carbon atoms of o-carboranes to realize facile
modulations of their solubilities and reduction potentials. For example, it has been demonstrated
that 1,2-diphenyl-o-carborane (21) could serve as an efficient reductive mediator in the indirect
electrochemical debromination of 1,2-dibromo-1,2-diphenylethane (22) (Scheme 15.23) [105].
Based on their reduction potentials, the dianion of 21 acted as a bulk reductant to induce the debro-
mination. After the reduction of 22, the radical anion of 21 was reduced again at the surface of the
cathodes to catalyze the reactions. In contrast, no direct electrochemical debromination of 22 took
place at this potential.
–1.3 V vs SCE
Br Ph
2F
21 (Cat.)
Br 0.1 M Et4NClO4
DMF Ph
22
(+)Pt–C(–)
21 ( = BH)
Amount of 21 (mol%) Yield (%)
0 0
20 65
10 93
1 95
•– Br
Ph
Br
Ph
22
+e– –e–
2–
Ph
Ph
Cathode
SchEME 15.23 Cathodic debromination of 1,2-dibromo-1,2-diphenylethane (22) using 1,2-diphenyl-o-

carborane (21) as a reductive mediator.
IV. OxiDATivE ChAiN REAcTiONS

As indicated earlier, electrochemical chain reactions can be defined as autoactivating chemical
transformations induced by direct heterogeneous electron transfer. Generally, there are three
stages in the chain reactions: initiation, propagation, and termination. For example, in a radical
chain reaction, the initiation stage consists of the use of chemical radical initiators to generate
the reactive radical substrates. The resulting reactive radical substrates then induce autoactivat-
ing chemical transformations, which is the propagation stage. Finally, in the termination stage,
the resulting radicals are consumed by several chemical reactions such as radical coupling. In
the case of electrochemical chain reactions, initially, the starting substrate is activated through
electron transfer at the surface of the electrode to give the reactive intermediate, which is then
responsible for the subsequent activation in the homogeneous bulk electrolyte solution to drive
the chain cycle without the use of additional electricity. In analogy with the redox mediators,
there are also two types of electrochemical chain reactions: oxidative and reductive. Oxidative
chain reactions are initiated through anodic oxidation and the resulting intermediates function
as subsequent oxidants, which are regenerated through the reactions to drive the chain cycle
(Scheme 15.24).
In this section, typical oxidative chain reactions directed by reactive radical cations and cat-
ions are discussed in detail using inter- and intramolecular carbon–carbon bond formations as
models.
Anodic oxidation Bulk oxidation reaction
Starting
substrate Chemical
–
transformations
–e
Reactive Reactive
Anode
SchEME 15.24 Schematic illustration of an anodic chain reaction.
B. RaDICaL CaTIoN CHaIN REaCTIoN

Anodic oxidation of electron-rich olefins has proven to be an effective approach for reversing the
polarity of olefins and triggering radical cation-based intramolecular cyclizations, which provide
powerful tools to construct various ring systems [106–110]. In particular, electrochemical ole-
fin cross-couplings between electron-rich olefins and unactivated olefin nucleophiles took place
through radical cation chain reactions involving intermolecular carbon–carbon bond formations
[111–114]. For example, the anodic oxidation of 3,4-dihydro-2H-pyran (23) in the presence of sev-
eral substituted allylbenzenes (24) affords the corresponding cycloadducts (Scheme 15.25) [115]. In
these cases, the electron densities of the aromatic rings were critical for the reactions.
Based on their oxidation potentials, an oxidative chain reaction mechanism was proposed
(Scheme 15.26). Because the oxidation potential of 23 was lower than that of 24, 23 was first selec-
tively oxidized at the anode to generate the corresponding radical cation. The radical cation of 23
was then trapped by 24 to form a relatively long-lived aromatic radical cation, which was finally
reduced by the starting 23 to construct the corresponding cycloadduct with regeneration of the radi-
cal cation of 23, enabling the radical cation chain mechanism.
C. CaTIoN CHaIN REaCTIoN

As described earlier, radical chain reactions have been widely utilized in both academic and
industrial synthetic chemistry to efficiently produce various organic molecules. In contrast,
R2 R1
1.0 V vs Ag/AgCl R2 R1
0.5 F
+ O 1.0 M LiClO4
R3 23 CH3NO2 O
R3
24 (+)C–C(–)
R 1 = H , R 2 = H, R3 = H 0
1= H , R 2 = Me, R3 = H 13
R
R 1 = Me, R 2 = Me, R3 = H 60
R 1 = Me, R 2 = Me, R3 = Me 84
R 1 = H, R 2 = OMe, R3 = H 94
SchEME 15.25 Anodic intermolecular cyclization of 3,4-dihydro-2H-pyran (23) and substituted allylben-
zenes (24).
Anodic oxidation Radical cation chain reaction

R2 R1
O O
23 23 O
R3
–e– –e– +e–
R2 R1
+
+ +
O O O
R3
Anode
R2 R1
R3
24
SchEME 15.26 Proposed mechanism of an anodic intermolecular cyclization of 3,4-dihydro-2H-pyran (23)

and substituted allylbenzenes (24).
O F
R 25 (Cat.) O
+ S
ArS 0.1 M Bu4NB(C6F5)4 R SAr S
= ''ArS+''
26 CH2Cl2 S
F
Substrates Yield (%) 25
F
R = c-Hex 88
R = C7H15 82
R = CH2Ph 75
R = Ph 65
R = CH2CH2OMe 62
SchEME 15.27 Anodic intramolecular cyclization of thioacetals (26).
cation chain reactions are still limited. In organic electrochemistry, it has been well estab-
lished that several carbocations could be accumulated through the anodic oxidation of sub-
strates in the absence of nucleophiles at low temperature, known as the “cation pool” method
[116–118]. In particular, ArS(ArSSAr) +, an equivalent of ArS+, could be generated through the
anodic oxidation of ArSSAr in dichloromethane electrolyte solution [119–122]. For example,
“ArS+” (25) was accumulated at a low temperature to induce the intramolecular carbon–carbon
bond formations of various thioacetals (26), which occurred through cation chain reactions
(Scheme 15.27) [123].
Initially, 25 was accumulated through the anodic oxidation of the corresponding ArSSAr
without 26 in dichloromethane electrolyte solution at a low temperature (Scheme 15.28). After
the electrolysis, 26 was then added into the solution to give the corresponding alkoxycarbe-
nium ions and ArSSAr. The alkoxycarbenium ions were trapped by intramolecular olefin nucleo-
philes to form the corresponding reactive carbocation intermediates, which finally reacted with
ArSSAr to regenerate 25 with the formation of the cyclization products, realizing the cation
chain mechanism.
Cation chain reaction

Anodic oxidation
O
R O
ArSSAr ArSSAr ArSSAr
ArS R SAr
26
–2e–, H+
+
''ArS+'' ''ArS+'' O O ''ArS+''
25 25 + 25
R R
Anode
SchEME 15.28 Proposed mechanism of an anodic intramolecular cyclization of thioacetals (26).
V. REDUcTivE ChAiN REAcTiONS

While oxidative chain reactions are initiated by anodic oxidations, reductive chain reactions are
triggered through cathodic reductions. The cathodic reductions generate reactive intermediates that
function as subsequent reductants, which are regenerated through the reactions to drive the chain
cycle (Scheme 15.29).
Representative reductive chain reactions are aromatic nucleophilic substitutions, known as SRN1
reactions (Scheme 15.30) [124,125]. Initially, the haloarene was reduced to the corresponding radi-
cal anion, from which a halide ion was subsequently eliminated to form the aryl radical. The radical
was then trapped by a nucleophile to give the corresponding radical anion, which was finally oxi-
dized by the starting haloarene to construct the corresponding substituted arene with regeneration
Anodic oxidation Bulk reductive reaction
Starting
substrate Chemical
+e– transformations
Reactive Reactive
Anode
SchEME 15.29 Schematic illustration of a cathodic chain reaction.
Ar X Ar X Ar Nu Ar X = Haloarene
+e– +e– –e–
– – –
Ar
–X– +Nu–
SchEME 15.30 Proposed mechanism of a reductive aromatic nucleophilic substitution of haloarenes.

of the radical anion of the haloarene, enabling the SRN1 mechanism. In the termination stage, the
aryl radical was consumed through several chemical reactions such as trapping by solvents. For
example, the cross-couplings of aryl Grignard reagents and haloarenes have been reported to take
place through SRN1 pathways [126].
In this section, reductive chain reactions are discussed in detail using electrochemical SRN1 reac-
tions as models.
B. ELECTroCHEMICaL SRN1 REaCTIoN

Several types of SRN1 reactions can be induced through electrochemical approaches. The cathodic
reduction of haloarenes is responsible for the initiation of these reactions [127,128]. Generally, the use
of reductive mediators is effective for the initiation of electrochemical SRN1 reactions. For example,
the cross-couplings of 1-iodo-2-(trifluoromethyl)benzene (28) and the substituted 1H-imidazoles
(29) in the presence of phthalonitrile (30) as a reductive mediator occurred through SRN1 pathways
(Scheme 15.31) [129].
The electrochemical SRN1 reactions were initiated through the cathodic reduction of 30
(Scheme 15.32). The cathodically generated radical anion of 30 functioned as a bulk reductant to
reduce 28, forming the corresponding radical anion. An iodide ion was then eliminated from the
radical anion to give the corresponding radical, which was then trapped by the anion of 29 as a
nucleophile. The cross-coupling was completed through the oxidation of the resulting radical anion
by the starting 28 with regeneration of the radical anion of 28, realizing the reductive chain reaction.
–1.8 V vs SCE
NH CN
l N 0.8F
+ 30 (Cat.) R
N R N CN
CF3 H 0.1 M Et4NBF4
30
28 29 DMSO CF3
(+)Pt–C(–)

R = CHO 42
R = C6H4OMe 55
SchEME 15.31 Cathodic cross-coupling of 1-iodo-2-(trifluoromethyl)benzene (28) and substituted

1H-imidazoles (29) using phthalonitrile (30) as a reductive mediator.

Reductive chain reaction
CN l l NH
R
N
CN CF3 CF3
30 28 28 CF3
+e– –e– +e– +e– –e–
NH –
– –
CN – l l R
N
CN CF3 CF3
CF3
Cathode
–l– CF3 N
N R
SchEME 15.32 Proposed mechanism of a cathodic cross-coupling of 1-iodo-2-(trifluoromethyl)benzene

(28) and substituted 1H-imidazoles (29) using phthalonitrile (30) as a reductive mediator.
VI. MEASURiNG REDOx POTENTiALS

A. GENEraL ASpECTS
As discussed in this chapter, not only redox potentials of substrates but also those of redox mediators
are of considerable significance in the design of indirect electrochemical transformations. Redox
potential can be defined as a measure of the tendency of compounds to gain or lose an electron and
thereby be reduced or oxidized. Generally, the selectivity of the electrochemical transformations is
determined by the value of redox potentials, for example, the substrate of lower oxidation potential
can be oxidized preferentially even in the presence of the excess amount of the substrate of higher
oxidation potential. In this section, direct and indirect techniques to measure redox potentials are
discussed in detail.
B. DIrECT MEaSUrING
Cyclic voltammetry is the most basic and widely used technique to acquire information about
electron transfer of the compounds directly, for example, their redox potentials. Although the
value of redox potentials is highly dependent upon the measuring conditions, including electrode
materials and supporting electrolytes, the redox potentials of both ions and radical ions have been
systematically reviewed in the literatures. Cyclic voltammetry also provides information about
reaction mechanisms of electrochemical transformations [130–132]. For example, the electro-
chemical transformations of α-tocopherol (31) were studied in detail by using cyclic voltammetry
(Scheme 15.33) [133].
C. INDIrECT MEaSUrING
While the redox potentials of both ions and radical ions have been systematically reviewed in the
literatures, those of radicals are almost unknown because their reactivities are extremely high. On
the other hand, the Marcus theory has been well established to relate the kinetics of the electron
transfer to its thermodynamics, which are determined by the redox potentials. Accordingly, the
latter values of highly reactive radicals can be estimated reasonably through the investigation of
the reaction kinetics. In this context, the “competition” method has been developed to indirectly
determine the redox potentials of radicals [134–137]. For example, alkyl radicals can be generated
through the indirect cathodic reduction of the corresponding haloalkanes using anthracene (32) as
a reductive mediator (Scheme 15.34) [138]. Initially, 32 was reduced to the corresponding radical
anion, which then reduced the haloalkanes to their radical anions. The corresponding alkyl radicals
were formed through the subsequent elimination of halide ions. In electrochemical SRN1 reactions,
OH + 2+
–e– OH –e– OH
O +e– +e–
R O O
R R
31
+H+ –H+ +H+ –H+ +H+ –H+
O– –e– O O
–e–
+
O +e– O +e– O
R R R
R = (CH2CH2CH2CHCH3)2CH3
SchEME 15.33 Redox reaction of α-tocopherol (31).

33
+H+
R –
R–Br
32
+e– –e– +e– k1
– –
–Br–
R +
k2
Cathode
R– +
32
+H+
R–H +
32
SchEME 15.34 Redox reaction of haloalkanes using anthracene (32) as a reductive mediator.
the generated radical was trapped by a nucleophile. On the other hand, in this case, the radical
anion of 32 would be the only reaction partner for the radicals. Thus, there were two main different
pathways for the reaction between the alkyl radicals and the radical anion of 32, including cross-
coupling and reduction. While the corresponding anion of the alkyl anthracene (33) was formed
through the cross-coupling, the reduction gave the anion of alkane and 32. Because the rate con-
stant of the cross-coupling k1 could be measured experimentally, the rate constant of the reduction
k2 could also be calculated, enabling the reasonable estimation of the redox potentials of the alkyl
radicals based on the Marcus theory.
VII. CONcLUSiONS
As described in this chapter, indirect electrochemical transformations using redox mediators
can significantly expand the possibilities of organic electrochemistry. To date, a wide variety of
both oxidative and reductive mediators are available to synthetic chemists to realize useful elec-
trochemical transformations in unique ways. Homogeneous electron transfer between substrates
and activated redox mediators in bulk electrolyte solution appears to present a thermodynamic
paradox in that the substrates can be effectively oxidized or reduced even at lower potentials than
those required to be oxidized or reduced through heterogeneous electron transfer at the surface
of electrodes. Additionally, both oxidative and reductive chain reactions can be induced through
the electrochemically generated reactive intermediates in indirect ways, which is intriguing both
synthetically and mechanistically. Therefore, indirect electrochemical transformations should find
further potential applications to enable green sustainable reactions in both academic and industrial
fields of chemistry.
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Section IV
Organic Electrochemical
Reaction Types
16 Cleavages and Deprotections
Ole Hammerich
CONTENTS
I. Introduction ....................................................................................................................... 561
II. Carbon–Carbon Bonds ..................................................................................................... 562
A. Reductive C–C Cleavages ......................................................................................... 562
1. Esters .................................................................................................................. 562
2. Nitriles ................................................................................................................ 562
3. Ketones ............................................................................................................... 563
4. 1,2-Diols .............................................................................................................564
5. Halogen Compounds ..........................................................................................564
6. Hydrocarbons .....................................................................................................564
B. Oxidative C–C Cleavages ......................................................................................... 565
1. Carboxylic Acids ................................................................................................ 565
2. Ketones ............................................................................................................... 565
3. 1,2-Diols and Related Hydroxy Compounds ...................................................... 565
4. Alkoxy Compounds............................................................................................ 566
5. Alkenes ............................................................................................................... 567
6. Hydrocarbon Single Bonds ................................................................................ 568
III. Carbon–Nitrogen Bonds ................................................................................................... 569
A. Reductive C–N Cleavages ......................................................................................... 569
1. Quaternary Ammonium Ions ............................................................................. 569
2. Carboxamides and Related Compounds ............................................................ 570
3. Aminoketones .................................................................................................... 571
4. Amines ............................................................................................................... 571
5. Azides ................................................................................................................. 572
6. Diazo Compounds .............................................................................................. 572
7. Nitro Compounds ............................................................................................... 573
B. Oxidative C–N Cleavages ......................................................................................... 573
1. Amides ............................................................................................................... 573
2. Amines ............................................................................................................... 574
IV. Carbon–Phosphorus Bonds ............................................................................................... 574
A. Reductive C–P Cleavages.......................................................................................... 574
1. Phosphonium Ions .............................................................................................. 575
2. Phosphonates ...................................................................................................... 575
3. Phosphine Oxides ............................................................................................... 575
4. Phosphines.......................................................................................................... 575
V. Carbon–Arsenic Bonds ..................................................................................................... 576
A. Reductive C–As Cleavages ....................................................................................... 576
VI. Carbon–Oxygen Bonds ..................................................................................................... 577
A. Reductive C–O Cleavages ......................................................................................... 577
1. Acylphosphonium Salts ...................................................................................... 577
2. Carboxylates and Carbonates ............................................................................. 577
559
3. Sulfonates and Related Esters ............................................................................ 579

4. β-Arylthio- and β-Alkylthioesters and -Alcohols .............................................. 579
5. β-Nitroesters ....................................................................................................... 580
6. Phosphates .......................................................................................................... 580
7. Hydroxyketones .................................................................................................. 581
8. Hydroxysulfones ................................................................................................. 581
9. Alcohols.............................................................................................................. 581
10. Acyclic Ethers and Glycosides ........................................................................... 581
11. 1,3-Dioxolanes and 1,3-Dioxanes ....................................................................... 583
12. Oxiranes ............................................................................................................. 583
B. Oxidative C–O Cleavages ......................................................................................... 584
1. Enol Esters and Related Compounds ................................................................. 584
2. Ethers.................................................................................................................. 584
VII. Carbon–Sulfur Bonds ....................................................................................................... 585
A. Reductive C–S Cleavages.......................................................................................... 585
1. Sulfonium Ions ................................................................................................... 585
2. Thiol Esters ........................................................................................................ 587
3. Thioethers (Sulfides) .......................................................................................... 588
4. Sulfoxides ........................................................................................................... 589
5. Sulfones .............................................................................................................. 591
6. Thiocyanates ...................................................................................................... 594
B. Oxidative C–S Cleavages .......................................................................................... 594
1. Thiol Esters ........................................................................................................ 594
2. Thioethers (Sulfides) .......................................................................................... 595
3. Disulfides............................................................................................................ 596
VIII. Carbon–Selenium and Carbon–Tellurium Bonds ............................................................. 596
A. Reductive C–Se and C–Te Cleavages........................................................................ 596
B. Oxidative C–Se and C–Te Cleavages ........................................................................ 597
IX. Carbon–Halogen Bonds .................................................................................................... 597
A. Reductive C–Hal Cleavages ...................................................................................... 597
X. Nitrogen–Nitrogen Bonds ................................................................................................. 597
A. Reductive N–N Cleavages ......................................................................................... 598
1. Carboxylic Acid Hydrazides and Azides ........................................................... 598
2. Azines and Related Compounds ........................................................................ 598
3. Diazo Compounds .............................................................................................. 598
B. Oxidative N–N Cleavages ......................................................................................... 599
XI. Nitrogen–Phosphorus Bonds............................................................................................. 599
A. Reductive N–P Cleavages ......................................................................................... 599
XII. Nitrogen–Oxygen Bonds ................................................................................................... 599
A. Reductive N–O Cleavages......................................................................................... 599
XIII. Nitrogen–Sulfur Bonds .....................................................................................................600
A. Reductive N–S Cleavages .........................................................................................600
1. Sulfonamides ......................................................................................................600
2. Sulfenamides ......................................................................................................602
3. Sulfimides (Sulfilimines) ....................................................................................602
B. Oxidative N–S Cleavages..........................................................................................602
1. Sulfinamides .......................................................................................................602
2. Sulfenamides ......................................................................................................603
XIV. Nitrogen–Halogen Bonds ..................................................................................................603
A. Reductive N–Hal Cleavages ......................................................................................603
Cleavages and Deprotections 561
XV. Phosphorus–Phosphorus Bonds ........................................................................................603

A. Reductive P–P Cleavages ..........................................................................................603
XVI. Phosphorus–Oxygen Bonds ..............................................................................................603
A. Reductive P–O Cleavages .........................................................................................603
B. Oxidative P–O Cleavages..........................................................................................604
XVII. Phosphorus–Sulfur Bonds ................................................................................................604
A. Reductive P–S Cleavages ..........................................................................................604
XVIII. Phosphorus–Selenium Bonds............................................................................................605
A. Reductive P–Se Cleavages ........................................................................................605
XIX. Phosphorus–Halogen Bonds .............................................................................................605
A. Reductive P–Hal Cleavages ......................................................................................605
XX. Arsenic–Arsenic Bonds ....................................................................................................605
A. Reductive As–As Cleavage .......................................................................................605
XXI. Oxygen–Oxygen Bonds ....................................................................................................606
A. Reductive O–O Cleavages ........................................................................................606
XXII. Oxygen–Sulfur Bonds .......................................................................................................606
A. Reductive O–S Cleavages .........................................................................................606
1. Alkoxysulfonium Ions ........................................................................................606
2. Sulfonates ...........................................................................................................606
3. Sulfinates ............................................................................................................607
4. Sulfenates ...........................................................................................................607
5. Sulfoxides ...........................................................................................................608
XXIII. Sulfur–Sulfur Bonds .........................................................................................................608
A. Reductive S–S Cleavages ..........................................................................................608
B. Oxidative S–S Cleavages ..........................................................................................608
XXIV. Sulfur–Halogen Bonds ......................................................................................................609
A. Reductive S–Hal Cleavages ......................................................................................609
1. Sulfonylhalides ...................................................................................................609
2. Sulfenylchlorides ................................................................................................609
XXV. Selenium–Selenium and Tellurium–Tellurium Bonds ...................................................... 610
A. Reductive Se–Se and Te–Te Cleavages ..................................................................... 610
B. Oxidative Se–Se and Te–Te Cleavages ..................................................................... 610
References ...................................................................................................................................... 610
I. INTRODUcTiON
Most electrochemical conversions include the cleavage of a covalent bond as a part of the route from
starting materials to products, for instance, substitution reactions, deprotonation of radical cations,
and elimination of anionic leaving groups during many reductions just to mention a few examples.
Still, the cleavage step is often the characteristic feature of the electrochemical process and for this
reason chapters dedicated to cleavages are often included in electrochemistry books [1,2], and it
has been decided by the editors of this book to maintain this tradition also in this fifth edition of
Organic Electrochemistry.
Owing to the widespread occurrence of electrochemical cleavages, some tough decisions had to
be made when preparing this chapter in order to limit the size of the presentation. Only the cleav-
age of bonds between what traditionally is being considered as nonmetals is included. Cleavages
observed during the electrochemistry of organometallic compounds are treated separately in
Chapter 36. Even so, some of the cleavages observed for organic compounds containing only non-
metallic heteroatoms belong more naturally in other chapters in this book; this concerns the reduc-
tive cleavage of the carbon–halogen bond that is treated in detail in Chapters 24 and 25 as well
as organoboron and organosilicon compounds, and to some extent organophosphorus compounds,

that are included in the chapter dedicated to the electrochemistry of organoelemental compounds
(Chapter 35). In addition to the chapters already mentioned, the reader may also find discussions
of cleavage reactions including the group 16 elements in Chapter 27 and N–N bond in Chapters
29 and 30. In many cases, cleavage processes have been studied in great detail and the results have
been discussed within the theory of dissociative and stepwise electron transfers. Such aspects are
treated in Chapters 13 and 14.
II. CARBON–CARBON BONDS

A. REDUCTIVE C–C CLEaVaGES
1. Esters
Reduction of tetramethyl ethane-1,1,2,2-tetracarboxylate, in a DMF–10% water mixture at a mer-
cury cathode at 60–65°C, proceeds with cleavage of the central C–C bond to dimethyl malonate
Equation 16.1 [3]. Related substituted and cyclic compounds react similarly, the latter accompanied
by ring opening. The yields are generally in the range 90–100%.
O O O
O O O
+2e–, +2H+
2 (16.1)
O O O
O O O

Analogous to these is the retro-Bingel reaction observed for the dianions of bis(methoxycarbonyl)
methanofullerenes and phosphorylated methanofullerenes Equation 16.2 [4,5].
2–
ROOC P(O)(OR)2
2– P(O)(OR)2
+2e–, +2HB
+ CH2 (16.2)
–2B–
COOR

2. Nitriles
Reductive cleavage of the C–CN bond is observed under nonacidic conditions during the reduc-
tion of aromatic nitriles in which the aromatic ring is π-electron deficient owing to the presence
of a heteroatom, such as in cyanopyridines [6,7], or to an electron-withdrawing substituent, such
as in benzenedicarbonitriles [8,9] and alkoxycarbonylbenzonitriles [10–12]. Reduction of 2- and
4-cyanopyridine in nonacidic aqueous solution at the potential of the second CV peak gives pyri-
dine and cyanide ion according to the stoichiometry shown in Equation 16.3. In contrast, reduction
in acidic solution proceeds to the aminomethylpyridines [6,7]; the radical anion of isophthalonitrile
undergoes a practically irreversible dimerization in aprotic solvents [11].
CN
+2e–, +H2O
+ CN– (16.3)
–OH–
N N
The reduction of aliphatic nitriles at a zinc cathode in DMF/Et4NOTs leads to decyanation in yields
that often exceed 70% [13]. The reaction in the last step is a convenient procedure for α-alkylation of
amines, Equation 16.4, the first step being an anodic α-methoxylation (see Chapter 19).
–2e–, –2H+, MeOH Me3SiCN, TiCl4
N N OMe N CN
COOR΄ COOR΄ COOR΄

(16.4)
R–X –, +H+
Base +2e
– –X– R –CN–
N CN N N R
CN
COOR΄ COOR΄ COOR΄
3. Ketones
Reduction of α-diketones [14] in DMF, in the presence of oxygen, results in cleavage of the
central C–C bond and, after alkylation, in the formation of the corresponding esters (62–98%),
Equation 16.5.
O O O
O
1) +2e–, +O2
(16.5)
2) Mel
O
O
The reaction is suggested to include the attack of electrogenerated superoxide ion on the
carbonyl group followed by a series of steps that include cleavage of the central C–C bond.
Symmetrical α-diimines are reductively cleaved to the corresponding amides (40–70%) in a
similar fashion [15].
The reaction between electrogenerated superoxide and chalcones leads to a series of cleavages
and eventually the formation of the corresponding carboxylic acids (Scheme 16.1) [16].
The radical anion of 2-phenylbenzoylcyclopropane undergoes irreversible cleavage with the
formation, after further reduction, of 1,4-diphenyl-l-butanone (66%), Equation 16.6 [17]. In con-
trast, the cleavage observed for the radical anion of the unsubstituted benzoylcyclopropane is
reversible; the ring-opened radical anion reacts with the substrate to give dimeric or trimeric
products.
O O– O
– +
Ph Ph +e , +2H Ph (16.6)
Ph Ph Ph

The radical anion of phenyltritylketone, prepared by reduction in DMF, undergoes cleavage of the
C–C bond according to Equation 16.7 at the time scale of a preparative electrolysis [18]. Protonation
of the trityl anion leads to triphenylmethane (80–85%), whereas the arylcarbonyl radical reacts
O O–
O2
Ar΄ Ar Ar΄ COO– + Ar CHO
Ar΄ Ar
O O
O2
Ar CHO ArCH2COO– + ArCOO–
SchEME 16.1 Superoxide induced cleavage reactions.
with DMF resulting in the formation of methylene dibenzoate as the other major product (~85%).
2-Naphthyltritylketone reacts similarly.
Ph Ph Ph
slow
Ph Ph O + Ph (16.7)
O Ph Ph

4. 1,2-Diols
Pinacols are reduced in protic media to the corresponding hydrocarbons in a process that involves
cleavage of both C–O and C–C bonds [19,20]. An example, the reduction of 9,9′,10,10′-tetrahydro-
9,9′-bianthracene-9,9′-diol to 9,10-dihydroanthracene (90%), is shown in Equation 16.8 [19].
HO
2.8 F
2
(16.8)
In strongly basic media, the pinacol is cleaved by base to the radical anion of the parent ketone in a
nonelectrochemical process.
5. Halogen Compounds
Substituted diphenylamines may be prepared by reduction of N-(4-methyl-4-(trichloromethyl)
cyclohexa-2,5-dienylidene)anilines in a process that includes the reductive two-step elimination of
the CCl3 group, the first being a C–Cl cleavage and the second an elimination of dichlorocarbene,
Equation 16.9 [21].
Me p-TolSO3H Me
X NH2 + O X N
CCl3 CCl3
Me
+2e– +H+ H
X N X N Me
–Cl– – :CCl2
CCl2

(16.9)
6. Hydrocarbons
Reduction of 9,9′-bianthryl in DMF leads to anthracene [22]; in this case via cleavage at the dianion
stage and subsequent protonation of the strongly basic anthracene anion by solvent/supporting elec-
trolyte components; the radical anion of 9,9′-bianthryl is a stable species in aprotic solvents.
B. OXIDaTIVE C–C CLEaVaGES

1. Carboxylic Acids
The electrochemical oxidative cleavage of aliphatic carboxylic acids to alkyl radicals, R·, and car-
bon dioxide is a classic reaction in organic electrochemistry. The radical may either dimerize to
R–R (the Kolbe reaction) or be further oxidized to a carbocation, R+, that subsequently reacts with a
suitable nucleophile (see Chapter 33 for details). Here only two examples will be given. Electrolysis
of a vicinal dicarboxylic acid may be used to introduce a double bond in a ring system as, for
example, in the transformation of a 3-oxo-2-azabicyclo[2.2.2]oct-5-ene-7,8-dicarboxylic acid to a
2-azabicyclo[2.2.2]octa-5,7-dien-3-one, Equation 16.10 [23].
O O
Me Me
N COOH –2e–, –2H+, –2CO2 N (16.10)
COOH
Instead, the conversion of l-nonyl-3-oxocyclohexanecarboxylic acid ethylene ketal to methyl

5-nonyl-5-hexenoate by oxidation at a carbon anode in methanol containing K2CO3 includes a car-
bocation intermediate, Equation 16.11 [24].
COOH
+ C9H19
C9H19 – +
–2e , –H , –CO2
O O O O
(16.11)
C9H19 C9H19
MeOH
+ COOCH3
O O

2. Ketones
Ketones with branching in the α-position may be cleaved at a platinum anode in MeCN–
LiC1O4 [25]. A mechanism that involved generation of a carbenium ion by α-cleavage of the ketone
radical cation, Equation 16.12, analogous to reactions in photochemistry and mass spectroscopy,
was proposed.
O
–2e– + MeCN, H2O
R3C+ + Me C O
R 3C Me (16.12)
R 3C NHCOMe + Me COOH

3. 1,2-Diols and Related Hydroxy Compounds

Vicinal glycols and related monohydroxy compounds may be cleaved to carbonyl compounds or
acetals, Equation 16.13, by oxidation at a carbon anode in MeOH/Et4NOTs [26,27]. The anodic
oxidation does not show the stereochemical limitations usually observed when the cleavage is
c arried out with chemical oxidizing agents. 1,2-Diols may also be cleaved by indirect oxidation by
using the periodate–iodate redox system as a mediator [28,29].
R2 R3 R2 R3
R1 R4 O + O (16.13)
1 4
RO OR R R

Symmetrical ketones may be prepared in this way, for example, by alkylation of methyl methoxy-
acetate with RMgX to the dialkyl methoxymethylcarbinol that is then oxidized [27]. Yields are
typically around 80%. Unsymmetrical ketones may be obtained from symmetrical ketones
by anodic oxidation of the enol ethers to the α-methoxyketone [27,30], reaction with R′MgX and
then anodic oxidation of the glycol monomethyl ether. Alternatively, the ketone may be oxidatively
a minated, alkylated at C═O, and oxidized, Equation 16.14, Y═OCH3 or NR2.
O OH O
R΄MgX ~3F, MeOH
RCH2 CHR RCH2 + RCOOH (16.14)
RCH2 CHR R΄
R΄ Y
Y
Unexpectedly, it was observed that for the oxidation of the racemic and meso forms of
4,4′-dihydroxyhydrobenzoin at an anode of mild steel at pH 13.5 only the racemic form was
cleaved to p-hydroxybenzaldehyde at a measurable rate, whereas the meso form could be recovered
unchanged [31].
An indirect oxidative cleavage by oxidation with “Cl+” has been reported for 2-amino-1-
cycloalkanols, resulting in the formation of the corresponding keto nitriles [32]. Related to this is
the oxidative cleavage of N-o-phenylbenzoyl prolinols in MeOH to the α-methoxylated pyrrolidine
derivative [33] and of the retro Paterno–Büchi reaction observed during the oxidative cleavage of
oxetanes mimicking DNA (6–4) photoproducts [34].
β-Hydroxyhydroxylamines may be cleaved to aldehydes and oximes upon anodic oxidation at
pH 8, Equation 16.15 [35].
R΄ R΄
–2e–, –2H+
R CH NHOH R CHO + NOH (16.15)
pH 8
OH R˝ R˝
4. Alkoxy Compounds
1,1,2-Trimethoxycyclohexane may be oxidized to the acetal ester [36]. The starting material for this
reaction may itself be prepared by anodic addition of MeOH to cyclohexanone enol ether leading to
the overall reaction shown in Equation 16.16.
OMe OMe
MeO O
MeO
MeO
MeOH H2O
OMe (16.16)
–2e–, –2H+ –2e–, –2H+ H
OMe
Related to this reaction is the oxidation of veratrole in MeOH/KOH to, among other
products, 5,5,6,6-tetramethoxy-l,3-cyclohexadiene and hexamethyl cis,cis-orthomuconate,
Equation 16.17 [37]; carried out independently as a separate step, the latter cleavage gives a
yield of 77%. It is noteworthy that only the least stable cis,cis isomer is formed; this may indi-
cate that the intermediates are short-lived and/or adsorbed on the electrode during the fixation
of the geometry of the product.
OMe MeO
OMe OMe
MeOH OMe MeOH OMe
(16.17)
–2e–, –2H+ OMe –2e–, –2H+ OMe
OMe OMe
OMe MeO
Alkoxycyclopropane rings may be opened by anodic oxidation, which of the bonds that are
cleaved depends on the substituents and the experimental conditions. Thus, 7,7-dichloro-1-
ethoxybicyclo[4.1.0]heptane [38] gives methyl 7,7-dichlorohept-6-enoate (86%) by anodic oxidation
at a carbon anode in MeOH in the presence of lutidine, Equation 16.18, whereas 7,7-dichloro-l-
trimethylsilyloxybicyclo[4.1.0]heptane upon oxidation in MeOH at –13 to –10°C in the presence of
Fe(NO3)3 [39] gives methyl 2-oxocyclohexanecarboxylate (72%), Equation 16.19.
Cl
Cl
–2e–, –2H+
MeOH/lutidine (16.18)
Cl Cl COOMe
OEt
COOMe
Cl
i = 18 mA
(16.19)
MeOH
Cl
O
OSiMe3

Anodic oxidation of l-methoxy-2-phenylthiocyclopropanes [40] in MeOH/K2CO3 proceeds with

cleavage of the ring between C–l and C–2; the product is the corresponding 2-[methoxy(phenylthio)
methyl]alkanone, 79%, Equation 16.20. The oxidation of 2-phenylthio-1-cycloalkanols proceeds in
a fashion similar to that of diketones [41].
OMe
2.3F SPh
SPh (16.20)
MeOH
O
OMe
5. Alkenes
Alkenylarenes may undergo cleavage of the double bond by oxidation at a dimensionally stable
anode or a Pb anode in MeOH or EtOH containing CF3COONa as the electrolyte [42]. The reaction
proceeds through an initial oxidative addition of RO – to the double bond followed by cleavage to the
dialkyl acetal in a reaction similar to that in Equation 16.13.
The cleavage of a 1,2-diol is an intermediate step in the oxidation of stilbenes carrying
electron-withdrawing substituents to the corresponding aldehydes [43]. The oxidative addition
of –OH and the subsequent cleavage were carried out in MeCN/water using triarylamines as redox
catalysts.
A rather complicated reaction sequence, including the oxidative cleavage of a C–C bond carry-
ing a methoxy substituent, has been proposed to account for conversion of 1,2-,5,6-bis[trimethylene]
cyclooctatetraene to methyl 5-(2,3-dihydro-1H-inden-5-yl)-5-oxopentanoate by oxidation in MeOH,
Equation 16.21 [44].
OMe 1) Electrocyclization
2 MeOH 2) –e–
–2e–, –2H+
OMe
OMe
MeO MeOH
–e–, –2H+
OMe OMe
+
+
+
(16.21)
OMe OMe
MeO +
MeOH OMe
MeO OMe –2e–, –H+
O O
OMe
Oxidative cleavage of alkenes and cycloalkenes to carboxylic acids and diacids, isolated as
the methyl esters, in 70–90% yields has been accomplished by using a IO 4 −/RuCl3 mediator
system [45]. For example, cyclohexene could be converted in this way to dimethyl hexanedio-
ate in 76% yield.
Oxiranes may be ring opened in acidic methanol to diols that in turn may be cleaved anodically;
this sequence has been used to convert a propylene side chain, via electrochemical epoxidation (not
shown below), to an aldehyde, Equation 16.22 [46].
O O O
THF, 10%H2SO4 3–7F

MeOH, H2SO4
O Ph O Ph O Ph (16.22)
CHO
HO
O
OH
6. Hydrocarbon Single Bonds

Cleavage of the central C–C bond has been observed during the oxidation of 1,2-di-(p-tert-butylphenyl)-
ethane using boron-doped diamond electrodes [47]. The reaction products, p-tert-butylbenzalde-
hyde dimethyl acetal and p-tert-butylbenzyl methyl ether were believed to arise via a mechanism
including attack by methoxy radicals resulting from the oxidation of MeOH at the BDD electrodes.
III. CARBON–NiTROGEN BONDS

A. REDUCTIVE C–N CLEaVaGES
1. Quaternary Ammonium Ions
Salts of tetraalkylammonium, R4N+, and related ions are widely used as supporting electrolytes
in organic electrochemistry in aprotic solvents (see Chapter 7). One reason for that is that R4N+ is
difficult to reduce and this allows for electrochemical studies of a broad range of substrates with-
out interference from the reduction of the supporting electrolyte cation. However, at sufficiently
low potentials, R4N+ is reduced and the nature of the reduction products turns out to depend on
both the cathode material and the concentration of residual water in the solvent [48–52]. At mer-
cury, tetraalkyl ammonium amalgams are formed [48,53], whereas reductive cleavage of the type
shown in Scheme 16.2 for R = Et is observed at most other cathode materials [49,50,52,54]. The
reaction includes a dissociative electron transfer as the first step followed by reduction of the ethyl
radical. The resulting ethane anion reacts with Et4N+ in a Hofmann elimination producing ethene
and ethane. Also, the cathodic breakdown of ionic liquid cations may involve C–N cleavage [55].
Early work [56] has shown that anilinium salts with three N-alkyl groups are reduced at a Pb cath-
ode to benzene and the corresponding tertiary amine. Reduction of N-allyl-N,N-dimethylanilinium
ions (or N-benzyl-N,N-dimethylanilinium ions) gives propylene (or toluene) and dimethylani-
line [57]; in general, it is found that ease of cleavage follows the order benzyl > allyl > phenyl >
alkyl. The same type of cleavage is observed in DMF and it was found that quaternary ammo-
nium ions containing allyl, benzyl, fluorenyl, acenaphthenyl, benzhydryl, and cinnamyl groups gave
propylene, toluene, fluorene, acenapthene, diphenylmethane, and a mixture of allylbenzene and
propenylbenzene, respectively [58]. Occasionally, dimers such as bibenzyl derived from the neutral
free radical formed in the initial electron transfer process have been observed [59–61]. The forma-
tion of a mixture of meso- and d,l-2,3-diphenylbutane in the reduction of enantiomerically pure
d-α-phenylethyl-l-trimethylammonium nitrate in DMF [59] as well as data from ESR spectroscopy
[61] support a mechanism including radical intermediates.
Reductive ring opening of anilinium salts in which one of the N-alkyl groups is attached to the
2-position of the benzene ring is a useful synthetic procedure, Equation 16.23 [62]. Other heterocy-
clic quaternary ammonium salts behave similarly [63].
n = 2, 90%
(CH2)n +2e–, +H+
(CH2)n N n = 3, 88% (16.23)
+
N n = 4, 90%

+e– + H3C CH2

N+ N
+e–
H3C CH2 H3C CH2–
H H
N+ + H 3C CH–2 N + C C + H3C CH3
H H
SchEME 16.2 Reductive cleavage of tetraethylammonium ion.

2. Carboxamides and Related Compounds

The products resulting from reduction of amides depends on the acidity of medium [6]. For
example, reduction of isonicotinic anilide gives 4-pyridinylmethanol at pH 5, whereas a mixture
of N-(4-pyridinylmethyl)aniline and 4-pyridinylmethanol is obtained in 1 N HCl. A gem-amino
alcohol that may lose either the amine forming an aldehyde, or water forming an imine, is a likely
intermediate. The aldehyde is then reduced to the alcohol, whereas the imine is reduced to an
amine, Equation 16.24. A similar gem-amino alcohol is formed during the reduction of oxaziri-
dines [64].
OH
CONHPh CHNHPh +
H N+ CH2NH2–Ph + H2O
+2e–, +2H+ +2e–, +3H+
(16.24)
N+ N+
H N+ CH2OH + Ph NH3+
H H

Simple carboxamides are difficult to reduce [65] and for that reason not suitable in protection/
deprotection chemistry of amines or amino acids. However, the corresponding nitro derivatives are
easily cleaved, in acidic media [66] to the deprotected amine and benzisoxazolone via the hydrox-
ylamine, Equation 16.25, or in DMF [67].
O O O
NHR +4e–, +4H+ NHR

O + RNH2 (16.25)
–H2O
NO2 NHOH N
H
Benzyloxycarbonyl derivatives of primary and secondary amines may be reduced at vitre-

ous carbon cathodes in DMF with cleavage to toluene and the free amine in good yields (>80%),
Equation 16.26, [68]. By using a high-surface area, Pd cathode cleavage may be carried out under
mild conditions; selectivities in this type of deprotection are excellent [69]:
O
+2e–, +2H+
C6H5CH2O NHR C6H5CH3 + CO2 + RNH2 (16.26)

The reduction may be made easier by using 4-nitrobenzyloxycarbonyl [70] or cinnamyloxycarbonyl

[71] derivatives making these derivatives suitable in amine protection/deprotection chemistry.
Another approach includes the reductive deprotection of allyl carbamates in a [Ni(bipy)3](BF4)2
catalyzed decarboxylation-type process [72]; the reactions were carried out in DMF in a single-
compartment cell with a consumable Zn rod anode. tert-Butoxycarbonyl-substituted acyl amides
may be selectively deacylated by electrochemical reduction [73]. Chloro-, bromo-, and iodoethoxy-
carbonyl as well as trifluoro-, trichloro, and tribromoethoxycarbonyl have been used as easily
removed protection groups in peptide synthesis [74,75].
N-acylureas undergo reductive cleavage of a C–N bond to the corresponding isocyanate and an
amide anion. Hydrolysis and protonation gave the final products (Scheme 16.3) [76].
N-(Diethylaminothiocarbamoyl)benzamidines undergo C–N cleavage upon cathodic reduction.
It was found that the nature of the substituent at the amidine nitrogen affected which of the C–N
bonds that undergoes cleavage as illustrated by Scheme 16.4 [77].
O O
+e– –
R NH C N R R NH C N R
–½H2
COR΄ COR΄
O
Li+
R N C O + R N– C R΄
H2O H2O
O
H
RNH2 + CO2 R N C R΄
SchEME 16.3 Reductive cleavage of N-acylureas.
NH
R = H, n-C3H7 +HS CH2 N(Et)2
N
H R
N N(Et)2 +4e–, +4H+
N S R = Ph H H2N N(Et)2
H R CH2 N +
R S
SchEME 16.4 Reductive cleavage of N-(diethylaminothiocarbamoyl)benzamidines.
3. Aminoketones
The reduction of α-aminocarbonyl compounds, Equation 16.27 [78–80], or α-aminonitriles [81]
proceeds similarly to the reductive cleavage of the α-hydroxy compounds, in this case with elimina-
tion of the amine.
R˝ R˝
R R
+2e–, +2H+
NR΄2 H + R΄2NH (16.27)
O R΄˝ O
R΄˝
An exception to this general scheme was found for the reduction of two alkaloids, quininone and
dihydrocinchoninone, in 35% sulfuric acid; under these conditions, reduction took place at the car-
bonyl group leaving the C–N bonds intact [82]. Reduction in MeCN resulted in “normal” C–N
cleavage.
4. Amines
Reduction of 4-aminobenzonitrile in DMF resulted in the formation of the radical anion of
4, 4′-dicyanobiphenyl [8]. This product was proposed to arise from elimination of NH2− at the
radical anion stage followed by dimerization of the neutral radical and further reduction.
2,6-Di-tert-butyl-4-phenylcyclohexa-2,5-dienones may be used as protecting groups for amino

acids and peptides [83]; protection is easily accomplished by anodic oxidation of 3,5-di-tert-
butylbiphenyl-4-ol in the presence of the amino acid in CH2Cl2/Et4NBF4 [84] and deprotection by
reductive cleavage in MeOH/HCl [83], Equation 16.28.
OH
O
R΄
–1.1 V vs Ag/Ag+ Ph
and/or + NH2 COOR (16.28)
R΄ MeOH, HCl
OH
R˝
Ph NH COOR Cl
R˝
Ph
5. Azides
Reduction of azides activated by a neighboring >C=O or >C=N–NH–CS–NH 2 function
leads to cleavage of the C–N bond and elimination of azide ion, Equation 16.29. The final
products are imidazole derivatives (70–80%) resulting from a complex cascade of follow-up
reactions [85].
O
O O N
+2e– Ar CH2N3 Many steps
–N3– Ar COAr (16.29)
Ar CH2N3 Ar CH2– N
6. Diazo Compounds
The reactivity of the radical anions resulting from electrochemical reduction of organic diazo com-
pounds is often sufficiently low to allow for studies of the kinetics and mechanisms of the follow-up
reactions by CV using moderate sweep rates. In a number of cases such as azibenzil [86,87] and
diethyl diazomalonate [87], it has been shown that the radical anion decomposes in a unimolecu-
lar reaction generating the corresponding carbene radical anions and dinitrogen, Equation 16.30.
Hydrogen-bonding to water deliberately added to the MeCN solution facilitates the cleavage reac-
tion and so does the neighboring carbonyl group.
– –
O O
+ N2 (16.30)
N2

The radical anion of 2,3,4,5-tetraphenyldiazocyclopentadiene was found to decompose in a

similar fashion [88]. A more complicated behavior was observed for the decomposition of the
diazodiphenylmethane radical anion to largely diphenylmethane and benzophenone azine [89],

a reaction that had earlier been suggested to involve unimolecular decomposition as in Equation
16.30 [90]. However, although the radical anion decay was observed to give rise to a first order
rate law, a rate decrease of a factor of 20 was found when using CD3CN instead of CH3CN as the
solvent indicating the participation of hydrogen-abstraction from the solvent as an important part
of the decay mechanism that includes several parallel paths. In contrast, the 9-diazofluorene radi-
cal anion undergoes rate determining dimerization as the first step in a complex chain reaction
that leads to the product, fluorenone azine [91]. Reduction of the related bis(diazo) compounds
of indenofluorenes results in the formation of oligomeric polyazines with chain lengths varying
from 3–4 up to around 16 [92].
Related to these reactions is the reductive conversion of diethyl diazo(phenyl)methylphosphonate
to diethyl benzylphosphonate in aqueous dioxane, Equation 16.31 [93].
OEt OEt
O O
P P
OEt +2e–, +2H+ OEt
+ N2 (16.31)
N2
7. Nitro Compounds
It has been observed in a number of cases that the reduction of organic nitro compounds is accom-
panied with cleavage of the C–N bond and the formation of nitrite ions. A few examples have
been reported for the reduction of aromatic nitro compounds, including 1,4-dinitrobenzene [94] and
l,2,4,5-tetrafluoro-3,5-dinitrobenzene [95]. However, more often this type of cleavage is met during
the reduction of compounds in which the nitro group is attached to an aliphatic carbon as in nitro-
cumenes [96,97] and 2-(4-nitrophenyl)-2-nitropropane [98] and in the reduction of purely aliphatic
compounds such as 2,2-dinitropropane [99,100] and 1,1-dinitrocyclohexane [101–104]. The reader
is referred to Chapter 30 for details.
B. OXIDaTIVE C–N CLEaVaGES

1. Amides
Electrochemical oxidation of peptides and proteins has been shown to lead specifically to C–N
cleavage next to tyrosine and to tryptophan [105], here illustrated by cleavage next to tyrosine,
Equation 16.32.
OH O O O
+
–2e–, –H+ H2O
O O O O + H2N R˝ (16.32)
O O –H+ O
O +
N N R˝ N N R˝ N N R˝ N O
R΄ H H R΄ H H R΄ H H R΄ H
Coupled to EC-MS analysis this approach was suggested as an alternative to chemical and enzy-
matic cleavages.
N-(4-Methoxyphenyl)-2-azetidinones and N-(2,4-dimethoxyphenyl)-2-azetidinones may be

oxidatively deprotected under mild conditions in a MeCN/H2O (1/1) mixture containing 1%
LiClO4; it was suggested that C–N cleavage took place at the dication stage, Equation 16.33 [106].
R R΄ R R΄ R R΄
–2e– H2O
N N –H+ N
+ +
O O O
OMe
OMe OMe
+ OH
R R΄
H2O
+ O O + MeOH (16.33)
–H+ N
O H
2. Amines
Anodic oxidations that proceed beyond the formation of radical cations and dications are usually accom-
panied by the liberation of protons in one or more of the steps on the way to the final products. During the
investigation of the electrochemical oxidation of, for instance, aliphatic amines that are often the stron-
gest bases in the solution, this inevitably gives rise to rather complicated mechanism schemes including
acid–base reactions that involve the substrate. In addition, the oxidation of aliphatic amines is markedly
dependent on the concentration of residual water owing to the possibility that reaction intermediates con-
taining imine-like structures undergo in situ hydrolysis. As an example, tripropylamine has been found
to be oxidatively cleaved in MeCN that has not been scrupulously dried according to Scheme 16.5 [107];
only the most important steps on the way to dipropylamine and propanal are shown and it is not specified
either how the protons are distributed among the various amine species.
N-(4-Methoxyphenyl) amines are easily oxidized owing to the presence of the methoxyphenyl
group; this has been put to use in the protection/deprotection chemistry of amines [108]. When the
oxidative cleavage is carried out under acidic, nonaqueous conditions, the methoxyphenyl group is
converted to p-quinone. The yields obtained by electrochemical oxidation are generally higher than
those obtained by cerium ammonium nitrate oxidation, typically 70–90%.
IV. CARBON–PhOSPhORUS BONDS

A. REDUCTIVE C–P CLEaVaGES
The reduction of organophosphorus compounds often includes cleavage of a C–P bond. A number
of such reactions are included in a recent review [109]. The oxidation of organophosphorus com-
pounds leads to the formation of products that do not include C–P cleavage [109,110]; accordingly,
this section focuses on reductions only.
–e– +
(C3H7)3N (C3H7)3N
+
(C3H7)3N (C3H7)2NCHC2H5 + H+
–e– +
(C3H7)2NCHC2H5 (C3H7)2N = CHC2H5
+ H2O
(C3H7)2N = CHC2H5 (C3H7)2NH + C2H5CHO + H+
SchEME 16.5 Oxidative cleavage of tripropylamine.

1. Phosphonium Ions
Phosphonium ions are more easily reduced than the corresponding ammonium ions; the reduction
proceeds in a fashion similar to that of the ammonium ions and includes the cleavage of a C–P bond
[49,111–116]. The effect of the electrode material, the potential, and the temperature on the relative
rate of cleavage of a variety of alkyl and aryl groups has been studied in detail and it was found, for
instance, that the ease of cleavage at an Hg cathode increases in the order methyl < phenyl < ethyl
< n-butyl < iso-propyl < tert-butyl < benzyl [111]. The facile cleavage of the bond to the benzyl
group is the basis of a convenient procedure for the preparation of mixed tertiary phosphines and
quaternary phosphonium salts [111], Equation 16.34. This method also provides a simple means
for preparing phosphonium salts with four different ligands that after resolution into their optical
antipodes may be cleaved reductively providing optically active tertiary phosphines [117]:
R1X +2e–, +H+

(PhCH2)3P (PhCH2)3R1P+ (PhCH2)2R1P
–X – –PhCH3
R2X +2e–, +H+ R3X

(PhCH2)2R1R2P+ PhCH2R1R2P (16.34)
–X– –PhCH3 –X–
+2e–, +H+ R4X

PhCH2R1R2R3P+ R1R2R3P R1R2R3R4P+
–PhCH3 –X–

Reduction of alkyltriphenylphosphonium salts in aprotic media leads to the formation of ylids

[118,119], resulting from deprotonation of the starting materials by an electrogenerated base [120],
in competition with the cleavage reaction [121]. Competition between ylid formation and cleavage
has been observed also during the reduction of benzyl-, allyl-, cinnamyl-, and polyenylphosphonium
ions [122] and of 1,2-vinylene and 1,4-butadienylene bis-phosphonium ions [123] (See Sections XVI
and XIX).
2. Phosphonates
Reduction of dialkyl aroylphosphonates in MeCN in the presence of benzoic acid as a proton donor
gives the corresponding dialkyl α-hydroxyarylmethylphosphonates resulting from reduction of the
carbonyl group [124]. This is in contrast to the reduction in the absence of acid; in this case cleavage
of the C–P bond was observed resulting in the formation of the benzoins and the dialkyl hydrogen-
phosphonates as the only products.
3. Phosphine Oxides
The reduction of triphenylphosphine oxide directly to triphenylphosphine is accompanied by a
number of side reactions [125,126] and is as such not a synthetically useful reaction; in aprotic
media a C–P bond is cleaved in preference to the P–O bond. (See Sections XVI and XIX.)
4. Phosphines
The electrochemical reduction of Ph3P and related compounds in aprotic solvents (MeCN, DMF,
and HMPA) leads to the formation of the radical anion as the first step [125–128]. The follow-up
reaction is complicated, and in the presence of an R4N+ salt as the supporting electrolyte, a cata-
lytic reduction of the R4N+ cation takes place resulting in the formation of RPh2P among other
products [126] (Scheme 16.6). In addition to the steps shown, the alkyl radical may dimerize or
undergo disproportionation to the corresponding alkane and alkene. The formation of biphe-
nyl, presumably resulting from dimerization of the phenyl radicals, was reported in earlier work
carried out in DMF [125]:
+e–
Ph3P Ph3P –
–e–
Ph3P – + R4N+ RPh3P + R3N
RPh2P + Ph
Ph3P + R
HB
Ph Ph– PhH
–B–
Ph3P – + Ph3P +
HB
R R– RH
–B–
SchEME 16.6 Reduction of triphenylphosphine in the presence of tetraalkylammonium ions.
The reductive cleavage of a C–P bond has been observed also for the carborane shown in
Equation 16.35 [129] (the noncarbon atoms in the icosahedron are all boron).
Ph2P H
C C
Ph2P C +2e–, +2H+ H C
(16.35)
–2 PPh2
V. CARBON–ARSENic BONDS
A. REDUCTIVE C–AS CLEaVaGES
Quaternary arsonium ions are easier to reduce than the corresponding phosphonium ions by
approximately 0.3 V [113]. The ease of cleavage of the C–As bond is mostly similar to that for the
corresponding phosphonium ions and the preparative aspects are similar as well [113,130].
Tertiary arsines behave during electrochemical reduction essentially as the corresponding
phosphines (see Section IV.A.3). For instance, 1-naphthyldiphenylarsine is reduced to the radical
anion that subsequently undergoes cleavage of the Ph–As bond, Equation 16.36 [127]:
+e–
Ph2AsNaph Ph2AsNaph – PhAsNaph– (16.36)
–e– –Ph
Cleavage of the Carom–As bond is observed during the reduction of methyl 4-(diethylarsino)
benzoate, the corresponding oxide, methyl 4-(diethylarsoryl)benzoate, and the sulfide, methyl
4-(diethylarsorothioyl)benzoate. The radical anion of the resulting methyl benzoate was detected
by ESR spectroscopy [131].
VI. CARBON–OxYGEN BONDS

A. REDUCTIVE C–O CLEaVaGES
The reductive cleavage of a C–O bond requires as the rule activation of the bond; this can be
obtained in different ways. Conjugated carbinols, like allylic and benzylic alcohols, π-electron-
deficient heterocyclic carbinols, and α-hydroxyketones and the ethers of these compounds, may
be reductively cleaved. Unactivated aliphatic and aromatic hydroxyl groups may be reductively
removed after esterification with a suitable inorganic acid whereby the hydroxyl group is trans-
formed into a better leaving group. Reductive elimination of two vicinal hydroxyl groups or deriva-
tives thereof may also be possible. Many of the systems described later may be used as protecting
groups for alcohol functions [132,133], and the choice between them will depend, among other
factors, on the presence of electrophores in the protected molecule.
1. Acylphosphonium Salts
Acylphosphonium salts, obtained by constant current electrolysis of Ph3P in the presence of a
carboxylic acid in CH2C12 [134], may be reduced to triphenylphosphine oxide and the aldehyde in a
process that includes cleavage of the O–CO bond, Equation 16.37 [135]:
+ +2e–, +H+
Ph3P OCOR Ph3P = O + RCHO (16.37)

By using Ph3PH+, ClO4− as the supporting electrolyte, the reaction has been used for the conversion of
α-amino acids to α-amino aldehydes [135]. Paired electrolysis in MeCN containing R3P and Et4NBr
may be used in a similar way to deoxygenate primary and secondary alcohols to alkanes, Equation
16.38 [110]. The anodic process includes the formation of R3PBr2 that on reaction with R′–OH gives
R′O–PR3+,Br− and elimination of R3P=O gives R′–Br that is reduced at the cathode to R′–H.
Paired electrosynthesis
R΄ OH R΄ H (16.38)
R3P, (R = Ph, Bu, PhO), Et4NBr 48–96%

2. Carboxylates and Carbonates

Alkyl and benzyl esters of aromatic [136,137] or heteroaromatic acids [138] undergo C–O cleavage
upon reduction in an aprotic solvent to the carboxylate ion and alkyl or benzyl radical, here illus-
trated by the reduction of benzyl benzoate, Equation 16.39 [136]. The latter is further reduced to the
anion under the conditions and finally protonated to toluene.
O O
+2e–, +H2O
+ H3C Ph (16.39)
Ph O Ph –OH– Ph O–
A study of the relative rates of cleavage of a series of p-methoxycarbonylbenzyl carboxylates dem-

onstrated that there is no simple relation between the leaving group ability and structure [139]. If a
proton donor is not added, the base inevitably generated during the reduction may cause cleavage
of the ester to benzoate and benzyl alcohol. The cleavage may be carried out indirectly by reduc-
tion with electrogenerated superoxide ion [140]. In that case, the reaction proceeds “only” to the
carboxylate and the alcohol/alcoholate. Similarly, α-benzoyloxyacetophenone is reduced to benzoic
acid and acetophenone [141] and benzyl ethyl oxalate to 2-ethoxy-2-oxoacetate and toluene [142].
During the reduction of benzyl carbonates, the intermediate benzyl anion may be trapped by carbon
dioxide; the overall reaction provides an efficient synthesis of arylacetic acids in good yields [143].
The reductive cleavage of phenyl benzoate in DMF follows a different route including the initial
dimerization of the radical anion followed by elimination of phenoxide ion. The resulting benzil is
further reduced to the dianion, Equation 16.40 [144].
O–
–O
O –
O O O–
Ph OPh +2e–
2 Ph –
(16.40)
Ph O Ph OPh –2 O Ph
Ph Ph Ph Ph
O–
Reductive cleavage including an initial dimerization step is observed in MeCN and DMF also for
nitrobenzoates [145]. Benzil also results from the reductive cleavage of O-acylated benzaldehyde
cyanohydrins [146].
The ease of reduction of 2-haloethyl esters depends on the number and type of the halogen atoms
in the manner intuitively expected. Reductive cleavage of a trichloroderivative in MeOH/LiClO4
proceeds according to Equation 16.41 [74]. This type of protecting group has been employed during
a nucleotide synthesis using the triester method (see Section VI.A.6).
O O
+2e– MeOH
–Cl– -MeO–
Ph OCH2CCl3 Ph OCH2CCl2–
(16.41)
O O
+ H 2C CCl2 +
Ph OCH2CHCl2
Ph O– 6%
87%
Allyl carboxylates may be reductively cleaved to alkenes in a reaction catalyzed by Pd(0)(PPh3)4,

Equation 16.42, or to the corresponding allyltrimethylsilanes if the reduction is carried out in the
presence of trimethylsilyl chloride [147]. The reaction has been successfully used in protection/
deprotection chemistry as illustrated by the conversion of allyl benzoate to benzoic acid in 97%
yield.
R
R OAc +2e– R + E+ R E (16.42)
PdLn –AcO– –
AcO
In addition to allyl, the cinnamyl [148], p-tolyl [149], benzhydryl [150], triphenylmethyl [150],
and 4-picolyl [151] groups are suitable in protection/deprotection chemistry as they are easily
removed electrochemically. In uncatalyzed reductions, cinnamyl esters are reduced in preference
to allyl esters, and cinnamyloxy carbonates are reduced easier than cinnamyloxy carbamates [148].
Propargyl acetate has been reductively cleaved to the corresponding allenes in DMF in the pres-
ence of a catalytic amount of PdCl2(PPh3)2/PPh3 in a “less than 2F” process indicating that PPh3
acts as a reducing agent through formation of an acetyltriphenylphosphonium salt that is then hydro-
lyzed to triphenylphosphine oxide [152].
Cleavage including an initial dimerization step is observed for the reduction in MeCN and DMF
of benzoate diesters of 1,2-diols to benzil in a reaction that is likely to proceed via the formation of
a cyclic 2,3-diphenyl-1,4-dioxane-2,3-diol dianion [153].
Reduction of aliphatic esters of 1,2-diols often proceeds as a reductive elimination to the corre-
sponding alkene. For example, vicinal dioxalates are cleaved electrochemically to alkenes in DMF,
Equation 16.43 [154]. The oxalates of 1,2-diols may be formed by base-catalyzed transesterification
with diethyl oxalate [155]. Related to this is the formation of alkenes and alkanes from pinacols by
reductive cleavage of cyclic carbonates and aryl boronates [156].
O–
O R΄ O O R΄
EtO OEt EtO
–EtOOC–COO–
O R O O R
O O (16.43)
O R΄ R΄
+e– –
EtO
–EtOOC–COO–
O R R
O
Related to this is the reductive elimination of acetate from 1,2-diacetoxy-l,2-diphenylethylene in

DMF to diphenylacetylene [157]. In the presence of phenol, diphenylacetylene is further reduced to
the stilbene.
3. Sulfonates and Related Esters

The reductive conversion of an aliphatic alcohol to an alkane may be carried out in high yield by
preparing first the methanesulfonate of the alcohol after which the methanesulfonate is reduced at
a lead cathode in DMF containing a tetrabutylammonium salt as supporting electrolyte, Equation
16.44 [158]:
+2e–, +H+
R OSO2Me RH + MeSO3– (16.44)

Similarly, tert-butyl benzenesulfenate is reduced to isobutane and the benzenesulfenate anion;

the reaction proceeds via a stepwise dissociative mechanism [159]. In contrast, the reduction of
benzyl benzenesulfenate involves cleavage of the S–O bond.
Cyclic sulfates of unactivated diols such as 2,3-butanediol are reduced in DMF/Et4NC1O4 at
a mercury electrode to 2-butene (cis–trans, 5:95) in moderate yields; minor amounts of several
unidentified compounds were observed by GLC, Equation 16.45 [160].
H3C CH3
~1F
H3C CH CH CH3
(16.45)
O O
–SO4 2– 39–49%
S
O O
4. β-Arylthio- and β-Alkylthioesters and -Alcohols

The reductive elimination of a hydroxyl and a phenylthio group from a β-hydroxysulfide is a
key step in a convenient method for the conversion of carbonyl compounds to the corresponding
alkenes, Equation 16.46 [161]. If the alcohol is first converted to the methanesulfonate, reduction
leads instead to the cyclopropane [162].
R΄ R΄ R΄
1) PhSCH2Li +2e–
O HO CH2 (16.46)
2) H3O+ –OH–, –PhS–
R˝ R˝ SPh R˝

A modification of this process in which the carbonyl compound is treated instead with (PhS)2CHLi
or PhS(CH3O)CHLi has been used to convert an aldehyde to the next higher homolog, Equation
16.47 [163]. The resulting enol ether or thioenol ether may be transformed into an aldehyde by
hydrolysis or reaction with mercuric chloride.
R΄ R΄ SPh R΄ SPh R΄
1) (PhS)2CHLi +2e– H3O+
O HO CH CHO (16.47)
2) H3O+ –OH–, –PhS–
R˝ SPh R˝ R˝
R˝
1,2-Diphenyl-2-(phenylthio)ethyl acetate may be converted to stilbene by reductive elimination

of PhS− and AcO − in DMF in a similar way. However, in this case the product, stilbene, is more
easily reduced than the substrate and the stilbene radical anion thus formed enters a catalytic cycle
in which an electron is transferred to the substrate, Equation 16.48 [164].
Ph Ph Ph Ph –
+e– +e–, –PhS–, –AcO–
(3 steps)
PhS OCOCH3 PhS OCOCH3
+e–
Ph CH CH Ph Ph CH CH Ph –
(16.48)
Ph Ph
Ph Ph –
PhS OCOCH3 +e–, –PhS–, –AcO–
etc.
(3 steps)
–Ph CH CH Ph PhS OCOCH3

5. β-Nitroesters
Acylated β-nitroalcohols, prepared by condensation of an aldehyde with a nitroalkane followed by
acetylation, may be reduced to alkenes in moderate to good yields, Equation 16.49 [165].
R R˝ R˝
+2e–
NO2 RCH (16.49)
–NO2 – , –R΄O–
R΄O R΄˝ R΄˝

6. Phosphates
Aromatic hydroxyl groups may be removed by conversion first to an aryl diethyl phosphate that is
then electrochemically cleaved in DMF to the hydrocarbon and diethyl phosphate anion, Equation
16.50 [166].
O O
+2e–, +H+
ArO P OEt ArH + –O P OEt (16.50)
OEt OEt
Simple triaryl phosphates are cleaved in a similar fashion [109,167]. This is in contrast to tris
(4-nitrophenyl) phosphate that owing to the electron-withdrawing nitro groups undergoes cleavage
at the dianion stage accompanied by dimerization [168] similar to what is observed during the
reduction of 4-cyanodiphenyl ether [169] (see Section VI.A.10).
2-Haloethyl diphenylphosphates are cleaved reductively to diphenylphosphate [170]. Protection/
deprotection based on these types of compounds has been employed during nucleotide synthesis
using the triester method to achieve selective cleavage of one of the ester groups. The 5-trityl pro-
tected nucleoside was first treated with 2,2,2-trichloroethylphosphoric acid dichloride and then with
2,2,2-tribromoethanol. By electrochemical reduction in MeCN, the tribromoderivative could be
selectively removed, whereas the detritylation could be carried out with 1% trifluoroacetic acid in
methylene chloride [171].
7. Hydroxyketones
The hydroxy groups in α-hydroxyketones [172,173], as, for example, in 16-hydroxy-17-ketosteroids,
may be reductively cleaved according to Equation 16.51.
R OH R H
+2e–, +2H+
–H2O (16.51)
O R' O R'
8. Hydroxysulfones
Alkenes result also from the reduction of β-hydroxysulfones [174,175] that are easily prepared
from the corresponding esters by reaction with ArSO2CH2MgI followed by reduction with NaBH4
Equation 16.52. This route provides a convenient way to convert an ester to an alkene [174]:
O
1) ArSO2CH2MgI NaBH4
RCOOCH3 RCCH2SO2Ar
2) H3O+ MeOH
(16.52)
OH
~4F
RCHCH2SO2Ar RCH CH2

9. Alcohols
The C–OH bond in an α,β-unsaturated alcohol, such as allylalcohol and cinnamylalcohol, may be
reductively cleaved by direct electrolysis [176,177] or electrocatalytically at a platinized Pt electrode
in acidic medium [178] to the alkene and further to the corresponding hydrocarbon, Equation 16.53
[176–178]:
+2e–, +2H+ +2e–, +2H+

Ph CH CH CH2OH Ph CH CH CH3 Ph CH2 CH2 CH3 (16.53)
–H2O
Another approach includes reduction under acidic conditions in the presence of iodide ion; the
in situ generated iodo compound is then reduced at a mercury cathode in a reaction that includes a
shift of the double bond to the terminal position. Crotyl alcohol may be reduced in this way to a 95/5
mixture of 1- and 2-butene in a total yield close to quantitative [179].
10. Acyclic Ethers and Glycosides

The radical anion of diphenyl ether undergoes C–O cleavage in DMF to the phenyl radical and
a phenoxide ion with a first-order rate constant equal to 4·105 s−1 [180]. The phenyl radical is
subsequently reduced to the anion and then protonated. The reduction of alkyl aryl ethers follows
the same mechanism [181]. This is in contrast to the radical anions of 2- and 4-cyanodiphenyl ether
that were found to dimerize. In the case of 4-cyanodiphenyl ether, the resulting dimer dianion
undergoes loss of phenoxide giving the 4,4′-dicyanobiphenyl that is further reduced [169]. The cou-
pling pattern of 2-cyanodiphenyl ether radical anion includes three dimer dianions.
Allyl aryl ethers such as allyl phenyl ether are reduced in a Ni(bpy)32+ catalyzed reaction to the
phenols in high yield [182]. A chlorine atom in phenyl group is not affected. Allyl alkyl ethers are
cleaved similarly. Since the allyl aryl ethers are easily obtained from the corresponding phenols by
reaction with an allyl halide under basic conditions, the reaction is useful in protection/deprotection
chemistry. Similarly, the 4-picolyl derivative of, for instance, l-tyrosine is easy to prepare and to
remove electrolytically [183].
Cleavage of an ether bond is observed also during the 6F+6F reduction of 4-alkoxy-1,3-dinitro-
benzenes under acidic conditions. The first 6F reduction process is accompanied by hydrolysis of
the OR substituent leading to 2-amino-4-nitrophenol that is further reduced to 2,4-diaminophenol
in the second 6F process [184].
Benzyl methoxymethyl ethers carrying electron-withdrawing substituents such as p-cyano and
o- or p-methoxycarbonyl in the benzyl group are reduced in MeOH to the corresponding toluenes in
fair to good yields in reactions that include elimination of methoxide ion at the radical anion stage,
Equation 16.54 [185]. In addition, the ester group is reduced to the aldehyde and alcohol stage when
the reduction is carried out in the presence of acetic acid.
CH2OMe CH2OMe – CH3

+e– –MeO– +e–, +H+ (16.54)
COOMe COOMe COOMe

O OMe
Trityl [186] and cinnamyl [187,188] groups are useful in alcohol protection/deprotection chemistry
as they are easily removed electrochemically and similar to what was observed for the cleavage of
esters [148], cinnamyl ethers are reduced in preference to allyl ethers. Related to these groups is the
tritylone group (9,10-dihydro-10-oxo-9-phenyl-9-anthracenyl) and selective protection/deprotection of
alcohols may be achieved by using a combination of the tritylone and p-cyanobenzyl groups. Tritylone
alcohol (TrOH) reacts preferentially with primary hydroxy groups and is the more easily reduced
group. This has resulted in the following reaction sequence for 1,4-pentanediol, Equation 16.55 [189].
By adjusting the reduction potential, either one or both of the protecting groups may be removed.
OH CN
OH OH
O CH2Br
OH OTr
(16.55)
O –1.4 V vs Ag/AgCl O
OTr OH
NC NC
–2.1 V vs Ag/AgCl OH
OH
Glycosidic bonds may be reductively cleaved in DMF by using a redox catalyst such as
anthracene, Equation 16.56 [190]. The radical is further reduced by the anthracene radical
anion and then protonated. The redox catalysis may be carried out intramolecularly by attach-
ing acetophenone covalently to the aliphatic chain.
O O
HO HO
OCH2(CH2)7CH2CH3 –OCH
(16.56)
2(CH2)7CH3CH3
O O O O
–
OH OH
11. 1,3-Dioxolanes and 1,3-Dioxanes

The protection of carbonyl groups by conversion to 1,3-dioxolane derivatives is a classic reac-
tion in carbonyl chemistry. 1,2- and 1,3-Diols substituted with, for instance, a p-nitrophenyl
group give 1,3-dioxolanes and 1,3-dioxanes that are easily reductively cleaved. Examples include
4-(4′-nitrophenyl)-1,3-dioxolanes, 5-nitro-1,3-benzodioxane and 7-nitro-1,3-benzodioxane, Equation
16.57, here illustrated by the deprotection of cyclohexanone [191].
O O
O +e– O
O2N O2N
– O (16.57)
O O–
–O
+e–, +H+
N+ O2N
–O

12. Oxiranes
Oxiranes carrying phenyl substituents are reduced with ring opening in DMF to a variety of prod-
ucts, including phenyl substituted alcohols, alkenes, and alkanes, the composition of the product
mixture being dependent on both the number and position of the phenyl groups [192]. A typical
example is given by Equation 16.58. Slightly different product compositions are observed when the
reduction is carried out by indirect electrolysis.
Ph Ph Ph Ph Ph
2F
+ +
O (16.58)
Ph HO Ph Ph
70% 22% 8%
Benzoyloxiranes are reduced in MeCN to the corresponding aldoles; addition of acetic acid
prevents the retro-aldol reaction catalyzed by the base generated during reduction [193]. The ring
opening is analogous to that observed in the reduction of 2-alkoxyacetophenone to acetophenone.
Acetyloxiranes react similarly. If the reduction is carried out in aqueous EtOH/Me4NBr in the
presence of catalytic amounts of HBr, the product is the corresponding β-acetoxyketone, which
has been used in the reductive conversion of epoxypregnenone (16α,17α-epoxypregn-5-en-3β-ol-20-
one) to acetoxypregnenone [194].
B. OXIDaTIVE C–O CLEaVaGES

1. Enol Esters and Related Compounds
The radical cations of enol derivatives such as carboxylic acid esters, carbonates, carbamates, and
anhydrides undergo cleavage of the O–CO bond, resulting in the formation of a benzofuran deriva-
tive as the final product, here shown for a mixed carbonate, Equation 16.59, Mes = mesityl [195].
The rate constants for the cleavage step were determined by fast sweep CV in MeCN and found to
be in the range (2–5) · 103 s−1.
O O +
Mes O Mes O
–e–
OCH2Ph OCH2Ph
–PhCH2OCO
Mes R Mes R
(16.59)
Mes + O O
+ [1,2]-Me
R R
–H+
Mes R
Mes Mes
2. Ethers
It was observed early that anodic oxidation of hydroquinone mono- and dimethyl ethers in dilute
sulfuric acid resulted in the formation of benzoquinone [196]. Similarly, the oxidation of dime-
thoxydurene in acetonitrile gave duroquinone rather than the side-chain substitution product that
might have been expected [197] (see Chapter 23). The reaction sequence shown in Equation 16.60,
including the elimination of R+, was offered to explain the observation.
OR OR O
+
–e–
–R+
(16.60)
OR OR OR
O O
–e–
–R+
+
OR O
Related to this is the electrochemical oxidation of vitamin E model compounds [198,199]. The reac-
tion has been shown to proceed as illustrated by Equation 16.61 with the key step being the water-
assisted cleavage of a C–O bond (see also Chapter 40).
OH O O
–2e–, –H+ H2O

+2e–, +H+ –H+
(16.61)
O O O
+
HO

The substituted benzoquinone product may be reduced back to the 2,2,5,7,8-pentamethylchroman-
6-ol starting material in MeCN/AcOH containing sodium acetate [199].
The electrochemical oxidation of benzyl ethers, ArCH 2OR, leads to the corresponding benzal-
dehydes, ArCHO, and alcohols, ROH, in a process that includes cleavage of the C–O bond [200].
The reaction has been put to use in the oxidative cleavage of benzyl ether protected alcohols.
Anisyl ethers are preferred owing to their relatively low oxidation potential, 1.65 V versus SCE
[201]; the yields of the deprotected alcohols were typically close to 90%. Deprotection may pref-
erably be carried out in MeCN containing a base such as 2,6-dimethylpyridine or NaHCO3 using
a redox catalyst such as tris(p-bromophenyl)amine; in that case, the operating potential may be
lowered by ~550 mV relative to that for the direct electrochemical oxidation [202]. Unsubstituted
benzyl ethers cannot be cleaved by the tris(p-bromophenyl)amine radical cation. However, tri-
phenylamines containing bromine atoms not only in the three p-positions, but also in one or more
o-positions have oxidation potentials high enough to cleave the simple benzyl ethers [203]. Thus,
the oxidation potential of the catalyst may be fine-tuned by adjustment of the number of bromine
atoms in the triphenylamine. Alternatively dioxo-bridged binuclear manganese complexes may
be used as mediators in MeCN [204].
Also, the p-methoxyphenyl group has been used successfully in alcohol protection/deprotection;
in this case, the deprotection step includes the oxidation at platinum electrodes in a MeCN/water
(9/1) mixture containing NaHCO3/NaClO4 [205].
Carbonyl groups protected by conversion to 4-phenyl-l,3-dioxolanes may be deprotected by
oxidation in MeCN/pyridine using N-hydroxyphthalimide as a redox catalyst [206].
Advantage has been taken of electrochemical deprotection by oxidative C–O cleavage in activat-
ing self-assembled monolayers as shown schematically in Scheme 16.7 [207,208]. In this way, long-
chain aldehydes (left) [208] and carboxylic acids (right) [207] attached to a gold electrode could be
exposed for further reaction by a single CV scan.
VII. CARBON–SULfUR BONDS

The reader interested in the electrochemical cleavage of the C–S, C–Se, and C–Te bonds is referred
also to Chapter 27.
A. REDUCTIVE C–S CLEaVaGES

1. Sulfonium Ions
The first step in the electrochemical reduction of a sulfonium ion is a one-electron process accompa-
nied by cleavage of a C–S bond [209–212] similarly to what is observed for other organic “onium”
OH
O O H O O O HO O
+0.7 V +0.2 V
S S S S
Au Au
SchEME 16.7 Oxidative deprotection/activation of self-assembled monolayers.
ions, Equation 16.62. The one-electron transfer and the bond breakage may proceed in a stepwise or
concerted manner dependent on the structure of the sulfonium ion [211,213] (see Chapter 14 for details):
R1
+e–
S+ R2 R1 S R2 + R (16.62)
The reversible one-electron reduction of sulfonium ions to the corresponding free radicals has
been observed only for diarylalkylsulfonium ions carrying one or more nitro groups in one of the
aryl groups and only at low temperature (−40°C) [214]. Amalgams may be formed by reduction at
mercury electrodes [53,215].
For sulfonium ions in which R, R1, and R2 in Equation 16.62 are not all identical, the question of
the relative ease of cleavage of the three bonds has received considerable attention [211,212,216–218].
For a series of monophenylalkylsulfonium ions, reduction resulted in cleavage of the weaker S-alkyl
bonds in the order benzyl > secondary > primary > methyl > phenyl [209,216] reflecting the stability
of the resulting radical. In contrast, the stronger S-aryl bond is preferentially cleaved during reduc-
tion of diphenylmethylsulfonium ions [212,216,218]. Results from indirect electrolysis have shown
that the ratio of S-aryl/S-alkyl cleavage depends on the reduction potential of the reducing agent, and
it was concluded that the differences between the reductive cleavage of mono- and diarylsulfonium
ions are direct consequences of the structures of the sulfuranyl radicals and the bond dissociation
energies of S-alkyl and S-aryl bonds [217].
The radical, R•, formed during the cleavage reaction has been detected by spin trap experiments
[214,219,220] and dimers derived from R· have occasionally been detected [54,221]. Radicals gener-
ated by electrochemical reduction of sulfonium ions have been utilized in surface derivatization of
glassy carbon electrodes [222] (see also Chapter 42).
During coulometry or preparative electrolysis, reduction may proceed as a 2F process includ-
ing the further reduction of R• to R− that finally may be protonated to RH. However, RH may arise
also via a hydrogen-abstraction reaction between R• and a solvent component. When the reduction
is being studied by redox catalysis, products resulting from coupling between R• and the catalyst
radical anion are observed [223,224].
H3C
+e–
S+ CH2Ph H3C S CH2 + PhCH2
H3C
+e–
PhCH2 PhCH 2–
H3C H3C
–
S+ CH2Ph + PhCH2– S+ CHPh + PhCH3
H 3C H3C
SchEME 16.8 Ylid formation resulting from reductive cleavage of a benzylsulfonium ion.
The product distribution resulting from reduction of triphenylsulfonium ion depends on both
the electrode material and the potential [212,215]. Reduction of triphenylsulfonium bromide at a
mercury cathode at the potential of the first wave gives quantitatively diphenylsulfide and diphe-
nylmercury. At potentials lower than the second wave, diphenylsulfide and benzene are formed,
provided low-substrate concentrations are used. With increasing substrate concentrations, the yield
of diphenylmercury increases at the expense of benzene. Reduction in aqueous solution at an alumi-
num cathode produces diphenylsulfide and minor amounts of benzene; addition of DMF increases
the yield of benzene indicating that benzene is formed (at least partly) in a hydrogen-abstraction
reaction [212].
The base produced during reduction may react with sulfonium ions carrying a hydrogen atom in
the α-position resulting in formation of the corresponding ylid (Scheme 16.8) [54,225,226]; the ylid
could be trapped by, for instance, benzaldehyde to give an epoxide by the Corey–Chaykovsky reac-
tion. Ylid formation has been attributed to be the origin of the inhibition of the reduction process
observed at graphite cathodes [116].
Attempts to utilize the anion, R−, in a Michael condensation with acrylonitrile resulted in only
moderate yields of the expected products [227].
2. Thiol Esters
The product distribution resulting from reduction of thiol esters in DMF/LiClO4 [228], DMF/
Bu4NI [229], or MeCN/Et4NBF4 [138] is dependent on the nature of the two groups attached
to the –CO–S– function [138,228] and also on the supporting electrolyte cation [228,229]. The
major products observed in DMF/LiClO4 [228] may be summarized as follows: (a) R–CO–S–R
gives R–CO–SH, (b) R–CO–S–Ar gives R–CO–NMe2 (with the NMe2 part originating from
DMF), (c) Ar–CO–S–R gives Ar–CO–CO–Ar, and (d) Ar–CO–S–Ar gives Ar–CO–CO–Ar,
where R in all cases is an alkyl-type group and Ar an aryl group. In DMF/Bu4NI [229] reduction
of Ph–CO–S–Ar and Ph–CO–S–R proceeds all the way to the 1,2-diphenylacetylene. If oxygen
is present during the reduction, R–CO–OH is formed in a reaction with super oxide ion [140].
Thus, it appears that the primarily formed radical anion may undergo cleavage of either the CO–S
bond or the S–Y bond (Scheme 16.9), where Z and Y are the alkyl/aryl groups. When Z = Ar,
O
–S Y
+
O Path a Z
Y
O
Z S Path b + Y
Z S–
SchEME 16.9 Competition between CO-S and S-Y cleavage during reduction of thiol esters.
path (a) is preferentially followed and dimerization of the radical then leads to the diketones,
whereas Z = R results in products preferentially derived from path (b). However, another pathway
leading also to α-diketones includes the dimerization of the radical anions followed by elimina-
tion of YS−. This was found to the likely mechanism for reduction of benzenecarbodithioic esters
to diphenylacetylenes [229].
Cleavage of a C–S bond in the initially formed radical anion has been shown to be the first chem-
ical step following electron transfer in the electrochemically induced rearrangement of S,S-diaryl
benzene-l,2-bis(carbothioates) to 3,3-bis(arylthio)isobenzofuran-1(3H)-ones in DMF by Equation
16.63 [230]. Complete conversion required less than 0.1F indicating that an SRN1-type mechanism
with elimination of ArS− at the radical anion stage is followed.
O
O
SAr
~0.1F
O (16.63)
SAr
SAr
O ArS

The S-carbobenzoxy group has been used as a protection group for cysteine and could be
removed by reductive cleavage in 72% yield [231]. The differences in reduction potentials for
N-carbobenzoxybutylamine, O-carbobenzoxybutanol, and S-carbobenzoxycysteine make possible
the selective removal of the protective groups.
Dialkyl, alkyl aryl, and diaryl trithiocarbonates are reduced in DMF to the corresponding radical
anions followed by loss of thiolate ion [232–234]. The rate constant for the cleavage was found to
vary linearly with Hammett’s substituent constant σ; the radical anions of the mono- and dithiocar-
bonates having a >C=O group were cleaved faster than those having a >C=S group. The effect of
structure on the electron transfer kinetics was rationalized by using a multisphere solvation model
for the solvent reorganization within the Marcus–Hush theory. When the reduction was carried
out in the presence of a suitable alkylating agent such as dimethyl sulfate or ethyl iodide, the cor-
responding 1,1,2,2-tetrakis(alkylthio)ethene was obtained, Equation 16.64 [232,234].
S
RS SR
1) +4e–
2 + 2PhSR + 4X– (16.64)
PhS SR 2) +4RX
RS SR
3. Thioethers (Sulfides)
The C–S bond in dialkylsulfides is difficult to cleave by electrochemical reduction; however, cleav-
age at a silver cathode has been reported [235]. In contrast, most alkyl aryl and diaryl sulfides are
reduced in DMF [236] at a low potential (~ –2.5 V vs. SCE), or in THF at low temperature [237], to
ArS− and R− (or RH) in an altogether 2F process via the one-electron reductive cleavage of the C–S
bond, Equation 16.65:
+e–
Ar S R Ar S– + R (16.65)
For Ar = 2-naphthyl, it was observed that the mode of cleavage in THF could be controlled by
the temperature [238]. At 20°C, the reaction proceeded predominantly via cleavage of the alkyl-S
bond as in Equation 16.65, whereas cleavage of the aryl-S bond at the dianion stage was observed
at −78°C. When naphthalene was used as a redox catalyst in THF at low temperature, the cleavage
of Ar–S–R could be carried out at a potential approximately 500 mV higher than that for the direct
process. Under those conditions, not only RH was isolated, but also PhSSPh [239].
The bond-breaking details have been investigated by redox catalysis for phenyl triphenylmethyl
sulfide [240–242] and a series of p-substituted phenyl triphenylmethyl sulfides [241,242]. For the
cleavage of diphenylmethyl p-methoxyphenyl sulfide, the mechanism includes the protonation of
the diphenylmethyl anion by the starting material (self-protonation) [243]. The data obtained for
strongly electron-withdrawing substituents were in agreement with a stepwise mechanism; a grad-
ual transition toward a pathway including a loose radical anion was observed in passing through the
unsubstituted compound to the p-methoxy-substituted (see Chapter 14 for details).
Phenacyl phenyl sulfide is reduced in an aqueous-alcoholic solvent mixture to acetophenone
and thiophenol [173]. This particular reaction has been put to use in the cleavage (deprotection)
of 2-acyl-3-aminothiophene derivatives in DMF containing phenol as the proton donor, Equation
16.66 [244]. The starting material was easily prepared by reaction between an α-haloketone and
sodium cyanophenyldithioacetate.
H2N Ph H2N Ph
– +
Ar +2e , +2H
Ar Ar (16.66)
–ArCOCH3
S SH
S O S
O O
Deprotection of thiols in general may be accomplished by reduction of the corresponding benzyl

thioethers, the prominent example being the deprotection of the thiol group in cysteine by reduction
at a platinum cathode in liquid ammonia [245] or a mercury cathode in MeOH [246]. Other thiol-
protecting groups that may easily be removed by electrochemical reduction include trityl [231] and
4-picolyl [183,247].
The reduction of gem-disulfides such as 3,3-bis(methylthio)-1-phenylprop-2-en-1-one leads to
cleavage of the C–S bond and elimination of CH3S−, Equation 16.67 [248]. The free radical was
reported to polymerize. In the presence of carbon dioxide, substitution of the CH3S group by COO −
was observed.
O O O
Ph SCH3 Ph SCH3 Ph SCH3
+e– + C H3S– (16.67)
H SCH3 H SCH3 H

Related to this is the reductive cleavage of arylthiophenylacetylenes in DMF in the presence of

phenol; the C(sp)–S bond is cleaved resulting in the formation of the ArS− anion and the Ph–C≡C·
radical [249]. The reaction was also studied by redox catalysis. It was concluded that the bond cleav-
age was the rate determining step.
An exotic example of a reductive C–S cleavage is the removal of 2,2′-oxydiethanethiol and simi-
lar fragments from o-carboranyl derivatives such as that shown in Scheme 16.10 [129] (the noncar-
bon atoms in the icosahedron are all boron). However, the fate of the 2,2′-oxydiethanethiol fragment
is not clear, but it was observed that in the presence of the larger 2,2′-(ethane-1,2-diylbis(oxy))
diethanethio ring system, the reductive elimination of the ring system was accompanied by loss of
a boron fragment from the o-carborane structure.
4. Sulfoxides
The electrochemical reduction of DMSO at a platinum cathode and in the presence of Bu4NBF4
leads to C–S and S–O cleavage and the formation of MeS− and Me2S, respectively [250].
S
C
O
S C
SchEME 16.10 Example of an o-carboranyl derivative that undergoes reductive C-S cleavage.
Ar1
Ar1 Ar1 S O Ar1 Ar1

+e– Ar2
S O S O– S O S O–
Ar2 Ar2 Ar2
Ar2
Ar1 Ar1 Ar1

Ar1
+e–
S– O S O– S + –O S O–
Ar2 Ar2 Ar2 Ar2
Ar1
Ar1SO2– + Ar2H
–O S O– or
Ar2SO2– + Ar1H
Ar2
SchEME 16.11 Reductive disproportionation of diarylsulfoxides.
Diarylsulfoxides undergo disproportionation to the corresponding sulfide and sulfone upon

reduction in aprotic solvents followed in most cases by reductive cleavage of the sulfone (see Section
VII.A.5) [251]. The disproportionation reaction was suggested to proceed as shown in Scheme 16.11.
Reductive cleavage of β-ketosulfoxides is a practical way of preparing methylketones [252,253];
ω-(methylsulfinyl)-p-methoxyacetophenone, for example, gives acetophenone (74%) upon reduction
at a mercury cathode, Equation 16.68 [252].
O O
+2e–, +H+
H3CO O H3CO + CH3SO–
H2C S CH3
(16.68)
CH3
The major products resulting from the reduction of vinyl aryl sulfoxides in DMF/Bu4NBF4 are
the corresponding arenesulfinate anions resulting from disproportionation (see Scheme 16.11) and
subsequent cleavage of the ArSO2–CHCHR bond [254]. Direct cleavage of the ArSO–CHCHR
bond has been reported to take place for vinyl phenyl sulfones that carry an α-CF3 substitu-
ent. The resulting phenylsulfanolate anion undergoes reduction to the thiophenolate that reacts
with the starting material in an altogether very complex reaction scheme [255]. Reduction of
(E)-l-methylsulfinyl-l-methylthio-2-phenylethene with excess of phenol includes the selective
cleavage of one C–S bond and the formation of (E)-l-methylthio-2-phenyl-ethene, Equation 16.69.
The dependence of the CV curves on the phenol-to-substrate ratio and the stereochemistry of the
reaction supported the mechanism shown including as the second step the elimination of the meth-
ylsulfanolate anion [256]. Other α,β-unsaturated sulfoxides react similarly [255,257].
O O
H S CH3 H S CH3 H SCH3

+2e–, +H+ – (16.69)
–CH3SO–
Ph S CH3 Ph S CH3 Ph H

5. Sulfones
The electrochemical reduction of sulfones has been the subject of a number of reviews to which the
reader is referred for details [209,258].
Simple dialkyl sulfones and bis(alkylsulfonyl)methanes are difficult to reduce electrochemically.
An exception is the disulfone derived from 1,3-dithietane that is reduced in a 2F process with ring
opening to methylsulfonylmethanesulfinate, Equation 16.70 [259].
+2e–, +H+
O2S SO2 CH3SO2CH2SO2– (16.70)

The general reaction scheme for the reduction of alkyl aryl sulfones includes cleavage of the
ArSO2–R bond at the radical anion stage; the resulting alkyl radical is further reduced to the anion
that is finally protonated to RH (Scheme 16.12) [259–262]. However, when the reduction is carried
out at low temperature in THF, the radical anion has a lifetime that is sufficient to allow for the
observation of its oxidation back to the substrate during CV [263].
The presence of electron-withdrawing substituents such as p-NO2 and p-CN causes the radical
anions to be long-lived and they can easily be detected by CV at room temperature [264]. For sul-
fones of this type [264,265], cleavage of the Ar–SO2R bond with elimination of the alkane sulfinate
anion is the predominant reaction pathway; the cleavage reactions in those cases may be so slow
that other follow-up reactions such as protonation and dimerization may take place [266]. Similarly,
2- and 4-(alkylsulfonyl)pyridines and related sulfones undergo Ar–SO2R cleavage [267]. This offers
a convenient route to alkylsulfinic acids and thus to alkylsulfones with two different alkyl groups.
For long-chain alkyl groups, the basic conditions created during reduction in, for instance, DMF
may cause the formation of alkenes by β-elimination [261].
The reduction of seven-membered ring sulfones such as dibenz[b,e]-thiepin-11-one-5,5-dioxide
(Scheme 16.13) and the related 11-thione is accompanied by cleavage of the CH2–SO2 bond as
expected [268]. An unexpected cleavage reaction was observed for the reduction of 4-phenylthio-tert-
butylsulfonylbenzene; in that case, the elimination involved the 2-methylpropane-2-sulfinate anion
that subsequently attacked the starting material in a substitution reaction, resulting in the formation
of the symmetrical 1,4-bis(tert-butylsulfonyl)benzene [269].
+e–
ArSO2R ArSO2R – ArSO2– + R
+e–
+H+
R R– RH
+ArSO2R –
–ArSO2R
SchEME 16.12 Reductive cleavage of alkyl aryl sulfones.

O
O
S
SchEME 16.13 Structure of dibenz[b,e]-thiepin-11-one-5,5-dioxide.
The reduction of diaryl sulfones follows a mechanism similar to that in Scheme 16.12 [260,270–272].
For mono-substituted diphenyl sulfones, the selectivity of the bond cleavage was dependent on the
electronic nature of the substituent. For reduction at mercury in MeOH containing Me4NCl/Me4NOH
(2/1), it was found that electron-donating substituents resulted in cleavage of the S–Ph bond, whereas
the bond between sulfur and the substituted phenyl group was cleavaged exclusively when the substit-
uent was electron withdrawing [271]. Substituents in the o-position facilitated cleavage of the neigh-
boring C–S bond, probably by steric hindrance of the conjugation between the aromatic ring and the
sulfone group [271,273]. A special case is 1-(4-biphenylyl)-2-phenylsulfonyl-3,3,3-trifluoropropene
that in a +2e−, +H+ process including the cleavage of a C–S bond is converted to Ar–CH=CH–CF3
and PhSO2− [255].
The central hydrogen atoms in bis(arylsulfonyl)methanes are acidic (pKa = 12.5 for bis
(phenylsulfonyl)methane) owing to the two neighboring SO2-groups and, accordingly, the mecha-
nism for reduction depends on the availability of protons in the solvent-supporting electrolyte mix-
ture. In a nonbuffered DMF/water mixture (20/80) with Et4NBr as the electrolyte, reduction proceeds
according to Equation 16.71 with cleavage of the C–S bond taking place at the dianion stage [259]:
+e–, +e– H2O

ArSO2CH2SO2Ar ArSO2CH2SO2Ar2– ArSO2CH3 + ArSO2– (16.71)
–OH–
This is in contrast to the mechanism observed in strictly aprotic solvent in which a self-protonation
scheme is observed (Scheme 16.14). In both cases, the alkyl aryl sulfone produced may be further
reduced, but the benzenesulfinate anion is not electroactive in the potential range applied.
Self-protonation reactions are observed also for the reductive cleavage of allylic and benzylic
sulfones in aprotic solvents [274], whereas reduction of vinyl sulfones results in cleavage to the
corresponding alkenes and benzenesulfinate [114,255,275]. Analogous to this is the reductive
cleavage of the C–S bond in β,β-bis(methylsulfonyl)styrene to β-(methylsulfonyl)styrene [276]. In
mixed disulfones that have both the ArSO2CH2R and the ArSO2CH2CH=CH2R structural features,
the allylic benzenesulfonyl group is preferentially cleaved; the selectivity is higher when indirect
electrolysis is being used [277]. For cyclic 1-cycloalken-1-yl phenyl sulfones, the cleavage reaction
is accompanied by isomerization into the corresponding allyl sulfones triggered by the electrogen-
erated base [278]. 1-Methylthio-1-p-tolylsulphonyl-2-arylethenes are reduced in a fashion analogous
+e–
ArSO2CH2SO2Ar ArSO2CH2SO2Ar –
ArSO2CH2SO2Ar – + ArSO2CH2SO2Ar
[ArSO2CH2SO2Ar]H + ArSO2CHSO2Ar–
+e–,+H+
[ArSO2CH2SO2Ar]H ArSO2CH3 + ArSO2–
SchEME 16.14 Reductive cleavage and self-protonation of a bis(arylsulfonyl)methane.

to the reduction of l-methylsulfinyl-l-methylthio-2-phenylethene described earlier, Equation 16.69,

in this case with the elimination of the p-methylbenzenesulfinate anion as the second step [279].
The ability to act as a leaving group during the reductive cleavage of diaryl sulfones or alkyl aryl
sulfones is benzyl ~ allyl > alkyl > phenyl [260,261,271,272].
The reductive cleavage of benzene substituted with more than one alkyl- or arylsulfonyl group has
been studied in detail [280–284]. The products resulting from reduction of the disubstituted compounds
depend on the substitution pattern and on whether the substituent is an alkyl- or arylsulfonyl group.
Reduction of 1,2-bis(alkylsulfonyl)benzenes [282,285] and 1,4-bis(alkylsulfonyl)benzenes [283] leads
via the formation of the radical anions to the formation of self-alkylation products in addition to the
expected cleavage products, here shown for a 1,2-bis(alkylsulfonyl)benzene, Equation 16.72.
SO2 SO2 SO2

R +2e– R R
+
R H+ (solvent) (16.72)
SO2 SO 2 –
–RSO2–
The reduction of 1,2-bis(phenylsulfonyl)benzenes proceeds in a slightly different manner. The

free radical resulting from elimination of the benzenesulfinate anion undergoes hydrogen abstrac-
tion to the diphenyl sulfone and cyclization followed by elimination of a hydrogen atom giving the
dibenzothiophene dioxide (Scheme 16.15) [280].
The reduction of 1,3-bis(alkylsulfonyl)benzenes and 1,3,5-tris(alkylsulfonyl)benzenes proceeds
completely different; the radical anions were found to dimerize to a dimer dianion [282,284] simi-
larly to what is observed for other benzenes substituted in the 1- and 3-positions with strongly
electron-withdrawing groups (see Chapter 17).
The radical anions of tetra- and pentasulfones are stable at the time scale of slow sweep CV,
whereas those of the hexasulfones undergo reductive coupling accompanied by the loss of sulfinate
anions, Equation 16.73, in addition to the cleavage reaction [281,282].
SO2R SO2R RO2S SO2R

RO2S
RO2S SO2R
+2e– RO2S
(16.73)
SO2R
–2RSO2–
RO2S SO2R
RO2S SO2R RO2S SO2R
SO2R
SO2 SO2
Ph +e– Ph –
Ph –PhSO2– Ph
Ph
SO2 SO2 SO2
Hydrogen
abstraction Ph
SO2
Ph
SO2 Cyclization and
hydrogen elimination
SO2
SchEME 16.15 Reductive cleavage of 1,2-bis(phenylsulfonyl)benzene.

The reductive cleavage of β-ketosulfones [286], RCOCHR′SO2R″, in DMF at a mercury cath-

ode is a practical way of preparing alkyl ketones and proceeds analogously to the reduction of
β-ketosulfoxides, Equation 16.68. The anode reaction is the oxidation of R″SO2− to R″SO3− and an
undivided cell may then be used.
The sulfamoyl group in benzenesulfonamides carrying strongly electron-withdrawing substitu-
ents may be eliminated as sulfur dioxide and ammonia in a pH independent step by reduction at a
mercury cathode in aqueous solution [287]; thus, cleavage of the C–S bond occurs before cleavage
of the S–N bond. The sulfamoyl groups in benzene-1,3,5-trisulfonamide and benzene-1,3-disulfon-
amide may be eliminated one-by-one in this way.
6. Thiocyanates
The electrochemical reduction of p-CN and p-NO2 substituted benzyl thiocyanates in MeCN leads
exclusively to cleavage of the ArCH2–SCN bond (Scheme 16.16, path (a)) and the formation of the
corresponding bibenzyls [288]. Reduction in the presence of an excess of phenol gave the toluene,
ArCH3, which was taken as an indication that the bibenzyl was formed in a substitution reaction
between ArCH2−, formed by reduction of the benzyl radical, and the starting material and rather
than by dimerization of the benzyl radicals.
In contrast, benzyl thiocyanates substituted in the p-position with MeO, Me, H, Cl, and F gave
the corresponding mono- and disulfides together with the toluenes resulting from cleavages by
both path (a) and (b) in Scheme 16.16. The analysis of the voltammetry data showed that a step-
wise mechanism including a distinct radical anion was followed for p-NO2 substituted compound,
whereas the compounds substituted with the weaker electron-withdrawing p-CN and all the elec-
tron-donating substituents were following a concerted cleavage mechanism. Theoretical DFT data
(B3LYP 6–31G+(d,p)) showed the existence of stronger interactions between the produced frag-
ments for path (b) than for path (a); this seems to account for regioselectivity of the cleavage.
The effect of a strongly electron-withdrawing group is observed also for the reduction of other
thiocyanates. For instance, for 1-phenyl-2-thiocyanatoethanone in which the thiocyanato group
has the electron-withdrawing ArCO in the α-position, reduction proceeds with cleavage of the
ArCOCH2–SCN bond, Equation 16.74 [173] analogously to the cleavage shown in Equation 16.66.
In most other thiocyanates, reduction results in loss of a cyanide ion [289] and macroscale reduc-
tions at a mercury cathode gives the mercaptans.
O O
+2e–, +H+
SCN + SCN– (16.74)
Ar CH2 Ar CH3

B. OXIDaTIVE C–S CLEaVaGES

1. Thiol Esters
S-tert-butyl thioates can be deprotected by indirect electrochemical oxidation using the bromide/bromine
redox system as mediator, Equation 16.75 [290]. By direct anodic oxidation, 4-methoxyphenylthiomethyl
X CH2 + S CN–
Path a
X CH2 S CN –
Path b
X CH2 S + CN–
SchEME 16.16 Competitive cleavages observed during reduction of benzylthiocyanates.

esters are readily converted to carboxylic acids, Equation 16.75 [290]. The initially formed radical cation
cleaves on reaction with water to the acylated hemiacetal and further to the acid.
–2e–
Anodic
Br+ Br– O
O oxidation O
10–11F (16.75)
R R R
MeCN/H2O MeCN/H2O
S OH OCH2SAr

Triarylamine radical cations may also be used in an indirect electrochemical oxidative cleavage
of thiol esters [291].
2. Thioethers (Sulfides)
Anodic oxidation of thioethers usually results in the formation of sulfoxides, sulfones, or sulfonates
(see Chapter 27). However, if R in ArSR is a good leaving group such as benzyl or trityl, oxidation
in MeCN may lead to cleavage of the C–S bond. Phenyl trityl sulfide, for example, is oxidized to
diphenyl disulfide (48%) and triphenylmethanol (52%) (Scheme 16.17) [292].
[4-Hydroxy-3-coumarinyl]-phenylthiomethanes are oxidized in a similar fashion. However,
in this case, the intermediate carbocation is trapped by MeCN in a Ritter reaction, resulting in
the formation of N-[4-hydroxy-3-coumarinyl]methylacetamide [293]. Related to these is the low-
temperature oxidative cleavage of thioglycosides such as thioglucosides, thiogalactosides, and
thiomannosides that when the reaction is carried out in dichloromethane with tetrabutylammonium
triflate as supporting electrolyte leads to the corresponding glycosyl triflate pools [294].
The methylthiomethyl group may be used as a protecting group for alcohols; deprotection may
be carried out by oxidation in an undivided cell at a platinum anode in AcOH-containing NaOAc.
The resulting acetoxymethyl ether may then be hydrolyzed in weakly alkaline solution back to the
alcohol, Equation 16.76 [295]:
–e–, –H+ +OH–

R O SCH3 R O OAc R OH (16.76)
AcOH/AcONa –AcO–
Electrooxidative desulfenylation of Michael-type thiol adducts of activated olefins may be car-

ried out indirectly in an undivided cell at platinum electrodes with EtOH and Bu4NBr as solvent
and supporting electrolyte, Equation 16.77, Y = COOEt, COMe, and CN [296]. The alkylthio (or
phenylthio) residues are oxidized mostly to the sulfinates. The resulting activated olefins are formed
in good to excellent yields.
Anodic
SEt oxidation
3–4F (16.77)
R CH CH2 Y R CH CH Y
Br–/EtOH
–e–
Ph S CPh3 Ph S CPh3 + Ph S + +
CPh3
2 Ph S Ph S S Ph
+H2O
+CPh
3 Ph3C OH
–H+
SchEME 16.17 Oxidative cleavage of phenyl trityl sulfide.

–2e– +
S S 2
–1/4 S8
+ +RCN, +H2O
RCONH
–H+
SchEME 16.18 Oxidative cleavage of di-tert-butyl disulfide.
The C–S bonds in gem-disulfides may be cleaved by anodic oxidation in aqueous MeCN to
the corresponding carbonyl compounds [297–300]. This has been put to use for the removal
of the 1,3-dithian protecting group, Equation 16.78 [298]. The oxidation may be carried out
indirectly in MeCN/LiClO 4 containing NaHCO3 by using tris(p-tolyl)amine as the electron
transfer agent; carried out this way the yields of the recovered carbonyl compound were almost
quantitative [301].
R1 OH
R1 S R1 S+
–2e– H2O
R2 S+
–H+
R2 S R2 S+ S
(16.78)
R1
H2O S
O+ (–S[CH2]3S–)n
+
–H S
R2
3. Disulfides
The electrochemical oxidation of disulfides results in most cases in cleavage of the S–S bond.
An exception is the oxidation of di-tert-butyl disulfide that undergoes cleavage of the C–S bond
according to Scheme 16.18 [302]. The yields of the resulting amides are close to quantitative
in most cases.
VIII. CARBON–SELENiUM AND CARBON–TELLURiUM BONDS

A. REDUCTIVE C–Se aND C–Te CLEaVaGES
The electrochemical reduction of diphenyl selenide in MeCN leads to cleavage of the C–Se bond
with the formation of PhSe – and Ph– anions [303]; the latter are protonated by MeCN resulting in the
formation of CH2CN–. The PhSe – anion may be oxidized to diphenyl diselenide by air and reaction
of the diselenide with CH2CN– finally leads to 1-phenylseleno-1-cyano-2-aminopropene in moder-
ate yield in a many step process. Unsymmetrical phenylselenobenzonitriles [304] suffer preferen-
tially cleavage of the Ph–S bond, resulting in the formation of the cyanobenzeneselenolate anion in
~85% yield. Reduction of p-ArC6H4SeC≡CAr [305] in MeCN or DMF at a mercury cathode results
in cleavage of the C(sp)–Se bond.
Similarly to the corresponding selenium compounds, unsymmetrical phenyltellurobenzonitriles
suffer cleavage of the Ph–Te bond, resulting in the formation of the cyanobenzenetellurolate anion
[306]. Reduction of p-ArC6H4TeC≡CAr [305,307] in MeCN or DMF at a mercury cathode results
in cleavage of the C(sp)-Te bond.
B. OXIDaTIVE C–Se aND C–Te CLEaVaGES

Electrochemical oxidation of organoselenium and organotellurium compounds usually does not
include C–Se/C–Te cleavages. However, an oxidative cleavage reaction has been reported for cyclic
alkyl phenyl selenides such as selenochromanone [308] and for compounds of the general structure
R–Te–C≡C–Te–R [309].
IX. CARBON–HALOGEN BONDS

A. REDUCTIVE C–Hal CLEaVaGES
The reductive cleavage of the C–Hal bond is probably the most studied electrochemical cleavage
reaction. For that reason, Chapters 24 and 25 have been devoted to various aspects of this important
process. In addition, a detailed description of the C–Hal reduction process is included in Chapter 14.
In this chapter, we shall restrict ourselves to mention briefly a few cases in which halogens have
been used as protecting groups.
Vicinal dibromides can be converted into olefins by electrochemical reduction and the reduction
potential is shifted to higher values with increasing alkyl substitution. This has been used as selective
protection of the less alkylated double bond in dienes. The diene is converted into the tetrabromide
with bromine and subsequently deprotected by controlled potential electrolysis (Scheme 16.19) [310].
β-Halogenethyl groups have been used as protecting groups for several types of functional groups.
Deprotection can be carried out electrochemically by direct [74,75] and indirect [311] electrolysis.
Using a vitamin B12-derivative as mediator, penicillin V β-bromoethyl esters can be deprotected to
penicillin V under conditions so mild that even the β-lactam ring is kept intact [311].
X. NiTROGEN–NiTROGEN BONDS
In addition to the reactions discussed later, processes that include cleavage of the N–N bond are
found also in Chapters 29 through 31.
(C5H11)2BH OH
Br
Br2
Br
Br
+2e–, –2Br– Br
Br
B2H6 Br
Br
+2e–, –2Br– HO
Br
HO
SchEME 16.19 Protection-deprotection sequence for 4-vinylcyclohex-1-ene.

A. REDUCTIVE N–N CLEaVaGES

1. Carboxylic Acid Hydrazides and Azides
Activated hydrazides [312], such as isonicotinic hydrazide (isoniazid), are reduced to the amides
under acidic conditions in a reaction that includes the cleavage of the N–N bond and the formation
of ammonium ion, Equation 16.79.
O NHNH3+ O NH2
+2e–, +2H+
+ NH4+
(16.79)
+ +
N N
H H

The reduction of isonicotinoyl azide also leads to isonicotinic amide, in this case by elimination
of a molecule of dinitrogen; most other azides react similarly [313]. The reaction has been put to use
in the synthesis of saturated and unsaturated amino acids by cathodic reduction of azidocinnamic
esters [314,315]. Reduction of azides in DMF in the presence of acetic anhydride gives diacetylated
amines [316]. In contrast, the reduction of azides carrying a neighboring carbonyl or thiosemicar-
bazone function [85] leads to cleavage of the C–N bond and elimination of azide ions (see subsec-
tion III.A.5 on C–N cleavage).
2. Azines and Related Compounds

Organic compounds with the common structural feature >C=N–N< may undergo reductive cleav-
age of the N–N bond under acidic conditions in reactions that include also saturation of the >C=N–
double bond. Examples of this behavior include the reduction of benzalazine [316], phenylhydrazones,
[316,317], Equation 16.80, semicarbazones [316], and arylidene benzohydrazides [317,318]:
R R
+4e–, +6H+
N NHPh NH3+ + PhNH 3+ (16.80)
R΄ R΄
In aprotic media, the N–N bond appears to be cleaved at the radical anion stage and the rate of
cleavage for a series of N,N-dimethylhydrazones of arylaldehydes was found to be a linear function
of the potential for the reversible reduction of the hydrazone. Under the basic conditions generated
by the reduction, elimination of the amine part of the hydrazone may take place, resulting in forma-
tion of a nitrile [319].
3. Diazo Compounds
The reduction of diazo compounds such as diazoacetophenones [320], 3-diazocamphor, Equation
16.81 [321], and 3-diazoindole [322] in aqueous buffers at pH 6–9 proceeds to the corresponding
amines in a 6F process including cleavage of the N–N bond. At pH > 9, reduction takes place in
two steps, first to the hydrazone in a 2F process and then to the amine in a 4F process. In other cases,
reduction of organic diazo compounds is accompanied by cleavage of the C–N bond (see subsection
III.A.6 on C–N cleavage).
O O
+6e–, +6H+
+ NH3 (16.81)
N+ NH2
N–
B. OXIDaTIVE N–N CLEaVaGES

Electrochemical oxidation of benzaldehyde hydrazones may result in cleavage of the nitrogen–
nitrogen bond and formation of the corresponding benzonitrile [323]. Oxidative cleavage of an
N–N bond has been observed also during the oxidation of N-nitrosoarylamines in MeCN [324]. In
one case, N,N′-dimethyl-N,N′-dinitroso-p-phenylendiamine, the results indicated that cleavage took
place at the dication stage by elimination of two nitrosonium ions. In two other cases, the ammo-
nium salt of N-nitrosophenylhydroxylamine (known as Cupferron) and N-nitrosodiphenylamine
self-inhibition of the electrode process owing to adsorption was observed.
XI. NiTROGEN–PhOSPhORUS BONDS

A. REDUCTIVE N–P CLEaVaGES
Dimethylaminotriphenylphosphonium ion, Equation 16.82, and related phosphonium ions undergo
cleavage of the N–P bond during electrochemical reduction in MeOH [115]:
+2e–, +H+
Ph3P+ NMe2 Ph3P + Me2NH (16.82)
The outcome of the cleavages observed for bifunctional phosphonium ions is less easy to predict.
When both a diethylamino and an ethylthio group are present, the N–P bond is preferably cleaved
(in MeCN) and a Me2N–P bond is cleaved in preference to a MePhN–P bond (in water), Equations
16.83 and 16.84 [115]:
Ph SEt Ph
+2e–, +H+
P+ P SEt + Et2NH (16.83)
Me NEt2 Me

Ph
Ph Ph Ph
N Me +2e–, +H+
P+ P N + Me2NH (16.84)
Me NMe2 Me Me

The N–P bond in triphenylphosphinephenylimine may be cleavaged electrochemically by both

reduction and oxidation [325]. The oxidative cleavage leading to triphenylphosphine oxide and
polyanilines is believed to occur at the radical cation stage.
XII. NiTROGEN–OxYGEN BONDS

A. REDUCTIVE N–O CLEaVaGES
Nitrile-N-oxides are easily reduced to the corresponding nitriles; 2,4,6-trimethylbenzonitrile-N-oxide,
for example, may be reduced at –0.7 V (vs. SCE) at pH 6 in aqueous ethanol to the nitrile [326].
The reductive cleavage of the N–O bond in oximes generally occurs prior to the saturation of
the double bond, Equation 16.85 [316]. However, in alkaline solution at low temperature, reduc-
tion of aldoximes to hydroxylamines may take place to some extent. Similarly, cleavage of an
N–O bond has been observed during the reduction of amide oximes [316] and hydroxamic acids
[313]. The suggestion that cleavage of the N–O bond takes place for oximes bearing a positive
charge on nitrogen was supported by the observation that, after quaternization, isoxazoles, or
4,5-dihydroisoxazoles may undergo N–O cleavage in neutral solution without saturation of the
C=N bond [327]:
R R OH R H R
H+ +2e–, +2H+ +2e–, +2H+
NOH N+ N+ NH3+ (16.85)
–H2O
R΄ R΄ H R΄ H R΄

XIII. NiTROGEN–SULfUR BONDS

A. REDUCTIVE N–S CLEaVaGES
1. Sulfonamides
The widespread interest in the electrochemical cleavage of the N–S bond in sulfonamides has been
driven primarily by the applications of the process in the protection–deprotection chemistry of
amines [132]. The stoichiometry of the cleavage of, typically, p-toluenesulfonamides in the presence
of a suitable proton donor is given by Equation 16.86:
O R O R
+2e–, +H+
H3C S N H3C S + NH (16.86)
O R' O– R'

The solvents most often used are aqueous dioxane [328], MeOH or aqueous MeOH [260,329,330],
MeCN [331], and DMF [332–338]. Lead was found to be a good cathode material for the cleavage
of N-tosyl amino acids and peptides [330]. Yields have been reported to be in the range 55–98%.
Similarly, benzene-1,4-disulfonic acid diamides may be reductively cleavaged to the amine and the
monosulfonamide-sulfinic acid [339].
N-tert-butyl-α-phenylnitrone (BNP) spin trap studies of the reductive cleavage of aromatic sul-
fonamides under aprotic conditions have been found to be in agreement with a mechanism including
the initial formation of a radical anion that subsequently undergoes N–S cleavage to the arenesul-
finate ion and an amine radical (Scheme 16.20) [340] that may be further reduced and protonated
to the amine.
When the reductive cleavage is conducted under aprotic conditions, complications caused by
the strongly basic conditions are unavoidable. If the protected amine is primary, the resulting
secondary sulfonamide may act as a proton donor in the protonation of the electrogenerated
–
O R O R O R
+e
Ar S N Ar S N Ar S + N
O R' O R' O– R'
R R Ph O
BNP
N N C N
R' R' H t-Bu
SchEME 16.20 Reductive cleavage of an aromatic sulfonamide followed by trapping of the resulting aminyl
radical.
amide ions, resulting in an overall 1F process and recovery of 50% of the sulfonamide during
work-up, Equation 16.87 [334].
O
R
+2e–
2H3C S N
O H
(16.87)
O R O
R
H3C S + NH + H3C S N–
O– R' O

Even when the protected amine is secondary, the resulting tertiary sulfonamide may be depro-
tonated if the substituents on the nitrogen carry an α-hydrogen atom. Under those conditions,
β-elimination with formation of an aldimine or ketimine may occur, Equation 16.88, and the imine
may be reducible at the potential required for cleavage of the sulfonamide [335].
O R R
+2e–
2H3C S N N–
–Ts–
O CH R˝ CH R˝
R΄ R΄
(16.88)
R R
HN N
Ts–NR–CHR΄R˝
CH R˝ + C R˝
–Ts–
R΄ R΄
The reduction potentials of aromatic sulfonamides are low [328,332], in 75% dioxane typically
–2.3 to –2.4 V vs. NCE [328], and are dependent on the nature of the substituents as expected;
electron-donating substituents make the sulfonamide more difficult to reduce, whereas electron-
withdrawing substituents make the sulfonamide more easy to reduce. These effects could be ratio-
nalized in terms of a Hammett relation [329]. The low potentials needed may cause problems if
other reducible functions are present in the protected molecule. For that reason, efforts have been
made to find ways to make cleavage occurring more easily, for instance, by indirect electrolysis
using a mediator.
Indirect electrolysis using radical anions of aromatic hydrocarbons or Ni(acacen) as the media-
tors has made it possible to determine the formal potentials of a series of tosylamides in DMF
and also to estimate the rate of cleavage of the sulfonamide radical anions [333]. The results were
similar to those for the tosylates; when the amine was aliphatic, the cleavage of the anion radical
was the rate-determining step, whereas the homogeneous electron transfer from the electron donor
became rate determining when the amine was aromatic. Other systems for indirect electrolysis of
sulfonamides in DMF include anthracene [336] or naphthalene [341] as mediators.
Another way to make reduction easier is to use nitrobenzenesulfonyl protected amines [337,338]. The
radical anions of N,N-dibutyl-4-nitrobenzenesulfonamide and N-butyl-2-nitrobenzenesulfonamide
are persistent in DMF at the time scale of CV, but reduction of the radical anion to the dianion
induced a rapid cleavage of the N–S bond with formation of the amine in good yield [337]. Also,
the introduction of the N-Boc group was found to make reduction easier by 0.2–0.3 V [342]. Thus,
tert-butyl sulfonylcarbamates such as RSO2N(Boc)CH2Ph could be cleavaged in MeCN to Boc-
NHCH2Ph in MeCN.
The electrochemical cleavage in MeCN with Bu4NHSO4 as the electrolyte has been demon-
strated to work well for β-amino alcohols protected at nitrogen as the N-benzenesulfonyl derivative
and at oxygen as the tert-butyldimethylsilyl derivative or for N-benzoyl substituted derivatives [343].
In N-tosylcarboxamides, competition between the C–N and N–S might be expected. However,
during reduction in DMF containing acetic acid, the N–S bond is preferably cleavaged. The yield of
the deprotection amine was highest when a mercury cathode was used [344].
Besides being used for the deprotection of amino acids and peptides, electrochemical cleavage
has been employed in the synthesis of polyaza and polyaza–polyoxa ligands [345]; the deprotection
may be performed by direct as well as by indirect electrolysis.
2. Sulfenamides
N-tert-butyl-2-benzothiazolesulfenamide [346,347] and the corresponding morpholino derivative [348]
are vulcanization accelerators. Electrochemical reduction at mercury leads to cleavage of the N–S bond
and the formation of the substituted amine via the prior formation of a mercury mercaptide [346].
3. Sulfimides (Sulfilimines)
Sulfimides of the general structure shown in Scheme 16.21 undergo reductive cleavage, predomi-
nantly of the N–S(IV) bond to give the sulfonamide and the sulfide [349]. A minor pathway includes
cleavage of the N–S(VI) bond. A variant of this scheme, presumably including disproportionation
of the initially formed radical anion, was suggested for the case Ar = p-nitrophenyl [350].
B. OXIDaTIVE N–S CLEaVaGES

1. Sulfinamides
The structures of the products resulting from constant current electrochemical oxidation of
N-p-toluenesulfinamides depend on the degree of substitution on the nitrogen atom [351].
Sulfinamides derived from secondary alkylamines and primary arylamines undergo oxidative N–S
cleavage in MeOH with the formation of the amines and the methyl sulfinate (Scheme 16.22, top),
whereas sulfonamides derived from primary alkylamines are oxidized to the corresponding
sulfonamides in good yields (Scheme 16.22, bottom).
–
+e–
Ar SO2 N SPh2 Ar SO2 N SPh2
SolvH
Ar SO2 NH + Ph2S
–Solv
+e–, +H+
Ar SO2 NH2
SchEME 16.21 Reductive cleavage of a sulfimide (sulfilimine).
R = alkyl, R΄= alkyl R O

R = aryl, R΄= H
N H + S p-Tol
R' MeO
R O
–2e–, MeOH
N S
Pt cathode
R' p-Tol RVC anode O
R
N S O
R = alkyl, R΄= H
R΄ p-Tol
SchEME 16.22 Oxidative cleavage of p-toluenesulfinamides.

2. Sulfenamides
The radical cations of sulfenamides generally react only slowly [352,353]. However, results from
ESR spectroscopy have shown that the radical cations generated by electrochemical oxidation
of 4′-unsubstituted N-alkyl-2-nitrobenzenesulfenanilides are indeed due to the dimers that upon
further oxidation undergo N–S cleavage and the formation of RS+ [352].
XIV. NiTROGEN–HALOGEN BONDS

A. REDUCTIVE N–Hal CLEaVaGES
A study of the reductive cleavage of the N–Hal bonds in saccharin derived N-halosultams and their
4-nitro-substituted analogues (Scheme 16.23) in MeCN demonstrated that the two main factors
determining the occurrence of a stepwise or a concerted mechanism are the energy of the π* orbital
that accommodates the incoming electron and the strength of the bond to be broken; the weaker
the bond, the more chance for the concerted mechanism to overrun the stepwise mechanism [354].
Thus, a concerted cleavage was observed for R = H, Hal = F and R = NO2, Hal = Cl whereas
a stepwise mechanism was observed for R = NO2, Hal = F (see also Chapter 14).
XV. PhOSPhORUS–PhOSPhORUS BONDS

A. REDUCTIVE P–P CLEaVaGES
The polarographic reduction of diphosphines and cyclic polyphosphines in DMF proceeds as irre-
versible 2F processes resulting in the cleavage of the P–P bond as illustrated by Equation 16.89 for
1,1,2,2-tetraphenyldiphosphine [355]. The mono- and disulfides react similarly:
Ph Ph Ph
+2e–
P P 2 P– (16.89)
Ph Ph Ph
XVI. PhOSPhORUS–OxYGEN BONDS

A. REDUCTIVE P–O CLEaVaGES
(Diethylamino)(phenoxy)diphenylphosphonium ions are reduced in aqueous solution with cleavage
of the P–O bond and the formation of N,N-diethyl-1,1-diphenylphosphinamine [115].
Triphenylphosphine oxide is a well-known by-product from the Wittig reaction and the possibility
of regenerating triphenylphosphine by electrochemical reduction of the oxide has received special
attention. Usually, direct electrochemical reduction results in C–P bond cleavage and is for that rea-
son not useful although it has been reported that deoxygenation may be accomplished by reduction
in a cell containing a zinc cathode and an aluminum anode [356]. However, the oxide may easily
be converted to the dichloride by the in situ reaction with, for instance, oxalyl chloride or trimeth-
ylsilyl chloride in MeCN; the resulting dichloride may in turn be reduced to triphenylphosphine in
R = H, NO2
N Hal Hal = F, Cl, Br
R S
O
O
SchEME 16.23 Structure of a saccharin derived N-halosultam.

a high yield in an undivided cell using a platinum cathode and aluminum or zinc anodes, Equation
16.90 [357]. Alternatively, triphenylphosphine may be regenerated via conversion of the oxide to the
methylthiotriphenylphosphonium ion followed by reduction (see the following) [358]:
Ph Ph Cl Ph
(COCl)2 +2e–
Ph P O Ph P Ph P (16.90)
–2Cl–
Ph Ph Cl Ph

Phenyl diphenylphosphinite undergoes P–O reductive cleavage in fashion similar to that found
for halodiphenylphosphines [359] (see Section XIX.A).
B. OXIDaTIVE P–O CLEaVaGES

The electrochemical oxidation of enol phosphates, phosphites, and phosphinates is accompanied by
cleavage of the P–O bond [360]; the reaction proceeds essentially as shown in Equation 16.59 for
other esters.
XVII. PhOSPhORUS–SULfUR BONDS

A. REDUCTIVE P–S CLEaVaGES
Ethylthiotriphenylphosphonium ion is reductively cleaved in an irreversible 2F process to triphe-
nylphosphine and ethanethiolate [115]. The reaction has been put to use in the electrochemical
regeneration of triphenylphosphine from triphenylphosphine oxide, the Wittig reaction by-product.
First, the oxide is converted to the sulfide by reaction with P4S10. Methylation then leads to the
methylthiotriphenylphosphonium ion that is finally reduced in MeOH at a mercury cathode to
triphenylphosphine and methanethiolate, Equation 16.91 [358]:
P4S10 Me2SO4
Ph3P+ O– Ph3P+ S–
(16.91)
+2e–
Ph3P+ SMe Ph3P + MeS–

Diphenylarylsulfophosphamides, ArSO2PPh2, are more easily reduced than the correspond-
ing sulfonamides; the radical anions undergo P–S cleavage to the sulfinate anion and the diphe-
nylphosphinyl radical that under the conditions is further reduced to the diphenylphosphine anion,
Ph2P– [361]. An in situ oxygen migration leads to the final products, the arylthiolate and diphe-
nylphosphinate anion, Equation 16.92.
O Ph O Ph
+e–
Ar S P Ar S P ArSO2– + Ph2P
O Ph O Ph +e–
(16.92)
in situ
ArS– + Ph2P(O)O– ArSO2– + Ph2P–

Triphenylphosphine sulfide and similar compounds are reduced in DMF in two steps; first to the
radical anion in a reversible one-electron process [128] and then to the dianion that undergoes P–S
cleavage to triphenylphosphine and sulfide ion and C–P cleavage to the mercaptodiphenylphosphine
anion and the benzene anion that is further protonated (Scheme 16.24) [127].
Ethylthiodiphenylphosphin is reductively cleaved in a 2F process to the diphenylphosphine anion
and thioethanolate [362]. In the absence of a proton donor, the diphenylphosphin anion attacks the
starting material in a substitution reaction leading to tetraphenyldiphosphin.
+e–
Ph3P+ S– Ph3P S–
–e–
+e– Ph2P S– + Ph–
Ph3P S–
+e–
Ph3P + SH2–
SchEME 16.24 Reductive cleavage of triphenylphosphine sulfide.
XVIII. PhOSPhORUS–SELENiUM BONDS

A. REDUCTIVE P–Se CLEaVaGES
The polarographic reduction of triphenylphosphineselenide in DMF results, in contrast to the reduc-
tion of triphenylphosphinesulfide (see Section XVII.A), in cleavage of the P–Se bond in an irrevers-
ible 2F process, Equation 16.93 [127]:
+2e–
Ph3P+ Se– Ph3P + Se2– (16.93)

XIX. PhOSPhORUS–HALOGEN BONDS

A. REDUCTIVE P–Hal CLEaVaGES
The P–Hal bond in halodiphenylphosphines may be cleavaged reductively [359]. A mechanism that
involves intermediate diphenylphosphinyl anions was proposed to account for the formation of tet-
raphenyldiphosphine as the only product (Scheme 16.25).
The conversion of the Wittig by-product, triphenylphosphine oxide, to the dichloroderivative and
reduction of the latter to regenerate triphenylphosphine [357] has been mentioned in Section XVI.A.
XX. ARSENic–ARSENic BONDS

A. REDUCTIVE AS–AS CLEaVaGE
The polarographic reduction of organic compounds containing an As–As bond proceeds analo-
gously to the 2F reductive cleavage observed for diphosphines. Thus, reduction of 1,2-diphenyl-1,2-
diarsacyclopentane in DMF, for example, results in cleavage of the As–As bond in the five-membered
ring as shown in Equation 16.94 [355].
Ph Ph
Ph Ph
As As
+2e– (16.94)
As– As–

+e– +e–
Ph2PX Ph2PX – – Ph2P Ph2P–
–X
Ph2P– + Ph2PX Ph2P PPh2

–X–
SchEME 16.25 Reductive cleavage of halodiphenylphosphines.

H
OR
O O O
O O O
O
O
H H
O
O
O
SchEME 16.26 Examples of cyclic peroxides that undergo reductive O–O cleavage.
XXI. OxYGEN–OxYGEN BONDS

A. REDUCTIVE O–O CLEaVaGES
Organic compounds with an oxygen–oxygen single bond such as hydroperoxides [363], dialkyl
peroxides [364], the acetone peroxide dimer [365], peracids [366], peroxy esters [367], and diacyl
peroxides [367] may all be reduced electrochemically. The reaction that has analytical applications
includes cleavage of the O–O bond [368] and proceeds for simple hydroperoxides and dialkyl per-
oxides to the corresponding alcohols. The electron transfer process has been studied in detail for
the naturally occurring ascaridole [369] (Scheme 16.26, left) and for the antimalarial artemisinin
[370] (Scheme 16.26, middle), and it was found that the reductions followed a concerted dissociative
mechanism leading to the distonic radical anions. In contrast, for the G3-factor endoperoxide [371]
(Scheme 16.26, R = H) and the methyl ether (R = Me), a transition from a stepwise mechanism to
one with a more concerted character was observed. In the presence of a proximal acid group, con-
certed heavy-atom cleavage and proton and electron transfers may take place [372].
Indirect reduction of di-tert-butyl peroxide and tert-butyl peracetate by aromatic radical anions
in DMF generates t-butoxy radicals that abstract a hydrogen atom from DMF. The resulting
N,N-dimethylaminocarbonyl radical was observed to undergo coupling with the mediator [364].
XXII. OxYGEN–SULfUR BONDS

A. REDUCTIVE O–S CLEaVaGES
1. Alkoxysulfonium Ions
Ethoxysulfonium ions are reduced in MeCN to a mixture of the corresponding sulfide and sulfoxide
in an overall 1F process [220]. Spin trapping with α-phenyl-tert-butylnitrone implicated radical
intermediates, Equation 16.95; the sulfoxide arises from a subsequent reaction between EtO – and
the starting material:
Spin trap
OEt Spin adduct
+e– (16.95)
S+ R΄ S R˝ + EtO +e–
R΄ R˝
EtO–
2. Sulfonates
The direct or indirect reductive O–S cleavage of sulfonic acid esters to sulfinate ions and alco-
hols, Equation 16.96, has been put to use in protection–deprotection chemistry; tosylates
[132,332,333,373,374] and nosylates [375] (esters of 4-nitrobenzenesulfonic acid) have featured in
particular in this area of chemistry.
O
+2e–, +H+
H3C S OR H3C SO2– + ROH (16.96)
O
Experiments with the esters of l-menthol and l-borneol have demonstrated that the stereochemical
identity of the alcohols is preserved during the reduction [373]. It was found that the S–O cleavage
takes place at the radical anion stage with a rate constant in the range 104 –108 s−1 when the reac-
tion is carried out under nonaqueous conditions [333]. In the absence of a suitable proton donor, the
deprotection is hampered by the nucleophilic attack of the RO – anion on the tosylate with formation
of the ether, ROR, as the result, Equation 16.97:
Ar SO2 OR + RO– Ar SO3– + ROR (16.97)

This side reaction can be suppressed by addition of, for instance, acetic acid. In that case, aromatic
radical anions cannot be used as catalysts in an indirect process; however, Ni(acacen) is suitable
under those conditions. The difference in yield of deprotected alcohol from direct and indirect
reduction was insignificant [333]. The esters of benzenedisulfonic acids react similarly to give the
mixed sulfonic ester-sulfinic acid and the alcohol [339].
Nosylates are reduced in two steps; the first reduction results in the formation a rather stable radi-
cal anion at a potential characteristic of substituted nitrobenzenes [375]. In the second step (–1.2 to
–1.7 V vs. SCE), a dianion that cleaves rapidly to ROH and the arylsulfinate ion is formed.
Bis(tosyloxy)benzene derivatives may be selectively cleaved; a tosyl group ortho or para to an
electron-withdrawing group (e.g., an ester group) is cleaved preferentially to one in the meta posi-
tion, whereas in derivatives of anisol, the tosyl group meta to the methoxy group is preferentially
cleaved [376].
The reduction of alicyclic vinyl triflates in the presence of CO2 results first in cleavage of the
O–S bond in an indirect process; in a second step, the enolate ion reacts with CO2, resulting in the
formation of a β-keto acid in yields that are often higher than 70%, Equation 16.98 [377].
O SO2 CF3 O– O
CO2–
+CO2 – +CO2
(16.98)
–CO2, –CF3SO2–

3. Sulfinates
The polarographic reduction of methyl benzenesulfinate under aqueous conditions results in the forma-
tion of thiophenol and methanol in a 4F O-S cleavage process. Under aprotic conditions a 2F process
leads to the benzenesulfenate anion and methoxide ion [378]; it has been suggested that the benzene-
sulfenate ion is likely to undergo disproportionation to benzenesulfinate and thiophenolate ion.
4. Sulfenates
Methyl benzenesulfenate undergoes cleavage of the S–O bond generating thiophenol and methanol
in a 2F process when reduced electrochemically in aqueous buffer at pH 7 [379]; methyl 2-nitro-
benzenesulfenate reacts similarly when reduced in DMF [380]. A detailed CV study of the reduc-
tion of benzyl benzenesulfenate in DMF showed that the S–O cleavage in this case takes place in
a stepwise dissociative mechanism [159]. In contrast, the reduction of tert-butyl benzenesulfenate
involves cleavage of the C–O bond.
5. Sulfoxides
Simple aliphatic sulfoxides are not reduced electrochemically—one of the reasons why DMSO is
a popular solvent for electrochemistry. However, a catalytic hydrogen reduction wave is observed
during polarography of methyl phenyl sulfoxide in acidic solution [381]. When the reduction is car-
ried out in DMF or MeCN with phenol as the proton donor, conversion to methyl phenyl sulfide is
observed [382]. Old reports indicate that diphenylsulfoxide [383] and dibenzylsulfoxide [384] may
be reduced to the sulfide at a lead cathode in alcoholic sulfuric acid.
XXIII. SULfUR–SULfUR BONDS

A. REDUCTIVE S–S CLEaVaGES
The reductive cleavage of the sulfur–sulfur bond is a classic reaction in organic electrochemistry
and has been observed for di-, tri-, and tetrasulfides [385]. The interest has mainly been focused
on disulfides that are easily reduced to the corresponding mercaptans; for instance, a high yield of
thioglycolic acid [386] was obtained by reducing dithiodiglycolic acid in 2N sulfuric acid at a lead
cathode at a potential of −0.55 V vs. SCE. (This is one of the few examples of a controlled potential
electrolysis prior to the invention of the potentiostat.) Similarly, polarographic reduction of alicy-
clic disulfides gives the corresponding dithiols in reactions that involve adsorption at the mercury
electrode [387,388]. Related to these is the reduction of thiolsulfonates to the corresponding sulfinic
acids and thiols (Equation 16.99), R = alkyl or Ph [389]:
+2e– , +2H+

R SO2 SR R SO2H + RSH (16.99)
The reduction of aromatic disulfides follows the same pattern and results in the formation of thio-
phenols [390,391]. The details of both the direct and the indirect reduction of aromatic disulfides
have attracted considerable interest over the years [392–397]. From the results of a series of studies
of the reduction of para-substituted diphenyl disulfides carried out in DMF by CV and convolution
analysis, and indirectly by using electrogenerated radical anions as solution electron donors, it was
concluded that the reduction is dissociative leading to cleavage of the S–S bond in a stepwise fash-
ion [395–397]. For the disulfides carrying electron-donating substituents, the inner reorganization
energies were particularly high reflecting considerable stretching of the S–S bond upon electron
transfer. On the other hand, for electron-withdrawing substituents, the extent of delocalization of
the SOMO into the aryl system increases, resulting in a decrease of the reorganization energy for
the formation of the radical anions.
Reduction of disulfides in the presence of an alkylating or acylating agent gives the S-alkylated
or S-acylated products in good yields [398]. If oxygen is present, sulfinic acids may be formed [399].
B. OXIDaTIVE S–S CLEaVaGES

Diphenyldisulfide may be oxidized at a platinum anode in a mixture of glacial acetic acid and
concentrated hydrochloric acid to benzenesulfonic acid [400]. When dimethyl, diphenyl, dibenzyl,
and heterocyclic disulfides are oxidized in MeCN in the presence of an alkene, products of acet-
amidosulphenylation are observed. The reaction has been suggested to proceed as shown in Scheme
16.27 [401]. With cyclic alkenes, a high selectivity for the trans-addition is observed. With terminal
alkenes, the terminal sulfides are formed with high regioselectivity.
A similar reaction has been used in the electrosynthesis of 2,2-bis(halomethyl)penam derivatives
from the related disulfides, Equation 16.100 [402]. It is of interest to notice that a five-membered
ring is formed and not a six-membered. Other synthetic aspects of this reaction type have been
reviewed [302].
–2e–
RS SR 2΄RS+΄
R
S+ CH3CN
΄RS+΄ +
H2O
RS N C+ CH3 RS NHCOCH3
–H+
SchEME 16.27 Mechanism for the oxidation of disulfides in acetonitrile in the presence of an alkene.
H S R΄˝ H
R΄CONH R΄CONH
S S
anodic ox CH2X΄
MeOH, HX˝
(16.100)
N N CH2X˝
O CH2X΄ O
COOR˝ COOR˝
XXIV. SULfUR–HALOGEN BONDS

A. REDUCTIVE S–Hal CLEaVaGES
1. Sulfonylhalides
Sulfonylhalides are in general easy to reduce [328]. The reduction of sulfonyl chlorides has been
studied in particular and proceeds with cleavage of the S–Cl bond [403–405]. In the absence of a
strong proton donor, sulfinate ion is produced in a 2F process, Equation 16.101 [403]; under suf-
ficiently acidic conditions, the sulfinate ion is protonated and may be further reduced to the thiol in
a 6F process, Equation 16.102 [406]:
+2e–
Ar SO2Cl Ar SO2– + Cl– (16.101)
+6e–, +5H+
Ar SO2Cl Ar SH + Cl– + 2H2O (16.102)
When the reduction is carried out in MeCN or DMF in the presence of alkylating agents, mixtures
of sulfones and sulfides, resulting from alkylation of the sulfinate and thiolate anions, respectively,
may be obtained [406].
2. Sulfenylchlorides
Benzenesulfenyl chloride is reduced in MeCN in a “less than 1F” process to diphenyl disulfide
and chloride ions [407]. The mechanism suggested that leads to the disulfide and accounts for the
low amount of charge required includes reaction between an intermediate benzenethiolate ion and
the benzenesulfenyl chloride starting material producing the disulfide and the reaction between
benzenesulfenyl chloride and residual water leading to the thiosulfinate than undergo dispropor-
tionation to the disulfide and the thiosulfonate. The details of the electron transfer process have
been addressed in detail [408]. For the para-substituted compounds, a dissociative process involv-
ing strong interactions between the produced fragments (“sticky” dissociative electron transfer,
RSe–SeR + Hg Hg(RSe)2
– +
Hg(RSe)2 +2e , +2H 2 RSeH + Hg
SchEME 16.28 Reductive cleavage of diselenides at mercury electrodes.
see Chapter 14) takes place, whereas the electron transfer process for ortho-substituted compounds
is stepwise with through-space S⋯O interactions playing an important role in stabilizing both the
neutral molecules and the radical anions.
XXV. SELENiUM–SELENiUM AND TELLURiUM–TELLURiUM BONDS

A. REDUCTIVE Se–Se aND Te–Te CLEaVaGES
The reductive cleavage of the Se–Se bond and the Te–Te bond proceeds in a fashion analogous to
that of the S–S bond that is to the corresponding selenols and tellurols; however, during polaro-
graphic studies in aqueous solution [388,391,409–411], the participation of mercury in the reduction
process is even more important than for disulfides, illustrated in Scheme 16.28 for the reduction of a
diselenide in aqueous solution [388,391,409,411]. A more complex variant of this scheme describes
the polarographic reduction in aprotic solvents [410,412].
B. OXIDaTIVE Se–Se aND Te–Te CLEaVaGES

The oxidative cleavage of diselenides in MeCN takes place essentially as described for disulfides
by Scheme 16.27; thus oxidation of, for instance, dibenzyl diselenide in MeCN in the presence of
cyclohexene results in the formation of N-(2-(benzylselanyl)cyclohexyl)acetamide [413].
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17 Reductive Coupling
James H.P. Utley, R. Daniel Little, and Merete Folmer Nielsen
CONTENTS
I. Introduction ............................................................................................................................. 622
II. Homocoupling by Electrohydrodimerization (EHD) ............................................................. 622
A. Intermolecular Hydrodimerizations ................................................................................ 623
1. General Mechanistic Considerations ..................................................................... 623
2. Common Methods for Mechanistic Analysis......................................................... 624
3. Relationships between Experiments on an Analytical and on a Preparative Scale ...625
4. Stereochemistry ..................................................................................................... 625
5. Slightly Activated Double Bonds ........................................................................... 626
6. Nitriles �� 628
7. Esters�� 631
8. Amides and Oxazolidinones .................................................................................. 636
9. Carboxylic Acids .................................................................................................... 638
10. Miscellaneous Activating Groups .......................................................................... 638
11. Ketones ................................................................................................................... 638
12. Aldehydes ............................................................................................................... 643
B. Intramolecular Hydrodimerizations (Hydrocyclizations) ...............................................644
1. Intramolecular Coupling of Electrophores Linked through the β-Carbons .......... 645
2. Intramolecular Coupling of Electrophores Linked through the EWG Groups......646
3. Intramolecular Coupling of Electrophores Linked through the α-Carbons .......... 647
C. Multiply Activated Alkenes ............................................................................................648
1. α,β-Diactivated Alkenes.........................................................................................648
2. α,α-Diactivated Alkenes ........................................................................................ 652
D. Hydrodimerization of CO2 .............................................................................................. 654
III. Mixed Hydrocoupling of Activated Alkenes .......................................................................... 655
A. Intermolecular Mixed Hydrocouplings ........................................................................... 655
1. Couplings with Acrylonitrile ................................................................................. 656
2. Couplings with Alkyl Acrylate and Crotonate....................................................... 658
3. Other Intermolecular Mixed Hydrocouplings........................................................ 658
B. Intramolecular Mixed Hydrocouplings........................................................................... 659
IV. Reductive Coupling of Alkenes with Other Types of Substrates............................................660
A. Intermolecular Reductive Coupling of Alkenes with Other Types of Substrates ...........660
1. Coupling with CO2 .................................................................................................660
2. Coupling with Aldehydes and Ketones ..................................................................664
3. Coupling with Esters and Anhydrides ...................................................................668
4. Coupling with Organic Halides .............................................................................669
B. Intramolecular Coupling of Alkenes or Alkynes with Other Types of Substrates ......... 676
1. Coupling of Activated Alkenes with Aldehydes and Ketones ............................... 676
2. Coupling of Unactivated Alkenes with Aldehydes and Ketones ........................... 678
3. Coupling of Alkynes or Allenes with Aldehydes and Ketones ............................. 679
4. Coupling of Alkenes with Esters ........................................................................... 679
621
5. Coupling of Activated Alkenes with Organic Halides .......................................... 681

6. Coupling of Unactivated Alkenes with Organic Halides....................................... 682
7. Coupling of Alkynes with Organic Halides ..........................................................684
V. Reductive Couplings Involving Atoms in an Aromatic Ring ................................................. 685
A. Intermolecular Couplings................................................................................................ 685
1. Coupling between Aromatic Halides ..................................................................... 685
2. Dimerization of Aromatic Compounds Activated with Electron-Withdrawing
Substituents ............................................................................................................ 685
3. Coupling of N-Heteroaromatic Compounds........................................................... 690
B. Intramolecular Couplings ............................................................................................... 691
C. Coupling between Aromatic Rings and Other Reagents ................................................ 694
D. Reductive Dimerization of Positively Charged Aromatic Systems ................................ 695
1. N-Alkylpyridinium and Related Systems .............................................................. 695
2. Other Positively Charged Systems ......................................................................... 697
References ...................................................................................................................................... 698
I. INTRODUcTiON
Electroreductive coupling reactions constitute an important class of carbon–carbon-bond-forming
reactions involving a multitude of compound types as starting materials. Not all types of cou-
pling reactions are covered in this chapter, and in a number of cases more details can be found
in other chapters covering the electrochemistry of specific classes of compounds. In this chapter,
the focus is on reductive couplings involving alkenes and other carbon–carbon multiple bonds as
a substrate, either in dimerization reactions or in cross-coupling reactions with other compounds.
In Section V, carbon–carbon-bond-forming reactions initiated by reduction of aromatic systems
are discussed.
It is beyond the scope of this chapter to cover the industrial applications of electroreductive
coupling reactions. However, the industrial importance of electrohydrodimerizations has initiated
an impressive amount of work on this particular type of reductive coupling since the early finding
by Baizer that the use of tetraalkylammonium p-toluenesulfonates as supporting electrolyte greatly
improved the yield of adiponitrile in the electrochemical reduction of acrylonitrile in partially aque-
ous media [1]. Further reports from Baizer and coworkers at Monsanto in the 1960s demonstrated
the possibility of electroreductive coupling of a great variety of α,β-unsaturated carboxylic acid
derivatives (nitriles, esters, and amides) [2–4]. Applications to organic synthesis considered here are
mainly concerned with improvements in yields, regio- and stereoselectivity of reductive coupling
reactions, in a number of cases by application of transition metal catalysts and templating cations,
and on intramolecular reductive couplings.
Kinetic and mechanistic studies on reductive couplings are abundant, particularly those explor-
ing possible mechanisms of electrohydrodimerization and dimerization of aromatic systems. It has
not been possible in this chapter to use a common scale for reduction potentials because of the many
differences in solvent, supporting electrolytes, added acids, electrode material, etc. In some cases,
however, the relative values may be of interest in a mechanistic discussion and unless stated other-
wise potentials have been measured versus SCE.
II. HOMOcOUPLiNG BY ELEcTROhYDRODiMERizATiON (EHD)

Mainly because of the commercial success of the adiponitrile process, hydrodimerization of
alkenes activated by electron-withdrawing substituents (Equation 17.1) has been widely and thor-
oughly explored. Consequently, this section cannot be exhaustive. Concentration on typical reac-
tions and general conclusions may serve as guidelines for further work. Special emphasis will be
Reductive Coupling 623
put on the effect of reaction conditions on the mechanisms, product selectivity, and stereochemistry.
Section II.A.1 deals with the monoactivated alkenes, that is, structures of the type 1, where
R1 and R2 are H, alkyl or aryl; Section II.B.1 deals with intramolecular coupling reactions where
two identically activated alkenes are linked together within the same molecule. The reactions of
alkenes activated by two electron-withdrawing groups either in α,α- or in α,β-positions are treated
in Section II.C.1.
R1 EWG
R2 EWG 2e–, 2H+
2 R2 * (17.1)
R1 R1 *
1 EWG
R2
A. INTErMoLECULar HYDroDIMErIZaTIoNS
1. General Mechanistic Considerations
The reactions of monoactivated alkenes following one-electron reduction may in most cases be
rationalized according to Scheme 17.1.
Two major side reactions compete with the coupling reaction: protonation of the radical anion
followed by further reduction and protonation leading to the saturated dihydro product, and
polymerization induced by the basic dianion formed by coupling of two radical anions. Other, less
typical reaction pathways include reaction between a radical anion and a molecule of substrate
(Scheme 17.2), dimerization of two radicals formed by protonation of the initial radical anion
(Scheme 17.3), or, infrequently, cleavage of the radical anion followed by coupling. However, for
radical anions derived from monoactivated alkenes, the pathway in Scheme 17.2 has only been
unequivocally established as a major pathway in a few cases in which the final zero-electron prod-
uct is a cyclobutane, that is, a cycloaddition product. The term zero-electron product is used where
reactions are initiated by electron transfer and very little charge is transferred, for example, less
than 0.1 F.
The pathway in Scheme 17.3 relates mainly to alkenes activated by keto or aldehyde groups for
reduction in hydroxylic solvents. Under these conditions, radical anions derived from carbonyl com-
pounds are protonated at oxygen, and the resulting enolic radical, H1•, is more difficult to reduce
than the starting compound. Consequently, fast dimerization of the enol radicals may compete with
further reduction. For other substrate types, especially in aprotic solvents containing added acids,
R2 EWG 1– R2 EWG HB R2 EWG

– H
R1 H –1 R1 H –B– 1 H
– R
1H 1H 1H2
HB
–B– Hydrogenation
R2 R2 EWG R2 EWG
EWG e– R2 EWG
– 1– R1 – 1 R1 –
2 EWG n × 1
R1 R
1 R1 1– R1 – R1 –
R2 EWG R1
R2 EWG Polymerization
HB –B–
R2 H
R2 EWG R2 EWG
R1 – R1 HB R1 H
CHD EWG
R1 R1 – H –B– R1 H
(cyclic hydrodimer)
R2 EWG R2 EWG R2 EWG
LHD
(linear hydrodimer)
SchEME 17.1 Overview of reaction mechanisms open to reduction to radical anion.

–
R2 EWG R2 EWG
R1 1 R1
Cycloaddition
1 R1 – 1– R1
R2 EWG e– R2 EWG (catalytic)
R2 EWG R2 EWG
–
R1 1 R1 1– 1 R2 EWG R2 EWG
R1 – 1– R1 – Dimers as in
R1 –1 R1 – Scheme 17.1
R2 EWG R2 EWG
SchEME 17.2 "Zero electron," (<0.1 F), conversion of some monoactivated alkenes.
R2 EWG R2 EWG R2 EWGH R2 EWGH

e– HB H1 1
R LHD
R1 R1 –B– R1 H1 R1
1 1–
R2 EWGH
SchEME 17.3 Consequence of rapid protonation prior to dimerization.
proton transfer is to carbon (Scheme 17.1) and the resulting radical (1H•) is more easily reduced
than the substrate that leads to the dihydro product (1H2). The competing reactions in Scheme 17.1
are influenced by the nature of the substrate and the reaction conditions. In dry aprotic solvents,
polymerization is common on a preparative scale, whereas on voltammetric time scales reversible
dimerization or enhanced chemical stability of the radical anion may be observed. Addition of pro-
ton donors may prevent polymerization. However, hydrogenation of the double bond competes with
dimerization if the proton donor is sufficiently acidic. The common hydrodimerization pathway
(Scheme 17.1), leading to the linear hydrodimer (LHD), is not always followed. When the activating
group is a carboxylic acid derivative, including cyano, or a carbonyl group, intramolecular addition
leading to a cyclic hydrodimer (CHD) is often favored over the final protonation step.
The hydrodimers may be formed by more than one pathway (Schemes 17.1 through 17.3). The main
distinctions, much discussed in the literature, are (1) coupling between two species in the same redox
state (often referred to as an RR or RRC mechanism), that is, coupling between two species at the one-
electron reduction level as in Schemes 17.1 and 17.3; (2) coupling between two species in different redox
states, that is, coupling between a substrate molecule and its counterpart reduced to the one-electron
level (Scheme 17.2, referred to as an RS or RSC mechanism); and (3) coupling between a substrate
molecule and its counterpart reduced to the two-electron level (referred to as ISC mechanism).
The ISC mechanism is generally considered to be unlikely. Both RR and RS mechanism may
be further classified according to the sequence of microscopic steps (electron transfer, coupling,
protonation, and/or cyclization) and with reference to which of the steps is rate determining. For the
RS mechanism, the second electron transfer may take place by a reaction in solution (as indicated
in Scheme 17.2) or at the electrode if the coupling step is very fast.
2. Common Methods for Mechanistic Analysis

Distinction between different mechanistic pathways is not always straightforward (see Chapter 2).
Even minor changes in the experimental conditions may lead to changes in the sequence of reaction
steps and/or in the rate-determining step and several examples can be found in the literature where
different mechanistic conclusions have been drawn for the EHD reaction of a single substrate. Most
electroanalytical methods have been applied to the study of EHD reactions. It is beyond the scope
of this chapter to detail how different techniques are used and how the mechanistic and kinetic
information is extracted from the experimental data. In general, however, techniques that operate
on a time scale comparable to the half-life time of the electrogenerated intermediate can detect
the intermediate and are well suited for determination of rate constants. These methods include
cyclic voltammetry (CV), derivative cyclic voltammetry (DCV), double potential step chronoam-
perometry (DPSC), double potential step chronocoulometry (DPSCC), rotating ring disk electrodes
(RRDE), scanning electrochemical microscopy (SECM), and current-reversal chronopotentiom-
etry. The same is possible for spectroelectrochemical methods where the electrochemically formed
intermediate is detected by a spectroscopic method (ESR, UV, IR, etc.). The theoretical data nec-
essary for determination of rate constants, and to some extent to distinguish between different
EHD mechanisms, have been published for RRDE [5], current-reversal chronopotentiometry [6–9],
DPSC, DPSCC [10,11], and DCV [9]. Steady-state techniques where the time scale of the measure-
ment is long compared to the half-life of the intermediate generated at the electrode (polarography,
RDE, and LSV [linear sweep voltammetry]) are primarily used to obtain mechanistic rather than
kinetic information. Diagnostic criteria for different EHD mechanisms under steady-state condi-
tions were established in the 1970s [12]. More detailed description of the application of the different
methods can be found in Chapter 2.
3. Relationships between Experiments on an Analytical and on a Preparative Scale

EHD reactions have commonly been studied in polar aprotic solvents such as DMF,
N-methylpyrrolidone (NMP), DMSO, or MeCN with controlled addition of water or other weak
proton donors and in the presence of different types of cations. Experiments can be carried out in
scrupulously dried solvents on an electroanalytical scale (usually 1–10 mmol), but the stoichiom-
etry of the overall reaction (1) shows that formation of stable products requires the presence of a
proton source. Several preparative studies confirm that in the absence of water or metal cations, the
reduction process consumes less than 1 F, and unidentified polymeric products are formed instead
of dimers (see Scheme 17.1). In contrast, use of protic solvents usually leads to large amounts of the
hydrogenation product in a 2 F process and/or different product distributions.
The effect on the reaction mechanism of added proton donors, particularly water, has been much
debated. Study of the dimerization of a series of radical anions of α,β-unsaturated nitriles, esters,
and ketones under weakly acidic conditions (DMF or MeCN containing varying amounts of water)
led [13] to the conclusion that at low water concentration, the mechanism involved rate-determining
coupling of two radical anions. On an analytical scale, it is a common observation that the dimer-
ization process is accelerated upon addition of water, an effect that cannot be ascribed to initial
protonation of the radical anion or to protonation of the dimer dianion. The effect has been variously
described as solvation [14] or complexation [15] or hydrogen bonding [16], in each case between
the radical anion and one or more water molecules. The ensuing stabilization and dispersal of the
negative charge facilitates the dimerization step. Where dimerization is relatively slow, an effect of
added water on the formal reduction potential, Eo′, has been observed [14], which is consistent with
solvation/hydrogen-bonding interaction between water and the radical anion.
4. Stereochemistry
When R1 ≠ R 2 in 1, two new stereocenters are formed in the dimerization process (Equation
17.1), and stereoselectivity in the coupling step is likely to be important for applications to
organic synthesis. Much effort has been aimed at controlling the ratio of meso: (+/−) hydrodimers
and especially of introducing enantioselectivity in the (+/−) product, using chiral auxiliaries.
Stereoselectivity of the coupling step seems to be much higher, and in favor of the (±) isomer,
when the reduction is carried out in aprotic solvents (containing residual or added water) as
opposed to protic solvents. Templating of two radical anions by one or more water molecules has
been suggested as an explanation of the high stereoselectivity in favor of the (±) isomer in the
dimerization in DMF of alkyl cinnamate radical anions [16] (see Section II.A.7). Similar prefer-
ence for the (±) isomer has been observed for other EHD reactions in aprotic solvents [17–20], and
an analogous templating effect can be invoked as explanation of the enhanced stereoselectivity in
CO2Me
Me
5 6
4 Me3C Me
2e Dimerization Me
2 Me3C CO2Me CO2Me Me
1 2H+ Me
3 CMe3
2 Me 3
2 MeO2C CO2Me
R1 OR
RL H O–
–O H
RS R1 Ar
RS O
R2 Ar
O– H
RL
O–
R2 H
OR
4 Quinonemethide radical anions 5 Cinnamate esters in DMF–H2O
SchEME 17.4 Kinetic control and stereoselectivity.
the presence of metal cations [20–22]. Similar selectivity is observed when SmI2 in HMPA/THF
[23,24] or alkali amalgams [25] are used as chemical reductants.
The stereochemistry of the coupling of π-radical anions (radical behavior) and of addition to
alkenes or carbonyl functions (generally nucleophilic behavior) is conveniently viewed as being
under stereoelectronic control. In practice, this means that coupling of delocalized radical anions
is favored when orthogonal approach is unhindered. Thus, for dimerization of the alkyl cinnamate
radical anions, the templating involving hydrogen bonding to the two ester groups favors (±) β,β′-
coupling over the meso coupling that would involve eclipsing of the two phenyl groups. The example
in Scheme 17.4 also nicely illustrates stereoelectronic control in the coupling of radical anions [26].
The conformationally rigid 4-t-butylcycohexene-1-methoxycarbonyl 2, in which the double bond
is activated by the ester group, is reduced on a preparative scale to give the strained hydrodimer
3 as the sole product. The stereochemistry is dictated by the necessary orthogonal coupling of the
radical anions. Two further examples are 4 and 5 (see Sections II.A.7 and II.A.12). Intramolecular
cyclizations are discussed in Sections II.B, III.B and IV.B. In these cases, Baldwin’s rules usually
apply [27,28].
5. Slightly Activated Double Bonds

Hydrodimerization of slightly activated double bonds is exemplified by reduction of stilbene
in DMF (Bu4NI) [29], which gives a modest yield (≤30%) of the hydrodimer, 1,2,3,4-tetrap-
henylbutane, together with the 2 F product, bibenzyl. Similarly, 9-benzylidenefluorene, 6, and
2-phenylbutadiene give hydrodimers upon reduction in DMF/water (n-BuMe3NOTs) [30], 6 giving
66% of the dimer, whereas the major product formed from 2-phenylbutadiene was the 2 F hydro-
genation product.
Ph Ar
Ph Ar
10
Ar Ar S S a: Ar = 2-pyridinyl
7 8 b: Ar = 4-pyridinyl
9 c: Ar = 3-pyridinyl
6
The competition between hydrogenation and dimerization has been examined for
α-arylstyrenes, 7 [31]. Addition of an excess (30–100 times with respect to substrate) of D2O gave
TABLE 17.1
Effect of Substrate Concentration on the Competition between Dimerization
and Hydrogenation in the Reduction of α-Arylstyrene, 7a
Ar Epred /V nb Yield of Dimerb (%) nc Yield of Dimerc (%)
2-Naphthyl −2.30 1.37 66 1.32 79
2-Pyridinyl −2.27 0.93 >99 1.01 >99
Phenyl −2.52 1.97 0 1.66 43
2-Thiophenyl −2.33 1.63 39 1.51 48
2-Furanyl −2.48 1.77 29 1.60 39
a DMF, Et4NBF4, div. cell, Hg-cath., CPE: Ew = Epred + 0.1 V. Overall yield >95%. From [31].
b C = 8 mM.
c C = 40 mM.
rise to increasing values of n and enhanced yields of the hydrogenation product as a result of an
enhancement of the rate of protonation of the radical anions [31]. From the limited amount of
data in Table 17.1, higher substrate concentrations tend to give smaller coulometric n-values and
higher yields of the dimer, and it appears that the more easily the substrate is reduced the more
favored is dimerization.
Allylbenzene and ring-substituted derivatives, 8, show no reduction waves before the background
in DMF [32]. However, reduction at constant current gives an electrogenerated base (EGB), prob-
ably OH−, which catalyzes isomerization to the conjugated alkenes, β-methylstyrenes, which are
reducible at accessible potentials. Isomerization was complete after the passage of 0.5 F, and further
reduction resulted in mixtures of the hydrodimer of the β-methylstyrene and the corresponding
hydrogenation product (Table 17.2). The dimerization reaction showed a high degree of stereoselec-
tivity, the (±) isomer being the major isomer [32].
TABLE 17.2
Effect of Substrate Structure on the Competition between Dimerization and
Hydrogenation in the Reduction of Ring-Substituted Allylbenzenes, 8a
Ar Yield of Dimer (%) (±) Isomer (%) Yield of Hydrogenation Product (%)
Phenyl b 64 84 14
2-Tolylb 61 87 13
3-Tolylc 65 88 6
4-Tolylb 6 86 55
4-t-Butylphenylb 9 90 57
2-Anisyld 41 87 22
4-Anisyle 3 f 57
4-Cyanophenylb 54 f f
a DMF, Bu4NClO4, div. cell, Pt-cath., CCE. From [32].

b 2 F passed.
c 2.5 F.
d 4 F.
e 3 F.
f Not determined.
Compounds of the type 9 (4-ylidene-substituted cyclopentadithiophenes) form radical anions

that in the presence of water dimerize following the RR mechanism (as determined by LSV)
with k dim ≈ 105 M−1 s−1, yielding a stereoisomeric mixture of hydrodimers. In the absence of
water, the dimer dianions are relatively stable and may on a voltammetric time scale be reoxi-
dized at a potential 0.7–0.8 V anodic relative to the reduction potential of 9 [33]. Interestingly,
the polymers (linked through the thiophene rings) formed by oxidation of 9 may also undergo
reductive coupling, thereby forming cross-linked polymer chains. Oxidative polymerization of
the hydrodimers, formed by reduction of 9 in the presence of water, results in a polymer with
the same properties as the one obtained by reduction of a pre-formed polymer in the presence
of water [33].
Reduction of 2-vinylpyridine, 10a, in H 2O (Et4NOTs) and of 4-vinylpyridine, 10b, in DMF/
H2O (MeEt3NOTs) give good yields (69% and 82%, respectively) of the LHDs [34]. Later, experi-
ments in DMF have shown that electrolysis of 10 at a potential corresponding to the foot of
the reduction wave gives good yields of the 0 F product trans-1,2-dipyridinylcyclobutane. This
results from a radical anion catalyzed cycloaddition reaction [35] (see Scheme 17.2), that is, under
conditions where a high ratio of substrate to radical anion is maintained. The change in product
with the change in working potential indicates that the rate constant for reaction between radi-
cal anion and substrate is smaller but comparable to the rate constant for reaction between two
radical anions. It was shown [35] that the cyclobutane was reduced to the LHD compound at
the higher potentials, implying that the cyclobutane might be the common reactive intermediate
rapidly reduced at the higher potentials. The mechanistic details of the catalyzed cycloaddition
reaction are not known. The 0 F reaction of 10 is similar to the 0 F reaction of aryl vinyl sulfones
(see [36]).
6. Nitriles
Et
CN CN Et + +
CN a: R1 = H, R2 = Me Bu N
N Bu
b: R1 = CH2CH2CN, R2 = H Bu
R2 R1 Ph
Bu
c: R1 = Me, R2 = H
11 12 13 14
The industrially important hydrodimerization of acrylonitrile, 11, to the LHD, adiponitrile, is

carried out in water with high chemical yields despite the fact that aqueous conditions normally
favor hydrogenation of the double bond. The process was developed on the basis of the finding
[1] that when high concentration of 11 (>10%) was electrolyzed in aqueous solution containing
high concentrations of Et4NOTs (>0.5 M) as supporting electrolyte, dimerization was favored
over hydrogenation. Since then much effort has gone into the investigation of the effect of sur-
factants on the product distribution and the reaction mechanism for simple EHDs, especially that
of acrylonitrile, 11 [37–52]. The main effect of the surfactants seems to be the displacement of
water molecules from the electrode surface. The adsorption of such organic additives to electrode
surfaces is dependent on the electrode material, the potential, and the nature of other ions in the
solution [40,45] and can be probed by differential capacity measurements. Simple monoactivated
alkenes such as 11 are so difficult to reduce (<−1.8 V) that anionic, neutral, and some cationic
surfactants are desorbed at the required working potential. However, cationic surfactants such as
dodecyltrimethylammonium and methyltrioctylammonium ions are, like Et4N+, adsorbed at mer-
cury, cadmium, and glassy carbon electrodes in the potential range where simple activated alkenes
are reduced. With 11 present in solution, the effect of surfactants has been observed as a splitting
of the two-electron polarographic reduction wave into two one-electron waves when the concen-
tration of 11 was higher than 0.1 M [40]. Electrolysis at the potential of the first wave (−1.78 V)
was reported to give more than 98% yield of the LHD [40]. (The yield has been questioned [45]
since it may have included hydrotrimers; nevertheless, there was little hydrogenation.) In addition
to the displacement of water from the electrode surface, some surfactants have been suggested to
promote the co-adsorption of 11 [40,45–46].
Preparative scale reduction of 11 in aprotic solvents mainly gives oligomers/polymers. The
radical anion reacts rapidly and only few mechanistic studies have been reported. In DMF solu-
tion, the mechanism was suggested to be RS on the basis of LSV measurements at low scan rates
[45]. Scanning electrochemical microscopy (SECM) has also been used to study the EHD of 11
in DMF [53]. Low concentration (1–2 mM) of 11 in dry solvent was used in order to minimize
polymerization and hydrogenation, respectively. The results obtained were in accord with an RR
mechanism (although the RS mechanism was not ruled out). Assuming that the dimerization
proceeds by rate-determining coupling of two radical anions, a value of kdim = (6 ± 3)⋅107 M−1 s−1
was calculated.
In liquid NH3 (T = −43°C), reduction of 11 also leads to polymerization (n = 0.05) unless a proton
donor such as i-PrOH is added (n = 0.96). Stronger proton donors such as AcOH give n = 2 corre-
sponding to hydrogenation [54].
The conditions for operation of the commercial process differ greatly from those studied by elec-
troanalytical methods at millimolar concentrations. Conditions appear to have been optimized by
empirical variation of electrode material (lead or cadmium cathodes are favored with steel anodes),
flow rate (1–2 m3 s−1), current density (ca. 0.25 A cm−2), temperature (ca. 323 K), and supporting
electrolyte (14, hexamethylene-bis(ethyldibutylammonium), QAS2+). The electrodes corrode and
sequestering agents such as ethylenediamine tetraacetic acid (EDTA) are added to the electrolyte,
intended to minimize the deposition of metal cations, which would compete with reduction of acry-
lonitrile. Thus, it is clear that the mechanistic studies described earlier relate to conditions far from
those of the adiponitrile process.
Meanwhile, back on Earth, many of these questions have been addressed, and partly answered,
in a microelectrode study [55] of the cathode reactions that compete with reduction of acrylonitrile.
Significantly the study was sponsored by BASF and one of the authors (D.W. Sopher) actually
managed BASF’s UK adiponitrile plant. The microelectrodes used were ideally lead (Pb or Cd
are the preferred cathodes for the large-scale process), although they corroded easily and in many
experiments were substituted with carbon fiber. For voltammetric experiments in an undivided
two-electrode cell, the mass transfer coefficient is close to that of a parallel-plate reactor with an
electrolyte flow rate of 1 m3 s−1, that is, similar to the conditions used in the large-scale process.
A major conclusion is that not all of the predicted competing cathodic reactions occur. Crucially,
the deposition of iron and lead cations is strongly inhibited by the presence of the major reactant
(acrylonitrile) and the supporting electrolyte cation 14, and metal deposition is not responsible for
the roughly 3% of wasted current efficiency.
Electrolysis of other simple α,β-unsaturated nitriles, 12, in water–DMF mixtures containing
large amounts of Et4NOTs give LHDs in varying yields [2,56,57]. Electrolysis of crotonitrile,
12a, under these conditions was reported to give the LHD (55%) in a 1:1 ratio of (±) and meso
forms [57].
Cinnamonitrile, 13, and substituted analogs are easier to reduce than the simple nitriles and form
less reactive radical anions. The mechanism and kinetics of the EHD of 13 has therefore been much
studied, although results are sensitive to water concentrations. In DMF n ≈ 1, and RRDE measure-
ments were in agreement with the RR mechanism at substrate concentrations <8 mM [58]. The
rate constant for the rate-determining dimerization step (RR mechanism) has been determined by
several methods in DMF (Table 17.3). In liquid ammonia (T = −43°C), dimerization is considerably
slower (Table 17.3) and, significantly, even in the presence of i-PrOH, the coulometric n-value was
small (0.05–0.27), indicating considerable polymerization [54].
Reduction of α-phenylcinnamonitrile gives both LCD and CHD products (Equation 17.2) [59].
The LHD was assigned (NMR) to result from (±) coupling, and the CHD from meso coupling (on
the basis of X-ray crystallography these findings have been challenged [60]). In DMF (Et4NBF4)
containing no added water, only the CHD (55%) is formed by reduction of β-methylcinnamonitrile
TABLE 17.3
Selected Rate Constants for Dimerization of Monoactivated Alkenes
Substrate Conditions Method kdim(RR)/M−1 s−1 References
E-Ph-CH=CH–CN (13) DMF, Bu4NI, room temp. a RRDE (8.8 ± 0.4)⋅102 [58]
13 DMF, Bu4NI, 23°C ESR (2.1 ± 0.5)⋅103 [72]
13 DMF, Bu4NI, room temp. DPSC/DPSCC (8.77 ± 0.21)⋅102 [73]
13 DMF, Bu4NI, room temp. CV 7.9⋅102 [58]
13 NH3, MeBu3NI, 2 equiv i-PrOH, −43°Cb CV 5.7 [54]
E-Ph-CH=CH–COOR (15)
R = t-Bu DMF, 0.28 M H2O, Et4NBr, 22°C DCV (4.1 ± 0.1)⋅102 [16]
Eo′ = −1.833 V
R = menthyl DMF, 0.28 M H2O, Et4NBr, 22°C DCV (5.4 ± 0.1)⋅102 [16]
Eo′ = −1.794 V
R = bornyl DMF, 0.28 M H2O, Et4NBr, 22°C DCV (5.6 ± 0.2)⋅102 [16]
Eo′ = −1.794 V
R = Et (15a) DMF, 0.28 M H2O, Et4NBr, 22°C DCV (5.4 ± 0.7)⋅102 [16]
Eo′ = −1.789 V
R = Me (15b) DMF, 0.28 M H2O, Et4NBr, 22°C DCV (7.8 ± 0.7)⋅102 [16]
Eo′ = −1.778 V
R = N-butylephedrine DMF, 0.28 M H2O, Et4NBr, 22°C DCV (5.8 ± 0.8)⋅102 [16]
Eo′ = −1.767 V
R = N-tosylephedrine DMF, 0.28 M H2O, Et4NBr, 22°C DCV (1.6 ± 0.2)⋅103 [16]
Eo′ = −1.708 V
R = 4-methoxyphenyl DMF, 0.28 M H2O, Et4NBr, 22°C DCV (6.1 ± 0.6)⋅103 [16]
Eo′ = −1.654 V
R = 4-methoxyphenyl MeOH, Et4NBr, 22°C LSV 3.9⋅105 [67]
Eo′ = −1.547 V
R = Ph DMF, 0.28 M H2O, Et4NBr, 22°C DCV (8.1 ± 0.4)⋅103 [16]
Eo′ = −1.631 V
R = Ph Eo′ = −1.524 V MeOH, Et4NBr, 22°C LSV 7.3⋅105 [67]
R = 4-cyanophenyl DMF, 0.28 M H2O, Et4NBr, 22°C DCV (5.7 ± 0.4)⋅103 [16]
Eo′ = −1.521 V
R = 4-cyanophenyl MeOH, Et4NBr, 22°C LSV 2.0⋅106 [67]
Eo′ = −1.438 V
R = Et (15a) DMSO, Bu4NI RRDE (2.4⋅102)d [64]
15a DMSO, Et4NI RRDE (4.2⋅102)d [64]
15a DMSO, Me4NBF4 RRDE (5.6⋅102)d [64]
15a DMSO, KNO3 RRDE (4.7⋅103)d [64]
15a DMF, Bu4NI, room temp. DPSC/DPSCC 1.4⋅102 [73]
E-Ph-CH=(Me)NO2 (32b) DMF, Bu4NI, room temp.c RRDE 1.7⋅104 [74]
4-methylcoumarine (20b) DMF, Et4NBr, room temp. DCV 1.5⋅105 [75]
Eo′ = −1.813 V
20b MeOH, Et4NBr, room temp. LSV 1.7⋅107 [75]
Eo′ = −1.625 V
methyl 4-t-butylcyclohex- DMF, Et4NBr, 27°C DCV (9.7 ± 0.4) ⋅103 [75]
1-enecarboxylate (2)
a n = 0.96.
b n = 0.27.
c n = 0.98.
d The observed rate constant may be interpreted as arising from three parallel reactions, according to which species are
coupling: 2A−•, A−• + A−•/M+, or 2A−•/M+.
(together with 15% of the hydrogenated monomer) [61]. The CHD was a mixture (13:1) of two ste-
reoisomers resulting from (±) and meso coupling, respectively.
NH2
Ph Ph NC
Ph
CN CN + Ph
DMF/H2O,Et4NOTs NC Total: 67% yield (17.2)
Ph Ph Hg cathode Ph Ph
Ph Ph
(±) 1 : 3 (meso)

In most of these cases, the choice of aprotic solvent is important. In particular, the use of MeCN
(which is more acidic than DMF or DMSO) may initiate side reactions, possibly involving the basic
cyanomethyl anion, rendering electroreduction of little synthetic value [61].
7. Esters
Esters of cinnamic acid and ring substituted derivatives, 15, undergo clean preparative scale
cathodic reduction and have been much studied [2,62]. In particular, they have been model com-
pounds for early kinetic studies [10–11,63] and for examination of effects of medium [64], cations
[64], proton donors [65], and complexing agents [66] on products, mechanisms, or kinetics. Series
of cinnamates have been the subject of systematic stereochemical, kinetic, and mechanistic stud-
ies [16,60–67].
Electrolyses of substrates of the cinnamic acid ester family (Table 17.4) in anhydrous MeCN
were shown to result in formation of 7–60% of the CHD (Equation 17.3), corresponding exclu-
sively to the (±) coupling as determined from the stereochemistry of the cyclopentanone formed by
hydrolytic decarboxylation [62]. The stereochemistry was later verified by X-ray crystallography
[60]. The stereoselectivity in the coupling step was originally rationalized in terms of orientation of
the substrate molecules at the electrode surface [62]. However, later kinetic studies have shown that
dimerization of the radical anions is fairly slow (Table 17.3) and takes place in the diffusion layer at
a distance from the electrode.
COOR Ar
MeCN or DMF a: Ar = Ph, R = Et
O
Ar
R4NX, 1 F b: Ar = Ph, R = Me (17.3)
15 Ar
COOR
Higher yields of the CHD were obtained in another series of the cinnamic acid esters (Table 17.4)
upon reduction in DMF [68,69], and similar yields were obtained from substrates with a Me, Et, or
Ph substituent at the β-carbon in 15 [68].
For a series of cinnamic acid ester formed from chiral alcohols, reduction in DMF gave the CHD
from 0% de for the (−)-menthyl ester up to >95% de for the (−)-endo-bornyl ester [60] (Table 17.4).
This last result has been questioned [70], and one explanation for the higher value is that during
work-up preferential crystallization favoring one of the diastereoisomers skewed the stereoselectivity.
The menthyl and the bornyl cinnamates have virtually identical values of Eo′ and of the second-
order rate constant for dimerization [16] (Table 17.3).
Under identical experimental conditions (DMF, 0.28 M H2O, 0.1 M Et4NBr), a thorough study
of a large series of cinnamic acid esters led to the conclusion that the EHD reaction followed the
RR mechanism with rate-determining dimerization [16]. The rate constants for dimerization were
shown to correlate closely with the Eo′-values for the reduction process; the more easily the substrate
is reduced, the faster the dimerization (Table 17.3) [16]. The phenomenon can for this closely related
series of compounds be rationalized in terms of a systematic change of the unpaired electron density
at the position of dimerization [71].
TABLE 17.4
Effect of Substituents and Experimental Conditions on the Yields of LHD and CHD
from Cinnamates, 15
Ar R Conditionsa CHD LHD References
Ph Et A 52% (±) — [62]
Ph CH2C≡CPh A 8% (±) — [62]
Ph CH2CH=CHPh A 13% (±) — [62]
3,4-Dimethoxyphenyl Et A 52% (±) — [62]
3,4-Dimethoxyphenyl t-Bu A 7% (±) — [62]
3,4-(OCH2O)-phenyl Me A 60% (±) — [62]
3,5-Dimethoxyphenyl Et A 28% (±) — [62]
Ph Me B 76%b Trace [68,69]
2-Pyridinyl Me B 62%b — [68,69]
4-Anisyl Me B 52%b — [68,69]
4-Tolyl Me B 64%b — [68,69]
4-Chlorophenyl Me B 75%b — [68,69]
Ph Me C 74%b Trace [69]
Ph Me D 23%b 30%b [69]
Ph Me E 9%b 45%b [69]
Ph Me F Trace 75%b [69]
Ph (−)-menthyl G 92% (±) (de 0%) — [60]
Ph (+)-CH(CH3)COOEt H 86% (±) (de 33%) — [60]
Ph (−)-CH(Ph)COOMe H 99% (±) (de 45%) — [60]
Ph (−)-CH(Ph)COOiPr H 85% (±) (de 40%) — [60]
Ph (+)-N-methylephedrinyl H 69% (±) (de 36%) — [60]
Ph (+)-N-propionylephedrinyl H 95% (±)c — [60]
Ph (+)-N-tosylephedrinyl G 94% (±) (de 35%) — [60]
Ph (−)-endo-bornyl H 98% (±) (de > 95%)d — [60]
Ph Ph H 85%e (±):meso = 5 [16]
a A: MeCN, Et4NBr, div. cell, CPE, Hg-cath.

B: DMF, Et4NOTs, div. cell, CCE (4 F), Cu-cath., 10°C–15°C.
C: MeCN, Et4NOTs, div. cell, CCE (4 F), Cu-cath., 10°C–15°C.
D: DMSO, Et4NOTs, div. cell, CCE (4 F), Cu-cath., 10°C–15°C.
E: i-PrOH, Et4NOTs, div. cell, CCE (4 F), Cu-cath., 10°C–15°C.
F: MeOH, Et4NOTs, div. cell, CCE (4 F), Cu-cath., 10°C–15°C.
G: DMF, LiClO4, div. cell, CPE, Hg-cath.
H: DMF, Et4NBr, div. cell, CPE, Hg-cath.
b Stereochemistry not reported.
c The de could not be determined.
d This result has been challenged [70].
e Yield of the decarboxylated product, 3,4-cyclopentanone.
Electrolysis of aryl cinnamates in DMF gives lower yields of the CHD product, mainly as
3,4-diarylcyclopentanone, than is found for the alkyl cinnamates [16]. Furthermore, coupling is no
longer exclusive to the (±)-isomer and there is evidence of base-catalyzed hydrolysis (Table 17.4).
Examination of the reduction of 15b in a range of solvents [69] showed a significant change in
distribution of the dimer on the CHD and the LHD as the proton donor ability of the solvent was
changed (Table 17.4). The more protic the solvent, the higher the yield of the LHD. The effect of
even more protic conditions on the product distribution was examined for 15b in MeOH/DMF
(1:9) containing different amounts of AcOH. Electrolysis at constant current gave mixtures of the
hydrogenation product, the LHD ((±) and meso) and the CHD (±). The yields of hydrogenation prod-
uct increased (from 20 to 60%) while the total yield of dimers decreased with increasing amounts of
AcOH. Particularly, the yield of the CHD decreased, from 55 to <1%. However, the relative amounts
of dimers arising from (±)-coupling and from meso-coupling (ratio 5:1) were fairly independent of
*
CAcOH , current density, and mass transport efficiency (rotating cathode) [76].
In DMF, β-cyclodextrin and 15a form a 1:1 complex with the aromatic ring of 15a included in
the hydrophobic cavity of the β-cyclodextrin. Electrolysis under these conditions results in a product
distribution close to that obtained in DMF/MeOH mixtures: 71% 2F product, 19% LHD, and only
1% CHD [66], that is, the hydroxy groups at the rim of the cyclodextrin function as proton donor.
Reduction of 15a in aqueous H2SO4 gave the LHD with (±):meso ≈ 1 accompanied by forma-
tion of only traces of the hydrogenation product [57]. Most—if not all—of the preparative results
presented earlier for reduction of 15 can be rationalized within the RR mechanism when effects of
hydrogen-bonding and proton transfer are taken into account. Under conditions with very low proton
donor concentrations, DPSCC measurements on 15a,b in DMF indicate that the initial dimerization
step is reversible with a large equilibrium constant, and the rate-determining step is protonation
(or cyclization) of the dimer dianion [10,11]. Assuming this mechanism, the equilibrium constants
for the dimerization were determined: Kdim = 109 M−1 for 15a and Kdim = 53.1 M−1 for 15b at 25°C,
while the pseudo-first-order rate constants for the rate-determining protonation of the dimer dian-
ion at 25°C were 3.7 s−1 for 15a and 9.2 s−1 for 15b [11]. The overall energy of activation was also
determined for the reaction: 5.9 kcal/mol for 15a and 5.8 kcal/mol for 15b. Other measurements
by DCV under strictly anhydrous conditions for 15b in MeCN gave results that were interpreted as
a change to an RS mechanism with rate-determining electron transfer to the dimer radical anion
from 15b− • [63]. However, another possible interpretation of the data is that the RR dimerization
reaction is reversible as described earlier due to the absence of proton donors necessary to drive the
dimerization toward product and/or that the dimer dianion initiates a polymerization reaction (as
observed on a preparative scale) by a partially rate-determining addition to a molecule of substrate.
The overall rate of reaction for 15− • increases with increasing water content in DMF [16] and in
MeCN [63]. Above a certain (low) level, the accelerating effect of increasing amounts of water can-
not be ascribed to a shift in the rate-determining step but rather to stabilization of the radical anions
by hydrogen-bonding to the carbonyl oxygen, thereby facilitating the coupling of two negatively
charged species.
A similar accelerating effect of small cations has been observed. In DMSO, a clear correla-
tion between the radius of the supporting electrolyte cation and the magnitude of the observed
second-order rate constant was found for dimerization of 15a− •; the smaller the cation, the higher
the rate (Table 17.3) [64]. The data were interpreted as a result of three parallel dimerization reac-
tions: dimerization of two “free” radical anions, with a second-order rate constant ki, coupling of a
free radical anion with an ion-paired radical anion, kii, and dimerization of two ion-paired radical
anions, kiii, the rate constants increasing in the order ki < kii < kiii. Using Bu4N+ as supporting elec-
trolyte cation, a linear correlation between log(kobs/M−1 s−1) and the Gutmann donicity number (DN)
was observed for a range of solvents; the smaller the DN, the faster the reaction, indicating that the
less efficient the cation (even Bu4N+) is solvated, the larger the equilibrium constant for ion-pair
formation with 15a− • and, consequently, the larger the observed rate constant for dimerization [64].
From the data in Table 17.4, it is clear that the major product obtained by reduction of the cin-
namate esters 15 in aprotic solvents containing residual water or (small) amounts of added water is
the CHD resulting from initial (±)-coupling. This stereoselectivity has been rationalized as arising
by templating of two radical anions by one or more water molecules via hydrogen bonding to the
carbonyl oxygens [16] (see Section II.A.4). The smaller (±):meso ratio observed for reduction of
15b in DMF/MeOH (9:1) [76] compared to that in DMF/0.28 M H2O is likely to be caused by less
efficient templating under the former conditions.
Within a series of cinnamates, the strength of the water templating is expected to depend on
the basicity of the radical anions. One way to characterize the basicity of the radical anions is
to measure the rates of protonation by a common proton donor. For the series of cinnamates,
the rate of protonation by phenol in DMF has been measured [71] and was found to change
systematically. The more easily the substrate is reduced, the lower is the basicity of the radical
anion [71], that is, the opposite trend of the one found for the dimerization rate constants [16].
The change in basicity may then explain the reduced stereoselectivity of the CHD coupling
product from the aryl esters (which are more easily reduced than alkyl esters). All the aryl
esters form mixtures of the (±) and the meso form of the CHD, and the (±):meso ratio changes
from 5 (phenyl ester) to 2 (4-cyanophenyl ester); the 4-cyanophenyl ester is more easily reduced
than the phenyl ester [16].
The change in product distribution upon addition of increasing amounts of AcOH to DMF/
MeOH during the reduction of 15b can be understood as a competition between initial dimer-
ization of two hydrogen-bonded (by MeOH) radical anions and initial protonation of the radical
anion. Like PhOH in DMF [71], AcOH in DMF/MeOH seems to protonate at carbon, which
leads to further reduction and formation of the hydrogenation product. Because the (±):meso
ratio of the dimers was constant and independent of the amount of acid present, the conclu-
sion was [76] that the dimerization followed the RR mechanism at all acid concentrations. A
shift from coupling of two radical anions at low acid concentrations to coupling of two neutral
radicals formed by protonation at high acid concentrations would be expected to show up as a
change in the ratio [76].
In pure MeOH, trans-esterification of the cinnamates takes place under preparative conditions
except for 15b. However, electroanalytical experiments and coulometric experiments taken only to
partial conversion could be carried out for a series of cinnamates [67]. The change from an aprotic
to a hydroxylic solvent reveals distinct differences that may all be explained by the hydrogen-bond
donor and proton donor ability of the solvent: (1) the esters are more easily reduced due to specific
solvation by hydrogen bonding, (2) the rate of reaction of the radical anions is 2–3 orders of magni-
tude higher than in DMF, and (3) the most basic radical anions (alkyl cinnamates) undergo proton-
ation at the carbonyl oxygen in the rate-determining step, whereas the least basic (aryl cinnamates)
dimerize on a voltammetric time scale [67]. The neutral radicals formed by protonation at oxygen
either dimerize stereo-unselectively or tautomerize to the radical with the proton at carbon, which,
in contrast to the radical formed by protonation at oxygen, is reduced more easily than the substrate.
For 15b, this results in a mixture of the hydrogenation product and the (±) and meso LHD in a 1:1
ratio on a preparative scale [67].
The stereochemically unselective formation of the LHD formed upon reduction of 15a in aque-
ous H 2SO4 [57] can similarly be explained by dimerization of two neutral radicals, in this case
formed directly in the reduction step since pre-protonation (at oxygen) is expected.
a: R = Me, R1 = R2 = R3 = H
R3 COOR
b: R = Et, R1 = H, R2 = R3 = Me
R2 R1 c: R = Et, R1 = R3 = H, R2 = Me
16
d: R = Et, R1 = R2 = R3 = H
e: R = Et, R1 = Me, R2 = R3 = H
Ester-activated alkenes that contain no aromatic groups are more difficult to reduce and the
radical anions more reactive. Methyl acrylate, 16a, undergoes hydrodimerization in buffered aque-
ous solutions containing tetramethylammonium phosphate. The optimum conditions were found to
be a tin cathode, pH 8.5–12 and high concentrations of 16a, resulting in a yield around 50% using
constant current [77]. Side products were the hydrogenation product and a high boiling, probably
oligomeric material. The cinnamates are only very slightly soluble in water but, for example, 15a
may be solubilized either by the use of large amounts of Et4NOTs (>2 M) or by the use of micelle
forming surfactants such as Triton X-100 (<0.1 M is sufficient). Under these conditions, polarographic
analysis indicates that 15a undergoes hydrodimerization and not hydrogenation [50]. As in MeOH,
the dimerization reaction is much faster (kdim > 108 M−1s−1) than in aprotic solvents.
Ethyl 3,3-dimethylacrylate, 16b, gives the LHD upon reduction in DMF/H 2O (Et4NOTs)
[57]. Under similar conditions, ethyl crotonate, 16c, and the corresponding ethyl 3-buteno-
ate give the same LHD in near-identical yields, and the only unconverted monomer was 16e
[78]. During the electrolysis, the basicity of the medium is sufficiently high for base-catalyzed
isomerization of the two species to take place in a manner analogous to the nitriles. The side
products correspond to Michael addition of the conjugate base of the substrate (C-2 or C-4) to
starting material [78].
An exception to the high reactivity of radical anions derived from ester-activated alkenes lacking
aryl substituents is the radical anion derived from methyl 4-t-butylcyclohex-1-enecarboxylate, 2,
which undergoes coupling following the RR mechanism with a second-order rate constant compa-
rable to those found for aryl cinnamates [26] (see Table 17.3). The product isolated after reduction
was the LHD (3) formed by diaxial coupling, under stereoelectronic control [26] (see Section II.A.4
and Scheme 17.4).
The efficient cyclohydrodimerization of trimethyl aconitate (18)–(19) is of particular inter-
est because it is a biomass, renewable resource, easily prepared from citric acid (17) by fer-
mentation of glucose on a 400,000 tons per annum scale. Controlled potential reduction [79]
gave a good yield of the most stable of the 16 possible diastereoisomers (Scheme 17.5). The
reaction conditions are not “green” but doubtless, by analogy with cyclohydrodimerization of
α,β-unsaturated ketones [80], the reduction could be carried out in aqueous conditions and at
a lead cathode.
Lactones such as coumarin and its derivatives, 20, undergo efficient hydrodimerization at low
pH [81]. The mechanism of the reduction of 4-methylcoumarin, 20b, in DMF, MeOH, and MeOH/
H2O has been examined [75]. In all cases, the mechanism of dimerization was found to be of the RR
type, again with a considerable increase in the observed second-order rate constant in going from
aprotic to protic solvents (Table 17.3) [75].
Efforts to achieve the diastereoselective hydrodimerization of cinnamates and cinnamate
analogs have focused upon exploration of a variety of chiral auxiliaries including (–)-menthyl,
(–)-8-phenylmenthyl, and (–)-endo-norborneol esters [70], Evans oxazolidinones [82], and
camphor-based frameworks. The camphor-based systems 21a–h and the oxazolidinones
E
E
CO2H CO2Me
OH E
CPE E
HO2C CO2H
DMF/Et4NBr E 75%
CO2H HO2C CO2H MeO2C CO2Me E
Hg cathode
17 18 19
E = CO2Me
CO2Me
MeO2C CO2Me
5%
O O
a: R = H
b: R = Me
R
20
SchEME 17.5 Thermodynamic control in formation of 19.

22a–e proved the most effective at delivering both satisfactory yields and good-to-excellent
levels of diastereoselection.
a: Ar = Ph
Ph b: o-MeOC6H4 O O a: R1 = (S)-i-Bu: R2 = H
c: m-MeOC6H4 b: R1 = (S)-i-Pr: R2 = H
Ph d: p-MeOC6H4 Ph N O
O * * c: R1 = (S)-Bn: R2 = H
Ar e: p-FC6H4 d: R1 = (R)-Ph: R2 = H
O R1 R2 e: R1 = (S)-Me: R2 = (R)-Ph
f: 2-naphthyl
21 g: 1-furyl 22
h: 3:4-methylenedioxyphenyl
Of the camphor-based derivatives 21a,c–e,g,h, the electrohydrodimerization worked well, deliv-

ering 52–68% of the (R,R)-dimer with diastereomeric excesses in the range of 87–95%. As indi-
cated [70], electrohydrodimerization of ent-21a afforded the expected enantiomer. Removal of the
chiral auxiliary using LAH, followed by Jones oxidation and Fischer esterification, allowed the
authors to determine the ee to be 92%. The reactions were conducted at a constant current of 75 mA
in an undivided cell, with lead serving as the cathode material and platinum as the anode, Et4NOTs
as the supporting electrolyte, and acetonitrile as the solvent. For unknown reasons, 21b and 21f
proved unsatisfactory, the former leading to only 3% and the latter to 18% of the hydrodimer, 23.
In all cases, the chemistry was accompanied by the formation of 22–77% saturation of the α,β-
unsaturated unit of the starting material, the amount of 24 varying as a function of Ar (e.g., 22%
when starting from 21h and 77% starting with 21b). The diastereochemical preference was deemed
to be the consequence of what is clearly a least hindered Si-face approach of two radical anions.
Ph Ph Ph
Ph 75 mA, undivided cell Ph + Ph

O O O
Ar Pb cathode, Pt anode Ar Ar
O Et4NOTs, CH3CN O O
2
21a–h 23a–h 24a–h
8. Amides and Oxazolidinones

Activation of alkenes by amides and N-alkylamides has not been used as much as activation by
ester groups. The amides are more difficult to reduce than the corresponding esters but have been
reported to give the LHDs in 40–80% yields [2,4].
Chiral N-trans-cinnamoyl-2-oxazolidinones, 22, give upon reduction in dry MeCN the all-trans
CHD in high yields with a diastereoisomeric excess up to 66% [83] (see Table 17.5). The products
are hydrolyzed and esterified to give the dimethyl 3,4-diphenyladipate with up to 70% ee (Scheme
17.6). The chiral 2-oxazolidinones could be recovered in >90% yield.
Both a constant current and a controlled potential electrolysis (−1.8 V vs. SCE) of oxazolidinone
22a were explored. The constant current runs occurred most efficiently at a value of 0.1 A; when it
exceeded 0.1 A, or was smaller, then the amount of reduction product 25 increased at the expense of
hydrodimerization [82]. Utilization of either the constant current or the controlled potential protocol
led to the same level of diastereoselectivity, viz., an 85:15 preference for formation of the R,S,R-
keto ester 26 over the S,R,S form, 27. The influence of supporting electrolyte upon stereoselection
was also investigated. In contrast with the results obtained when Et4NX salts were used, the use
of lithium perchlorate in acetonitrile led to the deposition of lithium metal on the cathode, while
in THF only the uncyclized hydrodimer formed and as a mixture of d,l- and meso-forms. Table
17.5 illustrates the results for five substrates, 22a–e, electrolyzed at controlled current (CCE) or
controlled potential (CPE). This is a good example of the simplification of conditions to develop a
convenient electrosynthesis.
TABLE 17.5
Diastereoselectivity for Reduction of Oxazolidones: CPEa and CCEb
Yield (%) and Ratio:
R1 R2 26 (2R, 3S, 4R):27 (2S, 3R, 4S)
22a, (S)-i-Bu H 75a 85:15a
(95)c (83:17)c
22b, (S)-i-Pr H 76 83:17
(88) (81:19)
22c, (S)-Bn H 68 70:30
(83) (70:30)
22d, (R)-Ph H 70 30:70
(81) (32:68)
22e, (S)-Me (R)-Ph 72 75:25
(92) (76:24)
a MeCN, Et4NOTs, undiv. cell, Pb cath., CPE, Ew = −1.8 V. From [83].

b In all cases, the amount of the 2 F product (25) was <10%.
c (MeCN, Et4NOTs, undiv. cell, Pb cath., CCE, 0.1 A).
COX O O
O O COX
Ph Ph
CCE (0.1 A) Ph N
Ph N O O O
O
* * Et4NOTs, CH3CN
Ph Ph
R1 R2
22a–e 26 (2R, 3S, 4R) 27 (2S, 3R, 4S) 25
O O
O * R2
CON
Ph * Ph
CON O MeCN, Et4NOTs R1 MeO–, MeOH COOMe
Pb cathode O COOMe
* * Ph
Ph R1 R2 Ph
22
SchEME 17.6 Diastereoselectivity in EHD of oxazolidones.
The outcome obtained electrochemically for 22a was compared with those achieved by using
several common reducing protocols including Na in Et2O or THF, SmI2 in THF–HMPA, and TiCl4 –
Zn in THF. Surprisingly, of these only the latter led to hydrodimer and then in only a 35% yield as
a 70:30 mixture of the R,S,R/S,R,S diastereoisomers, 26 and 27.
Of mechanistic significance is the fact that the cis isomer of the oxazolidinone, 29, gave the same
results as its trans counterpart, 28 (* = either ∙ or −). This is in keeping with the notion that the
coupling occurs via the lowest energy conformation of two radical anions, in this case 28a and 29a,
with the two systems approaching one another from the least hindered side.
– – Ph O
O O O* O Ph O* O O
*
Ph N +e Ph N * N +e N
O O O O
i-Pr i-Pr i-Pr i-Pr

29a 29
28 28a
9. Carboxylic Acids
Few hydrodimerizations of alkenes activated by carboxylic acid groups have been reported [59,84–
87]. In all cases, the reductions were carried out in highly acidic media (e.g., 28% H2SO4 mixed
with an organic co-solvent) at Hg cathodes using constant current. The only example of usefulness
in synthesis gave the LHD of cinnamic acid (42–55%) with a (±):meso ratio close to one [85,87].
10. Miscellaneous Activating Groups

O O
NO2
SO2 Ar SO2 Ar2 PPh2
P(OEt)2
Ar1 R2 R1
30 31 32 33 34
a. R1 = H, R2 = n-pentyl
b. R1 = Me, R2 = Ph
Aryl vinyl sulfones, 30, undergo electrocatalytic [2 + 2] cycloaddition to trans-1,2-diarylsulfonyl-

cyclobutane (20–75%) in dry DMF (Et4NClO4) (see Scheme 17.2), when electrolysis (0.1–0.2 F) is car-
ried out at a potential corresponding to the foot of the reduction peak or by application of an electron
transfer mediator [36]. In DMSO (LiClO4), up to 95% of the cyclobutane could be obtained after pas-
sage of 0.1 F [88]. No cyclobutane was formed in MeCN [88]. Meanwhile, reduction of 2-aryl sulfones
31 in DMSO (LiClO4) afforded good yields of d,l- and meso hydrodimers, the former predominating
[88]. When reduction of 30b was carried out at the reduction peak potential in the presence of a small
excess of PhOH or AcOH, a 2:1 mixture of the hydrogenation product 35 and an unsaturated dimer 36
was obtained (Equation 17.4) in an overall 1 F process [89]. The reaction pathway is not known.
SO2–Ph
SO2–Ph DMF, Bu4NBF4, 1F SO2–Ph +
PhOH in excess Ph–SO2 (17.4)
30b 35 2 : 1 36
Alkenes activated by nitro groups show little tendency to undergo EHD compared to other acti-
vated alkenes due to lower spin density on the β-carbon [90]. Due to the acidity of the γ-hydrogens,
reduction in aprotic solvents gives mostly base-induced reactions of the type described for the corre-
sponding nitriles, which are catalytic with respect to current. In the presence of proton donors, either
reduction of the nitro group or cleavage takes place. However, by proper choice of reaction condi-
tions, it has been demonstrated [90,91] that the LHD (β,β′-coupling) may be obtained in 40–95% for
nitro-activated alkenes, 32a,b, in MeCN (Bu4NBF4) [90]. The dimerization reaction is favored over
the base-induced reaction (most likely induced by proton transfer from a substrate molecule to a radi-
cal anion or a dimer dianion) by high concentrations of the radical anion (RR mechanism), that is, by
high current densities obtained by the use of an undivided cell and closely positioned electrodes [90].
The vinyl phosphonate, 33, and vinyl phosphinoxide, 34, have been reported to give very low
yields of the LHDs upon reduction in MeCN/H2O (Et4NOTs) [56] accompanied by H2 evolution due
to the low reduction potentials (<−2 V) of the substrates.
11. Ketones
Enones may react either as ketones (see Chapter 31) or as activated alkenes, thus giving pinacols,
β,β′-coupling, or mixed coupling products. Another feature of enone reduction is that the radical
anions, A− •, in the presence of proton donors are protonated at oxygen in a fast process and the
resulting enol radical, B•, is more difficult to reduce than the neutral substrate (see Section II.A.1).
Radical anions derived from other activated double bonds tend to protonate at carbon in the pres-
ence of proton donors, and the resulting radical is more easily reduced than the neutral substrate
(see Schemes 17.1 and 17.3).
As a consequence, hydrogenation competes to a much smaller extent with coupling in the reduc-
tion of enones than in the reduction of other activated double bonds, since the enol radical also
participates in coupling reactions. Overall 1 F reduction is therefore observed in most experimental
conditions. Whether the coupling takes place at the radical anion stage, A− •, or at the radical stage,
B•, depends on the acidity of the medium.
A number of studies have been made of the reduction of model enones in buffered aqueous or
buffered ethanolic solutions in order to elucidate the sequence of electron transfer, proton transfer,
and coupling steps as a function of pH [41–44,92–96]. The experimental methods applied include
polarography, CV, LSV, and chronocoulometry.
The general conclusions are that under acidic conditions (pH < 5–6) the electroactive species is
the enone preprotonated at oxygen, which by a one-electron reduction gives directly the enol radi-
cal B•, which undergoes dimerization in the rate-determining step. For the less soluble substrates,
for example, 37a [42] and 38a (in aqueous buffers [43]), the coupling seems to take place in the
adsorbed state. At pH > 7–8, the neutral substrate is the species undergoing reduction but only at
high pH values (pH > 11) does a rate-determining dimerization of A− • take place. The simple vinyl
methyl ketone, 39a, is electroinactive at these pH values since the β-hydroxyketone anion is formed
[92]. For 37a, dimerization of A− • only takes place in the presence of a surfactant, Triton X-100 [41].
In the intermediate pH range, initially formed A− • is protonated to B• either in fast pre-equilibrium
or in a rate-determining step followed by coupling between two B• or between A− • and B•. The rate
constant for dimerization of two neutral radicals is high—for 37a (in the presence of a surfactant),
the value of kdim was estimated to be > 108 M−1s−1 [41]. Also for 38a, a value of kdim = 4⋅105 M−1s−1 was
determined at pH 11 (in the presence of surfactant) where the dimerization is between two A− • [41].
O
R3 R
Ar2 R4 R1 O O
O
R2 Ar
Ar1 R3
R1 R2
37 38 39 40
a: Ar1 = Ar2 = Ph a: R1 – R4 = H a: R1 = R2 = H, R3 = Me a: Ar = Ph, R = Me
b: Ar1 = Ph, Ar2 = 9-anthryl b: R1 = R2 = Me b: R1 = R2 = R3 = Me b: Ar = Ph, R = t-Bu
c: Ar1 = 4-MeOC6H4, R3 = R4 = H c: R1 = H, R2 = R3 = t-Bu
Ar2 = Ph c: R1 = R2 = R4 = Me,
d: Ar1 = 4-MeOC6H4, R3 = H
Ar2 = 2,4,6-Me3C6H2 d: R1 – R3 = Me, R4 = H
Structural and steric factors are important in determining the coupling position (β-carbon or
carbonyl carbon). Vinyl alkyl ketones, 39, and simple alkyl substituted cycloalkenones such as 38 in
general give mixtures of dimeric products arising from β,β′-coupling, carbonyl-carbonyl coupling,
or mixed carbonyl-β-coupling. In contrast, styryl alkyl ketones, 40, and styryl aryl ketones, 37a,
almost exclusively give “normal” LHDs or CHDs arising from initial β,β′-coupling.
The CHDs formed by intramolecular addition often eliminate water to give another α,β-
unsaturated ketone. For mesityl oxide (4-methyl-3-pentene-2-one), 39b, the influence of the reaction
conditions on the product distribution was examined in detail [97]. Mixtures of four dimeric spe-
cies were observed, resulting from initial 4,4′-coupling, 41b–d, or from mixed 2,4′-coupling, 41a.
Pinacol formation (2,2′-coupling) was not observed (Equation 17.5).
O O O
O Red.
+ +
O + (17.5)
OH O
39b 41a 41b 41c 41d

Optimization of the experimental conditions for selective formation of 41a–d in an undivided

cell was examined [97]. The product of mixed coupling, 41a, was favored (88%) by reduction in
AcOH/Ac2O (1:1). Most other conditions (strongly acidic, aprotic, or basic) favored 4,4′-coupling.
The dehydrated cyclic compound 41c (62%) and the hydrated form 41b (20%) were formed in
strongly acidic conditions (pH 1.1). Product 41b (cis/trans = 1:1) was favored by reduction in aprotic
solvents (DMF, Et4NOTs) or by basic conditions. Cyclization was best avoided by reduction at
elevated temperature (65°C) in a 1:1:1 (v:v:v) mixture of H2O, MeCN, and THF (HOAc/KOAc);
this gave 41d (56%) [97].
Hindrance at the carbonyl group (e.g., 41c) favors β,β′-coupling. The radical anion derived
from 41c is stable on a voltammetric time scale in DMF (n-Pr4NClO4) and reacts slowly under
preparative conditions giving 30% of the LHD, exclusively as the (±) isomer [20]. When water
or Li+ is added, the rate of reaction is increased. Electrolysis in a mixture of DMF and aqueous
buffer (pH 9 or pH 13) gave an increased yield of the LHD (55–60%) predominantly as the (±)
isomer (<5% meso). The (±) isomer was also the product obtained by chemical reduction using
Na in HMPA [20].
For the α,β-unsaturated ketones, 37a,c,d reduction in aqueous electrolyte (H 2O/Et4NOTs
[0.5 M]) gives clean reaction [80] to, mainly, three types of product arising from both linear
hydrodimerization (LHD) and cyclic hydrodimerization (CHD) (Scheme 17.7). The formation
of cyclic hydrodimers, with high stereoselectivity, is reminiscent of the electroreduction of
cinammates [67], and thus the stereoselectivity may result from templating of the dimeric anion
in aqueous solution. The stereochemistry originally reported [98] was unexpected and turned
out to be wrong according to X-ray crystallography [80].
In DMF solution, the rates of dimerization of the radical anions [16,67,80] can be measured and
they are similar (1c, 1.05 × 103 dm3 mol−1 s−1; see methyl cinammate, 6 × 102). These reactions are
much faster [67] in protic solvents, which precludes comparison in aqueous media.
Mono-enol ethers of β-diketones, 46, are formally alkoxy-substituted enones, and by reductive
coupling followed by hydrolysis, they yield conjugated bis-enones (Equation 17.6). This is the more
stable product independent of whether the initial coupling product is a pinacol, a bis-ketone, or a
mixed coupling product. Reduction of the substrates 46a,b in ethanol/water (1:1) (Me4NCl) gave the
corresponding bis-enones in 20–40% yield [99].
O Ar2
H
Ar1
– Ar2 1. Dimerisation, H+
2. Intramol. cycn., H+
H O H+
Ar1
(42)
Ar2 OH Ar2 Ar2
Ar2 O H Ar1 O 2 H Ar1 O
e 1 Ar+ +
Dimerisation, 1 OH
O – 2 2
3 3
Ar1 Ar2 2H+ 1
Ar 4 5 1
Ar 4 5
Ar1 H H H H
Ar2
CHD 43 CHD 44
(37a), Ar1 = Ar2 = Ph
Ar1 O [Major from 37a and 37c] [Minor]
(37c), Ar1 = 4–MeOC6H4, Ar2 = Ph
O Ar1
(37d), Ar1 = 4-MeOC6H4, Ar2 = 2,4,6-Me3.C6H2
Ar2 [Only product from 37d]
LHD 45, meso and (±) isomers,
1:2.5 or 1:5, depending on concentration
SchEME 17.7 EHD of α,β-unsaturated ketones.

R O R
R R
1) Red.
O a: R = H (17.6)
2) –2 MeOH b: R = Me
MeO R O
46 R

Formation of a LHD by exclusive coupling in the 5-position in a conjugated dienone is observed

for the quinonemethide 47 and is favored by the formation of an aromatic ring [100] (Equation 17.7).
The yield was improved to 80% when the product was methylated prior to work-up. Additional sub-
stituents in the 5-position prevented dimerization [100].
Me3C CMe3
Ph Me3C Ph
O DMF, Bu4NClO4 OH
Red. HO 58% (17.7)
Me3C Ph CMe3
47 Me3C (±): meso = 0.5

As mentioned, styryl alkyl ketones, 40, form only β,β′-coupled LHDs upon reduction. In DMF,
the yield of the LHD increased with increasing size of the alkyl group [101] (see Table 17.6). In
DMSO containing small amounts of water (<0.05 M), the dimerization of 40b− • takes place by the
RR mechanism, kdim = 1.4⋅103 M−1 s−1, according to current reversal chronopotentiometry [6]. The
value of kdim is enhanced remarkably upon addition of Na+ or Li+. Using LiClO4 as supporting elec-
trolyte gave a rate enhancement of approximately three orders of magnitude [17] for 40b, and on a
preparative scale 75% of the (±) LHD was formed (Table 17.6) [17].
In dry DMF, polymers were formed in addition to the (±) LHD (Table 17.6). However, in the
presence of a stoichiometric concentration of metal cations (Li+, Cr2+, Mn2+, Fe2+, Co2+, or Zn2+),
polymerization was avoided and a yield of >90% of dimers obtained [21]. With Li+ the (±) LHD
TABLE 17.6
Influence of Structure and Experimental Conditions on Product Structure and Yields
Obtained by Reduction of Alkyl Styryl Ketones, 40
Substrate Conditions Products and Yields References
E-Ph-CH=CH–COMe (40a) H2O, Et4NOTs, Hg-cath., div. cell LHD 74% [102]
40a EtOH/H2O (1:1), acetate buff., pH LHD (meso), n = 0.99 [17]
5, Hg-cath., CPE (−1.1 V)
40a DMF, Et4NBr, Hg-cath., CPE 0% LHD, polymer [101]
E-Ph-CH=CH–COPr DMF, Et4NBr, Hg-cath., CPE 25% LHD (±) and meso, polymer [101]
E-Ph-CH=CH–CO(i)Pr DMF, Et4NBr, Hg-cath., CPE 65% LHD (±) and meso, polymer [101]
E-Ph-CH=CH–CO(t)Bu (40b) DMF, Et4NBr, Hg-cath., CPE 95% LHD (±) and meso [101]
40b EtOH/H2O (1:1), acetate buff., pH 40% LHD (meso), smaller [17]
5, Hg-cath., CPE (−1.15 V) amounts of LHD (±), n = 0.96
40b DMSO/H2O (93:7), LiClO4, 75% LHD (±), n = 0.96 [17]
Hg-cath., CPE (−1.7V)
40b DMF, Bu4NBr, Hg-cath., CPE 50% LHD (±), 50% polymer [21]
40b DMF, LiClO4, Hg-cath., CPE 98% LHD (±) [21]
40b DMF, Bu4NBr, 1 eq. Fe2+, >95% CHD (±) (see text) [21]
Hg-cath., CPE
was obtained exclusively, whereas with Fe2+ or Co2+ the CHD was the sole product. The stereo-
chemistry of the CHD was assigned by NMR to arise from meso coupling [21], but later studies
have shown the stereochemistry to correspond to (±) coupling by application of 1H NOESY NMR
and X-ray crystallography [81]. The metal cations are expected to form ion-pairs with the radical
anions (an anodic shift of the reduction peak was observed). Thus, a templating effect is a likely
explanation of the stereoselectivity, and stabilization of the dimer dianion by ion pairing may
prevent polymerization.
The influence of the same metal cations on the yields and products of reduction of ring sub-
stituted chalcones, 37, in DMF (Bu4NBr) is similar to the effect described earlier for styryl alkyl
ketones. In all cases, polymerization was prevented and mixtures of the LHD and the CHD in an
overall yield of 70–90% were obtained; in most cases the presence of the metal ions favored the
CHD [22].
In MeCN, the radical anion derived from 9-anthryl styryl ketone, 37b, dimerizes (kdim = 105 M−1 s−1)
forming a stable dimeric dianion, most likely via coupling in the β-position [103]. On a coulometric
scale, the stable dimeric dianion can be reoxidized to the starting material at a potential ca. 1 V
anodic relative to the reduction of 37b. In contrast, the related 9,10-anthryl bis(styryl ketone) under-
goes two consecutive one-electron reductions (ΔEo′ = 36 mV corresponding to the statistical factor
for reduction of two identical, noninteracting electroactive groups) with formation of a monomeric
dianion, which is completely stable on a coulometric time scale. The lack of electronic interaction
between the two styryl-keto groups in the monomeric dianion as well as the rapid dimerization of
37b− • is probably caused by the styryl groups being rotated almost completely out of plane of the
anthracene ring.
In a few examples, radical anions derived from enones have been trapped by electrophiles other
than a proton, and the coupling reaction proceeds through neutral radicals. For instance, 48 is
reduced in DMF (Bu4NClO4) to give a stable solution of the radical anion. Subsequent addition of
Ac2O gives O-acylation in a fast process. The resulting neutral radicals dimerize slowly enough for
examination by ESR [104]. Since the unpaired electron density in the neutral radical as determined
by ESR is similar in positions 3, 4, 6, 7, and 9, the radicals may couple in several ways. Preparative
scale electrolysis on a 0.4–0.5 g scale, with subsequent addition of acetic anhydride, gave a mixture
of variously acetoxylated products of the hydrocarbon 49 [104].
2 1
O
3
4 9
5 8
6 7
48 49
Another example of a coupling reaction initiated by reaction of the radical anion with an
electrophile is the reductive coupling of substituted 4H-pyran-4-thiones, 50, in the presence
of alkyl halides (Scheme 17.8) [105,106]. The neutral radical formed by alkylation at sulfur is
R1 O R2 R1 O R2
S SR
S–
DMF, Et4NClO4 RX x2 RS SR
Red. –X– –RSSR
1
R O R2 1
R O R2
R1 O R2
50 R2 O R1 R2 O R1
51 52
45–90%
SchEME 17.8 Radical-radical coupling; first formed radical not easily reduced.
apparently not reduced at the potential of the electrolysis but undergoes dimerization. If the
substrate is methylated prior to reduction, the sulfonium cation is reduced more easily than the
neutral substrate to give the same dimeric product. The initially formed dimer, 51, eliminates
disulfide in an oxidatively induced process during the electrolysis, yielding the final bipyrani-
lidene, 52 [105].
12. Aldehydes
R2 R2
R1 O R1 O R1 O
R 1 OH R1
R2 R2 OH R2
a: R1 = R2 = Me R1 R 2 R1 R2 R1
R2 R1 R2
b: R1 = H, R2 = Me O O
53 54 55 56 57
In general, reduction of alkenes activated by CHO, for example, 53, gives preferentially products
of mixed coupling (1,3′-coupling). The 3,3′-coupling only takes place when R1 = H or R2 = H. Both
3,3′- and 1,3′-coupling products undergo cyclization to the cyclopentane, 54, or the tetrahydrofuran,
55, derivatives. Often these eliminate water to give cyclopentene, 56, or dihydrofuran, 57, deriva-
tives. The pinacol formed by 1,1′-coupling is the only linear dimer formed.
Ph OH Ph O OH Ph OH
O O Ph O OH O
+ + +
MeOH, NaClO4
Ph Total 56% Total 24% (17.8)
Red. Ph Ph Ph
Ph
Ratios 45 : 55 10 : 90
A mixture of pinacol and cyclized mixed coupling products, 55a and 57a, was formed upon
reduction of 3-methylcrotonaldehyde, 53a, at pH 5 (Table 17.7) [107]. Under these conditions,
the intermediates undergoing coupling are expected to be the neutral radicals obtained by
TABLE 17.7
Influence of Structure on Product Structure and Yields Obtained by Reduction
of α,β-Unsaturated Aldehydes, 53
R = R = Me (53a)
1 2 A 55a 46%, pinacol 8% [108]
53a B 55 28%, 57 10%, pinacol 4% [107]
R1 = H, R2 = Me (53b) C 54 26%, 55 53%, pinacol 15% [108]
R1 = H, R2 = Ph D 55 total 80% (see Equation 17.8) [109]
R1 = Me, R2 = Me2C=CHCH2CH2 A 55 36%, pinacol 18% [108]
(E,E) R1 = Me, A 55 33%, pinacol 18% [108]
R2 = Me2C=CHCH2CH2C(Me)=CHCH2CH2
A: EtOH/acetate buffer (1:1), pH 5, div. cell, Hg-cath., CPE.

B: Acetate buffer, pH 5, div. cell, Hg-cath., CPE.
C: Acetate buffer, pH 4.7, div. cell, Hg-cath., CPE.
D: MeOH, NaClO4, div. cell, Hg-cath., CPE.
TABLE 17.8
Influence of Structure on Hydrocyclizations of 59aa
EWG Link Products and Yields
COOEt –C(Me)2– HC 57%, cis/trans ≈1:1
COOEt –(CH2)2– HC 34%, cis and trans, 4 F prod. 20%, LHD 18%
COOEt –(CH2)3– HC 52%, cis/trans ≈1:4, LHD 8%
COOEt –O–(CH2)2–O– HC 42%
COOEt HC 48% only trans, 4 F prod. 19%
CN –(CH2)2– HC 16%, cis and trans, oligomers 54%
a MeCN/H2O, Et4NOTs, Hg-cath., div. cell, CPE. Yields based on current. From [113].
protonation at oxygen. The effect of increasing size of R 2 in 53 on the dimeric products [108]
is shown in Table 17.8. In all cases, 55 resulting from the mixed 1,3′-coupling was the major
isomer [108].
Unsymmetrical coupling is even more prominent in the reduction of cinnamaldehyde in MeOH,
which gives four stereoisomeric cyclic products (total 80% yield), all derived from mixed coupling
(Equation 17.8) [109] and probably under thermodynamic control.
B. INTraMoLECULar HYDroDIMErIZaTIoNS (HYDroCYCLIZaTIoNS)

When two identical activated alkene functions are included in the same molecule, then intermo-
lecular coupling has to compete with intramolecular hydrocyclization. In most cases, the intra-
molecular reaction, which corresponds to an overall two-electron process, takes precedence.
Few mechanistic studies of intramolecular couplings have been reported. The main question is
whether the coupling takes place at the mono radical anion stage in an RS-type reaction (one unit
reduced, the other not reduced) or at the bis(radical anion) stage in an RR type reaction (both
units reduced). The last case implies weak electronic interaction between the electrophores in the
initial state.
The formal kinetics and diagnostic criteria for the different mechanistic pathways for intramo-
lecular hydrodimerizations under steady-state conditions (LSV, RDE, and polarography) have been
established [110–112]. For the RS-type mechanisms, it is normally assumed that the cyclized radical
anion (or the neutral, cyclic radical formed by subsequent protonation) is more easily reduced than
the starting material. For the RR-type mechanisms, ΔEo′ (the difference in reduction potential of
the two electroactive groups) is normally assumed to equal the statistical difference expected for
two electronically isolated groups in the same molecule.
The two activated alkene functions may be linked via the β-carbons, 58a, via the activating
group, 58b, or, less commonly, via the α-carbons, 58c. Where the two alkene units are linked
by direct bonding between the α- or the β-carbons, the two alkenes form a single, conjugated
π-system.
R
R EWG R EWG
EWG
EWG
EWG R EWG
R R
58a 58b 58c

1. Intramolecular Coupling of Electrophores Linked through the β-Carbons

The efficiency of reductive coupling of 59a depends on the size of the resulting ring, 3–6-membered
rings in general being favored (Table 17.8) [113]. In the medium of choice, MeCN/water mixtures,
the hydrocyclization (HC) products formed from the general structure 59a by coupling in the
β-position were mixtures of the cis and trans isomers (Equation 17.9), analogous, respectively, to
the bimolecular meso and (±) couplings in the formation of LHDs. In most of the cases [113],
h ydrogenated products (2 F and 4 F) and oligomers were formed as well.
EWG EWG
R R
R EWG
2e–, 2H+
+ (17.9)
R EWG
R R
EWG EWG
58a Cis Trans
COOR´
R a: R = H, R´ = Et
b: R = R´ = Me
R
COOR´
59
A systematic study of the influence of added water on the reduction of 59a in MeCN revealed
that in the presence of 20% water the HC product (≈90%) was obtained as a mixture of cis and trans
isomers in a ratio of ≈1:3, but with a charge consumption slightly lower (1.8 F) than the expected 2 F.
Decreasing the water content gradually led, with concomitant reduction in charge, to decreasing
amounts of HC product and increasing amounts of cyclic (0 F) products arising from base-induced
intramolecular Michael addition [114]. With no added water, the HC product (27%) and the Michael
addition product (57%) were formed with consumption of 0.4 F. The suggested mechanistic inter-
pretation of these results were that at low water concentrations the intramolecular coupling involves
radical addition to the unreduced function (i.e., an RS-type coupling) followed by hydrogen atom
abstraction from the solvent, MeCN (the radical, •CH2CN, being consumed in an unidentified, non-
reductive chemical reaction). The resulting anion of the HC product abstracts a proton from unre-
acted substrate that initiates intramolecular Michael addition (see Scheme 17.9). At higher water
concentrations, the radical anion is stabilized. This allows formation of the bis(radical anion) and
subsequent RR-type coupling. At the same time, the water serves as proton donor, thereby inhibiting
the Michael addition [114].
A similar relationship between product distribution and water content was observed for the anal-
ogous substrate containing an extra methylene unit in the link [114]. The Michael addition products
were slightly more difficult to reduce than the parent compounds [114].
Formation of the trans isomer of the HC product is enhanced in the presence of metal cations and
by using a carbon rather than an oxygen acid. For reduction of 59a in MeCN, the trans:cis isomer
– – –
e– COOEt MeCN COOEt 59a COOEt
59a COOEt +
MeCN (dry) COOEt – CH2CN COOEt COOEt COOEt
– – –
COOEt COOEt COOEt 59a COOEt COOEt
+
COOEt COOEt COOEt COOEt
COOEt –
SchEME 17.9 Intramolecular coupling via Michael addition.

ratio changed from 2.6:1 in MeCN/H2O (9:1) using AcOH as proton source to 7.5:1 in MeCN using
diethyl malonate as proton source. The selectivity was further enhanced to 14.8:1 when 1.3 equiva-
lents of CeCl3 was added with a total 73% yield of the HC product [19]. As for the bimolecular EHD
reactions, the (±)-coupling is preferred in the presence of templating cations.
Intramolecular coupling by the RS mechanism would be expected for reduction of 60. Since
the two halves of the molecule interact electronically through the aromatic ring, the first and
the second electron transfers are separated by ≈300 mV [114]. Consequently, only the mono-
reduced substrate can participate in coupling following the first electron transfer. However, only
intermolecular coupling products (59%) were found upon reduction [115]. The fully hydrogenated
monomer (28%) and the half-hydrogenated monomer (7%) were also formed with an overall con-
sumption of 1.1 F. In the light of the mechanism for alkyl cinnamate reductions, the intermolecular
coupling will be of the RR type, and the initial dimer, 61, can then under the conditions of the
electrolysis undergo one or two Michael additions to yield 62 and 63 (62%). The products 62 and
63 were shown by X-ray crystallography to result from initial (±) coupling, whereas 61 resulted
from meso coupling [115].
COOMe CH2COOMe
CH2COOMe
COOMe COOMe COOMe
H CH2COOMe H H
DMF, 4% H2O + +
H H
1.1 F MeOOCCH2 H MeOOCCH2
MeOOC
CH2COOMe
COOMe MeOOC MeOOC
meso (±) (±)
60 61 62 63
2. Intramolecular Coupling of Electrophores Linked through the EWG Groups

Intramolecular reductive coupling of the substrates 64a–c, where (chiral) diols have been used
to link two cinnamoyl units through the activating group, has been tried [83]. The yields of HC,
intramolecular cyclized products, 66, are normally low (<50%) and the enantiomeric excess
modest (36–50%, as determined for the 3,4-diphenyladipates obtained after hydrolysis and esteri-
fication) [83]. The low yields are most likely due to the necessary formation of a 10-membered
cyclic intermediate such as 65, which subsequently may undergo Dieckmann condensation in
aprotic solvents (Scheme 17.10). Hydrolysis and polymerization have been found as the main reac-
tions in similar systems, 64d,e [60]. Voltammetric studies of 64f (which yields 33% of the HC
product) showed that ΔEo′ for reduction of the two electrophores was larger (80 mV) than the
statistical value of ΔEo′ and that the intramolecular coupling of the two units in this case takes
place at the bis(radical anion) stage [16]. The conclusion is that linking through the EWG via a
diol is an approach that is unlikely to be successful due to the necessary formation of large rings
in the course of reaction.
O
Ph Ph a: R = Me
O O b: R = COOEt
COO R Ph * R
* 2e–, H+ c: R = CH2OBn
Ph d: R = COOMe
Ph O O–
COO * R – O*R O O
* *
Ph R R e: R = O
O
64 66
65 f: R, R = (CH2)4
SchEME 17.10 Coupling through EWG groups.

3. Intramolecular Coupling of Electrophores Linked through the α-Carbons

Dibenzylidene succinic acid derivatives are examples of substrates with a direct link between the
α-carbons. Voltammetry of dimethyl dibenzylidenesuccinate shows two reduction peaks separated
by 200 mV, and preparative scale reduction under a variety of conditions gave none of the cyclobu-
tane derivatives expected from intramolecular cyclization. Monomeric products (2 or 4 F depending
on the working potential) were found together with varying amounts of oligomers [116].
Intramolecular coupling of two α-linked cyclohexenone units can in principle give products cor-
responding to intramolecular β,β′-coupling, carbonyl-carbonyl-coupling, and mixed β-carbonyl-
coupling. However, only the β,β′-coupling HC product corresponding to formation of the most
stable trans-anti-trans perhydrophenanthrene ring system (Equation 17.10) was formed upon
reduction [117].
Me
MeCN, Et4NCl, 20% H2O
O
Red. Me H (17.10)
O O H 72%
O
In a report from 2007, Handy and Omune [118] describe the influence of ring size and
β-substitution upon the efficiency of electrohydrocyclization. Five substrates, 67–69, were exam-
ined. A constant current electrolysis (CCE) was conducted at a platinum cathode with a sacrificial
tin foil anode, in acetonitrile/water (4:1 v/v) with ~0.3 M Et4NCl as the supporting electrolyte. In
accord with Mandell’s pioneering report [117] from 1976, electrohydrocyclization leads to a single
stereoisomer when R1 = R2 = methyl. Specifically, the reduction of 68d leads to a 50% yield of
the trans, anti, trans adduct, 70, while the five-membered ring analog, 68c, affords the cis, anti,
cis isomer 71 in a 73% yield. In contrast, the electrohydrocyclization of 67a and of 67b, substrates
where R1 and R2 = H, leads to mixtures of stereoisomers. Thus, the presence of at least one alkyl
group at the β-carbon appears to be a prerequisite for stereoselection. Several non-electrochemical
approaches were also explored including the use of samarium diiodide, tributyltin hydride, 2,2′-azo-
bisisobutyronitrile (AIBN), and photoinduced electron transfer. From the examples provided in the
accompanying table, it is evident that the electrochemical pathway proved superior in each instance
(Table 17.9).
R2
67a: n = 1, R1 = R2 = H
R1 67b: n = 2, R1 = R2 = H O
n O
68c: n = 1, R1 = R2 = CH3 H H
O 68d: n = 2, R1 = R2 = CH3
n O H O H
69: n = 2, R1 = H: R2 = CH3 O
70 71
R2
R1 R1
Conditions
R2 O
below H
O (Table 17.9)
O H
O
68d and 69
The chemistry was expanded to include other structural varieties, viz., to cyclic enones tethered
either to an acyclic unsaturated ester, 72, or to another cyclic ketone 73, or to a butenolide, 74. In
each case [119], an OR unit was appended to the tether linking the electrophores. Once again, a con-
stant current electrolysis was carried out using a platinum cathode and a sacrificial anode made of
tin foil. Yields for electrohydrocyclization ranged between 47% and 69%. Interestingly, in all cases
TABLE 17.9
Electrohydrocyclization of Cyclic Enones
Conditions Yield (%) of 70 from 68d Yield (%) beginning with 69
CPE, Et4NOTs, CH3CN/H2O 65a b
CCE, Et4NOTs, CH3CN/H2O 50 59

SmI2, HMPA, EtOH/THF 34 30
n-Bu4SnH, AIBN, PhH NR NR
hν, DCA, Ph3P NR b
From [117]
a
From [117].
b
NR, not reported.
where R = H (viz., 72a, 73d, and 74f) and for structure 74g where R = Ac, only the cyclized α,β-
unsaturated adducts, 75–77, were isolated. These substances result from an elimination that occurs
at some undetermined point along the reaction coordinate.
OR OR OR
O CO2Me O O O
O O
72 73 74
a: R = H; b: R = MEM d: R = H; e, R = MEM f: R = H; g: R = Ac
c: R = TBS h: R = MEM; i: R = TBS
O
CO2CH3
O
O
H H
H
O H H
O O
75 j: 69% from a 76 k: 69% from d 77 l: 59% from f and g
In contrast, elimination is not observed when R ≠ H with the exception of substrate 74g. With
the OR unit possibly serving as a stereocontrol element, cyclization leads to the formation of single
stereoisomers in reasonable yields, as illustrated later. This is a particularly attractive feature of the
chemistry that one can easily imagine applying to the total synthesis of polycyclic natural products.
O
CO2CH3 O
H
H H
O
OR H
H OR
O OMEM H
H O
m, 47% R = MEM O
p, 61% R = MEM
n, 49% R = TBS o, 58% q, 59% R = TBS
C. MULTIpLY ACTIVaTED ALkENES

1. α,β-Diactivated Alkenes
Alkenes activated by electron-withdrawing groups at both ends of the double bond are more
easily reduced than the analogous singly substituted alkenes, and the radical anions formed are
less reactive. Examples include fumarodinitrile 78, dialkylfumarate 79, dialkylmaleates 80, and
N-ethylmaleimides 81.
O
R1
CN COOR N Et a: R1 = R2 = H
ROOC COOR a: R = Et
NC ROOC b: R = Me R2 b: R1 = Me, R2 = H
c: R = Bu O c: R1 = R2 = Me
78 79 80 81
Fumarodinitrile, 78 [2,38,50,58,72–73,85,120], and simple alkyl fumarates, 79 [7,10,58,72,121,122],

have therefore been the subjects of a number of mechanistic studies as models for acrylonitrile and
alkyl acrylates. Examples of the formation of LHDs on a preparative scale are given in Table 17.11.
On electroanalytical scales, the reduction of 78 and 79 in DMF are 1 F processes and the data
obtained consistent with dimerization of two radical anions, that is, an RR mechanism. The rate
constants for dimerization have been determined by several methods (Table 17.10) and show a very
large difference between 78 and 79, the rate constant for dimerization of 78 − • being three to four
orders of magnitude higher than that for dimerization of 79− •.
On a coulometric scale, however, the n-values for reduction of 78 and 79 were found to be less than
one in DMF (see Table 17.10) probably due to polymerization under the dry conditions [7,58], that
is, a behavior similar to but less pronounced than that found for reduction of monoactivated alkenes.
Addition of alkali metal cations did not change the n-value significantly for 78 [73] but led to an increase
in n for 79 [7,73]. At the same time, the overall rate of reaction of 79− • increased considerably [73], an
effect interpreted similarly to that observed for monoactivated alkenes (Section II.A.7).
In dry MeCN, n = 0.6 was found for 78 but the value increased to 0.94 on addition of water up
to 10% [13]. For 79a in very dry MeCN, the mechanism of the reductive dimerization was exam-
ined and the experimental results interpreted as an RS mechanism under these conditions [121].
However, addition of water increased the rate of reaction considerably, and in the presence of water
the kinetic measurements were in accord with the RR mechanism [122]. In DMF, addition of water
also accelerates the dimerization process for 79 [7,10] similarly to what is observed for many mono-
activated alkenes (Section II.A.7). The accelerating effect of water in DMF on the dimerization of
79− • has been studied in greater detail [15]. On the basis of a reaction order in water close to one,
it was suggested that the dimerization reaction takes place between a “free” radical anion and a
hydrogen bonded radical anion [15]. The involvement of hydrogen bonding between radical anions
and water may also account for the low activation energies found for the reductive dimerization of
79a in MeCN [122] and in DMF [10] (see Table 17.10).
In aqueous solution (0.5 M NaBr), the reduction of 78 is a 2 F process, but addition of small amounts
of Bu4NBr (1 mM) has a pronounced influence on the reduction, which changes into a 1 F process [37].
Addition of Et4NOTs has the same effect but has to be used in higher concentrations (50 mM) [126].
Similar effects have been observed for other organic additives [37]. The presence of small amounts
(10 –4–10 –3 M) of strong surfactants has been shown—regardless of the charge of the surfactant—to
cause EHD to take place with high current yields in aqueous solution [126]. The effect of the additives
is proposed to be attenuation of the rate of protonation when water is excluded from the electrode sur-
face by adsorption of organic species. Similarly for 79a, small amounts of strong surfactants prevent
protonation in aqueous solution and favor the (fast) dimerization of the radical anions [50]. In these
conditions, the rate-determining step is suggested to be dimerization of two ion-paired radical anions
(ion-pairing with the supporting electrolyte cations) [38]. The rate constant for the dimerization step
was estimated to be in the range 108–1010 M−1 s−1 on the basis of DPSCC measurements [38], that is,
2–4 orders of magnitude higher than the value determined for dimerization in DMF (see Table 17.10).
Dialkyl maleates, 80, are more difficult to reduce (by ≈0.3 V) than the corresponding dialkyl
fumarates,79, but at the radical anion stage the maleates isomerize to the fumarates. The rate
constant for the isomerization increases with increasing size of the alkyl group (Table 17.10)
[123]. Interestingly, the rate constant for dimerization of 80 − • is more than three orders of mag-
nitude higher than that for the corresponding 79− • (Table 17.10), and the cross-coupling of 80 − •
and 79− • was found to be negligible [123].
TABLE 17.10
Selected Rate Constants for Dimerization of Diactivated Alkenes
Substrate Conditions Method kdim(RR)/M−1 s−1 References
E-NC–CH=CH–CN (78) DMF, Bu4NI, room temp. a RRDE 7⋅105 [58]
78 DMF, Bu4NI, 23°C ESR >105 [72]
78 DMF, Bu4NBF4 SECM 2.0⋅105 [120]
E-EtOOC–CH=CH–COOEt (79a) DMF, Bu4NI, 25°Cb DPSC 37 [7]
79a DMF, 50 mM H2O, Bu4NI, DPSC 46h [7]
25°C
79a DMF, Bu4NI, 23°C ESR 30 ± 5 [72]
79a DMF, Bu4NI, room temp. DPSC/DPSCC 44 [73]
79a MeCN, 35 mM H2O, DPSC 5.5⋅103 i [122]
Bu4NBF4, 0°C
79a MeCN, 555 mM H2O, DPSC 2.22⋅105 i [122]
Bu4NBF4, 0°C
79a NH3, MeBu3NI, −43°Cc CV 0.1 [54]
E-MeOOC–CH=CH–COOMe 79b DMF, Bu4NI, room temp.d RRDE 1.1⋅102 [58]
79b DMF, Bu4NI, room temp.d CV 1.6⋅102 [58]
79b DMF, Bu4NI, 23°C ESR (1.60 ± 0.26)⋅102 [72]
79b DMF, Bu4NBF4 SECM 1.7⋅102 [120]
79b DMF, Bu4NI, room temp. DPSC/DPSCC 1.2⋅102 [73]
E-BuOOC–CH=CH–COOBu 79c DMF, Bu4NI, room temp. DPSC/DPSCC 25 [73]
Z-EtOOC–CH=CH–COOEt 80a DMF, Bu4NI, room temp.e RRDE 9.1⋅104 [123]
Z-MeOOC–CH=CH–COOMe 80b DMF, Bu4NI, room temp.f RRDE 1.9⋅105 [123]
E-BuOOC–CH=CH–COOBu 80c DMF, Bu4NI, room temp.g RRDE 6.9⋅104 [123]
84a DMF, 0.05–0.4 M H2O, DCV 7.3⋅105 [124]
Bu4NBF4, 21.7°C
84b DMF, 0.05–0.4 M H2O, DCV 5.6⋅105 [124]
Bu4NBF4, 5.6°C
84b MeCN, 0.3–10% H2O, CPSV 1.3⋅107 [125]
Et4NClO4
84b DMF, 0.05–0.4 M H2O, DCV 6.6⋅105 [124]
Bu4NBF4, 6.5°C
84d DMF, 0.05–0.4 M H2O, DCV 2.2⋅106 [124]
Bu4NBF4, 17.5°C
84e DMF, 0.05–0.4 M H2O, DCV >107 [124]
Bu4NBF4
a n = 0.44.
b n = 0.6, increases to 1 when Li+ is added.
c n = 0.5, even when i-PrOH or HOAc are added as proton donors.
d n = 0.62.
e Rate constant for isomerization of 80a− • to 79a− • equal to 6.0 s−1.
f Rate constant for isomerization of 80b− • to 79b− • equal to 2.2 s−1.
g Rate constant for isomerization of 80c− • to 79c− • equal to 6.7 s−1.
h Ea = 4.6 kcal mol−1.
i ΔH≠ = −3.5 kcal mol−1, ΔS≠ = −50 cal K−1 mol−1 when CH2O in the range 70–278 mM.
Large-scale EHD of alkyl fumarates and maleates has been studied, since the tetracarboxylate
product has industrial interest [127]. In MeOH, the undesired hydrolysis of 80b is prevented during
electrolysis. The use of sodium or lithium acetate as supporting electrolyte rather than R4N+ salts
enhances the formation of dimer compared to hydrogenation product[127]. The best preparative results
(>80% LHD, ≈10% hydrogenation product, and ≈5% resulting from addition of MeOH to the double
bond) were obtained using a graphite felt cathode in an undivided flow cell [127]. There are significant
differences in the solubility of 80b and of 79b in MeOH: whereas 80b is miscible with MeOH up to
50% w:v, 79b is only soluble in 3% w:v. The rate constant for dimerization was found by application
of a RRDE to be 107 M−1 s−1 for both radical anions under these conditions [128]. At the same time,
isomerization of 80b to 79b took place at the radical anion stage. From FT-IR measurements in MeOH
(NaOAc), it was found that the amount of 79b present in the solution increased during the electrolysis,
and it was estimated that 30% of the 80b initially reduced was converted into 79b [128].
When substituted N-ethyl maleimides, 81, were reduced in aqueous buffers at neutral pH, two of
the substrates, 81a and 81b, gave predominantly the LHDs, whereas the third substrate, 81c, only
gave the hydrogenation product (Table 17.11). Under acidic conditions, all three substrates were
reduced to the hydrogenated monomer [130].
Hydrodimerization of unsymmetrically α,β-diactivated alkenes may in principle give rise to three
types of coupling products: the α,α′-LHD formed by coupling between the two α-carbons, the β,β′-
LHD formed by coupling between the two β-carbons, and the α,β′-LHD formed by coupling between
the α-carbon in one molecule and the β-carbon in the other. Examples are given in Table 17.11.
TABLE 17.11
Hydrodimerization of α,β-Diactivated Alkenes
Substrate Conditionsa Products and Yields References
NC–CH=CH–CN (78) A LHDb [2]
E-EtOOC–CH=CH–COOEt (79a) B LHD 83%c [4]
Z-EtOOC–CH=CH–COOEt (80a) B LHD 94%, 2 F prod. 5%d [129]
Z-BuOOC–CH=CH–COOBu C LHD 70%c [2]
E-[Me(CH2)3CH(Et)CH2OOCCH=]2 D LHD 80%c [2]
Z-[Me(CH2)3CH(Et)CH2OOCCH=]2 D LHD 66%c [2]
E-Ph(O)C–CH=CH–C(O)Ph B LHD 44%b,c [4]
81a (R1 = R2 = H) E½ = −0.77 E LHD 99%, 2 F prod 1%, n = 1.12 [130]
81b (R1 = Me, R2 = H) E½ = −0.90 E LHD 79%, 2 F prod. 21%, n = 1.31 [130]
81c (R1 = R2 = Me) E½ = −1.02 E LHD 0%, 2 F 100%, n = 1.73 [130]
NC–CβH=CαH–C(O)Ph Fe β,β′-LHD 55%b,c [4]
NC–CβH=CαH–COOEt B β,β′-LHD 80%, α,β′-LHD 4%c [4]
EtOOC–CβH=CαH–C(O)Ph F β,β′-LHD 69%,a α,β′-LHD 21%c [4]
Me2NOC–CβH=CαH–COOEt B β,β′-LHD 63%, α,β′-LHD 30%c [4]
a A: MeCN/H2O, Et4NOTs.
B: DMF/H2O, Et4NOTs, Hg-cath., div. cell, CCE.
C: H2O, MeBu3NOTs, Hg-cath., div. cell, CCE.
D: EtOH/H2O, MeBu3NOTs, Hg-cath., div. cell, CCE.
E: EtOH/buff. (1:3), KNO3, pH 6, Hg-cath., div. cell, CPE.
F: acrylonitrile/H2O, Et4NOTs, Hg-cath., div. cell, CCE.
b Mixture of meso and (±).
c Based on current passed.
d Based on substrate consumed. Two stereoisomers of the LHD were formed in the ratio 93:7 but not
assigned.
e Acid added during electrolysis to keep solution neutral.
2. α,α-Diactivated Alkenes
A significant difference is expected, between α,β- and α,α-diactivated alkenes, since α,α-
diactivation will tend to localize the unpaired spin density at the β-carbon, thereby facilitating
dimerization. Reduction of 3-carbethoxy- and 4-carbethoxy-coumarin, 82 (α,α-diactivated) and 83
(α,β-diactivated), in DMF and in aqueous/ethanolic buffers [131] shows distinct differences in the
competition between dimerization and hydrogenation. In hydroxylic media, 83 leads to the hydro-
genation product under acidic conditions and to product mixtures (1–2 F) under basic conditions.
In DMF, 83− • is stable on a voltammetric time scale. In contrast, reduction of 82 is a 1 F process in
both hydroxylic media (independently of pH) and in DMF, the product being a diastereoisomeric
mixture of LHDs [131].
O O O O
COOEt
82 83 COOEt
a: R1 = R2 = Me
a: Ar = Ph, R = H b: R1, R2 = –(CH(Me)CH2CH(Me)CH2CH(Me))– O
1 2
Ar CN b: Ar = 4-tolyl, R = H R1 CN c: R , R = –(CH2CH2CH(t-Bu)CH2CH2)– R O
a: R = 4-F–C6H4
c: Ar = 4-anisyl, R = H d: R1, R2 = –(CH2)5– b: R = i-Pr
R CN d: Ar = 4-F–C6H4, R = H R2 CN e: R1, R2 = –(CH ) – O
84
24 O
e: Ar = 4-CN–C6H4, R = H 85 f: R1 = Me, R2 = Et 86
f: Ar = Ph, R = Me g: R1 = Me, R2 = i-Pr
h: R1 = R2 = Et
i: R1 = Me, R2 =t-Bu
The presence of two electron-withdrawing groups at the α-carbon reduces the basicity of the rad-
ical anions considerably, and, for example, the radical anions derived from 84a [134,136] and 86a
[132] are not protonated by AcOH in DMF and MeCN, respectively. Also, alkylidenemalonitriles,
85, dimerize in competition with hydrogenation in the presence of AcOH (Table 17.12).
Kinetic data for the dimerization of the radical anions of substituted benzylidene malonitriles,
84, were in agreement with the simple RR mechanism, and the rate of reaction was not influ-
enced by the concentration of water (Table 17.10) [124]. Compound 84b was studied over a very
broad concentration range (2–100 mM) by chronopotentiometry [133] in order to investigate pos-
sible mechanistic changes in going from the low concentrations normally applied for analytical
work to the high concentrations suited for preparative work. When the water content in the DMF
solution was high relative to the substrate concentration (10% water), the dimerization followed
the RR mechanism independently of substrate concentration. In dry DMF, the data indicated that
although the mechanism was unchanged, changes in the (specific) solvation of the radical anions
with increasing substrate concentration affected the rate of the dimerization step [133]. The same
mechanistic conclusion was drawn in a study of 84b in MeCN with various amounts of water by
CPSV, where the rate constant for dimerization was considerably higher than the one measured in
DMF [125] (see Table 17.10).
On a preparative scale, different ratios of cis- and trans-isomers of the CHD, 2-amino-4,5-
diaryl-2-cyclopentene-1,1,3-tricarbonitrile, formed upon reduction of benzylidenemalonitrile,
84a, under apparently identical conditions (DMF, 1 M AcOH) have been reported: cis:trans =
1:1 [134] and exclusively trans [135]. In a later systematic study of the reduction of 84a in DMF
(1 M AcOH), the cis:trans ratio was shown to change within the range 1:1–0:1 as a function of
substrate concentration, nature of supporting electrolyte, and the degree of conversion. Only
the trans isomer was formed when an electron transfer catalyst was used [136]. Small cations
and low substrate concentrations favored formation of the cis-isomer, and progressively more
cis was formed as the electrolysis progressed. The authors invoke a competition between the
TABLE 17.12
Hydrodimerization of α,α-Diactivated Alkenes
84a DMF, Bu4NI, 1 M AcOH, C-cath., div. cell, CPE CHD 95% (±):meso = 1:1a [134]
84a MeCN, LiClO4, 1 M AcOH, Hg-cath., div. cell, CPE CHD 85%b [138]
84f DMF, Bu4NI, 1 M AcOH, C-cath., div. cell, CPE CHD 90% (±):meso = 3:2a [134]
84f MeCN, LiClO4, 1 M AcOH, Hg-cath., div. cell, CPE CHD 93%b [138]
85a MeCN, LiClO4, 1 M AcOH, Hg-cath., div. cell, CPE LHD 87%b [138]
85b DMF, LiClO4, 1 M AcOH, Hg-cath., div. cell, CPE CHD 60%b [138]
85b MeCN, LiClO4, 1 M AcOH, Hg-cath., div. cell, CPE CHD 75%b [138]
85c DMF, Bu4NI, 1 M AcOH, Hg-cath., div. cell, CPE CHD 70%,b 2 F prod. 15% [138]
85d DMF, Bu4NI, 1 M AcOH, Hg-cath., div. cell, CPE CHD 70%,b 2 F prod. 20% [138]
85e DMF, Bu4NI, 1 M AcOH, Hg-cath., div. cell, CPE CHD 64%,b 2 F prod. 15% [138]
87a DMF/H2O, Et4NOTs, Hg-cath., div. cell, CCE LHD 90%a [2]
87e DMF/H2O, Et4NOTs, Hg-cath., div. cell, CCE LHD 45%a [2]
87a MeOH, NaI, GC-cath., undiv. cell, CCE, 60°C 88a 73% trans/cis = 1.35 [137]
87b MeOH, NaI, GC-cath., undiv. cell, CCE, 60°C 88b 69% trans/cis = 1.30 [137]
87c MeOH, NaI, GC-cath., undiv. cell, CCE, 60°C 88c 58% trans/cis = 1.23 [137]
87d MeOH, NaI, GC-cath., undiv. cell, CCE, 60°C 88d 52% trans/cis = 1.17 [137]
87e MeOH, NaI, GC-cath., undiv. cell, CCE, 60°C 88e 56% trans/cis = 3.00 [137]
a Based on current passed.

b Stereochemistry not reported.
RR and the RS mechanism as a possible explanation although not all the experimental data are
in accord with the suggestion [136].
Reduction of alkylidene malonates, 87, in MeOH in an undivided cell using alkali metal
halides as supporting electrolytes results in the unusual formation of 3,4-disubstituted
1,1,2,2-cyclobutanetetracarboxylates, 88 [137]. Cyclobutane formation requires 4–7 F and is
not a radical anion catalyzed cycloaddition. The process was explained by the mechanism in
Scheme 17.11, where the cyclization takes place by chemical oxidation of the dianion of the
LHD by anodically formed halogen. The LHD, 89, was formed initially as determined by inter-
ruption of the electrolysis after the passage of 2 F. The yield of 88 decreased when the size of
R increased (Table 17.12), and the trans isomer was formed in slight excess. Electrolysis using
NaClO 4 as supporting electrolyte gave only the LHD, 89, with a (±):meso ratio close to one.
Hydrogenation, addition of MeOH to the double bond, and oxidative rearrangement of the sub-
strate were found to be side reactions [137].
COOMe
R – a: R = Me
R COOMe MeOH, Nal COOMe
2 b: R = Et
COOMe CCE, Undiv. cell COOMe c: R = Pr
R – d: R = heptyl
87
COOMe l2 e: R = Ph
COOMe H+ COOMe
–2l– R
R COOMe
COOMe COOMe
COOMe R COOMe
R
COOMe 88
89
SchEME 17.11 Reversible dimerization of radical anions generated from α,α-diactivated alkenes.
The derivatives of Meldrum’s acid, 86a,b, undergo reductive dimerization in MeCN, and the
mechanism has been studied [132,139]. An RS mechanism with rate-determining electron transfer
has been invoked either as the only mechanism (for 86b) or as one of two parallel reaction pathways
(for 86a) in order to explain the apparent reaction orders found by DCV or LSV in the presence of
AcOH [132]. However, AcOH (pK(AcOH) = 12.3 in DMSO [140]) is not likely to be strong enough
to protonate the dimer dianion, since the basicity of the dimer dianion is expected to be close to that
of the conjugate base of Meldrum’s acid (pK(Meldrum’s acid) = 7.3 in DMSO [141]). Consequently,
the dimerization may be reversible, and this, in turn, may lead to anomalous apparent reaction
orders although the coupling is of the RR type [71].
D. HYDroDIMErIZaTIoN oF CO2
Carbon–oxygen and carbon–nitrogen multiple bond functionality may undergo electrochemical
reduction resulting in carbon–carbon bond formation. This category includes aldehydes, ketones,
azomethines, esters, and other carboxylic derivatives all of which are covered in other chapters.
Carbon dioxide, O=C=O, is difficult to place within the categories referred to. However, its impor-
tance as a feedstock for C-1 chemistry, together with the environmental benefit to be gained by
discovering ways to convert it into useful products, suggests that attempts at electrochemical con-
version should be outlined.
Direct reduction of CO2 takes place at rather low potentials (<−2.2 V in aprotic medium) and
normally leads to mixtures of the C–C-coupling product, oxalate, and CO + CO32− when carried out
in aprotic solvents at electrodes such as Hg or Pb (Scheme 17.12a). Monomeric products dominate
when the reduction is carried out at electrodes at which either CO2 or the reduction products are
chemisorbed. Numerous attempts have been made to catalyze the reduction and optimize the yield
of oxalate.
For direct reduction at constant current in DMF (Bu4NClO4) at a Hg cathode, it was found that
low CO2 concentrations and high temperatures favored formation of oxalate vis-à-vis CO + CO32
[142]. Indirect reduction of CO2 using radical anions derived from aromatic esters and nitriles [143]
in anhydrous DMF leads exclusively to formation of oxalate (Scheme 17.12b). Based on these two
sets of experiments, it is proposed that oxalate formation takes place via the coupling of two radical
anions in solution (with a second-order rate constant around 5 ⋅ 108 M−1 s−1), whereas the formation
of CO + CO32− takes place via the two first reactions in Scheme 17.12a.
It is likely that the catalysts react via bond formation followed by homolytic bond cleavage lead-
ing to the CO2− • and the neutral catalyst precursor [143] (Scheme 17.12b). For other types of organic
radical anions, the reaction with CO2 may lead to carboxylation rather than to electron transfer (see
Section IV.A.1).
The electrochemical conversion of CO2 into hydrocarbon fuels is another goal that has been
pursued vigorously since the discovery [144] that ethene, together with methane, could be pro-
duced at up to 69% current efficiency at 5–10 mA cm−2 at a copper foil cathode in an aqueous
O O–
CO2– + CO2 O O– O C
O O– CO2 + Ar C Ar C
O OR O
CO2– or e– OR
O CO + CO2–
3 O–
O O– O C O
Ar C CO2– + Ar C
O
OR OR
2CO2– –OOC COO–

(a) (b)
SchEME 17.12 C-1-Chemistry involving carbon dioxide radical anion. Reduction pathways (a) and (b) are
discussed in the text.
O
CO2 O – CO2 – 1/2 Ph3SiH
O2 e – O
O Et4N+ O O
O2 O O Et4N+ Ph3SiCO2(NEt4)
CH3CN/Et4NClO4 25°C –
O O (Et N) C O
4 2 2 6
SchEME 17.13 Coupling between dioxygen radical anion and carbon dioxide.
electrolyte. The substantial body of mechanistic work arising from this discovery has been thor-
oughly reviewed [145–147], but seemingly a greater understanding of mechanism has had little
practical outcome.
Carbon dioxide couples with the dioxygen radical-anion, in a two-step process in acetonitrile
to form the peroxydicarbonate dianion ((Et4N)2C2O6 in Scheme 17.13). This appears to be strongly
basic under otherwise mild conditions and is effective as an electrogenerated base [148], potentially
useful in promoting organic reactions (see Chapter 43). Additionally, it has some utility in the prepa-
ration [149] of organosilicon intermediates (Scheme 17.13).
The possibility of using microbes as mediators in the electrochemical conversion of CO2 into
multicarbon compounds has been established [150]. Graphite cathodes, on which biofilms of the
microbe S. Ovata had been grown, facilitated the reduction of CO2 into acetate (and small amounts
of 2-oxobutyrate). Current efficiency appears to be 86% ± 21%(!).
III. MixED HYDROcOUPLiNG Of AcTivATED ALkENES

A. INTErMoLECULar MIXED HYDroCoUpLINGS
Co-electrolysis of different activated alkenes may lead to cross-coupling and formation of the mixed
hydrocoupling product (MHC) (Equation 17.11). Only cross-couplings where a simple activated
alkene (acrylonitrile, 11, or, e.g., methyl acrylate, 16a) is one of the substrates have been studied
systematically [4,30,102,151,152].
R1 R1
EWG1 R3 EWG2
+ 2e–, 2H+ R2 EWG1
R2 R4 (17.11)
R3 EWG2
R4
The MHCs are normally additional to the two LHDs formed by homocoupling. Mechanistic
studies on cross-couplings are scant and inconclusive. The two main mechanistic proposals are (1)
Michael addition of the radical anion (or dianion) of the more easily reduced substrate to the other,
neutral substrate and (2) coupling between the two types of radical anions. In preparative work, it
has been found that (a) the relative yield of the MHC increases at potentials where both substrates
are reduced [151,152]; (b) in controlled potential electrolysis at a mercury pool cathode, the potential
distribution is significantly nonuniform [152]; and (c) for reduction at the potential of the most eas-
ily reduced alkene, the yield of the MHC depends on the difference in reduction potentials and on
the relative concentrations, being favored by small differences and an excess of the more difficultly
reduced substrate. Under the latter conditions, formation of the LHD of the less-activated alkene is
suppressed.
These findings, together with those of more general mechanistic work on homocoupling of acti-
vated alkenes, indicate that the most likely pathway for MHC formation is coupling between the two
different radical anions. The beneficial effect of a small difference in reduction potentials is consis-
tent with electron transfer to the less-activated alkene either directly at the cathode or by electron
transfer in solution from the other radical anion. Similarly, formation of an adequate concentration
of the radical anion of the less-activated alkene is favored by the use of this alkene in excess.
Obviously, the relative magnitudes of the rate constants for the two LHD reactions and of that for
the cross-coupling of the two different radical anions will affect the efficiency of MHC production.
Even for equal concentrations of the two radical anions, the three individual rate constants must be
similar to result in the statistical distribution of MHC and LHD products.
1. Couplings with Acrylonitrile

Reduction of 11 takes place at ca. −1.9 V. Thus, 11 is normally the component that is most difficult
to reduce and used in excess or even as solvent (Table 17.13). In a few cases, mixed coupling of
11 with less-activated alkenes (hydrocarbons) has been attempted (Table 17.13). In most cases,
hydrogenation (2 F) of one or both of the alkenes takes place in addition to coupling, analogous to
results from attempted homocoupling of poorly activated alkenes. For some substrates, the prod-
uct of mixed coupling with 11 contains two or more acrylonitrile units, for example, Equation
17.12 [30], probably formed by Michael addition of relatively stable anionic intermediates to
acrylonitrile.
Ph NC CN
CN Ph
+ 2 DMF/H2O, Me3BuNOTs
76%
(17.12)
Ew = –1.5 to –1.64 V
1 : 10
One of the few mechanistic studies of mixed coupling reactions involves the reduction of
dimethyl fumarate, 79b, or diethyl maleate, 80a, in the presence of the less easily reduced com-
pounds 11 or cinnamonitrile, 13 [153]. In anhydrous DMF (Bu4NI), the individual rate constants
for dimerization of 79b− • and of 11− • are known (110 and 880 M−1 s−1, respectively; see Tables
17.10 and 17.3), that is, 11− • dimerizes faster than 79b− • by a factor of 8, and ΔE ½ = 0.41 V. With
a twofold excess of 11, RRDE experiments at potentials where only 79b is reduced indicated that
the normal RR homocoupling of 79b− • took place with a second-order rate constant identical to
that measured in the absence of 11. RRDE experiments at a potential where both substrates are
reduced revealed that electron transfer from 11− • to unreduced 79b was the major reaction of 11− •
[153]. No product studies were reported for mixed coupling of 79b with 11. For 11 and 79b, ΔE ½
>0.4 V, and direct formation of the dianion of 70b takes place before the reduction of 11. Even in
the presence of ≈50-fold excess of 11, the perturbation of the RRDE and CV response of 79b is
modest at the potential where 79b− • is formed, giving rise only to a slight increase in the rate of
disappearance of 79b− • [153].
The voltammogram of diethyl maleate, 80a, is, unlike that of 79b, significantly altered in the
presence of a 50-fold excess of 11. The reduction potentials of the maleates are shifted approxi-
mately 0.3 V cathodic relative to the reduction potentials of the fumarates (see Section II.C.1)
[153], and electron transfer from 80a − • to 11 is therefore expected to be faster than from 79b − •.
However, dimerization of 80a− • is much faster than of 79b − • (see Section II.C.1), and since
the presence of 11 affects the voltammogram of 80a, reaction between 80a− • and11 must also
be fast.
Co-electrolysis of equal amounts of 11 and α-methyleneglutaronitrile, 12b, (11 and 12b are
reduced at about the same potential) gives a mixture of the three products (the two LHDs and the
MHC) in relative amounts corresponding to random coupling of the radical anions [56]. In this
case, the two components are structurally similar, suggesting that the individual dimerization rate
constants may also be similar. The alkylidenemalonitriles, 85, which are all reduced around −1.7 V,
gave modest amounts of the MHC when co-electrolyzed with a twofold excess of 11 (Table 17.13),
the yield decreasing with increasing size of R2.
TABLE 17.13
Mixed Hydrocouplings with Acrylonitrile, 11, and Ethyl Acrylate, 16d
Substrate Csubstrate/CX Conditions Products and Yields References
X = 11
Hydrocarbons
Ph-CH=CH2 (≈ −2.4 V) 3:1a DMF, 2.5% H2O, MHC 48%,b LHD of 11, 2 F of [151]
Et4NOTs, div. cell, Ph-CH=CH2 (major)
Ew = −2.45 V
Ph2C=CH2 (≈ −2.2 V) 3:1a DMF/H2O, Et4NOTs, MHC (major), LHD of 11, LHD [151]
div. cell, Ew = −2.30 of Ph2C=CH2, 2 F of 11
V
Nitriles
CH2=C(CN)CH2CH2CN 1:1 DMF/H2O, MHC, LHD of 11, LHD of 12b [56]
(12b) MeEt3NOTs (statistical distribution)
NCCH=CHCH2CH2CN 1:1 H2O, K2HPO4, MHC 54%c [163]
(≈ −1.9 V) div.cell, CCE
CH2=CHCH=CHCN (−1.5 1:6 H2O, Et4NOTs, MHC 57%d,e [164]
V) Ew = −1.71 V
85a,e–i (≈ −1.7 V) 1:2 H2O, K2HPO4, pH MHC: 85a 24%, 85f 19%, 85g [165]
5–6, div. cell, Pb 13%, 85h 14%, 85i 6%, 85e
cath. 21%c
Esters
CH2=CHCOOMe (16a) 1.8:1 H2O, K2HPO4, pH MHC 50%, LHD of 16a 2.5%, [166]
6–8, undiv. cell, LHD of 11 15.5%c
graphite cath., CCE
CH2=CHCOOEt (16d) 1:5 H2O, Et4NOTs, MHC 60%,d LHD of 11 [167]
(≈ −1.8 V) Ew = −1.8 V
16d (≈ −1.8 V) 1:1 DMF/H2O, MHC, LHD of 11 major, LHD [164]
MeEt3NOTs, of CH2=CHCOOEt minor
Ew = −1.83 to
−1.85 V
CH2=(COOEt)(NHCOMe) 1:10 H2O, Et4NOTs, MHC 30%,d LHD of 11 [164]
Ew = −1.75 V
trans-EtOOCCH=CHCOOEt f H2O, Et4NOTsg MHC [4]
(79a) (−1.54 V)
cis-EtOOCCH=CHCOOEt 1:>10h DMF/H2O, Et4NOTs, MHC, LHD of 80a minor, LHD [152]
(80a) Ew = −1.5 Vg of 11, 2 F of 80a major
80a (≈ −1.4 V) 1:2 DMF/H2O, MHC 11%, LHD of 80a 80%d [164]
Et4NOSO2Ph,
Ew = −1.3 to −1.4 Vg
Ketones
CH2=CHCOMe (39a) f H2O, Et4NOTs MHC minor, CHD of 39a, LHD [152]
of 11
Me2C=CHCOMe (39b) 1:10 Et4NOTs, H2O, MHC major [102]
Ew = −1.65 to −1.7 V
PhCH=CHCOMe (40a) 1:8 Et4NOTs, Ew = −1.43 MHC small amount, LHD of [102]
to −1.5 Vg 40a major
Difunctional
trans-NCCH=CHCOOEt 1:>20 DMF/H2O, Et4NOTs, MHC, LHD of [152]
Ew = −1.5 Vg NCCH=CHCOOEt major, 2 F
of NCCH=CHCOOEt
(Continued)
TABLE 17.13 (Continued)

Mixed Hydrocouplings with Acrylonitrile, 11, and Ethyl Acrylate, 16d
Substrate Csubstrate/CX Conditions Products and Yields References
trans-NCCH=CHCOOEt f H2O, Et4NOTsg MHC trace [4]
(−1.45 V)
trans- f H2O, Et4NOTsg MHC 50%,d,i LHD of [4]
Me2NCOCH=CHCOOEt Me2NCOCH=CHCOOEt, 2 F
(−1.76 V) of Me2NCOCH=CHCOOEt
X = 16d
9-benzylidenfluorene (6) 1:10 DMF, H2O, MHC <20%,k 2 F of 6 [30]
Me3BuNOTs,
Ew = −1.5 to −1.0 Vj
NCCH=CHCH2CH2CN 1:2l H2O, K2HPO4, div. MHC [163]
(≈ −1.9 V) cell, CCE
CH2=CHCH=CHCN 1:8 MeCN, H2O, MHCm [164]
(−1.5 V) Et4NOTs, Ew = −1.67
to −1.70 V
85a,e-i (≈ −1.7 V) 1:2n H2O, K2HPO4, pH MHC: 85a 19%, 85f 15%, 85g [165]
5–6, div. cell, Pb 8%, 85h 8%, 85i 2%, 85e 13%k
cath.
cis-EtOOCCH=CHCOOEt 1:>10n DMF, H2O, Et4NOTs, MHC, LHD of 80a minor, 2 F of [152]
(80a) Ew = −1.5 Vj 80a major, 2 F of 16d
2 F indicates the 2 F reduction product.

a 11 added gradually.
b 5-phenylpentannitrile and 4-phenylpentannitrile (15:1), yield based on 11.
c Yield based on current.
d Based on substrate.
e 1,6-dicyanohexane isolated after catalytic hydrogenation, that is, product derived from coupling in δ-position.
f 11 as solvent, substrate added slowly during electrolysis.
g AcOH added during electrolysis to keep medium acidity constant.
h Substrate added slowly during electrolysis.
i Coupling α to COOEt/coupling α to CONMe (1:2).

2
j AcOH added during electrolysis to keep medium acidity constant.
k Based on substrate.
l Methyl acrylate was used instead of ethyl acrylate.
m The product derived from coupling in δ-position was isolated after catalytic hydrogenation (in small amounts).
n Substrate added slowly during electrolysis.
2. Couplings with Alkyl Acrylate and Crotonate

Simple alkyl acrylates have been used as partner in mixed hydrocoupling reactions in a number of
cases (Table 17.13). Like mixed couplings with 11, LHD formation and hydrogenation compete with
formation of the MHC of alkyl acrylates. Co-electrolysis of ethyl 3,4-dimethoxycinnamate (E½ =
−1.94 V) with ethyl crotonate (E½ = −2.37 V) in a molar ratio of 1:7.2 in MeCN at Ew = −2.03 V gave
none of the MHC but only the CHD of the cinnamate. The only product derived from the croton-
ate was diethyl 2-ethylidene-3-methylglutarate (49%) formed by action of an EGB, most likely the
dimer dianion of the cinnamate [62].
3. Other Intermolecular Mixed Hydrocouplings

Reduction of diethyl fumarate, 79a, and the simple enone 39a (1:10) in MeCN/water (Et4NOTs) at a
potential between the two reduction potentials (ΔE ≈ 0.2 V) gave the MHC as the major product [102].
Reduction of dibutyl maleate 80c, and 2-vinylpyridine, 10a (1:5), in DMF/water (Et4NOTs) at a

potential where only the maleate is reduced (ΔE ≈ 0.15 V) leads to a mixture of the two LHDs and
the MHC. Analogous results were found for co-electrolysis of 4-vinylpyridine, 10b, with an excess
of the simple enone, 39a (ΔE ≈ 0.1 V) [34]. The distribution between the different hydrodimers was
reported.
R2
4
R1 3
2 a: R1 = R2 = R3 = H
1 b: R1 = R2 = R3 = M
R3
90
Mixed hydrocoupling, in DMF, between simple 1,3-dienes, 90 (R1, R 2 , R 3 = H, Me), and

alkenes activated by ester or keto groups has been attempted [154]. Yields of the MHC are usu-
ally poor (0–58%), the LHD of the activated alkene predominating. Again, yields of the MHC
increase as the difference between the reduction potentials of the two components decreases,
for example, no MHC was formed when ethyl 3,3-diphenylacrylate (Ph 2C = CHCO2Et; −1.70 V)
or 40b (−1.89 V) was co-electrolyzed with butadiene, 90a (−2.66 V), or if cyclopentadiene
(< −2.8 V) was co-electrolyzed with ethyl 3-methylcrotonate, 16b (Me2C=CHCO2Et; −2.46 V).
The only combination giving reasonable yield (58%) of the MHC was co-electrolysis of 90a
with 16b (−2.46 V) [154]. This indicates that electron transfer in solution is required for mixed
coupling.
B. INTraMoLECULar MIXED HYDroCoUpLINGS

Intramolecular mixed hydrocoupling was achieved for the system displayed in Equation 17.13
(dimethyl malonate added as a proton donor). Two stereoisomeric tricyclic products (1:1) were
obtained (90% with EWG = COOMe and 23% with EWG = CN). For EWG = CN, higher yields and
higher stereoselectivity were obtained using as supporting electrolyte LiClO4 (77% yield with 3:1
ratio of isomers) or Mg(ClO4)2 (62%, 11.4:1). The stereoselectivity is probably due to chelation of the
metal cation with the carbonyl oxygen of the lactone and one of the cyano nitrogens, which favors
the two functions being on the same face of the new ring [155]. Reduction of the monoester and of
the mononitrile under identical conditions gives hydrogenation of the double bond of the lactone
unit and no cyclization. This indicates that the α,β-unsaturated lactone is more easily reduced than
the α,β-unsaturated monoester/mononitrile. The α,β-unsaturated dinitrile and diester are the elec-
trophores in the cases where cyclization was achieved.
EWG
EWG EWG EWG EWG
EWG O O
MeCN, CH2(COOMe)2
+
O Bu4NBr, CPE, Hg cathode O O (17.13)
H H
O
EWG = COOMe, CN
O O O
MeCN, CH2(COOEt)2 O
MeOOC +
O CPE, Hg cathode MeOOC (17.14)
MeOOC
O
1 : 1
Total yield 35–41%
Under similar conditions, reduction of an α,β-unsaturated lactone linked to a linear α,β-

unsaturated ester gave modest yields of two isomeric spirolactones (Equation 17.14). CV of simple
monofunctional compounds indicates that in this case the α,β-unsaturated ester function is the elec-
trophore [156]. The regioselective coupling (β- to the ester group) and the presence of a proton donor
(diethyl malonate) indicates that the probable reaction pathway is α-protonation of the radical anion,
further reduction and Michael addition of the resulting β-anion to the lactone.
The analogous α,β,γ,δ-unsaturated ester, on the other hand, did not undergo cyclization under
these conditions [156], whereas the methyl ester of abscisic acid (Equation 17.15), which also
c ontains an α,β-γ,δ-unsaturated ester function, undergoes cyclization upon reduction in MeCN
(containing AcOH) [157].
OH OH
MeCN, AcOH
51%
COOMe CPE, Hg cathode (17.15)
O
O
COOMe
Mixture of stereoisomers
Cyclic voltammetry of monofunctional model compounds indicated that the unsaturated ester
functionality is the one most easily reduced in the case of Equation 17.15. In the absence of the OH
group, coupling was not observed [157] since enolization of the enone to the enol with conjugation
of the four double bonds with the ester group takes place.
IV. REDUcTivE COUPLiNG Of ALkENES wiTh OThER TYPES Of SUBSTRATES

A. INTErMoLECULar REDUCTIVE CoUpLING oF ALkENES wITH OTHEr TYpES oF SUbSTraTES
1. Coupling with CO2
Radical anions derived from α,β-diactivated alkenes such as dialkyl maleates, 80, react with CO2,
and at high CO2 concentrations this process effectively competes with LHD formation [158,159].
Experimentally CV of 80b still shows a one-electron reduction peak in the presence of CO2 but higher
scan rates are required to detect the radical anion on the reverse scan than in the absence of CO2. At
the same time, a new reduction peak appears approximately 200 mV cathodic of the original reduc-
tion peak [160]. Preparative scale co-electrolysis of 80b and CO2 at the potential of the first reduction
peak gave the dicarboxylated dimer, 91, whereas electrolysis at the potential of the “new” peak gave
the dicarboxylated monomer, 92, in a 2 F process [160–162]. This can be interpreted according to the
mechanism in Scheme 17.14, that is, the initially generated 80b− • adds rapidly to CO2 forming a dis-
tonic radical anion that is not reduced at the potential of the initial reduction. The distonic radical anion
then dimerizes leading to the dianionic dicarboxylated dimer (which can be isolated after alkylation).
Electron transfer between 53b− • and CO2 is too slow to be important because of the large differ-
ence (>0.4 V) between the reductions potentials of 53b and CO2. The mechanism in Scheme 17.14
seems to be general for α,β-diactivated alkenes in their reaction with CO2 [158].
The kinetics of the reaction between the radical anions of fumarates, 79a–c, and maleates,
80a–c, with CO2 in DMF (Bu4NI) has been studied by RRDE [159]. Reaction between the radical
anion and CO2 prior to dimerization was confirmed for 80a by preparative and electroanalytical
experiments at different substrate concentrations [162]. The radical anions 80− • reacted with CO2
20–50 times faster than did the analogous species 79− • for which the pseudo-first-order rate con-
stants were determined to be in the range 0.35–1.5 s−1 [159].
Reduction of ethyl cinnamate in the presence of CO2 leads to the formation [168] of mono- and
dicarboxyated adducts, 93–95. The overall yield and product distribution was found to be depen-
dent upon the choice of electrode, potential, concentration of starting material, and temperature.
The highest efficiency was achieved using a Ni cathode and a sacrificial Mg anode at a temperature
–
EWG –O EWG
2C
+ CO2
EWG EWG
–O C EWG
–O2C 2
EWG EWG
2
EWG
EWG
EWG CO2–
91
–O2C EWG –O
e– 2C EWG CO2
–O
2C EWG
EWG 2 Peak –
EWG EWG CO2–
92
SchEME 17.14 Reductive carboxylation with coupling.
of −10°C and a 0.1 M concentration of ethyl cinnamate. In contrast, a poor overall yield (30%) was
obtained using a graphite electrode
– –
–1.7 V, Ni cathode, Mg anode, CH3CN, CO2Et CO2 CO2
CO2Et 0.1 M Et4NBF4, 0.1 M substrate, –10°C Ph + +
Ph – CO2Et CO2Et
CO2 Ph Ph
+CO2 (78%; 73:10:17 = ratio of 93:94:95) –
CO2
93 94 95
Alkyl cinnamates, 15, are more easily reduced than CO2 by ≈0.4 V. Reduction of 15 in DMF
(containing water) changes from a 1 F to a 2 F process in the presence of CO2. The radical anions
react much faster than in the absence of CO2, and much faster than can be accounted for by elec-
tron transfer to CO2 [158]. On a preparative scale, the isolated products are mainly β-carboxylated
monomer (see 94), together with the hydrogenation product. From methyl cinnamate, 15b, at low
water concentrations, small amounts of the dicarboxylated monomer, 95, are also formed (Table
17.14), whereas with increasing water concentration, the amount of hydrogenation product increases
at the expense of the β-carboxylated monomer [158]. This indicates that the H2O + CO2 equilibrium
increases the acidity of the medium sufficiently for protonation of the radical anion to compete with
both dimerization and nucleophilic addition to CO2. β-Carboxylation (rather than the expected α-)
can be rationalized by assuming that the neutral radical arising from α-protonation of the radical
anion is more easily reduced than the substrate [71], and the resulting β-carbanion adds to CO2 in
competition with further protonation (Scheme 17.15), R = Ar.
Like the reduction of ethyl cinnamate, the reduction of cinnamonitrile in the presence of CO2
leads to the formation of mono- and dicarboxyated adducts, 96–98. Once again, the overall yield
and product distribution was found to be dependent upon the choice of electrode, potential, concen-
tration of starting material, and temperature. The optimal combined yield is achieved [169] using
a Ni cathode, Mg anode, a potential of −1.75 V (vs. Ag/AgI), and substrate concentrations in the
range of 50–200 mM. In keeping with the fact that the solubility of CO2 increases as temperature
decreases, the overall yield improves from ca. 75 to 85% as the reaction temperature is decreased
from 15 to 0°C.
– –
–1.75 V, Ni cathode, Mg anode, CH3CN, CN CO2 CO2
CN 0.1 M Et4NBF4, 100 mM substrate, 0°C Ph + + CN
Ph – CN
CO2 Ph Ph
+ CO2 (85%; 38:8:54 = ratio of 96:97:98)
96 97 98 CO2
TABLE 17.14
Reductive Coupling of Alkenes and Alkynes with CO2a
Substrateb Conditions Products and Yields References
E-PhCH=CHPh DMF, Bu4NI, CCE 92 (meso) 92% [29]
CH2=CHCN (11) (−2.14 V) MeCN, Et4NOTs, CPEc 91 41%d [160]
7 CH3CH2CN, Bu4NBF4, 2.8 M H2O, see 94 50%d [160]
CCE
7 MeCN, Et4NOTs, CCEc see 91 41%d [161]
E-PhCH=CHCN (13) (−1.78 V)e DMF, Et4NClO4, H2O see 94, 2 F of 11, 91. [158]
No yields given
CH2=C(Me)CN (12c) (−2.31 V) MeCN, Et4NOTs, CCEc see 91 28%d [160]
E-PhCH=CHCOOMe (15b) DMF, Et4NClO4, H2O (0.056–2.78 M) see 94 25–70%, 2 F of 15b [158]
(−1.78 V)e 20–65%, 91 <10%f,g
E-PhCH=CHCOOEt (15a) (−1.80)e DMF, Et4NClO4, H2O (0.056–2.78 M) see 94 30–40%, 2 F of 15b [158]
5–50% (see section IV.A.1)f
CH2=CHCOOMe (16a) (−2.10 V) MeCN, Et4NOTs, CPEc see 911%d [160]
16a MeCN, Et4NOTs, CCEc see 91 52%d [161]
16a MeCN, Et4NOTs, CCEh see 92 47%, 67 8%d [162]
CH2=C(Me)COOMe (−2.27 V) MeCN, Et4NOTs, CCEc see 91 42%d [160]
MeCH=CHCOOMe (−2.48 V) MeCN, Et4NOTs, CCEc see 91 38%d [160]
MeOCH=CHCOOMe (−2.67 V) MeCN, Et4NOTs, CCEc see 91 10%d [160]
Z-MeOOCCH=CHCOOMe (80b) MeCN, Et4NOTs, CPE (new peak)c see 94 31%d [160,161]
(−1.53 V)
80b MeCN, Et4NOTs, CPE (first peak)c see 93 46%d [161,162]
CH2=CHCOMe (38a) (−1.91 V) MeCN, Et4NOTs, CPEc see 95 22%, 91 16%d [160]
39a (−1.91 V) MeCN, Et4NOTs, CPEc see 95 22%d [161]
[MeOOCCH=CH]2(CH2)2 MeCN, Et4NOTs, CPE 72%i [162]
[MeOOCCH=CH]2(CH2)3 MeCN/H2O, Et4NOTs, CPE 100%j [162]
[MeOOCCH=CH]2(CH2)4 MeCN/H2O, Et4NOTs, CPE 80%k [162]
H-Cα≡Cβ-Pr DMF, Bu4NBF4, 0.1 eq. Ni(bpy)3(BF4)2l Cα: 7%, Cβ: 59%m [173]
Pr-C≡C-Pr DMF, Bu4NBF4, 0.1 eq. Ni(bpy)3(BF4)2l 93%m [173]
H-Cα≡Cβ-Ph DMF, Bu4NBF4, 0.1 eq. Ni(bpy)3(BF4)2l Cα: 16%, Cβ: 39%m [173]
Me-Cα≡Cβ-Ph DMF, Bu4NBF4, 0.1 eq. Ni(bpy)3(BF4)2l Cα: 45%, Cβ: 27%m [173]
Ph-C≡C-Ph DMF, Bu4NBF4, 0.1 eq. Ni(bpy)3(BF4)2l 70%m [173]
a Solvent saturated with CO2.
b E½ vs. SCE.
c Alkene added dropwise.
d Current yield.
e Eo vs. SCE.
f Chemical yield.
g More 92 formed at low water concentration; (see section IV.A.1).
h High alkene concentration (1.32 M), low current, electrolysis run to 20% conversion, that is, alkene concentration >0 at
electrode surface.
i Product: lower yield in MeCN/H2O
j Product: lower yield in MeCN/H2O
k Product: only 7% yield in MeCN
l Undiv. cell, Mg-anode, Ew = −1.2 V.
m Carboxylation at α- or β-carbon as indicated; see Equations 17.19 and 17.20.
MeOOC COOMe MeOOC COOMe

MeOOC COOMe
COOMe
COOMe COOMe
COOMe
COOMe
COOMe
Proton donor present (H2O+CO2) Proton donor absent (–H2O), R = Ar

– EWG – EWG
EWG + H+ EWG + CO2
R
R
–
R CO–2
– R EWG
EWG EWG – EWG + EWG
+ EWG – EWG + EWG
R
+
CO–2 R
R R R CO–2 R
R R EWG –O C EWG
EWG – + CO2 2
– –O C EWG R CO–2
+ CO2 2 R CO–2
R R 95 92
EWG EWG
– + H +
R R Proton donor absent (–H2O), R = H, or R = alkyl
– EWG
EWG + CO2 + CO2–
Proton donor absent (–H2O), high substrate conc. R R
EWG
– R EWG EWG – + CO– EWG
2 – – 2 – –
R O2C
R EWG R –
R EWG O2C EWG
R EWG R EWG – – + CO
–
2 CO2 O C
–
2
OC
2
2 R CO–2
– CO2– 92
EWG R EWG R
99
SchEME 17.15 The fate of radical anions generated from activated alkenes: protic, aprotic and CO2 condi-
tions for follow up reactions.
Much smaller potential differences (<0.2 V) between alkene and CO2 reduction are found
for monoactivated alkenes such as acrylonitrile, 11, or methyl acrylate, 16a, and the electron
transfer pathway is expected to be significant. For ethyl acrylate, 16d, reduction in DMF under
very dry conditions is a catalytic process in the presence of CO2, the height of the reduction peak
increasing approximately threefold [158,170]. In DMF or MeCN containing residual water, the
height of the peak corresponding to reduction of the acrylate only doubles when a relatively high
concentration of CO2 is introduced, corresponding to a transition from a 1 to 2 F process [158].
Preparative scale reduction gives predominantly the α,β-dicarboxylated monomer, 92, when car-
ried out with a large excess of CO2 (see Table 17.14). The most plausible mechanism is outlined
in Scheme 17.15, R = H or R = alkyl, that is, initial electron transfer from the acrylate radical
anion to CO2, coupling of CO2− • with an acrylate radical anion in the normal β-position with
formation of a distonic dianion that from the α-position adds to CO2. Further evidence for CO2− •
formation is that oxalic acid derivatives are side products [160] (see Section II.D). At high acry-
late concentrations, homocoupling is favored over coupling with CO2− •, and the major product
is the dicarboxylated dimer, 99, probably formed as outlined in Scheme 17.15. In the presence
of water (2.8 M), 7 behaves similarly to 12 when reduced in the presence of CO2 and gives the
β-carboxylated monomer [160].
Bis(activated alkenes) such as 58a have been reduced in the presence of CO2, and the extent to
which intramolecular coupling takes place was shown to depend on the length of the link and on the
medium [162] (Table 17.14). In this case, electron transfer from the radical anion of the substrate to
CO2 is also possible.
For alkenes more difficult to reduce than CO2, for example, butadiene, 90a, electron transfer
from CO2− • to the alkene may be involved. Cross-coupling of CO2 and 90a in MeCN has been
carried out in an undivided flow cell at constant current. Using Et4N+ salts of formate or oxalate
as supporting electrolyte the anode process is formation of CO2 and H+ which are both consumed
in the cathode process [171]. The outcome (up to 63% total yield) was a mixture of isomers of C5,
C6, and C10 unsaturated carboxylic acids and diacids. The detailed mechanism is not known but
the products may arise from initial addition of CO2− • to the unreduced butadiene [171], although
electron transfer from CO2− • to 90a or direct reduction of 90a (present in large excess) cannot be
ruled out. Based on the observed influence of experimental parameters on the distribution of the
C5, C6, and C10 acid products, the authors suggest that the reactions take place between adsorbed
intermediates [171].
Reduction of ethene is so difficult that electron transfer from CO2− • is prohibited. Reduction of
mixtures of CO2 and ethene in DMF using sacrificial Al-anodes gives mixtures of aluminium salts of
mono- and dicarboxylates containing one to four ethylene units [172]. Alkynes and allenes undergo
carboxylation to a mixture of products in modest yields upon direct reduction in a divided cell. In
these cases, CO2 is the more easily reduced partner and for unactivated alkynes (Ered < −2.8 V)
electron transfer is unlikely to take place. Product selectivity and yields (up to 80%) are enhanced
using Ni-complexes with nitrogen-containing polydentate ligands as catalysts in an undivided cell
with sacrificial Mg-anodes (see [172] and refs. therein). For unactivated alkynes in DMF, the cou-
pling reaction takes place at −1.2 V in the presence of Ni(II)(bpy)32+, that is, at the potential of
Ni(0)(bpy)2 formation [173], but stoichiometric amounts of the Ni-complex are necessary, when the
reaction is carried out in a divided cell.
The metallacycle, 100, has been identified after electrolysis and the mono-carboxylated
alkene can be isolated after hydrolysis. Catalytic amounts of the Ni-complex are, however,
sufficient for reaction in an undivided cell using a sacrificial Mg-anode. Here the intermedi-
ate, 100, can be cleaved by Mg2+ to give the magnesium carboxylate, which is not reducible
under the reaction conditions. Subsequent hydrolysis yields the product of monocarboxylation
(60–80% based on the alkyne) (Equation 17.16). Cis addition of H and CO2 is preferred but
Ni(0) catalyzes the cis-trans isomerization, and under the catalytic conditions 15% of the trans
product was formed (see Table 17.14). For terminal alkynes, the ratio of the two possible car-
boxylation products was always in favor of the 2-carboxylated product (Equation 17.17), with
ratios up to (10:1) [173].
R1 R2
Red. Mg2+ ½ R1 R2
R1 R2 + CO2 Mg2+ (17.16)
Ni(0)(bpy)2 cathode bpy-Ni O COO– 2
100
1) Red., Mg anode
Ni(0)(bpy)2 cathode R R
H + CO2 + (17.17)
R
2) Hydrolysis HOOC COOH
Major Minor
2. Coupling with Aldehydes and Ketones

Reduction potentials of simple ketones depend strongly on pH in aqueous media (see Chapter 31)
due to preprotonation or preassociation of the ketone carbonyl group. In acidic conditions often used
for coupling with simple ketones (H2O, 20% H2SO4), reduction of the ketone is easier than reduction
of most monoactivated alkenes and leads directly to the neutral radical. Cross-coupling of alkenes
activated by carboxylic acid derivatives with ketones is often followed by lactone formation at low
pH (Equation 17.18). The yield of cross-coupling products, 101 and 102, decreases upon substitu-
tion at the β-position of the alkene (Table 17.15), and the current yield decreases at working poten-
tials where proton reduction becomes more important [174]. Alkenes without electron-withdrawing
groups, for example, butadiene and styrene, generally give poor yields of the coupling products
(Table 17.15).
When the reduction potential of the alkene is close to that of the (protonated) ketone, as is the
case for α,β-diactivated alkenes, hydrogenation of the alkene takes precedence (2 F) due to rapid
protonation of the alkene radical anion in the highly acidic medium [175] (Table 17.15). In neutral
aqueous solution, even monoactivated alkenes are more easily reduced than acetone, and LHD for-
mation and hydrogenation compete with cross-coupling [176] (see Table 17.15).
TABLE 17.15
Reductive Coupling
Examples of Reductive Coupling of Alkenes with Aldehydes and Ketones in (Acidic) Aqueous Medium
Alkene Aldehyde/Ketone R1-CO-R2R1 R2 Conditions Products and Yields References
CH2=CHCN (11) Me H H2SO4, H2O, div. cell, CCE, Hg cath. 102 12%, 101 6%, polymer of 7 a [181]
11 Me Meb H2SO4, H2O, div. cell, Ew = −1.2 V, Hg cath. 102 8%, 101 67%a [176,181]
11 Me Meb H2O, Et4NOTs, div. cell, Ew = −1.9 V, Hg cath. 102 12%, LHD of 7 39%, 2 F of 7 34%a [176]
11 Me Meb H2O, K2HPO4, pH 7–8, div. cell, graphite cath., CCE 102 48%, 101 (4%), 2 F of 7 [182]
11 Me Etc H2O, K2HPO4, pH 7–8, div. cell, graphite cath., CCE 101 35%, LHD of 7a [181,183]
11 Me hexyld H2SO4, H2O, MeOH, div. cell, Ew = −1.20V, Hg cath. 102 48%, 101 24%a [174]
11 –(CH2)4– H2O, K2HPO4, pH 7–8, div. cell, graphite cath., CCE 101 13%a [183]
CH2=C(Me)CN (12c) Me Meb H2O, K2HPO4, pH 7–8, div. cell, graphite cath., CCE 101 20%a [183]
NCCH=CHCH2CH2CN Me Mee 20% H2SO4, H2O, div. cell, CCE, Hg cath. 101 30%a [183]
CH2=CHCOOMe (16a) Me Meb H2O, K2HPO4, pH 7–8, div. cell, graphite cath., CCE 102 70%, LHD of 13aa [183]
16a Me Meb H2SO4, H2O, div. cell, Ew = −1.2 V, Hg cath. 102 40%, 101 28%a [181]
CH2=CHCOOEt (16d) Me Meb 20% H2SO4, H2O, undiv. cell, CCE, Hg cath. 102 95%f [175]
16d Me Etd H2SO4, H2O, MeOH, div. cell, Ew = −1.26 V, Hg cath. 102 80%a [174]
16d Me Prd H2SO4, H2O, MeOH, div. cell, Ew = −1.26 V, Hg cath. 102 70%a [174]
16d Me pentyld H2SO4, H2O, MeOH, div. cell, Ew = −1.26 V, Hg cath. 102 74%, 51%a,g [174]
16d Me hexyld H2SO4, H2O, MeOH, div. cell, Ew = −1.26 V, Hg cath. 102 47%, 42%a,g [174]
CH2=C(Me)COOMe Me Meb H2O, K2HPO4, pH 7–8, div. cell, graphite cath., CCE 102 19%a [183]
MeCH=CHCOOMe Me Meb H2O, 20% H2SO4, div. cell, CCE, Hg cath. 102 38%f [178]
(Continued )
665
666

Examples of Reductive Coupling of Alkenes with Aldehydes and Ketones in (Acidic) Aqueous Medium
Alkene Aldehyde/KetoneR1-CO-R2R1 R2 Conditions Products and Yields References
MeCH=CHCOOEt (16c) Me Meb 20% H2SO4, H2O, undiv. cell, CCE, Hg cath. 102 30%f [175]
Me2C=CHCOOEt (16b) Me Meb 20% H2SO4, H2O, undiv. cell, CCE, Hg cath. 102 trace [175]
E-PhCH=CHCOOEt (15a) Me Meb 20% H2SO4, H2O, undiv. cell, CCE, Hg cath. No coupling [175]
E-EtOOCCH=CHCOOEt (79a) Me Meb 20% H2SO4, H2O, undiv. cell, CCE, Hg cath. 102 21%,f,h 2 F of 79a [175]
Z-EtOOCCH=CHCOOEt (80a) Me Meb 20% H2SO4, H2O, undiv. cell, CCE, Hg cath. 102 59%,f,h 2 F of 80a [175]
MeCH=CHCOOH Me Meb 20% H2SO4, H2O, undiv. cell, CCE, Hg cath. 102 26%f [175]
CH2=CHCOOH Me Meb H2SO4, H2O, div. cell, Ew = −1.2 V, Hg cath. 102 51%a [181]
cis-HOOCCH=CHCOOH Me Meb 20% H2SO4, H2O, div. cell, Ew = −0.85 V, Hg cath. 102 2%, succinic acid 94%a [176]
CH2=CHPh Me Meb H2O, K2HPO4, pH 7–8, div. cell, graphite cath., CCE 101 8%a [183]
Butadiene (90a) Me Meb H2O, K2HPO4, pH 7–8, div. cell, graphite cath., CCE 2,7-dimethyl-2,7-octanediol 6%a,i [183]
a Yields based on current.

b In excess.
c Equal amounts of alkene and ketone.
d Ketone in 25 times excess.
e In two times excess.
f Chemical yield based on alkene.
g Yields depending on amount of material and working potential, lower yields obtained on larger scale.
h Distribution on products depend on water content and acidity: less water and more H2SO4 favors coupling; optimum yields given.
i Coupling of acetone to both terminal carbons.
R΄ R΄ R˝
EWG O EWG
+ H2O, 20% H2SO4 R1 + R1
R΄ R˝ R1 R2 Red. R˝ O (17.18)
R2 OH O
R2
EWG = COOR, CN 101 102
The mechanistic discussion has focused on whether the radical formed by reduction of the pre-
protonated ketone is the reactive species attacking the alkene or whether it is the anion formed by
further reduction, and data supporting both views have been presented [176–179].
In aprotic media, only unactivated alkenes are more difficult to reduce than dialkyl ketones.
Reduction of dialkyl ketones in DMF in the presence of unactivated terminal alkenes give
coupling at the terminal carbon atom (Equation 17.19) [180]. In similar conditions, conjugated
dienes also undergo regioselective reductive coupling with dialkyl ketones at the least substituted
carbon [180].
However, terminal disubstituted alkenes give much lower yields of the coupling product unless
one of the substituents is a trimethylsilyl group. In this case, the trimethylsilyl substituted tertiary
alcohol is obtained (ca. 70%) [184]. Unsaturated silanes are not reducible in DMF so the mecha-
nism is assumed to be attack of the radical anion of the ketone on the terminal carbon of the alkene
Equation 17.19. The silyl group may then stabilize the anion formed by further reduction of the
distonic radical anion [184].
R΄ O DMG, ET4NOTs
or DMF, Bu4NBF4 R1 R2 R΄
+
R1 R2
R˝ 2.5–3 F HO R˝ (17.19)
R˝ = H, SiMe3 50–80%

When the alkene is activated and undergoes reduction more easily than the ketone, cross-cou-
pling generally fails in DMF. However, addition of trimethylchlorosilane, Me3SiCl, to DMF facili-
tates reductive coupling of monoactivated alkenes with aliphatic aldehydes or dialkyl ketones. The
lactones, 102, are obtained in good chemical yields when the alkene is activated by an ester group
[185], Equation 17.20, but it is necessary to use a considerable excess of charge. For cyano-activated
alkenes, the coupling product is the hydroxy-nitrile, 101 (EWG = CN). The role of Me3SiCl is not
known but an intermediate of the type shown in Equation 17.20 has been suggested [185]. Addition
of Me3SiCl does not lead to cross-coupling if the reduction potentials are reversed as is the case
when aromatic aldehydes or aryl ketones are co-electrolyzed with monoactivated alkenes.
R΄ R˝
COOR O R΄ COOR
DMF, ET4NOTs R1 55–85%
+ R1 (17.20)
R΄ R˝ R˝ –Me3SiOR O
R1 R2 Me3SiCl, CCE, 6 F O
R2 OSiMe3 R2
102
Reduction of diaryl ketones in DMF in the presence of an excess of the less easily reduced enol
acetates gives cross-coupling products of the type 103. This involves coupling at the α-position
of the enol acetate (Equation 17.21). For R1 ≠ H, the cross-coupling product is only obtained if
R 2 = H [186].
2
R3 OAc O Ar1 OH R
+ DMF/H2O, Et4NOTs
45–75%
R1 Ar1 Ar2 Ar2 R3 (17.21)
R2 CCE
R1 OAc
10 : 1 103
Reductive coupling of alkenes with ketones can also be carried out chemically using SmI2 in
THF/HMPA (10:1) with added i-PrOH or t-BuOH [187]. For reduction of unactivated terminal
alkenes, the yields are generally high, 70–100% [187].
For terminal alkynes, it has been demonstrated [188] that direct proton reduction in DMSO
(Pt-cathode) leading to the anion is possible. When carried out in the presence of dialkyl ketones,
nucleophilic attack leads to alkynylation of the ketone in high current yields (up to 1000%), since
the alcoholate is able to deprotonate another alkyne molecule [188].
3. Coupling with Esters and Anhydrides

Anodically generated Mg2+, in undivided cells, acts as an ion-pairing/bonding template for reac-
tions of cathodically generated radical anions or dianions. In several cases, such conditions have led
to highly efficient coupling, especially when very reactive anionic intermediates are involved. An
example is the reduction of 2,3-disubstituted butadienes in THF in the presence of esters of aliphatic
carboxylic acids [189], which leads to substituted 3-cyclopentenols (Equation 17.22).
R2 R2
THF, LiClO4 R3COOMe R3
R1 Mg
R2 CCE, Mg anode 56–88% (17.22)
R1 R1 OH
104
The authors suggest that the key intermediate is 104, formed by two-electron reduction of the
butadiene. This is supported by the fact that the same product is obtained if the butadiene is com-
pletely reduced prior to addition of the ester [189]. The reaction also proceeds if one of the double
bonds is part of a ring (endocyclic). For styrene, the reaction is stereospecific giving one diastereo-
isomer of the phenyl substituted cyclopropane (Equation 17.23). The presence of Mg2+ is essential
but its role is unclear [189].
R1
R1 OH
THF, LiClO4 (17.23)

+ R2COOMe R2 82–96%
CCE, Mg anode

Reduction of activated alkenes in dry DMF or MeCN in the presence of an excess of acetic
anhydride or other simple anhydrides gives the corresponding β-acylated compound, 105 (Equation
17.24), in moderate to good yields.
EWG O R R´ = H, Me, Ph
MeCN, Et4NOTs EWG = CN, COOMe
+ (RCO)2O 43–82%
R´ CPE (4 F )
EWG R = Me, ET, Pr, i-Pr (17.24)
R´
1 : 10 105
The mechanism is not clear. The alkene is the more easily reduced reactant, since in MeCN (at a
carbon electrode) acetic anhydride is reduced at ca. −2.8 V [190]. Thus, electron transfer from the radical
anion of the activated alkene to acetic anhydride seems unlikely, although the acylation at the β-position is
the expected product of coupling between the radical anions. An alternative mechanism involves nucleo-
philic attack of the radical anion on the anhydride giving rise to carboxylate and a neutral radical, which
is further reduced and protonated. Initial α-acylation would be expected here because the charge density
in α-position is assumed to be higher than in β-position. Also, significant amounts of α,β-diacylated
product would be expected, formed by nucleophilic attack on acetic anhydride from the anion formed
in the second electron transfer (see Scheme 17.15). Less than 3% α,β-diacylated product was formed
except when the alkene was α-Me substituted. For ethyl cinnamate, 15a, an additional side reaction is
hydrogenation (14%) [190]. Thus, conditions were sufficiently acidic for protonation of the radical anion
to compete with dimerization and reaction with acetic anhydride. A mechanism for β-acylation analo-
gous to that for carboxylation in Scheme 17.15 (proton donor present) can then be envisaged. In dry DMF
(Al2O3 present in the cell), 2% α-acylation together with the LHD of 15a were reported as side products
[191], that is, the composition of the electrolyte plays a significant role. For cinnamonitrile, 13, the major
product in dry DMF is 106, presumably formed by nucleophilic attack of the enolate ion of 105 on the
anhydride (Equation 17.25) [191]. In MeCN, only 105 was isolated [190].
CN O –O O
DMF (dry) Base (MeCO)2O
+ (MeCO)2O CN
Ph 4F CN –H+ CN –AcO– O
Ph
(17.25)
13 Ph Ph
105 106
In a single case (Equation 17.26), the coupling reaction was accompanied by ring enlargement
[190].
COOEt COOEt
MeCN, Et4NOTs
+ (MeCO)2O 74%, cis/trans = 1:3 (17.26)
Hg cathode
COMe
4. Coupling with Organic Halides

Easily reduced polyhalides such as CCl4 (−0.75 V) and Cl3CCOOEt (−0.65 V) form anions upon
two-electron reduction and cleavage of a halide ion. The anion may add to activated, but less easily
reduced, alkenes, for example, acrylonitrile or alkyl acrylates. With excess alkene and no added
proton donor cyclopropanes are formed via Michael addition followed by intramolecular SN2 reac-
tion [192] (Scheme 17.16).
EWG
2 e– –
EWG EWG
CCl4 CCl3 CHCl3 (17.27)
–Cl– – + –CCl
Cl3C Cl3C 3

Catalytic reaction, with respect to current, is found for reduction of CCl4 in the presence of
CHCl3, which acts as a proton donor. The reaction becomes catalytic since the anion, − CCl3, is
regenerated upon proton transfer to the anion of the coupling product (Equation 17.27). Current
yields up to 350% have been reported for the reaction between acrylonitrile, 11, and CCl4 in DMF
containing CHCl3 [192] (Table 17.16).
N-Haloamides such as 107 are reductively cleaved (2 F) to give an anion by loss of a halide ion;
coupling takes place when an excess of an activated alkene is added (Equation 17.28) [193].
O EWG O
O MeOH/CHCl3, LiClO4 1)
EWG
EtO NH–Li+ EtO NH (17.28)
EtO NHCl Ew = –0.3 V 2) protonation
50–60%
107
EWG
2e– – EWG
Cl3CCOOEt –
Cl2CCOOEt EtOOCCCl2CH2 –
–Cl
HB –Cl–
Cl Cl Cl
EWG EtOOC
EtOOC EWG
SchEME 17.16 Catalytic formation of EGBs from some haloalkanes.

TABLE 17.16
Reductive Coupling of Alkenes with Very Easily Reduced Alkyl Halides in Aprotic Mediuma
Alkene Alkyl Halide Conditions Products and Yields
CH2=CHCN (11)b CCl4 (−0.75 V) CHCl3, Et4NOTs, Cl3CH2CH2CN 347%, H2
Ew = −0.98 V
7c Cl3CCOOEt (−0.65 V) DMF, LiCl, Ew = −0.84 V Cyclopropane 80%,d
EtOOCCCl2CH2CHClCN 20%
7e BrCH2COOEt (−0.88 V) Et4NOTs (H2O), Ew = −1.83 V Ethyl
2-cyanocyclopropylcarboxylate
<34%,f CH3COOH, polymer
CH2=CHCOOEt (16d)g CCl4 (−0.75 V) CHCl3, CH2Cl2, Et4NCl, Cl3CH2CH2COOEt 114%
Ew = −1.30 V
16db Cl3CCOOEt (−0.65 V) DMF, Et4NCl, Ew = −0.85 V Cyclopropane 100%d
16db BrCH2COOEt (−0.88 V) DMF, Et4NOTs (H2O), Diethyl c-propandicarboxylate
Ew = −1.50 V 76%,f CH3COOH 15%
E-EtOOCCH=CHCOOEt CCl4 (−0.75 V) DMF, CHCl3, Et4NCl, Linear 38%, cycl. 28%d
(79a)h Ew = −1.20 V EtOOC-C(CCl3)=C–COOEt
50%
Z-EtOOCCH=CHCOOEt Cl3CCOOEt (−0.65 V) DMF, LiCl, Ew = −0.75 V Cyclopropane 55%d
(80a)i
Source: Baizer, M.M. and Chruma, J.L., J. Org. Chem., 37, 1951, 1972.
a General conditions: div. cell, CPE, Hg cath. Yields based on current passed.
b 10× excess.
c 2× excess, Cl CCOOEt added slowly.

3
d See Scheme 17.16.
e 7 used as solvent.
f Probably formed via initial deprotonation of BrCH COOEt.

2
g 5× excess.
h Equimolar amount, Cl CCOOEt added slowly.

3
i Equimolar amount.
Allyl chloride is more difficult to reduce than diethyl fumarate, 79a, by ≈0.5 V, but allyl bromide
and iodide are only slightly more difficult to reduce than 79a. Co-electrolysis of allyl halides and
79a (in excess) results in cross-coupling [194], the bromide giving the highest yield (Table 17.17).
Based on these results and results for reduction of other combinations of allyl halides and acti-
vated alkenes, it has been suggested that when the allyl halide is more easily reduced than the
alkene, the allylic anion (2 F reduction) adds to the activated double bond of the alkene, giving pre-
dominantly the terminal alkene (Equation 17.29). In contrast, initial formation of the radical anion
of the (di)activated alkene may lead to an SN2 reaction between the radical anion and the allyl halide
followed by further reduction of the intermediate radical and final protonation (Equation 17.30)
[194,195]. However, electron transfer between the alkene radical anion and especially allyl iodide
followed by coupling of the allyl radical and a radical anion cannot be ruled out.
R1 EWG EWG EWG

2 e– R1 HB
X – (17.29)
R2 –X– – –B– R2
R2 R1 R2 R1
EWG – 1) Reduction
R1 SN2 R1 EWG 2) Protonation R1
+ EWG
EWG R2
X –X– R2 (17.30)
R2
EWG EWG
TABLE 17.17
Reductive Coupling of Alkenes with Allyl Halides in Aprotic Mediuma
Alkene Allyl Halide Products and Yields (%)
MeCβH=CαHCOOMe Me2C=CHCH2Cl β-coupl. 22b
E-EtOOCCH=CHCOOEt (79a)c CH2=CHCH2Cl 15d
79ac CH2=CHCH2Br 70d
79ac CH2=CHCH2I 39d
79ae Me2CCH=CHCH2Cl 15d
79ac MeOOCCαH=CHCH2Br α-coupl. 39
79ac MeOOCCαH=CHCH2I α-coupl. 11
Source: Satoh, S. et al., Bull. Chem. Soc. Jpn., 54, 3456, 1981.
a General conditions: DMF, Et NOTs, undiv. cell, CCE, Pt cath., chemical yield, based on halide after passage of 2 F.
4
b See Equation 17.29.
c 10× excess.
d See Equation 17.30.
e 2× excess.
The SN2 mechanism is ruled out for reaction between the tertiary halide, t-BuBr, and radical
anions derived from the more easily reduced compounds cinnamonitrile, 13, ethyl cinnamate, 15a,
methyl styryl ketone, 40a, and phenyl styryl ketone, 37a. Reduction of the activated alkenes in
the presence of an excess of t-BuBr leads to mixtures of products where a t-Bu group has been
introduced in α- or β-position or in the phenyl ring. For 13 and 15a, small amounts of butylated
hydrodimers were obtained in addition, and for the enone 39a, formation of the unsaturated alcohol
with introduction of the t-Bu group at C-1 was a major product [196]. In this case, the mechanism is
unambiguously reduction of the activated alkene followed by electron transfer to t-BuBr concerted
with halide cleavage, in competition with dimerization of the alkene radical anions. The t-butylated
products arise from coupling between t-Bu• and the radical anion of the activated alkene, or from
attack of t-Bu• on the alkene or the hydrodimer [196]. Consistent with this is the fact that if a very
easily reduced activated alkene as, for example, 37a (E½ = −1.34 V) is used, no mixed coupling
product is found since electron transfer from radical anion to halide is very slow owing to the
large difference in reduction potentials. The general problem of electron transfer from (more stable)
organic radical anions to alkyl halides and the competition between coupling and further reduc-
tion of the alkyl radical has been investigated in great detail (see [197] and references therein, also
Chapters 14, 24, and 25).
Sacrificial anodes (typically Mg, Fe, Zn, or Al), in undivided cells, offer advantages also in
the reductive couplings between alkenes and halides. One example is the reductive coupling of
dihalides with activated alkenes leading to formation of three-, five- or six-membered rings in NMP
using a sacrificial Al anode [198,199], whereas mainly a linear coupling product was obtained in
a divided cell [199]. Generally, yields are higher when the alkene is more easily reduced than the
dihalide, but only by a few hundred mV (Table 17.18). For instance, reduction of dimethyl fumarate,
79b (−1.45 V), dimethyl maleate, 80b (−1.6 V), and methyl cinnamate, 15b (−1.85 V), in the pres-
ence of a twofold excess of 1,3-dibromopropane (−2.1 V) gives the corresponding trans-substituted
cyclopentanes (respective yields 18%, 50%, and 66%). Reduction of an excess of methyl acrylate,
16a (ca. −2.1 V), gives only 10% of the cyclopentane.
Whether the radical anion of the alkene reacts by electron transfer to the dihalide, by SN2 reaction
with the dihalide or undergoes further reduction to an ion-paired dianion could not be distinguished.
Further studies of the formation of substituted cyclopropanes from reduction of different com-
binations of diactivated alkenes (79b, 80b) and gem-polyhalo compounds in DMF using an undi-
vided cell with an Al anode [200] showed that (a) increased temperature (70°C) in general led to
TABLE 17.18
Reductive Coupling of Alkenes with Polyhalides in Aprotic Mediuma
Alkene Polyhalide Products and Yields References
CH2=CHPh (−2.2 V)b BrCH2CH2CH2Br (−2.0 V) Cyclopentane 10%c,d [199]
CH2=CHCOOMe (16a) (−2.1 V)b BrCH2CH2CH2Br (−2.0 V) Cyclopentane 10%, [199]
CH2=CH(CH2)3COOEt 9%c
20 (−2.1 V)b PhCHCl2 trans cyclopropane 30%c,d [199]
E-PhCH=CHCOOMe (15b) BrCH2CH2CH2Br (−2.0 V)e trans cyclopentane 66%, lin. 5%f [199]
(−1.85 V)
15b (−1.85 V) CH2Cl2 trans cyclopropane 40%f [199]
E-MeOOCCH=CHCOOMe (79b) CH3CBr2CH3 (−2.1 V)e trans cyclopentane 60%f [200]
(−1.45 V)g
79b (−1.45 V)g CH3CHBr2 (−2.3 V)e trans cyclopropane 35%f [200]
79b (−1.45 V)g Cl3CCOOMe (−1.6 V)e trans cyclopropane 40%f [200]
79b (−1.45V) BrCH2CH2CH2Br (−2.0 V)e trans cyclohexane 18%f [199]
cis-MeOOCCH=CHCOOMe (80b) CH2Br2 (−2.1 V) trans cyclopropane 41%f [199]
(−1.6 V)
80b (−1.6 V) ClCH2CH2Cl trans cyclobutane 5%f [199]
80b (−1.6 V) BrCH2CH2CH2Br (−2.0 V)e trans cyclopentane 50%, lin. 10%f [199]
80b (−1.6 V) CH2=C(CH2Cl)2e trans cyclopentane 16%, lin. 10%f [199]
80b (−1.6 V) BrCH2(CH2)2CH2Bre trans cyclohexane 40%f [199]
80b (−1.6 V) cis-ClCH2CH=CHCH2Cle trans cyclohexene 15%f [199]
E-PhCH=CHCOMe (40a) (−1.7 V) BrCH2CH2CH2Br (−2.0 V)e trans cyclopentane 35%f [199]
a General conditions: NMP, Bu4NBF4 + Bu4NI, undiv. cell, CCE, stainless steel cath., Al anode.
b 4× excess.
c Chemical yield, based on halide.
d See Scheme 17.16.
e 2× excess.
f Chemical yield, based on activated alkene.
g As in (a) but DMF, 70°C.
improved yields of the cyclopropanes (up to 60%), (b) 79b in all cases gave better yields (of the same
product) than 80b, (c) the LHDs of the alkenes and hydrogenation products of the halo compounds
(occasionally also dimers of the halo compounds) were found as side products, and (d) no mixed
coupling products were obtained if very easily reduced halides (CBr4, BrCCl3, Br2C(COOMe)2, and
Cl3CCN) were used in combination with any of the alkenes (all more difficult to reduce than the
halides) [200]. Michael addition therefore seems not to be operating when a sacrificial Al anode is
used. The main mechanism appears to be electron transfer from the radical anion of the alkene to
the gem-dihalo compound leading to an α-halo radical that can couple with an alkene radical anion
followed by an intramolecular SN2 reaction to give the cyclopropane. The products yields are, how-
ever, low to moderate.
Later, two different mechanisms for the coupling between activated alkenes and less easily
reduced alkyl halides were suggested depending on whether the reduction takes place in a divided
cell or in an undivided cell equipped with a sacrificial Al anode [201] (Scheme 17.17). For bromo-
methylcyclopropane (−2.3 V), the product distribution was shown to depend on the experimental
conditions (Table 17.19). The cyclopropylmethyl radical formed by electron transfer from the alkene
radical anion is known to ring-open to the linear radical with a first-order rate constant close to
108 s−1 and coupling of the cyclopropylmethyl radical with the alkene radical anion can therefore
not compete. Consequently, only linear coupling products are found when the reaction is carried
– –
EWG EWG
EWG
EWG –
Br– , –Br–
HB EWG
–B– Reduction
undivided cell Br
– Al3+ EWG–Al3+ – EWG–Al3+ EWG–Al3+
EWG
Sacrificial Al anode –
–Br
HB
EWG
–B–, –Al3+
SchEME 17.17 Reductive coupling of alkenes with (cyclpropyl)CH2Br in aprotic solvent.
TABLE 17.19
Reductive Coupling of Alkenes with (cyclopropyl)CH2Br (−2.3 V) in Aprotic Mediuma
(see Scheme 17.17)
Alkene Conditions Products and Yields
CH2=CHPh (−2.2 V) Div. cell. Open chain 60%
CH2=CHPh (−2.2 V) Undiv. cell, Al anode Open chain 70%
PhCH=CHCOOMe (15b) (−1.7 V) Div. cell Open chain 35%, LHD of 15b
15b (−1.7 V) Undiv. cell, Al anode Open chain 20%, cycl. 30%
Z-MeOOCCH=CHCOOMe (80b) (−1.5 V) Div. cell Open chain 28%, LHD of 80b
80b (−1.5 V) Undiv. cell, Al anode Open chain 16%, cycl. 24%
Source: Lachaise, I. et al., Res. Chem. Intermed., 15, 253, 1991.

a General conditions: NMP, Bu NBF + Bu NI, CCE, stainless steel cath. Alkene used in 2× excess.
4 4 4
out in a divided cell. The amount of cross-coupling product increases at the expense of the LHD of
the activated alkene, when the reduction potential of the alkene approaches that of the bromometh-
ylcyclopropane. This observation is consistent with an increase in the rate of electron transfer and
thereby in the concentration of the ring-opened radical, when the difference in reduction potentials
is diminished.
In the undivided cell, on the other hand, a significant amount of cross-coupling products con-
taining the cyclopropyl group is found (for 15b and 80b), indicating an SN2 pathway rather than an
electron transfer pathway. According to the authors, formation of the dianion of the activated alkene
is now competing with the electron transfer to the bromide due to strong interaction between the
Al3+ (generated at the anode) and the radical anions of 15b and 80b. The resulting dianion (strongly
ion-paired) may then react with the bromide in an SN2 reaction leading to the cyclopropyl contain-
ing cross-coupling product (Scheme 17.17). The radical anion derived from the nonpolar styrene
interacts more weakly with Al3+ and the electron transfer pathway is the only one operating [201].
The electrosynthesis of cyclopropylphosphonates by reductive coupling of trichloromethyl-phos-
phonates with activated alkenes in DMF also benefits from the use of a Mg anode [202]. Firstly, the
amount of charge passed (based on the trichloromethylphosphonate) for full conversion decreases
from the required 2 to 0.8 F, which has been explained as a chemical reduction of the trichlo-
romethylphophonate initiated by the Mg anode. Similar observations have been made in other
cases and are discussed in Chapters 24 and 36. Secondly, the diastereoselectivity of the reaction is
greatly enhanced (to 80–100%) when the activating group of the alkene is an ester, 16a, 16c, 16e
COOR R´ R´
O O – H H H Cl
2e– – Cl
(i–PrO)2P CCl3 (i–PrO)2P CCl2 R´ H Cl
–Cl– +Mn+ –Cl–, Mn+ C P(OiPr)2
C P(OiPr)2 RO O
RO O
O Mn+ O
SchEME 17.18 The Mg2+ ion as a template in a reductive conversion.
or PhCH=C(COOEt)2, which is attributed to the templating effect of Mg2+ as outlined in Scheme

17.18, keeping the phosphonate and the ester group at the same side of the cyclopropane ring in the
product.
The low yields generally obtained from cross-coupling of simple mono-halides with alkenes via
direct reduction of the halides are due to the fact that the radicals formed by loss of halide often are
reduced at the potential where they are formed in competition with radical addition to the alkene.
The resulting anions are highly basic and are normally protonated by the medium. As an example,
direct reduction of 108 (Ep = −1.45V) in MeCN (Et4NBF4) in a divided cell in the presence of an
excess of electron rich alkenes only leads to the 2 F product of 108 where Cl has been replaced by H.
However, if the reaction is carried out using nitrobenzene (Eo = −1.10 V) or 4-nitropyridine-N-
oxide (Eo = −0.70 V) as a redox catalyst, the initial cleavage of Cl− from 108 − • is not followed by
further reduction and protonation. The radical adds to the alkene followed by cyclization, finally
leading to the tricyclic ring system in an overall 2 F process. Upon work-up the product is re-
aromatized to 109 (Scheme 17.19) [203].
Transition metal catalysts have been successfully used in a number of coupling reactions involv-
ing organic halides during the last decade [204], and also in the mixed coupling of alkenes with
halides. One example is the coupling between simple butyl iodides and α-methylenebutyrolactones
[205,206] catalyzed by Ni(II)(tmc)2+ (tmc = a cyclic tetradentate nitrogen ligand), which is reduced
at −0.95 V. A fuller explanation is given in Section IV.B.5. This Ni(II)-complex and other similar
Ni(II)-complexes with macrocyclic tetradentate nitrogen ligands are reduced to the correspond-
ing Ni(I)-complexes that are the active species. The catalytic effect appears to be an inner-sphere
reduction of alkyl halides to alkyl radicals and halide ions. Since the reduction of the Ni(II)-species
takes place at a potential that is anodic with respect to the reduction of simple alkyl radicals [197],
the follow-up reaction is of the radical type. In the case of α-methylenebutyrolactones, the double
bond is attacked by the alkyl radical, leading to a new radical that is more easily reduced (due to the
α-carbonyl group). The protonation of the resulting anion by residual water from the less hindered
side of the ring determines the stereochemistry of the product (Equation 17.31) [206]. That the
major reaction pathway of the product radical is further reduction rather than hydrogen abstraction
NMe2 NMe2 R3 NMe2 NMe2

R1 R1
A– R1 R1
R2
–A, –Cl– R3 R3
O CF2Cl O CF2 O R2 O R2
108 F F F F
NMe2
R1 = H, R2, R3 = –OCH2CH2–
R1
Work-up R1 = COCF2Cl, R2, R3 = –OCH2CH2–
R3 30–60% R1 = COCF2H, R2, R3 = –OCH2CH2–
R1 = H, R2 = H, R3 = imidazole
O R2 R1 = H, R2 = H, R3 = OBu
F F
109
SchEME 17.19 Coupling to give persistent radical reactive in intramolecular cyclization.

from the solvent (DMF) is supported by the fact that addition of D2O to the reaction mixture led to
80% D at the α-carbon, whereas the use of DMF-d7 gave no deuteration. Except for t-BuI the yields
are generally in the range 50–70% with a high cis/trans ratio when both R1 and R2 are different
from H [206].
R2 R2 R2
R1 R1 R1
DMF, Et4NClO4 R + R
+ Rl O O (17.31)
O Red., Ni(l) cathode
O O O
1 : 1 Major Minor
The yield of cyclized product for coupling between simple activated alkenes and butynyl iodides
depends on the reduction potential of the Ni-catalyst [205] since the radical resulting from the initial
attack of the butynyl radical may either be reduced or cyclize (5-exo) on to the triple bond (Equation
17.32). The lower the reduction potential of the catalyst, the more non-cyclized product is formed.
The yield of the cyclized product was in the range 30–60% [205].
R R
EWG DMSO, Et4NClO4
EWG (17.32)
R +
l EWG +
Excess Red., Ni(l) cathode

Coupling between cyclohexenone and alkyliodides can be catalyzed by Co(I)-species formed

in situ from vitamin B12 or similar Co(III)-complexes at ≈ −0.85 V [207]. The alkyl halide
reacts with the Co(I)-complex by oxidative addition, and the alkyl radical can be obtained
photochemically (visible light), with subsequent addition to the double bond in the β-position
(in competition with hydrogen abstraction). Alternatively, the Co-alkyl species can be further
reduced at −1.45 V, giving the alkyl anion. The yields of coupling products were significantly
higher (40–80%) using the photochemical than using the reductive method. Only when the
reaction was carried out in a microemulsion cetyltrimethylammonium bromide (CTAB)/1-
pentanol/tetradecane/water (17.5/35/12.5/35, w/w%) did the coupling reaction compete to some
extent with protonation of the alkyl anion formed by the reductive method, giving 10–40%
coupling [207].
The mechanism of Ni(0)-catalysis of cross-couplings between vinyl or aryl halides and alkenes
is believed to be quite different from the Ni(I)- or Co(I)-catalyzed reactions discussed earlier, since
both reaction partners are bonded to the metal and the coupling takes place within the ligand sphere
(see Chapter 36). The reductive coupling between simple activated alkenes and alkenyl halides can
be carried out in good yields in an undivided cell using 0.2 eq. NiBr2 as Ni(0)-catalyst precursor and
a sacrificial Fe-anode (Equation 17.33) [208]. Alkenyl bromides and iodides give similar or higher
yields than the chlorides, with the E,Z isomeric purity of the products >93%.
X R2 EWG
EWG R2 DMF/MeCN, 60°C–80°C
+ (17.33)
R3 R1 Red., Ni(0) cathode R3 R1
50–85%
EWG = COMe, CN, COOEt
X = Cl, Br, l
Reduction (2 F) of 1,2-bis(bromomethyl)benzene leads to a highly reactive o-quinodimethane, which

in the presence of a dienophile may serve as the diene in a Diels–Alder reaction. The dienophiles
are typically analogues of maleic anhydride, 110, N-phenylmaleimide and benzoquinone, which are
O
R1 R1
Br DMF, Et4NBr
+ O O
Br
R2 2F R2 60–90%
O
O
O
110
110
Br 2 110–
Br –2 110, –2 Br–
SchEME 17.20 Catalytic electrogeneration of o-quinodimethane; Diels–Alder reaction.
all more easily reduced than the 1,2-bis(bromomethyl)benzene. The radical anion of the dienophile
mediates the reductive cleavage of the 1,2-bis(bromomethyl)benzene to give the o-quinodimethane.
This then undergoes Diels–Alder reaction with the dienophile as shown in Scheme 17.20 [209,210].
B. INTraMoLECULar CoUpLING oF ALkENES or ALkYNES wITH OTHEr TYpES oF SUbSTraTES

Reductive cyclizations have been reviewed [211] and applications to natural product synthesis can
be found in Chapter 37. In this section, only intramolecular reactions involving carbon–carbon mul-
tiple bonds (i.e., similar to the intermolecular reactions discussed earlier) will be treated.
1. Coupling of Activated Alkenes with Aldehydes and Ketones
R
O HO R O R
COOMe O
MeCN/H2O (9:1), Et4NOTs +
OMe n O Total yield: (17.34)
n Hg cathode 70–80%
n
n = 1,2 R = H, Me Trans Cis
In aprotic solvents, the activated alkene rather than the aldehyde or keto group is the moiety under-
going electrochemical reduction. Electrochemical reduction of α,β-unsaturated esters linked to
aldehydes or ketones leads to five- or six-membered cyclization products in which the new bond is
formed between the β-carbon of the unsaturated ester and the carbonyl carbon of the aldehyde or
keto group (Equation 17.34). The trans isomer was formed in excess with the trans/cis ratio in the
range (1.4:1)–(11.4:1) [212,213]. The trans/cis ratio increased with decreasing temperature [213],
and the cis isomer was detected as the lactone. Hydrogenation of the alkene was found to be a side
product, but the importance of this side reaction was minimized in dry MeCN using 2 eq. of diethyl
malonate as proton source instead of AcOH [212].
Using a cyano group for activation of the alkene may also lead to the cyclized product [213] as
illustrated in Equation 17.35. Reductive coupling also worked well for cyclopentanone or cyclo-
hexanone functionalized at the 2-positions by a chain containing an α,β-unsaturated ester (Equation
17.36). Attempted formation of a spiro compound, through reductive cyclization in MeCN of com-
pound 111 (Scheme 17.21), afforded ca. 1% of the spiro adduct [214]. This is in contrast to the intra-
molecular coupling product obtained when the α,β-unsaturated lactone was linked to an unsaturated
ester (see Equation 17.14) in Section III.B rather than to the aldehyde. Reduction of 111 gave mainly
the bicyclic compound 112 arising by self-protonation of the radical anion by the acidic hydrogen
at C-1 of the side chain. The conjugate base of the starting material then cyclizes on to the aldehyde
group leading, after hydrogenation of the C–C double bond in the lactone ring, to 112 (Scheme 17.21)
[156]. The self-protonation reaction took place even if the reduction was carried out in the presence
of 4 eq. of diethyl malonate as an external proton donor [156]. The localized anion adds to the car-
bonyl group and the alcoholate is finally protonated [112].
O O O
O + 111– O + O
CHO CHO CHO
H H –
H
111 Further reduction
and protonation
O OH O
O Further reduction O OH
and protonation O
60% O
CHO
112
SchEME 17.21 Self-protonation.
OH
NC CN
CHO
MeCN/H2O, Et4NOTs
(17.35)
Hg cathode 73%

COOMe
O
COOMe HO
DMF, Bu4NPF6 (17.36)
CPE

Based on the results of LSV at low scan rates, it was concluded that the mechanistic pathway
involves initial, rate-determining protonation of the radical anion at the α-carbon of the activated
double bond followed by further reduction in solution of the resulting radical. Cyclization at the
anion stage was supported by the fact that the substrate 113 exclusively gave products derived
from cyclization on to the carbonyl group and not to the alkene double bond (Scheme 17.22).
In both cases, a five-membered ring would be obtained but it is known that anions react much
faster with carbon–oxygen than with carbon–carbon double bonds, whereas radicals react with
comparable rates with the two types of double bonds upon formation of five-membered rings,
but the reaction with the carbon–oxygen double bond being reversible and thermodynamically
unfavored [112,215].
O
COOMe COOMe (ArOH = 3,5-dimethylphenol)
O HO O
DMF, Bu4NPF6 +
ArOH, Red.
113 43% 38%
e–
COOMe COOMe COOMe

O – ArOH O 113– O
–
–ArO– –113
SchEME 17.22 Cyclization at carbonyl vis a vis alkene function.

A similar mechanism has been suggested for the reductive cyclization of ketones linked to
α,β-unsaturated esters by Mg in MeOH at −23°C, which give high chemical yields (80–100%) of
the cyclic alcohols [216].
Reductive cyclization of a keto group linked to an ester-activated allene affords cyclization to the
cyclopentenol, which is isolated as the lactone (Equation 17.37) [217]. Higher yields (64–96% as a
mixture of diastereoisomers) are obtained when the keto group is replaced with an α,β-unsaturated
ester group. That cyclization, however, only takes place in an undivided cell (and with a consump-
tion of 4.5–11.3 F) [217].
Bu COOMe O
HO O
COOMe
O DMF
–MeOH
(17.37)
2.6 F Bu Bu
35%
2. Coupling of Unactivated Alkenes with Aldehydes and Ketones

For intramolecular reductive coupling between aldehyde or ketone functions and less easily reduced
alkenes, the carbonyl radical anion (or radical resulting from O-protonation) is the species attack-
ing the alkene to give in almost all cases exclusively 5-exo- or 6-exo-cyclization. Cyclobutanes and
rings containing more than six atoms are seldom formed [218]. The chemical yields are reported to
be high when the reduction is carried out at constant current in an undivided cell (carbon cathode)
(Equation 17.38). Substituents on the alkene carbon to which the bond is formed normally inhibit
the cyclization, while bulky R2- and R3-substitutents lower the yield to somewhat below 50%, with
concomitantly higher amounts of the linear, unsaturated alcohol [218,219]. The reaction is highly
stereoselective (OH and CHR2R3 trans). Formation of bicyclic tertiary alcohols from cyclic ketones
linked to terminal alkenes also proceeds smoothly (37–87%) [219].
R1 OH R2
O
R2 MeOH/dioxane R3 (17.38)
R1
2 M Et4NOTs, 10 F
R3 R3 = H, 75–98% R2 and R3 = H, <50%

Reduction of 7-octen-2-one mediated by (DMP)Hg (DMP+ = dimethylpyrrolidinium) formed

in situ gave the cyclized product with higher current yields (72%) than by direct reduction (35%).
Similar results were obtained for 6-hepten-2-one [220].
Outersphere electron transfer by organic catalysts also promotes the reductive cyclization of
6-hepten-2-one in DMF [221]. From a study of the effect of variation of the amount of the catalyst
and its reduction potential and from the reaction in DMF-d7, it was concluded that the ketyl radical
anion cyclizes to the carbon–carbon double bond giving preferentially the product where the two
methyl groups are cis. The distonic radical anion thus produced does not abstract hydrogen but is
further reduced. When the further reduction or the protonation at oxygen is a fast follow-up reaction
(high concentration of the mediator or high concentrations of water), equilibration to the more stable
product (methyl groups trans) is prevented [221].
O
OH OH
DMF, Bu4NBF4 +
(17.39)
2.3 F
H H
Major Minor
(kinetic prod.) (thermodynamic prod.)
Total yield: 50%
Cyclization also takes place when the alkene and the keto group are included in a macrocyclic
system such as 4-cycloocten-1-one (64%) [218]. When the dienone (Z,E)-4,8-cyclododecadien-1-one
is reduced, 5-exo-cyclization gives a mixture of the two diastereoisomers (Equation 17.39) [222].
The isomer which is the major product has a higher calculated strain energy, but the ratio between
the two isomers decreases with time from (2:1) in the beginning to (1.5:1) at the end of the elec-
trolysis. This suggests that the ring formation is reversible, probably due to proton deficiency at later
stages of the electrolysis. The relative yield of the thermodynamically favored product therefore
increases with time [222].
In the case of 6-trimethylsilyl-6-hepten-2-one, the 6-endo-cyclization product was obtained
exclusively, probably due to steric inhibition of 5-exo-cyclization (normally favored according to
Baldwin’s rules [27]) and electronic effects favoring radical formation in the 6-endo-cyclization
(Equation 17.40) [184].
Me OH
SiMe3 O DMF, Et4NOTS
3F (17.40)
SiMe3
55%
3. Coupling of Alkynes or Allenes with Aldehydes and Ketones

Reduction of nonconjugated acetylenic ketones at constant current gives methylidenecyclo-penta-
nols (Equation 17.41) [223]. The highest yields were obtained from terminal alkynes, and bicyclic
systems could be formed from alkyne-functionalized cyclopentanones and cyclohexanones [223].
R
O HO
DMF, Et4NOTs (17.41)
R
4F 55–95%

Unactivated allenes linked to ketones undergo reduction to give exclusively five-membered rings
[224], affording either trans methyl cyclopentenols or ethenyl cyclopentanols depending on the
length of the link (Equation 17.42).
OH OH
O DMF, Et4NOTs
4F (17.42)
n H H
n = 1,2 n = 1: 43% n = 2: 23%
4. Coupling of Alkenes with Esters

Intramolecular coupling between unactivated terminal alkenes and ester groups has been reported
[225], and the reaction is very similar to the intramolecular coupling between alkenes and keto
groups (Section IV.B.2). Good yields of the alcohols are obtained (Equation 17.43), with the isomer
in excess that has the hydroxy and the methyl groups trans, but only five-membered rings can be
formed. The reduction is carried out in an undivided cell, and the use of Mg-electrodes (the polar-
ization alternated every 15 s) is crucial [226].
OH
O R1
THF, LiClO4, t-BuOH
OMe Undiv. cell, 5 F, Mg electrode R2 (17.43)
R1 R2
64–80%
R1 R1
DMF, Bu4NClO4
(CH2)n – 1CH2OSO2R (CH2)n
CPE
O R2 O R2
(17.44)
80–82%
n = 1, R1 = Me, R2 = H
n = 3, R1 = H, R2 = Me
A completely different type of intramolecular reductive coupling involving ester groups are
reactions in which sulfonates or phosphates function as anionic leaving groups. Reduction of
α,β-unsaturated ketones linked through the β-position to an alkyl group with a terminal sulfonate
group gives, in dry DMF, ring closure to the β-position in good yields [227,228] (Equation 17.44).
Direct reduction of sulfonates is known to cleave the S–O bond to give the alcohol, and reduc-
tion of the activated alkene is therefore the initial step. A possible pathway involves protonation
and further reduction (overall 2 F), leading to the β-anion that cyclizes by an intramolecular SN2
reaction.
The yields depend on the size of the ring formed, decreasing in the order 3 > 5 > 6 ≫ 4 ≈ 7.
Formation of five-membered rings is inhibited in the presence of a proton donor (dimethyl malo-
nate) and cyclization to four- six- and seven-membered rings is completely prevented. However,
these conditions have little effect on the formation of the three-membered rings [228]. The authors
interpret the results of their preparative studies as a competition between protonation and intramo-
lecular SN2 reaction on the radical anion stage. However, it seems more likely that the competition
is between protonation and cyclization of the β-carbanion formed en route to hydrogenation.
Initial, electrochemical reduction of β-dicarbonyl enol phosphates linked to an olefinic chain
gives cleavage of the phosphate with formation of a vinylic radical [229–231]. Reduction in DMF
takes place in the potential range −2.0 to −2.3 V and may lead to bicyclic products as illustrated in
Scheme 17.23.
The vinylic radical participates in a tandem cyclization either through a radical mechanism or
through an anion mechanism (Scheme 17.23). The radical pathway seems the more likely, with
reduction of the final bicyclic radical being facilitated by the electron-withdrawing group. The ste-
reochemistry at this center is determined by preferred protonation from the least hindered side.
Ketones and esters can both function as the activating group. Generally formation of six-membered
rings is less favored than that of five-membered rings, and if R3 ≠ H the yields are also lowered
[229]. More examples are given in [230,231].
O EtOOC
COOEt +e–, –(EtO)2PO–2 COOEt
(EtO)2PO R2
DMF, Bu4NClO4 R1 R1 R2
R1 R2
e– R3 R3
R3
COOEt
R2 EtOOC
– EtOOC –
R1 e–
R3 R1 R2
R1
R2
H+ R3
EtOOC R3 H
EtOOC
R1 R2
– R1
R2
R3 50–60%
R3
SchEME 17.23 Tandem cyclization—vinylic radical or anion intermediate?

5. Coupling of Activated Alkenes with Organic Halides

Formation of four- or five-membered rings follows reduction of dialkyl bromoalkylidenemalonates
by cyclization to the β-carbon of the diactivated double bond (Equation 17.45) [232].
COOR DMF, Bu4NBr COOR

Br n
Ew = –1.85 V 60–80%
(17.45)
COOR n COOR
n = 1, 2
A plausible mechanism may involve C-Br cleavage through inter- or intramolecular electron
transfer from the initially formed radical anion to the σ*-orbital. The radical so formed may add
intramolecularly to the activated alkene function. An alternative, SN2 reaction between the alkene
radical anion and the bromide would be expected to occur from the α-carbon of the activated alkene,
which bears the higher charge density.
2+ 2+ 2+ 2+
2+
N N N N HN H HN NH
N
Ni Ni Ni Ni
N
N N N N
N Ni N HN NH HN NH
N
H
–0.70 V Ni(CR)2+ –0.95 V Ni(tmc)2+ –1.16 V –1.38 V Ni(tet a)2+ Ni(cyclam)2+
Similarly to the intermolecular couplings between alkenes and halides (Section IV.A.4), yields
of intramolecular couplings may be improved by using the same type of transition metal cata-
lysts. Examples of some commonly used Ni(II)-catalyst precursors are shown above. Here and
in Section IV.B.6 only a few examples of their application will be given, more can be found in
Chapters 24 and 36.
Six-membered rings are formed in reductions, catalyzed by electrogenerated Co(I)- or Ni(I)-
complexes, of α,β-unsaturated esters linked through the β-position to a chain bearing a bromine
atom. The complexes include vitamin B12a (Co) and Ni(II)(tmc)2+ [233], which, as mentioned in
Section IV.A.4, are both known to cleave organic halides to alkyl radicals rather than carbanions.
Coupling therefore involves radical attack on the activated carbon–carbon double bond, in this
case with 6-exo-cyclization (Equation 17.46). The yields are in the range 40–85% being higher for
monoactivated alkenes than for diactivated ones. For diactivated alkenes (R1 being a carbonyl oxy-
gen), the yields are lower (≈20%), which may be accounted for by competing, direct reduction of the
alkene. The products were mixtures of stereoisomers except in a single case where the configuration
at the double bond was cis. Here the trans product was formed exclusively (85%) [233].
Br COOR
R3
R3 DMF, Et4NClO4 COOR
(17.46)
Red., Ni(l) or Co(l) cathode R 2
O R 1 20–85%
R2 O R1
Vitamin B12a has been used as catalyst precursor for the reductive coupling of 114 to 115
[207,234–236]. The electrochemical reduction at −1.5 V of the Co(III)-alkyl complex formed
by oxidative addition of the bromide to the Co(I)-species (formed at ≈ −0.9 V) probably
leads to the anion that may add to the double bond in competition with protonation. In DMF,
reduction at −1.54 V gave the cyclized product 115 but with no trans/cis selectivity (Scheme
17.24) [234].
In a microemulsion of CTAB/1-pentanol/tetradecane/water (17.5/35/12.5/35 w/w%) with the
same Co(I) catalyst, the same reaction led to 115 with a trans/cis ratio of 14:1, independently of
O O
Br Microemulsion
n n
Co(I) cathode, Ew = –0.9 V or –1.5 V
114 115
n = 1, 90%, trans/cis = 14:1
DMF, LiClO4, NH4Br, Co(l) cathode
Ew = –1.54 V
n
n = 1, 95%
trans/cis = 1:1
n = 2, 70%
115
SchEME 17.24 Competition between protonation and Michael addition.
whether the reduction was carried out at −0.9 V or at −1.5 V [207] (Scheme 17.24). The stereoselec-
tive formation of the trans-1-decalone in the microemulsion was ascribed to equilibration of the two
isomers via OH− catalyzed keto-enol tautomerization [237].
For 114 with n = 3, reduction at −0.9 V gave little cyclization (20%) in DMF as well as in micro-
emulsions, indicating that the radical is not significantly undergoing 5-endo-cyclization [235].
At −1.5 V, where the anion is formed, the competition between Michael addition and proton-
ation was different for reaction in DMF and in microemulsions, giving 19% cyclization in DMF
and 62–70% in microemulsions, indicating that the anion is formed in a water-free part of the
microemulsion.
6. Coupling of Unactivated Alkenes with Organic Halides

Unactivated alkenes give intramolecular coupling with halide functions only in catalyzed reac-
tions since the low potentials required for direct reduction result in formation of highly reactive
carbanionic intermediates. Even the direct reduction of aryl halides, linked to an ortho-alkene
side chain, normally give the aryl anion rather than the radical since the potential of the initial
reduction is lower than that required for furhter reduction of the phenyl radical. Cyclized products
may be obtained but normally in low yields due to competing protonation of the phenyl anion, as
demonstrated by addition of D2O to the solvent [238]. Outersphere electron transfer reagents may
afford reduction at potentials where either the phenyl radical is stable toward further reduction
or the rate of reduction by bimolecular reaction with the catalyst is so slow that intramolecular
coupling or hydrogen abstraction competes. This has been tested for o-(3-butenyl)bromobenzene
where the results of direct reduction (Ew = −2.65 V) were compared with reductions using m-tol-
unitrile as an electron transfer mediator (Ew = −2.25 V) [238]. The mediated reduction afforded
a higher ratio of cyclized to uncyclized product (8:1 vs. 1:1) and, in contrast to direct reduction,
the mediated reduction was little affected by added proton donor. Radical cyclization to the five-
membered ring was estimated to have a rate constant of ≥107 s−1 [238]. The carbon–fluorine bond
of an aryl radical anion cleaves more slowly than does the carbon–bromine bond, and conse-
quently aryl radical formation takes place in solution following direct reduction. In this case, a
ratio of cyclized to uncyclized product of 2.5:1 was found for direct reduction [239] even in the
presence of 0.5 M H2O.
Another example is the direct reduction of 116a,b, where the presence of the cyano group facili-
tates reduction and which gave hydroindole coupling products (30–35%) (Equation 17.47). The major
side products were the dehalogenated starting materials. Intramolecular coupling of the analogous
116c containing no cyano group was only obtained by indirect electrolysis using either anthracene
or stilbene as mediator [240].
COMe COMe
R2 N MeCN, Et4NBF4 R2 N
R1 Hg cathode
Cl R1
116 (17.47)
1 2 a–b: 30%
a: R = CN, R = H c: 80%, stilbene as catalyst
b: R1=H, R2=CN
c: R1 = R2 = H
A variety of Ni(II)-complexes with macrocyclic tetradentate nitrogen ligands (see the exam-
ples in Section IV.B.5) has been applied as catalyst precursors for coupling of unactivated
alkene functions with halides. The reactivity of the active, reduced Ni(I)-form varies with the
reduction potential. Selected Ni-complexes can therefore be used to catalyze intramolecular
reductive couplings for different types of halogen compounds with varying carbon–halogen
bond strengths.
The Ni-complexes have been used to perform intramolecular cyclizations to five-membered
rings with a range of substrate types containing unactivated double bonds linked to various
halides, for example, alkyl [241–243], vinyl [244,245], and aryl halides [243,246]. Standard
conditions are reduction at the potential of the Ni(II)-complex (0.1–0.2 eq.), in DMF with
tetraalkylammonium salts as supporting electrolyte. The appropriate Ni(II)-complex can be
chosen as the one most easily reduced for which catalysis takes place on a voltammetric time
scale [242].
Since the Ni(I)-catalysis gives radicals, the initial products of the 5-exo-cyclizations are also
radicals, which (in contrast to those obtained by addition to activated alkenes) are normally not
reduced under the conditions of the electrolysis. The follow-up processes are therefore radical reac-
tions, normally assumed to be H-atom abstraction from the solvent. This has been demonstrated for
117a (Equation 17.48), where the yield of cyclized product was shown to be higher in DMF than in
MeCN, DMF being a better H-atom donor than MeCN [242]. Cyclization from 117a in MeCN could
be improved by addition of Ph 2PH as an external H-atom donor, otherwise the main product was
the halogenated cyclized compound formed by halogen atom abstraction from another molecule of
starting material. However, addition of Ph2PH also increased formation of acyclic products due to
competing H-atom abstraction of the initially formed radical [242]. Using 117b rather than 117a and
carrying out the electrolysis in MeCN without Ph2PH it was possible to obtain the iodo compound
as the only cyclic product due to the lower activation energy for iodine radical abstraction than for
bromine radical abstraction [243].
H X
X
Et4NClO4
+ + (17.48)
Red., Ni(l) cathode
N O N O N O N O
–
–
–
Ts a: X = Br Ts Ts Ts
117 b: X = I
117a, DMF: 41% 5% 14%
117a, DMF, 2 eq. Ph2PH 59% 8% —
117a, MeCN 8% — 33%
117a, MeCN, 2 eq. Ph2PH 58% 15% —
117b, MeCN — 14% 61%
Under conditions similar to those in Equation 17.51 (DMF as solvent, divided cell), reduction
of 118 (X = I) gives 75% of the cyclized product [241]. The yield was improved (90%) using an
undivided cell and a sacrificial Mg anode (Equation 17.49) [246]. The yields increased in the order
Cl < Br < I.
X
DMF, Bu4NBF4
Ni(l) cathode, undiv. cell, Mg anode 60–90%
O
O (17.49)
118
X = Cl, Br, l
The carbon–halogen bond is stronger in vinyl halides than in alkyl halides, and Ni-complexes
with slightly lower reduction potentials have to be used to catalyze the reductive cyclization of
vinyl halides on to alkene functions. Using conditions similar to those for the alkyl and aryl halides
5-exo-cyclized products were obtained from 119 [241]. In a single case (methyl substitution at the
position of 5-exo-attack), only the 6-endo-product was obtained (Equation 17.50) [241].
R2
R2
Br R1
R1 DMF, Et4NClO4 R3
R3
Red., Ni(l) cathode
MeOOC COOMe MeOOC COOMe (17.50)
MeOOC COOMe
119 45–85% 32%
R1 = H R1 = Me
R2, R3 = H, Me R2, R3 = H, H
Tandem cyclization was not obtained for 119. However, this could be achieved for 120 in which
the vinyl halide was further activated with an acetyl group (Equation 17.51), and the catalyst was
used in a larger amount (0.3–0.5 eq.) [245].
R1 R1
X COMe DMF, Et4NClO4 COMe
Red., Ni(l) cathode
Y Y 40–50%
(17.51)
120
R1 = H, Me, Ph
X = Br, l
Y = C(COOEt)2,N-Ts, N-allyl
In explanation of the difference, it was proposed that the subsequent formation of the cyclopropyl
ring by 3-exo-cyclization is reversible. The electron-withdrawing group at the final radical center pro-
motes its rapid reduction (by the “excess” Ni(I)-complex) to a carbanion that is rapidly protonated [245].
The substrate, 121, has been cyclized using reduced vitamin B12a as a catalyst (0.01 eq.). The radi-
cal formed by cyclization can be trapped with an activated alkene (added in excess) to form a new
radical that probably undergoes reduction and protonation to give a mixture of diastereoisomeric
products [247] (Equation 17.52).
EtO
OEt
OEt O
O O CN
DMF, LiClO4
Br
OAc (17.52)
Red., Co(l) cathode CN
63%
121
OAc
7. Coupling of Alkynes with Organic Halides

Cyclization by direct reduction of alkynes linked to halides is usually ineffective. Phenyl sub-
stituted alkynes are more easily reduced than alkyl chlorides but more difficult to reduce than
alkyl bromides and iodides. Simple alkynes are more difficult to reduce than any of the halides.
Consequently, direct reduction of 6-bromo-1-phenyl-1-hexyne at the potential of cleavage of the
C–Br bond only affords 12% of benzylidenecyclopentane, whereas the corresponding chloride gives
the saturated benzylcyclopentane in 45% yield [248] or, at low substrate concentrations (<2 mM),
the benzylidene cyclopentane (80%) [249].
Predictably, Ni(I)-catalyzed reductive cyclization of halides onto alkynes requires conditions
similar to those for Ni(I)-catalyzed reductive cyclization of halides onto alkenes. The alkynes are
converted into alkylidene or benzylidene substituted five-membered rings [241–243,250].
Cobaloxim(I) has been shown to catalyze intramolecular reductive coupling of cyclic bromo
acetals with double and triple bonds, although fairly large amounts of the catalyst (0.5 eq.) had to
be used [251]. Significantly better yields (75–87%) were obtained when MeOH was used as sol-
vent instead of MeCN or DMF (Equation 17.53). Formation of six-membered rings could not be
achieved [252].
In contrast to the allyl ethers, 118, the analogous propargyl ethers were cyclized to the corre-
sponding benzofuran in poor yield (≈30%) using the same conditions as in Equation 17.49 [253].
R
R
Br MeOH (17.53)
Red., Co(l) cathode
O O
O O
V. REDUcTivE COUPLiNGS INvOLviNG ATOMS iN AN AROMATic RiNG

Intramolecular reductive couplings between alkenes and aromatic halides have been mentioned in
Sections IV.B.5 and IV.B.6. Here discussion centers on reductive coupling either between two aro-
matic rings or between an aromatic ring and another, nonolefinic molecule.
A. INTErMoLECULar CoUpLINGS
Intermolecular reductive couplings between aromatic rings mostly involve either reactive aryl
σ-radicals, for example, derived from aromatic halides by cleavage of the radical anions, or rela-
tively stable π-radical anions derived from aromatic compounds activated by electron-withdrawing
substituents.
1. Coupling between Aromatic Halides

Homo- and heterocouplings of aromatic halides are almost always carried out using transition metal
catalysts, commonly Ni(0) or Pd(0) species. The practicability of these inner-sphere reactions has
been developed in the last two decades and mechanistic details elucidated in a number of cases.
Preparative aspects of transition metal catalyzed couplings of aryl halides have been reviewed [204]
(see also Chapter 25). The subject will therefore not be treated here.
2. Dimerization of Aromatic Compounds Activated

with Electron-Withdrawing Substituents
Reduction of electron-poor aromatics gives radical anions which, because of the electron-with-
drawing substituents, are quite stable with respect to protonation and cleavage in aprotic sol-
vents. The products are the “tail-to-tail” dimeric dianions, Equation 17.54, which are stable in
the absence of acids [254–265]; in the early studies in only one case was the structure verified, by
electrolysis at semi-preparative scale, in DMSO-d 6 with 1H-NMR examination of the electrolyte
[256]. These reactions, which have little utility for synthesis, have nevertheless attracted much
study by most available electroanalytical techniques as model systems for the exploration of the
kinetics and thermodynamic features of reductive dimerization.
EWG H EWG
EWG EWG – –
2e kdim 2H+
2 2 H H
kdiss H H
122 a: EWG = NO2 –

b: EWG = COMe H EWG
c: EWG = COOMe EWG
d: EWG = CHO R,R; S,S; and meso
e: EWG = CN 123 124 125
O O O O
OH O O
(17.54)
Cl CN

Cl CN
O O
126 127 128 129
NO2 CN NO2
CN
O2N NO2 O2N NO2

CN
F
130 131 132 133
In CV, a new peak on the reverse scan at a potential several hundred mV anodic relative to the
potential of radical anion formation has been assigned to oxidation of the dimer dianion. Oxidative
electrolysis of the dimer dianions in most cases restores the starting material. In some cases, air
oxidation will affect the regeneration of starting material [256,261].
The tetrahydrobianthryl products, formed by protonation of the dimeric dianions, have been
isolated (up to 90% yield) in some cases after addition of acids [260,262,263]. The dimer dianion is
trapped by acid (or in a single case by methyl iodide [266]).
Reversibility of the dimerization step on a voltammetric time scale has been verified for sev-
eral of the 9-substituted anthracenes in the absence of added acids [266]. For 122a and 122e, the
reversibility of the dimerization step is prevented by addition of AcOH, which protonates the
dimer dianion in a fast follow-up reaction (the radical anions are not protonated by AcOH) [258].
Since the rate and equilibrium constants for dimerization, kdim and Kdim, for 122e are of a mag-
nitude that can conveniently be measured using CV and DPSC [254,255,257–260,264,266,267],
122e has been used as a model compound for mechanistic studies of systems undergoing revers-
ible dimerization, and values of kdim and Kdim have been determined under a number of different
conditions (Table 17.20).
The addition of AcOH simplifies the kinetics by making the dimerization irreversible but
had little influence on the measured values of k dim [258]. Addition of a metal cation or water
to the aprotic solvents accelerates the dimerization reaction of 122e− •, that is, effects similar
to those observed for EHD of some activated alkenes (see Section II) and the interpretation
is similar. Acceleration of the dimerization reaction with increasing water concentration was
demonstrated for 122e in DMF and DMSO [258,268] and is entirely related to solvation of the
anionic intermediates since water is too weak an acid to protonate either the radical anion or
the dimer dianion.
TABLE 17.20
Selected Rate and Equilibrium Constants for Dimerization of Radical Anions Derived
from Substituted Aromatics
Substrate Conditions kdim/M−1 s−1 Kdim/M−1 Comments References
9-Cyanoanthracene DMSO, LiClO4, 2.8⋅10 5 5.7⋅104 α = 0.4, ks = 0.8 cm s−1 [260]
(122e) 20°C, DPSC, LSV
122e DMSO, Bu4NBF4, 1.9⋅105 4.5⋅104 Ea(dim) = 10.2 kJ [260]
20.5°C, DPSC mol−1, A = 7.9⋅108
M−1 s−1,
Ea(diss) = 72.8 kJ
mol−1
≠
122e DMF, Bu4NBF4, 1.9⋅105 a
∆H dim = 1.2 kcal [258]
≠
AcOH, 20.6°C, mol−1, ∆Sdim = −30
DPSC cal K mol−1
−1
≠
122e DMF, Bu4NBF4, 1.6⋅105 2.2⋅104 ∆H dim = 1.7 kcal [267]
≠
25°C, DPSC mol−1, ∆Sdim = −29
cal K−1 mol−1
≠
122e MeCN, Bu4NBF4, 5.3⋅105 8.2⋅104 ∆H dim = 2.2 kcal [267]
≠
cal K mol−1
−1
≠
122e PC, Bu4NBF4, 25°C, 1.5⋅105 2.9⋅104 ∆H dim = −0.5 kcal [267]
≠
DPSC mol−1, ∆Sdim = −37
cal K−1 mol−1
≠
122e HMPA, Bu4NBF4, 4.1⋅104 2.2⋅103 ∆H dim = 4.5 kcal [267]
≠
cal K mol−1
−1
≠
122e Pyridine, Bu4NBF4, 2.2⋅105 2.3⋅104 ∆H dim = 0.7 kcal [267]
≠
cal K−1 mol−1
≠
122e CHCl2, Bu4NBF4, 1.5⋅105 ∆H dim = 2.7 kcal [267]
≠
cal K mol−1
−1
≠
9-Formylanthracene DMF, Bu4NBF4, 3.1⋅105 a ∆H dim = 2.6 kcal [258, 267]
≠
(122d) 22°C, DCV mol−1, ∆Sdim = −25
cal K−1 mol−1
122d DMF, Et4NClO4, CV 105 b [280]
122d MeCN, Et4NClO4, >4⋅105 b [280]
CV
122d HMPA, LiClO4, CV 2⋅104 b [261]
9-Formyl-10- DMF, Et4NClO4, CV c [261]
methylanthracene
≠
9-Nitroanthracene (122a) DMF, Bu4NBF4, 1.6⋅106 d ∆H dim < 1.2 kcal [266]
≠
22°C, DCV mol−1, ∆Sdim < −26
cal K mol−1
−1
≠
122a DMF, Bu4NBF4, 2.3⋅106 a ∆H dim = −0.2 kcal [258]
≠
AcOH, 22°C, DCV mol−1, ∆Sdim = −30
cal K mol−1
−1
122a DMF, Bu4NClO4, 106 e [258]

DCV
1,3-Benzenedicarbonitrile DMF, Bu4NClO4, 1.1⋅105 106 [274]
25°C, CV, LSV
(Continued)

Selected Rate and Equilibrium Constants for Dimerization of Radical Anions Derived
from Substituted Aromatics
Substrate Conditions kdim/M−1 s−1 Kdim/M−1 Comments References
≠
9-Fluoro-10- CH3CH2CN, 1.8.10 5
∆H = 2.4 kcal
dim [271]
≠
cyanoanthracene (132) Bu4NPF6, CV mol , ∆Sdim
−1 = −26
cal K−1 mol−1
1,3,5-Trinitrobenzene MeCN, Bu4NPF6, CV 1.8.105 [273]
(133)
Acridine (138) DMF, Bu4NClO4, 2.8.105 b [263]
DCV
Quinoline (139) NH3, CF3SO3K, 4.8.103 8.4⋅102 Ea(dim) = 12 kJ mol−1; [282]
21°C, 8.1 bar A = 7.105 M−1 s−1
a Dissociation reaction not taken into account.

b Not reversible on CV time scale.
c Radical anion stable on CV time scale but dimer dianion formed on preparative time scale.
d Irreversible due to protonation.
e Reversibility not considered.
For 122e, the effect on kdim and on Kdim induced by change of the solvent (Table 17.20) is modest
≠
and not easily interpreted [267]. The activation enthalpies for the dimerization step, ∆H dim , are small
(<5 kcal mol−1, and even negative for 122a). For reference, the values of kdim [255,258,266,267] are
included.
This blizzard of electroanalytical activity led to the postulation of two mechanisms (Scheme
17.25): (a) pre-association of two radical anions in a fast pre-equilibrium followed by reversible
bond formation [258,266,267] and (b) simple, reversible dimerization of two radical anions [264].
Since the rate laws are identical for the two mechanisms as long as the equilibrium constant for
formation of the intermediate precomplex is small, kinetic measurements cannot be used to distin-
guish between them. The “precomplex” is often termed a π-complex, although it is not clear what
≠
the bonding would be. For mechanistic interpretation (a), the low ∆H dim -values are explained by a
negative enthalpy of formation of the precomplex, whereas for interpretation (b) the low values of
≠
∆H dim are explained by opposing effects of coulombic repulsion and increased solvation when the
two negatively charged radical anions become located within the same solvent cage.
Digital simulation of voltammograms of a quinone (129), well known to form π-complexes,
required the inclusion of π-dimer formation and UV absorption at 720 nm supported this [269]. For
the quinones (126)–(128), simulation of their voltammograms required participation of π-dimers
for (126) and (128), but for (127) assumption of the simple stepwise reaction to the ø-dimer dianion
was required to give the best fit [269,270].
(b)
2–
H Ar 2–
2e – (a) HAr ArH
2 ArH 2 ArH
ArH
π-complex σ-dimer dianion
SchEME 17.25 Alternative routes proposed for dimerization of activated aromatic hydrocarbons. Mechanistic
alternatives (a) and (b) are explained in the text.
9-Fluoro-10-cyanoanthracene (132) was expected to reduce with loss of fluoride ion from the
first-formed radical anion (see, for example, the mechanism illustrated in Scheme 17.27). However,
fluoride loss occurred after radical-anion coupling to give, as expected, 9,9′-bianthryl-10,10′-
dicarbonitrile. Digital simulation of voltammograms revealed [271] a low activation energy for
the dimerization step (Table 17.20) and the formation of a σ-dimer with no evidence for π-dimer
participation.
More weight to the view that π-dimer participation was likely to be rare in this series of reductive
coupling reactions comes from a voltammetric study [272] of compounds (122e), (130), and (131)
at high pressures (up to 300 MPa). This enabled the measurement of reaction volumes. These are
negative, for example, for (122e) the activation volume is −33 cm3 mol−1 and the activation energy
is 8.9 kJ mol−1. The reaction volumes are similar for both acetonitrile and dichloromethane solu-
tion and these results are interpreted in terms of the radical-anion dimerization step being favored
by increased pressure, with little solvation, and simple stepwise formation of the σ-dimer dianion.
However, for reduction of 1,3,5-trinitrobenzene (133) in acetonitrile a π-dimer dianion (134) was
isolated in crystalline form as its tetraethylammonium salt and the structure unambiguously char-
acterized by X-ray crystallography [273]. Furthermore a remarkable series of transformations was
revealed, with convincing proof of structure at each stage, the fate of the π-dimer dianion depend-
ing on whether the reaction was carried out under argon or dinitrogen. Dinitrogen reacts with the
π-dimer dianion reversibly to give 136 (Scheme 17.26), whereas under argon 134 is converted into
a σ-dianion, 135.
Similar reversible dimerization has also been observed for 1,3-benzenedicarbonitrile, followed
by ESR spectroscopy and CV [274], for dialkyl benzene-1,3-dicarboxylate, dialkyl pyridine-1,3-
dicarboxylate, also characterized by CV and ESR spectroscopy [275]. On a preparative scale a
competing slow, but irreversible, first-order reaction gave the monocarboxylate anions as the sole
product [275]. For aromatic compounds substituted both with an electron-withdrawing group and a
potential leaving group, dimerization of the radical anions competes with cleavage. In cases where
dimerization is the favored pathway, the initially formed dimer dianion may subsequently lose two
anions in a fast reaction leading to stable biaryl products rather than to the dihydro products dis-
cussed earlier. This is the case for 4-fluorobenzonitrile, 137 [276], polyhalonitrobenzenes [277],
9-cyano-10-chloroanthracene [278], and cyanodiphenyl ether, 138 [279]. Reduction of 137 in DMF
NO2
2x 133
O2N NO2
Argon
N2
NO2
NO2
H
2e H O2N
O 2N –
N O2N O2N –
– NO2
NO2 N
136 – NO2 NO2 H
H NO2 O2N 135
O2N Argon
O2N –
N2 O2N
NO2
– NO2
O2N 134
SchEME 17.26 Remarkable transformations in the reduction of 1,3,5-trinitrobenzene.

CN CN
CN –
CN –1
s –
e– = 11.2 CN CN
k cleav
kd
im =
10 3
F M –1
F s –1 F 137–
137 –
– CN –2 F–
NC –137
F
CN CN
SchEME 17.27 Competing pathways in the reduction of 4-fluorobenzonitrile.
leads at high substrate concentrations to formation of 4,4′-dicyanobiphenyl (in the reduced form,
since the product is more easily reduced than the substrate) (Scheme 17.27). In contrast, reduction
of 2-fluorobenzonitrile leads only to formation of benzonitrile, although the primary reaction also
in this case is dimerization of two radical anions. The values of kdim are comparable for 2- and
4-fluorobenzonitrile radical anions but since both radical anions are assumed to undergo coupling
in the 4-position (largest unpaired spin density) only the dimer dianion of 137 can re-establish the
aromatic structure by loss of two F− [276].
Reduction of pentafluoronitrobenzene in DMF or MeCN also leads to a radical anion that under-
goes dimerization, kdim = 3.8⋅105 M−1 s−1, followed by rapid loss of two F− to give 4,4′-dinitroocta-
fluorobiphenyl. However, this compound is more easily reduced than the starting material and is
further reduced to either the mixed amino-nitro or the diamino derivative [277]. Significantly, the
radical anion of pentafluoronitrobenzene is stable on a voltammetric time scale when MeOH/water
mixtures are used as solvent, indicating important differences in the solvation of the radical anion
in protic and aprotic solvents [277]. The carbon–chlorine bond is cleaved more rapidly than the
carbon–fluorine bond, suggesting that first-order cleavage of the pentachloronitrobenzene radical
anion is favored over dimerization, and a mixture of dimeric and monomeric products is formed
[277]. A similar change from second-order to first-order reaction was observed for radical anions of
9-cyano-10-haloanthracenes, the chloro compound undergoing a second-order reaction to give the
dimer, 9,9′-bianthryl-10,10′-dicarbonitrile (65%), in MeCN, whereas the bromo compound under-
went cleavage [278].
3. Coupling of N-Heteroaromatic Compounds

Radical anions derived from N-heteroaromatic compounds are more distonic than their hydrocar-
bon analogs because of the electronegative nitrogen atom. As a consequence, these radical anions
are generally more reactive.
Radical anions of acridine, 138, dimerize in DMF to give the corresponding dimer dianion
[281] (see Table 17.20). The reduction remained a 1 F process upon addition of 10% (v:v) water
but led to a fivefold increase in the value of kdim. On a voltammetric time scale, the dimerization
appeared irreversible in the absence as well as in the presence of water. On a preparative scale the
dimer, 9,9′-10,10′-tetrahydro-9,9′-biacridyl, could be isolated (60–70%) only when the reduction
was carried out in DMF containing 7–10% water [281]. The dimerization in ammonia (CF3SO3K as
supporting electrolyte) of the radical anions of 138 and of quinoline, 139, has been studied over a
220° temperature range (−70 to 150°C) utilizing a special cell constructed for working in ammonia
at high pressures and high temperatures [282]. Several electroanalytical techniques (CV, LSV, and
DPSC) were applied in order to characterize the kinetics and thermodynamics of the dimerization
reactions. In both cases, the dimer dianions were stable with respect to further irreversible reac-
tions, and by varying the temperature and the scan rate, the dimerization processes could be shifted
through several kinetic zones in which the dimerization either did not take place at all, appeared
reversible, or appeared irreversible. The choice of supporting electrolyte cation was important,
when K+ was changed to Bu4N+ kdim decreased by about two orders of magnitude for 139− • [282].
Kinetic and thermodynamic data for the two dimerization processes are found in Table 17.20. Low
activation energies are also found for these dimerizations (see Table 17.20).
H Ph
N N N S N S
N N
138 139 140b 140c

(17.55)
1
6 N N N
2
2e –N N–
5 N
3
4 Not isolated
140a
Pyrimidine, 140a, undergoes one-electron reduction in MeCN to a radical anion, which under-
goes a second-order reaction, and on a coulometric time scale, n = 1.05 was found (Equation 17.55).
The product was not isolated but dimerization at the 4-position was assumed to take place [283].
A new anodic peak corresponding to oxidation of the dimer dianion (or its monoprotonated form)
was observed. The value of kdim was estimated by CV to ≈8 ± 5⋅105 M−1 s−1 [283]. In acidic aque-
ous solution (pH < 5), reduction of 140a is also a one-electron process since the pre-protonated
(at nitrogen) species is more easily reduced than the resulting neutral radical [283]. Because the
initial reduction is pH dependent whereas the reduction of the radical is not, the two reduction
steps merge into a two-electron process at pH > 5. The dimerization in acidic aqueous solution has
been studied by a variety of electroanalytical methods [284]. Preparative scale reduction of 140a in
aqueous solution at pH 0.6 gave the hydrodimer, 4,4′-tetrahydrobipyrimidine, in a clean 1 F process
[285]. The product could subsequently be oxidized by KMnO4 to bipyrimidine.
In DMF, the two substituted thio derivatives of pyrimidine, 140b and 140c, were found to dimer-
ize upon reduction in the absence as well as in the presence of acid [286]. For 140b, however, the
coulometric n-value was close to 0.5 in the absence of proton donors, indicating that the N-proton in
140b is sufficiently acidic to protonate either the radical anion or the dimer dianion, thereby leaving
half of the substrate as the irreducible anionic form. In the presence of stoichiometric amounts of
HClO4, the reduction takes place via the preprotonated substrate as for 140a [286]. The rate constant
for dimerization of 140c− • (in the absence of acid) was found to be close to that for 140a− • [286].
B. INTraMoLECULar CoUpLINGS
The major reason for using transition metal catalysts in the intermolecular coupling of aryl halides
is to minimize the competition from further reduction of the radical formed by carbon–halogen
bond cleavage of the radical anion. Intramolecular reaction outruns further reduction when the
σ-aryl radical is sterically placed to react with a second aryl group. The slower the cleavage reac-
tion the further away from the electrode is the radical formed, which favors coupling in competition
with further reduction. However, since coupling between phenyl radicals and aryl groups normally
is slower than between phenyl radicals and alkenes, the same drawbacks as discussed in Section
IV.B.6 pertain to these reactions.
The scope of the reaction type has been explored in particular by Grimshaw and coworkers
[287–297]. Since the rate constant for cleavage of the carbon–halogen bond decreases in the order
I > Br > Cl > F, yields of coupling products are usually higher using chloro rather than bromo com-
pounds. Most of the studies have been carried out by controlled potential electrolysis (Ew ≈ −2.1 V
for the chloro compounds) in DMF using divided cells and Hg-cathodes [287–296].
Where an aryl halide is connected to the “receiving” aryl function by an amide linkage, as in
Equation 17.56, two different types of cyclization occur, depending on where the initial radical
attack takes place [287,289–291]. The relative yields of the two cyclization products depend on the
substitution pattern in the aryl group being attacked [289]. Only the syn-conformation of the radi-
cal anion can give rise to coupling, and rotation about the amide bond is particularly slow when
o-substituents are present. Where the aryl group under attack is o-disubstituted <40% cyclization is
obtained, and only if both o-positions are unsubstituted is the tricyclic product formed [289].
O
O CONHMe
N
N R 1 DMF, Pr4NClO4 R2 + R1
X Hg cathode (17.56)
R1
R1 = H R1 = Me R2 R1 = H
X = Cl, Br, l R2 X = Cl, 45% X = Cl, 76% X = Cl, 38%
X = Br, 38% X = Br, 49% X = Br, 33%
X = l, 24% X = l, 23% X = l, 26%
The process that leads to the final, formal, loss of a hydrogen atom to the 0 F tricyclic products
is not clear. In contrast, the formation of the 2 F biaryl products can be explained by further reduc-
tion of the cyclized radical followed by cleavage of the carbon–nitrogen bond and protonation.
Unless the two aryl groups in the substrate are linked through an electron-withdrawing function
with respect to the aryl halide ring, the reduction potential is shifted cathodic and the current yields
drop significantly due to hydrogen formation [292]. A series of N-phenyl nitrogen heterocyclic sys-
tems such as pyrroles [294], imidazoles [292,294], oxazolinones [288], triazoles [293], and tetra-
zoles [294,295,297] have also been used as “linkers” to the aryl halide. The N-heterocycles give
exclusively coupling of the chloro substrates to tetracyclic products (formally 0 F products) in yields
up to 90% when reduced under conditions similar to those in Equation 17.56.
The reduction of the tetrazoles (Equation 17.57) has been used as a model for optimization
of the chemical yield using an undivided cell and constant current rather than constant potential
electrolysis [296,297]. Electrolysis under air rather than under nitrogen lowered the current yield
(from 43 to 20%) but increased the product selectivity (from 50 to 94%) since the intermediate,
partly hydrogenated fluorophenyl ring was dehydrogenated, probably by electrogenerated super-
oxide ion [297].
N N N
N N
N MeCN, Et4NBF4 N Current yield: 20%
N
Mild-steel cathode, Product selectivity: 94%
Ar (17.57)
Cl Mg anode, air,
undiv. cell, CCE
Ar = 4-F-phenyl
F
Reduction, in dry DMF, of 1,1′-binaphthyl systems of the type 141 has been shown to result in
“double” intramolecular couplings giving the enlarged aromatic anthanthrene system (Equation
17.58) in almost quantitative yields [298].
–
COR R R
DMF, Et4Nl O2
ROC 3F R R (17.58)
141
R = H, Me
SO2Ph
SO2Ph
SO2
143 142
142 Reduction
– PhSO–2
142
– Reduction
H Intramolecular
Cyclisation Protonation SO2Ph
SO2Ph
SO2 Base SO2
144
143 –
SchEME 17.28 Rare case of radical anion formation by deprotonation of a radical.
The reaction is most probably initiated by radical attack of a reduced carbonyl function on the
aromatic ring in the adjacent system. The product is formed as the radical anion but reoxidized by
air during work-up. In the presence of proton donors, or in alcoholic solvents, reduction of 141 gives
a mixture of acyclic and partly hydrogenated cyclic products [299]. Substituted 141, for example,
the 4,4′,5,5′-tetracarboxylic acid, gives coupling in basic alcoholic medium but not in DMF [300].
When the methyl substituted derivatives of o-bis(phenylsulfonyl)benzene, 142, are reduced in
DMSO, good yields of the intramolecularly coupled products are obtained. These are methyl substi-
tuted dibenzothiophene dioxides, 143, formed after initial cleavage of PhSO2− from the radical anion
followed by intramolecular attack of the aryl radical on the phenyl group [301] (Scheme 17.28).
The reaction was shown to be catalytic with respect to current in the presence of an external base,
which indicates, for one example, the reaction pathway in Scheme 17.28, that is, formation of the
radical anion of the product by deprotonation of the intermediate radical. In the presence of 2 eq.
of AcO − as base, the reaction became a 0.14 F process, and the yield of cyclized product increased
to >95%. In the absence of added base, PhSO2− is probably the active but less efficient base leading
only to 68% of 143 along with a hydrogenated derivative and the noncyclized 2 F product, 144 [301]
(see Scheme 17.28). Although the electron transfer from 143− • to 144 is endothermic, the overall
reaction is driven by the fast cleavage of 143− •.
Intramolecular reductive coupling between aromatic rings (phenyl, naphthyl, anthryl) and non-
conjugated keto groups have been achieved in 25–70% yield [302] (Equation 17.59). Lower yields
were obtained with other combinations of solvents and electrolytes and by application of other
cathode materials.
O Me
H OH
i-PrOH, Et4NOTs (17.59)
70%
Sn cathode, div. cell, 4 F
However, only six-membered rings were formed successfully, and only nonaromatic ketones
could be used [302]. The reaction is initiated by reduction of the keto group, and the reaction is
highly stereoselective with a cis arrangement for the hydroxy group and the hydrogen at the cou-
pling site. The neutral medium and observed effects of substituents in the aromatic ring indicates
that the coupling involves an ion-paired radical anion and that the diastereoselectivity is controlled
by coulombic interactions.
Compounds 145 are nonplanar and undergo 1 F reduction in MeCN around −2 V [303]. The radi-
cal anions derived from 145a–d undergo stereoselective cyclization according to Equation 17.60,
whereas 145e–h give stable radical anions. The initial product, the cyclized radical anion, is air-
oxidized upon work-up giving the 0 F cyclized product, which is identical to the product obtained
by photoexcitation [303]. The radical anions that fail to cyclize are those in which extended delo-
calization is not achieved by flattening of the ring systems or in which steric hindrance prevents
co-planarity of the ring systems [303].
W W – Y Z – Y Z
Y Z O O
Y Z e– a–d W O2 W
X X
O O –O2–
X X O O
O e–h
O (17.60)
145
a: W = X = O, Y = Z = Me e: W = X = O, Y, Z = adamantylidene
b: W = X = O, Y = H, Z = Me f : W = S, X = NPh, Y = Z = Me
c: W = S, X = O, Y = Z = Me g: W = S, X = NC6H4NO2, Y = Z = Me
d: W = S, X = NBz, Y = Z = Me h: W = S, X = NCH2COH, Y = Z = Me
C. CoUpLING bETwEEN AroMaTIC RINGS aND OTHEr REaGENTS

OCOCH3
DMF, Bu4Nl, Ac2O

66–75% (17.61)
Hg cathode

Reductive coupling, in aprotic solvents, of aromatic hydrocarbons with CO2 has long been known.
Reduction of naphthalene in DMF in the presence of CO2 leads to 1,4-dicarboxy-1,4-dihydronaph-
thalene (≈50%) [304]. Under similar conditions, phenanthrene gives trans-9,10-dicarboxy-9,
10-dihydrophenanthrene (≈30%) [304]. Carboxylation of aromatic halides can be achieved in
aprotic solvents either by using transition metal catalysts or by direct reduction using sacrificial
anodes in undivided cells (see Chapters 24, 25, and 36).
Reduction of anthracene in the presence of an excess of acetic anhydride led to formation of the
enol acetate of 9-acetyl-9,10-dihydroanthracene (Equation 17.61) [305]. In each case, the hydro-
carbon is the species reduced, but whether or not the ensuing radical anion is involved in electron
transfer to CO2 or Ac2O prior to coupling was not investigated.
Intermolecular coupling between aromatic rings and nonaromatic organic halides have been
observed in a number of cases [306] and refs. therein. The mechanism of these reactions is well
understood. The aromatic compound is reduced and electron transfer to the halide takes place in
solution; the radical resulting from cleavage of the halide may either be reduced or undergo coupling
with the aromatic radical anion depending on the relative reduction potentials of the radical and the
aromatic system. In cases where coupling takes place, the anion formed in the coupling process
may either be protonated by the medium or undergo SN2 reaction with another molecule of halide.
An example of the first type of coupling reaction is the t-butylation of pyrene [307]. Upon reduction
of pyrene in DMF in the presence of t-BuCl, 1-t-butylpyrene is formed as the major product (52%)
after coupling, protonation and oxidation of the dihydro compound [307]. An example of the sec-
ond type of coupling is the formation of 9,10-ethano-9,10-dihydroanthracene (57%) by reduction of
anthracene in DMF in the presence of a moderate excess of 1,2-dichloroethane [308]. The reaction
type is further discussed in Chapters 25 and 36.
Intermolecular coupling of pyridines with ketones under acidic conditions has received attention,
but like the intramolecular reductive coupling of aromatic rings linked to aliphatic ketones (Equation
17.59), the reaction is essentially a ketone reduction and the reader is referred to Chapter 31.
D. REDUCTIVE DIMErIZaTIoN oF PoSITIVELY CHarGED AroMaTIC SYSTEMS

One-electron reduction of positively charged systems leads to neutral radicals, and independently
of the structure the most common follow-up reaction is fast dimerization of two neutral radicals.
In contrast to neutral radicals formed by cleavage, those formed by reduction of positively charged
aromatic systems are not reduced at the potential where they are formed, and formation of 2 F prod-
ucts therefore only competes via H-atom abstraction. For N-heterocyclic systems in aqueous acidic
media, protonation of the radical and further reduction leading to the dihydro-monomeric system
may compete with dimerization.
1. N-Alkylpyridinium and Related Systems

The electrochemical reduction of pyridinium cations and other positively charged N-heteroaromatic
systems has received considerable attention as models for nicotinamide adenine dinucleotide
(NAD+) and nicotinamide adenine dinucleotide phosphate (NADP+).
The major reaction pathway in all cases consists of reduction to the neutral radical followed
by coupling, primarily or exclusively in the 4-position with respect to the ring-nitrogen. Like the
dimeric dianions formed by dimerization of, for example, 122 − •, the neutral dimeric products
obtained from positively charged N-heteroaromatic systems are in many cases difficult to isolate
since they are easily reoxidized back to the substrate cations.
Reduction of the simple N-methylpyridinium ion, 146, is believed initially to give the expected
N,N′-dimethyltetrahydro-4,4′-bipyridine but the end-product (in the absence of oxygen) is the N,N′-
dimethylbipyridine radical cation formed by a formal loss of two hydride ions and one-electron
reduction of N,N′-dimethylbipyridinium [309,310]. The isolated product, N,N′-dimethylbipyridinium
dication, results from air oxidation of the radical cation (Equation 17.62) [310].
e– kdim H
2+
N Me
–
Me N N Me
– –
+
Me N
–
N N –2 H–
H
–
Me Me (17.62)
e–
146
+
Me N N Me
– –

CONH2 CONH2 CN
+ +
N + + N
N N N +
CH2Ph CH2Ph CH2Ph Me
147a 147b 147c 148 149
The reaction pathway in Equation 17.62 dominates for pyridinum ions unsubstituted in the 4-posi-
tion, whereas 4-alkylpyridinium ions undergo reductive coupling to the 4,4′-tetrahydrobipyridine
derivatives [311]. Values of kdim have been determined for several pyridinyl radicals in MeCN
[311] (see Table 17.21). Despite the complication of air oxidation, the dimers have been isolated in
40–70% yield.
Reductive dimerization of the NAD+-analogs 147a–c, in MeCN, and the reoxidation of the
dimers have been studied in detail by CV and LSV [312]. This allowed the estimation of the
Eo′-values and the dimerization rate constants (Table 17.21). Also in aqueous medium, 147a under-
goes fast reductive dimerization, and the 4,4′-tetrahydrodimer was isolated as a mixture of two
diastereoisomers [313].
The kinetics of the reductive dimerization of NAD+ in aqueous buffer (pH 9.1) has been stud-
ied by DPSC, CV, and LSV (see Table 17.21) [314]. Reduction of NADP+ on a preparative scale in
0.1 M NH4Cl/NH3 buffer (pH 9.3) leads to a mixture of dimers formed by coupling of the pyridine
TABLE 17.21
Rate Constants for Reductive Coupling of N-Substituted Pyridinium, Quinolinium,
and Acridinium Compounds
Substrate Conditions kdim/M−1 s−1 Eo′/V References
N-Methylpyridinium (146) H2O, KCl, pH 5–11, 25°C, polarogr. >10 7 −1.372 a [317]
1,2,4,6-Tetramethylpyridinium MeCN, Et4NClO4, CV 2.5⋅106 [311]
2-ethyl-1,4,6-Trimethylpyridinium MeCN, Et4NClO4, CV 2.5⋅106 [311]
4-ethyl-1,2,6-Trimethylpyridinium MeCN, Et4NClO4, CV 1.8⋅106 [311]
2,6-diethyl-1,4-Dimethylpyridinium MeCN, Et4NClO4, CV 2.6⋅106 [311]
2,4,6-Triethyl-1-methylpyridinium MeCN, Et4NClO4, CV 1.5⋅106 [311]
1-Ethyl-2,4,6-trimethylpyridinium MeCN, Et4NClO4, CV 2.0⋅106 [311]
1,4-Diethyl-2,6-dimethylpyridinium MeCN, Et4NClO4, CV 8.0⋅105 [311]
NAD+ H2O, Et4NCl, pH 9.1, 25°C, CV, 3⋅107 −1.155 [314]
LSV, DPSC
147a MeCN, Et4NBF4, 20°C, CV, LSV 7.9⋅108 −1.105 [312]
147b MeCN, Et4NBF4, 20°C, CV, LSV 2.0⋅108 −0.720 [312]
147c MeCN, Et4NBF4, 20°C, CV, LSV 5.0⋅108 −0.520 [312]
148 MeCN, Et4NBF4, 20°C, CV, LSV 2.5⋅107 −0.465 [312]
148 MeCN, Et4NBF4, 20°C, DPSC (3 ± 1)⋅107 −0.460 [316]
a V vs. NHE. Strong adsorption of the dimer was found for C° > 2⋅10–4 M.
ring systems. The three diasteromeric 4,4′-dimers were the major products (≈70%) formed along
with minor amounts of the 4,6′-dimers [315]. Reduction of N-methylacridinium ion, 148, in MeCN
gives the expected dimer, 10,10′-dimethyl-9,9′-biacridine [312]. The value of kdim for 148 was found
[312,316] to be about an order of magnitude smaller than that for the radical derived from 147 (see
Table 17.21), probably due to the greater delocalization in the radical derived from 148.
Reduction of acridizinium ion, 149, and substituted acridizinium ions in MeCN or DMF gives a
dimer (≈80%) [318]. Although not confirmed experimentally, the most likely positions for coupling
are indicated. The results of LSV measurements were in agreement with rate-determining dimer-
ization of neutral radicals, and for 149 a lower limit for the rate constant of 107 M−1 s−1 was obtained
by CV measurements [318]. The dimer could be quantitatively reoxidized to the substrate cations
either electrochemically (at a potential ≈0.5 V anodic relative to the initial reduction peak) or by
action of oxygen [318].
Rn
Rn Rn
10% aq. H2SO4 Total yield
+ H H
N O Hg cathode OH + OH (17.63)
N N n = 1, 2; 40–62%
n n n n = 3, 15%
n = 1–3
Inter- and intramolecular cross-couplings involving pyridinium rings are known. The cross-
coupling of pyridine with acetone in acidic medium mentioned earlier is analogous to the intra-
molecular reductive cross-coupling of 1-(oxoalkyl)pyridinium ions (Equation 17.63). In contrast
to the intramolecular coupling between phenyl groups and keto groups (Equation 17.59), which
only gives rise to six-membered rings, good chemical yields are obtained of both five- and six-
membered rings in the case of pyridinium ions (whereas formation of seven-membered rings
is inefficient) [319]. The reaction is 4 F overall since the pyridine ring also undergoes partial
hydrogenation to form almost equal amounts of two tetrahydro isomers (Equation 17.63). The
current efficiency is low due to competing proton reduction. The diastereoselectivity of the
reaction is high and opposite of that found in Equation 17.59 in which coupling was expected to
involve the radical anion. The acidic medium used in Equation 17.63 ensures that the coupling
involves the neutral radical formed by ketone reduction. The diastereoselectivity in this case
has been explained by hydrogen-bond interaction between the OH-group and the ring nitrogen
in the transition state leading to the preferred diastereoisomer and an unfavorable steric interac-
tion between the ring and the alkyl group in the transition state leading to the other diastereo-
isomer [319].
Intramolecular reductive coupling between the isoquinolinium system, 150, and an attached aro-
matic halide (Equation 17.64 [320]) gives products similar to those obtained by the intramolecular
coupling of aromatic halides with other aryl groups (Section V.B).
N+
MeCN, Et4NBr N
I
R Hg cathode
R R = H, 86% (17.64)
R = MeO, 74%
R 150 R

2. Other Positively Charged Systems

The pyranyl radicals formed by reduction of pyrylium cations, 151, dimerize at the 4-position, and
anodic oxidation of the dimers leads to regeneration of the pyrylium cations [321] and references
therein. Where the 4-position is unsubstituted, the dimerization process is very fast and irreversible,
and a rate constant of 2.5⋅109 M−1 s−1 has been measured for the dimerization step in the reduction
of 2,6-diphenylpyrylium cation, 151a, in MeCN by combination of LSV and fast CV using micro-
electrodes [322]. If a substituent other than H or Me is present in the 4-position, the dimerization
process becomes reversible and in favor of the free radicals [321].
R4
R3 R5 a: R2 = R6 = Ph, R3 = R4=R5 = H
b: R2 = R6 = p-tolyl, R3 = R4 = R5 = H
2 +
R O R6 c: R2 = R6 = p-anisyl, R3 = R4 = R5 = H
151
In preparative scale, reduction of 151a in MeCN, bipyrilene, 153, has been observed as a side
product in addition to the bi-4H-pyran, 152 [323]. Clean 1 F reduction was found (n = 0.8–1.0) in all
cases, and at low substrate concentrations (5 mM) 152 was the only product. However, at substrate
concentrations in the range 30–100 mM up to 48% of the product was 153 together with ≈15%
1,3-dibenzoylpropane. The conversion was not initiated by base or by the presence of oxygen,
and the mechanistic explanation includes (Scheme 17.29) slow hydride transfer from the initially
formed 152 to the substrate cation, followed by elimination of a proton and formation of 153. The
4H-pyran formed by hydride transfer reacts with water during work-up to give the dibenzoylpro-
pane, and the apparent 1 F coulometry may be due to reduction of the liberated proton since the
reduction was carried out using a Pt cathode [323]. Similar results were obtained in the reduction
of 151b and 151c.
The 1,2,3-triphenylcyclopropenyl cation, 154a, and cycloheptatrienyl cation, 155, give, like the
heteroaromatic cations, free radicals by one-electron reduction, and these undergo almost quantita-
tive dimerization in aprotic solvents [324,325]. Also, 154b undergoes reductive dimerization, the
coupling position being exclusively at a phenyl substituted carbon atom [326]. After reduction of
154c in MeCN, only the rearranged dimer, 1,2,4,5-tetraphenylbenzene, was isolated (39%) together
with N-acetyldiphenylcyclopropenylamine (24%) formed in a reaction with the solvent [324].
Ar Ar H
Ar Ar H
H
O + O +
O + O +
Ar O Ar Ar O Ar
H H
Ar Ar
Ar Ar
152 Aq. workup
Ar Ar –H+
O O Ar CO (CH2)3 CO Ar
Ar Ar
153
SchEME 17.29 Cathodic reduction of pyrilium cations with fast irreversible follow up.
Ph Ph Ph
+ Ph + Et + H +
Ph Ph Ph
154a 154b 154c 155
AckNOwLEDGMENTS
One of us (JHPU), who has impaired mobility, is especially grateful to Jessica Pancholi and Linda
Malek (of SBCS) and Martin Beeson (QMUL Library) for help in accessing material.
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18 Oxidative Coupling
Hans J. Schäfer
CONTENTS
I. Introduction ............................................................................................................................. 706
II. General Survey ....................................................................................................................... 706
III. Coupling via Radical Cations ................................................................................................. 707
A. Mechanism and Favorable Solvents ................................................................................ 707
B. Aromatic Compounds ..................................................................................................... 708
1. Hydrocarbons.......................................................................................................... 708
2. Phenols�� 710
3. Aryl Ethers ............................................................................................................. 714
4. Aryl Amines ........................................................................................................... 714
C. Heterocycles .................................................................................................................... 716
D. Olefins ............................................................................................................................. 718
1. General ................................................................................................................... 718
2. Aryl Olefins ............................................................................................................ 718
3. Dienes�� 720
4. Enols and Enol Ethers............................................................................................. 720
5. Enamines ................................................................................................................ 721
6. Alkenes with Alkyl Substituents ............................................................................ 725
7. Alkynes................................................................................................................... 726
8. Alkanes ................................................................................................................... 726
E. Intramolecular Coupling ................................................................................................. 726
1. Aromatic Compounds............................................................................................. 726
2. Olefins�� 734
F. Anodically Induced Cycloadditions ................................................................................ 740
1. [2 + 2] Cycloadditions............................................................................................. 740
2. [4 + 2] Cycloadditions ............................................................................................. 742
IV. Coupling via Radicals ............................................................................................................. 747
A. General Comments ......................................................................................................... 747
B. Anodic Decarboxylation of Carboxylates as Radical Source ......................................... 748
1. Experimental Procedure ......................................................................................... 748
2. Homocoupling ........................................................................................................ 749
3. Heterocoupling ....................................................................................................... 752
4. Diastereoselective Coupling ................................................................................... 754
5. Addition of Radicals from Anodic Decarboxylation of Carboxylic Acids to Olefins ....756
6. Oxidation to Carbocations ...................................................................................... 761
C. Anions from CH-Acids as Radical Source ..................................................................... 761
1. Coupling ................................................................................................................. 761
2. Addition .................................................................................................................. 762
V. Outlook ................................................................................................................................... 765
References ...................................................................................................................................... 766
705
I. INTRODUcTiON
For the synthesis of organic molecules, two types of reaction are used: carbon–carbon bond–form-
ing reactions and functional group interconversions. The former assembles larger molecules from
smaller units; the latter introduces functional groups into a molecule or converts functional groups
that are present in the molecule. The large number of carbon–carbon bond–forming reactions can
be summarized in four groups:
1. Polar reactions between an activated acceptor and a donor or vice versa

2. Radical coupling and addition reactions
3. Pericyclic reactions, especially cycloadditions
4. Transition metal catalyzed and organocatalyzed reactions
Electrochemistry can contribute to these synthetic transformations, especially to polar reactions,

to radical reactions, and partially to cycloadditions. The reactive intermediates being involved,
namely, radical ions, cations, and radicals, can be generated at the electrode simply, in large variety,
cheap, and with reduced production of waste. There are several books and reviews that deal with
the topic: organic electrosynthesis [1]. It should be added that organic electrosynthesis is in good
accord with many rules of green chemistry [2]. The selectivity in organic electrosynthesis has been
improved in the last decade by new developments in flow cells, microreactors, and reaction condi-
tions (see Chapters 7 through 9) [1b,3].
This chapter deals with carbon–carbon bond–forming reactions at the anode and in laboratory
scale.
II. GENERAL SURvEY

Anodic coupling reactions may be arranged according to the reactive intermediates that are involved.
These are radical cations that can undergo radical cation–radical cation coupling (Scheme 18.1,
path a) or radical cation–substrate coupling with the starting compound (Scheme 18.1, path b).
Radicals can be generated by deprotonation of C–H acids to form an anion, which is then oxidized.
Furthermore, radicals can be formed by the one-electron oxidation of a compound R–H to a cation
radical, which is subsequently deprotonated. The radicals can dimerize (Scheme 18.2, path a) or
add to double bonds that subsequently lead to additive monomers 1 or additive dimers 2 (Scheme
18.2, path b). Furthermore, the radicals can be further oxidized to carbocations that can undergo
electrophilic additions or substitutions with nucleophiles being in most cases nucleophiles that react
at a heteroatom (Scheme 18.2, path c).
These reactions can lead to carbon–carbon or carbon–heteroatom bond formation, and their course
can be inter- or intramolecular. Furthermore, cycloadditions can be initiated by anodic generation of
the dienophile or by inducing a chain reaction with a radical cation as initiator (see Chapter 15).
a + +
+ HR RH
RH –2H+
–e– +
RH RH R R
b + –e–
HR RH
RH –2H+
SchEME 18.1 Coupling reactions of electrogenerated radical cations.

Oxidative Coupling 707
a R
+ R–R R
–e– RH –H+ Y R
R Y
RH R 1
b
R– c –e– Y Y
–H+ –e– R
R+ R
R–RNu
HRNu, –H+ Y
2
SchEME 18.2 Coupling reactions of electrogenerated radicals.
The oxidation can occur in a direct electron transfer from the substrate to the anode or in an indirect
oxidation via a chemical oxidant (mediator) being generated at the anode.
The conversions are ordered in the first level according to reactive intermediates. However,
one must keep in mind that this organization is not free from uncertainty since the mechanisms
of anodic couplings are frequently just reasonable assumptions that are more or less supported by
experiments.
The mechanisms, shown in Schemes 18.1 and 18.2, illustrate additionally the principle of anodic
umpolung [4]. In an electrochemical reaction, substrates of equal polarity can be coupled in a one-
pot reaction by combination of an electron transfer with a chemical reaction; nonelectrochemical
reactions need at least two steps to achieve the coupling of substrates with equal polarity by apply-
ing chemical umpolung [5]. Furthermore by anodic umpolung synthetic building blocks can—in
principle—be used in several reactivities, namely, by anodic oxidation of a nucleophilic building
block to a radical, an electrophilic radical cation, or a carbocation.
III. COUPLiNG viA RADicAL CATiONS

A. MECHaNISM aND FaVorabLE SoLVENTS
A review on the reactivity patterns of radical cations, which is supported by 562 references, describes
reactions of a large variety of radical cations, which are prepared by chemical, electrochemical, and
photochemical one-electron oxidation. The radical cations can undergo deprotonation, C–C or C–X
bond cleavage, reaction with a nucleophile, cycloaddition, rearrangement, electron transfer, dimer-
ization, radical reaction, or atom abstraction. Examples of these conversions are provided, and if
available, thermochemical and kinetic data are given [6].
The stability of radical cations increases with increasing charge delocalization, blocking of reac-
tive sites, and stabilization by electron-donating groups (hydroxy, alkoxy, and amino group) [7].
The complex reaction mechanisms of radical cations have been reviewed in detail [8]. Radical ions
of conjugated systems can reversibly dimerize to form relatively stable σ-dimers as seen by cyclo-
voltammetric measurements [9].
Radical cations of 9-aryl- and 9,10-diarylanthracene derivatives with substituents in the 4-position
of the aryl rings have been generated by photoionization in acetonitrile (AN). Their reactivity with
n-butylamine and 1,4-diazabicyclo[2.2.2]octane and with anions as acetate, cyanide, bromide, and
azide has been studied using nanosecond laser flash photolysis. The reactions proceed by electron
transfer and/or nucleophilic addition. When electron transfer is thermodynamically feasible, this
pathway dominates. For endothermic electron transfer, an inner sphere process can compete. The
studies show that reactivity trends in the radical cation chemistry cannot be generalized as easily as
those in carbocation chemistry [10].
The linear sweep voltammetry response to competitive radical ion–substrate coupling and radi-
cal ion dimerization mechanisms was determined by digital simulation. The simulations were car-
ried out to mimic the conditions under which experimental studies had previously shown that the
radical ion–substrate coupling mechanism is the preferred reaction pathway. The configuration
mixing (CM) model predicts an electronic reaction barrier for the radical ion–substrate coupling
but not for the radical ion dimerization. The difference in standard free energy changes for the reac-
tions is of the order of 7 kcal mol−1 or greater with the radical ion dimerization being energetically
more favorable. In the discussed cases, the opposite result is observed experimentally: the radical
ion–substrate coupling is the preferred pathway. The overall conclusion is that the CM model does
not give reliable estimates of the reaction barriers for radical ion reactions [11].
In a review with 86 references, it is proposed that both polar and radical reactivity should be
considered when discussing radical ion reactivity. In the past, the polar reactivity has dominated
discussions. The following hypothesis is presented and supported by the literature: In the absence
of severe steric effects, the reactivity of radical ions is dominated by the degree of coupling between
charge and radical centers. Further work to test the validity of the hypothesis is proposed for many
of the reaction types. It is concluded that the radical cation–carbenium ion comparison (for the
reaction with acetate ion) would show similar reactivities. However, the radical cation–free radical
comparison (for the reaction with dioxygen) would fail, since no reaction at all would be observed
with the radical cation, while the free radical reacts rapidly [12].
Favorable reaction conditions for radical cations are provided by 1,1,1,3,3,3-hexafluoropropan-
2-ol (HFP). HFP is a solvent of low nucleophilicity, high hydrogen bonding donor strength, low
hydrogen bonding acceptor strength, high polarity, and high ionizing power; this makes it an
ideal solvent for radical cations in EPR spectroscopy, mechanistic studies, photochemistry, spin
trapping, and synthesis [13a]. For the latter, see Section III.B.2. With HFP, the half-life of inter-
mediate radical cations has been increased by a factor of 102 compared to trifluoroacetic acid
(TFA) [13b].
B. AroMaTIC CoMpoUNDS
1. Hydrocarbons
Alkyl-substituted aromatic hydrocarbons 3 can be coupled to diphenyls 6, probably by a radical cation–
substrate or radical cation–radical cation coupling of the first formed radical cation 4 (Scheme 18.3,
path a). Path b (Scheme 18.3, path b) leads to diphenylmethanes 7, probably by deprotonation of the
3
–e–
R
R
a
4,–2H+ R 6
4
–H+, –e–
R
b R R
3,–H+
7
SchEME 18.3 Coupling of alkyl-substituted aromatic hydrocarbons 3 to diphenyl compounds 6 (path a)

and diphenylmethanes 7 (path b).
first formed radical cation 4 at the benzylic position; further oxidation of the benzyl radical leads to
a benzyl cation 5 that afterward reacts in an electrophilic substitution with the starting compound.
In the radical cation, a high positive charge density on an unsubstituted aryl carbon atom
favors the diphenyl 6; a high positive charge density at the alkyl-substituted carbon atom supports
the formation of diphenylmethane 7 [14]. To favor the coupling reaction, competing side reac-
tions with nucleophiles must be suppressed by using an electrolyte of low nucleophilicity. A good
choice is dichloromethane (DCM), tetrabutylammonium tetrafluoroborate (TBABF4), and small
amounts of a strong acid to suppress a cathodic cleavage of DCM and subsequent chlorination,
when electrolyzed in an undivided cell. Another solvent could be HFP that has been successfully
used in phenol coupling (see Sections III.B.2 and III.B.3; there, HFP is named hexafluoroisopro-
panol [HFIP]).
Applications are illustrated with some examples in Scheme 18.4. p-Xylene affords a diphenylmeth-
ane 8 in 22% yield at a carbon electrode in DCM, TFA, and TBABF4 [15]; 1,3,5-trimethylbenzene
is dimerized exceptionally well in 71% yield at a platinum electrode in AN and TBABF4 to the diphe-
nyl 9 [14]; and 1,2,4,5-tetramethylbenzene couples to the diphenylmethane 10 in 85% yield in DCM
and TBABF4 [14]. Simpler conditions, namely, electrolysis in acetic acid, toluene, water and sodium
benzenesulfonate in an undivided cell equipped with graphite felt electrodes, have been reported for
the coupling of 2-methylnaphthalene to 2,2′-dimethyl-1,1′-binaphthyl and its isomer [16].
Cross-couplings are reported for naphthalene and pentamethylbenzene forming in 64% yield the
diphenyl 11 (Pt, Bu4NBF4, AN, AcOH) [17] and for anthracene and anisole yielding 70% of anthra-
cene 12 (Pt, Bu4NBF4, DCM, TFA, trifluoroacetic acid anhydride [TFAn]) [18]. Further examples
can be found in References 17 and 19.
The cyanation of aromatic hydrocarbons, which is also a C–C coupling reaction, is achieved with
anthracene in AN, Et4NCN to yield 54% of 9,10-dicyanoanthracene [20]. The procedure is simpli-
fied by electrolysis in an emulsion system (water, DCM, NaCN, TBAHSO4) [21]. In this mode,
4-alkoxy-4-cyanobiphenyls, a class of liquid crystals, have been prepared.
In an indirect anodic oxidation with Pd(OAc)2 and 2,2,6,6-tetramethylpiperidin-1-yl)oxyl
(TEMPO), a stable radical as mediators arylboronic acids or arylboronates gave the corresponding
biaryls in moderate to excellent yields [22].
Electrochemical oxidation of anisole, mesitylene, naphthalene, and anthracene in various ionic
liquids (ILs) provided coupling products in an undivided cell. With 1,2-dimethoxybenzene (vera-
trole), a stable blue-colored doped polyveratrole was obtained [23].
8 9 10
OCH3
12
11
OCH3
SchEME 18.4 Diphenylmethanes 8 and 10 and diphenyls 9, 11, and 12 in the anodic coupling of alkyl-
substituted aromatic hydrocarbons.
R1 R1 R1 R1
–H+, –e–
R3 + R3
2 3 2 3 2 2
R R R R R R O R2
2
OH O O O
13 14 15 16 R3
–e– –e– R1
R1 R1 R1
R1 Nu
Nu–
+ + +
R3
R2 R3 R2 R3 R2 R3 R2
Nu
OH O O O
17 18 19
Alkene Diene
[5 + 2] and [3 + 2] [4 + 2] cycloadducts
cycloadducts
SchEME 18.5 Anodic conversion of phenol 13 via phenoxy radicals 14, phenol radical cations 17, and
phenoxonium cations 18. (Adapted from Yamamura, S. and Nishiyama, S., Synlett, 4, 533, 2002.)
2. Phenols
Earlier literature on anodic coupling of phenols can be found in Reference 24. Furthermore, com-
prehensive, more recent reviews, which describe the anodic and chemical oxidation of phenols and
phenol ethers, have appeared [25].
The oxidative conversion of phenols 13 can be described as shown in Scheme 18.5. From phenol
13, reactive intermediates as phenoxy radicals 14, phenol radical cations 17, and phenoxonium cat-
ions 18 are formed by electron transfer and deprotonation. The radical 14 can undergo C–C coupling
to 15 and the p,p′- and o,p′-isomer of 15 and C–O coupling to 16 and the p,p′- and o,p′-isomer of 16.
The cation 18 can react with alkenes to form [5 + 2] and [3 + 2] cycloadducts or with nucleophiles to
form 19, which can produce [4 + 2] cycloadducts with dienes. If R3 = H, the dienone tautomerizes to
the phenol. Radical cations 17 can undergo a C–C coupling or can be deprotonated to 14.
Selected examples for the C–C coupling of phenols are shown in Scheme 18.6. The phenoxy radi-
cals react by carbon–carbon and carbon–oxygen coupling to dimers that can be further oxidized,
and in this way, product mixtures can arise. Blocking of the 2-, 4-, or 6-position makes the coupling
reaction more selective. Phenols with an unsubstituted p-position usually form p,p′-coupling prod-
ucts as the major dimer (Scheme 18.6). From the corresponding phenols, the p,p′-dimers have been
obtained: 20 (at a nickelhydroxide electrode and at 70°C) [26]; 21 in MeOH, DCM, LiClO4, at a
Pt anode [27]; 22 (R = Me, Et, benzyl, i-Pr, t-Bu, CH2CH(CH3)CO2H) at a glassy carbon anode in
MeCN (AN) and NaClO4 [28]; 23 at a graphite felt anode in MeONa, AN, and Et4NClO4 [29]; 24 at a
Pt anode in MeOH, LiClO4, and NaOH [30]; and 25 at a Pt anode in AN, and NaClO4, Et4NOH [31].
If the 4-position is blocked, o,o′-coupling becomes the main reaction as found in 26–30 in HFIP
(HFIP = HFP) and at a boron-doped-diamond anode (BDD anode) [32]. When the o- and p-position
are blocked, an addition can occur as found in the cross-coupling between 2,6-di-t-butyl-cresol and
anisole to form 31 [33].
In a template-directed anodic phenol-coupling reaction, eight different phenols were converted
into the corresponding sodium (tetraphenoxy)borates. Their controlled-current electrolysis (CCE)
in an undivided cell at a platinum electrode in AN afforded 2,2′-diphenols in 85–20% yield. This
selective ortho-coupling reaction can be performed on a kilogram scale [34].
Using the BDD electrode (BDD anode) and hexafluoroisopropanol as additive, several phenols
could be coupled to the o,o′-dimers in good to moderate yields (26–30, Scheme 18.6) [32,35].
O OH OH
t-Bu t-Bu t-Bu MeO
t-Bu MeO CH=NR
NMe
HO
2 2 2 2 Me
20 (90%) 21 (93%) 22 (41–100%) 23 (69%)
CHO CH3
HO O
MeO 2 MeO 2 O CH3

2 2
OH OH OH
24 (100%) 25 (65%) 26 (74%) 27 (47%)
O
CH3 CH3 t-Bu t-Bu
CH3
2 Cl Br HO
2 2
OH OH OCH3
28 (30%) 29 (30%) 30 (41%) 31 (81%)
SchEME 18.6 Selected examples for the anodic coupling of different phenols.
The two concepts of template-directed coupling and use of the BDD anode have been reviewed [36].
The procedure using the BDD anode was further developed to allow the application of a less
expensive electrode (graphite) and a fluorinated solvent (TFA), both permitting the selective o,o′-
coupling in broad scope [37].
The cross-coupling of 4-methylguajacol with different arylethers affords at the BBD anode
unsymmetrical biaryls in a one-step reaction without using activating auxiliaries. Depending on
the reaction conditions, selectivities of unsymmetrical to symmetrical coupling product of 1.5:1 to
>50:1 with yields of 16–47% are obtained [38].
In a very recently reported cross-coupling reaction, phenol (5 mmol) and arene (15 mmol) have been
oxidized in N-methyl-N,N,N-triethylammonium methylsulfate, HFIP, and methanol in an undivided
cell at a platinum anode and a nickel cathode. At a current density of 2.8 mA cm−2, the heterocoupling
product was obtained in 67% yield and 69% current efficiency; the ratio of unsymmetrical to sym-
metrical product was >100:1 (Scheme 18.7). The large scope of the reaction is demonstrated with 13
different phenols and 8 different arenes, and partly selectivities >100:1; a mechanism is proposed [39].
Anodic oxidation of 2,4-dimethylphenol at platinum electrodes and Ba(OH)2·8H2O in methanol
as electrolyte provides in an undivided cell a pentacyclic dehydrotetramer as single diastereoisomer
in up to 24 g per run (52% yield) [40]. This dehydrotetramer was used to create a variety of polycyclic
scaffolds that partially occur as core structures in natural products [41]. The 2,4-dimethylphenoxy
group could be substituted by several amines; there primary amines provided the best yields [42].
OCH3 OCH3
–
BDD anode, –e
Et3NMe+ –O3SOMe OH
OH
HFIP, MeOH
+ OCH3
CH3O OCH3
CH3O
OCH3 OCH3
SchEME 18.7 Highly selective cross-coupling of 4-methylguajacol with 1,2,4-trimethoxybenzene.

Electrochemical applications of the BDD electrode have been reviewed [43]. The electrochemical
activation of the BDD electrode for electroanalytical investigations in organic media is described
[44]. The electroanalytical oxidation of different phenols at the BDD anode and the glassy carbon
electrode in aqueous and methanolic media and in microemulsions has been compared [45]. A
recent review covers the applications of the BDD electrode in electroorganic synthesis. It reports
cathodic carboxylations and reductions of oximes. At the anode, alkoxylation, fluorination, cyana-
tion, C–C bond cleavage, and phenol coupling are described. Furthermore, informations on the
stability of the BDD electrode and on electrolysis cells for BDD electrodes are communicated [46].
In the products shown in Scheme 18.5, by variation of the phenol structure and reaction con-
ditions as oxidation potential, solvent—supporting electrolyte, electrode material, partially good
selectivities toward single products can be achieved, and these have been used to synthesize com-
plex natural products in few steps.
An example in Scheme 18.8 shows that substituents can efficiently control the mode of coupling.
The dibromo derivative of N-protected l-tyrosine is anodically oxidized in a current controlled
electrolysis (CCE: 0.11 mA cm−2, LiClO4, MeOH) to afford 45% of the C–O coupling product that is
deprotected quantitatively to iso-dityrosine [47]. With iodo instead of the bromo substituents under
the same reaction conditions, 28% of the C–C coupling product was obtained that was deprotected
in 72% yield to dityrosine.
Scheme 18.9 shows an intramolecular electrophilic addition of a presumably anisole radical cation
to a nucleophilic enol ether to form 51% of a spiro compound (CCE: 11.2 mA, LiClO4, 20% MeOH,
DCM, 2,6-lutidine, reticulated vitreous carbon [RVC] anode) [48]. Similarly, 4-(2-alkenylaryl)-
phenols have been cyclized to the corresponding spiro compounds. There, the oxidation at the anode
has been compared with the use of iodobenzene diacetate as oxidant. Yields up to 92% (PhI(OAc)2,
MeOH)) and 80% (anode, AN, MeOH) have been obtained. With the exception of two cases, the
same phenols, which gave good yields of spiro dienones in the anodic oxidation, gave also good
yields with iodobenzene diacetate [49].
CO2Me
1. –e–, MeOH, NHZ

LiClO4 Br CO2Me
2. Zn/HOAc
CO2Me
CO2Me Br O
OH Br
NHZ 45%
CO2Me
1. –e–, MeOH,
X X LiClO4 NHZ
OH 2. Zn/HOAc
X = Br or I
I 2
OH
28%
SchEME 18.8 C–O or C–C coupling controlled by the bromo or iodo substituent.
–e–, 51%
MeO O OMe
MeO
MeO
SchEME 18.9 Intramolecular reaction of a presumably anisole radical cation with a nucleophilic enol ether
to a spiro compound.
OCH3
CPE, –e– OCH3
AcOH, MeNO2 +
HO
O
O O
OCH3 OCH3 OCH3
H H
O O O
H O H O
SchEME 18.10 Anodically initiated [3 + 2] cycloadditions between methyl hydroquinone and alkenes;
CPE = controlled potential electrolysis.
Formal [3 + 2] cycloadditions were observed in the oxidation of methyl hydroquinone in the

presence of styrene, dihydrofuran, and dihydropyran in 95%, 11%, and 33% yield, respectively
(Scheme 18.10) [50].
In the anodic oxidation of 2-methyl-4,5-dimethoxyphenol and 1-(3,4-dimethoxyphenyl)-1-
propene, a [5 + 2] cycloadduct of the phenoxonium cation is obtained in 80% yield (Scheme 18.11)
[51]. For additional anodic cycloadditions of phenols, see Section III.E.2.
The anodic oxidation of 2,6-di-t-butylphenol was studied in Bmim ILs at platinum electrodes
[52]. The electrolysis led to the diphenoquinone; however, better results were achieved with the
electrolytes: methanol, DCM, and LiClO4.
Phenol coupling can be achieved by Michael additions to o-quinones that are performed by
in situ anodic oxidation of catechol in the presence of Michael donors (Scheme 18.12) [53]. For this
OCH3 CH3
CH3
OCH3
CCE, –e–
+ OCH3
Ac2O,HOAc O
CH3 MeO Bu4NBF4
OH OMe
MeO
OMe
SchEME 18.11 [5 + 2] cycloaddition in the anodic oxidation of 2-methyl-4,5-dimethoxyphenol and

1-(3,4-dimethoxyphenyl)-1-propene.
OH
OH O OH
OH H2O, NaOAc
+ –e–, 1.1 V
OH O O 95% O O
SchEME 18.12 Anodic cross-coupling of catechol with a Michael donor.

reaction, a wide scope has been demonstrated with differently substituted 1,2-d ihydroxybenzenes
and different Michael donors [54].
The anodic oxidation of catechols in the presence of α-oxo heterocyclic ketene N,N-acetals was
investigated by using cyclic voltammetry and controlled-potential electrolysis. The results indicate
that α-oxo heterocyclic ketene N,N-acetals can undergo a Michael addition at the anodically gener-
ated o-benzoquinones and selectively form arylated products in good yields. In addition calcula-
tions were performed to explain the exclusive formation of these products [55]. For further details
on the coupling of phenols at the anode, see Chapter 26.
3. Aryl Ethers
The anodic coupling of aryl ethers has been reviewed before [56]. Aryl ethers are more selectively
coupled than phenols. The C–O coupling is excluded; the o-coupling and the oxidation to quinones
become more difficult. A mixture of TFA and DCM proves to be a very suitable electrolyte [57].
Some selected examples are shown in Scheme 18.13. Anisol was dimerized in TFA, DCM (1:2),
Bu4NBF4 at a Pt anode to diphenyl 32 (63%) [57], 1,2-dimethoxybenzene was converted under
the same conditions to the dimer 33 (86%) [57]. 9-Methoxyanthracene afforded in AN, TFA, and
Bu4NBF4 the dimer 34 (95%) [58], and 1,2-dimethoxybenzene led in DCM, TFA, and Bu4NBF4 to
the cyclotrimer 35 (50%) [59]. 9-Anisyl-anthracene formed with anisole in DCM, AN, TFA, and
Bu4NBF4 the cross-coupling product 36 (90%) [60]. From a catechol ketal in AN and Bu4NBF4, the
cyclotrimer 37 (90%) was obtained in a 20 g scale; it was applied as platform structure for rigid
receptors [61]. From 4-t-butyl-anisole in 0.1 M TBABF4 in AN, an o,o′-dimer (33%) and a trimer
(20%) with an o,m′-coupling of 4-t-butyl-anisole to the dimer have been obtained [62].
4. Aryl Amines
The anodic coupling of aryl amines leads to three major products: benzidines, aminodiphenyl-
amines, and azo compounds. The first intermediate in these oxidations is mostly the radical cation
OCH3
OCH3 OCH3 OCH3 OCH3
OCH3
CH3O
2 2 CH3O
2
32 (63%) 33 (86%) 34 (95%) 35 (50%) OCH3
CH3O
CO2Et
OCH3
O
O
O
EtO2C
O
37 (90%)
O
O
OCH3
36 (90%)
CO2Et
SchEME 18.13 Intermolecular anodic coupling of aryl ethers to dimers and trimers.
2 NR2 R2N NR2
–2e– a –2H+ + o,p– + o, o-product

R
+ b
2 NR2 N NHR
–2H+
+ + o -product
c –2H
R R
N N
SchEME 18.14 Anodic coupling of an aryl amine to benzidine, aminodiphenylmethane, and hydrazobenzene.
OMe CH3
OMe
NR2
CH3
NH N
N
2 OMe CH3
R: C2H5, C4H9
38 (40–50%) OMe
2
39 (42%) CH3
40 (90%)
N O N N N N O
H t-Bu N N t-Bu
N 42 (25%) 43 (80%)
41 (98%)
SchEME 18.15 Anodic coupling of amines.
of the amine. This can couple in three different ways (Scheme 18.14): (a) In a C–C coupling reaction,
benzidines are formed; (b) in a C–N coupling reaction, aminodiphenylamines are obtained; and (c)
in an N–N coupling reaction, hydrazobenzenes are produced. These compounds are often easily
further oxidized. Earlier work is reviewed by Adams [7]. Some amine oxidations are presented in
Scheme 18.15.
Diethyl- and dibutylaniline are coupled in AN and Et4NClO4 to benzidine 38 in moderate
yield, while with dimethylaniline a complex product mixture is obtained [63]; under the same
conditions, the benzidine 39 is formed from a substituted naphthylamine, instead of the desired
cyclization product [64]. Electrolysis of di-p-tolylamine affords in AN, Et4NCN in 90% yield the
hydrazine 40; with lutidine as base, however, a dihydrophenazine is formed as major product [65];
1,2,3,4-tetrahydrocarbazole affords in AN, H2O, and LiClO4 nearly quantitatively the coupling
product 41 by substitution at atom C1 of the carbazole [66]; the mechanism of this interesting reac-
tion has been investigated using electroanalytical techniques [67]. t-Butylamine has been deproton-
ated with lithium cyclohexylamide, and the resulting amide was oxidized in tetrahydrofuran (THF)
and LiClO4 to the azo compound 42 [68]. At the nickelhydroxide electrode, N-amino-morpholine
was converted in 80% yield to the azo compound 43 [69].
The combination of electrochemistry with organocatalysis allows the substitution of a
4-hydroxyaniline in m-position; this selectivity cannot be achieved in a Friedel–Crafts reaction.
Thereby, an intermediate enamine, formed from an aldehyde and a secondary amine, undergoes
a Michael addition to an iminoquinone that results from an anodic oxidation of the 4-hydroxy-
aniline. The electrolysis is conducted current controlled in an undivided cell in AN, H2O, and
NHTs NHTs
Ph
RCH —
—O + Ph + –e–
N
OTMS R
H
OH O
OH
SchEME 18.16 Regio- and enantioselective m-substitution of 4-hydroxyaniline by combining anodic oxi-
dation with organocatalysis.
0.1M NaClO4. With a chiral amine and five different aldehydes, the corresponding products are
obtained in 69–87% yield and 81–96% enantioselectivity. Similar yields can be also obtained with
iodosobenzene diacetate as oxidant (Scheme 18.16) [70].
DFT calculations have been used to determine theoretical values for the oxidation potentials for
indole and carbazole derivatives. For an oxidative indole trimerization, the computed electron spin
distributions of the involved radical cations support the proposed mechanism [71].
C. HETEroCYCLES
Anodic syntheses of heterocyclic compounds dealing with the formation of C–N, C–O, and C–S
bonds have been reviewed [72]. Cyclic amines as pyrrolidines, piperidines, tetrahydroquinolines,
and tetrahydroisoquinolines can undergo anodic C–C coupling with the cyanide anion to form
nitriles in α-position to the amino group [73]. Thereby, the nitrogen atom is oxidized to a radical
cation that is deprotonated at the α-carbon atom, which is further oxidized to an amino methyl cat-
ion that subsequently reacts with the cyanide anion. For further anodic cyanations of heterocycles,
see Reference 74.
1,3-Dithioles can be dimerized in AN and pyridine in moderate to low yields to tetrathiofulva-
lenes (Scheme 18.17) [75].
2-Thiobarbituric acids can be coupled under ultrasonication in AN and DCM, 18-crown-6 in
10–27% yield to the corresponding dimers (Scheme 18.18) [76].
The electrochemical oxidation of 2,4-dimethyl-3-ethylpyrrole in AN was studied using cyclic
voltammetry, constant current coulometry, preparative electrolysis, and ab initio calculations.
S –e– S S
AN, pyr
S S S
40%
SchEME 18.17 Anodic dimerization of a 1,3-dithiole to a tetrathiafulvalene.
S
R2 R2
R1 N N
H
O O –e–, K2CO3 O O
AN, DCM, Pt R1 R1
N N O
R2 R2 O
S N N
R1 = C12, C14, C16, R2 = CH3 R2 R2
S
SchEME 18.18 Anodic dimerization of thiobarbituric acid.

N
H
1. –e–(1.1 V); 2. +e–(0.0 V SCE)
OH AN, TFA, LiClO4, 60%
MeO N OAc
H
CH3 CO2Me
MeO2C CH3
AcO H
N OMe N
OH H
H OH
N
MeO N OAc
H
CH3 CO2Me
SchEME 18.19 Anodic dimerization of vindoline to 10,10′-bisvindoline.
The major product from preparative electrolysis was a trimer, for which a central 2H-pyrrole unit
was proposed. Since 2H-pyrroles are stronger bases than the corresponding 1H-pyrroles, the trimer
is effectively protected against further oxidation by protonation [77].
Pyrrole and thiophene derivatives can be polymerized in non nucleophilic solvents as AN,
1,2-propylene carbonate (PC), or DCM to conducting polymer films [78].
The anodic oxidation of catharanthine in the presence of vindoline was performed in AN and
Et4NClO4 at a controlled potential to yield the alkaloid anhydrovinblastine. In this elegant synthesis,
it is concluded from electroanalytical studies that the radical cation of catharanthine undergoes a
fragmentation to a distonic radical cation, which after oxidation to a dication reacts in an electro-
philic aromatic substitution with vindoline to afford the alkaloid [79].
Anodic oxidation of vindoline, at a Pt electrode and a controlled potential of E = 1.1 V versus SCE
followed by reduction of the formed intermediate at E = 0.0 V versus SCE gave 10,10′-bisvindoline
in 60% yield (Scheme 18.19) [80].
Cyclo[8]pyrrole was obtained efficiently, when 3,3′,4,4′-tetraethylbipyrrole was subjected to
bulk electrolysis. The yields varied from close to 0% with Bu4NF as the electrolyte, to almost
70% when Bu4NSO4H was used for this purpose. These observations are consistent with the con-
clusion that the reaction is controlled by anion-related factors such as a specific templating effect
(Scheme 18.20) [81].
–e–
N N
H H
3
N
H N
NH
2H+ HN
N HN
SchEME 18.20 Anodic cyclotetramerization of 3,3′,4,4′-tetraethylbipyrrole to cyclo[8]pyrrole.

Carbazoles were successfully synthesized by oxidative cyclization of 2-aryl-N-acetylanilines

using electrochemically generated hypervalent iodine as oxidant. The electron-withdrawing nitro
group and the electron-donating methoxy group at the para-position of the acetamide group inter-
fered with the cyclization. For the preparation of the oxidant, iodobenzene in trifluoroethanol (TFE),
LiClO4 was electrolyzed at a glassy carbon beaker anode. After electrolysis, the substrate was added,
and after stirring, 83% (97% based on conversion) of the carbazole was obtained. Electrolysis with-
out the iodobenzene gave no carbazole [82].
D. OLEFINS
1. General
Olefins with electron-donating substituents as the aryl, alkoxy, N-acylamino, thioalkyl, or vinyl
group can be coupled in methanol to give 1,4-dimethoxy-dimers and/or dienes (Scheme 18.21). The
first intermediate in this coupling reaction is a radical cation, which by a radical cation–substrate
coupling and subsequent 1e-oxidation (path a) or by radical cation–radical cation coupling (path b)
leads to a dimer dication. This undergoes a reaction with nucleophiles, in many cases a methano-
lysis and/or deprotonation. A further competing reaction is the reaction of the radical cation with
a nucleophile from the electrolyte, which is methanol in many cases. This is followed by a further
oxidation of the radical to a carbenium ion that reacts with a nucleophile. Thereby, an addition prod-
uct of two nucleophiles to the olefin monomer is formed (Scheme 18.21, path c).
2. Aryl Olefins
Styrene and indene derivatives (Scheme 18.21, Y = Ph) are dimerized to 1,4-diphenylbutanes or
1,4-diphenylbutadienes (Scheme 18.22) [83,84]. The product distribution depends in some cases
on the anode potential and the supporting electrolyte. By substitution of sodium perchlorate for
sodium camphorsulfonate or by increasing the anode potential, olefins are formed at the expense
of methyl ethers. This could be due to an increased displacement of methanol from the anode
surface by changing the more hydrophilic perchlorate anion to the more lipophilic camphorsul-
fonate anion. A similar trend is found in intramolecular cyclizations (see also Section III.E.2).
Methanol depletion at higher anode potential might be due to the increased adsorption of anions
with increasing potential. The surface concentrations of the reactants (solvent and styrene) govern
the relative rates for the pathways a–c, which determine the product distribution. Furthermore,
the styrene concentration at the electrode surface is controlled by different adsorption equilibria
dependent on the electrode material (C, PbO 2, and Pt) [85]. β-Alkyl substituents decrease the
yield of dimers and favor the formation of dimethoxylated monomers. On the other hand, the
Y
Y Nu
–e– Y
–e– +2HNu, Y
a Nu
–2H+
+ Y +
Y
+ Y
b –2H+ Y
Y
+ Y
c Y Y HNu,–H+ Y
–e–
+
HNu,–H +
Nu Nu Nu
Nu
Y: phenyl, vinyl, alkoxy, amino, alkyl; Nu: RO, RCO2
SchEME 18.21 Pathways for the anodic coupling of olefins (Y = aryl, alkoxy, N-acylamino, thioalkyl,
vinyl): path a, radical cation–substrate coupling; path b, radical cation–radical cation coupling; and path c,
reaction of the radical cation with nucleophiles from the electrolyte.
Soft graphite, MeOH

NaOCH3, NaClO4,–e–
2
67%
Soft graphite, MeOH
CH3O OCH3
a) Nal, NaOCH3
b) NaClO4, NaOCH3
+ OCH3
–e–
OCH3 a) 38% a) 20%

b) 45%
b) 20%
SchEME 18.22 Anodic coupling of styrene and indene.
4-MeO-C6H4 C6H5 C6H5

38–26% A
H
79% A 67% A 64% A 20–45% B l–, CH3O–; ClO4–, CH3O–

E pa: 1.14 V 1.59 V 1.68 V 1.56 V
a) Glassy carbon vs. Ag/AgCl
A: Coupling to dimer, B: methanolysis to dimethoxylated monomer
SchEME 18.23 Dependence of the coupling yield on the oxidation potential and the β-substitution of the
aryl olefin; the arrows indicate the coupling site; %, yield; Ep, oxidation potential in cyclic voltammetry.
coupling is favored by hydrogen in the β-position and a better stabilization of the positive charge
in the radical cation, which is related to the oxidation potential of the olefin (Scheme 18.23).
Reasons for the increased coupling would be a lower steric hindrance for the β-coupling and a
better separation of the positive charge at the α-carbon and the spin at the β-carbon atom [12]
(see also Section III.E.2).
For the dimerization of 4,4′-dimethoxystilbene, it has been possible to demonstrate spectro-
electrochemically [86] and at the rotating disc electrode [87] that the product is formed mainly
by radical dimerization of the intermediate radical cations (Scheme 18.21, path b). Fast derivative
cyclovoltammetry (CV), however, supports for the same olefin a complex electron transfer–chemi-
cal reaction–electron transfer (ECE) pathway (Scheme 18.21, path a) [88]. Depending on the kind
of nucleophiles (acetate, water, or methanol) and the anode potential, one obtains a tetrahydronaph-
thalene derivative 44 by dimerization and electrophilic aromatic substitution (Scheme 18.24) [89],
a monomer diacetate [89], or a 1,4-dimethoxy dimer [83]. When methanol is replaced by aqueous
DCM or by an aqueous AN emulsions as solvent, styrene and α-methyl styrene yield 2,5-diphe-
nyltetrahydrofuran (45) (Scheme 18.24) [90] and 2,5-diphenyl-2,5-dimethyl-tetrahydrofuran [91],
respectively.
OCH3
AcO
CH3O O
OCH3 45
OCH3 44
SchEME 18.24 Products from anodic oxidation of styrene.

3. Dienes
Butadiene is dimerized to dimethoxyoctadienes and forms trimers and dimethoxylated monomers
as side products (Scheme 18.25) [92]. Dimerization of dienes is favored by soft graphite or carbon
cloth anodes, by high olefin concentrations, and by terminally unsubstituted dienes (Table 18.1)
[93,94]. Anodes with a smooth surface, such as platinum, gold, and glassy carbon, promote the
formation of monomers; porous materials, such as soft graphite, favor the dimers. Qualitatively,
the result can be explained by lower current densities due to the larger real surface of the electrode;
this favors the coupling of the radical cation with the substrate (Scheme 18.21, path a). On the other
hand, dimethoxylated monomers are favored against dimethoxylated dimers by alkyl substituents
in the terminal position that hinder the C–C bond formation of the radical cation. 1,4-Dimethoxy
adducts are the major isomers in monomers formed from dienes; a 1,2-dimethoxy product is formed
in the monomer from the triene: β-ionone (Table 18.1).
4. Enols and Enol Ethers

Oxidation potentials of 40 enols, enolates, and some selected α-carbonyl radicals are presented
along with their characterization by various techniques (X-ray, EPR, ENDOR, general TRIPLE
Monomer
OCH3 OCH3 +
+
CH3O
CH3O CH3O
C 0% Pt 24% OCH3 OCH3
+
MeOH, CH3O
CH3O OCH3 Dimer
NaClO4 +
C, Pt, –e–
+
+
OCH3
C 49% Pt 9% OCH3
+ + 2 isomers
Trimer
CH3O +
C 10% Pt 0% +
SchEME 18.25 Anodic coupling of butadiene: C, soft graphite anode; Pt, smooth platinum anode; in the
boxes, assumed cationic intermediates.
TABLE 18.1
Dienes: Oxidation Potentials and Products of Anodic Oxidation
Diene Ep (V)a Monomer (%) Dimer (%) Trimer (%) Oligomer (%)
1,3-Butadiene 2.0 0 49 10 —
Isoprene 1.75 — 26 8 >30
1,3-Pentadiene 1.48 24 29 — —
2,4-Hexadiene 1.28 54 6 — —
1,3-Cyclohexadiene 1.36 39 6 — —
β-Ionone 1.12 73b — — —
a At a glassy carbon electrode, versus Ag/AgCl.

b 9,10-Dimethoxy-9,10-dihydro-β-ionone.
magnetic susceptibility measurements, UV–vis, fast-scan cyclic voltammetry, isotope effects). The
compounds comprise stable enols linked to a multitude of substituents (alkyl, alkenyl, alkynyl, aryl,
heteroaryl, propargyl alcohol) and stable enols of amides. The results allow to clarify the primary
reaction pathway of enol radical cations as a rapid deprotonation and—if permitted by the oxidation
potential and the strength of the oxidant—a follow-up oxidation of the α-carbonyl radical to the
α-carbonyl cation. Moreover, the experimental oxidation potentials were linearly correlated with
AM1-computed ionization potentials after correction for solvation. The correlation allows a reliable
prediction of oxidation potentials of radicals including α-carbonyl radicals [95].
Enol ethers can be easily prepared from carbonyl compounds. Their anodic oxidation in metha-
nol, NaI or methanol, and NaClO4 provides in 30–60% yield acetals or ketals from 1,4-dicarbonyl
compounds (Scheme 18.26) [92,96–98]. The dimer yield is much less susceptible to an alkyl group
at the coupling site than the aryl olefins and dienes. Apparently the good stabilization of the positive
charge by the alkoxy group allows a good separation of positive charge and spin density in the radi-
cal cation that favors radical coupling. The β,β′-coupling of the monomers and the electrochemical
reaction order (υenolether = 1.0, υmethanol = 0) support the radical cation as intermediate in the dimeriza-
tion (Scheme 18.27).
Silyl enol ethers (Scheme 18.21, Y = OSi(CH3)3) can be dimerized to 1,4-dicarbonyl compounds
in good yields (Scheme 18.28) [99]. This way, unsymmetrical ketones can be coupled selectively
in the α- or α′-position, since the corresponding silyl enol ethers can be prepared regioselectively.
To suppress the methanolysis of the silyl enol ethers, AN and 5% MeOH are used as solvents
and the electrolysis is conducted within 1 h by the use of a capillary gap cell, which allows a fast
conversion.
Vinyl ethyl ether can be linked to styrene in a cross-coupling reaction (Scheme 18.29)
[100]. Further cross-couplings were obtained with α-ethoxystyrene and vinyl ethyl ether (17%),
α-methylstyrene and vinyl ethyl ether (32%), and styrene and butadiene (22%).
5. Enamines
Dimethylamino-substituted alkenes are easily oxidized at the anode. Their oxidation potentials range
from −0.9 to 0.7 V (vs. SCE). The cation radicals can have long lifetimes, and ESR studies show that
O ROH, H+ OR
R1 R1
R1
–2e–, –2H+ OMe
+2MeOH RO
OR
MeO
R1
SchEME 18.26 Preparation of enol ethers and their anodic dimerization.
OMe OEt
OEt
51% (E1/2 = 1.72 V, n = 2.2) 59% (1.44, 1.7)
61% (1.30, 1.1)

OEt OEt
EtO
50% (1.25, 1.0) 48% (1.28, 1.15) 50% (1.27, 1.1)
SchEME 18.27 Anodic coupling of enol ethers in β-position to the alkoxy group: yields, oxidation poten-
tials (vs. Ag/AgCl), and n-values. (Adapted from Koch, D. et al., Chem. Ber., 107, 3640, 1974.)
OTMS
OTMS
1.3 V, n = 1.0, 58% 1.33 V, n = 1.1, 66%

OTMS
OTMS
C4H9
1.42 V, n = 0.7, 58% 1.35 V, n = 1.2, 78%
TMSO
0.95 V, n = 1.0, Hydrolysis only
SchEME 18.28 Anodic coupling of silyl enol ethers: oxidation potentials (vs. Ag/AgCl), n-values, and
dimer yields.
C2H5O OCH3
+ OC2H5
–e–, C-anode
MeOH, NaClO4 OCH3
38%
SchEME 18.29 Cross-coupling between vinyl ethyl ether and styrene.
they are strongly polarized with only a small spin density at the dimethylamino group. The oxidation
step and the fates of the radical cations are well characterized by cyclic voltammetry and ESR spec-
troscopy. However, preparative scale electrolyses with the isolation of products are not reported [101].
On the other hand, when vinylidinebisdialkylamines were oxidized by silver ion in AN, diamidinium
salts were obtained as dimerization products [102]. Enaminoketones or enaminoesters yield via dimer-
ization of the intermediate radical cations and subsequent ring closure pyrrole derivatives (Scheme
18.30) [103]. In 2-alkyl enaminoesters and amides, the deprotonation to pyrroles is blocked. Here
2,3-dibenzoyl-2,3-dialkyl-succinic dimethyl esters are isolated in moderate yield and high diastereose-
lectivity for the meso-product (Scheme 18.31) [104]. In the intermediate radical cation, charge and spin
are well stabilized allowing the coupling to vicinal quaternary carbon atoms. The yields of dimer are
decreased due to a competing hydrogen abstraction of the sterically shielded radical cation; thereby,
the ketoester or ketoamide is formed that is used to prepare the enaminoester or amide, respectively.
H R1
–e–, NaClO4
NHR2 MeOH, graphite anode

H3C
R1 R1 R1 R1
–2H+,–R2NH2
+ +
NH NHR2 N
R 2 R2
R1 R2 Yield (%)
CO2Me Bzl 45
CO2Me H 34
CO2Me CH3 36
SchEME 18.30 Anodic coupling of enaminoesters to pyrrole derivatives.

O O
R O O
Bnz H
N O Pt, NaClO4 Ph OMe
+ OMe
MeOH, –e– Ph OMe
OMe R
R
R O O
R = Me, i–Pr: 36%, 35%, meso 15%, 27%
O O
Bnz H O O
N O Pt, NaClO4 Ph R'
+ R'
R' MeOH, –e– Ph R'
R' = –N
O O
27%
32% meso
SchEME 18.31 Anodic coupling of 2-alkyl enaminoesters and amides to meso-2,3-dibenzoyl-2,3-dialkyl-

succinic dimethyl esters and amides.
NC CN
CN –e–, MeOH, NaClO4
H 2N
Ep = 1.25 V vs. SCE N
H
n = 1.26 21.5%
NC CN
CN –e–, MeOH, NaClO
H2N 4
Ep = 1.20 V vs. SCE N

H
n = 1.26 23%
NC CN
C6H4X
–e–, MeOH, NaClO 4
CN
H2N XC6H4 C6H4X
N
H
X Ep (V vs. SCE) n X Yield (%)
H 1.27 1.4 H 27
4–CH3O 1.27 1.53 4-CH3O 29
SchEME 18.32 Anodic coupling of enaminonitriles to pyrrole derivatives in methanol and NaClO4: oxida-
tion potentials, n-values, and yields.
Likewise enaminonitriles can be cyclodimerized by oxidation in MeOH and NaClO4 at a

graphite electrode. The yields are moderate as the product is consumed due to further oxidation
(Scheme 18.32) [105]. When the product precipitates from the electrolyte, the yield is much better
(Scheme 18.33). The five-membered cyclic enaminonitrile affords the heterocyclic product 46 in
62% yield, whose low solubility prevents it from further oxidation. The reaction possibly proceeds,
via a radical cation, coupling of the two mesomeric forms leading to a dication, which undergoes
methanolysis, intramolecular addition to the ketimine, and deprotonation to the product. With the
six-membered cyclic enaminonitrile, no corresponding dimer is obtained [105]. The structure of
the product 46 is confirmed by an x-ray structure [106].
Aryl enaminones (with aryl substituents: X = NO2, Br, H, Me, and MeO) were prepared from
p-substituted acetophenones. Their preparative oxidation in a divided cell at a Pt anode in MeOH
and LiClO4 yielded the dimer and 2,5-bis-aryl-furane (Scheme 18.34) [107].
MeOH, NH2
Na, THF CN CN
NaClO4 N
NC–(CH2)4–CN
–e–, graphite
NH2 N
H OCH3
–e– 46
61%
CH3OH,
CN –2H+
+ NH2
CN
NH2 + N
+
H2N
HOCH3
N
C
+
NH2
SchEME 18.33 Anodic coupling of a cyclic enaminonitrile to the heterocyclic compound 46.
O O Ar
–e–, 1.2 V vs. SCE
Ar N N+ + Ar Ar
MeOH, LiClO4 N O
50% 20%
O Ar
Ar = NO2
SchEME 18.34 Anodic coupling of aryl enaminones.
Enamines were oxidized in alkaline medium in the presence of anions of 1,3-dicarbonyl com-
pounds derived from methyl acetoacetate, acetylacetone, and dimethyl malonate, to afford coupling
products. Presumably the enamines are oxidized at the platinum anode to their radical cations at a
lower potential than that of the anions. The radical cations react then with the anionic substrates to
form substitution products by addition–deprotonation (Scheme 18.35) [108].
Chiral secondary amines react with aldehydes to form transient enamines that were oxidized
with ceric ammonium nitrate (CAN) to electrophilic radical cations. These react with silyl enol
ethers to yield α-substituted aldehydes with high levels of asymmetric induction. A wide choice of
both the aldehyde and the enolsilane component can be applied giving access to a diverse assort-
ment of enantioenriched 1,4-dicarbonyl compounds [109].
O O
N MeOH, NaOMe, –e– N

+ RH
Pt, 0.4–0.9 V vs. SCE R
+ Double bond
isomer
R Yield
CH(COCH3)2 60%
CH(COCH3)CO2CH3 67%
CH(CO2CH3)2 61%
SchEME 18.35 Anodic addition of organic anions to enamines.

O H
–e–,N
+ O
H N
H N Bu4NClO4 (TBAP), DCM
O
88%
O Ph
Ph
H
O Ph N OTMS
+ H O
Ph N
H N TPAB, DCM,–e–
O
57% yield
64% ee
SchEME 18.36 α-Oxyamination of aldehydes with TEMPO by anodic oxidation in the presence of
sec-amines.
In an undivided cell, TEMPO was oxidized to TEMPO+ in the presence of aldehydes and sub-
stoichiometric amounts of secondary amines to yield an aldehyde with TEMPO as α-substituent in
good yield. The asymmetric variant of this α-oxyamination was examined using chiral secondary
amines. It was confirmed by cyclic voltammetry that the radical cation of the enamine, arising from
the sec-amine and the aldehyde, is the intermediate (Scheme 18.36) [110].
The enantioselective organocatalyzed α-alkylation of aldehydes with xanthene was achieved by
anodic oxidation in the presence of chiral cyclic amines. The best yield (80%) and highest enanti-
oselectivity (70% ee) were obtained with the chiral catalyst 47. On the basis of CV and DFT calcula-
tions, the authors propose the coupling of a xanthene radical with an enamine radical cation; both
are generated at the anode (Scheme 18.37) [111].
6. Alkenes with Alkyl Substituents

Alkenes without electron-donating substituents are oxidized at potentials >1.6 V versus SCE
and undergo allylic substitution by the solvent and formation of ketones by rearrangement [112].
Coupling becomes possible, when an unsymmetrical intermediate radical cation with a tertiary
cationic site is involved (Scheme 18.38) [113].
H Ph
O
–e–, Pt anode
+
H Ph DCM, TBAP
O O
O CH3
N
t-Bu
Bn N
H
47
SchEME 18.37 Organocatalyzed anodic α-alkylation of aldehydes with xanthene.

0.5 m NaClO4 OMe

MeOH, 1.6 V
+
–e–
OMe
6% 4% OMe
OMe
+
OMe
MeO OMe
8%
59%
SchEME 18.38 Coupling in the anodic oxidation of 2-ethyl-1-butene.
–e–, HO
H2O, –H+
Ar Ar Ar Ar
48 49
HO Ar O Ar
Ar Oxdn. Ar
50
2 51 2
Ar OH Ar O
Oxdn.
–e–,
H2O, –H+ HO Ar O Ar
52
SchEME 18.39 Anodic coupling of 1,2-diarylethyne.
7. Alkynes
The activated alkyne, diarylethyne (48), has been coupled at the anode [114]. When ethyne 48
is oxidized in AN and LiClO4 at a graphite anode, the dimer 51 and the benzil (52) are obtained
as main products (Scheme 18.39). For the product formation, the following pathway is assumed:
The radical cation reacts with residual water to the enol radical 49 that dimerizes to 50. Further
o xidation converts 50 to 1,2-diaroyl-stilbene (51) (Ar = Ph: 17%; Ar = 4-CH3OC6H4: 47%). Further
oxidation and hydrolysis of 49 leads to benzil (52) (Ar = Ph: 20%; Ar = 4-CH3OC6H4: 12%).
According to a literature search, since this publication, no further examples of this interesting reac-
tion have been reported.
8. Alkanes
The dehydrodimerization of short-chain hydrocarbons has been achieved in some examples.
Coupling of methane at a Ag/Bi2O3 anode in a solid electrolyte yielded at 700°C and 2% conver-
sion in 72% selectivity ethane and in 18% selectivity ethene [115]. Further dehydrodimerizations of
methane are reported at 500–900°C for a Y2O3/ZrO2 solid electrolyte and different anode materials
like Ag, Ni, Cu, Bi, Pt, Sm, and Mn [116,117].
E. INTraMoLECULar CoUpLING
1. Aromatic Compounds
A large number of 1,n-bis(methoxyphenyl)alkanes have been coupled intramolecularly to afford
biphenyls being integrated into rings of different size. The method allows preparing in few steps
meta-cyclophanes, polycyclic hydroaromatic compounds, and intermediates for the synthesis of ste-
roids, heterocyclic compounds, and alkaloids. The section is organized according to an increasing
number n of methylene groups, which in some cases are replaced by a heteroatom, mainly nitrogen.
The coupling sites and the yields depend on the integer n, the position of the aryl substituent, the
choice of the electrode–electrolyte system, the current density, and the oxidation potential.
The coupling products are easily further oxidized to their radical cations. In AN these are fairly
unstable, which causes lower yields in this solvent. In DCM and TFA, the cyclized products are
also further oxidized, but in this solvent, the radical cations are stable. After the electrolysis, they
are reduced with zinc dust to the neutral products that can then be isolated in high yield [118]. Two
examples are shown in Table 18.2, entry 1 and 2.
1,n-Bis(methoxyphenyl)alkanes with n = 1–4 and without a heteroatom in the alkyl chain cyclize
in moderate to high yield (Table 18.2, entries 1–7, 11, 12). CV and products of unsymmetrically
methoxylated diphenylalkanes permit conclusions on the mechanism of the dimerization. The
results point to the dimerization of two radical cations [122]. On the other hand, kinetic studies indi-
cate a cyclization by a radical cation–substrate coupling, followed by a rate-determining electron
transfer [127]. Diarylalkanes with a phenol ether group at one end and a phenolic group at the other
end afford high yields of spirodienones (Table 18.2, entries 3 and 4).
The 2-methyl-tetramethoxybibenzyl derivative 53 cyclizes in an anodic 2,6′-coupling reaction
followed by a dienone–phenol rearrangement to afford a 98% yield of the dihydrophenanthrene
54 (Scheme 18.40). Compound 54 contains essential structural elements of the B, C, and D ring of
steroids [128].
With the corresponding dimethoxybibenzyl derivative, ring closure takes place without rear-
rangement to form a structure analogous to the A, B, and C ring of steroids [129]; however, the yield
is moderate (22%) because of the lower activation of the arene system. A remote substituent can
strongly influence the occurrence or absence of a further dienone–phenol rearrangement (Table 18.2,
entries 6 and 7).
In the case of the [2.2]-meta-cyclophane 55, two anisyl radical cations couple in 90% yield to
give the tetrahydropyrene derivative 56 (Scheme 18.41) [130]. [2.2]-Meta-cyclophanes with other
substituents than methoxy—for example, with CH3, Br, CN, or NO2—can also be cyclized [131].
The anodic cyclization of benzyltetrahydroisoquinolines 57 (Scheme 18.42, Table 18.3) with
n = 2 and no heteroatom in the methylene chain to the morphinane skeleton is particularly inter-
esting from the preparative point of view, since the cyclization cannot be achieved so simply with
chemical oxidants. Compounds 58a,b can be obtained in good yield in AN and sodium bicarbonate
using a divided cell [129,132–135]. Flavinantines 58c–f can even be prepared in an undivided cell
and an acidic electrolyte [136]. The reaction has also been used to prepare optically active 9-(R)-O-
methylflavinantine [137].
However, in order to obtain the desired morphine-type compound, one needs a C2′–C4a cou-
pling in 57, but the −I effect and the steric shielding by the 3′-methoxy group favors the unwanted
C6′–C4a coupling in 57 to the flavinantine type of compound.
Attempts to enforce the coupling to the morphine type compound have so far been partially
successful. Compound 59a (Scheme 18.43, Table 18.4) cyclizes at C2′ with debromination (due to
R1 = Br, the numbering has changed in the benzyl ring compared to 57) [135]. In compounds 59b
[129,135] and 59c,d [138], oxidative cleavage of the molecule is occurring at C1. In compounds
59e,f, the C2′ ring closure is not hindered by the iodo or bromo atom at C3′ [129,135].
In compound 59g, however, where the C2′ and C6′ coupling is identical, a C–C bond ortho to the
methoxy group is obtained in 35–55% yield [133,135]. Compound 59h, which also has two identical
ortho-coupling sites could be cyclized in 65% yield, and the cyclization product subsequently has
been converted into 3-desoxythebain [139].
Benzyltetrahydroisoquinoline 60 with a differently substituted 3′- and 5′-position in the benzyl
ring could be cyclized in 65% yield to compound 61, which was further converted to the thebaine
derivative 62 (Scheme 18.44) [140].
A major mechanistic study, using mainly CV, and seeking common denominators in the oxida-
tion of methoxybibenzyls including benzyltetrahydroisoquinolines, has been published [134].
TABLE 18.2
Intramolecular Coupling of Aryl Compounds and Tin-Compounds
Entry Substrate Condition Product Yield (%) References
1 OMe DCM, TFA, OMe 95 [119]
OMe TBABF4, Pt OMe
OMe OMe
OMe OMe
2 OMe DCM, TFA, OMe 95 [119]
OMe TBABF4, Pt OMe
OMe OMe
OMe OMe
3 MeO AN, MeO 85 [120, 121]
TMABF4, Pt
MeO 0.74V(SCE) MeO
MeO OMe MeO OMe

OH O
4 OH Pt, AN, O 75 [120, 121]
NaClO4
O O
O O
5 MeO Pt, DCM, MeO 33 [122]
TFA (3:1)
MeO MeO
TBABF4
MeO MeO
MeO MeO
6 NRMe AN, HBF4, NRMe 75 [123]
Pt, R =
MeO CO2Et MeO
OMe 1.0 V(SCE)
MeO
O
OMe
OMe
OMe
(Continued)

7 NRMe AN, HBF4 OMe 75 [123]
Pt, R = MeO
MeO
COCF3
OMe
MeO
OMe
MeO NRMe
O
8 O NaOH, O 45 [124]
NaClO4, C
O O
NH N
O O
9 O NaOH, O 43 [124]
NaClO4, C
MeO MeO
NH NH
MeO MeO
10 O C, AN 62 [143]
O H
NaClO4 O
n
N
H
MeO N
OMe
O
11 MeO H2O, C MeO 36 [125]

Et4NClO4
NCH3 NCH3
HO HO
O
OMe
MeO
OH
12 MeO An, NaClO4 MeO [126]

CH3 1.2 V(SCE) CH3
N OMe N OMe
MeO MeO +
OMe OMe
(Continued)

13 SnBu3 DCM, Y 50–98 [146]
Bu4NBF4
Y molecular R n F
R n sieve, C
R = C7H15,C6H12
Y = O, NCO2Me
n = 1,2
14 SnBu3 DCM, Y [147]
Bu4NClO4 Y = O, R = H 55
Y R Y = O, R = F 80
R Y = NCO2Me, 54
R=H
OMe OMe
OMe OMe
+
MeO 6' MeO
2 –2e–
+
MeO 1 MeO
53
Rearrangement OMe
–2H+
O
MeO
OMe
54
SchEME 18.40 Anodic 2,6′-coupling of the 2-methyl-tetramethoxybibenzyl derivative 53 to the dihydro-

phenanthrene 54.
–2e–, –2H+
MeO OMe MeO OMe
90%
55 56
SchEME 18.41 Anodic coupling of the [2.2]-meta-cyclophane 55 to the tetrahydropyrene derivative 56.
OR3
R1O 4a R4O
NMe
R2O –e–
2´
OR3 AN,NaHCO3
or AN, HBF4 NMe
6' OR 4 1
RO
57 58
O
SchEME 18.42 Anodic cyclization of benzyltetrahydroisoquinolines 57 to flavinantines 58.

TABLE 18.3
Structure and Yields of Flavinantines 58
R1 R2 R3 R4 Yield (%)
a CH3 CH3 CH3 CH3 52–85
b CH3 CH3 CH3 Bn 43–63
c CH3 CH3 CH3 H 63
d CH3 CH3 H CH3 50
e CH3 CH3 –(CH2)– 80
f CH3 CH3 CH3 CH3 70
R4
R3
6'
2'
R2
R1 1
NR5
MeO
OMe
59
SchEME 18.43 Attempts to enforce the coupling of benyltetrahydroisoquinolines 59 to morphine-type

compounds.
TABLE 18.4
Substituents in 59
R1 R2 R3 R4 R5
a Br H MeO MeO Me
b Cl H MeO MeO Me
c NO2 H MeO MeO Me
d NHCOCH3 H MeO MeO Me
e H I MeO MeO Me
f H Br MeO MeO Me
g H MeO MeO MeO Me
h H BnO H BnO COCF3
Benzyl- and 2-phenethyl-enaminoketones can be cyclized in good yields to quinolines and benz
azepines (Table 18.2, entries 8 and 9). The cyclization has been also used to prepare a precursor of
the alkaloid lycorane (Scheme 18.45) [141].
In indoles, the oxidation of the heterocycle must be suppressed by electron-withdrawing sub-
stituents, which is the case in 3-keto-substituted indoles. α-Phenacetyl-indole (Table 18.2, entry 10,
n = 1) undergoes no cyclization, which has been attributed to a geometrically unfavorable transition
state [142]; on the other hand, the β-phenylpropionyl indole (Table 18.2, entry 10, n = 2) cyclizes
in 62% yield [143]. The radical cation first couples to a spiro-intermediate, which then undergoes
oxidation, bond breaking, rearrangement, and tautomerization to the indolenine.
Unsymmetrical 1,3-diaryl propanes with phenolic hydroxy groups react to spirodienones,
presumably via a phenoxonium ion (Table 18.2, entry 3). Trimethoxy-substituted diphenylpro-
panes form different products depending on the reaction conditions. In MeCN and HBF4 a
spiro dienone is obtained (Scheme 18.46) [122]; in DCM and TFA (3:1), a seven-membered ring
O
O
O 5' O
3' 1. 0.01 M HBF4, AN

BnO BnO
–20°C, 2.5 mAcm–2
–e–
NCH3 NCH3
CH3O CH3O
OCH3 O
60 61
O
O
2. a) NaBH4, MeOH, 99%; b) Pd/C,
1,4-cyclohexadiene, EtOH, 91%;
c) (i-Pr)2CHN(CH3)2, DCM, 68% O
NCH3
CH3O
62
SchEME 18.44 Cyclization of the benzyltetrahydroisoquinoline 60 to compound 61 that was further con-
verted into thebaine 62.
O N –e–, 38% O N
MeOH
O O
O O
SchEME 18.45 Cyclization of a benzylenaminoketone to a precursor of the alkaloid lycorane.
OMe OMe
MeO MeO
AN, HBF4
–e–, 90%
MeO O
DCM, TFA
–e–
OMe MeO
MeO
MeO
71%
+ MeO
MeO
SchEME 18.46 Trimethoxy-substituted 1,3-diphenylpropane forms different products depending on the

reaction conditions.
MeO
OAc
R2
MeO R1
MeO
OMe
OH 64
63
OMe OMe
O 62%
80%
O N BnO NCOCF3
COCF3
65 MeO Br
66
OMe OMe OMe

MeO MeO OMe
(CH2)n
(CH2)n
MeO MeO OMe

OMe OMe OMe
68
67
SchEME 18.47 Substrates and products from various cyclizations of aryl compounds.
is formed. The latter result is explained by the low nucleophilicity of the medium and catalysis
of the dienone–phenol-like rearrangement by TFA.
A 2-phenethyltetrahydroisoquinoline with hydroxyl groups as substituents leads to an ortho,
para-coupled spiro compound (Table 18.2, entry 11); with alkoxy groups, a tetracyclic compound
by nitrogen-aryl coupling is obtained (Table 18.2, entry 12). The intramolecular coupling of 63
(Scheme 18.47) has been used in a synthesis of colchicines [144].
Unsaturated enolacetates 64 (n = 3 and no heteroatom) have been cyclized to cyclohexenyl
ketones [145].
With the stannyl group as electroauxiliary, oxonium or N-acylium ions can be generated, which
react in an electrophilic intramolecular addition or substitution to afford cyclic six-membered ethers
or amines or their benzo analogues (Table 18.2, entries 13 and 14).
In the intramolecular coupling between phenols and olefins, Swenton has explored the depen-
dence of the yield on the substituents in the aryl ring and in the olefin (Scheme 18.48) [49,148,149].
In these cyclizations, the intermediate phenoxonium ion adds to the double bond and the resulting
cation is subsequently trapped by methanol.
1,4-Di(methoxyphenyl)butane (n = 4) forms in DCM and TFA initially a seven-membered ring
followed by rearrangement to the eight-membered ring (Table 18.2, entry 5). The amide 65 in
Scheme 18.47 (n = 3 and with the heteroatom substituted by the trifluoroacetyl group) has been
cyclized to a precursor of (+)-oxocrinine [150]. Amide 66 has been coupled intramolecularly to a
precursor of galanthamine [151].
1,5-Bis(dimethoxyphenyl)pentane (n = 5) forms a seven-membered ring compound 67 by an
aryl–benzyl coupling [119]. With bis(dimethoxyphenyl)alkanes, (n > 6) coupling occurs intermo-
lecularly and with partial subsequent cyclization to form up to 40-membered rings 68 [152].
R1 R2 R1 R2
–2e–, –H+
HO O +
Pt, –e–, AN/MeOH/

AcOH, LiClO4
R1 R2 R1 R2
OMe
MeOH, –H+
O O
R1 R2 Yield(%)
H H 16
H CH3 85
H Ph 65
CH3 H 35
–(CH2)3– 69
SchEME 18.48 Dependence of the yield on the substituents in the intramolecular coupling between phenols
and olefins.
2. Olefins
The intramolecular anodic coupling of olefins derived from enol ethers, vinyl sulfides, and ketene
acetals has been reviewed recently [4a]. Thereby, radical cations are involved that react with carbon,
oxygen, and nitrogen nucleophiles as trapping groups.
Intramolecular coupling is used to construct five-membered rings that could be applied for the
synthesis of tricyclopentanoid ring systems, which are core structures in some biological active
natural products. Thereby, an enol ether radical cation can be trapped intramolecularly by an allylsi-
lane. The results show that the reaction is compatible with an allylic alkoxy group that is frequently
needed in the target molecule. In addition, the reactions using either a trisubstituted allylsilane or
a cis-disubstituted allylsilane group as the terminating group were found to lead to the formation
of five-membered rings with kinetic control of the relative stereochemistry. The stereoselectivity of
these reactions originated from an A1,3-interaction (allylic strain: 1,3-interaction between substitu-
ents at C1 and C3 of an allyl group that favors one conformer [153]) with the allyloxy group that
raised the energy of the transition state leading to the cis-product. When the size of R in the allyloxy
group was increased from t-butyldimethylsilyl (TBDMS) to triisopropylsilyl (TIPS), the stereose-
lectivity was further improved (Scheme 18.49) [154].
TMS
RO RO RO
C anode, –e–
Pt cathode
+
LiClO4, MeOH/ OMe OMe
THF, 2,6-lutidine
OMe OMe OMe
R = TBDMS 67% 8%
R = TIPS 81% —
SchEME 18.49 Cyclization between an enol ether and an allyl silane as trap; kinetic control of the stereo-
chemistry by the allylic alkoxy group.
H
O H H
Me Me Me
RVC anode O O
C cathode H
X OMe
H R + O
AN, 10% MeOH, Y
LiClO4, 2,6-lutidine OMe O
Ot-Bu
OMe OMe
MeO
R = OMe — —
R = Me 73% (X = OMe, Y = Me) —
R = OC(O)Ot-Bu 38% (X = Y = OC(O)O) 26%
R = OTf — —
SchEME 18.50 A polarized radical cation favors cyclization by C–C bond formation (RVC = reticulated
vitreous carbon).
The ability of the intramolecular olefin coupling at the anode to form new C–C bonds depends on
the polarization of the intermediate radical cation rather than on how electron-rich it is. Substrates
were studied that allowed for a direct comparison of these two parameters, namely, NMR data and
oxidation potential. The successful cyclizations gave highly functionalized bicyclic molecules con-
taining four contiguous stereogenic atoms, one of which was tetrasubstituted. Additionally, it was
shown for the first time that an enediol ether derivative with an alkyl group and a t-butyloxycarbonyl
group is compatible with the cyclization reaction. The cyclization tolerates a second donor group on
the olefin leading to the radical cation, but only if such a group increases or maintains the polariza-
tion of the radical cation. Hence, for a ketene acetal–type substrate, it is beneficial to add the second
donor group, but for an enediol-type substrate, it is important to make sure that the second oxygen
substituent on the initiating olefin is electronically neutral. That means a more polarized radical
cation favors C–C bond formation, while a less polarized radical cation supports a C–heteroatom
bond formation (Scheme 18.50) [155]. The importance of polarized bonds in radical cations, when
discussing their chemistry, has been also pointed out for aromatic compounds earlier [12].
The intramolecular anodic coupling of a ketene dithioacetal radical cation and an amide trapping
group leads to a furanone; the coupling benefits greatly from the addition of water to the reaction
medium. After optimization a yield of 83% has been obtained (Scheme 18.51) [156].
Intramolecular anodic olefin addition reactions can be used to synthesize furanose and pyranose
C-glycosides [157]. Similarly, carbon–nitrogen bonds can be created to prepare pyrrolidine and
piperidine rings [158] and proline derivatives [159].
The key step in the asymmetric synthesis of the sesquiterpene lactone (−)-alliacol A is the intra-
molecular anodic coupling of a silyl enol ether and a furan (Scheme 18.52) [160]. The electrolysis
could be accomplished with a simple, cheap, and readily available equipment, namely, a three-
necked round-bottom flask, graphite electrodes, and the use of a 6 V lantern battery [161].
The anodic cyclization to a tetrahydrofuran by trapping the radical cation of a ketene dithioacetal
by an alcohol was used as a step in the asymmetric synthesis of (+)-nemorensic acid. Thereby, steric
factors of the large ketene dithioacetal group led to high levels of stereoselectivity [162].
An anodic cyclization reaction between an enol ether radical cation and an oxygen nucleophile has
been used to prepare a tetrahydropyran building block for the C10–C16 fragment of the biologically
Et S RVC anode, –e–, S

C cathode
N
Et O S 10% H2O, MeOH O S
Et4NOTos, 2,6-lutidine O OMe
83%
SchEME 18.51 C–O bond formation by trapping a ketene dithioacetal radical cation with an amide group.
TBSO CH3 O CH3

a) RVC anode, –e–
LiClO4, 2,6-lutidine,
20% MeOH/DCM
TBSO O HO O
b) TsOH
88%
SchEME 18.52 Anodic intramolecular coupling of a silyl enol ether as key step in the asymmetric synthesis
of (–)-alliacol A.
RVC anode, –e–

Et4NOTs
S S 30% MeOH/THF S S MeO OMe
2,6-lutidine,
+
45°C
MeO
HO O HO
MeO OBn MeO OBn MeO OBn
10%
70%
+S S S S
+
HO HO
MeO OBn MeO OBn
SchEME 18.53 Product formation via an intramolecular electron transfer.
active, natural product bryostatin. The oxidative cyclization was successful despite the presence of
a thioacetal group that has a lower oxidation potential than the enol ether. Experimental evidence
suggested that the reaction proceeded through an initial oxidation of the thioacetal followed by an
intramolecular electron transfer to form the enol ether radical cation that was subsequently trapped
by the oxygen nucleophile (Scheme 18.53). The formation of the desired cyclic product could be
explained using the Curtin–Hammett principle [163].
The scope of Curtin–Hammett-controlled anodic cyclizations has been further extended by
examining the compatibility of coupling reactions conducted in the presence of a dithioketal pro-
tecting group with both the formation of medium-size rings and the generation of carbon–carbon
bonds. Cyclizations utilizing an alcohol as trapping group are fast and show no signs of competitive
trapping of the dithioketal radical cation even when forming a seven-membered ring. Carbon–car-
bon bond–forming reactions utilizing reactive furan trapping groups are also fast, although not fast
enough to allow for seven-membered ring formation. Slower carbon–carbon bond–forming reac-
tions benefit strongly from the use of less polar electrolytes that selectively lower the concentration
of methanol in the region of the reaction at the anode surface [164].
Intramolecular coupling reactions between enol ether radical cations and oxygen nucleophiles
are also governed by stereoelectronics. By taking advantage of this observation, a THF building
block for use in constructing (+)-linalool oxide and rotundisine has been synthesized in four steps
from a commercially available starting material [165].
Intramolecular anodic coupling of two enol ethers can be used to build bicyclo[3.2.1]octane ring
skeletons. Wider applications are limited due the formation of dimethoxy acetals at both the terminat-
ing and initiating ends of the cyclization reactions. However, these ends can be differentiated by using
a ketene dithioacetal group and an enol ether as initiating and terminating group (Scheme 18.54) [166].
RVC anode, –e– S

S Pt cathode
S
30% MeOH/THF MeO
S 2,6-lutidine OMe
OMe MeO
75%
SchEME 18.54 Intramolecular coupling between an enol ether and a ketene dithioacetal.
S
R1 RVC anode, –e–
Pt cathode H S S
NH2 S N
R3 OMe
LiOMe
R1
R3 n R2 MeOH, Et4NOTs
n
R2
R1 = Me, CH = CHMe; R2 = H, Me; R3 = H, Me

Yield: 72–92%, high diastereoselectivity
SchEME 18.55 Intramolecular trapping of a dithioketene acetal by an unprotected amine to generate

amino acid derivatives.
Anodic oxidation of enol ethers, for example, HOCH2(CH2)nCHRCH=CHOMe (n = 1, 2), was

used to accomplish the formation of both tetrahydrofurans and tetrahydropyrans. The method com-
pliments existing chemical routes to related ring systems [167].
Inexpensive, readily available photovoltaic cells can been used to conduct electrochemical oxi-
dation reactions. It has been applied to intramolecular coupling reactions between two enol ethers
and between enol ethers and oxygen or nitrogen nucleophiles. In this way, the energy efficiency of
sunlight-driven reactions can be combined with the versatility of electrochemistry to create new,
sustainable methods for conducting oxidations [168].
A radical cation generated from a dithioketene acetal can be trapped by an unprotected amine.
The reaction generates amino acid derivatives with a tetrasubstituted α-carbon atom. In this reaction
the cyclization lowers the oxidation potential of the substrate. In the examples reported, the cycliza-
tions are fast enough that the substrate potential is decreased to such an extent that it is significantly
lower than that of the product, which this way can be prevented from further oxidation. The thioke-
tal can be hydrolyzed with N-chlorosuccinimide (NCS) in acetone and water to unmask the amino
acid derivative (Scheme 18.55) [169].
The anodic oxidation of bis-enol ethers can effectively lead to the formation of five-, six-, and
seven-membered ring products in good yields. Besides leading to potentially useful 1,4-dicarbonyl
equivalents, the cyclizations are compatible with the formation of quaternary carbon atoms [170].
Enol ethers could be coupled with aryl rings to form a fused six-membered ring in 57%
yield. The cyclization profited from a 3-alkoxy group in the aryl ring. Furan rings were found
to be excellent coupling partners for the reactions and afforded products having fused, bicy-
clic furan ring skeletons. Cyclizations involving furans were shown to be compatible with the
formation of both six- and seven-membered rings, the generation of quaternary carbon atoms,
and the use of a variety of electron-rich olefins as the other coupling partner. The yields ranged
between 10% and 71%. It appeared that the furan can serve as either the initiating group or the
terminating group for the cyclizations. Also N-acylpyrroles could be coupled to thioenol ethers
in 66% yield [171].
Two enol ethers or an enol ether and an allylsilane could be coupled to form fused bicy-
clic compounds consisting of five- and six-membered rings. The resulting 1,4-dicarbonyl com-
pounds could be subsequently used for aldol reactions to form angularly fused tricyclic ring
systems [172]. Enol ethers could be coupled intramolecularly to simple alkyl olefins, styrenes,
O
O RVC anode and cathode O
TIPSO
2,6-lutidine, MeOH/THF
N O
N O ET4NOTos, –e–
n
n
OMe
OMe
OMe
n = 1 87%
n = 2 65%
O
O RVC anode and cathode O
TIPSO
2,6-lutidine, MeOH/THF N O
N O ET4NOTos, –e–
n
n
CH2TMS
n = 1 70%
n = 2 71%
SchEME 18.56 Intramolecular coupling reactions of N,O-ketene acetals with enol ethers and with an
allylsilane.
and allylsilanes in isolated yields ranging from 57 to 84%. The reactions were found to be effec-
tive for generating both five- and six-membered rings [173].
Intramolecular coupling reactions of N,O-ketene acetals with both enol ether and allylsilane
terminating groups were examined. The reactions of the N,O-ketene acetals with allylsilane groups
were found to be much more efficient than corresponding reactions with dithioketene acetal groups
and allylsilanes. The reactions were also more efficient than the intramolecular coupling reactions
between enol ethers and allylsilanes (Scheme 18.56) [174]. Both results support the observation that
more polar radical cations aid the formation of carbon–carbon bonds.
A competition experiment was designed where an N-nucleophile and an O-nucleophile compete
in the coupling reaction. The studies show that when a dithioketene acetal olefin is used in the reac-
tion, the use of LiOMe as a base leads to a mechanism, where probably the radical cation is trapped
by a sulfonamide anion. A similar result was obtained when an enol ether was used. However, the
data obtained with a vinyl sulfide were less conclusive [175].
Two intramolecular anodic olefin coupling reactions have been used to synthesize the arteannuin
ring skeleton. In one case an N,O-ketene acetal was the initiating group and a furan terminated the
reaction. In the second case a (Z)-enolether initiated the coupling and installed a tetrasubstituted
carbon atom (Scheme 18.57) [176].
A two-step electrochemical annulation has been developed for the preparation of fused furans.
The process involves an initial conjugate addition of a furylethyl cuprate and trapping of the enolate
as the corresponding silyl enol ether. The second step of the annulation involves the anodic coupling
of the furan and the silyl enol ether to form a six-membered ring [177].
Cyclic voltammetry indicates that in the anodic oxidation, the enol ether is converted to
a radical cation that is trapped by an electron-rich heterocyclic compound (furan, thiophene)
with the formation of six- and seven-membered rings. The dramatic influence of the methyl
group is attributed to a kind of gem-dialkyl effect. Mechanistic considerations are well sup-
ported by cyclic voltammetry, suitably chosen probes, and the use of competition experiments
(Scheme 18.58) [178,179].
The effect of the methyl group was extended to other groups as phenyl, i-propyl, ethyl, and vinyl
in this position that led to consistent good yields of around 60% of the seven-membered rings.
Voltammetric studies indicated that this effect lowers the oxidation potential by approximately 110 mV.
1) RVC anode, –e– O O CH3

O OTIPS CH3
carbon cathode
LiClO4, MeOH, DCM O N
N
O 2,6-lutidine
2) H3O+ work up O
O Ph
Ph
R
R R=H 70%
R = CH3 65%
Me Me
H
H
RVC anode
MeO carbon cathode
LiClO4, MeOH, DCM
O 2,6-lutidine O
O
R
R
MeO
R=H 70%
R = CH3 80%
SchEME 18.57 Two cyclization routes to the arteannuin skeleton.
R R
RVC anode,–e–,
LiClO4,
AN, iPrOH,
2,6-lutidine
O
TMSO O O
R=H 0%
R = CH3 70%
SchEME 18.58 Annulated heterocycles through a radical cation cyclization.
This result provides direct evidence for the importance of the reactive rotamer effect on an electron
transfer reaction [180]. The shift of the oxidation potential could be due to an assistance of the
electron transfer by the π-electrons of the furan ring. This would favor the coupling reaction against
other competing reactions of the enol ether radical cation.
A concise, stereoselective, and convergent total synthesis of the unnatural enantiomer of the
neodolastane diterpenoid heptemerone B was completed. Thereby, the central seven-membered ring
was closed by an electrochemical oxidation (Scheme 18.59) [181].
An alternative annulation of enol ethers located in five- and six-membered carbocyclic rings by
cyclization with furans and thiophenes has been developed. The connection of the furan or thio-
phene ring at C2 to the enol ether led to spiro compounds (Scheme 18.60) [182].
Me Me
Me RVC anode, –e– Me
2,6-lutidine H
TBDPSO LiClO4, TBDPSO
OBn 20% MeOH, DCM OBn
O O H
OTBS MeO O
81%
SchEME 18.59 Synthesis of the central 7-membered ring in the 17-step total synthesis of the diterpenoid
heptemerone B using anodic coupling as one of the key steps.
R R
R
C anode, –e–
n AN/iPrOH n
n
O LiClO4 +
TMSO 2,6-lutidine O O
O O
OiPr iPrO
59–69% 22–23%
R = H, Me, n = 1, 2
SchEME 18.60 Anodic annulation of five- and six-membered rings to furan leading to spiro compounds.
OMe OMe
MeO C anode, –e– MeO
0.5 mA cm–2
CH3 AN, LiClO4 CH3
67%
TMSO O
SchEME 18.61 Anodic coupling of a silyl enol ether to an electron-rich aryl ring as a way to the hamigeran
skeleton.
R R
OH O
MeOH, –e–
NaBr
N N Ph N N Ph
N N N O N
Ph OH Ph
84–97%
R: H, 3-Br, 2-Cl, 4-Me,
2-MeO, 3-Cl, 4-Et
SchEME 18.62 Mediated intramolecular coupling of heterocyclic compounds.
The tricyclic core of the hamigerans, which are unusual halogenated marine natural products,
has been prepared through the use of a two-step electrochemical benzannulation reaction. The
annulation proceeds through an initial conjugate addition of a phenethyl cuprate to 3-methylcy-
clopentenone with in situ silylation of the resulting enolate. Anodic oxidation couples the pendant
arene and the silyl enol ether to produce a key intermediate for the hamigeran synthesis. Careful
optimization revealed that the use of alcohol-free AN as solvent was critical to obtain high yields of
the annulated product (Scheme 18.61) [183].
The intramolecular coupling of electron-rich heterocyclic compounds has been achieved in
methanol with NaBr as mediator in high yields (Scheme 18.62) [184].
F. ANoDICaLLY INDUCED CYCLoaDDITIoNS

1. [2 + 2] Cycloadditions
Vinylcarbazoles and 1,1-bis(4-dimethylaminophenyl)-ethylene can be converted with Fe(NO3)3 in
methanol in 60–90% yield to the cyclodimers. When the vinyl group is attached to the N-atom,
head-to-head cyclobutanes are obtained, and in case the vinyl group is attached to the aryl ring and
in 1,1-diarylethylenes, head-to-tail cyclobutanes are formed. As for the mechanism, it is assumed
CH3O H H
CH3O OCH3
–e–
CH3O
CH3O OCH3
H H
30%
SchEME 18.63 Cycloaddition of dimethoxyindene to a cyclobutane.
CH3
+ Ph –e–, AN, Et4NClO4
CH3 O
O
CH3 Ph H3C
Ph
+ H
O Ph
CH3 CH3
O O O
15% 50%
SchEME 18.64 [2 + 2] and [4 + 2] cycloadducts from dimethylindenone and 1-benzoyl-1-phenyl-ethene.
that the olefin is oxidized to a radical cation that couples with the olefin to a 1,4-radical cation that
undergoes cyclization. The cyclic radical cation is reduced to the cyclobutane by an electron transfer
from the olefin, which continues the chain reaction [185,186].
At the anode, N-vinylcarbazole has been cyclodimerized in AN even earlier, however, in only
8% yield [187]. In acetic acid KOAc as supporting electrolyte, a concentrated solution of dime-
thoxyindene is dimerized with 1.4 F in 30% yield in a formal [2 + 2] cycloaddition to a cyclodimer;
polymers, however, are the major products (Scheme 18.63) [188].
Dimethylindenone and 1-benzoyl-1-phenyl-ethene combine, when electrolyzed in AN and
Et4NClO4 to form 15% of a [2 + 2] cycloadduct and 50% of a [4 + 2] cycloadduct (Scheme 18.64) [189].
Cis-cyclooctene shows no voltammetric response in the electrolyte DCM and Bu4NB(C6H5)4
prior to the anodic background. However, in the presence of catalytic amounts of ReCp(CO)3
and its oxidation at 1.16 V versus FeCp2 to the strong oxidant [ReCp(CO)3]+, cis-cyclooctene
is oxidized to form the cyclodimer in 70–80% yield. Presumably, [ReCp(CO)3]+ converts the
cycloolefin to the radical cation that undergoes cyclodimerization with cis-cyclooctene as donor
(Scheme 18.65) [190].
Cross-metathesis between an enol ether and an aryl alkene can be selectively initiated at the
anode. Thereby, the 4-methoxy group at the aryl ring determines the pathway. The following mech-
anistic explanation is given: The enol ether is oxidized to a radical cation that undergoes a cycload-
dition with the 4-phenyl-1-butene to form a cyclobutane radical cation. This radical cation forms in
a retro-cycloaddition the cross-metathesis product and an enol ether radical cation, which carries on
the chain (Scheme 18.66a). With the anisole group instead of the phenyl group, the electron is faster
transferred from the electron-richer aryl ring to the cyclobutane radical cation, thus preventing the
retro-cycloadditions and leading selectively to the cross-coupling product (Scheme 18.66b) [191].
–e–, ReCp(CO)3
DCM, Bu4NB(C6H5)4
70–80%
SchEME 18.65 Anodic cyclodimerization of cis-cyclooctene mediated by ReCp(CO)3.

OCH3 –e–, 1.1 F

+ C8H17 C8H17
LiClO4, MeNO2 78%
(a) 20 mol equiv
CH3O
CH3O OMe
OCH3 –, 0.5 F
–e
+ C8H17
LiClO4, MeNO2 +
(b) 20 mol equiv C8H17
C8H17
3%
SchEME 18.66 Selective formation of either a (a) cross-metathesis product or (b) a cross-coupling product
controlled by the ease of the intramolecular electron transfer from the aryl group.
Further support on the reaction mechanism is given through deuterium-labeling studies [192].
The assumed intramolecular electron transfer from the alkoxyphenyl group was further sup-
ported by cyclic voltammetric studies and quantum chemical calculations [193].
Electron-transfer-induced intermolecular [2 + 2] cycloadditions between 3,4-dihydro-2H-pyran
and several unactivated olefins have been demonstrated to work on the basis of the aromatic “redox
tag” strategy. The anodically generated radical cation of the cyclic aliphatic enol ether was effec-
tively trapped by unactivated olefins possessing an aromatic redox tag to stabilize the corresponding
[2 + 2] cycloadducts. The aromatic redox tag is oxidized during the formation of the cyclobutane
ring, affording a relatively long-lived aromatic radical cation, which is then reduced to complete the
overall reaction. Aromatic tags with an oxidation potential between 1.46 and 1.76 V (vs. Ag/AgCl)
most effectively increase the cyclobutane yield to 84–94%. Furthermore, the aromatic redox tag was
also found to facilitate the electron-transfer-induced cycloreversion of the cyclobutane ring to the
corresponding radical cations [194].
Anodic processes in the lithium perchlorate and nitromethane (LPC, NM) electrolyte system
provide a wide variety of carbon–carbon bond–forming reactions. The electrolyte solution acts as
a Lewis acid catalyst that enables intermolecular reactions between unactivated alkenes and anodi-
cally generated intermediates. The properties of the electrolyte solution and applications to electro-
chemical reactions are reviewed [195].
Alkyl enol ethers with a methoxyphenyl group attached to the alkyl group lead to high yields of
cyclobutanes with methylene cyclohexane and other unactivated alkenes [196].
Further examples of electrocatalytic formal [2 + 2] cycloadditions between anodically activated
aliphatic enol ethers and unactivated olefins possessing an alkoxyphenyl group were accomplished
in an LPC and NM electrolyte solution [197]. Enyloxy benzene gave consistently high yields of
cyclobutanes with enol ethers, an activated alkene and even an alkyne (Scheme 18.67) [198].
Formal hetero Diels–Alder reactions and [3 + 2] cycloadditions could be achieved by electrolysis
of benzylic thioacetals in NM and LiClO4 in the presence of alkenes or allylsilanes. The reaction
proceeded possibly by selective oxidation of the thiogroup to a radical cation and subsequent loss
of a thioradical. Electrophilic addition of the benzyl cation to the alkene and subsequent aromatic
substitution led to the product. With an o-hydroxy group in the aryl ring, an intermediate quinodi-
methane can be formed and react as a dienophile (Scheme 18.68) [199].
2. [4 + 2] Cycloadditions
At the anode [4 + 2] cycloadditions between two electron-rich dienes can be induced. Most probably,
the diene is oxidized to the radical cation. This reacts with the dienophile to the cycloadduct radi-
cal cation, which is reduced to the product by the diene that thereby is transformed into the radical
cation that continues the chain. 1,3-Cyclohexadiene forms in 24% yield the cycloadduct with a high
endo/exo selectivity of 28:1. The yield, however, is much lower than in the photosensitized cycload-
dition (95%, endo/exo = 8:1) (Scheme 18.69) [200].
–e–, LiClO4, MeNO2 O

+
0.1 F
90%

+
0.1 F
O O
96%

+ 1.0 F
35%
SchEME 18.67 The prop-1-enyloxy benzene group improves the yield in cycloadducts.
OMe OMe OMe

–e– –e–
TMS TMS
LiClO4, MeNO2 LiClO4, MeNO2
PhS SPh –PhS PhS –PhS
100% 70%
–
–e
OH LiClO4, MeNO2 O
–PhS
PhS SPh PhS
86%
OCH3 OCH3
–e–
CH3O OCH3 CH3O OCH3
LiClO4, MeNO2
–PhS
PhS SPh PhS
79%
SchEME 18.68 Hetero Diels–Alder reactions and [3 + 2] cycloadditions by anodic oxidation of benzyl
thioacetals in the presence of alkenes.
AN, DCM, LiClO4

2,6-lutidine, –e–
2
SchEME 18.69 Cycloaddition between two electron-rich dienes induced by single electron transfer (SET)
at the anode.
CO2CH3
HN
CN CN
AN, LiClO4
N N
H –e–
CO2CH3 CO2CH3
HN
HN 91%
–2H+, –e–
CN CN
+
N N
H H +
CO2CH3
HN
HN
SchEME 18.70 [4 + 2] cycloaddition between an indole and an enaminoester.
[4 + 2] Cycloadditions between 2-vinylindoles acting as heterodienes and α-acceptor substi-

tuted cyclic and acyclic enamines can be induced by formation of 2-vinylindole radical cations
either via anodic oxidation or photoelectron transfer (PET) using a catalytic amount of tri-
arylpyrylium tetrafluoroborate as sensitizer. In this way, pyrido[1,2-a]indoles or indolo[1,2-a]
hexahydro-1,8-naphthyridines are formed in one step with complete regiochemical and ste-
reochemical control. The products formed are interesting as they incorporate the skeleton of
indole alkaloids. Product formation occurs presumably by electrophilic addition of the radical
cation to the enaminoester. This is followed by a ring closure through electrophilic attack of
the carbocation at nitrogen. The reaction is finished by oxidation of the radical to a cation and
deprotonation (Scheme 18.70) [201].
In other cases, formal cycloadditions are initiated by oxidation of phenols to quinones, which can
react in Michael addition with enols (see Section III.B.2, Scheme 18.12).
Diels–Alder reactions of in situ generated quinones with dienes are accomplished in excellent
yield in an aqueous sodium dodecyl sulfate (SDS) solution by selective anodic oxidation on a glassy
carbon electrode being modified by a cation-exchange resin. Under these conditions the Diels–
Alder reaction is markedly accelerated. This procedure provided Diels–Alder adducts in high yield
(84–100%) and current efficiency (88–96%) (Scheme 18.71) [202].
OH OH
O
HO –e–, SDS
+
PTFE-coated
CO2Et anode CO2Et
100%
OH O
CO2C8H17
CO2C8H17
–
–e , SDS
+
PTFE-coated
anode H
OH O
95%
SchEME 18.71 Diels–Alder reaction of anodically generated o- and p-quinones in micellar solution and a
polytetrafluoroethylene (PTFE)-coated anode.
R1 OMe R1 OMe
R2 OMe R2 OMe
–2e–, –H+ +
R3 R3
R OH R O
[5 + 2] [3 + 2] [2 + 2]
O O
R
MeO CH3O O
R R1
R3 O
O R2
R CH3O
R2 R 3 R3
R1
R1 R2 O
SchEME 18.72 Intramolecular coupling of a phenol derivative to [5 + 2], [3 + 2], and [2 + 2] cycloadducts.
The intramolecular coupling of phenol derivatives to a double bond can lead to three different prod-
uct types [25]. The phenol is oxidized to a phenoxonium cation that can undergo either a [5 + 2] cyclo-
addition, a [3 + 2] cycloaddition, or a [2 + 2] cycloaddition (Scheme 18.72); see also Section III.B.2.
The selectivity for the three pathways depends strongly on the configuration of the double bond and the
groups R. The electrolyses are performed frequently in Ac2O and Bu4NBF4. Selective formation of the
[5 + 2] adduct (59%) has been found with R = R2 = R3 = Me and R1 = H [203,204]. The [3 + 2] adduct
(69%) has been obtained with the E-isomer and R = R1 = Me, R2 = H, and R3 = Ar [205]. With the same
substituents but the Z-configuration of the double bond, the [2 + 2] cycloadduct (66%) was formed [206].
The [2 + 2] cycloadduct was also formed with R = Me, R1 = R2 = H, and R3 = Ar [207,208].
In a multistep one-pot electrochemical synthesis, a variety of 2-alkylamino-1,4-benzoxazine
derivatives 73 are prepared, which are potential neuroprotective compounds (Scheme 18.73)
[209]. Thereby, the monoanion of 1-benzoyl-3-amino-2,4-dihydroxybenzene (70) is oxidized at a
Hg-anode at 0.05 V in MeOH and TEAP to the o-iminoquinone 69. The o-iminoquinone 69 is in
equilibrium with 70 and works as a redox mediator for the indirect electrochemical oxidation of
amines to the corresponding imines 71. The imines equilibrate with the enamines 72, which can
OH O
R1
HN
Ph + R3–NH2
R2 NH2
O
69
–e–
OH O
R1 R1
H2N
Ph
R2 NR3 R2 NHR3
–
O 72
70 71
OH O OH O
R1 H
R2 R1 N
HN Ph
Ph R2
+
R3NH O R3NH O
72 69 73
R1, R2 = Me, Me; Ph, Ph; cyclohexyl

R3: (MeO)2CHCH2NH, cyclohexyl
SchEME 18.73 Preparation of 1,4-benzoxazine derivatives 73 by an inverse Diels–Alder reaction between

an in situ electrogenerated azaquinone 69 and an enamine 72.
OH O
HO
Ph N
+
– O
O
Br
OH O
O
–e–, MeOH, Hg anode Ph
0.05 V vs. SCE
N O
O Br
76%
SchEME 18.74 Hetero Diels–Alder reaction of electrogenerated o-quinones with enamines.
undergo an inverse Diels–Alder reaction with the o-iminoquinone 69. When only one amine with
R1 and R2 is used, the yields are up to 76%. With two amines—as shown—three groups R1, R2, and
R3 are introduced with yields of 68–70%. To widen the molecular diversity, the o-iminoquinone 69
has been generated in the presence of different enamines [209].
The scope of the cascade reaction is extended by using substituted aryl rings in the benzoyl group and
by replacing the benzoyl group by the cyclohexylcarbonyl, isobutylcarbonyl, and nitro group. Consistent
high yields (71–80%) of 2-alkylaminobenzoxazines are obtained in the cascade reaction [210].
The anodic oxidation of pyrogallol derivatives produces chemically unstable o-quinones as het-
erodienes, which are trapped in situ by enamine dienophiles through inverse Diels–Alder reactions.
The possibility of introducing variations in both cycloaddition partners gives rise to highly sub-
stituted 1,4-benzodioxin cycloadducts with up to five elements of diversity. The reactions proceed
under mild conditions with good yields ranging between 25% and 77% as shown in 17 examples.
The methodology should be amenable to the assembly of libraries of biologically relevant hetero-
cycles (Scheme 18.74) [211].
The electrochemistry of selected benzoxazine derivatives has been studied, and furthermore,
the compounds have been tested as neuroprotective agents for the treatment of cerebral palsy [212].
Anodic oxidation of appropriately substituted 2-methoxyphenols or (2-methoxyphenoxy)-2-
methylpropionic acids in the presence of methanol furnishes stable o-quinone monoketals in a CCE.
The propionic acid derivatives are initially obtained as O-spirolactonic quinone bisketals that are
then selectively hydrolyzed into the desired monoketals. In the absence of blocking substituents,
o-quinone monoketals spontaneously undergo Diels–Alder dimerizations into tricyclododecadiene-
dienones with high site selectivity, regioselectivity, and stereoselectivity (Scheme 18.75) [213].
O
O
O –e–, MeOH O OOMe
HO OCH3 LiCIO4, CCE
OMe
O O
H+,H2O [4 + 2]-CA O
O O
O O O
O O
O
100% O
SchEME 18.75 Anodic oxidation of (2-methoxyphenoxy)-2-methylpropionic acid to a stable bisketal and

the hydrolysis to a monoketal with a subsequent Diels–Alder dimerization.
Ph Ph
–e–, 0.5 eq. HCIO4
N +
NC O 0.5 F, 1.8 V vs. SCE NC N O
n n
OEt Ph O
OEt
NC N
n = 1: 52%
n n = 2: 72%
n = 3: 72%
SchEME 18.76 Electrocatalytic cycloaddition of vinyl ethyl ether to an N-cyanomethyl-oxazolidine.
The anodic oxidation of N-cyanomethyloxazolidine initiates an electrocatalytic cycloaddition of

vinyl ethyl ether at the N,O-acetal function, affording a two-carbon ring enlargement. As mechanism
of the formation of a radical cation that undergoes ring opening to a distonic radical cation is postu-
lated. Subsequent addition to vinyl ethyl ether, ring closure and 1e-reduction of the radical cation by
the starting material yields both the product and a radical cation for continuation of the chain reac-
tion. This assumption is supported by cyclic voltammetry and the understoichiometric consumption
of electricity (Scheme 18.76) [214].
IV. COUPLiNG viA RADicALS

A. GENEraL CoMMENTS
Radicals can be generated at the anode in two ways. In the first way, a C–H acidic compound is
deprotonated to an anion that is oxidized. In preparative scale electrolyses, one uses mostly com-
pounds with pKa values <15, to allow the fast generation of the anion with a fairly strong base; the
fast conversion of the entire C–H acid into the conjugated anion helps to suppress competing base-
catalyzed conversions of the substrate into unwanted products. Less basic organometallic com-
pound can be a good alternative to suppress base-catalyzed reactions.
In the second way, the neutral compound is oxidized to a radical cation, which has a high C–H
acidity and is deprotonated fast by a weak base. This radical cation, however, can react fast in a
radical cation–radical cation coupling or in a radical cation–substrate coupling, and these reactions
can differ strongly from that of a radical. Additionally and more important, the neutral C–H acidic
compound has a much higher oxidation potential than the anion; as a result, the radical is in most
cases immediately further oxidized to the carbocation before it is able to react as radical. In the
anion or organometallic species, the oxidation potential is mostly lower than that of the radical,
which retards the further oxidation.
The radicals generated at the anode are free radicals, except when reactive metals are used as
anode that can rapidly form organometallic compounds with the radical. However, this is rarely
the case for anode reactions with platinum or graphite electrodes that are mostly used in prepara-
tive scale electrolyses. However, higher radical concentrations in heterogeneous electrode processes
compared to radical concentrations in homogeneous reactions can influence the follow-up reaction.
In the electrolyte layer at the anode surface, the concentration of the radicals is high. Compared to
their reaction rate, their diffusion rate into the solution is much slower. The slower diffusion leads
to high stationary concentrations of radicals at the electrode that favor second-order reactions, like
coupling, compared to pseudo-first-order reactions, like additions to double bonds. This effect can
be partly compensated by using a low current density that decreases the radical concentration.
As in free radical reactions, the principal reactions leading to C–C bonds are coupling and addi-
tion. The selectivity for the C–C bond formation may be decreased by a competing disproportion-
ation and a further oxidation of the radical.
Very useful substrates for a preparative scale anodic oxidation are carboxylates. They are weak
bases and chemically stable in solution, and they are easily available at low cost and high diversity.
Section IV.B deals with the anodic conversion of carboxylates to radicals.
B. ANoDIC DECarboXYLaTIoN oF CarboXYLaTES aS RaDICaL SoUrCE

1. Experimental Procedure
The first anodic decarboxylations of carboxylic acids to form dimers of the alkyl group have been
described more than 150 years ago by Kolbe [215]. For that reason, this reaction is also termed
Kolbe electrolysis. The large amount of literature dealing with the Kolbe electrolysis is summarized
in several reviews and chapters in books [216] (see also Chapter 33).
The advantage of this important reaction for C–C bond formation in organic synthesis is a simple
experimental procedure: use of an undivided cell, CCE, easy scale-up, and a large scope of readily
available and different carboxylic acids as substrates.
The carboxylate anion RCO2– • is discharged at 2.1–2.8 V (vs. NHE) to an alkylcarbonyloxy
radical RCO2•, which undergoes a fast decarboxylation to an alkyl radical. Favorable conditions for
an electrolysis are a fairly concentrated solution (about 0.5 M) of the carboxylic acid that is neu-
tralized to 5–10% with sodium methoxide, pyridine, triethylamine, pyridine, or solid-supported
bases [217]. Whenever possible, electrolysis is conducted at a high current density (>250 mA cm−2)
with current control in an undivided cell. High current densities favor coupling and increase the
anode potential. For electrostatic reasons at a higher anode potential, the solvent methanol is dis-
placed from the electrode surface and replaced by the negatively charged carboxylate. This way,
the competing oxidation of methanol is suppressed. A supporting electrolyte is not needed as the
carboxylate and the countercation act as supporting electrolyte. Foreign anions should be excluded
because they can disturb the necessary formation of a carboxylate layer at the anode. Alkali and
alkyl ammonium ions have no negative effect. In an undivided cell, the carboxylate concentra-
tion is held constant as, with each carboxylate ion that is converted at the anode, the equivalent of
methoxide is formed by discharge of protons at the cathode. Thereby, the carboxylate is continu-
ously regenerated from the excess acid. The endpoint of the electrolysis is reached, when the pH
of the electrolyte changes from weakly acidic to alkaline, when the free acid is consumed. Due to
the proton discharge at the cathode, one can use an undivided cell; except when easily reducible
functional groups, as the nitro group, are present, a divided cell with a diaphragm is needed. As
solvents, mostly methanol, but also aqueous methanol or aqueous AN is used. As an anode mate-
rial, universally platinum in thin foils or as net is applied. Glassy carbon, hard graphite [218], and,
as recently shown, the BDD electrode can be additionally used. The latter has been shown to pro-
duce the same yield of dimer as the platinum electrode, when the electrolysis of a water-insoluble
acid is conducted in water and the electrolyte is emulsified by sonication (see also Chapter 8)
[219,220]. For the use of the BBD electrode in phenol oxidations, see Section III.B.2. Soft graphite
is not a useful anode material as it promotes further oxidation of the radical to a carbocation, thus
disfavoring the radical reaction. As a cathode material, often stainless steel or platinum is used.
The former should be applied for substrates with double or triple bonds to avoid an unwanted
cathodic hydrogenation.
As an electrolysis cell, a beaker-type cell with platinum foils supported on a Teflon frame or a
flow-through cell have been applied by the author [2b,221]. Kolbe electrolysis of acetic acid was also
performed in the gaseous state using a cell with a permeable electrolyte membrane (PEM) [222].
Problems sometimes arise because of deposits of sparingly soluble products, insoluble poly-
mers, inorganic oxides, or salts being formed at the anode surface; these nonconducting layers can
strongly decrease the current and in this way increase the duration of the electrolysis. The addition
of small amounts of a less polar solvent (THF, dioxane, 1,2-dimethoxyethane, pentane), freezing
out the product, periodical extraction of the electrolyte, mechanical cleaning of the anode, or short
polarity reversals of the anode can be helpful in such cases.
External temperatures of −20 to 50°C are regularly applied. At higher temperatures, a conversion
of the acid into the electro-inactive methyl ester has to be kept in mind [223]. For more experimental
details, the named reviews [216] and Chapter 33 should be consulted.
2. Homocoupling
The anodic oxidation of identical carboxylic acids affords homocoupling products. Despite the high
discharge potential of the carboxylic acid, a fair number of functional groups are tolerated. These
are alkyls, arylalkyls, and groups (CH2)nX with X = COR or CO2R and n > 1 and with X = OAc,
NHAc, or Hal and n > 4.
The stereochemistry of the products indicates that adsorption of saturated alkyl radicals is unim-
portant. Carboxylates, which are chiral and nonracemic at the α-position, totally lose their optical
activity in heterocoupling [224,225]. This racemization indicates either a free radical as intermedi-
ate or its fast adsorption–desorption at the anode.
Polar substituents can be handled without protection because nonpolar radicals are involved.
This saves steps for protection and deprotection of substrates, whose substituents can react with
strong bases, nucleophiles, and electrophiles.
Homocoupling via Kolbe electrolysis is a unique and attractive method for the synthesis of
symmetrical compounds. A great number of homocoupling reactions have been tabulated in
Reference 216. Furthermore, Table 18.5 and the structures in Scheme 18.77 show some selected
examples. In general, mainly the substituent in α-position is critical for the yield of the coupling
product. Electron-donating substituents (phenyl, vinyl, halo, or amino substituents, and more
than one alkyl group) more or less shift the reaction toward products that originate from carbe-
nium ions being formed by further oxidation of the radical (see Section IV.B.6). On the other
hand, electron-attracting groups (cyano-, carbonyl substituents or carboxylic acid derivatives)
or hydrogen favor dimerization. Carboxylic acids with a double bond in α-position form only
small amounts of dimer or no dimers at all. These acids include aromatic acids, pyridine car-
boxylic acids, and α,β-unsaturated carboxylic acids. Reasons are the slow decarboxylation of the
aroyloxy, pyridoyloxy, and acryloyloxy radical and in the latter case additionally the fast radical
polymerization of acrylic acid derivatives as competing reaction.
TABLE 18.5
Anodic Homocoupling of Carboxylic Acids
Entry Carboxylic Acid Yield (%) References
1. CH3(CH2)nCO2H, n = 5–15 60–90 [216b]
2. RO2C(CH2)nCO2H, n = 4–16, R = CH3, C2H5 45–95 [216b]
3. (CH3)2CH–CH(CO2Et)CO2H 67 [226]
4. AcO(CH2)nCO2H, n = 3–5 73–83 [227]
5. F(CH2)nCO2H, n = 4–10 45–70 [228]
6. EtCO(CH2)4CO2H 75 [229]
7. (Z)–CH3–(CH2)7CH═CH(CH2)7CO2H (oleic acid) 75 [230]
8. (Z)–CH3–(CH2)7CH═CH(CH2)11CO2H (erucic acid) 70 [230]
9. CF3(CF2)7CO2H 61 [230]
10. CH3O2C(CH2)7CO2H 80 [230]
11. O n = 1, 2 60–65 [231]
CH3 P (CH2)nCO2H
t-C8H17
40% (MeOH. Pt)

50%
CO2H 81%
O CO2H
CO2H
76 [234]
AcO
H
74 [232] 75 [233] CH2OAc
62% (Pyr, H2O, Et3N) AcO
EtO2C
CO2H AcO
MeO2C
CO2H CO2tBu OAc
28%
EtO2C CH2
77 [235] 78 [236] 52%
CH2
65% O AcO
OAc
O OAc
CO2H
CH2OAc
O
79 [237] 80 [230] 81 [238]
93% (SiO2 · pip) 52% (SiO2 · pip) 72% 62%

F
F 3C
F
CO2H CO2H
CH3O Si CO2H
OCH3 CO2H
F F
82 [217] 84 [239]
F 85 [240]
83 [217]
R 15–79%
3
CO2H Boc O
R1 CO2H 30% HN
OtBu
R2 R1: octyl, iBu, iPr
CO2H
R2: H,Me R3: H MeO2C
87 [243] 38%
86 [241, 242] 88 [244]
SchEME 18.77 Anodic homocoupling of different carboxylic acids; the arrows indicate the carbon atom,
where the homocoupling occurs; the percentage is the coupling yield.
The dimerization of half-esters of diacids (Table 18.5, entry 2) is also of industrial interest
because in this way 1, n-diesters for the preparation of polyesters are easily accessible [245]. Methyl
hydrogen azelate, available by double bond cleavage from methyl oleate, has been coupled to the
1,ω-C16 -diester. The diester has been converted into homomuscone (80) (Scheme 18.77), using an
acyloin condensation and deoxygenation, and a subsequent 1,4-addition of lithium dimethylcu-
prate [230].
Hydroxy and amino acids can be dimerized in moderate to good yields, when the substituents
are not in α- or β-position and when they are protected against oxidation by acylation (Table 18.5,
entry 4; Scheme 18.77: 88) [244].
Efficient syntheses of substituted succinic acids from substituted methyl malonates have been
developed in the past [246]; a more recent application is the coupling of 78 (Scheme 18.77) as part
of a semibullvalene synthesis [236].
While keto carboxylic acids can be dimerized satisfactorily (Table 18.5, entry 6), the correspond-
ing aldehydes couple poorly. However, good yields can be obtained in these cases, when the acetals,
for example 79 (Scheme 18.77), are electrolyzed instead [237].
1,4-Disilyl compounds, like the dimer of 85 in Scheme 18.77, and others with a variety of sub-
stituents at the silicon atom were obtained by Kolbe electrolysis of the corresponding β-silyl car-
boxylic acids in 60–70% yield. The α-silyl group in the intermediate obviously stabilized the radical
and led to good dimer yields by retarding the competing further oxidation. Polymerization could be
suppressed by using 1,2-dimethoxyethane as cosolvent. The coelectrolysis of this additive appar-
ently helped to inhibit the polymerization. Kolbe dimers of [2.2.2]-bicyclooctane dicarboxylic acid
half-esters 87 (Scheme 18.77) were applied for the synthesis of rigid, rod-shaped carbon skeletons.
The homocoupling of carboxylic acids has been successfully used in the synthesis of further
target molecules. Kolbe electrolysis of 74 is part of a (+)-α-onocerin synthesis [232], the electrolysis
of 75 afforded a dimer with two quaternary C-atoms separated by two methylene groups and was
used to study physical properties of such type of compounds [233], and 2,6,10,15,19,23-hexamethyl-
tetracontane, a base of cosmetics and drugs, has been synthesized from 76 [234]. The cyclopropyl-
carboxylic acid 77 could be coupled to a dicyclopropyl compound [235]. C-Disaccharide 81, which
is a potential glucosidase inhibitor, is accessible in few steps [238].
3-Alkenoic acids 89 dimerize to a mixture of three 1,5-dienes 91a–c (Scheme 18.78); the
dimers arise by 1,1′-, 1,3′-, and 3,3′-coupling of the intermediate allyl radical 90. When the
3-position of the allyl radical is increasingly shielded, the portion of 3-coupling decreases.
The relative amount of the 1,1′-dimer thus can vary from 52% in 3-dodecenoic acid to 76% in
3-cyclohexylidene–propanoic acid. The configuration of the nonterminal double bond is retained
to a high degree (~90%) [242]. With 3-alkenoic acids the dimer yield can be improved by neutral-
ization of the acid with a tertiary amine [247].
(Z)-4-Enoic acids partially isomerize to products with a (E)-configuration. Results from
methyl- and deuterium-labeled carboxylic acids support an isomerization by way of a revers-
ible ring closure to a cyclopropylcarbinyl radical. (Z)-n-Enoic acids with n > 5 fully retain their
configuration [248].
Using 6-alkenoic acids 92, the intermediate radical 93 partially cyclizes to a cyclopentylmethyl
radical 94; the radicals 93 and 94 couple to two homodimers and one heterodimer (Scheme 18.79)
[248]. See also Section IV.B.5 for such cyclization.
R
R
91a
1,1'
3 1 R
1,3' R
–e–, –CO2 91b
R CO2–
3,3'
89 90
R
R 91c
SchEME 18.78 Regioisomeric 1,5-dienes from 3-alkenoic acids.
–e–, –CO2
CH2=CH–(CH2)4CO2– CH2=CH–(CH2)3CH2 CH2
40%
92 93 94
CH2=CH–(CH2)8–CH =CH2 CH2=CH–(CH2)5 (CH2)2
42% 37% 21%
SchEME 18.79 Partial cyclization of radicals from a 6-alkenoic acid.

–e–
4 R1CO2H + 4R2CO2H 4 R1 + 4 R2
–CO2
R1–R1 + 2 R1–R2 + R2–R2
SchEME 18.80 Unsymmetrical and symmetrical products in the anodic decarboxylation of two different
carboxylates.
3. Heterocoupling
Heterocoupling (cross-coupling) of two different carboxylates allows the synthesis of unsymmetri-
cal compounds (Scheme 18.80). However, as the intermediate radicals combine in most cases statis-
tically, the cross-coupling product contains two symmetrical dimers as major side products.
To increase the yield of the wanted heterodimer, the easier available and less costly acid is used
in an up to 10-fold excess. This way, only two major products are formed, which makes the isolation
of the heterodimer easier. Additionally, more costly acid is incorporated to a large extent into the
heterodimer. The two acids should be chosen in a way that allows separating the excess homodimer
by distillation or crystallization. Problems due to passivation or due to a follow-up oxidation of the
radicals to carbocations are often less pronounced in cross-coupling.
Cross-coupling products are also obtained in moderate to good yields with a base supported on
a solid polymer. The base could be recycled even when high current densities were applied [249].
Due to its simple procedure and broad scope, cross-coupling by Kolbe electrolysis has found
wide application despite the formation of symmetrical dimers as side products. Cross-coupling
of carboxylic acids allows the synthesis of rare and new fatty acids, pheromones, chiral building
blocks, C-glycosides, or nonproteinogenic amino acids.
Selected examples of cross-coupling of carboxylates are given in Table 18.6 and in Schemes
18.81 and 18.82.
Entries 2 and 13 in Table 18.6 give examples for the preparation of ω-bromofatty acids. Entries
4 and 5 display chain extensions of unsaturated fatty acids by coelectrolysis with half-esters of
diacids. In entries 6 and 7, the preparation of trimethylsilyl compounds with a long alkyl chain by
coelectrolysis of trimethylsilyl acetic acid with fatty acids is demonstrated. Entries 8 and 9 show
the synthesis of fatty acids that are partially perfluorinated. Entries 10 and 11 give examples for the
preparation of long-chain fatty acids with a terminal double bond. Entries 15–17 display the cou-
pling to C-glycosides that are potential enzyme inhibitors. Electrolysis of the ketogulonic acid in
entry 15 without a coacid affords no radical dimer but nearly quantitatively the non-Kolbe product
[238]. In the presence of a coacid, the non-Kolbe product is still the main product, but a consider-
able part of the carbohydrate radical can now be trapped prior to oxidation by the radical of the
coacid to form the heterocoupling product. In entry 18 (Table 18.6), homologues of dihydro-12-oxo-
phytodienoic acid and jasmonic acid are prepared in one step and a flexible synthesis.
Heterocoupling has been used for the extension of the carbon chain in fatty acids [216b].
Furthermore, the method has been applied for the synthesis of pheromones [263]. Some examples
are displayed in Scheme 18.81.
Muscalure (95), the pheromone of the housefly, has been synthesized by coelectrolysis of hepta-
noic acid with oleic acid in 14% yield [264]. The moderate yield could be increased to 80% by using
a 10-fold excess of heptanoic acid and a lower temperature [265]. Muscalure has been also prepared
by coelectrolysis of erucic acid with propionic acid in 59% yield [266]. Furthermore have been
prepared: the antagonist of muscalure (Z)-11-heneicosene [265], looplure (96) [267], brevicomin
(97) [268], disparlure (98) [269], optically active compound 100, a Trogoderma pheromone [270],
and pheromones with a diene or triene structure, such as compound 99 [271]. The chiral acid 101
is one of the building blocks prepared for the total synthesis of the antibiotic myxovirescine [272].
Furthermore, chiral building blocks have been obtained by heterocoupling reactions with (S)-2-(1,1-
dimethylethyl)-1,3-dioxolane-5-oxo-4-acetic acid 102 [273]. In addition, alkyne carboxylic esters
TABLE 18.6
Anodic Cross-Coupling of Two Different Carboxylates
R1COOH R2COOH Yield R1–R2 References
1. CH3O2C(CH2)4CO2H CH3(CH2)nCO2H n = 2, 4, 8, 12 12 – 48% [250]
2. EtO2C(CH2)8CO2H Br(CH2)10CO2H 54% [251]
3. CH3O2C(CH2)7CO2H CH3(CH2)16CO2H 36% [252]
4. CH3O2C(CH2)7CO2H CH3(CH2)7CH═CH(CH2)7CO2H 51% [252]
5. CH3O2C(CH2)7CO2H CH3(CH2)11CH═CH(CH2)7CO2H 47% [252]
6. (CH3)3SiCH2CO2H CH2═CH(CH2)8CO2H 54% [253]
7. (CH3)3SiCH2CO2H CH3(CH2)10CO2H 80% [253]
8. C6F13(CH2)2CO2H CH3O2C(CH2)7CO2H 41% [252]
9. C8F17(CH2)2CO2H CH3O2C(CH2)7CO2H 56% [252]
10. CH2═CH(CH2)8CO2H CH3O2C(CH2)5CO2H 40% [254]
11. CH2═CH(CH2)8CO2H CH3O2C(CH2)7CO2H 40% [255]
12. H3CONH(CH2)10CO2H CH3O2C(CH2)8CO2H 32% [256]
13. Br(CH2)10CO2H CH3O2C(CH2)7CO2H 79% [257]
14. [EtO]2P(O)CH2CO2H CH3O2C(CH2)8CO2H 27% [255]
15. O O C11H23CO2H 33% [258]
O Br(CH2)10CO2H 33% [259]
O
CO2H CH2═CH(CH2)9CO2H 31% [259]
O
16. CO2H C7H15CO2H 70% [260]

O O C13H27CO2H 51%
O
(Z)-CH3(CH2)7CH═CH(CH2)7CO2H 46%
O
O
17. HO2C OMe C7H15CO2H 40% [258]
O
O O
18. O RO2C(CH2)nCO2H 10 – 43% [261]

R = Me, Et; n = 4 – 7
CO2H
19. CO2H RCO2H 33 – 60% [262]
R = C2H5, C5H11, C8H17
N C11H23, C15H31
H
with different chain lengths can be obtained [274]; they can be hydrogenated selectively to either
(E)- or (Z)-pheromones. Furthermore, useful intermediates for the synthesis of dicarba analogs of
cystine peptides have been prepared from l-glutamate [275]. Orthogonally protected 2,5-diami-
noadipic acid, 2,6-diaminopimelic acid, and 2,7-diaminosuberic acid derivatives bearing up to four
different protecting groups are prepared in one step by mixed Kolbe electrolysis [276]. Branched
hydrocarbons for use in emollients and cosmetic compositions have been prepared by anodic cross-
coupling of a mixture of linear and branched C6 –C22 fatty acids [277]. Anodic cross-coupling of
fatty acids has been recently reviewed [278].
A heterocoupling reaction has been applied in the synthesis of (±)-nephromopsinic acid [279],
and for the preparation of 3-alkyl-substituted indoles (Table 18.6, entry 19).
Carbohydrates without an electron-donating substituent at the radical center as 103 yield hetero-
coupling products with different coacids in fair to good yield (Scheme 18.82) [260].
80% 68% 33% O

H H H H
H3C(CH2)7 (CH2)7-(CH2)5CH3 H9C4 (CH2)2-(CH2)4OAc O
95 96 97
48% 62% 52%

O
H H
H3C(CH2)-(CH2)2 (CH2)2-(CH2)2CH(CH3)2 (CH2)7-C4H9
98 99
56%
tBu
20% O
O CO2H
2
H 2 5 OH TBDMSO CO2H O
100 101 102
SchEME 18.81 Cross-coupling as a key step in the synthesis of selected pheromones, another biologically
active compound, and chiral building blocks; the arrows indicate the bond that is formed in the heterocoupling
reaction and the percentage is the yield of the heterocoupling.
CO2H R
H H H H
RCO2H
AcO H AcO H
–e–, –CO2
H OAc H OAc
H OAc H OAc
CH2OAc CH2OAc
103
R Yield (%)
C5H11 69
C7H15 54
MeO2C(CH2)7 46
SchEME 18.82 Heterocoupling of 3,4,5,6-tetra-O-acetyl-2-deoxy-d-gluconic acid (103).
4. Diastereoselective Coupling
Enantioenriched carboxylates with a nonracemic stereogenic center in the α-position totally lose
their optical activity in heterocoupling [224,225]. This result indicates that in anodic decarbox-
ylation, either a free radical or a radical that undergoes fast desorption–adsorption at the anode is
involved. This is different, if radicals are generated in pairs from diacyl peroxides. If the diacyl per-
oxide from optically pure ethyl ethylmethylmalonate and dodecanoic acid is photolyzed at −78°C,
the cross-coupling product, ethyl 2-ethyl-2-methyl-tridecanoate, is formed in 17% yield and 60% ee
with retention of the configuration [280].
a. Facial Selectivity Due to a Chiral Auxiliary

Carboxylates with nonracemic chiral auxiliaries have been anodically decarboxylated to explore the
face-selective hetero- and homocoupling of the intermediate radicals. 2-Substituted malonamides
were subjected to heterocoupling with different coacids; (2R,5R)-2,5-dimethylpyrrolidine served as
chiral amido group. Heterocoupling of the acids 104a,b with the coacids 105a–d led to the amides
106a–d with a different diastereomeric excess (Scheme 18.83, Table 18.7) [281].
O O
O O
R1 R1
–e–, –CO2 N N
N OH + R2CO2H +
R2 R2
R1
104 a–d 105 a–d 2R-106 a–d 2S-106 a–d
SchEME 18.83 Diastereoselective coupling of 2-substituted malonamides 104a–d with the coacids 105a–d
to amides 106a–d (R1 and R2 are defined in Table 18.7).
TABLE 18.7
Diastereoselective Heterocoupling to 106a–d
106 R1 R2 Yield (%) de (%)
a CH2C6H5 C4H9 38 25.9
b C(CH3)2C2H5 C4H9 69 53.5
c C(CH3)2C2H5 CH2C(CH3)3 42 69.2
d C(CH3)2C2H5 C(CH3)2CO2Et 13 86.1
As side products of 106a–d, compounds arising from hydrogen abstraction and further oxidation
of the radical 107a–d originating from 104a–d to a carbocation were found. This was especially
pronounced in the case of 106d, where these compounds became the major products.
As α-amido radicals assume preferentially the (Z)-conformation [282], the prostereogenic car-
bon atom in the intermediate radical 107a–d originating from 104a–d is differently shielded by
the methyl groups of the chiral auxiliary. For that reason, the coradicals from the coacids 105a–d
will approach the radical 107a–d for steric reasons preferentially from the re-face. The diastere-
oselectivity increases with growing size of R1 and R2, which points to an increasing portion of the
(Z)-conformer of 107a–d and a growing steric hindrance for the si-approach (see Scheme 18.84).
Besides the chiral auxiliary (2R,5R)-2,5-dimethylpyrrolidine (108), the pyrrolidine 109, the
oxazolidine 110, the 2,10-camphersultam 111, and the menthol derivates 112 were used (Scheme
18.85). Thereby moderate yields of the cross-coupling product and a diastereomeric excess of up to
80% de were obtained [283].
b. Facial Selectivity Due to a Stereogenic Carbon Atom in α-Position to the Radical Center
Facial selectivity induced by a stereogenic center in α-position to the radical center has been probed
with acyclic and cyclic radicals (Scheme 18.86) [284]. The acyclic carboxylate 113 afforded a dia-
stereomeric excess of up to 71.4% (R1 = tBu, R2 = Me; coradical: R3 = C(CH3)2CO2Et) and a 31%
yield of the cross-coupling product. Photolysis of peroxides consisting of a dodecanoyl group and
a peracetylated tartaric acid or d-gluconic acid group in the solid state at −78°C led to a selective
cross-coupling. The chemical yields are 40–60% and the diastereoselectivities 90–95% de [285].
For the acyclic carboxylate 113, a diastereomeric excess (de) of up to 71% (R1 = tBu, R2 = Me,
R3 = C(CH3)2CO2Et) and a yield of 31% for the cross-coupling product was found. For the cyclic
O
R1
N
H R2
107a–d
SchEME 18.84 Preferred re-approach to the intermediate radical 107a–d.

CH3O
O
N N N
108 CH3O 109 Ph 110
R = Ph, tBu, iPr
N
O2S O 112
111
SchEME 18.85 Chiral auxiliaries 108–112 for the diastereoselective heterocoupling of carboxylic acids.
R3
R2 H OMe
CO2Me R3CO2– R2
R1 O
–e–,–CO2 H
113 COO
– R1
R2
R2
CO2Me
CO2Me + R1
R1
R3
R3 Minor
Major
R1 CO–2
R3CO2–
R2
O –e–,–CO2
R2 O
114
R1 R3 R1 R3
R2 + R2
R2 O R2 O
O O
trans (major) cis(minor)
SchEME 18.86 Facial selectivity induced by a stereogenic center in α-position to the radical center in an
acyclic carboxylate 113 and a cyclic carboxylate 114.
carboxylate 114, a de of up to 88 % (R1 = tBu, R2 = H, R3 = C(CH3)2CO2Et) and a yield of 33% for

the cross-coupling product was obtained [248].
5. Addition of Radicals from Anodic Decarboxylation of Carboxylic Acids to Olefins

The anodic decarboxylation of carboxylic acids in the presence of olefins leads to additive dimers
115 and additive monomers 117 (Scheme 18.87, Table 18.8). The products can be rationalized by
the following pathway: The radical R• obtained after anodic decarboxylation adds to the alkene to
R– RCO2– Y
–e– –e–
R R
–CO2
Y Y Y 115
R R
Y
R
116
R R 117
–e–
R-R
Y Y Y
Nu– R
R + + Nu
R
118 119 120
SchEME 18.87 Products from the addition of anodically generated radicals to olefins.
TABLE 18.8
Addition of Radicals from Anodic Decarboxylation of Carboxylic Acids to Olefins
Entry Radical Precursor Olefin Conditions Product Yield References
1 EtOOCCOOH Butadiene MeOH, Pt (EtOOCCH2CH═CHCH2)2 + isomers 66% [286]
2 MeOOC(CH2)4COOH CH2═CH2 MeOH, Pt MeOOC(CH2)12COOMe 95% [287]
MeOOC(CH2)10COOMe
3 MeOOCCH2COOH CH2═CHOEt MeOH, Pt [MeOOC(CH2)CH(OEt)]2 35% [288]
4 MeO2CCH2COOH CH2═CHPh MeOH, Pt [MeOOC(CH2)2CH(Ph)]2 38% [286]
5 MeOOC(CH2)4COOH Butadiene MeOH, Pt (MeOOC(CH2)5CH═CH(CH2)2 47% [289]
(MeOOC(CH2)5CH═CHCH2)5COOMe 47%
6 F3CCOOH CH2═CHnPr MeCN, [CF3CH2CH(nPr)]2 40% [290]
NaOH, Pt
7 CH3COOH CH2═C(Me)CHO MeCN, [CH3CH2C(Me)(CHO)]2 80% [291]
H2O, Pt
8 CF3COOH CH2═CHOAc MeCN, [CF3CH2CH(OAc)]2 24% [292]
H2O,
NaOH
9 CH3COOH Dimethylfumarate MeCN, H2O [MeOOCCH(Me)]2 80% [293]
10 CO2H MeOOCCH2COOH MeOH, MeO2C 41% [294]
H
5% NaOH
O O
H
11 CO2H MeOOC(CH2)4COOH MeOH, 53% [295]
MeO2C(CH2)4
5% NaOH
N N
Ac Ac
12 CF3COOH EtO2CCH═CHCO2Et AN, water, [EtOOCCH(CF3)]2 47% [292]

NaOH [EtOOCCH(CF3)CH(COOEt)]2 27%
13 CF3COOH AN, water, F3C CF3 44% [292]
O O NaOH
N
Et O O
N
Et
yield the primary adduct 116, which can dimerize to the additive dimer 115 with a regiospecific
head-to-head connection of the two olefins. Furthermore, the radical 116 can couple with the radi-
cal R• to form the additive monomer 117. If electron-donating substituents Y in the olefin stabilize
a carbenium ion, 116 can be oxidized to the cation 118. The cation can react intramolecularly
with a nucleophilic site in R to 119 or intermolecularly with a nucleophile in the electrolyte to
afford 120.
Satisfactory to good yields of adducts have been found for styrenes (Scheme 18.87, Y = phenyl),
conjugated dienes (Y = vinyl), enamines (Y = NR2), and enol ethers (Y = alkoxy), particularly if
the olefins are not substituted at the carbon atom in β-position to Y (Table 18.8 and Section IV.C.2,
Table 18.13). Nonactivated alkenes react less satisfactorily.
Radicals generated by anodic oxidation of carboxylates in the presence of olefins form addi-
tive dimers 115 (Table 18.8, entries 1, 3–8) and additive monomers (Table 18.8, entries 9–13). In
the electrolysis of methyl malonate with vicinal disubstituted styrenes, the adduct yields decrease
with increasing size of the substituent in β-position to the phenyl group: H = 42%, Me = 27%, and
Et = 11% [296]. The ratio of additive dimer 115 to additive monomer 117 can be influenced to some
extent by the current density. In the electrolysis of trifluoroacetate in AN and H2O in the presence
of electron-deficient olefins, additive dimers and additive monomers are obtained. The selectivity
can be controlled by current density, temperature, and the substitution pattern of the olefin [297].
Trifluormethylation of aromatic compounds with –M substituents, such as benzonitrile, benzalde-
hyde, acetophenone, and nitrobenzene, has been achieved in moderate yield by the electrolysis of
pyridinium trifluoroacetate in AN [298]. Electrolysis of methyl oxalate in methanol with ethylene
under pressure yielded 70–90% of the dimethyl esters of succinic, adipic, suberic, and sebacic acids.
Increase of the ethylene pressure or decrease of the current density led to an increase in the portion
of higher esters in the product mixture [299].
The influence of mechanism and rate on yield and selectivity in the addition of anodically
generated radicals to olefins has been calculated and the prediction tested in preparative elec-
trolyses [300].
Good yields can be obtained with nonactivated alkenes, when the addition proceeds intramo-
lecularly. β-Allyloxypropionates and β-allylaminopropionates cyclize in an intramolecular addition
and a subsequent cross-coupling of the exocyclic radical to form 3-substituted tetrahydrofurans and
pyrrolidines (Table 18.8, entries 10 and 11). This intramolecular addition has been used to synthe-
size a precursor of prostaglandin PGF2α (Scheme 18.88) [301] and a branched carbohydrate (Scheme
18.89) [302].
CO2H R
RCO2H OEt
+
AcO O –e–, –CO2 AcO O
OEt a
R
R: CH3(CH2)7, 54%, a:b = 3.1:1 OEt
R: PhMe2SiCH2, 38%, a:b 4.3:1 O
AcO
b
SchEME 18.88 Synthesis of a precursor of prostaglandin PGF2α via an intramolecular addition and a sub-
sequent cross-coupling reaction.
H H
O O O O
AcO CH3CO2H AcO
–e–, –CO2
AcO CO2H AcO
50%
SchEME 18.89 Synthesis of a branched carbohydrate via an intramolecular addition and a subsequent
cross-coupling reaction.
The extension of the cyclization reaction from tetrahydrofurans and pyrrolidines to carbocycles
led to a sharp decrease in the yield of the cyclized product [303]. The reason for that is the slower
cyclization rate of 5-hexenyl radicals compared to 5-(3-oxahexenyl) radicals [304], which favors the
competing bimolecular coupling to the acyclic product. Changes in the reaction conditions helped
to increase the yield of the cyclization product.
The geminal dialkyl effect, namely, the introduction of two geminal methyl groups into the
3-position of the 5-hexenyl radical, increases the cyclization rate of the 5-hexenyl radical [304] and
leads to a higher portion of cyclization product [303].
The current density controls the concentration of radicals at the electrode surface. A low cur-
rent density favors the monomolecular cyclization against the bimolecular coupling to an acyclic
product. A decrease in the current density by a factor of 30 increased the ratio of cyclic to acyclic
product by a factor of 10 [303].
The electrophilicity of the double bond also influences the addition rate of the mostly nucleo-
philic radical. With vinylic electron-attracting groups, the yield of the carbocyclic compound could
be increased to more than 70% (Scheme 18.90, Table 18.9) [303].
This improvement has been extended with further examples including six-membered carbocy-
cles as well as tetrahydrofurans and tetrahydropyrans; good to excellent yields have been obtained
by using ethoxycarbonyl- and Boc-substituted double bonds and geminal substitution (Schemes
18.91 and 18.92, Tables 18.10 and 18.11) [305].
A radical tandem cyclization, consisting of two carbocyclizations and a terminating cross-coupling
reaction, has been achieved in the coelectrolysis of sodium acetate with carboxylate 121 (Scheme 18.93)
R3
CO2H
R1 R3CO2H R1
+, –e–, –CO
–H 2
R2 R2 R2 R2
SchEME 18.90 Improved carbocyclization of 5-hexenyl radicals with electron-attracting groups R1 at the
double bond.
TABLE 18.9
Yields in the Carbocyclization of 5-Hexenyl Radicals
with Electron-Attracting Groups R1 at the Double Bond
Entry R1 R2 R3 Yield (%)
1 CN CH3 (CH2)4CO2CH3 75
2 CO2Et CH3 (CH2)4CO2CH3 76
3 CN H (CH2)4CO2CH3 71
4 COCH3 H CH3 71
R1 R1
CO2H
R2
R2CO2H
O O
–H+, –e–, –CO2
n O n O
SchEME 18.91 Carbocyclizations of 5- and 6-alkenyl radicals with electron-attracting groups R1 at the
double bond.
R1 R1
CO2H
R3CO2H R3
R2 R2
n O –H+, –e–, –CO2 n O
R2 R2
SchEME 18.92 Cyclizations to substituted tetrahydrofurans and tetrahydropyrans.
TABLE 18.10
Yields in Carbocyclizations of 5- and 6-Alkenyl Radicals with
Electron-Attracting Groups R1 at the Double Bond
Entry R1 R2 n Yield (%)
1 Boc CH3 1 90
2 Boc (CH3)2CH 1 75
3 CN CH3 1 65
4 Boc CH3 2 64a
a Additionally 16% acyclic product.
TABLE 18.11
Yields in the Cyclizations to Substituted Tetrahydrofurans and Tetrahydropyrans
Entry R1 R2 R3 n Yield (%)
1 CO2Et H CH3 1 86
2 CO2Et H CH3O2C(CH2)2 1 90
3 CO2Et H CH2═CH–CH2 1 89
4 CO2Et H 1 87
O O
CH3 CH2
5 CO2Et CH3 CH3 2 89
O 1. LDA O
2. I(CH2)3CO2Na(85%)
3. C4H7MgBr
+
OEt 4. H (74%)
CO2H
121
O O O
5 eq. CH3CO2H
–e–, –CO2 + +
122 123 124

42% 15% 8%
2 diastereomers 2.7:1
SchEME 18.93 Radical tandem cyclization to tricyclic products.

having two double bonds with 1,5-distances to the intermediate radicals. This reaction provides a short
synthetic sequence to tricyclic products, for example, triquinanes [306]. The selectivity for the formation
of the tricyclic, bicyclic, and monocyclic products 122–124 could be predicted by using a mathematical
simulation based on the proposed mechanism and a reasonable choice of rates.
These radical cyclizations can also be achieved by tin-mediated radical chain reactions of alke-
nyl iodides [304]. However, the electrochemical cyclization has advantages: it avoids the toxic tin
hydride and forms two C–C bonds in a one-pot reaction. Thereby, the second C–C bond can be cre-
ated simply and with a wide variety of groups by the suitable choice of the coacid.
6. Oxidation to Carbocations
In anodic decarboxylation of carboxylic acids, products arising from radicals (Kolbe electrolysis)
and from carbocations (non-Kolbe electrolysis) are formed.
The radical pathway is favored by a high current density, a smooth anode surface (platinum,
glassy carbon, BDD electrode), an acidic electrolyte (5–10% neutralization of the acid), and hydro-
gen or electron-withdrawing substituents in the α-position of the carboxylic acid.
The route to carbocations is supported by a low current density, a rough electrode surface
(soft graphite), additives (e.g., perchlorate anion, Cu2+), and electron-donating substituents in the
α-position. Intermediate radicals with ionization potentials above 8 eV lead preferentially to cou-
pling products, while those with ionization potentials below 8 eV are further oxidized to carbenium
ions [307].
The anodic decarboxylation of 3-oxanonanoic acid and 3-oxapentadecanoic acid in methanol
leads exclusively to products of the non-Kolbe electrolysis. To investigate whether the outcome of
this electrolysis can be shifted toward products of the Kolbe electrolysis, the influence of coelec-
trolysis, solvent, current density, degree of neutralization, and chain length of the alkoxy group
on the anodic decarboxylation of the two acids has been investigated. The results show the Kolbe
coupling product can be favored against the non-Kolbe product by an extended alkyl chain in the
alkoxy group, coelectrolysis with long-chain fatty acids, ethanol or dimethylformamide as solvent,
and a high current density [308].
The non-Kolbe electrolysis has found many synthetic applications. The carboxylic group in an
acid can be replaced this way by a hydroxy, alkoxy, or amino group or a double bond. Furthermore,
cationic rearrangements or β-cleavages can be induced [216d,g].
The non-Kolbe electrolysis leads to precursors for C–C coupling reactions, but usually does not
form directly a new C–C bond via a coupling reaction.
C. ANIoNS FroM CH-ACIDS aS RaDICaL SoUrCE

1. Coupling
Besides carboxylates, other organic anions can be coupled at the anode via radicals. Anions of
CH-acids couple in satisfactory yields (Table 18.12, entries 1–6).
With some substrates, the yield can be substantially improved with sodium iodide as supporting
electrolyte or additive. The iodide anion probably acts as mediator. Thereby, dehydrodimers, tetra-
substituted ethylenes, and cyclopropanes can be obtained in up to 90% yield [317]. Electrolysis of
methylene malonates in the presence of sodium iodide in an undivided cell results in 50–70% yield
of stereoisomeric cyclobutane tetracarboxylates. Thereby at first, the activated methylene com-
pound is reductively dimerized at the cathode and subsequently the two CH-acids undergo a medi-
ated intramolecular coupling [318]. Triacetylmethane forms in a remarkable and stereoselective
reaction in high yield a bicyclic trioxabicylooctane (Table 18.12, entry 5). Furthermore, anions of
nitroaliphatic compounds are coupled to give vicinal dinitroalkanes (Table 18.12, entry 6). Grignard
compounds and borates (Table 18.12, entries 7 and 8) couple to give alkanes; alkyne anions can be
coupled to give dialkynes (Table 18.12, entry 9).
TABLE 18.12
Anodic Coupling of Carbanions
Entry Precursor for Carbanion Conditions Product Yield (%) References
1 (R O2C)2CHR
1 2 AN, NaOR [(R O2C)2C(R )]2
1 2 10–90 [309]
R1 = Me,Et
R2 = C1–C8, Ph, allyl, Bzl
2 (EtOOC)3CH H2O, acetone [(EtOOC)3C]2 50 [310]
NaOH, EtOH
3 n AN, NaOR n 50–98 [309]
(RO2C)2CH CH(CO2R)2 (RO2C)2C C(CO2R)2
R = Me, Et n = 3,4 R = Me, Et n = 3,4
4 Me pH 1, H2O Me 69 [311]
O N O O N O
H
N N 2
Me Me
Me Me
O O
5 (MeCO)3CH Et3N, AN MeCO O Me 92 [312]
MeCO COMe
O
Me O
Me
6 2-Nitrobutane 25% NaOH 3.4-Dimethyl-3,4- dinitrohexane 70 [313]
7 RMgBr Et2O R–R 54–60 [314]
R = C5H11, C18H37, Ph
8 R3B MeOH, KOH R–R 24–82 [315]
R = C5H11–C8H17
9 Phenylethyne THF, LiClO4 1,4-Diphenyl-1,3-butadiyne 35 [316]
The electrochemical oxidation of carbanions, p-Me-C6H4-C(Z1Z2) – with (Z1 = Z2 = CN; Z1 = CN,

Z = COOEt; Z1 = Z2 = COOEt), was studied in AN and Bu4NBF4 by voltammetry and macroscale
2
electrolysis. The carbanions, generated by cathodic reduction of the conjugated acids, show a chem-
ically irreversible oxidation peak, whose position reflects the relative basicity of the anions. Kinetic
data indicate that neutral radicals are generated at the electrode and that a fast radical–radical cou-
pling is the most effective dimerization process for all the substrates. Homodimers are formed in
high yield after exhaustive, one-electron macroscale electrolysis [319].
2. Addition
The oxidation of anions from 1,3-dicarbonyl compounds in the presence of olefins leads to different
products depending on the structure of the olefin and the applied anode potential. In the presence
of butadiene, only the additive dimer 115 (Scheme 18.87) is obtained (Table 18.13, entry 8); on the
other hand, with ethyl vinyl ether, only disubstituted monomers 119 and 120 arise (Table 18.13,
entries 1–3). With styrene, 119 and 120 are found as main products and 115 as side product (Table
18.13, entries 4, 7). These results indicate that at a potential between 0.6 and 1.4 V, the intermediate
ethoxymethyl radical 116 (Y = OEt) is rapidly oxidized to 118, while the oxidation of the allyl radi-
cal 116 (Y = vinyl) is much slower. If styrene and oxygen are present, the electrogenerated radical
adds successively to both (Table 18.13, entry 5).
With Mn(OAc)3, generated by oxidation of Mn(OAc)2 as mediator, a tandem reaction consist-
ing of an intermolecular radical addition followed by an intramolecular electrophilic aromatic
TABLE 18.13
Anodic Addition of Carbanions to Olefins
Entry Radical precursor Olefin Conditions Product Yield References
1 MeOCH2COMe CH2═CHOEt MeONa, O 36% [320]
MeOH, Pt
Me O OEt
2 (MeOOC)2CH2 CH2═CHOEt MeONa, MeOOC OEt 37% [320]
MeOH, Pt
MeOOC OMe
3 O CH2═CHOEt EtOH, O 79% [321]
EtONa OEt
O O OEt
O
OEt
O
4 O CH2═CHPh MeCN, O 85% [322]
Et4NOTos
Ph
O O
5 O CH2═CHPh, O2 MeCN, O 79% [322]
Et4NOTos Ph
O
O
O OH
6 CH3COCH2CO2Me MeOH, 67% [108]
N O MeONa N O
CO2Me
MeOC + isomer
7 (MeO2C)2CH2 CH2═CHPh MeOH, MeO2C 40% [320]
MeONa, MeO
Pt O Ph
MeO
8 (MeO2C)2CH2 Butadiene MeOH, [(MeO2C)2CHCH2CH═CHCH2]2 46% [320]
MeONa, + isomer
Pt
9 CH3COCH2CO2Et HOAc, CO2Et 80–86% [323]
R2
1 EtOAc, R2
R
NaOAc R1 O Me
R1 = Propyl, (0.1 eq.),
Pentyl, t-Bu
Mn(OAc)2,
R2 = H, Me
C-anode
10 PhCH2CH(CO2Me)2 R H KOAc, CO2Et 40–91% [324]
R = Hexyl HOAc
TMS, Ph CO2Et
0.25 eq.
Mn(OAc)2, R
C-anode
11 PhCOCH2NO2 CH2═CHR HOAc, O 37–59% [325]
R = Bu, CH2OAc Bu4NBF4 R
Ph
C anode Mn(OAc)2,
N+ O
60oC O–
(Continued)

Anodic Addition of Carbanions to Olefins
Entry Radical precursor Olefin Conditions Product Yield References
12 (CH3)2CHNO2 CH2═CHPh MeOH, NO2 Ph 43% [326]
MeONa, Pt
OMe
13 nBuMgBr CH2═CHPh Et2O, [nBu-CH2-CH(C6H5)]2 29% [327]
LiClO4, Pt
14 (C6H13)3B(OMe)• Butadiene MeOH, (C6H13CH2CH═CHCH2)2 5% [328]
MeONa, C C6H13CH2CH═CHCH2C6H13 14%
C6H13CH2CH═CHCH2OMe
+ isomers
substitution can be accomplished (Scheme 18.94) [329]. Further, Mn(III)-mediated additions of

1,3-dicarbonyl compounds are shown in Table 18.13 entries 9–11. Mediated by in situ generated
Mn(III), methyl dibromoacetate, trichlorobromomethane, perfluoroctyl iodide, dibromomalonate,
and active methylene compounds have been added to olefins via radicals [330].
Recently, a large number of anodic additions of CH-acids to olefins mediated with Mn(III) or
Ce(IV) have been compiled [317].
Sorbic acid precursors have been obtained in larger scale and high current efficiency by a Mn(III)/
Cu(II)-mediated oxidation of acetic acid and acetic anhydride in the presence of butadiene [331].
Also other anions, such as the 2-nitropropanate anion, Grignard reagents, and borates, can be
added to olefins (Table 18.13, entries 12–14).
In compounds bearing a silicon and a tin atom on the same carbon atom, the tin–carbon bond
can be selectively cleaved at the anode and the resulting intermediate added to a silyl enol ether or
an allylsilane (Scheme 18.95) [332].
CO2Et
R3 R3
X
R2 R2
R1 R1
a
+ X CO2Et
–e–
R1 = H, F, Me; R2 = H, Me; R3 = H, Me; X = CN, CO2Et

a: C anode; NaOAc, HOAc, AcOEt (13:3),
0.2 eq. Mn(OAc)2, 60°C
SchEME 18.94 Subsequent inter- and intramolecular addition of an anodically generated radical.
OMe –e–, DCM, OMe

+ 0.2 M Bu4NBF4
Bu3Sn SiMe3 SiMe3 SiMe3
99%
OSiMe3 O SPh
SPh –e–, DCM,
+ 0.2 M Bu4NBF4 SiMe3
Bu3Sn SiMe3
70%
SchEME 18.95 Selective cleavage of a tin–carbon bond at the anode and addition of the electrophilic inter-
mediate to double bonds.
V. OUTLOOk
C–C bond formation at the electrode consists of two reactions: (a) Electrons are transferred between
substrate and electrode forming radical cations or radicals as reactive intermediates and (b) chemi-
cal reaction of these intermediates lead to C–C bond formation. Reaction (a) depends on the facil-
ity for the transfer of an electron to or from the substrate. This is determined by the energy of the
π- or σ-bonds, the lone electron pairs, the interaction of substrate and electrode, and the electrode
potential. Reaction (b) is controlled by the reactivity of the intermediate and the composition of the
reaction layer.
Most reactive species being involved in electrosynthesis react in a reaction layer close to the elec-
trode surface. The faster they react, the less they can diffuse away from the electrode and the more
the electrode and the reaction layer close to the electrode surface influence the chemical reaction.
This can be due to the electrostatic field of the electrode, a further electron transfer to or from the
electrode, and a different electrolyte composition and substrate concentration in the reaction layer
than in the bulk solution. Much information on the rate and facility of electron transfer at the elec-
trode is available or accessible by experimental methods and quantum chemical calculations (see
Chapters 1 to 6). Much less is known on the composition of the reaction layer. Knowledge is emerg-
ing from well-supported interpretations on the selectivity in the intramolecular reaction of radical
cations with double bonds or in the intermolecular cross-coupling of phenols. (See Sections III.E.1
and III.E.2.) It is to be expected that these analyses will stimulate others in the interpretation of their
results and this way widen our knowledge on the reaction layer. Possibly established tools available
from bulk reactions as the linear free energy relationship, salt effects, or competition experiments
will be applied to further characterize the properties of the reaction layer.
Increasing the hydrophobicity of the supporting electrolyte by exchanging LiClO4 for Et4NOTos
has led to a lower content of methanol in the reaction layer, and this way has favored an intramolecu-
lar cyclization against the methanolysis of the intermediate radical cation [164].
Helpful would be to find, for larger-scale conversions (>0.1 F ), reliable ways to regenerate or
retain the activity of the electrode surface or to concentrate catalysts in the reaction layer by using
electrostatic attraction or by linking them with flexible tethers to the electrode surface.
The principle of redox umpolung to save reaction steps, couple substrates of equal reactivity, and
use the same building block as anion, radical, radical ion, or cation should be more systematically
investigated.
Sometimes one can learn from a related conversion that works well with a chemical oxidizing or
reducing agent about the deficits of the electrochemical reaction, or one can use such a species as a
mediator of an indirect electrolysis.
Worthwhile would be a look on combinations of electron transfer with organocatalysis or transi-
tion metal catalysis and also include such combinations into indirect electrolyses. Transition metal
catalyst can be oxidized to higher oxidation states, where they can be more powerful oxidants and
this way may lead to yet unexplored catalytic reactions.
Whenever possible, simple and inexpensive equipment should be used: many anodic oxidations
can be done in an undivided cell that simplifies the cells and keeps the cell voltage low and the
acidity of the electrolyte constant. A CCE with a cheap direct current (dc) power supply saves a
coulometer and an expensive potentiostat. The electrodes should be used as solid plates or in case of
thin foils be mounted on Teflon frames. Each glassblower can manufacture a beaker-type cell, and
the machine shop can produce a Teflon stopper with holes for the current feeders and, if needed for a
Luggin capillary, thermometer and inert gas inlet. The experimental part in a publication should be
written up in a way that somebody without expertise in electrochemistry understands the procedure,
all that helps to repeat, to evaluate, and possibly to use an electrochemical reaction quickly in most
chemical laboratories.
At teaching institutions, the basis of electrosynthesis should be presented in lectures and labora-
tory courses to decrease the barrier against using electrosynthesis.
Finally, there are a number of advantages—being partly unique—that are offered by electrosyn-
thesis. These are redox umpolung, the use of the same synthetic building block in different reac-
tivity, access to reactions being not available in nonelectrochemical reactions, accord with many
rules of green chemistry, high atom economy, cheap reagents, easy scale-up, or facile application in
microreactors. However, one should keep in mind that electrosynthesis cannot create miracles, but
it can offer alternatives to nonelectrochemical syntheses that may be a better solution for a synthetic
problem.
REfERENcES
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19 Oxidative Substitution
and Addition Reactions
Ole Hammerich and James H.P. Utley
CONTENTS
I. Introduction ............................................................................................................................ 776
II. Formation of Carbon-to-Carbon Bonds ................................................................................. 777
A. Aromatic Hydrocarbons and Alkenes as Nucleophiles .................................................. 777
B. Trifluoromethylation ....................................................................................................... 778
C. Cyanation ........................................................................................................................ 778
D. Carbomethoxylation ........................................................................................................ 780
E. Allyltrimethylsilane as Nucleophile ............................................................................... 781
III. Formation of Carbon-to-Nitrogen Bonds ............................................................................... 781
A. Acetamidation ................................................................................................................. 781
B. N-Cyanomethylation and Amination.............................................................................. 784
C. Nitration .......................................................................................................................... 784
D. Cyanate Ion as Nucleophile ............................................................................................ 785
E. Pyridination .................................................................................................................... 785
F. N-Heterocyclic Compounds as Nucleophiles ................................................................. 786
IV. Formation of Carbon-to-Oxygen Bonds ................................................................................. 787
A. Hydroxylation.................................................................................................................. 787
B. Alkoxylation (Methoxylation) ......................................................................................... 789
C. Acyloxylation (Acetoxylation) ........................................................................................ 795
D. Nitrate Ion as Nucleophile .............................................................................................. 798
V. Formation of Carbon-to-Sulfur Bonds ................................................................................... 798
A. Thiols as Nucleophiles .................................................................................................... 798
B. Thiocyanation ................................................................................................................. 798
VI. Formation of Carbon-to-Halogen Bonds ................................................................................ 798
A. Fluorination..................................................................................................................... 798
B. Chlorination and Bromination ........................................................................................ 799
C. Iodination ........................................................................................................................ 799
References ......................................................................................................................................800
This chapter is dedicated to the late professor Lennart Eberson, who was not only one of our col-
leagues but also a close friend. Lennart Eberson was a world-leading physical-organic chemist who
made seminal contributions to many areas of the subject. These included pioneering achievements
in the application and theory of homogeneous and heterogeneous electron transfer reactions of
organic compounds. He was one of a small band of scientists who shaped modern organic electro-
chemistry and who also contributed to this book from the very beginning.
775
I. INTRODUcTiON
Anodic substitution and addition reactions are among the most important reactions in organic elec-
trochemistry, and new, interesting examples are added to the literature every year. The overall reac-
tions may be represented as in the following:
R E + Nu– R Nu + E+ + 2e– (19.1)
C C + 2 Nu– Nu C C Nu + 2e– (19.2)

The nucleophile [Nu– (or NuH)] may include H2O, ROH, OH–, RO –, RCOO –, NO3–, SCN–, SeCN–,
CH3CN, NO2–, N3–, OCN–, pyridine, halide ion, and CN–; the electrophile [E+] in substitution reac-
tions is most commonly H+ but might be a carbocation or an alkyloxonium ion. The cases in which
the electrophile is CO2 (the Kolbe reaction and similar) are treated in Chapter 33 and will not be
dealt with here. Anodic substitution and addition reactions therefore allow for a net reaction with a
nucleophile that is not easily achieved by ordinary chemical means. Specifically, it makes possible
the direct formation of a C–O or C–N bond, which is of considerable synthetic interest.
The mechanisms of anodic substitution and addition reactions can be divided into direct and
indirect processes.
In the direct process, oxidation of the organic substrate takes place at the anode with formation
of a radical cation as the first step, Equation 19.3, which is followed by reaction with a nucleophile
and/or base present in the electrolyte, Equation 19.4 and/or Equation 19.5. The resulting neutral
radical, I or II, is usually more easily oxidized than the starting material and undergoes further
oxidation at the applied potential to a cation, III or IV, Equation 19.6 or Equation 19.7, which in turn
is converted to the final product, V, in a fourth step, Equation 19.8 or Equation 19.9:
+
R H R H + e– (19.3)
+ H H
R H + Nu– (or NuH) R (or R ) (19.4)
Nu NuH+
I I'
+
R H + B R + BH+ (19.5)
II
Electrode
– e–
H H
R +R (19.6)
Nu Nu
Solution
I III
+
+R H , –R H
Electrode
–e–
R R+
(19.7)
II IV
Solution
+
+R H , –R H
H
+R + B R Nu + BH+ (19.8)
Nu V
III
Oxidative Substitution and Addition Reactions 777
R+ + Nu– R Nu (19.9)
IV V
Nu C C + + Nu– Nu C C Nu (19.10)

The mechanism composed by Equations 19.3 through 19.6 and 19.8 is observed typically for nuclear
substitution in aromatic compounds, whereas side-chain substitutions, for instance, typically
proceed according to Equations 19.3, 19.5, 19.7, and 19.9. (For a more thorough discussion of the
reactions between radical cations and nucleophiles, the reader is referred to the rich literature on this
subject [1].) Essentially, the same mechanistic pattern is found in oxidative substitution driven by
high-valent inorganic ions [2–5]. Like in conventional organic chemistry, the competition between
substitution and addition reflects whether the cation, in electrochemistry resulting from a −2e–, −H+
process, deprotonates, Equation 19.8, or reacts with a second nucleophile, Equation 19.10.
In an indirect process, the anode merely serves as a convenient source of an oxidant, for example,
Cl2 by oxidation of Cl– or NO3• by oxidation of NO3–, or of an organic radical, for example, methoxy
radical from methoxide ion, which then attacks the organic substrate in a reaction similar to that
taking place when the reagent is generated in any other way. The indirect processes also encompass
reactions in which an organic compound is oxidized by an electrochemically generated oxidant, a
so-called mediator, the reduced form of which is continuously reoxidized and therefore, in prin-
ciple, needs only to be present in catalytic amounts.
In this chapter, we shall emphasize reactions proceeding according to the direct mechanism,
since in many cases the indirect processes do not differ in any important respects from analogous
homogeneous processes. The subject has been extensively reviewed [6–10].
II. FORMATiON Of CARBON-TO-CARBON BONDS

A. AroMaTIC HYDroCarboNS aND ALkENES aS NUCLEopHILES
Reaction conditions for anodic substitution may often be arranged so that the starting material is
the most nucleophilic species present. Consequently, many synthetically useful inter- and intramo-
lecular reactions with carbon-based nucleophiles may be accomplished (see Chapter 18 for details
of anodic coupling reactions).
An obvious case is the oxidation of electron-rich hydrocarbons in nonnucleophilic media,
typically CH2Cl2/R4NBF4 or CH2Cl2 mixed with strong acids such as CF3COOH, CH3SO3H, or
CF3SO3H [11,12]. The radical cations formed by one-electron oxidation either dimerize or attack the
starting material; an example is given in Equation 19.11. Such couplings have also been achieved
using a large-scale capillary gap cell with a graphite anode [12].
CH3
CH3
H3C CH3
+CH
CH3 2
CH3 CH3 H3C H3C CH3
CH3
CH2 (19.11)
–2e–, –H+ –H+
H3C H3C CH3
CH3 CH3
H3C
CH3
Intramolecular coupling of aromatic systems based on this principle has been particularly fruitful.
Phenols or aromatic ethers are usually involved: if the activation of the aromatic system is suffi-
cient, the reactions do not require especially nonnucleophilic solvents. In the simplest case, anisole
may be anodically coupled in CH2Cl2/CF3COOH to give, after work-up in the presence of Zn dust,
4,4′-dimethoxybiphenyl in 60% yield [13].
Related to these coupling reactions is the reaction between an anodically generated radical
cation, for example, derived from anthracene or 9-phenylanthracene, and a carbon nucleophile such
as anisole, toluene, or benzene [14]:
CH3
CH3
(19.12)
~100%
–2e–, –2H+
B. TrIFLUoroMETHYLaTIoN
There is a growing interest in the synthesis of fluorinated organic compounds (see, e.g., Chapter 20),
and new methods of preparing, for example, trifluoromethyl-substituted compounds are desired.
Oxidation of trifluoromethanesulfonate ion in MeCN or N,N-dimethylformamide (DMF) has been
shown to lead to the formation of the trifluoromethyl radical that in a subsequent step may react with
a suitable olefin such as 1-phenylcyclohexene, Equation 19.13 [15]. The total yield of CF3 products
is 35–70%.
CF3SO2– CF3 + (19.13)

–e–, –SO2
F3C F3 C

C. CYaNaTIoN
Anodic cyanation is a reaction of considerable preparative interest since it allows for the direct
introduction of a cyano group into an aromatic ring [16–24]. Contrary to the situation in acyloxyl-
ation (see Section IV.C) and alkoxylation (see Section IV.B), the product is more resistant toward
oxidation than the starting material owing to the strong electron-withdrawing effect of the cyano
group, and in principle, good yields should be obtainable. The reaction is often run in MeOH/NaCN
[16–20], which gives concurrent methoxylation [25]. This is avoided if MeCN/Et4NCN is used [21].
An important advance is the use of emulsions with phase-transfer agents [23].
The reaction was initially believed to be a homolytic substitution reaction by anodically gener-
ated cyano radicals [16]. However, while significant oxidation of CN- takes place at a potential as
low as 0.5 V versus SCE, the cyanation process will occur only in the region around or above E1/2
of the substrate. This strongly implies a direct mechanism [17,20,21].
Isomer distribution for cyanation of aromatic compounds has been determined in a number of
cases [18–21], and the regioselectivity is often high. This has been put to good use for the prepara-
tion of 2-cyanopyrroles and 2-cyanoindoles [24,26,27]:
CH3OH, CN–
CN 64% (19.14)
N –2e–, –H+ N
CH3 CH3
If the 2-position is blocked, cyanation occurs at the 3-position. Similarly, cyanation of 1-meth-
ylpyrazole gives a mixture of the 4- and 5-carbonitrile [28]. The efficient substitution observed
for many pyrroles, imidazoles [29], and indoles contrasts markedly the addition reactions
observed for furans and thiophenes [30]. However, this difference may only be apparent. At
least for two of the cases cited earlier [24], it has been demonstrated [31] that the cyano-
substituted pyrroles arise as a result of elimination during work-up of the 2,5-addition prod-
uct originally formed. For benzo[b]thiophenes, cyanation leads predominantly to substitution
products [32]:
CN
CH3 OH, CN– (19.15)
CH3 CH3 75%
S –2e–, –H+ S

The direct nature of attack of CN– on the radical cations of aromatic compounds has been demon-
strated by cyclic voltammetry [22]. The reversible one-electron oxidation of anthracene becomes
chemically irreversible in the presence of CN–, and 2F electrolysis gives a mixture of cyano and
isocyano addition across the 9,10-position. Interestingly, it appears that cyanation of 9,10-diphenyl-
anthracene gives the 9,10-diphenyl-9,10-dicyano-9,10-dihydroanthracene only [33].
The best conditions for nuclear cyanation involve the use of emulsions, typically CH2Cl2/H2O/
NaCN, with a phase-transfer agent. This has been described in detail for the monocyanation of
naphthalene and anisole with isolated yields in the region 50–70% [23]. For dimethoxybenzenes,
the yields are somewhat lower [23].
For trans-stilbene and trans-4,4'-dimethoxystilbene, cyanation in an emulsion system gives for
the former a mixture of addition and substitution products (including substitution of the vinylic
protons), whereas for the latter substitution of the vinylic protons is the predominant reaction [23].
Alkylaromatic compounds do not give any side-chain substitution product under conditions
that produce nuclear cyanation products [18–20] (see previous text). Anodic cyanation of tert-
butylanisoles leads to mixtures of addition and substitution products [34].
In most cases, cyanation involves loss of a proton, but in some cases, an alkoxy group may be dis-
placed with very good yields of substitution products [21,23]. Thus, 1,2- and 1,4-dimethoxybenzene
undergo cyanation by displacement of one of the methoxy groups, presumably via an eCe-type
mechanism. On the other hand, anisole and 1,3-dimethoxybenzene do not undergo methoxy dis-
placement but, instead, give nuclear substitution in the usual manner. The presence of an activat-
ing group in the ortho and para positions thus seems essential for methoxy group displacement.
However, the selectivity is less pronounced when the reactions are carried out in aqueous micellar
solution [35,36]. The fate of the displaced alkoxy group is not always clear; the observation of
aldehyde and alcohol among the products of anodic cyanation of 4,4′-dialkoxybiphenyls [23] and
the proven loss of benzyloxy radical from the radical cation of dibenzyl ether [37] support the
mechanism shown in Equation 19.16. The cyanation of the 4,4′-dialkoxybiphenyls, Equation 19.16,
shows the use of emulsion systems to good advantage; the products include an important class of
liquid crystals.
OCH2R NC OCH2R CN
CN–
+ ½RCH2OH + ½RCHO (19.16)
–e– –RCH2O
OCH2R OCH2R OCH2R

Tertiary (cyclic) amines are particularly useful substrates for cyanation [21,23,38–44] with substitu-
tion taking place at the carbon atom α to the nitrogen atom as in N-methylpiperidine, Equation 19.17
[38]. Related to these is the α-cyanation of N-(methoxycarbonyl)piperidine [45]. Current–potential
curves have been used to show that discharge of, for example, triethylamine occurs prior to the
oxidation of the MeOH/NaCN electrolyte. The reaction works well even for complex amines such
as benzyl germatranes, Equation 19.18 [46]:
CN
CN–
N CH3 N CH2CN + N CH3 (19.17)
–2e–, –H+
38% 62%
CN
N N
O O
CN– O Ge
O Ge O (19.18)
O –2e–, –H+ Br
Br
For aniline derivatives, substitution often occurs preferentially at a primary carbon atom as in, for
example, N-ethyl-N-methylaniline [21]:
CH3 CN– CH2CN CH3

N N + N
CH2CH3 –2e–, –H+ CH2CH3 CHCH3
(19.19)
64% 36% CN
D. CarboMETHoXYLaTIoN
An unusual and interesting carbomethoxylation reaction occurs during electrolysis of an arylolefin
in MeOH/NaOMe under CO pressure between two Pt electrodes [47]:
R R
C CH2 Pt anode C CHCOOCH3
+ CO + CH3O– –, –H+
(19.20)
–2e

It has been shown that the Pt cathode dissolves to give a Pt(CO) complex. This is transformed at the
anode to a carbomethoxy–Pt(CO) complex that attacks the arylolefin to give the carbomethoxylation
product.
Carbomethoxylation of styrene derivatives may also be effectively accomplished by oxidation
in AcOH/Ac2O/NaOAc mixtures containing small amounts of Cu(OAc)2 and Mn(OAc)2, the latter
serving as a mediator. However, under these conditions, the reaction takes a slightly different course
and leads predominantly to cyclized products as illustrated by one, Equation 19.21, of the several
examples reported [48]. Related to this reaction is the oxidation of 5-arylpent-1-enes in the presence
of, for example, diethyl malonate, Equation 19.22, [48]:
H CH3COOH, (CH3CO)2O, CH3COO–

CH2 Mn(OCOCH3)2, Cu(OCOCH3)2
75% (19.21)
O
O
R3 CH3COOH, CH3COOCH2CH3, CH3COO–

R1 R2
Mn(OCOCH3)2
+ X CH2 COOCH2CH3
R3
COOCH2CH3
R2 CH
R1 X = CN, COOCH2CH3 (19.22)
X

E. ALLYLTrIMETHYLSILaNE aS NUCLEopHILE
Allyltrimethylsilane has been used as the nucleophile for the introduction of the α-allyl group in
N-(methoxycarbonyl)pyrrolidine, Equation 19.23, and related compounds using a microflow reactor or
by taking advantage of acoustic emulsification [49]. Yields are typically in the range 40–70%. In a series
of similar substitution reactions, a phenylthio substituent has been replaced by an allyl substituent [50],
mostly likely via a carbocation intermediate (see also Equation 19.32). Other examples of the application
of allyltrimethylsilane as a nucleophile are based on the so-called cation pool method (see Chapters 9
and 35) that includes the electrochemical generation and accumulation of highly reactive cations, such
as the (methoxyphenyl)methylium cation, at low temperature and subsequent reaction with, for exam-
ple, allyltrimethylsilane to afford (1-methoxybut-3-enyl)benzene in up to 90% yield [51]. A spectacular
example of the application of allyltrimethylsilane as a nucleophile is the oxidation of cyclooctatetraene.
As seen in the following, the original eight-membered ring is preserved in resulting product, VI [52]:
Si(CH3)3
+
N –2e–, –H+ N
COOCH3 COOCH3
Si(CH3)3
(19.23)
VI
III. FORMATiON Of CARBON-TO-NiTROGEN BONDS

A. ACETaMIDaTIoN
Oxidation of anthracene in MeCN containing (CF3CO)2O (to remove water and suppress hydrox-
ylation) leads to the formation of the acetamidation product in 85% yield [53]. Results obtained by
cyclic voltammetry supported the mechanism shown in the following:
+
CH3CN
–e–
+ +
N C CH3 NHCOCH3
H N C CH3
H2O
(19.24)
–e–, –H+ –H+

The rapid reaction of the anthracene radical cation with MeCN is nicely illustrated by the
observation of an irreversible, two-electron oxidation peak in the voltammogram at +1.2 V
versus SCE, whereas in CH2Cl2/(CF3CO)2O, the oxidation peak corresponds to a reversible one-
electron process.
Methyl-substituted benzenes are particularly good substrates for side-chain acetamidation and
have featured in numerous product and mechanistic studies [7–10,54–59]; ethylbenzene and iso-
propylbenzene give other products predominantly [60]. Hexamethylbenzene has been a favored
substrate for mechanistic investigations of acetamidation [57,61], and in this case, there is evidence
[62] that on time scale of conventional cyclic voltammetry, proton loss is rapid from hexamethylben-
zene radical cation but relatively slow from hexaethylbenzene.
Aromatic carbonyl compounds undergo fairly efficient nuclear acetamidation at a Pt anode in
moist MeCN/Et4NBF4 [63].
Alkenes undergo the combined addition of NHCOCH3 and F when oxidized in MeCN containing
Et4NF,3HF [64] and of NHCOCH3 and PhSe when oxidized in MeCN containing PhSeSePh [65].
It is of interest to notice that while fluoroacetamidation of cyclic alkenes results predominantly in
cis-addition, selenoacetamidation gives the trans-isomer as the major product.
n-Alkanes can be oxidized in MeCN/R4NBF4 solutions (see Chapter 23). The observation of
well-defined oxidation waves, the consumption of 2F, and the formation of acetamides at secondary
carbon atoms supports the mechanism outlined in Equation 19.25 for n-octane [66]. In some cases,
prior cleavage of carbon–carbon bonds is observed, again in a manner that suggests a carbocation
intermediate, Equation 19.26 [67]:
CH3CN
(+ Isomers)
–2e––H+ +
H2O (anodically generated halogen (19.25)

and thus position 3: 35%)
–H+
+N C CH3 NHCOCH3 (position 4: 32%)
33%
CH3CN, H2O
NHCOCH3 + NHCOCH3 (19.26)
–2e–, –2H+
In the wake of the aforementioned early work, several investigations of anodic acetamidation of
polycyclic hydrocarbons were initiated; substituted adamantanes were much used in this work
because of their availability and their relative ease of oxidation [68–70]. The results are generally
explicable in terms of expected stabilities of intermediate carbocations and competition between
proton loss and C–C bond cleavage. Difunctionalization of adamantanes is also possible using
anodic acetamidation [70]:
R NHCOCH3 R
E = 2.5 V vs. Ag/Ag+
CH3CN, H2O
+
NHCOCH3
E = 3.0 V vs. Ag/Ag+ (R = H: 74%)
as above (R = tert-Bu: 62%) (19.27)
NHCOCH3
(R = H: 58%)
NHCOCH3
Esters, ketones, and alcohols may also undergo substitution in MeCN [71–73]. Some of these
substrates are oxidized in a region where oxidation of the electrolyte is concurrent and, certainly
for esters, it may well be that an indirect mechanism operates with necessary initial abstraction of
hydrogen by a radical derived from the electrolyte [71]. Examples are given in Equations 19.28 and
19.29. In one case, the anodic oxidation of 2-octanone in MeCN/LiClO4, the reaction mechanism
has unambiguously been demonstrated to involve specific abstraction of one hydrogen atom at C-5
by the carbonyl oxygen in a six-membered ring cyclic transition state, reminiscent of the first chemi-
cal step in the gas-phase McLafferty rearrangement [73].
NHCOCH3
CH3CN, H2O
(19.28)
–2e–, –2H+
O O
NHCOCH3
OCH3 CH3CN, H2O OCH3 OCH3
+ (19.29)
–2e–, –2H+
O O NHCOCH3 O

Acetamidation is also a result of the anodic oxidation in MeCN solution of carboxylates

(see Chapter 33) and alkyl halides [68,74–77]. Much discussion and experimentation has focused
on the mechanism of cleavage of the alkyl halides, particularly the iodides. From the extent of
rearrangement of cations supposedly produced by alkyl iodide oxidation compared with that for
the same cations produced by solvolysis of tosylates, it has been suggested that in electrolysis,
MeCN assists cation formation [74]. The SN2 character of this process receives support from the
20% inversion observed for oxidation of optically active 2-iodooctane, Equation 19.30. An alterna-
tive mechanism must, however, be considered that is based on the known anodic oxidation, at the
potentials used for alkyl iodide cleavage, of iodine to an iodine (I) species [75]. The process given
in Equation 19.31, which is catalytic in iodine, is therefore plausible, given the initial generation of
some iodine by direct cleavage:
Pt anode, CH3CN
(-) + 3- and 4-Isomers
I NHCOCH3
(19.30)
70% (75% Racemization) 30%
CH3CN, H2O
R I + I+ I2 + R+ R NHCOCH3
–H+ (19.31)
Anode
A Ritter-type reaction is also observed during the anodic oxidation of phenylthiomethane derivatives
[78] of the type shown in Equation 19.32, which summarizes the proposed reaction mechanism:
+
OH SPh OH SPh
R R
–e– –SPh
O O O O
(19.32)
OH OH NHCOCH3
+
R CH3CN, H2O R
–H+
O O O O
B. N-CYaNoMETHYLaTIoN aND AMINaTIoN

The solvent, MeCN, may be incorporated in the product in an altogether different type of process,
which leads to formation of substituted acetonitriles. For instance, the oxidation of 2,2,6,6-tetra-
methylpiperidine, or the corresponding morpholine, in MeCN/NaClO4 under oxygen-free conditions
leads to the formation of an aminoacetonitrile derivative [79]. The reaction was suggested to follow
the mechanism given in the following [X = CH2,O]:
+
X NH X NH X N
–e– –H+
X N + CH3CN X NH + CH2CN (19.33)
X N + CH2CN X N CH2CN
Essentially, the same mechanism has been proposed for anodic α-amination of tetrahydrofuran,
which may be accomplished by oxidation of, for example, R2NH or R2NLi, in this solvent [80]. The
best yields (70–80%) were observed when R2NH was piperidine.
C. NITraTIoN
The formation of nitro compounds upon electrolysis of a suspension of an aromatic hydrocarbon
in dilute aqueous HNO3 has been known for a long time [81]. It has been interpreted in terms of
the formation of a high concentration of HNO3 near the anode surface, in which region an ordi-
nary electrophilic nitration process would take place. Studies on the anodic oxidation of NO3– in
nitromethane [82] would seem to confirm this assumption; N2O5 is the oxidation product, probably
formed via reactions (19.34) and (19.35). In aqueous solution, this would lead to the formation
of HNO3.
2 NO3– 2 NO2+ + O2 (19.34)

–4e–
NO2+ + NO3– N2O5 (19.35)

Similarly, the oxidation of N2O4 in, for example, concentrated HNO3 or H2SO4 [83], MeCN [84], or
sulfolane [85] has been shown to lead to nitrating mixtures containing NO2+.
Another mechanism of anodic nitration involves the generation of a radical cation in the pres-
ence of NO2, Equation 19.36. This mechanism has attracted considerable attention [86–88] in the
vivid discussion of electron transfer as a general step in conventional nitration, where in Equation
19.36, the nitronium ion instead of the anode serves to oxidize the substrate to the radical cation
state in the first step. Here, it is sufficient to notice that, using naphthalene and methyl-substituted
naphthalene radical cations as substrates in CH2Cl2/Bu4NPF6, it was shown [86] that the coupling
reaction between ArH• + and NO2 is more selective than nitration by acetyl nitrate in (CH3CO)2O or
N2O4 in CH2Cl2.
+ NO2 + H
ArH ArH Ar ArNO2 (19.36)
–e– NO2 –H+

The anodic oxidation of solutions of aromatic hydrocarbons and AgNO2 in MeCN gives mononitra-
tion with a substitution pattern that is held to support initial formation of a radical cation [89]. Alkenes
may similarly be oxidized in the presence of AgNO2, and depending on the alkene, nitro products
are formed by substitution or addition. In probably the best example, coelectrolysis of anthracene
and AgNO2 at 1.3 V versus SCE gave 9-nitroanthracene in 47% yield (current efficiency 28%),
and from 1,1-diphenylethylene, electrolyzed at 1.5 V, 1,1-diphenyl-2-nitroethylene was obtained in
40% yield. In each case, 1F was consumed. However, since NO2– is more easily oxidized than both
anthracene and 1,1-diphenylethylene, it cannot be excluded that NO2– is oxidized at the anode to
give NO2/N2O4, in itself a good nitrating reagent in homogeneous medium [86]. Constant potential
electrolysis of 1,4-dimethoxybenzene in micellar solutions containing NO2– showed, however, that
the nitration product, 2,5-dimethoxynitrobenzene, was only formed at potentials sufficiently high
to oxidize both NO2– and 1,4-dimethoxybenzene. This was taken as evidence in support of a reac-
tion including the coupling between the radical cation and NO2 [90]. The same type of mechanism
was proposed for the electrochemical nitration of naphthalene in the presence of NO2– in aqueous
nonionic surfactant solutions [91].
Aliphatic gem-dinitro compounds can be prepared by anodic oxidation of a nitroparaffin in
aqueous alkaline solution in the presence of an excess of NO2– [92]. Yields are considerably better
when Ag+ is the oxidizing agent [93], so that an indirect oxidation process involving the generation
of Ag+ at an Ag anode was found to give excellent results [94].
Electrochemical nitration has been applied also to functionalize single-wall carbon nanotubes
[95] and for the introduction of the nitro group in horse heart myoglobin [96].
D. CYaNaTE IoN aS NUCLEopHILE

Both nuclear and side-chain substitutions of alkylaromatics by NCO– have been observed [97].
Thus, electrolysis of anisole in MeOH/KOCN results in substitution of hydrogen by a methylcar-
bamoyl group, via the isocyanate. The reaction has been pictured as a direct oxidation process.
Yields are fairly low (<20%).
E. PYrIDINaTIoN
Nitrogen bases (e.g., amines) are not generally good nucleophiles for anodic substitution
reactions, as they are themselves easily oxidized (see Chapters 28 and 34). Pyridine bases,
which are difficult to oxidize (E p = 1.4 V vs. Ag/Ag+ [98]), provide exceptions. The vinylic
proton of the very easily oxidized tris(p-methoxyphenyl)ethylene may be substituted anodi-
cally by pyridine to give the corresponding pyridinium ion [99], and similarly, the oxidation of
1,2-dimethoxybenzene in MeCN containing pyridine resulted in the formation of the substitu-
tion product, 3,4-dimethoxyphenylpyridinium ion [100]. In contrast, the oxidation of 1,2-dime-
thoxy-4-prop-1-enylbenzene under the same conditions leads to the formation of a dipyridinium
salt resulting from the addition of pyridine over the side-chain C–C double bond [100]. This
is in analogy to the addition of pyridine over the 9,10-positions in anthracene derivatives
[101–103]. Anodic pyridination of 2,6-di-tert-butyl-4-methylphenol in MeCN gives a mixture
of the corresponding 4-pyridinated cyclohexadienone and the side-chain pyridinated phenol
[104]. The anodic pyridination of Schiff’s bases and N-methyl-4-methoxybenzanilide [105] has
been reported and investigated in detail.
The reaction has been put to good preparative use for the formation (yield ~50%) of some hetero-
cyclic zwitterions [106a], with the leaving group being a carbocation rather than a proton:
N N
+N
Slow
OH O O– (19.37)
–2e–, –H+ + –(CH3)3C+
OCOCH3 OCOCH3 OCOCH3

Anodic pyridination of the magnesium (II) porphine in Equation 19.38 [106], at controlled poten-
tial, is regioselective resulting in meso-functionalization. Cyclic voltammetry allowed identification
of the radical cation that underwent rapid chemical reaction with pyridine with subsequent one-
electron oxidation (eCe-type mechanism). Similar meso-functionalization is obtained [106] with
Ph3P as nucleophile and 2,6-dimethylpyridine as base.
2 PF6–
N N N N N
+
Mg
0.72 V vs. SCE, –2e–
Mg N + (19.38)
N N N N N
pyridine, 0.1 M Bu4NPF6 H
77%
An unusual application of electrochemical pyridination is the postfunctionalization of poly(3-

hexylthiophene) with pyridine derivatives [107]. It is believed that this type of process will open
new ways to tuning the electronic band structure of conjugated polymers.
F. N-HETEroCYCLIC CoMpoUNDS aS NUCLEopHILES

Anodic oxidation of, for example, 1,4-dimethoxybenzene in an undivided cell containing a tetrazole
or triazole derivative together with the corresponding anion leads to the formation of the substituted
product, presumably through the mechanism shown in Equation 19.39 [108]. A variety of azoles
have been used in similar reactions with 1,4-dimethoxybenzene [109].
N
N– N
–– –
OCH3 OCH3 N– OCH3

N N
– –
N
N H
–e–
OCH3 OCH3 OCH3

(19.39)
N
N–
–– –
N OCH N– N–– N OCH3

3 N
–
N N
– –
N
–
H N
N N N
+ + NH
–e– N
OCH3 OCH3

Adenine has been used as a nucleophile in reactions with the dibenzo[a,l]pyrene radical cation
with the aim of investigating the role of radical cations of polycyclic aromatic hydrocarbons in the
tumor initiation [110]. Substitution took place in the 10-position of dibenzo[a,l]pyrene with adenine
behaving as an ambident nucleophile. The major product (47%) resulted from attack through the
adenine 1-position:
NH2
N N DMF
+ (19.40)
N N –2e–, –2H+
N NH 2
H
N
N
N
IV. FORMATiON Of CARBON-TO-OxYGEN BONDS

A. HYDroXYLaTIoN
The possibility of the direct introduction of a carbon-to-oxygen bond in a substitution process, for
example, an anodic hydroxylation, is of considerable preparative interest, since in principle cheap
starting materials could be used. Consequently, it would be possible to prepare phenols using only
hydrocarbon, water, and current in the process, Equation 19.41. However, apart from the practi-
cal problems associated with this type of process, there are theoretical grounds why this reaction
should not be feasible in general.
H2O
Ar H Ar OH (19.41)
–2e– , –2H+
In this case, the starting material is considerably more difficult to oxidize than the product;
under comparable conditions, benzene is oxidized at a potential ca. 1.3 V higher than phenol.
Consequently, it is observed that the reaction usually cannot be stopped at the phenol stage but pro-
ceeds to benzoquinone [111]. Similarly, the oxidation of 9,10-dihaloanthracenes leads to anthra-
quinone in an addition–elimination reaction [112]. However, the problem may to some extent be
overcome if the degree of substrate conversion is kept low (e.g., the anodic oxidation of phenol to
hydroquinone [113]) or if the oxidation product is continuously removed (e.g., the indirect oxida-
tion of methylarenes to the corresponding carbonyl compounds [114]). In other cases, such as the
anodic hydroxylation of fluorenone to 2-hydroxyfluorenone [115], the product partially survives
further oxidation.
In nonaqueous solvents, water is an impurity that on a preparative scale even rigorous drying
fails to remove completely [116]. Hydroxylation products are, therefore, common by-products. An
example is the oxidation of alkylaromatic compounds in a nominally anhydrous solution of MeCN/
NaClO4, Equations 19.42 and 19.43, which gives mainly the product of acetamidation [54–56] (see
Section III.A). The side reaction gives the corresponding benzyl alcohol, and its oxidation prod-
uct, the aldehyde, similar to what is observed when diphenylmethane derivatives are oxidized to
the corresponding ketones [117]. Recently, it was demonstrated that toluenes and alkenes could be
oxidized to the corresponding benzyl alcohols and 1,2-diols without overoxidation by trapping the
intermediate carbocations with DMSO; the resulting alkoxysulfonium ions were hydrolyzed to the
alcohols in a subsequent step [118].
Ar CH2OH (Ar CHO) (19.42)

H2O
+
–H
Ar CH3 Ar CH2+
–2e–, –H+
CH3CN
+ H2O
Ar CH2N CCH3 Ar CH2NHCOCH3 (19.43)
–H+
Related to these reactions is the anodic hydroxylation of 1-carbomethoxy-1,2,3,4-tetrahydrocarba-

zoles to the corresponding 1-hydroxy-1-carbomethoxy-1,2,3,4-tetrahydrocarbazoles in MeCN/H2O
mixtures [119].
The anodic hydroxylation of phenols at PbO2 in aqueous H2SO4 has been studied in detail [120].
Substitution is invariably at the 4-position to give benzoquinones; if the 4-position is already occu-
pied, then 4-substituted-4-hydroxycyclohexa-2,5-dienones are formed, for example, as shown in the
following:
OH O
CH3 CH3
H2O
–2e–, –2H+
(19.44)
HO CH3
CH3
The reaction may sometimes be preparatively useful, for example, 4-allyl-phenols give good yields of
4-allyl-4-hydroxycyclohexa-2,5-dienones. Similarly, mesitylene is converted to 2,4,6-trimethyl-4-
hydroxycyclohexa-2,5-dienone upon anodic oxidation in a mixture of H2O, MeCN, and H2SO4 [121].
Anodic hydroxylation of quinones, substituted at the 2-position with an electron-withdrawing
group, may be achieved at low potentials in aqueous solution [122]. In this case, it is likely that
nucleophilic attack is on the intermediate quinone:
OH O OH O
X X X X
H2O
–2e–, –2H+
(19.45)
–2e–, –2H+
OH OH
OH O OH O
Anodic hydroxylation of furans provides a high-yield route to substituted maleic anhydrides,

Equation 19.46 [123].
R R R R R R
2 H2O
(19.46)
–2e–, –2H+ HO OH –2e–, –2H+ O O
O O O
The introduction of a hydroxy group in an aliphatic compound already containing a simple oxygen
function, for example, an ether, does not affect the oxidation potential significantly. Consequently,
the products of anodic hydroxylation of aliphatic ethers may survive the conditions necessary
for the oxidation of substrate. For example, tetrahydrofuran has successfully been converted to
2-hydroxytetrahydrofuran by anodic oxidation in 1 M H2SO4 at Pt, Equation 19.47 [124]. However,
the hydroxylation of diisoalkyl ethers results in highly oxidized products such as ketones and acids.
H2O
–2e–, –2H+ OH
(19.47)
O O
B. ALkoXYLaTIoN (METHoXYLaTIoN)
Alkoxylation may be achieved by anodic oxidation in an alcohol, most often MeOH, containing a
suitable electrolyte, such as KOH, NaOMe, NaCN, NaBF4, or NH4NO3 [7–10].
Methanolic electrolytes have been shown to undergo oxidation at lower potentials than many
aromatic substrates, which may indicate that in some cases, an indirect mechanism operates in the
α-methoxylation of, for example, toluene, ethylbenzene, and cumene [125]. Further support for the
indirect mechanism is indicated by the fact that α-methoxylation of tetralin in MeOH/NaCN takes
place at potentials as low as 0.5 V versus SCE, whereas the half-wave potential, E1/2, of tetralin must
be around 1.9 V [126].
The nature of the anion present greatly affects the yield of α-methoxylation product, the effec-
tiveness decreasing in the series F− ≈ ClO4 – > CN– ≈ OH– > Cl– ≈ CH3O – > Br –. The mechanistic
possibilities are given in the following:
CH3OH CH2OH or CH3O– CH3O (19.48)

–e–, –H+ –e–
RH + X R + HX (X = CH2OH or CH3O ) (19.49)
R R+ (19.50)
–e–
R + CH3O
and/or
ROCH3 (19.51)
R+ + CH3OH –H+

One would not expect F– or ClO4 – to be oxidized under the conditions used, which suggests that
MeOH might be the electroactive species, forming a radical intermediate that then functions as X•
•
in Equation 19.49. The radical CH2OH is the most likely candidate since the O–H bond in MeOH is
much stronger than the C–H bond. In alkaline medium, MeO – is probably the electroactive species,
and MeO• would then be X•.
Allylic methoxylation is often the result of anodic oxidation of alkenes and dienes in methanolic
media [127,128]. Cyclopropanes behave similarly [129]. The reactions are usually accompanied by
products of addition and combination as shown in Scheme 19.1 although even more complex reac-
tion mixtures may result.
The same is true for the methoxylation of styrenes [130] and stilbenes [131]. The yields for allylic
methoxylation are only moderate (ca. 25%) and compare unfavorably with those for the analogous
allylic acetoxylation (see following text) [132].
The methoxylated products that result from substitution of aromatic hydrocarbons are as the
rule more easily oxidized than the starting materials, and for that reason, the reaction usually
leads to mixtures of di- and trimethoxylated products as observed, for example, for naphthalene
[133]. Exceptions are the methoxylation of anthracene [134] that results in the substitution–addition
product (~20%), Equation 19.52, and of acenaphthylene [135] that results in the addition product
(60–80%, mixture of cis- and trans-isomers), Equation 19.53:
H3CO OCH3
CH3OH
–6e–, –6H+ (19.52)
H3CO OCH3

R1 R2
–e–
R1
x2
R2 R1 R2 R1 R2
R2 –2H+ + –H+
R1
CH3OH –H+ –e–
x2
2CH3OH
R1 R2
R1 OCH3 OCH3 +
R2 x2
R1 R2
R2 CH3OH –H+
CH3O R1
CH3OH –e–, –H+
R1 R2
OCH3
OCH3
R1 R2
OCH3
(+ Isomers)
SchEME 19.1 Oxidation of alkenes in methanol—products and pathways.
H3CO OCH3
CH3OH (19.53)
–2e–, –2H+

As mentioned earlier, the methoxylation of alkylbenzenes to the side-chain-substituted products

appears to proceed via in an indirect mechanism, and it is (still) not easy to predict the combination
of substrate concentration, conversion, and supporting electrolyte that result in the maximum yield
of product. This is illustrated by a careful study [136] of the methoxylation of 1,3-diisopropylbenzene
that with potassium bromate as supporting electrolyte gives 1,3-bis(2-methoxypropan-2-yl)benzene
in 80% isolated yield:
CH3OH H3CO OCH3

(19.54)
KBrO3, i = 40 mA

Attempted direct anodic methoxylation of substituted 2-methyl and 2-benzylnaphthalenes results in

dimerization for electron-rich derivatives and in nuclear substitution, in the 6-position, for electron-
poor derivatives. Only traces of side-chain oxidation were found [137]. However, indirect oxida-
tion, Equation 19.55, with DDQ mediation results in clean conversion (70%) and on a preparative
scale into the corresponding carboxaldehyde or ketone [137]. The conversion of 2-methoxy-6-
methylnaphthalene into the carboxaldehyde is important because it is potentially an intermediate
for the preparation of the nonsteroidal anti-inflammatory drug naproxen.
Undivided cell, graphite electodes
CH3 constant current CHO
aq. HOAc, Et4NOTs, 80°C
CH3O DDQ CH3O 70% (19.55)
–2e–, –2 H+
DDQH2

The products of methoxylation of phenols are usually further oxidized under the reaction conditions
used [104,138]. Experimental conditions can be found, however, which in some cases allow selec-
tive formation of para-methoxylated dienones, ortho-methoxylated dienones, or dimeric products.
It is believed that methoxylation involves attack of MeOH on anodically generated phenoxylium
ions, whereas dimeric products arise by combination of phenoxyl radicals:
Dimers
OH O
–e–, –H+ O O O (19.56)

H
–e– CH3OH
+ + OCH3
–H+
H OCH3

The methoxylation of anisoles [139–150] and other alkoxybenzenes [146], methoxynaphthalenes

[139], and methoxyanthracenes [143,147] has received considerable attention. For the oxidation of
alkylanisoles in MeOH containing various electrolytes [140], the current–potential curves support
the scheme given, for p-methylanisole in the following:
+OCH
3 CH3O OCH3
CH3OH
+ –H+
OCH3 OCH3 H3C OCH3 H3C OCH3
CH3OH
–e–, –H+
–e– (19.57)
CH3 CH3 –H+, –e– OCH3 OCH3
CH3OH
–H+
CH+2 CH2OCH3

The oxidation of 1,4-dimethoxybenzene in MeOH to yield the corresponding quinone bisketal,

Equation 19.58, is the prototype example of the numerous related 1,4-addition reactions that may be
accomplished electrochemically [139–148]:
OCH3 CH3O OCH3

2 CH3OH
–2e–, –2H+
(19.58)
CH3O OCH3
OCH3
Thioanisoles behave differently, and usually sulfonium ions result from oxidation. However,
substitution reactions are favored in the presence of a silica-supported base and when electron-
withdrawing groups are present in the α-position [151]:
0.1 M NaClO4, CH3OH

Base OCH3
S S (19.59)
CHF2 Undivided cell CHF2

Additions similar to those reported for methoxy-substituted aromatic compounds are observed also
for vinyl ethers, Equation 19.60 [152,153], inden-1-one [154], furans [155,156], thiophenes [157], and
pyrroles [158]:
RO 2CH3OH RO
(19.60)
–2e–, –2H+ CH O OCH3
3
In contrast, methoxylation of N,N-dimethylaniline in MeOH/KOH leads predominantly to side-

chain substitution [159,160] most likely according to the following mechanism:
+ H3C CH2 H3C CH2+ H3C CH2OCH3

N(CH3)2 N(CH3)2 N N N
(19.61)
CH3OH
–e– –H+ –e– –H+

N,N-Dimethylbenzylamine [161,162], 2,4,6-tris(dialkylamino)-1,3,5-triazines [163], N-(2,2,2-

trifluoroethyl)amines [164,165], and N-(2,2-difluoroethyl)amines [165] exhibit similar behavior.
Methoxylation of enamines results in substitution at both the vinylic and the allylic posi-
tions [153], whereas methoxylation of imines and the related oxazolines gives rise to α-substituted
products [166]. Oxidation of anilides such as N-benzyl-4-methylaniline in 5% aqueous methanol
in the presence of sodium bicarbonate affords 4-methoxy-4-methylbenzoquinol N-benzoylimine
and a dimer, 4-[N-benzoyl-N-(4-methylphenyl)amino]-4-methylbenzoquinol N-benzoylimine [167]:
O
O O
NaHCO3
H– LiClO4 N
N N
CH3OH
+
O
(19.62)
H3C
H3C OCH3 N
CH3
CH3

Another reaction that has attracted considerable attention is the alkoxylation of N,N-dialkylamides
and related compounds [168–184]. A typical example is the oxidation of N,N-dimethylamides in
ROH/NH4NO3 [169]:
O CH3 O CH3
R2OH R1 = H, CH3, C6H5
R1 C N R1 C N (19.63)
CH3 –2e–, –2H+ CH2OR2 R2 = CH3, CH3CH2, CH3CH2CH2CH2

The use of a nitrate salt results in better yields and cleaner reaction than is observed with NaOR.
A mechanism involving initial discharge of NO3– to form NO3•, which then abstracts a hydrogen
atom from one of the N-alkyl groups, is considered the most likely one in this case. When, for exam-
ple, NaOMe is used as supporting electrolyte, the reaction most likely involves the substrate radical
cation as the primary intermediate followed by deprotonation and oxidation to the corresponding
carbocation, which finally reacts with methanol. In this context, it is of interest to notice that the
intramolecular alkoxylation expected for the series of hydroxyamides shown in Equation 19.64,
n = 0−4, did not take place in MeCN; only polymeric material was formed [170]. When the reaction
was instead carried out in MeOH, only the normal methoxylation products were formed, Equation
19.65. These, however, could easily be converted to the cyclized products by addition of acid.
H3C O H3C O
CH3CN
N C N C
H3C H2C (19.64)
–2e–, –2H+
n n
HO O
H3C O H3C O
N C CH3OH N C
H3C CH3OCH2 (19.65)
–2e–, –2H+
n HO n
HO
Numerous examples of the application of this synthetically useful reaction have been reported.
Illustrative examples include the synthesis of eneamides and enecarbamates [171,172] and a large
series of pyrrolidine, piperidine, and perhydroazepine derivatives [171,173–176].
Attempts to methoxylate smaller ring systems like N-acetylaziridine and N-formylazetidine
failed and resulted in ring-opened products [177].
Methoxylation lends itself well to operation on a relatively large scale [178–182]. For instance,
several N-formyl derivatives have been anodically methoxylated on a 0.5 kg scale using a capillary
gap cell with a graphite anode [179,181]. An example is given in Equation 19.66. Polyalkoxylation of
N,N-dimethylformamide has also been achieved [180].
O O
CH3OH (92%) (19.66)
N 8.4 F N OCH3
CHO CHO
The selectivity and stereochemistry of the anodic methoxylation of the cyclic amides are notewor-
thy. First, N-formyl-2-methylpiperidine gives the 6-methoxy-substituted product in spite of the fact
that loss of the proton in the 2-position would give a tertiary carbocation, which intuitively would
be expected to be the more stable intermediate. Second, 4-substituted N-formylpiperidines give the
corresponding 2-methoxy derivative with the methoxy group occupying an axial position [184].
Both these experimental facts were attributed to the steric constraints imposed by the N-formyl
group. A good example of the selectivity is shown in Equation 19.67; the methoxylated product
could be cyclized to the bicyclic amide by reaction with TiCl4 in CH2Cl2 [183]:
R O R O R O
N CH3OH, CH3CN N TiCl4, CH2Cl2 N

n n n (19.67)
–2e–, –2H+
Cl
OCH3
Cyclic amides carrying a carboxylic acid group in the α-position to the nitrogen atom have been
observed to undergo a non-Kolbe-type substitution reaction by oxidation in methanol [185,186], for
example, with silica-supported piperidine as the base [185]:
Si N
H3C O H3C O (19.68)

CH3OH
N COOH N OCH3
4F

The anodic methoxylation of amides is not restricted to simple formic and AcOH derivatives,
but has been performed also with peptides, Equation 19.69, [187], N-substituted carbamates
[188–190], and cyclic derivatives such as N-(methoxycarbonyl)pyrrolidines [135c,190–192],
N-methoxycarbonylpiperidines [190,193,194], and oxazolidin-2-ones [195–197]:
H O H O OCH3
N CH3OH N OCH3
OCH3
Boc N –2e–, –2H+ Boc N (19.69)
H O H O

The prototype reaction [188] for methoxylation of a carbamate is shown in Equation 19.70, and the
applicability is further illustrated by the examples given in Equations 19.71 [191], 19.72 [194a], and
19.73 [196]. It is seen that the stereochemical configuration of the starting material is preserved in
all cases.
O CH3 O CH3
CH3OH
RO C N RO C N (19.70)
CH3 –2e–, –2H+ CH2OCH3

CH3OH
N COOCH3 CH3O N COOCH3 (19.71)
–2e–, –2H+
COOCH3 COOCH3
CH3COO CH3COO
OCOCH3 OCOCH3
CH3OH
N –2e–, –2H+ N (19.72)
CH3O
COOCH3 COOCH3
O O
HN O CH3OH HN O trans/cis = 8/1 (19.73)

–2e–, –2H+
CH2OH CH3O CH2OH

The presence of α-silyl [198] or α-phenylthio [199] groups activates carbamates toward oxidation by
500–600 mV and results in regioselective introduction of a methoxy group at the α-carbon carrying
the activating substituent:
O O
C C
N OCH3 CH3OH N OCH3 (19.74)
X = Si(CH3)3, SPh
X 2–3 F OCH3

In all the examples given so far, the substrate carries at least one N-α-hydrogen atom. The anodic
oxidation of fully substituted amides, like N,N-di-tert-butylformamide and N-formyl-2,2,6,6-
tetramethylpiperidine, in MeOH would be expected to follow a different pathway. The products isolated
after 12–14F, methyl N-tert-butylcarbamate and N-methoxycarbonyl-2,2,6,6-tetramethylpiperidine,
respectively, Equation 19.75 [200], indicated that the primarily formed substrate radical cation loses
the formyl proton. Further oxidation of the neutral radical leads to the cation, which may either
undergo cleavage, Equation 19.76, or nucleophilic attack by the solvent, Equation 19.77:
(CH3)3C (CH3)3C +
N CHO N C O (19.75)
(CH3)3C –2e–, –H+ (CH3)3C

(CH3)3C N C O 2CH3OH (CH3)3C NHCOOCH3

(CH3)3C + (CH3)3C+ –H+ (CH3)3C OCH3 (19.76)
N C O
(CH3)3C CH3OH
(CH3)3C
NCOOCH3 (19.77)
(CH3)3C
Sulfonamides [201,202], sulfinylamines [203], and amidophosphates [201,204] have been used as
starting materials as well.
Saturated ethers, for example, 1,4-dioxane, can be α-methoxylated by electrolysis in MeOH/
NaOMe or MeOH/NH4NO3 in 10–30% yield, Equation 19.78 [205]. Yields are considerably higher,
45–70%, for the heterocyclic 1,3-benzodioxoles [206].
O O
CH3OH
(19.78)
–2e–, –2H+
O O OCH3

Related to these reactions is the anodic methoxylation of sulfides carrying an electron-withdrawing

substituent, for example, cyano [207], fluoromethyl [208], difluoromethyl [208], or trifluoromethyl
[208,209] in the α-position, Equation 19.79, and the fluoride-mediated methoxylation of thiazoli-
dines, 1,3-oxathiolanes and 1,3-dithiolanes [210]. An analogous reaction has been reported for
selenides carrying electron-withdrawing perfluoroalkyl or cyano substituents [211].
CH3OH
Ar S CH2 X Ar S CH X X = CN, CH2F, CHF2, CF3 (19.79)
–2e–, –2H+
OCH3
In analogy with what has been observed for carbamates, the trimethylsilyl substituent in, for exam-
ple, 1-phenylthio-1-trimethylsilylalkanes is easily replaced by methoxy during anodic oxidation in
MeOH [212,213]. Similarly, the anodic oxidation of α,α′-bis(trimethylsilyl)xylenes in MeOH results
in replacement of one trimethylsilyl group by methoxy [214].
C. ACYLoXYLaTIoN (ACEToXYLaTIoN)
Substitution by an acyloxy group can be accomplished by electrolysis of a variety of organic com-
pounds in the presence of a carboxylate in a suitable solvent. The most commonly encountered
process is acetoxylation that takes place in AcOH or AcOH/Ac2O. The supporting electrolyte in this
case normally is NaOAc, although Me4NNO3, Bu4NBF4, NaClO4, and others can be employed in
special cases. Other acyloxylations using carboxylates whose corresponding acids cannot be used
as solvent may be performed in DMF or MeCN. For trifluoroacetoxylation (see following text), a
variety of relatively deactivated aromatic substrates or aliphatic compounds may be employed.
Acetoxylation of alkenes takes place in the allylic position [132,215,216] concurrent with addi-
tion of acetoxy groups across the double bond or double-bond system. The mechanism is almost
certainly analogous to that shown in Scheme 19.1 for methoxylation. Because AcO – is difficult
to oxidize, the anodic discharge of simple, unactivated alkenes may be achieved in its presence.
Subsequent reactions of the cationic intermediates are not very selective, but several experimental
parameters may be controlled, and the method can compare well with the few competing chemi-
cal methods.
The oxidation of n-alkanes is possible in CF3COOH containing R4NBF4 with the carbocations
so formed being trapped to give secondary trifluoroacetates [66,217,218]. Anodic trifluoroacetox-
ylation of long-chain aliphatic ketones [219] or carboxylic acids [217] gives rise to mixtures of
positional isomers. The substitution pattern for the ketones indicates that the reaction proceeds
via intramolecular abstraction of a hydrogen atom from the 5-position by the carbonyl group. This
reaction has been observed to take place during the oxidation of aliphatic ketones in MeCN (see
previous text). The trifluoroacetoxylation of carboxylic acids is less selective, and the product distri-
bution gives little indication of the mechanism.
The yields of acetoxylation products for aromatic and alkylaromatic compounds vary greatly
[3,7–10,220–222], depending on the oxidation potential of the product(s) formed. As a general rule,
they tend to be low in nuclear acetoxylation of aromatic compounds and fair to good in acetoxyl-
ations at activated C atoms.
A characteristic feature of the reaction is that nuclear acetoxylation of aromatic compounds
requires the presence of AcO – [223], whereas acetoxylation of the other types of substrates takes
place with either AcO – or other anions present [132,169,224]. Both nuclear and side-chain acetoxyl-
ation may be rationalized according to the general mechanism given in the following:
CH2 CH2+ CH2OCOCH3

CH3 COO–
+ –e–
CH3 CH3
–H+
–e– (19.80)
CH3 CH3 CH3
CH3COO–
–e– +
–H+
H OCOCH3 H OCOCH3 OCOCH3
(+ ortho isomer)
In the context of the direct mechanism, several perplexing features concerning nuclear and side-chain
substitution of aromatic compounds have been highlighted [225], and in the search for explanations,
attempts have been made to estimate, by thermochemical calculations, free energies of activation
for reactions between radical cations and nucleophiles. Long-standing puzzles in this area include
the dependence of the ratio of side-chain-/nuclear-substituted products on the nucleophile; for alkyl-
benzenes, side-chain acetoxylation predominates in AcOH unless AcO – is present, when nuclear
substitution becomes important.
The isomer distribution for anodic acetoxylation of a number of monosubstituted benzenes has
been determined [223]. The reaction closely resembles ordinary electrophilic aromatic substitution
processes, perhaps on the side of low-selectivity reactions. The deuterium kinetic isotope effect,
k H/k D, for nuclear acetoxylation in anisole was found to be 1.0, whereas for α-substitution in ethyl-
benzene, a value of 2.6 was observed. The interpretation of these values is not straightforward [225].
From a preparative point of view, it is of interest to notice that selective nuclear substitution may
be obtained when the oxidation is carried out in an undivided cell using a cathode made of Pd/C
[220]. With this experimental setup, the side-chain acetoxylated product is reduced back to starting
material at the cathode. The nuclear-substituted product is unaffected and will accumulate during
the electrolysis.
Acetoxylation of 1,4-dimethoxybenzene results in the ortho-substituted product [226]:
OCH3 OCH3
CH3 COO– OCOCH3
–2e–, –2H+
(19.81)
OCH3 OCH3
Aromatic compounds, in particular those carrying electron-withdrawing substituents, may be

oxidized in the presence of CF3COO − with consequent trifluoroacetoxylation [63,227–234]. For
compounds PhX, X may be (CH3)3C, COOMe, NO2, CF3, COMe, COPh, and CN; the trifluoroace-
toxy derivatives produced by anodic oxidation in CH2Cl2/CF3COOH/Et4NBF4 [224], CF3COOH/
CF3COONa [228], or CH3NO2/CF3COOH [229] are hydrolyzed during work-up to phenols. Yields
of the phenols so produced are in the region 20–80%, and usually, substantial amounts of the
meta-substituted phenols are formed. For chlorobenzene, prolonged electrolysis in CF3COOH/
CF3COONa, followed by hydrolysis, leads to good yields of the corresponding resorcinol and pyro-
catechol derivatives [230].
A number of intramolecular acyloxylations have been reported [235–243], two examples of
which are given in the following:
HO CH2CH2COO– O (19.82)
–2e–, –H+
O O

–O CH3OH
O (19.83)
–2e–, –H+ O O
CH3O

The α-acyloxylation of N-alkyl-substituted amides has received attention [169,174,244] from both
mechanistic and preparative points of view. In electrolytes containing alkali metal carboxylates, the
direct mechanism probably operates, whereas in case where a nitrate salt is the supporting electro-
lyte, an indirect mechanism involving hydrogen abstraction from the N-alkyl group by anodically
generated NO3• is indicated. Similarly, 1-(p-tolylsulfonyl)azetidine is converted to the correspond-
ing 2-acetoxy derivative by anodic oxidation in AcOH/AcONa, [245]:
CH3COOH OCOCH3
CH3COONa (19.84)
N N
Ts –2e–, –H+ Ts

Acyloxylation of a number of benzyl ethers has been reported, Equation 19.85 [246]. A hemiacetal
acetate is presumably formed and subsequently hydrolyzed during the work-up procedure to give
the aldehyde.
+ CH3COO– OCOCH3 H+, H2O

Ar CH2OCH3 Ar CHOCH3 Ar CH Ar CHO (19.85)
–2e–, –H+ OCH3
30–70%
Aryl alkyl sulfides and selenides containing an electron-withdrawing substituent such as trifluoro-
methyl in the α- or β-position may be α-acetoxylated in good-to-excellent yields [209,247–252]. In
the absence of the electron-withdrawing substituent, the yields are usually poor [209,247] and give a
mixture of the S-oxide and the α-acetoxylated product [252]. However, if the oxidation is carried out
in boiling AcOH/Ac2O/AcONa, the corresponding α-acetoxy derivatives may be obtained in almost
quantitative yields [252]. Under these conditions, the S-oxide, if formed at all, is converted to the
desired α-acetoxy derivative in a Pummerer reaction parallel to the direct electrochemical acetoxyl-
ation. This illustrates that reactions that at room temperature give rise to mixtures of products may
be synthetically useful when carried out at higher temperatures at which the thermodynamically
more stable products are formed.
D. NITraTE IoN aS NUCLEopHILE

Concurrent with side-chain acetoxylation of alkylaromatic compounds in AcOH/NH4NO3, the
formation of benzyl nitrates, ArCH2ONO2, is observed in about the same yield as the ArCH2OAc
[224,253,254]. It seems likely that NO3− and AcOH compete as nucleophiles for an intermediate
benzyl cation, although an indirect mechanism cannot be ruled out completely because of the
complexity of the supporting electrolyte behavior [255].
V. FORMATiON Of CARBON-TO-SULfUR BONDS

A. THIoLS aS NUCLEopHILES
Thiols are easier to oxidize than most organic substrates and can for that reason usually not be used
as nucleophiles in anodic substitution processes. An exception is the cooxidation of catechols and
2-mercaptopyrimidines that leads to fair-to-good yields of the corresponding substitution products
in reactions that most likely include the ortho-benzoquinones as intermediates [256]:
R3
N
R1 R1 SH R3 R1
R2 OH R2 O N R2 OH
–2e–, –2H+ N
(19.86)
OH O N S OH
B. THIoCYaNaTIoN
Phenols [6c], anisoles, Equation 19.87 [257], and aromatic amines [6c] are thiocyanated on elec-
trolysis in aqueous or acetic acid solutions containing SCN–. The reaction is indirect since there is
compelling evidence that the thiocyanating reagent must be (SCN)2, formed by anodic oxidation of
SCN– [258]. In MeCN solution, oxidation of SCN– and SeCN– in the presence of phenol or various
aromatic amines leads to thiocyanation and selenocyanation in 55–80% yields [259].
OCH3 OCH3
CH3COOH, SCN–
(~80%)
(19.87)
1.5–2.2 F

SCN
The direct reaction between a radical cation derived from an aromatic hydrocarbon (naphthalene)
and SCN− has been studied by mixing the salt (C10H8)2PF6 with a solution of Bu4NSCN in CH2Cl2
at −78°C [260]. Two major products were isolated: 1-naphthylthiocyanate (kinetic control, 28%)
and 2-naphthylisothiocyanate (thermodynamic control, 8%). The mechanistic details leading to this
product distribution are not clear.
VI. FORMATiON Of CARBON-TO-HALOGEN BONDS

A. FLUorINaTIoN
The virtually unique suitability of electrochemical methodology for preparing fluorinated com-
pounds warrants the inclusion of a separate treatment on this subject (Chapter 20).
B. CHLorINaTIoN aND BroMINaTIoN

The oxidation of chloride or bromide ions to the atomic or molecular halogen is relatively easy; con-
sequently, the mechanism of anodic halogenation, brought about by oxidation of organic substrates
in the presence of chloride [261–269] or bromide [270–274], is not always clear. In many cases, it
may involve halogenation by anodically generated halogen and thus, resembles conventional organic
halogenations. In other cases, where the substrate is easily oxidized, the halide plays the role of a
nucleophile and attacks a radical cation. Examples include the chlorination of alkenes [262,269]
and of aromatic hydrocarbons [261,268] and substituted derivatives such as 1,4-dimethoxy-2-tert-
butylbenzene [265] and aniline [263] as well as substituted azulenes, Equation 19.88 [267]. Anodic
chlorination has been used also for the postfunctionalization of poly(3-hexylthiophene) [275].
COOCH3 COOCH3
+ Cl–
–2e–, –H+ (19.88)
Cl
Similarly, successful brominations have been reported for, for instance, alkenes [273,274], aromatic
hydrocarbons [270], acetanilide [271], and acetylated d-glycals [272]:
OAc OAc OAc

Br
AcO O +2 Br– AcO O
+ AcO O
(19.89)
–2e– AcO AcO
AcO Br
Br Br
9:1
C. IoDINaTIoN
The oxidation of I2 in MeCN produces a very reactive although ill-defined iodine(I) species [75,276].
The production of this species, in either MeCN or CH2Cl2 in the presence of a variety of substituted
benzenes, results [276] in efficient iodination, for example, as shown in the following:
OCH3
CH3CN +
½ I2 “H3C C N I” I OCH3 90% (19.90)
–e– –H +
Formation of a C–I bond is also the result of anodic oxidation of, for example, iodobenzene in
the presence of benzene [277–279]. Two reactions are in competition, Equation 19.91; a careful
investigation of the electrode kinetics supports the mechanism given and also allows optimization
of conditions to the point where a 95% yield of the diphenyliodonium cation is obtained [278].
Hydrolysis of this species completes a route from benzene to phenol.
+
PhI or PhI Dimeric products
+
I I
–e– PhI (19.91)
–e–, –H+
+ H2O
I OH

Electrochemical oxidation of terminal alkynes in MeOH in the presence of NaI as supporting

electrolyte has been reported to result in the formation of the corresponding 1-iodo derivatives in
70–80% yield [280]:
CH3OH, NaI
R H R I (19.92)
–2e–
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20 Fluorination
CONTENTS
I. Introduction ...........................................................................................................................807
II. Selective Electrochemical Fluorination in Organic Solvents ................................................808
A. Anodic Fluorination of Aromatic Compounds..............................................................808
B. Anodic Benzylic Fluorination .......................................................................................808
C. Anodic Fluorination of Olefins ......................................................................................809
D. Anodic Fluorination of Aldehydes ................................................................................ 810
E. Anodic Fluorination of Organosulfur Compounds ....................................................... 810
F. Anodic Fluorination of Other Heteroatom Compounds ................................................ 811
G. Anodic Fluorination of Heterocyclic Compounds......................................................... 812
1. Anodic Fluorination of Heterocyclic Rings Having a Phenylthio Electroauxiliary .... 812
2. Anodic Fluorination at the Side Chain of Heterocyclic Sulfides ............................ 813
3. Anodic Fluorination of Heterocyclic Ring ............................................................. 814
III. Anodic Fluorination in Ionic Liquids.................................................................................... 816
A. Solvent-Free Anodic Fluorination ................................................................................. 816
B. Anodic Fluorination in Ionic Liquids Under Ultrasonication ....................................... 819
C. Double Ionic Liquid System for Anodic Fluorination ................................................... 820
D. Effects of Ethereal Additives on Anodic Fluorination .................................................. 820
IV. Anodic Fluorination of Macromolecules .............................................................................. 821
V. Indirect Anodic Fluorination ................................................................................................ 821
VI. Anodic Fluorination Using Alkali Metal Salts ..................................................................... 823
VII. Conclusion ............................................................................................................................. 823
References ......................................................................................................................................824
I. INTRODUcTiON
Organofluorine compounds are classified into two groups: perfluoro-compounds and partially fluo-
rinated compounds. The compounds in the former class are widely utilized as functional materials,
while those in the latter family find biological uses such as pharmaceuticals and agrochemicals.
Perfluoro-compounds are manufactured by converting all C–H bonds to C–F bonds using electro-
chemical fluorination in anhydrous liquid HF as a solvent with a nickel anode. This process was
developed more than 60 years ago. Later, electrochemical perfluorination in a KF–2HF melt at a
carbon anode was developed for the preparation of perfluorinated low-molecular-weight organic
compounds [1]. Both of these processes are now used commercially.
In contrast, selective electrochemical fluorination is a rather new field and methodology, but it
has not been well developed because of low reaction selectivity, the low nucleophilicity of fluo-
ride ions, and competitive anode passivation (the formation of a nonconducting polymer film on
the anode surface that suppresses faradaic current). The fluorination can be commonly achieved
in aprotic solvents (acetonitrile, dichloromethane, dimethoxyethane [DME], nitromethane, sulfo-
lane, etc.) containing fluoride ions to provide mostly mono- and/or difluorinated products [1–4].
Electrolyses are conducted at constant potentials slightly higher than the first oxidation potential of
807
the substrate by using a platinum or graphite anode. Constant current electrolysis is also effective
for selective fluorination in many cases. The choice of the combination of a supporting fluoride salt
and an electrolytic solvent is most important to accomplish efficient selective fluorination because
competitive anode passivation takes place very often during the electrolysis. Pulse electrolysis is in
many cases effective in order to avoid such passivation. Therefore, difficult-to-oxidize fluoride salts,
which do not cause the passivation of the anode and have strongly nucleophilic F−, are generally
recommended as the supporting fluoride salts. Thus, room temperature molten salts such as R3N-
nHF (n = 3–5), R4NF-nHF (n = 3–5), and 70% HF/pyridine (Olah's reagent) are most often used and
even R4NBF4 and R4NPF6 salts are effective in some cases [1–4]. Particularly when HF supporting
salts and low hydrogen overpotential cathodes such as platinum are used, the reduction of pro-
tons (hydrogen evolution) occurs predominantly at the cathode during the electrolysis. Therefore, a
divided cell is not always necessary for the fluorination under such conditions.
In aprotic solvent, F− becomes more nucleophilic; however, the reactivity of F− is quite sensitive to
the water content of the electrolysis system because a hydrated F− is a weak nucleophile. Drying of both
the solvent and electrolyte is therefore necessary to optimize the formation of fluorinated products.
Since the discharge potential of the fluoride ion is extremely high (>+2.9 V vs. SCE [saturated
calomel electrode] at Pt anode in acetonitrile [MeCN]), the fluorination proceeds via a (radical)
cation intermediate as shown in Equation 20.1, which is the general pathway for anodic nucleophilic
substitutions.
F –e F
+R
R
F– H H –H+
–e
RH RH+ R F (20.1)
–H+ F–
–e
R +R
II. SELEcTivE ELEcTROchEMicAL FLUORiNATiON iN ORGANic SOLvENTS

A. ANoDIC FLUorINaTIoN oF AroMaTIC CoMpoUNDS
In 1970, Rozhkov et al. reported the first example of selective electrochemical fluorination of aro-
matic compounds such as benzene and naphthalene in MeCN containing the ionic liquid Et4NF-
3HF (Equation 20.2) [5]. Since that time, selective electrochemical fluorination of various aromatic
compounds such as benzene, substituted benzenes, anthracene, and 9,10-diphenylanthracene has
been accomplished similarly by constant potential anodic oxidation [1,2,6–10].
F F
+
–2e, –H
+ (20.2)
Et4NF-3HF/MeCN
1.8 V vs. SCE
F
27% 3%
B. ANoDIC BENZYLIC FLUorINaTIoN

Generally, anodic benzylic substitution reactions take place readily. However, anodic benzylic fluo-
rination does not always occur. The major competitive reaction is acetamidation when MeCN is
used as a solvent. Laurent et al. found that anodic benzylic mono- and difluorination proceeds selec-
tively when the benzylic position is substituted by electron-withdrawing groups (EWGs) (Equation
20.3) [11]. In these cases, p-methoxy or p-chloro substituents on the benzene are necessary for the
operation of efficient fluorination. In their absence, benzylic acetamidation becomes a major reac-
tion (Equation 20.4).
Fluorination 809
–2e, –H+ –2e,–H+

p-XC6H4CH2-EWG p-XC6H4CHF-EWG p-XC6H4CF2-EWG
Et3N-3HF/MeCN (36–73%) Et3N-3HF/MeCN (48–95%)
(20.3)
X = MeO, Cl
EWG = COAr, COOEt, CN, SO3Et
–2e, –H+ Ar COMe Ar COMe

Ar COMe +
F–/MeCN F NHCOMe (20.4)
Ar = Ph: 7% 34%
Ar = p-MeOC6H4: 69% <1%
In the case of anodic α-fluorination of toluene, ethylbenzene, and cumene in MeCN, the effi-
ciency of the fluorination is in the following order: cumene > ethylbenzene > toluene [12]. On the
other hand, the efficiency of acetamidation is reverse. Moreover, triphenylmethane is selectively
monofluorinated to provide fluorotriphenylmethane in high yield (80%) even in MeCN [13].
These facts suggest that the more stable benzylic cation intermediate reacts with fluoride ion
more efficiently.
C. ANoDIC FLUorINaTIoN oF OLEFINS

Anodic oxidation of olefins in the presence of fluoride ions provides mono- and/or difluorinated
products (Equation 20.5) [14–16].
R –2e R Y
Et3N-3HF/MeCN or AcOH
R1 F R1 (20.5)
Y = F, NHCOMe, OAc
Anodic fluorination of vinyl sulfides such as 2-(phenylthio)styrene provides vicinal difluorides [17].
1-Phenylhexene undergoes stereoselective difluorination and fluoroacetamidation upon anodic oxi-
dation in MeCN, while the difluorination predominates in the less nucleophilic solvent, dichloro-
methane (CH2Cl2) [18].
Recently, it was shown that nitromethane (MeNO2) significantly promoted electrochemical flu-
oro-selenenylation and iodofluorination of electron-deficient olefins such as α,β-unsaturated esters,
amides, and phosphonates (Equation 20.6) [19,20].
Me –2e Me Y
PhSeSePh or n-Bu4NI + Et3N-5HF/MeNO2
COOEt F COOEt (20.6)
Y = PhSe (quant.), l (75%)
Anodic fluorination of α-acetoxystyrene and 1-acetoxy-3,4-dihydronaphthalene provides the cor-

responding α-fluoroketones (Equation 20.7) [21,22].
OCOMe OCOMe O
F
R R R
–2e aq. NaHCO3
Et3N-3HF
F F (20.7)
R = H, Me
Yoshida et al. achieved anodic fluorination accompanied by carbon–carbon bond formation using
silyl, stannyl, or thio groups as electroauxiliaries (EAs) as shown in Equation 20.8 [23–25].
EA
O –2e O
Bu4NBF4/CH2Cl2 (20.8)
C7H15 C7H15 F
EA = MeS, Bu3Sn, Me3Si 50–98%

D. ANoDIC FLUorINaTIoN oF ALDEHYDES

Selective anodic formyl hydrogen-exchange fluorination of aliphatic aldehydes in Et3N-5HF/MeCN
provides the corresponding acyl fluorides in good yields as shown in Equation 20.9 [26]. In these
reactions, fluoride salts like Et3N-3HF lead to lower yields, reflecting the fact that this salt is dis-
charged prior to oxidation of the carbonyl group. In the case of aromatic aldehydes, the aromatic
ring is also fluorinated simultaneously.
O –2e O
R C H Et3N-5HF/MeCN R C F (20.9)
2.4–2.6 V vs. Ag/Ag+
R = 3-Heptyl: 89%
R = Cyclohexyl: 84%
R = tert-Butyl: 66%
E. ANoDIC FLUorINaTIoN oF OrGaNoSULFUr CoMpoUNDS

Fuchigami et al. and Laurent et al. independently found that anodic fluorination of sulfides is mark-
edly promoted by α-electron-withdrawing groups (EWGs) such as fluoroalkyl, ester, and cyano
groups to provide the corresponding α-fluorinated products in good yields as shown in Equation
20.10 [27–31]. This was the first successful example of selective electrochemical fluorination of
chalcogen compounds. The anodic fluorination is highly regioselective and widely applicable, even
though α-thio-substituted esters have several positions susceptible to substitution by a fluorine.
A fluorine is introduced exclusively α to the ester group, and no fluorination of the p-tolyl, benzyl,
or heptyl groups is observed (Equation 20.10) [31]. As shown in Equation 20.10, the electron-with-
drawing ability of the fluoroalkyl group does not affect the efficiency of anodic monofluorination
of sulfides. Even simple alkyl phenyl sulfides devoid of an EWG undergo fluorination in ethereal
solvents such as tetrahydrofuran (THF) and DME to provide monofluorinated products in moder-
ate yields [30].
–2e, –H+ F
R1 R1 (20.10)
S R2 Et3N-3HF/MeCN S R2
~88%
R1 = Ph, R2 = CF3 (62%); CF2H (53%); CFH2 (69%)

R1 = Ph, p-MeC6H4, PhCH2, C7H15
R2 = CH3, C CH, COOEt, CN, COMe, COPh, CONH2, PO(OEt)2

The fluorination proceeds by way of a Pummerer-type mechanism via the fluorosulfonium cation
(A), as shown in Equation 20.11 [28,30]. Thus, when R is an EWG, the deprotonation of A is signifi-
cantly facilitated, and consequently, the fluorination proceeds efficiently.
Fluorination 811
F–
H F–
–2e + +
PhS CH2R
F–
PhS CHR
–HF
PhS CHR PhS CHFR (20.11)
F
A
Since then, several groups have studied the selective electrochemical fluorination of various hetero-
atom compounds including heterocyclic compounds in organic solvents as follows. Simonet et al.
similarly performed regioselective anodic α-monofluorination in an Et3N-3HF/MeCN solution of
alkyl aryl sulfides, having an EWG on the aromatic ring [32].
Interestingly, anodic fluorination of α-thio α-arylesters provides fluorodesulfurization products
while that of α-thioacids provides fluorinated products accompanying decarboxylation as shown in
Me Me Me
–2e, –PhS+ –2e,–H+, –CO2
p-XC6H4 C COOEt p-XC6H4 C COOR p-XC6H4 C F
F– F–
F (R = Et) SPh (R = H) SPh (20.12)
55–84% 65–70%
X = Cl, MeO, Me2CHCH2

F. ANoDIC FLUorINaTIoN oF OTHEr HETEroaToM CoMpoUNDS

Anodic α-monofluorination of selenides bearing α-electron-withdrawing cyano and ester
groups can be performed in Et3N-3HF/MeCN using an undivided cell, while the fluorination of
α-selenoacetoamide requires an anion-exchange membrane diaphragm (Equation 20.13) [34].
–2e, –H+
PhSeCH2R PhSeCHFR (20.13)
Et3N-3HF/MeCN
R = CN, COOEt, CONH2 (60–70%)

In contrast, anodic oxidation of organotellurium compounds in the presence of fluoride ions results
in difluorination at the tellurium atom predominantly in excellent yields and with high current effi-
ciencies (Equation 20.14) [35]. In this case, α-fluorination does not occur.
F
–2e
Ph Te R Ph Te R
Et3N-3HF
(20.14)
F
75–86%
R = Me, CHF2, CH2CF3, PH

Anodic oxidation of tetra-alkylsilanes in the presence of fluoride ions provides the corresponding
fluorosilanes derived from cleavage of the C–Si bond [36]. Becker and Shakkour found that anodic
oxidation of cyclic peralkylsilanes results in the formation of α,ω-difluorosilanes via Si–Si bond
cleavage (Equation 20.15) [37].
Pr Pr
Pr Pr Pr
Si Pr –2e Pr Pr Pr
Si Si Pr Pr
Si
Pr Et Si Si + Si Si (20.15)
Si Si Pr 4NBF4 Pr Pr Pr Pr
Pr F F F F
Pr Pr
30% 54%
Anodic fluorination of ethers such as DME and diethyleneglycol dimethylether results in mono-
fluorination at the terminal carbon selectively, while that of crown ethers undergoes carbon–carbon
bond cleavage preferentially on fluorination to provide the α,ω-difluorinated products in good yields
(Equation 20.16) [38,39].
O O –2e, –H+ O O F
O O
n F– n (20.16)
n = 0 (62%), 1 (55%)
Anodic fluorodeiodination of alkyl iodides provides the corresponding alkyl fluorides chemoselec-
tively (Equation 20.17) [40].
–e, –1/2 l2
R–l R–F (20.17)
F–
72–85%
R = Me(CH2)3, AcO(CH2)10,
Cl(CH2)10, MeCO(CH2)10
Anodic oxidation of benzophenone hydrazone in Et3N-3HF/CH2Cl2 gives mainly diphenylmono-

fluoromethane (Equation 20.18) [41].
Ph F H F F
–ne +
NNH2
Et3N-3HF/CH2Cl2 Ph Ph Ph Ph (20.18)
Ph
95% 3%
Anodic oxidation of organic compounds containing group 15 elements in the presence of fluoride
ions provides the corresponding fluorinated products (Equation 20.19) [42]. Fluorination occurs at
the heteroatoms selectively.
Ph Ph F
–2e Y
Y Ph F
Ph Ph Et3N-3HF
Ph
(20.19)
Y = P, Sb
G. ANoDIC FLUorINaTIoN oF HETEroCYCLIC CoMpoUNDS

Partially fluorinated heterocycles very often show unique and pronounced biological activities,
they are essential for development of new types of agrochemicals and medicines. However, limited
examples of selective anodic fluorination of heterocycles have been reported [43–46]. These pro-
cesses are limited to only nitrogen- and oxygen-containing heterocycles, and the yields are gener-
ally quite low. In addition, no successful anodic fluorination of sulfur-containing heterocycles has
been reported until 1991. Fuchigami et al. have developed conditions for highly selective anodic
fluorination reactions of various heterocyclic compounds [3,4].
1. Anodic Fluorination of Heterocyclic Rings Having a Phenylthio Electroauxiliary

Heterocyclic compounds having a phenylthio group as an electroauxiliary are selectively oxidized
to result in regioselective α-fluorination. Thus, various α-phenylthio lactones and lactams includ-
ing β-lactams can be anodically fluorinated efficiently Equations 20.20 and 20.21 [47,48] (SSCE =
saturated sodium calomel electrode). Cyclic phosphonate can be also similarly fluorinated as shown
in Equation 20.22 [49].
Fluorination 813
O O
–2e, –H+
X SPh X SPh
Et3N-3HF
F (20.20)
n n
n = 1, X = O (84%)
n = 0,1,2, X = NR (69–92%)
SPh F
–2e, –H+ SPh
N Et3N-3HF/MeCN N
R O R O (20.21)
1.8–2.0 V vs. SSCE
2.3–4.0 F
R = Et, i-Pr, n-Bu, t-Bu, c-Hexyl, Bn
Yield: 65–92%
ArS SAr O
O F
–2e, –H+ P O
P O
Et4NF-3HF/DME O (20.22)
O
58%
Highly regioselective, anodic monofluorination of oxindole and 3-oxo-1,2,3,4-tetrahydroisoquino-

line can be achieved by using Et4NF-mHF (m = 3, 4) (Equation 20.23) [50]. Although three kinds
of benzylic carbons exist in a molecule (n = 1 in Equation 20.23), the fluorination takes place at the
4-position exclusively.
SPh F SPh
O –2e, –H+ O
Et4NF-mHF/MeCN N (20.23)
N
n R
n R
n = 0, R = Ph, p-Tol: 50–64% (m = 4)

n = 1, R = PhCH2: 71% (m = 3)
2. Anodic Fluorination at the Side Chain of Heterocyclic Sulfides

Anodic monofluorination at the side chain of various heterocyclic compounds has been systemati-
cally studied [51,52]. The active methylenethio group attached to heterocycles is selectively fluori-
nated to give the corresponding α-fluorinated products (Equation 20.24). Notably, the use of MeCN
prevented the formation of fluorinated products, while the use of DME markedly increased their
yields [51–56]. The pronounced solvent effect of DME could be explained in terms of the signifi-
cantly enhanced nucleophilicity of fluoride ions, as well as the suppression of anode passivation and
overoxidation of fluorinated products.
O O
COPh COPh
N –2e, –H+ N F
Et4NF-4HF (20.24)
Me N S COPh Me N S COPh
in MeCN: 0%
DME: 78%
Heterocyclic propargyl sulfides are also anodically fluorinated to give the α-fluoro products
(Equation 20.25) [57]. In sharp contrast, in the case of thiazolyl sulfides and oxazolyl sulfides,
the fluorination takes place on the heteroaromatic rings and no α-fluorinated products are formed
(Equation 20.26) [58,59].
F
Het –2e, –H+ Het
S S
F– (20.25)
35–60%
Het = 2-Pyridyl, 4-Pyridyl, 2-Pyrimidyl, 2-Quinolyl, 2-Benzothiazolyl
Me Me
N –2e, –H+ F N
S R Et4NF-4HF F S R
(20.26)
O O
R = H, COMe, CN 55–70%
3. Anodic Fluorination of Heterocyclic Ring

Highly regioselective anodic monofluorination of 2-aryl-4-thiazolidinones can be performed by
using pulse electrolysis in Et3N-3HF/MeCN (Equation 20.27) [60]. However, this electrolytic
system is not suitable for anodic monofluorination of 2-substituted 1,3-dithiolan-4-ones and
1,3-oxathiolan-4-ones owing to severe passivation of the anode. In contrast, Et4NF-4HF provides
monofluorinated products selectively (Equation 20.27) [61,62]. In these cases, benzylic fluorina-
tion does not take place at all although anodic benzylic substitution easily takes place in general.
The high regioselectivity can be explained in terms of facilitation of deprotonation of radical
cation intermediate of the substrates by the electron-withdrawing carbonyl group (i.e., kinetic
acidity control).
S S
R –2e, –H+ F R
X X
(20.27)
Et3NF-nHF/MeCN
O Yeild: 58–86% O
(trans major)
R = Ph, 2-Naphthyl, Mesityl, Et, n-Pr

X = NH, MeN, i-PrN, PhN, BnN (n = 3)
X = O,S (n = 4)
Diastereoselective electrochemical fluorination of various heterocyclic compounds derived from
optically active amino acids and 1,2-diol has also been demonstrated, as depicted in Equations
20.28 and 20.29 [63–65]. Electrochemical fluorination of N-substituted pyrroles and its applica-
tion to the synthesis of gem-difluorinated fused heterocyclic compounds has also been reported
(Equation 20.30) [66]. Interestingly, dehydrodimers readily derived from benzothiazines
underwent electrochemical fluorination accompanied by C–C double bond cleavage to provide
gem-difluorinated benzothiazine derivatives, as shown in Equation 20.31 [67]. Quite recently,
synthesis of fluorinated indole derivatives was also achieved by electrochemical fluorination of
indoles [68].
COOMe F COOMe
–2e, –H+
S NCOR S NCOR (20.28)
Et3N-4HF/DME
R = p-Tol, Ph, Me, H 52–91% yield, 59–95% de

Fluorination 815
–2e, –H+ HCI HO OH

m-CPBA
O O Et3N-3HF O O 50% aq.
MeOH SO2Ph
SPh
F (20.29)
SPh
B F 81% from B
in MeCN: 66% (80% de)

DME/MeCN (1:1): 92% (61% de)
Me Me F
F
N –4e Water F N
CN O N Me
Et3N–3HF/MeCN F (20.30)
O
54% quant
N Ar
N Ar
–4e
S 2
S Et3N-3HF/DME F
S (20.31)
F
Ar N
A r = Ph: 67%
p-BrC6H4: 62%

The selectivity of fluorination was strongly influenced by supporting fluoride salts (Equation 20.32)
[69]. Since Et3N-3HF contains the free base Et3N, the difluorinated product, once formed, was dehy-
drofluorinated to the monofluoro product.
O O O
H
F –2e F
–2e
F Et4NF-4HF/MeCN Et3N-3HF/MeCN (20.32)
O O Ph O Ph
Ph
58%
68%
(cis/trans = 2)
On the other hand, in the case of chroman-4-one derivatives, the fluorination does not take place
at the olefin moiety but resulted at the α-position to the ring-oxygen atom to give the correspond-
ing 2-fluorochromanones [70]. The same fluorinated product could also be obtained stereoselectively
from an alternative anodic fluorination of homoisoflavone derivative, as shown in Equation 20.33 [70].
In these cases, Et4NF-4HF/DME is a suitable electrolytic solution.
O H O H O
CH2Ar
Ar –2e, –H+ Ar –2e, –H+
Et4NF-4HF/DME Et4NF-4HF/DME
O O F O
Ar = Ph, p-ClC6H4, p-BrC6H4 60–72% Ar = p-ClC6H4

(20.33)
It is notable that DME also shows unique fluorination product selectivity (Equation 20.34) [71],
which could be explained in terms of the stability of the anodically generated radical cation interme-
diate C (Equation 20.35). DME strongly stabilized the intermediate C, while CH2Cl2 destabilized
C. Therefore, α-fluorination proceeded without desulfurization in DME, while fluorodesulfuriza-
tion took place in CH2Cl2.
F SAr F
SAr
–e, –PhS –2e, –H+
O O O O O O
F–/CH2Cl2 F–/DME (20.34)
O O O
Ar = p-ClC6H4

+ +
SAr SAr SAr
–e –e, –H+
O O O O O O
O O O
C
Ar = p-ClC6H4
in CH2Cl2 –PhS (20.35)

in DME F–
F–
F F
SAr
O O O O
O O

III. ANODic FLUORiNATiON iN IONic LiqUiDS

A. SoLVENT-FrEE ANoDIC FLUorINaTIoN
Solvent-free electrochemical fluorination is an alternative method for preventing anode passivation
and acetoamidation. Handling extremely corrosive and poisonous anhydrous HF in a laboratory set-
ting is accompanied by serious hazards and experimental difficulties. Ionic liquids such as 70% HF/
pyridine and commercially available Et3N-3HF [72] are often used to replace anhydrous HF. Meurs
and Eilenberg first carried out solvent-free selective electrochemical fluorination, using the ionic liq-
uid Et3N-3HF as the reaction medium, supporting electrolyte and fluorine source for anodic fluorina-
tion of benzenes, naphthalene, olefins, furan, benzofuran, and phenanthroline [73]. They obtained the
corresponding partially fluorinated products in less than 50% yield (Equation 20.36).
F F
F F
–2e, –H+
(20.36)
N N Et3N-3HF N N
34%
Middleton et al. similarly used the 70% HF/pyridine ionic liquid for anodic fluorination of
4-nitrotoluene and various compounds containing benzylic hydrogen atoms [74]. As shown in
Equation 20.37, electrochemical fluorination of 4-fluorophenylacetonitrile in MeCN gave only
17% yield of α-fluorinated product, whereas a yield of 87% was obtained in the ionic liquid
without MeCN.
–2e, –H+
F CH2CN F CHFCN (20.37)
70% HF/Py
in MeCN: 17%
70% HF/Py: 87%
Fluorination 817
Noel and Suryanarayanan have studied the voltammetry and electrochemical fluorination of
PhSCH2CONH2 and PhCH2CN in Et3N-3HF [75]. They found that solvent-free Et3N-3HF had a
much wider anodic potential window and obtained the desired α-fluorinated products in moderate
to reasonable yields. However, Et3N-3HF and Olah's reagent are not anodically stable enough for
certain purposes, as they are easily oxidized at around 2 V vs. Ag/Ag+.
Momota et al. have developed a new series of ionic liquid fluoride salts with the general formula
R4NF-nHF (n > 3.5, R = Me, Et, and n-Pr), that were useful in selective electrochemical fluorination
[76]. These electrolytes were nonviscous liquids that had high conductivity and anodic stability. As
a result, anodic partial fluorination of arenes such as benzene [76]; mono-, di-, and trifluorobenzenes
[77]; chlorobenzene [78]; bromobenzene [79]; toluene [80,81]; and quinolones [82] was successfully
carried out at high current densities using these ionic liquid fluoride salts in the absence of organic
solvent with good to high current efficiencies (66–90%) (Equations 20.38 and 20.39).
F F F
–2e–
Et4NF-4HF (20.38)
2F
F F F
90%
CH3 CH2F
–2e, –H+ –2e, –H+
Et4NF-4HF Et4NF-4HF
2.0 F 2.0 F
1.9 V vs. Ag/Ag+ 52% 2.1 V
(20.39)
CHF2 CHF2
–2e, –H+
Et4NF-4HF
2.0 F F
47% 2.5 V
Yoneda et al. have also investigated the electrochemical stability (potential window) of the ionic liq-
uid Et3N-nHF (n = 3–5) by cyclic voltammetry [26]. They found that the anodic stability increased
with increasing HF content (n) in the fluoride salts, while the cathodic stability showed the reverse
tendency. Thus, Et3N-5HF was stable up to +3 V vs. Ag/Ag+, but was readily reduced at about −0.2 V
to generate hydrogen gas. The potential window of Et4NF-4HF was almost the same as that of
Et3N-5HF. Thus, the selective anodic fluorination of cyclic ketones and cyclic unsaturated esters
in Et3N-5HF was successfully carried out to provide ring-opening and ring-expansion fluorinated
products, respectively, as shown in Equations 20.40 and 20.41 [26,83].
O O
R1 R1
F
R2 –2e F R2
Et3N-5HF
n 2.0–2.4 V vs. Ag/Ag+ n
O
R1
F (20.40)
NaOMe MeO R2
n = 0, R1 = R2 = H 26%
n = 0, R1 = Me, R2 = H 29%
n = 0, R1 = R2 = Me 91%
n = 1, R1 = R2 = Me 81%
F F
CO2Et
CO2Et –2e
Et3NF-5HF
n (20.41)
n 2.2–2.3 V vs. Ag/Ag+
–20°C n=1 71%
n=0 56%
Noel et al. have employed Et3N-4HF as the electrolytic medium for electrochemical fluorination of
N-alkylphenylacetamides [84] and indanone derivatives [85], as shown in Equation 20.42. In both
cases, conversion and fluorinated product yield were moderate, and the products were a complex
mixture. The potentiostatic conditions improved the monofluorination selectivity.
O O O
Et3N-4HF
+ F
6F
F
Constant current 43.3% 16.2%
Constant potential 69.8% 7.3%
(20.42)
O O
F
+ + F + Others
F
F
16.1% 3.4%
0% 0%
The fluorination of cyclic ethers, esters, lactones, and cyclic and acyclic carbonates can be achieved
by anodic oxidation of a large amount of the liquid substrates and a small amount of Et4NF-4HF
(only 1.5–1.7 equiv. of F− to the ether) at a high current density (150 mA/cm2) (Equations 20.43
through 20.45) [86,87].
X X
–2e, –H+
n n
Et3NF-4HF
O 2.0 F O F
(20.43)
X = CH2, n = 0 83%
X = O, n = 1 80%
X = O, n = 0 77%
O O
–2e, –H+
Z O Z O
Et4NF-5HF
(20.44)
F
Z = CH2 75%
Z=O 87%
O O
–2e, –H+
X OCH2CH3 Et4NF-5HF X OCHCH3
2–2.5 F F (20.45)
X = EtO 97%
X = Et 44%
Fluorination 819
Yoneda et al. have successfully carried out electrochemical fluorination of phenols in Et3N-5HF to
provide 4,4-difluorocyclohexa-2,5-diene-1-ones, which were readily converted to p-fluorophenols
in good yields by subsequent reduction with Zn (Equation 20.46) [88,89]. Hara and coworkers
have investigated electrochemical fluorination of various phenols in Et3N-5HF and have found
that carbon fiber cloth was a suitable anode, with various phenol derivatives being converted to
4,4-difluorocycohexadienone derivatives in good yields (Equations 20.47 and 20.48) [90].
OH O OH
t-Bu t-Bu + t-Bu t-Bu t-Bu t-Bu
–4e, –2H Zn
Et3N-5HF H+ (20.46)
Pt anode F F
F
80% (current efficiency) 80%
OH O
R –4e, –2H+ R
Et3N-5HF
Carbon fiber cloth (20.47)
F F
R = H: 61%
t-Bu: 70%
Ph: 77%
OH O
+
–4e, –2H
Et3N-5HF
R Carbon fiber cloth R (20.48)
F F
R = H: 89%
Ph: 68%
The same group has also successfully carried out electrochemical fluorination of adamantanes in
Et3N-5HF [91]. Mono-, di-, tri-, and tetrafluoroadamantanes were selectively prepared from ada-
mantanes by controlling oxidation potentials, and the fluorine atoms were introduced selectively at
the tertiary carbons, as shown in Equation 20.49. Adamantanes bearing functional groups such as
ester, cyano, and acetoxymethyl moieties were also selectively fluorinated.
–2e, –H+ –2e, –H+

Et3N-5HF F Et3N-5HF F
2.3 V vs. Ag/Ag+ 2.5 V
F
74% 79%
F F (20.49)
–2e, –H+ –2e, –H+
Et3N-5HF F Et3N-5HF F F
2.7 V 3.0 V
F F
61% 41%
B. ANoDIC FLUorINaTIoN IN IoNIC LIqUIDS UNDEr ULTraSoNICaTIoN

The viscosity of ionic liquid fluoride salts is little higher than that of ordinary molecular solvents,
which makes slow mass transport of substrate. However, Fuchigami et al. found that anodic fluori-
nation of ethyl α-(phenylthio)acetate in Et3N-3HF proceeded smoothly without anode passivation
under ultrasonication to provide the monofluorinated product in high yield and with high current
efficiency. Notably, anodic difluorination of the substrate could also be achieved in the same ionic
liquid under ultrasonication, as shown in Equation 20.50 [92].
O O
–4e, –2H+ SPh
SPh EtO
EtO 6 F Et3N-3HF
Under Ultrasonication F F
65% yield
–2e, –H+ –2e, –H+ (20.50)
Et3N-3HF/MeCN Et3N-3HF/MeCN
1.6 V vs. SSCE O 2.2 V vs. SSCE
2.5 F SPh 20.7 F
EtO 53% yield
76% yield
F
C. DoUbLE IoNIC LIqUID SYSTEM For ANoDIC FLUorINaTIoN

Fuchigami et al. have also found that a combination of Et4NF-nHF (n = 4, 5) and imidazolium ionic
liquids was highly effective for the anodic fluorination of phthalides [93]. Since the oxidation poten-
tial of phthalide is extremely high (2.81 V vs. SCE), the yield is low even in ionic liquid fluoride
salts due to simultaneous oxidation of the fluoride salts during electrolysis. In sharp contrast, when
the ionic liquid 1-ethyl-3-methylimidazolium trifluoromethanesulfonate ([EMIM][OTf]) was used,
the yield increased markedly as shown in Equation 20.51. The double ionic liquid system consisting
of [EMIM][OTf] and Et3N-5HF enhanced not only the nucleophilicity of F− but also the electro-
philicity of the cationic phthalide intermediate shown in Equation 20.51. The cationic intermediate
generated from the phthalide was expected to have a TfO − counter anion (activated cation D in
Equation 20.51), which readily reacted with F− to provide the fluorinated phthalide in good yield.
–
OTf F
–2e, –H+ + F–
O O O
Et3N-nHF (20.51)
O [C2mim][OTf ] O
O
n = 3 or 5
D n=3 78%
Activated cation n=5 90%

D. EFFECTS oF ETHErEaL ADDITIVES oN ANoDIC FLUorINaTIoN

In neat ionic liquid fluoride salts, the nucleophilicity of fluoride ions is rather low, resulting in poor
fluorination yields. Fuchigami et al. have successfully carried out the solvent-free electrochemi-
cal difluorodesulfurization of O-ethyl benzothioate in the presence of ether-containing additives
like poly(ethylene glycol) (PEG) [94,95]. As shown in Equation 20.52, the addition of ca. 3% PEG
additives to the reaction system greatly improved the yield due to its anodic stability and ability to
coordinate the counter cations of fluoride ions.
S F F Additive Yield (%)

–2e
O O 22 (20.52)
Et4NF-3HF DME 18
PEG [Mn ~ 200] 80
Fluorination 821
IV. ANODic FLUORiNATiON Of MAcROMOLEcULES

Electrochemical fluorination of conducting polymers has been demonstrated using anodic fluoro-
desulfurization of poly(fluorene) derivatives in ionic liquids Et4NF-nHF [96–98]. An alternating
copolymer of 9,9-dioctylfluorene and 9,9-disulfanylfluorene gave a tough film on a platinum plate
electrode by drop casting. This electrode was then placed in an undivided plastic cell filled with
Et4NF-nHF, and constant current electrolysis was performed to yield poly(9,9-difluorofluorene-
alt-9,9-dioctylfluorene). The progress of the fluorodesulfurization reaction could be followed by
NMR. The degree of fluorination gradually increased with the amount of charge passed and was
mostly completed after passage of 24 F. The electrochemical reaction proceeded selectively even
after a large amount of charge was passed (Equation 20.53) [96,97]. When the reaction was car-
ried out in MeCN containing Et4NF-nHF as a supporting electrolyte, the polymer film detached
from the platinum anode and is no longer electroactive. Thus, the choice of electrolytic media was
highly important.
S S F F
–2e, –2SAr
Et4NF-5HF
n 24 F n
Octyl Octyl Octyl Octyl
(20.53)
Anodic fluorodesulfurization of the alternating copolymer of N-decylcarbazole and 9,9-disul-

fanylfluorene was investigated, and yielded poly(9,9-difluorofluorene-alt-N-decylcarbazole);
however, the reaction resulted in only 50% conversion (Equation 20.54). In this case, the local-
ization of cation charge on the carbazole unit probably prevented the discharge of the sulfanyl
group [98].
C10H21 C10H21
N N
S F F
S –2e, –2SAr
(20.54)
Et4NF-5HF
24 F n
n
Conversion: 50%
V. INDiREcT ANODic FLUORiNATiON

As mentioned in Sections I, II.G.2 and II.G.3, anode passivation takes place very often, which
results in poor yield and low current efficiency. In order to avoid such passivation, Fuchigami et al.
developed an indirect electrochemical method using various mediators. Thus, Br+/Br− and triaryl-
amine redox mediators have been shown to be effective for selective mono- and difluorodesulfur-
ization of dithoacetals, respectively [99,100]. Furthermore, triarylamine has been shown to be a
highly effective mediator for monofluorodesulfurization of β-lactams (Equation 20.55) [101]. In
the absence of triarylamine, severe passivation of the anode takes place during anodic fluorination.
Et3N-3HF
Anode 2F– R1 SPh
+
2Ar3N N
2e
O R2
R1 F
2Ar3N + PhSF (20.55)
N
O R2
Ar = 2,4-Br2C6H3
R1 = H, R2 = C6H5CH2: 83%
R1 = H, R2 = p-BrC6H4CH2: 100%
R1 = Me2SiOCH–, R2 = C6H5CH2: 66%
t-Bu Me
They have also demonstrated the first catalytic use of hypervalent difluoroiodoarene anodically gen-
erated in situ for gem-difluorodesulfurization of dithioacetals, as shown in Equation 20.56 [102,103].
Pt anode S S
F
MeO I 1/2
2e F
X X
2F–
(20.56)
F F
MeO I
1/2
1.9 V vs. SSCE X X
X = Cl: 98%
F: 96%
Even in ionic liquid HF salts, severe passivation of the anode often occurs. Therefore, a novel
indirect electrochemical fluorination system was developed employing a task-specific ionic liquid
with an iodoarene moiety as the mediator in HF salts [104]. The mediator improved the reaction
efficiency for a variety of electrochemical fluorinations (Equation 20.57) and remained intact in the
ionic liquids after the extraction process for reuse in subsequent runs.
Et3N-3HF
N Mediator (10 mol%) N F
N S EWG Undivided cell
4F N S EWG
5 mA/cm2 (20.57)
Tf2N– EWG = COOEt, 87%

Mediator: l O N+
N (without mediator: 31%)
EWG = CN, 72%
Task-specific ionic liquid with triarylamine mediator has been also developed for anodic fluorode-
sulfurization [105].
In addition, a polymer-supported iodobenzene (PSIB) mediator was also effective for indirect
anodic fluorination in HF salts [106]. In this case, the iodobenzene moiety pendent from the solid
polymer support could not be directly oxidized; therefore, a double mediator system was necessary.
As shown in Equation 20.58, electrooxidation of Cl− gave Cl+, which reacted with the iodobenzene
moiety to form PhI+Cl. This species then captured a fluoride ion to give the hypervalent [(chloro)
(fluoro)iodo]benzene moiety. The hypervalent iodine moiety thus generated oxidizes the substrate,
Fluorination 823
and consequently, the starting PSIB was recovered. The recovered PSIB mediator was reused in
subsequent runs, maintaining a good yield (86–79%) of fluorinated product through to the 10th run.
1/2 1/2
F F S S
Ph Ph Ph Ph
Anode
Cl–
F
Ph l Ph l
Cl
(20.58)
–2e
+ F–
Cl Ph l+
Cl
n m
Ph l =
PSIB mediator
l
VI. ANODic FLUORiNATiON USiNG ALkALi METAL SALTS

Tajima et al. developed anodic fluorination based on cation exchange between alkali-metal fluorides
and solid-supported acids like Amberlyst 15Dry [107]. However, in this system, anodically stable
bases such as 2,6-lutidine must be added in order to increase the nucleophilicity of fluoride ions
generated in situ.
It is known that poly(ethylene glycols) [HO(CH2CH2O)nH, n > 3] are highly active and selective in
catalyzing dehydrohalogenation in organic–aqueous hydroxide two-phase systems. Moreover, recently,
it was demonstrated that tetraethylene glycol (terminal group: OH) could dissociate MF (M = K, Cs)
into the fluoride ion and the metal cation in aprotic polar solvents. Based on these facts, Fuchigami
et al. developed a novel electrolytic system and have achieved anodic fluorination of various organic
compounds in tetraethylene glycol using alkali metal salts like KF (Equation 20.59) [108].
H F
3 3
SPh –ne F
KF + PEG [Mn ~ 200] (20.59)
2 SPh MeCN, Pt–Pt, r.t. ~40°C 2 SPh
4 F, 5 mA/cm2 F
Z Undivided cell Z
3 Z = P, Sb 3 F
VII. CONcLUSiON
In contrast to conventional chemical fluorination methods using hazardous and/or costly reagents such
as F2, FClO3, CF3OF, XeF2, Et2NSF3 (DAST), N-fluoropyridinium salts, N-fluorotriethylenediamine
derivative (Selectfluor®), and 4-tert-butyl-2,6-dimethylphenylsulfur trifluoride (Fluolead™), selec-
tive anodic fluorination can be readily carried out under mild conditions and does not require any
hazardous reagents. As described earlier, selective electrochemical fluorination is a promising pro-
cedure for the preparation of various partially fluorinated organic substances.
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Section V
Electrochemical Conversions
of Organic Compounds
21 Electrochemistry of
Fullerenes, Derivatives,
and Related Compounds
Frederic Melin, Lourdes E. Echegoyen, and Luis Echegoyen
CONTENTS
I. Introduction ............................................................................................................................. 830
II. General Trends in the Redox Properties of Fullerenes and Related Compounds .................. 831
A. Cage Effects in Empty Fullerenes .................................................................................. 831
B. Cage and Encapsulated Species Effects in Endohedral Metallofullerenes .................... 831
1. Monometallofullerenes ............................................................................................ 832
2. Dimetallofullerenes.................................................................................................. 833
3. Clusterfullerenes ...................................................................................................... 835
C. Influence of Exohedral Derivatization ............................................................................ 839
1. Empty Fullerenes ..................................................................................................... 839
2. Endohedral Metallofullerenes Sharing the C80 (Ih) Cage ........................................840
3. M@C82 (C2v) Endohedral Metallofullerenes ............................................................ 841
4. Endohedral Metallofullerenes Incorporated in Donor–Acceptor Dyads................. 843
D. Larger Carbon Nanostructures: Structure, Defects, and Impurity Effects ..................... 845
III. Preparation, Purification, and Derivatization of Fullerenes and Related Compounds
Based on Their Redox Properties ...........................................................................................846
A. Isolation of Kinetically Unstable Empty and Endohedral Fullerenes ............................846
1. Looking for the Missing Empty Carbon Cages .......................................................846
2. Separating Endohedral Metallofullerenes from Empty Fullerenes ......................... 847
3. Looking for the Missing Endohedral Metallofullerenes .........................................848
B. Separation of Isomeric Carbon Cages ............................................................................848
1. By Selective Oxidation.............................................................................................848
2. Using the Retrocyclopropanation Reaction.............................................................. 849
C. Preparation of Exohedral Derivatives of Fullerenes ....................................................... 849
1. By Nucleophilic Substitution ................................................................................... 849
2. Using the Retrocyclopropanation Reaction.............................................................. 850
3. Fine-Tuning the Reactivity of Endohedral Fullerenes ............................................. 850
D. Solution Processing of Larger Carbon Nanostructures .................................................. 852
IV. Conclusion............................................................................................................................... 852
References ...................................................................................................................................... 853
829
I. INTRODUcTiON
The most intriguing property of buckminsterfullerene C60, discovered in 1985, is without doubt
its outstanding ability to accept electrons with very low reorganization energy. Using either cyclic
voltammetry (CV), differential pulse voltammetry (DPV), or Osteryoung square wave voltamme-
try (OSWV), six reversible waves are observed for C60 at low temperature (Figure 21.1) [1], which
was predicted by theory, based on its energetically low-lying triply degenerate lowest unoccupied
molecular orbital (LUMO) [2]. Each one of the reduction steps has a relatively constant separation
between them of 450 ± 50 mV. Most importantly, with each addition of one electron, no Jahn–
Teller distortion is observed, that is, the C60 cage does not suffer any structural modification from
its highly symmetrical, quasi-spherical architecture [3]. This latter characteristic is necessary for
the long-lived charge-separated states required for photovoltaic applications [4], an area that has
recently made the fullerene field one of the most active in chemistry. The sister molecule, C70, exhib-
its a very comparable electron-accepting behavior, except that all six waves are observable at room
temperature [1]. The larger fullerenes also possess very rich electrochemistry and high symmetry
and exhibit no Jahn–Teller distortion. Consequently, they have also attracted considerable interest
in the scientific community in the last two decades. Numerous studies comprising members of the
fullerene family are focusing on tuning their redox chemistry by surface functionalization or by
trapping metals and clusters inside the cages. The search for compounds with encaged moieties (the
so-called endohedral fullerenes) has resulted in the synthesis of carbon cages with unusual sizes
and symmetries, including some with fused pentagon rings [5]. Fullerene molecules with carefully
designed physicochemical properties have been produced by functionalization of various carbon
cages [6]. These new molecules all possess redox properties that can be used either as a synthetic
tool to prepare, separate, or purify them or as an analytical tool to characterize and classify the
carbon cages, predict their reactivity, or understand the electronic interplay between encapsulated
species and carbon cages in the case of endohedral fullerenes.
In this chapter, we will first review the main trends in the electrochemical properties of fuller-
enes and related compounds, with a special emphasis on the growing family of endohedral fullerenes.
We will then focus on representative examples that show how these unique redox properties can
C60 at –10°C
10 μA
(a)
5 μA
–1.0 –2.0 –3.0

(b) Potential (V vs. Fc/Fc+)
FiGURE 21.1 CV (a) and OSWV (b) of C60 in acetonitrile/toluene + 0.1 M (n-Bu)4NPF6 at −10°C using
glassy carbon working electrode (GCE) and ferrocene/ferrocenium (Fc/Fc+) couple as internal reference.
(Reprinted from Xie, Q. et al., J. Am. Chem. Soc., 114, 3978, 1992. With permission.)
Electrochemistry of Fullerenes, Derivatives, and Related Compounds 831
be exploited to prepare some of these compounds. Due to space limitations, it is impossible to be

exhaustive on this rapidly expanding research domain. Therefore, we suggest the reader to also
consult several comprehensive reviews for more details on this subject [7–8].
II. GENERAL TRENDS iN ThE REDOx PROPERTiES

Of FULLERENES AND RELATED COMPOUNDS
A. CaGE EFFECTS IN EMpTY FULLErENES
The electrochemical properties of fullerenes are highly dependent on the cage size and symmetry.
Early studies dealt mainly with empty carbon cages under various solvents, supporting electrolytes
and temperature conditions. A noteworthy example is the comparison between C60 and C70. Their
corresponding first and second reduction potential values are nearly identical in acetonitrile/tolu-
ene. However, from the trianion to the hexa-anion, C70 becomes increasingly easier to reduce than
C60. In other solvents, the differences, although still small, may be slightly more pronounced (see
Table 21.1).
Of electrosynthetic relevance is the fact that C60 anions are stable on the voltammetric time scale,
but when electrogenerated by controlled potential coulometry in solution, only the mono- through
tetra-anions are stable [7a,b]. Furthermore, neutral C60 is insoluble in solvents such as DMF, ace-
tonitrile, or THF, but its anions dissolve readily. Therefore, these anions can be generated from a
suspension of C60 [9]. These properties have been used to prepare several C60 derivatives starting
from the electrogenerated anions [11].
The soot collected from graphite arcing yields, albeit in very small quantities after separation,
isomerically pure samples of C76, C78, C82, and C84 and isomeric mixtures of C86, C90, C92, and C96.
Studies on the cathodic electrochemistry of C60 to C84 indicate a very distinct trend: as the size of
the cage increases, the first reduction is systematically shifted toward more positive potentials.
However, there is no apparent trend for the first oxidation potential (see Table 21.2).
Generally, the larger cages have a lower electrochemical gap ΔEgap than C60 and C70. Beyond C84,
unfortunately, only electrochemical studies of isomeric mixtures are available. As an example, C92,
as isolated and purified by high-performance liquid chromatography (HPLC), exhibits eight revers-
ible reductions that can be grouped into two distinct sets, based on their intensity and assigned to
two different cage isomers [12]. This study clearly demonstrates that the electrochemical properties
of two fullerene isomers can be dramatically different.
B. CaGE aND ENCapSULaTED SpECIES EFFECTS IN ENDoHEDraL METaLLoFULLErENES

Most of the current reports on fullerene electrochemistry focus on endohedral metallofullerenes
(EMFs) with the aim to elucidate the electronic interplay between encaged species and carbon
cages. A substantial amount of knowledge has been obtained through systematic studies of simple
metallofullerene families such as the M@C82 (M = La, Pr, Gd, Ce, Tm, and Y) [14,15], Yb [16],
TABLE 21.1
Half-Wave Reduction Potentials (vs. Fc/Fc+) of C60 and C70 in Acetonitrile/Toluene
(PhMe/MeCN) and Dichloromethane (DCM)
Compound Solvent Temperature (°C) E1 E2 E3 E4 E5 E6 Reference
C60 PhMe/MeCN −10 −0.98 −1.37 −1.87 −2.35 −2.85 −3.26 [1]
C70 PhMe/MeCN −10 −0.97 −1.34 −1.78 −2.21 −2.70 −3.70 [1]
C60 DCM +25 −1.02 −1.41 −1.87 [9]
C70 DCM +25 −0.93 −1.31 −1.73 −2.09 [10]
TABLE 21.2
Redox Potentials versus Fc/Fc+ of Some Isomerically Pure Empty Fullerenes
in 1,1,2,2-Tetrachloroethane Unless Otherwise Stated
Compound E1ox (V ) E1red (V ) ΔEgap (V) b Reference

C60 1.26 −1.06 2.32 [13]
C70 1.20 −1.02 2.22 [13]
C76 0.81 −0.83 1.64 [13]
C78 (C2v) 0.95 −0.77 1.72 [13]
C82a 0.72 −0.69 1.41 [14a]
C84 0.93 −0.67 1.60 [13]
a 1,2-Dichlorobenzene.
b Electrochemical bandgap ΔEgap = E1ox − E1red.
Sm [17], and Ca@C2n (n = 37–48) [18], as well as the trimetallic nitride cluster fullerenes M3N@C2n
(M = Sc, Y, and most lanthanides, n = 34–48) [19].
1. Monometallofullerenes
In the simple metallofullerenes, there is a clear dependency of the electrochemical properties on the
number of electrons transferred by the metal to the cage (i.e., the oxidation number of the metal). Sc,
Y, and the majority of the lanthanides can give three electrons to the cage and form the so-called tri-
valent EMFs. It seems that these metals are preferentially encapsulated inside the C2v and Cs isomers
of C82, with the C2v as the most abundant [20]. These metallofullerenes are both easier to oxidize
and easier to reduce than the empty fullerenes and their first redox processes are reversible. Their
strong electron-accepting behavior is quite unexpected, when considering that the C82 cage already
bears a formal 3− charge. Their small electrochemical HOMO–LUMO gap (less than 0.5 V, see
Table 21.3) is a remarkable characteristic and reflects their open-shell electronic structure. Overall,
their oxidation state can be changed from 2+ down to 6−. Interestingly, no major differences exist
in the electrochemical properties of the C2v and Cs isomers, which suggests that their behavior is
mostly controlled by their radical nature and not by the structure of the cage. However, good linear
relationships between the first redox potentials of these metallofullerenes and the ionic radii of
the encapsulated metals were found (see Figure 21.2) [14a]. These relationships can be understood
by taking into account the probable structure of these endohedral fullerenes: that is, a positively
TABLE 21.3
Half-Wave Potentials versus Fc/Fc+ of Trivalent Mono Endohedral Metallofullerenes
Measured in 1,2-Dichlorobenzene
ox2
Fullerene E1/2 ox1
E1/2 red1
E1/2 red2
E1/2 red3
E1/2 red4
E1/2 ΔEgap a Reference
La@C82 (C2v) 1.07 0.07 −0.42 −1.37 −1.53 −2.26 0.49 [14a]
La@C82 (Cs) 1.08 −0.07 −0.47 −1.40 −2.01 −2.40 0.54 [15b]
Pr@C82 (C2v) 1.08 0.07 −0.39 −1.35 −1.46 −2.21 0.46 [15b]
Pr@C82 (Cs) 1.05 −0.07 −0.48 −1.39 −1.99 −1.99 0.55 [15b]
Ce@C82 (C2v) 1.08 0.08 −0.41 −1.41 −1.53 −1.79 0.49 [14a]
Gd@C82 (C2v) 1.08 0.09 −0.39 −1.38 −2.22 0.48 [14a]
Y@C82 (C2v) 1.07 0.10 −0.37 −1.34 −2.22 −2.47 0.47 [14a]
a ΔEgap = E1ox/ 21 − E1red

/2 .
1
Y
0.10 E ox1
Gd
Ce
0.08
La
0.06 Y
E red1
E (V) vs. Fc/Fc+ –0.38
Gd
–0.40
Ce
–0.42
La
–0.44
1.16 1.12 1.08 1.04
Ionic radius (Å)
FiGURE 21.2 Linear relationships between the redox potential of the La@C82 C2v compounds and the ionic
radii of M3+. (Reprinted from Suzuki, T. et al., Tetrahedron, 52, 4973, 1996. With permission.)
charged metal (3+) that is not centered on but which strongly interacts with a hexagonal ring of the
cage along the C2 axis. The smaller the metal, the closer to the cage it can be and the tighter the
electrons are bound to the cage. Small metals such as Y thus form EMFs that are easy to reduce
and difficult to oxidize, whereas larger metals such as the lanthanides form EMFs that are easier to
oxidize but more difficult to reduce.
In contrast, alkaline earth metals such as Ca as well as some lanthanides such as Sm, Yb, and Eu
transfer only two electrons to the cage, and therefore form divalent EMFs. Their electron-accepting
character (see Table 21.4) is also stronger than that of the empty fullerenes. The large gap between
the second and third reduction steps is indicative of nondegenerate LUMO-1 and LUMO-2 orbitals
[16a]. Most of the electrochemical studies of these compounds were done in a mixture of toluene
and acetonitrile, and no oxidation was observed in this solvent system. Their electrochemical gaps
were therefore predicted to be larger than those of the trivalent EMFs, which was consistent with
their believed closed-shell electronic structure.
In 1,2-dichlorobenzene, however, one or two quasi-reversible oxidation waves were recently
observed for most ytterbium- and a few samarium-based compounds. These studies led to the
determination of the electrochemical bandgaps of these metallofullerenes (see Table 21.4) and to
a correlation between these values and the production yields [16b]. Divalent EMFs are found with
quite a large diversity of cage sizes and symmetries, and the influence of the cage structure on the
electrochemical properties is very significant in this family of compounds. As shown in Table 21.4,
dramatic differences in the electron-accepting abilities of isomeric endohedral fullerenes are some-
times observed. For instance, the C2 isomer of Sm or Yb@C82 is more difficult to reduce than the
Cs or C2v isomers by at least 0.25 V! When the cage becomes larger, the number of oxidation and
reduction processes also tends to increase. In contrast, divalent EMFs with the same carbon cage
but different metals usually exhibit very close electron-accepting abilities, which suggests that the
metal hardly contributes to the LUMO of these compounds.
2. Dimetallofullerenes
Dimetallofullerenes mainly with trivalent metals such as Sc [21], La [22], Er [23], Ce [22e,24], and
cages as small as C72 and as large as C82 have been characterized. In these structures, it was presumed
TABLE 21.4
Half-Wave Potentials against Fc/Fc+ of Divalent Mono Endohedral Metallofullerenes
Measured in Toluene/Acetonitrile Unless Otherwise Stated
Fullerene ox2
E1/2 ox1
E1/2 red1
E1/2 red2
E1/2 red3
E1/2 red4
E1/2 ΔEgapb Reference
Sm@C74 (D3h) — — −0.52 −0.98 −1.55 −1.96 — [17a]
Sm@C76 (I) — — −0.45 −0.85 −1.43 −1.74 — [17a]
Sm@ C80 (C2v(3)) 0.85 0.43a −0.59 −0.98 −1.58 −1.92 1.28a [17a]
−0.85a −1.23a −1.76a −2.07a [17c]
Sm@C82 (Cs(6)) — — −0.27 −0.59 −1.54 −1.80 — [17a]
Sm@ C82 (C2(5)) — 0.42a −0.54 −0.76 −1.27 −1.66 1.26a [17a]
— −0.84a −1.01a −1.51a −1.90a [17b]
Sm@C82 (C2v(9)) — — −0.22 −0.57 −1.45 −1.81 — [17a]
Sm@C84 (C2(13)) — — −0.66 −0.87 −1.12 −1.31 — [17a]
Sm@C84 (C1(12)) — — −0.39 −0.70 −1.58 −1.81 — [17a]
Sm@C86 — — −0.47 −0.78 −1.31 −1.71 — [17a]
Sm@C90 (C2(40)) — — −0.62 −0.87 −1.42 −1.78 — [17a]
Sm@C90 (C2(42)) — — −0.54 −0.86 −1.30 −1.65 — [17a]
Sm@C92 (C1(42)) — — −0.40 −0.61 −1.11 −1.28 — [17a]
Sm@C94 (C3v(134)) — — −0.51 −0.84 −1.33 −1.69 — [17a]
Sm@C96 — — −0.52 −0.85 −1.29 −1.50 — [17a]
Yb@C74 (D3h) — — −0.52 −0.96 −1.55 −1.99 — [16a]
Yb@C76 (I) — — −0.46 −0.83 −1.46 −1.89 — [16a]
Yb@C76 (II) — — −0.68 −1.02 −1.59 −2.01 — [16a]
Yb@C78 — — −0.48 −0.79 −1.46 −1.83 — [16a]
Yb@C80 (C2v(3)) 0.78a 0.34a −0.57 −0.95 −1.55 −1.90 1.23a [16a]
−0.89a −1.27a −1.87a −2.13a [16b]
Yb@C82 (Cs(6)) — 0.34a −0.33 −0.65 −1.58 −1.81 0.96a [16a]
— −0.62a −0.92a −1.81a −2.01a [16b]
Yb@C82 (C2(5)) 0.90a 0.38a −0.60 −0.76 −1.33 −1.73 1.24a [16a]
−0.86a −0.98a −1.50a −1.87a [16b]
Yb@C82 (C2v(9)) — 0.61a −0.33 −0.67 −1.56 −1.90 1.07a [16a]
— −0.46a −0.78a −1.60a −1.90a [16b]
Yb@C84 (C2(13)) — 0.46a −0.63 −0.88 −1.26 −1.64 1.41a [16a]
— −0.95a −1.16a −1.50a −1.86a [16b]
Yb@C84 (C1(12)) 0.68a 0.22a −0.49 −0.68 −1.57 −1.79 0.98a [16a]
−0.76a −0.94a −1.76a −1.97a [16b]
Yb@C84 (C2(11)) 0.48a 0.19a −0.46 −0.72 −1.34 −1.54 1.04a [16a]
−0.85a −1.14a −1.70a −2.06a [16b]
Ca@C76 — — −0.61 −0.99 −1.57 −1.97 — [18]
Ca@C82 (C2) — — −0.59 −0.74 −1.30 −1.70 — [18]
Ca@C82 (C3v(7)) — — −0.65 −0.96 −1.55 −1.90 — [18]
Ca@C84 (C2(13)) — — −0.64 −0.90 −1.27 −1.65 — [18]
a In 1,2-dichlorobenzene.
b ΔEgap = E1ox/ 21 − E1red
/ 2 . Attribution of the carbon cage symmetries is mostly based on recent x-ray studies [20].
1
that the carbon cage accepts six electrons from the encapsulated atoms and should therefore not be
prone to further reduction. Unexpectedly, these endohedrals exhibit both strong electron-accepting
and electron-donating abilities and thus relatively low electrochemical bandgaps (see Table 21.5).
In particular, La2@C80 and Ce2@C80 are even easier to reduce than La@C82 and Ce@C82 as a result
of the LUMO being localized primarily on the encapsulated atoms. The M2@C72 compounds are
TABLE 21.5
Half-Wave Potentials against Fc/Fc+ of Dimetallo-Endohedral Fullerenes Measured
in 1,2-Dichlorobenzene + 0.05 M (n-Bu)4NPF6 Unless Otherwise Stated
Compound Eox 2 Eox 1 Ered
1 Ered
2 Ered
3 ΔEgapa Reference
La2@C72 (D2) 0.75 0.24 −0.68 −1.92 — 0.92 [22a]
Ce2@C72 (D2) 0.82 0.18 −0.81 −1.86 — 0.99 [24a]
La2@C78 (D3h) 0.62 0.26 −0.40 −1.84 −2.28 0.66 [22b]
La2@C80 (Ih) 0.95 0.56 −0.31 −1.72 −2.13 0.87 [22c,d]
La2@C80 (D5h) 0.78 0.22 −0.36 −1.72 — 0.58 [22e]
Ce2@C80 (Ih) 0.95 0.57 −0.39 −1.71 — 0.96 [24b]
Ce2@C80 (D5h) 0.66 0.20 −0.40 −1.76 −2.16 0.60 [22e]
Sc2@C82 (C3v (8)) — 0.05 −1.10 — — 1.15 [21]
Er2@C82b — 0.19 −0.87 −1.26 — 1.06 [26]
a ΔEgap = E1ox/ 21 − E1red

/2 .
1
b In pyridine.
among the few examples of kinetically stable EMFs with a cage that violates the Isolated Pentagon
Rule (non IPR fullerenes) [25]. The stabilization of the fused pentagon system in these structures is
believed to occur through specific coordination with the metallic moiety and some degree of intra-
molecular ion pairing [22a].
3. Clusterfullerenes
Among the EMFs, the trimetallic nitride cluster fullerenes M3N@C2n (MNEFs) currently constitute
the most abundant and diverse, probably thanks to their larger electrochemical bandgaps, which
range from 1.10 to 2.08 V (see Table 21.6) [19]. Indeed, most of the lanthanides, except Sm, Yb, and
Eu, as well as Sc and Y form such compounds. After C60 and C70, Sc3N@C80 is the third most abun-
dant fullerene that can be prepared in an arc reactor, which was totally unexpected when consider-
ing that on their own, the C80 cage and Sc3N cluster are highly unstable [27]. In these endohedrals,
it is widely accepted that stability is reached through a transfer of six electrons from the cluster to
the cage, which requires a metal with a formal oxidation number of 3+. It is not a coincidence that
Sm, Yb, and Eu, which apparently do not form trimetallic nitride fullerenes, prefer also to form
divalent instead of trivalent EMFs (see Section II.B.1). For lanthanides smaller than Gd [28], the
most abundant cage formed is IPR isomer 7 of C80 with (Ih) symmetry, and thus a large number
of M3N@C80 (Ih) are available (see Table 21.6). For larger metals such as Nd, Pr, and Ce [29], C88
(presumably IPR isomer 35 with D2 symmetry) is preferred, while La prefers C96 (possibly IPR
isomer 186 with D2 symmetry) [30]. Several of these compounds feature a non IPR-cage, including
Sc3N@C68 (D3) [31], Sc3N@C70 (C2v) [32], Gd3N@C78 (C2) [33], Gd3N@C82 (Cs) [34], and Gd3N@C84
(Cs) [35]. MNEFs usually exhibit one or two reversible oxidation steps and at least two irreversible
reduction steps using CV, while their chemical reduction is reversible. The electrochemical irrevers-
ibility suggests that an internal structural reorganization occurs upon addition of electrons, which
may hinder the free rotation of the cluster [36]. Only Sc3N@C80 at high scan rates [36a], TiSc2N@
C80 [37a], TiSc2N@C80 [37b], and the C88 MNEFs [29,38] (see Figure 21.3) show reversible behavior
for both oxidation and reduction scans.
The nature of the metal does not appear to influence significantly the oxidation and reduction
potentials, and hence, it does not affect the value of the electrochemical gap of the MNEFs (see
Figure 21.3 and Table 21.6). These observations suggest that both the HOMO and the LUMO of
MNEFs are mainly cage localized orbitals. Only in the case of Sc3N@C80, it was demonstrated that
the cluster contributes significantly to the LUMO [39]. Mixed metal nitride compounds based on
TABLE 21.6
Reductive Cathodic Peak Potentials (Epc) and Oxidative Half-Wave Potentials (E1/2) against
Fc/Fc+ of Trimetallic Nitride Endohedral Fullerenes as Obtained by Cyclic Voltammetry
(Unless Otherwise Stated) in 1,2-Dichlorobenzene + 0.05 M (n-Bu)4NPF6
Compound ox2
E1/2 ox1
E1/2 Epred
c
1
Epred
c
2
Epred
c
3
ΔEgapa Reference
Sc3N@C68 (D3) 0.85 0.33 −1.45 −2.05 — 1.78 [42]
Sc3N@C78 (D3h) 0.68 0.21 −1.56 −1.91 — 1.77 [33]
Y3N@C78 (C2) 0.53 0.25 −1.62 −1.99 — 1.87 [43]
Dy3N@C78 (C2) — 0.47 −1.54 −1.93 — 2.01 [36b]
Gd3N@C78 (C2) — 0.47 −1.53 −1.89 — 2.00 [33]
Sc3N@C80 (Ih) 1.09 0.59 −1.26 −1.62 −2.37 1.85 [36a]
Y3N@C80 (Ih) — 0.64 −1.41 −1.83 −2.34 2.05 [44]
Lu3N@C80 (Ih) 1.11 0.64 −1.42 −1.80 −2.26 2.06 [45]
Tm3N@C80 (Ih) 1.15 0.65 −1.43 −1.78 — 2.08 [46]
Er3N@C80 (Ih) — 0.63 −1.40 −1.83 −2.16 2.05 [44]
Ho3N@C80 (Ih) — 0.60b −1.45b −1.91b −2.21b 2.05 [47]
Dy3N@C80 (Ih) — 0.70 −1.37 −1.86 — 2.07 [36b]
Tb3N@C80 (Ih) — 0.59b −1.38b −1.86b −2.16b 1.97 [47]
Gd3N@C80 (Ih) — 0.58 −1.44 −1.86 −2.18 2.02 [38]
Nd3N@C80 (Ih) — 0.63 −1.42 −1.89 — 2.05 [29b]
Pr3N@C80 (Ih) — 0.59 −1.41 −1.84 — 2.00 [29b]
ScYErN@C80 (Ih) — 0.64 −1.55 −1.97 — 2.19 [48]
CeSc2N@C80 (Ih) — 0.33 −1.34 −1.87 — 1.67 [40b]
CeY2N@C80 (Ih) — −0.07 −1.36 −1.88 — 1.30 [40b]
CeLu2N@C80 (Ih) — 0.01 −1.43 −1.92 — 1.44 [40a]
PrSc2N@C80 (Ih) — 0.64 −1.32 −1.91 — 1.96 [40b]
TiSc2N@C80 (Ih) — 0.16 −0.94 −1.58 −2.21 1.10 [37a]
TiY2N@C80 (Ih) — 0.00 −1.11 −1.79 — 1.11 [37b]
Sc3N@C80 (D5h) — 0.34 −1.33 — — 1.67 [49]
Lu3N@C80 (D5h) — 0.45 −1.41 — — 1.86 [49]
Tm3N@C80 (D5h) 0.79 0.39 −1.45 −1.81 −2.36 1.84 [46]
Dy3N@C80 (D5h) — 0.40 −1.40 −1.85 — 1.80 [36b]
Gd3N@C82 (Cs) — 0.37 −1.52 −1.86 — 1.89 [50]
Gd3N@C84 (Cs) — 0.32 −1.37 −1.76 — 1.69 [50]
Nd3N@C84 — 0.31 −1.44 −2.02 — 1.75 [29b]
Gd3N@C86 (D3) — 0.35 −1.35 −1.70 — 1.70 [50]
Nd3N@C86 — 0.36 −1.46 −1.79 — 1.72 [29b]
Pr3N@C86 — 0.31 −1.48 −1.80 — 1.79 [29b]
Lu3N@C88 0.44 0.02 −1.35 −1.68 — 1.37 [51]
Gd3N@C88 0.49 0.06 −1.43 −1.74 — 1.49 [50]
Nd3N@C88 0.53 0.07 −1.36 −1.75 −2.39 1.43 [29a]
Pr3N@C88 0.54 0.09 −1.34 −1.72 −2.35 1.43 [29b]
Ce3N@C88 0.63 0.08 −1.33 −1.60 −2.35 1.41 [29b]
La3N@C88 0.66 0.21 −1.36 −1.67 — 1.57 [30]
Pr3N@C92 0.79b 0.35 −1.46 −1.82 — 1.81 [41b]
Ce3N@C92 0.76b 0.35 −1.46 −1.82 −2.36 1.80 [41b]
La3N@C92 — 0.36 −1.44 −1.69 −2.29 1.80 [41b]
Pr3N@C96 0.53 0.14 −1.51 −1.86 — 1.65 [41b]
Ce3N@C96 0.67 0.18 −1.50 −1.84 — 1.68 [41b]
La3N@C96 0.53 0.14 −1.54 −1.77 — 1.68 [41b]
a ΔEgap = E1ox/ 21 − E1ox/ 21 − Epred

c
1
.
b OSWV peaks.
Ce3N@C88
Pr3N@C88
Current (arbitrary unit)
Nd3N@C88
Gd3N@C88
1.0 0.5 0.0 –0.5 –1.0 –1.5 –2.0 –2.5

Potential (V vs. Fc+/Fc)
FiGURE 21.3 CV of M3N@C88 (M = Gd, Nd, Pr, and Ce) obtained in o-DCB + 0.05 M (n-Bu)4 NPF6 (scan
rate 0.1 Vs−1).
Ce and Ti metals constitute other exceptions to this rule. For TiM2N@C80 compounds, the valence
state of the Ti atom is changed during both oxidation and reduction processes [37], whereas for
CeM2N@C80 compounds [40], oxidation occurs at the cerium metal and the corresponding redox
potential is highly dependent on the size of the second metal. Table 21.6 also emphasizes that the
first oxidation potential is very sensitive to the size and symmetry of the cage (see in particular the
difference between the (Ih) and (D5h) isomers of C80 MNEFs), whereas the first reduction potential is
only slightly influenced by the nature of the cage. Poblet et al. computed the orbital energies of the
cages by the density functional theory (DFT) and uncovered an excellent correlation between the
electrochemical gaps of the MNEFs and the (LUMO-4)–(LUMO-3) orbital gaps of the free cages
(Figure 21.4), which nicely confirmed the ionic bonding model M3N6+@C806− proposed for these
compounds [39,41]. Indeed, with such an electron transfer, the HOMO and the LUMO of the MNEF
should correspond respectively to the LUMO-3 and the LUMO-4 of the cage. In addition, the cluster
seems to select the cages with the largest (LUMO-4)–(LUMO-3) orbital gaps.
Other reported encapsulated clusters inside fullerene cages include metal carbides (M2C2, M3C2,
and M4C2; M = Sc, Ti, Y, Lu, Dy, and Gd) [52] and more recently metal oxides (M4O2 and M4O3,
M = Sc) [53], metal sulfides (M2S, M = Sc, Ti, Y, Dy, and Lu) [54], as well as unique Sc3NC
[55], Sc3CH [56], and YCN [57] moieties. The remarkable feature of the metal carbide endohedral
fullerenes is the high flexibility of charge displayed by the C2 moiety. The electronic structures of
Sc2C2@C82, Sc3C2@C80, and Sc4C2@C80 have been shown by DFT calculations to be, respectively,
(Sc3+)2C22− C824−[58], (Sc3+)3C23− C806− [59], and C26−(Sc3+)4C806− [59,60]. The unusual C23− moiety
confirms the ability of carbon cages to accommodate in their interior some species that cannot be
isolated in regular chemical environments. More surprisingly, it seems that reduction or oxidation
of Sc3C2@C80 affects only the charge of the C2 moiety, while the Sc and the cage keep their respec-
tive charges of 3+ and 6− [59]. As usual, a low electrochemical bandgap (0.50 V) characterizes
C80
Electrochemical gaps M3N@C2n/V

2 R2 = 0.98
C92
Sc
1.8
C96 C86 Sc
Y
Ce
1.6 C84 Pr
Nd
Gd
Lu
1.4 La
Lineal (average)
C88
0.8 1.0 1.2 1.4 1.6 1.8 2.0
Orbital gap free cage/eV
FiGURE 21.4 Linear relationship between the electrochemical gaps of MNEFs and calculated (LUMO-4)–
(LUMO-3) orbital gaps of the corresponding empty fullerenes. (Reprinted from Chaur, M.N. et al., Angew.
Chem. Int. Ed., 48, 1425, 2009. With permission.)
species with an open-shell electronic configuration (such as Sc3C2@C80 (Ih)). Compounds with the
same carbon cage usually exhibit striking similarities in their redox behavior provided their clus-
ters are valence isoelectronic. The analogous electrochemical properties of Sc2C2@C82, Sc2O@C82,
and Sc2S@C82 (Cs(6)), for instance, can be understood on the basis of a donation of 4 electrons to
the cage by the cluster in each case (see Table 21.7). Conversely, the electrochemical properties of
Sc3C2@C80 (Ih) and Sc4C2@C80 (Ih) are distinct despite the fact that they share the same carbon cage.
The differences arise from the Sc3C2 and Sc4C2 clusters that could have an open-shell [59] and a
closed-shell configuration, respectively [59,60]. Similarly, the electrochemical behavior of Sc2C2@
C82 (C3v(8)) is very different from that of Sc2@C82 (C3v(8)) [21]. Overall these new clusterfullerenes
TABLE 21.7
Redox Potentials against Fc/Fc+ of Metal Carbide, Metal Oxide, Metal Sulfide Cluster
Fullerenes, and Related Compounds Measured in 1,2-Dichlorobenzene
Fullerene Eox 2 Eox 1 Ered 1 Ered
2 Ered
3 ΔEgap Reference
Sc2C2@C82 (C3v (8)) — 0.47 −0.94 −1.15 −1.60 1.41 [58a]
Sc2C2@C82 (Cs (6)) 0.64 0.42 −0.93 −1.30 — 1.35 [61]
Sc2C2@C72(Cs (10528)) — 0.41 −1.18 −1.54 −1.75 1.59 [62]
Sc3C2@C80 (Ih) — −0.06 −0.50 −1.64 −1.82 0.44 [63]
Sc4C2@C80 (Ih) 1.10 0.40 −1.16 −1.65 — 1.56 [60]
Lu3C2@ C88 (D2) — 0.31 −1.34 −1.70 −2.15 1.65 [64]
Sc2O@C82 (Cs (6)) 0.72 0.35 −0.96 −1.28 −1.74 1.31 [54c]
Sc4O2@C80 (Ih) 0.00 −1.10 −1.73 −2.35 1.10 [53c]
Sc2S@C70 (C2(7892)) 0.65 0.14 −1.44 −1.87 −1.99 1.58 [54e]
Sc2S@C72 (Cs (10528)) 0.96 0.64 −1.14 −1.53 −2.24 1.78 [54d]
Ti2S@C78 (D3h (10528)) 0.65 0.23 −0.92 −1.53 −1.80 1.15 [54f]
Sc2S@C82 (Cs (6)) 0.65 0.39 −0.98 −1.12 −1.73 1.37 [54c]
Sc2S@C82 (C3v (8)) 0.96 0.52 −1.04 −1.19 −1.63 1.56 [54c]
Sc3NC@C80 (Ih (7)) — 0.60 −1.05 −1.68 — 1.65 [55a]
Sc3NC@C78 (C2) — 0.57 −1.05 −1.81 — 1.62 [55b]
YCN@C82 (Cs(6)) 0.56 −0.59 −0.84 −1.76 1.15 [57]
exhibit smaller electrochemical bandgaps and thus lower thermal stability than the corresponding
MNEFs with the same cage. This highlights once again the unique electronic interplay between
the trimetallic nitride clusters and the carbon cages that results in the exceptional stability of the
MNEFs.
C. INFLUENCE oF EXoHEDraL DErIVaTIZaTIoN

1. Empty Fullerenes
The electrochemical behavior of C60 mono or multiadducts has been the subject of numerous studies
and several reviews [7a–c,65]. We will thus recall here only the main conclusions of these studies
for comparison purposes with recent reports for endohedral fullerene derivatives. Most C60 adducts
and cycloadducts can be classified into either 1,2- or 1,4-derivatives if the new bonds are created
respectively on adjacent carbons or on opposite carbons of a 6-membered ring. 1,2-Derivatives can
be further divided into [6,6] or [5,6] adducts if the new bonds are formed respectively at the junc-
tion between two 6-membered rings or at the junction between a 5- and a 6-membered ring. The
[5,6] adducts are usually fulleroids, because the junction needs to be broken to form the new bonds.
Except in the case of [5,6] open adducts [66], derivatization results in partial loss of conjugation,
from 60 to 58π electrons, which usually leads to a cathodic shift of both oxidation and reduction
waves (between 30 and 350 mV per adduct) [7a,c]. However, the electronic properties of fullerenes
can be finely tuned by using various types of addends. Those containing electron-accepting groups
(such as −CN, −NO2, −F, ammonium salts) [67] or electronegative heteroatoms (O, N) [68] directly
attached to the cage increase the electron affinity of C60, whereas those containing electropositive
atoms (such as Si) [69] improve its electron-donating ability. For these derivatives, it is very impor-
tant to carefully analyze any irreversible electrochemical features since these can be an indica-
tion that the adduct is not stable when submitted to a redox process. Echegoyen et al. established
that some of the most commonly prepared C60 cycloadducts, that is, di(alkoxycarbonyl)-methano
(also known as Bingel adducts) [70] and pyrrolidino [71] derivatives, can undergo a retrocycload-
dition reaction under reductive and oxidative conditions, respectively. In CV studies, the methano
adducts exhibit an irreversible second reduction process, whereas the pyrrolidino adducts exhibit an
irreversible pyrrolidino-based first oxidation process [71]. Controlled potential electrolysis (CPE),
conducted at a potential more cathodic than the second reduction wave in the first case and more
anodic than the first oxidation wave in the second case, affords pure C60 in almost quantitative
yields (see Figure 21.5). The generality of the retrocyclopropanation (also termed retro-Bingel reac-
tion) was demonstrated with tris, tetrakis, and pentakis malonate adducts of C60 [70,72]. In these
multiple adducts, the number of cyclopropane rings removed could be controlled by the amount
of charge transferred. Retrocycloadditions were also successfully carried out with Bingel addends
of C70, C76, C78, and C84 [10,70], and the mechanism was investigated with methano C60 derivatives
bearing a paramagnetic probe, such as a para nitro phenyl substituted Bingel-like methanofullerene
[73]. Based on that study, a dicarbonylic radical derivative was proposed as a reasonable intermedi-
ate obtained after cleavage of the cyclopropane ring. Other electrochemically unstable C60 adducts
include silyl derivatives [69] and isoxazoles [74].
Finally, a large number of studies have focused on donor–acceptor systems [75], with C60 as the
electron acceptor and various groups such as ferrocenes, tetrathiafulvalenes, quinones, porphy-
rines, phthalocyanines as the donors and both covalent and noncovalent linkages between the two.
In this context, electrochemical techniques have served to establish the existence of ground-state
interactions between the fullerene and the donor and to determine the HOMO/LUMO gaps, both of
which are important factors in materials design for organic electronic applications. Fullerene-based
donor–acceptor dyads typically exhibit desirable bandgaps in the range of 1–2 eV.
The exohedral reactivity of EMFs appears at first sight to be more complex than that of pristine
C60, owing to the diversity and sometimes lower symmetry of the carbon cages [76]. Multiple stud-
ies have therefore focused on EMFs with the highly symmetric C80 (Ih) cage, which, provided the
O O
O O
1) CPE at –1.5 V vs. Ag wire

4 electrons added
2) Re-oxidation
(a) 82%
O O
O O
1) CPE at –1.5 V vs. Ag wire

O 6 electrons added
O 2) Re-oxidation
O
O
75%
(b)
1) CPE at + 1 V vs. Fc/Fc+

1.8 electrons removed
2) Re-reduction
(c) 73%
FiGURE 21.5 Retro-Bingel reaction of C60 methano derivatives: (a) Mono C60 Bingel adduct and (b) any C60
Bingel-bis adduct. (From Herranz, M.Á. et al., Eur. J. Org. Chem., 2299, 2004.) (c) Retro 1,3-dipolar cyclo-
addition of a N-ethyl-pyrrolidino-C60. (From Lukoyanova, O. et al., Angew. Chem. Int. Ed., 45, 7430, 2006.)
endohedral moiety is freely rotating inside the cage, features only two distinct sites for 1,2-double
bond addition reactions: the all equivalent [5,6] bonds and the all equivalent [6,6] bonds. In addition,
2 different sites exist for 1,4-addition reactions as well. The chemistry of M@C82 (C2v) EMFs has
also been well investigated for a completely different reason. In these compounds, the off-center
position of the endohedral atom induces high local strain on specific carbon atoms and a consequent
polarization of the cage (see Figure 21.6).
The carbon atoms closer to the metal bear a high negative charge density and are thus the target
of electrophiles, whereas some carbon atoms on the opposite site of the cage bear positive charges
and are preferentially attacked by nucleophiles. Overall, only a limited number of addition isomers
have been obtained despite the 24 nonequivalent carbons of these EMFs [8c,76]. Electrochemical
studies of such derivatives give insight into how the electronic properties of endohedral fullerenes
are modified upon derivatization.
2. Endohedral Metallofullerenes Sharing the C80 (Ih) Cage
The icosahedral C80 cage has been derivatized using the typical methods in fullerene chemistry includ-
ing 1,3 dipolar cycloadditions (leading to 1.2-pyrrolidino adducts) [44,77], Diels–Alder reactions [78],
Highest local strain

and negative charge density
Positive charge density Positive charge density
FiGURE 21.6 Localization of the local strain and high negative and positive charge density on La@C82 (C2v).
(Reprinted from Lu, X. et al., Chem. Commun., 47, 5942, 2011. With permission.)
and Bingel, carbene, or nucleophilic reactions (leading to 1,2-methano adducts) [44–45,79–81].

Often, both [5,6] and [6,6] adducts have been prepared, which offers the opportunity to compare
the electronic characteristics of both types of derivatives. In the MNEFs, thermal interconversion of
[6,6] adducts into [5,6] ones have been described, which suggests that the [5,6] and [6,6] derivatives
are the thermodynamic and kinetic products, respectively [82]. Several of these derivatives have
been identified as fulleroids [79–81]. 1,4-Adducts have also been obtained upon silylation [83] and
trifluoromethylation reactions [84]. The redox properties of these derivatives suggest that the elec-
tron affinity and the electrochemical gap of EMFs can be adjusted through derivatization. Similarly
to empty fullerenes, electron-donating addends (adamantylidene Ad, silanes) shift both the oxida-
tion and reduction potentials toward more negative values, whereas electron-withdrawing addends
(tetracyanotetrahydrofurane, trifluoromethyl) shift the redox potentials in the reverse direction (see
Table 21.8). These displacements are gradual: two Si atoms on La2@C80 and four CF3 groups on
Sc3N@C80 shift the reduction potentials approximately twice as much as one Si atom and two CF3
groups, respectively. Nevertheless, in contrast to empty fullerenes, there are no systematic potential
shifts for these derivatives due to bond saturation. A significant difference of up to 0.36 V in the
oxidation potentials of the [5,6] and [6,6] regioisomers of the pyrrolidino derivatives of M2@C80
has been observed. Remarkably, for the M3N@C80 (M = Er, Lu, Y) derivatives, electrochemical
reversibility also depends on the location of the addends: [5,6] adducts normally exhibit reversible
reduction processes, whereas [6,6] adducts typically maintain the irreversible reductive behavior of
the underivatized MNEFs (see Table 21.8) [44]. As a consequence, electrochemical methods can
be useful to determine the location of the addend. Until now, the only exceptions to this rule are
[6,6] diphenylmethane [81], tritylpyrrolidino [85] and benzyne adducts [86] of Sc3N@C80, which
also exhibit reversible reductive behavior. These results may be another consequence of the sig-
nificant contribution of the endohedral cluster to the LUMO of Sc3N@C80, which is unique among
the MNEFs. The pyrrolidino adducts of MNEFs generally exhibit an addend-based first oxidation
process, which is often irreversible. Similarly to C60, CPE at a slightly more positive potential than
the first oxidation process results in the removal of the addend [71].
3. M@C82 (C2v) Endohedral Metallofullerenes

The M@C82 (C2v) EMFs are paramagnetic species (see Section II.B.1), and both adducts with
open-shell and closed-shell electronic configuration have been described by Akasaka and coworkers
[89]. Electrophilic diazo compounds, such as 2-adamantane-2,3-(3H)-diaziridine, and electron-rich
dienes, such as pentamethylcyclopentadiene, both lead to paramagnetic doubly bonded monoad-
ducts in a highly regioselective way: the reagent attacks the electron-rich [6,6] bonds closest to the
TABLE 21.8
Redox Potentials against Fc/Fc+ of Endohedral Derivatives Sharing the C80 (Ih) Cage
Compound Eox 3 Eox 2 Eox 1 Ered
1 Ered
2 Ered
3 ΔEgapa Reference
La2@C80(Ih) — 0.95 0.56 −0.31 −1.72 −2.13 0.87 [22d]
Ce2@C80(Ih) — 0.95 0.57 −0.39 −1.71 — 0.96 [24b]
La2@C80-Ad [6,6 open] — 0.86 0.49 −0.36 −1.78 −2.33 0.85 [79a]
Ce2@C80-Ad [6,6 open] — 0.89 0.47 −0.43 — — 0.90 [79a]
La2@C80-(CClPh) [6,6 open] — 0.93 0.52 −0.26 −1.47 −1.67 0.78 [79b]
La2@C80-(CClPh)Ad [6,6 open] (A) — 1.11 0.46 −0.48 −1.66 −1.87 0.94 [79b]
La2@C80-(CClPh)Ad [6,6 open] (B) — — 0.45 −0.41 −1.63 −1.81 0.86 [79b]
La2@C80-(CClPh)Ad [6,6 open] (C) — 0.91 0.48 −0.41 −1.54 −1.89 0.89 [79b]
La2@C80-Dep2SiCH2CHtBp [5,6] (I) — — 0.11 −0.50b — — 0.61 [83c]
La2@C80-Dep2SiCH2CHtBp [5,6] (II) — — 0.13 −0.53b — — 0.66 [83c]
La2@C80-(Mes2Si)2(CH2) [1,4 adduct] — — −0.06 −0.76b — — 0.70 [83b]
La2@C80-(Dep2Si)2(CH2) [1,4 adduct] — — −0.03 −0.70b — — 0.67 [83b]
La2@C80- N-tritylpyrrolidine [6,6] — 0.95 0.55b −0.51b −1.65b −2.19b 1.06 [77b]
La2@C80- N-tritylpyrrolidine [5,6] 1.01 0.63b 0.23b −0.45b −1.71b −2.30b 0.68 [77b]
Ce2@C80- N-tritylpyrrolidine [6,6] — 0.99 0.56b −0.55b −1.75b −2.34b 1.11 [77b]
Ce2@C80- N-tritylpyrrolidine [5,6] 1.02 0.62b 0.22b −0.51b −1.76b −2.25b 0.73 [77b]
La2@C80-(CN)4THF [5,6] — — 0.64 −0.21b — — 0.85 [84]
Sc3N@C80 (Ih) — 1.09b 0.59b −1.26 −1.62 −2.37 1.85 [36a]
Y3N@C80 (Ih) — — 0.64b −1.41 −1.83 −2.34 2.05 [44]
Er3N@C80 (Ih) — — 0.63b −1.40 −1.83 −2.16 2.03 [44]
Lu3N@C80 (Ih) — 1.11b 0.64b −1.42 −1.80 −2.26 2.06 [45]
Gd3N@C80 (Ih) — — 0.58b −1.44 −1.86 −2.18 2.02 [38]
Sc3N@C80-N-tritylpyrrolidine [5,6] — 0.60b 0.35 −1.14b −1.54b −2.38b 1.49 [85]
Sc3N@C80-N-tritylpyrrolidine [6,6] — 0.60b 0.39b −1.06b −1.35b −2.35b 1.45 [85]
Sc3N@C80-C(CO2Et)2 [6,6] — 1.08b 0.56b −1.34 −1.90 −2.22 1.90 [45]
Sc3N@C80-spirofluorene [6,6] — 1.03b 0.52b −1.24 −1.96 −2.41 1.76 [45]
Sc3N@C80-CHPh [6,6 open] — 1.08* 0.50 −1.48 −2.01 −2.40 1.98 [80b]
Sc3N@C80-(p-C6H13O)2DPM — — −1.19 −1.51 −1.92 — [81]
[5,6 open]
Sc3N@C80-(p-C6H13O)2DPM — +0.52 −1.51* −1.61* −2.23* 2.03 [81]
[6,6 open]
Sc3N@C80-N-ethylpyrrolidine [5,6] — 0.62b 0.30 −1.18b −1.57b −2.29b 1.48 [44]
Sc3N@C80-C10H12O2 [5,6] — 0.62b 0.25b −1.16b −1.54b −2.26b 1.41 [44]
Sc3N@C80-C6H4 [5,6] — 0.92 0.34 −1.11b −1.50b −2.21b 1.45 [86]
Sc3N@C80-C6H4 [6,6] — 0.83b 0.42b −1.08b −1.29b −2.23b 1.50 [86]
Sc3N@C80-(Mes2Si)2CH2 — — 0.08b −1.45b — — 1.53 [83a]
[1,4 adduct]
Sc3N@C80-(CF3)2 [1,4 adduct] — 0.60b 0.47b −1.16b −1.65b −2.04b 1.59 [87b]
Sc3N@C80-(CF3)4 — — 0.55b −1.06b −1.55b −2.03b 1.61 [87c]
Sc3N@C80-(CF3)10 — — 0.86b −0.84b −1.32b −2.11b 1.70 [87c]
Y3N@C80-C(CO2Et)2 [6,6 open] — — 0.60b −1.43 −1.88 — 2.03 [44]
Y3N@C80-N-ethylpyrrolidine [5,6] — 0.64b 0.37 −1.30b −1.65b −2.36b 1.67 [44]
Y3N@C80-N-ethylpyrrolidine [6,6] — 0.65b 0.40 −1.40 −2.10 — 1.80 [44]
Er3N@C80-N-ethylpyrrolidine [5,6] — 0.64b 0.34 −1.28b −1.63b −2.33b 1.62 [44]
Er3N@C80-N-ethylpyrrolidine [6,6] — 0.64b 0.39 −1.36 −2.00 — 1.75 [44]
Er3N@C80-C(CO2Et)2 [6,6 open] — — 0.60b −1.43 −1.88 — 2.03 [44]
Lu3N@C80-N-tritylpyrrolidine [5,6] — — — −1.13b −1.42b −2.43b [85]
Lu3N@C80-N-tritylpyrrolidine [6,6] — 0.64b 0.43b −1.28 −2.03 −2.31 1.71 [85]
(Continued)

Redox Potentials against Fc/Fc+ of Endohedral Derivatives Sharing the C80 (Ih) Cage
Compound Eox 3 Eox 2 Eox 1 Ered
1 Ered 2 Ered
3 ΔEgapa Reference
Lu3N@C80-(SiDep2) [5,6 open] — — 0.27 −1.43 −1.72 −1.94 1.70 [83d]
Lu3N@C80-(SiDep2) [6,6] — — 0.43 −1.52 −1.73 −1.99 1.95 [83d]
Lu3N@C80-(Mes2Si)2CH2 — — 0.06 −1.55 −2.01 — 1.61 [83e]
[1,4 adduct]
Lu3N@C80-(Dep2Si)2CH2 — — 0.08 −1.61 −2.15 −2.58 1.69 [83e]
[1,4 adduct]
Lu3N@C80-C(CO2Et)2 [6,6] — 1.15b 0.62b −1.45 −1.88 −2.22 2.07 [45]
Lu3N@C80-CHPh [6,6 open] — 1.10b 0.59 −1.49 −1.95 −2.32 2.08 [80a]
Gd3N@C80-C(CO2Et)2 [6,6 open] — — 0.58b −1.39 −1.83 −2.17 1.97 [88]
Gd3N@C80-[C(CO2Et)2]2 — — 0.59b −1.40 −1.88 — 1.99 [88]
a ΔEgap = Eox − Ered ; DPM, diphenylmethane; Dep, 2,6-diethylphenyl; Mes, mesityl.

1 1
b Reversibility at 0.1 Vs−1 in the CV experiments.
metal atom in the former case and the positively charged carbon atoms on the other side of the cage
in the latter case as described earlier (Figure 21.5). In contrast to empty fullerenes, these EMFs
also react thermally with disilirane reagents, as a consequence of their stronger electron-accepting
properties [90]. Several doubly bonded adducts active in electron paramagnetic resonance (EPR)
are obtained in this case. In the Bingel–Hirsch reaction with bromomalonate, one EPR-silent sin-
gly bonded adduct (La@C82–CBr(COOC2H5)2) is dominant. When malonate is used, a bis-adduct
is preferentially formed, La@C82–[CH(COOC2H5)2]2, which retains an open-shell configuration.
Under irradiation, direct radical coupling occurs with toluene derivatives, leading to EPR-silent
benzyl derivatives. Radical pairing with NO2 has also been observed in benzyne adducts of La@
C82. The paramagnetic adducts retain an electrochemical gap in the range of 0.4–0.6 V, but their
reduction and oxidation potentials are shifted with respect to the parent EMF. Studies of this fam-
ily of compounds (see Table 21.9) confirm that silanes and adamantylidene addends decrease the
electron affinity of EMFs. The redox potentials and electrochemical bandgaps of the adamantyli-
dene derivatives are only slightly influenced by the position of the addend [91–93]. As expected,
the diamagnetic derivatives exhibit larger electrochemical bandgaps. Their redox potentials are
highly dependent on the position of the addend on the carbon cage. A difference in the reduction
potentials of up to 0.37 V has been observed for La@C82–CH2C6H5 regioisomers [98].
4. Endohedral Metallofullerenes Incorporated in Donor–Acceptor Dyads

Researchers have started to investigate the highly tunable electrochemical bandgap of EMFs in
various donor–acceptor dyads [102]. Like their empty fullerene analogs, EMFs can act as electron
acceptors in these assemblies due to their high electron affinity. However, some EMFs also exhibit
good electron donor properties (see Section II.B.1) making them potential donors as well [103].
Most interestingly, the role of the donor and acceptor in a Ce2@C80-zinc porphyrin system has
been switched by changing only the nature of the solvent [104]. Other donor molecules considered
thus far include aza and thiacrown ethers [105], triphenylamine [106a], ferrocene [106b], extended
TTF [106b,107], and phthalocyanine [106b]. Covalent linkages via methano bridges or pyrrolidines
as well as supramolecular assemblies have been reported [102,108]. These studies have identified
electronic interactions between the donor and acceptor groups in the ground state in several of the
described systems. In covalently linked triphenyl amine Sc3N@C80 conjugates, for instance [106a],
the reduction of the fullerene is shifted toward more positive potentials, while the oxidation of the
TPA moiety is shifted toward more negative potentials. The magnitude of the shift depends on the
connection between the groups, in this case the substitution on the pyrrolidine. In a very interesting
TABLE 21.9
Redox Potentials against Fc/Fc+ of M@C82 (C2v) and Some Exohedral Derivatives
Compound Eox 2 Eox 1 Ered
1 Ered
2 Ered
3 ΔEgapa Reference
La@C82 (C2v) b 1.07 0.07 −0.42 −1.37 −1.53 0.49 [14a]
Gd@C82 (C2v)b 1.08 0.09 −0.39 −1.22 — 0.48 [14a]
Ce@C82 (C2v)b — 0.08 −0.41 −1.36 −1.72 0.49 [14a]
Y@C82 (C2v)b 1.07 0.10 −0.37 −1.34 −2.22 0.47 [14a]
La@C82-adamantylideneb 1.01 −0.01 −0.49 −1.44 −1.79 0.48 [94]
Ce@C82-adamantylidene (I)b — 0.01 −0.41 −1.36 −1.72 0.42 [92]
Ce@C82-adamantylidene (II)b — 0.02 −0.42 −1.35 −1.74 0.44 [92]
Gd@C82-adamantylideneb — 0.06 −0.62 −1.48 −1.76 0.68 [95]
Y@C82-adamantylidene (I)b — −0.02 −0.54 −1.51 −1.84 0.56 [91]
Y@C82-adamantylidene (II)b — 0.05 −0.43 −1.37 −1.70 0.48 [91]
Sc@C82-adamantylidene (I)b — 0.09 −0.39 −1.43 — 0.48 [93]
Sc@C82-adamantylidene (II)b — 0.09 −0.37 −1.39 — 0.46 [93]
Sc@C82-adamantylidene (III)b — 0.05 −0.42 −1.40 — 0.47 [93]
Sc@C82-adamantylidene (IV)b — −0.04 −0.43 — — 0.47 [93]
La@C82-Me5Cpb — 0.02 −0.45 −1.71 −2.22 0.47 [96]
La@C82-(Mes2Si)2CH2 (I)b — −0.07 −0.50 −1.71 −1.75 0.43 [97]
Y@C82-(Mes2Si)2CH2 (I)b 0.10 −0.10 −0.55 −1.36 — 0.45 [97]
Y@C82-(Mes2Si)2CH2 (II)b — −0.03 −0.42 — — 0.39 [97]
La@C82-[CH(COOC2H5)2]2b — 0.08 −0.32 −1.57 — 0.40 [98]
La@C82-CBr(COOC2H5)2 0.85 0.38 −0.66 −1.31 −1.47 1.04 [99]
La@C82-CH2C6H5 (2a)c — 0.25 −0.68 −1.02 −1.21 0.93 [100]
La@C82-CH2C6H5 (2b)c — 0.21 −0.95 −1.40 — 1.16 [100]
La@C82-CH2C6H5 (2c)c — 0.17 −0.84 −1.42 −1.74 1.01 [100]
La@C82-CH2C6H5 (2d)c — 0.15 −1.05 −1.15 −1.81 1.20 [100]
La@C82-CHClC6H3Cl2 (3b)b — 0.24 −0.91 −1.39 — 1.15 [100]
La@C82-CHClC6H3Cl2 (3d)b — 0.25 −0.98 −1.07 −1.34 1.23 [100]
La@C82(C6H4)2NO2 — 0.25 −0.39 −1.39 — 0.64 [101]
a ΔEgap = E1ox/ 21 − Epred

c
1
.
b EPR activity.
c Compounds 2a–d and 3b–d in [100].
report [109], two covalently linked zinc tetraphenylporphyrin hybrids with La2@C80 and Sc3N@C80
were compared. Studies by nuclear magnetic resonance (NMR) suggested that La2@C80 interacts
more with the porphyrin (presumably through strong π–π and electrostatic interactions) than with
Sc3N@C80. Electrochemical studies confirmed that the reduction of La2@C80 in the presence of the
porphyrin is significantly hindered while that of Sc3N@C80 is almost unaltered. Charge transfer com-
plexes between endohedral fullerenes and organic donor molecules such as N,N,N′,N′-tetramethyl-
p-phenylenediamine (TMPD) have also been reported, in particular (La@C82)• −/(TMPD)• + [110]
and (La2@C80)• −/(TMPD)• + [111]. This complexation requires EMFs with not too negative reduction
potentials and is temperature and solvent-dependent. The analog complexation with Sc3N@C80 is
very weak due to the lower electron affinity of this compound.
Upon photoexcitation of the donor, charge-separated states with exceptional lifetimes, often
longer than C60 analogs, have been obtained, which means that EMFs could have better electronic
properties than empty fullerenes for organic electronic applications. In a Sc3N@C80-ferrocene (Fc)
dyad, for instance, after excitation at 388 nm, a charge-separated state (Sc3N@C80)• −/Fc• + with a
lifetime three times longer than an equivalent C60 dyad has been observed [106b,112]. More recently,
long-range (45 Å) photoinduced electron transfer and charge-separated states with lifetimes on the
order of μs have been achieved for Sc3N@C80-zinc porphyrin dyads [113]. Last but not the least,
the first organic bulk-heterojunction solar cell incorporating a clusterfullerene, Lu3N@C80, exhib-
ited a promising open circuit voltage 0.3 V higher than the classical devices using [6,6]-phenyl-C61
butyric acid methyl ester [114]. The short circuit current of this device, however, still needs some
improvement.
D. LarGEr CarboN NaNoSTrUCTUrES: STrUCTUrE, DEFECTS, aND IMpUrITY EFFECTS

Carbon nanotubes (CNTs) and carbon nano-onions (CNOs) belong to the same family of new car-
bon allotropes as fullerenes and were discovered almost simultaneously by Iijima [115] and Ugarte
[116], respectively, in the early 1990s. CNTs are made of either one (the so-called single-wall carbon
nanotubes [SWNTs]) or several graphene layers (multiwall carbon nanotubes [MWNTs]) rolled up
into concentric cylinders. They can be metallic or semiconducting depending on their diameter and
helicity [117]. CNOs are best described as multishelled fullerenes (see Figure 21.7).
In contrast to fullerenes, the solution electrochemistry of pristine CNTs and CNOs is still largely
unexplored due to the tedious methods of purification as well as their difficult processibility in
solution. Samples of CNTs are highly heterogeneous and contain significant amounts of amor-
phous carbon, nanographite particles, and metallic impurities [118] that taint the results. In addition,
CNTs are essentially insoluble materials, and, consequently, they must either be dispersed using
surfactants or functionalized to improve their solubility [119], otherwise studies on CNTs must be
performed in the solid state [120]. All of these approaches give valuable information, yet results are
obscured by interactions with other tubes (bundling) or other materials in solution (such as surfac-
tants), the substrate (in the solid state), or disruption of the π network (for functionalized nanotubes).
Reasonable progress has recently been made by Prato et al., who reported the electrochemical
characterization of SWNTs derivatized with pyrrolidines on their sidewalls [121]. The cyclic voltam-
mogram exhibited no discrete peaks, as in the case of fullerenes, but a continuum of diffusion-
controlled reduction current with onset at −0.5 V. This current was related to the electronic density
of states of the SWNTs, and from quantum chemical calculations of this density of states, the authors
claimed that derivatization alters significantly only the low-lying electronic states but not the overall
electronic properties of the nanotubes. A similar behavior was reported for CNTs derivatized with
poly(sodium 4-styrenesulfonate) [122] as well as lithium salts of reduced CNTs [119b]. Acid-treated
CNTs [123] and CNOs [124], in contrast, exhibit voltammograms with broad anodic and cathodic
peaks, attributed to the presence of oxygenated groups on the carbon surface such as carboxylates,
ethers, ketones, and lactones. These groups are converted into hydroxyl groups upon reduction.
(a) (b) (c)

(d)
FiGURE 21.7 Structures of SWNTs, CNOs, and graphene sheets. (a) C60. (b) Ideal single-wall carbon nano-
tube (SWNT). (c) Ideal carbon nano-onion (CNO). (d) Ideal graphene sheet.
CNTs, however, have received considerable attention as electrode materials [125] due to their unique
electrical conductivity, mechanical strength, and high surface-to-volume ratio. They are sometimes
considered as the ideal nanometer-sized electrode and have potential applications in electrochemi-
cal sensing [126] and energy storage [127]. Numerous studies with various electrochemical probes,
including dopamine, ascorbic acid, oxygen, hydrogen peroxide, nicotinamide adenine dinucleotide,
norepinephrine, and potassium ferrocyanide [123,128] at CNT-modified electrodes suggested that
these materials might enhance voltammetric currents, exchange electrons faster than graphite elec-
trodes, and even exhibit an electrocatalytic effect. The origin of these properties remains highly con-
troversial and is presently strongly debated in the scientific community. Compton et al. have shown
that in both MWNT- [129] and SWNT [130]-modified electrodes, electron transfer probably takes
place either at the edge-like sites located at the tips of the tubes or at defect sites. In other words, the
sidewalls of the tubes might be as much electrochemically inactive as basal planes of graphite, which
means that CNT-based electrodes and edge-plane pyrolytic graphite electrodes should in principle
exhibit similar properties. The high heterogeneous electron transfer rate and electrocatalytic behavior
sometimes observed with CNT-based electrodes actually could be due to some nanographite [131] and
metallic impurities [132] contained in the CNT samples or to the oxygenated groups at their tips [133].
Dekker et al., however, have shown that individual SWNTs grown by chemical vapor deposition on
a silicon wafer with no tips exposed to the solution could exchange electrons with ferrocenylmethyl-
trimethylammonium at their sidewalls [134]. Dai et al. suggested recently that the location of the
electron transfer could ultimately depend on the electrochemical probe used for the studies [135].
Given these often contradictory reports, the authors recommend to exercise caution and to take into
consideration the structure of the CNTs, their purity, as well as all the chemical treatments they have
undergone before claiming any advantage of these materials. These recommendations also apply to
graphene and CNOs, which are also being exploited as promising electrode materials [136,137].
Research on CNTs is also directed toward donor–acceptor assemblies for photovoltaic applica-
tions. Similarly to endohedral fullerenes, CNTs can act both as electron donors and acceptors,
depending on the interaction with photoexcitable molecules [138]. The usual electron donors in the
photoexcited state include porphyrins, phthalocyanines, and ferrocene, whereas C60, upon excita-
tion, can accept one electron from SWNTs. As expected, the photoinduced electron transfer rates
depend on the diameter of the CNTs as well as their electronic structure.
Undoubtedly, electrochemical methods have greatly contributed to the electronic characteriza-
tion of fullerenes, endohedral fullerenes, and larger carbon nanostructures. The high sensitivity is
particularly adept to the small amounts of material that are typically available. The most recent
studies have revealed that the electronic properties of EMFs, including their electrochemical band-
gaps, can be fine-tuned by changing the encapsulated moiety or the nature of the cage or by adding
e xohedral groups. This tunability makes EMFs promising candidates for molecular electronics
applications. Other carbon nanostructures, including CNTs, are used as electrode materials for
promising applications in sensing and energy storage. Where more conventional chromatographic
or synthetic methods would fail, electrochemical methods make it possible to isolate and purify
fullerenes and related compounds and to prepare specific isomers of multiple derivatives.
III. PREPARATiON, PURificATiON, AND DERivATizATiON Of FULLERENES

AND RELATED COMPOUNDS BASED ON ThEiR REDOx PROPERTiES
A. ISoLaTIoN oF KINETICaLLY UNSTabLE EMpTY aND ENDoHEDraL FULLErENES
1. Looking for the Missing Empty Carbon Cages
A surprising feature of the HPLC traces of the crude mixture of fullerenes obtained from graphite
arcing or laser ablation of carbon targets is the absence of empty C72, C74, C80 (Ih), and C88, while
larger fullerenes such as C90, C92, and C96 can still be detected. Alford and Diener suggested that
the unexpected absence of these empty fullerenes is linked to their very small HOMO–LUMO gap,
as predicted by DFT [139]. Electrochemical studies have confirmed that all the isolated fullerenes
feature a HOMO–LUMO gap of 1.0 eV or greater (see ΔEgap in Table 21.3) [12–13], whereas C74, for
instance, is predicted to have a bandgap of 0.05 eV and probably a diradical-like electronic structure
at ambient temperature [139a]. This carbon cage is thus kinetically unstable and should exist only as
an oligomer or polymer, or as a charge transfer complex with a metal like most of the small bandgap
fullerenes. Consequently, through electrochemical or chemical reduction, these compounds should
in principle get a closed-shell electronic configuration, and therefore increased kinetic stability.
Alford and Diener reported the isolation of C74 and fullerenes up to C100 by electrolysis of sublimed
raw carbon soot obtained after the arcing process [139a]. At −1.0 V versus Ag/AgNO3 reference
electrode both the low and high bandgap fullerenes are reduced to anionic forms and stay in solu-
tion due to electrostatic repulsions. Upon reoxidation at 0.4 V, the low bandgap fullerenes return to
their polymerized solid state and can be selectively deposited on the working electrode. A second
electrochemical reduction eventually yields a solution of low bandgap fullerene anions devoid of
C60 and C70.
2. Separating Endohedral Metallofullerenes from Empty Fullerenes

Smalley et al. discovered the first EMF (La@C2n) almost at the same time as C60 after laser
vaporization of composite targets made of graphite and lanthanum oxide or chloride [140].
Studying these fascinating compounds has not been an easy task due to their availability in very
small quantities, laborious separation from empty fullerenes, and kinetic instability. Fortunately,
EMFs are often easier to reduce than the corresponding empty cages (see Section II.B. and
Table 21.10), and therefore selective electrochemical or chemical reduction of soot extracts
containing a mixture of endohedral and empty fullerenes is a very useful technique to isolate
these compounds. Neutral La@C82 and Pr@C82 are radical species. However, their correspond-
ing monoanions are diamagnetic, stable, and very soluble [141]. Along these lines, Akasaka
et al. successfully isolated lanthanide-containing metallofullerenes by CPE at 0 V versus stan-
dard calomel electrode (about −0.5 V vs. Fc/Fc+) [142]. At that potential (see Table 21.9), the
metallofullerenes are selectively reduced and become soluble in a mixture of acetone and CS2,
whereas the empty fullerenes remain insoluble. Filtration of the resulting mixture yields a filtrate
free of any empty fullerene.
TABLE 21.10
Comparison of the Redox Potentials of Some Endohedral Metallofullerenes and Empty
Fullerenes (in V vs. Fc/Fc+)
Compound E1ox (V ) E1red (V ) ΔEgapa Reference
La@C82 (C2v) 0.07 −0.42 0.49 [14a]
La@C82 (Cs) −0.07 −0.48 0.54 [15b]
Pr@C82 (C2v) 0.07 −0.39 0.46 [15b]
Pr@C82 (Cs) −0.07 −0.48 0.55 [15b]
Gd@C82 (C2v) 0.09 −0.39 0.48 [14a]
[Li@C60]+ — −0.39 — [144]
C60 1.26 −1.06 2.32 [13]
C70 1.20 −1.02 2.22 [13]
C76 0.81 −0.83 1.64 [13]
C78 (C2v) 0.95 −0.77 1.72 [13]
C82 0.72 −0.69 1.41 [14a]
C84 0.93 −0.67 1.60 [13]
a ΔEgap = E1ox − E1red.

Alternatively, electrochemical or chemical oxidation can also be used to separate or purify

some EMFs. Indeed, as a consequence of the electron transfer between the metal and the cage,
metallofullerenes are expected to be more easily oxidized than empty fullerenes (see Table 21.10).
Solutions of cationic fullerenes can usually be kept over several days in weakly coordinating sol-
vents in the absence of any nucleophile. Bolskar et al. reported the separation of Gd metallofuller-
enes into three different fractions by selective chemical oxidation [143]. The soot sublimate was
first treated with 1,2-dichlorobenzene to remove the soluble empty and metallofullerenes (including
Gd@C82). The insoluble Gd@C2n mixture was then treated with the oxidant tris(4-bromophenyl)
ammoniumyl hexachloroantimonate (TPBAH) to solubilize and remove the easily oxidizable com-
pounds (Gd@C2n with 72 < 2n < 106). Finally, some of the empty C74 was removed from the insol-
uble material by oxidation with the stronger oxidant AlCl3. This procedure yielded up to 500 mg
of a fraction enriched in Gd@C60, out of 2.5 g of soot sublimate. Other C60 metallofullerenes have
turned out to be very difficult to isolate due to their high reactivity toward empty fullerenes, which
are also formed in the arc reactor. Only recently, Tobita et al. reported the complete isolation and
characterization of Li@C60, as a Li+@C60, SbCl6 − salt [144].
This endohedral fullerene was synthetized by a plasma method in the presence of Li. The car-
bon deposit was then reacted with TPBAH as oxidant in 1,2-dichlorobenzene at 100°C, yielding
the cationic metallofullerene, which proved sufficiently stable for getting a crystal structure. Its
ability to form supramolecular complexes with electron donor hosts was also demonstrated [145].
This procedure should be easily extended to other M@C60 metallofullerenes, such as Gd@C60 and
La@C60.
3. Looking for the Missing Endohedral Metallofullerenes

Since the pioneer work of Smalley et al., it is known that several EMFs are formed during the laser
ablation of graphite and lanthanum targets, including La@C60, La@C74, and La@C82 [146]. Until
recently, however, only two isomers of La@C82 were easily isolated: the (C2v) and the (Cs) [147] (see
Section II.B.1.). This is a consequence of the transfer of three electrons from lanthanum to the cage,
which results in paramagnetic and thus potentially reactive EMF species. An important milestone
was achieved by Akasaka and coworkers in 2005 with the isolation of La@C74 (D3h) [148a]. The
extraction was achieved in 1,2,4-trichlorobenzene, which produces dichlorophenyl radicals upon
heating. These radicals react with the paramagnetic fullerenes during the extraction procedure
and form diamagnetic adducts with larger electrochemical bandgaps and thus higher stability. In
this case, up to six regioisomers of La@C74 –C6H3Cl2 with electrochemical bandgaps in the range
of 1.2–1.4 V were obtained [148]. This procedure was also successfully applied for the isolation
of La@C72 (C2) [149], La@C80 (C2v) [150], La@C82 (C3v) [151], and more recently for the elusive
M@C60 and M@C70 [152].
B. SEparaTIoN oF ISoMErIC CarboN CaGES

1. By Selective Oxidation
Sc3N@C80 was first prepared by Dorn and coworkers in 1999 by arcing graphite rods packed with
Sc2O3 under a mixture of helium and nitrogen gases [27]. After purification by HPLC of the soluble
soot extract, a mixture of two isomers of Sc3N@C80 was obtained: the predominant (Ih) isomer and
the less abundant (D5h). The voltammogram of the HPLC-pure sample clearly shows the superposi-
tion of waves from both isomers in the anodic region (Figure 21.8a) [36a].
Interestingly, the (D5h) isomer is easier to oxidize than the icosahedral one by about 0.3 V, which
allowed Echegoyen et al. to separate the two isomers [36a]. TPBAH that has a redox potential inter-
mediate between those of the two isomers (Figure 21.8b), preferentially oxidizes the (D5h) isomer. It
could thus be removed from the mixture by simple filtration over a plug of SiO2. An electrochemical
analysis of the pure icosahedral isomer of Sc3N@C80 was then reported as proof (Figure 21.8c). The
isolation of the (D5h) isomer was not described, but reductive desorption from the silica could lead to
Ih+D5h(?) mixture
(a)
Oxidative couple of TPBAH
Current/a.u.
(b)
Pure Ih
(c)
1.2 1.0 0.8 0.6 0.4 0.2 0.0 –0.2

Potential/V vs. Fc/Fc+
FiGURE 21.8 OSWV of (a) mixture of (Ih) and (D5h) isomers of Sc3N@C80; (b) TPBAH; (c) pure (Ih) isomer
of Sc3N@C80. (Reprinted from Elliott, B. et al., J. Am. Chem. Soc., 127, 10885, 2005. With permission.)
the recovery of this pure isomer. Milder oxidants such as acetylferrocenium salts [Fe(COCH3C5H4)
Cp]+can also be used, which improve the yield of Sc3N@C80 (Ih) recovery [153].
2. Using the Retrocyclopropanation Reaction

The electrochemically induced retrocyclopropanation reaction has found an important applica-
tion in the isolation of enantiomerically pure chiral fullerene cages. Optically active malonates
have been attached to these fullerene cages as chiral auxiliaries. The resulting diastereoisomers
were separated by HPLC, and removal of the methano addends by CPE (the retrocyclopropanation
r eaction) yielded the pure fullerene enantiomers, as confirmed by circular dichroism measurements.
This strategy has been successfully applied to C76 [70,73,154] and C84 (D2) [155].
C. PrEparaTIoN oF EXoHEDraL DErIVaTIVES oF FULLErENES

1. By Nucleophilic Substitution
Chemical derivatization of fullerenes is usually carried out using cycloaddition, radical addition,
metal complex formation, or nucleophilic substitution [156]. The latter involves fullerene anions,
which can be easily prepared in aprotic solvents either by chemical or electrochemical reduction.
Electrochemical reduction, however, allows for better control of the amount of charge on the car-
bon cage. In 1993, Kadish et al. reported for the first time the preparation of a mixture of 1,2- and
1,4-dimethyl C60 isomers by the reaction of C602− generated by CPE with methyl iodide in benzo-
nitrile [157]. Different organic halides were later explored, including dibromo substrates and ben-
zyl bromide, leading to substituted methanofullerenes [158] and to a 1,4-(C6H5CH2)2C60 derivative
[159a], respectively. Further electrolysis of 1,4-(C6H5CH2)2C60 to generate (C6H5CH2)2C602− by CPE,
yielded a mixture of the 1,4;1,4 (Figure 21.9a) and 1,4;1,2 isomers of (C6H5CH2)4C60 [159b]. It should
be pointed out that these derivatives are very difficult to prepare by other methods. Interestingly,
when carrying out the nucleophilic substitution of benzyl bromide still in benzonitrile but with
(a) (b)
FiGURE 21.9 X-ray structures of (a) the 1,4;1,4 isomer of (C6H5CH2)4C60 and (b) fullerooxazole obtained
by reaction of electrochemically generated C602− and C603−, respectively, with benzyl bromide in benzonitrile.
Hydrogen atoms were removed for clarity. For (b), analysis of the electron density did not allow discrimination
between nitrogen and oxygen; however, NMR and mass spectrometry confirmed the presence of an oxazoline
heterocycle. These structures were drawn using Mercury and crystallographic information files QAWRUB
[159b] and PBCA [160a].
C603− instead of C602−, Gao et al. recently obtained a new and unexpected C60 cycloadduct: a fullero-
oxazole (Figure 21.9b) [160a]. Surprisingly, it turned out that the solvent was the source of nitrogen,
whereas the oxygen atom came from traces of water in the reaction mixture. This reaction was
reproduced in the absence of benzyl bromide [160a], with various substituted benzonitriles [160b]
and a methano derivative of C60 (C61HPh) to reveal the regioselectivity [160b].
2. Using the Retrocyclopropanation Reaction

Since malonate methano addends can be easily and selectively removed in the presence of pyr-
rolidino addends, they have also been used as blocking groups on the carbon sphere to get better
control of the regiochemistry of multiple additions. Using the orthogonal transposition method
introduced by Kräutler et al. in 1997 [161], four di(ethoxycarbonyl)-methano groups can be added
to the equatorial position of C60. Due to steric reasons, further addition of pyrrolidine groups will
occur at the two poles of the carbon sphere. Subsequently, some of the methano groups can be
selectively removed by retrocyclopropanation. Along these lines, the selective formation of an
improbable (e,e,e,e)-tetrakis-[60] fullerene derivative was recently reported. The compound bears
two pyrrolidine groups trans-1 to each other and two cyclopropane rings also trans-1 to each
other (Figure 21.10) [162]. The reductive behavior of this compound was surprisingly reversible
(see Figure 21.11), which suggests that the remaining two cyclopropane rings cannot be easily
removed.
3. Fine-Tuning the Reactivity of Endohedral Fullerenes

So far, the chemistry of endohedral fullerenes has not been studied as extensively as that of the
empty fullerenes, mainly due to the small amounts of most of the compounds that can be obtained
from the soot. However, some very interesting studies have suggested that the chemical properties
of these molecules can be fine-tuned by redox treatment prior to the reaction.
Akasaka et al. compared the reactivity of M@C82, (M@C82)+, and (M@C82)− (M = Y, La, Ce)
toward 1,1,2,2-tetramesityl-1,2-disilirane [163]. This nucleophilic reagent has been frequently used as
a probe of fullerene reactivity. The cationic and anionic fullerenes were generated by oxidation with
N N
1) anthracene, 180° C
2) diethylbromomalonate/
diazabicycloundecene, N N
pyridine glycine,
CH2Cl2, room temperature 1) CPE at – 1.9V vs. Ag wire
paraformaldehyde,
6 electrons added
3) 195° C o-dichlorobenzene, 2) Reoxidation
R R R R reflux R R R R R R
R R R R R R R R
R R
Orthogonal transposition Two successive 1,3-dipolar Retro-Bingel reaction

R = CO2Et cycloaddition N N
N N
3% 18%
FiGURE 21.10 Synthesis of an (e,e,e,e)-tetrakis-[60] fullerene derivative using the orthogonal transposition
strategy and a selective retrocyclopropanation. (Reprinted from Ortiz, A.L. and Echegoyen, L., J. Mater.
Chem., 21, 1362, 2011. With permission.)
1.4
1.2
1.0
0.8
0.6
Current (μA)
0.4
0.2
0.0
–0.2
–0.4
–0.6
–1.0 –1.5 –2.0
Potential/V vs. Fc/Fc+1
FiGURE 21.11 CV of the (e,e,e,e)-tetrakis-[60] fullerene derivative obtained in CH2Cl2 + 0.1 M (n-Bu)4NPF6
(scan rate 0.1 Vs−1).
TPBAH and reduction with sodium thiomethoxide, respectively. As summarized in Table 21.11, the
cationic fullerenes exhibited enhanced thermal reactivity, when compared to their corresponding neu-
tral species. In contrast, the anionic fullerenes did not react at all. These observations were correlated
to the redox potentials of the different species. Easily reducible fullerenes are electrophilic and react
easily with disilirane, whereas less reducible fullerenes do not react (see Table 21.11).
Conversely, more nucleophilic endohedral fullerene species should react more easily with
electrophiles. A very recent study by Echegoyen et al., involving trimetallic nitride cluster fuller-
ene dianions and benzyl bromide as electrophile confirmed this fact [80a]. In that report, the
dianions of Sc3N@C80 (I h) and Lu3N@C80 (I h) were generated by CPE at −1.6 V versus silver
wire reference electrode. DFT calculations, as well as the electrochemical properties of these
two compounds (see Table 21.10), suggested that Lu3N@C80 dianion is more nucleophilic than its
scandium analog. Indeed, only the dianion of Lu3N@C80 reacted with benzyl bromide, leading
TABLE 21.11
Redox Potentials against Ferrocene/Ferrocenium Fc/Fc+ of Some Endohedral
Metallofullerenes and Reactivity toward Disilirane and Benzyl Bromide
Compound E1ox (V ) E1red (V ) Reaction with Disilirane Reaction with Benzyl Bromide Reference
La@C82 (C2v) 0.07 −0.42 Yes (80°C) [163]
Y@C82 (C2v) 0.10 −0.37 Yes (80°C) [163]
Ce@C82 (C2v) 0.08 −0.41 Yes (80°C) [163]
(La@C82)+ (C2v) 1.07 0.07 Yes (r.t.) [163]
(Y@C82)+ (C2v) 1.07 0.10 Yes (r.t.) [163]
(Ce@C82)+ (C2v) 1.08 0.08 Yes (r.t.) [163]
(La@C82)− (C2v) −0.42 −1.37 No [163]
(Y@C82)− (C2v) −0.37 −1.34 No [163]
(Ce@C82)− (C2v) −0.41 −1.41 No [163]
(Sc3N@C80)2− (Ih) −1.56a −0.83a No [164]
(Lu3N@C80)2− (Ih) −1.80b −2.26b Yes (r.t.) [164]
a 2nd and 3rd reduction waves of Sc3N@C80.

b 2nd and 3rd reduction waves of Sc3N@C80.
to the open methano adduct (fulleroid) at the junction between two six-member rings ([6,6] ring
junction). Interestingly, nucleophilic addition to Sc3N@C80 (I h) becomes possible if the trianion
is prepared [80b].
D. SoLUTIoN ProCESSING oF LarGEr CarboN NaNoSTrUCTUrES

Interestingly, redox-based methods have not only advanced the field of nanocarbon as it applies to
the fullerene families, but it is also playing a crucial role in advancing the chemistry of nanotubes
and graphene. For example, reduction with alkali metals breaks the bundles of CNTs in polar sol-
vents without the need of surfactants, thanks to the electrostatic repulsion between the charges
introduced on the tubes [119b,c], and allows their further functionalization [164]. This process has
allowed investigators to report the electrochemical characterization of individual semiconducting
SWNTs in solution.
Electrochemical exfoliation of graphite is also becoming one of the cleanest and easiest methods
to obtain dispersions of graphene layers. In initial reports, a high potential was applied between two
high purity graphite electrodes immersed in an ionic liquid or an ionomer solution [165]. Exfoliation
of graphite occurred at the anode and formed a black precipitate that could be redispersed in polar
aprotic solvents. Very recently, exfoliation was also achieved by applying a high negative voltage to
a carbon assembly in propylene carbonate, followed by addition of LiCl and sonication [166]. The
so-called electrochemical unzipping of CNTs proposed by Pillai et al. is an alternative method to
produce graphene nanoribbons [167]. An anodic potential is applied first to break the sp2 carbon
bonds and to open the tubes. Then, application of a cathodic potential yields graphene materials
with smooth edges.
IV. CONcLUSiON
Information about the electronic properties of fullerenes obtained from their electrochemical char-
acterization can be successfully exploited to prepare, isolate and/or purify fullerenes that would be
otherwise very challenging to obtain. In particular, a series of highly reactive empty fullerenes as
well as endohedral fullerenes have been extracted from soot mixtures by either electrolysis or redox
processes. The main advantage of these methods is that they produce large amounts of these species
in short periods of time, as opposed to the labor-intensive, time-consuming separation by HPLC.

Also, fullerene anions can be easily produced by CPE and reacted with various substrates, leading
to new adducts and cycloadducts. These derivatives are usually not accessible by commonly used
fullerene derivatization procedures. Electrochemical or chemical reduction can also help to process
CNT and graphene layers in solution. Electrochemically induced retrocycloaddition reactions have
found some important applications in the isolation of enantiomerically pure chiral carbon cages, as
well as in the preparation of derivatives with complicated addition patterns.
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22 Aliphatic and Aromatic
Hydrocarbons
Reduction
Jürgen Heinze
CONTENTS
I. Introduction .......................................................................................................................... 861
II. Formation of Radical Anions, Dianions, and Polyanions .................................................... 862
A. Experimental Aspects ................................................................................................... 862
B. Redox Properties ........................................................................................................... 863
C. Electron Transfer Kinetics ............................................................................................ 873
III. Chemical Reactions of Electrogenerated Anions ................................................................. 874
A. Homogeneous Electron Transfer................................................................................... 874
B. Electrophilic and Related Reactions ............................................................................. 876
1. Protonation ............................................................................................................. 876
2. Alkylation .............................................................................................................. 878
3. Acylation ................................................................................................................ 879
4. Addition of CO2 ..................................................................................................... 879
C. Reductive Coupling....................................................................................................... 880
D. Intramolecular Reactions .............................................................................................. 881
1. Conformational Changes ....................................................................................... 881
2. Bond-Breaking and Bond-Making Reactions........................................................ 881
References ......................................................................................................................................884
I. INTRODUcTiON
Hydrocarbons are the simplest organic compounds consisting only of carbon and hydrogen atoms.
There are two basic structures, saturated (aliphatic) and unsaturated (olefinic or aromatic) systems.
Saturated compounds solely contain σ-bonds within the carbon skeleton, whereas unsaturated
compounds at least contain one π-bond. The electrochemical reduction of such species is exclu-
sively restricted to olefinic or aromatic compounds. The reason is that aliphatic hydrocarbons have
extremely low electron affinities that render their reduction impossible, despite a gain of solvation
energy within the stability limits of conventional solvent–electrolyte systems.
Thus, electrochemical data involving both thermodynamic and kinetic parameters of hydrocar-
bons are available for only olefinic and aromatic π-systems. The reduction of aromatics in particular
had already attracted much interest in the late 1950s and early 1960s. The correlation between the
reduction potentials and molecular orbital (MO) energies of a series of aromatic hydrocarbons was
one of the first successful applications of the Hückel molecular orbital (HMO) theory, and allowed
to develop a coherent picture of cathodic reduction [1]. The early research on this subject has been
reviewed several times [2–4].
861
Later, during the golden age of mechanistic chemistry, interest focused on the elucidation of
reaction paths of cathodically generated species, including disproportionations [5] and chemical
follow-up processes [6]. Techniques were developed and improved to measure both the kinetics of
coupled chemical reactions [7] and thermodynamic parameters such as redox potentials of higher
charged aromatics [8]. The discovery of the redox properties of conducting polymers in 1978 and
later of the fullerenes [9] gave new impetus to the electrochemistry of unsaturated hydrocarbons,
initiating extended studies on the redox properties of these species (Chapter 21) [10]. However, the
new challenges also document that the period of basic research on these systems has been concluded
and now trends to applied sciences dominate.
II. FORMATiON Of RADicAL ANiONS, DiANiONS, AND POLYANiONS

A. EXpErIMENTaL ASpECTS
Thermodynamic reduction potentials of numerous aromatics were first measured by Hoijtink and van
Schooten in 96% aqueous dioxane, using polarography [11]. These fundamental works were deci-
sive tests of the HMO theory, showing that the polarographic half-wave potentials vary linearly with
the HMO energies of the lowest unoccupied molecular orbitals (LUMOs) of the hydrocarbons [1].
Hoijtink et al. had already noticed that most aromatics can be further reduced to their respective
dianions [12]. They proposed a two-step reduction scheme, in which both redox potentials E10 and
E20 are on average separated by about 500 mV:
E10
−•

A A (22.1)
E20
A− •

2−
A (22.2)
However, their careful analysis also showed that most of the dianions were not stable in the
polarographic or voltammetric time scale, and even less so after bulk electrolysis, and underwent
follow-up reactions with water or other electrophilic impurities, details of which are discussed in
Section III.
Aprotic solvents such as acetonitrile [13,14] or dimethylformamide [15–17] considerably
improved the stability of the radical anions but normally had little effect on the reactions of the
more basic dianions [17,18]. The increased irreversibility of the dianion formation is probably due to
the ability of dianions to abstract protons even from the solvent, or, by Hofmann elimination, from
the tetraalkylammonium salts that are common supporting electrolytes in aprotic solvents [19].
Progress in electrochemical instrumentation soon stimulated the application of more elaborated
measurement methods than simple dc polarography, which facilitated studies of heterogeneous
kinetics and detection of follow-up reactions of the electrogenerated species. Thus, conclusions
originally drawn from the shape and height of polarographic curves have been amply confirmed by
straightforward diagnostic criteria in cyclic voltammetry [7,20,21], nowadays the standard method
for mechanistic studies in organic electrochemistry [22].
A fundamental improvement in the facilities for studying electrode processes of reactive inter-
mediates was the purification technique of Parker and Hammerich [8]. They used neutral, highly
activated alumina suspended in the solvent electrolyte system as a scavenger of spurious impurities.
Thus, it was possible to generate a large number of dianions of aromatic hydrocarbons in common
electrolytic solvents containing tetraalkylammonium ions. It was the first time that such dianions
were stable in the time scale of slow-sweep voltammetry. As the presence of alumina in the solvent–
electrolyte systems may produce adsorption effects at the electrode, or in some cases chemisorption
and decomposition of electroactive species, Kiesele constructed a new electrochemical cell with an
Aliphatic and Aromatic Hydrocarbons 863
integrated alumina column for electrochemical studies under superdry conditions [23]. Such sophis-
ticated methods made it possible to generate reversibly polyanions up to octaanions of aromatic and
olefinic hydrocarbons [24].
Further progress in stabilizing highly charged anions was achieved by the application of uncon-
ventional solvents such as ammonia or dimethylamine (DMA) at low temperatures. Using these
solvents, it was possible to observe the reversible generation of supercharged anions at low scan
rates in voltammetric experiments [25,26].
B. REDoX PropErTIES
For purpose of description, the electrochemistry of unsaturated hydrocarbons may usefully be
classified in three categories: benzenoid, nonbenzenoid, and olefinic hydrocarbons, each of which
exhibit characteristic properties upon reduction.
Benzenoid hydrocarbons have been studied in greatest detail [2,4,27]. In aprotic solvents, they can
be reversibly reduced to their respective anions without difficulties. Even the electrochemical reduc-
tion of benzene in dimethoxyethane has been described [28]. In many cases, the electrogenerated
radical anions are stable enough to allow the simultaneous measurements of their ESR spectra [29].
Generally, it can be stated that the positions of the thermodynamic reduction potentials depend on
the magnitude of the π-systems. They are shifted to more positive potentials with the increase of
the conjugation lengths or the rise in numbers of π-electrons (Table 22.1). The main reason for these
changes is the increase of the electron affinity as a function of the π-electron structure [30].
A very striking feature of benzenoid hydrocarbons is the excellent correlation between their ther-
modynamic reduction potentials and the predictions of semiempirical π-electron theories, especially
of the Hückel approximation (HMO). As the thermodynamic reduction potentials are a measure of
the electron affinities of the respective compounds, they can be compared with the theoretically
calculated energies in the simple MO picture, in which additional electrons have been added to
antibonding MOs of the π-systems. Therefore, assuming that the solvation energies for a series of
aromatic hydrocarbons are constant, there should be a linear correlation between the thermody-
namic reduction potentials (half-wave potentials E1/2) and the calculated energies mm +1 of the lowest
unoccupied MO (LUMO) in units of an effective β in the HMO approximation (Equation 22.3):
E1/ 2 = −bmm +1 + C (22.3)
where
b corresponds to an effective value of the resonance integral β
C is a constant within a series of hydrocarbons
Independent voltammetric and polarographic measurements carried out in different solvents such as
2-methoxyethanol, 96% dioxane and dimethylformamide (DMF) confirm the relationship through
excellent linear correlations with slopes b of approximately 2.40 [1,15,31]. Later on, Fry [32] applied
a modified HMO approximation (ω-technique) and improved the validity of Equation 22.3 by intro-
ducing nonbenzenoid polycyclic alternant and nonalternant hydrocarbons, annulenes, cyclophanes,
and polyenes. Recently, based on the density functional theory and well-developed computational
solvation methods, Fry and Davis succeeded in computing absolute reduction potentials that then
were linearly correlated with experimental data (R2 = 0.9981) [33].
Rather surprisingly, the differences in half-wave potentials of hydrocarbons from one solvent
to another are very small. This constancy in energy values as well as slopes of correlation lines in
widely varying solvents and supporting electrolytes implies that solvation energies, provided that
they are not small, change in the same way from system to system.
As already observed by Hoijtink [12], nearly all benzenoid hydrocarbons can be reduced to
their respective dianions—only benzene and naphthalene are exceptions. In all experiments, these
TABLE 22.1
Redox Potentials E 0 for the Reduction of Aromatic and Olefinic Hydrocarbons
Compounds 0
ER/R − (V) ER0− /R2− (V) ER02− /R3− (V) ER03− /R4− (V) References
Benzene a −3.42 — — — [26,28]
Naphthalenea −2.53 — — — [26]
Anthracenea −2.04 −2.64 — — [26]
Tetracenea −1.55 −2.15 — — [26]
Pentacenef −1.28 −1.87 [36]
Chryseneb −2.27 −2.77 [8b]
Coroneneb −1.99 −2.63 — — [8b]
1,2-Benzanthraceneb −1.92 −2.58 — — [8b]
Phenanthrenea −2.49 −3.13 — — [26]
Triphenylenea −2.42 −2.97 — — [26]
Pyrenea −2.29 −2.91 — — [26]
Biphenylc −2.68 −3.18 — — [10a]
p-Terphenyla −2.40 −2.70 — — [26]
o-Terphenyl −2.62 −2.72 — — [103a]
Quaterphenyla −2.28 −2.455 — — [26]
Stilbenea −2.26 −2.72 — — [26]
Bianthryla −1.92 −2.14 −2.82 −3.17 [26]
Biphenanthryla −2.35 −2.51 −3.23 — [26]
Decacyclenec −1.74 −2.14 −2.35 −2.68 (−2.88) [22]
2,2′-Distyryl-biphenyla −2.12 −2.21 −2.81 −3.13 [205b]
4,4′-Distyryl-biphenylc −2.30 −2.52 −3.06 — [205b]
p-Oligophenylenevinylene (n = 1)a −2.00 −2.24 − − [24a]
(n = 2)a −1.86 −1.97 −2.79 −3.10 [24a]
(n = 3)a −1.85 −1.91 −2.46 −2.88 [24a]
Acepleiadylene c −1.85 −2.51 −3.11 −3.14 [37]
COTd −1.71 −1.84 — — [48]
Azulenea −1.62 −2.6 [26]
1,3,5-Tri-tert-butylpentalened −1.41 — — — [70]
Heptalenef −1.41 −2.11 — — [69]
[12]Annulenee −1.35 −2.00 — — [60]
1,7-Methano[12]annulenef −1.42 −1.74 — — [69]
15,16-Dihydropyrene([14]annulene)g −2.22 −3.01 — — [54]
[16]Annulenef −1.19 −1.48 — — [57]
[18]Annulenef −1.52 −1.86 — — [59]
Heptalenef −1.41 −2.11 — — [69]
C60h −0.98 −1.37 −1.87 −2.35 (−2.85, [10c]
−3.26)
a Cyclic voltammetry was performed at a Pt electrode with solutions of 10−3 to 10−4 M in substrate. All potentials are
expressed in V versus Ag/AgCl; solvent, dimethylamine-TBABr; temperature between −40°C and −65°C.
b DMF-Me4NBr, potentials versus Ag/AgCl (corrected from SCE).
c THF-NaBPh4 or LiBPh4, potentials versus Ag/AgCl, in parentheses potentials for penta- and hexaanion formation.
d COT = cyclooctatetraene; ACN-TEAP, potentials versus Ag/AgCl (corrected from SCE).
e THF-TBAClO4, potentials versus Hg pool.
f DMF-TBAClO4, potentials versus Ag/AgCl (corrected from SCE).
g DMF-TBAClO4, potentials versus Ag/0.1 M AgNO3.
h Toluene/ACN-TBAPF6, potentials versus Fc/Fc+ at –10°C, in parentheses potentials for penta- and hexaanion
formation.
second reduction steps appear approximately −0.55 ± 0.10 V more negative than the first reduction,
provided that the supporting electrolytes used were tetraalkylammonium salts. Therefore, these
reduction potentials were also correlated with the LUMO energies of the HMO model [3]. It was
suggested that the energy difference of 0.55 eV corresponds to the repulsion energy between both
electrons in the LUMOs of the dianions [1], despite the differences in their structures. On the other
hand, quantum-mechanical calculations show that the repulsion energies are much larger. Dewar
has calculated values in the range of 5 eV [34]. The discrepancy between experiment and theory
results from the fact that ion-pairing effects and solvation influences have been neglected in the
calculations. Experimental data clearly reveal that counterion effects that efficiently shield the nega-
tive excess charge have in the past been underestimated and are considerably stronger for di- and
polyanions than for radical anions [35–37].
In polar solvents such as DMF or acetonitrile, the interaction increases in the order But4N <
Prop4N < Et4N < K < Na < Li and, consequently, reduction potentials shift in a positive direction
[6,38]. Obviously, ion pairing is greatest for the small lithium ions, in agreement with the prediction
of Born’s equation [39]. Surprisingly, in the case of Me4N+ as counterion, the ion-pairing effect is
significantly diminished [40]. In the case of solvents with low dielectricity constants, the pattern is
different, and ion pairing becomes dominant as the radius of alkali cations increases [37,41,42]. The
reasons for this behavior have not yet been studied in detail, but it has been proposed that in ethereal
solvents the solvation of small cations remains stronger than that of larger ones, and therefore ion
pairing of potassium should be more pronounced than that of lithium.
Ion-pairing effects may considerably influence disproportionation mechanisms that involve homo-
geneous redox reactions of anions to their respective dianionic and neutral species (Equation 22.4) [43]:
2A− • A 2− + A (22.4)
Disproportionation mechanisms have been proposed for protonation reactions and intramolecular rear-
rangements (see Sections III.B and III.C) [44]. Their prominent feature is that follow-up processes at
the level of the dianion can already take place at potentials corresponding to radical anion formation.
In order to evaluate data for disproportionation reactions, it is necessary to know the value of the dis-
proportionation equilibrium constant:
[ A 2− ][ A]
KD = (22.5a)
[ A− • ]2
RT
ln K D = E20 − E10 (22.5b)
nF
This can be determined from the difference in reversible potentials of the couples A/A− • and A− •/A2−
(Equation 22.5).
In the case of benzenoid aromatics, KD values range between 10 −9 and 10 −13, provided that tet-
raalkylammonium salts have been used as supporting electrolytes [8b]. In solvents of low dielec-
tricity constant, additional effects are observed, showing influences of the supporting electrolyte
concentration and of the nature of the cations [6]. In the tetraalkylammonium series, the strongest
(contact) ion pairs are formed by Et4N+, and KD is largest for that cation [8b,45].
Drastic changes in the disproportionation constants occur when alkali cations are used instead of
tetraalkylammonium ions. Typically, the potentials of the radical anion formation are less affected than
that of the dianion formation. In the presence of alkali cations, ΔE0 shifts may reach values of more than
600 mV, which correspond to an increase in the K constant of more than 10 orders of magnitude [43].
However, in a recent publication Fry claimed that disproportionation is driven by solvation, not ion pair-
ing [43c]. It might be that the strong solvation effects at the dianion level have been overlooked.
TABLE 22.2
Structure Formula of Annulenes and Cyclic Conjugated Systems (1–17)
1 2 3 4
5 6 7 8 9
10 11 12 13
+
–
+ –
14 15 16 17
The electrochemistry of nonbenzenoid hydrocarbons (see Table 22.2) has attracted much interest
because their structures offer unusual insights into π-electron systems that undergo geometric
changes upon reduction and obey both the Hückel 4n and 4n + 2 rules.
The most widely studied examples are cyclooctatetraene (COT, 1) and its derivatives. In such
conventional aprotic solvents as DMF, dimethyl sulfoxide (DMSO), or acetonitrile containing tet-
raalkylammonium salts, two distinct one-electron reduction waves are observed at approximately
−1.64 and −1.80 V versus SCE, with ΔE 0 separations varying from −130 to −240 mV [36,46–49].
In THF and NH3, this separation reduces further [50–52], and in the presence of alkali salts [52,53]
even two-electron reduction waves with positive ΔE0 differences were obtained, indicating large
disproportionation constants. The unusually small separation of the two redox steps in comparison
to the data of benzenoid aromatics was ascribed to the fact that the planar COT dianion forms a
4n + 2 π-electron system that is stabilized by its gain in Hückel resonance energy (Figure 22.1) [54].
Obviously, strong ion-pairing effects additionally favor the formation of the dianion [52,53]. On the
other hand, it was argued that a negative shift of the first reduction step, leading to small ΔE 0 values,
is caused by energy requirements accompanying the transition from the tube-shaped to the planar
molecule.
This is supported by electrochemical results obtained with methyl-substituted COT derivatives.
Thus, all methyl-substituted derivatives due to a steric barrier are harder to reduce than 1 itself, and
in 1,2,3,4-tetramethylcyclooctatetraene (2) reduction occurs at the extremely negative potential of
−3.6 V (HMPA vs. SCE) [55]. In the case of phenyl-substituted COTs, the steric demand is by and
large energetically compensated through the planarization of the system and the subsequent reso-
nance interaction between the phenyl moieties and the COT ring. Therefore, the reduction poten-
tials are similar to that of unsubstituted 1. In addition, the resonance-stabilizing effect upon the
dianion is sufficient to shift the second redox potential E20 positively to E10 , thus producing a single
1 μA
0.5 μA
–1.0 –1.5 –2.0

E (vs. Ag/AgCl)(V)
FiGURE 22.1 Experimental cyclic voltammograms of the reduction of COT in THF/0.1 M TBAPF6, ν = 100
mV/s, ΔE0 = 170 mV; obtained from simulations: (at the top) activated (after purification of surface by polishing)
Pt electrode, k1 = 1.3 × 10 −3 cm/s, k2 = 10 −2 cm/s; (below) passivated Pt electrode k1 = 3.0 × 10 −4 cm/s, k2 = 10 −2
cm/s. The spike results from homogeneous comproportionation reactions between the dianion and the neutral
species (see Section III.A).
two-electron reduction wave [48]. It is interesting to note that the electrochemistry of the doubly
decked [8]annulene (= [22](1,5)-cyclooctatetraenophane) also indicates some sterical strain [56].
The formation of the monoanion occurs at a potential of −2.43 V (DMA vs. Ag/AgCl). It can be
reduced up to its tetraanion at a potential of −3.22 V.
The redox behavior of a number of higher annulenes than 1 has been studied during the 1970s
and 1980s. The evaluation of their electronic properties has attracted much interest because it offers a
good comparison of the fundamental differences between 4n and 4n + 2 π-systems. As predicted by
the simple MO theories, the transfer of an electron to a [4n]annulene should be energetically favorable
because the electron is inserted into a low-lying nonbonding orbital. The further reduction to the dian-
ion leads to a stabilized (aromatic) 4n + 2 π-system, which therefore should also be easily accessible.
In contrast, during the reduction of an aromatic [4n + 2] annulene electrons are injected into a LUMO
with high energy, and in the second reduction step an unstable 4n dianion is generated.
Consequently, the reduction of [4n]annulenes should be observed at relatively positive potentials with
small ΔE0 separations for the dianion formation, while the reduction of the [4n+2]annulenes should
occur at more negative potentials with large ΔE0 separations for the dianion formation. This is exactly
what is observed (see Table 22.1). Although benzene [28], the classical Hückel aromatic with 4 × 1 +
2 = 6 π−electrons, is reduced at −3.42 V (vs. Ag/AgCl), the reduction of the [8]annulene COT occurs at
−1.71 V. Similarly, the [16]annulene (3) [57,58] is more easily reduced than the corresponding [18]annu-
lene (4) [59], although the reduction of the larger π-systems should be more favorable for electrostatic
reasons. The only exception is [12]annulene where the ΔE0 separation is quite large [60].
For larger annulenes, even the reduction to tetraanions is possible [37,61,62]. This is especially
favorable for neutral 4n + 2 species, which, after the injection of four electrons, reform a stabilized
4n + 2 π-system. On the other hand, the existence of four excess charges in one molecule gives rise
to strong electron repulsion. It can be shielded only by ion pairing that drives the formation of the
tetraanion to a potential sufficiently positive for reduction to occur within the stability range of the
solvent–electrolyte system. Thus, the electrochemical reduction of acepleiadylene (5) to its tetraan-
ion was only achieved in THF in the presence of LiBPh4 as supporting electrolyte [37]. Attempts to
generate the same species in the presence of tetrabutylammonium ions were unsuccessful.
Several studies have been published concerning the problem of homoaromaticity and its influence
on reduction potentials. The term homoaromaticity is applied to cyclic resonance-stabilized systems
in which a carbon–carbon double bond is replaced by a cyclopropane ring, or a saturated carbon
atom is introduced into the conjugated chain. Paquette et al. investigated the reduction of cis-bicy-
clo-[6.1.0]-nona-2,4,6-triene (6) and similar derivatives [63]. They found that it is reduced (−2.59,
−2.79 V) more negatively than 1 but more easily than cyclooctatriene (7) (−2.77 V), thus proving a
degree of homoconjugative stabilization in the radical anion of 6. Analogously, dibenzonorcaradiene
(8) is easier to reduce than biphenyl, but harder to reduce than phenanthrene [64]. The electrochemi-
cal reduction of 1,6-dimethylbicyclo[4.4.1]undeca-2,4,7,9-tetraene (9) was also interpreted in terms
of homoconjugation in the anions. The reduction appears to proceed via an ECE scheme in which
the initial reduction produces an unstable radical anion that undergoes a structural change, produc-
ing another radical anion with a conjugatively stabilized π-system. The second electron transfer
occurs more easily than the first one, thus producing a typical two-electron reduction [65].
Of the condensed nonbenzenoid aromatics, azulene (10) has gained greatest popularity [66].
Although it is an isomer of naphthalene, its electrochemical behavior differs markedly from its ben-
zenoid counterpart. Azulene is reversibly reduced at −1.62 V (vs. Ag/AgCl), while the reduction of
naphthalene takes place at −2.53 V [26,67]. Furthermore, the anion of azulene is extremely stable
against the attack of protons [67]. The bicyclus octalene (11) has 14 π-electrons. 1H-NMR data show
that it possesses a nonplanar structure with polyolefinic properties and therefore resembles its mono-
cyclic relative COT. Cyclic voltammetry reveals that it is reversibly reduced to the radical anion
at E1/2 = −1.67 V and, rather surprisingly, in a three-electron process at E1/2 = −1.70 V to its stable
tetraanion [68]. This unusual behavior can be only explained by assuming that the energy gain from
delocalization in the planar 18 π-system is higher than torsional and electronic repulsions. Other
bicyclic systems such as heptalene (12) [69] and pentalene (13) [70] can also be reduced to their
respective anions. Nevertheless, in comparison with equivalent monocyclic π-systems such as 1, their
reduction behavior is still not properly understood.
A further group of nonbenzenoid aromatics is the series of odd-membered cations and anions such
as cyclopropenium (14) and tropylium cations (15) as well as cyclopentadienyl (16) and cyclonona-
tetracenyl anions (17). Regarding the arguments for the properties of Hückel-like 4n + 2 π-systems,
all these molecules should be energetically stabilized. Obviously, this is not fulfilled in all cases. The
tropylium cation (15) can be reduced in a one-electron step to the tropyl radical even at E = +0.06 V
versus SCE [71]. The radical is unstable and rapidly dimerizes to bitropyl. The heptaphenyl tro-
pylium radical is stable on the voltammetric time scale, but decays slowly producing a dimeric
species involving coupling via the phenyl groups [72]. Similarly, 2,3-diphenylethyl-cyclopropenyl
is irreversibly reduced in CH3CN at Ep = −0.04 V. On the other hand, the reduction of trimethylcy-
clopropenyl occurs at −1.32 V, which is in better agreement with the prediction of the Hückel theory
[73–75]. Otherwise, relatively positive reduction potentials seem to be typical for most carbocations
[76]. The easy reducibility is probably caused by the excess positive charge.
The discovery of the metal-like properties of conducting polymers has once again focused atten-
tion on the oxidation and reduction characteristics of aromatic systems. It turns out that most of these
conducting materials consist of chainlike connected carbocyclic or heterocyclic aromatics [77–79].
The simplest molecules in these series are dimers, followed by oligomers of increasing chain
length and polymers. As the current–voltage curves of polymers are difficult to interpret, quantita-
tive information on the redox properties of such systems was preferentially obtained from reduction
experiments with dimers and defined oligomers. Redox data on dimers are available for biphenyl
[10a,26], bianthryl [43b,80], biazulenyl [81], bicyclooctatetraenyl [82], and dimeric [14]annulenes
[83]. All species can be reduced to at least their respective dianions. In the case of bianthryl and
bicyclooctatetraene, even the formation of tetraanions has been observed. In general, the observed
203 K
2 V/s 5 μA
233 K
0.5 μA
100 mV/s
268 K
100 mV/s
0.2 μA
–3.5 –3.0 –2.5 –2.5 –1.5

E [vs. Ag/AgCl](V)
FiGURE 22.2 Cyclic voltammograms for the reduction of biphenyl, terphenyl, and quaterphenyl in dimeth-
ylamine/0.1 M TBABr. Redox potentials have been published in Reference 26.
redox potentials of the monoanion formation differ significantly from those of the monomeric par-
ent compounds and shift to less negative values. This is evidence of conjugative stabilization in the
charged oligomeric unit [84]. On the other hand, large ΔE 0 separations between the redox potentials
of the respective mono- and dianions indicate strong electron repulsion between both electrophores.
A typical example is biphenyl, which is reduced to the radical anion at −2.68 V and to the dianion at
−3.18 V (Figure 22.2) [10a,26], whereas the reduction of the monomeric benzene occurs at −3.42 V
[28]. Obviously, the biphenyl anion has gained a considerable amount of conjugative stabilization
energy, while in the dianion strong electron–electron repulsion dominates. On the other hand, the
difference between the redox potentials of COT and bicyclooctatetraenyl is relatively small (−1.71 →
−1.61 V vs. Ag/AgCl), indicating a low stabilization of the dimer in comparison to COT. Moreover,
the Coulombic through-space repulsion between the excess charges in the dianion of the dimer is
also small (ΔE0 ≤ 80 mV) [48,82]. However, it is unclear whether this dianion really represents a
system with excess charges in the two COT units. It cannot be excluded that the first two redox steps
generate the dianion of one COT subunit and only the trianion formation at −2.42 V (vs. Ag/AgCl)
produces the first excess charge in the second COT subunit.
In the course of the investigations, the concept of the oligomeric approach has been developed,
which includes electrochemical studies of a great number of monodisperse chainlike hydrocarbons.
Voltammetric measurements carried out with several oligomers of the p-phenylenevinylene (18,
n = 1–6) [24] and the p-phenylene [26] series, respectively, clearly demonstrate that the reduction
properties of such oligomers and polymers depend on the chain length of the systems. The follow-
ing general trends have been developed as function of increasing chain length. First, the number of
accessible redox states increases. The potentials of already existing redox states shift to less nega-
tive values when the next higher homologue is reduced. Obviously, the redox energies of different
states gradually approach a common convergence limit with increasing chain length. Second, the
redox states degenerate pairwise with increasing chain length, and third, in agreement with expec-
tations, adding successive monomeric subunits in the molecular chain enlarges the stability of the
system (Figures 22.2 and 22.3). From these results, it becomes clear that in charged oligomers a
N=5
N=7
N = 10
N = 11
N = 15
N = 19
N = 23
–3.5 –3.0 –2.5 –2.0 –1.5 –1.0 –0.5 0.0

E (vs. Ag/AgCl) (V)
FiGURE 22.3 Voltammograms of the reduction of β-carotenoids (22) in DMA/0.1 M TBABr, T = 213 K,
ν = 0.1 V/s, N = number of olefinic double bonds. The small waves in the reverse scans of N = 5 and 7 prob-
ably indicate dimeric coupling products of the anions or dianions. (With kind permission from Springer
Science+Business Media: J. Solid State Electrochem., 2, 1998, 102, Heinze, J., Tschuncky, P., and Smie, A.)
reasonable number of energetically low-lying redox states are degenerated, followed by redox states
with increasingly higher energies [10a].
π
π = 18
π
π
n
π = 19
π = 20
Quite a large number of publications that have appeared since that time support these findings,
but have also introduced new aspects that show the complexity of redox mechanisms in such sys-
tems [85]. Very systematic studies have been carried out by the Müllen group, who have varied in
chainlike oligomers the type and coupling position of the electroactive monomeric building blocks
and the modes of linkage, using both saturated and unsaturated species with different lengths [86].
Their results clearly show that the size of the aromatic subunit, the overall number of π-electrons,
the π-topology and steric effects are important factors for the redox behavior of all these species.
Thus, in the series of oligoarylenevinylenes, replacement of the phenylene unit by larger arylene
units enlarges the charge capacity of the respective systems. While the p-oligophenylenevinylene 18
(n = 1) with three phenylene units can be electrochemically reduced up to a dianion, the correspond-
ing naphthalene derivative 19 (n = 1) reaches a trianion level and the anthracene derivative 20 (n = 1)
even a hexaanion state [86–88].
An important reason for this phenomenon is the fact that the better the excess charges in con-
densed aromatic units are stabilized, the larger the π-structure is. Of course, the energetic stabi-
lization of an excess charge in a large aromatic unit diminishes the trend for its delocalization
and Coulombic repulsion effects along the chain. Therefore, the shift of the first redox potential in
dependence on the chain length is less pronounced for the naphthalene and anthracene derivatives
than for the phenylene system or the pure oligoene chain, and, moreover, the separation between suc-
cessive redox steps becomes substantially smaller as the number of π-subunits increases. A further
influence on the redox properties results from the coupling pattern between the vinylene and the
arylene units. Measurements on para-, meta-, and ortho-coupled phenylenevinylenes reveal that it
is more difficult to charge meta- and ortho-homologues than the corresponding para-homologues.
However, the conjugative uncoupling of two meta-groups in a phenylene ring diminishes Coulombic
repulsion, and therefore the energetic separation between successive redox steps decreases.
The redox properties of oligo-p-phenylenes change when sterically relevant methyl groups exist
in the central rings. Thus, in comparison with the unsubstituted oligomers in methyl-substituted
homologues, for example, 21, with four or more phenylene units, the first reductive redox step is
shifted to a more negative potential and a two-electron wave appears in the voltammetric response
[89]. This can be interpreted by assuming that, due to steric hindrance, additional energy is needed
to planarize the phenylene chain for the first electron transfer, and that the second electron is able to
enter the then flattened system at the same or even a more positive potential.
21
Within the hydrocarbons containing olefinic double bonds, polyacetylene (PA) is the most thor-
oughly studied system. The great interest results from its extremely high conductivity up to 100,000
S/cm, which emerges on oxidative or reductive charging of the polymer [77–79,90]. As already
found by MacDiarmid [9a], PA can be reversibly reduced to a polyanionic material.
Despite the great interest in PA, there are only a few electrochemical studies of monodisperse
oligoene systems. The reason is the high reactivity of doped alkyl-substituted oligoenes in the pres-
ence of nucleophiles or electrophiles. Normally, these oligomers consist of a carbon chain with
alternating single and double bonds and two terminating groups, which are equal in most cases.
Thus, a t-butyl group [91–93] or, in the case of α- and β-carotenoids, a cyclohexenyl group [94], has
been used, while phenyl or other aromatic substituents have been used as end groups in the so-called
arylpolyenes [95]. The chain length N (N = number of double bonds in the conjugated system) again
determines the electronic properties of the oligomers.
22
n n
(N = 0–4)
A series of carotenes [96] 22 (number of double bonds N = 5 and higher; compounds with N = 5
and 10 are not shown in structure 22) may serve as an illustration of this redox behavior. For all
related states within the series, a strictly linear dependence of the redox potentials versus the chain
length of the oligomers is observed. As can be seen, the reduction for the oligomer with N = 5 starts
with two well-separated one-electron redox steps. With increasing chain length, there are additional
weakly separated redox pairs. The potential gaps in the single pairs and between them decrease
(Figure 22.3). Thus, two-electron transfer steps are most likely to occur for the longer polyenes
(N ≥ 19). In the literature, even potential inversion for the second e-transfer is discussed [94]. The
factors that control this inversion are essentially two. One is the weakening of the Coulombic repul-
sion brought about by the localization of the two charges of the di-ion at the end of the molecule.
Additionally, localization of the charges at the end of the di-ion contributes to its stabilization by
interaction with the solvent. In the case of the mono-ion, this stabilization is significantly lower.
A further interesting point concerns unusually small differences between the reduction poten-
tials of mono- and dianions of some molecules containing olefinic double bonds. Although in trans-
stilbene the formation of the dianion occurs approximately 500 mV negatively to the radical anion
0
formation [26,97], for tetraphenylethylene the standard potentials for the R/R− couple ( ER/R − ) and
the R−/R2− couple ( ER − /R2− ) are very closely spaced. The ΔE 0 separation amounts in HMPA to
0
−138 mV, in DMF to −35 mV, and reaches in ACN even positive values of approximately 150 mV
[98–100]. Consequently, the disproportionation constant K varies within five orders of magnitude,
a phenomenon mainly ascribed to increasing ion pairing on going from HMPA to ACN [100].
Nevertheless, intermolecular phenomena alone are not sufficient to explain the dramatic decrease
of the ΔE 0 separation in tetraphenylethylenes in comparison to stilbene. It is now generally accepted
that structural changes involving twisting of the ethylenic bond and accompanying the dianion for-
mation are the main reason for the energetic stabilization of the dianion of tetraphenylethylene [101].
Similar effects also observed with 9,9′-bifluorenylidene [102].
23 24
25
Apart from investigations of chainlike conjugated systems, studies of molecules including

orthogonal [103] as well as parallel π-systems [104] such as [2.2]paracyclophanes have attracted
considerable interest. In that case, the intramolecular electronic interactions between the π-segments
depend on the position of the connecting alkane bridges. Thus, the voltammetry of the dianion of
23 (∆E 0 = E10 − E20 = 420 mV) with a face-to-face arrangement of anthracene units indicates a strong
through-space repulsion. This is lowered by going to the 1,4-bridged analog 24 (ΔE0 = 275 mV)
or the orthocyclophane 25 (ΔE0 ≤ 80 mV) [104a]. Substitution of anthracene by pentacene electro-
phores weakens the repulsion [104b].
The reduction behavior of cyclooctatetraphenophane [56] shows one characteristic similarity to
that of bicyclooctatetraenyl. Again, the ΔE 0 separation between the first two redox steps is small
(≤80 mV), indicating a weak Coulombic repulsion between the negative excess charges in both COT
subunits. In principle, one may also assume the formation of a dianion with two electrons in one
subunit. Then the ΔE0 separation (0.38 V) between the redox potentials of the dianion and trianion
would reflect the Coulombic repulsion between a dianionic and monoanionic subunit. Interestingly,
the reduction of cyclooctatetraphenophane to the dianion occurs at potentials of about −2.50 V.
Obviously, a considerable steric strain within the cyclooctatetraenyl subunit has caused this strong
potential shift in comparison with the reduction potential of COT (−1.71 V).
R R
26
R R
A very interesting group of [2.2]paracyclophanes are dibenzoannelated compounds of the general

structure 26 with mutually orthogonal π-systems [103]. In the literature it has been speculated that
the orthogonal π-systems of 26 are sufficiently isolated to be reduced independently. Cyclic voltam-
metric measurements show, however, that there are considerable interactions between the “isolated”
π-systems. Thus, the unsubstituted [2.2]paracyclophane containing only two benzene groups in
face-to-face position is reduced to its radical anion at −3.01 V [105]. By contrast, the benzoan-
nealed cyclophane 26 with R = tert-butylphenyl could be reduced to its tetraanion (E10 = −2.54 V,
E20 = −2.61 V, E30 = −2.80 V, E40 = −2.89 V). In conjunction with ESR measurements [106] and elec-
trochemical data of ortho-terphenyl (E10 = −2.62 V, E20 = −2.72 V) [103], this gives evidence that the
mono- and dianion formation of 26 takes place in the lateral subunits whereby the redox states are
almost degenerated and easier accessible than in o-terphenyl. The most interesting finding is that the
third electron is localized in the central paracyclophane subunit and its reduction potential is consid-
erably less negative than that of [2.2]paracyclophane, given the fact that both annealed o-terphenyl
units are already charged.
A new class of conjugated hydrocarbons is that of fullerenes [9b], which represent an allotropic
modification of graphite. Their electrochemistry has been studied in great detail during the last
decade [107] (see Chapter 21). The basic entity within this series is the C60 molecule. Due to its high
electron affinity, it can be reduced up to its hexaanion [10c,108]. Solid-state measurements indicate
that the radical anion of C60 reversibly dimerizes. NMR measurements confirm a σ-bond formation
between two radical anion moieties [109].
C. ELECTroN TraNSFEr KINETICS

Conversion of an oxidized species into the reduced form and vice versa requires the reorganiza-
tion of the solvent in the immediate neighborhood of the reactant, together with some structural
changes within the reactant. In the case of heterogeneous charge transfer, additional double
layer effects are operative, which depend, inter alia, on type and concentration of the support-
ing electrolyte, but may be also influenced by the electrode material used as well as adsorp-
tion phenomena. Theoretical concepts have been developed by Hush, Marcus, and Dogonadze
[110–112]. Applications of the Marcus theory to problems in organic electrochemistry have
been discussed by Eberson [113]. As most studies on the reduction of hydrocarbons were car-
ried out in aprotic solvents in the presence of excess supporting electrolyte, double layer influ-
ences on electron transfer kinetics were usually regarded as less important [2,114]. Normally,
the rates of heterogeneous electron transfer to aromatic and olefinic hydrocarbons are high. It is
assumed that the activation barrier is mainly caused by the solvent reorganization. Such reac-
tions are termed outer-sphere processes. Their heterogeneous rate constants may reach values
up to 5 cm/s [115]. Reductions of systems that require in addition a large conformational energy
change in the transition state are rare [116]. The most widely discussed example from this class
is the COT molecule (1), which exhibits a slow heterogeneous electron transfer for the anion
formation, while the rate between the anion and the dianion is significantly faster [46,47,52].
In the literature, it has been suggested that upon reduction the tube-shaped ring passes through
at least a partially flattened transition state to form a planar anion radical. The experimentally
determined activation energy (10–11 kcal/mol), which is similar to the activation energy of ring
inversion (13.7 kcal/mol), has been interpreted as supporting evidence [114]. However, indepen-
dent studies of Fry et al. [36] and Parker et al. [117] have shown that the rate constant for the first
reduction step increased as the cation size of the supporting electrolyte decreased from tetra-
heptylammonium to tetramethylammonium. This contradicts the assumption of pure structural
reorganization effects during the reduction of 1 and points to adsorption phenomena of the elec-
trolyte cations. Nevertheless, in a very recent EPR investigation, homogeneous rate constants
for the COT− •/COT electron self-exchange process were found to be close to 10 6 M−1 s−1, which
is a thousand times slower than those of planar aromatics and confirms the concept of a strong
inner-sphere reorganization upon electron transfer [118]. Similarly, Evans discussed electron
transfer reactions of some fully α-methylated cycloalkane-1,2-diones in which the contributions
of internal reorganization are substantial [119]. In that case, both homogeneous (self-exchange)
and heterogeneous electron transfer rate constants are affected by the structural differences
among these diketones.
Tetraphenylethylene is another example of a slow charge transfer. Here, the radical anion forma-
tion is relatively fast, whereas the second charge transfer is slow [98]. In agreement with the thermo-
dynamic findings, the second charge transfer suggests that considerable structural reorganization
occurs at the activation barrier of the second reduction step. It is not yet clear to what extent solvent
reorganization as well influences the activation energy [98].
III. ChEMicAL REAcTiONS Of ELEcTROGENERATED ANiONS

With one or even more electrons in antibonding orbitals, reduced hydrocarbons are highly reactive
species capable of both inter- and intramolecular reactions. The preferred pathway of the follow-up
reaction depends not only on the electronic and steric structure of the reduced species but also on its
chemical environment, especially on the counterion and the solvent.
A. HoMoGENEoUS ELECTroN TraNSFEr

The most elementary follow-up reaction is the homogeneous electron transfer (ET) to another
s olution species, which may be identical with the donor molecule itself [43a]. The equilibria of
homogeneous ET reactions are governed by the standard potentials of the involved redox couples
and are easily calculated with given data according to Equations 22.6 through 22.9:
K
A1− • + A 2

−•
A1 + A 2 (22.6)
E10
A1 + e −

−•
A1 (22.7)
E20
A2 + e−

−•
A2 (22.8)
RT
ln K = E20 − E10 (22.9)
F
The kinetics are much more complex and depend on the reorganization of the molecular framework
[120], the solvation shell, and the electrostatic interaction. A semiquantitative estimation of rate con-
stants may be obtained with the well-known Marcus equation [121]. The calculated data compare
quite well with experimental values. Most of the experimental hydrocarbon data have been provided
by Szwarc and his school [5]. The state of the art has been discussed in an excellent review [113].
Homogeneous ET has to be taken into account whenever dealing with electrode reactions, as
was pointed out by Marcoux [122]. It is of special importance when the heterogeneous ET is slow,
providing an additional and more effective pathway to reduced species. The
−
+e
1 slow
 → 1− • (22.10a)

−
1 +
e
→ 12− (22.10b)
↑------------
↓
12 − + 1 2 × 1− • (22.10c)
homogeneous rate constant for the second charge transfer in 1, similar to the heterogeneous charge
transfer, is considerably larger than the first one. The difference greatly depends on the experimental
conditions. It has been shown by cyclic voltammetry in superdry THF/TBAPF6 that the first ET can be
catalyzed by the dianion of COT itself in a homogeneous synproportionation (Equation 22.10), giving
rise to a catalytic spike (Figure 22.1). The mechanism has been confirmed by digital simulation [50].
Quite often the resulting anionic species undergoes a fast follow-up reaction. Thus, homoge-
neous ET becomes a crucial step in many electrode reactions: a well-known example is the cathodic
reduction of organic halides (see Chapters 24 and 25). At mercury, heterogeneous electron transfer
to most halides is slow. This kinetic barrier may be circumvented by addition of aromatic hydro-
carbons “A” such as phenanthrene, naphthalene [123], and anthracene [124]. These compounds are
easily reduced at the cathode and transfer their excess electron to the organic halide. The resulting
halide anion radical undergoes a fast follow-up reaction. The whole reaction sequence is
A + e− A− • (22.11)
A − • + PhCl A + PhCl − • (22.12)
PhCl − • → Ph • + Cl − (22.13)
Ph • + A − • Ph − + A (22.14)
Ph − + H + → Ph H (22.15)

Regeneration of hydrocarbon in Equations 22.12 and 22.14 makes the process catalytic.
The reduction of organic halides in the presence of aromatic hydrocarbons has been the subject
of detailed kinetic studies, which provide rate constants for the homogeneous ET [125] and the
follow-up reaction [126]. The theoretical basis for this kind of experiment (homogeneous redox
catalysis) was laid by Savéant’s group in a series of papers in 1978–1980 [127–129]. Homogeneous
ET also plays an important role in the protonation of anion radicals [130].
When an anion radical undergoes heterogeneous ET, formation of the neutral molecule in the
ground state is strongly favored over formation of an excited state [131]. No such restriction applies
to homogeneous ET, which, if sufficiently exothermic, may yield excited states of hydrocarbons.
One may naively suppose that an electron is removed from the bonding MO of highest energy to
give either the first excited singlet or triplet; electrochemiluminescence [132] may then occur.
The emission observed is usually the fluorescent band of the hydrocarbon, corresponding to the
decay of the first excited singlet. The energy released by homogeneous electron transfer is given by
the difference between the redox potentials of donor and acceptor plus a small entropy term [133],
and in many cases of electrochemiluminescence falls short of the energy needed to populate the
singlet state directly. In these energy-deficient cases, there is sufficient energy to populate the lowest
triplet state, and singlets can then be produced by diffusion-controlled triplet–triplet annihilation.
Emissions observed at wavelengths other than that of the main singlet have been ascribed to excited
dimers (excimers) [134,135], excited charge-transfer complexes (exciplexes) [136,137], and fluores-
cent products of radical-ion decay. Acceptors in electrochemiluminescence may be the correspond-
ing hydrocarbon radical cations, added alkyl halides [138] or benzoyl peroxide [139], or adventitious
impurities, which need be present at only 10 −7 M levels. The experimental technique for the method
is demanding [140].
B. ELECTropHILIC aND RELaTED REaCTIoNS

1. Protonation
Under protic conditions, aromatic hydrocarbons and compounds with activated double bonds usu-
ally undergo Birch-like reactions [141]. The reaction sequence has been elucidated by the classical
work of Hoytink [11,12,142], who used HMO theory to rationalize both chemical and electrochemi-
cal steps.
The anion radical produced by homogeneous ET is monoprotonated to give a Wheland-like
π-radical. It readily accepts another electron because its bonding or nonbonding singly occupied
molecular orbital (SOMO) always has a lower energy than the antibonding LUMO of the parent
hydrocarbon. The second ET preferably occurs by disproportionation [130]. In a fast follow-up
reaction, the resulting carbanion takes another proton to eventually yield the final dihydro product
(Equations 22.16 through 22.20):
A + e− A− • (22.16)
A − • + H + AH • (22.17)
AH • + e − AH − (22.18)
or
AH • + A − • AH − + A (22.19)
AH − + H + → AH 2 (22.20)
If the reduction potential of the resulting dihydro product is sufficiently positive, it can undergo
another reduction cycle. One of many examples is provided by the reduction of benz[a]anthracene
in 75% aqueous dioxane [11,12,143].
Because of its general importance to organic electrochemistry, the reaction scheme just out-
lined has been the subject of detailed mechanistic studies [16,144–151]. As a model reaction,
protonation of anthracene anion radicals by phenol in dimethylformamide has been selected. Of
five limiting kinetic variants, ECErev, ECEirr, DISP1, DISP2, and DISP3, the favored pathway was
found to be DISP1 [130]. (The different types of rate-determining disproportionation reactions
have been discussed in Reference 130.) It involves the protonation of the anion radical as the
rate-determining step (Equation 22.17), followed by homogeneous ET between the anion radical
and the protonated anion radical (Equation 22.19), yielding the monohydrogenated anion, which
is itself rapidly and irreversibly protonated to the final dihydrogenated product. This mecha-
nism has been disputed because of apparent deviations from predicted reaction orders [145–148].
Recently, it turned out that the inconsistencies are largely due to the formation of homoconju-
gated complexes between phenol and the phenolate anion [150]. Thus, DISP1 now seems to be
generally accepted.
The rate-determining step of the DISP1 mechanism, the protonation of the radical anion, largely
depends on its electronic structure. As a guideline, LUMO energies of the parent hydrocarbon may
be used [32]. The attempt to correlate rate constants with highest local charge densities failed [152].
Therefore, Eberson suggested the application of the Dewar–Zimmermann rules [153].
Under highly protic conditions, the major products of cathodic reductions of cyclic conjugated
hydrocarbons are usually dihydro derivatives [46,154]. In 2-methoxyethanol, for example, naph-
thalene yields 1,4-dihydronaphthalene [154] and COT provides mainly 1,3,6-cyclooctatriene [46].
Under nominally aprotic conditions, 1,2-protonation dominates in naphthalene. Reduction of
naphthalene in anhydrous acetonitrile containing tetraethylammonium p-toluenesulfonate yields
1,2-dihydronaphthalene, which is subsequently reduced to tetralin [155]. Similarly, reduction of 1 in
anhydrous DMF gives 1,3,5-cyclooctatriene almost exclusively [46]. The formation of thermody-
namically stable products is most probably due to base-catalyzed isomerization.
An interesting situation arises from the reduction of CH-acidic hydrocarbons because these
compounds can undergo self-protonation. Actually, a voltammetric investigation of 1,3-d iphenyl-
2-methylindene and 4,5-methylenephenanthrene in DMF/TBAP or DMSO/TBAP clearly
indicated a DISP1 mechanism, analogous to that described earlier [156a]. Similar results have
been obtained for variously substituted indenes where the stoichiometry is in perfect agreement
with a two-electron, two-proton reduction process involving 1/3 starting material under self-
protonation conditions, the remaining 2/3 acting as a proton donor [156b]. Generally, under
self-protonation conditions the DISP1 pathway operates (Equations 22.21 through 22.24), in
which the protonation reaction between the radical anion (AH− •) and the neutral species (AH) is
the rate-determining step:
AH + e − AH − • (22.21)
AH − • + AH AH 2 • + A − (22.22)
AH 2 • + AH − • AH 2 − + AH (22.23)
AH 2 − + AH → AH 3 + A − (22.24)
On the other hand, reduction of fluorene [157,158] results in a homolytic cleavage of the CH bond
(discussed in Section III.D).
To study the stereochemistry of protonation reactions, substituted indenes have been cathodi-
cally reduced in DMF/TBAP with added water or phenol [156b,159,160]. In the presence of water, a
formal anti addition of protons was observed, whereas addition of phenol led to the prevalent forma-
tion of products, formally deriving from syn protonation. Obviously, steric effects and/or acidities of
proton donor and the dihydro product play an important role.
Quite often, ion pairing causes a substantial positive shift of the reduction potential. For elec-
trostatic reasons, the shift is especially large for the formation of higher valency ions. Therefore,
with increasing interaction of the counterion, di- and polyanion formation becomes thermodynami-
cally more favorable. Under these conditions, cathodic reduction immediately produces dianions
via disproportionation and heterogeneous ET. Because of their high basicity, the dianions read-
ily undergo protonation. Such a dianion mechanism was observed when tetraphenylethylene was
reduced in acetonitrile/TEAP in the presence of water or alcohols. Kinetic measurements led to a
mixed-order rate law, rationalized by the existence of a hydrogen-bonded complex between the ion-
paired dianion and the proton donor [100].
The classical Hoijtink mechanism and the dianion mechanism have been observed at electrodes
with a high hydrogen overvoltage, such as mercury. If mercury is replaced by platinum with its
low hydrogen overvoltage, a radical pathway seems to be favored [161a], which is closely related to
catalytic hydrogenations of hydrocarbons. Spectroelectrochemical experiments provided evidence
for an additional hydride mechanism (Equations 22.25 through 22.27) [161b]:
2H + + 2e − H 2ads (22.25)
H 2ads + e − H − + H ads
•
(22.26)
A + H − AH − (22.27)
These results illustrate that the reaction sequence and the stereochemistry of cathodic hydrogena-
tions are controlled by the solvent, electrolyte, proton donor, electrode material, etc. Thus, with
increasing mechanistic knowledge, electrochemistry offers the chance to realize highly selective
hydrogenations.
The addition of protons certainly is the most common nucleophilic reaction of reduced hydrocar-
bon species because of the almost ubiquitous availability of proton donors, which may be wanted or
not. However, under strictly aprotic conditions it is also possible to add other electrophilic reagents
such as alkyl halides, acyl halides, CO2, and SO2.
2. Alkylation
The addition of alkyl halides to aromatic anion radicals, generated by alkali metal reduction in
ethereal solvents, was already known in the 1950s [162] and was reviewed by Garst in 1971 [163].
The first electrochemical analog was observed by Lund et al. [164]. These authors cathodically
reduced hydrocarbons such as naphthalene, anthracene, stilbene [123,124], and perylene [125] in the
presence of alkyl halides and isolated hydrogenated and alkylated products. Similar reactions are
observed when the halides are replaced by ammonium or sulfonium [165].
These alkylations can be looked upon as aliphatic nucleophilic substitutions, usually thought
to proceed via SN1, SN2, or hybrids of these mechanisms. However, in recent years more and more
evidence for a single-electron transfer (SET) mechanism, represented in Equations 22.28 through
22.31, was obtained, and it was suggested that SN2 and SET are just limiting cases of the same SET
mechanism [166]. The SET pathway involves first a transfer of an electron from the nucleophile to
the electrophile followed by bond formation, whereas the SN2 reaction involves a synchronous shift
of a single electron and bond formation (Equations 22.32 and 22.33). In addition, the generated
anions may be protonated (Equation 22.34).
Because of these fundamental aspects, the mechanism of cathodically induced alkylations has
been the subject of detailed studies [125,167]. In a stereochemical investigation, it was found that
racemization is much more effective than inversion. This result was interpreted as evidence of
competition between the SET pathway and the SN2 mechanism, with SET being the more important
route [167]. The SET mechanism is represented in Equations 22.28 through 22.34:
A + e− A− • (22.28)
A − • + BX → A + B• + X − (22.29)
A − • + B• → AB− (22.30)
A − • + B• A + B− (22.31)
A − • + BX → AB• + X − (22.32)
A − • + AB• A + AB− (22.33)
B− , AB− + H + → BH, ABH (22.34)

The rate-determining step (Equation 22.29) of the SET mechanism consists of an electron transfer
concerted with a cleavage of the carbon–halide bond in the alkyl halide and resulting in the genera-
tion of an alkyl radical. Numerous investigations have focused on the measurement of these rate
constants [125]. As expected, the rate constant increases when the redox potential of the aromatic
compound becomes more negative. The coupling step between alkyl radicals and aromatic anions
is fast, with rate constants at the level of diffusion control. This indicates the lack of significant
activation barriers, which consequently results in insensitivity to structural differences in the alkyl
radical and in the aromatic radical anion [168]. Moreover, radical anions with very different redox
potentials (∆EA0 = 0.9 V) couple with primary radicals with approximately the same rate constant.
The competing SN2 mechanism (Equations 22.32 and 22.33) may be favored if the reacting species
are not too sterically hindered, and the driving force for an electron transfer reaction is low. In gen-
eral, the more positive the redox potential of the aromatic compound is or the poorer the alkylhalide
is an electron acceptor, the more important the SN2 mechanism becomes [169].
3. Acylation
Formally related reactions are observed, when anthracene [170] or arylolefines [171] are reduced
in the presence of carboxylic acid derivatives such as anhydrides, esters, amides, or nitriles. Under
these conditions, mono- or diacylated compounds are obtained. It is interesting to note that the
yield of acylated products largely depends on the counterion of the reduced hydrocarbon species.
It is especially high when lithium is used, which is supposed to prevent hydrodimerization of the
carboxylic acid by ion pair formation. In contrast to alkylation, acylation is assumed to prefer an
SN2 mechanism. However, it is not clear if the radical anion or the dianion are the reactive species.
The addition of nitriles is usually followed by hydrolysis of the resulting ketimines [171].
4. Addition of CO2
In the pioneering publications of Wawzonek et al. [13,172], it was demonstrated that CO2 can react
with cathodically reduced hydrocarbons to yield dihydrodicarbonylates. Examples of this kind of
reaction described in the literature include naphthalene, phenanthrene, anthracene, and 9,10-diphe-
nylanthracene. An ECE mechanism was proposed by several authors [172,173]. This includes the
generation of the radical anion of the hydrocarbon, its nucleophilic addition to CO2, and a second
electron transfer involving an additional coupling of CO2 with the dianion. However, studies of
Lund and Simonet indicated that additional mechanistic variants such as redox catalysis should be
considered [174]. A very careful analysis of possible reaction pathways was carried out by Avaca
et al. [175]. They showed that the overall reaction mechanism could be different depending on the
reduction potential of the aromatic hydrocarbons relative to that of CO2. There exist at least two
essential variants.
CO2 is reduced at more positive potential than naphthalene or phenanthrene. Thus, the first steps
of the reaction are the reduction of CO2 to its radical anion and the subsequent coupling between
CO2− • and the neutral aromatic. Then, a further electron transfer occurs accompanied by a second
coupling with CO2. In the case of anthracene or 9,10-diphenylanthracene with reduction potentials
positive to that of CO2, a DISP1 mechanism has been confirmed using different electrochemical
techniques. This is similar to that proposed for aromatic hydrocarbons in the presence of proton
donors.
C. REDUCTIVE CoUpLING
Cathodically reduced hydrocarbons undergo not only homogeneous ET and nucleophilic attack but
also coupling reactions resulting in hydrodimerization and polymerization.
Reduction of stilbene [13] or diphenylacetylene [172] in DMF yields 1,2,3,4-tetraphenylbutane,
whereas phenanthrene [172] provides 9,9′,10,10′-tetrahydro-9.9′-biphenanthrene. Hydrodimerization
was also observed with benzalfluorene [176]. If DMF is replaced by acetonitrile, protonation com-
pletely dominates hydrodimerization [13]. In carefully dried ethers, using alkali or alkaline earth
metals salts as supporting electrolyte, 1,1-diphenylethylene can be reduced cathodically to give
stable solutions of 1,1,4,4-tetraphenylbutane dianions [177]. These dianions can be cleaved by
flash photolysis in the presence of excess 1,1-diphenylethylene to give transient anion radicals of
1,1-diphenylethylene. Kinetic analysis of the subsequent recombination confirmed the postulated
radical–radical mechanism (RR route); the rate constant was found to be 0.5 × 109 M−1 s−1 [178].
In the literature, the nucleophilic attack of an olefinic radical anion on the double bond of a second
neutral olefin, the so-called RS route (radical–substrate coupling), has been postulated as a mecha-
nistic variant for hydrodimerization reactions, but unambiguous experimental results have not been
presented [179]. 9-Cyanoanthracene undergoes a reversible electrodimerization with almost no
side reactions, making a perfect model compound [180–184]. Again, it turned out that the dimer-
ization follows the RR route. It is also interesting to note that water accelerates the dimerization.
This effect was rationalized by specific salvation [184]. A careful study of the dimerization kinet-
ics of 9-cyanoanthracene in different solvents and at low temperatures gives evidence that the
coupling reaction is diffusion controlled and that its rate constant increases with increasing polar-
ity of the solvent as predicted by the Debye–Smoluchovsky theory [185]. It should be noted that
several authors have suggested a more complex reaction pattern, which at least involves a two-step
mechanism [186].
Many alkenes, activated by electron-withdrawing groups, readily undergo hydrodimerizations.
The best known example is the electrodimerization of acrylonitrile, the base of the commercial
Monsanto process [187]. Evidence is presented there that the essential step is a coupling of two
radical anions (RR route). Using the SECM technique, Bard has also shown that only the radical
anions of acrylonitrile dimerize [188]. Sterically less demanding arylalkenes and dienes undergo
not only dimerization but also polymerization. Styrene is polymerized in ethers by alkali metal
reduction [189] or addition of cumyl potassium [190]. The mechanism of ET-induced polymeriza-
tion was extensively studied by Szwarc and his school [191]. It turned out that the first step is dimer-
ization of the styrene anion radical, usually obtained by addition of sodium naphthalene. Under
aprotic conditions, the resulting dianion adds to monomers, forming polymeric living anions. It is
interesting to note that the rate of the polymerization largely depends on the counterion.
With conventional techniques and electrolytes, it was not possible to obtain living anions
because they are rapidly protonated by tetraalkylammonium salts and residual water. The first
report of the production of living polymers by an electrolytic method has to be attributed to
Yamazaki et al. [192], who used tetrahydrofuran as solvent, and LiAlH 4 or NaAl(C2H5)4 as elec-
trolyte for the polymerization of α-methylstyrene. A similar technique was used to polymerize
styrene as well as derivatives [193–195]. The suggested mechanism agrees with the pathway
described earlier.
D. INTraMoLECULar REaCTIoNS
For many years, intramolecular reactions such as conformational changes, bond cleavage, bond
formation, and valence isomerizations have been observed only when hydrocarbons were reduced
with alkali metals in ethereal solvents. In most electrochemical experiments, these reactions were
dominated by the electrophilic processes already described here. However, progress in experimen-
tal techniques [8,22,23] has made these reactions accessible to electroanalytical investigations,
providing new mechanistic insight.
1. Conformational Changes
In recent years, it has become more and more obvious that ET is frequently accompanied by
conformational changes. The interconversion may precede or follow ET; the majority of these
processes have to be classified as CE (as yet this mechanism has not been observed in the hydro-
carbon series), EC, EEC, or ECE mechanisms, whereas only a few systems follow an EE pathway.
An example for an EC process is the interconversion of the anion radical of cis-stilbene, which is
quite slow on the voltammetric time scale [97], whereas cis-azobenzene anion radicals isomer-
ize very rapidly [196]. Tetraphenylethylene undergoes two closely separated reversible additions
of one electron [99,197]. The small difference of standard potentials, equivalent to a high
disproportionation constant (see Equation 22.5), has been interpreted as interconversion from an
almost planar to an orthogonal conformation when going from the neutral molecule to the dian-
ion [198]. The thermodynamics and kinetics of ET-induced interconversions of substituted tetra-
phenylethylenes have been studied in great detail [120]. Reduction of 1,6-dimethylbicyclo[4.4.1]
undeca-2,4,7,9-tetraene appears to proceed via an ECE scheme in which the initial reduction
gives an unstable radical anion, which undergoes a structural change, giving another anion with
a conjugatively stabilized π-system [65]. Conformational changes concurrent with ET (EE path-
way) are observed upon reduction of 1, as cited earlier. Details were reviewed by Evans and
O‘Connell [120].
2. Bond-Breaking and Bond-Making Reactions

Reductive cleavage of carbon–carbon bonds was already observed in the 1920s by Ziegler and
Thielemann upon alkali metal reduction of diarylalkanes in ethereal solvents [199]. As was shown
by Lagendijk and Szwarc [200] for 1,2-di(α-naphthyl)ethane, the primary anion radical undergoes
homogeneous disproportionation, which is supported by ion pairing. The resulting dianion decom-
poses by the fission of the CH2–CH2 bonds into the salts of α-naphthylmethyl carbanions. Similarly,
9,9′-bianthryl can be cathodically cleaved into anthracene and 9,9′-dihydroanthracene plus small
amounts of reduced dimers. The dianion mechanism is quite slow, whereas the tri- and tetraanions
are supposed to decay rapidly [201].
ESR spectroscopical investigations of the anion radical of fluorene indicated a first-order decay,
and it was concluded that the CH bond undergoes homolytic cleavage [202]. Voltammetric studies
of fluorene in DMF reached the same conclusion [157].
The thermal and photochemical ring-opening reactions of cyclobutene are classical examples
of pericyclic processes [203]. In 1976, Bauld et al. described an ET-induced analog [204]. They
observed that benzo- and phenanthrocyclobutene undergo ring opening upon alkali metal reduction
and suggested an ECE pathway. A voltammetric study of cis- and trans-tetrahydro-1,2-diphenyl
cyclobutanephenanthrene in THF-NaBPh4 confirmed this mechanism. However, it turned out that
the rate of the ring opening largely depends on the counterion. If ion pairing is prevented by addition
of 15-crown-5, the reaction rate slows down dramatically. At −50°C, the anion radical of the Z iso-
mer becomes stable on the voltammetric time scale, whereas the dianion exhibits a fast ring opening
(Figure 22.5c) [205].
R1 R 2 R1 R2 R1 R2
– 2e + – + – + 2e
X1 X1 X1,2 X1,2 X2 X2
+ 2e – 2e
R2 R1 R2 R 1 R2 R1
SchEME 22.1 Oxidation or reduction of 1,3-dimethylidenecyclobutanes.
Two-electron reduction [50] or oxidation [206] of 1,3-dimethylidenecyclobutanes yields bicy-

clo[1.1.0]butanes (Scheme 22.1). Cyclic voltammetry of 2,4-di-9H-fluoren-9-yliden-1,1,3,3-tetra-
methylcyclobutane in DMF at low temperatures has demonstrated that bond formation proceeds
via an EEC mechanism; the rate constant has been found to be 20 s−1 [50]. The most interesting
feature of the intramolecular bond formation is that it occurs at the dianion level (Figure 22.4). This
proves the validity of the RR route even for intramolecular reactions despite a strong Coulombic
repulsion.
ET-induced cycloadditions of polycyclic olefins and cycloreversions of cyclobutane species
have been studied by ESR spectroscopy [207]. Upon chemical and electrochemical reduction,
2,2′-distyrylbiphenyl rearranges by intramolecular coupling into a “bis-benzylic” dihydrophen-
anthrene dianion, which can be either protonated to a 9,10′-dibenzyl-9,10-dihydrophenanthrene
or oxidatively coupled to a cyclobutane species. It is interesting to note that the intramolecular
coupling between the styryl units takes place at the di- and triionic level, which is comparable
with a radical–radical coupling (RR route, EEC mechanism) [205a]. The experiments are again
evidence that RS coupling is generally improbable for ionic dimerization reactions. At low tem-
peratures, the coupling rate between the negatively charged styryl units slows down and the
0.5 μA
10.0 μA
–1.0 –1.4 –1.8 –2.2 –2.6

E (vs. Ag/AgCl)/(V)
FiGURE 22.4 Cyclic voltammograms of the reduction of 2,4-di-9H-fluoren-9-yliden-1,1,3,3-tetramethylcy-

clobutane in DMF/0.1 M TMAPF6, T = 223 K, Pt electrode; (top) ν = 100 mV/s, (bottom) ν = 100 V/s.
+e – +e – +e +e
A3– A4–
–e –e – –e –e
–2.12 V –2.21 V –2.81 V –3.13 V
hv Na+ (Li+) Na+ (Li+)
+e +e – +e
B3–
–e – –e – –e
–1.35 V –2.98 V
hv Na+ (Li+)
– 2–
+e +e
–e –e
–2.60 V <–3.0 V
SchEME 22.2 Reduction pathway of distyrylbiphenyl and its cyclobutane derivative.
tetraanion of the starting species can be obtained (Scheme 22.2, Figure 22.5b). Again, it turns out
that ion-pairing effects favor the formation of the bis-benzylic intermediate. Thus, the first-order
intramolecular coupling step between the negatively charged styryl units is significantly faster in
THF/NaBPh4 than in the presence of additional 15-crown-5 or in DMA/TBABr (Scheme 22.2,
Figure 22.5a) [205a].
1-Arylindenes undergo sigmatropic 1,5-shifts, induced oxidatively [208], thermally [209], pho-
tochemically [210], and reductively [211]. The reductive rearrangement of 1,1,3-triphenylindene,
yielding the dianion of 1,2,3-triphenyl-2H-indene, has been the subject of a voltammetric investiga-
tion in DMF-TBAP [156,212]. The reaction follows an EEC or EDispC pathway.
At room temperature in the presence of Na+ cations, the rearranging dianion is formed via homo-
geneous disproportionation, thermodynamically favored by ion pairing and kinetically supported
by the fast follow-up reaction. When ion pairing is suppressed by application of low temperatures or
the addition of sodium complexing 15-crown-5, the anion radical becomes persistent and the reac-
tive dianion species has to be generated via heterogeneous ET at much more negative potentials.
The same results are obtained when the bulky tetrabutylammonium ion is used as counterion [212].
Replacing 1,1,3-triphenylindene with 1-methyl-1-phenylindene or 1,2-dihydro-1,1′-spirobiindene,
the anion radical undergoes a quite unusual cleavage of the alkyl–aryl bond, whereas the dianion
rearranges in the same manner as triphenylindene [213].
0.2 μA
(c)
1 μA
(b)
5 μA
(a)
–3.5 –3.0 –2.5 –2.0 –1.5 –1.0

E (V) versus Ag/AgCl
FiGURE 22.5 Reduction of 2,2′-distyrylbiphenyl (a, b) and 1,2-tetrahydro-1,2 diphenylcyclobutanephenan-

threne (c); (a) in THF/NaBPH4, ν = 200 mV/s, T = 273 K, (b,c) in DMA/0.1 M TBABr, ν = 100 mV/s, T = 213 K.
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23 Oxidation of Hydrocarbons
Ole Hammerich
CONTENTS
I. Introduction ............................................................................................................................. 891
II. General Mechanistic Considerations ...................................................................................... 892
A. Direct Anodic Oxidation................................................................................................. 892
B. Indirect Anodic Oxidation .............................................................................................. 894
III. Common Reaction Types and Preparative Aspects ................................................................ 895
A. Addition Reactions .......................................................................................................... 895
B. Substitution Reactions ..................................................................................................... 896
1. Nuclear Aromatic Substitution ............................................................................... 896
2. Alkyne Substitution ................................................................................................ 897
3. Substitution at α-Carbon Atoms ............................................................................. 897
4. Substitution in Saturated Aliphatic Hydrocarbons ................................................. 898
C. Dimerization–Addition Reactions .................................................................................. 898
D. Dimerization–Elimination Reactions ............................................................................. 899
1. Nuclear Dimerization and Dimerization of Alkenes.............................................. 899
2. Dimerization at α-Carbon Atoms ...........................................................................900
E. Cleavages ........................................................................................................................ 901
F. Chain Reactions ..............................................................................................................902
G. Indirect Oxidations .........................................................................................................903
IV. Voltammetry and Studies of Kinetics and Mechanisms.........................................................903
A. Aromatic Hydrocarbons ..................................................................................................903
B. Arylalkenes .....................................................................................................................906
C. Alkyl-Substituted Arenes ................................................................................................907
D. Simple Alkenes, Alkadienes, and Related Compounds..................................................909
E. Alkanes ........................................................................................................................... 910
V. Conclusions ............................................................................................................................. 911
References ...................................................................................................................................... 911
I. INTRODUcTiON
For many years, electrochemical studies of hydrocarbon oxidation were confined to prepara-
tive studies of aromatic and alkyl aromatic hydrocarbons in water-containing electrolytes under
constant-current conditions [1,2]. Usually, complex mixtures were obtained. The use of nonaqueous
solvents led to significant advances in the study of the anodic behavior of hydrocarbons. A pioneer-
ing study [3] of the voltammetry of aromatic hydrocarbons in MeCN/NaClO4 at a vibrating Pt
electrode was followed by a large number of electrochemical investigations in nonaqueous solvents.
Concurrent preparative studies, although not always very helpful in clarifying the nature of the
initial electrochemical step, have been of great help in finding out about the nature of the chemical
reactions following electron transfer. Altogether these studies, the majority of which took place in
the 1970s and 1980s, have provided an excellent insight into the products that may be obtained by
891
electrochemical oxidation of hydrocarbons and also the mechanisms by which they are formed.
Possibly for that reason the activity in this particular area of organic electrochemistry has been
rather limited after the year 2000.
The purpose of this chapter is to summarize the electrochemical oxidation of hydrocarbons with
special reference to the type of electrode processes involved. The reader may also find material of
interest in Chapters 18, 19, and 41. The application of electrochemical oxidation of hydrocarbons in
fuel cells and in wastewater treatment is beyond the scope of this chapter; the reader interested in
this aspect of hydrocarbon oxidation should consult the specialized literature.
II. GENERAL MEchANiSTic CONSiDERATiONS

The exchange of an electron between an electrode and a molecule in solution is usually referred to
as a direct process, which for hydrocarbons is observed for unsaturated compounds and aromatics
and involves the removal of an electron from a bonding π-orbital resulting in the formation of the
corresponding radical cation. Radical cations are also the primary intermediates in the oxidation
of many hydrocarbons with high-valent metal ions [4]. The general properties and reactions of
radical cations (and dications) in solution have been described in several reviews and monographs
[5–10]. In contrast to the direct process, an indirect process is one in which a foreign molecule
or ion serves to shuttle electrons between the electrode and the substrate molecules. An indirect
oxidation process may also involve the transfer of a hydrogen atom from a suitable substrate to a
radical generated electrochemically. Indirect processes are typically observed for saturated ali-
phatic hydrocarbons and substrates that are more difficult to oxidize than the solvent-supporting
electrolyte system.
A. DIrECT ANoDIC OXIDaTIoN

The radical cations initially formed during the direct oxidation of hydrocarbons (Equation 23.1) are
highly reactive species and their formation is usually followed by a fast reaction in solution. This
involves typically a nucleophile (Nu− or NuH) or a base (B) as illustrated by Equations 23.2 and
23.3. Reaction (23.2) may be observed for almost any radical cation when a suitable nucleophile is
present, whereas reaction (23.3) is typically observed for alkyl-substituted aromatic hydrocarbons
having at least one hydrogen atom in an α-position. Other common follow-up reactions are dimer-
ization (Equation 23.4) and the coupling of a radical cation and a molecule of substrate (Equation
23.5). The neutral molecule in Equation 23.5 may be a hydrocarbon different from R-H:
+
R H R H + e – (23.1)
+
H H
R H + Nu– (or NuH) R or R (23.2)
Nu NuH+
1 1'
+
R H + B R + BH+ (23.3)
2
+ + +
2 R H H R R H (23.4)
3
+ + +
R H + R H (or R' H) H R R H (or H R R' H ) (23.5)
4 4'
Oxidation of Hydrocarbons 893
Radicals such as 1, 2, and 4 are as a rule more easily oxidized than R–H [11–14] making possible the
transfer of a second electron, at the electrode or in solution, where in the latter case R–H+• serves as
the oxidant (Equations 23.6 through 23.8):
Electrode
–e–
H H
R +R (23.6)
Nu Nu
Solution
1 + 5
+R H , –R H

Electrode
–e–
R R+ (23.7)
2 Solution 6
+
+R H , –R H

Electrode
– e–
+ + +
H R R H H R R H (23.8)
4 3
Solution
+
+R H , –R H

Whether this second electron transfer takes place at the electrode (an eCe mechanism) or in solution
(an eCeh or DISP mechanism) is a question of how close to the electrode the radicals are formed
and this again is related to the rate of the chemical reactions (Equations 23.2, 23.3, or 23.5). The
distinction between these two types of electron transfer is important when voltammetric curves are
used for kinetics and mechanism analysis (see Chapters 1 and 2). Products resulting from of the
dimerization of 2 are occasionally observed.
The cations 3, 5, and 6 are finally converted to neutral products by reaction with a nucleophile or
base as shown in Equations 23.9 through 23.13:
Overall reaction
Nu RH Nu Addition (23.9)
+Nu– 7
H
+R
Nu +B
5
–BH+
R Nu Substitution (add.–elim.) (23.10)
8
R+ + Nu– R Nu Substitution (elim.–add.) (23.11)

6 9
Nu RH RH Nu Dimerization–addition (23.12)
+2Nu–
10
+ +
H R R H
3 +2 B
–2BH+
R R Dimerization–elimination (23.13)
11

In rare cases, the reaction mechanism involves the disproportionation of the radical cations (Equation
23.14), resulting in the formation of the dication, 12, which rapidly reacts further to products:
+
Kdispr
2 R H R H2+ + R H (23.14)
12
This mechanism does not constitute a major reaction pathway for the anodic oxidation of alternant
aromatic hydrocarbons (AAHs) or alkyl-substituted AAH under common experimental conditions
[11,15–18], but has been found to be operative for, for example, tetraarylethylenes [19–21]. The dif-
ference in the reaction pattern of AAH and tetraarylethylenes is related to the rotational freedom
around the central C–C bond experienced by the radical cations of the latter [22]. This results in
a small or even negative difference between the standard potentials for the first and second one-
electron transfer, E1o and E2o , and accordingly, the value of Kdispr (Equation 23.15) may take relatively
large values:

(
ln K dispr = E1o − E2o ) RT
nF
(23.15)
Dications of simple AAH are only formed and survive in solution, for example, during cyclic
voltammetry, when the radical cations are stable on the time scale of the experiment.
B. INDIrECT ANoDIC OXIDaTIoN

Indirect oxidation mechanisms have been proposed in some cases, for example, for the oxidation of
aliphatic hydrocarbons [23], for which voltammetric studies do not give unambiguous information
about the nature of the electroactive species. Often, they are assumed to involve the oxidation of the
anion of the supporting electrolyte to form an inorganic radical (Equation 23.16) that subsequently
either attacks a C–H bond in the organic substrate (Equation 23.17) or oxidizes the substrate in an
electron transfer process (Equation 23.18):
X– X + e– (23.16)
X + R H HX + R (23.17)
+
X + R H X– + R H (23.18)
It is sometimes difficult to distinguish this type of mechanism from the direct one. The combination
of reactions (23.16) and (23.18) is an example of a so-called mediated electrolysis [24] in which a
mediator redox system, here the X−/X• system, serves to shuttle electrons between the electrode and
the substrate. In other cases, the mediator system is of the Mn+/M(n+1)+ type, where M(n+1)+ is a high-
valent metal ion such as Ce4+, Co3+, or Mn3+ [25,26] (see also Reference 4).
III. COMMON REAcTiON TYPES AND PREPARATivE ASPEcTS

The anodic oxidation of hydrocarbons is a convenient method for the preparation of a number of
useful products that in many cases can be prepared only with difficulty by other methods. Examples
are given later together with a short discussion of some preparative aspects. More comprehensive
treatments are available [27–29].
A. ADDITIoN REaCTIoNS
+ 2 Nu– Nu Nu (23.19)
– 2e–

The oxidative addition (Equations 23.1, 23.2, 23.6, and 23.9) of nucleophiles to an isolated double
bond or a larger π-system is a synthetically useful reaction (see also Chapter 19). The stoichiometry
of the overall reaction is given by Equation 23.19. Usually the addition is of the 1,2- or the 1,4-type
as illustrated by the 1,2-addition of MeOH to cyclohexene (Equation 23.20) [30] and acenaphthylene
(Equation 23.21) [31] and the 1,4-additions of MeOH to cyclopentadiene (Equation 23.22) [32] and of
AcOH to anthracenes (Equation 23.23) [33]. As a rule, mixtures of cis- and trans-isomers are obtained:
OCH3
2 CH3OH
(23.20)
–2e–, –2H+
OCH3

CH3O OCH3

2 CH3OH
(23.21)
–2e–, –2H+

OCH3
2 CH3OH
–2e–, –2H+ (23.22)
OCH3
R R OCOCH3
2 CH3COO–
(CH3CN, CH3COOH)
(R = H, CH3) (23.23)
–2e–
R OCOCH3
R
Addition reactions have been observed also for alkyl-substituted aromatics, but the yields are often
low, in particular for benzene derivatives, owing to competing side-chain substitution reactions.
Examples include the addition of MeOH to methyl-substituted benzenes [34], naphthalenes [35],
and anthracenes [35,36]. In a similar fashion, the anodic oxidation of 1,3-dienes in MeOH [37,38]
results in mixtures of 1,2- and 1,4-addition products accompanied by substitution products and
methoxy containing dimers and trimers [38]. Styrenes are oxidized in MeOH to the 1,2-addition
product together with products formed by dimerization–addition [39]. Dihydroxylation of stilbene
has been achieved in good yield in an oxidative process mediated by alkoxysulfonium ions followed
by hydrolysis [40]. Oxidation of allenes results in most cases in complicated product mixtures
resulting from single and double addition reactions [41].
In addition to MeOH and AcOH nucleophiles such as pyridine [3,42–47], azide ion [48], chloride
ion [49], and cyanide ion [50], as well as the anions of 1,3-dicarbonyl compounds and aliphatic nitro
compounds [48], and even Grignard reagents [48], have been used.
The 1,2-addition process results in a product with a π-system that expands over a carbon skeleton
that is two carbons less than that of the starting material and in the case of 1,4-additions the result-
ing π-system is even separated into two smaller systems. Simple alkenes result in products that are
fully saturated. For these reasons, the addition product is usually more difficult to oxidize than
the starting material and, accordingly, does not suffer further oxidation at the potential necessary
for the oxidation of the substrate. This feature is a major reason for the success of anodic addition
processes in synthetic organic electrochemistry. However, occasionally it happens that the addition
product is further oxidized resulting eventually in cleavage of the former double bond. This has
been observed, for example, during the oxidation of 1-phenylcycloalkenes (Equation 23.24) [51] and
vinylarenes [52] in MeOH:
OCH3
OCH3
4 CH3OH
OCH3 (23.24)
–4e–, –4H+
n n OCH3
n = 1, 2, or 3
B. SUbSTITUTIoN REaCTIoNS
1. Nuclear Aromatic Substitution
H Nu
+ Nu– (23.25)
–2e–, –H+
When the ring carbon at which the nucleophilic attack takes place carries a hydrogen atom, the
intermediate carbocation, 5, may deprotonate resulting in nuclear substitution (Equations 23.1, 23.2,
23.6, and 23.10; see also Chapter 19). The overall reaction includes reestablishment of the double
bond as illustrated by Equation 23.25. When Nu is electron withdrawing the product is less easy
to oxidize than the starting material and is not further converted. In such cases, the yields of the
substituted products are usually good. Examples are acetoxylation [53] and trifluoroacetoxylation,
which in the latter case after hydrolysis leads to phenolic products (Equation 23.26) [54,55] and
acetamidations via a nitrilium ion intermediate (Equation 23.27) [56]:
OCOCF3 OH
CF3COOH H2O (23.26)

– 2e–, – 2H+ –CF3COOH

CH3CN + H2O
N C CH3 NHCOCH3 (23.27)
–2e–, –H+ –H+
In addition, deactivating nitro, cyano, and halogen substituents have been introduced by electro-
chemical oxidation.
When Nu is electron donating such as OH, the product is as a rule more easily oxidized than the
starting material resulting in further oxidation under the reaction conditions as, for example, observed
for the oxidation of benzene to benzoquinone in aqueous sulfuric acid [57] and of anthracene to
anthraquinone and bianthrone in “wet” acetonitrile [58]. The anodic methoxylation of naphthalene,
which results in 1-methoxy-, 1,2-dimethoxy-, and 1,4-dimethoxynaphthalene, approximately in a 1:2:1
ratio, is another illustration of this problem [59]. Even more complex reaction mixtures that include
dimers result from the methoxylation of 2-methyl- and 2-benzylnaphthalenes [60]. However, in other
cases, a single major product is obtained after a sequence of reactions, for example, the oxidation
of mesitylene in MeCN-diluted H2SO4 to 2,4,6-trimethyl-4-hydroxycyclohexa-2,5-dien-1-one in a
substitution–elimination reaction [61] or the oxidation of anthracene in MeOH to 9,9,10,10-tetramethoxy-
9,10-dihydroanthracene in a substitution–addition reaction (Equation 23.28) [62].
CH3O OCH3
4 CH3OH
–6e–, –6H+
(23.28)
CH3O OCH3
2. Alkyne Substitution
H + Nu– Nu (23.29)
–2e–, –H+
The electrochemical oxidation of a variety of terminal alkynes (Equation 23.29) in MeOH in the
presence of iodide ion (Nu− = I−) has been demonstrated to be an easy route to the corresponding
1-iodoacetylenes with yields being typically in the 70–85% range [63].
3. Substitution at α-Carbon Atoms

H Nu
+ Nu– (23.30)
–2e–, –H+
An important case is the oxidation of alkenes or alkyl arenes containing at least one hydrogen
in an α-position [64–70]. The reaction sequence that leads to α-substitution (Equation 23.30) for
alkylbenzenes and alkylnaphthalenes most likely includes Equations 23.1, 23.3, 23.7, and 23.11,
whereas for alkylanthracenes there is evidence that substitution may take place as an addition–
elimination process (see Section IV for details). Typical examples are the oxidation of cyclohexene
to 3-acetoxycyclohexene in AcOH (Equation 23.31) [69]; the oxidation of 1,3,5-cycloheptatriene to
7-methoxy-1,3,5-cycloheptatriene in MeOH [67]; the two-step oxidations of toluene, p-xylene, and
p-tert-butyltoluene to the corresponding dimethyl acetals in MeOH (Equation 23.32) [68,71,72]; and
the functionalization of 1,3-diisopropylbenzene [73]. Oxidation of toluene derivatives to the cor-
responding benzyl alcohols may be achieved by alkoxysulfonium ion–mediated oxidation followed
by hydrolysis [40].
CH3COOH
(CH3COOH, Et4NOTs)
OCOCH3 (23.31)
–2e–, –2H+
CH3 CH3 OCH3 CH3 OCH3

CH3OH CH3OH
H3C CH3 H3C H H3C H
–2e–, –2H+ –2e–, –2H+
CH3 CH3 H CH3 OCH3

(23.32)
In moist MeCN, electrolysis of alkylaromatics at the first oxidation potential gives moderate to high
yields of the corresponding N-benzylacetamides, which are themselves relatively easily oxidized.
In contrast, the oxidation of diphenylmethane gives benzophenone in good yield [74]. In some cases
the corresponding bibenzyls were isolated [75]. The oxidation of hexamethylbenzene at the poten-
tial of the second voltammetric wave results in side-chain bisacetamidation at the 1,3-positions [76].
α-Substitution in alkyl arenes is often accompanied by nuclear substitution. In an elegant study
of the acetoxylation of alkylbenzenes, good yields of the nuclear substitution product were obtained
by taking advantage of the fact that the α-substituted product selectively could be reduced back
to the starting material by using a Pd/C cathode in an undivided cell, here illustrated for p-xylene
(Equation 23.33) [65].
CH3COOH, CH3COO–
H 3C CH3 H3C CH2OCOCH3 + H3C CH3
–2e–, –H+
OCOCH3
2e–, H+ at Pd/C
–CH3COO– (23.33)
4. Substitution in Saturated Aliphatic Hydrocarbons

R H + Nu– R Nu (23.34)
–2e–, –H+
The anodic oxidation of saturated aliphatic hydrocarbons takes place at potentials close to those
for the decomposition of most solvent-supporting electrolyte systems [77] and for that reason
detailed kinetic and mechanistic studies are in most cases difficult or impossible. Thus, it is usu-
ally not known whether the reaction proceeds in a direct fashion involving removal of an elec-
tron from a σ-type bond or in an indirect fashion via hydrogen abstraction (Equation 23.17). In
any case, it is not a surprise that the oxidation of long-chain aliphatic hydrocarbons is nonselec-
tive. However, anodic substitution (Equation 23.34) is a useful method for the functionalization
of saturated aliphatic hydrocarbons having a high degree of symmetry; this reduces the number
of possible products considerably, sometimes to the extent that a single major product may be
obtained. Examples include the oxidation of cyclohexane and other cyclic and bicyclic hydro-
carbons in CH 2Cl2/CF3COOH/(CF3CO)2O or CH2Cl2/CF3COOH to the corresponding trifluoro-
acetates (Equation 23.35) [78,79] and the oxidation of adamantane in MeCN that leads to the
corresponding acetamide (Equation 23.36) [80].
CF3COOH
(CH2Cl2)
OCOCF3 (23.35)
–2e–, –2H+
CH3CN, H2O
(23.36)
–2e–, –2H+ NHCOCH3

C. DIMErIZaTIoN–ADDITIoN REaCTIoNS
2 + 2 Nu– Nu Nu (23.37)
–2e–

Dimerization followed by addition (Equations 23.1, 23.4, and 23.12 or 23.1, 23.5, 23.8, and 23.12),
resulting in overall Equation 23.37, is a useful reaction [48,81,82] taking place during the anodic
oxidation of suitable substituted alkenes, for example, arylalkenes and butadiene, in an electrolyte
usually consisting of MeOH/NaOMe or MeOH/NaI (see also Chapter 18). The reaction is favored
by the use of a carbon anode [48]. Styrene, for instance, may be oxidized in this way to 1,4-diphenyl-
1,4-dimethoxybutane (Equation 23.38) [81].
OCH3
2 CH3O–
2 C CH2 (23.38)
–2e–
H
OCH3

This reaction may also be carried out in an intramolecular fashion by oxidation of bis-styrylalkanes
giving rise to cyclized products [83].
D. DIMErIZaTIoN–ELIMINaTIoN REaCTIoNS
1. Nuclear Dimerization and Dimerization of Alkenes
H
2 (23.39)
–2e–, –2H+

Nuclear dimerization and dimerization of alkenes (Equation 23.39) may proceed by either of two
mechanisms (Equations 23.1, 23.4, and 23.13 or Equations 23.1, 23.5, 23.8, and 23.13) dependent
on the nature of the substrate and the reaction conditions (see also Chapter 18). Similarly to what is
being observed for nuclear substitution with electron donating substituents, the products of nuclear
dimerization are as a rule more easily oxidized than the starting materials resulting in further
oxidation. However, under conditions of low nucleophilicity, the radical cation of the dimer may
survive as long as the concentrations are kept at the millimolar level and the dimer may then be
obtained after back reduction to the neutral stage. The failure to conduct reactions of this type at
higher concentrations is most likely caused by formation of the highly reactive dimer dication by
disproportionation (Equation 23.14). In some cases, the dimers, which as a rule are less soluble
than the substrates, precipitate and in this way avoid further oxidation. This has been observed,
for instance, during the dimerization of 9-phenylanthracene to the 10,10′-dimer in MeCN [84] or
MeCN/CF3COOH (Equation 23.40) [85].
2 (23.40)
–2e–, –2H+
An interesting example is the anodic dimerization of 2-phenylnorbornene (Equation 23.41) [86].

The experimental results indicate that the dimer radical cation in this case oxidizes the substrate to
the corresponding radical cation in solution (Equation 23.42) so fast that follow-up reactions leading
to the degradation of the dimer are avoided.
+
Ph Ph
2 (23.41)
–2e–, –2H+ –e–
Ph
Ph Ph
+
Ph + Ph
+ + (23.42)
Ph Ph
Ph Ph
Under conditions that are not strictly nonaqueous, the oxidized dimer may be trapped by water
as it was observed during the oxidation of 1,1-diphenylethylene catalyzed by the radical cation
of dibenzo-1,4-dioxin [87]. The dimer dication upon reaction with water undergoes a 1,2-phenyl
shift resulting finally in 1,2,4,4-tetraphenyl-3-buten-1-one (Equation 23.43) reminiscent of the
1,2-shifts observed during anodic oxidation of 1-phenyl- and 1,4-diphenylnaphthalene in acidic
DMF [88].
1) –2e–
2 C CH2 –, – 2H+
C CH CH C C CH CH C
– 2e 2) H2O
O

(23.43)
Oxidation of arenes under nonaqueous conditions often results in polymerization [89], which has
been observed for most of the simple arenes, for example, benzene [90–93], naphthalene [94],
pyrene [95], biphenyl [92], triphenylene [95], fluoranthene [95], and fluorene [95–97] (see Chapter
41 for details). Polymerization is often accompanied by severe electrode passivation [96].
An intramolecular reaction has been observed for the oxidation of tetraphenylethylene
(Equation 23.44) in MeCN/Et4NClO4 [98] and in CH2Cl2/CF3COOH [19,21].
C C (23.44)
–2e–, –2H+
2. Dimerization at α-Carbon Atoms

H
2 (23.45)
–2e–, –2H+
Dimers linked through the α-carbon (Equation 23.45) may be observed when dimerization of
the radical, 2, competes favorably with further oxidation (Equation 23.7). For instance, oxidation
of 9,10-dimethylanthracene in the presence of the hindered base, 2,6-lutidine, results in the sym-
metrical dimer (Equation 23.46) [99].
CH3
H3C N CH3
2 H3C CH2CH2 CH3 (23.46)
–2e–, –2H+
CH3

However, the outcome of the oxidation of alkyl-substituted arenes is not easy to predict owing to
the competition between nuclear dimerization and dimerization through an α-carbon. For instance,
a major product from oxidation of mesitylene in CH2Cl2 is bimesityl (Equation 23.47) and from
durene in CH2Cl2/CF3SO3H, the heptamethyldiphenylmethane (Equation 23.48) [100]; neither
diphenylmethane is formed from mesitylene, nor a biphenyl from durene.
CH3 CH3 H3C
CH2Cl2, Bu4NBF4
2 H3C CH3 (23.47)
–2e–, –2H+
H3C CH3
CH3 H3C
H3C H3C CH3
H 3C CH3
CH2Cl2, Bu4NBF4
2 H3C CH2 (23.48)
–2e–, –2H+
H3C CH3
CH3 H3C CH3
Related to these reactions is the formation of mixed biaryls, for example, during the anodic oxida-
tion of naphthalene in the presence of alkylbenzenes [101].
E. CLEaVaGES
The release of steric strain plays a central role in the anodic oxidative ring opening of cyclopro-
panes. For instance, 1,1,2,2-tetraphenylcyclopropane is via the 1,1,3,3-tetraphenylpropenyl cation
converted to 1,3,3-triphenylindene or tetraphenylallene depending on the basicity of the solvent
system (Equation 23.49) [102,103].
MeCN
–H+
+ MeCN +
–2e–, –H+
2,6-lutidine
–H+
C C C

(23.49)
Similarly, the oxidation of 1-cyclopropylnaphthalene in MeOH gives 1-(1,3-dimethoxypropyl)

naphthalene and other ring-opened products [104] and oxidation of cyclopropylbenzene
gives 1,3-dimethoxypropylbenzene [105]. Related to these reactions are the oxidation of
1,1,2,2-tetramethylcyclopropane in MeOH (Equation 23.50) [106] and of polycyclic cyclopropanes
in AcOH/triethylamine to ring-opened products [107].
H3C CH3 H3C CH3 H3C CH3

CH3OH
H3C CH3 H2C CH3 + H3C CH3 (23.50)
–2e–, –H+ H3CO
OCH3 OCH3

Release of steric strain is also an important factor in the oxidation of tetra-tert-butyltetrahedrane to

the radical cation of tetra-tert-butylcyclobutadiene (Equation 23.51) [108].
–e–
(23.51)
Cleavage of a C–C single bond is observed also during the electrochemical oxidation of (−)−α-pinene
[109] and even of the C–C double bond in alkenes. The latter reaction has been accomplished either
by an initial anodic bromo-formyloxylation, as for cyclohexene, the product from which is cleaved
oxidatively to hexane-1,6-dial derivatives [110] or indirectly using an IO4−/RuCl3 mediator system.
In the latter case, the products are the corresponding diacids that can be isolated in good yields as
the methyl esters. The examples include the cleavage of the double bond in 1-decene, cyclododecene
(Equation 23.52), and norbornene [111]. The reactions are carried out with either in-cell or ex-cell
oxidation of the mediator.
IO4–, RuCl3
COOCH3
ex cell oxidation H3COOC (23.52)
F. CHaIN REaCTIoNS
The radical cation catalyzed cycloadditions of the Diels–Alder type are well known and have been
the subject of a number of studies to which the reader is referred for details [112–116]. The prototype
cyclodimerization of 1,3-cyclohexadiene catalyzed by tris(4-bromophenyl)aminium ion (Ar3N+·)
proceeds smoothly in CH2Cl2 at room temperature or below to a 70% yield of the Diels–Alder dimer
(Equation 23.53) [113]. The direct anodic oxidation of 1,3-cyclohexadiene results in formation of
the Diels–Alder product only in low yield, the major product being a polymer linked through the
1,4-positions [117].
+
Ar3N
2 endo:exo = 4.5:1 (23.53)

A chain reaction is involved also in the anodically stimulated [2+2] cycloreversion (Equation
23.54) [118].
Ph CH3 Ph CH3
Ph Ph
CH3 CH3 (23.54)
Pt anode
Another type of chain reaction is sometimes observed when electrochemical oxidation of unsatu-
rated hydrocarbons is carried out in the presence of atmospheric oxygen, which may result in the
formation of dioxetanes exemplified by the oxidation of biadamantylidene (Equation 23.55) and
related compounds [119–121]. Similar behavior has been observed for other alkenes [122].
O O
anode, O2
(23.55)

G. INDIrECT OXIDaTIoNS
The situation in which the supporting electrolyte and/or the solvent is oxidized at a lower potential
than the organic substrate is frequently encountered. Anodic methoxylation and cyanation are two
typical cases for which homolytic processes involving methoxy and cyano radicals, respectively,
have been invoked [123,124]. However, it can be shown that in cyanation [125–127] and at least
some cases of methoxylation [128] one must work at an anode potential around or higher than the
half-wave potential of the organic substrate in order to get any substitution product. Similar mecha-
nism problems are apparent for the side-chain acetoxylation of alkylaromatic compounds in AcOH/
Me4NNO3 [129,130].
Organic electron transfer reactions are often accompanied by large activation energies (over-
potentials) and in such cases it is sometimes advantageous to include a mediator in the solvent-
supporting electrolyte system. Examples are the oxidation of anthracene to anthraquinone in
a slurry containing both a surfactant and a redox mediator, Mn3+ [26], and the oxidation of
toluenes to benzaldehydes or more complex reaction mixtures by electrochemically generated
Ce 4+, Co3+, or Mn3+ [25,131]. The oxidation of benzene at a glassy carbon electrode in the oxygen
evolution region in aqueous sulfuric acid has been suggested to involve “active” oxygen adsorbed
to the anode [57].
IV. VOLTAMMETRY AND STUDiES Of KiNETicS AND MEchANiSMS

A. AroMaTIC HYDroCarboNS
The gathering of standard potentials, Eo, or rather formal potentials, Eo′ (see Chapter 1), for the
one-electron process leading to the corresponding radical cation was earlier greatly hindered by the
occurrence of the rapid follow-up reactions of these species. Reaction with impurities in the solvent,
or even the solvent itself, and/or rapid proton loss are common reasons for not observing the revers-
ible formation of the radical cations and the consequent irreversibility is in CV associated with a
shift in Ep, in the negative direction, relative to that for the reversible process. Only in rare cases are
the radical cations and dications resulting from one-electron oxidations of hydrocarbons sufficiently
stable to survive at the CV time scale and conditions [132]. Considerable progress has been made in
countering these difficulties.
The use of acidic solutions greatly slows down proton loss [11,133], the rigorous drying of
solvents precludes rapid hydroxylation of cationic species [17,134–136], and the use of nonnucleo-
philic solvents, such as liquid SO2 [137–140], 1,1,1,3,3,3-hexafluoropropan-2-ol (HFP) [141], or
CF3COOH/(CF3CO)2O, alone [17,142] or mixed with CH2Cl2 [11,135,143–146], also permits the
formation of several persistent radical cations and dications. For 9,9′-bianthryl, even the tetraca-
tion has been observed in liquid SO2 [138]. The application of phase-selective second harmonic
ac (SHAC) voltammetry to organic systems has proved to be fruitful [147,148]. This method may
be used for determining Eo′ even when the radical cation undergoes a moderately rapid reaction.
Another approach for obtaining Eo′ for the formation of reactive radical cations is the application of
CV with voltage sweep rates in the kV s−1 range [149–155].
Finally, the stability of radical cations and other reactive intermediates is, of course, enhanced at
low temperatures [11,156–159]. This is an additional reason why follow-up reactions are effectively
suppressed in liquid SO2. Another aspect of low-temperature conditions is the possibility to prepare
stable salts of highly reactive radical cations as demonstrated by the formation of a solid with the
composition (ArH)2PF6 by oxidation of ArH in CH2Cl2 between −30°C and −70°C with Bu4NPF6 as
supporting electrolyte [160–162].
A much used approach to the study of the primary electrochemical step of aromatic hydrocar-
bons involves the use of model compounds whose radical cations (and in some cases dications) are
relatively stable. Substituted anthracenes, particularly 9,10-diphenylanthracene (9,10-DPA), have
featured largely in such work [11,42–47,135,137,151,163–168]. For instance, on slow sweep CV in
MeCN purified without critical regard to dryness, 9,10-DPA is reversibly oxidized to the radical
cation at Ep = 1.22 V versus SCE, followed by irreversible oxidation to the dication at ca. 1.6 V.
Anthracenes without substituents in the 9,10-positions as well as most benzenes and naphthalenes
give rise to irreversible oxidation in, for example, MeCN and CH2Cl2 during CV at moderate volt-
age sweep rates.
Voltammetric data for a number of representative aromatic hydrocarbons are summarized
in Table 23.1, and it is seen that the ease of oxidation, as expected, increases when the π-system
becomes more extended. A more comprehensive collection of such information is available else-
where [141,152,153,169,170]; in addition, the progress in computer technology and user-friendly
software has now made it possible to obtain oxidation potentials by calculation [171,172] (see
Chapter 6 for details).
It has long been realized that excellent correlations exist between E1/2 or Ep and molecular orbital
parameters [174,180–183]. Correlations between voltammetric data and experimental observables
such as ionization potentials (IP) [174,180,184,185], charge-transfer transition energies [174] and
positions of p-bands in the UV spectra of the hydrocarbons [3,174] have been reported as well. The
basis and limitations of such correlations were early examined critically [147,177,186] and they are
not in much use anymore.
Phase-selective SHAC voltammetry has been used to evaluate the temperature dependence of
Eo′ for a number of aromatic hydrocarbons [148] and hence the entropy changes associated with the
formation of the radical cations:
dE o′ ∆S
= (23.56)
dT F
The values of −ΔS273.2 were observed to be in the range 5–20 e.u. and were attributed to reflect
mainly differences in solvation. A slight increase in −ΔS273.2 was observed with increasing concen-
tration of the supporting electrolyte and in going through the solvent series: PC < DMF < MeCN.
Convincing evidence has been put forward that the reaction pathway in the oxidative addition
of two molecules of a pyridine derivative to 9,10-DPA [42–47] includes Equations 23.1, 23.2, 23.6,
and 23.9. By studying the number of electrons transferred (nobs) in the oxidation of 9,10-DPA in the
TABLE 23.1
Oxidation Potentials of Aromatic Hydrocarbons and Substituted Aromatic Hydrocarbons
E1/2 (V) Ep (V) or Ep/2 (V)
Compound vs. SCE a vs. Ag/Ag + vs. SCE vs. Ag/Ag+
Benzene 2.62b
Toluene 1.98c; 1.93d 1.93e
p-Xylene 1.56c 1.64e
Mesitylene 1.90 1.55c 1.69e; 1.72f
1,2,3,4-Tetramethylbenzene 1.77g
Durene 1.62 1.29c 1.75g 1.41e; 1.70h
Pentamethylbenzene 1.62 1.28c 1.69g 1.33e; 1.63h
Hexamethylbenzene 1.52 1.16c 1.58g 1.20e; 1.50h
Naphthalene 1.72 1.34c; 1.31d 1.87a
Anthracene 1.20f 0.84i 1.31j; 1.40k,l 1.13m
9,10-Diphenylanthracene 0.86i 1.20j; 1.27l
Biphenyl 1.91f 1.48c
Fluorene 1.65 1.32n; 1.25c
Perylene 1.0 1.09a
a AcOH–NaOAc [173].
b MeCN–Bu4NClO4 [152].
c MeCN–NaClO4 [3].
d MeCN–NaClO4 [174].
e CF3COOH–(CF3CO)2O-Bu4NClO4 [153].
f MeCN–Bu4NBF4 [175].
g Values of Eo in MeCN–Bu4NBF4 [155].
h MeCN–Bu4NClO4 [153].
i MeCN–NaClO4 [176].
j CH2Cl2–AcOH–(CF3CO)2O–NaClO4 [135].
k MeCN–Bu4NBF4–Al2O3 [177].
l CH2Cl2–CF3COOH–(CF3CO)2O–Bu4NBF4 [11].
m C6H5Cl–Bu4NBF4 [178].
n MeCN–(CF3CO)2O–Bu4NBF4 [179].
presence of different nucleophiles at the rotating disk electrode as a function of the rotation rate
ω, it was possible to show [42] that the strength of the nucleophile strongly affects the dependence
of nobs on ω. Approximate pseudo first-order rate constants for the rate determining attack by the
nucleophile on 9,10-DPA+• were obtained by fitting the experimental data for nobs versus ω to the
working curve calculated for the eCe mechanism. The results demonstrated that the rates follow
the order of nucleophilicity of the pyridines. This conclusion is not affected by the fact that the
working curves were calculated for an eCe mechanism instead of the DISP mechanism that is
actually followed.
The rate law for the reaction between 9,10-DPA+· and pyridine (PYR) at the millimolar concentration
level is given by Equation 23.57. The value of k57 has been determined by spectroelectrochemical
methods [43–45] and by homogeneous kinetics [44–46] and was found to be in the range
2 · 104 –4 · 104 M−1 s−1 in MeCN at room temperature (see Chapter 3 for a discussion of spectroelec-
trochemical methods). However, at much lower concentrations (0.01 mM), stopped-flow experiments
demonstrated that the reaction was following a rate law (Equation 23.58) second order in the 9,10-
DPA+• concentration and first order in the PYR concentration. These data indicate a transition from
rate determining nucleophilic attack at high concentrations of 9,10-DPA+• to rate determining elec-
tron transfer at low concentrations [45]. The same rate law was found for reaction with Cl− [49]:
−d[9,10-DPA + • ]
= k57[9,10 - DPA + • ][ PYR ] (23.57)
dt
−d[9,10-DPA + • ]
= k58[9,10 - DPA + • ]2 [ PYR ] (23.58)
dt
The rate constant for the corresponding reaction with rubrene radical cation is approximately one
order of magnitude lower [187]. The solvent used in these studies, MeCN, is in itself a nucleophile,
but much too weak to interfere kinetically in the presence of pyridines. For instance, the pseudo
first-order rate constant for the reaction between unsubstituted anthracene and MeCN has been
estimated to be 125 s−1 [56].
B. ArYLaLkENES
Oxidation potentials for typical arylalkenes are summarized in Table 23.2. Data for other substrates
have been summarized elsewhere [29].
Oxidation of tetraphenylethylene (TPE) in CF3COOH or CH2Cl2/CF3COOH [19,21] gives
a radical cation stable on the CV time scale, but which undergoes second-order decomposition
TABLE 23.2
Oxidation Potentials of Arylalkenes, Alkenes, Alkadienes, and Carotenes
E1/2 (V) Ep (V) or Ep/2 (V)
Compound vs. SCE a vs. Ag/Ag +b vs. SCEc vs. Ag/AgCld
Styrene 1.68
Indene 1.56
cis-Stilbene 1.57
trans-Stilbene 1.40
2-Phenylnorbornene 1.1e
Ethylene 2.90
1-Alkenes 2.7–2.8
2-Alkenes 2.2–2.3
Cyclohexene 2.14 2.05; 1.95f
1,3-Butadiene 2.09 2.0
Biadamantylidene 1.65g
Norbornadiene 1.54 1.62
1,4-Cyclohexadiene 1.74 ≈1.3
β-Carotene 0.51h 0.54
a MeCN–LiClO4 [64].
b MeCN–Et4NBF4 unless otherwise stated [188].
c CH2Cl2–Bu4NPF6 [189].
d MeOH–NaClO4 unless otherwise stated [81].
e MeCN–Bu4NClO4 (V vs. Ag/Ag+) [86].
f MeCN–NaClO4 [174].
g CH2Cl2–CF3COOH–(CF3CO)2O–Bu4NBF4 (V vs. SCE) [119].
h MeCN/Benzene (2/1)–Et4NClO4 [190].
according to the rate law, rate = kobs[TPE+•]2/[TPE]. The product is 9,10-diphenylphenanthrene,

Equation 23.44, and the reaction seems to be a clear-cut example of a mechanism involving dispro-
portionation followed by rate determining intramolecular cyclization of the resulting dication. The
rate constant for the coupling reaction at 298 K was determined by derivative LSV and found to
be equal to 3.2 · 103 s−1 with an Arrhenius activation energy equal to 11.4 kcal mol−1. This relatively
high value was believed to reflect charge–charge repulsion in the transition state. The activation
entropy at 298 K was −6 cal K−1 mol−1 indicating solvent reorganization around the more localized
charges in the transition state.
C. ALkYL-SUbSTITUTED ArENES
As it appears earlier, the radical cations of unsubstituted or aryl-substituted arenes are usually long-
lived species under nonnucleophilic conditions. This is at variance with the radical cations of most
alkyl-substituted arenes that as the rule are strong acids [191–193]. For instance, the pKa of toluene
changes from approximately 40 to −13 upon oxidation to the radical cation. Accordingly, the radical
cations of alkyl arenes would be expected to deprotonate readily, which is indeed the case. However,
the application of CV in the kV · s−1 range has allowed for the determination of Eo′ (Table 23.1) for
the oxidation of a series of methylbenzenes [152,153]. The deprotonation of the methylbenzene
radical cations has been studied extensively [75,76,133,152,153,175,194–200]. Cyclic voltammetry
of these compounds at low-voltage sweep rates in MeCN typically results in two irreversible oxida-
tion peaks, in both cases corresponding to the transfer of two electrons. The first of these oxidation
processes results in the formation of the corresponding benzyl cation, presumably formed in an
eCe/DISP-type process with the chemical step being deprotonation of the initially formed radical
cation (Equation 23.3). The fate of the benzyl cation depends on the composition of the solvent. For
instance, in CF3COOH or CH2Cl2/CF3COOH the intermediate pentamethylbenzyl cation, formed
by oxidation of hexamethylbenzene, is converted to ArCH2OOCCF3. Further oxidation of this prod-
uct leads to a radical cation persistent on the time scale of slow sweep CV [133].
The mechanistic details of the anodic alkylbenzene oxidation have been under intense investiga-
tion. In the early stages of this research, the major issue was the order of the electron and proton
transfer steps leading to the benzyl cations and whether the second electron transfer reaction took
place at the anode (eCe) or in solution (DISP); see Equation 23.7. By the application of a combina-
tion of voltammetry and specular reflectance spectroscopy [175,194] it was possible to monitor the
electrode surface by UV/Vis spectroscopy during electrolysis at controlled potential or to monitor
the absorption at a predetermined λmax value as a function of potential. In this way, absorption spec-
tra attributed to the radical cation, 13, the benzyl radical, 14, formed by deprotonation (Equation
23.59), the benzyl cation, 15, and the N-benzylnitrilium ions, 16, have been recorded in MeCN:
+ +
CH3 CH3 CH2 CH+2 CH2 N C CH3
–e– k59 13 CH3CN (23.59)

+e– – H+
R R R R R
13 14 15 16
The total analysis of the data from this and other electrochemical techniques was found to be in
agreement with mechanism (23.59) and allowed for the evaluation of the deprotonation rate con-
stants, k59, for a number of methylbenzene radical cations. The values of k59 measured in this way
varied from 100 s−1 (1,3,5-trimethylbenzene) to 870 s−1 (1,2,4-trimethylbenzene). On the other hand,
reduction of the radical cation of hexamethylbenzene in MeCN at −40°C could not be observed by
CV [196]; this led to the conclusion that the lifetime was less than 10 −4 s corresponding to a pseudo
first-order rate constant approximately one order of magnitude higher than the range reported earlier.
The simplest compound to study with respect to deprotonation of the radical cation is hexa-
methylbenzene because the nucleus is blocked toward competing substitution reactions. For other
alkylaromatics an alternative reaction is available, that is, attack by starting material on the radical
cation or benzyl cation. The balance between these pathways has been studied by the combination
of LSV and specular reflectance spectroscopy for durene and mesitylene. The conclusions were
that proton loss is slower from the radical cation of mesitylene than from that of durene [75,175].
Consequently, bimolecular reaction with substrate (Equation 23.60), resulting in formation of the
dimer, 18, is more likely for mesitylene than for durene, which will be acetamidated after proton
loss and further oxidation. Attack of radical cation on mesitylene rather than dimerization of two
radical cations is preferred since the yield of 18 increases appreciably with increasing concentration
of mesitylene but is not affected by changes in the current density. However, it should be pointed
out that some authors have suggested that dimer formation may take place as a coupling between
two radical cations, as in the formation of 6,6′-bibenzo[a]pyrene from benzo[a]pyrene [201].
CH3
+
CH3 CH3
–e– H3C CH3
+e–
H3C CH3 H3C CH3
17
CH3 H3C (23.60)
CH3 H3C
H
–e– or 17
H3C + CH3 H3C CH3
–2H+
H
CH3 H3C CH3 H3C
18
The exact nature of the base is not clear in these studies and the difference in the rate constants might
be attributed to differences in solvent quality. More insight into the nature of the proton transfer reac-
tion has been gained through studies in MeCN of the homogeneous electron transfer from a series of
methylbenzenes to Fe(III) complexes followed by proton transfer from the resulting methylbenzene
radical cations to a series of pyridine derivatives [153,197]. For hexamethylbenzene radical cation, the
rate constants for proton transfer varied between 4 · 102 and 9 · 105 M−1 s−1 in passing from 2-fluoro-
pyridine to 2,4,6-trimethylpyridine. The rate of deprotonation followed a general Brønsted relation-
ship with a slope of 0.26 indicative of an overall free energy change in the exergonic region of the
driving force. This together with a deuterium kinetic isotope effect that was observed to decrease with
increasing driving force for proton transfer seems to indicate an early transition state in which the pro-
ton transfer has not proceeded beyond a symmetrical arrangement. Other results have cast some doubt
on the general validity of the mechanism including simple deprotonation of the radical cations, that is,
Equation 23.59 [198]. Data obtained for durene, penta-, and hexamethylbenzene in MeCN indicated
a rate law (Equation 23.61), second order in radical cation. This together with the unusual observa-
tion that the apparent rate constant decreased with increasing temperature at T > 20°C, resulting in
a curved Arrhenius plot and a deuterium kinetic isotope effect that decreased with decreasing tem-
perature pointed toward a reaction scheme including the reversible dimerization of the radical cation
followed by the irreversible formation of ArCH2+, ArCH3, and a proton (Equations 23.62 and 23.63):
+
−d  ArCH 3•  + 2
= k62  ArCH3•  (23.61)
dt
+ +
2ArCH3 (ArCH3 )2 (23.62)

+
(ArCH3 )2 + B ArCH+2 + ArCH3 + BH+ (23.63)

The implications of these unexpected results on the conclusions drawn from previous studies, in
particular the work based on spectroelectrochemical measurements, are still not clear. The structure
of the dimer dication (ArCH3+•)2, is not known. However, the reversible formation of dimers from
hydrocarbon radical cations is not exceptional and has been observed in other cases [202–204] and
is probably a general phenomenon, but usually the dimers do not manifest themselves kinetically.
Another unexpected result is the observation that deprotonation of the radical cations of
9-methylanthracene and related substrates in the presence of pyridine bases appears to proceed via
an initial complexation prior to the proton transfer (Equation 23.64) rather than by direct proton
transfer (Equation 23.3) [205]. The important feature of the reaction is kinetic isotope effects that
indicate a significant degree of quantum mechanical proton tunneling:
CH3 CH3
+ +
+ Base
Base
(23.64)
CH2
+ BaseH+

Remotely related to this is the oxidation of, for example, 9,10-DMA, by Ce4+ in MeOH/MeCN that
at 0°C leads exclusively to the 9,10-adduct, 19, which upon heating to 45°C was converted to the side
chain oxidation product, 20, by elimination of MeOH [206].
CH3 OCH3 CH3
CH3 OCH3 CH2OCH3
19 20
In the absence of a proton in the α-position, for example, when the alkyl group is tert-butyl, the
radical cation may instead undergo slow C–C cleavage resulting in formation of the parent hydro-
carbon and a tert-butyl fragment. This has been observed during the voltammetric oxidation of
9-tert-butylanthracene in HFP [207].
D. SIMpLE ALkENES, ALkaDIENES, aND RELaTED CoMpoUNDS

The electrochemical oxidation of nonbenzenoid unsaturated hydrocarbons is believed to include
also the formation of the corresponding radical cation as the first step. However, radical cations
derived from alkenes are only in rare cases sufficiently stable to allow for the observation of their
reduction back to starting material during CV. Accordingly, the oxidation potentials, such as those
listed in Table 23.2, have in most cases no thermodynamic significance. A notable exception is the
oxidation of hydrocarbons of the carotenoid type, which are oxidized in two closely spaced revers-
ible or quasi-reversible one-electron transfers to the corresponding dications [189,190] and even the
quasi-reversible oxidation to the radical trication has been observed [208].
E. ALkaNES
The anodic limit of MeCN containing a perchlorate salt is not high enough to allow a more
general study of aliphatic hydrocarbons, except in a few favorable cases [174,209,210]. With the
introduction of tetrafluoroborates and hexafluorophosphates [188] as supporting electrolytes the
anodic limit in MeCN can be extended considerably, so that certain saturated aliphatic hydro-
carbons can be studied voltammetrically. The application of ultramicroelectrodes has even made
it possible to record voltammograms for short-chain alkanes in MeCN in the absence of inten-
tionally added supporting electrolyte [211]. Oxidation potentials for a number of aliphatic and
alicyclic hydrocarbons are listed in Table 23.3. The table is organized to include a representative
range of alkanes; common conditions for voltammetry are displayed, as are the relationships
between oxidation potentials measured against different reference electrodes. From the diffusion
currents it can be estimated that two electrons are involved in the majority of these oxidations
[188,209,212]. Radical cations of aliphatic hydrocarbons are not observed as a result of electro-
chemical oxidation, but insight into the nature of these species has been gained by high-level
computational methods [213].
It will be apparent from Table 23.3 that, apart from the use of tetrafluoroborates and hexafluoro-
phosphates, extended anodic limits can be obtained at low temperatures [215] or by the use of acidic
TABLE 23.3
Oxidation Potentials of Alkanes
E1/2 (V) Ep (V) or Ep/2 (V)
Compound vs. SCE vs. Ag/Ag+ vs. Pd/H2 vs. Ag/Ag+
n-Alkanes 3.4a; 2.7b 3.5c
3.5–3.9d
1.14–1.46e
1.7–2.3f
2,2-Dimethylbutane 3.28a 3.90c
2-Methylpentane 3.01a 1.68g
Cyclopropane 3.41d
1,1,2,2-Tetramethylcyclopropane 2.05h
Phenylcyclopropane 1.87i
Cyclopentane 2.01g
Cyclohexane 1.77g
Adamantane 2.36j; 1.75k; 2.38l
Cubane 1.73m
a MeCN–Et4NBF4 [188].
b MeCN–Bu4NBF4 [214].
c MeCN–Et4NBF4, −45°C [215].
d MeCN [211].
e V vs. Ag/AgCl, CF3SO3H,H2O [216].
f HF–BF3/BF4− (Ho ≈ −15.6).
g FSO3H–CH3COOH [188].
h MeCN–Et4NBF4 [106].
i MeCN–LiClO4 [105].
j MeCN–LiClO4 [217].
k V vs. a Ag wire, CF3COOH–Bu4NBF4 [212].
l MeCN–Bu4NBF4 [218].
m MeCN–LiClO4.
solvents such as CF3COOH [77,214,219], FSO3H [188,220–222], HF [223] and CF3SO3H (without
supporting electrolyte) [216]. In addition to the electrolyte systems included in Tables 23.1–23.3,
hydrocarbon oxidation has been realized in nitromethane, nitroethane, propylene carbonate, sulfo-
lane, and dichloromethane [224]. The observed potentials, invariably for irreversible oxidation, vary
in a reasonably predictable manner. Good correlations are often found with IP [210,212,225] and σ+
parameters [64,81,102].
There still remains some doubt about the first step of the overall reaction; however, in MeCN,
the final products are usually the N-alkylacetamides, for example, as shown in Equation 23.36. In
neutral solution, at extreme anodic potentials, it is difficult to decide between direct (Equations 23.1,
23.2, and/or 23.3) and indirect electron transfer (Equations 23.16, 23.17, and/or 23.18). For oxidation
in MeCN–BF4− solutions, the variation in potentials is best explained in terms of the direct mecha-
nism. An indirect oxidation mechanism involving hydrogen abstraction by electrogenerated nitrate
radical has recently been proposed for the electrolysis of linear alkanes in tert-BuOH/H2O mixtures
containing HNO3 and saturated with O2 [23].
In strongly acidic solution, it has been proposed that electron transfer is from the protonated
alkane [222]. The CV of alkanes in FSO3H was studied as a function of added AcOH (a base
under these conditions) and/or KFSO3; diffusion-controlled two-electron oxidations were found
and the current–potential curves shifted as base was added. Similar results for cyclohexane oxi-
dation in CF3COOH/FSO3H, CF3COOH/CH3SO3H, and CH2Cl2/FSO3H were also interpreted in
terms of initial protonation of the alkane [219]. The experimental basis for this conclusion has
been challenged. First, the addition of base-assisted alkane oxidation was claimed, which made
it unlikely that oxidation of protonated alkane was involved [220]. Second, for cyclopentene, no
oxidation peak could be observed for a solution of the alkene in FSO3H; 1H NMR spectroscopy
showed that in such solution the cyclopentene was substantially converted by proton addition
into the secondary carbenium ion [221]. It was suggested that this cation should be oxidized at
a potential similar to those claimed for the oxidation of protonated alkanes. The issue has been
confused further by the use of different reference electrodes and by variations in voltammograms
with temperature that are difficult to interpret unambiguously as well as nonelectrochemical
reactions of the alkanes in these highly acidic media [223]. However, there seems now to be
general agreement on a mechanism involving electron transfer from unprotonated RH involving
steps (23.1), (23.3), and (23.7).
V. CONcLUSiONS
In most cases, hydrocarbon oxidations occur via an initial one-electron transfer to the anode to form
a radical cation. The further fate of the radical cation depends on its reactivity toward other reagents
present. By suitable blocking of reactive sites and/or extensive delocalization of the positive charge,
the radical cation may be stable for long periods or at least during the time scale of slow sweep
voltammetry. In the majority of cases, the radical cation is very reactive as an electrophile, proton
donor, or electron acceptor and interacts with nucleophiles or bases present; cases are also known
where it can react as a radical, that is, in dimerization processes. The factors that govern the reactiv-
ity of radical cations are becoming increasingly better understood as a result of kinetic work using
conventional and voltammetric methods and also by theoretical studies.
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24 Activation of the Carbon–
Halogen Bond
Armando Gennaro, Abdirisak Ahmed Isse,
and Patrizia Romana Mussini
CONTENTS
I. Introduction .......................................................................................................................... 917
II. Homogeneous Catalysis ........................................................................................................920
A. Metal Complexes ..........................................................................................................920
1. Cobalt and Nickel Complexes with Schiff Base Ligands ......................................920
2. Oxidative Addition to Palladium and Nickel Complexes ......................................921
3. Copper Complexes ................................................................................................. 922
B. Organic Mediators ........................................................................................................ 923
III. Heterogeneous Electrocatalysis ............................................................................................924
A. Problem of the Reference, Noncatalytic Cathode Material ..........................................924
B. Electrocatalytic Materials for C–X Bond Cleavage: An Overview ..............................924
C. Electrocatalytic Cleavage of the C–X Bond on Silver ..................................................926
1. Ag…X Specific Affinity: Primacy from Compromise ...........................................926
2. Specific Adsorption of Halide Ions on Silver Surfaces .........................................926
3. Role of DET Mechanism on the Electrocatalytic Effect of Silver......................... 927
4. Electrocatalytic Effects of Silver: Role of Surface Morphology ........................... 932
5. Electrocatalytic Effects of Silver: The Role of the Supporting Electrolyte........... 933
6. Electrocatalytic Effects of Silver: The Role of the Solvent ................................... 934
D. Palladium, Copper, Gold .............................................................................................. 935
References ...................................................................................................................................... 936
I. INTRODUcTiON
The injection of one electron into an organic halide, RX, by reaction with an electron donor in
homogeneous conditions as well as by electrochemical or other means gives the fragmentation of
the molecule, by breaking the carbon–halogen σ bond. For this reason, such a process is named
dissociative electron transfer (DET). There are two possible reaction mechanisms for the reductive
cleavage of carbon–halogen bonds (see Chapter 14). Electron transfer (ET) and bond breaking can
occur either by a stepwise mechanism (Equations 24.1 and 24.2), with the intermediate formation of
a radical anion RX.−, or in a concerted way in which ET and bond fragmentation occur in a single
step (Equation 24.3):
RX + e − RX • − (24.1)
RX • − → R • + X − (24.2)
917
RX + e − → R • + X − (24.3)
R• + e− R − (24.4)
Depending on the value of the applied potential with respect to the reduction potential of R∙,
the latter may undergo typical radical reactions or be reduced to a carbanion R− (Equation 24.4).
In some cases, it is thus possible to trigger both a radical and an ionic chemistry [1].
In the case of the stepwise mechanism, two energy barriers must be taken into account:
the first one is related to the ET (Equation 24.1), whereas the second is due to the carbon–
halogen fragmentation (Equation 24.2), that is, the intramolecular ET from the orbital ini-
tially accommodating the incoming electron (generally a π* orbital) to the C–X σ* orbital
(see Figure 24.1). A voltammetric investigation on an extended series of aryl halides, afford-
ing a regular, well-defined sequence of increasingly more stable radical anion intermediates,
RX + e–
–
RX
ΔG≠c
ΔG≠e
(a)
Free energy
ΔG≠c
ΔG≠e
κ
(b)
ΔG≠c
ΔG≠e
(c)
Reaction coordinate
FiGURE 24.1 Potential energy diagrams for a DET to RX under kinetic control of (a) the bond cleavage
reaction, (b) both bond cleavage and ET reactions, and (c) ET. The subscripts e and c stand for the ET and
bond rupture reactions, respectively. (Reprinted from Isse, A.A. et al., J. Phys. Chem. C, 113, 14983, 2009.
With permission.)
Activation of the Carbon–Halogen Bond 919
has shown [2] that a kinetic parameter κ, linked to the peak potential variation with scan rate
in cyclic voltammetry (CV)
( RT /F )
κ = –1.15 (24.5)
(dEp /d log v)

and to the CV half-peak potential width
RT (24.6)
κ = 1.857
 F ( Ep / 2 − Ep ) 

is an efficient indicator of the relative kinetic influence of the aforementioned two barriers. In par-
ticular, the relative importance of the first, electrochemical barrier with respect to the second one
regularly decreases with increasing κ. When κ = 1, the DET process is kinetically controlled by the
bond rupture (Equation 24.2), the ET step (Equation 24.1) being relatively fast. Conversely, when
κ < 0.5, the ET step becomes the rate-determining step and κ coincides with the symmetry param-
eter of the energy barrier, α.
The radical may undergo very interesting reactions. For instance, it may react with suitable
nucleophiles present in the solution (Equation 24.7) to give nucleophilic substitution reactions [3]
or it may dimerize (Equation 24.8) and/or disproportionate (Equation 24.9). A very important pos-
sibility is the reaction with suitable olefins (Equation 24.10), which is the key step in living radical
polymerization processes such as atom transfer radical polymerization (ATRP) [4]:
R • + Nu − → RNu• − (24.7)
2R • → RR (24.8)
2R • → RH + R(−H) (24.9)
R • + C=C → R – C – C• (24.10)
Also, the reactivity of the carbanion, for example, with suitable electrophiles, may be exploited for the
development of important electrosynthetic pathways. In this connection, great interest is devoted to
reactions with carbon dioxide (Equation 24.11) to give carboxylate compounds (see Chapter 25) [5].
Of course, the possibility of father–son nucleophilic substitution (Equation 24.12), which is a parasitic
reaction leading to the dimer, must be considered and, if possible, avoided:
R − + CO2 → RCOO − (24.11)
R − + RX → RR + X − (24.12)
The electrochemical reduction of organic halides is an important topic, not only for the stimulating
and interesting mechanistic aspects, but also for the development of very useful electrosyntheses.
In this connection, however, two major drawbacks must be considered. The first is the highly
negative reduction potential required for the reduction of organic halides, which is an unfavorable
aspect, both for the energetic cost and for the greater probability of concomitant undesired reduc-
tion processes. As is well known, the reduction potential becomes more negative in the series RI,
RBr, RCl. The second problem is the possibility of parasitic reactions, in particular nucleophilic
substitution, which lower selectivity and yields of the desired products. Furthermore, parasitic reac-
tions are more important for the more easily reducible iodides, whereas chlorides are more resistant,
but also more difficult to be reduced.
For these reasons, much attention has been devoted to develop possible electrocatalytic processes
for the activation of carbon–halogen bonds.
II. HOMOGENEOUS CATALYSiS

One line of action for the activation of carbon–halogen bonds is the homogeneous catalysis, which
can involve an outer-sphere ET, between a suitable donor D.−, which can be produced by electro-
chemical reduction (Equation 24.13), and the halide (Equations 24.14 and 24.15):
D + e − D• − (24.13)
D• − + RX → R • + X − + D (24.14)
D• − + R • → R − + D (24.15)
where the donor D.− can be either a metal complex or a relatively stable organic radical anion.
However, in many cases, where the donor is a metal complex, Equation 24.14 involves an inner-
sphere ET (ISET), with specific chemical interactions between the donor and the halide.
A. METaL CoMpLEXES
Several transition metal complexes, mainly with phosphine or nitrogen-based ligands, have been
utilized for the activation of C–X bonds. The most widely investigated metals include Pd, Ni, Co,
and Cu. The reaction mechanisms are strongly influenced not only by the nature and the chemical
structure of the ligand but also by the chemical properties of the metal.
1. Cobalt and Nickel Complexes with Schiff Base Ligands

Cobalt complexes with tetradentate Schiff bases, such as salen (H2salen = N,N′-bis(salicylidene)-ethane-
1,2-diamine) and salophen (H2salophen = N,N′-bis(salicylidene)-phenylene-1,2-diamine) with different
substituent groups, have been largely studied, in particular as model compounds of vitamin B12 [6]:
O– –O
O– –O
N N
N N
salen salophen
In the case of Co complexes, CoII(L) is reduced to CoI(L)−, which reacts with RX to form an organo-
cobalt complex RCoIII(L); this Co(III) complex is reducible at more negative potentials to give
CoI(L)− and the radical R∙ [7–9]:
Co II (L) + e − Co I (L)− (24.16)
RX + Co I (L)− → RCo III (L) + X − (24.17)

RCo III (L) + e − RCo II (L)− (24.18)
RCo II (L)− → Co I (L)− + R • (24.19)
R • + e − [and/or Co I (L)− ] R − (24.20)

The reduction potential of RCoIII(L) is more negative than that of CoII(L), and it has been demonstrated
that RCoII(L)− undergoes a homolytic fragmentation, even if ER0 i / R is more positive than the standard
reduction potential of CoIII(L)R [9]. Reaction (24.17) has been shown to occur by an SN2 mechanism [10].
In contrast, a quite different behavior has been observed for Ni complexes with the same ligands.
In this case, in fact, NiII(L) is reduced to NiI(L)−, which reacts with RX via an ET mechanism [11–14]:
Ni II (L) + e − Ni I (L)− (24.21)
RX + Ni I (L)− → Ni II (L) + R • + X − (24.22)
R • + Ni I (L)− → Ni II (L) + R − (24.23)
2. Oxidative Addition to Palladium and Nickel Complexes

Palladium complexes are largely employed as catalysts in several important reactions (see Chapter
36), in particular those involving C–C bond formation [15], such as arylation of alkenes [16,17]
and alkynes [18,19], and cross-coupling reactions [20–26]. The key step of these reactions is
the oxidative addition of aryl halides to a Pd(0) complex, as first reported by Fitton [27,28] for
Pd0(PPh3)4 tetrakis(triphenylphosphine)palladium. This complex quantitatively dissociates to PPh3
and Pd0(PPh3)3 [29], but it has been demonstrated that the effective reactive species is Pd0(PPh3)2 in
equilibrium with Pd0(PPh3)3 [30,31]:
The kinetics of oxidative addition of aryl halides to Pd0(PPh3)2, quantified by k0a KL (Scheme
24.1), is quite insensitive to the solvent polarity [32]. This implies that the mechanism does not
involve an ET as in the case of Ni0(PEt3)4 [33].
Pd0(PPh3)2 can be formed by electrochemical reduction of PdIICl2(PPh3)2. It has been demon-
strated that the electrodic reduction of this precursor is really a bielectronic process that produces
the anionic Pd0(PPh3)2X−, which is the best catalyst, since its rate constant for the activation of RX
is higher than that of Pd0(PPh3)2 [34].
fast Pd0(PPh3)3 + PPh3

Pd0(PPh3)4
KL
Pd0(PPh3)3 Pd0(PPh3)2 + PPh3
k0aKL ArX k0a

= k app
[PPh3]
PPh3
X = I, Br Ar Pd X
PPh3
Rate = k0a[ArX][Pd0L2] = k0aKL[ArX][Pd0L3]/[L] = k app[ArX][Pd0L3]
SchEME 24.1 Mechanism of oxidative addition of ArX to Pd0 complex. (Reprinted from Jutand, A., Chem.
Rev., 108, 2300, 2008. With permission.)
Ni complexes can react by an ET mechanism [12–14,35–37] and also through oxidative addition
[38,39] and SN2 [40,41] mechanisms, depending on the nature of the ligand.
Square-planar Ni(I) complexes with Schiff base ligands [12–14] or tetraazamacrocycles [34–36]
have been reported to react with alkyl halides by a DET (Equation 24.22). These complexes act as
inner-sphere electron donors producing free alkyl radicals.
Instead, nickel complexes with labile ligands such as halides, phosphines, and bipyridines can
react through oxidative addition of RX. In the case of NiCl2(dppe) (dppe = PPh2–(CH2)2–PPh2),
electrochemical reduction of Ni(II) produces Ni0(dppe), by two successive ETs, with the expulsion
of the two chloride ions. Ni0(dppe) then reacts by oxidative addition with RX:
Ni IICl 2 (dppe) + e − → Ni ICl(dppe) + Cl − (24.24)

Ni ICl(dppe) + e − → Ni 0 (dppe) + Cl − (24.25)

Ni 0 (dppe) + RX → RNi II X(dppe) (24.26)

RNi II X(dppe) + e − → RNi I (dppe) + X − (24.27)

In the presence of a suitable electrophile such as CO2, RNiI(dppe) reacts to produce Ni0(dppe)
and RCO2− [38]. A similar reaction mechanism has been proposed also for nickel-bipyridine
complexes [39].
3. Copper Complexes
Copper complexes have been largely investigated in the framework of controlled/living radical
addition, cyclization, and polymerization reactions, in particular ATRP [4,42]. ATRP is, in fact, a
controlled/living radical polymerization [43,44] used extensively for the preparation of homopoly-
mers as well as random [45], gradient [46], block [47], graft [48], and dendritic polymers [49] with
well-defined structures. It is based on a reversible halogen atom transfer (Scheme 24.2) between an
alkyl halide RX (which can be either an initiator or a dormant macromolecular species Pm -X) and
a low oxidation state metal complex (activator), resulting in the formation of propagating radicals
(R• or Pm•) and the metal complex in a higher oxidation state (deactivator).
N N
N
N
N N
PMDETA Me6TREN
kp
kact + Monomer
MtzLn + R-X X-Mt(z + 1)Ln + R
kdeact
kact
KATRP = kt
kdeact
Bimolecular termination
SchEME 24.2 ATRP mechanism.

Although several transition metals have shown catalytic properties toward various organic halides
used as initiators [50,51], copper complexes with nitrogen ligands are the most used catalysts thanks
to their low cost and easy handling; typically, they are prepared in situ by adding the ligand to a
cuprous halide salt. The reaction between copper complex and RX has been shown to be an ISET,
which proceeds with a reasonable rate even if the standard potential of the CuII/CuI couple is much
more positive than that of RX. The ISET character of the reaction allows reduction of RX, but not
that of R•, which otherwise would terminate propagation [52,53]. Metallic copper has also been
used to activate alkyl halides toward formation of propagating radicals as well as regeneration of
active Cu(I) catalysts in ATRP [54–56].
Knowledge of Cu speciation in ATRP conditions [57] allowed the study of the kinetics of activa-
tion of RX by a CuI complex in MeCN in both the absence and presence of halide ions. For the sys-
tem CuI/L/X− (L = Me6TREN = tris(2-dimethylaminoethyl)amine), mainly composed of CuI(L)+,
XCuI(L) and CuIX2−, only CuI(L)+ was found to be an active catalyst reacting with RX [58].
In recent years, the ATRP process has seen a significant progress by the development of a method
known as activators regenerated by ET, which involves the use of reducing agents for the reduction
of air-stable deactivators to their respective activators in solution [59]. These systems are conducted
in the presence of excess reducing agent whereby the CuI/L/X− activator is continuously regener-
ated from CuIIX2/L, which accumulates as a by-product of unavoidable termination events. More
recently, a very innovative ATRP process (eATRP) based on electrochemical generation/regen-
eration of the activator complex has been developed [60–62]. In this process, air-stable CuIIBr2/
Me6TREN is electrochemically reduced to CuIBr/Me6TREN to invoke or trigger polymerization.
The feasibility of an electrochemical switch to modulate copper oxidation states in situ, and thereby
activate or deactivate polymerization, was demonstrated.
B. OrGaNIC MEDIaTorS
Aromatic radical anions (A• –) can act as outer-sphere electron donors toward organic halides [63].
In the case of an alkyl halide, RX, the principal steps of the reaction can be written as follows:
A + e − A• − (24.28)
A • − + RX → R • + X − + A (24.29)
A• − + R• → R − + A (24.30)
A• − + R• → A − R − (24.31)
This process is commonly known as homogeneous redox catalysis. It involves ET to RX, which
undergoes C–X bond rupture, followed by a second ET to the ensuing radical R• and/or radical–
radical coupling between A• – and R•. Some advantages of this method of C–X activation over metal
catalysis include the ease of generation, for example, by electroreduction, of A• – from stable aro-
matic or heteroaromatic compounds; the low propensity of A• – to bond formation owing to the
delocalization of the odd electron; the well-defined low self-exchange reorganization energy of the
A/A• – couple [64], which makes easy analysis of the dynamics of reaction (24.29); and the nonspeci-
ficity of the reaction for different classes of RX.
Activation of C–X bonds by electrogenerated aromatic radical anions has been used in differ-
ent synthetic applications [13,65–67]. The homogeneous redox catalysis approach has also been
widely used for measuring rate constants and theoretical analysis of DET processes [68]. Another
important application of the homogeneous reduction of alkyl halides by A• – is the determination of
the reduction potentials of short-lived alkyl radicals, according to a method developed by Lund and
coworkers [69,70] on the basis of the competition between reactions (24.30) and (24.31). This method
has been successfully used for the estimation of standard reduction potentials of a large variety of
alkyl radicals [71–74].
III. HETEROGENEOUS ELEcTROcATALYSiS

A. ProbLEM oF THE REFErENCE, NoNCaTaLYTIC CaTHoDE MaTErIaL
In the last decade, investigations on the electrocatalytic cleavage of carbon–halogen bonds have
usually dealt with electrocatalytic effects in terms of differences between reduction peak potentials
obtained in the same conditions on the electrode surface tested as a catalytic material and on a suit-
able electrode, acting as an inert (or noncatalytic) electron source ensuring outer-sphere ET. The
catalytic effect is therefore defined as
Catalytic effect = Ep,catalytic − Ep,noncatalytic (24.32)

This unofficial convention has been proposed to provide a sort of normalization with respect to the
substrate intrinsic reactivity, which is widely modulated by the molecular structure [75].
Glassy carbon (GC), boron-doped diamond (BDD), and fluorinated boron-doped diamond
(FBDD) have been tested for this role [76]. The reduction potential sequence of different model
organic halides on the three carbon-based electrodes is GC > BDD > FBDD, actually a sequence
of decreasing Lewis acidity of the reacting surfaces, considering that the GC surface is partially
functionalized with hydroxyl and carboxyl groups [77], while BDD is predominantly hydrogen-
terminated [78], and FBDD features a consistent number of fluoride atoms on its surface, result-
ing in an even more hydrophobic character [79], which however could exert a repulsive effect on
the approaching halide leaving group of the reacting molecule. Accordingly, BDD would appear
the most appropriate inert reference among the three surfaces tested. However, it is expensive and
difficultly available, particularly in an electrode setup suitable for working in nonaqueous solvents;
moreover, fundamental studies on organohalide electrochemical reduction in noncatalytic condi-
tions have mostly been carried out on the more popular GC electrode; thus, the latter has been com-
monly adopted as the reference for evaluating catalytic effects in the same process.
Care should, however, be exercised in the choice of GC electrodes when an accurate analysis of
DET dynamics is desired since their electrochemical performance is strongly influenced by their
surface microstructure [80,81]. In particular, edge-plane sites and defects are prone to oxidation
(also depending on the adopted method of surface preparation [77]), and therefore, several oxygen-
containing functional groups, mainly carbonyl, hydroxyl, and carboxyl moieties, are present on the
electrode surface. This significantly affects the reduction peak potential of RX, an increase of the
oxygen-to-carbon ratio apparently causing a positive shift of Ep [82]. This catalytic effect reproduc-
ibly depends on both GC electrode surface composition and DET mechanism, regularly increasing
with increasing importance of the initial ET step in the overall kinetics of the process [82]. The
highest observed peak potential difference between differently activated GC surfaces is on the order
of 0.1 V, found for some alkyl halides undergoing a concerted DET [82].
B. ELECTroCaTaLYTIC MaTErIaLS For C–X BoND CLEaVaGE: AN OVErVIEw

The use of electrocatalytic electrode surfaces is a convenient approach to the electrochemical
activation of carbon–halogen bonds in mild conditions. All metals having specific halide affinity
could potentially possess electrocatalytic activity for C–X bond cleavage; comparative investiga-
tions [76,83–89] encompassing a wide range of metals also in terms of electrocatalytic scale [76] or
volcano plot [83] are available in the literature.
The earliest studies on the electrocatalytic reduction of organic halides were rather involuntary
(sometimes even unconscious), mostly consisting in organohalide reactivity studies using polarogra-
phy, a ubiquitous voltammetric technique in the 1970s–1980s, implying to work on the noninnocent
mercury electrode; actually halide adsorption phenomena and intermediate formation of organo-
mercurials were found to play an important role in the process (see Chapter 25). Also, the first
approach to silver in the 1970s was fortuitous, consisting in clinical observation of the anomalously
high response of an oxygen Clark-type sensor in the presence of anesthetic halothane [90], an obser-
vation slowly exploited and rationalized in the following two decades [91–94]. Industrial applicative
screenings also involved some early testing of catalytic properties of materials such as Pd and Ag
[95], with some patents being deposited in the 1980s [96–100].
From the 1990s, synthetic [5,89,101–112] and, above all, environmental issues [87,88,113–126]
have prompted remarkable acceleration, rationalization, and refinement in this research field. In par-
ticular, Hg was put aside because of environmental concerns and operating problems together with
its only moderate catalytic effects [76,83], and investigations were concentrated on a series of solid
electrodes that are significantly more catalytic than Hg, in particular Ag, which was found to possess
a very high, reproducible and rationalizable catalytic activity for a very wide range of organic chlo-
rides, bromides, and iodides [75,127,128], including mono- and polyhaloalkanes [75,126,129–132]
as well as aryl [2,125,128,129,133], benzyl [1,134,135], glycosyl [106], and heteroaryl [108,128,136]
halides. Silver nanoparticles [118,137] and alloys [115] have also been considered. Pd, both as such
and as palladiated (even with nanoparticle Pd) surfaces of different nonmetals and metals, like GC,
Ag, Cu, Ni, Pt, and Au [138–155], and Cu [86,89,121–123,156–158], have also been found to pos-
sess good electrocatalytic properties for the reduction of many classes of organic halides. Au is also
sometimes considered [89,124,136,159–162]. It is important to stress, however, that although the
catalytic activity of this metal for C–X cleavage is intrinsically higher than that of Ag [163,164], it is
practically hampered by the huge negative charge density of the metal at the operating potentials (as
a consequence of its more positive pzc) [165] unless some auxiliary condition prevails, for example,
the availability of protons [159] or the presence of anchoring groups [136].
In recent years, the increasing interest of the process prompted detailed mechanistic investiga-
tions, particularly in the case of silver, on account of its remarkable and reproducible catalytic
activity and of the availability of a wide series of authoritative studies on specific halide adsorption.
Such investigations focused on different factors capable of modulating the process as, for instance,
the reactant molecular structure (organic moiety and halide leaving group) [2,128,129], morphol-
ogy [166], and state of cleanliness [127] of the electrode surface, adsorption phenomena involv-
ing the reagents and/or products [2,128,134,136,167–169], reaction medium (solvent and electrolyte)
[120,135,159,170,171], and the presence of adsorption auxiliaries [136]. Exhaustive mechanistic
rationalizations have been so far achieved for the electrocatalytic reduction of aryl [2] and benzyl
halides [1,134,135,172,173], in the latter case also with the support of a combined computational and
SERS investigation [172,173].
From the preparative point of view, the milder electrode potential and the involvement of the
catalytic metal surface in the formation of reaction intermediates can promote intermolecular radi-
cal reaction pathways, affording even difficult dimerizations [1,105,106,110]. This radical chem-
istry also affords addition to suitable coadsorbed intermediates, as in the case of α-C- [101] and
O-glycoside [102–104] synthesis from the catalytic reduction of α-acetobromoglucose. It is interest-
ing to note that the same process at noncatalytic electrodes evolves through intramolecular reaction
pathways hinging on a carbanion intermediate [174]. Instead, aryl halide reductions usually result in
simple hydrogenation of the halide position [113].
The electrocatalytic properties of silver have already been applied (a) in several electrosynthetic
processes, in particular the electrosynthesis of fine chemicals and pharmaceutical products by
electrocarboxylation of the corresponding halides [5,107,109,111,124] achieving, in some cases, a
first scale-up with very encouraging results [112], (b) for the treatment of environmentally relevant
organic halide pollutants [87,88,113–121,125,126,155], and (c) for organic halide monitoring [85].
C. ELECTroCaTaLYTIC CLEaVaGE oF THE C–X BoND oN SILVEr

1. Ag…X Specific Affinity: Primacy from Compromise
Quantum calculations in the vacuum on halide adsorption on the group 11 metals Cu, Ag, and
Au point out that Au has the strongest affinity for X−, the general trend of halide affinity for all
metals being I− < Br − < Cl− < F−, which is in disagreement with experimental results in solution
[163]. DFT studies on halide interactions in the vacuum with three much more different metals,
namely, Hg, Ag, and Pt, result in a metal sequence consistent with the experimental one (Ag >
Hg > Pt) but, again, in the I− < Br − < Cl− < F− reversed halogen sequence; the disagreement with
the experimental evidence is convincingly justified by the authors in terms of solvation energy
contributions [164].
Analysis of halide-specific adsorption on metals in water in terms of competition between metal–
water interactions (following the sequence Bi, Hg, Pb < Au(111) < Cd < Ag(111) < Ga < Cu(111))
and metal–halide interactions (following the sequence Bi, Pb < Hg < Cd, Ga < Cu(111) < Ag(111)
< Au(111)) shows that the degree of surface coverage by X− replacing water molecules at the pzc
increases in the order [175,176]
Bi, Pb < Hg < Cd, Ga < Cu(111) < Ag(111) < Au(111)

However, the catalytic activity of Au toward RX reduction is in practice greatly impaired [165] by
its pzc (−0.05 V vs. SCE in NaClO4 aqueous solution [177] to be compared with −0.716 V vs. NHE
[178] or −0.96 V vs. SCE for Ag), which is much more positive than the typical reduction potentials
of the C–X bond. Although specific halide adsorption can take place even at potentials negative to
the pzc, that is, with a negatively charged surface [179], increasingly negative charge densities do
hamper specific interactions. Now, in the reduction potential range of most organic halides, silver is
remarkably less negatively charged than gold. Accordingly, Ag is much more electrocatalytic than
Au for this process in its usual working conditions.
2. Specific Adsorption of Halide Ions on Silver Surfaces

Detailed studies on specific halide anion adsorption onto silver are available, most of them con-
cerning investigations on monocrystalline Ag in water based on capacitance and zero-charge
potential measurements [180–186], theoretical computations [187], computer simulations [188],
and various other techniques, including impedance [189], chronocoulometry [190,191], electro-
chemical STM [192], surface X-ray scattering (SXS) [193], and surface electron spectroscopies
(LEED, RHEED, and AES) [194]. These investigations show that specific adsorption of inorganic
halides onto silver is so strong as to hold until threshold potentials negative with respect to the
surface pzc, that is, about −0.8 V (SCE) for chlorides, −1.0 V (SCE) for bromides, and −1.2 V
(SCE) for iodides. Moreover, the aforementioned studies very finely evidence a sequence of pro-
gressive structural transitions of the adsorbed halide anion monolayers with increasingly negative
potential [190–192].
Recently, such investigations have been extended to controlled-surface polycrystalline silver
[166–168]. The adsorption CV patterns observed on polycrystalline Ag, obtained by an appropriate
electrodeposition protocol [169], are reproducible and intermediate with respect to the adsorption
characteristics of the single crystals. Capacitive experiments showed the polycrystalline pzc to
nearly coincide with that of the more open monocrystalline surface (110) [169]. More recently, such
studies were extended to nonaqueous solvents such as acetonitrile [166,195], propylene carbonate
[195], and dimethylformamide [195]), combining differential capacity and impedance experiments
with an indirect voltammetric method based on the monitoring of the negative shift of the reduc-
tion peak potential of a “probe” organic halide molecule induced by progressive additions of halide
anions, resulting in increasing adsorption competition [166]. Chloride, bromide, and iodide ions are
specifically adsorbed onto polycrystalline silver electrodes in the three organic solvents studied, in
the same Cl− < Br− < I− sequence as in water; threshold potentials for X− desorption in acetonitrile
are ∼−1.20, −1.32, −1.43 V versus SCE, respectively [166]. The adsorption strength increases with
decreasing solvent ability to coordinate the halide anions [185].
3. Role of DET Mechanism on the Electrocatalytic Effect of Silver

The electrocatalytic activity of silver toward the reduction of organic halides is strongly
affected by the DET mechanism [2,86,128,129]. In the case of concerted DET, which is usu-
ally followed by aliphatic and benzyl halides, remarkable electrocatalysis is always displayed,
independently of the nature of the halogen atom. It can be assumed [86] that an activated
complex characterized by strong interactions between the reacting C–X bond and the electrode
surface is formed; as a result, the intrinsic activation energy barrier (∆G0≠ = (λ 0 + BDE)/4,
with BDE = bond dissociation energy and λ 0 = solvent reorganization energy) is significantly
lowered. This decrease of ΔG ≠ results in a decrease in the required overpotential for the pro-
cess and hence in a positive shift of E p with respect to the value observed on a noncatalytic
electrode such as GC.
The extent of catalysis in concerted DETs is also strongly affected by possible specific
adsorption of the electrogenerated halide ion and/or the starting organic halide [134] if the
reduction potential at Ag is not so negative that electrostatic repulsions prevent X− adsorption
(see Section III.C.2). This specific adsorption effect decreases in the sequence I− > Br − > Cl−.
Adsorption processes also result in alterations, sometimes conspicuous, of the reduction peak
morphology with respect to the canonical diffusive feature.
The case of benzyl halides PhCH2X provides a good example of the implications of reactant
and product-specific adsorption as a function of the reduction potential (Figure 24.2). In the
chloride case, the reduction potential is far beyond the negative threshold for Cl− adsorption;
PhCH2Cl
0
–20
–40 0.2 V/s
–60
0
PhCH2Br
I (μA)
–20
0.1 V/s
–40
0 PhCH2I
–10
–20
0.1 V/s
–30
–2.0 –1.5 –1.0 –0.5
E (V vs. SCE)
FiGURE 24.2 CV patterns for the reduction of benzyl halides on Ag in MeCN. (Adapted from Isse, A.A.
et al., Electrochim. Acta, 51, 4956, 2006. With permission.)
consistently, the molecule exhibits on Ag a single diffusive two-electron reduction peak (indicat-
ing that the radical undergoes easy reduction to anion at the same potential at which it is formed),
although at a considerably less negative potential than at GC. A closer examination reveals that
some slow adsorption of the reactant PhCH2X molecule does take place, although so weak that
dissolved and adsorbed reactant molecules are reduced virtually at the same potential [134]. Very
recently, a combined CV, SERS, and DFT investigation [172,173] has provided some insight into
the process, confirming preadsorption of benzyl chloride, which after ET evolves into a benzyl
radical bound onto the Ag surface; the latter is then easily reduced into a benzyl-silver anionic
adduct that eventually dissociates.
In the case of PhCH2Br, the DET process takes place within the potential range for specific Br−
adsorption. At slow scan rates, the molecules exhibit two irreversible reduction peaks attributed to
the reduction of PhCH2Br (first peak) and PhCH2•. The sharpness of the first peak indicates specific
adsorption of one or both the reaction products. This peak gradually splits into two separate peaks
as scan rate is increased. Addition of Br− in the reaction medium also brings about the same peak
splitting even at low scan rates. These observations have been rationalized by considering the rate
and degree of adsorption of Br− during the voltammetric scan [134].
In the iodide case, the DET takes place well before the threshold potential for iodide anion
adsorption, and the adsorption of the PhCH2I reactant molecule at the Ag surface is so strong that
reduction of adsorbed PhCH2I is observed as a sharp post peak at a potential about 150 mV more
negative with respect to the diffusive one (Figure 24.2).
The combination of all the aforementioned effects results in a scale of catalytic effects (anodic
shift of Ep: 0.45, 0.72, and 0.48 V for X = Cl, Br, and I, respectively), which is at variance with the
familiar silver/halide ion interaction sequence in solution, that is, I− > Br− > Cl−. It is also worth-
while noticing that in both cases in which significant halide anion adsorption can take place, that is,
Br and I, a neat separation is observed between the potentials of the first and second electron uptake;
this allows triggering selectively either radical or carbanion chemistry, as confirmed by preparative
experiments [1].
The stepwise DET mechanism typically applies to aryl halides as a consequence of their abil-
ity to stabilize the incoming negative charge in a low-lying π* orbital delocalized on the aromatic
system, so the ensuing radical anion energy curve intersects those of the reagent and product. This
charge delocalization implies a much lower polarization degree and a higher BDE of the carbon
halide bond to be cleaved with respect to concerted DET cases. Aromatic bromides show catalytic
effects on Ag possibly arising from interactions between the electrode and various species, mainly
ArBr • − and Br−, involved in the DET. These catalytic effects have recently been shown [2] to be
regularly linked to the degree of negative charge localization on the halide atom in ArBr • −, sug-
gesting that charge localization promotes specific interaction of the intermediate with the silver
surface. Thus, for example, in the limiting case represented by 4-nitro-halobenzene, where the ET
is circumscribed to the nitro group and therefore the negative charge in the radical anion is local-
ized far away from the C–X bond, no electrocatalysis is displayed by Ag, independently of the type
of the halogen atom [128].
Total absence of catalytic effects was also observed in the reduction of all aryl chlorides, at
least in aprotic organic solvents [128,129]. This can be justified in terms of both the high value of
the C–Cl BDE in aryl chlorides (396 kJ mol−1 for chlorobenzene) [196] and the negligible polariza-
tion of the C–Cl bond in the aryl radical anion intermediate ArX• − [197]. Therefore, with organic
chlorides in aprotic solvents, electrocatalysis appears to be clearly discriminated by the DET mech-
anism, being remarkable in all concerted DET cases and absent in all stepwise ones [129].
As compared to aryl chlorides, aryl bromides have lower BDEs and give rise to radical anions
with higher C–X bond polarization [197]. Accordingly, when dealing with a bromide leaving group,
significant electrocatalytic effects of Ag are observed, regardless of the mechanism of DET. Such
effects regularly depend on the molecular structure, and a rationalization has been recently achieved
[2] by considering a systematic aryl bromide series with different substituents
Br
R Br
9
R=H 1
C2H5 2 Br
OCH3 3
10
C6H5 4
COC6H5 5
Br
COCH3 6
CN 7 11
CO2C2H5 8
appropriately selected so as to modulate the kinetics of decomposition of the intermediate radical

anion ArBr • −, from the limiting case of a process controlled by the first heterogeneous ET, as in the
case of bromobenzene, to the other extreme, in which the process is controlled by the intramolecular
ET, that is, the dehalogenation reaction, as in the case of bromoanthracene.
These different kinetic regimes can be well described by a kinetic parameter κ (see Section I).
As shown in Figure 24.3a, a plot of κ as a function of E p exhibits for both Ag and GC a linear
increase of κ with increasing peak potential, which is increasing the electron-withdrawing abil-
ity of the substituent, or the number of fused aromatic rings stabilizes ArBr • − and consequently
shifts the kinetic regime of the DET process toward kinetic control by the bond rupture reac-
tion. We can see, however, a quite different slope for the two plots, which reflects a remarkable
difference in the electrocatalytic effect played by Ag, which, in turn, is well correlated to κ
(Figure 24.3b).
The correlation between inductive effects in the aryl bromide molecular structure and Ag elec-
trocatalytic effects is evidenced in the plots of Ep values at both GC and Ag electrodes versus
Hammett substituent constants reported in Figure 24.4. As can be seen, both electrodes show the
same trend; that is, Ep becomes more positive upon increasing the electron-withdrawing power
of the substituent. For both electrodes, the dependence of Ep on σ− can be fit to a linear equation
of the classical form. It is worth noting that reduction of the aromatic bromides at GC is ca. four
times more sensitive to the substituents with respect to Ag since at the catalytic Ag electrode the
1.0
1.0 5 2
3
6 10 0.8 1
0.8
EpAg – EpGC (V )
4 9 11
7 0.6
0.6 3 6 75 11
8 4
κ
2 8
11 0.4 9
0.4 1 1 9 10
7 10
4 0.2
0.2 3 2 5
6
0.0
–2.4 –2.0 –1.6 0.4 0.6 0.8 1.0
(a) Ep (V) vs. SCE (b) κ
FiGURE 24.3 Correlation between the kinetic parameter κ and (a) the reduction peak potentials on noncata-
lytic GC (squares) and catalytic Ag (circles) (Reprinted from Isse, A.A. et al., J. Phys. Chem. C, 113, 14983,
2009. With permission.) and (b) the catalytic effects of Ag, for the aryl bromide series.
5 7
4 8 5
–1.6
3 2 6
1 6
Ep (V) vs. SCE

–2.0 7
8
4
–2.4
3 2
1
–2.8
2 1
0.8 3
p – E p (V)
4
GC
0.4 8 7
E Ag
6
0.0 5
0.0 0.4 0.8

σ–
FiGURE 24.4 Reduction peak potentials measured on noncatalytic GC (circles) and catalytic Ag (triangles)
and catalytic effects of Ag (squares) plotted versus σ− Hammett parameters, for the aryl bromide series.
(Reprinted from Isse, A.A. et al., J. Phys. Chem. C, 113, 14983, 2009. With permission.)
molecular structure has a quite limited effect on Ep. It appears that the presence of the catalytic
surface shifts, at least partially, the site of the negative charge in the 1e− reduced species. Probably
now the charge is mainly located at the bromine atom so that the electron-withdrawing power of the
substituent becomes less important.
Consistent with such observations, a reduction mechanism has been proposed in which, as
illustrated in Scheme 24.3, all reactions occur on the electrode surface. As a consequence, the
potential energy profiles of reagents, intermediates, and products at the catalytic surface are low-
ered with respect to the noncatalytic electrode (Figure 24.5). This is mainly due to adsorption,
especially in the case of ArBr • − and the reduction products Ar • and Br−, which strongly interact
with the Ag surface, whereas for the starting reagents (ArBr + e−), their potential energy profile
is lowered mainly because now the process occurs at less negative potentials. The combination
of the decrease of the Gibbs free energy of the reaction and the enhancement of the cleavage rate
of the radical anion results in a positive shift of E p at the catalytic electrode with respect to the
noncatalytic one.
In some cases, there is a change of mechanism from stepwise to concerted on passing from the
noncatalytic electrode to the catalytic one (Figure 24.6). As before, the potential energy profiles of
the reagents, intermediates, and products of the catalytic process are lowered by surface interactions
and by the increase of the reduction potential at the catalytic electrode. It is worth noting that the
change of DET mechanism from stepwise at GC to concerted at Ag causes a drastic change of both
the standard free energy, ΔrG 0, and the activation free energy, ΔG ≠, of the ET.
0 0
It is well recognized that Estepwise is considerably more negative than Econcerted , even without
taking into account adsorption phenomena, which would shift the latter to more positive values
because of the preferential adsorption of the products with respect to the reagents. On the other
hand, since the concerted process involves rupture of a chemical bond, its activation free energy is
often greater than that of the stepwise process. Catalysis arises from a combination of these kinetic
and thermodynamic effects, both related to the ET to ArBr. The process at Ag has a remarkable
IHP OHP
RBrads
+e–
+e– –
RBr ads
Ag electrode
Rads + Br–ads
+e–
Br–ads+ R–
R– + Br–
SchEME 24.3 Reduction mechanism of aryl bromides at catalytic electrodes. (Reprinted from Isse, A.A.
et al., J. Phys. Chem. C, 113, 14983, 2009. With permission.)
–
RX
RX + e–
Free energy
ΔrGθ –
RXads
ΔrGθ R + X–
RXads + e–
Rads + X–ads
Reaction coordinate
FiGURE 24.5 Potential energy profiles of reagents, intermediates, and products for aryl bromide reduction
at the noncatalytic (full lines) and catalytic surface (dashed lines). (Reprinted from Isse, A.A. et al., J. Phys.
Chem. C, 113, 14983, 2009. With permission.)
thermodynamic advantage over ET at a noncatalytic electrode but loses something from the kinetic
standpoint. The overall result, however, favors the catalytic surface with a net positive shift of the
reduction potential.
A high electrocatalytic effect has also been observed for p-iodotoluene [128]. In this case, there
is undoubtedly an important thermodynamic contribution due to the specific adsorption of I− at
Ag. On the other hand, in this case even at the noncatalytic electrode, the DET mechanism is in a
–
RX
RX + e–
–Fη
ΔrGo
–
Free energy RX ads
–Fη
R + X–
RXads + e– ΔrGo
Rads + X–ads
Reaction coordinate
FiGURE 24.6 Potential energy profiles of reagents, intermediates, and products for aryl bromide reduction
at the noncatalytic (thin lines) and catalytic surface (thick lines), in the case of DET mechanism change from
stepwise to concerted. (Reprinted from Isse, A.A. et al., J. Phys. Chem. C, 113, 14983, 2009. With permission.)
borderline situation [198] and it is highly likely to shift to the concerted limiting situation as the
driving force of the reaction decreases owing to the electrocatalytic effect of Ag; this appears con-
sistent with the peculiar peak sharpness observed at Ag, accounting for a determining adsorption
process, which had been so far observed only for halides undergoing reduction according to the
concerted mechanism.
As discussed before, the nature of the halogen atom and the extent of charge localization on the
C–X bond modulate the ability of the incipient leaving group to interact with the silver surface at a
given potential, determining the extent of the catalytic effects.
A further molecular feature that can enhance such interactions is the presence of adsorption
auxiliary groups, having themselves specific affinity for the surface but undergoing no ET pro-
cesses at the operating potential and therefore acting as anchoring groups, keeping the reacting
C–X bond close to the surface. An example is the presence of a sulfur atom: Ag exhibits a higher
catalytic activity for 2-bromothiophene than for bromobenzene, although both aryl halides reduce
at similar potentials with a similar stepwise mechanism [136]. This finer molecular effect is some-
how overshadowed by the high catalytic activity of silver but becomes much more relevant in the
case of Au. This metal has for bromobenzene a lower and less reproducible catalytic effect than Ag
on account of the repulsive effect of its very negative surface charge in the working potential range
(see Section III.C.1). However, it approaches Ag activity in the case of 2-bromothiophene, where
the anchoring S group is adjacent to the Br group to be cleaved. The beneficial anchoring effect is
lower when it has to be shared between two Br leaving groups adjacent to the S group and becomes
negligible in the case of a bromide leaving group in the 3-position [136].
4. Electrocatalytic Effects of Silver: Role of Surface Morphology

The surface morphology modulates the electrocatalytic effects of silver for organic halide reduction,
although to a moderate extent. An exhaustive comparative investigation has been carried out on
the reduction of several model halides on Ag(111), (110), and (100) monocrystals and on controlled
polycrystalline silver surfaces of increasing roughness, in acetonitrile + 0.1 M tetraethylammonium
perchlorate [166]. The reduction potentials of the alkyl, glycosyl, and benzyl halides are signifi-
cantly shifted in the positive direction with increasing surface roughness (for polycrystals) or atomic
densities and/or surface faceting (for monocrystals, indicating the following trend for the catalytic
properties of the metal: 110 < 100 < 111). The Ep span for a given molecule on the different surfaces
tested appears to be larger for molecular structures with higher electrocatalytic effects on silver; in
particular, the maximum, 0.12 V, was found for acetobromoglucose.
Evaluation of the effective surface area of the aforementioned polycrystalline Ag electrodes with
respect to GC is important for the elucidation of the reaction mechanism in the catalytic case. To
achieve it, overcoming the problem of the mechanism change on the catalytic surface, a procedure has
been proposed [199], based on the comparative analysis of the CV features of a suitable set of probe
molecules on both the catalytic and noncatalytic electrodes and evidencing inter alia the different
surface perspectives of molecules reacting at the IHP rather than at the OHP.
Of course, all the aforementioned observations hold for clean surfaces; filming by sparingly
s oluble reaction products or specifically adsorbed ions from the supporting electrolyte can result in
signal irreproducibility and in significantly hindering the surface catalytic properties. In situ surface
regeneration can be sometimes achieved by appropriate potential sweeps [106].
In view of industrial applications, some silver alloys were investigated in comparison to bulk
silver to improve lifetime and shelf life of the electrode material [115]; all the tested alloys were
found to be less electrocatalytic than silver, but some AgBi and AgSn alloys can be considered
promising alternatives. The electrocatalytic activity of microsized silver powders supported on cav-
ity microelectrodes was also investigated [200]. These supports are quite attractive because of their
low impact on the supported materials (they require neither special manipulations nor sticking
agents) and of the offered possibility of quick and reliable renovation of the electrode surface. These
innovative Ag electrodes gave better performances than Ag electrodes prepared according to the
conventional electrodeposition procedures, in terms of improvement of the electrocatalytic activity,
insignificance of ohmic drop and double-layer capacitance in the voltammetric response, and the
simplicity offered by the experimental procedure for renovating the electrode material and surface.
More recently, several research groups tested the electrocatalytic activity of Ag nanoparticles
[86,137]. Stable Ag nanoclusters were deposited on GC by a single potential pulse method in CH3CN
+ 0.1 M LiClO4 containing millimolar amounts of AgClO4. The particles, obtained by applying a
pulse from rest potential to −0.4 V versus Ag|Ag+, are spherical in shape and are uniformly dis-
tributed over the GC surface with areal density number and particle size depending on applied
d eposition potential and deposition time, respectively. These Ag nanoclusters show comparable
activity to that of the bulk metal for a wide range of compounds. Ag/GC electrodes of suitable
active surface can be employed in macroscale electrolyses for important catalytic electrosyntheses.
For example, electrocatalytic reduction of benzyl chloride gives satisfactory yields of toluene or
phenylacetic acid, the latter being the main product obtained in electrocarboxylation conditions,
that is, in CO2-saturated CH3CN. It is important to note that the performance of the Ag-modified
GC electrode described here is comparable to that of bulk silver, but the catalyst metal load is very
different, only a few micrograms of Ag per cm2 being present in the former. This is a very important
economic aspect, which should be taken into consideration in large-scale electrosynthesis processes.
In the same perspective, a study has been carried out [118] on silver nanoparticles (Ag_NP), syn-
thesized by chemical reduction of an aqueous silver salt in the presence of six different stabilizing
agents and supported on carbon powder (10% loading) for further characterization and use, and gas-
diffusion electrodes (GDEs) based on the most promising Ag_NP composite have been successfully
tested in an electrolytic process for the progressive conversion of gaseous trichloromethane to less
chlorinated compounds and ultimately to methane.
5. Electrocatalytic Effects of Silver: The Role of the Supporting Electrolyte

a. Nonspecifically Adsorbed Anions
When both the supporting electrolyte ions have no specific affinity for the catalytic surface,
d ouble-layer effects should be determined by the supporting electrolyte cation, usually a quaternary
ammonium ion when operating in nonaqueous solvents, which must be located on the OHP accord-
ing to the negative operating potentials with respect to the pzc. A comparative rationalization has
very recently been proposed on the effect of quaternary ammonium supporting electrolyte cations
(with C2, C3, C4, C6, and C8 alkyl chains), at constant counter anion, in aryl halide reduction on GC
and silver electrodes [171].
On both electrode surfaces, increasing the electrolyte cation length results in a regularly increas-
ing hindering effect, evident from both the negative potential shift and the widening of the reduction
peaks. This effect, which is significantly higher on Ag than on GC in spite of the less extreme oper-
ating potentials, is remarkably dependent on the aryl halide molecular structure, regularly increas-
ing with decreasing κ, that is, with the ET barrier becoming increasingly more determining with
respect to the chemical one.
In the case of the noncatalytic GC, the effect can be rationalized in terms of increasing double-
layer thickness, resulting in an increased hindrance of the electron tunneling between electrode and
molecule, an effect becoming more and more determining with decreasing κ (which appears to be
related to the β parameter in the electron tunneling probability equation), whereas in the catalytic
Ag case, it has been proposed to depend on the increasingly smaller effective potential difference
available to the molecule reacting close to the electrode when the double-layer thickness increases
as a consequence of increasing the bulkiness of TAA+ cations [171].
b. Specifically Adsorbed Anions

If supporting electrolytes containing halide anions are used, the latter can be specifically adsorbed
on silver in a significant portion of the usual operating potential range for organic halide reductions,
as discussed previously (see Section III.C.2) [127,166,168,195]. This results in a screening effect
evidenced by a significant shift of the peak potential in the negative direction with respect to a given
nonspecifically interacting medium, corresponding to an additional term in the activation energy
accounting for halide anion desorption and increasing with both the halide anion affinity for silver
(Cl− < Br− < I−) and the halide concentration.
In experiments done with increasing I− concentrations, strikingly linear Ep versus log cI− char-
acteristics are obtained, both on poly- and monocrystalline surfaces, at least in the case of the
strongly adsorbed iodide. Such linearity and the relevant slopes (in terms of both negative sign and
quasi-Nernstian values) are consistent with classic equations (Frumkin, Esin–Markov) describing
simple electrochemical adsorption/desorption equilibria under the condition of constant surface
coverage or charge. This indicates that the halide desorption step proves determining on the overall
process, so the faradaic Ep values at each cI− can be regarded as indicators of a particular surface
state, allowing the faradaic process to take place. In the case of the less strongly adsorbed chlorides
and bromides, the same considerations apply, not surprisingly, only to a restricted, relatively high
concentration range, below which such halide anions prove nearly ineffective.
Another key feature of the Ep versus cX− characteristics is that all of them tend to an asymptote
for concentrations as high as 0.1 M, which is perfectly reasonable in dealing with a surface phenom-
enon, that is, implying that a saturation condition must be reached. Accordingly, the maximum shift
of ΔEp increases in the Cl− < Br− < I− sequence (50, 130, and 250 mV, respectively). They can be
correlated to the logarithms of their respective equilibrium constants for chemical adsorption onto
silver and exhibit a strikingly linear correlation with the logarithms of the solubility products of the
corresponding silver halides. This implies, reasonably, that the halide adsorption constants on silver
are proportional to the solubility constants of the corresponding silver halide.
6. Electrocatalytic Effects of Silver: The Role of the Solvent

A recent systematic study shows that the catalytic effects of Ag for organic halide reduction hold,
with the earlier described general features, both in aprotic (MeCN, DMF, PC, ACE, DMSO) and
in protic solvents (BuOH, PrOH, EtOH, MeOH, H2O) [120,135,159,170]. However, while in the first
group the catalytic effects appear nearly constant, in the second one they are higher and regularly
increase with the solvent proticity; moreover, they appear to linearly increase with increasing
p rimary medium effect (PME) on the halide leaving group, that is, the transfer activity coeffi-
cient of the halide leaving group from water to a solvent S [201] log γ t(X− ,W →S), a quantity directly
p roportional to the standard Gibbs energy of transfer of the same ion from infinite dilution in water
to infinite dilution in S:
∆Gt0( X− ,W →S)
log γ t(X− ,W →S) = (24.33)
(2.303RT )
The more positive the PME, the weaker the solvent coordinating ability for the halide anion com-
pared to water. In the alcohol series, PMEs are lower than in aprotic solvents and regularly decrease
with increasing proticity. Actually, Ag catalytic effects also exhibit a fairly linear dependency on the
alcohol pKa (Ka = autoprotolysis constant).
Solvent proticity not only enhances the catalytic effects (maybe on account of faster turnover
of halide ions in the catalytic sites of the electrode), but it can also affect the reaction mechanism;
for example, in protic solvents, silver shows some catalytic effects also in the case of aryl chloride
reduction, whereas in aprotic solvents, aromatic C–Cl bonds are not catalytically reduced on Ag
[86,128,129]. Moreover, adsorption/desorption processes of straight-chain alcohols, regularly mod-
ulated by their chain length, are perceivable when working in such media.
Water (PME = 0) appears to be the limiting case, resulting in the highest catalytic effects observed
for each model molecule tested in the aforementioned solvent series (often ≥1 V). This feature is
particularly valuable for synthetic and analytical applications in the environmental field, typically
involving the aqueous medium. In fact, working on noncatalytic electrodes in water, the background
reaction overshadows most organic halide reduction peaks, while working on Ag, a large number
of halide molecules can be reduced well before the background cathodic limit; moreover, the cor-
responding reduction peaks are much more differentiated since catalytic effects depend on molecu-
lar structures (see Section III.C.3). Accordingly, working on silver widely increases the range of
organohalide pollutants that can be abated by direct electroreductive dehalogenation and that can
be monitored by voltammetric sensors [120].
Extension of the present studies to ionic liquid media, acting as both solvent and supporting
electrolyte, could open further interesting perspectives.
D. PaLLaDIUM, CoppEr, GoLD

Palladium and copper also exhibit a remarkable catalytic effect for carbon–halogen bond cleavage;
as an example, they both appear comparable to silver in a systematic parallel test carried out on a
series of organic chlorides, including chloroaromatics, benzyl chlorides, activated chloroalkanes,
and polychloromethane (PCM) [86].
Palladium has been, so far, more extensively investigated. At smooth palladium electrodes,
palladiated surfaces (such as Cu, Ni, Au, Pt, GC) [138,139,145,151,155,162,202], and above all palla-
dized silver [150,203], a large palette of substrates, including alkyl iodides [138,139], alkyl bromides
[173,174], aryl halides [204], benzyl halides [148], allyl bromides [153], propargyl bromides [205],
and vinyl bromides [206], have been investigated in different organic solvents (DMF, propylene car-
bonate, MeCN) with tetraalkylammonium quaternary salts as supporting electrolytes. In all cases,
two subsequent reduction CV peaks were observed, the first of which is shifted to remarkably more
positive potentials with respect to noncatalytic Pt and GC electrodes. In preparative experiments,
the monoelectronic stoichiometry and the radical coupling and cross-coupling products pointed
to a radical rather than an anion intermediate (as in the silver case), which was also supported by
ESR experiments [139,148]. An organometallic intermediate was assumed for the catalytic process,
possibly leading to significant chemical modifications of the catalytic metal surface and even to its
partial dissolution [207].
From a preparative point of view, the catalytic process resulted inter alia in arene alkylations [145],
mono- and di-benzylations [148], formation of homo dimers from long-chain α,ω-dibromoalkanes
[146], and aryl dimerizations in propylene carbonate (for which a probable concomitance of electro-
catalytic and redox catalytic processes was assumed [208]).
More recently, research also focused on copper [86,121–124,132,158] as smooth metal or in
other forms (such as copper powder suspensions, palladium copper alloy, or galvanostatically elec-
trodeposited copper onto several conducting substrates). Of applicative interest for environmental
remediation processes is the copper performance in the electrocatalytic reductive dehalogenation
of chlorinated compounds such as PCMs [121], geminal polychloroethanes (PCAs, in particu-
lar 1,1,1-trichloroethane (TCA) and 1,1-dichloroethane (DCA), which are the simplest molecules
belonging to the homologous series of CHCl3 and CH2Cl2 [122]), and polychloroethylenes [124].
Although in DMF the Cu catalytic effects for the process are modest, they are significantly enhanced
by the addition of proton donors, which also affect the nature of the intermediates and products in
preparative experiments. In particular, sequential hydrodehalogenation leading to ethane as the final
product becomes the principal reaction pathway in the presence of acetic acid, whereas in the pres-
ence of H2O both hydrodehalogenation and dehydrodehalogenation (with α,β-elimination of H+ and
Cl− resulting in chlorinated olefins and acetylene) are possible.
Gold is also currently studied [124,136,159,160–162], focusing on conditions in which its intrin-
sic catalytic properties can be exploited in spite of the high negative surface charge, such as in the
presence of adsorption auxiliaries [136] or in protic solvents [159].
The electrocatalytic reduction of organohalides on the aforementioned metals has been proposed
for electrode surface functionalization (e.g., [160–162]).
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25 Conversions Aliphatic and Aromatic Halides
Dennis G. Peters
CONTENTS
I. Introduction .......................................................................................................................... 942
II. Monohalogenated Alkanes ................................................................................................... 942
A. Reduction at Mercury Cathodes ................................................................................... 943
1. Primary Alkyl Monohalides ................................................................................. 943
2. Secondary Alkyl Monohalides .............................................................................. 943
3. Tertiary Alkyl Monohalides .................................................................................. 943
B. Reduction at Carbon Cathodes .....................................................................................944
C. Reduction at Other Electrodes......................................................................................944
D. Electrolyte Effects ........................................................................................................ 945
III. Polyhalogenated Alkanes ..................................................................................................... 945
A. gem-Dihaloalkanes, gem-Trihaloalkanes, and Carbon Tetrachloride .......................... 945
B. Vicinal Dihaloalkanes and Trihaloalkanes ..................................................................946
C. α,ω-Dihaloalkanes ........................................................................................................ 947
IV. Halogenated Alkenes and Alkynes ...................................................................................... 947
A. Vinyl Halides ................................................................................................................ 947
B. Allyl Halides................................................................................................................. 947
C. Acetylenic Halides........................................................................................................948
V. Benzyl Halides and Related Compounds ............................................................................. 948
VI. Alicyclic Halides .................................................................................................................. 950
A. Monohalogenated Species ............................................................................................ 950
B. Dihalogenated Species ................................................................................................. 951
C. Other Species................................................................................................................ 951
VII. Halogenated Aromatic Compounds ..................................................................................... 952
A. Monohalobenzenes ....................................................................................................... 952
B. Polyhalobenzenes ......................................................................................................... 953
C. Halogenated Nitrobenzenes and Cyanobenzenes......................................................... 954
D. Halogenated Aryl Carbonyls ........................................................................................ 954
E. Halogenated Biphenyls ................................................................................................. 954
VIII. Acyl Halides ......................................................................................................................... 955
IX. Phenacyl Halides .................................................................................................................. 955
X. Aliphatic α-Halocarbonyl Compounds ................................................................................ 956
XI. Halogenated Heterocyclic Compounds ................................................................................ 958
A. Heterocyclic Compounds with One Nitrogen Atom .................................................... 958
B. Heterocyclic Compounds with Two Nitrogen Atoms ................................................... 959
C. Other Heterocyclic Species .......................................................................................... 959
941
XII. Indirect or Catalytic Cleavage of Carbon–Halogen Bonds .................................................. 959

A. Electrogenerated Radical–Anions as Mediators ..........................................................960
B. Transition-Metal Complexes as Mediators ...................................................................960
1. Nickel Complexes .................................................................................................. 961
2. Cobalt Complexes .................................................................................................. 963
3. Other Catalysts ...................................................................................................... 965
C. Reduction of Carbon–Halogen Bonds at Chemically Modified Electrodes ................ 965
References ......................................................................................................................................966
I. INTRODUcTiON
Electrochemical reduction of halogenated organic compounds, including mechanistic features, as
well as synthetic applications associated with reductive cleavage of carbon–halogen bonds, has
been treated in earlier editions of this work [1–4] and in several other reviews [5–11]. This chapter
focuses both on the classic material described in these earlier references and, more importantly, on
new achievements published since 2000.
II. MONOhALOGENATED ALkANES

Electrochemical reduction of a simple alkyl monohalide (RX) has been visualized classically in
terms of the following mechanistic picture:
RX + e [RX –]
[RX –] R + X–
R +e R–
Combination
R2
2R
Disproportionation
RH + R(–H)
R + SH RH + S
R– + SH RH + S–
R– + RX R2 + X–
R– + HB RH + B–
E2
RX + B– R(–H) + X– + HB
SN2
RX + B– RB + X–
However, recent publications by Isse and coworkers [12–14] have offered new perspective on
whether the radical–anion of RX actually exists and on other details about the cleavage of carbon–
halogen bonds (see Chapter 24). Nevertheless, depending on the solvent, supporting electrolyte,
Aliphatic and Aromatic Halides 943
electrode material, and potential, it is possible to electrogenerate either alkyl radicals or carbanions
that can lead to the formation of dimers (R2), alkanes (RH), and olefins [R(–H)]. In addition, the
solvent (SH) can act as a hydrogen atom donor or a proton donor. Also, olefins can arise from the
base-promoted dehydrohalogenation of RX, and other products (RB) can be formed via displace-
ment of halide from RX by a base (B−). When cathode materials such as mercury, lead, and tin are
employed, electrogenerated alkyl radicals can interact strongly with the electrode to enhance the
reduction of the alkyl monohalide and to afford organometallic compounds.
Tertiary alkyl halides are easier to reduce than secondary alkyl halides, which are, in turn, easier
to reduce than primary alkyl halides. Ease of reduction of a carbon–halogen bond depends on the
identity of the halogen atom: (1) iodides are easier to reduce than bromides, (2) chlorides are so dif-
ficult to reduce that they often appear to undergo no direct reduction, and (3) direct reduction of an
alkyl monofluoride has not been observed. Finally, the existence of the radical–anion [RX• –], formed
by the addition of one electron to RX, has not been demonstrated; Andrieux and coworkers [15] dis-
cussed why the radical–anion is not expected for simple alkyl monohalides, whereas radical–anions
of aromatic halides are distinct intermediates in the electrochemical reduction of aryl halides.
A. REDUCTIoN aT MErCUrY CaTHoDES

1. Primary Alkyl Monohalides
Many studies of the reduction of primary alkyl monohalides at mercury electrodes have been
undertaken. Reduction of iodoethane and 1-iodobutane in ethanol affords diethylmercury and dibu-
tylmercury, respectively, in essentially quantitative yields [16]. When 1-iododecane is reduced at
mercury in DMF, successive formation of the decyl radical (to afford only didecylmercury) and the
decyl carbanion (to yield mainly decane and 1-decene) takes place [17,18]. Bilewicz and Osteryoung
[19] found that the reductions of iodoethane, 1-iodobutane, and 1-iododecane at mercury in MeCN
are similar to those seen in DMF.
Primary alkyl monobromides, such as 1-bromodecane, typically undergo a one-step, two-
electron reduction to alkyl carbanions in DMF, a process leading to alkanes and alkenes [18].
However, Fry [20] reported that reduction of 1-bromohexane in DMF containing TEABr yields
hexane, 1-hexene, dihexylmercury, and 1-hexanol. Wagenknecht and coworkers [21,22] investigated
the reductions of bromoethane and 1-bromobutane at mercury in carbon dioxide–saturated DMF.
For the 1-bromobutane–carbon dioxide system, dibutylmercury, dibutyl oxalate, and butyl valerate
are produced in comparable yields; to account for the formation of the dialkylmercury compound,
the intermediacy of a short-lived adsorbed alkylmercury radical is proposed.
2. Secondary Alkyl Monohalides

One detailed report [23] about the reduction of secondary alkyl monohalides at mercury has
appeared. In DMF containing tetraalkylammonium salts, 2-iodooctane undergoes stepwise reduc-
tion, whereas 2-bromooctane exhibits just one stage of reduction. One-electron reduction of
2-iodooctane affords the sec-octyl radical, which leads to a mixture of octane, 1-octene, 2-octene,
7,8-dimethyltetradecane, and di-sec-octylmercury. Products obtained from the two-electron reduc-
tion of either 2-bromo- or 2-iodooctane are as just mentioned, but the yield of octane is higher and
the amounts of di-sec-octylmercury and 7,8-dimethyltetradecane are lower. Montero and coworkers
[24] found that reduction of 2-bromo-2-nitropropane at mercury in dichloromethane containing
dimethyl but-2-ynedioate gives two unexpected products—namely, dimethyl 2-(2-nitropropan-2-yl)-
but-2-enedioate and trimethyl 2,2-dimethyl-2H-pyrrole-3,4,5-tricarboxylate.
3. Tertiary Alkyl Monohalides

Polarographic and voltammetric investigations [25–28] of the behavior of tert-butyl iodide and tert-
butyl bromide at mercury revealed that, depending on the solvent and supporting electrolyte, the
iodide undergoes stepwise reduction and the bromide exhibits either a single two-electron reduction
or a pair of one-electron reductions. Bulk electrolyses of tert-butyl bromide at potentials corre-

sponding to the first wave produce tert-butyl radicals, which form isobutane, isobutylene, and
2,2,3,3-tetramethylbutane; however, at more negative potentials, where tert-butyl carbanions are
generated, one obtains isobutane and isobutylene in equal yields [29].
B. REDUCTIoN aT CarboN CaTHoDES

An advantage of carbon electrodes over mercury cathodes for the reduction of alkyl monohalides is
the avoidance of dialkylmercury species. As pointed out by Lambert and Ingall [30], it is possible
with carbon cathodes to observe the direct reductive cleavage of the carbon–chlorine bond in com-
pounds such as 1-chloropentane, 1-chlorohexane, 2-chlorobutane, and tert-butyl chloride in DMF.
Reduction of 1-bromobutane at graphite in carbon dioxide–saturated DMF is a two-electron
process that affords butane, 1-butene, octane, butyl valerate, butyl-N,N-dimethyloxamate, and
dibutyl-2-methylmalonate [22]. Kaabak and coworkers [31] found that reduction of iodoethane and
1-bromobutane at graphite in DMF yields alkanes, olefins, dimers, and solvent-derived products.
Using glassy carbon in DMF containing TBABF4, Andrieux and coworkers [15,32] concluded
that 1-bromobutane, 2-bromobutane, tert-butyl bromide, and 1-iodobutane undergo one-step, two-
electron reductions, whereas 2-iodobutane and tert-butyl iodide exhibit a pair of one-electron
reduction waves. Products derived from bulk electrolyses of primary, secondary, and tertiary alkyl
iodides and bromides at reticulated vitreous carbon cathodes have been determined in DMF [33].
In work involving the use of reticulated vitreous carbon cathodes in DMF [34], the reductions of
iodoethane and 2-iodopropane were examined and product distributions were reported. After it
was discovered that reduction of secondary alkyl halides (RR′CHX) causes RR′CH– groups to be
grafted onto carbon surfaces [35] (see also Chapter 42), Jouikov and Simonet [36] verified this pro-
cess by reducing ferrocene bearing an alkyl iodide substituent to graft alkylferrocenyl moieties as
probes of this surface phenomenon. Another paper deals with the grafting of pendant alkanoic acid
moieties onto carbon via the reduction of ω-bromoalkanoic acids [37]. Gennaro and coworkers [38]
report that changes in the oxygen-to-carbon ratio on the surface of glassy carbon plays an important
role in the reduction of carbon–halogen bonds.
C. REDUCTIoN aT OTHEr ELECTroDES

Methyl, ethyl, propyl, and butyl halides are reduced at lead and tin cathodes to produce, respec-
tively, the corresponding tetraalkyllead and tetraalkyltin compounds in excellent yield. Bismuth,
gallium, indium, and thallium can be employed to prepare a variety of organometallic compounds.
Feoktistov [2] and Hawley [5] have summarized many of these electrosyntheses.
Sock et al. [39] synthesized carboxylic acids by reducing alkyl bromides at platinum, gold, stain-
less steel, and graphite in the presence of carbon dioxide in either DMF or a THF–HMPA mixture.
Reduction of an alkyl monobromide at nickel in DMF and in the presence of an arylalkene and a
sacrificial aluminum anode leads to an addition product [40].
Simonet and coworkers [41–43] discovered that, when platinum cathodes are employed for the
direct reduction of alkyl halides in superdry DMF containing tetramethylammonium tetrafluorobo-
rate, the original alkyl halide is converted into an alkene and the surface of the platinum electrode is
transformed into an ionometallic layer. A host of reports have appeared that focus on the reduction
of alkyl monohalides at nontraditional electrodes such as palladized carbon, copper, nickel, or
platinum; copper–palladium or silver–palladium alloys; and silver [44–55]. The emphasis in these
papers is on the ability of the electrode to promote the facile one-electron scission of the carbon–
halogen bond.
Isse et al. [56] have compared mechanisms for the reduction of alkyl and aromatic halides at
glassy carbon and silver, pointing out that silver exhibits an amazing ability to catalyze cleavage
of the carbon–halogen bond; similar effects have been seen with palladium and copper electrodes [57]
(see also Chapter 24). Dissociative electron-transfer processes, as they influence the reductive cleav-
age of carbon–halogen bonds at silver cathodes, have been studied by the same group of workers
[58]. Synthesis of cyanoacetic acid via reduction of haloacetonitriles in the presence of carbon
dioxide has been compared for silver and glassy carbon electrodes, and important mechanistic
conclusions have emerged [59–62]. A comparison of the reduction of various bromonitriles at both
mercury and glassy carbon was undertaken [63]. Reactions of Br(CH2)nCN (n = 2–4) with the anion
arising from the reduction of 2-bromo-2-methylpropanenitrile have been investigated [64], and the
reduction of a series of bromonitriles at mercury and glassy carbon has been studied [65]. Mono-
and polycrystalline silver electrodes have been employed to study the reductions of alkyl halides
(as well as benzyl and glycosyl halides) [63,64].
D. ELECTroLYTE EFFECTS
For electrosyntheses, it is important to be aware of the substantial shifts in the potentials needed
to reduce carbon–halogen bonds when different supporting electrolytes are used. Many workers
[18,19,23,27,28,68] have noticed that carbon–halogen bonds become more difficult to cleave elec-
trolytically as the size of the tetraalkylammonium cation of the supporting electrolyte increases. Fry
and Krieger [27] determined the relative electron-transfer rates in DMSO for the reduction of some
alkyl and aryl halides as a function of the identity of the tetraalkylammonium cation comprising
the supporting electrolyte.
Alkyl carbanions are potent bases, so they are protonated by almost any source of hydrogen ions,
especially adventitious water in the solvent or supporting electrolyte. In the absence of water and
other added proton donors, tetraalkylammonium cations can serve as proton donors toward alkyl
carbanions; deprotonation of tetraalkylammonium ions leads, via the Hofmann elimination, to the
corresponding trialkylamine and olefin. When tetramethylammonium salts are used as supporting
electrolytes, there is evidence that trimethylammonium methylide is formed [69,70].
III. POLYhALOGENATED ALkANES

A. gem-DIHaLoaLkaNES, gem-TrIHaLoaLkaNES, aND CarboN TETraCHLorIDE
Electroreduction of polyhalogenated alkanes is a useful strategy for organic synthesis and envi-
ronmental remediation. Among studies in this area are the following: reduction of polychloro-
methanes and polychloroethanes at activated silver cathodes [71–73]; selective dechlorination of
1,1-dichloro-2,2-bis(p-chlorophenyl)ethane and 1,1-dichloro-2-hydroxy-2,2-bis(p-chlorophenyl)-
ethane [74]; formation of cyclopropanes via reduction of dichloromethane in the presence of
alkenes [75,76]; cross-coupling of activated alkyl halides with gem-trichloroalkanes or carbon
tetrachloride [77,78]; electrochemical coupling of gem-trichloroalkanes with aldehydes or ketones
[79]; preparation of cyclopropanes by indirect electroreductive coupling of activated olefins and
gem-dichloro or gem-trichloro compounds [80]; synthesis of epoxides via indirect reductive cou-
pling of carbonyl compounds with activated gem-dichloro species [81]; conversion of tetra- and
trichloropentanes into less chlorinated analogues [82]; reduction of 1,1,1-trichloro-2-hydroxy-4-
methyl-4-pentene to afford 1,1-dichloro-4-methyl-2,4-pentadiene and 1,1-dichloro-2-hydroxy-4-
methyl-4-pentene [83]; electrolysis of trichloromethylphosphonate in the presence of an alkyl halide
to form a diethyl 1,1-dichloroalkylphosphonate [84]; reductive coupling of 1,1,1-trichloro-2,2,2-
trifluoroethane, methyl chlorodifluoroacetate, trifluorobromomethane, and perfluoroiodobutane
with aldehydes [85]; reductive cyclization of 2,2-dimethyl-3-oxopropyl 2,2,2-trichloroacetate
to afford 3,3-dichloro-4-hydroxy-5,5-d imethyltetrahydro-2H-pyran-2-one [86]; synthesis
of 3-chloro-1-methyl-4-phenylquinolin-2(1H)-one from N-(2-benzoylphenyl)-2,2,2-trichloro-
N-methylacetamide [87]; reductive cyclization of 2-acetylphenyl 2,2,2-trichloroacetate to
produce 3,3-dichloro-4-hydroxy-4-methylchroman-2-one [88]; reductive dechlorination of
4,4,4-trichloro-1-phenylbut-2-en-1-ones [89–91], N-(1-alkoxy-2,2,2-trichloroethyl)benzamides [92,93],

N-(1,2,2,2-tetrachloroethyl)benzamides [94], 2,2,2-trichloroethylideneacetophenones [95], and
3,3,6,6-tetrachloro-1,2-cyclohexanedione [96,97]; dechlorination of alkyl and aryl carbonimidoyl
dichlorides to give the corresponding isocyanides [98]; electroreductive coupling of activated
olefins and gem-polyhalo compounds [99]; selective removal of gem-polyhaloethoxy protecting
groups from carboxylic acids [100]; and electrochemical conversion of 2,2-dichloroethylamides to
4,5-dihydrooxazoles [101,102]. An example of the last conversion is the reduction of N-(2,2-dichloro-
1-phenylethyl)benzamide to give 2,4-diphenyl-4,5-dihydrooxazole in 78% yield:
Ph O
O Ph
2e, –2Cl–
Hg cathode
CH3CN, TBAClO4 N
Ph N CHCl2
H
Ph
Carbon tetrachloride undergoes stepwise reduction at mercury in DMF [103]. Several groups of
workers [104–110] have electrogenerated the trichloromethyl anion, which reacts with acryloni-
trile, ethyl acrylate, diethyl fumarate, alkyl monohalides, aldehydes, and ketones. Dichlorocarbene,
formed via reduction of carbon tetrachloride, reacts with 2,3-dimethylindole to afford 3-chloro-
2,4-dimethylquinoline and 3-(dichloromethyl)-2,3-dimethyl-3H-indole [111]; electrolysis of
carbon tetrachloride or tetrabromide in the presence of aryl aldehydes gives benzal chlorides
and bromides, respectively [112]. Reduction of bromotrifluoromethane at stainless steel in cells
with sacrificial anodes of cadmium, copper, and zinc can be used to prepare CF3Cd, CF3Cu, and
CF3Zn [113–115]. Reduction of carbonimidoyl dichlorides at mercury gives isocyanides in excel-
lent yield [116]. Reduction of chlorodifluoromethyl enol ethers results in two-electron cleavage
of the carbon–chlorine bond, and the resulting anion can react with t rimethylchlorosilane to
afford functionalized difluoromethyl allylsilanes [117]. Comparative studies of the dehalogena-
tion of polychlorinated methanes at glassy carbon and silver cathodes have been recently reported
[118,119].
B. VICINaL DIHaLoaLkaNES aND TrIHaLoaLkaNES

These compounds undergo a two-electron reduction with the loss of two halide ions to give an
olefin. Casanova and Rogers [120] demonstrated the reductions of 1,2-dibromo-2-phenylpropane
to 2-phenylpropane, of meso-2,3-dibromobutane to trans-2-butene, and of d,l-2,3-dibromobu-
tane to cis-2-butene. For the reduction of d,l-1,2-dibromo-1,2-diphenylethane at mercury in
DMF, the ratio of cis- to trans-stilbene seems to depend on the identity and concentration of
the supporting electrolyte [121,122]. Reduction of vicinal dibromides has been carried out by
Závada and coworkers [123] and by Lund and coworkers [124]. Papers concerning the reduction
of polyhalogenated ethanes have been published by Feoktistov, Gol’din, and coworkers [125–129].
Rampazzo and coworkers [130] studied the reductions of α,α,α′,α′-tetrabromo-o-xylene and
1,2-dibromobenzocyclobutene.
Various mechanistic aspects of the electroreduction of vicinal dihalides have been probed
[120,131–135]. In an investigation of the meso- and d,l forms of 3,4-dibromohexane and
2,5-dimethyl-3,4-dibromohexane, Brown and coworkers [136] found that the meso compounds are
easier to reduce than the d,l species. Evans and coworkers [137,138] employed cyclic voltammetry
to probe the temperature-dependent conformational equilibrium for a number of vicinal dibromides,
and Lexa and coworkers [139] have discussed inner- and outer-sphere processes for the reduction of
vicinal dibromides.
C. α,ω-DIHaLoaLkaNES
In early work, Rifi [140–142] investigated the reduction of α,ω-dibromoalkanes (such as
1,3-dibromopropane and 1,4-dibromobutane) at mercury in DMF. Studies of α,ω-dibromoalkanes were
conducted by Wiberg and Epling [143] and by Fry and Britton [144,145], and Casanova and Rogers
[146] synthesized dialkylmercury species via controlled-potential electrolysis of a family of com-
pounds (ranging from 1,4-dibromobutane to 1,12-dibromododecane) at mercury in DMF. A number of
other publications have dealt with the behavior of α,ω-dibromoalkanes at mercury cathodes [147–152].
Derivatives of cyclopentane and cyclohexane have been prepared by the reduction of
1,3-dibromopropane or 1,4-dibromobutane, respectively, in the presence of an alkene [40,75]. In a
series of papers pertaining to the reduction of α,ω-dihaloalkanes at carbon in DMF, the behavior
of 1,3-dihalopropanes [153], 1,4-dihalobutanes [154], 1,5-dihalopentanes [155], 1,6-dihalohexanes
[156], 1,8-dihalooctanes [157], and 1,10-dihalodecanes [157] was probed. Simonet [158] has inves-
tigated the reduction of several α,ω-dihaloalkanes at copper cathodes. Tokuda and coworkers [159]
carried out reductive intramolecular cyclization of compounds such as 1,12-dibromo-2,10-dodeca-
diene to form the corresponding 1,5-cycloalkadienes.
IV. HALOGENATED ALkENES AND ALkYNES

A. VINYL HaLIDES
Reduction of a vinyl halide involves the uptake of one electron and the loss of a halide ion to give
a vinyl radical, which then undergoes further reduction and protonation to yield an alkene; before
accepting an electron and a proton, the vinyl radical rearranges to afford either a cis or trans alkene.
Compounds that have been specifically investigated include aryl-substituted vinyl bromides [160],
cis- and trans-3-iodo-3-hexene [161], bromomaleate and bromofumarate [162], and aryl-substituted
3-chloroacrylonitriles [163]. Reductive carboxylation of phenyl-substituted vinyl bromides affords
α,β-unsaturated carboxylic acids [164]. Yoshida and coworkers [165] electrolyzed vinyl halides at
platinum in DMF in the presence of trimethylchlorosilane to obtain silylation products.
Vicinal dibromoalkenes and diiodoalkenes undergo reduction, with the loss of both halide ions,
to yield alkynes that are further reduced to olefins and saturated species; work by Rosenthal and
coworkers [166] on the electrochemistry of diethyl dibromofumarate and diethyl dibromomaleate
exemplifies this behavior. Vicinal dichloroalkenes show more complicated electrochemistry; in
some instances, the two carbon–chlorine bonds simply undergo successive two-electron, one-proton
reductive cleavage [167], whereas in other cases the reduction leads to an alkyne [168]. Feroci and
coworkers [169] converted substituted 1,1-dibromoalkenes, for example, 2-(2,2-dibromovinyl)naph-
thalene, to vinyl bromides via electrolysis at a carbon, gold, mercury, or silver cathode; the E/Z ratio
for the products depends on the choice of electrode.
B. ALLYL HaLIDES
Baizer and coworkers [104,170] demonstrated that reduction of allyl bromide and allyl chloride
depends on the medium. In DMSO containing TEAP, allyl bromide undergoes stepwise reduction
to the radical and to the carbanion, whereas allyl chloride exhibits a single two-electron reduction
[170]. In DMF containing TEAOTs or TEABr, allyl bromide and allyl chloride are each reduced in
a one-step, two-electron process to the carbanion, which then undergoes various follow-up reactions
with a proton donor, with unreduced starting material, with carbon dioxide, or with species such as
acrylonitrile and ethyl acrylate [104]. Reduction of allyl halides, 1-chloro-3-methyl-2-butene, and
methyl-4-halo-2-butenoates at platinum in DMF containing diethyl fumarate gives the conjugate
addition products [171]; and reduction of 4-bromo- and 4-chloro-2-butene can be used to allylate
acetone and benzaldehyde [172]. Methallyl chloride undergoes reductive coupling with ketones and
aldehydes to afford alcohols [173] as well as electrodimerization [174]. Reduction of allylic halides
in the presence of anhydrides leads to the formation of ketones [175], as seen in the following
process:
2e, –Cl–
H2C C CH2Cl H2C C CH2–
Ni cathode
DMF, TBAI
CH3 CH3
O O
CH2 – C C CH3
H2C C O CH3 H2C CH2
H3C
–CH3COO– O
CH3 CH3
Bard and Merz [176] reported that allyl bromide and allyl iodide interact chemically with a mercury
electrode to form allylmercury halides, which are reduced to electroactive diallylmercury. Allyl
bromide and allyl iodide are reduced at platinum in MeCN in a two-electron process to give the
allyl anion. Reduction of allyl halides at platinum in DMF containing trimethylchlorosilane pro-
duces silylated compounds [165]. Simonet [177] has shown that reduction of allyl bromide at noble
metals (Au, Pd, Pt, and Rh) results in the surface allylation of those electrodes. Electrochemical
conjugate addition of the allyl moiety of a substituted allyl halide to an α,β-unsaturated ester has
been described [171,178]. Electrolysis of allyl chloride in the presence of excess acetone gives
2-methyl-4-penten-2-ol [179]. Reduction of an allyl halide in the presence of copper(II) acetylace-
tonate leads to the formation of biallyl [180].
According to Brillas and Costa [181], 1,3-butadiene is an intermediate in the reduction of trans-
1,4-dibromo-2-butene and trans-1,4-dichloro-2-butene at mercury. Doupeux and Simonet [182,183]
studied the electrochemical behavior of polyhalogenated allyl halides.
C. ACETYLENIC HaLIDES
Several investigations [184–187] have dealt with acetylenic halides that undergo reductive intramo-
lecular cyclization. Electrolysis of 6-bromo- or 6-iodo-1-phenyl-1-hexyne at mercury in DMF gives
a potential-dependent product distribution [184]. Reduction of 1-iodo-5-decyne at mercury displays
two waves, indicating stepwise formation of radical and carbanion intermediates, whereas reduction
of 1-bromo-5-decyne gives a single wave, which corresponds to a net two-electron process [185];
bulk electrolyses of these compounds afford potential-dependent product distributions.
When 1-halo-5-decynes are electrolyzed at carbon in DMF [186], the yield of pentylidene
cyclopentane increases dramatically; two other products are 5-decyne and 1-decen-5-yne. Reduction
of 6-iodo-1-phenyl-1-hexyne at carbon in DMF affords benzylidenecyclopentane and 1-phenyl-1-
hexyne [187].
V. BENzYL HALiDES AND RELATED COMPOUNDS

Reduction of benzyl iodide at mercury appears to proceed via an electroinitiated chain reaction
that involves the formation of benzylmercuric iodide, C6H5CH2HgI [188,189]; benzyl bromide and
benzyl chloride probably exhibit similar behavior [190–192].
Electrolyses of benzyl bromide in MeCN [192] or DMF [104] and of benzyl chloride in aqueous
EtOH [192] at mercury afford dibenzylmercury, toluene, and sometimes bibenzyl; in the litera-
ture, there is much debate about mechanistic details of the reduction of benzyl halides [104,193].
Reduction of benzyl chloride at mercury in DMF and in the presence of carbon dioxide provides
evidence for the generation of the benzyl carbanion; benzyl phenylacetate [104] and phenylacetic
acid [189] are obtained as electrolysis products. In carbon dioxide–saturated MeCN, benzyl chlo-
rides undergo facile electrocarboxylation at a silver cathode [194,195]; similar studies of the reduc-
tive carboxylation of benzyl bromide at graphite and mercury have been reported [196]. Benzyl
chloride undergoes electrodimerization at a stainless-steel cathode in DMF [174]. Reduction of
benzyl iodide at glassy carbon in the presence of nitric oxide has been investigated [197]. In the
presence of copper(II) acetylacetonate, benzyl bromide undergoes reductive coupling to give biben-
zyl [180]. Electrochemical reduction of several derivatives of 4-(bromomethyl)-2H-chromen-2-one
at vitreous carbon has been investigated [198,199]. Electrolyses of 1-(2-chloroethyl)-2-nitrobenzene
and 1-(2-bromoethyl)-2-nitrobenzene at glassy carbon electrodes in the absence of an added proton
donor afford mainly 1-nitro-2-vinylbenzene; however, in the presence of an excess of a proton donor
(e.g., phenol or 2,4-pentanedione), 1H-indole is obtained in good yield (>80%) [200]:
X
4e
C cathode, DMF,
NO2 excess proton donor N
H
Reduction of N′-(2-bromo-1-phenylethylidene)acetohydrazide to (1E,4E)-1,4-bis(2-methylhydrazono)-

1,4-diphenylbutane has been reported [201]. Isse et al. [202–205] have compared the reduction of benzyl
halides at silver and glassy carbon, and Amatore and coworkers [206,207] used electrochemistry along
with spectroscopic and computational methods to elucidate the mechanism of the reduction of benzyl
c hloride at silver.
Reduction of o- and p-nitrobenzyl halides at mercury or platinum gives mainly the bibenzyl
derivative, with nitrotoluene as a minor product [193,208–212]. However, m-nitrotoluene is the pre-
dominant product of the electrolysis of m-nitrobenzyl halides [209]. Andrieux and coworkers [213]
probed the mechanism of reductive cleavage of a family of substituted benzyl halides. Reduction
of 4-nitrobenzyl bromide and benzyl bromide at highly ordered pyrolytic graphite results in the
creation of a film of benzylic moieties on the cathode surface [214].
Koch and coworkers [215] investigated the reduction of benzyl halides at both platinum and car-
bon in MeCN. For the electrolysis of benzyl iodide at platinum, the products are toluene, bibenzyl,
and hydrocinnamonitrile; in the presence of carbon dioxide or diethyl malonate, the electrogene-
rated benzyl anion is converted, respectively, into benzyl phenylacetate or the diethyl ester of benzyl
malonate. Shono and coworkers [216] electrolyzed benzyl chloride or (1-chloroethyl)benzene at car-
bon in MeCN containing various acyl chlorides to prepare alkyl benzyl ketones. Ketones have been
obtained from the reduction of benzyl halides in the presence of anhydrides [175]. Catalytic electro-
carboxylation of (1-chloroethyl)benzene has been carried out [217], and 2-arylpropanoic acids have
been synthesized via reduction of several 1-aryl-1-chloroethanes at silver and carbon cathodes in the
presence of carbon dioxide [218]. Electrolysis of benzyl chloride in the presence of various ketones
and aldehydes can be used to synthesize alcohols [110]:
2e, –Cl–
PhCH2Cl PhCH2–
Stainless-steel cathode
DMF, TBAI
O
CH3
H3C C CH3
PhCH2– PhCH2 C CH3
+H+
OH
For the reduction of 1-bromo-1-phenylethane at mercury in DMF, Yamasaki and coworkers [219]
found a potential-dependent product distribution. At less negative potentials, the products are meso-
2,3-diphenylbutane, d,l-2,3-diphenylbutane, and phenylethane, whereas phenylethane is the only
species obtained at more negative potentials. Using (1-bromo-2,2-dimethylpropyl)benzene, Fry and
Powers [220] obtained more insight into the mechanism of the formation of bibenzyl from the
reduction of benzyl bromides, and Fry and coworkers [221] described steric effects on the reductive
coupling of α-substituted benzyl bromides.
Other compounds that have been studied are benzhydryl halides [222,223] and α,α′-
dibromoxylenes [224]. Electrolyses of trifluoromethylbenzene, chlorodifluoromethylbenzene, and
dichlorofluoromethylbenzene [225] at mercury afford a series of species, each possessing one less
halogen atom than its precursor. Trifluoromethyl arenes undergo reductive coupling with electro-
philes such as carbon dioxide, dimethylformamide, and acetone [226]. Trichloromethylbenzene
undergoes stepwise reduction with the loss of chloride in DMF [103,227] to yield a mixture of
1,2-diphenyl-1,1,2,2-tetrachloroethane, diphenylacetylene, 1,2-dichloro-1,2-diphenylethene, and
dichloromethylbenzene [227]; however, reduction of trichloromethylbenzene in the presence of
acetic anhydride gives, besides the preceding products, 2-acetoxy-1-chloro-1-phenyl-1-propene and
1,2-diacetoxy-1-phenyl-1-propene [228]. Cathodic addition of trichloromethylbenzene to ketones
gives α,β-unsaturated ketones [229]. Methyl esters of trifluoromethylbenzoic acid can be defluori-
nated by reduction at lead cathodes in MeOH [230,231]. Fry and Touster [232] electrolyzed a benzal
halide in DMF containing trimethylchlorosilane to synthesize both the (α-halobenzyl)silane and the
benzal disilane. Amino acids can be synthesized via the coupling of Schiff bases with carbanions
generated by the reduction of benzyl halides [233,234]:
2e, –Cl–
PhCH2Cl PhCH2–
Hg cathode
DMF, TBAI
CH3
1. PhCH2N C CO2C2H5
2. H+
CH3 CH3
H2 (Pd/C)
H2N C CO2H PhCH2NH C CO2C2H5
CH2Ph CH2Ph
VI. ALicYcLic HALiDES

A. MoNoHaLoGENaTED SpECIES
An early concern about the reduction of substituted and optically active 1-bromocyclopropanes and
1-iodocyclopropanes at mercury and carbon cathodes was whether cleavage of the carbon–halogen
bond involves a radical or carbanion intermediate [235–237]. Mann and Barnes [238] have discussed
the mechanism of the reduction of the carbon–halogen bond in these species. Hazard and coworkers
[239] investigated how the identity of the supporting electrolyte cation or the presence of an adsorbed
alkaloid influences the stereochemistry of the reduction of derivatives of 1-bromo-1-carboxy-
2,2-diphenylcyclopropane and of optically active derivatives of 2,2-dibromocyclopropane [239–242].
Monobromocycloalkanes, ranging from cyclobutyl bromide to cyclohexadecyl bromide, have
been examined polarographically in DMF [25,243]; and polarographic data for 1-bromo- and
2-bromonorbornane [27,244–246], 1-bromobicyclo[2.2.2]octane [244,245], 1,7,7-trimethyl-3-

halobicyclo[2.2.1]heptan-2-ones [247], and derivatives of 1-bromo- and 2-bromo-7-oxabicyclo[2.2.1]-
heptane [246] have been compiled. Electrolyses of 1-bromo- and 1-iodonorbornane at mercury in
DMF involve two-electron cleavage of the carbon–halogen bond to afford norbornane [248]; how-
ever, at a platinum cathode, the reductions of 1-bromo-, 1-chloro-, and 1-iodonorbornane give mainly
norbornane, along with some 1,1′-binorbornyl [249]. In work involving the use of silver cathodes
by Rondinini et al., the mechanism for the reduction of haloadamantanes was probed [250,251],
and reductive coupling of a glycosyl halide (tri-O-acetyl-α-d-fucopyranosyl bromide) was studied
[66,67,251,252]. Electrochemical reduction of 2-bromo or 2-chlorocycloalkanones leads to either
coupling or coupling with ring contraction [253].
B. DIHaLoGENaTED SpECIES
Electrolysis of 2,2-dichloronorbornane, 2-exo-bromo-2-endo-chloronorbornane, and 2-endo-
bromo-2-exo-chloronorbornane at mercury cathodes in DMF is a two-electron process, giving a
mixture of nortricyclene and endo-2-chloronorbornane [254]. Reduction of 7,7-dihalobicyclo[4.1.0]
heptanes revealed that formation of the less stable endo-7-halobicyclo[4.1.0]heptane is
preferred over the exo isomer [255,256]. According to Rifi [140,142], electrolysis of 1-bromo-3-
chlorocyclobutane at mercury yields bicyclo[1.1.0]butane, cyclobutane, and cyclobutene, and a simi-
lar pattern prevails for 1,3-dibromo-1,3-dimethylcyclobutane. Hoffmann and Voss [257] found that
1,3-dibromocyclopentane and 1,3-dibromocyclohexane undergo reductive ring-closure reactions at
a platinum cathode to yield bicyclo[2.1.0]pentane and bicyclo[3.1.0]hexane, respectively.
Low-temperature reduction of 1-bromo-4-chlorobicyclo[2.2.0]hexane at mercury in DMF affords
Δ1,4-bicyclo[2.2.0]hexane, which can be trapped with cyclopentadiene [258,259]. Rifi [142], as well
as Wiberg and coworkers [260], electrolyzed 1,4-dibromobicyclo[2.2.2]octane in DMF and obtained
evidence for the transient formation of [2.2.2]propellane. Rifi [142] reported that electrolysis of
1,5-dibromobicyclo[3.2.1]octane yields the stable [3.2.1]propellane, and Leibzon and coworkers
[261] found that reduction of 3,7-dibromo-3,7-dinitrobicyclo[3.3.1]nonane affords 3,7-dinitroada-
mantane in good yield. Adcock and coworkers [262] have studied the reductions of 1,3-dihaloada-
mantanes, 1,4-dihalobicyclo[2.2.2]octanes, and 1,3-dihalobicyclo[1.1.1]pentanes.
For the reduction of 1,4-dihalonorbornanes at platinum in DMF, Wiberg and coworkers [249]
found that the products are norbornane and 1,1′-binorbornyl. However, when 1,4-dihalonorbornanes
are electrolyzed at mercury in DMF [263,264], the major products are norbornane and
bis(1-norbornyl)mercury, along with a small amount of 1,1′-binorbornyl, and it was concluded that
[2.2.1]propellane is an intermediate.
C. OTHEr SpECIES
Semmelhack and coworkers [265] reduced 1,2-dimethyl-4,5,6,6-tetrachlorospiro[2.3]hexadiene
at mercury in DMF containing D2O to prepare 1,2-dimethyl-4,5,6-trichloro-6-deuteriospiro[2.3]-
hexadiene. Reductive monodechlorination of 4,4,8,8-tetrachlorodispiro[2.1.2.1]octane has
been reported [266]. Selective trimethylsilylation of tetrachlorocyclopropene to afford
1-(t rimethylsilyl)trichlorocyclopropene has been described [267]. Polyfluorocyclohexadienes
can be reduced at a mercury cathode in aqueous EtOH [268]. Strelow and coworkers [269]
have reviewed the literature on the reduction of 1,1,3,3-tetrachlorodispirocyclobutanes to
1,3-dichlorodispirobicyclo[1.1.0]butanes. Chlorinated insecticides (chlordane, aldrin, alodan,
and endosulfan) can be electrochemically dechlorinated at lead cathodes in MeOH [270,271].
Lindane (γ-hexachlorocyclohexane) undergoes stepwise dechlorination at a palladium-modified
carbon-cloth cathode in MeOH [272]; one-step dechlorination of lindane to afford benzene
takes place at glassy carbon in DMF [273].
VII. HALOGENATED AROMATic COMPOUNDS

A. MoNoHaLobENZENES
Originally, reduction of a monohalobenzene was believed to entail irreversible two-electron
scission of the carbon–halogen bond followed by rapid protonation of the phenyl carbanion
to give benzene. Andrieux and coworkers [15,274] provided quantitative evidence that in
nonaqueous media a more intricate mechanistic picture for the reductive cleavage of these com-
pounds must be drawn. As shown in reaction (25.1), a reversible, one-electron transfer occurs
to give a radical–anion, which decomposes (reaction (25.2)) to yield the phenyl radical. Once
formed, the phenyl radical can accept an electron (reaction (25.3)) or can react homogeneously
with the initially generated radical–anion (reaction (25.4)), and the resulting phenyl anion can
be protonated by the medium (reaction (25.5)):
C6H5X + e [C6H5X –] (25.1)
k
[C6H5X –] C6H5 + X– (25.2)
C6H5 + e C6H5– (25.3)
C6H5 + [C6H5X –] C6H5– + C6H5X (25.4)
C6H5– + H+ C6H6 (25.5)
Other reactions to be considered are abstraction of a hydrogen atom from the solvent by the phenyl
radical, homogeneous reduction of a solvent radical by the halobenzene radical–anion, and het-
erogeneous reduction of a solvent radical at the electrode surface. A paper by Isse and coworkers
[275] provides a fresh look at dissociative electron-transfer processes for the reduction of aromatic
bromides at carbon and silver electrodes.
Examples of electrosyntheses based on the reduction of monohalobenzenes are numerous.
Reductions of iodobenzene or bromobenzene at mercury [276] or bromobenzene at silver [277]
in carbon dioxide–saturated DMF afford benzoic acid. Bromobenzene, 3-methoxybromoben-
zene, 4-bromofluorobenzene, 4-(trifluoromethyl)chlorobenzene, and 1,2,4-trichlorobenzene can
be converted into aldehydes at a cadmium-coated stainless-steel cathode in DMF [278]. In the
presence of trimethylchlorosilane, silylation products arise from the reduction of various aryl
halides at platinum in DMF [165]. Reduction of p-iodoanisole at mercury in carbon dioxide–
saturated DMF produces p-anisic acid, anisole, and bis(p-anisyl)mercury [279]. Electrolysis
at a mercury cathode in diglyme containing a mixture of TBABF4 and dimethylpyrrolidinium
tetrafluoroborate has been used by Kariv-Miller and Vajtner [280] to convert fluorobenzene
to benzene. Chami and coworkers [281,282] electrolyzed substituted aryl halides in the pres-
ence of an olefin and a redox catalyst to synthesize arylated addition compounds; for example,
the reduction of 4-chlorobenzonitrile at platinum in liquid ammonia containing 4-chlorosty-
rene and 4,4′-bipyridine affords 1-(p-chlorophenyl)-2-(p-cyanophenyl)ethane. Bromobenzene
bearing an o-substituent can undergo electroreductive coupling with ethyl acrylate to form
an intermediate used to prepare benzolactones [283–285]. Aromatic aldehydes can be elec-
trosynthesized via the palladium-catalyzed carbonylation of aryl iodides (e.g., 4-iodophenol,
iodobenzene, and 1-iodo-2-methylbenzene) in the presence of formic acid [286]. Rondinini and
coworkers [250,251,287,288] have taken advantage of the electrocatalytic properties of silver

for the reduction of aromatic halides (see also Chapter 24).
Donnelly and coworkers [289,290] reported that the following intramolecular cyclization can be
performed at a mild-steel cathode in MeCN:
X N N N N
N N
N N
Mild-steel cathode
MeCN, TEABF4
F F
Electrolysis of an aryl halide at a cadmium-modified nickel cathode in DMF induces a for-

mylation reaction between aryl carbanions and the solvent [291]. Reduction of aryl halides
gives an aryl carbanion which, by acting as a base to deprotonate a nitrile, can cause coupling
of the nitrile with esters, aldehydes, and ketones [292,293]. Electrolysis of 1-iodonaphthalene
at carbon in propylene carbonate produces an aryl carbanion that attacks the solvent to form
an aryl ester [294], whereas reduction of aryl halides at copper, silver, and palladium cathodes
in propylene carbonate can be used to prepare biaryl compounds [295]. Electrochemical tri-
methylsilylation of aryl halides can be effected at a stainless-steel or carbon-cloth cathode in
THF–HMPA containing trimethylchlorosilane [296]. It has been shown [297–299] that aryl
boronic acids and esters can be synthesized via the reductive coupling of aryl halides (such as
p-chlorotoluene and o-bromoanisole) with a reagent such as a trialkylborate or pinacolborane;
this work has been extended to the use of benzyl halides [300], polyhaloarenes [301], and allylic
halides [302].
B. PoLYHaLobENZENES
Benzene bearing two different halogens (except for fluorine) can be reduced in a stepwise fashion.
For example, electrolysis of p-bromoiodobenzene gives bromobenzene (which can be further
reduced to benzene) [303], and reduction of p-fluoroiodobenzene yields fluorobenzene (which is
not reducible) [304]. Polychlorobenzenes can be selectively dechlorinated in DMSO by electrolysis
at mercury [305]. Studies have been made of the reductive dehalogenation of 1,3-difluorobenzene
[280], the electrocarboxylation of dichlorobenzenes [306], the electrochemical behavior of the
entire family of chlorinated benzenes [307] as well as their reductive carboxylation [308], and the
reductive coupling between 1,4-dichlorobenzene and 2,6-di-tert-butyl phenoxide [309]. In a study
of the reduction of di-, tri-, and tetrahalobenzenes at carbon in DMF [310], it was discovered that
1,2,4,5-tetrabromobenzene undergoes an electrolytically induced halogen dance. For the electroly-
sis of o-dihalobenzenes, benzyne has been proposed as an intermediate [311–315]. Mechanistic
studies of the reductive coupling of polyhalogenated nitrobenzenes have been reported by Andrieux
and coworkers [316].
A palladium-modified carbon-cloth cathode has been used by Kulikov and coworkers [272] for the
stepwise dechlorination of 1,2,3,5-tetrachlorobenzene and by Tsyganok and Otsuka [317] to carry out
the dechlorination of 2,4-dichlorophenoxyacetic acid. Electroreductive dechlorination of 5-chloro-2-
(2,4-dichlorophenoxy)phenol (triclosan) at a carbon cathode has been accomplished [318]. Voss and
coworkers [319] employed lead cathodes for the dehalogenation of chlorinated dibenzofurans and
dibenzo-p-dioxins; reductive carboxylation of the same compounds was investigated later [308].
C. HaLoGENaTED NITrobENZENES aND CYaNobENZENES

Radical–anions formed by the addition of a single electron to a monohalobenzene are extremely
short-lived. However, for some mono- and polyhalogenated nitrobenzenes and cyanobenzenes,
the electrogenerated radical–anions are sufficiently stable that their EPR spectra can be recorded.
Hawley [5] reviewed information about the electrochemistry of halogenated nitrobenzenes and cya-
nobenzenes, and Andrieux and coworkers [316] investigated the reduction of pentafluoronitroben-
zene and pentachloronitrobenzene at glassy carbon in MeCN.
D. HaLoGENaTED ArYL CarboNYLS

Product distributions have been determined for the electrolyses of pentafluorobenzaldehyde, pentaf-
luorobenzoic acid, and pentafluorobenzamide at mercury in aqueous media [320]. Reduction of the
a ldehyde gives pentafluorobenzyl alcohol and 2,3,5,6-tetrafluorobenzyl alcohol. Pentafluorobenzoic
acid is initially converted to a mixture of 2,3,5,6-tetrafluorobenzoic acid, pentafluorobenzyl alco-
hol, and 2,3,5,6-tetrafluorobenzyl alcohol; however, at a more negative potential, only the last two
products are obtained. Pentafluorobenzaldehyde and 2,3,5,6-tetrafluorobenzaldehyde are easier
to reduce than their benzoic acid analogues; therefore, the aldehydes cannot be isolated from elec-
trolyses of the acids. In sulfuric acid, electrolysis of pentafluorobenzamide gives pentafluorobenzyl
alcohol and 2,3,5,6-tetrafluorobenzyl alcohol. Using a lead cathode in sulfuric acid, Sato and cowork-
ers [321] selectively reduced pentafluorobenzoic acid to either 2,3,5,6-tetrafluorobenzyl alcohol or
2,3,5,6-tetrafluorobenzaldehyde.
Fry and coworkers [303] observed that electrolysis of m-bromoacetophenone at mercury
in DMF affords acetophenone, whereas reduction of p-bromo-γ-chlorobutyrophenone gives
γ-chlorobutyrophenone.
Halogenated benzophenones behave in two different ways in nonaqueous solvents such as
DMF, DMSO, and MeCN [322]. For m-fluoro-, p-fluoro-, and m-chlorobenzophenone, a pair of
electrons is apparently involved in the reduction, and benzophenone is produced quantitatively.
However, for the electrolysis of p-chloro-, m-bromo-, and p-bromobenzophenone, fewer than
two electrons per molecule are transferred, and benzophenone is obtained in less than 100%
yield. Reduction and carboxylation of halobenzophenones have been investigated by Isse and
coworkers [323].
Reduction of 2-bromo- and 2-iodo-4′-methoxy-N-methylbenzanilide at mercury in DMF
involves one-electron cleavage of the carbon–halogen bond to yield a radical intermediate [324,325],
which can undergo (1) further reduction and protonation to give 4′-methoxy-N-methylbenzanilide,
(2) intramolecular cyclization to afford 2-methoxy-N-methylphenanthridinone, or (3) rearrange-
ment followed by hydrogen atom abstraction to yield 4′-methoxy-N-methylbiphenyl-2-carboxamide.
E. HaLoGENaTED BIpHENYLS
Electroreduction of mono- and polychlorobiphenyls at mercury proceeds via sequential two-elec-
tron loss of chloride; however, due to the varied pattern of chlorine substitution, more than one
product can form [326,327]. Maruyama and Murakami [328] reported that chlorinated biphenyls
are reduced in DMF via one-electron cleavage of a carbon–chlorine bond to yield chloride and an
aryl radical, which subsequently abstracts a hydrogen atom from the solvent. Several monochlorobi-
phenyls have been reduced at lead [307], and their reductive carboxylation has been achieved [308].
Rusling and Arena [329] have probed the reduction of 4-bromo-, 4,4′-dibromo-, 3,4-dichloro-, and
2,2′,5,5′-tetrachlorobiphenyl at mercury.
Using a variety of electrodes, including glassy carbon, gold, palladium, and platinum, Simonet
and Jouikov [330] found that reduction of 9-bromofluorene produces the 9-fluorenyl radical that
appears to be grafted onto the surface of the cathode (see also Chapter 42).
VIII. AcYL HALiDES

Using mercury cathodes, Barba and coworkers have investigated the electrochemical reduction of
benzoyl chloride [331], 1-naphthoyl chloride [331], 2-naphthoyl chloride [331], phthaloyl dichloride
[332], cinnamoyl chloride [333], and 2- and 4-nitrobenzoyl chloride [334] (see also Chapter 32).
Electrolysis of benzoyl chloride gives an acyl radical that dimerizes to yield benzil; the latter spe-
cies accepts two electrons and undergoes double acylation by benzoyl chloride to afford a mixture
of (E)- and (Z)-1,2-diphenylethene-1,2-diyl dibenzoate [232]. Cinnamoyl chloride [333] accepts one
electron to form an acyl radical that abstracts a hydrogen atom from the medium to give an interme-
diate ketene, which then dimerizes.
Reduction of benzoyl chloride and benzoyl fluoride at carbon and platinum cathodes in
MeCN has been carried out by Cheek and Horine [335]. A study [336] of the effect of poten-
tial on the reduction of benzoyl chloride at mercury and carbon in MeCN revealed that acyl
radicals and acyl anions are both involved as intermediates. In the same work [336], reduc-
tion of heptanoyl chloride was explored. Folest and coworkers [337] obtained symmetrical di-
ketones by reducing aroyl and arylacetyl chlorides at nickel in MeCN. Other acyl chlorides that
have been investigated include glutaryl dichloride [338], trimethylacetyl chloride [339], cyclo-
hexanecarbonyl chloride [340], phenylacetyl chloride [341], hydrocinnamoyl chloride [341],
phthaloyl dichloride [342], 2-furoyl chloride [343], and 2,4,6-trimethylbenzoyl chloride [344].
Quantitative conversion of 1-adamantanecarbonyl chloride to 1-adamantanecarboxaldehyde
has been accomplished [345].
Lozano and Barba [346] reduced 2-chloro-2-phenylacetyl chloride at mercury to synthesize
derivatives of pyran-2-one and pyran-4-one (see also Chapter 34):
H O
2e, –2Cl–
Ph C C Ph C C O
H
Cl Cl
Trimerization
OH O
Ph Ph Ph Ph
+
O O O OH
Ph Ph
In addition, these workers investigated the reduction of 2-bromo-2,2-diphenylacetyl bromide at

graphite in the presence of inorganic sulfur compounds and obtained a new sulfurated heterocyclic
product [347–349].
IX. PhENAcYL HALiDES

Papers concerning the electrochemistry of phenacyl bromides have been published by Barba and
coworkers [350–360]. Reduction of 2-bromo-1-phenylethanone at mercury affords 2,4-diphenylfuran
[350,351]. Other compounds similarly synthesized include 2,4-bis(4-methoxyphenyl)furan,
2,4-bis(4-biphenylyl)furan, 2,4-bis(4-bromophenyl)furan, and 2,4-bis(4-nitrophenyl)furan. Products
arising from the reduction of 2-bromo-1-phenylethanone are strongly influenced by the addi-
tion of proton donors and other reagents; for example, electrolysis of 2-bromo-1-phenylethanone
in the presence of ethyl bromoacetate gives cyclopropane-1,2,3-triyltris(phenylmethanone) and
3,5-diphenylfuran-2(3H)-one [352].
By protecting the carbonyl group of a phenacyl bromide through reaction with semicarbazide
hydrochloride, one can synthesize a variety of 2,5-diarylfurans [353]. In addition, reductive dimer-
ization of the semicarbazone derivative of 2-bromo-1-phenylethanone can be employed to form
3,6-diphenylpyridazine in excellent yield; this method is suitable for the preparation of a variety of
3,6-diarylpyridazines [354].
Reduction of α-bromopropiophenone at mercury gives 1,4-diphenyl-2,3-dimethylbutan-1,4-dione
[355], but electrolysis of α-bromopropiophenone in the presence of benzoyl chloride affords only
1,3-diphenyl-2-methylpropan-1,3-dione. Other studies involving reduction of phenacyl bromides
include the synthesis of 4-aryl-2-methylfurans [356] and of enol carbonates [357]. Semicarbazones
of 2-bromo-1-phenylethanone can be converted into 3,7-diaryl-2H-imidazo[2,1-b][1,3,4]oxadiazines
[358]. Reduction of 1,2-dibenzoylchloroethane at mercury in DMF affords mixtures of phenyl
tribenzoyl cyclopentanols and diphenyl dibenzoyl butanediones [359]. Electrolysis of 2-bromo-
3-oxo-3-phenylpropanenitrile results in the formation of (2-amino-5-isocyano-4-phenylfuran-3-yl)-
(phenyl)methanone [360]:
O
NC NH2
O Br
H5C6 C CH
H5C6 C6H5
CN
Electrolytic reduction of 2,2-dibromo-1-phenylethanone in DMF gives (E)-(3-(dibromomethyl)-

3-phenyloxiran-2-yl)(phenyl)methanone and trans-cyclopropane-1,2,3-triyl(phenylmethanone) [361].
X. ALiPhATic α-HALOcARBONYL COMPOUNDS

Polarographic studies of aliphatic α-haloaldehydes in water–dioxane [362,363] have shown
that reduction of these compounds is influenced by the equilibrium involving the hydrated
and unhydrated forms of the aldehyde. Each carbon–halogen bond is cleaved in a two-electron,
one-proton process, and the final nonhalogenated aldehyde is reduced at a more negative
potential [364].
At a mercury cathode in DMF, 2-bromo-1-phenylethanone can undergo either simple
carbon–bromine bond cleavage or reductive coupling [365]. Reduction of 2-bromo-3-p entanone
in DMF–H 2O affords a mixture of 3-pentanone and 1-hydroxy-3-pentanone [366]. In the same
study, electrolysis of α,α′-dibromoacetone in the presence of benzoate resulted in both
cleavage of a carbon–bromine bond and SN2 displacement of bromide by benzoate. In an acetic
acid–sodium acetate buffer, reduction of branched dibromo ketones, such as 2,4-dibromo-
2,4-d imethyl-3-pentanone, gives α-acetoxyketones in excellent yield; less highly substituted
s pecies, such as 4,6-dibromo-5-nonanone, undergo reductive cleavage of both carbon–bromine
bonds [367–369].
Depending on experimental conditions, reduction of bis(α-bromocyclopropyl) ketone in an acetic
acid–sodium acetate buffer can yield either α-bromocyclopropyl cyclopropyl ketone or dicyclopropyl
ketone [370]. Electrolyses of 2,4-dibromo-2-methylpentan-3-one and of 2,4-dibromo-1,5-diphenyl-
1,4-pentadien-3-one have been reported [371,372]. Low-temperature reduction of alkylated α,α′-
dihaloketones to cyclopropanones can be accomplished with highly alkylated starting materials,
and electrochemical cyclization of 1,3-dihaloketones (with carbonyl moieties protected as acetals,
acylals, or aminals) can produce cyclopropanone derivatives [373]. Using mercury cathodes in
DMF, Inesi et al. [374] reduced α,α′-dichloroketones in the presence of carboxylic acids, phenols,
or diethyl malonate to obtain a variety of products. Reduction of 1,1,3-tribromo- or 1,1,3-trichloro-
3-methyl-2-pentanone in the presence of amines or phenols gives the α,β-unsaturated amides or
esters [375]:
O O
H5C2 Cl H5C2 C
C
H 2e, –2Cl–
C C C CH
Cl CH3 Cl H3C Cl
PhCH2NH2
H5C2 O
C C CH2Ph
H3C C N
H
Inesi and coworkers [376] carried out the diastereoselective electrocarboxylation of chiral N-(2-
bromoacyl)oxazolidin-2-ones. In earlier work, reduction of α,α′-di- and trichloroketones in the pres-
ence of oxazolidin-2-ones provided a synthetic route to N-enoyloxazolidin-2-ones [377].
Barba and coworkers [378] reported that α-bromodibenzoylmethane is the only product
obtained via reduction of α,α-dibromodibenzoylmethane at platinum or mercury in DMF.
In aqueous media, α-halocarboxylic acids as well as their esters undergo two-electron, one-
proton reductive cleavage [379–381]; reduction of chloro- and dichloroacetic acids and their
ethyl esters has been studied in DMF [382]. Electrolysis of ethyl bromoacetate at mercury in
slightly wet DMF gives mainly ethyl acetate and diethyl succinate, whereas reduction of ethyl
trichloroacetate in the presence of acrylonitrile affords 1-carbethoxy-1-chloro-2-cyanocyclo-
propane and 1-carbethoxy-1,1,3-trichloro-3-cyanopropane [95]. Electroreductive activation of
methyl 2,2,2-trichloroacetate in the presence of cyclohex-2-enone yields a bicyclic chlorocy-
clopropane [383]. Reduction of ethyl 2-bromo-2-phenylacetate affords a mixture of meso- and
d,l-diethyl-2,3-diphenylsuccinate [384]; analogous behavior is exhibited by methyl 2-bromo-
2-phenylpropanoate [385] and by ethyl α-bromonaphthalene-1-acetate [386]. Direct and indirect
reduction of ethyl 3-bromopropanoate and ethyl 4-bromopentanoate has been investigated with
carbon, gold, and mercury cathodes [387]. Reactions of carbanions (formed via reduction of
bromoesters) with β-, γ- and δ-bromoesters have been probed [388,389]. Electrolysis of diethyl
2,2′-(1,2-phenylene)bis(2-bromoacetate) affords a mixture of carbocyclic products [390].
Reduction of ethyl α-bromo-9-anthrylacetate at glassy carbon yields 9,10-anthraquinone [391].
Electrolysis of decyl dichloroacetate or trichloroacetate at stainless steel in the presence of a
trialkylborane causes loss of a chlorine moiety and its replacement with an alkyl group [392].
Preparative-scale reduction of ethyl 2-bromo-3-(3′,4′-dimethoxyphenyl)-3-(propargyloxy)pro-
panoate has been carried out at vitreous carbon cathodes [393]. Giomini et al. [394,395] inves-
tigated the reduction of ethyl α,β-dibromopropanoate, ethyl α,γ-dibromobutyrate, and methyl
α,δ-dibromovalerate. Reduction of 2,2-dibromo-1H-indene-1,3(2H)-dione in dichloromethane
has been studied [396]. Two papers deal with the electroreductive intramolecular cyclization of
dimethyl dibromoalkanedioates [397,398]:
O
O Br
OCH3
H CH OCH3 2e
H3CO C Pt cathode OCH3
Br O
O
Reduction of α-haloamides at mercury in DMF has been reported [399,400]; biologically active
N-benzyloxazolidine-2,4-dione was prepared by the electrolysis of a solution containing α-chloro-
N-benzylacetamide, carbon dioxide, and a probase. Maran et al. examined the electrochemical
reductions of 2-bromocarboxamides [401] and 2-bromo-2-methylpropanamides [402] as well as the
electrocarboxylation of 2-bromoisobutyramides [403]. In other research, Maran [404] studied the
reduction of several α-haloamides, and Casadei and coworkers carried out the reductive dehalogena-
tions of 1-acetamido-2,2,2-trichloroethyl acetate [405] and of substituted N-(2,2,2-trichloroethyl)-
acetamides [406–408]. Reduction of compounds such as 2-bromo-N-cyclohexylacetamide to
N-cyclohexylacetamide has been examined [409], and reductive cyclization of diethyl 2-(2-bromo-
N-(4-methoxyphenyl)acetamido)malonate and its analogues affords a lactam [410,411]; reduction
of a 3-halo-β-lactam in the presence of acetic anhydride gives the corresponding 3-acetyl-β-lactam
[412]. Electrochemical reduction of additional haloamides has been carried out [413–416].
XI. HALOGENATED HETEROcYcLic COMPOUNDS

Halogenated heterocyclic substances tend to display electrochemical behavior similar to that of aryl
halides; the carbon–halogen bond is reductively cleaved in a process involving two electrons and a
proton to give a hydrogenated product.
A. HETEroCYCLIC CoMpoUNDS wITH ONE NITroGEN AToM

Polarographic studies of aqueous solutions of monohalogenated pyridines (e.g., 4-chloro, 2-bromo-,
and 3-iodopyridine), in either their unprotonated or protonated form, reveal a two-electron cleav-
age of the carbon–halogen bond, followed by protonation to give pyridine [417–422]. Reduction
of 2-chloro-3-nitropyridine in DMSO initially yields a stable radical–anion [423], which is
dechlorinated at a more negative potential to form the 3-nitropyridine radical–anion. Andrieux
and coworkers [274] employed redox catalysis to probe the reduction of 2-bromo-, 3-bromo-,
2-chloro-, and 3-chloropyridine at mercury in DMF. Reduction of 2,5-dibromo-, 2,3-dichloro-,
and 2,6-dichloropyridine in EtOH–water was studied by means of polarography [424], and bulk
reduction of mono- and dihalopyridines at carbon cathodes in DMF has been carried out [425].
Reductive coupling of monohalopyridines with carbon dioxide affords the corresponding carbox-
ylic acids [426]. Electrochemical reduction of pentafluoropyridine and pentachloropyridine has
been reported [427], and several patents pertaining to reductive dechlorination of pentachloropyri-
dine have appeared [428–430]. Gennaro and coworkers [431] synthesized 6-aminonicotinic acid by
electrolyzing 2-amino-5-halopyridines at silver in the presence of carbon dioxide:
Br CO2H
e, –Br–, e, CO2, H+
Ag cathode
H2N N H2N N
Alwair and Grimshaw [432] studied the reduction of 6-chloroquinoline. In subsequent research by
Fuchs and coworkers [433], the electrochemical carboxylation of a number of chlorinated quino-
lines was investigated in the absence and presence of carbon dioxide. According to Kyriacou
et al. [434], reduction of 3,4,5,6-tetrachloro-2-picolinic acid at a silver electrode in an aqueous
medium yields 3,4,6-trichloro-2-picolinic acid, which can be further reduced to 3,6-dichloro-2-
picolinic acid.
B. HETEroCYCLIC CoMpoUNDS wITH Two NITroGEN AToMS

Electrochemical reduction of 6-chloroquinoxaline in DMF affords a stable radical–anion,
whereas the bromo and iodo analogues accept one electron to yield radical–anions, which undergo
f ragmentation and hydrogen atom abstraction to form quinoxaline [432]. In similar fashion,
2-bromo- and 2-chlorophenazine are reversibly reduced to stable radical–anions, but the radical–
anion of 2-iodophenazine decomposes to yield iodide ion and phenazine [432]. Lund [435] observed
that reduction of 4-chloroquinazoline results in two-electron cleavage of the carbon–chlorine bond
to form quinazoline. In addition, the electrochemical reduction of halogenated pyrimidines has
been described in several publications [436–440]. A survey of the electrochemistry of chlorinated
pyrazines, quinoxalines, and pyridazines has appeared [441].
C. OTHEr HETEroCYCLIC SpECIES

Laviron [417] investigated the polarography of halogenated thiazoles, and Iversen [442] synthesized
thiazole in 88% yield by reducing 2-bromothiazole at mercury in an acidic water–EtOH medium.
Reduction of 2-bromothiazole at carbon in MeCN involves both radical and carbanion intermedi-
ates, with thiazole being the only product [443].
Polarographic studies of brominated and iodinated thiophenes in aqueous and nonaqueous
media have been undertaken [444–448]. Feldmann and Koberstein [449] probed the reduction
of 2,3,5-tribromothiophene at mercury, and Pletcher and Razaq [450] synthesized 3-bromothio-
phene by reducing 2,3,5-tribromothiophene at various cathodes in dioxane–water. Reduction of
tetrabromothiophene, tetraiodothiophene, 2,3,4-tribromothiophene, and 3,4-dibromothiophene
in DMF has been described by Gedye and coworkers [451]. Electrosyntheses of 3-bromo- or
3,4-dibromothiophene, of 3,4-dibromo-2-chlorothiophene, and of 3-bromo-4-chlorothiophene have
been developed by Dapperheld and coworkers [452]. Reduction of several dihalothiophenes at car-
bon in DMF involves an electrolytically induced halogen dance [453]. Justice and Hall [454] synthe-
sized 3-hydrobenzo[b]thiophene by reducing a substituted 3-chlorobenzo[b]thiophene. Reduction
of 3,3-dichloroisobenzofuran-1(3H)-one provides a pathway to the synthesis of 3-substituted
phthalides [455].
Casadei and coworkers [456] studied the reduction of 3-halo-β-lactams and 3,3-dihalo-β-lactams
in DMF. In the presence of carbon dioxide, a trans-3-halo-1,4-diphenylazetidin-2-one can be con-
verted into trans-3-carboxy-1,4-diphenylazetidin-2-one; without carbon dioxide, the major product
is the dehalogenated β-lactam.
XII. INDiREcT OR CATALYTic CLEAvAGE Of CARBON–HALOGEN BONDS

Direct electrolytic cleavage of a carbon–halogen bond is an intrinsically irreversible process. Thus,
the potential needed to reduce a carbon–halogen bond heterogeneously at an electrode is often much
more negative than the thermodynamically reversible potential. However, carbon–halogen bonds
can be cleaved chemically with electron-transfer mediators (catalysts) that are electrogenerated at
potentials more positive than those required for direct reduction of the carbon–halogen bond. In a
classic application of this concept, Lund and coworkers [457] used the electrogenerated radical–
anion of chrysene to reduce bromobenzene catalytically.
A. ELECTroGENEraTED RaDICaL–ANIoNS aS MEDIaTorS

Numerous studies [457–463] have shown that the rate of electron transfer between an electrogen-
erated radical–anion (mediator) and a halogenated organic compound (substrate) increases as the
difference between the standard potentials for the reduction of the precursor of the mediator and for
the reduction of the substrate decreases.
Reactions of 1-bromo- and 1-chlorobutane with the electrogenerated radical–anions of
trans-stilbene and anthracene in DMSO have been examined [458]. Cyclization of N-allyl-2-
chloroacetanilide to 1-(3-methylindolin-1-yl)ethanone occurs in the presence of the radical–anion
of trans-stilbene [459]:
O O
CH3
ClCH2 N N
Radical-anion
of trans-stilbene
CH3
For the reaction between alkyl halides and the electrogenerated naphthalene radical–anion, Sease
and Reed [460] observed that only alkyl chlorides, such as 1-chlorohexane and 6-chloro-1-hexene,
are catalytically reduced. Britton and Fry [461] elucidated the kinetics of the electron-transfer reac-
tion between 1-chlorooctane and the phenanthrene radical–anion in DMF.
Another feature of reactions between alkyl halides and electrogenerated aromatic radical–anions
should be mentioned. After a single electron has been transferred to the alkyl halide (substrate) to
form an alkyl radical, that radical can (1) react with another radical–anion (mediator) to form an
alkyl carbanion (R−), which is protonated to form RH or (2) bond with the radical–anion to yield
an alkylated aromatic hydrocarbon. An example of the latter process is seen in the electrolysis of
stilbene in DMF containing tert-butyl chloride [464]. A recent expansion of this concept is the
catalytic reduction of alkyl halides at silver–palladium cathodes in the presence of arenes to afford
alkylated products [465].
Other studies of the reactions of alkyl halides with electrogenerated radical–anions include
reduction of diketones in the presence of methyl halides [466], reduction of nitrobenzene in the
presence of alkyl halides [467], reductive coupling of 1,2- and 1,3-dihaloalkanes with anthra-
cene [468], reductive coupling of phenylacetylene with alkyl halides [469], electron transfer
between meso- or d,l-1,2-dichloro-1,2-diphenylethane and electrogenerated radical–anions [470],
and reductive coupling of tert-butyl bromide with azobenzene, quinoxaline, and anthracene
[471]. Reactions between halogenated organic compounds and electrogenerated radical–anions
have been extended to unsubstituted and substituted benzyl chloride [472]; to vinyl bromides,
2-bromoindene, and 7,7-dichlorobicyclo[4.1.0]heptane [473]; to bornyl, isobornyl, and exo- and
endo-norbornyl bromides [474]; and to lindane [475]. Inesi [476] has investigated the indirect
reduction of bromo esters by the electrogenerated radical–anions of pyrene, anthracene, diphenyl-
anthracene, and fluoranthene.
B. TraNSITIoN-METaL CoMpLEXES aS MEDIaTorS

Nédélec and coworkers [477] have reviewed the subject of organic electroreductive coupling reac-
tions that utilize transition-metal complexes as catalysts. Durandetti and Périchon [478] published
a short review of nickel-catalyzed coupling reactions involving the reactions of aryl, heteroaryl,
and vinyl halides with activated alkyl halides. Papers by Duñach et al. [479,480] describe the use
of nickel and palladium species as catalysts for the reduction of halogenated organic compounds.
Classically, the two most important transition-metal catalysts for the reduction of halogenated
organic compounds have been electrogenerated low-valent nickel and cobalt species. Papers by
Pletcher and coworkers [481–485] introduced the catalytic reduction of various bromoalkanes by
electrogenerated nickel(I) complexes; ligands coordinated to nickel(I) included Schiff bases and
macrocyclic tetraamines. Although organonickel(III) intermediates were proposed for these reac-
tions, no definitive evidence for these species has been reported.
In contrast to the behavior of nickel(I) complexes as mediators, the catalytic reactions of alkyl
halides with electrogenerated cobalt(I) species such as vitamin B12s, cobaloximes(I), and cobalt(I)
salen exhibit a significant difference. Cobalt(I) species, acting as potent nucleophiles in SN2 reac-
tions with alkyl halides, give stable and identifiable organocobalt(III) intermediates. Lexa and
coworkers [486] articulated the mechanism for the catalytic reduction of 1-bromobutane by electro-
generated cobalt(I) tetraphenylporphin.
In Sections XII.B.1 through XII.B.3, examples of catalytic reductions of halogenated organic
compounds by electrogenerated nickel(0), nickel(I), cobalt(I), and other species are mentioned.
1. Nickel Complexes
Electrogenerated (2,2′-bipyridine)nickel(0) complexes serve as catalysts for many syntheses:
(1) formation of ketones from acyl halides and either alkyl or aryl halides [487,488]; (2) pro-
duction of β,γ-unsaturated esters via coupling of α-haloesters with aryl or vinyl halides [489];
(3) coupling of α-chloroesters or α-chloronitriles with carbonyl compounds [490]; (4) formation
of unsymmetrical biaryls from a mixture of two aryl halides [491]; (5) reduction of alkyl halides
or α,ω-dibromoalkanes to form dimers [492]; (6) coupling of alkyl, benzyl, and aryl halides [493];
(7) formation of α-arylated ketones via coupling of α-chloroketones with aryl halides [494];
(8) cross-coupling of aryl halides and ethyl chloroacetate [495]; (9) coupling of aryl halides
and activated olefins [496]; (10) cross-coupling between aryl halides and activated alkyl halides
[497]; (11) formation of ketones via coupling of organic halides with carbon monoxide [498–500];
(12) production of ketones via reduction of a mixture of a benzyl or alkyl halide with a metal
carbonyl [501]; (13) preparation of symmetrical ketones from alkyl, benzyl, and aryl halides [502];
(14) synthesis of 2-arylpyrimidines and 2-arylpyrazines from 2-chloropyrimidine and 2-chloro-
pyrazine (in the presence of aryl halides) [503]; (15) formation of aryl thioethers from aryl halides
and thiophenol [504]; (16) preparation of aryl propan-2-ones via coupling of benzylic chlorides
with an acyl donor species [505]; (17) dehalogenation of chlorinated benzenes and dibenzofurans
[506]; (18) homocoupling of 2-bromomethylpyridines [507]; (19) electrocarboxylation of substi-
tuted aryl halides [508]; (20) synthesis of 2-arylpyridines via cross-coupling of aryl and pyridyl
halides [509,510]; (21) coupling of 2- and 3-bromothiophene with alkyl and alkenyl halides [511];
(22) synthesis of 3-thienylzinc bromide from 3-bromothiophene [512]; (23) preparation of unsym-
metrical ketones via reduction of mixtures of benzyl and aryl halides in the presence of iron
pentacarbonyl [513]; (24) synthesis of 2,2-difluoro-3-hydroxyesters from methyl chlorodifluo-
roacetate and carbonyl compounds [514]; (25) preparation of conjugated dienes via homocou-
pling of alkenyl halides [515]; and (26) coupling of aryl halides with chlorodiphenylphosphine or
dichlorophenylphosphine [516].
Additional electrosyntheses based on the use of (2,2′-bipyridine)nickel(0) species include cross-
coupling of aryl halides with arenecarboxaldehydes to afford arylated secondary alcohols [517,518],
reductive polymerization of 3-substituted 2,5-dihalothiophenes [519], homocoupling of 2-bromo-
methylpyridines [520], cross-coupling of aryl halides with 3-chloropyridazines to yield arylpyr-
idazines [521], homo- and cross-couplings of alkenyl halides [522], cross-coupling between aryl
halides and α-chloropropanoic acids bearing chiral auxiliaries [523], synthesis of arylzinc com-
pounds via reduction of aryl halides in a cell with a sacrificial zinc anode [524], reductive coupling
of a variety of organic halides [525,526], coupling of methyl 2-chloroacetate with ketones [173],
coupling of 3-chloro-2-methylprop-1-ene with ketones and aldehydes [173], homocoupling of
o-substituted aryl halides and their heterocoupling with m- or p-substituted aryl halides [527], cou-
pling of allylic chlorides or acetates with carbonyl compounds to form homoallylic alcohols [528],
and coupling of α-haloesters with aryl or vinyl halides [489,529].
Nickel-catalyzed formation of cyclopropyl derivatives via coupling of activated olefins with
gem-dibromoalkanes has been described [530], along with homocoupling of alkyl halides as well
as cross-coupling of organic halides with activated olefins in an ionic liquid [531]. Reductive nickel-
catalyzed conjugate addition of (Z)- or (E)-alkenyl halides to electron-deficient olefins affords
functionalized pure (Z)- or (E)-olefins in high yield [532], and heteroaryl halides (e.g., monohalo-
genated pyridines, quinolines, and thiophenes) can be coupled with 3-buten-2-one [533]. Nickel(0)
in the presence of potassium iodide promotes the conversion of nonactivated aryl bromides to
aryl iodides [534]. Dimerization of halobenzenes as well as arylation of activated olefins can be
accomplished with electrogenerated low-valent nickel complexes involving bipyridylamine ligands
[535]. Electrogenerated nickel(0) pyridine complexes serve as catalysts for the coupling of aryl
halides with 3,3-diethoxyprop-1-ene [536], the conjugate addition of substituted aryl bromides to
but-3-en-2-one [537], and the synthesis of lactones via the arylation of α,β-unsaturated carboxylic
esters [538].
Nickel(0) triphenylphosphine species have been used for the conversion of allyl halides
to 1,5-hexadiene [539], for the reductive coupling of ethylene with aryl halides to give
1,1-diarylethanes [540,541] and styrene [542], for the coupling of aryl halides and alkenes to pre-
pare substituted olefins [543], for the synthesis of ethyl 2-phenylacetate from ethyl-2-haloacetates
[544], for the preparation of biaryls from aryl halides [545,546], and for the electrosynthesis
of aryl carboxylates from aryl halides and carbon dioxide [547]. Nickel(0) tributylphosphine
complexes have been used to catalyze the reduction of aryl and alkyl halides [548]. In addition,
1,2-bis[(di-2-propylphosphino)benzene]nickel(0) has been used for the reductive coupling of aryl
halides [549]; 1,3-bis[(diphenylphosphino)propane]nickel(0) catalyzes the reductive carboxyl-
ation of 1-chloroethylbenzenes [550]; and 1,2-bis[(diphenylphosphino)ethane]nickel(0) has been
employed to synthesize biphenyl from bromobenzene [551,552], to prepare benzoic acid from
bromobenzene in the presence of carbon dioxide [553,554], to electropolymerize 1,4-dibromo-
benzene into poly(1,4-phenylene) [555], and to catalyze the reductive carboxylation of bromoben-
zene to benzoic acid [556].
Electrogenerated nickel(I) salen has been used as a catalyst for the reductive intramolecu-
lar cyclizations of 6-bromo- and 6-iodo-1-phenyl-1-hexyne [557], 6-bromo-1-hexene [558–561],
and other acetylenic halides [562]; the reduction of several α,ω-dihaloalkanes [563]; the reduc-
tive coupling of 2-bromo- and 2-iodoethanol to prepare 1,4-butanediol [564]; the conversion
of cyclohexanecarbonyl chloride to a tetramer [565]; electrocarboxylation of benzylic halides
[566] and arylethyl chlorides [567]; and the reductions of benzal chloride [568] and 1-bromooctane
[569]. In the presence of dioxygen, light, and water, electrogenerated nickel(I) salen can pro-
mote the reduction of alkyl monohalides to aldehydes and ketones [570–572]. An unanticipated
consequence of the use of nickel(I) salen (or of nickel(I) with salen-like ligands) is that the
phenyl-conjugated imino bonds of the ligand become alkylated by fragments of the original
substrate [573,574]; this phenomenon, which destroys the action of the nickel(I) species as a
mediator, is linked to the occurrence of ligand-centered (instead of metal-centered) reduction
of the parent nickel(II) complex [575], a problem that can be overcome, at least in part, by the
synthesis of ligands with sterically bulky groups on the imino bonds [576]. Electrogenerated
nickel(I) salen has been used to promote ring-expansion reactions of some 1-haloalkyl-2-
oxocycloalkanecarboxylates [577]. Duñach and coworkers have utilized electrogenerated
nickel(I) salen species for the intramolecular cyclizaton of some unsaturated 2-bromophenyl
ethers [578,579]:
Br
CH3
Nickel(I)
C cathode
O CH3 DMF, TBABF4
H3C H3C
CH3 CH2
O O
Various electrogenerated nickel(I) tetraazamacrocycles with ligands such as cyclam, tetramethylcy-

clam, and hexamethylcyclam act as catalysts for the reduction of allyl o-halophenyl ethers [580] as
well as the reductive intramolecular cyclizations of o-haloaryl compounds possessing unsaturated
side chains [581–583] and of bromo propargyloxy esters [584–589]. Recent papers have extended the
preceding applications to environmentally friendly media such as alcohols and water–alcohol mix-
tures [590–595]. Espenson and coworkers used such catalysts to reduce alkyl and benzyl halides [596–
599], α,ω-dihaloalkanes [600,601], 1-bromo-4-cyanobutane [602], and other halogenated compounds
[603]. Using this same class of catalysts, Ozaki and coworkers carried out a number of interesting
electrosyntheses: (1) intramolecular cyclization of 2-bromoalkyl- and 3-bromoalkyl-2-cyclohexen-1-
ones [604]; (2) radical cyclization of halogenated ethers [605]; (3) intermolecular addition of alkyl
radicals to activated olefins [606]; (4) intramolecular cyclization of n-allylic and n-propargylic
α-bromoamides and of o-bromoacryloylanilides to give five-membered lactams [607]; (5) cyclization
of vinyl and aryl halides [608]; (6) cyclization of α-bromo- and α-iodoamides [609]; (7) cyclization of
acetylenic halides to prepare functionalized (methylene)cyclopentanes [610]; (8) stereoselective addi-
tion of n-, sec-, and tert-butyl radicals to α-methylenebutyrolactones [611]; (9) reduction of 2-bromo-
and 2-iodo-1,6-dienes to give bicyclo[3.1.0]-, 3-azabicyclo[3.1.0]-, and 3-oxabicyclo[3.1.0]hexane
derivatives [612], and preparation of pyrrolopyridines and pyrrolopyrrole derivatives via reductive
cycloaddition of 1-(2-iodoethyl)pyrrole to activated olefins or cyclization of 1-(ω-iodoalkyl)pyrroles
[613]. Production of ethylene oxide via catalytic reduction of 2-haloethanol by nickel(I) cyclam has
been reported [614]. Gómez and coworkers [615] converted nickel and palladium tetraazamacrocyclic
complexes to their corresponding zero-valent states to reduce unsaturated o-haloaryl and o-halobenzyl
ethers; the nickel(0) complex induced intramolecular cyclization, whereas the palladium(0) complex
caused cleavage of the carbon–oxygen bond of the ethers. Electrogenerated nickel(I) cyclam has been
used by Pelletier et al. [616] to produce dihydrobenzo[b]thiophenes from o-haloaryl allyl thioethers
and by Nunnecke and Voss [506] to dehalogenate chlorinated benzenes and dibenzofurans.
Stolzenberg and coworkers used electrogenerated nickel(I) tetrapyrrole complexes for the cata-
lytic reduction of dichloromethane and methyl iodide [617], alkyl halides [618–620], and aryl halides
[620]. Catalytic reduction of trans-1,2-dibromocyclohexane to cyclohexene by electrogenerated
nickel(I), cobalt(I), and iron(I) porphyrin complexes was investigated by Lexa et al. [621], whereas
reactions of simple alkyl bromides with aromatic radical–anions and low-valent iron porphyrins
were considered in a later study [622]. Electrochemical polymerization of 1,4-bis(chloromethyl)
benzene in the presence of catalytic amounts of nickel(II) chloride has been employed to prepare
poly-p-xylylene [623]. Functionalized indanes and naphthalenes have been electrosynthesized via a
nickel-catalyzed arylation of activated olefins (e.g., acrylonitrile or ethyl acrylate) [624].
2. Cobalt Complexes
Allyl halides have been reduced with electrogenerated tris(2,2′-bipyridine)cobalt(I) to afford
1,5-hexadiene [625,626]. Early work with cobalt(I) salen involved its use for the catalytic reduction
of bromoethane [627], bromobenzene [627], and tert-butyl bromide and chloride [628]. Fry and
coworkers examined the cobalt(I) salen-catalyzed reductions of benzal chloride [629–631] and
of benzotrichloride [632]. Cobalt(I) salen-mediated reductions of 1-bromobutane [633,634],
1-iodobutane [634], 1,2-dibromobutane [634], benzyl and 4-(trifluoromethyl)benzyl chlorides [635],
arylmethyl chlorides [636], iodoethane [637], diphenyl disulfide [638], 1,8-diiodooctane [639],
3-chloro-2,4-pentanedione [640], ethyl chloroacetate [641], 2,6-bis(chloromethyl)pyridine [642],
(3-chloro-1-propen-1-yl)benzene [643], and 1-halonaphthalenes [644] have been investigated. Folest
et al. [645] studied the cobalt(I) salen-promoted carboxylation of benzylic and allylic chlorides.
A report concerning the catalytic reduction of ethyl chloroacetate by electrogenerated cobalt(I)
salophen has appeared [646].
Rusling and coworkers carried out extensive studies of the use of electrogenerated cobalt(I)
c omplexes (including cobalt(I) salen, vitamin B12s, and cobalt(I) phthalocyanine) as catalysts both in
homogeneous phase and in bicontinuous microemulsions [647] (see also Chapter 8) for the reductions
of 1,2-dibromoethane and 1,2-dibromobutane [648]; the debromination of alkyl vicinal dibromides
[649]; the dechlorination of DDT [650]; the reductions of 1-bromobutane, 1-bromododecane, and
trans-1,2-dibromocyclohexane [651–653]; the reduction of benzyl bromide [654]; the addition of
primary alkyl iodides to 2-cyclohexen-1-one to afford 3-alkylcyclohexanones [655]; and the reduc-
tive intramolecular cyclization of 2-(4-bromobutyl)-2-cyclohexen-1-one to 1-decalone [653,655].
Cobalt(I) salen is a mediator for the dechlorination of DDT and its less chlorinated congeners
[656], CFC-113 [657,658], CFC-113a [659], and hexa- and pentachlorobenzene [660]. Moreover,
4-methylcoumarin has been synthesized via the cobalt(I) salen-catalyzed reduction of 2-acetylphe-
nyl 2-chloroacetate or 2-acetylphenyl 2,2-dichloroacetate [661].
Hisaeda and coworkers have synthesized a number of vitamin B12 model compounds with either
one or two metal centers. Studies of the electrochemical behavior of these species, especially
with respect to the use of their cobalt(I) states as catalysts for the reductive cleavage of carbon–
halogen bonds, have been undertaken. Among the halogenated compounds that have been cata-
lytically reduced are DDT as well as less-chlorinated members of the DDT family [662–664],
(2-bromoethyl)benzene [665], benzyl bromide [666], diethyl 2-(bromomethyl)-2-methylmalonate
[667–670], diethyl 2-(bromomethyl)-2-phenylmalonate [671], alkyl bromides bearing electron-
withdrawing groups (e.g., 4-bromo-3-methyl-2-butanone, methyl 3-bromo-2-methylpropanoate,
and 3-bromo-2-methylpropionitrile) [672,673], ethyl 4-bromo-5-oxohexanoate [674], 1-ethyl
3-phenyl 2-(bromomethyl)-2-methylmalonate [675], and a family of ethyl 1-(bromomethyl)-2-
oxocycloalkanecarboxylates [676].
Other uses of cobalt(I) catalysts include the reductive intramolecular cyclization of bromocy-
clohexenones to form bicyclic ketones [677] and the radical cyclization of bromoacetals [678,679].
Cross-coupling of functionalized aryl halides catalyzed by cobalt(I) pyridine complexes has been
achieved [680]. Arylcobalt(II) complexes are reportedly formed via the reduction of aryl bromides
in DMF–pyridine containing cobalt(II) bromide [681]. Electrogenerated cobalt(I) pyridine spe-
cies can be used to cross-couple aryl halides with allylic esters [682,683]. Kräutler and cowork-
ers [684] found that 1,4-dibromobutane interacts with electrogenerated cob(I)alamin to afford a
tetramethylene-1,4-di-Coβ-cobalamin species. In a study of the reactions of cobalt(I) tetraphenyl
porphyrin with benzyl chloride or 1-chlorobutane, Zheng and coworkers [685] reported that alkyl
radicals are transferred from the cobalt center to a nitrogen of a pyrrole ring, leading to formation
of an N-alkyl cobalt porphyrin complex. Electrogenerated (2,2′-bipyridine)cobalt(I) has been used
to promote the Heck reaction between aryl halides and ethyl acrylate [686], to catalyze the addition
of aryl halides to activated olefins [687], and to couple aryl halides with vinylic acetates to give sty-
renes [688–690]. Electrogenerated cobalt(I) complexes [691] can be employed to cross-couple aryl
halides with 4-chloroquinolines [692], to synthesize arylzinc species from aryl halides [693–696],
to produce organodizinc compounds from aromatic dihalides [697], and to couple aryl halides and
allylic acetates [698].
3. Other Catalysts
Several papers have appeared that describe the use of electrogenerated samarium(II) for the
catalytic reduction of organic halides at a nickel cathode in DMF [699], for the reductive cou-
pling of 3-chloropropanoate with ketones to yield γ-butyrolactones [700], and for the reductive
coupling of allyl chloride with ketones [701]. Torii et al. [702] developed procedures for the
palladium(0) triphenylphosphine-catalyzed carboxylation of aryl halides, β-bromostyrene, and
allyl acetates. Homocoupling of aryl halides, catalyzed by anionic aryl-ligated palladium(0)
bis(triphenylphosphine) species, has been examined [703]. Aromatic aldehydes have been electro-
synthesized via the palladium-catalyzed carbonylation of aryl iodides in the presence of formic
acid [286]. Hall and coworkers [704] electrogenerated tris(acetylacetonato)iron(II) for the reduc-
tive coupling and disproportionation of 1-bromooctane, and Wade and Castro [705] investigated
the reactions of iron(II) porphyrin with vicinal dihalides as well as alkyl, allyl, benzyl, and
propargyl halides. Catalytic dehalogenation of ethylene dibromide and trichloroacetic acid has
been accomplished with iron(II) myoglobin in biomembrane-like surfactant films on pyrolytic
graphite electrodes [706]. A report by Buriez et al. [707] concerns the mediation by iron(I) bipyri-
dine complexes of the formation of β-hydroxyesters via coupling of α-haloesters and carbonyl
compounds.
Vanhoye and coworkers [708] synthesized aldehydes by using the electrogenerated radical–anion
of iron pentacarbonyl to reduce iodoethane and benzyl bromide in the presence of carbon monoxide.
Esters can be prepared catalytically from alkyl halides and alcohols in the presence of iron penta-
carbonyl [709]. Yoshida and coworkers reduced mixtures of organic halides and iron pentacarbonyl
and then introduced an electrophile to obtain carbonyl compounds [710] and converted alkyl halides
into aldehydes by using iron pentacarbonyl as a catalyst [711,712]. A review by Torii [713] provides
an overview of papers that deal with catalytic processes involving complexes of nickel, cobalt, iron,
palladium, rhodium, platinum, chromium, molybdenum, tungsten, manganese, rhenium, tin, lead,
zinc, mercury, and titanium.
C. REDUCTIoN oF CarboN–HaLoGEN BoNDS aT CHEMICaLLY MoDIFIED ELECTroDES

Some papers have appeared that deal with the use of electrodes whose surfaces are modified
with materials suitable for the catalytic reduction of halogenated organic compounds. Kerr and
coworkers [714] employed a platinum electrode coated with poly-p-nitrostyrene for the catalytic
reduction of 1,2-dibromo-1,2-diphenylethane. Catalytic reduction of 1,2-dibromo-1,2-diphenyl-
ethane, 1,2-dibromophenylethane, and 1,2-dibromopropane has been achieved with an electrode
coated with covalently immobilized cobalt(II) or copper(II) tetraphenylporphyrin [715]. Carbon
electrodes modified with meso-tetra(p-aminophenyl)porphyrinatoiron(III) can be used for the
catalytic reduction of benzyl bromide, triphenylmethyl bromide, and hexachloroethane when the
surface-bound porphyrin is in the Fe(I) state [716]. Metal phthalocyanine-containing films on
pyrolytic graphite have been utilized for the catalytic reduction of trans-1,2-dibromocyclohexane
and trichloroacetic acid [717], and copper and nickel phthalocyanines adsorbed onto carbon pro-
mote the catalytic reduction of 1,2-dibromobutane, trans-1,2-dibromocyclohexane, and trichloro-
acetic acid in bicontinuous microemulsions [718]. When carbon electrodes coated with anodically
polymerized films of nickel(II) salen are cathodically polarized to generate nickel(I) sites, it is
possible to carry out the catalytic reduction of iodoethane and 2-iodopropane [34] and the reduc-
tive intramolecular cyclizations of 1,3-dibromopropane and of 1,4-dibromo- and 1,4-diiodobu-
tane [719]. Vaze and Rusling [720] employed a vitamin B12 analogue immobilized on carbon cloth
for the catalytic reduction of 1,2-dibromocyclohexane, and Njue and Rusling [721] used a similar
strategy for the catalytic reductive cyclization of n-bromoalkyl-2-cyclohexanones. A volume
edited by Murray [722] contains a valuable set of review chapters by experts in the field of chemi-
cally modified electrodes.
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26 Oxygen-Containing
Compounds
Alcohols, Ethers, and Phenols
Robert Francke, Thomas Quell, Anton Wiebe,
and Siegfried R. Waldvogel
CONTENTS
I. Aliphatic, Allylic, and Benzylic Alcohols ............................................................................ 982
A. Oxidation ...................................................................................................................... 982
1. Direct Oxidation .................................................................................................... 982
2. Indirect Oxidation .................................................................................................. 986
B. Reduction ......................................................................................................................990
1. Direct Reduction .................................................................................................... 991
2. Cathodic Deoxygenation after Introduction of Leaving Groups ........................... 991
II. Electrochemical Conversion of Ethers ................................................................................. 993
A. Oxidation ...................................................................................................................... 993
1. Saturated Ethers .....................................................................................................994
2. Unsaturated Ethers ................................................................................................. 995
B. Reduction ......................................................................................................................999
III. Aromatic Alcohols (Phenols)..............................................................................................1000
A. Oxidation ....................................................................................................................1000
1. Acetoxylation ....................................................................................................... 1001
2. Quinone Formation .............................................................................................. 1003
3. Phenol Coupling....................................................................................................1010
B. Reduction .....................................................................................................................1018
1. Electroreductive Hydroxylation of Aromatic Compounds ..................................1018
2. Electroreductive Birch-Type Reaction .................................................................1021
3. Electroreductive Hydrogenation and Hydrodeoxygenation of Phenolic Moieties ... 1024
4. Deoxygenation of Phenolic Compounds .............................................................1025
5. Reduction of Quinones ........................................................................................ 1026
References .................................................................................................................................... 1029
981
I. ALiPhATic, ALLYLic, AND BENzYLic ALcOhOLS

The hydroxy group represents the most abundant functional group and is therefore a very common
moiety. Consequently, its electrochemical behavior in electroorganic conversion is of high interest.
Due to the ability of alcohols to dissolve salts and their low reactivity, simple alcohols often serve
as solvents or electrolyte components for electrochemical conversions.
A. OXIDaTIoN
1. Direct Oxidation
Generally, a direct electrochemical oxidation of alcohols is not very practical for preparative pur-
poses. As high potentials have to be applied, most functional groups are not inert at the required
conditions [1,2]. In particular, most aliphatic alcohols are unsuitable for direct electrolysis due to
their extremely high stability toward anodic oxidation (see Table 26.1).
Usually, the free electron pairs of a hydroxy group are more difficult to ionize than π elec-
tron systems of aromatic systems, which can be observed using photoelectron spectroscopy [3].
A comparison of the oxidation potentials of aromatic compounds with alcohols leads to the same
conclusion. For instance, the half-wave potential E1/2 of toluene is 1.98 V vs. Ag/Ag+, whereas for
TABLE 26.1
Half-Wave Oxidation Potentials E1/2 of Several Aliphatic, Benzylic, and Allylic Alcohols
Obtained by Cyclic Voltammetry
E1/2 vs. E1/2 vs.
Ag/0.01 M Ag/0.01 M
Entry Compound Ag+ (V) References Entry Compound Ag+ (V) References
1 MeOH 2.69 a [2] 5 OH 1.59 b [5]
2 EtOH 2.57a [2] 6 OH 1.22/1.64b [5]
O
3 iPrOH 2.46a [2] 7 OH 1.31b [5]
4 OH >2.0b [5] 8 OH >2.0b [5]
Solvent, acetonitrile; working electrode, platinum.

Supporting electrolyte:
a 0.15 M NBu BF .
4 4
b 0.5 M NaClO .
4
Oxygen-Containing Compounds 983
CPE
divided cell
OH O
CH3CN/LiClO4
R = o - OMe, p-OMe: 60%

MeO R = m-OMe: <1% MeO
SchEME 26.1 Preparative scale electro-oxidation of primary benzyl alcohols.
H H
–H+ O –e– O –H+ O
+
Path 1 Ph R Ph R Ph R
+ 2
OH OH
R –e– R
Ph H Ph H
1
+ H
–R O –H+ O
Path 2a
Ph H Ph H
H H
–R+ O –e– O –H+ O
Path 2b +
Ph H Ph H Ph H
SchEME 26.2 Different reaction pathways following the anodic oxidation of secondary benzyl alcohols.
methanol, it is 2.69 V [2,4]. Consequently, the oxidation potentials of benzylic alcohols are lower
and can be further decreased with electron-releasing groups at the aromatic core [5,6].
In accordance with these analytical results (Table 26.1), primary benzylic alcohols can be oxi-
dized on preparative scale at reasonably low potentials. The corresponding aldehyde can be selec-
tively generated when an activating group is present in position ortho or para (see Scheme 26.1*) [3].
As the resulting carbonyl functionality lowers the susceptibility toward oxidation, overreaction to
the carboxylic acid can be avoided when electrolysis is carried out with controlled potential and
under anhydrous conditions. Since electron-donating substituents in meta position are facilitating
the electrophilic side reactions, the desired m-anisyl aldehyde is merely obtained in traces. The
applicability of this protocol was also demonstrated with further electron-rich model compounds
such as cumyl alcohol and o-benzylvanillyl alcohol [3].
For primary benzyl alcohols, an ECEC mechanism was proposed (see Scheme 26.2, path 1, R = H)
[3,6]. Upon anodic treatment, radical cation 1 is formed, followed by proton abstraction. After a fur-
ther oxidation step, the corresponding carbenium ion 2 is formed, which quickly loses a proton to give
the corresponding carbonyl compound. In order to avoid oligomerization reactions, the addition of a
base such as K2CO3 or pyridine is helpful. In the presence of water, overoxidation to the carboxylic
acid also proceeds via the hydrate that is formed from the α-hydroxybenzyl carbocation 2.
In contrast, the anodic conversion of secondary benzyl alcohols does not necessarily provide the
corresponding ketones. The concurrent liberation of an alkyl radical (see Scheme 26.2, path 2a) or
carbenium ion from 1 (path 2b) results in the formation of benzaldehyde [7]. Whereas anodic oxida-
tion of 1-phenyl-1-ethanol and 1-phenyl-1-propanol mainly yields the phenones (see Scheme 26.3,
right), the dealkylated products are preferentially formed when iPr and tBu leaving groups are
involved (see Scheme 26.3, left). Path 2 becomes more favored with increasing stabilization of the
leaving group. Generally, the relative leaving group quality exhibits the following order: tBu > iPr >
* The abbreviations CPE and CCE will be used for controlled potential and controlled current electrolysis throughout
this chapter.
CPE CPE
divided cell divided cell
O OH O
CH3CN/NBu4BF4 CH3CN/NBu4BF4
K2CO3 R K2CO3 R
R = iPr: 63% R = Me: 83%

R = tBu: 61% R = Et: 75%
SchEME 26.3 Preparative scale electro-oxidation of different secondary benzyl alcohols.
Et > Me. Tertiary alkylphenyl alcohols were found to cleave alkyl fragments to yield the respective
ketone [7]. The nature of the leaving group for path 2 was studied in more detail. The liberated car-
bocation R+ could undergo a Ritter-type reaction with acetonitrile to form the corresponding amide.
For radical R•, either H abstraction from the solvent or further oxidation with subsequent Ritter-type
reaction is conceivable. When 1-methyl- and 1-ethyl-substituted benzyl alcohols were electrolyzed, the
formation of methane and ethane was observed exclusively. This indicates that the course of the reac-
tion is more likely represented by path 2a. However, after the conversion of iPr- and tBu-substituted
benzyl alcohols, the corresponding amides can be found as by-products. As iPr- and tBu-radicals have
a much longer lifetime, they can be anodically oxidized to undergo the Ritter-type reaction and the
formation of the respective amides was indeed confirmed.
The electrochemical oxidation of naturally occurring allylic alcohols is despite their abundance
only scarcely studied. For instance, when geraniol or crotyl alcohol is directly electrolyzed in an
acetonitrile/methanol mixture containing pyridine and LiClO4 (undivided cell, galvanostatic con-
ditions), the corresponding α,β-unsaturated aldehydes (citral and crotylaldehyde) or, respectively,
their dimethyl acetals are obtained in good yields [8]. In contrast, electrolysis of prenol unexpect-
edly leads to γ-hydroxy acetal 3 in 75% yield and not to prenyl aldehyde (4) (see Scheme 26.4).
An unusual rearrangement starting from 4 and presumably occurring at the electrode surface was
proposed. The initial oxidation step of the sequence depicted in Scheme 26.4 was confirmed, since
subjection of 4 to the same electrolysis conditions equally leads to the formation of 3.
The anodic treatment of 1,2-glycols in methanol containing tetraethylammonium
p-toluenesulfonate at potentials between 1.7 and 2.3 V vs. SCE leads to the oxidative cleavage under
the formation of the carbonyl compounds or acetals (Scheme 26.5) [9]. This method is quite useful
compared to methods involving Pb(OAc)4, NaIO4 or O3, since a tedious work-up is avoided and no
toxic reagents are employed. Moreover, no stereochemical limitations, which typically occur using
conventional methods [10], were found. 1-Hydroxy-2-methoxy and 1,2-dimethoxy compounds can
be transformed in similar current efficiencies to those of the respective diols.
CCE
OH undivided cell MeO OH
CH3CN/MeOH/ 3
OMe 75%
pyridine 10:10:1
LiClO4
MeOH
MeOH
O MeO
O
O
4
H+
SchEME 26.4 Anodic oxidation of prenol.

R R O
O O
O
HO CPE
MeOH/p–TsONEt4 n + n + O n
R
R n
O O
O
HO R R O
R = H, Me, iPr
n = 3, 4
35– 96%
SchEME 26.5 Anodic conversion of cyclic 1,2-diols.
CCE
OH undivided cell O OH
OH
NEt4BF4
F 3C F3C O CF3 F3C F3C OEt
5 6 7
>70%
SchEME 26.6 Electrochemical oxidation of 2,2,2-trifluoroethanol.
CCE n
R1 O undivided cell R1 O
OH
n EtOH/NaOEt/LiBF4 O
R2 R2
R1 = C6H13, (C2H5)2CH 8
R2 = H, CH3 51–61%
n = 1, 2
SchEME 26.7 Oxidative cyclization of ω-hydroxy tetrahydropyranes.
Despite the high redox stability of fluorinated alcohols toward oxidation [11–14], 2,2,2-trifluo-
roethanol can be converted under galvanostatic and solvent-free conditions to 2,2,2-trifluoroethyl
hemiacetal 5 (see Scheme 26.6) [15]. The hemiacetal represents a useful alternative to fluoral (6),
which is an important building block for compounds exhibiting trifluoromethyl groups. However,
fluoral is difficult to handle due to its low boiling point [16–18]. In laboratory-scale preparations, the
commercially available ethyl hemiacetal 7 is mostly employed as a substitute for 6. It was demon-
strated that 5 has a better reactivity compared to 7 when employed for Grignard reactions or acid-
catalyzed electrophilic aromatic substitutions [15].
Oxidative cyclization of ω-hydroxy tetrahydropyrans under full stereocontrol can be achieved
by the anodic oxidation of the starting material in the presence of a suitable base (see Scheme 26.7)
[19]. An electrolyte consisting of NaOEt and LiBF4 in ethanol provides the best conditions for the
preparation of the desired [4,5] and [5,5] spiroketals (8), which represent a common structural motif
in numerous natural products and pharmaceutics [20].
A plausible mechanism involves initial deprotonation of the ω-hydroxy functionality followed by
anodic oxidation to alkoxyl radical 9. Subsequent intramolecular hydrogen abstraction and further
oxidation lead to oxonium ion 10, which is attacked by the ω-hydroxy group to form the desired
spiroketal 8 (Scheme 26.8).
R1 O R1 O – R1 O
OH NaOEt O –e– n O
n n
H
R2 R2 R2
9
+
R1 O R1 O n
OH –e– R1 O
n n OH
O
R2 R2 R2
10
8
SchEME 26.8 Proposed mechanism for the oxidative cyclization of ω-hydroxy tetrahydropyranes.
2. Indirect Oxidation
Compared to direct oxidation of alcohols, mediated electrolysis renders by far superior results
in terms of selectivity, compatibility with functional groups, and energy efficiency. For instance,
the employment of iodide salts under galvanostatic conditions allows for efficient transformation
of aliphatic primary and secondary alcohols to the corresponding carboxylic acids and ketones,
respectively [21]. It should be pointed out that such transformations are not possible with direct elec-
trolysis. Furthermore, when iodide salts are used as mediators, the addition of base is not necessary.
Other successfully tested mediating systems for the oxidation of aliphatic alcohols are alkali
metal nitrates in acetonitrile or in biphasic solution [22,23], thioanisole in benzonitrile or 2,2,2-tri-
fluoroethanol [24,25], and a double mediatory system consisting of RuO4/RuO2 and Cl−/Cl+ in a
biphasic system [26].
A very successful and convenient approach for the oxidation of all types of alcohols is the
employment of Ni(OH)2 electrodes in aqueous alkaline media (see Scheme 26.9) [27–30]. In this
type of reaction, the electron transfer to the alcohol substrate is heterogeneously catalyzed by the
anode material, which means that no mediator has to be separated from the reaction mixture. The
scope of this method comprises numerous oxidations of primary and secondary aliphatic and ben-
zylic alcohols [27,29], oxidative cleavage of vicinal diols, and chemoselective oxidation of hydroxyl-
steroids and partially protected sugars [27,28,30].
The nickel electrode has to be activated prior to electrolysis by the deposition of a thin Ni(OH)2
film from an aqueous basic Ni(II) salt solution. From this film, a black surface layer of Ni(III) oxide
hydroxide is continuously electrogenerated during electrolysis (see Scheme 26.10) [31,32]. After the
rate-determining radical hydrogen abstraction, an α-hydroxyl radical is formed that is readily oxidized
CCE O
Ni(OH)2 anode
RCH2OH + 5OH– R C O– + 4H2O + 4e–
H2O/NaOH
SchEME 26.9 Alcohol oxidation on the Ni(OH)2 electrode.
0.6 V
vs. SCE
Ni(OH)2 + OH– NiOOH + H2O + e–
H
NiOOH + RCH2OH Ni(OH)2 + R C OH
H O
R C OH
R C O–
SchEME 26.10 Mechanism for electro-oxidations on the Ni(OH)2 electrode.

to the ketone in the case of secondary alcohols and to carboxylic acid in the case of aldehydes [27].
The formation of the catalytically active film already takes place around 0.6 V vs. SCE, which is a dra-
matic decrease compared to the potentials for direct alcohol oxidation depicted in Table 26.1. Hence,
functional groups such as ester, alkyne, or electron-rich aromatic rings such as furans are tolerated.
The most frequently studied type of mediatory system for the oxidation of alcohols is the class of
N-oxyl radicals. Particularly, 2,2,6,6-tetramethylpiperidinyl-N-oxyl (TEMPO) and corresponding
derivatives are well studied. Basically, the employment of N-hydroxyphthalimides renders similar
results [33]. In contrast to the use of such mediators in conventional organic synthesis, the employ-
ment of a stoichiometric amount of oxidant (e.g., NaClO) is avoided. This indirect method allows for
a selective transformation of primary and secondary alcohols to carbonyl compounds at very low
potentials (typically around 0.4 V vs. Ag/AgNO3) [34,35]. Overoxidation of aldehydes to carboxylic
acids can be avoided in aprotic media [34], whereas electrolysis in aqueous basic solution generally
affords the carboxylic acid [35]. The method requires potential control and operation in a divided
cell [34]. Slow reaction of secondary alcohols allows for a selective transformation of primary alco-
hols in the presence of secondary hydroxy groups. Further advantages are rapid conversion at low
temperatures of up to –60 °C and high turnover rates of the catalyst. The reaction can be conducted
either homogeneously in solution or with immobilized TEMPO on a modified carbon felt electrode
[34,36]. Despite the classical organic and aqueous electrolyte systems, further electrolysis media
such as oil-in-water nanoemulsions and ionic liquids were found to be suitable [37,38].
By anodic oxidation of the nitrosyl radical, the active oxoammonium ion is formed, which
reacts with an alcohol to give the corresponding hydroxylamine and carbonyl compound (see
Scheme 26.11). Reasonable reaction rates are only achieved in the presence of a suitable base such
as lutidine. In aqueous systems, a buffer system such as K2CO3/KHCO3 is useful. Direct anodic
regeneration of the active species requires a potential of 0.8 V vs. Ag/Ag+. As the hydroxylamine
undergoes comproportionation with the oxoammonium compound to give the N-oxyl radical, the
catalytic cycle can be set up at the lower oxidation potential of the latter species.
A significant improvement of the method described earlier is the employment of a double media-
tory system in biphasic media (see Scheme 26.12), wherein the active bromine species is generated
anodically in the aqueous phase to react with the N-oxyl radical to form the oxoammonium species
[39]. The conversion of alcohols to carbonyl compounds then proceeds in the organic phase. The
advantage of this method is a simple experimental setup. In contrast to the single mediatory system
(see Scheme 26.11), the operation in an undivided cell at galvanostatic conditions within a wide
range of current densities is possible.
Based on the initial studies carried out with TEMPO, numerous modifications of this type of media-
tor were designed in order to tailor the system for specific purposes (see Figure 26.1). From the environ-
mental point of view, the employment of water-soluble TEMPO derivatives 11a and 11b (WS-TEMPOs)
0.4 V
R R vs. Ag/AgNO3 R + R O– Base OH
N 2 N
2
O O R΄ R΄
0.8 V
vs. Ag/AgNO3 R + O R΄
N
R O H
R R
Comproportionation N
OH
+ O
R + R
N R΄
O
SchEME 26.11 Electro-oxidation of alcohols mediated by N-oxyl radical species.

Anode
Br– Alcohol
R
+ 2 +N O Carbonyl
2OH– R compound
R
N OH
R
2e– OBr– R
+ 2 N O
H2O R
Aqueous Organic
phase phase
SchEME 26.12 Double mediatory system in biphasic medium based on TEMPO and bromide salt.
H iPr
N O
Y
N
O N O N O R
O N
– AcHN Cl
11a: Y = –NR3+ Br
+
11b: Y = –SO3– H 12 13 14
FiGURE 26.1 Several developments in the field of N-oxyl-based mediators for electrooxidation of alcohols.
is attractive, since they allow for the use of aqueous electrolytes [40,41]. With this type of mediator, the
scope is not just limited to water-soluble alcohols, as nanoemulsions are formed upon ultrasonic irradia-
tion of a solution of WS-TEMPO and lipophilic alcohol in aqueous electrolyte. After electrolysis, the
resulting aldehyde can easily be isolated by extraction with an organic solvent. The aqueous electrolyte
can be reused for several cycles, since the concentration of the mediator remains almost unaffected.
When an optically active N-oxyl species is used for the oxidation of racemic sec-alcohols, a
kinetic resolution can be accomplished. In this case, the product mixture contains ketone and
enantiomerically enriched alcohol. This concept was first developed for the conventional oxidation
method and later transferred to the electrocatalytic reaction using 12 as optically active mediator
[42–44]. The employment of a double-mediatory system such as sodium bromide combined with
13 in biphasic solution again proved to be beneficial (see Scheme 26.13), allowing for operation in
an undivided cell under galvanostatic conditions [45]. Similar results can be obtained in an organic
solvent-free method using an aqueous silica gel supported system [46].
The enantioselective oxidation of racemic sec-alcohols mentioned earlier can also be achieved
upon the employment of an optically active amine base such as (−)-sparteine in combination
with a TEMPO-modified graphite felt electrode [47,48]. The slow reaction with sec-alcohols as
a typical feature of TEMPO derivatives is clearly advantageous for the discrimination between
hydroxy groups at different positions of a molecule. However, it turns into a drawback when the
oxidation of sterically hindered alcohols such as (−)-menthol is intended (see Scheme 26.14) [49].
OH CCE (3 F ) O OH
undivided cell
NaBr/cat. 13 +
R R R
CH2Cl2
R = aryl aq. NaHCO3 42–61% 23–55%
ee: 54–91%
SchEME 26.13 Kinetic resolution of racemic alcohols using optically active N-oxyl radical species 13.
CCE
14 or TEMPO
OH CH2Cl2
O
sat. aq. Na2CO3
TEMPO: 23%
14: 99%
SchEME 26.14 Indirect electro-oxidation of (─)-menthol using N-oxyl radical species 14 or TEMPO.
R CCE
R O Br2 O Bu2SnO R OH R O
undivided cell
SnBu2
O cat. Bu2SnCl2
R OH R R OH R OH
15 Et4NBr/MeOH
R = alkyl
Conventional method up to 96%
SchEME 26.15 Selective anodic oxidation of vicinal diols to α-hydroxy ketones.
Azabicyclo-N-oxyls 14 offer the advantage of a well-accessible N-oxyl group and exhibit a superior
performance compared to TEMPO when sterically demanding groups adjacent to the secondary
hydroxy functionality are involved. Analogous to 12 and 13, optically active versions of 14 are
efficient electrocatalysts for kinetic resolution of racemic sec-alcohols (compare Scheme 26.13) [50].
Common oxidizing reagents or methods such as Pb(OAc)4, IO4−, Swern conditions, or direct
electrolysis lead to the oxidative cleavage of vicinal diols or oxidation to the diketones, respec-
tively [9,51–54]. Hence, the selective conversion of 1,2-diols to α-ketoalcohols is a quite challenging
task. Nonelectrochemically, it can be accomplished by conventional methods when a vicinal diol
is transformed to the corresponding stannylene acetal (15) followed by subjection to brominolysis
(see Scheme 26.15, left) [55]. However, this method suffers from some disadvantages such as the
employment of excess Bu2SnO and addition of bromine, which often causes side reactions and
requires a tedious work-up. An elegant way to circumvent these restrictions is the indirect anodic
oxidation using alkylammonium bromides as mediator/supporting electrolyte and catalytic amounts
of Bu2SnCl2 (see Scheme 26.15, right) [56].
In a plausible mechanism (see Scheme 26.16), the diol reacts with (OMe)2SnBu2 to form stanny-
lene acetal 15 or the related zwitterion 16. After reaction with the anodically formed oxidant (Br+)
R OH
Cl2SnR2
R O
Br– (MeO)2SnR2
R OH
2MeO–
+
–2e– R OSnR2 R OH
anode –1/2H2 + 2e–
cathode
R OBr
2 MeOH
+
Br
+
R OSnR2 R O
SnR2
R O– R O
16 15
SchEME 26.16 Proposed mechanism for the anodic oxidation of vicinal diols.
and cathodically formed base (MeO −), the hydroxyketone is obtained and the organotin catalyst will
be regenerated. The method was successfully applied to a broad scope of 1,2-glycol derivatives, and
some important characteristics of this type of reaction were concluded [57]. In terms of selectivity,
it was found that primary and tertiary alcohols cannot be oxidized using this method. This feature
can be exploited for the determination of the regioselectivity, when primary/secondary and tertiary/
secondary alcohols are oxidized. Furthermore, in the presence of a third hydroxy group as, for
example, in glycerol, a high selectivity for 1,2-diols was observed. In the case of two secondary
hydroxy groups, the sterically less hindered one was predominantly oxidized.
B. REDUCTIoN
The transformation of alcohols into the corresponding alkanes by the removal of the hydroxy func-
tion is of high importance in organic chemistry, and selective conversion in the presence of sensi-
tive functional groups still remains a challenge. Aside from other multistep sequences [58–60], the
Barton–McCombie reaction and its variants are most frequently employed for deoxygenation on
laboratory scale [61,62]. However, this type of reaction involves some serious limitations such as the
employment of toxic organotin reagents and the preparation of the sensitive xanthates.
Similar to direct anodic transformations, the cathodic conversion of alcohols to alkanes is dif-
ficult, as very negative potentials have to be applied. For catalytically active electrode materials,
proton discharge under the formation of the hardly reducible alcoholate is the preferred reaction. In
contrast, the employment of materials with high overpotential for hydrogen evolution such as mer-
cury, lead, or carbon allows for a direct deoxygenation in very few examples [63,64]. At the required
potentials of up to –2.9 V, the presence of most functional groups is not tolerated (see Table 26.2).
Furthermore, only benzylic and allylic alcohols are cathodically active within the potential win-
dows of common organic electrolytes. The scope of possible substrates for direct cathodic deoxy-
genation is therefore narrow. However, the oxidation potentials can be significantly decreased when
the oxygen is functionalized into suitable leaving groups.
TABLE 26.2
Half-Wave Reduction Potentials E1/2 of Several Benzylic, Allylic, and Propargyl Alcohols
Obtained by Polarography
Entry Compound E1/2 vs. SCE (V) Entry Compound E1/2 vs. SCE (V)
1 OH — 4 OH –2.44
Ph
2 OH –2.90 5 –2.57/–2.80
Ph OH
Ph Ph
3 Ph –2.81 6 OH –2.74
Ph OH
Ph
Ph
Source: Lund, H. et al., Electrochim. Acta, 19, 629, 1974.

Solvent, DMF; supporting electrolyte, 0.1 M NBu4I. Working electrode: mercury.
1. Direct Reduction
The cathodic deoxygenation proceeds selectively on mercury or lead electrodes when the hydroxy func-
tionality is situated in benzylic position [63]. As the required potentials are very high, further C–C double
or triple bonds in the substrate are reduced as well (see Scheme 26.17). As most other functional groups
are not tolerated at these harsh conditions, the practical use of this method is rather limited [65].
2. Cathodic Deoxygenation after Introduction of Leaving Groups
A more promising approach for C–O bond cleavage is the employment of leaving groups that sig-
nificantly lower the reduction potential of the substrate (see Scheme 26.18). Typically, these leaving
groups are anions of strong acids.
For instance, methanesulfonates can be converted under galvanostatic conditions using a lead
cathode. The transformation into the corresponding deoxygenated product proceeds selectively and
tolerates several functional groups such as ester, nitrile, and epoxide [66]. In the case of 1,3-diols,
the electroreduction proceeds with the formation of cyclopropanes according to Scheme 26.19 [67].
As oxalic acid esters are easily reduced (around –1.4 V vs. Ag/AgI), their leaving group ability
was exploited for the deoxygenation of a broad range of benzyl alcohols (see Scheme 26.20) [68,69].
No additional preparative step is required, since the active species is formed in the electrochemical
cell via base-catalyzed transesterification.
The course of this reductive cleavage was studied in more detail with coulometry, cyclic voltam-
metry, and product analysis, and the mechanism depicted in Schemes 26.21 through 26.25 was
proposed [69]. As initiation step, the electrogenerated base 17 deprotonates the substrate ROH that
subsequently undergoes transesterification (Scheme 26.22). Ester 18 is reduced in the next step fol-
lowed by decomposition into benzyl radical (19) and leaving group EtOCOCO2− (Scheme 26.24). The
fate of the radical is most probably proton abstraction from a solvent molecule S–H (Scheme 26.25),
since the consumption of only one F was observed and further reduction and protonation would
require a second F. As radical 19 needs to be stabilized by conjugation, the scope of this method is
restricted to benzyl alcohols.
OH CPE R1 = R2 = Ph: 95%
R1
R1 mercury cathode R1 = Ph, R2 = Me: 90%
DMF/NBu4I R2 R1 = R2 = Me: 0%
R2
SchEME 26.17 Electrochemical reduction of alkynols.
OX
R R΄
OH X = leaving group
H H
R R΄ R R΄
Difficult
SchEME 26.18 Electro-reductive deoxygenation of alcohols.
R1 CCE R1
OMs divided cell
R2 R2
DMF/TsONEt4
OMs
R3
R3
R2 = alkyl, H
Up to 97%
R1, R3 = alkyl, alkoxy
SchEME 26.19 Electrochemical synthesis of substituted cyclopropanes.

CPE
divided cell
OH DMF/Bu4NClO4
R1 R2 O OEt R1 R2
EtO O
R1 = aryl
R2 = aryl, alkyl Up to 97%
SchEME 26.20 Electro-reductive deoxygenation of alcohols using oxalic acid ester.
Initiation:
EtO O +e– EtO O– R OH EtO OH

+
OEt OEt
R O–
O OEt O O
17
SchEME 26.21 Initiation step for the deoxygenation of alcohols using oxalic acid ester.
Base-catalyzed transesterification:
EtO O EtO O
+ R O– R + EtO–
O OET O O
18
SchEME 26.22 Base-catalyzed transesterification.
EtO– + R OH EtOH + R O–
SchEME 26.23 Deprotonation.
Cathodic cleavage:
EtO O +e– EtO O– EtO O

R R + R – CH2
O O O O O O–
18 19
SchEME 26.24 Cathodic cleavage.
Termination:
19 + S H R CH3 + S
SchEME 26.25 Termination step.
The employment of toluates or diphenylphosphinates as leaving groups represents a significant

improvement of this type of reaction (see Scheme 26.26) [70–72]. With both types of esters, the
scope of the reaction is broadened compared to the oxalate-based method, since the hydroxy func-
tionality of the substrate must not necessarily be situated in benzylic position.
Similar to the process depicted in Schemes 26.24 and 26.25, the cathodic reduction of such esters
leads to the formation of a radical cation followed by the decomposition into alkyl fragment and
anion. The desired product is then formed by proton abstraction from the solvent. As only 1 F is con-
sumed and the nature of the leaving group can unambiguously be identified, an EC type mechanism
CCE
divided cell –
R O R΄ R O R΄ R H + R΄ O–
DMP or DMF
NBu4BF4
R = alkyl, benzyl; R΄ = C(O)aryl, P(O)(Ph)2
SchEME 26.26 Electrochemical reduction of toluates and diphenylphosphinates.
CCE
R΄
undivided cell +
R OH + PR΄3 R H + O=PR΄3 via O R΄
CH3CN/Et4NBr R R΄
R = alkyl, benzyl
48–96% 20
R΄ = Ph, Bu, OPh
SchEME 26.27 Electrochemical deoxygenation of alcohols in the presence of tertiary phosphine.
can be proposed. For the studied reactions, the decomposition rate can be clearly correlated with
the stability of the produced radical [71]. Consequently, diphenylphosphinate radical anions exhibit
a much faster decomposition rate compared to the toluate species. This is advantageous from the
preparative point of view, since this highly reactive species is less prone to side reactions.
For secondary and tertiary alcohols, the toluate ester has to be prepared separately prior to elec-
trolysis [70], whereas in situ transesterification in the presence of methyl toluate is the method of
choice for primary alcohols [72]. The diphenylphosphinates are prepared ex situ for all kinds of
alcohols [71].
Primary and secondary alcohols can also be efficiently deoxygenated by a double electrolysis in
the presence of phosphine (see Scheme 26.27) [73,74]. The active phosphonium species 20 is formed
in situ by anodic oxidation of the phosphine and subsequent reaction with the alcohol. 20 is then
cathodically reduced to give the alkane and phosphine oxide. The scope of this reaction comprises
benzylic and aliphatic alcohols. In contrast, tertiary alcohols cannot be deoxygenated at these con-
ditions. As this method requires no basic conditions, ester groups are tolerated.
Although some of the electrolytic conversions seem to be limited for aliphatic alcohols, there
are two major developments that might overcome the current limitations: Novel electrode materials
such as boron-doped diamond (BDD) allow the direct generation of oxyl radical by anodic treatment
or the cathodic operation at highly negative potential [75,76]. For nondestructive purposes, these
pathways are yet not well investigated. Another strategy will be the development of novel and highly
specific mediators to circumvent a direct conversion at the electrode surface [77].
II. ELEcTROchEMicAL CONvERSiON Of EThERS

The ether moiety is a very common motif and therefore omnipresent. The pronounced electro-
chemical stability of saturated aliphatic ethers and their ability to dissolve salts allow the usage of
ethers as a solvent component in the electrolyte. Therefore, unsaturated ethers are much more easily
converted. However, ethers are in particular prone to hydrogen atom abstraction, since the interme-
diate radical experiences stabilization by the oxygen atom.
A. OXIDaTIoN
Similar to aliphatic alcohols, the direct anodic oxidation of saturated monoethers proceeds at rela-
tively high potentials. For instance, THF is electrochemically inert up to 2.0 V vs. SCE [78]. Hence,
only few examples for preparative anodic conversions of saturated ethers can be found in literature
as many functional groups are not tolerated at such high potentials [79,80].
TABLE 26.3
Half-Wave Oxidation Potentials E1/2 of Several Aliphatic, Phenyl, and Vinyl Ethers
Obtained by Cyclic Voltammetry
Entry Compound E1/2 vs. SCE (V) References Entry Compound E1/2 vs. SCE (V) References
1 O >2.0 a [78] 4 1.42 b [85]
MeO OMe
2 OMe 1.76b [85] 5 OMe 1.12b [85]
MeO OMe
3 OMe 1.45b [85] 6 1.4c [86]
OMe O
Solvent, acetonitrile; working electrode, platinum.

Supporting electrolyte:
a Electrolyte, THF/0.65 M NEt BF .
4 4
b Electrolyte, CH CN/0.1 M Pr NClO .
3 4 4
c Value refers to peak potential; Electrolyte, CH NO /1 M LiClO .
3 2 4
In contrast, unsaturated ethers cover a wide range of oxidation potentials and are generally easier
to oxidize compared to their saturated congeners (see Table 26.3, entries 2–6). Consequently, the
preparative electrochemistry of such compounds is well explored and their reactivity exploited for
numerous useful synthetic transformations [81–84].
1. Saturated Ethers
Anodic oxidation of aliphatic ethers typically leads to oxonium ion 21, which is subsequently
attacked to give the α-substituted product (see Scheme 26.28). For instance, electrolysis of nonsub-
stituted, cyclic, and acyclic ethers in basic methanolic or aqueous solution allows for the oxidation
to the corresponding acetals and hemiacetals in moderate yields [87,88]. Significantly better results
for the oxidation of ethers to acetals can be obtained when a solvent mixture of methanol and acetic
acid is used (see Scheme 26.29) [79].
An intriguing example for such reactivity was reported more recently in the context of the three-
component synthesis of protected homoallylic alcohols in THF-based electrolyte (see Scheme 26.30) [80].
–2e–, –H+ Nu Nu
R2 R2
R1 O R1 O R2
R1 O
21
SchEME 26.28 Anodic oxidation of aliphatic ethers.
CCE
undivided cell
O O
CH3OH/AcOH OMe
n 76% (n = 1)
n
71% (n = 2)
SchEME 26.29 Preparative scale electro-oxidation of cyclic ethers to the corresponding acetals.
CCE O O
O O
Br + undivided cell
+ Ph
Ph Indium cathode
platinum anode 22
60–70%
SchEME 26.30 Electrochemical three-component synthesis of protected homoallylic alcohols.
O
ln III
Cathode Anode
Br +
Oln III O
ln0
Ph
Ph O 23 24
O O
Ph
22
SchEME 26.31 Proposed mechanism for the three-component synthesis of homoallylic alcohols.
In this process, benzaldehyde, allylbromide, and THF react under indium mediation in a convergent
paired electrolysis at galvanostatic conditions to form 22 in good yields.
The course of the reaction is depicted in Scheme 26.31. Reaction of allyl bromide with the indium
metal of the cathode affords an allylindium species that reacts with benzaldehyde to form homoallyl
alcoholate 23. During electrolysis, the In(III) salts generated by the chemical reaction are constantly
reduced, while the solvent THF is anodically oxidized to oxonium ion 24, which reacts with 23 to
give homoallyl acetal 22.
The application of indium metal as cathode material is crucial for the process, since the reduc-
tion of In(III) salts on typical electrodes such as platinum or glassy carbon proceeds at very negative
potentials. Hence, the employment of catalytic amounts of In(I) salts in combination with a standard
electrode material is not possible. In order to favor the oxidation of the solvent, high current densi-
ties at the anode have to be realized by using an undersized platinum wire (quasidivided cell) [89].
2. Unsaturated Ethers
In contrast to saturated ethers, the oxidation of vinyl ethers proceeds at relatively low potentials
(compare Table 26.3). Typically, this reaction proceeds in a single-electron transfer step, leading to
the relatively stable radical cation 26 according to Scheme 26.32 [81]. The type of the subsequent
reaction strongly depends on the properties of the electrolyte. In strongly basic or nucleophilic
Nu– RO RO
Path a
Nu Nu Nu
RO
RO –e– RO + +
Path b RO
OR Nu
Nu–
25 26 RO
RO + OR
+
Path c RO Nu
OR
+
SchEME 26.32 Typical pathways for the electro-oxidation of vinyl ethers.

CCE OMe
undivided cell
OR MeO
OR
MeOH/KOH
–5°C 27
R = alkyl
40–75%
SchEME 26.33 Preparative scale electro-oxidation of vinyl alkyl ethers.
environment, the electrophilic reaction of 26 is preferred (path a), whereas under neutral or slightly
basic conditions, the fate of 26 is determined by radical dimerization (path b) or electrophilic addi-
tion to 25 (path c), both leading to dimers of 25.
For instance, anodic treatment of aliphatic vinyl ethers in methanolic KOH renders predomi-
nantly the methoxylated product 27 (see Scheme 26.33) [90]. Under these conditions, the yield of the
desired product is significantly impaired by the dimerization reaction (yield of the dimer, 15–24%).
The potential use of this side reaction as a C–C bond formation method was realized soon after,
followed by the optimization of the electrolysis conditions for this purpose [81]. In this context, it was
found that under less basic conditions, the conversion of aliphatic vinyl ethers leads preferentially
to the dimerization product 28 (Scheme 26.34). The use of a MeOH/NaClO4 electrolyte containing
2,6-lutidine proved to be beneficial. The addition of a weak base is essential and serves the trap-
ping of protons, which are released upon nucleophilic attack of methanol on the cationic or radical
cationic dimer intermediate. When the reaction is carried out in the absence of base, the concurrent
proton-catalyzed acetalization of the enol ether significantly lowers the yield of the desired product.
The C–C bond forming reaction discussed earlier was also used for intramolecular cyclizations
(Scheme 26.35) [82]. Using similar electrolysis conditions as depicted in Scheme 26.34, five-, six-,
and seven-membered rings can be obtained from the corresponding bis(enol ether) substrates in
reasonable yield without stereoselectivity. It was found that the method is unsuitable for the synthe-
sis of compounds with larger ring sizes and that the yield decreases with increasing chain length.
Moreover, it was demonstrated that this method allows for the generation of one or even two vicinal
quaternary carbon centers upon cyclization [82]. Silyl enol ethers proved to be similarly suitable
substrates for this type of electroorganic transformation [82,91].
This reaction principle was extended to intramolecular radical-cation cyclizations of vinyl ether
substrates containing electron-rich aromatic rings as nucleophilic element (Scheme 26.36) [92]. The
product selectivity was observed to be strongly influenced by the position of the activating groups
on the aryl moiety. For instance, constant current oxidation of m,m-dimethoxy-substituted 29 leads
CPE R4
R2
R1O R4 undivided cell R3
2 MeO OR1
R2 R3 CH3OH/NaClO4 R1O OMe
4
lutidine R2 R3 R
–10°C 28
R1 = Me, Et
R2, R3, R4 = H, alkyl Up to 61%
SchEME 26.34 Electrochemical dimerization of enol ethers.
MeO
CCE
OMe undivided cell OMe
R R
R OMe CH3OH/CH3CN R
n n OMe
NaClO4/lutidine
MeO
R = H, Me
n = 1, 2, 3 50–70%
SchEME 26.35 Anodic intramolecular cyclization of enol ether substrates.

MeO
R1 = R3 = H
30
R2 = OMe OMe 31%
MeO
OMe
CCE
R2 undivided cell R1 = OMe
CH3OH/CH2Cl2
LiClO4/lutidine R2 = R3 = H 31
R1 OMe 51%
R2 O
OMe OMe
R3
R 1 = R2 = H
29
R3 = Me
32
51%
SchEME 26.36 Intramolecular cyclization of enol ether substrates containing electron-rich aromatic rings.
to fused bicyclic structure 30, whereas under the same electrolysis conditions, the conversion of
p-methoxy-substituted 29 affords spirodienone 31. In the presence of two or more activating sub-
stituents on the ring, overoxidation of the desired products was found to significantly decrease the
yield. The resulting limitation of the scope of substrates can be circumvented using vinyl thioether
derivatives of 29. When a nonactivated aryl ring is appended, a different reaction path is opened up.
In this case, elimination of a proton in α-position to the radical cation leading to α,β-unsaturated
ketone 32 preferentially occurs. Hence, the presence of electron-donating groups seems to be cru-
cial for the cyclization reaction. Additionally, it was demonstrated that other electron-rich aromatic
compounds such as furan and pyrrole are also suitable for this type of cyclization reaction [92].
The electrochemical conversion of enol ethers in [2+2] cycloaddition reactions was explored more
recently [84,86,93,94]. In a plausible mechanism, the anodically generated radical cation attacks
an α-aryl-substituted olefin under the formation of cycloadduct intermediate 33 (Scheme 26.37).
Rn +
OR
Rn 33
+
R
O Rn +
34 OR
Anode Cathode
R Rn
O
35 OR
SchEME 26.37 Plausible mechanism for the electrochemical conversion of enol ethers in [2+2] cycloaddi-
tion reactions.
R2 R2
R3 R1 R3 R1
CPE
+ LiClO4/CH3NO2
R4 O
R4
O
R5 Eox = 1.4 V R5
36
Up to 94%
Ri = H, Me, OMe, OPh d.r.: up to 25:1
SchEME 26.38 Electrochemical conversion of dihydropyran in [2+2] cycloaddition reactions.
Intramolecular electron transfer proceeds to give 34, which is then reduced to give cyclobutane
structure 35. The electron-rich aromatic ring is a crucial component for intermediate stabilization
of the cyclobutane radical cation (“redox tag”). A very delightful aspect of this reaction is the pos-
sibility of 34 to be reduced by the enolether substrate, which means that only catalytic or substoi-
chiometric amounts of charge have to be passed (typically between 0.1 and 0.5 F). In order to avoid
side reactions, the electrolysis should be carried out with controlled potential. The scope of enol
ether substrates includes enyloxy benzenes [93], aliphatic acyclic [86], and cyclic enol ethers [84],
rendering good to excellent yields. On the olefinic side, numerous unactivated, mono, and gem-
disubstituted substrates have been successfully tested. It should be noted that the aromatic redox
tag may be attached both to the olefinic substrate as depicted in Scheme 26.37 and to the enol ether
substrate [93,94].
The influence of the substitution pattern of the aromatic ring on this type of conversion was
studied extensively (Scheme 26.38) [84]. A clear correlation between oxidation potential of the
olefinic substrate 36, which is determined by the activating groups on the aromatic ring, and the
product yield could be established. As the enol ether substrate has to be oxidized first, the oxidation
potential of olefin 36 should be higher than 1.4 V vs. SCE for successful conversion. With potentials
above 1.8 V, the yield of the desired product decreases significantly, indicating that the intramolecu-
lar electron transfer in intermediate 33 (Scheme 26.37) from cyclobutane radical cation to the aro-
matic redox tag is inhibited. Among many tested substrates, p-methoxy- or p-phenoxy-substituted
phenyl rings rendered the best results with isolated yields of up to 94%. Furthermore, the reaction
proceeds diastereoselectively when a cyclic enol ether such as 3,4-dihydro-2H-pyran is employed.
The electrochemical conversion of phenyl ethers was studied in the context of protecting group
chemistry, particularly in the case of p-methoxyphenyl ether (PMP). This structural element is sta-
ble under strongly acidic or basic conditions and has therefore become very useful for the protection
of alcohols [95,96]. It is classically cleaved off by the employment of stoichiometric amounts of
ceric ammonium nitrate (CAN). Due to the strong oxidative conditions, the presence of several
functional groups can be problematic due to degradation of the starting material. In some cases,
direct anodic cleavage provides a milder and more selective alternative. The deprotection of several
alkyl and allylic PMP ethers was studied with both the electrochemical method and the classic
method using CAN as oxidant (Scheme 26.39) [97]. When the electrolysis was carried out in a water
OMe
1.7 V vs. SCE
NaClO4/NaHCO3
R OH
CH3CN/H2O
R O
R = alkyl, allyl Up to 92%
SchEME 26.39 Anodic cleavage of p-methoxyphenyl ethers.

acetonitrile mixture containing NaHCO3 and LiClO4 at 1.7 V vs. SCE using a divided cell, it was
found to be superior to the classic method. The orthogonality of this method could be demonstrated,
since several acid-, base-, and even oxidation-sensitive protecting groups are tolerated.
B. REDUCTIoN
Generally, ethers are very stable toward electrochemical reduction, and thus, preparatively use-
ful cathodic conversions are hard to achieve. This point becomes clearer in the context of lithium
ion battery electrolytes, whereby ethers were initially proposed as solvents [98]. Aliphatic ethers
such as THF and diethyl ether are stable on glassy carbon electrodes at 0 V vs. Li/Li+ (–3.2 V
vs. Ag/Ag+), whereas despite some further drawbacks, their sensitivity toward anodic oxidation
restricts their practical use in energy storage electrolytes [98]. Consequently, only few examples
for preparative cathodic reduction of ether compounds are reported in literature. For instance, the
cleavage of cinnamyl ethers from conduritol derivatives 37 in the presence of allyl ethers was
achieved using a mercury cathode (Scheme 26.40) [99,100]. In contrast to the nonelectrochemical
method using sodium in liquid ammonia, the cleavage proceeds selectively in the presence of allyl
ethers. The need for a very negative potential (–2.9 V vs. Ag/Ag+) indicates the challenge of such
cathodic conversions.
In another example, organic electrochemistry was combined with organometallic catalysis in
order to achieve efficient conversion of phenyl allyl ethers under galvanostatic conditions to the
corresponding phenols in high yields [101]. As active species serves a cathodically generated Ni(0)
species, which is constantly formed from the catalytically employed Ni(II) bipyridine complex.
A magnesium rod is used as sacrificial anode. It was found that using this cleavage method, several
functional groups such as nitril, ester, and halogen atoms are tolerated. Interestingly, for o-(allyloxy)
benzaldehydes (38), this reactivity leads to an intramolecular allylation of the carbonyl group by
cleavage and transfer of the allyl moiety (Scheme 26.41) [102].
The variety of reaction pathways, which are feasible with ether moieties, allows on the one hand
their use as inert tether and on the other hand their selective conversion. This Janus-type structural
motif is consequently very valuable for electroorganic synthesis.
R R R
–2.9 V
O O O
vs. Ag/AgNO3 Na/NH3
HO O O O
O HO
O O OH
Ph
37
78–83% R = Ph, H
SchEME 26.40 Reductive treatment of conduritol-derived compounds (37).
O OH
Ni(bipy)3(BF4)2
Mg anode
Bu4NBF4/DMF
O OH
38 87%
SchEME 26.41 Electrochemically induced intramolecular allylic transfer.

III. AROMATic ALcOhOLS (PhENOLS)

Phenols are very common structural entities and in contrast to the aliphatic congeners, the aromatic
alcohols represent unique electrophoric groups [103]. Since phenols are usually electron rich and
easily deprotonated, the anodic conversion of this particular substrate class has the higher relevance
compared to the aliphatic congener.
A. OXIDaTIoN
The oxidation potential of phenols is not only strongly affected by substituents on the aromatic core
but rather by the nature of the electrolyte employed. Upon the oxidation of 39, the corresponding
radical cation is formed. 40 represents a relatively strong acid and a proton will be spontaneously
expelled. The anodic treatment of phenols in basic media is facilitated, since the oxidation potential
is significantly lowered. The phenoxyl radical 41 has spin densities at several positions as indicated
by the mesomeric structures. As a neutral molecule, 41 is not well solvated by a polar electrolyte. In
particular, in protic media like sulfuric acid, it will be further oxidized to phenoxonium species 42.
If 39 is equipped with electron-releasing groups, the formation is more likely. A radical recombina-
tion of 41 is not very likely, since the applied current densities are far too low. Both phenoxyl radi-
cal and phenoxonium represent electrophiles and will attack the substrate 39 or other nucleophiles
leading to a bond formation. Since different reactive sites are present in intermediate 42, a variety
of by-products can be formed apart from the desired 2,2’-biphenol 43. Among these by-products,
2,4’-biphenol 44 and C,O-coupling product 45 play a dominant role. Consequently, the control of
the electroorganic conversion of phenols can be challenging [104] (Scheme 26.42).
+
OH OH O O O
Anode –H+ R R R
R R
39 40 41
Anode
+ 39 Anode
O O O
–H+
R R R
R OH
39 OH OH
42 R
+
–H+ +
R R
OH
43 44
OH
O
+ R +
45
SchEME 26.42 Possible reaction pathway for phenol oxidation.

1. Acetoxylation
One of the first anodic acetoxylation reactions was reported in 1952 [105]. The authors describe the
anodic transformation of naphthalene 46 in acetic acid and sodium acetate to form 1-acetoxynaphthalene
47. The acetoxylation product 47 was hydrolyzed to provide α-naphthol 48 in 24% yield (Scheme 26.43).
Scheme 26.44 shows a plausible mechanism for the acetoxylation of toluene 49 [106]. The first
step involves the abstraction of an electron from the aromatic hydrocarbon compound to generate an
aromatic radical cation 50. This step is followed by the nucleophilic attack of acetate onto the posi-
tion of the highest positive charge density. In this case, the attack should occur in para-position 51,
but other isomers are also possible. A subsequent oxidation leads to the carbenium species 52.
Elimination of a proton for rearomatization accomplishes the product 55. The carbenium species
allows the migration of the acetyl group by a 1,2-bridging process to form different isomeric prod-
ucts 55–57. So the final isomeric ratio depends not only on the position of the nucleophilic attack
but also on the relative energy of the isomeric cation intermediates 52–54.
The half-wave potential of the different monoacetoxy derivates can influence the isomeric ratio,
too. Table 26.4 displays the half-wave potentials of anisole and its monoacetoxylation products.
The potential of 4-acetoxyanisole is about 0.6 V lower than the potential of the starting material
[107]. Investigations on anisole under constant potential conditions yield 27% of a mixture of 2- and
OAc OH
NaOAc/HOAc H2 O/OH–
Pt-anode
46 47 48
SchEME 26.43 Anodic acetoxylation of naphthalene (46).
+
OAc
–e– +AcO– –e– H
+ +
OAc
H
H OAc H OAc
49 50 51 52 53 54
–H+ –H+ –H+
OAc
OAc
OAc
55 56 57
SchEME 26.44 Plausible mechanism for the acetoxylation of toluene (49).
TABLE 26.4
Half-Wave Potentials of Anisole and Its Acetoxylation Products
Entry Compound E1/2 vs. SCE (V)
1 Anisole 1.67
2 2-Acetoxyanisole 1.74
Source: Eberson, L. and Nyberg, K., J. Am. Chem. Soc., 88, 1686, 1966.
+ +
CH3 CH3 CH2 CH2 CH2OAc
–e– –H+ –e– +AcO–
49 58 59 60 61
SchEME 26.45 Mechanism of side-chain acetoxylation of toluene (49).
4-acetoxyanisole with an isomer ratio of 9:1 [107]. Electrolysis with only 50% of the required cur-
rent gave 40% of the acetoxylation product with an ortho/para ratio of 6:1. This reveals that the
para-compound with lower oxidation potential would be consumed at the anode at a higher rate
than the other compounds. This directly influences the isomer distribution.
Besides the reaction pathway described in Scheme 26.44, loss of a proton can take place at the
benzylic position (Scheme 26.45). This step is irreversible and leads to the benzylic radical 59.
Another one-electron transfer generates the cation 60, which is attacked by the acetate to form the
side-chain acetoxylation product 61.
The nuclear isomer ratio for the toluene of 43.2% ortho (57), 11.1% meta (56), and 45.7% para
(55) acetoxylation occurs with a ratio of nuclear to side-chain acetoxylation of 71.4–28.6%.
The amount of side-chain acetoxylation species depends on different facts: loss of the benzylic
proton leads to a benzylic radical with an electron in a p-orbital, which is able to overlap with the
aromatic π-system. This elimination is energetically disfavored if the benzylic orbital is sp3-hybrid-
ized like the benzylic position in triptycene. In this case, the radical and carbocation species would
be highly strained [108]. For this reason, triptycene shows 31.0% acetoxylation in the position 1,
68.5% in the position 2, and only 0.5% in the α-position [109].
One other factor that influences the ratio between side-chain and nuclear acetoxylations is the
electrode material. Mesitylene 62 is a good model compound for such studies, because there is only
one possible monoacetoxylation product 63 at the aromatic core and one side-chain acetoxylation
product 64 (Scheme 26.46).
Table 26.5 shows the effect of different anode materials on the ratio between side-chain acetox-
ylation and the acetoxylation of the aromatic core. The isolated yields are given in Table 26.5 [110].
CH3 CH3 CH2OAc

OAc
HOAc/NaOAc
+
Anode
62 63 64
SchEME 26.46 Side-chain and acetoxylation of the aromatic core of mesitylene (60).
TABLE 26.5
Influence of the Electrode Material on the Ratio between Side-Chain
Acetoxylation Products and Substitution at the Aromatic Core
Entry Anode Material Ratio 63/64 Isolated Product (%)
1 Gold 3.6 23
2 Platinum 4.4 19
3 Rhodium 7.6 57
4 Carbon cloth 23 34
5 Glassy carbon 21 35
6 Graphite 23 56
Source: Eberson, L. et al., Acta Chem. Scand., 29b, 168, 1975.

The supporting electrolyte could also influence the product distribution. Acetoxylation of toluene
in acetic acid with tetrabutylammonium tetrafluoroborate instead of sodium acetate as supporting
electrolyte produces benzyl acetate as major product [110]. Under these conditions, the loss of the
benzylic proton of the cationic species seems to be much faster than the nucleophilic attack of acetic
acid. Therefore, the substitution on the aromatic core is disfavored.
One way to increase the yield of nuclear substitution product is the simultaneous reduction of the
α-acetoxylation by-products [111]. This reduction can be performed by adding palladium on char-
coal to the electrolyte system. The cathodically generated hydrogen can be consumed to regenerate
the starting material. Experiments with p-xylene without Pd/C lead to a ratio of 40% nuclear acetate
and 60% α-acetoxylation. Adding only 10% of the catalyst raises the ratio of 2,5-dimethylphenyl
acetate up to 98% by the simultaneous increase of total yield from 30% up to 75%.
Other examples of acetoxylation are shown at the end of the Section III.A.2.
2. Quinone Formation
The anodic oxidation of phenols is frequently studied but represents rather complex chemistry [112].
The different reaction pathways heavily depend on the applied conditions, for example, basic or
acidic media, electrolyte, potential, and electrode materials [113]. Sequences of electron and proton
transfers lead to different highly reactive intermediates. A well-studied example is the oxidation of
2,4,6-tri-tert-butylphenol (65) [114]. When performing the electrolysis in the presence of a base,
the formation of the deprotonated species, the phenoxide ion 66, will happen instantaneously (see
Scheme 26.47). After deprotonation, a single-electron transfer leads to the conversion to the phenoxyl
radical 67. Under acidic conditions, the removal of one electron generates a radical cation 65a. This
radical cation is a rather strong acid. Therefore, a proton transfer occurs and the phenoxyl radical 67
is formed which may further be oxidized to phenoxenium cation 68.
A common product of such oxidative phenol treatment is quinone. Phenols equipped with
hydroxy groups, para or ortho, yield the corresponding-para or ortho-quinones 69, 70 upon two-
electron transfer (see Scheme 26.48) [115].
Cyclic voltammetry studies were conducted to elucidate the mechanism for the anodic quinone
formation. A possible reaction pathway for the quinone generation is depicted in Scheme 26.49. This
transformation starts with an initial electron transfer at oxidation potential E1 followed by fast depro-
tonation to form the radical 72 (see Scheme 26.49). In the second electron transfer, the potential E2
is lower than E1; thus, the oxidation of this radical 72 is easier than that of the hydroquinone 71.
The desired quinone 73 is accomplished via another rapid proton elimination [115].
OH OH +
t-Bu t-Bu t-Bu t-Bu
–e–
+e–
t-Bu t-Bu
65 65a
+H+ –H+ +H+ –H+
O– O O
t-Bu t-Bu t-Bu t-Bu t-Bu t-Bu
–e– –e–
+e–
t-Bu t-Bu t-Bu
66 67 68
SchEME 26.47 Anodic oxidation of 2,4,6-tri-tert-butylphenol (65).

OH O O
–2H+
Z Z O
–2e–
or
(Y = OH,
Y Z = H, R O Y
or Y = H, R,
Z = OH) 69 70
R = alkyl
SchEME 26.48 Generation of ortho- and para-quinone.
OH OH O O O
–e– –e–
+
+e– –H+ +e– + –H+
OH OH OH OH O
71 E1 72 E2 73
SchEME 26.49 Proposed mechanism for the quinone formation.
OH O
–2e–
Cl CN Cl CN
–2H+
graphite electrode
Cl CN Cl CN
MeCN/LiClO4
OH O
74 75
SchEME 26.50 Reoxidation of 2,3-dichloro-5,6-dicyanohydroquinone (74).
2,3-Dichloro-5,6-dicyano-1,4-benzoquinone (75) is a well-known and synthetically useful oxi-

dant, for example, for the oxidative treatment of alcohols, ethers, or arenes [116]. For synthetic appli-
cation on larger-scale significant amounts are necessary and problematic waste is produced. From
the ecological as well as economical point of view, the reoxidation of 2,3-dichloro-5,6-dicyanohy-
droquinone (74) to 75 is of interest. The recycling of 74 can be achieved by an electrochemical oxi-
dation in acetonitrile with lithium perchlorate as supporting electrolyte using a divided cell design
[117]. Graphite rods as electrode material allow isolated yields of up to 77% (see Scheme 26.50).
The anodic conversion of hydroquinones into the corresponding quinones can be interesting
in many ways. The generated quinones can serve as intermediates in further transformations like
insertions or cycloadditions reactions [118,119]. By this way, complex molecules can be made using
theses quinones.
A typical application of this hydroquinone conversion is the generation of 3-hydroxy-substituted
quinones. After initial electron transfers in aqueous solution from para-hydroquinone 76 equipped
with electron-withdrawing moieties like nitro or a carbonyl group, the corresponding para-quinones
77 are provided (see Scheme 26.51). Subsequently, addition of water followed by aromatization
generates a trihydroxybenzene 78 [118]. Further anodic two-electron oxidation yields the expected
OH O OH O
–2e– –2e– R
R R R
–2H+ H2O –2H+
(R = –CHO,
OH OH
–COCH3, –NO2)
OH O OH O
76 77 78 79
SchEME 26.51 Electrochemical generation of para-quinone with electron-withdrawing groups.

OH
OH OH
O OH
OH
+ –4e–
H2O, NaOAc
O O
O O
80 81 82
SchEME 26.52 Intermolecular coupling of electrochemically generated ortho-quinone with nucleophiles.
OH O OH OH
O O
OH OH OH
O
O O O
O O OH OH
O O
O OH OH
O
HO
SchEME 26.53 Coupling products of catechol with β- or α-dicarbonyl compounds.
3-hydroxy-substituted quinone 79. If the starting material exhibits Cl, CH3, OH, or H as substituents
in position 2, no insertion of water occurs.
Other applications exploit the conversion of ortho-hydroquinone into ortho-quinones. These are
highly reactive chemical compounds that can be used as intermediates for intermolecular coupling
with different kinds of nucleophiles. Tabaković et al. reported a potential-controlled oxidation of
catechol (80) in aqueous sodium acetate including 4-hydroxycoumarin (81) as nucleophile (see
Scheme 26.52) [120]. After addition to the ortho-quinone, the intermediate is once more oxidized to
a quinoid system and a formal [3+2]-cycloaddition occurs. The desired product 82 of this sequence
could be isolated in 95% yields.
Scheme 26.53 displays a collection of products obtained by similar treatment of catechol with
β- or α-dicarbonyl compounds, respectively [121].
In situ generated quinones can also be used as substrates for Diels–Alder reaction [119]. Scheme 26.54
describes a more elaborated version of such a transformation. The reaction was carried out in an
emulsion of 0.5% acetic acid, including water-soluble hydroquinone and water-insoluble dienes.
OH
HO OH
O O
CO2Et O CO2Et
CO2Et EtO2C
CO2Et
Hydrophobic area
Nafion
Anode
SchEME 26.54 In-situ generated para-quinone at Nafion-coated and hydrophobic anodes.

TABLE 26.6
Anodic Formation of Ortho-Quinones with Subsequent Diels–Alder Reaction
Entry Hydroquinone Diene Product Yield (%)
1 83 86 89 88
2 83 87 90 94
3 83 88 91 96
4 84 88 92 94
5 84 85 93 Quant.
OH
OH
R2
HO R2 R3 –2e–
+
R4 –2H+ R3
CO2R1 4RO
2C R4
83 R1 = Et 85 R2 = R3 = Me, R4 = H 88 R1 = Et, R2 = R3 = Me, R4 = H
84 R1 = C8H17 86 R2 = R3 = H, R4 = CH2CO2Et 90 R1 = Et, R2 = R3 = H, R4 = CH2CO2Et
87 R2 = H, R3 = Me, R4 = CH2CO2Et 91 R1 = Et, R2 = H, R3 = Me, R4 = CH2CO2Et
88 R2 = H, R3 = Me, R4 = CH2CH = CMe2 92 R1 = C8H17, R2 = H, R3 = Me, R4 = CH2CH = CMe2
93 R1 = C8H17, R2 = R3 = Me, R4 = H
SchEME 26.55 Scope of Diels–Alder reaction.
Sodium dodecyl sulfate was used as emulsifier to generate micelles containing the diene. Particularly
advantageous is the fact that sodium dodecyl sulfate also serves as supporting electrolyte. For this
reason, no further ingredients are required. When performing on bare glassy carbon, only low yields
(0–30%) of the desired product were produced. For this reason, the anode was firstly coated with
Nafion and after that the surface sulfonic acid moieties were converted to sulfonamide groups to get
a hydrophobic layer. Transformations at such type of modified anodes lead to excellent yields up to
96% (see Table 26.6).
The conditions described earlier allow the conversion of different hydroquinone and dienes (see
Scheme 26.55).
Besides the intermolecular conversion of electrochemically generated ortho-quinones, an intra-
molecular follow-up reaction can take place. Scheme 26.56 depicts the anodic oxidation of tetrahy-
dropapaveroline (94), a dopamine metabolite. Under controlled potential, the corresponding double
quinone 95 is formed [122]. In the absence of strong nucleophiles, this product is able to undergo
intramolecular Michael addition as subsequent transformation.
Instead of hydroquinones, appropriately alkyl-substituted phenols may serve as starting materi-
als to generate dienones. Here, first oxidation steps generate the phenoxonium ion, which repre-
sents a highly reactive electrophile. For this reason, it can react with a broad variety of different
HO O
NH NH
HO O
–4e–
–4H+
OH O
OH O
94 95
SchEME 26.56 Electrochemical generation of Michael acceptor.

OH O O
–2e– R˝
R΄ R˝ R΄ R˝ R΄
–2H+ Nu
or
NuH
R R Nu R
NuH = H2O, ROH, RCO2H, RCN, ArOH, ArOR, ROCH CHR, RSCH CHR
SchEME 26.57 Mechanism of phenol-oxidation with subsequent nucleophilic attack of impurities.
TABLE 26.7
Anodic Formation of Cyclohexandienones via Nucleophile Trapping of Phenoxonium Ions
Entry Starting Material, Phenol Product, Dienone Yield (%) Anode Electrolyte System References
1 2,6-Di-tert-bu-4-Me 4-Methoxy-4-methyl 95 C MeOH, LiClO4, NaHCO3 [123]
2 2,6-Di-tert-bu-4-Me 4-Methoxy-4-anisyl 81 Pt MeCN–anisole, Bu4NBF4 [124]
3 4-Methoxy 4,4-Dimethoxy 97 Pt MeOH, LiClO4 [125]
4 4-Phenyl 4-Methoxy-4-phenyl 87 Pt MeOH, LiClO4 [123]
5 2,6-Di-tert-Bu-4-Ph 4-Ph-4-(l-ala-O-) 94 Pt CH2Cl2, Bu4NBF4, [126]
2,6-lutidine
OH O O
t-Bu t-Bu –2e– t-Bu t-Bu –2e– t-Bu t-Bu
–2H+ –H+
H2O –t-Bu+
t-Bu HO t-Bu O
96 97 98
SchEME 26.58 Transformation of 2,4,6-tri-tert-butylphenol (96) in presence of water.
nucleophiles, including solvent, electrolyte, additives, or impurities. Scheme 26.57 displays the
general procedure of this useful phenol oxidation, and Table 26.7 provides some examples of this
transformation.
Table 26.7 includes no example for the nucleophilic trapping of the phenoxonium ion by water.
Such syntheses of quinones have been carried out by the oxidation of phenols or para-alkoxyphenols
in the presence of water [123,127]. The para-alkoxyphenols yield the desired quinone via the gen-
eration of the corresponding hemiacetals. Scheme 26.58 shows the transformation of 2,4,6-tri-tert-
butylphenol (96) into quinone 98. The reaction was conducted in acetonitrile involving traces of
water [128]. The initial electron transfer followed by nucleophilic attack of water gives access to
para-quinol 97. Para-alkoxyphenols under comparable conditions lead to the formation of hemi
acetals. Extrusion of a tert-butyl cation and subsequent oxidation generates the quinone.
A useful application of this transformation is depicted in Scheme 26.59. The conversion of
p-substituted phenols with formaldehyde results in an architecture called calix[4]arene, which is
widely used in supramolecular chemistry (99) [129]. These structures and their corresponding
quinones are interesting as redox-sensitive sensors [130]. The oxidation takes place on platinum
anode in acetonitrile involving traces of water with tetrabutylammonium perchlorate as supporting
electrolyte. Beneficially, the oxidation is accompanied with the loss of the tert-butyl moieties and
due to the cationic charges, a selective conversion of opposite arene moieties is achieved to form
calix[4]arenediquinone (100).
Electrolysis of para-alkoxyphenols in alcoholic solvents like methanol allows access to syntheti-
cally useful quinone monoketals, which can be used as precursors for a rich follow-up chemistry
[125,131]. A variety of alkyl substituents in position 2 are tolerated (Scheme 26.60). The electrolytic
HO O
Oxidation
Pt, CH3CN
O O O O OH O O O O O O O
H HC CH3 H H3C CH3 H H 3C CH3 H
3
99
OH O
O O
O O O HO O O O O
H 3C CH3 H 3C CH3
100
SchEME 26.59 Electrochemical preparation of calix[4]arenediquinone (100).
OH O
R R
MeOH, LiClO4
R = H, CH2Me, CH2t-Bu
OMe MeO OMe
SchEME 26.60 Synthesis of quinone monoketals.
conversions were carried out in methanol with lithium perchlorate as supporting electrolyte by
using platinum as anode material. Good yields up to 85% were reported.
Investigations of wastewater degradation at BDD anodes and carbon–PTFE gas diffusion cath-
odes indicate that oxidation of sulfanilic acid (101) to 1,4-benzoquinone (102) is possible (see
Scheme 26.61) [132]. In this case, no direct electron transfer to the sulfanilic acid occurs. Instead,
the hydroxyl radicals act as oxidizer. There are two ways to generate hydroxyl radicals for the
hydroxylation of sulfanilic acid (see Scheme 26.62). On the one hand, cathodic reduction of oxygen
can be used to generate hydrogen peroxide to form the radical by the action of Fe2+ (electro-Fenton).
Fe2+ can be regenerated by the reduction of Fe3+ to Fe2+ on the cathodic surface. On the other hand,
hydroxyl radicals are obtained by the anodic oxidation of water on BDD.
In contrast to the previously described methods, quinones can also be formed by the oxidation
of polyfluorinated benzenes involving a 1,4-difluoro situation [133]. Despite the electron-deficient
nature of the substrates, the access to such highly fluorinated products is of significant interest,
O2 + 2H+
+2e–
H2O2
SO3H Fe2+ OH O
OH +2 OH
–SO42–, –NH4+ –2H2O

NH2 OH O
101 102
SchEME 26.61 Wastewater degradation to form 1,4-benzoquinone (102) from sulfanilic acid (101).
O2 + 2H+ + 2e– H2O2
Fe2+ + H2O2 Fe3+ + OH + OH–
H2O OH + H+ + e–
Fe3+ + e– Fe2+
SchEME 26.62 Different ways to produce hydroxyl radicals.
F –2e– O
F F 1) TFA/CH2Cl2 F F
NEt3 Yield: 72%
F F 2) H2O F F
F O
103
–2e–
F F F O
1) TFA/CH2Cl2
F F NEt3 F F
Yield: 52%
2) H 2O
F F F F
F F F O
104
SchEME 26.63 Conversion of 1,4-difluoro arenes into para-quinone.
since the conversion is tremendously easier than the installation of the fluorine moieties in the final
product. Scheme 26.63 displays two examples of the electrochemical perfluoro-1,4-benzoquinone
synthesis 103, 104. These electrolyses were performed on platinum electrodes in divided cells with
methylene chloride and trifluoroacetic acid as solvents and triethylamine as supporting electrolyte.
The quinones are afforded upon aqueous work-up.
The detailed reaction mechanism of this trifluoroacetoxylation is postulated and plausible for the
conditions applied (Scheme 26.64) [133]. Basically, there are two pathways for the generation of cat-
ion 107. Path A starts with the oxidation of hexafluorobenzene (105) to cation radical 106 followed
by a nucleophilic attack of the trifluoroacetate and another oxidation step to cation 107. Path B
Path A
F F F OOCCF3 F OOCCF3
F F F F F F F F
–e– CF3COO–
F F F F TFA F F F F
F F F F3CCOO F
105 106 107
–e– Hydrolysis
Path B F OOCCF3 O
– F F F F
–e +105
CF3CO2H CF3CO2
+
–H
108 F F F F
F O
109
SchEME 26.64 Mechanism of quinone formation from 1,4-difluoro arenes.

NR2 NHR2H
+ AcOH + AcO–
SchEME 26.65 Acetoxylation with solid support bases.
OH N O
t-Bu t-Bu O t-Bu t-Bu
AcOH/MeCN
t-Bu t-Bu OAc
110 111
SchEME 26.66 Para-acetoxylation of of 2,4,6-tri-tert-butylphenol (110) with solid support bases.
starts with the oxidation of trifluoroacetic acid to get the trifluoroacetyl radical (108). This radical is
powerful enough to attack hexafluorobenzene. The open-shell intermediate is oxidized directly or
indirectly, resulting in cation 107. Subsequent nucleophilic attack of trifluoroacetate and hydrolysis
accomplishes the final quinone 109.
For understanding the mechanistic course of the acetoxylation reaction of hydrocarbons, oxida-
tion potentials of the acetate and the hydrocarbon compounds were determined [107]. In acidic
media, the oxidation potential of the acetate ion is higher than the potential of hydrocarbon com-
pounds like naphthalene. Mechanistic investigations of the acetoxylation reaction indicate that this
reaction takes place at a potential closer to the potential of hydrocarbon substrate than the one of
the acetate. In that case, reaction path A seems to be more realistic. The oxidation potential for the
trifluoroacetate is significantly higher than the one for acetate. Consequently, both pathways seem
to be viable and most probably occur.
Recent investigations of the acetoxylation of phenols deal with the application of solid sup-
ported bases [134]. The concept relies on an acid–base reaction between acetic acid and bases
supported on silica gel. The immobilized base is able to form acetate required for the reaction
course (see Scheme 26.65), but these bases are stable under acidic and electrochemical conditions.
Therefore, separation of base after electrolysis is easy and recycling for subsequent runs possible.
Beneficially, no further electrolyte has to be added, which generates a significant green aspect onto
such conversions.
Scheme 26.66 shows a representative example for such a solid supported base acetoxylation
reaction. The electrolysis was carried out in an undivided cell equipped with platinum electrodes.
Acetoxylation of 2,4,6-tri-tert-butylphenol (110) yields 95% of the para-acetoxylation product 111.
In summary, the electrochemical conversion of phenols into the corresponding quinones is a
very useful reaction, which can be synthetically exploited on a preparative scale. Different start-
ing materials can be transformed into the desired quinones in good to excellent yields. This par-
ticular fact might have an impact on the use of substrates mixture originating from waste streams.
In addition, highly reactive quinones can be generated in situ as intermediates for following up
sequences.
3. Phenol Coupling
Despite the ongoing discussion on which mechanism applies when aryl–aryl bonds are formed, the
anodic coupling will definitely start with an initial oxidation step. For phenolic substrates, this will
be particularly the case, since the electrolyses are often carried out in basic electrolytes and trans-
formation is dependent on the oxidation potential. Therefore, the term oxidative coupling should
be rather used instead of Scholl reaction [135a]. The use of electroorganic methods instead of stoi-
chiometric reagents for the generation of phenol coupling products is of great practical interest,
since several of the products are useful building blocks for ligands [135b]. In addition, the moieties
formed are also present in naturally occurring products [135b].
a. Homocoupling of Phenols

As already outlined, phenols exhibit a variety of reaction modes and several reactive positions of the
occurring intermediates. The electrolysis conditions applied are crucial and determine the molecular
architecture that is obtained. In particular, simple alkyl-substituted phenols show a broad scope of
products. When p-cresol (112) is anodically treated at carbon anodes in acetonitrile, the Pummerer
ketone scaffold 116 is formed and isolated in 37% yield (Scheme 26.67) [136]. The Pummerer
ketone originates from an ortho–para coupling with a subsequent 1,4-addition. The key for isolat-
ing substantial amounts from the complex product mixture is the addition of sodium hydroxide
to the electrolyte. Consequently, the substrates for electrolysis are the corresponding phenoxides,
which were treated with 1 F (Scheme 26.67).
2,4-Dimethylphenol (114) represents a rather simple substrate but experienced significant atten-
tion in the anodic coupling reaction, since the ortho, ortho-coupled product is a 2,2′-biphenol and
an important precursor for several catalysts [137]. The treatment on lead dioxide anodes in diluted
sulfuric acid provides mostly the hydroxylation product 120 in 44% isolated yield, whereas the
2,2′-biphenol 121 is only obtained in 18% yield (Scheme 26.68). The conversion for the electrolysis
is about 94% [127].
Switching with the substrate 114 to basic electrolytes creates a vast variety of anodic products,
which underlines the pronounced tendency of 114 for manifold reactions. The anodic transforma-
tion can be focused when using, for example, barium hydroxide as supporting electrolyte in metha-
nol (Scheme 26.69) [138]. In accordance with the results obtained with cresol [136], the desired
biphenol represents only a minor component. The major is the Pummerer ketone 118 and some
follow-up pentacyclic products 122–124.
An efficient electrolysis protocol for the synthesis of the diastereomerically pure spiropenta-
cycle 122 was elaborated. The anodic treatment in an undivided cell equipped with platinum elec-
trodes and in the presence of barium hydroxide results in the precipitation of intermediate 125
(Scheme 26.70), which represents a dehydrotetramer of 114 [139]. Since the dehydrotetramer 125
precipitates during the course of electrolysis, the isolation is easy to perform and applicable in
OH R3
Carbon anode
R3 H3CCN, Et4NBF4 R2 O H O
NaOH
R2 R1 R3
R1 R1
R2
112 R1 = CH3 R2 = R3 = H 116 = 37%

113 R1 = R2 = CH3 R3 = H 117 = 31%
114 R1 = R3 = CH3 R 2= H 118 = 20%
115 R1 = Et R2 = R3 = H 119 = 25%
SchEME 26.67 Formation of Pummerer ketone on carbon anodes in alkaline media.
OH O HO
PbO2 anode
+
dil. H2SO4
OH OH
114
44% 18%
120 121
SchEME 26.68 Acetoxylation product of 2,4-dimethylphenol (114) on lead dioxide anodes.

OH Pt electrodes HO
12.5 mA cm–2 O H
+
MeOH, base O
OH
114
32% 3%
118 121
O
O
O
+ +
O O
18% 5%
122 123
+ O O
O
O
4%
124 (two isomers 1:1)
SchEME 26.69 Variety of anodic products from 2,4-dimethylphenol using basic conditions.
HO O
OH O
Pt electrodes O
Ba(OH)2∙8H2O H+ or TiCl4
MeOH O O
O
114
52–60% 75%
125 122
TFA, Et3SiH
BF3∙OEt2
–65°C
O O
65% 83%
127 128
SchEME 26.70 Dehydrotetramer 125 of 2,4-dimethylphenol (114) as starting material for different poly-
cyclic architectures
multigram scale. Removal of one equivalent 2,4-dimethylphenol induces a stereospecific rearrange-

ment to the spiropentacycle 122. The latter step can be effected thermally or by acidic treatment.
125 represents a key intermediate for the selective synthesis of a diversity of polycyclic architec-
tures, whose selective formation from 114 can be controlled by the reaction conditions [140]. More
than 14 scaffolds, including, for example, propellanes and dibenzofuranes, are more or less exclu-
sively obtained from this electrochemically generated precursor [141]. Further formations of unique
architectures by anodic treatment are treated in Chapter 18.
The direct and selective conversion of 2,4-dimethylphenol to the desired 2,2′-biphenol 121 can
be synthetically achieved when using specific carbon electrodes and suitable electrolytes. When
employing BDD electrodes, a selectivity for the desired 121 compared to the Pummerer ketone
derivative is better than 18:1 [142]. The electrolysis is conducted in almost neat phenol at 70°C and
about 11% water in the electrolyte system. Although a supporting electrolyte is present, water is nec-
essary to provide sufficient conductivity. Using solvent-based electrolytes results mostly in an elec-
trochemical incineration [143]. The electrolysis only provides 2,2′-biphenol 121 in 56% yield and
with 29% current efficiency. Overoxidation of the desired product limits the yield in a batch-type
electrolysis. Performing only partial conversion of phenol 114 with approximately 0.4 F avoids sig-
nificant oligomer formation, and the nonconverted substrate can be redistilled by short-path distilla-
tion [144]. The unique properties of BDD can be imitated by glassy carbon and trifluoroacetic acid
as electrolyte system. The electrolysis of 114 to 2,2′-biphenol 121 is accomplished in 64% yield on
recovered starting material. The current efficiency is 53%, and the corresponding Pummerer ketone
is not anymore detected [145]. The addition of 1,1,1,3,3,3-hexafluoroisopropanol to the electrolyte
allows a control of the reactivity when using BDD anodes [12]. The electrolysis of 114 in an undi-
vided cell provides 47% isolated yield of 2,2′-biphenol 121. This protocol seems to be general for
the electrolytic generation of symmetric biphenols in acceptable yields [146]. The successful tun-
ing in reactivity is underlined in the anodic treatment of sesamol to the corresponding 5,5′-linked
dehydrodimer 130. The isolated yield is 74%, whereas other electrochemical conditions only pro-
vide tar-type residues [12]. For less activated phenols, it is not necessarily the more productive
protocol. 2-Bromo-p-cresol or 2-fluoro-p-cresol is more efficiently coupled at a graphite anode with
trifluoroacetic acid as electrolyte component. Although the conversion of 2-fluoro-p-cresol is rather
moderate, it represents the first direct anodic coupling of a fluorophenol. Methyl-triethylammonium
methylsulfate (MTES) served as inexpensive electrolyte and gave the best results among all tested
supporting electrolytes [145] (Table 26.8).
The coupling of guaiacol derivatives 137, 139, and 141 are best performed at BDD anodes with
1,1,1,3,3,3-hexafluoroisopropanol, since this combination renders the best isolated yields [147].
Remarkably, the anodic treatment of 4-methylguaiacol yields selectively the ortho–meta coupling
product 136. This indicates that an intermediate phenoxyl radical attacks a closed shell reaction
partner on its most electron-rich position. Consequently, other substitution patterns, for example,
2,4-dimethoxyphenol, yield the expected 2,2′-biphenolic product 138 in 45% isolated yield [147].
Steric as well as electronic reasons direct the course of electrolysis and provide the biphenols 140
and 142, in 44% and 83% isolated yield, respectively. The undivided electrolysis is easy to perform
and generates these products in exclusive selectivity [147]. The electroorganic coupling of Schiff
bases derived from ortho-vanillin results in the dehydrodimers 144 in good to excellent yields [148].
The use of glassy carbon as anode and acetonitrile with perchlorate as electrolyte turned out to be
suitable. In general, 2,6-dialkyl-substituted phenols are prone to the formation of quinoide dehy-
drodimers. However, electrolysis at low voltage in a divided cell with frequent reversal of polarity
provides the 4,4′-biphenol in excellent yield [149]. The anodic conversion of eugenol in basic electro-
lyte at platinum anodes to the 2,2′-biphenol 148 is reported to be a quantitative process [150]. When
less electron-rich phenols, for example, 2-acetyl-p-cresol, are treated under analogue conditions,
only a moderate amount of the 2,2′-biphenol 150 is obtained [151]. Having an additional methoxy
group in the substrate for electrolysis, for example, in vanillin, is rewarded by significant better
results of 65% yield [152].
TABLE 26.8
Homocoupling of Different Phenols
Substrate Electrolysis Conditions Product Yield (%) References
OH BDD anode, MTES, 11% 56 a [142]

H2O OH
BDD anode, MTES, HFIP 47 [12]
Graphite, MTES, TFA 64 [145]
OH
114
121
OH BDD anode, MTES, HFIP O 74 [12]

O
O
O OH
129
OH
O
130 O
Br BDD anode, MTES, HFIP 30 [12]

OH Graphite, MTES, TFA OH 76 [145]
Br
Br
131 OH
132
F BDD anode, MTES, HFIP 19 [12]

F
F
133 OH
134
O BDD anode, MTES, HFIP O 33 [147]

OH
135 O
136
O BDD, MTES, HFIP O 45 [147]

OH
OH
O
O O
137 OH
138 O
OH BDD, MTES, HFIP OH 44 [147]
O O O O
O
139
OH
140
O
(continued )

OH BDD, MTES, HFIP HO O 83 [147]
O
O
O
O O OH
141
142
OH Glassy carbon, NaClO4, 41–100 [148]
O
O H3CCN
NR HO
RN O
R = alkyl, benzyl
143
OH
144
NR
OH Pt, LiClO4, MeOH/CH2Cl2, tBu 93 [149]
divided cell
tBu tBu HO
tBu
tBu
145
OH
146
tBu
OH Pt, LiClO4, NaOH, MeOH 100 [150]
O
OH
O
O
OH
148
147
O OH Pt, NaOH, MeOH/H2O 26 [151]
OH O
O OH
149 150
(continued )

OH Pt, NaClO4, Et4NOH, O 65 [152]
H3CCN
O
OH
O
O
OH
O
151
152 O
MTES, Et3NCH3+ −O3SOCH3; HFIP, 1,1,1,3,3,3-hexafluoroisopropanol; TFA, trifluoroacetic acid.

a Based on recovered starting material.
In order to circumvent the nondesired pathways upon the oxidation of phenols and to gain selec-
tivity, the introduction of a template at the phenolic oxygen atoms is a common and actual topic [153].
For employing conventional reagents for the oxidative transformation, covalently tethered phenolates
were successfully applied. Several elements, such as titanium, zirconium, silicon, and phosphorus,
have been studied as oxophilic templates for enolates or phenolates in oxidative coupling processes
[154]. Silicon-tethered substrates turned out to exhibit the best synthetic practicability [155]. For the
anodic treatment, boron is the element of choice, since the limited coordination number, stability,
and hydrolytic cleavage are ensured. Moreover, 153 can be prepared from the corresponding phenols
in a two-step protocol or a one-pot procedure [156]. As sodium base, either a piece of sodium metal
is added after removal of water or sodium methanolate is used. Moreover, these tetraphenoxy borates
153 are anionic and serve as substrates as well as supporting electrolytes. Consequently, phenoxy
borates are ideal substrates in terms of tethered phenolates [157]. The oxidation potential corresponds
to the one of the individual phenolates. The anodic treatment in acetonitrile results in 154, which can
be hydrolyzed with hot water. The broad scope of this transformation is demonstrated in more than
20 examples [157]. This electroorganic approach can be applied to a variety of phenolic substrates
and is scalable to a multi-kg range [158]. The electrolysis can be performed on platinum or graphite
anodes. The overall yields are acceptable to good with a superb product quality. The scope is limited
by the necessity of a substituent in position 4 of the phenolic substrate and the ligand exchange dur-
ing electrolysis. Because of the latter the electrolysis is best carried out at elevated temperature and a
chiral dummy ligand cannot be exploited for stereo induction (Scheme 26.71).
b. Cross Coupling with Phenols

The direct electrochemical cross coupling faces the challenge that usually the individual oxidation
potential of the components is a strong selectivity directing argument. This will result in a strong
preference for homo-coupling products 158 and 159, whereas the desired cross coupling product
160 is often only obtained in traces. Even when the more stable component is used in excess, the
mixed biaryl is obtained in far less amounts than statistics would predict (Scheme 26.72).
Yoshida et al. circumvented this dilemma with the cation-pool method and established an elegant
electroorganic access to unsymmetrical biaryls [159]. So far, this method cannot be extended to
biphenols and is not scalable, since electrolysis at very low temperature and expensive supporting
electrolytes is required. However, the spatially and timely separated oxidation of one phenol to a
quinone ketal by hypervalent iodine reagents and subsequent conversion with another phenol deriv-
ative provides mixed biphenols [160]. The strong electrophilic conditions, the two-step sequence,
OH
R
B(OH)3, –H2O Anode
4 R Na B O
Then Na or Na base H3CCN
4
153
R Na+
R
OH
O – O Hydrolysis R
B 2
O O R
OH
R R
154
OH
OH OH
OH OH
HO
85% 66% 48%

155 156 157
SchEME 26.71 Selective biphenol preparation via boron templates.
H H
R΄ R
Oxidation
R + R΄ +
R΄ R
158 159
R
+
R΄
160
SchEME 26.72 Anodic phenol-phenol cross-coupling.
and excess of oxidizer limit the scope of this conventional phenol cross coupling. A direct arylation
of phenols was achieved by using guaiacol derivatives and electron-rich arene components [13]. A
rationale is outlined in Scheme 26.73. At a BDD anode, the phenolic substrate is oxidized, and after
extrusion of a proton, a phenoxyl radical 161 is generated. The electrophilic behavior of this inter-
mediate allows conversion with electron-rich arenes. The second oxidation step of 164 can occur
directly or indirectly and accomplishes the mixed biaryl. Because of the two oxidation steps, the
process is highly sensitive to the current density applied. Typically low current density in the range
of 2–6 mA cm−2 is employed. It turned out to be an electrolyte-dominated process, and the presence
of methanol or water in 1,1,1,3,3,3-hexafluoroisopropanol (HFIP) is crucial for a good yield and
unique selectivity for the cross coupling product [161,162]. More examples about the coupling of
phenols with nucleophilic partners are provided in Chapter 18, whereas this section is dealing with
the phenol–phenol cross coupling.
Since the found selectivity for the cross coupling can only be explained by the formation of
strong solvates, this transformation was extended to the phenol–phenol cross coupling. Dependent
+
OH
A
H+ O O
N
R R R΄
O
D 161 162
E
OH O
H
R΄ R΄
R R
H H
164 163
H+ OH
R΄
SchEME 26.73 Mechanism for the anodic phenol-phenol cross-coupling.
on the substitution pattern of the phenol, the nucleophilicity and oxidation potential can be decou-
pled in a certain range. The more electron-rich component experiences tight solvation and the
nucleophilicity is strongly decreased, whereas the less oxidizable phenol can act as nucleophile
and starts the cross coupling sequence. Besides the highly fluorinated alcohol HFIP, other sol-
vents like formic acid are also suitable for the electroorganic cross coupling [163]. Both solvents
have in common a very strong hydrogen bonding capability. The selectivity for the phenol–phenol
cross coupling product is in both solvent mixtures higher than 100:1 (see Table 26.9). Because the
anodic stability of formic acid is not given, the isolated yields are significantly lower compared
to the electrolyses performed in HFIP/MeOH mixtures [164]. The scope for the formation of the
unsymmetrical 2,2′-biphenols covers products that combine electronically and sterically different
moieties (Scheme 26.74).
The example of the solvent-directed cross coupling underlines that this particular field is emerg-
ing and similar advances can be expected for other substrates in near future. The full potential of
electrosynthesis will be demonstrated when several steps of conventional synthesis can be short-cut,
because different pathways could be employed.
B. REDUCTIoN
1. Electroreductive Hydroxylation of Aromatic Compounds
One-step synthesis of phenol from benzene can be used as an attractive alternative for the Hock
process, which generates phenol from cumene on an industrial scale. The electrochemical synthe-
sis of phenol uses the reductive regeneration of oxidizing agents like Fenton’s reagent or generates
H2O2 reductively from molecular oxygen for the chemical oxidation of benzene. Advantages of this
approach are the conversion to phenol at ambient temperature and pressure compared to the Hock
process, wherein high temperatures and high partial oxygen pressure are required. In addition,
stoichiometric side products, like acetone, are avoided. When using Fenton’s reagent, the electro-
chemical reduction usually regenerates Fe2+ from Fe3+, which is consumed due to side reactions.
TABLE 26.9
Anodic Cross Coupling of Phenols with Different Solvent Mixtures
Yield (%)
Product HFIP/MeOH HCOOH/MeOH References
OH
O 50 28 [164]
OH
OH
O 36 13 [164]
OH
OH
O 61 45 [164]
OH
OH
63 34 [164]
OH
MTES, Et3NCH3+ −O3SOCH3; HFIP, 1,1,1,3,3,3-hexafluoroisopropanol; TFA, trifluoroacetic acid.
OH OH
BDD anode OH
H H R
MTES
R + R΄ R΄
Solvent mixture OH
Selectivity: >100:1
SchEME 26.74 Direct anodic phenol-phenol cross-coupling reaction.

Cathode
Fe3+ Fe2+
H2O2 + Fe2+ Fe3+ + HO– + OH
H
H OH
R + OH R
OH
H OH
R + Fe3+ Fe2+ + H+ + R
With R=H 64%

R = Cl 18% (o:p = 60:40)
Usage of H2O2
R=F 80% (o:p = 85:15)
R = CN 21% (o:m:p = 27:18:55)
SchEME 26.75 Cathodic hydroxylation of benzene derivatives using Fenton’s reagent.
The Fe2+ ions react with hydrogen peroxide to provide hydroxyl radicals. These hydroxyl radicals can
oxidize benzene and analogue substrates to phenols (see Scheme 26.75) [165]. The displayed yields
in Scheme 26.75 were obtained by employing H2O2, which was not electrochemically generated.
When adding copper salts to Fenton’s reagent, oxidation takes place more easily, since Cu2+ is
a better oxidizer for carbon-centered radicals than Fe3+ [165,166]. Regeneration of resulting Cu+ is
achieved by redox reaction with Fe3+. With this method, various benzene species could be oxidized
to their corresponding phenols in moderate-to-good yields (see Scheme 26.75). To prevent further
functionalization to hydroquinone or catechol, which represents a general problem in this electro-
reductive synthesis of phenols, continuous extraction of the phenolic products is a viable strategy
[165]. In this conversion, hydroxyl radicals, generated from hydrogen peroxide, act as oxidizer.
Direct synthesis of phenol from benzene and oxygen has been achieved in trifluoromethanesulfonic
acid as electrolyte on a graphite cathode with current efficiencies of 22–41% [167]. The postulated
mechanism involves an electrochemical reduction of oxygen to H3O2+, which is capable of oxidizing
benzene (Scheme 26.76).
The combination of both methods, reductive generation of hydrogen peroxide in the presence
and absence of Fenton’s reagent, was carried out in 0.1 M H2SO4 on mercury, lead, copper, and
silver electrodes. In the presence of Fenton’s reagent, hydroxylation of benzene to phenol, hydroqui-
none, and catechol and the hydroxylation of phenol to hydroquinone and catechol are considerably
accelerated compared to the same reaction without Fenton’s reagent [168]. A similar approach was
investigated by the oxidation of benzene in 0.1 N H2SO4/acetonitrile (9:1) with Cu+ and oxygen.
Consumed Cu+ was regenerated from Cu2+ electrochemically [166].
Hibino et al. described the cathodic formation of phenol from benzene at vanadium oxide–based
electrodes under direct and alternating current conditions with high current efficiencies and selec-
tivities. Although the only noticeable side product mentioned is CO2, the selectivity of the reaction
is questionable, because the electrochemical reaction was carried out only to low conversions and
possible side products may occur on the synthetic scale [169,170].
Another approach for electroreductive synthesis of substituted phenols was investigated by the
reduction of nitrobenzene compounds in voltammetric studies and preparative scale electrolysis.
+
OH2
–
–
– None +
– OH2
– OX
–
–
– H3O2+
– or OX
– "OH+"
–
–
–
–
– RED
–
–
– CF3SO3H
–
–
O2
Cathode
SchEME 26.76 Direct synthesis of phenol from benzene and oxygen.
NO2 NHOH NH2

Cu(Hg) cathode
4e–, 4H+ H+
20% H2SO4(aq)
OH
Cu(Hg) cathode 76.9%
20% H2SO4(aq)
2e–, 2H+
NH2
18.8%
SchEME 26.77 Reduction of nitrobenzene to p-aminophenol and aniline.
Reduction of nitrobenzene with an amalgamated copper cathode in 20% aqueous H2SO4 yields
almost 77% p-aminophenol after Bamberger rearrangement and 18.8% aniline as a side product
[171] (Scheme 26.77).
2. Electroreductive Birch-Type Reaction

Electrochemical Birch-type reactions (see Scheme 26.78) of different aromatic systems have
become a synthetically important alternative to the classic Birch reduction using alkali metal in
liquid ammonia, even for presumably more electron rich and consequently more difficult to reduce
systems like methoxyaromatics and phenol [172]. It is noteworthy that only after the protection
of phenols as ether a practical method is established. Generally, the cathodic Birch reduction has
been carried out successfully in various solvents, such as liquid ammonia [173], methylamine [174],
ethylenediamine [175], hexamethylphosphoramide [176], aqueous diglyme [177], anhydrous THF
[178], and water [172].
The advantages of a cathodic Birch reduction compared to the classic protocol are mostly
due to the possibility to avoid working with large quantities of alkali metal and a much simpler
experimental procedure. For instance, it is possible to avoid liquid ammonia, which is a strongly
O O
Cathode
+2H+
R R
SchEME 26.78 Electrochemical Birch-type reaction.
Hg cathode
(C4H9)4N+ (C4H9)4N (Hg)n
O O –
(C4H9)N (Hg)n + R + (C4H9)4N+ + nHg

R
O – O
–
+ H 2O + OH
R R
O O
R + (C4H9)4N (Hg)n R + (C4H9)4N+ + nHg
O O
–
+ H 2O + OH
R R
SchEME 26.79 Electrochemical Birch-reaction at a mercury cathode.
basic solvent and has to be constantly kept below −33°C; also solubility of the reactants becomes a
minor issue due to the larger variety of solvents, which can be employed. In particular, for upscal-
ing, the electroorganic approach provides several beneficial safety aspects. The mechanism of a
cathodic Birch reduction strongly depends on the used electrolyte and electrode system. Studies
on the electroreduction of methoxybenzene, 1,2,3,4-tetrahydro-6-methoxynaphthalene, and ste-
roidal systems using aqueous tetrabutylammonium hydroxide and a mercury cathode report a
suggested single-electron transfer from an electrogenerated tetrabutylammonium amalgam [172]
(Scheme 26.79).
In contrast to this postulated mechanism, electrolyte systems based on lithium salts in combina-
tion with magnesium electrodes in THF suggest an electron transfer from electrogenerated lithium
species similar to the conventional Birch reduction [178]. In all cases, the product yield is highly
sensitive to solvents, electrode materials, and temperature applied.
Besides various studies on substituted benzene and naphthalene systems, further investigations
were carried out on cathodic Birch reduction of methoxy-substituted steroids (see Table 26.10).
Cathodic Birch reduction on steroids became an important synthetic alternative to the classic proce-
dure of the Birch reduction, since many substrates exhibit a challenging solubility in liquid ammonia
[180]. Kashimura et al. described a method to incorporate deuterium in position 1 and 4 of aromatic
systems when electrochemical Birch reduction is performed in anhydrous THF in the presence of
10 equiv. t-BuOD instead of t-BuOH as proton source [178]. The latter was not performed directly
on phenols as substrates.
TABLE 26.10
Electrochemical Birch Reaction for Different Substrates
Electrolyte Yield
Substrate (Cathode) Product (%) References
H2O–Bu4NOH 80 [172]
O O
(Hg)
H2O–Bu4NOH 85 [172]
(Hg)
O O
THF–LiClO4 (Mg) 91 [178]
O O
O THF–LiClO4 (Mg) O 80 [178]
O O
O MeOH/MeCN O 93 [179]
(20/3)–Et4NCl
(Pb/Pt)
O O
O O
+ O
O
O
O THF/MeOH– O 92 [179]
Et4NCl (Pb/Pt)
O O
+ O
O
OH Liq. NH3–NaCl/ OH 70 [173]
NaI (Mg/Al)
(continued )

Electrochemical Birch Reaction for Different Substrates
Electrolyte Yield
Substrate (Cathode) Product (%) References
OH THF/ OH n.d.a [180]
H2O–Bu4NBF4
O O
OH n.d.a
+
O
OH H2O–Bu4NOH OH 90 [172]
R (Hg) R
O O
R = H or C2H5 R = H or C2H5
a Ratio of depicted products 10:90, but no clear data of isolated yield are given.
3. Electroreductive Hydrogenation and Hydrodeoxygenation of Phenolic Moieties

Electrocatalytic hydrogenation of unsaturated molecules is a process wherein acidic solvents are
used as a proton source to generate chemisorbed hydrogen at the cathode. Further hydrogena-
tion reaction mostly proceeds similar to catalytic hydrogenation reactions. This method avoids
the need for an external, fossil-based hydrogen supply and therefore allows a mild reaction at
ambient conditions. This implies less safety aspects compared to typical hydrogenation reactions.
Electrocatalytic hydrogenation of organic molecules is of current and high interest in the context
of green chemistry [181].
Electroreductive conversion of phenol to cyclohexanol has been reported in a 2 N aqueous HClO4 –
Et4NBr system at a platinum cathode in 82.7% yield with a current efficiency of 69.5%. Under similar
conditions, 2-naphthol could be converted to trans-decalol in 70% yield (see Scheme 26.80) [182].
OH OH
Pt cathode
2 N HClO4 in H2O
Et4NBr
82%
Pt cathode
2 N HClO4 in H2O
HO HO
Et4NBr
70%
SchEME 26.80 Electrochemical hydrogenation of phenol and naphthol.

OH OH
Pt cathode
H2O/H2SO4
100% c.e.
X X
X = H, OH, OMe, Me, COOH, NH3+ NH2CH3+ , CN, Et, tert-Bu
SchEME 26.81 Electroreductive hydrogenation of phenol derivatives.
To reduce phenol to cyclohexanol with a reasonable current efficiency, the reaction has to be carried
out at low current densities (0.67 mA cm−2) [166]. Therefore, large amounts of solid platinum foil have
to be employed to ensure a high reaction rate. In order to avoid the use of high amounts of platinum, the
electrocatalytic hydrogenation of phenol to cyclohexanol on highly dispersed platinum electrodes has
been developed [183]. Current efficiencies of 85% could be achieved on electrodes with a platinum load-
ing of 2%. Due to the small amount of platinum, which is used in highly dispersed platinum electrodes,
the cost in the fabrication of these electrodes is much less than bare or platinized platinum [183]. Recent
investigations are carried out on finding an effective support material/catalyst pair for catalytic nano-
aggregates, since the support material of the electrode has been found to play an important role in the
effectiveness of electrocatalytic hydrogenation reactions [181]. Electrocatalytic hydrogenation can be
used for stabilizing biooil by hydrogenation and hydrodeoxygenation of phenolic compounds. Therefore,
the reduction of three model substrates, phenol, 2-methoxyphenol, and 2,6-dimethoxyphenol, has been
investigated. The electrocatalytic species was generated by ruthenium on activated carbon cloth. The
conversion was achieved at mild temperatures and ambient pressure [184].
Another mechanistic procedure has been found in the reduction of phenol and anisole nuclei
when reduction to cyclohexanol and methoxycyclohexane was carried out in an EtOH–HMPA–LiCl
system at an aluminum cathode in 45.4–51.7% yield. In this protocol, solvated electrons as reducing
agent were proposed [185]. Therefore, the reaction mechanism is more similar to cathodic Birch
reductions. Sasaki et al. describe the electroreductive hydrogenation of the aromatic core of differ-
ent phenols [166]. Unfortunately, this represents only a cyclic voltammetric study without the isola-
tion of any product. The synthetic utility is consequently questionable (Scheme 26.81).
4. Deoxygenation of Phenolic Compounds

Deoxygenation reactions are still one of the major challenges in organic electrochemistry. Indirect
deoxygenation of phenolic compounds by electrochemical reductive processes can be achieved
when the hydroxyl group is converted into a good leaving group like phosphate esters [186] or tet-
razolium ethers [187].
The electrochemical reduction of aryl diethyl phosphates has been carried out on a lead cathode
in DMF/p-toluenesulfonate on various substrates giving isolated products in 43–73% yield. The
initiation step of this deoxygenation reaction is found to be a one-electron transfer to the aromatic
nucleus [186]. Although this procedure is not applicable for all kinds of phenolic compounds, for
example, conjugated double bonds in side chains and half of the naphthalene nucleus of 2-naphthyl
diethyl phosphate were also hydrogenated along this pathway, it gives good yields especially for
methoxy-substituted electron-rich phenols (see Scheme 26.82).
A conventional method for the removal of phenolic hydroxyl groups is the conversion into tetrazol-5-yl
ethers followed by catalytic hydrogenation in the presence of a noble metal catalyst [187]. The electro-
chemical pathway has been investigated at a Hg pool cathode in DMF–H2O (95:5 v/v%). The proposed
mechanism describes a required one-electron transfer to the phenolic core for a successful cleavage of the
aryl-oxygen bond. As anticipated, phenols exhibiting electron-withdrawing groups like p-cyanophenol are
more selectively converted. If the substrate is based on electron-rich phenol derivatives, the first electron
transfer is addressed to the tetrazole moiety, and therefore, bond cleavage happens in the way that pheno-
lates can be recovered as a side reaction or even as the only conversion product (see Scheme 26.83) [187].
O O
P
O O Pb cathode O O
O O divided cell
DMF
Et4NOTs
67%
SchEME 26.82 Cathodic deoxygenation of aryl diethyl phosphates.
N=N
Ph N N H OH
O Hg cathode
+
Et4NBr
DMF–H2O (5 vol%)
R R
R R = CN 53% (isolated yield) 0%

R = OMe 30% g.l.c analysis 30% g.l.c analysis
SchEME 26.83 Deoxygenation of phenols via derivatization with tetrazoles.
OAc OAc
Hg cathode
Et4NI
DMF
O OH
R
75% R
SchEME 26.84 Electrochemical cleavage of a carbon oxygen bond on phenol ethers at a mercury cathode.
Cleavage of a carbon–oxygen bond on phenol ethers has been carried out in DMF–Et4NI on a
mercury cathode in chemical yields of 75% for a vitamin K precursor (see Scheme 26.84) [188].
5. Reduction of Quinones
Quinone-based redox couples have been investigated intensively because of their chemical and
biological importance, for example, as prototypical reversible redox systems in chemical reactions,
in quinoenzymes, and anticancer drugs. The most important function of quinones is the reversible
electron and proton transfer. The related thermodynamic parameters of interest are the standard
redox potential E° and the pK values. The standard redox potential E° of different quinone systems
strongly depends on the quinone series, for example, benzoquinone, naphthoquinone, or anthra-
quinone, the substituents of the quinone ring, and the stabilization of the reduced species. Solvent
polarity, pH, intra- and intermolecular hydrogen bonding, and ion-pair formation play an important
role in the stabilization of the reduced species [188].
In aprotic solvents, quinones are reduced in two successive one-electron steps to an anion radical
Q• − and the hydroquinone dianion Q2− (see Scheme 26.85) [189].
–
Q + e– Q
Q – + e– Q2–
SchEME 26.85 Reduction sequence of quinones in aprotic solvents.

O OH
+ 2e– + 2H+
O OH
(a)
O O–
+ 2e–
O O–
(b)
SchEME 26.86 Possible reduction products of quinones in acidic (a) and alkaline media (b).
O O
–e–, –H+
Electrooxidation
OH O O O O
Cytotoxic ROS
O22–
O O
n
+2e–, +2H+
+2e–, +2H+
OH
O2
OH O
Cathode
n
SchEME 26.87 Electrochemical reduction of oxygen via quinone polymer films on cathodes.
In acidic solutions, the reduction is a single-step two-electron two-proton process (see Scheme
26.86a), while in alkaline pH, the reduction does not involve protons and is only a two-electron
reduction (see Scheme 26.86b) [190]. At neutral pH, reduction is either a one-proton two-electron or
only two-electron process without the participation of protons [190].
The electrochemical reduction of quinones can be used synthetically to reduce oxygen as the resulting
hydroquinones work as reducers for oxygen. It was possible to use quinones as a polymer film on elec-
trodes capable of serving as a controllable source of reactive oxygen species (see Scheme 26.87) [191].
Electroreductive coupling of 3,4-estrone-o-quinone with adenine has been achieved in a DMF–
LiClO4 at a platinum cathode with a chemical yield of 14.1% (see Scheme 26.88) [192].
Polyether-bridged quinones (see Scheme 26.89) can be used as crown ethers equipped with
redox systems and are known for complexation with lithium, sodium, and potassium cations [193].
Coupling between the complexation behavior and redox properties of these systems has been proved
by cyclic voltammetry [193].
N
O H2N N
NH2
O
N N NH
N + Pt cathode
N N DMF
H O LiClO4
O HO
OH
SchEME 26.88 Electroreductive coupling of 3,4-estrone-o-quinone with adenine.
O n O n
O O
O O O O OH O
[H]
[O]
R R R R
O OH
R = H, Me
n = 1–4
SchEME 26.89 Polyether-bridged quinones as redox sensitive crown ethers.
O OH
Hg cathode
EtOH/H2SO4
O OH
+
OH2 OH
Hg cathode
EtOH/H2SO4
OH
SchEME 26.90 Electrochemical reduction of anthrahydroquinone to anthrol and anthrone.
The reversible reduction of anthraquinone to anthrahydroquinone has been carried out in EtOH
(50%)/H2SO4 (50%) system on a mercury electrode with further reduction of protonated anthrahy-
droquinone to anthrol and isomerization to anthrone (see Scheme 26.90) [194].
An intramolecular cyclization product was isolated in 14% yield after the reduction of a bridged
benzoquinone in anhydrous CH2Cl2–Bu4NBF4 at a mercury cathode and stabilization of the reaction
product by acylation (see Scheme 26.91) [195].
1) Hg cathode AcO
O CH2Cl2 AcO
O
Bu4NBF4
O O
2) Ac2O OAc
O 14%
SchEME 26.91 Intramolecular cyclization of tethered benzoquinones.

In summary, the cathodic treatments of phenols or to obtain phenols are viable electrosynthetic
pathways that are still far underrepresented. The reason for that might be the limited number of suit-
able cathode materials, which cause also severe toxicity concerns. Consequently, future research in
that particular field is required.
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27 Sulfur-, Selenium-, and
Tellurium-Containing
Compounds
Richard S. Glass
CONTENTS
I. Introduction ........................................................................................................................ 1035
II. Thiols .................................................................................................................................. 1035
III. Disulfides............................................................................................................................ 1037
A. Reduction .................................................................................................................... 1037
B. Oxidation .................................................................................................................... 1041
IV. Thioethers (Sulfides) and Thioketals.................................................................................. 1045
A. Oxidation .................................................................................................................... 1045
B. Reduction .................................................................................................................... 1050
V. 1,4-Dithiin and Thianthrene............................................................................................... 1052
VI. Tetrathiafulvalene and Analogues...................................................................................... 1055
VII. Thiophene and Analogues .................................................................................................. 1072
VIII. Polythio and Sulfur-Nitrogen Unsaturated Heterocycles ................................................... 1076
IX. Sulfonium Salts, Sulfoxides, Sulfones, Sulfinyl, and Sulfonyl Derivatives ....................... 1078
X. Selenium and Tellurium Compounds ................................................................................. 1080
References .................................................................................................................................... 1087
I. INTRODUcTiON
The electrochemistry of organosulfur, selenium, and tellurium compounds is reviewed with particu-
lar emphasis on studies published from 2000 to the time of writing. There have been recent reviews
of organosulfur electrochemistry [1,2], and this review brings them up to date and also includes
the less studied electrochemistry of organoselenium and tellurium compounds. The reviewed work
draws from many diverse areas, including organic synthesis, reaction mechanisms, and materials
science. Therefore, in addition to summarizing the electrochemical results, insight into the signifi-
cance of the electrochemical results to the relevant areas will be briefly presented.
II. ThiOLS
The oxidation of thiols depends on pH owing to the acidity of the thiol [1,2]. On increasing the pH,
oxidation peak potentials become more negative until the thiolate is completely formed after which
the oxidation potential is constant. Traditionally, mercury electrodes have been used for this reversible
oxidation to the corresponding disulfides. This redox process occurs via the intermediacy of mercury
thiolates [2]. Use of solid electrodes such as Pt, Au, or carbon for this process suffers from slow het-
erogeneous electron-transfer rates as well as adsorption (although a Pt electrode was recently used for
cv studies of 2-pyrimidinethiols in ethanenitrile in which irreversible oxidation was reported to give
1035
the corresponding disulfides and only on repetitive scans was adsorption identified) [3]. Consequently,
several strategies have been developed to overcome these problems. These developments have been
particularly motivated by interest in detecting biologically important thiols such as l-cysteine.
Boron-doped diamond electrodes show negligible adsorption and favorable electron-transfer kinet-
ics suitable for electrooxidation of thiols [4–6], and even proteins containing cysteine residues have
been studied [7,8]. However, other residues in proteins are oxidized in addition to cysteine. Although
carbon paste and glassy carbon electrodes typically suffer from the drawbacks outlined earlier, use of
mesoporous carbon-modified glassy carbon electrodes permits detection of l-cysteine electrochemi-
cally [9] as do carbon nanotube electrodes [10]. Although use of platinum electrodes is also problem-
atic, as mentioned earlier, platinum nanoparticles supported on nickel–cobalt nanofilms show high
sensitivity and long-term stability for the determination of cysteine by anodic oxidation [11].
Homogenous redox mediators such as ferricyanide [12] and ferrocenyl trimethylammonium [13]
have been used for l-cysteine oxidation using boron-doped diamond or glassy carbon electrodes,
respectively. The redox catalyst has also been incorporated into the electrode for cysteine oxida-
tion: quinizarine (1,4-dihydroxy-9,10-anthraquinone) adsorbed on glassy carbon [14], ruthenium
(IV) oxide-modified carbon paste [15], or Nafion-lead oxide-manganese oxide [16] electrodes.
2-Aminoethanethiol [17] and glutathione [18] have been electrochemically oxidized using cobalt
phthalocyanine adsorbed on a graphite electrode [17]. Similarly, 2-aminoethanethiol has been anod-
ically oxidized using electropolymerized cobalt porphyrin and phthalocyanine-based films depos-
ited on vitreous carbon electrodes [19].
An alternative approach has been developed for the electrochemical determination of thi-
ols not involving oxidation of the thiol to the corresponding disulfide. Here N,N-dimethyl-1,4-
phenylenediamine in solution is electrochemically oxidized to the corresponding 1,4-diimine. The
thiol then adds conjugatively to the 1,4-diimine to give an adduct, which is again electro-oxidized
to a sulfur substituted 1,4-diimine as shown in Scheme 27.1 [20].
A monolayer of thiophenolate has been grafted onto glassy carbon and this surface-confined spe-
cies can apparently be reversibly oxidized to the corresponding disulfide despite steric constraints
[21]. Electrochemical oxidation of thiols to disulfides involves the intermediacy of thiyl radicals.
Such an intermediate from 1,2,4-triazole-3-thiols has been trapped with dimethyl or diethyl acety-
lenedicarboxylate in an electrosynthesis of sulfur heterocycles as illustrated in Scheme 27.2 [22].
NH2 NH NH2 NH
–2e–, –H+ RSH –2e–, –H+
+2e–, +H+ +2e–, +H+

SR SR
NMe2 NMe2 NMe2 NMe2
+ +
SchEME 27.1 Electrochemical thiol determination with N,N-dimethyl-1,4-phenylenediamine.
H
O CO2R΄
H H H
N N N S R N S
R S R SH R
–e– R΄O2CC CCO2R΄
NH N N –H+ N N R΄= Me, Et N N

N
R = Me, Ph 86–90%
SchEME 27.2 Trapping of a thiol radical with dialkyl acetylenedicarboxylates.

Sulfur-, Selenium-, and Tellurium-Containing Compounds 1037
Anodic oxidation of C6S82−, 1a, and C6S6O22−, 1b, occurs in two reversible one-electron transfer steps
as shown by cyclic voltammetric studies, to the corresponding disulfide 2a and b, respectively [23]
S S S S
X
S– S
S S S
–S
S S
S S X S S
X
S
X S–
S 2
1a, X = S 2a, X = S
b, X = O b, X = O 3
The one-electron oxidation product from 1a is stable in solution in equilibrium with disulfide dimer
3 [24]. While removal of an electron from an RS− moiety in 1a formally gives RS•, it has been
reasonably suggested that the RS• moiety bonds intramolecularly with the RS− moiety forming the
disulfide anion radical of 2a [24].
III. DiSULfiDES
A. REDUCTIoN
As pointed out in Section II, electrochemical oxidation of thiols produces disulfides that may be
electrochemically reduced back to thiols/thiolates and such electro reductions have been reviewed
[25]. Owing to its commercial interest, the electrochemical reduction of l-cystine to l-cysteine
has attracted particular attention. The key chemical issue is that this reduction must be run in acid
because of the low solubility of these amino acids in aqueous solution of pH > 2. However, at low
pH, reduction of protons to produce H2 becomes a competitive reaction. Consequently, electrodes
at which there is a high overpotential for H2 production have been utilized. Early work has been
reviewed [26], and there have been recent studies using lead [27], mercury [28], and dispersed lead–
carbon black electrodes [29]. The thiolates produced by electrochemical reduction have been used
as nucleophiles in synthetically useful reactions [2]. A recent example utilizes the thiolate produced
by reduction of disulfide 4 to react with thio-glycosyl bromide 5a to produce 5b in 40–70% yield
depending on reaction conditions [30]. This electrosynthesis is performed in an undivided cell using
zinc as a sacrificial anode.
AcO S
O AcO
X
NC C S AcO
2 O
5a, X = Br
4 b, X = S C CN

Electrochemical reduction of disulfides played a key role in the construction of a monolayer of

thiophenolate grafted onto glassy carbon whose electrooxidation was outlined in Section II [21].
Here, selective electrochemical reductions of the diazonium, not disulfide, moiety in diazonium salt
6 generated the corresponding radical that covalently bonded to the glassy carbon electrode surface
as outlined in Scheme 27.3.
SSAr
e–
+N S S X S S X
2
6, X = H, Cl 7 SSAr
n(2e–)
S–
SchEME 27.3 Electrochemical grafting of disulfides by diazonium salt reduction.
RSSR + e– RS + RS–
RS + e– RS–
Overall: RSSR + 2e– 2RS–
SchEME 27.4 Mechanism for electrochemical reduction of disulfides.
Typically such electrografting results in intertwining multilayers attached to the surface. However,
here the more accessible aromatic ring remote from the surface preferentially reacts further with
aryl radicals, for steric reasons, thereby protecting the inner ring yielding species such as 7.
Electroreduction of the disulfides removes these superfluous moieties, resulting in a monolayer of
phenylthiolate. This methodology has also been applied to functionalizing carbon nanotubes [31].
Unfortunately, further studies have revealed that there is not solely a homogenous monolayer of
phenylthiolates because there is apparently some carbon–carbon and carbon–sulfur coupling lead-
ing to biphenyl dithiol- and phenylthiobenzenethiol moieties attached to the surface [32].
Comprehensive studies on the mechanism of electron transfer to disulfides have provided a trea-
sure trove of understanding about the details of this process [33,34]. Addition of an electron to a
disulfide results in a dissociative reduction in which the disulfide bond is cleaved to form a thiyl
radical and thiolate. Addition of another electron results in reduction of the thiyl radical to thiolate.
Thus, two-electron reduction of the disulfide produces two thiolates as shown in Scheme 27.4. The
key issue concerns the details of the first step: addition of an electron to the disulfide. Does it occur
stepwise, that is, via the formation of an anion radical or is the addition of an electron concerted
with fragmentation? [35]. To address this question, a variety of techniques including voltamme-
try with heterogeneous electron transfer and homogeneous electron transfer via electrogenerated
anion radicals, convolution voltammetry, and computational methods were employed [33,34]. Thus,
a series of diaryl disulfides 8, X = NH2, MeO, H, F, Cl, CO2Et, CN, NO2 were studied [36–38].
N N O O
X S ArCH2S R S S
2 2
2
S
10a, R = SH n
8 9 11
b, R = Me
The heterogeneous and homogeneous electron transfer parameters correlated with each other, indi-
cating that the reaction mechanism is the same for both reductions. Typically the reorganization
energy ∆GO≠ for stepwise reductions is modest (2.3–3 kcal/mol) and is determined by the solvent
≠ ≠
reorganization energy ∆GO,s rather than the inner reorganization energy ∆GO,i . This is due to typi-
≠
cally low values for ∆GO,i because addition of an electron to an aromatic ring results in minimal
change in geometry, for example, bond lengths. On the other hand, if the reaction is concerted then
∆GO≠ is larger owing to an increased ∆GO,i ≠
in which the bond dissociation energy of the breaking
≠
bond contributes substantially. For most diaryl disulfides 8, ∆GO,i is high, suggesting concerted
dissociative reduction. However, computations and other experimental evidence implicate the inter-
≠
mediacy of disulfide radical anions and a stepwise mechanism. Consequently, the large ∆GO,i is
ascribed to the formation of a “loose radical anion” with a substantially elongated S–S bond in the
σ∗ (2c, 3e bonded) anion radical [39]. These results bridge the previous work on stepwise and con-
certed limiting mechanisms for dissociative electron transfer and deepen our understanding of these
≠
processes. For diaryl disulfide 8, X = NO2, ∆GO,i is reduced—consistent with a conventional step-
wise mechanism. Calculations suggest that, in this case, a conventional π∗ radical anion is formed
that undergoes intramolecular electron transfer to the S-S moiety providing a σ∗ anion radical that
then cleaves. Electrochemical studies on dibenzyl disulfides 9 also show stepwise dissociative elec-
tron transfer via a loose disulfide anion radical [40].
Reductions of disulfides have also been of interest for potential use in rechargeable lithium
batteries [41–43] and organic dye-sensitized solar cells. Here, a particular concern is the sluggish
kinetics of disulfide reduction at conventional electrodes, for example, glassy carbon. Redox reac-
tions of disulfide 10a are dramatically accelerated at a glassy carbon electrode modified with a
poly(3,4-ethylenedioxythiophene), PEDOT, 11 film than the unmodified electrode [44,45]. Similarly
for reduction of 10b on a PEDOT film rather than on a platinized glass electrode [46]. Reduction
of disulfides on gold electrodes is complicated by the formation of gold thiolates. This has recently
been illustrated by comparing the reduction of diphenyl disulfide on a glassy carbon electrode with
that on a gold electrode [47]. Cyclic voltammetric studies of di- and trisulfides 12a and 12b, respec-
tively, have been reported on gold and gold coated with a single-atom monolayer of β-cyclodextrin
thiol electrodes [48].
S S S–
Ph3CSXR l l l l
–
S
12a, X = 2
b, X = 3 13 14
The reduction of a disulfide moiety mediated by duplex DNA has been reported [49]. A monolayer
of DNA, modified to bear a disulfide linkage, was assembled on pyrolytic graphite anchored by
an appended pyrene moiety. Square wave voltammetric studies revealed an irreversible reduction
centered at −160 mV and a reversible reduction at −290 mV versus NHE. The irreversible, but not
the reversible, reduction is suppressed in acid. The reversible process is suggested to be a concerted
2e−, 2H+ reduction mediated by the DNA because a mismatch in the DNA duplex in the DNA closer
to the electrode surface than the disulfide link substantially lowers the peak current but a mismatch
after the disulfide does not.
S S S– –S
H2N NH2 H2N NH2

–S
S–
S S
15 16
1,2-Dithiins represent disulfides in which reduction results in a dithiolate in which the two thiolate
moieties are in the same molecule facilitating reoxidation to disulfide. Furthermore, the preferred
geometry of the two species, disulfide and dithiolate, are different, and this has attracted interest
for designing molecular memory devices and electrochemical switches. It also raises intriguing
issues concerning the mechanism of electroreduction: specifically the timing of electron transfers
and geometric changes. 1,2-Dithiin 13 has a dihedral angle of 34° about the S–S bond and an
S–S bond length of 2.055 Å [50,51]. It undergoes this two electron reduction to dithiolate 14 in
which the dihedral angle between the two aromatic rings is 130° and the S,S distance is calcu-
lated to be 5.35 Å. Clearly there is a dramatic change in geometry on reduction. Cyclic voltam-
metric studies on 1,2-dithiin 2b in DMF show two reversible reductions at −0.07 and −0.21 V
versus SSCE [23]. The structures of the reduction products and their reoxidation were discussed in
Section II. Irreversible electrochemical reduction of 15 in CH2Cl2 was reported [52] and presumed,
but not proven, to produce 16. The interesting reduction of 1,2-dithiin fused to the 4,4′-bipyridinium
system of methyl viologen has been reported. Four reversible one-electron waves are reported cor-
responding to overall two-electron reduction of the 4,4′-bipyridinium and two-electron reduction of
the disulfide moieties [53].
The electrochemical reduction of sulfenyl chlorides and sulfenyl thiocyanates is discussed here
because of their relevance to disulfide reduction. Electroreduction of arenesulfenyl chlorides 17
occurs with dissociative reduction to give the corresponding disulfides.
O2N
X SCl X CH2SCN
SCN
Y Y
O2N
19
17a, X = Me, Y = H 18a, X = Me, Y = H
b, X = Y = H b, X = Y = H
c, X = Cl, Y = H c, X = MeO, Y = H X SCN
d, X = NO2, Y = H d, X = Cl, Y = H
e, X = F, Y = H
e, X = H, Y = NO2
f, X = CN, Y = H 20a, X = Me
f, X = Y = NO2
g, X = NO2, Y = H b, X = OMe
h, X = M, Y = NO2

Cyclic voltammetric studies show an irreversible one-electron reduction and similar voltammo-
grams for 17a–d, on the one hand, and 17e and f, on the other hand, but the peak potential for 17e
is 420 mV more negative than that for the isomeric 17d [54,55]. DFT computational studies sug-
gest that electron transfer to 17a–d is concerted with S–Cl bond cleavage to yield a radical/anion
pair (“sticky” dissociative electron transfer). Whereas electron transfer to 17e and f involves the
formation of π∗ radical anions and subsequent bond cleavage, that is, a stepwise dissociative mecha-
nism. Sulfenyl chlorides 17e and f form π∗ radical anions owing to S⋯O intramolecular interaction
involving the o-nitro group that can occur in 17e and f but is geometrically precluded in p-nitro
substituted 17d.
Cyclic voltammetric studies of benzyl thiocyanates have been reported [56,57]. Compounds
18a–e undergo a one-electron irreversible reduction to produce the corresponding thiyl radicals
that are reduced at a lower potential to thiolates. The thiolates, in turn, react with starting thio-
cyanate to form the corresponding dibenzyl disulfides that are more difficult to reduce than the
corresponding thiocyanates. The addition of an electron to the benzyl thiocyanates is suggested
to occur concertedly with S–CN bond cleavage, although CH2–S bond cleavage is also observed.
Thiocyanate 18f behaves similarly except that only CH2–S not the S–CN bond cleaves. Compounds
18g and h undergo irreversible one-electron reduction, but their electrochemical behavior suggests
stepwise electron transfer. DFT computational studies suggest formation of an aromatic π∗ radi-
cal anion in these cases followed by CH2–S cleavage. Product studies reveal the corresponding
ArCH2CH2Ar resulting from CH2–S cleavage of the radical anion. Addition of phenol results in the
formation of ArCH3 instead of ArCH2CH2Ar. Consequently, it is suggested that the ArCH2 formed
by CH2–S cleavage of the thiocyanate radical anion does not form ArCH2CH2Ar by dimerizing.
+e–
ArSCN ArS
+e–
–
CN +e–
ArS– ArSSAr
–CN
ArSCN
SchEME 27.5 Autocatalytic reduction of aryl thiocyanates.
Rather the benzyl radical is reduced to the corresponding anion that attacks the benzyl thiocyanate
displacing −SCN and forming ArCH2CH2Ar. Voltammetric studies and convolution analysis of the
electrochemical reduction of aryl thiocyanate 19 show a stepwise mechanism via a π∗ radical anion.
Investigations with 20a and b suggest electron transfer is borderline between a stepwise and a
mechanism concerted with S–CN cleavage [58]. However, an autocatalytic process was also found.
In these cases, the reduction potential of the product diaryl disulfide is less negative than that for the
corresponding aryl thiocyanates. Consequently, the arylthiolates, produced by aryl disulfide reduc-
tion, chemically react with the starting arylthiocyanates to produce diaryl disulfide, resulting in a
catalytic cycle as shown in Scheme 27.5. The result of this autocatalytic mechanism is a lowering of
the potential for reducing aryl thiocyanates.
B. OXIDaTIoN
Electrochemical oxidation of disulfides has been reviewed recently [1,2]. Consequently, the
emphasis here is on results published subsequent to the prior reviews. Disulfides may undergo
one- and two electron oxidation [59,60], depending on the solvent and nature of the attached
groups: alkyl versus aryl, under anhydrous conditions and in the absence of oxygen donors, to
afford cationic species. The structures of these cationic species have not been established defini-
tively but they function as RS+ donors [61]. Although, recently, detection of diaryl disulfide radi-
cal cations generated electrochemically has been achieved in CH2Cl2 with tetrabutylammonium
tetrakis(pentafluorophenyl)borate as supporting electrolyte [62]. The mechanistic complexities of
electrochemical oxidation of disulfides are well illustrated in detailed studies on anodic oxidation
of disulfides 21–23 [63–65].
O
O (CH2)n OCCH2
O N (CH2)3S(CH2)2
Me O
N S N
RN O S
O N (CH2)nS S MeN O
N
N O S
(CH2)n OCCH2 N
Me O
2 O (CH2)3S(CH2)2
O
21, n = 2, 3, 4, 6 22, R = Me, Ph; 23
n = 2, 3
While mechanistic aspects of disulfide oxidation are complex, the synthetic use of the oxidized
species as RS+ donors, a potent electrophile, has been very fruitful. Thus, controlled potential elec-
trolysis of dimethyl disulfide or diphenyl disulfide in dichloromethane followed by reaction with
phenols or aromatic ethers results in electrophilic aromatic substitution as illustrated in Equation
27.1 [61,66]. Such electrochemical methylthiation reactions occur in better yield using liquid SO2
instead of dichloromethane as solvent, p-substitution is favored over o- and weakly activated arenes
react as well [67].
OR΄ OR΄
R˝ R˝ R˝ R˝
+ RS+-donor (27.1)
SR
Controlled potential electrolysis of disulfides until the charge corresponding to two-electron

oxidation is passed followed by the addition of a thiol generates unsymmetrical disulfides [68].
Reaction of electrochemically generated RS+ donors with alkenes provides thiiranium ions that
can be trapped with a variety of nucleophiles both inter- and intramolecularly, resulting in antiad-
dition of sulfur and nucleophile [1,2,69]. Further advances in the synthetic application of these
reactions have been made by conducting the controlled potential electrolysis of diaryl disulfides
in dichloromethane containing Bu4NBF4 as supporting electrolyte with alkenes at low tempera-
ture. Reaction with alkenes at low temperature followed by addition of a nucleophile such as
water or methanol gave addition products with regio- and stereochemical control as exemplified in
Equation 27.2 [70] via the corresponding thiiranium salt. Apparently the dialkyl disulfide formed
after transfer of ArS+ can react with the intermediary thiiranium ion because addition of Et3N,
Me2C=C(OTMS)OMe or 3-trimethylsilylcyclohexene results in the formation of 1,2-arylthio
addition products [70].
H2O OH
(p–FC6H4S)3+ + (27.2)
SC6H4pF

A reasonable mechanism for this reaction is shown in Scheme 27.6.

Proposed intermediate 24 is an ArS+ donor. Consequently, (ArS)3+ can catalyze the addition of
ArSSAr to alkenes. Indeed, 0.2 equivalents of (ArS)3+ catalyze the stereospecific antiaddition of
ArSSAr to cis- and trans-1-phenyl propene in good yield as shown in Scheme 27.7 [71].
Alternatively, these catalytic reactions can be carried out by passing a catalytic amount of current
in a solution containing ArSSAr and alkene. These disulfide additions work well with B(C6F5)4−
but not BF4− as the counterion. Addition of ArSSAr to alkynes also occurs stereoselectively as
ArS
Ar
S+ ArSSAr
ArSSAr 24 +
+ (ArS)3+
ArS
SAr
SchEME 27.6 Mechanism for the formation of 1,2-di(arylthio) addition products.
Ph (ArS)3+ Ph SAr
+ ArSSAr
0.2 equiv
Me ArS Me
(ArS)3+ Ph Me
Ph Me + ArSSAr
0.2 equiv ArS SAr
SchEME 27.7 (ArS)3+ catalysis of stereospecific ArSSAr addition to alkenes.

ArS
(ArS)3 +
+ ArSSAr
0.2 equiv CMe2SAr
77%
ArS
(ArS)3+
CHPh + ArSSAr CH(Ph)SAr
0.2 equiv
58%
ArS Ph
Ph
(ArS)3 +
Ph + ArSSAr CH(Ph)SAr
0.2 equiv
SchEME 27.8 Intramolecular cyclization of thiiranium ions with alkenes.
illustrated in Equation 27.3 [70]. If the reaction of electrochemically generated (ArS)3+ with alkenes
or alkynes is done at 0°C rather than −78°C, BF4− can act as a fluoride donor, resulting in thiofluo-
rination [72] as illustrated in Equation 27.4:
PhC CR + ArSSAr Ph SAr

R = Ph, Me, H (27.3)
ArS R
F
RCH CH2 + (ArS)3+BF4– RCHCH2SAr (27.4)
52–99%
Thiiranium ions produced under these conditions can react intramolecularly with alkenes as nucleo-
philes. Thus, the reactions shown in Scheme 27.8 proceed regioselectively [71].
Reactions of electrochemically generated (ArS)3+ in which ArS+ is donated have been extended
to enolizable ketones, enol acetates, ketene silylacetals, and allyl silanes [72]. These electrochemi-
cally produced ArS+ donor species are not only potent carbon electrophiles but also thiophilic elec-
trophiles are well. Thus, monothioacetals 25 react rapidly with electrogenerated (ArS)3+ at −78°C
to afford alkoxycarbenium ions 26. These species in turn react with carbon nucleophiles, such as
allylsilanes, silyl enol ethers, silyl ketene acetals, and enol acetates to form carbon–carbon bonds.
An example is shown in Equation 27.5 [73]. In addition, monothioacetals 27–29 have been also used
advantageously in this reaction.
OMe SiMe3 OMe

+
+
(ArS)3 + RCHSPh RCH OMe RCH – CH2CH CH2
(27.5)
R C18H17, Ph 69–98%
25 26
Styrene also reacts with alkoxycarbenium ions 26 to ultimately produce thiochromans in a series of
steps involving reaction with the diaryl disulfide in solution [74].
OMe
SPh
O SPh O SPh
27 28 29
Intramolecular cyclization involving alkenes could be effected as well. Thus, synthesis of tetrahy-
dropyrans 30 could be accomplished as shown in Equation 27.6 [75]:
O (ArS)3+
O (27.6)
R 0.2 equiv
R΄
R΄ –78°
ArS R SAr
30
R = R΄= H 62–88%
R = C7H15; R΄= Me R = Ph; R΄= H
R = C7H15; R΄= H R = PhCH2; R΄= H
R = c-Hex; R΄= H R = MeOCH2CH2; R΄= H

Glycosyl thioethers are thioacetals and glycosyl cations can be formed by treatment of glycosyl
thioethers with (ArS)3+ [76]. However, glycosyl cations are less stable than the cations obtained from
the monothioacetals described earlier. Consequently, a flow microreactor system was developed to
rapidly prepare these cations and couple them with sugar alcohols to synthesize disaccharides [77].
A perspective on the preparation of (ArS)3+ by electrolysis of ArSSAr at low temperature and its
synthetic uses has recently been published [78].
R R΄
S S S S
31a, R = CH2 = CHC CC C–; R΄= MeC C– 32

b, R = R΄ = H; c, R = R΄= Ph;
d, R = R' = CH2OH; e, R = R΄= Me
f, R = R΄= t-Bu; g, R = R΄ = i-Pr
Electrochemical studies on 1, 2-dithiin 31 in CH 2Cl2 and CH3CN report reversible one-electron

oxidation followed by an irreversible oxidation [79] with peak potentials for 31a–d the range of
0.80–1.04 V for the first oxidation and 1.13–1.40 V for the second in CH 2Cl2 versus Ag/0.1 M
Ag+ and 0.58–0.96 and 0.99–1.26 V, respectively, for 31a–g in CH3CN. Interestingly, neutral
1,2-dithiins 31 are calculated to be nonplanar while the corresponding radical cations are calcu-
lated to be planar or near planar. Consequently, the first oxidation occurs by an EC mechanism
for which electrochemical parameters show the electron transfer and geometry change to be
sequential. 1,2-Dithiin 32 undergoes two reversible one-electron oxidations in CH 2Cl2 at −78°C
with E1/2 + 0.18 and + 0.72 versus Fc/Fc+ (at room temperature the second oxidation is irrevers-
ible) [80]. The lowered first oxidation potential for 32 compared with 3,6-dialkyldithiins (oxida-
tion peak potentials are estimated to be +0.46 to +0.53 V vs. Fc/Fc+ from potentials in CH3CN
vs. Ag/0.1 M Ag+ reported in Reference 79) are ascribed to inductive effects and C–C σ–π
conjugation. Cyclic voltammetric studies on a dithiete fused to a sterically hindered o-quinone
show two reversible 1e-reductions centered on the quinone moiety and one quasi-reversible
oxidation [81].
IV. ThiOEThERS (SULfiDES) AND ThiOkETALS

A. OXIDaTIoN
Electrochemical oxidation of thioethers and thioketals has been reviewed previously [1,2]. Anodic oxi-
dation of thioethers under anhydrous conditions and typical cyclic voltammetric conditions involves an
EC mechanism. Usually peak potentials for such oxidations are reported. However, using second har-
monic ac voltammetry, formal (thermodynamic E1) potentials for one-electron oxidation of a variety of
thioethers in acetonitrile were reported [82]. The chemical step following the formation of sulfur radi-
cal cations by one-electron oxidation is nucleophilic attack, loss of α-proton, or bond cleavage (C–S, α
C–M, decarboxylation) [83]. Nevertheless, sulfur radical cations can be stabilized by their propensity
to form 2c-, 3e-bonds. Such a propensity not only stabilizes such species as the one-electron oxidation
product, such as that formed from 1,5-dithiocane 33, resulting in electrochemically reversible oxida-
tion, but substantially less anodic (by ca. 1 V) oxidation potentials and potential inversion [84].
S COX
S
MeS COX MeS S + C
Me O X
33 34a, X = NH2 35a, X = NH2 36a, X = NH2

b, X = N(CH2)4 b, X = N(CH2)4 b, X = N(CH2)4

Removal of a second electron is less anodic than the first by about 0.15 V. This result is ascribed to
2c, 3e-S, S-bonding in the radical cation of 33, illustrated in Scheme 27.9, in which an antibond-
ing σ* electron is removed to afford the corresponding dication [84,85]. Two-center, three-electron
bonds between sulfur and other heteroatoms are also known [39].
Consequently, juxtaposing moieties with such atoms close to thioethers may render their anodic
peak potentials less positive. Thus, endo-amide 34a, in which the sulfur is held close to the amide
group, oxidizes irreversibly at a peak potential 330 mV less positive than exo-amide 35a, in which
these moieties are precluded from forming a 2c, 3e S, O-bond [86]. Pulse radiolysis studies confirm
the formation of transient 36a on one-electron oxidation of 34a. That 37 and 38, whose geometry
permits S,O interaction but precludes S,N-interaction, show similar facilitated oxidation potentials
as 34a provides additional evidence that 2c, 3e S,O-bonds, rather than 2c, 3e S,N-bonds, are formed
on one-electron oxidation of endo-amide 34a.
H H
N N O
O
MeS MeS CONH2
O N O N SMe
H H
37 38 39
σ*
p p
SchEME 27.9 2c, 3e-Bonding.

In the presence of trace amounts of bromide ion, 34a, but not 35a, shows electrochemical redox
catalysis. Amide 39, a regioisomer of 34a in which 2c, 3e S,O-bond formation results in a five-
membered rather than a six-membered ring, also undergoes facilitated oxidation. Again pulse
radiolysis studies confirmed the formation of a transient with a 2c, 3e S,O-bond on one-electron
oxidation of 39, which is even longer lived than 36a.
Tertiary amides, as in 34b, are more electron-rich than primary amides, as in 34a, therefore,
one might anticipate a less positive oxidation potential for 34b than for 34a. Indeed, the irreversible
oxidation potential for 34b is 330 mV less anodic than that for 34a, 660 mV less positive than that
for 35a, and 530 mV less positive than that for 35b [87].
Aromatic rings juxtaposed with thioethers as in 40 undergo irreversible anodic oxidation at less
positive peak potentials than their isomers 41, in which through space interaction is precluded [88].
Ar
SMe
MeS Ar X
MeS X
40 41 42

DFT calculations suggest that the lowered oxidation potentials are due to interaction of the sulfur lone
pair and aromatic π MOs. That is, the HOMO from which the electron is removed in 40 is a combina-
tion of sulfur 3p and arene π orbitals. m-Terphenylthioethers 42 preferentially adopt a conformation that
favors sulfur 3p-arene π interaction as shown [89]. This results in less anodic oxidation potentials [90].
An important factor contributing to the lowered electrochemical oxidation potentials for 40 has been
reported [91] to be due to a new type of S∴π bonding in the corresponding radical cation.
Interest in applying electrochemical oxidation of thioethers and the subsequent reactions of
the sulfur radical cations to synthesis has continued, and recent developments will be reviewed.
Electrochemical oxidation of thioethers followed by α-deprotonation gives an α-thioradical 43 that
undergoes one-electron oxidation (at lower potential than the corresponding thioether) to yield thio-
nium ion 44 as shown in Equation 27.7. An alternative mechanism for the formation of thionium ion
44 by electrochemical oxidation of sulfides is shown in Equation 27.8.
–e– + –H+ –e– +

RCH2SR΄ RCH2SR΄ RCHSR΄ RCH =SR
(27.7)
43 44
Thionium ions 44 are believed to be intermediates in the Pummerer reaction [92–96].

X
–e– + X– –HX
RCH2SR΄ RCH2SR΄ RCH2SR΄ 44 (27.8)
–e– +
45
They are electrophilic and react both intra- and intermolecularly with a variety of nucleophiles.
Electrochemical oxidation of thioether 46, X = H in the presence of methanol, acetate, or fluoride
affords the corresponding derivative 46, X = OMe, OAc or F [97].
PhSCH(X)CF3
46
Here, the CF3 group promotes deprotonation. Similarly, other electron-withdrawing group esters
[98,99], amides [98], ketones [98,99], cyano [98], acetylene [100], phosphonate [98,101,102], and sulfo-
nyl [103] promote deprotonation and regioselectivity in anodic fluorination. The diastereoselectivity
of these reactions has been investigated [104,105] and a particularly impressive example in which
only diastereomer 47 is detectable by 1H NMR spectroscopy is illustrated in Equation 27.9 [106].
–2e, –H+
S Et4NF . 4HF S F
(27.9)
R2NSO2 O DME R2NSO2 O
O 88% yield O
47
Anodic α,α-difluorination has also been reported, for example, anodic fluorination as shown in
–2e–, –H+ –2e, –H+

PhSCH2CO2Et PhSCH (F)CO2Et PhSCF2CO2Et
F– F– (27.10)
48 49
Occasionally anodic fluorination results in fluorination of the aromatic ring appended to sulfur as
with oxazolyl [107] and thiazolyl [108]-2-sulfides rather than Pummerer reaction. Electrochemical
α-fluorination of thioethers and anodic difluorination accompanied by desulfurization of dithioac-
etals has been included in a review of fluoro-Pummerer rearrangements [109]. A review focused on
these reactions, as well as those carried out in ionic liquids, has also appeared [110].
In cases in which acidifying substituents are not attached to the carbon α to the sulfur, anodic
α-fluorination can still be achieved. The suggested explanation is that the reaction course follows
the mechanism shown in Equation 27.8 in which the electron-withdrawing fluorine in intermedi-
ate 45, X = F contributes to acidifying the α-proton [108,111–114]. Indeed, this explanation also
accounts for the reported promotion of anodic methoxylation and acetoxylation of thiazolidines,
1,3-oxathiolanes and 1,3-dithiolanes [115]. Even more remarkable than anodic fluorination of unac-
tivated thioethers is α-fluorination in systems in which competing C–S bond cleavage of the interme-
diary sulfur radical cation is promoted by substituents that stabilize the carbocation resulting from
such C-S cleavage. For example, anodic oxidation of monothioacetals, such as phenyl-thioglucoside
50a, generates a radical cation which on C–S bond cleavage gives an oxygen stabilized carbocation,
that is, oxonium ion [112].
OAc BnCONH S
OAc
AcO O X AcO
AcO F N SAr
AcO
AcO
AcO SPh O
CO2PMB
50a, X = SPh 51 52
b, X = F
Indeed, anodic fluorination with Et3N · 4HF produces fluoride 50b. However, anodic fluorination
with Et3N·3HF in THF as solvent affords 51 as a mixture of anomers [112]. Thus, a number of
factors have been found to affect the product formed and its yield. In the anodic methoxylation
of cephem derivatives 52, the nature of the aryl substituent plays a key role in product selectiv-
ity [116]. As already mentioned, solvent [112,117,118] supporting electrolyte and fluoride source
(Et3N · nHF, Et4NF · nHF) [112,119–124] are important as are use of mediators: Ar3N [125] or iodo-
arene incorporated into ionic liquid [126], ultrasonication [127], and use of additives such as the
polyether PEG [128].
To avoid the necessity of handing HF in anodic fluorination, an in situ method for generating it
has been introduced [129]. The idea is that alkali metal fluorides will generate HF in acetonitrile
solution with solid supporting sulfonic acids (cation exchange resins in the acid form). Furthermore,
2,6-lutidine is added so that it will react with HF to generate salts that will act as supporting elec-
trolyte and fluoride source. Thus, anodic oxidation of ethyl α-phenyl-thioacetate 48 in acetonitrile
solution containing KF, 2,6-lutidine and Amberlyst 15 Dry resin at reflux produces the correspond-
ing α-fluoride 49 in 60% isolated yield. A comparable yield of the monofluorinated product was
also obtained from PhSCH2CN. A novel approach to avoid the use of supporting electrolyte in the
anodic methoxylation [130,131] and acetoxylation [132] of 46 has been reported. The idea is to use
recyclable solid supported bases that form salts by acid–base reaction between the immobilized
base and methanol or acetic acid in acetonitrile. The yields for such reactions of 46 with methanol
and acetic acid are 89% and 81%, respectively. Such anodic methoxylation of PhSCHF2 has also
been achieved in 86% yield [133].
The electrochemistry of hexakis(benzylthio)benzene 53 has been studied by cyclic voltamme-
try in CH2Cl2 [134]. The corresponding radical cation is formed on one-electron oxidation and
characterized as a π-delocalized system by EPR spectroscopy. Analysis of fractional electrolysis
(potentiometric titration) of this compound shows that it undergoes a second electron transfer with
strong potential compression for the two one-electron transfer steps (E1° = 0.798 V, E2° = 0.821 V vs.
Ag/0.01 M AgClO4 · H2O, 0.1 M Bu4NPF6, CH3CN from simulation) with ΔE° = 23 mV.
As already pointed out, sulfur radical cations are known to undergo C–S bond cleavage to
form carbocations particularly when the carbocation so formed is stabilized. Thus, electrochemi-
cal oxidation of thioethers followed by C–S bond cleavage has also been synthetically exploited.
Electrolysis of benzylic sulfides in nitroalkane solutions in an undivided cell results in oxidation
and C–S bond cleavage at the anode and α-nitrocarbanion formation at the cathode. Carbon–carbon
bond formation then ensues as shown in Equation 27.11 (p-OMe or p-OH groups are required in the
Ar moiety for successful reactions) [135].
electrolysis
ArCH(R)SR′ R
′′CH2 NO2
→ ArCH(R)CH(R′′)NO2 (27.11)
R′ = Me,Ph
Anodic oxidation of arylthioether derivatives of cholesterol and, even better 6β-3α,5α–cyclocholes-

terol, in the presence of partially protected monosaccharides provides glycoconjugates of choles-
terol in moderate yields [136]. In this case, heterolysis of the C–S bond in the corresponding sulfur
radical cation is favored by stabilization of the carbocation. Anodic oxidation of benzylic sulfides
54 results in C–S as well as C–Sn bond cleavage to generate o-quinodimethanes 55, which can be
trapped with in situ dienophiles to give Diels–Alder adducts in excellent yields [137].
SCH2Ph
PhCH2S SCH2Ph CH2SnBu3 CH2
ArCOX
PhCH2S SCH2Ph CH(R)SPh CHR
SCH2Ph
56a, X = SAr΄
53 54 55 b, X = OMe

Anodic oxidation of S-arylthiobenzoates 56a mediated by a triarylamine occurs with C–S bond
cleavage to yield the corresponding methyl ester 56b in the presence of methanol [138] or benzoyl
fluoride (from 56a, Ar = Ph) if Et4NF·3HF is used as the supporting electrolyte [139]. As described
earlier, α-deprotonation and C–S bond cleavage are often competitive pathways and conditions
favoring C–S bond cleavage over α-deprotonation have been reported [112,116,118,125].
Cleavage of the C–S bond in monothioacetals is favored by stabilization of the carbocation pro-
duced by the oxygen atom, although as reported earlier, conditions that favor α-deprotonation are
known [112]. As previously reviewed, anodic oxidation of monothioacetal 57 in the presence of all-
yltrimethylsilane produces 58 via alkoxycarbenium ions resulting from C–S bond cleavage [1]. More
recently, it has been shown that alkoxycarbenium ions are sufficiently stable that solutions of them can
be electrosynthesized by anodic oxidation of monothioacetals in CH2Cl2 with Bu4NBF4 as the support-
ing electrolyte at −78°C. These electrophilic species then react with carbon nucleophiles (such as allyl-
silanes and silyl enol ethers) to form carbon–carbon bonds as illustrated in Equation 27.12 [140,141].
SiMe3
Anodic ox +
C8H17CH(OMe)SPh C8H17CH = OMe C8H17CH(OMe)CH2CH=CH2
Bu4NBF4 (27.12)
CH2Cl2
57 –78° 58

An alternative approach to this valuable methodology is to synthesize the alkoxycarbenium ion

indirectly. Here, diaryl disulfides are electrooxidized to give an electrophilic sulfur species (see
Section III.B) believed to be [ArS(ArSSAr)]+. Reaction of this species with monothioacetals affords
the corresponding alkoxycarbenium ion [141].
Thioglycosides are monothioacetals and their electroxidation has attracted attention because
C–S cleavage results in a glycosyl cation that on reaction with a sugar alcohol provides a disac-
charide [1]. Efforts to improve the methodology have been reported [142], including a recent study
on solvent and protecting group effects on the yields and stereochemistry at the anomeric center
[143]. The oxidation peak potentials of the thioglycoside depend on the aryl substituent attached to
sulfur [142,144]. This enables selective activation of glycosyl donors. A detailed electrochemical
study of the formal (thermodynamic) potential of such glycosyl donors has been studied and found
to correlate with peak potentials [145]. A review on the synthetic application of anodic oxidation of
thioglycosides was recently published [146].
It would be advantageous to generate solutions of glycosyl cations by anodic oxidation of thiogly-
cosides as was done with simple monothioacetals as outlined earlier. However, glycosyl cations are
not very stable. Consequently, solutions of such cations cannot be electrosynthesized. For example,
anodic oxidation under the conditions used for simple monothioethers, CH2Cl2, Bu4NBF4, −78°C,
apparently provides the glycosyl fluoride. Use of Bu4NClO4 as the supporting electrolyte instead of
Bu4NBF4 apparently gives the glycosyl perchlorate that reacts with sugar alcohols to yield disaccha-
rides. Even better is to use Bu4NOTf as supporting electrolyte to provide solutions of glycosyl triflates
[147,148]. It should be noted that it has also been reported that anodic oxidation of thioglycosides
with 12.5 mol% sodium triflate as the supporting electrolyte in acetonitrile in the presence of sugar
alcohols provides disaccharides [149]. Similarly, reaction of solutions of glycoside triflates with sugar
alcohols affords disaccharides and even a pentasaccharide [147,148]. Although glycoside triflates are
too reactive to be stored and must be used immediately, they can be converted to glycosyl sulfonium
salts that can be stored and subsequently used in coupling reactions [150]. Electrocatalysis by Br− (or
NBS or Br2) of the formation of nucleosides from protected thio-ribosides [151] and 1-arylthio-2,3-
dideoxy riboside [152] with silylated pyrimidines as shown in Equation 27.13 has been reported.
O
R΄˝
NH
ROCH2 OTMS
O
ROCH2
O (27.13)
SAr R΄˝ N
N O
+
R΄ R˝
N OTMS R΄ R˝
Anodic oxidation of dithioacetals and ketals has been reviewed previously [1,2]. More recently,
intermolecular C–C bond formation has been achieved as shown in Equation 27.14 forming 59 in
80–90% yield [153].
OMe OMe
MeO R Anodic ox. MeO R
LiClO4
CH3NO2 (27.14)
PhSCHSPh SiMe3 PhSCHCH2CH = CH2
R = H, OMe
59
Anodic oxidation of dithioacetal 60 in the presence of substituted alkenes also results in C–C bond
formation.
OH O
CH(SPh)2
PhS
60 61
For example, anodic oxidation of 60 in the presence of tetramethylethylene gives 61 in 82% yield
[153]. Anodic oxidation of dithioketals derived from diaryl ketones mediated by an iodobenzene
ionic liquid [126], triarylamines [154], PhIClF [155], and Et3N·3HF as supporting electrolyte and
F− donor as well as polymer supported iodobenzene and Cl− with Et3N·HF [156] produce the cor-
responding difluoride Ar2CF2. Oxidation of benzoyl ketene dithioacetals by a presumed ECEC
mechanism has been reported to give mainly the product shown in Equation 27.15 [157] in 31%
yield.
Anodic ox
PhCOCH=C(SMe)2 PhCOC(F)2COSMe (27.15)
Et4NF . 4HF
DME
B. REDUCTIoN
Electrochemical reduction of aryl alkyl thioethers typically occurs with C–S bond cleavage in an
overall two-electron process. For example, cathodic reduction of 62 proceeds as shown in Equation
27.16 [158]. The details for the dissociative electron transfer in such reductions have been investi-
gated for Ph2CHSC6H4pOMe and found to be a stepwise process for the electron transfer with a
large reorganization energy [159].
O(CH2)3SPh O(CH2)CH3
+ PhS– (27.16)
OCH2OMe OCH2OMe
62 63
As the structure of the sulfide is varied, stiff π* radical anions or loose σ* radical anions are
formed [40]. Reduction of thioethers using mediators was found to be advantageous. For exam-
ple, reduction of 62 mediated by naphthalene in THF at low temperature occurred at a potential
500 mV more positive than that for direct reduction [160]. Furthermore, the mediated reduc-
tion was a 1e − process providing PhSSPh in addition to 63. 4,4′-Di-t-butylbiphenyl was also an
effective mediator for electro-reduction of sulfides [161]. Apparent electrochemical reduction of
benzyl or tritylthiophenyl modified nucleotides and DNA in the presence of cobalt ions has been
reported [162].
Cathodic reduction of aryl polythioethers has provided very interesting results. First, the reduc-
tion occurs at surprisingly low potentials and is reversible. For example, 1e− reduction of 64, Ar = Ph
occurs at a formal potential of −1.56 V [163] −1.60 V [164] in DMF versus SCE.
PhS SPh
SAr Ar X Ar
ArS SAr S S 66a, Ar = C6(SPh)5;
PhS SPh X= – CH = CHC6H4CH = CH–
b, Ar=C6(SPh)5;
ArS SAr
N O O N X = –Ch = N–N = CH–
SAr O O c, Ar=C6(SPh)5;
X = –C C – C C–
64 65
The reduction potentials of 64 with p-substituents in the Ar groups afforded a linear Hammett plot
using σp parameters for these substituents [163]. Compound 65 has been studied as a redox sensor
for K+ [165]. The idea is that the reduction of the aryl polythioether moiety will be affected by the
binding of K+ to the cryptate moiety. Indeed, it was found that for 65 the binding constant for KPF6
was about 4000 M−1 and that there was a +170 mV shift for the reduction of this complex compared
with uncomplexed 65.
Electrochemical studies on linked perphenylthiobenzenes provided insight into the coupling of
these centers. Thus, 66a and b showed 2e− reductions at −1.39 and −1.19 V, respectively, but 66c
showed two 1e− reductions at −1.12 and −1.38 V in DMF versus SCE [166,167]. Therefore, the two
Ar centers in 66a and b do not interact (class I in the Robin–Day classification system [168]), but
addition of an electron to 66c results in an anion radical spread over the two Ar systems making
it more difficult to add a second electron (borderline class II/class III system). This conclusion is
validated by spectroelectrochemical studies in which the anion radical of 66c shows an interva-
lence charge-transfer band at 1310 nm in the near IR. This suggests the possibility of a molecular
wire based on this structural motif and molecular rods 67 have been made and studied by cyclic
voltammetry [169].
X X
X X
X X
Ar'S SAr' X X
X X
Ar Ar X
X
n X X
Ar'S SAr' X
X
X X
X X
67a, Ar = C6(SPh)5; X X
Ar' = Ph; n = 0
b, Ar = C6(SC6H4p–tBu)5; 68a, X = p –TolS 69a, X = SPh
Ar' = C6H4p–tBu, n = 0 b, X = iPrO S S; b, X = H
c, Ar = C6(SC6H4p–tBu)5; n = 1-3 n
Ar' = C6H4p–tBu, n = 1 c, X = H

Compounds 67a and b show two reversible 1e− reductions at −1.12, −1.38 and −1.17, −1.44 V,
respectively, in DMF versus Fc/Fc+ compared with 64, Ar = Ph or Ar = C6H4tBu, which show one
reversible reduction at −1.56 and −1.7 V, respectively, under the same conditions. Extending the
conjugated system to that in 67c results in a 1e− reduction at −0.98 V and a 2e− reduction at −1.19 V.
Alternatively, arenepolythioethers with m-diacetylene bridges, in which the m-nature of the link-
ages prevents the possibility of full interaction, have been studied by cyclic voltammetry. In these
cases, their multiple reversible reductions enable them to reversibly store several electrons, thereby
acting as molecular batteries [170,171]. Cyclic voltammetric studies of perarylthiolated coronenes
68a and b also show two reversible 1e− reductions in DMF at potentials over 1 V less cathodic than
coronene 68c [163,172] owing to stabilization by the sulfur substituents. Cyclic voltammetric studies
of perphenylthiocorannulene 69a in acetonitrile show four reduction waves at −1.22, −1.62, −2.04,
and −2.28 V versus Ag/AgNO3 [173]. Again the sulfur substituents lower the reduction potentials
compared with the parent corannulene 69b (−2.23 and −2.84 V under comparable conditions). Here,
FMO analysis provides further insight into the role of the sulfur substituents in rendering the first
reduction potential less cathodic. The LUMO of 69a includes the sulfur atoms as well as the core π
system, thereby lowering its energy and consequently the reduction potential.
V. 1,4-DiThiiN AND ThiANThRENE

The electrochemistry of 1,4-dithiins and its derivatives has been reviewed previously [1,83,174].
More recently, the electrochemistry of substituted 1,4-dithiin 70 has been studied in dichlorometh-
ane by cyclic voltammetry [175,176].
X S X
S
X S X
S
70 71a, X = H
b, X = OMe
A reversible one-electron oxidation is followed by an irreversible oxidation [175]. However, at −78°

both oxidations are reversible with E11/ 2 = +0.00 and E12/ 2 = +0.82 V versus Fc/Fc+[175]. The annu-
lated bicyclo[2.2.2]octane framework stabilizes the oxidation products and the oxidation potentials
are lowered owing to inductive and σ–π conjugation effects as suggested earlier for 1,2-dithiin
derivative 32. Such effects by the bicyclo[2.2.2]octene moiety have been reviewed [177].
Electrochemical studies on thianthrene, 71a, and its derivatives have been reviewed previously
[1,2,178]. Thianthrene undergoes two reversible, one-electron oxidations but the corresponding
dication reacts with even trace amounts of water rendering the second oxidation of thianthrene
irreversible. However, in dry solvents, the second oxidation is reversible [178–180]. In addition,
zeolite modified electrodes show reversibility even in the presence of water owing to zeolite pro-
tection of the dication [181]. The PF6 − salt of thianthrene radical cation was electrosynthesized
in CH2Cl2 with tetrabutylammonium hexafluorophosphate as the supporting electrolyte [182].
X-ray crystal structural analysis showed planar cations associated as dimers with two weak S,S
bonds. Aggregation of this and related radical cations have been studied computationally [183].
2,3,6,7-Tetramethoxythianthrene, 71b, also shows two reversible one-electron oxidations even
under conditions in which the second oxidation of thianthrene, 71a, is irreversible owing to the
greater stability of the dication of 71b [184,185]. However, more recent studies have provided a more
nuanced picture of the redox chemistry of these species. Using fast scan voltammetry at reduced
temperatures, reversible dimerization of the radical cations of 71a and 71b has been detected [186].
Furthermore, in situ UV–vis and EPR/UV-vis-NIR spectroelectrochemical studies provide evi-
dence for dimer formation that depends on temperature, concentration, solvent, and supporting
electrolyte [187]. The dimer is diamagnetic as shown by EPR studies, but its structure in solution
has proven controversial. In the solid state (71a)+ • AlCl4− [188] and (71b)+ • I3− [189] form dimers 72a
and b, respectively, with planar heterocyclic rings.
2+ 2+
X S X
S
X S X S
S
X S X
S
X S X
72a, X = H 73
b, X = OMe
However, on the basis of PM3 calculations, it was suggested that 71a+ • forms σ-dimer 73 with bent
heterocyclic rings [186], but it has been argued the low −ΔG value for dimerization in solution favors
π-dimer formation [190]. Near IR spectroscopic absorbance has also suggested the presence of a
charge-transfer complex of thianthrene 71a with its corresponding radical cation [187]. Thianthrene
71a has also been reported to function as a redox catalyst in the oxidation of 2,3-dimethyl-2-butene
[191], guanosine and DNA in acetonitrile [192]. Thianthrene has also been shown to participate
in electrogenerated chemiluminescence [193]. Here the idea is that electrochemically generated
thianthrene radical cation reacts by electron transfer with an electrochemically generated radical
anion, such as that generated from 74 [194] or carbon dioxide radical anion [195] (produced by one-
electron oxidation of oxalate by thianthrene radical cation).
S+
S+
N S
N S
O + S
CH2COp–MeC6H4
74 75 76
Owing to the energetics and rapidity of the electron transfer an excited state species is formed that
luminesces. Chemiluminescence is also achieved by injection of hot electrons from oxide coated
metal (Ta, Pt) electrodes into thianthrene radical cation [196,197].
The reactions of thianthrene radical cation with nucleophiles have generated considerable inter-
est [88]. An overview of such chemical studies has recently been published [198]. Surprisingly the
reaction is second order in radical cation, which suggests a disproportionation mechanism followed
by rapid reaction of the dication with water. However, electrochemical studies [199–201] revealed
that water first associates with the radical cation and this complex undergoes rate-determining elec-
tron transfer with another radical cation. The nucleophile-radical cation is a π-complex devoid of a
covalent bond between nucleophile and radical cation until electron transfer occurs (complexation
mechanism). In the related half-regeneration mechanism, a bond is formed between nucleophile and
radical cation. Pulse-electrolysis stopped-flow methods have been used to determine the kinetics of
the reactions of 71b radical cation and dication with methanol and pyridine [202,203]. As expected,
the dication reacts faster with nucleophiles than the radical cation. With methanol the reactions
of the dication and radical cation are both second order in methanol, but first order in dication
and second order in radical cation. Thus, in both cases, complexes of the ions with methanol must
be deprotonated by another methanol molecule in (dication) or preceding (radical cation) the rate-
determining step. With pyridine the dication reacts directly in the rate-determining step, resulting in
first-order dependence in dication and pyridine. With the radical cation, the reaction is second order
in radical cation and first order in pyridine. Hence, the rate-determining step involves the well-prec-
edented electron transfer from the radical cation complex to another radical cation. The reactions
of thianthrene radical cation with nucleophiles are not only of mechanistic interest but of synthetic
interest as well. The electrosynthesis of 75 and 76 have been reported [204] by controlled potential
electrolysis in acetonitrile of thianthrene with 4-methylacetophenone and cyclohexene, respectively.
The electrochemistry of other thianthrene derivatives and analogues has been investigated. The
electrochemistry of thianthrene appended with one or two ferrocene rings have been reported [205].
Cyclic voltammetric studies of 77a and b in dichloromethane with Bu4N+ [B(C6F5)4]− as supporting
electrolyte shows two reversible oxidations for 77a with E1/2 = +0.33 and +1.32V and three reversible
oxidations for 77b with E1/2 = +0.27, +0.44, +1.55 V versus Ag/Ag+.
X Y
S S
S S
2
77a, X = Fc; Y = H
b, X = Y = Fc 78
The first peak for 77a and the first two peaks for 77b are ascribed to one-electron oxidation of the
ferrocene moieties and the peak at highest oxidation potential for both is ascribed to one-electron
oxidation of the thianthrene moiety. The separation of the two ferrocene oxidations in 77b indicates
interaction between these moieties. 1,1′-Bithianthrene 78 shows two not totally separable two elec-
tron oxidations in acetonitrile [206]. Cyclic voltammetric studies on thianthrenes substituted with
heterocycles and bridged with heterocycles have been reported [207]. Cyclic voltammetric studies in
acetonitrile or dichloromethane of thianthrene derivatives 79a and 79b and c show one or two revers-
ible oxidation potentials, respectively [206,208], and 80 exhibits a quasi-reversible oxidation [208].
Et Et Et Et Et Et
R S R R S S S R
R΄ S R΄ R S S S R
Et Et Et Et Et Et
79a, R = R΄= H 80, R = SC8H17

b, R = R΄= SC8H17
c, R = R΄= SCH2CH2S

When coated on a glassy carbon electrode, 81 shows a reversible oxidation [209].
S S
S S
81
VI. TETRAThiAfULvALENE AND ANALOGUES

Interest in electron transfer from TTF, 82, began with the report that it underwent two reversible
one-electron oxidations at relatively modest potentials [210]. This interest was spurred on by the
discovery of unexpectedly high conductivity in its charge transfer complexes [211], thereby earning
the sobriquet of “organic metals” (although one-dimensional conductors) for these complexes and
even superconductivity in so-called “Bechgaard salts” [212,213].
S S
S S
S S
S S
82 83
Interest in hybrid salts: TTF radical cation-inorganic anions with unpaired spin (in part to couple
conductivity with magnetic properties) [214,215], single-component molecular metals [216], cova-
lently linked substituted TTF and TTF analogues with electron-acceptor moieties [217,218] and
with each other [219] have blossomed. An important driver in this research is the development not
only of organic conductors and superconductors [220,221] but organic field effect transistors [222],
nonlinear optical materials [223,224], molecular rectifiers [224], chemical sensors [224,225], redox
switchable ligands [224–226] for molecular shuttles, switches [224], and photovoltaic and solar cells
[227]. A brief perspective on “organic metals” and applications to other areas of molecular elec-
tronics has been presented [228]. To monitor drugs, appending them with an electroactive group is
attractive and a recent example involves affixing TTF to benzodiazepines [229]. This update from
previous reviews [1,230] will be selective rather than comprehensive and focus on electrochemical
studies of TTF, its derivatives, analogues—especially its π-extended analogues 83 and the signifi-
cance of these studies.
Some recent studies on some substituent effects on the oxidation potentials of substituted
TTF have been reported. The first oxidation potentials for 84a and b and 85a are comparable to
those of 84c and 85b, respectively, but the second oxidation potentials are moved to more anodic
potentials [231].
X S S X΄ S S X
Y Y
Y΄
Y Y΄ S S Y
X S S X
X΄
84a, X = Y΄ = S; X΄ = Y = CH2 85a, X = S , Y = CH2
b, X = X΄ = CH2; Y= Y΄= S b, X = CH2 , Y = S
c, X = X΄ = S; Y= Y΄ = CH2

Both first and second oxidation potentials are rendered more anodic for 86 than 84c [232]. Both
oxidation potentials are rendered more anodic with electron-withdrawing substituents (in monoaryl)
and less anodic with electron-donating substituents in the arene ring of monoaryl monocyclic TTF
87a relative to TTF, 82.
S S S S S Ar S Ar΄
S
S
S S S Ar΄ S S
S S Ar΄
86 87a, Ar΄= H
b, Ar = Ar΄
The effect is even larger with tetraryl TTF, 87b [233]. Other recent electrochemical studies pro-
vide additional information on subsituent effects on TTF oxidation potentials: esters, phthalimides
substituted benzo TTF [234], 1,4-dithiin [235], and thiophene, substituted dibenzo TTF [236].
Thiophene annulated TTF 88 has attracted particular interest because of its high mobility in field
effect transistors [237,238]. Cyclic voltammetry of 88 in DMF shows two reversible 1e− oxidations
with E1/2 = +0.78 and +0.96 V versus SCE [237].
C6H13 C6H13
S S
S S S S Me
S Me S S S S
S S
88 S
S
2
89
Preliminary cyclic voltammetric studies on oligothiophene TTF derivative 89 have been reported,
but interpretation of the complex results awaits further studies [239]. Additional substituent effects
on the electrochemical oxidation of substituted derivatives of TTF have been reported [240–244]
and an overview of such tuning for molecular electronics applications published [245]. A TTF
derivative appended with two pyridine moieties was immobilized on a Pt electrode to determine
the effect of solvent and air on its electrochemical oxidation [246]. A single pyrrolo-TTF molecule
attached to gold in ionic liquid provided electrochemical potential control of its conductance
[247]. Electrochemical responses to TTF moieties appended with metal binding sites have been
reported [248]. Self-assembly of bis(pyrrolo)TTF appended with pyridine moieties on complex-
ation with Pt to afford electroactive cages has been achieved and characterized [249].
Remarkably, the 4e− reduction of O2 to H2O is accomplished by TTF in acidic ClCH2CH2Cl and
at an acidified water ClCH2CH2Cl interface [250]. Ion transfer voltammetry showed the transfer of
82 • + in this reaction. The proposed mechanism for the reaction is protonation of TTF, 82 to give 90
and then reduction of O2 to water generating 82 • + perhaps via TTF-90 aggregates. Electron transfer
from TTF, 82, to 90 to generate 82• + has been proposed in hydrogen-bonding assisted self-doping
of TTF salt 91 [251].
MeS
S S
MeS S S S
H MeS S
S S S S S S
+
S MeS SMe
S S S CO2–NH4+ S S
90 91 92
The interaction of two TTF moieties especially on oxidation has attracted interest. Studies on TTF
units linked by σ-bonds, conjugated π-systems, halogen atoms, or flexible chains have been reported in
which through-bond or through-space interactions are possible [219]. Electrochemical and spectroelec-
trochemical studies provide evidence for such interaction. For example, the weak interaction between
TTF• + and TTF, which is the basis for conducting Bechgaard salts in the solid state, is typically not
observed in solution unless the moieties are constrained by covalent linkages. For example, the first two
electron oxidation wave for 92, determined by cyclic voltammetry in benzonitrile, can be deconvoluted
into two waves, suggesting interaction between one TTF• + unit with the other TTF unit (the effect is
intramolecular because it is observed even on dilution) and NIR absorption at 1880 nm confirms the
formation of the mixed valence species [252]. A tetracarbonyl-t-butyl calix[4]arene scaffold appended
with two TTF moieties shows a broad first oxidation and a narrow second oxidation on cyclic voltam-
metric analysis. Chemical oxidation (NO+SbF6−) and spectroscopic studies show radical cation absorp-
tion and bands at 1750 and 765 nm ascribed to the mixed valence dimer (TTF)2• + and π-dimer (TTF)22+,
respectively. Interestingly, addition of Na+ results in a new and sharp reversible redox system at more
positive potential for the first wave, suggesting that Na+ complexation results in a conformation in which
the two TTF moieties cannot interact [253]. Recently, interaction between two separate TTF molecules
has been observed in a self-assembled coordination cage in which cyclic voltammetric behavior pro-
vides evidence for a (TTF)2+• mixed valence complex [254]. Two oxidation waves (200 and 500 mV vs.
Ag/AgCl) are observed for oxidation to the radical cation and dication but square wave voltammetry
shows the first oxidation wave to be split (152 and 304 mV vs. Ag/AgCl). Controlled potential elec-
trolysis at a potential of 180 mV afforded the mixed valence complex (TTF)2+ •, which showed broad
absorption in the near IR at 2000 nm. Further oxidation at a potential of 400 mV generated the radical
cation π-dimer, (TTF)22+ [255,256], which escapes the cage due to electrostatic repulsion between cat-
ions as evidenced by the next oxidation peak potential that is comparable to that for the oxidation of free
(TTF)• + to TTF2+. An analogous π-dimer identified by its visible absorption is formed in the cavity of
cucurbit[8]uril [257]. Interestingly, cyclic voltammetric studies show that chiral TTF derivative 93, but
not its meso-analog, shows that the typical first oxidation wave is split into two waves [258].
O S S O
O O
S S
93
This is interpreted in terms of association of the radical cation formed after 1e− oxidation with
another molecule to form the mixed valent (TTF)2+ • in the chiral but not meso species. Near IR
absorption at 2000 nm for this species supported this suggestion. Electrocrystallization of chiral
dimethylethylenedithio TTF provided enantiopure and racemic cation dimers [259]. The enantio-
pure salts were semiconducting, but the racemic salt is an “organic metal.” Redox modulation of the
chirooptical signal of chiral TTF fused to helicenes has been accomplished [260]. The observation
of overlapped first oxidation waves in compounds 94, 95 suggests interaction between TTF units,
but this needs to be clarified [261].
R΄ S RH2C
BuS
RH2C CH2R R= S S
BuO
BuS S S SMe
RH2C 2
R΄ R΄
CH2R
R΄ = Me, Et, OMe
94 95
There are other recent examples using electrochemistry that demonstrate the lack of intramolecular
interaction between TTF units. Thus, two reversible waves are found for 96 by cyclic voltammetry
in PhCN as with TTF, but the first oxidation potential for 96 occurs at a more positive potential
than that for TTF (E11/ 2 = 0.23 V, E12/ 2 = 0.57 V and E11/ 2 = −0.07 V, E12/ 2 = 0.48 V vs. Ag/AgNO3 in
PhCN, respectively) [262]. Thus, there is no interaction between TTF units in 96, but the electron-
withdrawing acetylene substituents render the first oxidation more difficult. The smaller ΔE for 96
than for TTF (0.34 vs. 0.55 V) is cited as evidence for greater charge delocalization in 96 on oxida-
tion than for TTF and consequent reduction of Coulomb repulsion. Cyclic voltammetry of 97–99
in CH2Cl2 shows two redox couples in the range of E11/ 2 = 0.23 − 0.51 V and E12/ 2 = 0.84 − 0.90 V,
versus SCE [263]. This is comparable to a model mono-TTF derivative (BEDT-TTF), which shows
two redox processes with E11/ 2 = 0.48 V and E12/ 2 = 0.89 V versus SCE under the same conditions,
demonstrating that this is no intramolecular interaction between TTF units in 97–99.
Bu
R
S
S CO2(CH2)2R R CH(CH2CH2R)2
R
Bu
R R
S S CH(CH2CH2R)2
R= CO2(CH2)2R
S S
96 97
S SR΄
R= S S
S S SR΄
R΄= CH3 R΄, R΄= ( CH2)2
98 99
R R
NC(CH2)2S SBu
R= S S
S S SBu
CH2S
R R
R
R
100
CH2R
RCH2 CH2R MeS SMe
S S
R =
S S S
RCH2 CH2R MeS
CH2R
101
Similarly, a variety of TTF moieties appended to the triptycene, for example, 100 showed only
two reversible oxidations by cyclic and differential pulse voltammetry in CH2Cl2 [264]. Thus, the
TTF moieties oxidize independently, a conclusion that is also supported by spectroelectrochemical
studies. The TTF units in 101 also do not interact electronically as evidenced by only two oxida-
tion peaks (the first of which was shown to be a 6e− oxidation) in cyclic voltammetry studies [265].
Cyclic voltammetric studies in PhCN reveal no interaction between the pyrrole fused TTF moieties
in 102–104 because two reversible oxidations are observed [266]. Although analogue 103a shows
a broad first oxidation wave and analog 104a shows a split oxidation wave, these results are not
ascribed to intramolecular interaction because they are not found for 102a, but rather to intermo-
lecular interaction.
R R
R R R R
R R R R R R
R
SR΄
S S a, R΄= nBu
R= N
b, R΄= nC12H25
S S SR΄
102 103 104
In addition, the redox chemistry of a bis-TTF calix[2]pyrrole[2]thiophene shows that the two TTF
moieties do not interact. Cyclic voltammetry in CH2Cl2 shows two reversible 2e− oxidations at
the same potential as that for the mono TTF model, indicating that the 1e− oxidation of both TTF
moieties occurs at the same potentials [267]. Similarly, cyclic voltammetric studies of a bis-TTF
calix[4]arene in which the TTF moieties bridge the “upper rim” also demonstrate that there is
no electronic communication between the TTF moieties [268]. In addition to calixarenes bearing
two TTF moieties, TTF bridging two calix[4]arenes has been reported and studied electrochemi-
cally [269]. Cyclic voltammetric studies in CH2Cl2 –CH3CN (1:1, v/v) show the expected two
redox processes with the first reversible (E11/ 2 = 0.43 V vs. Ag/AgCl) but the second at Epox = 1.07 V
is broadened and quasi-reversible for unknown reasons. Interestingly, TTF dendrimers have been
studied electrochemically and the TTF units act independently and are all oxidized, as ascer-
tained quantitatively by current measurements, at the same potentials, resulting in multiradical
cations in the first oxidation step and multidications in the second step [270]. In the presence of
nonredox active electron-rich oligomers, complexation with oxidized TTF oligomer has been
inferred from the substantial decreases in the redox currents compared with that in the absence of
the electron-rich complexing oligomer owing to a decrease in the diffusion rate of the complexed
species [271].
A review on these mixed valence complexes and related systems has recently appeared [272],
and the significance of splittings in electrochemical oxidation of such systems discussed. Interaction
between TTF and triarylmethyl radicals linked by an ethylene moiety has been evaluated electro-
chemically [273]. Dimerization between two different TTF moieties can be controlled in redox
active [2]catenanes [274].
π-Extended TTF analogues, exTTF, in which two 1,3-dithiolenes are separated by a conjugated
π-system have attracted much interest and show unusual electrochemical behavior [275]. Cyclic
voltammetric studies of TTF vinylogues 105 show that substituents affect the oxidation potentials
but, in addition, increasing the conjugation length (i.e., increasing n) lowers the first oxidation
potential and decreases the difference between the first and second oxidation potentials [276]. Even
more interesting is the behavior of 106 that is synthesized by controlled potential electrolysis of
1,4-dithiafulvalene 107 [277].
R
S Me
S Ar Me
R SMe S
R S S
S
MeS S
S Me MeS S Ar
n S R Ar
105 106 107
Electrochemical studies show that the mechanism for this synthesis involves the dimerization of the
radical cation of 107. Two reversible 1e− oxidations or one 2e− oxidation occurs depending on the
Ar substituents, their positions (o– vs. p–), and the solvent [277]. These results are rationalized in
terms of electronic and steric factors in which there is a large conformational change on oxidation
[277,278] underlying the potential inversion [279] and consequent a single 2e− oxidation wave. This
analysis is supported by X-ray structural studies and DFT computations. Cyclic voltammetric stud-
ies on 108 provided insight into its unusual redox behavior [280]. In CH2Cl2, 108 undergoes two 1e−
oxidations followed by a 2e− oxidation to afford the corresponding tetracation 1084+. However, on
the reverse scan at scan rates greater than 100 mV/s, in addition to reduction waves corresponding
to the oxidations, an additional more negative reduction peak is observed. On the basis of theoreti-
cal calculations, the nonplanar s-trans isomer (about bond a,b) is favored for 108, but the nonplanar
s-cis isomer is favored for 1084+. Consequently, at fast scan rates the reduction of s-cis-108+• can be
observed in addition to that of s-trans 108+•.
The effect of aromatic rings connecting 1,3-dithiafulvalene units has been reviewed [275]. More
recent studies have probed the consequences of such connectors on the use of such compounds as
organic field effect transistors [281]. The redox chemistry of one such system connected by a ben-
zene ring but with thiophene appended as well 109 has been reported [282].
MeS SMe
S S
Me C8H17
Me S S
S b
a Me
S S
Me S C8H17
S S
S MeS SMe
108 109
Notably the oxidation is dominated by the exTTF core and electropolymerization of the thiophene
moiety does not occur. Electrochemical studies on 110, in which thiophene bridges 1,3-dithiaful-
valene and exTTF moieties, have been reported in PhCN as solvent [283]. Deconvoluted cyclic
voltammetry shows four pairs of reversible redox waves. The first two waves are 2e− processes and
the following two 1e− processes.
p-Quinodimethane TTF analogue 111 undergoes two reversible 1e− oxidations at −0.11 and
−0.04 V versus SCE in acetonitrile, which is much less anodic than that for the oxidation of TTF
(0.28 and 0.64 V vs. SCE) under the same conditions [284] owing to reduced Coulombic repulsion
on oxidation. However, analogue 112a undergoes 2e− oxidation at a potential slightly more positive
than the first 1e− oxidation for TTF (0.44 and 0.37 V, respectively, in CH2Cl2 vs. SCE) [285]. Thus,
there is potential inversion; that is, the radical cation of 112a oxidizes at a lower potential than 112a.
Cyclic voltammetric analysis in DMF led to an estimated potential inversion for 112a of 0.28 V
[286]. Similar results for benzo-annulated analogues of 112a have been reported [285]. Thus, the
radical cation of 112a appears to be destabilized relative to the dication and indeed, the radical
cation of 112a generated by pulse radiolysis [287] or the radical cation of 112b generated by flash
photolysis [288] disproportionates.
R R
R R R R
S S S S
S S S S
S S
S S S S S S S S
S S
R R R R R R R R
110a, R = SMe 111 112a, R = H
b, R = Me b, R = SMe
The role of aromaticity in potential inversion is illustrated on electrochemical studies comparing

113 with 114.
S S+
+
S S S S S S
113 114 115
Potential inversion is found for 114 but two 1e− oxidations are found for 113 [289]. Potential inver-
sion is ascribed to aromaticity of the dication 115 obtained from 113. The importance of substantial
geometry change on oxidation of 112, in which the saddle-shaped central ring of 112 becomes pla-
nar on 2e− oxidation with almost perpendicular 1,3-dithiolium substituents has been well illustrated
by molecular constraints that prevent planarization [290].
S S MeS SMe
S S S S
SMe
(CH2)5 (CH2)5 S S
S S SMe
S S
S S
S S MeS SMe
116 117
Thus, doubly bridged derivative 116 shows two reversible 1e− oxidations in CH2Cl2 at more anodic
potentials than the 2e− oxidation for comparable nonbridged analogues [290].
Electrochemical studies were used to evaluate electronic interactions between a TTF and an
exTTF moiety linked by π-systems. Cyclic voltammetry of 117 in CH2Cl2 revealed three revers-
ible peaks with oxidation potentials of 0.27, 0.71, and 1.12 V versus SCE [291]. The first peak
corresponds to a 2e− oxidation and was assigned to the exTTF moiety. Cyclic and square wave
voltammetry of 118a–c were solvent dependent (THF, CH2Cl2, and CH3CN were used as solvents)
and showed a 3e− oxidation, for which separation of oxidation peaks was only observed for 118a in
THF, followed by a 1e− oxidation [292]. Thus, the 2e− oxidation of the exTTF moiety and the 1e−
oxidation of the TTF moiety overlap (except for 118a in THF) followed by further 1e− oxidation of
the TTF moiety.
R R
S S S S
S S
S S S
S
SMe
S S
S S S S SMe
R R S S
118a, R = H S S
b, R = SMe
c, R, R = (SCH2)2 119

Comparison with models with either exTTF or TTF moieties but not both showed features ascribable
to each moiety in 118 and also electronic interations between them. However, far more consequen-
tial electronic interactions between exTTF and TTF moieties were demonstrated by electrochemi-
cal studies of 119 in which the moieties are directly connected without an intervening π-system
(unlike 117). Here, deconvoluted cyclic voltammograms with CH2Cl2 as solvent showed four sepa-
rate reversible oxidations [293].
Compounds with exTTF moieties attached by unstrained saturated linkages as illustrated by 120
do not interact electronically. Consequently, cyclic voltammetry shows a typical quasireversible
oxidation peak for all of the exTTF moieties, which for 120 results in a 6e− oxidation [294].
SMe
S S
SR
Me Me
R=
RS SR
Me
S S
MeS SMe
120
Likewise cyclic voltammetry studies show one pair of quasi-reversible waves for the noninteract-
ing 1,3-dithiafulvalene moieties in 121 [295]. However, for compound 122 in which two exTTF
moieties are directly linked by a σ-bond, two closely spaced 2e− oxidations are observed electro-
chemically ascribed to separate 2e− oxidations of each exTTF moiety [296]. This interpretation is
supported by spectroelectrochemical studies and DFT calculations.
RS SR Me
S S S S Me
RS S S SR S S
Me
2
121, R = Me, Et, Bu 122
As pointed out in the introduction to TTF and analogues, interest in these systems is driven by their
applications. The following text is organized in terms of these applications, but the emphasis is on the
electrochemistry of the organosulfur components. A review on TTF and exTTF vinylogues as building
blocks for organic materials and redox chemistry control of their conformational switching has been pub-
lished [297], and a review of the application of exTTF moieties in organic electronics has appeared [298].
Compound 123 has been shown to be a selective chemiluminescent probe for singlet oxygen.
MeS S(CH2)2O
S S S S
O
MeS S CONH(CH2)2NHCAr
S S S
123 124, Ar = 3,4,5–(C12H13O)3C6H2
Cyclic voltammetric studies in CH3CN show three oxidation waves at 0.47, 0.80, and 1.3 V versus
SCE [299]. Stepwise electrochemical and chemical oxidation of TTF serves as input signals and the
consequent distinct absorptions for the cation radical and dication as output signals in a molecular
logic gate (half-adder) that, owing to the facile reduction of TTF oxidation, is resettable [300].
Compound 124 shows oxidation potentials shifted to less positive values when assembled as a gel
than in PhCN solution ascribed to π-stacking in the assembled gel [301]. Compound 125a shows
two 1e− oxidations by cyclic voltammetry and oxidized xerogel from 125a is a semiconductor [302].
On the other hand, electrochemical oxidation of the gel formed from 125b in ClCH2CH2Cl destroys
the gel by impairing intermolecular hydrogen bonding by the urea moiety [303]. Oxidation of end
functionalized TTF poly (N-isopropylacrylamide) micelles also disrupts the micelles [304].
S SR
S S S S Ar
S R΄ S S
S S
125a, R = CH2CONHC18H37 126a, Ar = pNO2C6H4

R΄= SMe b, Ar = pNCC6H4
b, R = (CH2)2NHCONHC12H25 c, Ar = 4-pyridyl
R΄= H d, Ar = 4(NMe)pyridinium
Chiral TTF compounds have attracted interest because of the possibility of synergism between con-
ductivity due to the TTF moiety and chirality due to the chiral moiety [305,306]. Chiroptical molecular
switches have been reported [307,308]. For example, cyclic voltammetry of a chiral polymer containing
TTF moieties shows two quasireversible waves that enable the production of different oxidation states
that display different CD effects [308]. Conjugation of TTF moieties with π-electron-accepting moi-
eties has attracted interest for their nonlinear optical properties. Here, intramolecular charge transfer is
evaluated electrochemically. Thus, cyclic voltammetry shows anodic shifts for the two 1e− oxidations
in 126a and b [223], 126c and d [309], 127 [310], 128a–c [311], and analogues. π-Extended donors with
TTF moieties attached to a vinyldithiolene show two reversible oxidation waves [312].
Molecular motions controlled by the redox state of TTF moieties forming the basis of molecular
tweezers, clips, and switches have garnered much attention recently.
R
S S Ar
S S CN
R
n CN S S
S S Ar
R = MeS, H, S(CH2)2S
127 128a, Ar = 2–pyridyl
b, Ar = 3–pyridyl
c, Ar = 2–quinolyl
Cyclic voltammetric studies on 129 in CH2Cl2 show that there are two 1e− oxidation waves followed
by a reversible 2e− oxidation [313].
OR S(CH2)nS
RS S S
S S S S SR
S S S S
RS S S S S
S S SR
OR Ar H H Ar
129, R = C6H13
130
Thus, the conformation of 129 changes from closed, where the radical cation of one TTF unit
interacts with the other TTF unit, to open owing to electostatic repulsion between TTF dication
units [314]. Anodic oxidation of 130 resulted in intramolecular coupling of the 1,3-dithiafulvalene
moieties via the cis-radical cation to give 131 dication that is reduced to 131 [315].
MeS SMe MeS SMe

SMe
SMe
S S S S S
S(CH2)nS S
R=
S S S S
S
MeS S
Ar Ar SMe
R R
131 132
S S
S S
+ +
R R
S S
N+
+
S S
R= OCH2CH2O
4
133 134
Whether two 1e− or one 2e− process occurs depends on the chain length, n, and the Ar substituents.
With a short link, compound 131 acts as reversible molecular clips that close on oxidation [315].
Other cis-locked analogues have been studied recently [316] as has compound 132, which acts as
an electrochemically activated tweezer [317]. Cyclic voltammetry of 132 in CH2Cl2 shows only
one oxidation peak at +0.68V corresponding to a 6e− oxidation (resulting from oxidation of the
bis-tetrathiafulvalene and both exTTF units) but on scanning cathodically two reduction peaks are
observed at +0.55 and +0.23 V versus Ag/AgCl [317]. Electrochemical data have been cited as evi-
dence for conformational change in TTF-bridged resorcin[4]arene cavitands [318]. In this molecule
with two TTF moieties, cyclic and differential pulse voltammetry show a broadened 2e− reversible
step followed by a sharper second 2e− reversible oxidation. It is argued that in the first oxidation step
the conformation is such that the two TTF moieties are close enough to interact but the oxidized
TTF moieties repel each other electrostatically, resulting in a conformational change in which the
two moieties do not interact with each other and further oxidize in the second step.
Pseudorotaxanes, rotaxanes, and catenanes containing TTF units have been studied as redox
activated switches [319] (see also Chapter 12). Electrochemistry is used to probe the structures
of these materials and their precursors and, in particular, electronic interactions affecting TTF
redox chemistry. For example, an acyclic polyether with a central TTF moiety threads through
cyclophane 133, resulting in attractive interactions between the electron-rich TTF and electron-
deficient bipyridinium moieties. This results in an anodic shift for the first oxidation but not the
second oxidation and scan rate dependence of the first but not the second oxidation of the TTF
moiety [320,321]. The first oxidation is rendered more positive by the donor–acceptor interaction,
but the second oxidation occurs after dethreading of the TTF polyether. Interestingly, the dethread-
ing is reversed on reduction, resulting in electrochemical control of the threading/dethreading
process. In another example, a rotaxane is formed in which a TTF polyether is threaded through
an α-cyclodextrin cavity and stoppered (larger groups are appended to the ends of the TTF poly-
ether) [322]. Cyclic voltammetry shows two reversible 1e− oxidations for the TTF moiety in this
rotaxane with a shift in oxidation potential for the first but not second process (0.32, 0.55 and 0.17,
0.54 V, respectively, vs. SCE). Thus, the electrochemical evidence suggests that the α-cyclodextrin
encloses the TTF moiety but on oxidation of the cyclodextrin moves away from the TTF radical
cation. This interpretation is supported by spectroscopic results. Reduction reverses this process.
Electrochemical studies of an analogous system with cholesterol stoppers that enable gel forma-
tion have been reported [323] as a well as another rotaxane capable of forming liquid crystals in
which rearrangement occurs on oxidation and is reversed on reduction. These redox controlled
movements change the liquid crystal ordering resulting in electrochromism [324]. [2]Catenanes
are formed by interlocking 133 with a cyclic polyether with a TTF moiety and a 1,4-dioxybenzene
or 1,5-dioxynaphthalene moiety transannular to each other. Here, the first oxidation of the TTF
moiety is anodically shifted and scan rate dependent and results in rearrangement owing to the
Columbic repulsion [321]. The rearrangement involves rotation resulting in removal of the TTF
radical cation moiety from the cyclophane cavity and its replacement by the dioxyaromatic unit.
A [3]catenane in which two cyclic polyethers each containing a TTF moiety are interlocked with
cyclophane 133 gave interesting electrochemical results. Four separate 1e− oxidations occurred,
indicating interaction between TTF units and, of particular interest, mixed valence (TTF)2+• and
radical cation dimer (TTF)22+ formation within the 4+ cyclophane despite electrostatic repul-
sion [325]. A pseudorotaxane consisting of 134 threaded by dibenzylammonium salts has been
reported [326]. Cyclic and differential pulse voltammetry on 134 shows two closely spaced oxi-
dations, indicating that oxidation of one exTTF unit influences the oxidation of the other. Other
examples of switches and other TTF and exTTF-containing molecules designed for switches and
molecular electronics and their electrochemistry have been reviewed [327].
Use of TTF-based molecules as electrochemical sensors for metal cations has been reported.
Thus, 135 shows two reversible oxidations. On addition of Pb2+, the first oxidation shifts anodically
but not the second.
MeS
RN S S S S S O O OMe
NR
S S RS S O O OMe
S S
OCH2 CH2OCH2 CH2O(CH2)2

R= 136a, R = Me
OCH2 CH2OCH2 CH2O(CH)2 b, R = O(CH2)6
2
O O
135
S n
The shift in the first oxidation is due to complexation by the crown moiety in 135. The peak potential for
the Pb2+ complex of 135 is 140 mV more anodic than that for 135. On oxidation of the lead complex, the
Pb2+ is released, resulting in no shift in potential for the second oxidation. In addition, Ba2+ complexes
also result in anodic shift of the first oxidation of 135 by 90 mV [328]. Addition of Pb2+ to 136a gave
analogous results, that is, owing to metal complexation anodic shift of the first but not the second oxida-
tion potential because the metal ions have been released. Furthermore, polymeric films of 136b show
similar behavior as 136a enabling redox control of Pb2+ binding to the surface [329]. However, append-
ing TTF vinylogues with polyether metal cation complexation sites results in the unusual feature that
Ba(ClO4)2 and Pb(ClO4)2 complexes more strongly associate with the dication than monocation despite
the increase in charge [330]. This is ascribed to a conformational change on oxidation (clip motion) and
conformational switching with TTF vinylogues with naphthyl substituents [331] has also been reported.
Dendrimers featuring 137 units electrodeposited on the electrode surface also show redox depen-
dent complexation of Ba2+ and, in particular, anodic shift of the first oxidation in potential on addi-
tion of Ba2+ [332]. Electrochemistry shows a modest but analogous effect with a bis (calix crown)
TTF species and Na+ in solution [333].
RS
S S SMe
S S O O
S O O S S
S S S
S S O O
O O O S S
O O
137 138
Cyclic and square-wave voltammetric studies show a quasi-reversible 2e− oxidation of 138. Addition
of metal cations results in anodic shift of the first 2e− oxidation due to metal complexation with the
crown ether moieties. The largest measured shift of 115 mV was found for Ag+ and the shifts follow
the order Li+ < K+ < Ba2+ < Na+ < Ag+ [334].
Compounds with TTF moieties appended with metal binding sites more remote from the redox
moiety but conjugated with it have been reported. Cyclic voltammetry of 139a and b in CH3CN
shows two reversible waves at more anodic potentials than TTF owing to charge transfer from the
TTF moiety to pyridine moiety.
X
S X N S
S S N
S S S S
139a, X = CH CH 140a, X = CH
b, X = C C b, X = N
c, X = C N
This charge transfer is increased on addition of Pb2+, which coordinates to the pyridine moiety,
resulting in spectroscopic and electrochemical changes. In particular, both oxidation potentials are
rendered more anodic, demonstrating that, in contrast to the preceding examples, the metal ion is
not liberated on TTF oxidation [335,336]. Similar spectroscopic and electrochemical results were
reported for Pb2+ addition to 139c [337] and electrochemical oxidation potential shifts for 140a on
addition of Cu2+ [338]. Compound 140b shows two 1e− oxidation waves anodically shifted from
those of TTF owing to the electron-withdrawing pyrazine moiety. Further anodic shifts of both
oxidation waves are seen on metal coordination, for example, Mn(hexafluoroacetylacetonate)2. In
this case, cyclic voltammetric studies over time enable the monitoring of dissociation of the Mn(II)
complex [339]. Redox potentials for a TTF derivative fused to a pyrazine ring have been reported
[340]. Compounds with two TTF moieties bridged by a pyridine moiety, for metal coordination,
have been prepared. In this case, coordination of a magnetic metal to obtain conducting magnetic
materials rather than metal ion detection is the goal, but the ligand electrochemistry is of interest.
Thus, 141 shows two 1e− oxidations, separated by 166 mV, and a 2e− oxidation.
MeS S S N
S S
S S SMe N
S S H SC5H11
MeS HN S S
S S SMe
S S NH
N S S SC5H11
H
N
141 142
The observation of two 1e− oxidations (each TTF unit oxidizing at a different potential) rather than
a 2e− oxidation suggests interaction between the two TTF moieties forming π-dimers (owing to ring
flexibility) on oxidation [341].
In addition to electrochemical sensors for metal cations, anion sensors based on TTF have been
reported as well. Thus, addition of Cl− or Br− to 142 in CH3CN results in a cathodic shift in its
first oxidation potential, reaching a limit of about 40 mV with a stoichiometric amount (1:1) of
halide [342]. In a related example, an analogue of 142 with four benzo-TTF moieties fused to the
calix[4]pyrrole core forms a molecular complex with Li+@C60. On addition of Cl− electron transfer
from TTF to C60, moieties occurs based on cyclic voltammetric analysis in which the 1e− oxida-
tion potential of the TTF moiety shifts anodically by 130 mV [343]. Cyclic voltammetric studies of
143 shows that on addition of F− the first oxidation wave is shifted cathodically up to a maximum of
140 mV when 1.0 equiv of F− is added.
C6H11S S S
MeS S S CONH
S N B N
C6H11S S
2 MeS S S
143 144
The shift is ascribed to binding of F− to B that reduces the electron withdrawal by B [344]. Another
sensor with TTF attached to a boron-dipyrromethene also shows a 17 mV cathodic shift of the first
oxidation potential of the TTF moiety [345]. Larger electrochemical shifts in reponse to F− have
been reported for another TTF-based sensor [346].
Addition of AcO −, F−, Cl−, or Br− to 144 resulted in no changes in its cyclic voltammogram,
but addition of H2PO4− resulted in two new oxidation waves cathodically shifted from those in its
absence by 100 and 158 mV. Complexation of 144 with H2PO4− renders it easier to oxidize and the
complex has a 2:1 stoichiometry (144 to H2PO4−). Thus, 144 serves as a selective electrochemical
sensor for H2PO4− [347]. Compound 145 also shows a cathodic shift in its first oxidation potential
of its TTF moiety on addition of H2PO4− of up to 172 mV [348].
SO2NH(CH2)2NHCOR C5H11 C5H11
S S
NC CN
SO2NH(CH2)2NHCOR
S S
SMe O
S S
Me
R=
S S SMe O NC CN
145 146
Cathodic shift of 112 mV of the first oxidation potential is found by addition of 2 equiv. of H2PO4− to
a sensor with TTF fused to a diindolylquinoxaline [349]. Curiously the second oxidation potential
in this system undergoes an anodic shift on addition of H2PO4−. Analogous behavior has been noted
in other systems [345], but the most dramatic manifestation of anodic shifts in TTF oxidation on
addition of anions is manifested in a calix[4]arene appended with four TTF moieties [350]. This
compound shows unusual electrochemical behavior in that four redox processes are found by cyclic
voltammetry, suggesting interaction of the TTF moieties on oxidation. Furthermore, addition of
anions results in anodic not cathodic shift of all of the oxidation peaks. Addition of H2P2O72− results
in a dramatic shift of the fourth oxidation of up to 453 mV. Clearly binding of anions to TTF recep-
tors may result in changes other than increasing the electron richness of the TTF moiety. Other
redox sensors based on TTF have also been recently reported [351–353].
As referenced in the introduction of this section, the charge transfer complex formed from
electron-donating TTF and electron-accepting TCNQ is highly conducting. Consequently, much
effort has been expended on investigating systems in which TTF or analogues (D, donor) are cova-
lently linked to an acceptor (A) in so-called D-A dyads. Furthermore, such compounds might
serve as molecular rectifiers [354]. The DA link may involve σ-bonds, π-systems, or direct fusion.
Electrochemistry has been used to evaluate D,A interaction in such systems and provide insight into
the HOMO–LUMO gap as illustrated in the following selected examples.
Electrochemical studies on 146 in which there is a flexible σ-linkage between TTF and TCNQ
moieties show modest shift (20 mV) of the first oxidation potential of the TTF moiety and first reduc-
tion potential of the TCNQ moiety compared with the respective parent molecules [355]. This indi-
cates little interaction between redox centers. However, their difference in potentials of only 170 mV
equates to an exceptionally low HOMO–LUMO gap (which is substantially lower than that deter-
mined spectroscopically). The more rigidly σ-linked 147 exhibits two reversible 1e− oxidation waves
that are shifted anodically by 200 and 60 mV, respectively, from the model TTF derivatives [356].
NC CN S S SPr
NC CN
S S N
S S
SPr
N
S S R
NC CN
2 NC CN
147 148
In compound 148, the first and second oxidation potentials are anodically shifted from 148, R = H with
more electron-withdrawing sulfonamide substituents 148, R = p-MeC6H4SO2, p-O2NC6H4SO2 [357].
CN
NC
O
S SMe SMe
N S S R S S S
S SMe S SMe
S S R΄ S S
O 150a, R = R΄= H
NC b, R = H, R΄= Cl
CN 149 c, R = R΄= Cl
In compound 149, a TTF moiety is rigidly connected via a π-linkage to a TCNQ-like moiety.
Remarkably, electrochemical studies show little shift in the reduction potentials of the A portion
but anodically shifted oxidation potentials for the TTF moiety [358]. The cyclic voltammetric data
correspond to a HOMO–LUMO gap of 0.52 eV. DFT calculations show that the LUMO is localized
on the TCNQ-like moiety and, although the HOMO interacts, it is substantially localized on the
TTF moiety despite the fused π-connection between D and A.
p-Benzoquinones have been used as the acceptor in D-A dyads with TTF. The first oxidation
potentials (but, surprisingly, not the second) for the TTF moiety in the series 150a–c are shifted
anodically as well as the first reduction potentials [359]. These shifts were ascribed to increasing
charge transfer from TTF to benzoquinone moiety on going from 150a to b to c. Correlation of
these redox changes with the spectroscopically measured charge-transfer band supports this sug-
gestion (indeed both measure the HOMO–LUMO gap). Electrochemical studies on TTF linked to
anthraquinone D-A dyads have also been reported [360]. Cyclic voltammetric studies have also been
reported for A-D-A triad with a p-benzoquinone moiety fused to each end of TTF [361,362]. Here, the
most interesting feature is that deconvolution of the cyclic voltammogram shows that the first reduc-
tion wave is split, indicating electronic communication in the mixed valence 1e− reduction product.
Thus, the bridging TTF promotes electron transfer from the semiquinone to quinone moieties. Cyclic
voltammetry was used to demonstrate no interaction between TTF and quinone moieties attached by
a flexible polyether σ-linker until coordination by Pb2+, Sc3+, and Zn2+ ions that promote intramolecu-
lar electron transfer [363–365]. Similar electrochemical studies on TTF-naphthalenediimide dyads
and DAD-triad σ-linked with a flexible polyether chain have been reported [366] as well as TTF-
perylenediimide-TTF triads [367]. Electrochemical studies with the rigid TTF-naphthalenediimide
dyad 151 show three reversible oxidations, the first two due to the TTF moiety anodically shifted
from a TTF model, and the third due to the 1,4-dihydropyrazine moiety [368].
C8H17
O N O H NO2 NO
O 2
Br N SPr
S S C5H11 XC(CH2)2SO2
S S
S S SPr
Br N NO2
C5H11 S S
N O H NC
O CN
152a, X = CH2O
C8H17 151 b, X = CH2N(Ph)

Linear and cyclic linked TTF-naphthalenediimides have also been studied electrochemically [366].
The thermodynamic driving forces for charge combination and charge-separation processes for a
TTF moiety rigidly fused to a perylenediimide were calculated from electrochemically determined
potentials [369]. Dyads 152a and b show two reversible 1e− oxidation waves due to the TTF moi-
ety and three reversible 1e− reduction waves due to the A moiety. The first oxidation potentials are
shifted anodically (40–70 mV) owing to electron withdrawal by the A moiety and both show small
HOMO–LUMO gaps of ca. 0.3 eV [370–372].
Anodic shift (0.10–0.15 V) in TTF moieties singly bonded to semisquarates relative to models pro-
vide evidence for charge delocalization [373] and the lack of such shift shows the lack of charge transfer
in TTF moieties attached through several σ-bonds to perylene [374]. In compounds 153a and b, there
are slight anodic shifts in TTF oxidation potentials compared with TTF and the somewhat broadened
oxidation waves in 153b is suggestive of weak electronic interaction between the TTF moieties [375].
R
R
OMe
N
N N
R N N
R N R'
R N N
S S N
153a, R = , R΄= OMe
S S
R
S S R
b, R = R΄=
S S SPr
S S
154, R,R =
S S SPr

Connecting a TTF moiety via a flexible polyether chain to a flavin shows little interaction as evidenced
by comparable oxidation potentials with a model, but on addition of Pb2+ or Sc3+ there is a dramatic
shift in reduction potential of the flavin moiety as a result of metal coordination [376]. Annulating
π-systems to connect a TTF moiety with a dipyridophenazine [377] or quinoxaline [378,379] moiety
results in anodic shifts of their oxidation potentials. Anodic shifts in the oxidation potentials of the
TTF moiety in an analogous compound with two quinoxaline moieties fused in an A-D-A fashion has
been reported [380]. Thin layer cyclic voltammetric studies of 154 that features three TTF moieties
π-linked through a hexazatriphenylene reveals that the first oxidation wave consists of three overlap-
ping 1e− oxidations [381]. That is, each TTF moiety undergoes 1e− oxidation successively, but the
second wave is very narrow, indicating that all three TTF radical cations are oxidized at the same
potential to the corresponding hexacation. The TTF moiety in compounds 155a–c shows two revers-
ible 1e− oxidations in CH2Cl2. On addition of HCl, both oxidation potentials are rendered more posi-
tive, but on addition of excess HCl the first oxidation is even more positive but the second oxidation
potential is now about the same as that for the unprotonated species [382]. Linking an electron-rich
methoxy thiazole by a σ-bond to TTF results in a cathodic shift in the two reversible 1e− oxidations of
the TTF and the difference in these two oxidation potentials is solvent dependent [383].
Ph
R΄ R
R΄ R
N HN
H Ph
SPr NH N
N S S
Ar R R΄
SPr
N S S R R΄
Ph
155a, Ar = 2-pyridinyl
S SC5H11
b, Ar = 2-quinolinyl S
c, Ar = 6-MeO-2-quinolinyl 156a, R =
S S SC5H11
R΄= H
S SC5H11
S
b, R = R΄=
S S SC5H11

Electrochemical studies of 156a in THF show two 1e− oxidations at −0.150 and −0.020 V versus
Fc/Fc+, clearly indicating interaction between the two TTF rings mediated by the porphyrin ring
[384,385]. Comparable interaction between the four TTF moieties in 156b is evidenced by the
observation of at least five oxidation processes ascribable to the TTF moieties [384]. TTF moieties
fused to porphyrins by quinoxaline linkers have been studied electrochemically [386]. Interestingly,
a TTF moiety annulated to a porphyrin ring quenches porphyrin fluorescence by electron transfer
from the TTF to porphyrin excited state but on oxidation of the TTF moiety to its radical cation,
porphyrin fluorescence is no longer quenched [387]. Multielectron oxidations have been reported
for TTF annelated to an expanded porphyrin [388]. Annulation of four TTF moieties to a phthalo-
cyanine, like the porphyrin example, also results in interaction mediated by the phthalocyanine, but
here the first reversible overall 4e− oxidation is resolved into two broad overlapping waves but not
the second 4e− oxidation [389–391]. A related system was reported, but cyclic voltammetric studies
were rendered difficult owing to aggregation in solution although two reversible oxidation waves
were observed [392]. In contrast to the effect of TTF oxidation on the fluorescence quenching of
a porphyrin outlined earlier, oxidation of TTF to its radical cation had no effect in a silyl phthalo-
cyanine with a flexible link from the silicon to TTF moiety. That is, fluorescence quenching occurs
whether or not the TTF is oxidized or not. It is suggested that quenching occurs in the oxidized
TTF system by electron transfer from the TTF radical cation to the excited state phthalocyanine
[393]. Neutral radical 157 in PhCN shows three reversible waves at potentials close to that of the
compounds with constituent moieties. Use of PhCN/CF3CH2OH as solvent results in an anodic
shift in the reduction potential of the oxophenalenoxyl moiety but no shift in the oxidation poten-
tials of the TTF in 157 [394] constituent moieties. Electrochemical studies have also been reported
for D-A dyads with TTF fused to pyridazine [395], benzothiazole [395], and directly attached to
1,3,5-triazine [396,397].
S S C8H17
S
S X N
S
S
C60
O O S S
OC6H11
157 158 X= S S
C6H11O
There has been much interest in D-A dyads with TTF or exTTF donors and C60 fullerene
acceptors for use in solar cells. Those systems with exTTF donors have particular appeal because
the lifetimes of the charge separated states exTTF+•/C60 −• can be unusually long (typically longer
than TTF-C60 D-A systems) and consequently, may be especially serviceable in solar photovol-
taic cells [227]. Again, here as before, electrochemistry is used to evaluate electronic interaction,
or lack thereof, in the ground state, effect of substituents and determination of ΔGo for elec-
tron transfer. In an effort to control charge recombination in charge separated states, a dithienyl
photoswitch was reported [398], applied to TTF-fullerene dyads [399] and both the open and
closed form studied electrochemically. Electrochemical studies with TTF linked (saturated or
unsaturated chain links) with pyrrolidine[60]fullerene show no significant interactions between
moieties [400], as well as a comparable A-D-A triad and the redox data used to calculate ΔG o
for electron transfer [401]. Similarly, electrochemical evidence reveals negligible electronic
communication between exTTF and [60]fullerene moieties in compounds in which exTTF is
covalently linked to pyrrolidine [60]fullerene [402] as well as comparable A-D-A triads [403].
Similar analysis shows no significant interaction between exTTF linked through chiral binaph-
thyls to pyrrolidine[60]fullerene [404] as well as in a pseudorotaxane supramolecular structure
with an exTTF derivative appended with a dibenzyl ammonium functionality threaded through a
pyrrolidine[60]fullerene bearing a dibenzocrown ether [405]. However, a cathodic shift in the oxi-
dation potential of an exTTF moiety attached by a π-conjugated bridge to pyrrolidine[60]fullerene:
158 relative to exTTF (+0.50 and +0.55 V, respectively vs. SCE) has been observed and indicates
electronic communication between the two units [406] and, perhaps another related example has
been reported in which the 2e− oxidation potential for exTTF is ca. 0.45 V versus SCE [407],
although such studies on a similar system with a π-conjugated phenylvinylene link showed no
shift in the oxidation potential of the of the exTTF moiety [408]. A 40–60 mV cathodic shift in
the first reduction potential in A-D dyads of exTTF moieties π-linked to pyrrolidine[60]fullerene
also indicates electronic interaction between A and D moieties [409]. Cyclic voltammetry study of
TTF [410] or exTTF [411] attached to triazolino[60]fullerene show no significant D-A interactions.
Electrochemical studies of exTTF directly linked to methano[60]fullerene were reported [412].
Connecting these units similarily with longer σ-bonded linkages and A-D-A and D-A-D triads
gave compounds that showed no interaction between units electrochemically [413]. Interesting
studies on the effect of the linker on the interaction between two redox centers connected by
acetylene moieties and Pt (two TTF moieties) [414], acetylene moieties and ruthenium (ferrocene
and TTF) [415], have been reported.
Electrochemical evidence for the tuning of exTTF donor acceptor complexes by aryl sub-
stituents has been presented [416]. Redox control of exTTF porphyrin donor acceptor complexes
by metal ion coordination has been shown [417]. A review of the application of exTTF moieties
in organic electronics has appeared [228]. Self-assembly of exTTF appended with pyridine
groups by Pd(II) and Pt(II) into electroactive containers has been reported [418]. Cyclic and
Osteryoung square-wave voltammetry of exTTF σ-linked to pyrene shows the same oxida-
tion potential for exTTF oxidation in solution as for that anchored in a single-walled carbon
nanotube (SWNT) by the pyrene moiety (although with broadening), but the embedded pyrene
moiety shows 100 mV shift compared with that in solution [419]. Electrochemistry of TTF
and exTTF moieties covalently attached via spacers to SWNTs has been measured to provide
estimates of the energy required for forming the corresponding charge separated states [420].
Differential pulse voltammetry of exTTF moieties conjugated with cyanoacrylic acids provided
estimates of the HOMO–LUMO gap in these compounds that after attachment to mesoporous
TiO2 are used in a dye-sensitized solar cell [421]. Electrochemical studies of polythiophenes
annulated with TTF obtained by electropolymerization of the monomers have been reported
[422,423] as well as for oligothiophenes linked on one end to TTF and at the other end to pyr-
rolidino [60]fullerene [424].
VII. ThiOPhENE AND ANALOGUES

Electropolymerization of thiophene and its derivatives [425,426] is arguably the most impor-
tant electrochemical behavior of thiophene because activated (“doped”) polythiophenes such as
poly(ethylenedioxy)thiophene PEDOT or PEDT are the most useful organic conducting polymers
[427–429]. Oligothiophenes are also of great interest as components in organic electronic devices
and molecular electronics [430]. The electrochemistry of oligo- and polythiophenes has been exten-
sively studied and recently reviewed [431]. Consequently, these areas are excluded from the present
overview but are included in Chapter 41 of this volume.
Anodic oxidation of thiophene and its alkyl derivatives is typically irreversible leading to elec-
tropolymerization. However, annulations of thiophene with bicyclo[2.2.2]octane moieties as in 159
results in reversible 1e− oxidation in CH2Cl2 with E1/2 = +0.79 V versus Fc/Fc+ [432].
As pointed out in Section V, the bicyclo [2.2.2]octene moieties stabilize the radical cation by
inductive, σ-π conjugative and steric effects [177].
159
160
Ar S Ar
161a, Ar = Ph
b, Ar = p-MeOC6H4
c, Ar = p-CF3C6H4

Similarily, the dibenzothiophene derivative 160 shows a reversible 1e− oxidation in CH2Cl2 with
E1/2 = +0.67 V versus Fc/Fc+ and a quasi-reversible second oxidation [433]. Compounds 161a–c exhibit
a reversible 1e− oxidation as well as a reversible 1e− reduction in THF [434]. 2,5-Di(alkylthio)thio-
phenes also show reversible 1e− oxidations in CH2Cl2 or (CF3)2CHOH [435,436] followed by an irre-
versible oxidation. However, 2,2′-di(alkythio) bithiophenes show two reversible oxidations [435,436].
The effect of nitro substituents appended to thiophene and benzothiophene was evaluated by cyclic
voltammetry [437]. The reduction potential of thiophenes bridged by carbonyl or 1,2-dicarbonyl
groups has been recorded [438]. Bulky aryl substituents have been shown to improve the stability of
the electrochemical oxidation products from dithieno-thiophenes, that is, the first oxidation waves
are reversible and electropolymerization is thwarted by cyclic voltammetric studies in CH2Cl2 [439].
Reversible 1e− oxidation in acetonitrile has also been reported for alkoxysubstituted dibenzothiophene
[440]. The products of further oxidation may be sulfonium salts, 5-oxides or 5,5-dioxides [440,441].
Thiophenes fused to benzenoid aromatic rings have been of much interest as semiconductors for
organic field effect transistors and their electrochemistry reported in an effort to establish HOMO–
LUMO energy gaps.
R
S
S
R
162a, Ar = C6H5
S
b, Ar = S CH3
S
c, Ar = Ph
d, R = 2-naphthyl
e, R =
S Ph
Ph S
163
R R
S S
S S
R R
164a, R = H
b, R = C6H13

Thus, cyclic voltammetric studies in CH2Cl2 of 162a–e show oxidation potentials of +0.06, +0.02,
+0.29, +0.22, and +0.25 V versus Fc/Fc+, respectively [442]. Compound 163 exhibits a revers-
ible oxidation wave in PhCN with E1/2 = 0.91 V versus Fc/Fc+ [443]. Cyclic voltammetry of 164a
shows irreversible oxidation owing to polymerization but if the α-sites in the thiophene moieties
are blocked as in 164b, oxidation is reversible and differential pulse voltammetry shows oxidation
to the radical cation followed by oxidation to the dication. Similar results occur with the isomeric
system [444]. Cyclic voltammetric studies on compounds 165, R = H, C12H25 or ethylhexyl show
strong reduction and weak oxidation waves from whose onset potentials LUMO and HOMO ener-
gies were estimated [445].
R
R
165
R΄
R R
O N O
S S
S S
O N O
R R
R΄
166, R = C12H25, R΄= C8H17

Donor–acceptor complexes with thiophene and carborane [446], substituted anthracenes [447],
or 1,3,4-thiadiazole [448] have been studied electrochemically. Electrochemical studies to assess
the role of thiophene and its position in linking donor and acceptor moieties have been stud-
ied [449]. Cyclic voltammetric studies on four substituted thiophenes annelated to anthracene
[450] and three aryl substituted thiophenes annelated to naphthalene [451] have been reported.
Electrosynthesis of a cyclo[9]pyrrole with three symmetrically interspaced thiophenes has
appeared [452]. Electrochemical reduction of thiophene fused to a 1,3,2-dithiazolium ring
afforded the corresponding radical as substantiated by EPR spectroscopy [453]. A selective elec-
trochemical thiophene-based sensor for Ca2+ has been reported [454]. Spectroelectrochemical
studies on an end-capped thiophene tetramer have been done and, on cooling, the one electron
oxidized product forms a dimer whose structure was elucidated by the use of NMR spectros-
copy, a spectroscopic technique rarely used in spectroelectrochemical studies [455]. The redox
chemistry of oligo- and polythiophenes, polythienylene vinylenes and A-D polymers, where D is
thiophene, has been reported but is beyond the scope of this review. Conjugated D-A polymers,
in which the donor is benzodithiophene, have attracted much attention for use in solar cells.
Monomeric 166 illustrates such a conjugated D-A motif and undergoes a reversible 1e − oxidation
and two reversible 1e− reductions (the onset potentials gave a low HOMO–LUMO gap of 1.52 eV)
[456]. A recent, related, nonpolymer example incorporating naphthodithiophene 167 as donor
has been reported. Oxidation of 167 using cyclic voltammetry was used to estimate its HOMO
energy [457].
OR΄
R S
S R
OR΄
R΄
O N
S
167, R =
S
N
R΄ O
R΄= 2-ethylhexyl
S
S
S
SiMe3
S
Br
S Br
S SiMe3
S
168
Cyclic voltammetric studies in CH2Cl2 of chiral [7]helicene 168 show two reversible waves at oxidation
potentials much more positive than typical for alkyl oligothiophenes [458]. Spectroelectrochemistry
shows that the first oxidation wave for 168 produces the corresponding radical cation that is also
obtained by chemical oxidation with NOPF6. Interestingly, this radical cation is configurationally
stable at room temperature. Octathio[8]circulene 169 is not soluble in organic solvents but solid state
cyclic voltammetric measurements have been made on sublimed films [459] or thin films on ITO
with ionic liquids [460]. Interestingly, the films show color changes depending on their oxidation
state, that is, electrochromism [460].
S
R R
S S
S S
S S X
X
S S S
S
S R R
169 170a, X = SiMe2, R = H

b, X = S, R = TMS
Compounds 170a and b, in which planarity of the central cyclooctatetraene can be tuned by bond
length changes of the bridging X group, show oxidation at +0.45 and 0.54 V and two reduction
potentials at −2.09, −2.54 and −1.79, −2.25 V, respectively, in CH2Cl2 for the oxidation and in
THF for the reduction versus Fc/Fc+ [461]. The oxidation results in production of the correspond-
ing radical cation and the reduction results in the formation of the radical anion and dianion,
sequentially. Note that the less cathodic reduction potentials for 170b than 170a are ascribed to
increased planarity of 170b over 170a, resulting in a lowered LUMO due to enhanced antiaro-
maticity of the central 8π cyclooctatetraene moiety. Finally, the electrochemistry in CH2Cl2 of
imine-linked thiophenes 171 shows two consecutive 1e − oxidations to the corresponding radi-
cal cation and dication, respectively, and the first oxidations used to calculate their ionization
potentials [462].
R΄ R΄ R΄ R΄ O
N S N NR
S S S
(O)n
R2 R2
172a, R = H, n = 0
171a, R΄= H; R2 = CO2Et
b, R = H, n = 1
b, R΄= C10H21; R2 = CO2Et c, R = H, n = 2
d, R = Ph, n = 0
e, R = Ph, n = 1
The radical cations undergo coupling but are sufficiently stable under electrochemical conditions
so that the first 1e− oxidation is quasi-reversible. In addition, the products from coupling the radical
cations show reversible oxidation when deposited on the ITO electrode. Electrooxidation of tetra
phenylthiophene S-oxide and reduction of thiophene-S-oxide has been reviewed recently [463,464].
The electrochemical oxidation and reduction potentials of a series of thiophenes linked to bithio-
phene S,S-dioxides have been reported [465].
VIII. POLYThiO AND SULfUR-NiTROGEN UNSATURATED HETEROcYcLES

Heterocycle 172a undergoes irreversible oxidation to afford the corresponding sulfonamide 172c in
CH3CN and sulfinamide 172b in the presence of Na2CO3 in modest yields. However, indirect oxida-
tion of 172a as well as 172d using Et4NCl results in high yield of 172b and e, respectively [466].
The redox chemistry of five-membered (and larger) ring polythio and sulfur-nitrogen unsaturated
heterocycles [467] has been studied primarily to obtain stable, neutral radicals that are conducting
and show magnetic ordering in the solid state [468–470]. A recent review on persistent organic radi-
cals in molecular materials has appeared [471]. Here, the focus is on their electrochemical proper-
ties in solution. The redox potentials for five–eight–membered ring heterocycles has been reviewed
[467], and this review updates this previous review.
Cyclic voltammetry of 173a in ClCH2CH2Cl shows a reversible 1e− oxidation wave with
E1/2 = −0.34 V and a quasi-reversible 1e− reduction at −0.71 V versus SCE [472].
Et E E΄
S S
S S S N
S
S S
S S
Et
S Sn
174 175a, E = E΄= S
173a, n = 0 b, E = S ; E΄= Se
b, n = 1 c, E = Se; E΄= S
d, E = E΄= Se
Two reversible redox waves are reported for the hexathio-phenalenyl system 173b [473] and ana-
logues of 173 with borate bridging two moieties and acyclic disulfides rather than cyclic disulfide
moieties has been investigated [474]. Benzotrithiole undergoes reversible 1e− oxidation and 174
shows two reversible 1e− oxidations, indicating interaction between the two trithiole rings [208].
The first oxidation gives the corresponding radical cation, and the second the corresponding dica-
tion. Interestingly, the difference in energy between the singlet and the triplet dication appears to
be small [475].
Cyclic voltammetric studies in CH2Cl2 of a series of 1,2,3-dithiazoles show irreversible oxidation
and reduction waves [476]. However, radicals 175 undergo reversible 1e− oxidation but irreversible
1e− reduction [477]. The redox chemistry of 1,2,3-dithiazolyl radical 176 was elicited by cyclic
voltammetry in CH3CN starting with the corresponding monocation salt [478–480]. The radical is
stable in solution and shows two reversible oxidation waves owing to the +1/0 and +1/+2 couples for
176, X = CH, R = Me or Et; X = CCl, R = H, Me or Et; X = CF, R = Et and a reversible −1/0 couple
for 176, X = CCl, R = Me or Et but an irreversible −1/0 couple for 176, X = CH, R = Me or Et;
X = CF, R = Et due to S–S or S–N cleavage.
R O
N N N N N X S
S S S S N
S S S S S
X X
Ph
176 177 178a, X = CH
b, X = N
Compound 176, X = CCl, R = H shows anomalous behavior on reduction that is tentatively ascribed
to proton tautomerization of the anion with S–S bond cleavage [479]. Interestingly, a crystallomorph
of 176, X = CF, R = Et shows unusual spin crossover between the radical and the diamagnetic
dimer with a 4c, 6e− S···S–S···S σ-bond [480]. Such switchable bistability may be advantageous
[481]. The electrochemistry of radicals 176, X = N, R = Me or Et with two 1,2,3-dithiazoles fused
to a pyrazine ring have been studied [482,483]. Cyclic voltammetry in CH3CN shows a reversible
0/+1 couple, anodically shifted from the pyridine analogues 176, X = CH, R = Me or Et by 120 mV,
a reversible +1/+2 couple and, like the pyridine analogues, an irreversible reduction to the anion
owing to S-S or S-N cleavage. Interestingly, 176, X = N, R = Et dimerizes forming a C–C σ-bond,
which thermally isomerizes to a dimer with a 4c, 6e− S···S–S···S σ-bond [482]. Cyclic voltammetry
of 177 in CH3CN reveals a reversible +1/0 couple and an irreversible −1/0 couple [484]. A series
of 1,3,2-dithiazolyl radicals, including 178a and b, have been studied electrochemically. The com-
pounds studied have one or two of these rings fused to benzene (178a), naphthalene, pyrazine (178b)
or quinoxaline [485]. Cyclic voltammetry shows a reversible 1e− oxidation (+1/0 couple) in which
the 1,3,2-dithiazolyl fused to a benzene or naphthalene ring oxidizes less anodically by almost
1 V than those fused to a pyrazine or quinoxaline ring. All of the compounds studied showed an
irreversible 1e− reduction (−1/0 couple) except for 179 and bis-1,3,2-dithiazolyl fused to pyrazine,
which showed a reversible reduction [486]. Cyclic voltammetric studies on an analogue of 177 but
with a chloro group in place of Ph show a similar behavior [487]. Cyclic voltammetric studies of
1,2,4-thiadiazinyls 180a and b in CH2Cl2 show irreversible oxidation and a reversible reduction.
A prepeak, more positive than the anodic peak is due to adsorption of the reduced species [488].
O
S N
Ar N CF3
N
S N
S N N
S
O X4
179 180a, X = CI 181
b, X = F
Since increasing the scan rate decreases this prepeak current, the prepeak is ascribed to adsorption
of the reduced species. Similar results were obtained for 1,2,4,6-thiatriazinyls 181 but at higher
concentrations dimer formation occurred resulting in a reversible oxidation process [489]. Cyclic
voltammtetry of 182 in CH3CN show reversible reduction to the corresponding anion radical, which
was characterized by spectroelectrochemistry (EPR spectroscopy) [490], and irreversible oxidation
with the parent 182, X = CH more difficult to oxidize or reduce [491].
O(CH2)3SO2Ph
N S
X N
SO2
N X
S N PhSO2
OCH2OCH3
184
182a, X = CAr, CNMe2, 183
CtBu, or PPh2
IX. SULfONiUM SALTS, SULfOxiDES, SULfONES,

SULfiNYL, AND SULfONYL DERivATivES
Electrochemical reduction of triaryl, diaryl alkyl, and aryl dialkyl sulfonium salts has been studied
[2] and results in C–S bond cleavage. Whether the cleavage occurs concertedly with electron transfer
or stepwise via the corresponding sulfuranyl radical depends on the structure of the sulfonium salt
and energy of the electron added [492]. Recent studies on indirect electrolyses mediated by cyano-
aromatics show that the C–S bond cleaved in diaryl alkyl and aryl dialkylsulfonium salts depends
on the sulfuranyl radical structure and bond dissociation energies [493]. The aryl radicals produced
by electrochemical reduction of triaryl sulfonium salts have been grafted onto glassy carbon [494].
Electrochemical reduction of S-benzyl [495], S-allyl [496], or S-cyano [497] thiolanium or diethyl
sulfonium salts produces sulfonium ylides, as shown by trapping with benzaldehyde, which then rear-
range. The mechanism for deprotonation in these reactions is unclear, but electrochemical base gen-
eration has been effectively used to provide the anion of DMSO. Such generation from DMSO and
KClO4 has been reported and subsequent reaction of the anion studied [498,499]. Electrochemical
reduction of sulfones has been extensively studied [2]. For aryl alkyl sulfones, the correspond-
ing anion radical is formed that preferentially undergoes alkyl C–S bond cleavage. However,
electron-withdrawing substituents on the aromatic ring favor aryl C–S bond cleavage [500,501].
Low-temperature electrochemistry and fast scan voltammetry in THF of sulfone 183, which under-
goes alkyl C–S cleavage, facilitated chronoamperometric and voltammetric analysis [502]. Cyclic
voltammetric studies on the reduction of 2-methyl-thioxanthen-9-one, S-oxide and S,S-dioxide have
been reported and studies on their radical anions [503]. Aryl polysulfones undergo complex behavior,
including C–S cleavage, coupling, and self-alkylation. The electrochemical results have been cor-
related with DFT calculations [504]. With hexakis(alkylsulfonyl)benzenes, the electrochemistry is
complicated by the presence of conformers of both the neutral and anion radical forms that can be
modeled by a four-membered square scheme [505].
The anion of allyl phenyl sulfone is formed by electrogenerated base. Reprotonation at the
γ-position results in isomerization to PhSO2CH=CHCH3, which undergoes nucleophilic addition
with allyl phenyl sulfone anion. Such nucleophilic addition also occurs with this anion generated in
the presence of phenyl or tolyl vinyl sulfone. Since such nucleophilic additions generate a carbanion
that regenerates the initial base, the electrogenerated base serves as a catalyst [506]. The yields are
high for these reactions and even the eight-membered ring 184 is formed in 41% yield by this reac-
tion of allyl phenyl sulfone with divinyl sulfone. Alternatively, aryl vinyl sulfones undergo [2+2]
cycloaddition on electrochemical reduction via an ECE mechanism featuring the initial formation
of the corresponding radical anion [507]. This reaction is also catalytic because the product radical
anion transfers an electron to the vinyl sulfone. This electrochemical [2+2] cycloaddition has been
extended to the reactions of vinyl sulfones with α, β-unsaturated ketones although in modest yields
[508]. Analogues of 182 with X = C(2-thienyl) and other analogues show irreversible reduction and
oxidation with no evidence for electropolymerization [509].
Anodic oxidation of N-monoalkyl p-toluenesulfinamides [RNHS(O)Ar] under controlled current
conditions in MeOH affords the corresponding sulfonamides (S-oxidation) in good yields, whereas
such oxidation of N,N-disubstituted and N-phenyl p-toluenesulfinamides results in N–S cleavage to
produce the corresponding amine and methyl p-toluenesulfinate [510]. The difference in products is
ascribed to preferential electron transfer from sulfur in the first case (S-oxidation) and from nitrogen
in the second case. However, in the presence of base (KHCO3) α-deprotonation follows N-oxidation
of chiral N-arylsulfinyl piperidine to afford α-methoxy-N-sulfinyl piperidine 185 in good yield as
mixture of diasteromers as well as small amounts of N–S cleavage products [511].
O Ar R R
S
N N
TsNHCH2CH2 NR
N OMe
N N 2
R R
185 186a, R = Ts 187a, R = Ts

b, R = H b, R = H
Electrochemical studies on sulfonamides have been reviewed [512,513] and the mechanism for
electrochemical reduction of aryl sulfonyl phthalimides explored [514]. Of particular importance
is the electrochemical reductive cleavage of the SO2–N bond. A detailed study on the potentio-
static cleavage, in CH3CN using carbon electrodes, of the sulfonamide moieties in 186a to give
186b in 80% yield and 55% faradaic efficiency has recently been reported, and the effects of
supporting electrolyte, concentration of substrate and proton donor elucidated [515]. Good yield
of reductive detosylation of a variety of arenesulfonamides was achieved at constant current in
DMF in an undivided cell, Pt cathode and naphthalene mediator [516]. Selective detosylation of
187a to 187b was also achieved in good yield. Electrochemical reduction of N-phenylsulfonyl
N-substituted (R)-phenylglycinol in MeCN with Bu4N+HSO4− at constant current at a Hg cathode
has been reported [517]. The mechanism for ArSO2–NRR′ electroreduction is shown in Equation
27.17. Evidence for this mechanism was obtained by the the observation of β-elimination from the
intervening RR′N• species.
+e–
ArSO2NRR΄ ArSO2NRR΄ RR΄N + ArSO2–
(27.17)
+e– H+
RR΄N RR΄N– RR’NH
The mechanism for electrochemical reduction of sulfonyl fluorides [518] and sulfonyl chlorides
[519] using dissociative electron-transfer theory has been reported.
X. SELENiUM AND TELLURiUM COMPOUNDS

Electrochemical studies of organoselenium and organotellurium compounds have been recently
reviewed in an article discussing chemical and electrochemical oxidations and reductions of the
compounds [520]. Cyclic voltammetric studies of 188, Fc3P = Se (Fc = ferrocene) and (tBu)2(2-
PhC6H4)P = Se in CH2Cl2 show an irreversible oxidation by an EE mechanism to give the corre-
sponding product with an Se–Se bond (this product with an intramolecular Se–Se bond obtained
from 188, R = t-Bu by chemical oxidation, was unequivocally characterized by x-ray crystallo-
graphic analysis) [521–523].
Se
PR2
R
R S
Fe Se N
O
PR2 CO2CH2(pMeOC6H4)
189a, R = Br
188 b, R = H
Electrochemical reduction of Ph2Se2 produces PhSe−, which debrominates 189a to 189b. Since
Ph2Se2 is reformed in this reaction, it is used as a catalytic mediator [524]. Ph2Te2 may be used
similarly as an electrochemical reduction mediator. Another sequence initiated by electrochemical
reduction of Ph2Se2 occurs in the reaction shown in Equation 27.18. Selective reduction of Ph2Se2
to generate
RCH 2 =CH 2 + CF2 BrX + Ph 2Se 2 → XCF2CH 2CH(SePh)R (27.18)
PhSe− is followed by an SET mechanism to yield the product [525,526]. Bromine reacts with Ph2Se2
to produce PhSeBr, which is a useful electrophile for effecting alkoxyselenylation. Furthermore, the
addition products so obtained can be oxidatively cleaved resulting in the transformation shown in
Equation 27.19.
OMe
Ar CO2R Ar CO2R (27.19)

(or corresponding lactone)
This entire sequence can be effected electrochemically using 10 mol% of Ph2Se2 and Et4NBr as the
redox catalyst in MeOH with a catalytic amount of H2SO4 [527–531]. A related electrochemical pro-
cess can be effected with Ph2Se2, Et3N · 3HF and internal aliphatic alkenes (and alkynes) [526,532].
Here, Ph2Se2 is electrooxidized in CH2Cl2 and reacts with F− to form PhSeF that fluorosulfenylates
the alkene (or alkyne). Further electrochemical oxidation effects elimination to afford the allylic
fluoride. With electron-deficient alkenes, this procedure does not work but oxidation of Ph2Se2
with Et3N · 5HF in CH3NO2 again generates PhSeF that fluoroselenylates electron-deficient alkenes
(α,β-unsaturated esters, acids, amides, and phosphonates) whose regiochemistry depends on sub-
stituents [533]. Electrophilic selenium produced on electrochemical oxidation of Ph2Se2 in MeOH
readily reacts with enols, resulting in the selenium-catalyzed overall transformation of ArCOCH3
to ArCOCH(OMe)2 [534].
The quasireversible oxidation potentials for 2,7-dimethoxynaphthalene-1,8-dichalcogenides
(S, Se and Te) have been reported [535].
As with thioethers, anodic oxidation of seleno- and telluroethers involves an EC mechanism
[520]. However, as outlined for dithioether 33, diselena- and ditelluraethers 190a and b, respec-
tively, undergo two reversible one-electron oxidations [536,537] with potential inversion [84,538].
X
M M
X΄
Se Se Se
190a, X = X’ = S e;
Se Se Se Se Se Se
M = M’ = C H 2
b, X = X’ = Te ;
M=CH2
c, X = S , X’ = S e
M=CH2
191 192 193
d, X = S , X’ = Te ;
M=CH2
Interestingly, the mixed dichalcogenaethers 190c and d undergo irreversible 1e− oxidation and a
reduction peak associated with the oxidation. These results are explained by rapid dimerization of the
radical cations of 190c and d to give dications with an Se+–Se+ and Te+–Te+ bond, respectively. Thus,
190a and b form dications with intramolecular Se+–Se+ and Te+–Te+ bonds respectively; whereas
190c and d form dications with intermolecular Se+–Se+ and Te+–Te+ bonds rather than intramolecu-
lar Se+–S+ and Te+–S+ bonds, respectively. These results are ascribed to thermodynamic control of
dication formation because the relative bond strengths are Te+–Te+ > Se+–Se+ > S+–S+ and Te+–Te+ >
Te+–S+ and Se+–Se+ > Se+–S+ based on calculations [539]. Polyselenides 191–193 showed reversible
oxidations at potentials that are substantially less anodic than the irreversible oxidations of 1-methyl-
selenylnaphthalene or diphenyl selenide [540]. The facilitated oxidations are ascribed to lone pair-
lone pair destabilization in the neutral compounds and bond formation in the oxidized compounds.
2+
XPh XPh
Se Se
TePh TePh
Se Se
XPh XPh
194a, X = S 195a, X = S 196

b, X = Se b, X = Se
Cyclic voltammetric studies in acetonitrile of 194a and b show pseudoreversible oxidations with
oxidation potentials 234 and 277 mV less anodic, respectively, that for Ph2Te which undergoes irre-
versible oxidation [541]. Since chemical oxidation (NOBF4) give dications 195a and b, respectively,
whose structure was unequivocally established by X-ray crystallographic studies, it is surmised
that these are formed on electrochemical oxidation as well. Such 1,2-di-chalcogenadications and
related species have been reviewed [542,543], and hypervalent bonding as displayed in 195 has also
been reviewed [544,545]. Tetraselenaether 196 shows two quasi-reversible 1e− oxidations separated
by 0.9 V first to the radical cation and then to the dication [546]. Unlike 190a, there is no potential
inversion. Compounds 190; X = Se, M = SiMe2 or SnMe2 and X = Te, M = SiMe2 or Si(SiMe3)2 have
been studied electrochemically [84]. The selenium compounds show irreversible oxidations owing
to C–Si or C–Sn bond cleavage as shown by chemical oxidation [547]. However, the tellurium com-
pounds show reversible oxidations [84].
The chemical steps following oxidation of selenides may be nucleophilic attack, loss of an
α-proton, bond cleavage (C–Se), dimerization or disproportionation. Anodic oxidation of diarylsel-
enides in the presence of water affords the corresponding selenoxide or its hydrate [548]. However,
disproportionation of the intervening radical can occur followed by electrophilic aromatic sub-
stitution leading to PhSeC6H4Se+Ph2 or Ph2Se+Ar in the presence of excess benzene or toluene in
the case of Ph2Se+ • [549]. Although PhSeC6H4Se+Ph2 could arise via dimerization of Ph2Se+ •, the
disproportionation mechanism is favored by electrochemical analysis. The oxidation potentials of
diaryl selenides and tellurides have been recently reviewed and discussed [520]. Further electro-
chemical determinations of the oxidation potentials of such compounds has been aimed at correlat-
ing these values with catalytic antioxidant activity [550] and ability of these compounds to serve
as biological redox modulators or sensitizers [551,552] in the treatment of diseases associated with
oxidative stress [553]. For example, compounds 197 show a quasi-reversible reduction due to the
quinone moiety and an irreversible oxidation due to the chalcogen on glassy carbon [554]. The oxi-
dation potentials are rendered more positive than the corresponding ArXAr, X = Se, Te owing to the
electron-withdrawing quinone moiety. Electrochemical oxidation of arylmethyl selenides typically
results in an ECE mechanism with α-proton loss as the chemical step. This loss of an α-proton can
be suppressed by the addition of acid, in which case bimolecular reactions of the intervening radical
cation occur [555]. Nevertheless, the selenium analogue 198 of Wurster’s blue undergoes selenoxide
formation of both selenium moieties at different oxidation potentials [556].
SeMe
XAr
O
PhSeCXX’CO2Et
197a, X = Se;
SeMe 199a, X = X’= H;
Ar = p-MeOC6H4
b, X = F; X’= H;
b, X = Te; c, X = X’= F;
198
Ar = Ph
c, X = Te;
Ar = p-MeOC6H4

Perhaps greater charge delocalization in this case mitigates α-deprotonation. In “superdry” CH3CN,
198 reversibly oxidizes to its radical cation that reversibly dimerizes. α-Proton loss is favored by
electron-withdrawing groups (CN, CO2Et, CONH2) appended to the α-carbon. Consequently,
anodic oxidation of 199a in CH2Cl2 with Et3NHF leads to sequential α-mono- and α,α-difluoro
compounds 199b and c [557,558]. Electrochemical oxidation of aryl alkyl selenides can also lead
to Se–C cleavage of the radical cation, particularly with substituted alkyl groups that form more
stable carbocations on cleavage, yielding ArSe•, which leads to ArSeSeAr. However, electrochemi-
cal studies suggest that the oxidation of ArSeCH2SiMe3 results in ArSeSeAr by dimerization of the
intermediary radical cation followed by Se–C heterolysis [559].
As outlined earlier, thioacetals and ketals undergo electrochemical oxidation via an EC mechanism
with α-C–S cleavage of the radical cation owing to the stabilization of the resulting carbocation by oxy-
gen. Thus seleno- and telluroglycosides serve as glycosyl donors on anodic oxidation. Electrochemical
oxidation of seleno- [142,144,145] and telluroglycosides [144,145] in the presence of partially protected
monosaccharides results in disaccharide formation. Since the oxidation potentials for chalcogenogly-
cosides follow the order S > Se > Te (and for the same chalcogen correlates with Hammett σ+ for
p-substituted phenyl chalcogenoglycosides [142]), selective electrochemical activation is possible.
OBn
O
OBn OBn O
+1.7V BnO
BnO O BnO O BnO
SePh + STol BnO (27.20)
BnO BnO STol
BnO OBn BnO
OBn
200 201 202
In this way, 200 was coupled with 201 at a potential of +1.7 V versus SCE in acetonitrile (a solvent
that favors β-glycoside formation) to give 202 as shown in Equation 27.20. Further coupling of 202
with 203 at a potential of +2.0 V verusus SCE resulted in the expected trisaccharide [145].
OH
O RO X OR
X
O
O RO Y OR
Y
O 204a, X = Y = Se 205
O b, X = Se; Y = SeO
c, X = Se ;Y = S
d, X = SeO; Y = S
203
Although trisaccharide synthesis could be achieved, an interesting problem was uncovered in the
first step. That is, electrochemical oxidation of 200 produces PhSeSePh. Furthermore, the oxidation
potential of PhSeSePh is 1.45 V versus SCE under these conditions and its oxidation product acti-
vates thioglycosides, even though they are not directly oxidized. This side reaction results in a low
yield (35%) of 202. Redox catalysis of phenylselenoglycoside oxidation has been reported [560]. The
electrochemical mediator was tris(p-bromophenyl) amine. Interestingly the corresponding triaryl
aminium radical cation was not a good enough oxidant to effect the desired oxidation, but in the
presence of 2,6-lutidine, oxidation occurred.
Electrochemical generation of H2Se using a selenium cathode was used in the synthesis of
2,4,6-triphenylselenopyran [561]. The electrochemistry of extended chalcogenapyrans has attracted
interest [562]. Chalcoxanthylium dyes are of interest in solar cells and electrochemical studies on
them [563] and related dyes reported.
Selenium and tellurium analogues of thianthrene 71a have been studied electrochemically.
Selenanthrene 204a undergoes two irreversible oxidations in acetonitrile under conventional condi-
tions and controlled potential electrolysis gives the corresponding oxide 204b, but the first oxidation
is reversible at high scan rates [564]. Thioselenanthrene 204c undergoes two oxidation processes in
acetonitrile. Controlled potential electrolysis shows that the first oxidation is a two-electron oxida-
tion, and spectroscopic studies provide evidence for the formation of selenoxide 204d. Detailed
electrochemical studies support a disproportionation mechanism, as discussed earlier, for the reac-
tion of nucleophiles with thianthrene radical cation, in which the radical cation oxidizes the hydrox-
ylated radical cation [565]. The order of reactivity of the radicals with water is selenanthrene >
thioselenanthrene > thianthrene. This reactivity sequence was extended to phenoxathiin 204, X = O,
Y = S and phenoxaselenin 204, X = O, Y = Se radical cations in which the former is comparable
to thianthrene and the latter to selenanthrene radical cations: (Se, Se)+• ~ (Se, O)+• < (Se, S)+• ≫
(S, O)+• ~ (S, S)+• [565]. In a similar way, alkoxylation of chalcogenanthrenes, as in 205, has been
shown to lower their oxidation potential and stabilize the corresponding radical cations [566]. Like
selenanthrene, dibenzo[c,e]-1,2-diselenin 206 shows two oxidation peaks on cyclic voltammetry and
the first oxidation is a 2e− process that yields the corresponding SeSe(O) species [567]. The initially
formed radical cation is more reactive toward water than the isomeric 204a radical cation. A reduc-
tion step believed to be due to Se–Se cleavage is also observed as well as an associated oxidation.
Y Y
R R X X
X Y
R Y X X Y
R X Y
Se-Se
206 207a, X = Y = Se; R = H 208a, X = Se; Y = O
b, X = Y = Te; R = H b, X = S, Y = O
c, X = S; Y = Se; R = H
d, X = Y = Se; R = Me
e, X = Y = Se; R = CnH2n+1

The selenium and tellurium analogues of tetrathiafulvalene, 207a and b, have been studied elec-
trochemically as well as mixed chalogen species, for example, 207c and reviewed previously
[1,230,568,569]. Two reversible 1e− oxidations are observed and, interestingly, the first oxidation
potential follows the order 82 lower than 207b lower than 207a and ΔE for the first and second
oxidation potentials follow the order 207b < 207a < 82. The first oxidation potentials show that,
despite the lower ionization energy of Se and Te compared with S, the π-delocalization in the radical
cation dominates Eo′. Better overlap of the sulfur 3p orbitals than Se 4p or the Te 5p orbitals with
carbon 2p orbitals accounts for this difference in delocalization. It is also notable that the ΔE values
that reflect the Coulombic repulsion in the dications are lower for Te than Se than S. These com-
pounds are of interest because of the conductivity and magnetic properties of their salts, as already
discussed for the sulfur analogues. Indeed, the first molecule-based superconductors were deriva-
tives of 207a [212,213]. The Bechgaard salts are synthesized by electro- or chemical oxidation.
A recent interesting example involves the electrooxidation of 207d, in an ionic liquid as electrolyte
to prepare (207d)2 NbF6 [570]. The effect of substituents on the oxidation potentials of 207a and b
has been reviewed and obey the Hammett equation [1,230,568,569]. The standard redox potentials
for 207a and some of its derivatives have been calculated using DFT and a polarized continuum
model for the solvent [571]. Owing to the importance of ethylene-dioxytetrathiafulvalene and eth-
ylene dithioxytetrathiafulvalene, the corresponding selenium compounds and analogues have been
studied as well. Thus, 208a undergoes two 1e− reversible oxidations at lower potentials due to the
electron-donating substituents than the parent 207a but at slightly more positive potentials than the
corresponding 208b [572]. Galvanostatic oxidation was used for synthesis of the corresponding
cation radical salts [573]. Alkylthio substituents appended to tetraselenafulvalene render the oxida-
tion potentials more positive in 207e, but the length of the alkyl chain (C1–C15) has little effect
[574]. Cyclic voltammetric studies of 208, X, Y = S, Se and analogues (mixed S,Se compounds)
in benzonitrile show two reversible 1e− oxidations with the oxidation potentials, particularly E01 ,
more anodic than the corresponding parent [575]. The electrochemistry of 209 and analogues was
reported [576,577] and, as expected, the methyl groups lower the oxidation potential and the sulfur
substituents raise it. However, the corresponding cation radical perchorate shows extraordinary con-
ductivity (1500 S/cm) at room temperature.
S R
Me R
Se Se S X S
S R
Me Se Se S X
R
209 S
210a, X = Se; R = H
b, X = Se; R = CO2Me
c, X = Se; R , R = S(CH2)2S
π-Extended (dendralene) systems 210a–c have been reported and studied by cyclic and Osteryoung
square-wave voltammetry in CH2Cl2 [578,579]. Three waves are reported. The interesting 1,3-ditel-
luretane π-extended system 211 as a mixture of E/Z isomers was studied using cyclic voltam-
metry in CH2Cl2 [580]. A reversible oxidation followed by three irreversible oxidation peaks was
reported. Cyclic voltammetric studies in benzonitrile of bitetetraselenafulvalene 212 show two oxi-
dation peaks each apparently involving 2e− oxidations with the second oxidation irreversible [581].
Electrocrystallization gave conducting salts.
Se Se R
S S Se Se X Y
Te Se Se
S S
Te Se Se Se
211 212 213a, X = Y = O; R = H
b, X = O; Y = S; R = H
c, X = O; Y = S; R = Me
d, X = Y = S; R = H
Owing to the great interest in polythiophenes and especially PEDOT [poly(ethylenedioxy)thio-

phene], the electrochemistry and electropolymerization of selenophene and its derivatives has
been studied [582–585]. Electrochemical or chemical oxidation of 3-alkylselenophenes provides a
regiorandom polymer. However, chemical coupling reactions provide regioregular poly(3-hexyl)-
selenophene [586]. From the onset of the oxidation and reduction peaks obtained by cyclic voltam-
metry of the polymer, the band gap was determined (which was 0.3 eV larger than the optical
band gap) and is smaller than the polythiophene analogues. Selenophene derivative 213a shows
an irreversible oxidation at 1.18 V in CH3CN versus SCE, which is less positive than that for the
thiophene analogues (1.44 V) [587,588]. Repetitive scans lead to a deep blue polymer deposited on
the electrode surface. Oxidative polymerization could also be achieved by chemical oxidation with
FeCl3. Other selenophenes 213b–d behave similarily, that is, they have lower irreversible oxidation
potentials than the corresponding thiophenes (by ca. 100 mV) and electropolymerize [589,590]. The
band gaps of these polymers are determined spectroelectrochemically and, despite the changes in
the peripheral atoms, are all approximately 1.4 eV. The data and calculations for these polymers
argue for greater planarity in the backbone of polyselenophenes than polythiophenes due to increas-
ing the extended π-conjugation in the selenium polymers as a result of greater “quinoid” character.
MeO OMe
Te
Te R R R R
214 215, R = C6H13

Cyclic voltammetric studies of 3,4-dimethoxytellurophene 214 show two oxidation peaks at poten-
tials well below the corresponding selenophene and thiophene analogues [591]. However, electropo-
lymerization of 214 proved problematic. Consequently, a polytellurophene derivative was prepared
by Pd-catalyzed coupling reactions and its HOMO level was determined from the onset of its oxi-
dation determined electrochemically [592]. However, its degree of polymerization is less than that
achieved with thiophenes [593]. Tellurophene derivative 215 and its Br2 adduct have been studied
by cyclic voltammetry [594]. Two reversible 1e− oxidations are observed for 215, and its Br2 adduct
shows irreversible oxidation and reduction. The HOMO energy for the Br2 adduct is lower than that
for 215 based on the oxidation onsets. Reversible electrochemical oxidation in water of a water-
soluble tellurophene has been reported [595]. Cyclic voltammetric studies were used to determine
frontier molecular orbital energies for a 2,5-diaryltellurophene and its corresponding tellurium
dibromide [594]. Electropolymerization of 3-hexyltellurophene has been studied and its regioregu-
lar polymer, obtained by chemical coupling, has been examined electrochemically to assess its
HOMO–LUMO gap [596].
Cyclic voltammetric studies of benzodichalcogenophenes 216a–c show irreversible oxidation
peaks with the tellurium analogue oxidizing at much lower potential (+0.48 V vs. Fc/Fc+) than the
selenium (+0.89 V) or sulfur analogues (+0.95 V) [597] (a second oxidation peak was also observed
for the tellurium compound 216c).
Se R
X
R Se Se
Se Se
X R R Se
216a, X = S; R = H 217a, R = H
b, X = Se; R = H b, R = Ph 218
c, X = Te; R = H
d, X = Se; R = Ph
The onset of their anodic peak was used for estimating HOMO levels in these compounds. Similar
studies on the directly fused diselenophenes 217a and b have been reported [598], and their irrevers-
ible oxidation (+1.06 and +0.86 V vs. Fc/Fc+, respectively) occur at higher potential than that of 218
(+0.41 V) or 216d (+0.80 V). Interestingly, high-performance organic field effect transistors were
fabricated with 217b [598]. Two reversible 1e− reductions of 219a–c are shown by cyclic voltam-
metric studies in acetonitrile [588,599].
R
R O N N
N
N
X X
Se
NH Y Y
N
R Se Cl
219a, R = CN 220 221a, X = S; Y = Se; R = Et

b, E = CO2Et b, X = Se; Y = S; R = Et
c, E = CHO c, X = Y= Se; R = Et
d, X = Y= Se; R = Me
Cyclic voltammetric studies on the [8]circulene (see 169) in which thiophene and selenophene rings
alternate have been reported, and its oxidation potential is substantially less anodic than that for the
all thiophene 169 [459].
The electrochemistry of selenium–nitrogen heterocycles has attracted attention. Cyclic voltam-
metric studies on 220 show a prepeak at +1.24 V in acetonitrile and a well-defined irreversible
oxidation at +1.44 V [600]. Controlled potential electrolysis provided the corresponding SeO com-
pound. As already pointed out, selenium radicals 175b–d undergo reversible 0/+1 but irreversible
0/−1 couples [477]. The redox chemistry of 1,2,3-dithiazolyl radicals 176 has been discussed and
the selenium analogues 221 have also been studied electrochemically [601]. Starting with the cor-
responding cations, three reversible waves owing to the 0/+1, 0/−1, and +1/+2 couples are observed
as is the case for the all sulfur analogue 176, X = Cl, R = Et. For 221c, two additional more posi-
tive reversible waves are found as well. There is an anodic shift in the 0/+1 couple with increasing
selenium content in the series 176, X = Cl; R = Et, 221a–c. Electrochemical reduction was found
to be the best way for converting nonafluorobutanesulfonate (−ONf) salt 222 into the corresponding
radical 221d [602]. The redox chemistry of GaCl4− salts of 223a–c was studied in acetonitrile using
cyclic voltammetry [603]. A reversible +1/0 wave is observed for 223a and b with comparable E1/2
(0.260 and 0.283 V vs. SCE, respectively). With 223c, a reversible +1/0 couple is not observed, only
a weak peak at more anodic potentials than 223a and b is seen.
Me
N N N N
N
Se Se+ E E
Se Se S+ NMe+
–ONf
Cl 223a, E = S 224a, E = S
b, E = Se b, E = Se
222 c, E = Te
c, E = Te
EPR spectroscopy of the radicals produced on reduction of 223a and b but not c support their
structures. It is suggested that the radical produced by reduction of 223c is dimeric in solution.
Compounds 223a and b also show an irreversible 0/−1 couple (E1/2 −0.96 and −0.90 V, respec-
tively). Similar behavior was observed for the redox chemistry of 224a–c [604]. That is, cyclic
voltammetry in CH3CN shows a reversible +1/0 wave for 224a and b (E1/2 −0.351 and −0.308 V vs.
SCE, respectively) and a much more anodic, although reversible, wave for 224c.
R'
– F N S
N R2 N F N
E
X
N R3 N F F
R4 F F
225a, E = S 226a, R1 = R2 = R3 = R4 = H; X = S 227

b, E = Se b, R1 = R2 = R3 = R4 = H; X = Se
c, E = Te
c, R1 = R2 = R3 = R4 = F; X = S
d, R1 = R2 = R3 = R4 = F; X = Se
e, R1 = R2 = R4 = F; R3= CF3; X = S
f, R1 = R2 = H; R3 = R4 = F; X = S
g, R1 = R3 = R4 = F; R2 = CH3; X = Se
h, R1 = R2 = R4 = H; R3 = CF3; X = Se

EPR spectra of radical anions 225a and b obtained on chemical reduction of 226a and b vali-
dated their structures. Radical 225 was not observed, but its dimer was suggested to persist in
solution. The redox potentials of a series of sulfur and selenium heterocycles 226a–h, 227 in
acetonitrile by cyclic voltammetry has been reported [605]. The first reduction peak is revers-
ible and the EPR spectra of the radical anions produced electrochemically have been measured.
Several of these heterocycles 226b–e, g, 227 show a second irreversible reduction at more nega-
tive potentials. An irreversible oxidation is also observed. The analogous selenium compounds
show more positive reduction and more negative oxidation potentials than the corresponding
sulfur compounds in this series. The reduction potentials for these compounds linearly corre-
lated with the calculated EA values (with separate lines for the sulfur 226a, c, e, f and selenium
226b, d, g, h compounds).
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28 Aliphatic Nitrogen–Containing
Compounds
Amines, Amino Alcohols,
and Amino Acids
Osamu Onomura
CONTENTS
I. Introduction ........................................................................................................................ 1103
II. Aliphatic Amines ............................................................................................................... 1104
A. Primary Amines ......................................................................................................... 1104
B. Secondary and Tertiary Amines ................................................................................ 1104
III. N-Protected Amines ........................................................................................................... 1105
A. Regioselectivity .......................................................................................................... 1105
B. Electrochemical Cyanation ........................................................................................ 1106
C. Electrochemical α,β-Functionalization ...................................................................... 1107
D. Preparation of Imides ................................................................................................. 1107
IV. N-Protected α-Amino Acids............................................................................................... 1108
A. Chemoselectivity ........................................................................................................ 1108
B. Enantioselectivity ....................................................................................................... 1108
V. N-Protected β-Amino Alcohols...........................................................................................1110
VI. N-Protected α-Allyl or Benzyl Amines...............................................................................1111
VII. Intramolecular Anodic Coupling of N-Protected Amines ..................................................1111
A. Carbon–Carbon Bond–Forming Reaction ..................................................................1111
B. Carbon–Nitrogen Bond–Forming Reaction ................................................................1112
VIII. N-Protected Enamines.........................................................................................................1112
IX. Hydroxylamines ..................................................................................................................1114
X. Carboxamides......................................................................................................................1116
XI. Hydroxamic Acids ...............................................................................................................1117
References .....................................................................................................................................1117
I. INTRODUcTiON
The electrochemical oxidation of nitrogen compounds is useful for the syntheses of complex organic
molecules starting from easily available organic molecules. The oxidation reverses the polarity of
functional groups, and therefore, molecules with nucleophilic nitrogens can be converted into elec-
trophiles. Also, the oxidation selectively functionalizes starting amines and amino acids to afford
building blocks for constructing a variety of more complex structures. The result has simplified the
construction of synthetically useful nitrogen-containing compounds.
1103
Many of the electrochemical oxidation reactions have excellent characteristics different from
the reactions using traditional chemical oxidants. For this reason, the electrochemical oxidation of
nitrogen-containing compounds is a valuable tool for any synthetic chemist to have at their disposal.
This chapter majorly describes recent progress for electrochemical oxidations of aliphatic amines,
N-protected aliphatic amines, N-protected amino alcohols, N-protected amino acids, hydroxylamines,
carboxamides, and hydroxamic acids from a synthetic point of view. Accordingly, some books in
these areas might help readers to comprehend important concepts and results sufficiently [1–3].
The electrochemical oxidation of easily oxidized nitrogen-containing compounds having lone-
pair electrons has been studied quite intensively. The selectivity of the reaction depends on the
structures of such compounds. For example, electrochemical oxidation of aliphatic amines in many
cases leads to a variety of products while the electrochemical oxidation of amides or carbamates
results in the formation of only one major product [1,2].
II. ALiPhATic AMiNES

A. PrIMarY AMINES
The oxidation potentials of aliphatic amines depend on their structure. Primary amines are more
difficult to oxidize than secondary or tertiary ones. The electrochemical oxidation of simple pri-
mary amines is usually quite complex and may lead to a variety of products. Among them, some
methods for the transformation of primary amines into the corresponding nitriles were developed.
Direct electrochemical oxidation using a nickel hydroxide electrode [4], and also indirect ones using
2,2,6,6-tetramethylpiperidinyl-1-oxyl (TEMPO) [5], or halogen ions (Scheme 28.1) [6] as mediators
effectively transformed primary amines into the corresponding nitriles. In the latter reaction, anodi-
cally generated “Br+” promoted the oxidation in cooperation with cathodically generated MeO −.
B. SECoNDarY aND TErTIarY AMINES

Indirect electrochemical oxidation using halogen ions as mediator effectively transformed cyclic
amino esters into relatively stable imines or enamines (Equation 28.1) [6].
–2e–
N CO2Me or N CO2Me or
NaBr/MeOH
H N CO2Me N CO2Me (28.1)
H H
80% 67%
–4e–
RCH2NH2 RCN
NaBr/MeOH R = alkyl, aralkyl: 50–95%
MeO– –2e– Br–

Br+ Br–
–2e–
MeOH MeO–
Br+
RCH2NHBr RCH NH RCH NBr
MeO– MeOH MeO– MeOH
+4e–
4MeOH 4MeO– + 2H2
SchEME 28.1 Indirect electrochemical oxidation of primary amines to nitriles.

Aliphatic Nitrogen–Containing Compounds 1105
–2e–
N + NaCN N + N CN N
(6 equiv) NaOMe (6 equiv) H
LiClO4/MeOH Ph Me Ph Me
Ph Me CN
6% 85%
MeO MeO
MeO –2e– 1) LDA
+ NaCN N Ph Ph
N
MeO
N Ph (2.5 eqiv) AcOH (0.5 equiv) MeO 2) RX MeO
LiClO4/MeOH CN Me NC R Me
Me 85%
RX = Mel 67% yield, 80% de
MeO MeO 4-MeO-PhCH2Br 77% yield, 80% de
NaBH4 H2 3,4-(MeO)2-PhCH2Br 75% yield, 80% de
N Ph MeO NH
MeO
R Me R
R = Me 76% yield, 98% de
4-MeO-PhCH2 85% yield, 80% de
3,4-(MeO)2-PhCH2 88% yield, 80% de
SchEME 28.2 Electrochemical cyanation of tert-aliphatic amines.
Electrochemical oxidation of sec- or tert-aliphatic amines in many cases led to a complex mixture
or decomposed products while α-cyanation of cyclic amines proceeded selectively (Scheme 28.2) [7].
Electrochemical oxidation of tert-aminoalkylmalonates or tert-aminoalcohols smoothly pro-
ceeded to afford relatively stable cyclized products (Equations 28.2 and 28.3) [8].
CO2Me
CO2Me
–2e– N CO2Me
N CO2Me (28.2)
NaCN/MeOH
73%
–2e–
N N
Kl (0.25 equiv) (28.3)
HO NaOMe (1.25 equiv) O
MeOH
69%
III. N-PROTEcTED AMiNES

A. REGIoSELECTIVITY
The electrochemical oxidation of amides, lactams, carbamates, and N-acylated amino acids is of
considerable synthetic value because in contrast to aliphatic amines, the N,O-acetals formed by
α-oxidation [9–11] are quite stable precursors of N-acyliminium ions and can be used effectively
in amidoalkylation reactions (Scheme 28.3) [12,13]. In such amidoalkylations, the use of a chiral
Lewis acid afforded optically active substituted products (Equation 28.4) [14].
n n
Chiral Lewis acid (28.4)
*
N OMe Nu– N Nu
PG PG
n = 0–2 Up to 97% ee
PG: protecting group
Nu: active methylene compounds, silyl enol ether, etc.
OMe Lewis acid Nu

–2e–
R1 R1 – R1
NCOR4 MeOH Nu
NCOR4
R2 NCOR4
R2 R2
R3
R3 R3
R1 +
NCOR4
Nu: Ar, Het-Ar, alkyl, allyl, CN, PO(OR)2, etc.
2
R R3
SchEME 28.3 Electrochemical oxidation of N-protected amines and successive amidoalkylation.
OH
MeO
F3C OEt –2e– CF3CO2H +
N N N
N p-TsOH MeOH in CH2Cl2
in benzene O O O
OH H CF3
reflux CF3 65% CF3
SiMe3 10% HCl

N N
75% O in MeOH
CF3 OH H
SchEME 28.4 Electrochemical synthesis of (S)-α-allylprolinol.
( )n –2e– ( )n ( )n
OMe Nu
R Graphite electrodes R Lewis acid R
N N N
CN Et4NBF4, MeOH Nu–
CN CN
n = 1–2 Major
R: Alkyl, Ph, Allyl Up to 100% regioselectivity
SchEME 28.5 Electrochemical oxidation of N-cyano cyclic amines.
Also, excellent methods for oxidation and/or amidoalkylation of carbamates, such as the cation
pool method, the cation flow method, recyclable solid supported bases, and parallel electrosynthe-
sis (for these techniques, see Chapter 9), were developed [15,16].
As shown in Scheme 28.3, direct electrochemical oxidation occurred at the less substituted
carbon, while some methods for electrochemical oxidation at the more substituted carbon were
developed. Namely, electrochemical oxidation of a bicyclic amine prepared from (S)-prolinol and
trifluoroacetaldehyde proceeded to afford an enantiomerically pure methoxylated compound in
excellent regioselectivity. This product was easily transformed into (S)-α-allylprolinol (Scheme
28.4) [17]. Also, N-cyano-substituted cyclic amines were regioselectively methoxylated at the more
substituted carbon by electrochemical oxidation (Scheme 28.5) [18]. Such opposite selectivity might
be explained by the stability of the corresponding intermediary iminium ions.
B. ELECTroCHEMICaL CYaNaTIoN
There are several publications available on electrochemical cyanation. However, most of the reac-
tions reported suffer from low yield and long reaction time due to the use of a divided cell, several
reaction steps, or specialized starting material [19]. Pilli and Santos published their work [20] on
NC ( )n n = 1–2 ( )n n = 1–4 ( )n
PG = CN PG = CO2Me, COPh, etc.
R N R R N CN
–2e– N
–2e–
CN PG PG
–2e–
Me3SiCN
5 92% yield
MeO2C N MeO2C N CN
Et4NBF4, MeSO3H cis/trans = 100:0
Tr CH2Cl2/MeCN Tr
Tr = triphenylmethyl
SchEME 28.6 Regio- and/or diastereoselective cyanation.
electrochemical cyanation using two methods. In the case of the cation pool method [21] using a
combination of TMSCN and TMSOTf, they achieved high yield and enantioselectivity; on the other
hand, the use of the noncation pool electrochemical method using TMSCN gave very low yield and
required low temperatures (−78°C). In addition, Tajima et al. have published their work on electro-
chemical cyanation based on the concept of site isolation [22]. The yields using this method were
moderate to high, while the current efficiency was somewhat low.
Recently, a highly efficient direct cyanation of N-protected cyclic amines by noncation pool
electrochemical oxidation was reported [23]. This electrochemical cyanation of l-proline deriva-
tives proceeded to afford 5-cis-substituted products in excellent diastereoselectivity (Scheme 28.6).
C. ELECTroCHEMICaL α,β-FUNCTIoNaLIZaTIoN
In relatively acidic reaction media, electrochemical α,β-functionalization of N-protected cyclic
amines was achieved (Scheme 28.7) [24]. In these reactions, α-alkoxylated intermediates are some-
what unstable and easily convert into α,β-unsaturated cyclic amines, which might be successively
oxidized. Such anodic diacetoxylation was applied to the kilogram-scale production of cis-
3-methylamino-4-methylpiperidines [24d].
D. PrEparaTIoN oF IMIDES
Indirect electrochemical oxidation mediated by N-hydroxyphthalimide was applicable to amides to
afford imides (Scheme 28.8) [25]. In this oxidation, electrochemically generated phthalimide N-oxyl
abstracts a hydrogen atom at the α-position of the starting amide to afford a radical intermediate,
which was successively oxidized to imide.
Cl OAc
( )n n = 1–2 ( )n n=2 ( )n
–4e– –4e–
R N OR R N R N OAc
NH4Cl/ROH AcOK/AcOH
PG PG PG
–2e–
ROH –2e–
Cl– ( )n ( )n
Cl+ Acidic media
R N
R N OR
–2e–
PG
PG
SchEME 28.7 Electrochemical α,β-functionalization.

R2 –e– R2
R1 NHPI (0.25 equiv), pyridine (0.25 equiv) R 1
N N O
0.85 V vs. SCE
O R3 0.1 M NaClO4 in MeCN O R3
O O
–
–e
N O N OH
PINO O NHPI O
R2
R1
N
O R3
(MeCO)2NH: 60% N O : 60% O N O : 81%

Me
O Me
SchEME 28.8 Oxidation of amides to imides.
IV. N-PROTEcTED α-AMiNO AciDS

A. CHEMoSELECTIVITY
Discrimination of similar functional groups in a molecule is applicable to a chemoselective reaction.
Since there was a big difference between direct and indirect (chloride ion as mediator) electrochem-
ical oxidation with respect to chemoselectivity, two regioisomeric unsaturated cyclic amines were
obtained from an l-lysine derivative (Scheme 28.9) [26].
Indirect electrochemical oxidation of N-tosylamino compounds using halogen ions as a mediator
in the presence of additional base promoted the migration of N-tosylamino groups via enamides to
afford the corresponding aminoacetals (Scheme 28.10) [27].
B. ENaNTIoSELECTIVITY
A decarboxylative methoxylation of an N-acylated amino acid (Hofer–Moest reaction, non-Kolbe
reaction, see Chapter 33) leads to N-acyl-iminium ion intermediates [28]. Although the transformation
of an optically active α-amino acid into an active intermediate without any loss of optical purity is useful
OMe –2e– –2e–

CO2Me CO2Me CO2Me
NH NH—CO Me NaCl, MeOH NH NH—CO Me Et4NOTs, MeOH MeO NH NH—CO Me
2 2 2
CO2Me CO2Me CO2Me
N CO2Me
N CO2Me
CO2Me CO2Me
SchEME 28.9 Chemoselective oxidation.

HN Tos OMe
H –4e– H
Tos N N
N KBr (0.5 equiv), OMe Tos
Tos N N
H KOH (0.5 equiv),
MeOH Tos 91% Tos
base
Br–
–2e–
–2e–
OMe H
H Br+
H Tos N Tos N
Tos N N Tos MeOH N Tos
N Tos H H Br
H
Tos N
H H –4e– NH NH4Cl Tos
H
N N KI (0.5 equiv), MeO N
Tos Ac Ac Δ N CO2Me
NaOMe (0.5 equiv),
CO2Me MeOH OMe CO2Me Ac
92% 82%
SchEME 28.10 Oxidative migration of N-tosylamino groups.
–2e– Nu
CO2H R1 + Nu–
R1 * NCOR3 R1
NCOR3 NCOR3
R2 R2
R2
chiral sp2 carbon intermediate racemic
SchEME 28.11 Usual electrochemical decarboxylative substitution of N-acyl α-amino acids.
for the synthesis of optically active nitrogen-containing compounds, the intermediary iminium ion,
which is a typical sp2 cation, might lose the original chirality to afford racemic products (Scheme 28.11).
However, when N-o-phenylbenzoylated oxazoline and thiazoline derivatives were electrochemi-
cally oxidized, the memory of chirality via carbenium ion chemistry occurred to afford optically
active products (83% and 91% enantiomeric excess [ee], respectively, in Equation 28.5) [29,30].
Me Me
Me O Me S Me Me O Me S Me
Me COOH Me N COOH –2e– Me OMe Me OMe
N N N
or NaOMe (28.5)
O O O O
MeOH
–30°C
83% ee 91% ee
Scheme 28.12 shows a plausible stereochemical course for the memory of chirality. The initial
step involves the oxidative decarboxylation of the amino acid to form the iminium ion, which can
be attacked by nucleophiles (MeO −) from the syn or the anti side. The observed 85% ee could be
attributed to the presence of the bulky o-phenyl group beneath the carboxylic group and the fixation
of the conformation of the amino acid and the iminium ion intermediate at low temperature. The
restricted rotation could favor the formation of a chiral iminium ion with the conformation of an
o-phenyl group similar to that of the amino acid. The bulky o-phenyl group could preclude an effec-
tive approach from the anti side due to the steric repulsion between the o-phenyl group and MeO −,
and hence, the nucleophilic attack was predominantly from the less hindered syn side resulting in
the 4R-isomer.
Me OMe
S
MeO– N
n Me
tio O
syn n
CO2H te
Me Re
S Me
–2e– S 4R-isomer 92.5%
N +
Me NaOMe N
O
Pt cathode O Me
Inversion
Pt anode Me
MeOH, –30°C S
anti N
Me
MeO– O OMe
: Steric repulsion
4S-isomer 7.5%
Chiral iminium ion
SchEME 28.12 Plausible stereochemical course for the memory of chirality.
V. N-PROTEcTED β-AMiNO ALcOhOLS

Electrochemical oxidation of N-acyl-β-amino alcohols smoothly cleaves the carbon–carbon bond to
afford N,O-acetals [31]. A memory of chirality was observed in the electrochemical substitution of
optically active β-amino alcohol derivatives (Equation 28.6) [32].
α β R
–2e–
N CAr2 N OMe Ar Ar
Pt electrodes
OH + (28.6)
O NaOMe (1.2 equiv) O
O
in MeOH, at –30°C
Ph Ph
Up to 73% ee
On the other hand, indirect electrochemical oxidation in the presence of a chiral copper catalyst
transformed racemic N-protected aminoalcohols into optically active amino esters by kinetic resolu-
tion (Scheme 28.13) [33]. Similar kinetic resolution of racemic N-protected aminoalcohols proceeded
to afford optically active amino esters. In this reaction, chelation of the amino alcohol or the amino
aldehyde with the Lewis acid activates their hydroxyl or formyl group to form alkoxide ion, which is
easily oxidizable compared with the original amino alcohol or aldehyde (Scheme 28.14) [34].
–4e–
OH Pt electrodes, rt OH
N N COOMe N
Et4NBr (1.0 equiv)
Bz Bz + Bz
MeOH
racemic Cu(OTf )2 (0.1 equiv) (R)-ester (S)-alcohol
(R,R)-Ph-BOX (0.1 equiv)
27% yield 50% yield
70% ee 15% ee O O
N N
–2e– Ph Ph
Pt electrodes, rt COOMe CHO L* (R,R)-Ph-BOX
N CHO Et4NBr (1.0 equiv) N N
Bz Bz + Bz
MeOH
rac-16–19 Cu(OTf )2 (0.1 equiv) (R)-ester (S)-alcohol
(R,R)-Ph-BOX (0.1 equiv)
43% yield 34% yield
86% ee 27% ee
SchEME 28.13 Enantioselective oxidation of amino alcohol derivatives.

R4 Br+ R4
Br–
R3 OH R3
N N CHO
R4 Bz Anode 2e– R4 Bz
H
R3 R3
N O H Cu2+ R4 N O Cu2+ R4
Bz Cu2+ R3 Bz Cu2+ R3
L* L*
N * CHO N* COOMe
L* L*
L*: (R,R)-Ph-BOX Bz L*: (R,R)-Ph-BOX Bz
MeO – MeOH + Br– MeO– MeOH + Br–
R4 R4 R4
MeOH MeO– OMe R4 OMe MeO–
R3 R3 R3
N O Br R3
N O– 2MeOH 2MeO– + H2 N O– N O Br
Bz Cu2+ Bz Cu2+ Bz Cu2+ Bz Cu2+
Br+ L* Br+
L* 2e– Cathode L* L*
SchEME 28.14 Reaction mechanism for enantioselective oxidation of amino alcohols or aldehydes.
VI. N-PROTEcTED α-ALLYL OR BENzYL AMiNES

Electrochemical oxidation of N-acyl-α-allyl or benzyl amines smoothly cleaves the carbon–carbon
bond to afford N,O-acetals. The allyl groups work as chiral auxiliary to afford optically active qua-
ternary cyclic amino acids (Scheme 28.15) [35]. Similarly, electrochemical oxidation of α-silyl-or
α-thio-substituted carbamates or azetidin-2-ones smoothly proceed to afford the corresponding
N,O-acetals [36,37].
VII. INTRAMOLEcULAR ANODic COUPLiNG Of N-PROTEcTED AMiNES

A. CarboN–CarboN BoND –ForMING REaCTIoN
An important intermediate for the preparation of carbapenem antibiotics was synthesized by an
indirect electrochemical intramolecular carbon–carbon bond–forming reaction and direct electro-
chemical decarboxylative methoxylation (Scheme 28.16) [38]. In this cyclization, the (R)-phenylethyl
group works as a good chiral auxiliary.
–2e–
N or
or Et4NBF4 OMe N
N N Ph OMe
in MeOH–MeCN Cbz
Cbz Cbz
Cbz
76% 74%
Allyl–TMS (1.2 equiv)

–2e– BF3· OEt2 (1.2 equiv)
N CO2Me Et4NBF4 MeO N CO2Me N CO2Me
CH2Cl2
Cbz MeOH 0°C Cbz –78°C to rt Cbz
92% 88% cis isomer
–2e–
NaHMDS (1.2 equiv) Et3SiH (1.5 equiv)
Et4NBF4
MeI (3.0 equiv) MeSO3H (1.2 equiv) Me
Me MeOH–MeCN Me
N MeO N N
THF CO2Me –10°C CO2Me CH2Cl2 CO2Me
–78°C to rt 81% Cbz Cbz –78°C to rt Cbz
79%
90% >99% ee
SchEME 28.15 Electrochemical deallylation or debenzylation of α-allyl- or benzyl-cyclic amine derivatives.

O O
CO2-t-Bu OH
Me –2e– H CO2-t-Bu NaBH4 R H
Me Me CO2-t-Bu
CO2-t-Bu NaI (0.5 equiv) in THF
S CO2-t-Bu S CO2-t-Bu
N 85°C in MeCN N
O N
O O
Me R 94% yield Me R 83% yield Me R
80% de 84% de
OAc OH
OSiMe2-t-Bu
R H CO2H 1) –2e–, NaOMe R H OMe
Me Me R H OMe
S MeOH/MeCN (1/4) S R Me
S R
N N
2) Chromatography O NH
O
O
Me R Me R
75% yield 73% yield 4R:4S = 100:0 63% yield
SchEME 28.16 Electrochemical carbon–carbon bond–forming reaction between active methylene groups.
CO2Me I CO Me CO2Me CO2H O

–2e– 2
EGB n n
n CO2Me KI n CO2Me n CO2Me
NH N N N
MeOH NH
Tos Tos Tos
Tos Tos
n=1–3
Up to 100% yield
SchEME 28.17 Coupling of nitrogen and active methylene.
OMe
–e–, RVC anode EDG EDG EDG
( )n
EDG
LiOMe, Et4NOTs ( )n + ( )n ( )n
NH N– N N
MeOH-THF
Tos Tos Tos Tos
n = 2– 4
Up to 91% yield
SchEME 28.18 Coupling of nitrogen and alkene.
B. CarboN–NITroGEN BoND –ForMING REaCTIoN

The electrochemical intramolecular carbon–nitrogen bond–forming reaction of N-tosyl-amino-
alkylmalonates smoothly proceeded to afford nitrogen heterocycles (Scheme 28.17) [39].
Electrogenerated radical cations from electron-rich alkenes were intramolecularly trapped with
nitrogen to afford nitrogen heterocycles (Scheme 28.18) [40].
VIII. N-PROTEcTED ENAMiNES

Since N-protected enamines are representative electron-rich olefins, they are relatively easy to oxi-
dize. Direct electrochemical oxidation of a 6-acetoxymethyl-2,3-didehydropiperidine derivative
afforded the 3,6-trans isomer, whereas indirect oxidation gave the 3,6-cis isomer in high diastere-
oselectivity. On the other hand, the indirect method using I− as a mediator proceeded via inversion
of the stereochemistry (Scheme 28.19) [41].
Direct electrochemical oxidation

AcO AcO
Et3SiH 3
–2e– 6
OAc OAc MeSO3H OAc
N AcOK AcO N N
CO2Bn AcOH CH2Cl2
CO2Bn CO2Bn
91% yield
cis/trans = 32/68
Indirect electrochemical oxidation
HO HO
Et3SiH 3
–2e–
OAc OAc 6 OAc
N NaI (0.1 equiv) HO N MeSO3H N
CO2Bn H2O–acetone (1:9) CH2Cl2
CO2Bn CO2Bn
72% yield
cis/trans = >99/<1
SchEME 28.19 Direct and indirect electrochemical oxidation of enamine derivatives.
–2e–
I HO
I+ I– 3 3 3
O
N HO N R EGB N R +OH– HO N R
R
CO2Bn +OH– CO2Bn –I– CO2Bn CO2Bn
R = CH2OAc
CO2Bn I+ I
N
I+ CO2Bn +OH–
N CO2Bn
N
R
H H OH
R I+ R R = CH2OAc
SchEME 28.20 Stereochemical course for indirect electrochemical oxidation of an enamine.
Although iodohydroxylation of the enamine afforded the 3-trans-iodinated intermediate, succes-

sive epoxidation by an electrogenerated base (EGB) (see Chapter 43) occurred with the inversion of
the stereochemistry at the 3-position (Scheme 28.20).
The direct oxidation in acetic acid was applicable to α-methoxy-β,γ-didehydropiperidine deriva-
tives to afford optically active iminosugar precursors. In these reactions, the generated γ-acetoxy-
α,β-didehydropiperidine derivatives were electrochemically oxidized (Scheme 28.21) [42].
OAc OAc OAc

AcO AcO S
AcO
–2e– Et3SiH S S
OAc OAc OAc N OAc
MeO N AcOH AcO N MeSO3H N Recrystallization
CO2Me CO2Me CO2Me CO2Me
53% (2 steps)
A 91:3:3:3 (2S,3S)-isomer
trans/cis = 94/6
OAc OAc
AcO AcO R
–2e – Et3SiH
R S
MeO N AcOH AcO N MeSO3H N
O O O O
O 57% (2 steps) O
B
(2R,3R)-isomer
SchEME 28.21 Diastereoselective preparation of iminosugar precursors.

IX. HYDROxYLAMiNES
Although electrochemical oxidation of N-cyclohexyl-N-hydroxylamine in the presence of pyridine
afforded the corresponding dimeric nitroso compound with a low yield, N-hydroxy-t-alkylamines
were transformed into the corresponding nitroso compounds (Equation 28.7) [43].
–e–
0.90 V vs. SCE
t-BuNHOH t-BuNO (28.7)
Divided cell
pyridine in MeCN 95%

Also, primary N-alkoxyalkylamines afforded the corresponding oxime ethers (Equation 28.8) [44].
–e–
1.15 V vs. SCE
EtNHOEt MeCH–
–NOEt (28.8)
Divided cell
pyridine in MeCN 70%
On the other hand, N-methoxyamines were more stable than styrenes under electrochemical oxida-
tion conditions. As a result, the electrooxidative intramolecular cyclized acetoxyamination product
was obtained in good yields (Equation 28.9) [45].
MeON OAc
–2e–
(28.9)
AcOH–AcOK
NHOMe
73%
Electrochemical oxidation of secondary N-hydroxylamines using halide ions as mediators

afforded the corresponding nitrones (Equation 28.10) [46]. Among the examined halide salts, NaI
was the most effective. The formation of nitrones might have proceeded by the anodically generated
I+ from I− and cathodically generated MeO − anion from MeOH as shown in Scheme 28.22. Since
–2e–, MX (0.2 equiv)

N MeOH N
OH O
MX = Nal: 92%
MX = Kl: 83%
MX = Et4Nl: 80%
MX = NaBr: 54%
MX = NaCl: 16% (28.10)
Anode
–2e–
‘’I+’’ I–
N N H N
OH MeO– MeOH Ol MeO– MeOH
O
Cathode
+2e–
2MeOH 2MeO–
SchEME 28.22 Reaction mechanism for the preparation of nitrones.
–e–
+
N N
O O
TEMPO N-oxoammonium ion
+
–e– –H H OH
–H+
1
R R2
N
OH O
N-hydroxylamine R1
R2
SchEME 28.23 Reaction mechanism for oxidation of alcohols by TEMPO.
paired electrosynthesis of nitrones from N-hydroxylamines can proceed by both anodic oxidation
and cathodic reduction, the current efficiencies are very high.
N-Hydroxy-2,2,6,6-tetramethylpiperidine and 2,2,6,6-tetramethylpiperidinyl-1-oxyl (TEMPO)
at +0.33V (vs. Ag/Ag+) are easily oxidized to the corresponding N-oxoammonium ion. Semmelhack
and coworkers found that the highly reactive N-oxoammonium ion might be a useful oxidant for
primary and secondary alcohols (Scheme 28.23) [47].
Recently, some chiral N-oxyls (shown in Scheme 28.24) were effective for asymmetric desymme-
trization or kinetic resolution to afford optically active lactone, alcohols, or amines (e.g., Equation
28.11) [48–51].
Graphite anode
divided cell
Ph NH2 –2e– at +0.80 V vs. Ag/AgCl Ph O Ph NH2
+
Me 2,6-lutidine Me Me
MeCN/NaClO4
rac-amine (R)-amine
65% 35%
O 78% ee (28.11)
NH
(0.05 equiv)
N
O

Azabicyclo-N-oxyls were prepared by utilizing electrochemical oxidation starting from l-hydroxy-

proline and d-pipecolinic acid derivatives as shown in Schemes 28.25 and 28.26.
NHAc
Me O O
Me Me
Me ArOCO
N BnHNOC N
N O
Me N
O Me Cl
Me
[48] [49] (Ar = 1-napht): [50] [51]
SchEME 28.24 Recently developed chiral N-oxyls.

HO HO HO
–2e– TMS
CO2Et MeO CO2Et CO2Et
N MeOH N TiCl4 N
CO2Me –MeCN CO2Me CO2Me
quant. 45%
Diastereomer mixture
HO MeO2C O
1) NaOH TiCl4 1) ArCOCl N
N ArOCO
2) –2e– HO 2) TMS-I
OMe
MeOH N 3) m-CPBA
CO2Me Cl Cl
59% 47%
SchEME 28.25 Preparation of a chiral N-oxyl.
Allyl-SiMe3
–2e– BF3 · Et2O
N CO2Me MeO N CO2Me N CO2Me
Et4NBF4 CH2Cl2
CO2Me MeCN/MeOH CO2Me –78°C to –40°C CO2Me
98%
cis:trans = 99.5:0.5
Silica gel column 1) O3, CH2Cl2 p-TsCl

chromatography –78°C Et3N TsO N CO2Me
cis- HO N CO2Me
isomer 2) NaBH4 DMAP CO2Me
CO2Me
72% (2 steps) MeOH, 50°C CH2Cl2, rt
81% 97%
CO2Me CO2Me O
NaHMDS MeO2C N HO2C N BnHNOC N

1 M NaOH aq.
THF, –78°C to rt
MeOH, 60°C
86%, >99% ee quant.
SchEME 28.26 Preparation of a chiral N-oxyl.
X. CARBOxAMiDES
Electrolysis of carboxamides in MeOH containing bromide ions efficiently led to products of the
Hofmann rearrangement. This reaction, named the electrochemically induced (E-I) Hofmann rear-
rangement, is achieved without any bromine and base under mild and neutral reaction conditions.
Thus, for example, an epoxy functional group in the alcohol part remained intact during the conver-
sion of carboxamides to carbamates (Scheme 28.27) [52].
However, the conditions for the E-I Hofmann rearrangement are not yet suitable for substrates
that are unstable under weakly basic conditions since EGBs may be present in the vicinity of the
cathode. For example, the E-I Hofmann rearrangement in MeOH containing bromide ions yielded
the desired Hofmann rearrangement product in only a low yield (28%) and a by-product that might
be generated by the base-catalyzed cyclization of the starting amide. On the other hand, the trans-
formation of carboxamides to carbamates was successfully achieved without any formation of
imides and no loss of the optical purity by electrolysis using the CF3CH2OH/MeCN solvent sys-
tem in which CF3CH2OH might play an important role to control the basicity caused by the EGB
(Scheme 28.28) [53].
O –2e–
O Et4NBr (0.5 equiv) H O
+ HO N O
NH2 MeCN
53% O
–2e–
EGB Br+ Br– O
HO
EGBH+
EGB EGBH+ O
O
– NCO
NHBr NBr
SchEME 28.27 The E-I Hofmann rearrangement.
NHBoc –2e–
NHBoc NHBoc
Et4NBr (0.5 equiv)
CO Me NH CO2Me +
O NH2 2 MeOH–MeCN O N O
at 60°C CO2Me H
28%
14%
(>99.9% ee)
(25% ee)
NHBoc –2e– NHBoc

NHBoc
Et4NBr (0.5 equiv)
CO Me NH CO2Me +
O NH2 2 CF3CH2OH–MeCN CO2CH2CF3 O N O
at 60°C H
80% 0%
(>99.9% ee)
SchEME 28.28 The E-I Hofmann rearrangement under neutral conditions.
+R2NH2
R1CONHR2
–2e–
R1CO N OH R1CO+
–O
–RN – +R3OH
R R1COOR3
SchEME 28.29 Electrochemical oxidation of hydroxamic acids.
XI. HYDROxAMic AciDS

Electrochemical oxidation of hydroxamic acids in the presence of amines or alcohols afforded the
corresponding amides or esters (Scheme 28.29) or carboxylic acids by reaction with water [54].
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29 Aromatic Nitrogen–Containing
Compounds
Jan S. Jaworski
CONTENTS
I. Aniline and Its Derivatives ....................................................................................................1121
A. Unsubstituted Aniline ....................................................................................................1121
B. Nitrogen-Substituted Anilines ...................................................................................... 1124
C. Ring-Substituted Anilines............................................................................................. 1127
II. Other Aromatic Amines ....................................................................................................... 1136
III. Azo and Azoxy Compounds ................................................................................................. 1137
IV. Aryl Diazonium Salts ............................................................................................................1142
V. Aromatic Triazenes ................................................................................................................1143
Acknowledgment ..........................................................................................................................1145
References .................................................................................................................................... 1146
Of all aromatic amines, aniline and its derivatives have been most extensively studied electrochemi-
cally for many years. The important aim of all those studies was to explain the mechanism of forma-
tion of a number of products of this complex oxidation process performed under different electrolysis
conditions and using reactants with various substituents. A lot of investigators have focused their
interest on understanding the early stages of electrode reactions that yield polyanilines giving rise
to many important applications. In view of these, the main part of this chapter is devoted to funda-
mental results concerning the mechanisms of anodic processes of unsubstituted aniline as well as
N-substituted and C-substituted anilines. For the last two groups, monosubstituted anilines in para-,
meta-, and ortho-positions are considered first, followed by the discussion of di- and tri-substituted
anilines. A brief review of the electrochemical reactions of other aromatic amines including poly-
aminobenzenes follows, and the electrode behavior of azo and azoxy compounds, diazonium salts, as
well as aromatic triazenes is reported at the end. In this chapter, only the main routes of the electrode
processes and the most important products are considered on the basis of some examples, and only
references to the selected examples are cited. A more comprehensive discussion and references to
investigations of a number of particular compounds can be found in recent monographic chapters
dealing with the electrochemistry of anilines [1] and azo compounds [2]. In earlier monographs, the
half-wave and cyclic voltammetric (CV) peak potentials as well as products of electrode processes
performed under different conditions are collected in tables for many aniline, diphenylamine, triphe-
nylamine, and phenylenediamine derivatives [3], as well as for azo, diazo, and azoxy compounds [4].
I. ANiLiNE AND ITS DERivATivES

A. UNSUbSTITUTED ANILINE
The first electron transfer from aniline (I) produces the radical cation C6H5NH2+ • (II) that can be
further oxidized to dication C6H5NH22+ (III). As usual, cations II and III are electrophilic and more
acidic than a parent molecule and thus, they have a tendency to deprotonation yielding the aniline
1121
–e –e
C6H5NH2 C6H5NH2+ C6H5NH22+
E1 E2
(I) (II) (III)
H+ pK1 H+ pK2
–e
C6H5NH C6H5NH+
E3
(IV) (V)
SchEME 29.1 Equilibria of electron and proton transfers during the oxidation of aniline I.
neutral radical (IV) and the nitrenium cation (V), respectively. The square diagram involving all
these electron and proton transfers is shown in Scheme 29.1 [5]. It explains why the whole oxidation
process and the properties of polyaniline formed are strongly dependent on the medium nature, first
of all on the acidity and the use of aqueous or nonaqueous solvents. No direct experimental evidence
could be found for the formation of unstable radical cation II under acidic conditions, for example,
in 1 M H2SO4 using fast CV measurements [6] or in a eutectic mixture NH4F + 2.3 HF using in situ
ESR techniques [5]. However, in acetonitrile solution for low aniline concentrations (0.05 mM)
using a platinum disk electrode of 25 μm diameter and a scan rate of 200 V s−1 the CV reduction
peak of the radical cation II was observed for the first time by Yang and Bard [6]. Moreover, the
high value (108 M−1 s−1) of the estimated rate constant for the further coupling of II explains unsuc-
cessful attempts at ESR measurements under acidic conditions. Note however that radical cations
and nitrenium ions of some substituted anilines are more stable as will be discussed at the end of
Section I.C.
The formation of the nitrenium cation (V) during the electrode oxidation of aniline in NH4F +
2.3 HF mixture was demonstrated as the only possible intermediate responsible for the formation of
a polymer containing the phenazine ring, which gives a characteristic peak in CV curves of poly-
aniline [7]. However, Yang and Bard explained later [6] that the aforementioned peak corresponds
to different redox couples depending on the aniline concentration and the experimental time scale.
Nevertheless, the band observed at 420 nm in spectroelectrochemical measurements was attributed
by Geniès et al. to V [7]. Additional support of the square diagram shown in Scheme 29.1 was
obtained using a rotating ring-disk platinum electrode where intermediates were collected at a ring
[8]. The oxidation of 0.2 M aniline in an aqueous solution containing 0.5 M KCl showed two dis-
tinct peaks at 1.0 and 1.1 V versus the Ag/AgCl/saturated KCl reference electrode that correspond
to potentials E1 and E3 in Scheme 29.1. However, only one intermediate II was formed in solutions
of high acidity when the radical cation II does not deprotonate.
It should be remembered that the molecules of all intermediates shown in Scheme 29.1 are super-
positions of resonance structures and the individual structure with charge and spin densities at
different nitrogen or carbon atoms can be considered in further coupling reactions. In particular,
primary products of the decay of radical cations II in acidic aqueous media, namely benzidine (VI)
and p-aminodiphenylamine (VII), are formed by tail-to-tail and head-to-tail coupling, respectively,
as is shown in Scheme 29.2. These two major products found in aqueous H2SO4 solutions are formed
by the radical cation–radical cation coupling in the DIM1 mechanism (Scheme 29.2) and not by the
dimerization of the radical cation II with the neutral parent molecule I (the DIM2 mechanism). This
conclusion was proven by digital simulations of CV curves obtained at a glassy carbon electrode [6].
However, the head-to-head coupling of radical cations II (Scheme 29.2) to form hydrazobenzene
(VIII) can also be observed in acidic [9] and alkaline [10] solutions. In general, products of all reac-
tions shown in Scheme 29.2, that is, tail-to-tail, tail-to-head, and head-to-head coupling, can exist at
electrodes forming different mixtures of higher oligomers. This is very important for the properties
of final polymers and their practical applications.
Aromatic Nitrogen–Containing Compounds 1123
–
N+
–
H H –2e
H2N NH2 HN NH
–2H+ –2H+
H H
–
+N H (VI) (XV)
–
–
H +N
–2e
–
(II) H H 2N N N NH2+
–2H+ –2H+
–
H
(VII) (XVII)
H H
–2e
–
–
N+ + + N N N N N
–2H+
–
–
–
–
H H H H
(II) (II) (VIII) (XVI)
SchEME 29.2 Coupling reactions of aniline radical cations II.
The distribution of primary dimers VI, VII, and VIII strongly depends on the detailed condi-
tions of electrolysis. Some typical examples are mentioned further on.
The oxidation of aniline in 1 M H2SO4 at a platinum electrode yields VI and VII. However,
VII, which is the dominant intermediate with the fastest reaction kinetics, is protonated in acidic
media forming IX (Scheme 29.3), which can be further oxidized to N-phenylquinonediimine (X)
in solutions having the pH of 1.2–4.8 [11]. Moreover, IX and X can comproportionate forming XI;
the corresponding equilibrium constant in DMSO containing 0.1–0.5 M sulfuric acid was found
to be Kcom = 0.027 [12]. Moreover, the formation of the radical cation XI in the reaction of II
with I in the aqueous solution of 0.5 M H2SO4 was observed using in situ time-resolved FT-IR
spectroscopy [13]. It should also be noted that X undergoes a slow oxidative decomposition to
N-phenylquinoneimine (XII) and next to the anilinium cation (XIII) and p-benzoquinone (XIV).
Products XII and XIV may be reversibly reduced as is shown in Scheme 29.3 [6].
–2e +IX
N NH+3 N NH+2 2 N NH+2
–2H+ Kcom
H H
(IX) (X) (XI)
H3 O+
2e
N O N OH
2H+
H
(XII)
H3O+
NH3+ O OH
2e
+
2H+
O OH
(XIII) (XIV)
SchEME 29.3 Reaction pathways for cation IX.

In a similar manner, benzidine (VI) formed in the tail-to-tail coupling can undergo reversible
oxidation [6] with the exchange of two electrons and two protons yielding (1,1′-biphenyl)-4,4′-
diimine (XV), as is shown in Scheme 29.2.
It can be added that further oxidation of the dimers to radical cations and their recombination
with monomer radical cations produce trimers that can be detected in solutions. However, higher
oligomers are not formed in solution but on the electrode [14] and the electrode filming by oxidation
products makes their identification rather difficult.
On the other hand, the head-to-head coupling of the radical cations II (besides two other coupling
modes discussed earlier) was observed in 0.1 M H2SO4 during the oxidation of aniline at graphite
electrodes [9]. The hydrazobenzene (VIII) formed in the last process is next oxidized to azobenzene
(XVI) as is shown in Scheme 29.2. However, VIII was not detected in 2.2 M sulfuric acid.
In more recent papers using the electrochemical thermospray mass spectrometry (MS), the only
deuterated dimer formed during the oxidation at a platinum foil of 0.01 M d5 -aniline in 0.1 M sul-
furic acid was identified as IX [14] and similarly VII was identified during the oxidation of 10 −3
M aniline in aqueous solutions buffered at pH = 5 [15]. Moreover, interesting results were reported
using a thin-layer electrochemical flow cell (with a glassy carbon electrode) coupled online with the
electrospray MS in buffered aqueous solutions and in 1/1 (v/v) aqueous methanol mixtures. All solu-
tions contained ammonium acetate and either acetic acid or ammonium hydroxide added to obtain a
proper pH. In methanol mixtures, the following soluble dimeric products were found: VI, VII, and
XVII at pH = 4, but VII, VIII, XVI, and XVII at pH = 9 [16].
Taking into account different competitions of electron transfer steps and homogeneous coupling
reactions during the electrode oxidation of aniline, as revealed in Schemes 29.1 and 29.2, a complex
pattern of multiple redox peaks can be observed in CV curves recorded in various conditions. It is
worth noting and highly recommended that their comparison and interpretation should be made
with great caution.
B. NITroGEN-SUbSTITUTED ANILINES
In general, the nitrogen substitution of aniline results in the formation of more stable radical cat-
ions as intermediates of the oxidation than in the case of the unsubstituted reactant. Therefore,
the main route of the electrode reaction is changed. The anodic oxidation of N-alkyl anilines in
acidic aqueous media produces radical cations with the positive charge delocalized at the ring
due to the inductive effect of the electron-releasing substituent in such a way that the tail-to-tail
coupling is favored. The increase of steric hindrance by the nitrogen substitution also favors
the –C–C– coupling. Thus, benzidine derivatives are the main products of dimerization, as will
be shown further on.
Protonated N,N′-dimethylbenzidine N(Me)H–C6H4 –C6H4 –N+(Me)H2 (XVIII) and protonated
N,N′-dimethyl-p-aminodiphenylamine C6H4 –N(Me)–C6H4 –N+(Me)H2 (XIX) in the ratio of 7:3
are the early products of the oxidation of N-methylaniline in 0.1 M H2SO4. These products were
identified by the electrochemical thermospray MS using the reactant deuterated at the N–H group
[14]. However, the aforementioned authors also found that dimers undergo dealkylation through the
formation of the –N+(H)=CH2 group by the loss of two electrons and a proton from the –N(H)Me
group. Further hydrolysis with the oxidation yields the radical cation possessing the –N+ •H2 group.
As a result, the dealkylated protonated dimers NH2–C6H4 –C6H4 –N+(Me)H2 and C6H4 –NH–C6H4 –
N+(Me)H2 were also indentified. Moreover, trimers formed from XVIII by C–C–N–C coupling and
two trimers from XIX formed by C–C–N–C and C–N–C–N coupling as well as dealkylated trimers
were found in the solution [14].
N,N-dialkyl anilines are more easily oxidized and the oxidation potentials shift to more
positive values in the order of aniline < N,N-di-n-butyl < N,N-diethyl < N-methyl-N-ethyl < N,
N-dimethylaniline. Two one-electron oxidation peaks were observed for these dialkyl anilines
in acidic solution of pH = 1 and both products, radical cations and dications, were consumed
in follow-up reactions making the observation of cathodic peaks on the reverse scan very dif-
ficult [17]. However, only one peak for N,N-dimethylaniline (XX) was observed without any
cathodic response in alkaline media of pH = 13, where the radical cation is less stable [18]. The
benzidine derivative was confirmed as the main product of the oxidation of XX. Side reactions
of the primary radical cation were investigated using the electrochemical thermospray MS tech-
nique [19]. Reactions of the neutral radical formed by the deprotonation at the α-carbon atom
of the alkyl group were considered in order to explain the formation of dimers with different
structures.
On the other hand, in acetonitrile solutions the radical cation formed in the one-electron oxida-
tion of XX is so stable that its reduction peak was observed in CV curves recorded at scan rates
above 500 V s−1 [20]. The fast radical cation–radical cation dimerization and deprotonation result
in the formation of N,N,N′,N′-tetramethylbenzidine as the final dimer, but no evidence of further
polymerization was observed.
The presence of ring substituents in the para-position in N,N-dimethylanilines can affect radical
cation coupling reactions. Radical cations of 4-bromo-N,N-dimethylaniline generated by anodic
oxidation in MeCN in the absence of parent molecules form tetramethylbenzidine dication in radical
cation–radical cation dimerization, but if parent molecules are present in the solution they dimer-
ize with the primary radical cation yielding tetramethylbenzidine radical cation [21]. In both of the
cases, C–C coupling occurs with C–Br bond cleavage. However, the oxidation of N,N-dimethyl-
p-toluidine (XXI) in similar conditions gives N,N,N′,N′-tetramethyl-α,α′-bi-p-toluidine (XXIII)
(Scheme 29.4) and rate constants for the formation of the neutral radical XXII· and the final product
XXIII were obtained by the simulation of CV curves [22].
The oxidation of diphenylamine (XXIV) in MeCN solution at platinum ultramicro electrodes
gives the radical cation XXIV+ • (Scheme 29.5), which can be detected in CV curves recorded at a
scan rate above 100 V s−1 [23]. Finally, N,N′-diphenylbenzidine (XXV) formed after the coupling of
two radical cations XXIV+ • is further oxidized to a dication. Even though different CV curves were
observed after the addition of 2,6-lutidine acting as a weak base, yet the same product XXV was
formed [24]. Stronger bases change the reaction pathway probably due to the deprotonation at the
nitrogen atom. A similar coupling is impossible in the presence of para-methoxy groups in dianisyl-
amine and the oxidation pathway is more complicated, but in this case not all oxidation products could
be identified [24]. Nevertheless, the oxidation at lower scan rates in the presence of lutidine probably
+ Me
Me Me Me Me Me Me H–+ Me
N N– N N
–e + XXI
+
Me Me CH2 Me
(XXI) (XXI+ ) (XXII )
+ XXII
Me H H Me
N C C N
Me H H Me
(XXIII)
SchEME 29.4 Pathways for the anodic oxidation of N,N-dimethyl-p-toluidine XXI in MeCN.
+
H H
–e
N N
(XXIV) (XXIV+ )
–2H+ +XXIV+
N N
H H
(XXV)
–e
+
N N
H H
–e
+ +
N N
H H
SchEME 29.5 Pathways for the electrochemical oxidation of diphenylamine XXIV in MeCN.
yields the cyclic product 2,6-dimethoxy-9,10-dianisyl-9,10-dihydrophenazine, also suggested in

earlier works. A similar cyclic product 2,6-dimethyl-9,10-diphenyl-9,10-dihydrophenazine is char-
acteristic of the oxidation of 3-methyl-diphenylamine and other 3-substituted and 3,3′-disubstituted
diphenylamines [25].
The aromatic substitution of diphenylamines with the formation of cyanodiphenylamines was
elaborated by the electrolysis in methanol solutions containing cyanide ions [26].
Two-electron oxidation of p-aminodiphenylamine (VII) observed in MeCN was explained by
a mechanism involving the proton transfer between the parent molecule and its radical cation (the
rate-determining step [rds]) and the immediate oxidation at the same potential of the neutral radical
to the final cation as is shown in Scheme 29.6 [27].
The N–N coupling of the aminyl radical of p-monosubstituted diphenylamines in MeCN under
basic conditions results in the formation of corresponding N,N,N′-triaryl p-phenylenediamines and
tetraarylhydrazines (p–XC6H4)2N–N(p–XC6H4)2 [28].
Among triarylamines the electrode oxidation in MeCN of triphenylamine (XXVI) to tetra
phenylbenzidine (XXVII) was most intensively investigated (Scheme 29.7). Radical cations XXVI+·
–e +VII +
VII VII+ N NH3
H
+
+
–e
N NH N NH
H H
SchEME 29.6 Mechanism for the anodic oxidation of p-aminodiphenylamine VII in MeCN.
–e XXVI+
N N
N N –2 H+
(XXVII)
–e
(XXVI) (XXVI+ )
XXVII+
–e
+N
N+
(XXVII2+)
SchEME 29.7 Mechanism for the electrode oxidation of phenylamine XXVI.
formed in the first step are relatively stable (their reversible reduction is observed at 20 V s−1) and the
stability increases for derivatives with para substituents when the deprotonation necessary for the
dimerization process is difficult [29]. The radical cation dimerization according to the DIM1 mech-
anism is the rds, and the dimeric product XXVII is consecutively oxidizable to the radical cation
and the quinoidal dication at less positive potentials than it was produced [30]. It can be added that
a number of tri-p-substituted triarylamines representing a wide range of their oxidation potentials
and giving stable radical cations were successfully used as mediators in indirect electrochemical
oxidation of different compounds [31] (see also Chapter 15).
C. RING-SUbSTITUTED ANILINES
In aqueous acidic media, para-substituted anilines (XXVIII) are oxidized to radical cat-
ions that undergo rapid head-to-tail coupling with the formation of protonated 4′-substituted
4-aminodiphenylamine (XXIX). The overall process given in Equation 29.1 corresponds to a one-
electron transfer for one aniline molecule if the leaving para-substituent is in the anionic form
(e.g., halide or methoxide ion), but it corresponds to a two-electron process if a neutral group is left
(e.g., CO2 for p-aminobenzoic acid) and the final dimer occurs in the reduced form [32].
2 p-X − C6H 4 − NH 2 − 2e → p-X − C6H 4 − N=C6H 4 =N + H 2 + X – + 2H + (29.1)

( XXVIII ) ( XXIX )
However, for the oxidation of p-toluidine in 0.1 M H2SO4 (and in MeCN), CV investigations showed the
head-to-head coupling of radical cations with the formation of 4,4′-dimethylhydrazobenzene, which
is irreversibly oxidized at the potential of formation to the main product 4,4′-dimethylazobenzene
[8]. In solutions with pH < 8, another product 2-amino-4′,5-dimethyldiphenylamine formed in the
ortho-coupling was proposed earlier [33].
A similar overall reaction as given by Equation 29.1 was found in aprotic media (DMF and MeCN);
however, the product may or may not be protonated depending on the medium basicity [34–37].
Moreover, during the oxidation of p-haloanilines in aprotic media, the leaving anions Cl− or Br− are
oxidized to dihalogens (Equation 29.2), which form with parent anilines 2,4-dihaloanilines as minor
+
NH2 NH2 H
+
–
–e + XXVIIIa MeO NH
OMe
OMe OMe
NH2
(XXVIIIa) –MeOH
+
H
MeO N NH2
–e
+ +
MeO N NH2
H
SchEME 29.8 Detailed mechanism for the electrooxidation of p-anisidine XXVIIIa in DMF.
products, as will be discussed further on [35–37]. Thus, depending on the fraction of the oxidized
halide ions the apparent number of electrons per aniline molecule changes from 1 to 1.5.
2 p-X − C6H 4 − NH 2 − 3e → p-X − C6H 4 − N =C6H 4 = NH + ½ X 2 + 3H + (29.2)

( XXVIIIb ) X = Cl ( XXX )
( XXVIIIc ) X = Br

At high scan rates using gold ultramicroelectrodes, reversible one-electron CV peaks were
found in DMF for the oxidation of p-anisidine (XXVIIIa), p-chloroaniline (XXVIIIb), and
p-bromoaniline (XXVIIIc) supporting the formation of corresponding radical cations in the first
step [34,35]. However, the mechanism of their decay is not the same for all aforementioned reac-
tants, as indicated by different slopes of the change of anodic peak potentials with the scan rate
∂E pa /∂logν and with the reactant concentration ∂Epa /∂logc. For XXVIIIa (X = OMe), both the
aforementioned slopes are equal to 30 mV per decade, indicating a dimerization according to
the DIM2 mechanism as the second-order rds. The detailed mechanism shown in Scheme 29.8
involves the nucleophilic attack of parent anisidine XXVIIIa onto its radical cation (the rate con-
stant of this rds is 7.7 M−1 s−1), further rearrangement of a radical, the elimination of methanol, and
the oxidation to the final dication [34]. It should be added that a more complicated mechanism of
the decay of radical cations of XXVIIIa was found in MeCN using the electron-transfer stopped-
flow method with spectral detection of intermediates that however are not formed in the vicinity
of the electrode [38].
On the other hand, for the oxidation of p-haloanilines, XXVIIIb and XXVIIIc in DMF slopes of
∂E pa /∂logν = 20 mV per decade were found [35], but peak potentials were not dependent on the reac-
tant concentration. Moreover, the addition of 2,6-lutidine at a higher concentration changes the slope
of ∂Epa /∂logν to 30 mV per decade, indicating the irreversible reaction with the base. Thus, the mech-
anism proposed (Scheme 29.9) involves a fast reversible deprotonation of the primary radical cation
by any base present in the solution with the formation of the neutral radical XXXI•, followed by its
coupling with the primary radical cation (the rds) and spontaneous elimination of HX giving the final
4-imino-4′-halodiphenylamine [35]. Note that no similar deprotonation occurs for p-anisidine radi-
cal cation XXVIIIa+ •, a much weaker acid, which explains the different DIM2 mechanism observed.
The controlled potential electrolysis of p-chloroaniline (XXVIIIb) and p-bromoaniline
(XXVIIIc) in MeCN affords a number of products besides halodiphenylamines XXX shown
in Equation 29.2. The product distribution was reported as the relative intensity of peaks in gas
+
NH2 NH2 Base BaseH+ NH NH
–e
X X X
X
(XXXI )
(XXVIIIb) X = Cl
(XXVIIIc) X = Br
NH
+ –HX H
+
–
X N NH N X
H
–
H
X
SchEME 29.9 Proposed mechanism for the anodic oxidation of p-haloanilines XXVIIIb and XXVIIIc in DMF.
chromatography-electrospray MS measurements [36,37]. For XXVIIIb, 4-amino-4′-chloro-

diphenylamine (78.4%) was the main product formed in the head-to-tail coupling, but the cou-
pling in the ortho-position yielded 2-amino-4,5′-dichlorodiphenylamine (30.4%) and the reaction
with elemental chlorine mentioned earlier gave 2,4-dichloroaniline (23%). On the other hand, for
XXVIIIc the main products were 2,4-dibromoaniline (58%) and 4-amino-4′-bromo-diphenylamine
(38.8%) but ortho-coupling was very small as expected for the larger bromine atom.
However, recent voltammetric and in situ ESR study of the oxidation of p-chloro, p-bromo, and
p-iodoaniline in MeCN at gold electrodes indicated that no single reaction mechanism alone can
explain all results found [39]. Apart from the fast route producing the nonparamagnetic dimer at a
higher oxidation state as shown in Scheme 29.9, there is the competitive slow reaction of deproton-
ated neutral radical XXXI• with the parent aniline resulting in the formation of the unstable dimeric
radical cation that can be detected by ESR using a tubular flow cell [39].
The electrochemical behavior of p-haloanilines is quite different in more basic media when
head-to-head coupling giving rise to azobenzene derivatives is the main oxidation route, similarly
as for unsubstituted aniline [10]. Such behavior was reported for p-chloroaniline (XXVIIIb) in
MeCN solutions containing 0.1 M pyridine [40]. In the last case, the main product of the large-scale
electrolysis of XXVIIIb was 4,4′-dichloroazobenzene (24.3%) formed by the radical–radical cou-
pling of neutral radical p–Cl–C6H4 –NH• produced in the deprotonation of primary radical cation
by pyridine.
The two-electron oxidation of p-aminophenol and its derivatives in acidic solutions gives quino-
neimine that hydrolyzes to p-quinone [41]. A similar two-electron oxidation to quinonediimine was
found for p-phenylenediamine H2N–C6H4 –NH2 (XXXII), but in solutions of pH from 2 to 6, the
radical cations formed after the one-electron step are stable and they were detected by ESR mea-
surements [42]. The reversible one-electron oxidation of XXXII yielding stable radical cations was
also observed in many aprotic solvents, and this redox couple was used as a model reactant for the
elucidation of solvent effects on heterogeneous rate constants [43,44]. Such investigations were then
extended to N,N,N′,N′-tetramethyl-p-phenylenediamine [45] and to binary solvent mixtures [46].
On the other hand, head-to-tail and tail-to-tail coupling was observed for the anodic oxida-
tion of ortho- and meta-substituted anilines (XXXIII) in aqueous acidic media resembling the
behavior of aniline itself [32]. A detailed mechanism of the oxidation in 3 M H 2SO 4 solutions
proposed by Hand and Nelson [47] is shown in Figure 29.1. The primary radical cations formed in
the first electron transfer undergo tail-to-tail coupling to benzidines XXXIV or produce diphe-
nylamines XXXV (in particular for molecules with electron-withdrawing ortho-substituents).
+ ++
NH2 NH2 NH2
–e + XXXIII+
H2N NH2
X X X X X
(XXXIII) (XXXIII+ ) (XXXIV)

H+ 2e
X
NH2 + +
NH H2N NH2
X X
+ XXXIII H
N NH2
X X X
meta (XXXV) ortho
NH 2e + 2H+
NH2
H3O+ H3O+
+ N NH N O
Fast Fast
X X X
X X X
O
Slow H3O+ Slow H3O+
O O NH2
H2O OH H2O X
X +
X X
O OH O
OH
2e + 2H+
O
X
OH
(XXXVI) O
FiGURE 29.1 Reaction pathways proposed for the anodic oxidation of ortho- and meta-substituted anilines
in 3 M H2SO4. (Adapted from Hand, R.L. and Nelson, R.F., J. Electrochem. Soc., 125, 1059, 1978. Reproduced
by permission of ECS—The Electrochemical Society.)
Further oxidation and hydrolysis occur by different routes for ortho- and meta-substituted reac-
tants, but the same final product, 2-substituted para-benzoquinone XXXVI, is formed. A simi-
lar mechanism was also observed in solutions of 2 M H2SO 4 [9], but not in 0.1 M H2SO 4 (and
MeCN) where the formation of hydrazobenzene, which is next oxidized to azobenzene, was
found for all three isomers of toluidine [9]. On the other hand, as a result of the anodic oxidation
of o-aminophenol (XXXVII) in aqueous neutral and alkaline solutions on a silver electrode,
the linear dimer 2,2′-dihydroxyazobenzene (XXXVIII) produced by the N–N coupling of two
neutral radicals XXXIX was obtained as the main product. However, the cyclic dimer 3-amino-
phenoxazone (XL) formed by C–N coupling was the dominant product in acidic solutions [48]
as is shown in Scheme 29.10. XL can be electrochemically reduced. Cyclic dimers produced by
the C–N coupling of radical cations are also proposed [49] for the oxidation of o-anisidine in
+ NH +XXXIX
+ OH–
NH2 NH2 N N
–H2O –2e, –2H+
OH OH OH
–e OH HO
(XXXIX) (XXXVIII)
N NH2
(XXXVII) (XXXVII+ ) +XXXVII+
O O
(XL)
+2e +2H+
H
N NH2
O OH
SchEME 29.10 Pathways for the anodic oxidation of o-aminophenol XXXVII in aqueous solutions.
acidic solutions on a platinum electrode. The aforementioned conclusions were obtained [48,49]
using surface enhanced Raman scattering spectra.
More recently, absorption spectra of the oxidation products of ortho- and meta- isomers of tolu-
idine and anisidine in MeCN were investigated using the electron-transfer stopped-flow technique
[50]. The formation of 3,3′-dimethylbenzidine (in the form of radical cation and dication) by the
C–C coupling in para-position was proven for the oxidation of o–toluidine. Consecutive reactions
of that dimer with monomer radical cations were reported. However, a similar Cpara –Cpara coupling
of o–anisidine radical cations was excluded, and moreover, for more reactive radical cations of
m-methyl and m-methoxy substituted anilines, the spectra could not be observed at all [50].
Among polysubstituted anilines, the anodic behavior of halogen derivatives in MeCN and in
aqueous solutions was investigated most intensively. The oxidation of 2,4-dihaloanilines (XLI) in
MeCN showed a few different products and the overall reactions for their formation are given in
Scheme 29.11 [36,37,51]. The main products are N-(2,4-X2–phenyl)-3′-X-quinone diimine (XLII)
X X
+XLI
X N NH
–4e, –4H+
X
(XLIV) X = Cl, Br
–
NH2 X X NH2
X X X
+2 XLI
X N NH +
–4e, –4H+
X (XLIIa) X = Cl X
(XLIIb) X = Br (XLIIIa) X = Cl
(XLIa) X = Cl (XLIIIb) X = Br
(XLIb) X = Br
Cl Cl
+3 XLIa
Cl N NH + XLIIa
–8e, –8H+
Cl Cl
(XLVa)
SchEME 29.11 Formation of different products during the oxidation of 2,4-dihaloanilines XLI in MeCN.
Br Br
–3e, –2 H+
2 XLIIIb Br N NH
–1/2 Br2
Br Br
(XLVb)
Cl Cl
H H
–e +XLIIIa+
XLIIIa XLIIIa+ Cl N N Cl
–2H+
Cl Cl
(XLVI)
SchEME 29.12 Anodic oxidation of 2,4,6-trihaloanilines XLIII in MeCN.
and trihalogenated aniline (XLIII). The formation of XLII in the head-to-tail coupling of radical
cations (and the elimination of halogen) is similar to the mechanism found by Bacon and Adams
[32] for para-substituted anilines in acidic media. Indeed in fast measurements using a rotating disk
electrode, the one-electron transfer corresponding to the oxidation of one XLI molecule was found
[51]. However, under the controlled potential electrolysis two-electron processes (for one reactant
molecule) give halogenated by-products XLIV and XLVa [36,37].
On the other hand, for the oxidation of 2,4,6-trihaloanilines (XLIII) in MeCN the apparent
number of electrons equal to 1.5 and additional CV peaks indicated the oxidation of halide ions
expelled from the para-position [36,37] similarly as it was observed for p-haloanilines. Thus,
the main product for the oxidation of XLIIIb is N-(2,4,6-Br3 –phenyl)-3′,5′-Br2-quinone diimine
(XLVb) as is shown in Scheme 29.12 [37]. However, XLVa is a minor product for the oxida-
tion of chloro-derivative XLIIIa, but the main product 2,2′,4,4′,6,6′-hexachlorohydrazobenzene
(XLVI) is formed by the head-to-head coupling of radical cations in the reaction shown also in
Scheme 29.12 [36].
In the presence of one or two methyl groups (which are electron-releasing) in ortho-position, a sta-
bilization of radical cations is observed. Therefore, two one-electron CV anodic peaks corresponding
to the consecutive formation of radical cations and dications were observed for the oxidation of 2,4-
and 2,6-dimethylanilines in 0.1 M H2SO4 [9]. In the case of 2,4-derivative, the ensuing dimerization
produces substituted hydrazobenzene and, after its instantaneous oxidation, azobenzene. However,
for the 2,6-derivative the para-position is vacant and all three types of coupling occur similarly as it
was reported for the aniline itself (cf. Scheme 29.2) [9]. On the other hand, in ACN the anodic behav-
ior of 2,4- and 2,6-dimethylanilines resembles that of p-toluidine and o-toluidine, respectively [9].
Anodic behavior of polyhaloanilines at platinum electrodes in aqueous media with higher
acidity (at least 1.0 M H 2SO 4) was quite different because the reactants are completely proton-
ated and no dimerization is observed but a hydrolysis of primary intermediates [52–55]. The
two-electron oxidation of protonated 2,4-dihaloanilines (XLVII), which is the rds, gives the
intermediate tripositive cation XLVIII that loses a proton (Scheme 29.13), and next by hydro-
lysis, it gives two products: 2-halo-p-benzoquinoneimine (XLIX) and 2-halo-p-benzoquinone
(L). Both these products can be reduced giving rise to characteristic CV peaks. The intermedi-
ate cation XLVIII can also lose two protons from the benzene ring producing the electroactive
species responsible for the different oxidation process observed at higher acidity but giving
the same final products XLIX and L. Both these processes of the oxidation of XLVII are con-
trolled either by diffusion or by adsorption depending on the medium acidity [53,54]. Moreover,
after prolonged electrolysis of the bromo-derivative XLVIIb, a slow hydration of bromobenzo-
quinone Lb produces 3-bromo-1,2,4-benzenetriol (LI), which is reversibly oxidized as shown
in Scheme 29.13 [53].
+ + ++ +
NH3 NH3 NH2 NH2 O
X X X X X
–2e –H+ +H2O +H2O
+
+ –2H+, –X– –NH4+
X X X O O
(XLVIIa) X = Cl (XLVIII) (XLIX) (L)

(XLVIIb) X = Br
+2e +2e
+2H+ +2H+
+
O OH O NH3 OH
Br Br Br X X
+H2O –2e
+
–2H
OH OH
O OH O OH OH
(Lb) (LI)
SchEME 29.13 Mechanism for the anodic oxidation of protonated 2,4-dihaloanilines XLVII in acidic media.
The anodic oxidation in acidic media of 2,4,6-trisubstituted anilines with the Br atom in para-
position depends on the nature of the ortho-substituents. For weak electron-withdrawing Br atoms,
a two-electron irreversible process is followed by deprotonation and further hydrolysis. Thus,
2,4,6-tribromoaniline in its protonated form LII, which predominates in strong acidic media, is
oxidized at platinum electrodes [52] with the formation of tripositive cation LIII (Scheme 29.14)
similarly as it was found for the oxidation of 2,4-dibromoaniline XLVIIb. The next loss of a proton
can occur at different positions giving two possible cations LIV and LV. The former is hydrolyzed
first to 2,6-dibromobenzoquinone (LVI), which is not electroactive in CV experiments. However,
its further hydrolysis yields 3,5-dibromo-1,2,4-trihydroxybenzene (LVII), which can be reversibly
oxidized (Scheme 29.14) [52]. The latter cation LV is oxidized in a two-electron process, but its
dimerization with the parent unprotonated aniline XLIIIb was also suggested [52].
On the other hand, in the presence of a stronger electron-withdrawing nitro substituent in the
ortho-position, the radical cation formed after the first electron transfer is more stable. Therefore,
2,4-dibromo-6-nitroaniline in solutions of sulfuric acid (where the amino group is protonated) is
+ + +
NH3 NH3 NH2 O
Br Br Br Br Br Br Br Br
–2e –H+ +2 H2O
+
+
+ –HBr, –H+, –NH4+
Br Br Br O
(LII) (LIII) (LIV) (LVI)
–H+ +H2O
+
NH3 O OH
Br Br Br Br Br Br
–2e
+ –2H+
OH OH
Br O OH
(LV) (LVII)
SchEME 29.14 Pathways for the anodic oxidation of 2,4,6-tribromoaniline LII in strong acidic media.
+ +
NH3 NH2
O
Me X Me X
–e –H+ Me Br
LVIII2+
+ LVIIIa
Br Br
Br
O
(LVIIIa) X = Br (LIX + ) (LXII)
(LVIIIb) X = Me
+LIX+ –Br–, –H+ +H2O, Br2 –Br–, –H+
Me Me Me Me
+ +H2O +
Br N NH+2 Br N O
H –NH4+ H
X X X X
(LXa) X = Br (LXIa) X = Br
(LXb) X = Me (LXIb) X = Me
+2e, +2H+ +2e, +2H+
Me Me Me Me
H2 H2
Br N NH3+ Br N OH
+ +
X X X X
SchEME 29.15 Mechanism for the anodic oxidation of protonated o-substituted p-bromoanilines LVIII.
oxidized according to the eCe mechanism where two reversible one-electron steps are divided by
the irreversible chemical reaction of the loss of one proton (the rds) [55]. Further hydrolysis of the
resulting dipositive cation (similar to LIV but with the nitro group instead of one ortho-Br atom)
with the loss of Br− and NH4+ ions gives rise to 2-bromo-6-nitro-p-benzoquinone that can be revers-
ibly reduced. Thus, the aforementioned oxidation process is similar to that proposed by Hand and
Nelson for ortho- and meta-monosubstituted anilines [47].
Finally, the presence of one or two electron-releasing o-methyl groups in p-bromoaniline sta-
bilizes radical cations due to the inductive effect of o-substituents changing the oxidation in
acidic media to the eC mechanism. It includes (Scheme 29.15) the reversible electron transfer
from the protonated reactant LVIII and the deprotonation of the formed dication radical LVIII 2+ •
to radical cation LIX+ • (the rds). The head-to-tail coupling of two LIX+ • gives finally diimine LX,
which is hydrolyzed to benzoquinoneimine LXI, and both these products can be further reduced
in CV experiments as is shown in Scheme 29.15 [56]. Therefore, the final product of the con-
trolled potential electrolysis of LVIIIb (X = Me) is LXIb. However, for only one ortho-methyl
group in LVIIIa (X = Br) a reactant has less electron-releasing character and further hydrolysis
and deprotonation of LXIa occurs followed by bromination. This gives 2-methyl-5,6-dibromo-
p-benzoquinone (LXII) as the final product that can be further reduced to the corresponding
hydroquinone [56].
Extremely stable intermediates—nitrenium ions, nitryl radicals, and dications—can be formed
in the anodic oxidation of sterically hindered anilines, in particular 2,6-di-tert-butyl-4-(4′-phenyl)-
anilines (or 4-amino-3,5-di-t-butyl-biphenyls, Scheme 29.16) investigated by Speiser and cowork-
ers [57–62]. The formation of radical cations LXIIIa+ •, LXIIIb+ •, and LXIIIc+ • coloring MeCN
solutions to deep blue, green, and orange, respectively, during the reversible anodic oxidation of the
corresponding anilines LXIII was confirmed by electroanalytical and ESR measurements as well
as by UV/Vis spectra obtained using modulated specular reflectance spectroscopy (MSRS) [57]. No
indication of follow-up reactions of these radical cations was found in the experimental time scale.
–e +
R-C6H5NH3+ R-C6H5NH3+
NH2
(LXV+) (LXV++ )
+H+ –H+ +H+ –H+
R –e –e
R-C6H5NH2 R-C6H5NH2+ R-C6H5NH22+
(LXIII) (LXIII+ ) (LXIII2+ )
(LXIIIa) R = Ph
(LXIIIb) R = p-C 6H4OMe
(LXIIIc) R = p-C 6H4NMe2
+H+ –H+ +H+ –H+ +H+ –H+
(LXIIId) R = p-C 6H4NO2
(LXIIIe) R = t-Bu –e –e
R-C6H5NH– R-C6H5N H R-C6H5NH+
(LXIV–) (LXIV ) (LXIV+)
SchEME 29.16 Detailed pathways for the anodic oxidation of a series of sterically hindered anilines LXIII
in MeCN.
Their stability was attributed to the electron-donating effect of 4-phenyl substitution, which is also
responsible for the shift of standard potentials to low values and the low wavelength bands to lower
energy. The observed decay of the radical cation LXIIIe+ • (with a 4-t-butyl group instead of phenyl)
confirmed the aforementioned explanation [57].
For a series of 18 anilines LXIII with different substituents, the formal potentials of the revers-
ible one-electron oxidation were correlated with Hammett σ constants and Taft’s dual substituent
parameters [59]. The results showed that the Gibbs free energy change depends mainly on the elec-
tronic structure of radical cations LXIII+ • in which two phenyl rings have a coplanar conformation
allowing strong π-electron interactions and the stabilization of the positive charge. On the other
hand, in neutral anilines LXIII a steric twisting between two phenyl rings prevents the conjuga-
tion. For electron-withdrawing substituents (e.g., –NO2), an additional cathodic peak is observed
probably corresponding to the reduction of the neutral radical LXIV •. Moreover, it was found that
the oxidation mechanism of LXIIIc with two reaction sites seems to be different; that is why the
oxidation of the –NMe2 group instead of the –NH2 one was considered.
The rate constants for the protonation of LXIII to anilinium cations LXV+ in MeCN containing
perchloric acid and the back deprotonation determined from voltammograms by the multiparameter
estimation [60] were considerably lower than expected for diffusion-controlled reactions supporting
the effects of the steric hindrance in ortho positions. Consequently, anilines LXIII are less basic than
the unsubstituted aniline: for the anilinium cation XIII pKa = 10.56 in MeCN whereas pKa values of
cations LXV+ are much smaller, ranging from 3.70 for LXVc+ to 4.61 for LXVa+ and LXVb+ [60].
Further oxidation of radical cations leads to dications (Scheme 29.16), but only LXIIIc2+ is stable
and a simulation of CV curves supported the ee mechanism for the oxidation of LXIIIc in two one-
electron steps. Dication LXIIIb2+ decays moderately fast, but the oxidation mechanism of LXIIIb
is complicated. It includes the deprotonation of LXIIIb2+ to nitrenium ion LXIVb+ (which can be
reduced to nitryl radical LXIVc• giving an additional CV peak) and the protonation of parent aniline
yielding cation LXVb+, which is oxidized at potentials close to the oxidation of LXIIIb+•. UV/Vis
spectra of dications LXIIIc2+ and LXIIIb2+ were obtained using MSRS technique. On the other
hand, dication LXIIIa2+ decays extremely fast and could not be detected [58]. Moreover, the anodic
oxidation of LXIIIc in MeCN with an excess of 2,6-lutidine resulted in the formation of persistent
nitrenium ion LXIVc+ giving a deep purple color of the solution. The last ion was identified on the
basis of CV experiments as well as UV and 1H NMR spectra. NMR signals confirmed the delocaliza-
tion of the positive charge over both rings of the biphenyl moiety [61]. Reactions of electrogenerated
nitrenium ions LXIVa+, LXIVb+, and LXIVc+ with a number of nucleophiles were also reported [62].
II. OThER AROMATic AMiNES

In general, the anodic behavior of polynuclear aromatic amines, for example, the derivatives of
anthracene and fluorene as well as the more recently studied 1-naphthylamine LXVI [63,64],
1-pyrenamine [65] and derivatives of dibenzothiophene [66], is similar to that observed for ani-
lines. In particular, the oxidation of LXVI in MeCN corresponds to the eCe mechanism with the
reversible formation of radical cations LXVI+ • in the first step and their very fast follow-up reac-
tions forming the dimer, which is easier to oxidize in a two-electron process than the parent amine.
Among three possible paths of dimerization (similarly as shown in Scheme 29.2 for aniline), the
main product 4-amino-1,1′-dinaphthylamine is formed by the head-to-tail (i.e., C4 –N) coupling.
Moreover, the effects of the addition of an acid and a base suggested that the deprotonation of
radical cations LXVI+ • to neutral radicals precedes their dimerization. However, naphthidine, the
product of the tail-to-tail (i.e., C4 –C4′) coupling was also identified in CV curves [63]. On the other
hand, in the more basic solvent DMSO the main oxidation product 1,1′-hydrazonaphthalene is pro-
duced in the head-to-head (i.e., N–N) coupling, but naphthidine was not found among the products
[64]. A similar eCe mechanism was proposed for the oxidation of 1-pyrenamine in MeCN [65].
The results of the double potential step chronoamperometry indicated the coupling of two radical
cations (but not the radical cation with the parent amine) and made it possible to determine the cor-
responding rate constant [65].
The reversible one-electron oxidation of p-phenylenediamine XXXII in aprotic solvents was
already mentioned in Section I.C, and many earlier investigations of their derivatives were reviewed
[3]. The slow two-electron oxidation of 3,6-bis(dimethylamino)durene and 9,10-bis(dimethylamino)
anthracene in MeCN [67] was ascribed to large inner reorganization energy due to substantial
structural changes. On the other hand, for the anodic oxidation of amino derivatives of diben-
zothiophenes in MeCN containing LiClO4, the reversible formation of stable radical cations was
shown, and the most stable of them obtained from 3,7-diamino and 3,7-bis(dimethylamino)diben-
zothiophene were isolated in the form of crystalline perchlorate salts and were characterized by
ESR spectra [66].
In recent years, the anodic behavior of polyaminobenzenes with an increasing number of –NH2
groups was also intensively investigated [68–73]. High-spin organic cations, inspiring for the
preparation of magnetic materials, were obtained [68] in the anodic oxidation of N,N,N′,N′,N″,N″-
hexaanisyl-1,3,5-triaminobenzene in butyronitrile solution. Two reversible one-electron steps at
room temperature and one more step reversible at −78°C were observed in CV curves at 0.2 V s−1.
These results indicated the consecutive formation of radical cation, dication and trication. ESR
spectra of those ions obtained by chemical oxidation showed the doublet, triplet, and quartet spin
state, respectively [68]. First oxidation potentials of similar 1,3,5-tris(diarylamino)benzenes with
other substituents were also reported [69].
An early study of the newly synthesized 1,2,4,5-tetrakis(dimethylamino)benzene LXVIIa
(Scheme 29.17) showed [70] that the first oxidation step in MeCN is a two-electron process pro-
ducing the structurally distorted dication with no through-conjugation in the molecule. That was
contrary to the successive one-electron oxidations of N,N,N′,N′-tetramethyl-p-phenylenediamine in
–e –e
Me2N NMe2 LXVIIa LXVIIa+ LXVIIa2+
in CH2Cl2
R R + Bu4N[B{C6H3(CF3)2}4]
Me2N NMe2
–2e –e –e –2e
(LXVIIa) R = H LXVIIb LXVIIb2+ LXVIIb3+ LXVIIb4+ LXVIIb6+
(LXVIIb) R = NMe2 in MeCN/CH2Cl2
+ Bu4NPF6
SchEME 29.17 Anodic oxidation of tetrakis and hexakis(dimethylamino)benzenes LXVII.

MeCN [71] and hexaaminobenzene in nitromethane [72] producing radical cations in the first step.
However, in a recent careful analysis of the anodic properties of LXVIIa and similar compounds
in different media, Adams et al. [73] showed that the difference between the first and the second
oxidation potentials depends not only on structural changes during these processes but also on the
solvent and the electrolyte used. In particular, the stability of dications is enhanced by their strong
solvation and ion pairing with electrolyte anions. Both these phenomena favor the disproportion-
ation of radical cations and thus the two-electron step. Consequently, it was shown in an elegant
way that two one-electron CV steps could be obtained for the oxidation of LXVIIa in the nonpo-
lar solvent CH2Cl2 containing as a supporting electrolyte [Bu4N][B{C6H3(CF3)2}4] with large and
noncoordinating anions (Scheme 29.17). Moreover, crystal salts of radical cations LXVIIa+ • and
dications LXVIIa2+ (and a few similar compounds) were isolated and their structures determined
by x-ray diffraction [73].
The electrochemical oxidation of hexakis(dimethylamino)benzene LXVIIb in an MeCN/
CH2Cl2 mixture (1:1, v/v) containing NBu4PF6 showed in the first step a two-electron electrochem-
ically quasi-reversible process [74,75], whereas the one-electron reversible process was reported
earlier in CH2Cl2 at −50°C [76]. Both results look consistent with the aforementioned findings
of Adams et al. [73]. The slow two-electron kinetics [74] was related to the significant distortion
of the planar aromatic ring during the oxidation. Namely, the stable dication formed has two
noncoplanar polymethine units carrying one positive charge in each and connected by two single
C–C bonds. Such a structure was confirmed by X-ray examination of the salt LXVIIb2+ (PF6 −)2.
Further oxidation produced tri-, tetra-, and hexacations (Scheme 29.17), which undergo slow fol-
low-up reactions [74,75]. Computer simulation of CV curves at different scan rates made it pos-
sible to estimate standard potentials and rate constants for those electrode and chemical reactions
[74,75]. The increasingly greater sluggishness of electron transfers related to greater structural
changes was observed for the two-electron oxidation of monomeric peralkylated hexaamino(1,3)-
metacyclophane in the same medium showing an unusually big separation of anodic and cathodic
peaks [77]. On the other hand, sterically rigid dodecaamino(1,3,5)-cyclophane with almost planar
and parallel two hexaaminobenzene units (for which the twisted structure in a higher oxidation
state is not possible) showed two reversible one-electron oxidation steps at close potentials [77].
CV investigations of a number of meta-connected oligoarylamines showing a number of con-
secutive oxidation products that are stable in aprotic solvents were recently overviewed [1]. Among
synthetic macromolecules, the redox-active dendrimers gained increased attention over the last two
decades. Highly symmetrical hexaarylbenzene derivatives with six triarylamine redox moieties
gave two reversible pairs of CV peaks during the overall six electrons oxidation in CH2Cl2 [78].
Moreover, the selectively generated radical trication showed a strong intervalence charge-transfer
band in the near infrared (NIR). Potentials of the one-electron oxidation of polyamidoamine-type
dendrimers with p-phenylenediamine redox core (reversible in methanol but slow in some aprotic
solvents) obtained from the differential pulse voltammetry decrease with increasing size (and the
related electronic nature) of low-generation dendrimer chains [79]. The oxidation process strongly
affects the preferred geometry of chains, but not that of the dendrimer core [79]. Electrochemically
generated radical cations were characterized by ESR and UV/Vis NIR spectra [80]. References to
earlier works can be found in Reference 79.
III. AzO AND AzOxY COMPOUNDS

Azo compounds can be electrochemically reduced in aprotic as well as protic media and some
substituted derivatives can also be oxidized. The cathodic reduction of azobenzene (XVI), the
most intensively investigated representative, in MeCN and DMF containing tetraalkylammo-
nium salts where ion pairing is absent, occurs at mercury electrodes in two one-electron steps
(Scheme 29.18). The first of them is reversible and produces relatively stable radical anions
XVI− • detectable by the ESR method [81–83]. The second electron transfer is generally also
+e +e
Ph N N Ph [ Ph N N Ph ] – [ Ph N N Ph ]2 –
fast +SH, –S–

(XVI) (XVI– )
[ Ph N NH Ph ] –
(LXVIII)
SchEME 29.18 Electroreduction of azobenzene XVI in aprotic solvents.
reversible, but it yields more basic dianions that are protonated in a fast chemical reaction with
any proton donors, SH, available in solutions [82–84]. For example, the protonation of XVI2−
ion in DMF by residual water is reversible and the pKa of the formed PhNHN−Ph is 38.1 [85].
The chemically reversible second electron transfer to XVI in DMF containing neutral activated
alumina was observed after cooling [86]. However, the corresponding anodic peak disappears
after the addition of MeCN due to its deprotonation by azobenzene dianions [86]. Thus, the
observed irreversibility of the second CV peak depends on the solvent and the sweep rate used.
The presence of substituents decreasing the basicity of the dianion (as e.g., the para-nitro group)
also favors the reversibility of the second step [87]. Products of both reduction steps are oxi-
dized in air to the parent azo compound. Slow decomposition of the dianion or the protonated
dianion to arylhydrazine in DMF was reported [82] but in the presence of an excess of pro-
ton donors hydrazobenzene (VIII) was the final product. Note that the electrolytic generation
of dianions of substituted azobenzene and other aromatic azo compounds for the preparative
use as strong bases is reviewed in Chapter 43.
LXVIII + OH − −
2e
 → XVI + H 2O (29.3)
XVI + LXVIII + OH − 2XVI −· + H 2O (29.4)
Radical anions XVI− • (and analogous reactants bearing some substituents) formed in the first reduc-
tion step in aprotic media can disproportionate to the parent neutral molecules and dianions. In
particular, this reaction occurs in the presence of alkali metal cations used in a supporting electro-
lyte due to ion pairing phenomena [88]. The complicated disproportionation kinetics of ion pairs
formed by XVI− • with lithium cations in DMF were studied and the corresponding rate constants
were estimated [89]. A rapid disproportionation of protonated radical anions of benzo[c]cinnoline
generated by the electroreduction in tetrahydrofuran containing benzoic acid was also investigated
[90]. The effects of added proton donors of different acidity on polarographic curves of azobenzenes
were reported by Boto and Thomas (cf., review [87]), whereas the effects on CV curves in DMF by
Cheng and Hawley [85] and more recently by Astudillo Sánchez and Evans [83] in MeCN. The for-
mation of the monoanion of hydrazobenzene LXVIII shown in Scheme 29.18 was confirmed [83]
by the additional anodic peak observed after the addition of water. This peak corresponded to the
oxidation of LXVIII in reaction (29.3), whereas it was absent without added water because LXVIII
vanishes in reaction (29.4), unless it is eliminated at scan rates higher than 10 V s−1. On the other
hand, after the addition of water, hydrogen-bonded complexes XVI− • (H2O) and XVI− • (H2O)2 were
formed by radical anions [83]. Their formation constants equal to 3 and 1 M−1, respectively were
found from the shift of formal potentials with the water concentration. However, the kinetic analysis
also indicated the formation of a very weak XVI− • (H2O)3 complex. The proton transfer from water
molecule to radical anion within that complex was proposed in a detailed reaction mechanism [83].
It is followed by the electron transfer from the electrode (or in solution from XVI− •), finally resulting
in the formation of hydrated LXVIII (H2O)2.
Strongly alkaline media
+2e +2H2O
Ph N N Ph Ph N N Ph2 Ph NH NH Ph
–2 OH–
(XVI) (VIII)
+H+ Acidic media +e
+e +H+
Ph N NH Ph Ph N NH Ph Ph NH NH Ph
+ +
SchEME 29.19 Electrode reduction and oxidation processes of azobenzene XVI in aqueous media.
+H+ + +H+ + + +2e

VIII Ph NH2 NH Ph Ph NH2 NH2 Ph 2 Ph NH2
(I)
+ +
H3N-C6H4-C6H4-NH3
SchEME 29.20 Formation of aniline I by further reactions of hydrazobenzene VIII in acidic solutions.
The reversible reduction–oxidation processes of azobenzene in protic media, in particular the

most widely investigated water/alcohol systems, correspond to equilibria of the azo-hydrazo redox
couple. They depend strongly on the medium used (first of all on its acidity, but also on the nature
of a nonaqueous component) and the concentration of the reactant because of its adsorption. The
reaction sequences in acidic and strongly alkaline solutions are shown separately in Scheme 29.19
[2,4]. In both media, linear dependences of reduction potentials on pH were observed; for exam-
ple, the results obtained in 50% aqueous methanol using a pyrolytic graphite electrode were com-
pared [91] with literature data obtained at mercury electrodes. Hydrazobenzene (VIII) is the same
final product of the reduction in protic media of different pH. However, in acidic solutions (pH < 4)
instead of a two-electron reversible reduction to VIII an overall four-electron irreversible process
occurs including protonation of VIII formed in the first electrochemical step (Scheme 29.20) and
its cathodic reduction in the next step with N–N bond cleavage and the formation of aniline (I) [92].
It was shown [92] that unprotonated VIII is not active at electrodes and monoprotonated cation
catalyzes the hydrogen evolution. Only diprotonated hydrazobenzene undergoes reduction, but its
rearrangement to diprotonated benzidine that adsorbs at electrodes can additionally complicate the
process at lower pH values (Scheme 29.20).
A similar mechanism including the two-electron reduction of the azo group to the hydrazo group
in basic aqueous solutions and the four-electron process with N–N bond cleavage yielding sub-
stituted anilines in acidic media was suggested for many azo dyes (cf., the review [2]). Because
the N–N bond cleavage is catalyzed by acids and bases, one four-electron polarographic wave
was observed not only for XVI in acidic media but also in alkaline media for its derivatives with
electron-withdrawing substituents [93]. However, the four-electron reduction of N,N-dimethyl-4-
amino-4′-hydroxyazobenzene in water–methanol mixtures in the whole pH range determined by
coulometry was explained [94] by fast disproportionation of the hydrazo derivative formed in the
first two-electron exchange yielding two derivatives of aniline and the parent azo compound that is
further reduced.
A small difference in reduction potentials of metastable cis and stable trans isomers of XVI
was observed on mercury [95,96] and pyrolytic graphite electrodes [91]. In DMF at low tempera-
tures, cis-azobenzene is reduced in the one-electron process at potentials 60 mV more negative than
for the trans-isomer and this process is followed by rapid isomerization of the radical anion [95].
Both isomers are reduced at the same potential in pure aqueous solutions (where they are strongly
adsorbed) and in pure ethanol due to fast isomerization [96]. The same potential for both isomers
was also found in pure ethanol up to pH 11 (where there is no adsorption). However, in alkaline
ethanol solutions with pH > 11 cis-azobenzene is reduced at more positive potentials [96], which
was confirmed later using a channel electrode [97].
More recently, photomodulated voltammetry was used to determine accurate reduction poten-
tials for in situ generated cis-azobenzene in eight aprotic solvents [98]. Solvent effect on potentials
for both isomers was described by the empirical solvent parameter π*. The proposed mechanism
involved reversible heterogeneous and solution electron transfers for both isomers as well as isom-
erization equilibria [98].
Substituent effects on the electrode behavior of substituted azobenzenes are mainly caused by affect-
ing its basicity. Namely, electron-withdrawing substituents (e.g., –COOH, –SO3H, –CN) lowering the
basicity of the azo group facilitate its two-electron reduction, whereas electron-donating substituents
(e.g., –OH, –NH2, –N(Me)2) facilitate protonation and cleavage of the N–N bond [92]. Substituent
effects on the reduction potentials of azobenzenes and related compounds in different media were
intensively investigated and described in terms of the Hammett equation or related approaches. For
example, polarographic data were used to calculate substituent constants for a series of pyridylazo and
thiazylazo dyes in 50% ethanol [99]. Some other examples are reviewed in Reference 4.
On the other hand, the presence of the o-nitro substituent leads to cyclization. In particular, the
mechanism of preparative formation of substituted benztriazole-N-oxide and next benztriazole by
the electroreduction of o-nitrophenylazo-p-cresol in basic solutions was discussed by Bourgeois
et al. [100].
The electroreduction of many azobenzene derivatives with a number of substituents as well as
some other aromoatic azo compounds was widely studied in aprotic solvents and some interesting
results will be mentioned further on. Reduction of azobenzene-4-sulfonic acid in MeCN involves
autoprotonation and thus four separate consecutive waves were observed for azonium species and
sulfonate ions formed in a sequence of protonation equilibria [101]. Two one-electron reversible
steps were observed for the reduction of 2,2′,4,4′,6,6′-hexanitroazobenzene in MeCN and hexanitro-
hydrazobenzene was the final product in the presence of proton donors [102]. The electroreduction
of substituted 2-nitroazobenzene and 2-nitrohydrazobenzene in DMF with n-Bu4NClO4 yield-
ing 1,3-dihydroxy-2-phenylbenztriazole was reported [103]. However, in the presence of sodium
and lithium cations, 2-phenyl-benztriazole-N-oxide (which could be further reduced to 2-amino-
azobenzene) was the two-electron reduction product.
The cathodic behavior of a series of aromatic azo compounds, including azonaphthalenes and azo-
anthracenes, is similar to that of XVI. In particular, it was well established that the first one-electron
step yielding radical anions is reversible [87]; for example, it was observed for 1,1′-azonaphthalene
and 4,4′-azopyridine in DMF [82], 2,2′- and 4,4′-azopyridine, 2-, 3- and 4-phenylazopyridine
in MeCN [86]. The formation of ion pairs between radical anions of 2,2′-azonaphthalene with
Li+ cations in DMF and kinetics of their disproportionation were described [104]. For a series of
2-a rylazaanthraquinones in benzonitrile solutions, the reduction of the azo group to the hydrazo
group was reported in the first step before the reduction of the quinone moiety [105]. The reaction
entropy of the formation of radical anions of aromatic azo compounds in MeCN was measured
and related to the reactant size and the spin density at the nitrogen atom of a radical anion [106].
On the other hand, the reduction of 1-azuleneazobenzene and other azo-1-azulene compounds in
MeCN exhibited [107] a quasi-reversible first electron transfer (which produces unstable radical
anions generating polymeric films) and an irreversible second step. Finally, two respective amines
were formed by N–N bond cleavage, but unstable 1-aminoazulene could only be produced at very
low temperature [107].
Thanks to a good understanding of the behavior of the azobenzene–hydrazobenzene redox cou-
ple, it was possible to broaden the scope of its use and look for some new applications. The elec-
trochemical study on Au(111) of self-assembled monolayers containing azobenzene [108] can be
mentioned here as well as a recently proposed azobenzene-functionalized electrode [109], which
– –
O O O OH
+e +e SH, –S–
Ph N N Ph Ph N N Ph Ph N N Ph Ph N N Ph
(LXIX) (LXIX– ) (LXIX2–) –OH–
XVI2– XVI– Ph N N Ph
+e +e
(XVI)
SchEME 29.21 Mechanism for the electroreduction of azoxybenzene LXIX in DMF.
could act either as a cathodic molecular rectifier stopping the anodic current or as an anodic recti-
fier. The CV behavior of azobenzene microcrystals attached to a graphite electrode can also be
mentioned [110].
Azobenzene itself could not be oxidized in acetate buffer solutions at a pyrolytic graphite
electrode [111]. However, after substitution by electron-donating groups, like the N,N-dimethyl
group, the oxidation of the substituent was observed at graphite [111] and platinum disk [112]
electrodes, without affecting the azo group. For azo-azulene compounds [107], the irrevers-
ible anodic oxidation of the azulene moiety having a higher electron density occurs more
easily than that of the azo group. On the other hand, it was recently proven that the oxidation
of azobenzene derivatives in aprotic solvents occurs easily. For example, 3-nitroazobenzene
gives two one-electron irreversible CV peaks in MeCN and the first electron transfer from
4-nitro-4′-methoxy-azobenzene in dry methylene chloride with the formation of radical cation
is reversible [113].
The electroreduction of azoxybenzene (LXIX) in DMF starts from the one-electron step, result-
ing in the reversible formation of the respective radical anions [114] (Scheme 29.21).
Similar behavior was also found for its derivatives, and the formation of radical anions of
2,2′-dimethylazoxybenzene was recently confirmed by in situ EPR experiments [115]. The second
electron transfer (also reversible according to recent investigations [115]) is followed by a rapid
reaction of dianions with the final formation of azobenzene XVI, which is immediately reduced
because its formal potential corresponds to more positive values, before the first reduction peak of
LXIX [114,115]. Thus, the azobenzene peak is observed in CV curves during the second scan [115].
However, after the addition of an effective proton donor, a “pre-peak” appears also in the first scan.
Careful analysis of CV behavior in dry DMF and after the addition of proton donors has allowed
Simonet and coworkers to identify [115] the follow-up reaction as the protonation of dianions by
acidic impurities or solvent molecules, SH. This reaction is followed by fast elimination of OH− ions
[115]. The general mechanism shown in Scheme 29.21 can explain different CV behavior reported
under different experimental conditions (using various scan rates and solvents of varying level of
impurities): the reduction of intermediate radical anions XVI− • was observed by Lipsztajn et al.
[114] as a separate third peak, whereas Simonet et al. [115] observed for substituted azoxybenzenes
one irreversible three-electron peak including the reduction of a radical anion to a dianion as well
as the two-electron reduction of substituted azobenzene. However, in the presence of alkali metal
cations of the supporting electrolyte, the CV behavior was seriously changed due to the follow-up
reactions of ion associates [114].
On the other hand, in protic solvents azoxybenzene and its derivatives undergo a four-electron
and four-proton reduction to hydrazobenzenes [91,92,116]. This process is more difficult than the
analogous reduction of azobenzenes that can be observed at more positive potentials in the second
scan. Linear dependencies of half-wave potentials on pH for the four-electron reduction of LXIX
in acidic and alkaline media were determined [91]. In acidic solutions with pH < 4, the polaro-
graphic reduction of azoxybenzene exhibits a second two-electron wave [91,92] that corresponds
to the reduction of diprotonated hydrazobenzene cations to aniline in the same process as is shown
in Scheme 29.20. This process is difficult to observe for the reduction of original hydrazobenzene
VIII because of its fast rearrangement to benzidine [92]. Moreover, VIII is not reducible at the
dropping mercury electrode in less acidic media. During the reduction of LXIX in MeOH with LiCl
as the supporting electrolyte, only one four-electron wave was observed [117]. The detailed reduc-
tion mechanism of substituted azoxybenzenes at the controlled potential mercury pool cathode was
investigated by Hazard and Tallec [116]. In particular, it was shown that p-, m-, and o- nitro and
dinitro derivatives undergo reduction in buffered solutions forming in the first four-electron pro-
cess the respective hydrazo compounds. Complicated schemes for further reactions including the
reduction of nitro groups and the disproportionation of ortho- and para-substituted intermediates to
substituted anilines as well as the formation of 2-phenyl-benztriazoles from o-nitro and o,o′-dinitro
compounds were proposed [116].
Quantitative reduction of azoxytoluene to hydrazotoluene on a stainless steel electrode in alka-
line ethanol–water solutions [118] can be pointed out as an example of the use of azoxy compounds
in preparative electrolysis.
IV. ARYL DiAzONiUM SALTS

Cathodic reduction of aryl diazonium salts in protic and aprotic media has been studied very inten-
sively for many years because of potential applications of such processes in preparative electro-
chemistry like phenylation of various compounds and more recently in the derivatization of the
electrode surface through the electrografting of aryl groups. The last process is discussed in detail
in Chapter 42 and will not be discussed here. However, the general mechanism of the formation of
aryl radicals from diazonium salts at electrodes and their further reactivity will be briefly reviewed.
In early polarographic studies of benzenediazonium salts (also bearing some substituents), it was
established [119–123] that the reduction process in aqueous acidic solutions exhibits two waves. The
first one is pH independent and corresponds to a one-electron process as confirmed by coulometric
data [119–122]. The last observation as well as the isolation of diaryl mercury and aryl-mercuric
chlorides [119,121] indicated the formation of radicals as intermediates. It was suggested [121,122]
that these intermediates are diazenyl radicals PhN2•, which adsorb on a mercury electrode and
decompose to phenyl radicals in further reactions. The second three-electron and pH dependent
process, complicated by side reactions, affords in acidic solutions phenylhydrazine PhNH–NH2 as
the final product during preparative electrolysis [122,123].
In aprotic solvents like sulfolane [124] and acetonitrile [125–128], the first electroreduction step
of benzenediazonium tetrafluoroborates (LXX) is also a one-electron process resulting in the for-
mation of phenyl radicals. This was confirmed indirectly by identification of final products. For
example, the isomer ratio of biaryls formed during the electrolysis in the presence of a number
of aromatic compounds and partial rate factors of these reactions were in accordance with those
obtained for well-known free radical phenylation [125]. Moreover, the low-temperature reduction of
LXXa in MeCN at a mercury pool cathode in the presence of α-phenyl-N-tert-butylnitrone showed
a strong ESR signal of the adduct with the phenyl radical [126]. However, the slope of the polaro-
graphic wave of the reduction of LXXb in sulfolane suggested a reversible process [124]. Thus,
the formation of intermediate PhN2• radicals in the first step followed by the C–N bond cleavage
in the second step was assumed in earlier papers [124,125]. However, when using glassy carbon
electrodes and small concentration (below 1 mM) of LXX in order to diminish fouling of the elec-
trode surface, it was recently established [109] that the first step is a concerted electron transfer and
bond cleavage (see also Chapters 13 and 14). This mechanism, shown in Scheme 29.22, was evident
from the observations that are presented further on. The reduction of LXXc in MeCN exhibits an
irreversible broad CV peak, followed by the reversible cathodic and anodic peaks of nitrobenzene
[127], which were formed after the C–N bond cleavage. The width of the first peak equal to 180 mV
is characteristic of concerted processes. Similar peak widths were found [128] for LXXa and LXXb
+e
X C
+ +e
X N N N2 + X C
–BF4–
BF4– +H
X
(LXXa) X = H
(LXXb) X = Me
(LXXc) X = NO2
SchEME 29.22 Pathways for the electroreduction of benzenediazonium tetrafluoroborates LXX in aprotic
media.
giving the apparent transfer coefficients α = 0.34 and 0.30, respectively. These low values of α indi-
cate a concerted mechanism with great reaction driving force that is necessary to overcome very
strong activation free energy, which includes additional contribution from the bond energy [129].
Moreover, a very small second peak was observed at more negative potentials in MeCN and DMSO
[128]. It corresponds to the reduction of phenyl (or substituted phenyl) radicals to anions. The simu-
lation of CV curves permitted the authors to confirm the proposed mechanism and to determine the
standard potential of the Ph·/Ph− couple in MeCN as being equal to 0.05 V versus SCE. Moreover,
Ph· radicals undergo a competitive reaction of a fast hydrogen atom transfer from solvent molecules
diminishing the second peak (Scheme 29.22). A good linear correlation of peak potentials for a
series of aryldiazonium salts against the Hammett substituent constants supported the validity of
the concerted mechanism for other compounds [128].
Application of phenyl radicals, generated electrochemically by the reduction of LXXa in MeCN,
to phenylation of naphthalene and benzene and its derivatives with total yields of different isomers
up to 33% was reported [125]. The low yields were caused by the competitive H atom abstraction
from the solvent by phenyl radicals. On the other hand, the cyclization of free radicals generated
by the reduction of diazonium salts of 2-amino-cinnamic acid derivatives at a mercury electrode
in MeCN affords phenanthrene-10-carboxylic acids with 80–96% yields [130]. Some reactions of
benzenediazonium cations formed in MeCN solutions during the anodic oxidation of triazenes will
be considered in Section V.
V. AROMATic TRiAzENES
Aromatic triazenes can be electrochemically reduced or oxidized. Most investigations performed
around 1972 were reviewed by Iversen [131] who collected half-wave potentials obtained as a result
of the polarographic reduction of 1,3-diphenyltriazene (LXXI) and its phenyl substituted derivatives
in aqueous-alcoholic solutions of different pH. After extensive research, Holleck and Kazemifard
concluded [132] that aniline and phenylhydrazine (or their derivatives in the case of substituted
LXXI) are formed as the final products of the overall four-electron reduction process in neutral
50% aqueous methanol as is shown in Equation 29.5. Only one polarographic wave was observed in
methanol solutions containing organic acids, but the same final products were found [133]. A tenta-
tive scheme of reduction pathways was proposed [132], but details were not proven.
C6H5–N = N–NH–C6H5 + 4e + 4H2O → C6H5–NH2 + C6H5–NH–NH2 + 4OH− (29.5)
Peak potentials for the one-step irreversible reduction and the two-step irreversible oxidation of a
series of asymmetric 1-phenyl-3-alkyltriazenes in MeCN were reported [134]. No signals were found
in simultaneous ESR experiments indicating a rapid consecutive reaction of primary radical products.
However, using spin-trapping some radical products of the fragmentation started by electrode processes
were identified. The obtained results suggest two tautomeric forms of the investigated triazenes [134].
Me + Me –Other Me
+ – +
N N N N N N N
Products
Me Me Me
2+)
–e (LXXIIb (LXXIVa)
+
R’ R’ – N2 Me Me
–e +
R N N N R N N N N N
Me Me (A) Me Me
(LXXIIa) R’ = Me, R = H
(LXXIIb) R’ = Me, R = N(Me)2 (LXXII+ ) (LXXIIIb+ )
(LXXIIc) R’ = Me, R = OEt
(LXXIId) R’ = Me, R = OMe
(LXXIIe) R’ = Me, R = Me
(LXXIIf) R’ = p-C6H4OMe, R = N(Me)2
(LXXIIg) R’ = p-C6H4OMe, R = NO2
(LXXIIh) R’ = p-C6H4OMe, R = OMe
(B)
(D) (C) +
N OMe + R N N
Me
+
Me Me +
(LXXIVa) R = N(Me)2
–
R N N + N N + R N N (LXXIVb) R = NO2
Me Me (LXXIVc) R = OMe
+e –e +e –e (LXXIVd) R = OEt Me
(LXXIVe) R = Me N
Me OMe
+N (LXXIVa)
+ (LXXIVb)
R N N Me
(LXXIVc) MeO N
Me
(LXXIV) + NH2
(LXXV)
Me-C CH-CN
(LXXVI) –e
LXXV+
R N N C-CN
H2N-C-Me
(LXXVII) R = OEt, OMe, Me, H, Br, CF3
SchEME 29.23 Proposed pathways for the anodic oxidation of aromatic triazenes LXXII in different media.
The anodic oxidation of 1-phenyl-3,3-dimethyltriazene (LXXIIa) in nitromethane solutions indi-

cated [135] the cleavage of the primary radical cation to phenyldiazonium ion as the main reaction
route, but this cleavage occurs only as a side reaction in MeCN. On the other hand, the oxidation of
1-(p-dimethylaminophenyl)-3,3-dimethyltriazene (LXXIIb) at a platinum-rotating disk electrode
in aqueous media showed [136] two waves independent of pH and corresponding to one-electron
steps with the formation of the radical cation LXXII+ • and next the dication LXXII2+ as is shown
in the top part of Scheme 29.23. However, the experimental detection of intermediates LXXII+ •
and LXXII2+ was possible only in aprotic media, and it was reported by Speiser and coworkers in
a series of papers [137–140] elucidating the details of the oxidation mechanism of aryl triazenes in
MeCN at Pt electrodes. Different pathways and products of the decay of radical cations LXXII+ •
were found depending on the nature of substituents. For the first oxidation step of LXXIIb, simula-
tions of CV peaks confirmed the eC mechanism with the reversible electron transfer (rate constant
equal to 0.01 s−1) followed by a slow and irreversible reaction [137]. ESR spectra during the elec-
trolysis of LXXIIb at room temperature indicated [137] the expulsion of nitrogen and the formation
–e + LXXI+ + H2O
N N N LXXI+ 2 LXXI + 2 H+
H –1/2O2
(LXXI)
2 N N N
H H
2 H2N N N
(LXXVIII)
SchEME 29.24 Anodic oxidation of 1,3-diphenyltriazene LXXI in MeCN.
of N,N,N′,N′-tetramethyl-p-phenylenediamine radical cation (Wursters Blue, LXXIIIb+ •) accord-

ing to the pathway (A) in Scheme 29.23. Moreover, the rapid decomposition of dications LXXIIb2+
resulted in the formation of p-dimethylaminobenzenediazonium cations (LXXIVa) as the main
product (Scheme 29.23). Benzenediazonium cations with different substituents were identified elec-
trochemically (by their reduction peaks) as decay products of radical cations LXXII+ • formed by
the oxidation of other 1-(p-substituted-phenyl)-3,3-dimethyltriazenes. Thus, the existence of the
bond cleavage between N(2) and N(3) was confirmed [138]. On the other hand, 2,7-dimethoxy-5,10-
dimethyl-5,10-dihydrophenazine radical cation (LXXV+ •) was identified using ESR and ENDOR
spectroscopy during the electrochemical as well as chemical oxidation of LXXIIf, LXXIIg, and
LXXIIh [138] according to the pathway (B) in Scheme 29.23.
Finally, evident ESR spectra of radical cations LXXII+ • were obtained using a rapid-scan spec-
trometer in situ for the anodic oxidation of LXXIIb and LXXIIc as well as for LXXIIf and LXXIIg
[139]. Uv–Vis spectra of LXXII+ • were also recorded during the voltammetric experiments. In par-
ticular, for the oxidation of LXXIIc, separate absorption bands were observed for the reactant (at
292 and 326 nm), for the radical cation (at 440 nm and a flat maximum above 600 nm), and for the
product 4-ethoxybenzenediazonium ion LXXIVd (at 317 nm) [139]. All experimental data support
the eCe mechanism with the bond cleavage as the chemical step that can occur either by afford-
ing directly LXXIV and dimethylaminyl radical according to the pathway (C) or by the formation
of diazenyl radical and its further oxidation through the pathway (D) [139]. Further reactions of
diazonium ions LXXIV generated in the anodic oxidation in MeCN solutions include first of all
the coupling with 3-aminocrotoninitrile (LXXVI) generated simultaneously at the cathode. This
reaction produced enamines LXXVII as the main product with estimated yields of 25–30% [140].
However, for LXXIIg with the electron-withdrawing NO2 substituent, 4-nitrobenzenediazonium
ions LXXIVb were formed only after the oxidation to dications LXXII2+ [139] and nitrobenzene is
the main product of the decay of LXXIVb [140].
On the other hand, the extensive study [135] of the oxidation of 1,3-diphenyltriazene LXXI in
MeCN solutions using voltammetry at a platinum-rotating electrode and the CV technique proved
the formation of a radical cation in the one-electron step and its back reduction in the homogeneous
reaction with residual water (Scheme 29.24). Further protonation of LXXI and next a rearrangement
result in the formation of p-aminoazobenzene (LXXVIII).
AckNOwLEDGMENT
The author wishes to express his indebtedness to the late Stanisław J. Jaworski, PhD student at the
University of Gdańsk, for his kind help in the preparation of schemes.
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30 Reduction of Nitro
Compounds and
Related Substrates
Ole Hammerich
CONTENTS
I. Introduction ........................................................................................................................... 1150
II. Nitro Compounds ...................................................................................................................1151
A. Aromatic Nitro Compounds...........................................................................................1151
1. Formation and Properties of the Radical Anions and Dianions............................1151
2. Mononitrobenzenes .............................................................................................. 1152
3. Other Mononitroarenes......................................................................................... 1166
4. Di- and Trinitroarenes .......................................................................................... 1166
5. Hetereoaromatic and Related Mono- and Dinitro Compounds.............................1170
B. Aliphatic Nitro Compounds ...........................................................................................1170
1. Formation and Properties of the Radical Anions ..................................................1171
2. Nitroalkenes and Related .......................................................................................1172
3. Mononitroalkanes and Related ..............................................................................1174
4. Dinitroalkanes .......................................................................................................1176
5. Trinitroalkanes ......................................................................................................1178
6. Tetranitroalkanes ...................................................................................................1179
7. α-Halonitroalkanes ................................................................................................1179
8. β-Substituted Nitroalkanes ................................................................................... 1180
9. α,β-Disubstituted Nitroalkanes..............................................................................1181
III. Nitroso Compounds ...............................................................................................................1181
A. Aromatic Nitroso Compounds .......................................................................................1181
1. Formation of and Properties of the Radical Anions and Dianions .......................1181
2. Routes to Phenylhydroxylamines and Anilines .....................................................1182
3. Routes to Azoxybenzenes, Azobenzenes, Hydrazobenzenes, and Benzidines .....1183
4. Other Reactions of Nitrosobenzenes .................................................................... 1184
5. Nitronitrosobenzenes ............................................................................................ 1184
6. Heteroaromatic and Related Nitroso Compounds .................................................1185
B. Aliphatic Nitroso Compounds .......................................................................................1185
1. Primary and Secondary Nitrosoalkanes................................................................1185
2. Tertiary Nitrosoalkanes .........................................................................................1185
3. α-Halonitrosoalkanes.............................................................................................1185
4. Nitronitrosoalkanes (Pseudonitroles) ................................................................... 1186
IV. Hydroxylamines .................................................................................................................... 1186
A. Aromatic Hydroxylamines ............................................................................................ 1186
B. Aliphatic Hydroxylamines ............................................................................................ 1186
1149
V. N-Nitramines, N-Nitrosamines, N-Nitramides, and N-Nitrosamides ................................... 1187

A. N-Nitramines and N-Nitrosamines ............................................................................... 1187
B. N-Nitramides and N-Nitrosamides................................................................................ 1188
VI. Nitric Acid Esters ...................................................................................................................1189
References .................................................................................................................................... 1190
I. INTRODUcTiON
The electrochemical reduction of nitro compounds played an important role in the development of
organic electrochemistry in the early period around 1900 [1]. For example, it was studies of the
stepwise reduction of nitrobenzene that originally led Haber [2] to realize the importance of the
potential of the working electrode in electrochemistry and to establish the redox relationship between
nitrobenzene, nitrosobenzene, phenylhydroxylamine, aniline, p-hydroxyaniline, azoxybenzene, azo-
benzene, hydrazobenzene, and benzidine [2,3]. The essential parts are reproduced in Scheme 30.1.
This early knowledge of the products that may result from reduction of nitro compounds stems
from reactions carried out in aqueous solutions or suspensions and the first insight into the reaction
details have resulted from early polarographic investigations, also in aqueous solution. Later this
was supplied by studies in nonaqueous and aprotic media. The latter in particular have allowed for
the observation of the primary electrode products, the radical anions and dianions.
In this chapter, we will discuss the reduction of organic nitro compounds and some of the reduc-
tion products. As seen in Scheme 30.1, nitroso compounds are intermediates in the reduction of
nitro compounds and their electrochemistry is therefore included under nitro compounds when
needed. Electrochemical processes in which the nitroso compounds are the starting materials are
treated separately. The electrochemistry of azoxybenzene, azobenzene, hydrazobenzene, and ben-
zidine is only included to the extent necessary for the discussion. A more detailed account of the
electrochemistry of these dimers is given in Chapter 29. The readers of this chapter may also find
discussions of interest in Chapter 44 and in other electrochemistry books [4–8]. Some preparative
aspects have been briefly reviewed [9].
Ph NO2
+2e–,+2H+ –H2O
Ph NO
Ph N+ N Ph
+2e–,+2H+
–H2O O –
Ph NHOH +2e–,+2H+ –H2O
+2e–,+2H+
Ph N N Ph
–H2O
HO NH2 Ph NH2 +2e–,+2H+
Acidic Ph NH NH Ph
Conditions
H2N NH2
SchEME 30.1 Overview of the products that may result from the reduction of nitrobenzene.
Reduction of Nitro Compounds and Related Substrates 1151
II. NiTRO COMPOUNDS

A. AroMaTIC NITro CoMpoUNDS
1. Formation and Properties of the Radical Anions and Dianions
The electrochemical reduction of nitrobenzene to a persistent radical anion may be observed
in almost any aprotic solvent. Examples include MeCN [10–13], DMF [11,14–20], DMSO [11],
CH 2Cl2 [21], THF [11], and propylene carbonate [22] and specialty solvents such as liquid [23] and
supercritical ammonia [24] and room temperature ionic liquids [25]. The same is true for many
substituted nitrobenzenes [10,11,13,16,19,22,26–57] and other aromatic [19,20,26,58–60] or het-
eroaromatic nitro compounds [61–68] as long as the structures do not include, for instance, acidic
hydrogens that may protonate the radical anions (self-protonation; see Section II.A.2.a.i). Other
exceptions include radical anions that owing to a high local spin density undergo (reversible)
dimerization as observed, for example, for 1,3,5-trinitrobenzene [19,69,70], 3,5-nitropyridine
[70], and 9-nitroanthracene [19,71] and radical anions that carry a potential leaving group such
as a halide ion [72–74].
The formation and reoxidation of the radical anions of nitrobenzene and substituted nitroben-
zenes in aqueous solution or in mixtures of an organic solvent and water require nonacidic condi-
tions in order to avoid protonation of the radical anion [75–78]. Radical anions have been observed
also in aqueous solutions containing micellar components [79].
Further reduction of the nitrobenzene radical anion to a persistent dianion requires the
strict absence of proton donors, including residual water [14], or low temperature as in liq-
uid ammonia [23]. Less reactive dianions are observed for nitrobenzenes carrying phenyl
substituents [31], one or more extra nitro groups [19,22,35,36,38–47,56,80], or another electron-
withdrawing group such as nitroso [48], azo [49], carbonyl [50,51], methylsulfonyl [55], N,N-
dialkylsulfamoyl [52], and 3-thioxo-3H-1,2-dithiol-5-yl [81] or a combination of some of these
structural features [53]. The dianions of 1,3-dinitrobenzene [40,42], 1,3,5-trinitrobenzene [69],
methyl 3,5-d initrobenzoate [42], and 2,2′,4,4′-tetranitrobiphenyl [46] have been reported to have
a biradical nature.
Radical trianions and even tetraanions have been observed for tetranitro compounds such as
2,2′,4,4′-tetranitrobiphenyl [46] and 2,2′,4,4′-tetranitrodiphenylmethane [19].
Reduction potentials have been recorded for a number of substituted nitrobenzenes [10,13,82,83],
and not unexpectedly electron-withdrawing substituents make the nitro compounds easier to reduce
and electron-donating substituents make them more difficult to reduce. Reduction potentials have
also been recorded in DMF for a large series of nitroarenes [19]. The experimental values of E°′ have
been found to correlate linearly with calculated values of E LUMO [10,84] illustrating the well-known
fact that the changes in solvation energies and other properties associated with electron transfer
usually vary gradually along a series of related compounds. Similarly, the relationship between
experimental values of E°′ and calculated electron affinities has been discussed [85]. Advances in
computer technology and the development of user-friendly software have now made it possible also
to obtain redox potentials for the reduction of nitrobenzenes by calculation, typically at the DFT
level of theory [86,87] (see Chapter 6 for details).
The solvation energy changes associated with the reduction of aromatic nitro compounds to
the radical anions in aprotic solvents are in the range −40 to −70 kcal mol−1 [11]. The entropy
of formation of the radical anions in MeCN has been determined for a series of mono-, di-,
and trinitrobenzenes and alkyl substituted derivatives and was found to be influenced by both
steric and electronic effects. Values are typically in the range −10 to −20 cal K−1 mol−1 [35].
The thermodynamics for the successive electron transfers for a series of polynitro compounds
addressing the effects of internal properties and the effects of solvation and ion-pairs have been
investigated as well [36,45]. Of course, any interaction that stabilizes the radical anion and
dianion in solution relative to the precursor will make reduction easier and not only stabilization
by solvation, but also by ion-pairing [22,39,45,60,79,88–97] and hydrogen-bonding [21,38,98],

facilitates reduction. In general, ion-pairing is stronger with alkali metal ions than with tetra-
alkylammonium ions, dications are more effective than monocations, and the dianions of the
nitro compounds are more affected than the radical anions. For example, the disodium salt of
the nitrobenzene dianion has been isolated from MeCN/NaClO 4 solutions [99] and ion pairs
with Mg2+, Ca 2+, and Ba 2+ have been observed as insoluble deposits at the working electrode
surface [89].
The first electron transfer resulting in the formation of the radical anion is reversible during
slow sweep cyclic voltammetry. Impedance measurements at mercury cathodes in MeCN have
shown [30,100–102] that the values of the heterogeneous electron transfer rate constants, k s, are
larger than approximately 2 cm s−1 unless substitution in the 2,6-positions hinders coplanar-
ity of the nitro group and the aromatic ring. In that case, the values of k s are lower, typically
in the range 0.1 < k s/cm s−1 < 0.8 illustrating the importance of the Marcus inner reorganiza-
tion energy in determining the kinetics of the electron transfer process [100]. Smaller values
than this have been observed for sulfur containing nitro compounds; this has been attributed
to adsorption effects [103]. The Marcus outer reorganization energy, related to the solvation
energy changes, appears to be a significant factor in determining k s in ionic liquids [30], where
also diffusion coefficients are observed to be much smaller than in, for instance, MeCN [29].
The reversibility of the first electron transfer process makes the radical anions suitable as elec-
tron donors in redox catalysis [104,105]. We are not aware of quantitative studies of the second
electron transfer for mononitrobenzenes. For dinitrobenzenes, the values of k s are typically
around 0.01 cm s−1 [80].
UV/Vis [16–18,20,26,31,32,59,69], IR [38], and ESR [12,13,27,33,34,42,44,57,58,61,62,64,65,74,
77,79,106–109] spectra have been recorded for the radical anions of a number of aromatic and het-
eroaromatic nitro compounds, and from the ESR spectra of the planar systems, it is evident that the
spin is well distributed over the entire molecule. More localized spins are observed for compounds
in which substituents in the 2- or 2,6-positions force the nitro group out of the plane defined by the
aromatic ring.
The acidity in DMSO of a series of nitrobenzene radical anions, such as nitrophenol radical
anions, has been determined via a thermochemical cycle and the pKa values were found to be typi-
cally 5–10 units higher than those for the neutral substrates [37].
2. Mononitrobenzenes
The electrochemistry of compounds in which a single nitro group is attached to a benzene ring or a
substituted benzene ring, including nitrophenyl substituted heterocyclic compounds, is discussed in
this section. Mechanism studies, mostly focused on protonations, are presented first and after this
some preparative aspects of nitrobenzene reduction are discussed.
a. Routes to Nitrosobenzenes, Phenylhydroxylamines, and Anilines

i. Mechanisms of Protonation in Aprotic Solvents As it appears from Section II.A.1, the acid-
ity of the residual water present in the commonly used aprotic solvents is not sufficient to protonate
the nitrobenzene radical anion at the time scale of slow sweep voltammetry. This is not so with the
more basic dianion. The voltammetric response of nitrobenzene in DMF [17,57,110,111] propylene
carbonate [22] and liquid ammonia containing 2-propanol [23] is composed of a one-electron pro-
cess leading to the radical anion (Equation 30.1), and, at lower potentials, a three-electron process
leading to phenylhydroxylamine (Equation 30.2). The anion of the latter, Ph-NHO−, was detected
by its oxidation peak during CV [23].
+e–
Ph NO2 Ph NO2 – (30.1)
–e–
+e– H2O OH +e–

Ph NO2 – Ph NO2– Ph N Ph NO
–e– 2
–OH– –OH– –e–
O–
(30.2)
+e– H2O H2O
Ph NO – Ph NO2– Ph NHO– Ph NHOH
–e– –OH– –OH–
Nitrosobenzene is more easily reduced than nitrobenzene and the nitrosobenzene dianion is there-
fore formed directly at the potential required to produce the nitrobenzene dianion. However, the
reaction scheme may be slightly more complex than shown here. For instance, solution electron
transfers, such as the reduction of nitrosobenzene by the nitrobenzene radical anion, are not included
and it is also known that nitrosobenzene and phenylhydroxylamine under strongly basic conditions
exist in equilibrium with the nitrosobenzene radical anion [112,113]. See Equation 30.13.
The unknown concentrations of residual water in the commonly used aprotic solvents make it
almost impossible to control the acid–base reactions that accompany the electrochemical reduc-
tion of aromatic nitro compounds in these solvents. For that reason, and for gaining more insight
into the protonation of the radical anions, a number of studies have addressed the effect of addition
of acids stronger than water [22,23,28,111,114–117]. The general observation is that a pre-wave
develops at the expense of the original one-electron wave with increasing concentrations of acid
and grows to the height of a 4F process. A variety of organic acids such as p-toluenesulfonic, tri-
chloroacetic, o-phthalic, salicylic and benzoic acid have been used and the results indicated that
the reduction proceeds via a hydrogen-bonded complex formed between the nitrobenzene and the
acid in the double layer [114–116]. Hydrogen-bonded complexes have been reported also for the
radical anions [21,92,118]. Protonation leads to the hydroxylamine [111,114], here illustrated by
the reduction of p-chloronitrobenzene (Equation 30.3) [114]. This is similar to what is observed
in aqueous solution (see Section II.A.2.a.ii). The sequence of the electron and proton transfers is
usually not addressed.
+4e–,+4H+
Cl NO2 Cl NHOH (30.3)
–H2O

A variant of the protonation reaction is observed when the nitrobenzene itself carries an acidic
function such as a phenol or a carboxylic acid group. In those cases, and in the absence of delib-
erately added acids, the primarily formed radical anion is protonated by the substrate in a so-
called self-protonation or father–son reaction, here illustrated by the reduction of m-nitrophenol to
m-hydroxylaminophenol in DMSO (Scheme 30.2) [33,119]. This particular reaction sequence leads
to an overall 0.8F stoichiometry (Equation 30.4).
+4e– –
5 m-HOC6H4NO2 m-HOC6H4NHOH + 4 m- OC6H4NO2 + H2O
(30.4)
A similar reaction scheme describes the reduction of nitrobenzoic acids [120,121], of nitroimid-
azoles and nitroindoles [63,122] and of nitrobenzenesulfonamides [123]. An additional complex-
ity is observed for p-nitrophenol [25,34,119,124]. In this case, the p-hydroxylaminophenol suffers
rapid dehydration to a quinone imine that under the conditions is further reduced to p-aminophe-
nol requiring an additional two electrons and two protons (see Section II.A.2.c.iv). Accordingly,
the stoichiometry in this case, and for o-nitrophenol, changes to an overall ∼0.85F process
(Equation 30.5).
+6e– –
7 p-HOC6H4NO2 p-HOC6H4NH2 + 6 p- OC6H4NO2 + 2H2O
(30.5)
+e–
m-HOC6H4NO2 m-HOC6H4NO2 –
–e–
–
m-HOC6H4NO2 – + m-HOC6H4NO2 m-HOC6H4NO2H + m- OC6H4NO2
m-HOC6H4NO2H + m-HOC6H4NO2 – m-HOC6H4NO2H– + m-HOC6H4NO2
–
m-HOC6H4NO2H– + m-HOC6H4NO2 m-HOC6H4NO + m- OC6H4NO2
–H2O
–
m-HOC6H4NO + m-HOC6H4NO2 – m-HOC6H4NO + m-HOC6H4NO2
– –
m-HOC6H4NO + m-HOC6H4NO2 m-HOC6H4NOH + m- OC6H4NO2
m-HOC6H4NOH + m-HOC6H4NO2 – m-HOC6H4NOH– + m-HOC6H4NO2
–
m-HOC6H4NOH– + m-HOC6H4NO2 m-HOC6H4NHOH + m- OC6H4NO2
SchEME 30.2 Self-protonation mechanism for the reduction of m-nitrophenol in DMSO.
In contrast, the radical anions of 3-nitro-1,2,4-triazole-5-ones that also carry labile hydrogen
atoms have been reported to undergo tautomerism in MeCN [61], but apparently not self-protonation.
ii. Mechanisms of Protonation in Water and Other Protic Solvents Studies of the reduction of
nitrobenzene in aqueous solutions have been in focus since the dawn of organic electrochemistry, and
it was observed early that the polarographic response for nitrobenzene and substituted nitrobenzenes
was dependent on pH and on the presence of surfactants. The pH dependence reflects the participa-
tion of protons in the reduction process, whereas the effect of the surfactants indicates that adsorption
of the starting material and/or intermediates and/or products contributes to the detailed description of
the reaction mechanism. The extent to which adsorption plays a role depends not only on the nature
of the electrode material [75,125] but also on the structure of the nitro compound, its concentration,
and solubility. Often it is assumed that adsorption plays only a minor role at substrate concentrations
<0.1 mM. The low solubility of most nitrobenzenes in water is the reason why mechanism studies
occasionally are conducted in the presence of an organic co-solvent, often an alcohol or DMF.
Two polarographic or voltammetric waves are observed for the reduction of nitrobenzene under
acidic conditions (0 < pH < 5) corresponding first to the formation of the protonated phenylhydrox-
ylamine (Equation 30.6) and at lower potentials to the further reduction of the protonated hydroxyl-
amine to the anilinium ion (Equation 30.7) [79,110,121,126–137].
+4e–,+4H+
(Ar NO2)H+ Ar NH2OH+ (30.6)
–H2O

+2e–,+2H+
Ar NH2OH+ Ar NH3+ (30.7)
–H2O

The abbreviation (Ar–NO2)H+ used in Equation 30.6 is meant to illustrate that the electroactive
species may be either the neutral hydrogen-bonded nitrobenzene or the monoprotonated species
[130,133,138] dependent on the structure of Ar and the acidity of reaction medium. Equation 30.7
illustrates that simple aromatic hydroxylamines are reduced in aqueous solution as the protonated
forms [139,140] (see Section IV).
If the scan direction during CV is reversed after the first reduction peak, the oxidation of
Ar–NHOH to Ar–NO may be observed and the re-reduction of Ar–NO to Ar–NHOH is observed
during the second forward scan. The redox couple appears as a reversible 2e−, 2H+ process (Equation
30.8) [75,79,121,128,141,142] reminiscent of the classical hydroquinone–quinone redox couple and
the hydrazobenzene–azobenzene couple.
–2e–,–2H+
Ar NHOH Ar NO (30.8)
–2e–,+2H+
This observation also illustrates that Ar–NO is easier to reduce than Ar–NO2 under comparable
conditions [23,41,83,133,143] and therefore that Ar–NO usually is an intermediate and not a product
during the reduction of aromatic nitro compounds (for exceptions, see Section II.A.2.c.i). The pres-
ence of nitrosobenzene as an intermediate has been demonstrated by trapping with p-toluenesulfinic
acid [144–146] or by detection in a flow cell [146–148].
In neutral or unbuffered solution, the reduction stops at the Ar–NHOH stage [132,134] (Equation
30.9), showing, as mentioned earlier, that unprotonated hydroxylamines are not reducible within the
potential window defined by the aqueous solutions.
+4e–,+3H2O
Ar NO2 Ar NHOH (30.9)
–4OH–
In basic solution, the four-electron wave splits up in a one-electron wave corresponding to

the formation of the radical anion (Equation 30.10) and a three-electron wave (Equation 30.11)
[75,76,110,129,132,133], indicating that the radical anion is protonated only slowly under basic con-
ditions similar to what is observed in aprotic solvents.
+e–
Ar NO2 Ar NO2– (30.10)
–e–
+3e–,+3H2O
Ar NO2– Ar NHOH (30.11)
–4OH–
As mentioned earlier, the reduction of nitrobenzenes substituted in the o- or p-position with

hydroxyl or amino groups proceeds to the aniline in a 6F process [110,131,149,150–152] (Equation
30.12), owing to the formation of a quinone imine that, at the same potential, is reduced further to
the aniline. In contrast, m-nitrophenol is reduced only to m-hydroxyaminophenol [151] as in aprotic
solvents.
+6e–,+7H+
HO C6H4 NO2 HO C6H4 NH3+ (30.12)
–2H2O

Much effort has been made to detail the order of the electron and proton transfers that together
with the elimination of water lead to the stoichiometries shown earlier and to understand the role of
adsorption in the reduction process [108,110,125,126,128–130,133,138,153–166].
From studies carried out in aqueous solution in the 1960s and 1970s [108,129,164], it was con-
cluded that two paths are available for the adsorbed nitrobenzene radical anion, either heteroge-
neous protonation and further reduction in the adsorbed state, an eCe-type reaction, or diffusion
into the solution close to the electrode where protonation and further reduction by a radical anion, a
DISP-type reaction, take place. These first steps are summarized in Scheme 30.3.
Ph NO2–(aq)
Ph NO2H(aq) Ph NO2H–(aq)
–Ph NO2(aq)
H+
Ph NO2(aq)
Solution
Electrode surface
+e–
Ph NO2(ads) Ph NO2–(ads)
–e–
H+
+e–
Ph NO2H(ads) Ph NO2H–(ads)
SchEME 30.3 Initial steps proposed for the reduction of nitrobenzene in aqueous solution.
From a study carried out at low substrate concentration [130], where the effects of adsorption are
probably only small, it was found that the reduction of nitrobenzene all the way to hydroxylamine in
three different pH regimes could be described as summarized in Scheme 30.4.
A key intermediate, not specifically in focus in Scheme 30.4, is the nonreducible 2F species, the
dihydroxylamine, Ar–N(OH)2, that by elimination of water is converted to Ar–NO. Once formed
the nitroso compound is immediately further reduced to products as pointed out earlier. The elec-
tron transfer and protonation steps leading to Ar–N(OH)2 under nonbasic conditions may be sum-
marized by the nine-membered square scheme shown in Scheme 30.5 [153–155,163]. Diffusion
coefficients are assumed to be equal, and it is assumed also that protonations are equilibrium pro-
cesses much faster than the electron transfer reactions and that bimolecular reactions (dimerizations
and disproportionations) may be neglected.
The possible pathways through this scheme have been studied in detail in the range Ho ═ −6
to pH 9 and in concentrations up to 10 mM for nitrobenzenes carrying an electron-withdrawing
group, p-NO2 [153] and p-PhCO [153,162], and for related compounds such as 4-nitropyridine
[154] and 4-nitropyridine-N-oxide [153,155]. Common to these substrates is that they owing to the
presence of the electron-withdrawing group are easy to reduce and that elimination of water from
Ar–N(OH)2 is slow at 0 < pH < 5 [156–159]; this makes possible the study of the first 2F part of
the 4F process without the interference of the second 2F part, the reduction of the nitroso inter-
mediate to the hydroxylamine. It was concluded that the sequence of electron and proton transfers
appears to change gradually from e−, H+, H+, e− to e−, H+, e−, H+ in passing from more to less acidic
conditions.
After dehydration of Ar–N(OH)2, the resulting Ar–NO enters a new nine-membered square
scheme (Scheme 30.6), including the electron and proton transfers leading to Ar–NHOH or the
protonated form [153,160,163]. (Scheme 30.6 originally did not include Ar–NO2− and Ar–NOH22+;
these two species have, for the sake of completeness, been added here although they most likely do
not play a role in most cases.)
It was concluded that the sequence of electron and proton transfers changes gradually from H+,
e , H+, e− over e−, H+, H+, e− to e−, H+, e−, H+ in passing from acidic (pH ca 0.4) to basic conditions
−
(pH ca 13) [160].

Thus, the overall 4F reduction of Ar–NO2 to Ar–NHOH (Equation 30.6) may be described by
two nine-membered square schemes linked by the dehydration of Ar–N(OH)2. Pre-protonation of
the nitro group apparently is not important for this series of nitro compounds.
Unsubstituted nitrobenzene cannot be studied in this way owing to the rapid dehydra-
tion of Ph–N(OH)2. However, numerous other studies have addressed the reduction of unsub-
stituted nitrobenzene in aqueous solution and in mixtures of water and an organic co-solvent
[108,110,128–130,133,138,161,164–166].
2 < pH < 5
+e–,+H+
Ph NO2 Ph NO2H
+e–,–H+
+e–
Ph NO2H Ph NO2H–
rds
+2e–,+3H+,–H2O
Ph NO2H– Ph NHOH
–2e–,–3H+,+H2O
6 < pH < 9
+e–
Ph NO2 Ph NO2 –
–e–
+H+
Ph NO2 – Ph NO2H
rds
+3e–,+3H+,–H2O
Ph NO2H Ph NHOH
–3e–,–3H+,+H2O
10 < pH
+e–
Ph NO2 Ph NO2–
–e–
+H+ +3e–,+3H+,–H2O
Ph NO2H Ph NHOH
rds –3e–,–3H+,+H2O
Ph –
NO2
+e– +2e–,+4H+,–H2O
Ph NO22– Ph NHOH
–2e–,–4H+,+H2O
SchEME 30.4 The sequence of steps proposed for the reduction of nitrobenzene at low concentration in
three different pH regions.
The results of a careful polarographical study conducted in buffered 35% DMF/water mixtures sup-
ported an H+, e−, H+, e− sequence, including a pre-protonation step, shown in Scheme 30.7 for the 4F
route to PhNHOH [133,138]. However, from data obtained in HMPA/water mixtures it was concluded
that the species being reduced under basic conditions is rather the unprotonated nitrobenzene [166].
Looking back on the studies reported earlier, and also on some not reported, and on the different
conclusions, in particular, regarding the involvement of the protonated forms of nitro compounds,
it is important to notice that the shift in reduction potential caused by the introduction of electron-
withdrawing substituents shifts the whole process to a different region of double-layer composition
and this affects the adsorption of substrate, intermediates, and products and the kinetics of the reac-
tions taking place in the double layer. Also, the introduction of substituents affects the basicity of the
nitro compounds and therefore also the extent to which the first electron transfer involves a proton-
ated, a hydrogen-bonded, or a nonspecifically solvated species and, accordingly, the magnitudes of
the rate and equilibrium constants for the subsequent proton transfer reactions. Substitution and the
addition of organic co-solvents also affect solvation, not least of the charged intermediates, and the
distribution of species between the adsorbed and the solution state and of the acid–base reactions
O O O–
+e– +e–
Ar N+ Ar N Ar N
–e– –e–
O– O– O–
–H+ +H+ –H+ +H+ –H+ +H+
O O O–
+e– +e–
Ar N+ Ar N Ar N
–e– –e–
OH OH OH
–H+ +H+ –H+ +H+ –H+ +H+
OH OH OH
+e– +e–
+
Ar N2+ Ar N Ar N
–e– –e–
OH OH OH
SchEME 30.5 Square-scheme for the reduction of nitroarenes to the corresponding nitrosoarene water
adducts.
+e– +e–
Ar N O Ar N O– Ar N – O–
–e– –e–
–H+ +H+ –H+ +H+ –H+ +H+
+e– +e– H
Ar N OH+ Ar N OH Ar N O–
–e– –e–
–H+ +H+ –H+ +H+ –H+ +H+
+e– H + +e–
Ar N OH+ Ar N OH Ar NHOH
H+ –e– –e–
–H+ +H+
Ar NH2OH+
SchEME 30.6 Square-scheme for the reduction of nitrosoarenes to the corresponding hydroxylamines.
Ph NO2 + H+ Ph NO2H+
+e–
Ph NO2H+ Ph NO2H
–e–
Ph NO2H + H+ Ph NO2H2 +
+e–
Ph NO2H2 + Ph N(OH)2
–e–
Ph N(OH)2 Ph NO + H2O
+2e–
Ph NO + 2H+ Ph NHOH
–2e–
SchEME 30.7 Reaction sequence proposed for the reduction of nitrobenzene in a buffered DMF/water
mixture.
involved in the reduction processes. Thus, it appears evident that it is almost impossible to transfer
the conclusions made, for instance, for a series of substituted nitrobenzenes in aqueous solution to
unsubstituted nitrobenzene in a mixture of water and an organic solvent, even when the electrode
material, the supporting electrolyte, and the temperature are kept the same.
Additional insight into the properties of the species included in these schemes, and the kinetics
of some of the reactions not considered or relevant earlier, for instance, the second-order solution
electron transfer reactions, has been gained by electrochemical studies in flow cells [167] by appli-
cation of a specially designed electrochemical cell with a large-area, fast-rotating cathode [168], by
pulse radiolysis studies [168–171], and by kinetic studies using ESR spectroscopy to monitor the
concentration of nitrobenzene radical anion [148,172–174]. Data for the pKa values of protonated
nitrobenzenes are available also through standard compilations [175]. Although useful, data of this
kind cannot be transferred uncritically to the conditions that prevail close to an electrode surface in
an unstirred voltammetry solution or when adsorption is involved.
The further reduction of the phenylhydroxylamines to the corresponding anilines is briefly dis-
cussed in Section IV.
b. Routes to Azoxybenzenes, Azobenzenes, Hydrazobenzenes, and Benzidines

In Haber’s scheme for the reduction of nitrobenzene [2,3] (Scheme 30.1), azoxybenzene was assumed
to result from the reaction between nitrosobenzene and phenylhydroxylamine, and this view, or
closely related variants, has been adapted by other authors [75,126,156–159,176]. The reaction has
been studied separately under various conditions and has been shown to follow second-order kinetics
and to be catalyzed by both acid and base [177–179]. However, the decrease in the concentrations of
nitrosobenzene and phenylhydroxylamine during CV at pH 9.3 was found to be incompatible with
this classical mechanism [133,180]. In addition, it has been shown that the reaction between substi-
tuted substrates, X–C6H4 –NHOH and Y–C6H4NO, leads to scrambling of the substituents [177,179]
and also that the reaction between 15N-labeled nitrosobenzene and phenylhydroxylamine leads to
azoxybenzene with 15N equally distributed between the two nitrogen atoms [181]. These observations
together with other isotope exchange experiments [182] indicate an initial equilibrium between the
reactants or the participation of a symmetrical intermediate such as (Ph15NOH)2. Other independent
studies [112,113] have shown that a mixture of nitrosobenzene and phenylhydroxylamine in the pres-
ence of a strong base, B−, (tert-butoxide in DMSO/tert-butylalcohol) rapidly produces the nitrosoben-
zene radical anion (Equation 30.13), and this has led to the proposal [4,112,113,133] that the coupling
of nitrosobenzene radical anions should be considered in azoxybenzene formation (Equation 30.14).
+2B–
Ph NO + Ph NHOH 2Ph NO – (30.13)
–2BH
O– OH
+H2O
2Ph NO – Ph N N Ph Ph N N Ph Ph N+ N Ph (30.14)
–OH– –OH–
O– O– O–
Once formed the azoxybenzenes are usually further reduced to azobenzenes and hydrazoben-
zenes (benzidines) and even anilines. The details are discussed in Chapter 29. However, the condi-
tions for obtaining these products directly by reduction of nitrobenzenes in preparative experiments
are included below.
c. Preparative Aspects of the Reduction of Mononitrobenzenes under Protic Conditions

Examples of the reductive conversion of nitrobenzenes are given in this section. Owing to the low solu-
bility of most nitrobenzenes in aqueous solutions, the catholyte consists often of a two-phase system pro-
cessed to an emulsion by thorough agitation, sometimes at elevated temperature. This leads to successful
syntheses, but a drawback is that the results obtained from the mechanistic work referred to earlier may
only with difficulty, if at all, be transferred to the preparative conditions—and vice versa. Many of the
conditions reported later therefore are not the result of mechanistic work; in fact, a large bulk of the work
that still stands originates from 1895 to 1905 [183], that is, long time before the mechanism era of organic
electrochemistry. The subsections to follow have been organized according to the products observed.
Supplementary information and practical hints are available in books and reviews [7–9].
i. Nitrosobenzenes
+2e–,+2H+
Ar NO2 Ar NO (2F) (30.15)
–H2O

As mentioned earlier, nitrosobenzenes are easier to reduce than the corresponding nitrobenzenes
and are therefore, once formed, immediately reduced to the phenylhydroxylamines. However, it has
been reported that up to 33% of nitrosobenzene results from the reduction of nitrobenzene in basic
aqueous ethanol at a hypophosphite modified nickel cathode that makes further reduction difficult
[184]; also nitrosobenzene may escape further reduction by being dissolved in the nitrobenzene
phase in a two-phase system [185]. Otherwise, the normal strategy for preparing nitrosobenzenes
in high yields includes two steps. First, the nitrobenzene is reduced in a 4F process to the hydrox-
ylamine and the resulting solution is then, after current reversal, oxidized in a 2F process to the
nitroso stage; there is no need to isolate the hydroxylamine. The first step requires no special pre-
cautions, but a problem during the second step is that the electrolysis solution during the oxidation
process contains high concentrations of both the phenylhydroxylamine and the nitrosobenzene,
which inevitably will lead to the formation of the corresponding azoxybenzenes as side products.
Several solutions to the problem have been suggested. One is to carry out the oxidation at pH 5–8
where the rate of formation of the azoxybenzene is low, and in some cases also the use of a DMF/
water solvent mixture is profitable [186]. The competing coupling to the azoxy compound may be
further diminished by using a specially designed flow cell in which the substrate/electrolyte mixture
is first passed through a porous cathode for the exhaustive conversion of the nitrobenzene to the
hydroxylamine and then, downstream, the hydroxylamine solution is forced through a porous anode
in which oxidation to the nitroso compound takes place [146,186–188]. The yields in the first step
are often higher than 90%, in the second usually somewhat lower. The reduction of nitrobenzene to
phenylhydroxylamine and oxidation back to nitrosobenzene in an overall close-to-quantitative yield
has been achieved also in THF in the presence of benzoic acid [189].
In a different approach, the intermediate nitrosobenzene is protected against further reduction
by reaction with an arenesulfinic acid to a nonreducible hydroxylamine derivative [144,145]
(Equation 30.16).
SO2 Ar΄
Ar–N=O + Ar´-SO2H Ar N (30.16)
OH
Deprotection by hydrolysis of the latter under basic conditions gives the nitrosobenzene. In a similar
approach, nitrosobenzenes could be prepared by making the same hydrolysable sulfonated hydrox-
ylamine by reaction of the phenylhydroxylamine (lower oxidation state than above) with an arene-
sulfonyl chloride (higher oxidation state than above) [190].
ii. Phenylhydroxylamines
+4e–,+4H+
Ar NO2 Ar NHOH (4F) (30.17)
–H2O
The optimal conditions for conversion of nitrobenzenes to phenylhydroxylamines include

pH 3–9 and an ammonia [3] or acetate buffer [191] at room temperature or lower to minimize
degradation of the product. For nitrobenzenes carrying electron-withdrawing groups, hydrox-
ylamines may be prepared by reduction in mixtures of dilute sulfuric acid and ethanol [192].
Reduction in more acidic solutions is accompanied by rearrangement to the p-aminophenol (see
Section II.A.c.iv), and reduction at pH > 9 leads to the corresponding azoxybenzenes as the
major product (see Section II.A.2.c.vi). The electrode material is usually of minor importance.
Advantageous is also to keep the processing time short, for instance by using a flow cell with
a porous cathode, and to continuously remove the product that often separates as a crystalline
material from the electrolysis solution [191].
iii. Anilines in General
+6e–,+7H+
Ar NO2 Ar NH3+ (6F) (30.18)
–2H2O
In anilines, the nitrogen atom is in its lowest oxidation state, and the direct electrochemical conver-
sion of nitrobenzenes requires a relatively low pH to achieve reduction beyond the hydroxylamine
stage and often also the addition of small amounts of zinc, copper, tin, or other salts [193–196].
However, as already pointed out, earlier rearrangement of the hydroxylamine to the p-aminophenol
to some extent is unavoidable under the strongly acidic conditions, and therefore mixtures of aniline
and p-aminophenol usually result from the direct reduction of nitrobenzenes in acid [195] unless the
starting material has substituents in the p-position. For instance, p-nitrobenzoic acid [197–199] and
p-nitrophenetole [200] may be reduced almost quantitatively to the corresponding anilines in strong
sulfuric acid at elevated temperatures.
Rearrangement is less of a problem if the reduction is carried out indirectly, for example, by
using a Ti(IV) [201–203] mediator or a Ti/TiO2-cathode [204–206]. Useful conditions for the
close-to-quantitative conversion of nitrobenzenes to anilines include a 30–40% sulfuric acid
catholyte containing 2–3% Ti(IV) sulfate and a copper cathode [201,207]. The Ti(III) formed
serves as the reducing agent and is likely to assist also in the cleavage of the N–O bond in the
hydroxylamine. The product separates as the aniline hydrogen sulfate. The mediated reduction
may also be carried out as an ex-cell two-phase process [208–210] in which the Ti(III) spe-
cies, in this case (C5H5)2Ti+, is generated electrochemically in the aqueous solution and then
allowed to react with the nitrobenzene dissolved in CH 2Cl2. When nitrobenzenes substituted
in the o-position with an ester, carbonate, amide, or carbamate function are reduced in this
way, the resulting aniline rearranges in situ to the N-acylated o-aminophenols [209]. In another
indirect approach, nitrobenzenes have been reduced to anilines in an emulsion with solutions of
copper, iron, tin, or zinc salts at a high current density. The finely divided and oxide-free metal
powders resulting from the electrochemical reduction serve to effectively reduce nitrobenzene
to aniline [211,212].
Even though reduction of nitrobenzenes under basic conditions usually leads to azoxy derivatives,
reduction in basic aqueous methanol can be directed to produce anilines in high yields provided
that catalytically active electrodes such as Devarda copper, Raney nickel or copper preoxidized to
Cu(OH)2, are used [213–216]. Even if azoxybenzenes are formed, they are further reduced to ani-
lines under the conditions.
iv. Aminophenols and Phenylenediamines The reduction of nitrobenzenes carrying a hydroxy or

an amino group in the o- or p-position presents a special case. The initially formed phenylhydroxylamines
rapidly eliminate water to form easily reducible quinone mono- or diimines, as illustrated in Equation
30.19 for p-substitution (X ═ OH, NH2 or NMe2), resulting in an overall 6F process [151,152,217,218].
The elimination of water takes place in both acid and base; here is only shown the reaction in acid. The
values of the rate constant, k, for dehydration are typically in the range 0.4–1.0 s−1 [219–221].
NHOH NH2OH+ NH NH2
+H+ k +2e–,H+
(30.19)
–H+ –H2O
X X X+ X
The reaction has been studied at gold electrodes in neutral and acidic solutions by surface-
enhanced Raman spectroscopy, and for the p- and o-isomers, the formation of the phenylenedi-
amine could be detected in acidic, but not in neutral solution. An oxygen-gold adsorbate stretching
mode was detected between 400 and 430 cm−1 at positive potentials implying perpendicular adsorp-
tion via the nitro group [222].
Examples of the process include the pilot plant scale reduction of 4-hydroxy-3-nitrobenzoic acid
to 3-amino-4-hydroxybenzoic acid at a copper cathode under basic conditions [223] and the reduc-
tion of 4-nitroaniline, also at a copper cathode, in dilute hydrochloric acid to 1,4-phenylenediamine
in 93% yield [224]. The reduction of N,N-dimethyl-4-nitroaniline to the diamine at low temperature
[225] serves to illustrate the case X ═ N(CH3)2.
Alkoxy groups in the o- [226,227] or p-position [217,227] suffer partial hydrolysis during reduc-
tion of the nitrobenzenes. For instance, reduction of a suspension of o-nitroanisole at an amalgamated
monel electrode in diluted sulfuric acid in the presence of CuSO4 leads to a mixture of o-methoxy-
aniline and o-aminophenol [226] and N,N-dimethyl-4-nitroaniline is converted to 4-aminophenol
by reduction at elevated temperature [225]. A p-alkyl substituent may function in the same manner
as a hydroxyl group in facilitating loss of water from the phenylhydroxylamine and stabilizing the
quinonoid intermediate. Thus, 5-nitroacenaphthene is reduced to 5-aminoacenaphthene in a 6F
process in acidic solution [228]. Related to this is the 6F reduction of 2,4,6-triphenylnitrobenzene
to 2,4,6-triphenylaniline [31].
p-Aminophenols are the products even when nitrobenzenes without a hydroxy group in the
p-position are reduced in strong sulfuric acid at an elevated temperature [229–236]. This is the
result of the Bamberger rearrangement that in the “pH region” includes elimination of water from
the monoprotonated hydroxylamine to a carbocation that subsequently suffers nucleophilic attack
by water (Scheme 30.8) [237]. At higher acidity, in the “Ho region,” also the diprotonated hydroxyl-
amine is involved.
+
H OH2+ NH
N
NHOH NH NH2
H+
+H 2 O
H –H+
H+ –H2O
+
H N OH NH
H OH2+ OH
SchEME 30.8 Bamberger rearrangement of phenylhydroxylamine to p-aminophenol.

This synthetically important variant of nitrobenzene reduction was reported already by

Gattermann [238] and a variety of conditions have been described in books [7,8] and patents
[239]. Good conditions appears to be reduction of an agitated suspension of nitrobenzene in 50%
aqueous sulfuric acid at a nickel cathode at 25–60°C after which the product precipitates out in
65% yield [240]. Although successful, a complication is that the formation of p-aminophenol
is accompanied by a by-product, 4,4′-diaminodiphenyloxide [241], resulting from a reaction in
which the intermediate phenylhydroxylamine attacks itself as a nucleophile in competition with
water. The amount of 4,4′-diaminodiphenyloxide increases as expected with increasing concen-
trations of the phenylhydroxylamine. Unfortunately, the 4,4′-diaminodiphenyloxide is carcino-
genic and for this reason p-aminophenol prepared electrochemically is not suitable as a drug
intermediate.
The reduction of p-nitrotoluene at a mercury cathode in 25% sulfuric acid at 90°C was reported
to give the 4F product, 2-methylhydroquinone, apparently resulting from hydrolysis of a Bamberger-
like intermediate accompanied by methyl migration [192]. The same type of product was observed
for 2-methyl-5-nitrobenzoic acid.
v. Other Substituted Anilines Other nucleophiles than water may attack the intermediate car-
bocation shown in Scheme 30.8. Reduction of nitrobenzene in, for instance, hydrochloric acid leads
to a mixture of p- and o-chloroaniline and p-aminophenol [242,243] and reduction of 2-fluoroni-
trobenzene in HCl/propanol gives 4-chloro-2-fluoroaniline in ~50% current yield [244]. Reduction
of p-nitrotoluene in concentrated sulfuric acid results unexpectedly in the formation of 4-amino-
2′-methyl-5′-nitrodiphenylmethane [238,245]. The origin of this product is not clear. A similar
conversion has been observed during the reduction of p-nitroisopropylbenzene in sulfuric acid. In
an overall 4F process, 5-amino-3-(4-aminophenyl)-1,1,3-trimethylindan was formed; in this case,
loss of water from the initially formed phenylhydroxylamine was suggested to give p-amino-α-
methylstyrene that then dimerized to the indan derivative [246].
vi. Azoxybenzenes
+6e–,+6H+
2Ar NO2 Ar N+ –N Ar (3F) (30.20)
–3H2O
O–
Azoxybenzenes have been detected as minor products from the reduction of nitrobenzenes under a
variety of conditions. The classical preparative conditions include reduction of nitrobenzene under
basic conditions [247–252] and preferentially the reactions are carried out such that the product pre-
cipitates out and may be collected by filtration after electrolysis. In this way, azoxybenzene escapes
further reduction to azo- and/or hydrazobenzene. Examples of successful preparations include the
reduction of a well-stirred hot 2.5% NaOH suspension of nitrobenzene at lead or nickel cathodes
at low current density. The unreduced nitrobenzene may be removed by steam distillation after
which the remaining azoxybenzene solidifies upon cooling. Yields are typically around 85% [249].
Another recipe includes the reduction of a solution of the nitrobenzene in aqueous ethanol contain-
ing sodium or ammonium acetate as supporting electrolyte [252,253]. Reduction of 3-nitrobenzo-
phenone at a nickel gauze electrode gives under these conditions the corresponding azoxybenzene
in a close-to-quantitative yield [252]. The carbonyl group was not affected. Other examples have
been reported in two old reviews [247,248].
Occasionally, azoxybenzenes are formed also in fair yields by reduction of the corresponding
nitrobenzene under neutral or acidic conditions. For instance, it was reported that the reduction of
4-nitrodiphenylsulfone and 4-nitrobenzophenone at a mercury cathode at pH 2 under vigorous stir-
ring leads to the azoxybenzenes in 30–40% yield, in addition to the hydroxylamines. The azoxy com-
pounds precipitated out and could be isolated by filtration [157]. Reduction of p-iodosonitrobenzene
at a graphite cathode in neutral 1 M aqueous MgBr2 gives 4,4′-diiodoazoxybenzene in 88% yield.

Here it should be noticed that the reduction affects also the substituent that is reduced from the
iodoso to the iodo state [254].
An unusual reaction was observed when nitrobenzene was reduced at a mercury cathode in
MeCN/Bu4NClO4 saturated with carbon dioxide in the absence of acid. Under these conditions,
reduction was reported to give azoxybenzene and bis(tetrabutylammonium) carbonate as the major
products (Equation 30.21), accompanied by minor amounts of azobenzene and phenylhydroxyl-
amine [255]. The protons required for the latter were suggested to originate from the Bu4N+ ion
since also small amounts of 1-butene was detected.
+6e– +
2 NO2 + 3CO2 N N + 3CO32– (30.21)
O–
vii. Azobenzenes
+8e–,+8H+
2 Ar NO2 Ar N N Ar (4F) (30.22)
–4H2O

If, during the reduction of nitrobenzenes in basic solution, the current is allowed to flow until the
theoretical amount of charge corresponding to 4F has passed, and preferably at increased tem-
perature to avoid precipitation of the intermediate azoxybenzene, the reduction proceeds to the
azobenzenes in yields that are typically around 80–95% [225,248,253,256–258]. Nitrobenzenes
may also be reduced to azobenzenes in THF/LiClO 4, and by using magnesium electrodes, the
current was alternated at 30 s intervals in order to reduce the loss of magnesium. Yields up to
87% were reported [259]. However, the details of the reaction, including the role of magnesium,
are not clear.
viii. Hydrazobenzenes and Benzidines
+10e–,+11H+
2Ar NO2 Ar NH NH2+ Ar (5F)
–4H2O
(30.23)
R R
Benzidine
H2N NH3+
Rearr.

As mentioned earlier, a key issue in the preparation of azoxybenzenes is to avoid further reduction,
which may be accomplished by using a two-phase system. Obviously then, when further reduction
is wanted there is no reason to conduct the electrolysis in this way; on the contrary and therefore,
in order to increase solubility, reductions to hydrazobenzenes and benzidines are often carried out
in water/alcohol mixtures or in the presence of solubilizing McKee salts (mixtures of sodium and
potassium salts of xylenesulfonates) [260]. Still, reduction in basic aqueous suspensions of nitroben-
zene in concentrations up to 5% has been shown to be successful when cathodes having a spongy
layer of metals like lead, iron, and zinc were used [261]. Advances have been taken of using a rotat-
ing disk cathode made by mild steel with a coating of lead for the purpose [262,263]. In general, the
reduction of nitrobenzenes proceeds all the way to hydrazobenzenes when the current is allowed to
flow until charge corresponding to 5F has been exchanged [225,248,256,257,260].
Addition of the solutions resulting from preparation of the hydrazobenzenes to an excess of
hydrochloric or sulfuric acid causes the immediate rearrangement to the corresponding benzidine
[257,262,263]. Alternatively, the reduction may be carried out in base, stopped at the azoxy or the azo
stage, and then continued under acidic conditions to the benzidine [247,250,251]. In the latter case,
care should be taken to avoid the further reduction of the hydrazobenzene to the aniline stage [264].
d. Other Reactions of Mononitrobenzenes

i. Cleavages Nitrobenzylhalides undergo C–X cleavage upon electrochemical reduction in
MeCN or DMF [72–74]; the resulting nitrobenzyl radicals may dimerize to form 1,2-bis(nitrophenyl)
ethanes that are further reduced to the corresponding radical anions and dianions.
Reduction of p-nitrophenyl methyl sulfone in DMF produces p-nitrophenolate in a rather com-
plex cleavage reaction [55].
Reductive cleavage of 4-(4′-nitrophenyl)-1,3-dioxolane and 7-nitro-1,3-benzodioxane in basic
EtOH/water has been suggested as a key step in a protection-deprotection cycle for ketones, here
illustrated by cyclohexanone (Equation 30.24) [78,265].
–
OH O O O
HO O O
(30.24)
O
+e–
Products
O
NO2 NO2 NO2 N –

+
O O
Similarly, deprotection by reductive cleavage of the 4-nitrobenzyloxycarbonyl group from the ure-
thane derivatives of primary and secondary amines has been reported [266] (see also Chapter 16).
ii. Dimerizations Reversible dimerization of the radical anions derived from aromatic com-
pounds has been observed in a number of cases, as, for example, for 1,3,5-trinitrobenzene [19,69,70],
3,5-dinitropyridine [70], and 9-nitroanthracene [19,71]. Such dimerizations are discussed in Chapter 17.
iii. Radical Anions as Nucleophiles Nitroarene radical anions have nucleophilic properties, and
these have been put to use in reactions with acetic anhydride [82,267,268] and alkyl halides [269]
in MeCN or DMF. The products, N-acetoxy-N-arylacetamides from the reaction with acetic anhy-
dride and N,O-dialkyl-N-arylhydroxylamines from the reaction with alkyl halides, not easy to make
otherwise, are formed in 25–85% yields. In both cases, the reactions are believed to proceed via
the nitroso compound with the stoichiometry shown in Equation 30.25 for the reaction with acetic
anhydride.
O
CH3
+4e–
Ph NO2 + 3 (CH3CO)2O Ph N CH3 + 4 CH3COO
– (30.25)
O
O
The nitro group in 4-nitrobenzoyl chloride is easier to reduce than the acid chloride part. When
the reduction is carried out in MeCOMe/LiClO4, the resulting radical anion is attacked by the acid
chloride and a complex reaction leads to the mixed anhydride of 4-nitrobenzoic acid and 4-(4-nitro-
benzoylamino)benzoic acid (Equation 30.26) [270].
NO2 NHCOC6H4NO2-p
1.5F
(30.26)
COCl CO2COC6H4NO2-p

iv. Formation of Heterocyclic Compounds Reduction of nitrobenzenes substituted in the o-posi-

tion with a side chain that may react with the “reduced nitro group” often leads to ring closure and
the formation of heterocyclic compounds. Such conversions are treated in Chapter 34 to which the
reader is referred for details. Numerous examples are found also in Torii’s book [6]. Here it suffices
to present a few illustrative examples.
o-Nitrostyrenes are converted to 1H-indoles by reduction in DMF in the presence of a 10-fold
excess of a proton donor such as phenol [271]. Reduction of o-nitroazobenzene [272] and o-nitro-
hydrazobenzene [273] in DMF leads in both cases to 1,3-dihydroxy-2-phenylbenzotriazole, or in
the presence of alkali metal ions, to 2-phenylbenzotriazole-N-oxide. Related to these are the reduc-
tion of o-nitrophenylhydrazides to 1,2,4-benzotriazines [274] and of o-nitrophenylazo-p-cresols
to benzotriazole-N-oxide [275]. N-(o-Nitrobenzoyl) and N-(o-nitrobenzyl) amides or imides may
be reduced to quinazoline derivatives [276,277] and o-nitrobenzoic acid derivatives and o-nitro-
naphthalimides to isoxazole derivatives [278,279]. In a reduction–oxidation process, o-nitrobenzyl-
amines were converted to the resulting nitroso compounds that subsequently cyclized to indazoles
[280,281]. In basic aqueous media, 2-nitroazobenzenes are reduced to 2-arylbenzotriazole-N-
oxides [282,283]. In DMF, l,3-dihydroxy-2-phenylbenzotriazole is formed from 2-nitroazobenzene
[272,273].
3. Other Mononitroarenes
The products of the electrochemical reduction of mononitroarenes other than nitrobenzene are of
the same kind as those reported earlier. Most studied are the nitronaphthalenes [284–290] for which
the preparative electrochemistry can be summarized as follows. Under neutral conditions, reduc-
tion of 1- and 2-nitronaphthalene proceeds to the hydroxylamines, whereas reduction under acidic
conditions at low potentials gives the corresponding amines. At more moderate reduction poten-
tials, 1-nitronaphthalene gives 4-amino-1-naphthol, whereas 2-nitronaphthalene gives 2-amino-1-
naphthol [288]. Reduction of 1-nitronaphthalene at a Ti/TiO2 cathode under acidic conditions gives
1-aminonaphthalene [287]. Reduction at an amalgamated copper cathode in a sulfuric acid solution
containing SnCl2 has been reported to give 1-amino-5-naphthol [285], whereas reduction in >50%
H2SO4, MeOSO3H, MeSO3H containing an alcohol results in the formation of the corresponding
4-alkoxy-1-naphthylamines [286]. For instance, 2-methyl-1-nitronaphthalene could be converted to
4-methoxy-2-methyl-1-naphthylamine in 65% yield in this way. Reduction of the substituted nitro-
naphthalenes follows essentially the same rules as those that govern the products for the alkoxyni-
trobenzenes [289].
Heterocyclic compounds may result from 1-nitronaphthalenes substituted in 2- or 8-position and
2-nitronaphthalenes substituted in 1- or 3-position with CONH2, CN, and NHCOCH3 [290].
4-Nitrobiphenyl is reduced at pH ≤ 9 in a 4F and a 2F step, presumably to the hydroxylamine
and the amine [291].
4. Di- and Trinitroarenes

The mechanisms of the electrochemical reduction of di- and trinitrobenzenes (DNB and TNB)
and other polynitroarenes are basically the same as those discussed earlier; still there are some
characteristic features of the reaction patterns that originate from the presence of one or more
additional nitro groups and that justify a separate section. The reactivity of the radical anions and
dianions of, for instance, dinitrobenzenes is lower than that for the mononitrobenzenes, and this has
allowed for studies of the kinetics of the protonation of the radical anions and dianions by using
conventional electroanalytical methods. Also, the electronic coupling between the two nitro groups
is dependent on their relative position. The 1,4-DNB dianion, for instance, is well described by a
quinoid structure, whereas the 1,3-DNB dianion has biradical character as mentioned earlier and
this affects the products of reduction. Finally, dinitrobenzenes carrying a substituent are most often
unsymmetrical and this raises the question of which of the two nitro groups is first converted to a
lower oxidation state by reduction.
a. Mechanisms and Preparative Aspects of the Protonation in Aprotic Solvents

The kinetics of protonation of the radical anions and dianions derived from the three simple dini-
trobenzenes have been studied in DMF for a variety of proton donors including phenol and benzoic
acid [41,43,292,293]. The rate constants for protonation of the radical anions by benzoic acid were
k12 ═ 6.3·102 M−1 s−1, k13 ═ 3.6·102 M−1 s−1, and k14 ═ 670 M−1 s−1 [293], where the subscripts refer to
the substitution pattern of the dinitrobenzenes, reflecting the general trend that the rate constants
decrease in the order k12 > k13 >> k14 for both the radical anions and the dianions. Thus, the radical
anions and dianions of 1,4-DNB are by far the least reactive.
Reduction of 1,2-, 1,3- and 1,4-DNB in aprotic solvents in the presence of a suitable proton
donor leads first to the corresponding nitrophenylhydroxylamines, possibly by a DISP-like mech-
anism [22,41,47,294]. Further reduction then leads to the phenylenediamines for 1,2-DNB and
1,4-DNB [22,47], illustrated in Equation 30.27 for 1,2-DNB, and to the benzenedihydroxylamine
for 1,3-DNB [22,47] (Equation 30.28), illustrating that the two nitro groups in the latter case behave
essentially independently [295].
NO2 NO2 NH2

+4e–,+4H+ +8e–,+8H+
–H2O –3H2O
(30.27)
NO2 NHOH NH2

NO2 NO2 NHOH

+4e–,+4H+ +4e–,+4H+
–H2O –H2O (30.28)
NO2 NHOH NHOH

b. Mechanisms and Preparative Aspects of the Protonation

in Water and Other Protic Solvents
i. Unsubstituted Dinitrobenzenes and Dinitrobiphenyls The products resulting from electro-
chemical reduction of the three unsubstituted dinitrobenzenes [159,176,296–301] and of dinitrobi-
phenyls [291] in aqueous solution depend, as for the mononitrobenzenes, on pH of the solution. And
as given earlier, the 1,3-isomer differs from the 1,2- and 1,4-isomers.
Reduction of 1,2-DNB and 1,4-DNB at mercury or silver cathodes at low pH leads ultimately to
the phenylenediamines [176,296,301] in overall 12F processes, but a 10F process leading first to the
1,2-quinonediimine that subsequently dimerizes to 5,10-dihydrophenazine-2,3-diamine and related
compounds has been reported for 1,2-DNB as well [297]. The pathway to the phenylenediamines
includes the 2- and 4-nitrophenylhydroxylamines [159,176,296] as in Equation 30.27, but may partly
include also the azoxybenzene derivative [176]. In contrast, the final product resulting from reduc-
tion of 1,3-DNB at low pH is either 3-nitroaniline [300] or benzene-1,3-dihydroxylamine [296], in
latter case via the 3-nitrophenylhydroxylamine as in Equation 30.28.
Reduction of 1,2-DNB and 1,4-DNB at pH close to neutral gives the phenylenediamines

[176,296] via the nitrophenylhydroxylamines [296] and the azoxy derivative [176]. The 1,3-
DNB gives 3-nitrophenylhydroxylamine [300] or benzene-1,3-dihydroxylamine [296] via the
3-nitrophenylhydroxylamine.
Finally, reduction of 1,2-DNB and 1,4-DNB at high pH gives the phenylenediamines [176,296,299]
or the nitrophenylhydroxylamines [298,302], whereas 1,3-DNB gives the benzene-1,3-dihydroxyl-
amine [296] or 3,3′-dinitroazoxybenzene [298–300].
ii. Substituted Dinitrobenzenes and Dinitrobiphenyls The electrochemical reduction of sub-

stituted dinitrobenzenes has been investigated carefully [86,303–310], and the effect of substituents
on the reduction potentials has been reviewed [311].
Reduction of monosubstituted 1,2- and 1,4-dinitrobenzenes at a mercury cathode under acidic
conditions leads first to the nitrophenylhydroxylamines in a 4F process and then at a lower potential
to the 1,2-phenylenediamines in a 12F process [303–305]. At Ti/TiO2 cathodes the direct reduction
to the diamines is observed [204,312,313] similar to what was described to mononitrobenzenes
earlier. For 1,2-dinitrobenzenes (X ═ 3-Me, 3-OEt, 3-Br, 3-COOH, 4-Me, 4-OMe, 4-Cl), the 4F
process involves the nitro group situated meta to X. Only in one case (X ═ 4-COOH) the nitro group
in the para-position relative to X is being reduced [303]. For the related 1,4-dinitrobenzenes, the 4F
reduction of the nitro group ortho to X is involved for electron-withdrawing substituents (X ═ 2-Br,
2-COOH, 2-CONH2), whereas the nitro group meta to X is being reduced for electron-donating
substituents (X ═ 2-Me, 2-OH, 2-OMe) [304].
The substituted 1,3-dinitrobenzenes behave differently. Except for X ═ OR the reduction includes
three successive 4F processes, first to the nitrophenylhydroxylamines, then to the benzenedihydrox-
ylamines and finally to phenylenediamines [308]. Also in this case, the nature and position of X
affects the selectivity of the reduction. For the halides (X ═ 4-Cl, 4-Br, 4-I), the nitro group ortho
to X is first reduced, but for alkyl and carboxy substituents (X ═ 4-Me, 4-Et, 4-COOH), the nitro
group meta to X is first reduced. When X ═ 2-OR or 4-OR, two 6F processes are observed; the first
that includes hydrolysis of the OR substituent leads to 2-amino-4-nitrophenol and the second to the
2,4-diaminophenol.
The reduction of 2,6-dinitrotoluene follows the pattern outlined earlier for nitrobenzenes. Under
strongly acidic conditions (sulfuric acid), reduction leads to 2-methyl-3-nitroaniline, under weakly
acidic conditions (acetic acid/acetate buffer) the product is 2-methyl-3-nitrophenylhydroxylamine
and under slightly basic conditions (acetate in ethanol) 2,2′-dimethyl-3,3′-dinitroazoxybenzene is
produced [306]. Reduction of 2,4-dinitrotoluene [306], 2,4-dinitroanisole [309] and 2,4-dinitro-
chlorobenzene [309] proceeds in essentially the same way. Systematic studies of the conversion of
2,4-dinitrophenol [307] and 3,5-dinitro-2-methylphenol [310] to the corresponding diamines have
resulted in conditions for high yield processes (~80%).
An interesting variant is reported for the reduction of 2,3′-dinitrobenzidine that in buffered
aqueous methanol at all pH values is reduced in a 10F (4F + 4F + 2F) process to 2-amino-3′-
hydroxylaminobenzidine via a quinoid intermediate (Equation 30.29) [314], illustrating the effect
of having at same time a nitro group ortho and meta to the amino group in the starting material.
2.(+4e–,+4H+)
H2N NH2 H 2N NH2
2.(–H2O)
NO2 NO2 NHOH NHOH

(30.29)
+2e–,+2H+
H2N NH H2N NH2
–H2O
NH NHOH NH2 NHOH

iii. Dinitronaphthalenes A series of dinitronaphthalenes has been studied by polarography, cou-

lometry, and preparative electrolysis [284,288,315]. Two or three reduction processes are observed
under acidic or close-to-neutral conditions, the number of polarographic waves and the number of
electrons involved in each step being dependent on the substitution pattern. The behavior of the
1,2- and 1,4-isomers is similar to that of 1,2-DNB and 1,4-DNB, that is, the reduction proceeds as
a 4F process to the nitronaphtylhydroxylamine and as a 12F process to the naphthalenediamines.
The remaining isomers (1,3; 1,5; 1,6; 1,7; 2,3; 2,6; and 2,7), except for 1,8-isomer, give rise to three
waves corresponding to 4, 8, and 12F, respectively, with the 8F processes most likely corresponding
to the formation of the unstable naphthalenedihydroxylamines. Preparative electrolysis in aqueous
ammonium acetate/ethanol results in the formation of the nitronaphthylhydroxylamines in a 4F
process and the general trend observed is that the 1-nitro group is the one being reduced in the
unsymmetrically substituted compounds. Reduction under acidic conditions leads in all cases to the
naphthalenediamines in 12F processes.
The 1,8-isomer is a special case. This compound and related 4,5-disubstituted derivatives are
reduced in 8, 10, or 12F steps with the number of electrons decreasing with increasing pH [316]
corresponding to the formation of benzo[cd]indazole (1,8-naphthopyrazol, the 8F intramolecular
azo compound), 1,2-dihydrobenzo[cd]indazole (1,8-naphthodihydropyrazol, the 10F intramolecular
hydrazo compound), and naphthalene-1,8-diamine (the 12F product) (Scheme 30.9).
Electrosynthesis of naphthalene-1,8-diamine at a large scale may be carried out in a close-to-
quantitative yield by reduction of a suspension of 1,8-dinitronaphthalene at 70°C at a copper cath-
ode in aqueous sulfuric acid containing a titanium salt [317].
c. Other Reactions of Di- and Trinitroarenes

Elimination of a nitro group as a nitrite ion has been reported for the reduction of 1,4-DNB [318] and
of 1,2,4,5-tetrafluoro-3,5-dinitrobenzene in DMF containing a proton donor [319]. These reactions
are similar to what is observed for aliphatic nitro compounds (see Sections II.B.3.b.i and II.B.4.a),
but we are not aware of other examples of this type of cleavage for an aromatic nitro compound.
Another unusual reaction, in DMF in the presence of N-methylformamide, is the reductively
induced substitution of a hydrogen atom in 1,3,5-TNB with an N-methylformamido group to give
N-methyl-N-(2,4,6-trinitrophenyl)formamide in 78% yield [320]. The first step appears to be the
reaction between the 1,3,5-TNB radical anion and N-methylformamide to form a Meisenheimer-
type adduct.
N N
+8e–,+8H+
NO2 NO2 –4H2O HN NH
+10e–,+10H+
–4H2O
+12e–,+12H+ NH2 NH2
–4H2O
SchEME 30.9 The 8, 10 and 12F products resulting from the reduction of 1,8-dinitronaphthalene.
5. Hetereoaromatic and Related Mono- and Dinitro Compounds

This section includes compounds in which the nitro group is attached directly to a heteroaromatic
ring. Basically, heteroaromatic nitro compounds behave in much the same way as nitroarenes during
electrochemical reduction. However, occasionally the properties of the heteroaromatic ring add to the
complexity typically observed for the reduction of simple nitroarenes. For example, if the nitro group
is attached to the heteroatom, X, reduction often results in cleavage of the X–NO2 bond. Other exam-
ples include heteroaromatic systems that are inherently acidic owing to the presence of, for example,
an N–H group in the ring; this may lead to self-protonation reactions similar to those described ear-
lier for nitrophenols and nitrobenzoic acids. Finally, the heterocyclic chemistry is rich on positively
charged rings such as pyrazolium and imidazolium that have only few equivalents in arene chemistry.
a. Compounds with the Nitro Group Attached to Carbon

i. Reduction in Aprotic Solvents 1-Methyl-4-nitroimidazoles and 1-methyl-5-nitroimidazoles
are reduced in DMF to the corresponding radical anions in contrast to the unsubstituted 4- and
5-nitroimidazoles that owing to the acidic 1-NH proton are reduced to the corresponding hydrox-
ylamines in a self-protonation process [63,64,67]. Similarly, self-protonations have been observed
in DMSO for 4-substituted 7-nitro-3,4-dihydroquinoxalin derivatives and 5-nitro-2,3-dihydro-1H-
indazole derivatives [62].
ii. Reduction in Water and Other Protic Solvents The electrochemical reduction of this class of
compounds in aqueous solution follows closely that of the simple nitroarenes although with the addi-
tional complexity that protonation of the heterocyclic ring may take place at low pH. Thus, 4-nitro-
pyridine [154] and 4-nitropyridine-N-oxide [154,155] as well as nitrofurans [68], nitropyrazoles,
nitroimidazoles, and nitrotriazoles [63,64,321–328] are all reduced to the corresponding hydroxyl-
amines that at low pH may be further reduced to the amines [321,322] or oxidized to the nitroso com-
pound [328]. Under basic conditions, it is observed that the hydroxylamines resulting from reduction
of 2-alkyl-4-nitroimidazoles and 1,2-dialkyl-5-nitroimidazoles eliminate water easily to give the qui-
none imine that is further reduced to the amine in an overall 6F process [322]. Similarly, the 1-alkyl-
4-amino-5-nitroimidazole and 1-alkyl-4-nitro-5-aminoimidazole are reduced in 6F processes [322].
In contrast, the reduction of 5-nitro-1,2,4-triazol-3-one in aqueous sulfuric acid leads to the azoxy
derivative as the major product that owing to its low solubility can be isolated by filtration [327,329].
The reduction of nitropyridines and the hydroxy- and methoxy-substituted derivatives in protic
solvents follows essentially the same rules as discussed earlier for the analogous nitrobenzenes
[158,330]. For 4-nitropyridine, the +2e−, +2H+ reduction to the dihydroxyamine was found to be
reversible at −7°C in acidic ethanol [158].
b. Compounds with the Nitro Group Attached to a Heteroatom

The reduction of 1-nitropyrazole in acidic media results in cleavage of the N–N bond and the forma-
tion of nitrous acid [331] and thus resembles the reduction of nitramines (see Section V.A). At pH > 4,
competitive reduction to the nitrosamine takes place.
c. Positively Charged Compounds

The nitro group attached to a 1,2-dialkylpyrazolium or 1,2,3-trialkylimidazolium ring is reduced
preferentially to the positively charged heterocyclic system at pH up to approximately 9. Reduction
leads to the corresponding hydroxylamines with the sequence of the electron and proton transfer
steps, leading to the intermediate nitroso derivative being H+, e−, e−, H+ [331].
B. ALIpHaTIC NITro CoMpoUNDS

The electrochemical reduction of compounds in which the nitro group is attached to an sp3-hybridized
carbon (nitroalkanes and related) or a nonaromatic sp2-hybridized carbon (nitroalkenes and related)
is discussed in this section. We are not aware of reports addressing the electrochemical reduction
of compounds in which the nitro group is attached to an sp-hybridized carbon (nitroalkynes and
nitroallenes) in spite of the fact that such compounds are known. Aliphatic nitro compounds in which
an aromatic substituent is attached to a nonaromatic carbon are included in this section as well.
1. Formation and Properties of the Radical Anions

The half-life of the radical anions derived from nitroalkanes is as a rule shorter than that of radical
anions derived from aromatic nitro compounds, typically in the range, 0.1 < t ½/s−1 < 1. The radical
anions derived from primary and secondary nitroalkanes have been observed in aprotic solvents
such as MeCN by fast scan CV [101,332] or in high-speed channel cells [333]. Tertiary nitroalkanes
that lack the acidic α-hydrogens are less reactive and the one-electron reductions have been studied
in detail by slow sweep CV in MeCN [30,92,101,332,334–343], DMF [102,337,344–346], DMSO
[337,347–349], pyridine [337], 1,2-dimethoxyethane (glyme) [92,339,349,350], and room tempera-
ture ionic liquids [29,30].
Primary and secondary nitroalkanes exist as the nonreducible anions under basic aqueous con-
ditions, but deprotonation is usually slow and it has occasionally been possible to observe the one-
electron reduction in basic aqueous solutions [351]. The radical anions of tertiary nitroalkanes have
been observed in aqueous solution as well [352].
Radical anions have been observed also for di- and trinitroalkanes in DMF [344], glyme [350],
MeOH [353] and aqueous base [352,354] and for nitroalkenes in MeCN [355,356] and DMF
[357], but geminal dinitroalkanes are inherently unstable owing to the facile loss of a nitrite ion
(see Section II.B.4).
Reduction potentials (half-wave potentials) for a series of aliphatic primary and secondary
mono- and dinitro compounds [353] and tertiary nitro compounds [334,350] have been recorded in
various nonaqueous solvents and solvent mixtures and the dependence of ion-pair formation on the
reduction process has been discussed [92,332].
The kinetics of the heterogeneous electron transfer process for reduction of aliphatic nitro
compounds have been studied extensively [30,101,102,332,333,336–338,341–343,346–349].
In particular, 2-methyl-2-nitropropane has featured as a prototype compound in such studies
[30,101,102,332,336,337,341–343,346–349]; this compound is one of the few examples of organic
substrates for which the electron transfer process appears as quasireversible even at slow sweep CV
and at the same time the radical anion has an appreciable lifetime. The values of ks have been deter-
mined by CV and by impedance measurements and are typically in the range 10 –4 < ks/(cm s−1) < 10 −1
depending particularly on the size of the electrolyte cation (R4N+) [30,101,102,332,333,336–338,
341–343,346–349]. In general, the value of ks decreases with increasing size of R4N+, which is likely
to reflect different planes of closest approach [336]. The effect of solvent appears to be smaller than
predicted by the Marcus theory [337]; this may be caused by dielectric saturation effects and/or a
solvent-dependent frequency factor, and it is most likely that also ion-pair effects that vary with the
solvent are important in determining ks [101,332,336–338,348,349]. The value of the transfer coef-
ficient, α, is typically around 0.45 and varies with the potential as predicted by the Marcus theory;
typically it is found that dα/dE is in the range 0.25–0.5 V−1 [332,336,338,348,349]. As for nitroben-
zene, it is found that the diffusion coefficients in ionic liquids, ∼10 −7 cm2 s−1, are orders of magnitude
smaller than in conventional aprotic solvents [29,30].
2-Methyl-2-nitropropane has been used to evaluate the predictions made by the Marcus–Hush
and the Butler–Volmer kinetic formalisms (see Chapter 1 for details), and it was found that the
electrochemical data could be fitted satisfactorily to both models provided that the asymmetric
Marcus–Hush model was used [333,342,343,347].
The quasireversible electron transfer for 2-methyl-2-nitropropane may be catalyzed by a redox
mediator such as terephthalonitrile [332,338]. The rate constant for electron transfer from the radical
anion of terephthalonitrile to 2-methyl-2-nitropropane in MeCN was found to be 5·105 M−1 s−1 and the
self-exchange rate constant for 2-methyl-2-nitropropane was 5·103 M−1 s−1. The temperature depen-
dence gave access to the activation energy that was found to be 25–30 kJ mol−1. Intramolecular redox
catalysis has been studied also [358,359]. Finally, it should be mentioned that myoglobin has been
applied as a redox catalyst for nitromethane reduction [360].
The lifetime of the radical anions of many nitroalkanes and nitroalkenes is sufficiently long to
allow for recording of the ESR spectra [174,335,339,350,355,357,361]. In contrast to what is observed
for nitrobenzenes, the unpaired electron has been observed to be almost exclusively localized at the
nitro group.
2. Nitroalkenes and Related

a. Simple α,β-Unsaturated Nitro Compounds
i. Reduction in Aprotic Solvents Reduction of α,β-unsaturated nitro compounds in aprotic solvents
leads to the radical anions that subsequently dimerize. The resulting dimer dianions may be converted
by protonation to the corresponding 1,4-dinitroalkanes in good yields [362–365]. The dimerization
may also be carried out electrocatalytically; in this case, 1,3-dinitrodimers are formed [363].
A more thorough reduction occurs when the reaction is carried out at a carbon cathode in DMF
in the presence of TiCl4 and with Et4NTos as supporting electrolyte. In that case, nitriles are formed
in good yields (Equation 30.30) [366]. This is a convenient method for the conversion of aldehydes
to one-carbon elongated nitriles through the preparation of the nitroalkenes by condensation of the
aldehyde with nitromethane.
5–6 F
Ar CH CH NO2 Ar CH2CN (30.30)
64–95%
ii. Reduction in Water and Other Protic Solvents The reduction of α,β-unsaturated nitro com-
pounds under acidic conditions in the presence of an organic co-solvent leads first to the oxime
[362,367–371] in 40–90% yield, presumably via the enehydroxylamine (Equation 30.31). One of the
by-products, resulting from hydrolysis, is the corresponding ketone that in a separate step may be
converted to the oxime by reaction with hydroxylamine resulting in an overall yield of the oxime
better than 90% [362].
R1 R3 R1 R3
+2e–,+2H+ +2e–,+2H+
C C C C
–H2O
R2 NO2 R2 NO
(30.31)
R1 R3 R1 R3
C C CH C
R2 NHOH R2 NOH

The oxime may be further reduced to the amine [362,371]. Similar to the preparation of chain-
elongated nitriles reported earlier, these reactions are employed for the synthesis of oximes and
carbonyl compounds with a longer carbon chain. Reduction to the amine state has been put to use in
the preparation of amino acids, for instance, tryptophan ethyl ester (50–60%) by reduction of ethyl
3-(3-indolyl)-2-nitroacrylate [372].
2,3-Dinitro-2-butene gives rise to a 2F polarographic wave at all pH values followed in acidic
solution by another pH-dependent reduction wave [373,374]. Preparative reduction in acidic solu-
tion results in complex reaction mixtures containing 2-nitro-2-butene and diacetylmonoxime and
also hydrolysis products of the latter; the former is the major product at higher pH. Reduction of
the conjugated 1,4-dinitro-1,3-butadiene at pH 1.4 results in partial saturation of the butadiene

to give a 74% yield of 1,4-dinitro-2-butene [375].
b. Halogen-Substituted α,β-Unsaturated Nitro Compounds

When speaking here about α,β-unsaturated nitro compounds, the Greek letters refer to the position
of the double bond relative to the nitro group. However, in the conventional nomenclature for com-
pounds of this type, the assignment of the carbons is reversed. Thus, β-bromo-β-nitrostyrene in the
present context is an α,β-unsaturated nitro compound.
Reduction of β-bromo-β-nitrostyrene in acidic solution gives benzyl cyanide (80%) (Equation
30.32) and benzaldehyde (10%) [373,376]; the related 1-bromo-3-methyl-1-nitro-1-butene, in which
the phenyl group is replaced by an iso-propyl group, gives a complicated reaction mixture of various
nitriles suggested to arise via an allene-type oxime that after elimination of water gives a reactive
carbocation intermediate (Equation 30.33) [377].
Br +6e–,+5H+
Ph CH C Ph CH2CN + Br– + 2H2O (30.32)
NO2

H3C Br H 3C
+4e–,+3H+
CH CH C CH CH C NOH + Br– + H2O
H3C NO2 H 3C
+H+ –H2O
(30.33)
H3C
+
CH CH CN Various nitriles
H3C
α-Chloro-β-nitrostyrene gives a mixture of products including Ph-CHOHCHO that was believed

to arise from hydrolysis of the oxime initially formed by reduction (Equation 30.34) [375] similar to
the reaction for the unsubstituted compound (Equation 30.31).
Ph Ph
+4e–,+4H+
C CH NO2 CH CH NOH + H2O (30.34)
Cl Cl
c. Nitrohydrazones
Reduction of nitroacetaldehyde phenylhydrazone in 0.05 N sulfuric acid in 25% dioxane consumed
3.7F and the corresponding hydrazooxime, resulting from tautomerization of the initially formed
azooxime, was detected as the product (Equation 30.35) [378].
CH3 CH3
+4e–,+4H+
Ph NH N Ph NH N
–H2O
NO2 NHOH
(30.35)
CH3
Taut.
Ph NH NH
NOH
Related to this is the 6F reduction of o-nitrophenylazo phenylnitromethane to o-nitrophenylben-

zamidrazone that in turn may be converted to 3-phenylbenzo-1,2,4-triazine [379] reminiscent of the
reduction benzamidoxime to benzamidine [380].
3. Mononitroalkanes and Related

Compounds that have a functional group attached to the molecule without being in electronic con-
jugation with the nitro group as a nitroalkane such as Ph–CO–CH2–NO2 and EtO–CO–CH2–NO2
are included in this section. Nitroalkanes that have potential leaving groups attached are treated in
Section II.B.7.
a. Primary and Secondary Nitroalkanes

i. Reduction in Aprotic Solvents Usually nitroalkanes such as nitromethane cannot be reduced
to the corresponding nitrosoalkanes by reduction in aprotic solvents. However, it has been observed
that the trans-dimer of nitrosomethane may be obtained by reduction of nitromethane in 1-butyl-
3-methylimidazolium tetrafluoroborate on a copper disk cathode [381]. The dimers of the nitroso
compounds are more difficult to reduce than the monomers, and this may be the reason why the
nitroso compounds survive in this case.
Reduction of weak acids to hydrogen gas and the corresponding anion is a common method for
the preparation of a so-called electrogenerated base (see Chapter 43). However, in the case of nitro
compounds such as ethyl nitroacetate, reduction is accompanied by considerable C–N cleavage.
Instead, the nearly quantitative conversion to the anion was found when reduction was carried out
in air-saturated solutions; the electrogenerated superoxide ion then serves as a base that effectively
deprotonates the substrate (Equation 30.36) [382]. Only the first step is shown.
NO2 NO2
H2C + O2 – HC + HO2 (30.36)
COOEt COOEt
The anion shown and also those derived from nitromethane, ethyl 2-nitropropionate, diethyl 2-nitro-
glutarate, 2-nitropropane, nitrocyclopentane, ethyl 2-nitro-4-pentenoate, and dinitromethane, have
all been prepared in a similar fashion and have many applications in organic synthesis [383].
Similarly, the electrochemical reduction of a mixture of, for instance, an aldehyde in nitromethane
as the solvent and with a nickel cathode leads to the formation of the nitromethane anion that in
turn adds to the aldehyde in a Michael-type reaction [384–386]. The addition products are formed
in isolated yields in the range 60–90%.
ii. Reduction in Water and Other Protic Solvents Primary and secondary nitro compounds
are weakly acidic (pKa ═ 10.2 for nitromethane) and exist as the nonreducible anions under basic
conditions. The details of the first electron and proton transfer steps have been studied by polarog-
raphy [387], impedance measurements [388–392], and application of channel electrodes [393,394],
and the data have been analyzed in terms of an ECCe-type mechanism. Results from earlier work
were in agreement with the formation of a radical anion as the first step [395]. Under acidic or
neutral conditions, electrochemical reduction at room temperature leads to the corresponding
N-alkylhydroxylamines in 60–90% yield [396–402], for instance, isolated as the hydrochloride
[398], together with minor amounts of the N-alkylamine and a carbonyl compound. It has been
shown [399] that the N-alkylhydroxylamines are not further reduced under the conditions and the
origin of the N-alkylamine and the carbonyl compound was suggested to arise instead via tau-
tomerization of the intermediate nitrosoalkane to the oxime and hydrolysis of the latter (Scheme
30.10). Here it is assumed that the electroactive species is the protonated [161] or at least strongly
hydrogen-bonded nitroalkane. The reduction at mercury electrodes involves most likely adsorbed
species [161,403].
The product from reduction of nitromethane, N-methylhydroxylamine, is an important com-
pound in organic synthesis and detailed descriptions for carrying out the electrosynthesis of this
compound at a large (industrial) scale have been reported [404,405]. In an interesting variant,
+2e–,+2H+ +2e–,+2H+
HCR΄R NO2H+ HCR΄R NOH+ HCR΄R NH2OH+
–H2O
+4e–,+4H +
CR΄R NOH2+ RR΄CHNH3+
–H2 O
H2O
CR΄R O + H3NOH+
SchEME 30.10 Reduction of nitroalkanes to the oxime and hydroxylamine in aqueous solution.
the focus was on the formation of the oxime, and it was shown [406] that reduction of α-nitrobenzylic
compounds in aqueous acetic acid buffers mixed with ethanol resulted in a mixture of the oxime
and the hydroxylamine; the latter could then be oxidized, chemically or electrochemically, to
the oxime via the nitrosoderivative. The overall yields of the oximes were in the range 80–90%.
As seen from Scheme 30.10, the tautomerization of the nitrosoalkane competes with the further
reduction to the N-alkylhydroxylamine and accordingly it would be expected that lowering the
temperature would slow down tautomerization and thus favor the further reduction. In contrast,
increasing temperature would be expected to favor the formation of the N-alkylamine. This is
indeed what is observed and it has been reported that, for instance, the electrochemical reduc-
tion of α-hydroxynitroalkanes at 65–86°C leads preferentially to the aminoalcohols, whereas
hydroxylaminoalcohols are the products when the reduction is carried out at 0–35°C [407]. Also,
the rate of tautomerization of the nitrosoalkane to the oxime depends on pH and on the nature
of the substituents, R and R′ and, as the rule, the rate increases with increasing electronegativ-
ity of R and R′ [408–413] and, accordingly, a higher proportion of the amine is observed when
one or both of R and R′ are strongly electron withdrawing. In the extreme, the amine is the only
product as it has been observed during the reduction of 2-nitromalonic ester (R ═ R′ ═ COOEt)
to 2-aminomalonic ester at low pH [412,414]. The hydroxyiminomalonate that is an intermediate
in this reaction may be reduced electrocatalytically to the 2-aminomalonate at a Ti/nanoporous
TiO2 electrode [415]. Similar to what is observed for aromatic nitro compounds, the formation
of heterocyclic products is observed when the nitro group is positioned strategically relative to
another functional group. The reduction of γ-nitroesters to N-hydroxypyrrolidinones [401] serves
to illustrate this aspect (see Chapter 34 for a general discussion of the formation of heterocyclic
compounds).
b. Tertiary Mononitroalkanes

i. Reduction in Aprotic Solvents The radical anion of 2-methyl-2-nitropropane has a life
time, t½, of approximately 0.66 s in glyme (1,2-dimethoxyethane) [350] and decomposes into nitrite
ion and a tert-butyl radical [334,335,339,346,350,416]. When generated electrochemically, continued
electrolysis was found to give di-tert-butylnitroxide, ((CH 3 )3 C)2 N−O• [335,339,350]. However, other
products may arise from the follow-up reactions of electrogenerated tert-alkyl radicals depending on
whether the radical is further reduced under the reaction conditions and on the lifetime of the radical
anion. Some of these pathways are summarized in Scheme 30.11.
Dimerization of the free radicals, R3C•, was observed for tert-nitrocumene [350] and
2-(4-nitrophenyl)-2-nitropropane (Scheme 30.12) [345]. In the latter case, the radical anion was
found to cleave heterolytically as indicated [340]. Complete reduction to the alkane, and other prod-
ucts, was observed for 2-nitro-2,4,4-trimethylpentane [350].
When 2-methyl-2-nitropropane is reduced in MeCN in the presence of a proton donor such as
PhOH, protonation competes effectively with elimination of nitrite ion and the hydroxylamine is
formed [334].
+e– slow
R3C NO2 R3C NO2 – R 3C + NO2–
–e–
R3C R3C CR3
R3C NO2 –
R3C (R3C)2NO2– R3C NO + R3CO–
+e–
R3C– R3C
(R3C)2N O
R3C
(R3C)2N OCR3
SchEME 30.11 Pathways for the reduction of tert-nitroalkanes.
–
CH3 CH3
O2N NO2 – O2N
–NO2
CH3 CH3
CH3 CH3 CH3
2O2N O2N NO2

CH3 CH3 CH3
SchEME 30.12 Mechanism for the reduction of 2-(4-nitrophenyl)-2-nitropropane.
ii. Reduction in Water and Other Protic Solvents The tertiary nitroalkanes differ from the
primary and secondary compounds in that the intermediate nitroso derivatives cannot rearrange
into the oximes. Accordingly, the yield of alkylhydroxylamine is usually high (80–90%) [399].
The nitroso intermediate may in this case be detected directly in the reduction mixture by its blu-
ish green color and its polarographic wave. The hydroxylamines are reduced to the correspond-
ing amines at a lower potential [417] and resemble in that respects the aromatic nitro compounds.
Similar to what was observed in aprotic media, it was found that tert-nitrocumene could be reduced
at mercury in basic aqueous methanol to the R3C–CR3 dimer; however, if instead a porous Raney
nickel cathode was used, catalytic hydrogenation resulting in the formation of the amine took place
almost exclusively [418].
4. Dinitroalkanes
a. Reduction in Aprotic Solvents
The radical anions resulting from the reduction of nonacidic geminal nitroalkanes such as
2,2-dinitropropane [120,419] and 1,1-dinitrocyclohexane [344,354,420,421] in DMF undergo cleav-
age of a C–N bond forming a nitroalkyl radical and nitrite ion. The following steps for the reduction
of 1,1-dinitrocyclohexane leading to the formation of the vicinal 1,1′-dinitrobicyclohexyl include a
chain reaction between the nitronate anion and the starting material (Scheme 30.13). A minor prod-
uct is nitrocyclohexane resulting from further reaction of the nitrocyclohexyl radical.
Related compounds in which one of the nitro groups is replaced by another electron-withdrawing
group react similarly [344].
Vicinal dinitro compounds such as 1,1′-dinitrobicyclohexyl (the product given earlier) have been
investigated carefully [420]. Reduction in DMF, here illustrated by 2,3-dinitro-2,3-dimethylbutane,
proceeds according to Scheme 30.14. The rate constant for elimination of nitrite ion from the radical
anion was close to 103 s−1.
NO2
+e– NO2 –
NO2
–e– –NO2–
NO2 NO2
+e–
NO2 NO2 – NO2

–
+
NO2
NO2
–
NO2
NO2 NO2
–
NO2 + + NO2–
NO2
O2N
SchEME 30.13 Mechanism for the reduction of 1,1-dinitrocyclohexane.
H3C CH3 H3C CH3 – H3C CH3

+e–
O2N NO2 O2N NO2 O2N
–e– –NO2–
H3C CH3 H3C CH3 H3C CH3
+e–
H3C CH3 H3C CH3
–
H3C CH3
O2N + O2N NO2 + NO2–
H3C CH3
H3C CH3 H3C CH3
H3C CH3
O2N NO2
H3C CH3
–
H3C CH H3C CH3
+e–
O2N NO2
–2NO2–
H3C CH3 H3C CH3
SchEME 30.14 Mechanism for the reduction of 2,3-dinitro-2,3-dimethylbutane.
b. Reduction in Water and Other Protic Solvents

The reduction of geminal dinitroalkanes carrying an acidic hydrogen in the α-position depends on
both the structure and not least on pH of the electrolyte solution and related to this, the position of
the equilibrium between the nitro and aci-forms. An additional complication is that the aci-form
may suffer hydrolysis to the corresponding carbonyl compound under acidic conditions (the Nef
reaction).
The reduction of 1,1-dinitroethane in acidic solution required 5–6F and nitrous acid was
detected in the resulting solution [422]. The following sequence of steps (Equation 30.37) lead-
ing to the hydroxamic acid oxime via the intermediate formation of the nitrolic acid has been
proposed [423–425]. The reduction of dinitromethane appears to follow a similar route, but is
further complicated by nitrosation of the starting material with the nitrous acid liberated during
reduction [425].
H3C NO2 H3C O– H3C OH

+2e– +2H+
N+ + NO2– N+ + HNO2
H NO2 H O– H O–
(30.37)
NOH NOH
+4e–,+4H+
H 3C C H3C C
–H2O –H2O
NO2 NHOH

The anions resulting from deprotonation of acidic 1,1-dinitroalkanes are reduced in a reversible
or quasireversible one-electron process to ion-paired dianion radicals that suffer protonation and fur-
ther reduction to the corresponding nitrolic acids and hydroxamic acid oximes [426–428] or cleavage
of the C–N bond [429] depending on the conditions. The anions have a high affinity for mercury and
give rise to an anodic polarographic wave resulting from the formation of organomercurials [430].
The ESR spectra of the dianion radicals have been recorded in a number of cases [361,431].
In slightly acidic solution, 2,2-dinitropropane is first reduced to the nitronate anion and nitrite
in a 2F process; further reduction of the resulting pseudonitrole leads to acetone oxime (Equation
30.38) [422,432,433].
H3C NO2 H3C O– H3C NO

+2e– +2H+
N+ + NO2–
H3C NO2 H3C O– H3C NO2
(30.38)
+2e–,+2H+ H3C
NOH + HNO2
H3C
The formation of the pseudonitrole requires the presence of the nitrous acid also formed in the
first step. If the nitrous acid is removed by adding a scavenger or by reduction (to hydroxylamine
and ammonia), which may happen at lower potentials, the nitronate anion is instead protonated to
2-nitropropane that in turn is reduced to the 2-hydroxylamine [419]. In basic solution, reduction
stops after the formation of the 2-nitropropane anion and nitrite (Equation 30.39) [422,432,433].
Upon addition of acid to the resulting solution, the corresponding pseudonitrole is formed as earlier.
H3C NO2 H3C O–

+2e–
N+ + NO2– (30.39)
H3C NO2 H3C O–

Nitrolic acids are reduced in acidic solution to N-hydroxyacetamidoximes [434,435] and further
to N′-hydroxyacetimidamide and acetamidine [435]; the N-hydroxyacetamidoximes may be oxi-
dized anodically to the corresponding nitrosolic acids. In alkaline solution, nitrolic acids have been
reported to undergo reductive dimerization to azo derivatives (Equation 30.40) [436].
NO2 +8e–,+8H+ H3C C N N C CH3
2H3C C (30.40)
–4H2O NOH NOH
NOH
5. Trinitroalkanes
The reduction of trinitroalkanes [425,437–439] proceeds similarly to reduction of dinitroalkanes; how-
ever, the presence of the extra nitro group causes the intermediate nitronitrolic acid (dinitroformoxime)
[440] derived from trinitromethane to be reduced to 1,3-dihydroxyguanidine [425,437,439]. In base,

the 1,3-dihydroxyguanidine is slowly converted to nitrosoformimidamide that in turn is reduced to
1-hydroxyguanidine [437].
The first step in the reduction of 1,1,1-trinitroethane includes as expected from the pattern out-
lined earlier reductive cleavage to the dinitromethane anion and nitrite [361,441]. The anion may then
undergo nitrosation, protonation, and/or the Nef reaction [441]. The reduction of the anions leads to
elimination of nitrite [429], but detailed polarographic studies are hampered by adsorption [442].
6. Tetranitroalkanes
The tetranitromethane radical anion undergoes cleavage to the trinitromethane anion and nitrite ion
as expected [395,437,438,443]. The yield of trinitromethane is high (80%) when reduction is carried
out at a platinum electrode in acidic solution [438], but drops to around 45% in neutral solution.
A parallel, nonelectrochemical reaction between tetranitromethane and mercury has been observed;
the details of this reaction are not clear [437].
7. α-Halonitroalkanes
Nitroalkanes with a potential leaving group in the α-position are observed to undergo elimination
upon electrochemical reduction. Typically the leaving group is a halide ion (Cl−, Br−, or I−; see also
Chapters 24 and 25) but may also be other good leaving groups such as p-toluenesulfinate [344]
or NO2− as in the reduction of 1-cyano-l-nitrocyclohexane [344] and in the geminal dinitroalkanes
discussed earlier. This raises the question of which anion is eliminated during the reduction of an
aliphatic compound having a nitro group and a potential leaving group attached to the same carbon.
Using the halides as an example, the first step of the reductions may proceed according to one of
the following two 2F routes (Equations 30.41 and 30.42). The resulting carbanion may undergo a
variety of reactions. The abbreviations Y and Z symbolize a hydrogen atom, an alkyl group, an
additional halogen atom (Hal), or an additional nitro group.
Y Y O Y O–
+2e– + +
Hal NO2 – N N + Hal– (30.41)
Z Z O– Z O–

Y Y
+2e–
Hal NO2 – Hal + NO2– (30.42)
Z Z
Reduction of α-monohalo-α-mononitroalkanes (Hal ═ Cl, Br, I; Y ≠ NO2; Z ≠ NO2) proceeds

according to Equation 30.41 with the loss of Hal− and the formation of the nitronate ion that subse-
quently may undergo a variety of reactions, including protonation and further reduction, depending
on the structure of the substrate, the experimental conditions, and the addition of suitable reactants
to the electrolysis solution [423,444–446]. The reaction is governed by the stability of the resonance
stabilized nitronate anion that may gain additional stability by, for instance, the presence of a neigh-
boring carbonyl group as in 2-bromo-2-nitroacetophenone [400] and in α-halo α-nitro derivatives
of camphor [447].
Similarly, the reduction of α,α-dihalo-α-mononitroalkanes [423] and α,α,α-trihalonitromethanes
[423,448] follows Equation 30.41; in those case, the halogen atoms may be lost one-by-one in altogether
two or three reduction, elimination, protonation sequences. For example, reduction of 2-halo-2-nitro-
propanes (Y ═ Z ═ Me) in aprotic media results in the formation of 2,3-dimethyl-2,3-dinitrobutane
in good yields [444]. The reaction was suggested to most likely include a 2F reduction to the
2-nitropropane anion (Equation 30.41) that subsequently reacts with the starting material in nucleo-
philic substitution reaction. Similarly, reduction of 3,7-dibromo-3,7-dinitrobicyclo[3.3.1]nonane in
aqueous acetone gave 3,7-dinitronoradamantane in 75–80% yield [446]. Related to these reactions
is the reduction of 2-bromo-2-nitropropane at mercury in dichloromethane in the presence of methyl
propiolate that gives a mixture of 2,3-dimethyl-2,3-dinitrobutane, 2-nitropropane, methyl (E)-4-
methyl-4-nitro-2-pentenoate and an organomercurial. A more unusual reaction was observed in the
presence of dimethyl acetylenedicarboxylate from which the two products shown in Equation 30.43
could be identified [445]:
H3C NO2 H3C O– H 3 COOC COOC H 3

+2e– +
N
–Br–
H3C Br H3C O–
H3COOC H3COOC COOCH3

(30.43)
CHCOOCH3
+ H3C
H3C
COOCH3
N
O2N CH3 H3C

A variety of different products also resulted from the reduction of 5-halo-5-nitro-1,3-dioxanes

and 2-halo-2-nitro-1,3-propanediols and also in this case the first reaction proceeds according to
Equation 30.41 [449].
The first reduction step for α-monohalo-α,α-dinitroalkanes (Hal ═ Cl, Br, I; Y ═ NO2; Z ≠ NO2)
[441] and α-monohalotrinitromethanes (Hal ═ Cl, Br, I; Y ═ Z ═ NO2) [450] depends both on the halo-
gen and the number of nitro groups. For example, during the reduction of α-bromo-α,α-dinitroethane,
NO2− is eliminated (Equation 30.42), whereas for bromotrinitromethane elimination of Br− (Equation
30.41) is followed exclusively [450]. For chlorotrinitromethane, the two pathways compete [443,450].
Fluoride ion is not a leaving group during the reduction of fluoronitroalkanes [424,441,451–454].
Thus, for example, fluorotrinitromethane is first reduced to fluorodinitromethane, which in turn
may be reduced to fluoronitromethane.
8. β-Substituted Nitroalkanes
Studies of the electrochemical reduction of β-hydroxynitroalkanes in acidic solution may be
hampered by the parallel elimination of water to the more easily reduced α,β-unsaturated
nitroalkenes and in basic solution by deprotonation to the corresponding anions [455,456]. Still,
it is possible to convert, for instance, methyl α-nitro-β-hydroxybutyrate to the d,l-threonine
methyl ester in an overall 6F process [457,458]. Reduction of acylated β-hydroxynitroalkanes in
DMF results in the formation of the alkenes by elimination of nitrite and alkoxide ions (Equation
30.44) [459].
H R
–
H R
–
+2e–
RO NO2 + RO– + NO2– (30.44)
R R R R
–
––

–
––
The nitro group in 2-nitroacetophenone (a β-carbonylnitroalkane) is reduced in preference to

the carbonyl group. At pH < 5, the reduction involves the enol-form according to Equation 30.45
[400,460].
Ph O Ph O +4e–,+4H+ Ph H
N+ N+ N (30.45)
–H2O
O O– OH O– O OH
9. α,β-Disubstituted Nitroalkanes
The reduction of α,β-dibromonitroalkanes proceeds as a 2F process with the elimination of bromide
to the corresponding nitroalkene (Equation 30.46) [376], whereas reduction of 1-bromo-1-nitro-2-
butanol leads to 1-nitro-2-butanol in a 2F process with elimination of bromide ion accompanied by
the formation of 1-nitrobutene [400].
Ph NO2
+2e–
Ph CH CH NO2 (30.46)
–2Br–
Br Br
III. NiTROSO COMPOUNDS

The interest in the electrochemical reduction of nitroso compounds is partly related to the fact that
they are notable intermediates in the reduction of nitro compounds as discussed earlier. Another
driving force is the application of nitroso compounds as spin traps [461–466]. In this section, we
will discuss only reactions in which the nitroso compounds are the starting materials.
In spite of the fact that nitroso compounds are intermediates in the reduction of nitro compounds,
significant differences are often observed when the reduction sequence is initiated at the nitroso
level. For instance, aliphatic nitroso compounds and o-substituted nitrosobenzenes exist in solution
mainly as the N-N dimers [146,462,467–472] and this has consequences for the electrochemical
behavior. Also, the radical anions of nitrosobenzenes tend to dimerize (reversibly) and this of course
affects the competition between the formation of hydroxylamines and azoxybenzenes. Finally, it
should be recalled also that nitroso compounds are susceptible to nucleophilic attack and this is of
importance when reduction is carried out under nonacidic conditions [473]. These aspects, to be
discussed briefly later, are usually of no concern when the nitroso compounds result from reduction
of the corresponding nitro compounds since in that case the “side reactions” do not have the time
to manifest themselves, mechanistically or product-wise, before the nitroso compounds are further
reduced.
A summary of the electrochemistry of nitroso compounds is included in a 1994 review [473].
A. AroMaTIC NITroSo CoMpoUNDS

Compounds in which one or more nitroso groups are attached to a benzene ring or a substituted
benzene ring are included in this section. When an aromatic compound contains both a nitro and
a nitroso group, the nitroso group is reduced first, usually leaving the nitro group unaffected. Such
mixed compounds are therefore considered as nitroso compounds and treated in this section.
1. Formation of and Properties of the Radical Anions and Dianions

The electrochemical reduction of nitrosobenzene and substituted nitrosobenzenes to the radi-
cal anions has been observed by CV in aprotic solvents such as MeCN [465,474,475], DMF
[15,41,48,462,476–482], and DMSO [475] and in liquid ammonia [23]. The radical anions may, of
course, be formed during CV by reduction of the monomeric nitroso compounds (Equation 30.47)
but also by reductive cleavage of the dimers (Equation 30.48) [462]. It follows that the dissociation
of the dimers usually is slow at the time scale of routine CV.
+e–
R NO R NO – (30.47)
–e–
+2e–
(R NO)2 2R NO –
(30.48)
The radical anions derived from nitrosobenzenes are as the rule more reactive than the corre-
sponding nitrobenzene radical anions [15,23,478]. For example, the nitrosobenzene radical anion is
a stronger base than the nitrobenzene radical anion [23], and this of course strengthens the require-
ments of conducting the experiments under “water-free” conditions if protonation is to be avoided.
However, even under “dry” conditions, (reversible) dimerization of the radical anions, an inherent
property of these species, is frequently observed [48,474–480] (see Section III.A.3).
The effects of ion-pair formation follow the common rules; the stronger the ion-pair, the easier
the nitroso compound is to reduce [480]. Ion-pair formation is usually accompanied by charge
localization and thereby by spin localization. Thus, ion-pair formation accentuates the tendency of
nitrosobenzene radical anions to dimerize.
Reduction by CV of nitrosobenzene and substituted nitrosobenzenes in basic aqueous solution
have in few cases resulted in the reversible formation of the radical anions [497] and the nitrosoben-
zene radical anion has been detected in aqueous solution by pulse-radiolysis as a short-lived species
[483]. However, mostly reduction in aqueous solution proceeds to the hydroxylamine as a reversible
2e−, 2H+ process (Equation 30.8).
The reduction of the radical anion to a persistent dianion requires the strict absence of residual
water and has to the best of our knowledge not yet been observed at room temperature for unsub-
stituted nitrosobenzene: However, the reversible one-electron couple for the reduction of the radical
anion has been observed in liquid ammonia [23]. Less reactive dianions are observed for nitroso-
benzenes carrying an additional electron-withdrawing group such as a nitro group [41,48].
The reduction potentials have been recorded for a large number of substituted nitrosobenzenes
in various solvents [83,462,465,484]. The nitrosobenzenes are easier to reduce than the correspond-
ing nitrobenzenes under similar condition [23,41,83,133,143], and the monomers are more easily
reduced than the dimers [146,462].
We are not aware of studies in which the heterogeneous electron transfer rates of nitrobenzenes
and nitrosobenzenes are compared under identical conditions. However, the formation of the nitro-
sobenzene radical anion appears to be quasireversible at a CV sweep rate of 30 Vs−1 [474]. The
electron transfer rate for a series of 4-(3-nitrosophenyl)-1,4-dihydropyridine derivatives was found
to be two orders of magnitude smaller on glassy carbon than on mercury electrodes [485].
The UV/Vis [474,475,479] and ESR [148,465,466,475,478,479,486,487] spectra have been
recorded for the radical anions of a number of nitroso compounds
The preparative electrochemical reduction of nitroso compounds is only of practical use in rare
cases owing to the limited availability of the starting materials and separate sections are for that
reason not called for. Thus, the following sections will include both mechanistic and preparative
aspects.
2. Routes to Phenylhydroxylamines and Anilines

a. Protonation in Aprotic Solvents
The initial protonation of the nitrosobenzene radical anions that ultimately leads to the forma-
tion of phenylhydroxylamines and anilines has to be fast in order to compete with the tendency
of the radical anions to dimerize. Thus, it is typically observed that addition of an acid of
suitable strength in increasing amounts results in a gradual change from the formation of the
azoxybenzene to the formation of the hydroxylamine [23,474]. Another example that demon-
strates that even subtle differences in the reaction conditions may influence the competition
between dimerization and protonation is the effect of the nature of the supporting electrolyte
observed for reduction of nitrosobenzene in DMF [488]. When Et4NClO 4 was used, the route
to phenylhydroxylamine was found to dominate, whereas when alkalimetal perchlorates were
used, the route to azoxybenzene was dominating, in the last case likely to be governed by the
formation of ion-pairs [480] that localizes the spin and thereby the tendency of the radical
anions to dimerize.
b. Protonation in Water and Other Protic Solvents

The reduction of nitrosoarenes in aqueous solutions at all but the most high pH values proceeds as a
2e−, 2H+ reaction to the corresponding hydroxylamine [143,160,196,473,479,481,484,485,489,490] that
during polarography and CV is observed as a reversible or quasireversible redox couple (Equation
30.8). The sequence of electron and proton transfers [160] has already been discussed in Scheme 30.6.
At pH < 4, the reaction proceeds to the protonated hydroxylamine [484]. The hydroxylamine may in
turn be reduced to the aniline in another 2e−, 2H+ process (see Section IV).
Similarly to what was observed for the nitrobenzenes, the reduction of nitrosobenzenes sub-
stituted in the p-position with a hydroxy [206,219,484,491] or an amino group [220,221,484,492]
proceeds directly to the amine in yields that may exceed 90%. 1-Nitroso-2-naphthol reacts in the
same way [493,494]. The rate constants, k, for the dehydration steps (Equation 30.19) were found to
be in the range 0.4−1.0 s−1 [219–221].
3. Routes to Azoxybenzenes, Azobenzenes, Hydrazobenzenes, and Benzidines

The formation of the new N–N bond in the route to azoxybenzenes and the reduction products may
in principle occur via (1) reduction followed by dimerization or (2) dimerization followed by reduc-
tion. In the latter case, reduction proceeds all the way to the hydrazobenzene stage owing to the low
potential required to reduce the dimer, whereas electrolysis of the more easily reduced monomers
may stop at the azoxy- and azo stage.
The electrochemical process is accompanied by a nonelectrochemical route to azoxybenzenes ini-
tiated by the reaction between the nitrosobenzene and alkoxide or hydroxide ion [473,477,495–498],
the latter being formed during electrochemical reductions even in aprotic solvents owing to deprot-
onation of residual water. Several mechanism suggestions for the reaction have been offered, but all
the details are not yet fully understood. In addition to the azoxybenzene that results from the initial
nucleophilic attack of hydroxide ion on the nitroso function [495], variable amounts of the quinone
monoxime (or the anion = p-nitrosophenolate) resulting from competitive attack of hydroxide ion at
the p-position are formed as well [496]. This has led to the suggestion of the stoichiometry shown
in Equation 30.49 [477]. As a result of this nonelectrochemical route to azoxybenzene, the electro-
chemical process often consumes only 0.3–0.8F.
3Ph NO + OH– Ph N+ N Ph + –O NO + H2O (30.49)

O–
a. Reduction in Aprotic Solvents

Azoxybenzene is detected by CV during the reduction of PhNO in MeCN [15,474,475], and it is well
known that electrolysis of nitrosobenzenes in an aprotic solvent leads to the formation of the azoxy-
benzenes [476,479]. The yields of azoxybenzene in MeCN and DMF are typically 70–85% [477].
These results illustrate that dimerization of the electrogenerated nitrosobenzene radical
anions is the default reaction; the dimer dianions are subsequently protonated by residual water
(Equation 30.14) or deliberately added acids, resulting in the formation of the corresponding
azoxybenzenes [23,474–481]. The route from the radical anion to the azoxybenzene product
may vary from the one given by Equation 30.14, and several variants of the order of proton-
ation and elimination of hydroxide ion have been suggested, including dimerization of proton-
ated radical anions, depending on the proton availability. When the reaction is carried out
with alkali metal salts as supporting electrolytes, ion-pairs are involved in all the reaction
steps and the formation of azoxybenzene has been suggested to include the elimination of the
alkali metal oxide [480]. If acids are added, the azoxybenzene may arise via the classical reac-
tion between nitrosobenzene and phenylhydroxylamine [23]. In a special case, the reduction
of nitrosophenyl-1,4-dihydropyridines, it has been suggested that the protons required for the
formation of the azoxy compound originate from the N–H group of the parent compound in a
self-protonation–type reaction [478]. The rate constants for dimerization, k dim, have been deter-
mined in a number of cases [475,478,479] the values for o- and m-nitrosotoluene radical anion
being 4100 and 2700 M−1 s−1, respectively [479]. The results from a spectroelectrochemical
study have indicated that attack of the radical anion in p-position of the parent nitrobenzene to
produce N-(4-nitrosophenyl)-N-phenylhydroxylamine may proceed in parallel to the azoxyben-
zene pathway [474].
b. Reduction in Water and Other Protic Solvents

As discussed earlier, the reduction of nitrosobenzenes in aqueous solution at most pH values results
as the rule in the formation of phenylhydroxylamines. However, azoxybenzenes may be formed at
pH > 10 but, as discussed earlier, in that case studies are hampered by the parallel nonelectrochemi-
cal reaction between nitrosobenzene and hydroxide ion to azoxybenzene. It has been suggested that
the formation of azoxybenzenes under those conditions in special cases may follow the classical
reaction between the nitrosobenzene and the hydroxylamine [481].
During CV of o-nitrosobenzoic acid in an aqueous 1:1 H2PO4−/HPO42− buffer, the correspond-
ing azobenzene/hydrazobenzene reversible redox couple was observed when the scan was reversed
after reduction of the dimer has taken place according to Equation 30.50 [146]. This is an example
of reduction of a neutral nitrosobenzene dimer.
O– O–
+6e–,+6H+ H H –2e–,–2H+ (30.50)
Ar N+ N+ Ar Ar N N Ar Ar N N Ar
–2H2O +2e–,+2H+
4. Other Reactions of Nitrosobenzenes

Examples of using nitroso compounds as spin traps include trapping of the neutral free radicals
resulting from reduction of aliphatic halides [463] and pyrylium ions [464] by nitrosodurene and
related nitrosobenzenes.
The electrochemical reduction of nitrosobenzene in THF in the presence of a carbon acid such
as fluorene or indene induces a chain reaction resulting in a mixture of the anil, the nitrone and
azoxybenzene [497,499]. At low temperature, the anil is formed almost exclusively. When phenyl-
acetylene is used as the carbon acid, azoxybenzene is the main product.
Reduction of nitrosobenzene in MeCN in the presence of acetic anhydride results in the forma-
tion of the corresponding N-acetoxy-N-phenylacetamide. This reductive acylation is believed to
involve the steps shown in Equation 30.51 [82] (R ═ Ph):
O
CH3
+e– Ac2O +e– – Ac2O
R NO R NO – R NOHAc R NOHAc R N CH3 (30.51)
–e– –AcO– –AcO–
O
O
5. Nitronitrosobenzenes
The reduction of the three isomeric nitronitrosobenzenes has been investigated in DMF in the
presence of various carboxylic acids [48]. Mixtures of the corresponding hydroxylamines and
azoxybenzenes were obtained, in all cases resulting from reduction of the nitroso function. The
azoxybenzenes were favored in general, but the stronger the acid or the higher the concentration,
the higher the yield of the hydroxylamine. For 2-nitronitrosobenzene in the presence of a 10-fold
excess of benzoic acid, for example, the hydroxylamine was the main product that could be obtained
in 80% yield. The azoxy compounds were suggested to arise via the reversible dimerization of the
nitronitrosobenzene radical anions. The resulting dimer dianions were then trapped by acid.
6. Heteroaromatic and Related Nitroso Compounds

Reduction of 4-nitrosopyridine-N-oxide in aqueous solution between pH 2 and pH 9 results in the
formation of the azoxy derivative [500,501].
The electrochemical reduction of 6-amino-5-nitroso-1,3-dimethyluracil to 5,6-diamino-1,3-
dimethyluracil, an intermediate in the synthesis of caffeine and theophylline, has been investigated
intensely, and it was found that the conversion may be carried out in good yield at a variety of
cathodes including foamed nickel [502,503], platinum [503], Kh18N10T stainless steel [504], as
well as cathodes made of carbon fibers [505]. Related to this is the tin-ion catalyzed reduction of
2,4,6-triamino-5-nitrosopyrimidine to 2,4,5,6-tetraaminopyrimidine [506], a key substrate in the
synthesis of methotrexate.
B. ALIpHaTIC NITroSo CoMpoUNDS

Studies of the electrochemical generation of the radical anions of nitrosoalkanes seem to be limited
to the reduction of the tertiary 2-methyl-2-nitrosopropane [461,462,507] The radical anion has been
characterized by ESR spectroscopy [465,507].
1. Primary and Secondary Nitrosoalkanes

Primary and secondary nitrosoalkanes are unstable compounds and tautomerize readily in aque-
ous solution to the corresponding oximes in an acid/base catalyzed reaction. As a consequence, the
reduction products are those of the oximes, that is, the corresponding amines [380].
When monomer-dimer equilibrium for the nitrosoalkanes favors the dimer, reduction leads to
the hydrazo compounds in a 6F process as observed, for instance, for nitrosocyclohexane (Equation
30.52) [467]. This is in analogy to what is observed for the reduction of o-nitrosobenzoic acid
[146] but in contrast to the reversible 2e−, 2H+ reduction of nitroso monomers to hydroxylamine
(Equation 30.8):
O–
NO H H
+6e–,+6H+ H
2 N+ N (30.52)
N+ –2H2O N
H H H
–O H

2. Tertiary Nitrosoalkanes
The 2-methyl-2-nitrosopropane monomer is reduced in unbuffered aqueous solution or in MeCN to
N-tert-butylhydroxylamine [461], possibly with residual water serving as the proton donor in MeCN.
The reductive acylation described earlier (Equation 30.51) may be carried out also with 2-methyl-
2-nitrosopropane [82] (R ═ t-Bu).
3. α-Halonitrosoalkanes
The reduction of mono- and dihalogenated nitrosoalkanes proceeds analogously to the reduction of
the corresponding nitroalkanes; thus 2-chloro-2-nitrosopropane gives acetoxime in 98% yield upon
reduction at pH 3 (Equation 30.53) [423] and 1,1-dichloro-1-nitrosoethane gives chloroacetaldoxime
in 76% yield [423].
H3C X H3C
+2e–,+H+
NOH X = Cl, Br (30.53)
–X–
H3C NO H3C

4. Nitronitrosoalkanes (Pseudonitroles)
Pseudonitroles, such as 2-nitro-2-nitrosopropane, are reduced in weak acidic aqueous solution in
a 2F process, resulting in the elimination of nitrite ion and the formation of the oxime (Equation
30.54) [423].
H3C NO H3C
+2e–,+H+
NOH + NO2– (30.54)
H3C NO2 H 3C

IV. HYDROxYLAMiNES
A. AroMaTIC HYDroXYLaMINES
The electrochemical reduction of simple arylhydroxylamines in nonaqueous solvents does not seem
to have received attention. However, the reduction of 2- and 4-nitrophenylhydroxylamines in DMF
has been reported to proceed to the corresponding nitroanilines [41,508] in a self-protonation pro-
cess reflecting the acidity of the hydroxylamine [509].
Polarographic studies of phenylhydroxylamine in aqueous solution have shown that reduction
involves either the mono- or diprotonated form depending on the acidity of the solvent and that
adsorption plays an important role [139,140]. The proposed reaction sequence accounting for the
formation of aniline, and as side products hydrazobenzene and benzidine, is shown in Scheme 30.15
without specifying the adsorption equilibria.
B. ALIpHaTIC HYDroXYLaMINES
Aliphatic hydroxylamines are not easily reduced electrolytically. In acidic aqueous solution, the
polarographic wave is masked by hydrogen evolution, but a reduction wave is seen in a narrow pH
region around 7. Indirect reduction to amines may be accomplished by electrochemically generated
Ti3+ or Fe2+ [510].
+H+ +e–
Ph NHOH Ph NH2OH+ Ph NH2OH
–H+ –H2O
NH NH
+e– +H+ +H+

Ph NH Ph NH– Ph NH2 Ph NH3+
-H+
+H+
Ph NH2 + H2N NH3+

–H+
SchEME 30.15 Reduction pathways for phenylhydroxylamine in aqueous solution.

V. -NiTRAMiNES, N-NiTROSAMiNES, N-NiTRAMiDES,
N
AND N-NiTROSAMiDES
A. N-NITraMINES aND N-NITroSaMINES
The reduction of primary nitramines in MeCN proceeds via a father–son-type reaction with a stoi-
chiometry corresponding to 1F (Equation 30.55), owing to the presence of the acidic α-protons
[511]. In the presence of a proton donor such as PhOH, the stoichiometry changes as expected to 2F
(Equation 30.56):
+2e–
2R NH NO2 R NH2 + R N– NO2 + NO2–
(30.55)
+2e–
R NH NO2 R NH3 + NO2– (30.56)
PhOH
Secondary nitramines are reduced in MeCN and DMF in an irreversible two-electron process that
includes cleavage of the N–N bond (Equation 30.57) [512,513]. It has been proposed that the reduc-
tion proceeds via a nitramine radical anion in which the N–N bond is considerably weakened.
Protonation of the R1R2N− anion leads to the secondary amine, R1R2NH.
R1 R1
+2e– (30.57)
N NO2 N– + NO2–
R2 R2
In acidic aqueous solution, protonated N-nitramines are reduced to the unsymmetric hydrazine
in a six-electron process (Equation 30.58) [514–517] with the amine as a by-product [517].
R1 +6e–,+7H+ R1
N NO2 N NH3+ + 2H2O (30.58)
R2 R2
In alkaline solution, most N-nitro derivatives of primary amines are deprotonated to R–N–NO2−
that cannot be reduced, with nitraminopyridines as exceptions [517], whereas N-nitramines of
secondary amines are reduced in two steps. [514]. An N-nitrosamine is produced during the first
reduction step in a 2F process. It is noteworthy that N-nitrosamines in basic solution are more dif-
ficult to reduce than the corresponding N-nitramines.
N-Nitro-N-arylhydrazones such as 3-(N-nitro-N-arylhydrazono)pentane-2,4-diones are reduced
in acidic solution in two 4F steps; first, the nitro group is reduced to the hydroxylamine state, which
is followed by reductive cleavage of the C═N–N bond (Equation 30.59) [518]. Apparently, reductive
cleavage of the N–N bond does not take place in the first step. The resulting 3-aminopentane-2,4-
dione may be further reduced to pentane-2,4-dione.
NO2 +4e–,+4H+ NHOH

Ar N COCH3 Ar N COCH3
N –H2O N
COCH3 COCH3
(30.59)
+4e–,+4H+ COCH3
Ar NH NHOH + H2N CH
–H2O COCH3

O NH
+2e– (MeCN,H2O)
O N NO
+4e– (MeCN,HOAc)
O N NH2
SchEME 30.16 The 2 and 4F processes in the reduction of N-nitrosamines.
Reduction of 1-nitropyrazol in acidic media results in a cleavage of the N–N bond and formation
of nitrous acid; at pH > 4, a competitive reduction to the nitrosamine takes place [331].
The reduction of secondary N-nitrosamines in aprotic solvents (MeCN, DMF) in the presence
of protons donors may take two different routes depending on acidity of the solvent system. In the
presence of weak acids (water, PhOH), a two-electron process including N–N cleavage and the
formation of the amines is observed [519] (Scheme 30.16), similar to what has been observed in
aqueous base [520], whereas the preferred route in the presence of stronger acids (AcOH, PhCOOH)
leads to the formation of 1,1-dialkylhydrazines in a four-electron process [519].
This effect of acidity has been studied in detail in aqueous solution, and it was found that the 2F
process leading to the secondary amine is accompanied by the formation of N2O (Equation 30.60),
whereas the 4F process leading to the hydrazines involves the protonated N-nitrosamine (Equation
30.61) [521–524]. The latter reaction is a convenient synthetic route to 1,1-dialkylhydrazines [524–526].
R1 R1
+4e–
2 N NO + 3H2O 2 NH + N2O + 4OH– (30.60)
R2 R2
R1 R1
+4e–
N NOH+ + 4H+ N NH3+ + H2O (30.61)
R2 R2
The nitrosation of secondary amines in acidic solution is a reversible reaction and, accordingly,
N-nitrosamines may undergo hydrolysis at low pH. This is especially important for diaryl N-nitrosamines,
but also significant for aryl alkyl N-nitrosamines. The NO+ liberated during hydrolysis may react with
the reduction product from the N-nitrosamine, the unsymmetrical hydrazine, with the formation of the
secondary amine and N2O usually resulting under basic conditions [527] (Equation 30.62).
R1 R1
N NH2 + NO +
NH + N2O + H+ (30.62)
R2 R2
B. N-NITraMIDES aND N-NITroSaMIDES

The electrochemical reduction of N-nitramides and N-nitrosamides proceeds in essentially the same
manner as described earlier for the N-nitramines and N-nitrosamines.
In aprotic media such as DMF, the primarily formed radical anion of N-nitrosourea is protonated
by the substrate giving rise to a cascade of follow-up reactions including further reduction of the
protonated radical anion [528] (Equation 30.63).
R
H2N N O
R R N
H2N N O +e– H2N N O– O

N N
O O (30.63)
R R
H2N N OH + O N NH–
N N
O O
N-nitrosamides are reduced in acidic solution to the acylated hydrazines, which again may
be hydrolyzed to the corresponding alkylhydrazine. This has resulted in the following sequence
(Equation 30.64) as a convenient route from primary amines to the corresponding hydrazines [529].
CH3COOH NaNO2,HCl
R NH2 R NHCOCH3 R NCOCH3
>120°C,–H2O –H2O
NO
(30.64)
+4e–,4H+ H+,H2O
R NCOCH3 R NHNH2 + CH3COOH
–H2O (Recycled)
NH2
Similarly, nitro and nitroso derivatives of urea and guanidine have been reduced to semicarba-
zides [530,531] and aminoguanidines [516,532–535] in acidic solution.
VI. NiTRic AciD ESTERS

Studies of the electrochemical reduction of nitric acid esters (organic nitrates) in aprotic solvents are
rare [353,536]. The reduction of 2-substituted 1-oxo-2,3-dihydro-1H-inden-2-yl nitrate in DMF pro-
ceeds as an overall 2F process, resulting in concurrent C–O and N–O cleavage [536] (Scheme 30.17).
In aqueous solution, organic nitrates are reduced in a pH-independent 2F process to nitrite ion
and, after protonation, the corresponding alcohol [537–539] (Equation 30.65).
+2e– H+
R ONO2 –
R O– R OH (30.65)
–NO2
OH
38–50%
+2e– R
ONO2 –NO2– ,+H+
O
R +2e–
H
O –NO3– ,+H+ 16–18%
R
SchEME 30.17 Competition between C-O and N-O cleavage during the reduction of a 2-substituted 1-oxo-
2,3-dihydro-1H-inden-2-yl nitrate
It has been observed that the reduction of propylene glycol 1,2-dinitrate proceeds readily at cath-
odes made from silver, gold, copper, and mercury, but not at platinum, iridium, nickel, tungsten,
and molybdenum cathodes. It was proposed that the process includes first a one-electron reduction
of the organic nitrate to RO − and NO2, the latter in an adsorbed state, and then reduction of (NO2)ads
to free NO2− in a second one-electron step [539].
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31 Reduction of Aldehydes,
Ketones, and Azomethines
Jiří Ludvík
CONTENTS
I. Carbonyl Compounds ............................................................................................................. 1202
A. Introduction .................................................................................................................... 1202
1. General Mechanistic Considerations ....................................................................... 1203
2. Structure–Potential Correlations ............................................................................. 1206
B. Reduction of Individual Carbonyl Compounds to Alcohols and/or Pinacols ................ 1207
1. Aliphatic Carbonyl Compounds .............................................................................. 1207
2. Aromatic Carbonyl Compounds .............................................................................. 1208
C. Reduction of Carbonyl Compounds Influenced by α-Substitution................................. 1209
1. α,β-Unsaturated Carbonyl Compounds ................................................................... 1210
2. α-Substituted Carbonyls .......................................................................................... 1214
D. Reduction of Carbonyls with a Remote Unsaturation–Intramolecular Coupling .......... 1215
1. Remote Double Bond or Aromatics ........................................................................ 1215
2. Remote Unsaturated Groups ................................................................................... 1216
E. Reduction of Carbonyls in the Presence of Another Reactant–Intermolecular Coupling .... 1217
F. Reduction of Dicarbonyl Compounds ............................................................................ 1221
1. 1,2-, 1,3-, and 1,4-Dicarbonyls on an Aromatic Ring ............................................. 1221
2. 1,2-Dicarbonyls........................................................................................................ 1222
3. 1,3-Dicarbonyls and Remote Diones ....................................................................... 1223
4. β-Keto Esters ........................................................................................................... 1224
G. Reduction Mechanisms in Analytical Applications ....................................................... 1226
II. Azomethine Compounds ........................................................................................................ 1228
A. General Mechanistic Considerations .............................................................................. 1228
B. Derivatives of Ammonia (Imines, Schiff Bases, Iminium Cations) .............................. 1229
1. Protic Media ............................................................................................................ 1229
2. Aprotic Media .......................................................................................................... 1230
C. Derivatives of Hydroxylamine (Oximes, O-Alkylated Oximes,
N-alkylated Oximes–Nitrones)�� 1233
1. Protic Media ............................................................................................................ 1233
2. Aprotic Media .......................................................................................................... 1236
3. Mono- and Dioximes of α-Diketones ...................................................................... 1237
D. Derivatives of Hydrazine (Hydrazones) ......................................................................... 1238
1. Protic Media ............................................................................................................ 1238
2. Aprotic Media .......................................................................................................... 1239
E. Azines (Cyclic, Acyclic) .................................................................................................1240
1. Protic and Aprotic Media ........................................................................................ 1240
2. Hydrazonates ........................................................................................................... 1242
References .................................................................................................................................... 1242
1201
I. CARBONYL COMPOUNDS
A. INTroDUCTIoN
Carbonyl compounds (aldehydes, ketones, quinones, and their nitrogen derivatives—oximes,
imines, azines, and hydrazones) are broadly electrochemically investigated and thus, hundreds of
contributions and several review articles and chapters were published during the last five decades
(e.g., References 1–4). In this chapter, besides some fundamental information, the stress was given
to more recent results (particularly from the last 15 years) to follow the development in the field. For
classical original papers, please consult the respective contributions by various authors in previous
editions of this monograph [5–9].
For the carbonyl group—due to its “lack of electrons” (it belongs to the electron-withdrawing
groups [EWG])—reduction is its typical electrochemical process. The (electro)chemical behavior
of carbonyl compounds depends strongly on the structure of the rest of the molecule (aliphatic,
olefinic, aromatic, α- or β- or ω-substitution, planarity—electron delocalization, etc.) and on experi-
mental conditions (protic/aprotic medium, pH, electrode material, presence of other reactant, etc.).
Therefore, reduction potentials of carbonyl derivatives vary in the span of more than 2 V: for exam-
ple, p-benzoquinone (−0.4 V) and acetone (−2.5 V).
When only aldehydes or ketones are reduced, the pattern is in principle similar and simple. The
first electron transfer generates anion radical species. This reaction is followed either by another
one-electron reduction accompanied by protonation (a two-electron heterogeneous process) leading
to an alcohol or by coupling (a one-electron process followed by a homogeneous reaction) yielding
a pinacol [10–12] (Scheme 31.1).
The order and potentials (energetics) of individual electron and proton transfers, however,
differ substantially being influenced by the structure and aromaticity of the molecule bearing
the carbonyl group and by experimental conditions. As a consequence, various mechanisms are
involved, various intermediates are participating, and thus, different proportions of alcohol/pina-
col products result.
General rules:
• Aldehydes are reduced at less negative potentials than analogous ketones.

• Reduction of aromatic species proceeds always at less negative potentials than reduction
of aliphatic ones.
• Reduction in protic media (e.g., in water) occurs at less negative potentials than in aprotic
solvents due to (antecedent and/or follow-up) protonation reactions.
• Nitrogen derivatives of carbonyls (imines, oximes, hydrazones) and sulfur analogs
(thiocarbonyls) are reduced more easily than the “true” carbonyls.
Since the carbonyl group involves π-electrons, its conjugation with another, possibly present unsatu-
rated grouping in α-position (or in para-position at an aryl ring) generates a more delocalized and
OH
O +2e–, +2H+
R1 R2 R1 R2
OH OH
O O +2e–, +2H+
+ R1 R1
R1 R2 R1 R2 R2 R2
SchEME 31.1 Two-electron vs. one-electron reduction mechanism of carbonyls.

Reduction of Aldehydes, Ketones, and Azomethines 1203
more easily reducible system with more stable intermediates. The original (electro)chemical proper-
ties of the carbonyl are then changed and influenced by the rest of the molecule.
In the presence of another unsaturated group (alkene, aromatics, imine, oxime, nitrile, etc.)
either suitably remote in the same molecule or as a reaction partner dissolved in the solution,
coupling reactions can occur being of high importance in electrosynthesis. In protic media,
for example, methanol/tetrahydrofuran (MeOH/THF) or isopropylalcohol/dimethylformamide
(i-PrOH/DMF), the primary carbonyl radical anion is protonated and a σ-radical located at the
carbon atom is formed. This radical species attacks the unsaturated center and a new C–C bond
is formed after the second electron transfer and necessary protonation. Such a radical addition
can proceed either as an intramolecular cyclization or intermolecularly under formation of an
asymmetric coupling product. The reduction of the carbonyl group to the alcohol is always the
competing reaction.
Earlier in this section, only primary reduction of the carbonyl moiety was considered. Taking
into account generally the electrochemical reduction of carbonyl compounds, we can meet another
possibility: the carbonyl group itself is not reduced but it is acting as an “activator,” which means its
presence causes a more easy (primary) reduction of another reducible center of the same molecule.
This case may occur as a consequence of a very strong intramolecular electron interaction discussed
earlier when due to electron delocalization the displacement of the LUMO is changed (e.g., chal-
cones or benzalacetones) [13–15].
Finally, the carbonyl group represents not only an EWG but also a center of possible tautomer-
ism or a function promoting planarity and extending delocalization. In addition to this, due to the
polarity of the CO bond, formation of hydrogen bonds is possible. These additional properties must
be also taken into account when discussing the electroreduction mechanism.
1. General Mechanistic Considerations

From the mechanistic point of view, the fundamental (electro)chemical properties of the C=O bond
itself are given by the strong polarization of the carbon–oxygen double bond with a partly positive
charge at the carbon.
In the presence of protons (particularly in aqueous or mixed solutions at acidic, neutral and
slightly basic pH), an antecedent pre-protonation of the partly negatively charged oxygen [16] takes
place before the electron transfer. In addition to this, in the presence of nucleophiles (including water)
a nucleophilic addition to the C=O double bond (e.g., hydration, addition of amines, thioles, alcohols)
can occur parallel with protonation and reduction [17] Since these antecedent reactions represent
equilibria with various reaction rates of their restoration, the apparent kinetics of reduction of car-
bonyls may be very complicated and crucially depending on the reaction conditions (pH, tempera-
ture, concentration of nucleophiles, ratio of reacting components, etc.). A simplified general scheme
of possible electroreduction pathways of the carbonyl group itself is presented in Scheme 31.2.
In aprotic media, a pre-protonation does not take place. The lack of electrons on the carbon atom
of the parent carbonyl A causes its (mostly reversible) one-electron reduction at the potential E3,
yielding a radical anion B with the unpaired electron localized on the carbon. The stability of this
radical intermediate depends on the delocalization possibilities: Whereas the radical anion of a
saturated carbonyl molecule is highly unstable and thus reactive, the presence of an aromatic ring
or olefinic system in α-position increases the stability substantially. Primary radical anions of some
aromatic carbonyls then can be detected by cyclic voltammetry (CV) or by in situ EPR spectro-
electrochemical experiments. At more negative potentials (E4) formation of a dianion C is possible
(pathway A–B–C in Scheme 31.2). Eventual protonation of already reduced species can be caused
either by traces of moisture or by proton abstraction from the solvent. The typical sequence of steps
is EECC (e−, e−, H+, H+).
In protic solutions, the situation is determined mainly by acid–base equilibria, which means by
p rotonation before, during, and/or after the electron transfers. In addition to this, at a pH more basic than
C 2–
O
+H+
+e–
E4 F
B –
O– OH
+H+ +H+
+e– +e– G
E3
D E2
(+) (–) +e– HC OH
A +H+
O OH+ OH
E1
E
+OH– +e–, +H+ (x 2)
+ H–Nu Dim
J
(H–OH; +e– OH
O– H
H–NHR;
H–OR;...) OH OH
K OH Nu = NHR
Nu N-R +2e–, +2H+
–H2O
E5 HC NH–R
+e– L
M
SchEME 31.2 Possible pathways of carbonyl group electroreduction.
ilim
i2
i1 + i2 i3 + i2
i1
pH
E1/2 E3
E2 E1
pH
FiGURE 31.1 Typical i–pH and E1/2(red)–pH plots and the link between them for cathodic two-electron
reduction of carbonyl compounds in buffered aqueous solutions.
pKa by three to four units, the protonation rate becomes slow and the electroreduction process appears
to be kinetically controlled. Therefore, all electrochemical steps are apparently irreversible and the pH
of the solution is a very important factor for the chemoselectivity of the electroreduction mechanism.
The following behavior is typical particularly for aryl carbonyls (see Scheme 31.2 and Figure 31.1):
1. In the acidic and neutral pH region, a partly negative charge on oxygen allows its anteced-
ent protonation (pre-protonation), resulting in a positively charged molecule (D). Its respec-
tive “true” pKa is usually around 2–3; however, due to the fast acidobasic equilibrium,
the reduction of carbonyls occurs solely via pre-protonated species (D–E) up to pH 6–8.
Species D is reduced much more positively (at E1) than the parent compound (at E3). The
neutral radicalic intermediate (E) can be either reduced at more negative potential E2 to
an anion (F), which is protonated to alcohol (G), or it undergoes a dimerization yielding a
pinacol (H). The latter pathway is favored under these conditions due to the hydroxycarbi-
nyl radical (E) stability. In the first case, two one-electron reduction steps at E1 and E2 are
observed—pathway A–D–E–F–G with the sequence CEEC (H+, e−, e−, H+), pinacoliza-
tion is a one-electron process A–D–E–H, hence, CEdim (H+, e−, dim).
The reduction of pre-protonated species D is always pH-dependent, where the potential
(E1) is shifted to more negative values with increasing pH due to the decreasing rate of
pre-protonation. This pH dependence can be used as an indication of the pre-protonation
pathway. On the other hand, reduction of the neutral protonated radical E is pH-independent
and proceeds at the constant potential E2. Therefore at certain (still slightly acidic) pH, these
two dependencies have to cross and at pH values where E1 becomes more negative than E2,
the two originally one-electron waves merge to only one irreversible two-electron reduction
process (see Reference 4).
With further increasing pH, the rate of pre-protonation becomes the rate-determining
step (RDS) for the entire reduction. The two-electron wave (peak) is no more controlled
by transport but kinetically and its current decreases to zero. Simultaneously, the process
E1 + E2 is gradually replaced by a more negative reduction process (E3) corresponding to
the reduction of unprotonated parent molecule (A–B).
2. In medium–basic pH (or in slightly protic organic solvents), where pre-protonation does
not proceed, the parent compound is reduced at E3 (A–B) and the intermediate B is imme-
diately protonated. The protonation (B–E) represents another acidobasic system with pKa
in the range 11–12 for aliphatic carbonyls and 8–10 for aromatic ones. Since generally
the protonated radical anion (E) is more easily reducible than the parent compound (A),
the potential E3 is always more negative than E2 and a “classical” ECEC (e−, H+, e−, H+)
mechanism proceeds and only one irreversible, pH-independent two-electron reduction
under formation of alcohol is observed (pathway A–B–E–F–G).
3. Strongly basic solutions can be considered as similar to aprotic conditions since the rate
of protonation B–E is very slow. Therefore, the reduction starts at E3 and at more negative
potentials (E4) a dianion may be formed (A–B–C), resulting finally in the corresponding
alcohol and following the EECC (e−, e−, H+, H+) pathway. In very alkaline solutions, addi-
tion of hydroxyl anion (OH−) to the carbonyl carbon atom of the parent compound A may
occur, yielding a very difficultly reducible adduct J and due to that the total reduction
current decreases. The typical i–pH and E1/2(red)–pH plots and the link between them are
depicted in Figure 31.1.
In the presence of a nucleophile (water, alcohols, ammonia or primary amine, thiol, etc.), par-
ticularly when the carbonyl is further activated by a neighbor EWG making the carbon even more
electron deficient, an anteceding covalent nucleophilic addition to the C=O double bond occurs,
resulting in a gem-diol (with water), hemiacetal or hemiketal (with alcohol), carbinolamine (with
ammonia or amine), or similar structures (K). These adducts are generally nonreducible in the avail-
able potential range, but they should be considered as “masked” carbonyls (Scheme 31.3).
In the case of water, the hydrate is in equilibrium with the parent molecule. Hence, the bulk
concentration of the parent molecule is given by the equilibrium constant and thus reduction of the
parent carbonyl depends on the rate of dehydration. If the dehydration is slow, the reduction itself
becomes controlled by this antecedent kinetics. A novel approach to the analysis of the dehydration
kinetics of several carbonyl compounds allowed obtaining correct rate constants under steady-state
conditions, independently of the degree of the diffusion contribution [18].
In the case of primary amines, the carbinolamine K undergoes dehydration yielding an imine L,
which is reduced more easily than the parent carbonyl (E3 is more negative than E5), giving rise to
H
HO OH O HO N R3
O H2O H2N–R3
gem-diol
R2 R1 R2 R1
R2 R1 R2 R1
carbinolamine
O HO O R3 R3–OH R3 O O R3
R3–OH
+ H2O
R2 R1 R2 R1 R2 R1
hemiketal ketal
(hemiacetal if R1 H) (acetal if R1 H)
SchEME 31.3 Various covalent nucleophilic additions to the C=O double bond.
a secondary amine (pathway A–K–L–M). In the case of alcohols, hemiacetals or hemiketals may
either dissociate back to carbonyl and alcohol, or, under excess of alcohol (in acidic solution) acetals
or ketals are formed.
In aldehydes due to the polarity of the C=O bond, the aldehydic hydrogen is acidic and can act
as a proton donor toward strong nucleophiles (like primary radical anions). This reaction can be
important in aprotic media where autoprotonation may occur.
Carbonyl derivatives bearing a hydrogen atom in α-position may undergo also keto-enol tautom-
erism [19–21]. It is worth mentioning that both forms may be electrochemically reducible.
2. Structure–Potential Correlations
When studying electrochemical reduction or oxidation of a carbonyl compound bearing various
substituents and/or additional electroactive groups (often as an electrochemical characterization of
newly synthesized molecules), the carbonyl group may, but also may not, be reduced as the first. In
addition to this, within a homologous series of substitution or structural derivatives of the parent
carbonyl compound, various mechanisms may occur.
In the case of a series of relatively complicated organic substances with several possible redox
centers, using analysis of structure–potential correlations and substituent effects, it is possible to
localize at least the first oxidation and the first reduction center of the molecule, to estimate the
preferentially electrolyzed groups, to predict the redox potentials, and to interpret possible redox
mechanisms, including relative rates and equilibrium constants.
Among the relationships correlating measured potentials with nature of substituents, the
Hammett approach is the most widely applied [22]; in electrochemistry, it is known as linear free
energy relationship (LFER) [23].
Application of the LFER treatment for reduction of carbonyl derivatives is the first choice.
In a series of compounds with systematically changed substitution, the reduction potentials
should follow a linear plot against the substituent constants σ (sigma) where EWG (with positive
σ-values) facilitate the reduction and electron-donating groups (negative σ-values) shift the poten-
tial to more negative values. All derivatives whose reduction potentials fit the linear relationship
are reduced analogously, according to the same mechanism. The eventual anomalous values of
reduction potentials nonfitting the straight line indicate, however, a different reduction center,
different shape of LUMO, and thus different reactivity and properties worthy to be studied more
deeply [24].
The extent of intramolecular electronic communication between the substituent and the reduc-
tion center is reflected in the slope of the Ered versus σ relationship, so-called reaction constant,
ρ (rho) value. The experimentally acquired ρ-values and their treatment can be used for localization
of redox centers for the determination of the susceptibility of individual positions toward reduction
and for the evaluation of electron distribution within the molecule [25].
The LFER treatment is important particularly in cases when besides the studied carbonyl com-
pounds the molecule involves double- or triple bonds and/or another reducible grouping (including
carbonyl itself). In the case of reduction of mono- and disubstituted phenyl styryl ketones (chal-
cones), multiple substituent effects were analyzed using the Hammett equation and an interactive
Gibbs energy relationship. A cross-interaction was described and discussed in terms of redox reac-
tivity [14].
Seven diaryl ketones were reduced in eight aprotic solvents, and the measured potentials were
treated by the Hammett approach. The obtained reaction constants correlate with the solvent acid-
ity/basicity expressed by the acceptor/donor numbers pointing out the important role of the solva-
tion of participating species [26].
Recently, a quantitative structure–electrochemistry relationship (QSER) approach has been used
for prediction of reduction potentials in a series of 73 aldehydes and ketones. This most advanced
study of relationship between the structure and reduction potentials involves multiple liner regres-
sion (MLR), partial least square (PLS), artificial neural network (ANN), and wavelet neural network
(WNN) modeling methods. The mentioned nonlinear methods exhibited better predictive power
than the linear ones [27].
B. REDUCTIoN oF INDIVIDUaL CarboNYL CoMpoUNDS To ALCoHoLS aND/or PINaCoLS

First, let us consider the most simple case of carbonyl compounds: besides the carbonyl group,
neither the molecule nor the electrolyzed solution involves any other reactive function. For this
situation, the standard pathways are depicted in Scheme 31.1 and a mixture of alcohol (reduction
product G) and pinacol (hydrodimerization product H) is obtained. Their proportion depends
1. On the type of carbonyl compounds being reduced: Aromatic derivatives are able to form
a more extended delocalized system, which makes the reduction easier, stabilizes radi-
cal intermediates, and thus promotes their various coupling reactions, including pinacol
formation. On the other hand, (di)alkyl carbonyl compounds are reduced at more negative
potentials, their intermediates are unstable and undergo fast protonation and further reduc-
tion at the electrode, giving rise preferentially to a two-electron product, the alcohol.
2. On the solvent and pH: Protonation during reduction favors alcohol formation. On the
other hand, lack of protons stabilizing the primary radical anion B (in aprotic media)
facilitates pinacolization and the same effect has an antecedent protonation in strongly
acidic solutions making E1 less negative than E2.
1. Aliphatic Carbonyl Compounds

Generally, the main reduction product of aliphatic carbonyl substrates is the corresponding alco-
hol. Only in acidic media (pH 2–5) when processes E1 and E2 are still separated, the formation of
pinacol is more preferred (pathway A–D–E–H; see Section I.A.1). A detailed overview of classical
electrosynthetic reactions of nonolefinic aldehydes and ketones yielding alcohols is presented in
Reference 6.
Sugars should be also considered as saturated aliphatic aldehydes and electrochemically reduced
after conversion from the hemiacetal to the acyclic form. The most important reaction is reduction
of glucose to sorbitol, where a corresponding pinacol is the by-product. The reduction is either direct
at a lead cathode [28] or indirect electrocatalytic hydrogenation at the Raney nickel cathode [29].
Analogous reactions were observed in the case of pentose sugars [30].
As expected, aliphatic open-chain ketones are reduced at carbon, mercury, lead, or platinum
electrodes mainly to secondary alcohols. The presence of a pro-chiral center in α-position leads
to a mixture of erythro-threo isomers. Their ratio is discussed in terms of structure and solvent–
electrolyte system [31].
Aliphatic cyclic ketones (e.g., cyclohexanones) being reduced offer a mixture of axial-equatorial
isomers of the corresponding alcohols [32,33]. Reduction of ketosteroids in basic media gives rise,
however, prevalently to equatorial alcohols [34].
2. Aromatic Carbonyl Compounds

In contrast to aliphatic carbonyls, the reduction of aromatic ones [35] (including alkyl-aryl ketones)
leads to the pinacol as the main product, particularly in ethanolic or aqueous alkaline solutions on
nickel, lead, or mercury cathodes. Already at the beginning of the twentieth century synthetic elec-
trochemists were very active in this field. Pinacol can be, however, prepared also in acidic solution,
but its yield and the ratio of (±) : meso stereoisomers differ from the alkaline reduction [36–38].
This finding indicates a different reduction–dimerization mechanism in acidic and in basic media,
respectively. In acidic solution due to pre-protonation, only intermediate D is reduced, therefore
dimerization involves two neutral radicals E. On the other hand, in basic environment the first
reduction results in radical anion B (stabilized partly by conjugation with the present aromatic
system), which is slowly (lack of protons) protonized to E. The latter species is then readily attacked
by the excess of strongly nucleophilic radical anion B under the formation of pinacolate anion,
which gets finally protonated. This mechanism prefers the formation of (±)-pinacol over the meso-
form in basic media. The direct coupling of two radical anions should be in this case less probable
due to charge repulsion [12].
The electroreduction of aromatic aldehydes in aprotic solvents was investigated in dimethylfor-
mamide (DMF) or acetonitrile (AN) using CV. The dimerization to pinacols was the main reac-
tion process, and the reactivity sequence and properties of the radical species were evaluated [39].
Substituted benzaldehydes and acetophenones can be reduced in nonaqueous medium to pinacols
also with phenol as a proton donor [40].
In very dry aprotic solvents, the only reaction pathway includes the radical anion B. Instead of its
protonation, formation of ion pairs with cations of supporting electrolyte is possible. The eventual
simultaneous interaction of two radical anions with one cation promotes sterically the (±)-pinacol.
This effect was observed in acetonitrile or DMF with various cations like tetraethylammonium,
sodium, europium(III) [41–43], and more recently also in reduction of alkyl-aryl ketones in an
undivided cell with a magnesium or zinc sacrificial anode, where the generated Mg or Zn ions
participate in ion pairing [44,45].
An indirect reduction appears sometimes to be very successful: 9-fluorenone in aprotic solvent is
reduced in two reversible steps to anion radical and dianion, respectively (A–B–C). After prepara-
tive electrolysis at the first wave, only 10% of pinacol was isolated aside from 90% of the starting
compound. After adding of titanocene (Cp2 Ti Cl2) as a complexing agent, the corresponding pina-
col dominated (65–75%) among the products (A–B–E–H). At more negative potentials, however,
the percentage of fluorenol increased and in the presence of a proton donor the alcohol was formed
exclusively (A–B–C–F–G) [46]. A selective indirect reduction of aldehydes and ketones to alcohols
can be achieved also in EtOH, with Al cathode and anode. The latter provides Al-ions, which form
an intermediate Al(OEt)3 complex [47].
Pinacol, however, is not always the final product. At very negative potentials, the vic-diol can
be further reduced under splitting of the C–C bond and the radical intermediates are protonated to
alcohol (reduction H–G). Therefore, the reduction potential is the decisive factor for the proportion
of pinacol versus alcohol. This phenomenon was observed, for example, in the case of benzaldehyde
reduction in a membrane flow-cell using an acidic water–methanol mixture and a lead cathode [48]
or indirect fluorenone reduction [46].
Several attempts have been done to the reduction of aromatic ketones in order to prepare
optically active monoalcohols. For this purpose, an electrochemically generated chiral center
(surface layer of assembled chiral compounds at the electrode–solution interface) or chiral con-
ducting salt were used. However, the enantiomeric excess is still low and the results are rather
irreproducible [8].
Instead of dimerization leading to pinacols (type head-to-head), the reduced aromatic carbonyls
in aprotic media can undergo also coupling of the type head-to-tail. This can occur due to the fact
that the unpaired electron of the primary radical anion can be localized in various positions of the
conjugated π-aromatic system, particularly in para-, alternatively in ortho-position relative to the
carbonyl (according to the mesomeric scheme). As a result, carbonyl-to-ring coupling was observed,
for example, in the case of 1-acetylnaphthalene in EtOH [49] or acetophenone [50].
Crossed pinacol coupling leading to otherwise difficultly available unsymmetrical pinacols
(vic-diols) based on simultaneous electrolysis of aryl ketone and alkyl aldehyde accompanied by an
intermolecular coupling (e.g., Reference 51) will be discussed in Section I.E.
C. REDUCTIoN oF CarboNYL CoMpoUNDS INFLUENCED bY α-SUbSTITUTIoN

In Sections I.B.1 and I.B.2, the reduction of compounds with an isolated carbonyl group could lead
to alcohol, or to homo-coupling yielding a pinacol.
In this section, a more complicated situation will be discussed, when the reduction of carbonyl is
influenced by conjugation with an α,β-double bond or by substitution of the α-(β-) position, or when
the neighbor double bond or some other grouping is activated by the carbonyl. It was already men-
tioned that the carbonyl group involves π-electrons that are able to interact with adjacent groupings
under extension of the delocalized π-system due to mesomeric effects. If this interaction is strong
enough, the molecule looses (partly or completely) the properties of individual original parts and
exhibits a behavior characteristic for a new redox system.
Simultaneously, carbonyls belong to the EWG. They provoke inductive shift of electron den-
sity in its neighborhood. The carbonyl carbon is thus partly positively charged; moreover, via the
π-system of the double bond the β-position is also slightly positive (Scheme 31.4, upper four struc-
tures). Such an activated molecule can interact among others with the primary radical anion (father–
son reaction), resulting in a cyclic hydroxycarbonyl product (Scheme 31.5).
–0.51 O –0.43 O –0.51 O –0.50 O

+0.07 +0.07 +0.10
+0.48 +0.39 +0.48 +0.18 +0.41
H –0.19 –0.13
–0.12 –0.11
–0.51 O –0.51 O
+0.10 –0.27 –0.51 O
+0.51 S-CH3 +0.50 –0.07
NH2 +0.50 Cl
–0.13 0.00 –0.47 O
–0.51 O –0.30 +0.01
–0.33 +0.46 F
+0.49 O-CH3
F
+0.92
+0.12 F
SchEME 31.4 Selected atomic charges in various types of carbonyl compounds.
O
“Son” O
O
Ar –
+e– +e–, +2H+
Ar Ar OH
“Father”
+ O
Ar
Ar
“Father”
SchEME 31.5 Example of the “father–son” reduction mechanism of α,β-unsaturated carbonyls.

In the case of α-substituted carbonyls, the significantly positive charge on the carbonyl car-
bon activates the adjacent bond and makes the reductive splitting of a substituent more favorable
(Scheme 31.4, lower five structures), particularly when it is a good leaving group (selected atomic
charges were calculated using [52]).
As a result, the reduction of such activated carbonyl compounds does not necessarily lead to the
reduction of the carbonyl group itself, but the β-position could be reduced first and an inversion of
the expected sequence of reduction potentials may occur. In this case, the carbonyl acts as an activa-
tor, the C=O group is preserved in the first reduction step, and its reduction proceeds at more nega-
tive potentials. The composition of products and the individual mechanism then strongly depend on
the particular structure of the parent compound and on the experimental conditions, particularly on
the true working potential, solvent and cathode material.
This situation, however, needs a more detailed comment:
In the case of the electrochemical reduction of carbonyls influenced by α-substitution (this section),
always a mixture of products is obtained; moreover, different dominating products or different propor-
tions of isolated compounds were reported for the reduction of the same compound. How is it possible?
The serious discussion of all possible mechanisms and the formulation of more general rules for
the structure–reactivity relationship is very difficult because there are always two ultimate “target”
questions, two aspects, two types of research teams, and thus two different experimental approaches
and also two types of sources of experimental data:
1. From a fundamental point of view, the question is which part of the molecule is reduced
first (= at less negative potentials), what are the primary intermediates (and their follow-up
reactions), and what happens in the next reduction step at more negative potentials? For a
detailed elucidation of the mechanism, voltammetric experiments on small electrodes with
“analytical” (milimolar or sub-milimolar) concentrations are performed where direct het-
erogeneous reduction at the electrode may prevail (in connection with eventual adsorption
of protonated species). The attention is focused particularly on the first reduction step and
on the number of consumed electrons. The products of controlled-potential electrolyses are
then determined by the working potential and thus various products at various potentials
can be obtained and identified.
2. From an electrosynthetic point of view, the question is what are the final isolable products
after complete reduction (without taking special care about the individual steps of the over-
all process). For this research, very often controlled-current electrolyses are performed on
a preparative scale at large electrodes where the actual working potentials may reach very
negative values. Several reduction steps thus can proceed simultaneously together with all
accompanying chemical reactions. In addition to this, these reactions proceed at concentra-
tions up to three orders of magnitude higher than in the previous case, hence the homoge-
neous processes—including coupling of generated radical species—play a significant role.
It is necessary to stress that since the parent substances represent delocalized systems (particularly
those bearing conjugated aromatic rings), the site of the electron attack may not be so important
for the nature of the product, but rather the site of the subsequent protonation [4,53]. It should be
also mentioned that if the γ-carbon is bearing a hydrogen, the latter is acidic and may influence the
mechanism in aprotic media, particularly, when another EWG is attached to the γ-carbon.
In the frame of this section, two examples will be demonstrated and discussed: α,β-unsaturated
carbonyl compounds and molecules with a reducible substituent (often a good leaving group) in
α-position toward the carbonyl.
1. α,β-Unsaturated Carbonyl Compounds

Taking into account the generally known fact that the carbonyl function is reduced more easily (at
less negative potentials) than an isolated double bond, one can expect that in molecules bearing
O O– O– O
+e–
–
Head Tail
O OH O
+e–, +H+
SchEME 31.6 Mesomeric structures of the first reduction intermediates.
simultaneously carbonyl and a double bond, the C=O group will be always reduced first. However,
in α,β-unsaturated carbonyls, the conjugated system –CO–C=C– changes the situation: the same
molecule can be considered either as an aldehyde (ketone) with conjugated olefin or as an acti-
vated double bond. The presence of an aromatic ring attached either at the α-carbon adjacent to
the carbonyl or at the β-carbon of the α,β-double bond causes further extension of the delocalized
π-system. Due to this, the reduction center (LUMO) is not located exclusively at the carbonyl, but
involves a larger part of the molecule and the primary radical anion can exist in several mesomeric
structures (Scheme 31.6). Therefore, the electrochemical reduction of α,β-unsaturated aromatic car-
bonyls may result not only in the reduction of the carbonyl to alcohol or in the reductive coupling to
pinacol, but also to the exclusive saturation of the α,β-double bond. It is necessary to mention that
many coupling products form various stereoisomers. Their detailed discussion is, however, beyond
the scope of this chapter.
a. Aliphatic and Alicyclic Carbonyls

Taking into account Scheme 31.6, after the first one-electron reduction the unpaired electron is
localized either prevalently at the carbonyl carbon (head position) or at the β-carbon (tail position).
These two radical species are able to undergo radical coupling. Theoretically three combinations
can occur: a tail-to-tail coupling, when δ-diketones are formed, head-to-head hydrodimerization
yielding a pinacol, and head-to-tail coupling resulting in γ-hydroxyketone. Very often a mixture of
all products is obtained.
The predominant mechanism is structurally controlled. A freely accessible β-position or sterical
hindrance close to the carbonyl may give preference to tail-to-tail coupling; on the other hand, a
hindered β-position can favor the head-to-head link. The classic examples are reduction of mesityl
oxide [54] or ionone [55]. According to the reaction conditions, the primary coupling products
may undergo follow-up reactions giving rise to cyclic final products (Scheme 31.7). To increase
the proportion of the pinacol-type coupled products, the presence of Sn(II) or Cr(III) ions in the
solution has a positive effect. Due to their coordination with primary anion radicals through the
oxygen atom, the radical character of the intermediates is accentuated and the pinacolization is
preferred [42].
Similar reaction pathways were observed in the case of cyclohexenone [56,57]. For the nonsub-
stituted parent compound (R1, R2, R3 = H), exclusively tail-to-tail products were formed. For R1,
R3 = Me, R2 = H or R2, R3 = Me, R1 = H, preferentially head-to-head and head-to-tail derivatives
were produced.
Benzalacetones should be regarded as intermediate case between aromatic and aliphatic
carbonyls because the aromatic ring is not attached directly to the carbonyl. The final products
after galvanostatic reduction in acetonitrile are cyclic hydrodimers. The mechanism of their
formation follows the discussed principles: the first electron attacks the double bond under
formation of a radical with unpaired electron at the β-carbon. The tail-to-tail coupling results
in a linear hydrodimer that undergoes cyclization by attachment of the partly positive carbonyl
carbon to the negatively charged α-carbon (Scheme 31.8). Two stable diastereoisomers were
isolated [58].
Head-to-tail
Tail-to-tail
O +2e– +2H+ O
Hcetate buffer + HO
2
Hg-cathode O
Mesityl oxide O
OH
CH3
CH3 O
H
O
O
O OH OH R1
2 +2e– +2H+
R2
AN/acetate buffer R3 R3
Ionone or DMF/TBAI Head-to-head
Cyclohexenone
SchEME 31.7 Examples of “tail-to-tail,” “head-to-tail,” and “head-to-head” reductive coupling of α,β-
unsaturated carbonyls.
O
O
OH
+H+
+e–
O O
–
O
Dim.
– +H+ OH
C3 C1 +H+
C2
O
SchEME 31.8 Electroreduction pathway of benzalacetones.
The aforementioned electroreductive hydrocoupling of benzalacetone (and also of methyl cin-

namate, methyl crotonate, and coumarin) was studied by DFT calculations (B3LYP/6–311++G**).
[15]. The Mulliken spin densities and atomic polar tensor (APT)–derived charges for C1, C2, and
C3 of the primary radical anion (see Scheme 31.8) are shown in Table 31.1. The calculated data for
transition states correspond well to the experimental results and confirm the suggested mechanism.
TABLE 31.1
Spin Densities and Atomic Charge for Carbonyl Carbon (C1), α-Carbon (C2),
and β-Carbon (C3) of the Primary Radical Anion of Benzalacetone
Carbon Spin Densities Atomic Charge
C1 0.12 +1.18
C2 0.08 −0.66
C3 0.27 −0.11
Source: Kise, N., J. Org. Chem., 71, 9203, 2006.

Aryl O O O O
O O Aryl
Aryl Aryl Aryl Aryl
+
trans- cis-
SchEME 31.9 Electrochemical reduction of bis(α,β-unsaturated arylketones).
O
X O Electroredn.
+ DMF/AN 1:1,
Ni-cath.
Alkyl Alkyl
SchEME 31.10 Electrochemical reduction of methyl vinyl ketone in the presence of an aromatic halide;
X = halogen atom.
A special example of this type of reaction is the electrochemical reduction of bis(α,β-unsaturated

arylketones) [59] discussed later. The coupling (intramolecular) does not proceed like in Schemes
31.7 or 31.8, but symmetrically under the formation of a diketone (Scheme 31.9).
The reduction of methyl vinyl ketone in the presence of an aromatic halide is a very selective
electrosynthetic method for arylation of the carbonyl compound. It was used as a key step in prepa-
ration of a precursor for the synthesis of medium-ring benzolactones [60]. The unpaired electron
of the primary radical anion is localized at the activated vinyl double bond (see Scheme 31.6), but
instead of the expected homocoupling tail-to-tail, the vinylic radical reacts with the halogen. Hence,
the reductive coupling of the vinyl to the aromatic system occurs under splitting of the halide ion,
whereas the carbonyl function remains preserved (Scheme 31.10).
b. Aromatic Carbonyls

Whereas in aliphatic and alicyclic α,β-unsaturated carbonyls the reductive coupling prevails, in
aromatic α,β-unsaturated carbonyls the saturation of the double bond is more typical. Aromatic
carbonyls are primarily those bearing the aromatic ring directly at the carbonyl carbon (derivatives
of benzaldehyde or acetophenone).
Cathodic reduction of phenyl vinyl ketone [61,62] and chalcone [63] in buffered aqueous solu-
tions is the typical example of inversion of the expected sequence of reduction processes: at first
the two-electron two-proton reduction of the double bond occurs yielding the corresponding
alkyl aryl ketone, which is at more negative potentials reduced to alcohol. Similarly, aldehydes
like cinnamaldehyde [64] due to the presence of an aromate are reduced to saturated aldehydes,
whereas the reduction of alkenyl aldehydes (like crotonaldehydic ring) results in the unsaturated
alcohol [65].
An electrolysis of cinnamaldehyde in buffered aqueous media gave a mixture of 3-phenylpropio-
naldehyde and cinnamyl alcohol [66]. Even in this case, the first reduction step involved saturation
of the double bond, the cinnamyl alcohol is probably the product of reduction of pinacol at very
negative potentials (see Figure 31.1, reaction H−G).
More recently, a series of chalcones (phenyl styryl ketones) substituted at both phenyl rings was
investigated in nonaqueous DMF. Besides the evaluation of multiple substituent effects (see Section
I.A), it was concluded that two successive one-electron steps for the reduction of the chalcones
yielded always saturation of the double bond [14].
Chalcones and their mesityl- and anisyl- analogs were reduced also in aqueous butanol [13]. In all
cases, reduction of the double bond is dominating. In the mixture of products, the linear δ-diketones
formed in the tail-to-tail coupling were isolated together with their cyclic form (see Scheme 31.8).
2. α-Substituted Carbonyls
O
Y
Y = –NR2, –OH, –SR,

–F, –Cl, or Br
Like in Section I.C.1, it should be kept in mind that the isolated carbonyl group is electro-
chemically reduced less negatively (more easily) than the isolated C−Y bond of organic species
bearing groups Y like –NR 2 , –OH, –SR, or halogen. The latter substituents represent leaving
groups able to undergo a reductive elimination. The situation is changed when the group Y
is attached to the α-carbon adjacent to the carbonyl group. The electron-withdrawing ability
of C=O causes activation of the C–Y bond, which is reduced first contrary to expectations.
The carbonyl remains unchanged and is reduced at more negative potentials. This effect is
described for glycolaldehyde [67], α-aminoketones [68], phenacyl sulfonium ions [69,70], or
α-halogen-substituted carbonyl compounds [71].
In the case of electrochemical reduction of ω,ω,ω-trifluoroacetophenone, in acidic media below
pH 5, the protonated carbonyl is reduced to pinacol and alcohol. In neutral and basic pH range,
however, all C–F bonds are reductively split off prior to the reduction of carbonyl [72]. Besides the
pre-protonation, the hydration of the carbonyl group at higher pH values (preventing its reduction)
plays also an important role [73,74] The electroreductive defluorination of trifluoromethyl ketones
was utilized for electrosynthesis of various fluorinated derivatives in acetonitrile at a lead plate
cathode in the presence of chlorotrialkyl silane. Among others, 2,2-difluoroenol silyl ethers were
obtained [75,76].
A classical case of inversion of the expected sequence of reduction processes caused by mutual
electronic interaction of a carbonyl with an unsaturated substituent is represented by benzaldehydes
substituted in the para- (or ortho-) position by a –CN group. It is generally known that the elec-
trochemical reduction of a nitrile is more difficult than carbonyl reduction. However, even here the
carbonyl forms a π-electron delocalized system with the nitril via the phenyl ring. As a result, in
acidic media (pH < 3.5) the protonated nitrile group is reduced first by four electrons to an amine,
whereas the carbonyl is reduced at more negative potentials [77].
Electrochemical reduction of aliphatic carbonyl compounds activated by a nitrile function is a
bit different and more complicated. In the reduction of 2-cyanocycloalkanones (Scheme 31.11), the
reaction pathway strongly depends on the other α-substituent R and on the nature of the cation
of supporting electrolyte. When R = H, the carbonyl itself is reduced and the corresponding cis-
β-hydroxynitrile is formed. When, however, R = alkyl, and the supporting cation is large (e.g., Et4N+),
cleavage of the C−CN bond occurs. The role of the cation consists in stabilization of the primary
radical anion by ion pairing [78].
CN CN
+2e–, +2H+
O OH
–
R R R
CN +e– CN +e–, +H+
–CN–
O O O
SchEME 31.11 Electrochemical reduction of 2-cyanocycloalkanones.

D. REDUCTIoN oF CarboNYLS wITH a REMoTE UNSaTUraTIoN–INTraMoLECULar CoUpLING

1. Remote Double Bond or Aromatics
Reduction of a carbonyl compound with a remote double bond or an aromatic ring can be accom-
panied by intramolecular coupling of the primary radical anion with the double bond under closure
of a new ring. The C–C bond formation occurs on the more substituted carbon of the double bond,
closer to the carbonyl group (Scheme 31.12). The cyclization leading to a five- or six-membered
ring is the most effective, although the formation of four- as well as seven-membered rings is also
possible. The reaction proceeds usually in mixed organic solvents—mostly in MeOH/dioxan or
2-propanol/DMF.
The cyclization is regio- and stereoselective [79–82]. Sometimes, however, the direct reduc-
tion of the carbonyl for example, in DMF yields simply secondary alcohol without cyclization
(Scheme 31.13). The proportion of cyclic versus acyclic forms depends strongly on the cathode
material, solvent, and supporting electrolyte [83]. Upon addition of N,N′-dimethylpyrrolidinium tet-
rafluoroborate [84] or N,N′-dimethylquininium tetrafluoroborate as a mediator and cyclizing agent
controlling stereoselectivity, cis-cyclized products are obtained in good yield [85].
The mechanism was often discussed [86] and recently reconfirmed by ab initio as well as DFT
calculations [87]. After the first electron transfer, the spin density of the primary radical anion is
localized at the C2 atom, but during the progress of intramolecular coupling the terminal double
bond is approaching the carbonyl moiety (see Scheme 31.12) and the spin density is shared between
C2 and C6+C7. Based on optimization of various transition states, the comparisons of the relative
activation energies indicate that the regio- and stereoselectivities in the cyclizations of the ketyl
radicals are determined by kinetic control.
In the case of aromatic nonconjugated ketones, the intramolecular cyclization may occur when
the chain between the carbonyl and phenyl groups involves three (possibly also two or four) carbon
atoms, resulting in five- to seven-membered ring. It was proven that the presence of methyl groups
in positions C3, C4, or C5 (see Scheme 31.13) does not prevent the cyclization [83]. However, the
second substitution on the phenyl ring is important for this process: electron-donating substituents
(Me, OMe,…) in meta- position prevent the cyclization, whereas an EWG like CN or COOAlk in
meta-position (and/or Me, OMe in para-position) does not inhibit it. This finding points to the inter-
pretation that the reactive species attacking the aromatic ring has an anionic character.
O OH
O
C6 C4 C2 Electroreduction
CH3
C1
C7 C5 C3 C1 CH3
C7 OH
O
O
Electroreduction
CH3
SchEME 31.12 Ring closure during electrochemical reduction of a carbonyl compound with a remote dou-
ble bond.
OH HO
O H CH3
para- O Electroreduction
meta- C4
+
ortho- C5 C3
SchEME 31.13 Ring closure and alternative secondary alcohol formation during electrochemical reduction
of a carbonyl compound with remote aromatic rings.
H OH
+e– +e–, +2H+
O O– trans-cyclization N
N N
I
O — C–OMe
H
+e–, +2H+ OH
O O– trans-cyclization
O O N
+e– O — C–OMe
O O
N N H
+e–, +2H+
II cis-cyclization N OH
SchEME 31.14 Stereospecificity in the reduction of 1-indolealkanones (I) and 3-methoxy-carbonyl-1-

indolealkanones (II).
Another example of how substitution on the aromatic ring can influence the resulting stereo-
specificity is reported for 1-indolealkanones (I) and 3-methoxycarbonyl-1-indolealkanones (II)
in isopropanol [88]. The observed trans- and cis-cyclized products are formed according to two
different mechanisms: whereas the unpaired electron in the anion radical of I is located as usu-
ally at the carbonyl carbon, in the case of II the strong electron-withdrawing effect of the ester
group in position 3 changes the reduction center to the indole ring and thus the methoxycarbonyl
group is reduced more easily than the carbonyl. The attacking radical is located at a different
place causing the change of mechanism and thus stereospecificity. This interpretation was sup-
ported by DFT calculations where the highest spin density was found at position 2 of the hetero-
cycle (Scheme 31.14).
When the linear chain of nonconjugated enones contains a nitrogen or sulfur heteroatom, this
is the way how to prepare various saturated heterocyclic alcohols. Nevertheless, the nitrogen-
containing derivative exhibits some decrease in stereoselectivity in electroreductive intramolecular
cyclization in comparison with high stereoselectivity for the analogous enones possessing a sulfur-
containing chain or an all-carbon chain [89].
2. Remote Unsaturated Groups

An example of intramolecular coupling of a carbonyl with a remote reactive group is the cathodic
reduction of aromatic ketones with an imino-ether group in the ortho-position. In acetonitrile, the
carbonyl is reduced first and undergoes a cyclization under formation of a benzoxazine. In basic
solution, a quinoline is formed (Scheme 31.15). The presented electrosynthetic reaction can be an
alternative way to benzoxazines and quinolines [90].
R1 H
O
O
AN R2
N
R1
R2
Electroreduction
N R1
O–R Base R2
N O–R
SchEME 31.15 Reductive intramolecular coupling of an aromatic carbonyl with a remote unsaturated
group.
O OH
+e, Sn cath. +e, Sn cath.
No reaction
CN 2-PrOH 2-PrOH
O O
OH NH OH O
+e, Sn cath. H2O
+
CN 2-PrOH
SchEME 31.16 Electrochemical reduction of a saturated carbonyl compound bearing a nitrile group in the
γ- or δ-position.
Electroreductive cycloaddition of symmetric bis(α,β-unsaturated arylketones) leads among oth-

ers to cyclobutane derivatives (Scheme 31.9). Diastereoselectivity of this reaction is strongly con-
trolled by the nature of the electrolyte cation. The formation of cis-cyclobutanes is favored by Mg
or Ba ions, probably due to a chelation effect [59].
Cathodic reduction of a carbonyl molecule bearing a nitrile group in the γ- or δ-position is
accompanied by the intramolecular cyclization resulting in an α-hydroxy ketone. It was assumed
that the attacking reduced carbonyl has a radicalic nature rather than anionic since the reaction
proceeds in protic media (2-propanol). The reductive addition of the primary carbonyl radical gives
rise to a cyclic iminoalcohol, which is hydrolyzed (during the workup) to the α-hydroxyketon and
its dehydroxylated derivative as the major products [91] (Scheme 31.16). A more recent theoretical
study of reductive intramolecular coupling of carbonyl compounds offers a more detailed explana-
tion based on sharing of the unpaired electron upon sterical approach of the unsaturated group to
the primary carbonyl radical (anion) between these two—see Reference 87.
Also, the electroreductive coupling of a carbonyl group with an intramolecular O–Me oxime
moiety gave the corresponding cyclized product stereoselectively [92].
E. REDUCTIoN oF CarboNYLS IN THE PrESENCE oF ANoTHEr

REaCTaNT–INTErMoLECULar CoUpLING
In this section, the reported reactions are often analogous to those of the previous part concerning
intramolecular processes; the possible differences are caused by lower sterical requirements.
When a mixture of aryl ketone and alkyl aldehyde or ketone is electrolyzed in the presence of
chlorotrimethylsilane (CTMS), a crossed pinacol coupling occurs, leading to otherwise difficultly
available unsymmetrical pinacols (vic-diols) [51]. This type of rather general reactions starts with
the electroreduction of the aromatic carbonyl to the corresponding radical anion. Its immediate reac-
tion with CTMS present in the solution causes indirect reductive splitting of chloride anion under
formation of a silyl derivative with “umpolung” of the carbon–oxygen bond (see Scheme 31.17).
The nucleophilic carbanion adds to the electrophilic center of the still nonreduced carbonyl partner
(alkyl ketone, acyl or ester) and an unsymmetric pinacol is obtained.
When the second carbonyl partner contains a good leaving group, for example, imidazol (Im),
in the case of intermolecular electroreductive coupling of aromatic ketones with 1-acylimidazoles,
an α-hydroxy ketone is formed [93]. The aromatic carbonyls are first reduced in the presence of
CTMS and triethylamine (TEA), after the coupling with the acylimidazole, the desilylation using
TBAF in THF follows (Scheme 31.17). This reaction is effective also for the intramolecular
reductive coupling of γ-, δ-, ε-, and ζ-keto acylimidazoles, resulting in four- to seven-membered
rings [93].
Reductive allylation of carbonyls represents an important way to homoallylic alcohols. Electrolysis
of a mixture of an aldehyde or ketone with an allylic halide in hexamethylphosphor-amide (HMPA)
O
+
+2e–
R1 R2 CH3 R1
+CTMS
CH3 – CH3
–Cl –
TBAF/THF R2
O TMS-O OH OH
+ O
H3C lm
CH3 O– –Im– CH3 O TBAF CH3 O

lm THF
TMS-O CH3 OH CH3

TMS-O CH3
SchEME 31.17 Electrochemical reduction of an aryl ketone in the presence of a saturated carbonyl
compound.
results in the desired β,γ-unsaturated alcohol. The mechanism of this reaction and the regioselectiv-
ity depends, however, on the more readily reduced reaction partner. In the case of aryl aldehydes or
alkyl aryl ketones being reduced first, the primary radical anion attacks the halide in an SN2 fashion
(Scheme 31.18). In the case of aliphatic carbonyls (acetone, propanal), the allylic halide is primarily
reduced by two electrons, giving rise to an allylic carbanion that adds at the electrophilic carbonyl
carbon (Scheme 31.19). The influence of the electrode material on the yield is crucial [94]. An analo-
gous electrochemical allylation with high efficiency has been performed in mixed aqueous acidic
and basic media on a Zn cathode with Zn ions as catalysts [95].
Cathodic intermolecular coupling of aliphatic ketones with 1-olefins (or dienes or trienes)
leading to the corresponding tertiary alcohols has been satisfactorily accomplished with high
regioselectivity by using a carbon fiber cathode in DMF [96] (Scheme 31.20).
Coupling of ketones with dienol ethers under the same conditions (DMF, carbon fiber), however,
has only a very low yield. For the successful coupling, the addition of CTMS and TEA into the
O +e– O–
Ar R2 Ar R2
R4
O– R4 OH
SN2 : +e–, +H+
+ R3
–Cl– Ar
Ar R2 Cl R3 R2
SchEME 31.18 Reductive allylation of aromatic carbonyls resulting in homoallylic alcohols.
R4 +2e– R4
–Cl– –
Cl R3 R3
R4 O R4 R3
Addition; +H+
– + OH
R3 R1 R2
R1 R2
SchEME 31.19 Electroreduction of the mixture of a saturated carbonyl compound with an allylic halide.
O +e– O–
R1 R2 R1 R2
O– OH
+e–; +2H+
+ R3
R1 R2 R1 R3
R2
SchEME 31.20 Cathodic intermolecular coupling of aliphatic ketones with 1-olefins.
O–Me O O-Me O OH
el. redn. OH H3O+
+
CTMS/TEA
O OH OH
el. redn. Me-O H3O+ O
Me–O +
CTMS/TEA
SchEME 31.21 Reductive coupling of ketones with dienol ethers.
O Reductive OH
electrocatalysis
+ CH3NO2 NO2
R1 H MeOH R1
H
O O O HO
Reductive
NO2
electrocatalysis
+ CH3NO2
MeOH
SchEME 31.22 Electroreduction of the mixture of carbonyl compounds and nitromethane.
reaction system was necessary. The following acidic hydrolysis leads to the corresponding remote
hydroxy keton or aldehyde [96] (Scheme 31.21).
The electroreduction of the mixture of carbonyl compounds and nitromethane in methanol yields
the corresponding β-nitro alcohols according to the electrochemically induced Henry reaction (Scheme
31.22). This process is an example of an electrocatalytic system. The electrochemical reduction of the
reaction mixture (under galvanostatic conditions) yields an electrochemically generated base catalyz-
ing the desired reaction. The detailed mechanism depends on the composition of the solution [97].
Electroreduction of a mixture of various ketones with aliphatic O-methyl oximes gives rise a
β-methoxyamino alcohols that can be easily (chemically) reduced to β-amino alcohols (Scheme
31.23). A similar mechanism operates in the case of the electroreductive intermolecular coupling of
ketones with N,N-dimethylhydrazones or nitrones [92].
Analogously to previous reactions, when aldehydes are reduced together with phthalimides (in
the presence of CTMS and TEA) intermolecularly coupled products (3-hydroxy-3-(1-hydroxyalkyl)-
isoindolin-1-ones) are formed as an important precursor for further stereospecific syntheses [98]
(Scheme 31.24). When aromatic aldehydes are electrolyzed in the presence of aryldiindenylmeth-
anes, the monoarylidene derivatives are formed [99].
Intermolecular reductive coupling of carbonyl compounds with nitriles results in an α-hydroxy
carbonyl derivative that is equivalent to the product of acylation [93]. The suggested mechanism
is based on the fact that the unactivated carbonyl is reduced more easily than a nitrile. As the
O +e– O–
R1 R2 R1 R2
O– N–O–CH3 HO NH–O–CH3 HO NH2

+e–, +2H+ Redn.
+ R1 R4 R1 R4
R1 R2 R3 R4 R2 R3 R2 R3
SchEME 31.23 Electrochemical reduction of various ketones with aliphatic O-methyl oximes leading to
β-amino alcohols.
R
O 1) +2e– HO OH
O CTMS/TEA
N X +
2) Bu4NF N X
R H
O
O
SchEME 31.24 Electrochemical reduction of aldehydes with phthalimides.
OH OH R4
O Electroredn. O
+ R3(R4)CH–CN R1 + R1 CN
Sn-cathode
R1 R2 R2 CH(R4)R3 R2 R3
SchEME 31.25 Formation of α-hydroxy carbonyl derivatives in the intermolecular reductive coupling of
carbonyl compounds with nitriles.
COOH
O CH3
HO CH3
Electroredn.
+ O C O
DMF
R R
SchEME 31.26 Preparation of aromatic α-hydroxy acids using electrochemical reduction of aromatic car-
bonyl compounds in the presence of carbon dioxide.
b y-product, a β-hydroxy nitrile is formed. Its exclusive production occurs when only aprotic nitriles
serve as a solvent (acetonitrile or other alkylnitriles). When, however, a certain proportion of an
alcohol (i-PrOH, EtOH) is added, due to the protonation of the primary radical anion, a radical
addition takes place, leading (after hydrolysis of the imine intermediate) to the desired α-hydroxy
carbonyl [91] (Scheme 31.25).
Electrochemical reduction of aromatic carbonyl compounds (in DMF) in the presence of carbon
dioxide results in a carboxylated product. This process was used for synthesis of various aromatic
α-hydroxy acids [100–104] (Scheme 31.26).
Potential controlled reduction of a mixture of aldehydes or ketones with a 10 to 15-fold excess
of primary amines yields secondary amines. The reaction proceeds at a Hg cathode in the aque-
ous solution of the amine, half-neutralized with HCl, hence in buffered media of pH 10–11. The
detailed sequence of electron and proton transfers was not reported, most probably the pathway
involves the corresponding Schiff base as intermediate, which is reducible, giving rise to the prod-
uct (Scheme 31.27). In the case of cyclic ketones, the reaction is diastereoselective [105].
R1 R1 H
Controlled potential reduction
O + H2N–R3 N
Hg, pH 10-11
R2 R2 R3
SchEME 31.27 Cathodic reduction of aldehydes or ketones with an excess of primary amines.
F. REDUCTIoN oF DICarboNYL CoMpoUNDS

The dicarbonyl compounds can be divided into several categories: aromatic ones, where in
o- and p-dicarbonyls, the C=O groups are directly involved in the aromatic π-system (in contrast
to m-dicarbonyls, where the electronic communication between the two carbonyls is negligible),
α- and β-dicarbonyls on an aliphatic chain, where the two close C=O groups influence each other,
and “remote” dicarbonyls where the C=O groups are wide apart with lacking delocalization between
them—hence, practically independent (in fact, aromatic m-dicarbonyls belong to this type).
The main feature in the first two categories is that one of the C=O groups plays the role of a
strong EWG toward the other one. There are two main consequences: (1) the reduction of the first
carbonyl is shifted to less negative potentials due to the effect of the second one; (2) owing to the
fact that hydration is enhanced by the influence of an EWG, in aqueous media those dicarbonyls are
strongly hydrated under the formation of a geminal diol, which is electrochemically inactive. One
should also keep in mind that also keto-enol tautomery can play its role. Therefore, the reduction of
dicarbonyl compounds is very often complicated by simultaneous acidobasic, hydration/dehydra-
tion, and tautomeric equilibria.
1. 1,2-, 1,3-, and 1,4-Dicarbonyls on an Aromatic Ring

The most simple dialdehydes where both carbonyl groups are attached to a benzene ring (or more
generally to an aromatic system, e.g., naphthalene, etc.) can exist as three isomers: 1,2-benzenedialde-
hyde (phthalaldehyde, orthophthalaldehyde, OPA), 1,3-benzenedialdehyde (isophthalaldehyde, IPA),
and 1,4-benzenedialdehyde (terephthalaldehyde, TPA) [4]. In 1,2- and 1,4-isomers, the carbonyls are
in conjugation, their mutual influence is substantial, and they behave as benzaldehydes with a strong
EWG substituent. In contradistinction to this, the 1,3-isomer has an interrupted π-system between
the two C=O groups. Taking into account that the hydration reaction is promoted by the π-interaction
with EWG substituents, OPA is hydrated very strongly—approx. 85%, TPA is also considerably
hydrated (about 15%) whereas IPA is hydrated only negligibly (up to 3%, like benzaldehyde).
As a result, the reduction of IPA proceeds analogously to benzaldehyde (with double current)
[106]. The reduction of TPA (and other related p-dicarbonylaromatics) in acidic solutions is analo-
gous to the noteworthy mechanism of p-diacetylbenzene reduction, observed already in the 1960s,
which exhibits in this media a rare two-electron reversible process [107]: the diprotonated form
accepts simultaneously and reversibly two electrons giving rise to a tautomeric system where the
quinonemethide with limited stability is the most important intermediate that is at more negative
potentials reduced to diol (the biradical species in Scheme 31.28 was not proven yet). The same
mechanism was recently found and confirmed by quantum chemical calculations in nonsymmetric
analogs of such p-phenylene dicarbonyls where a carbene or imine moiety is located in para-position
with respect to the carbonyl [24].
The strong hydration of OPA (particularly at pH 2–6) is further complicated by steric reasons
(ortho-effect), resulting in two successive hydration equilibria: besides the simple addition of
water to the carbonyl yielding a geminal diol, a follow-up cyclization occurs giving rise to electro-
chemically inactive isobenzofurane-1,3-diol (Scheme 31.29). The hydration/dehydration kinetics is
strongly dependent on pH, hence at pH 2–6 the OPA is effectively nonreducible [108].
The complete electroreduction of these three benzene dialdehyde isomers in buffered solutions
yields the corresponding diols, the detailed mechanism and sequence of electron and proton trans-
fers depend on pH [108–110].
R O R OH
R = H, CH3 ,C6H5
R O R OH
+2H+
R OH+ R OH R O R H OH
C
+2H+
+2e– +2e–
C C
R OH+ R OH R H OH R H OH
SchEME 31.28 Electrochemical reduction of p-diacetylbenzene.
O OH OH
+H2O
OH
O
O O OH
SchEME 31.29 Hydration equilibria of phthalaldehyde.
2. 1,2-Dicarbonyls
A number of papers devoted to the electrochemical reduction of aliphatic (e.g., 2,3-pentanedione),
alicyclic (1,2-cyclohexanedione), and aromatic (1-phenylpropane-1,2-dione or 1,2-diphenylethane-
1,2-dione = benzil) α-dicarbonyl compounds in buffered aqueous solutions were reported [111–116].
Besides the dicarbonyl form, the parent compounds may exist in two other forms: as an enolic spe-
cies and in hydrated form due to the close vicinity of the other carbonyl (Scheme 31.30). Besides,
protonation (or diprotonation in acidic media [113]) may precede the electron transfers, whereas in
neutral and basic solution the first electron transfer is (quasi)reversible [115].
OH+
O
+2H+ OH+ +2e–
OH O OH+ OH O
+H+ +2e– +H+ Slow
O –H2O
O O OH OH
+H2O +e– +e– +2H+ +2e–
O– +
HO OH OH +2H
O
OH
SchEME 31.30 Tautomeric, acidobasic, hydration, and redox transformations of 1,2-dicarbonyl compounds.
The totally two-electron, two-proton reduction yields at first the enediol, which is oxidizable at
less negative potentials (the proof of its presence can be carried out by CV). The enediol is then
transformed into the α-hydroxy carbonyl (ketol), which is the first stable product for the majority
of α-diketones, particularly aliphatic and alicyclic (Scheme 31.30). At more negative potentials,
aromatic ketols can be further reduced to diols [113].
A typical example is benzil: in acidic-neutral buffers up to pH 8, the reaction sequence involves
pre-protonation (H+, e –, e –, H+); in more acidic solutions antecedent diprotonation occurs prior the
two-electron reduction (Scheme 31.30). The follow-up isomerization is surface-assisted, and the
trans-cis interconversion is generally slower than the cis-trans. The resulting enediol then slowly
tautomerizes into benzoin, which is again reducible by two electrons and two protons at more nega-
tive potentials giving rise to a diol. A recent study involves a detailed description of kinetics and
equilibria of the mentioned process in the H0/pH region −5 to 11 [117].
This mechanism is similar for both alkyl and aryl dicarbonyls as well as for diketones and keto-
aldehydes (like methylglyoxal). The minor differences are (a) in hydration, which is more typical
for alkyl dicarbonyls; (b) in protonation, which proceeds first at the aldehydic carbonyl (in ketoal-
dehydes) or at the aromatic one (in alkyl-aryl dicarbonyls [113]); (c) in tautomeric forms, where the
enol form is predominant in cyclic diones; and (d) in regioselectivity, which is particularly in asym-
metrical aliphatic diketones poor.
Although the hydroxyketone is the main electroreduction product of alkyl diketones in neutral
media, the aliphatic and aldehydic species may also undergo (as a side reaction) a reductive dimer-
ization to diastereomeric keto-pinacols [116]. The alternative way from diketones to stereochemi-
cally pure diols is also a microbial reduction combined with electrochemistry [116]. The correlation
of reduction potentials in a series of dicarbonyls and their analogs with structure and bioactivity has
been also discussed [118].
In aprotic solvents, the first step of electrochemical reduction of α-diketones proceeds reversibly.
In the presence of metal ions (group IA and IIA), ion pairing with the primary radical anion was
observed [119,120].
3. 1,3-Dicarbonyls and Remote Diones

1,3-Dicarbonyls exist in solution in equilibrium with their enol form, which is stabilized by hydro-
gen bonding as a six-membered ring (Scheme 31.31). In the case of aromatic species (e.g., dibenzoyl-
methane), the system is further conjugated with the two aromatic ring systems [121]. The hydrogen
atoms are labile and can be replaced by metal ions giving rise to a chelate ring [122].
Many derivatives with various combinations of electron-withdrawing and electron-donating sub-
stituents were electrochemically investigated and the results were successfully correlated with DFT
calculations [123]. The electroreduction mechanism was proposed already several decades ago: in
aprotic solvents, 1,3-diphenyl-1,3-propanedione (dibenzoylmethane) is reversibly reduced by one
electron to an enolate radical anion, which is protonated by proton transfer from the parent mol-
ecule. The formed radical then dimerizes to pinacol. As a result, in total a “half-electron” process
occurs (Scheme 31.32) [124]:
In the case of dicarbonyls separated by a longer aliphatic chain (three carbon atoms and more)
where no mutual interaction between them takes place, the cyclization like in the section on carbon-
yls with remote unsaturated bond occurs. As an example, the reduction of 1,3-dibenzoylpropanes—
III (1,5-dicarbonyls) gives rise to a 1,2-cyclic diol—IV (Scheme 31.33).
H
O O O O
SchEME 31.31 Tautomeric equilibrium of 1,3-Dicarbonyls.

H
O O
H Ph Ph O– O
4 O O +2e–
+ 2
Ph Ph Ph Ph Ph Ph
O O
H
SchEME 31.32 The formally “half-electron” process of 1,3-diphenyl-1,3-propanedione reduction.
O O
OH OH
+2e–, +2H+
R R R R
a: R = H
III b: R = phenyl IV H2
SchEME 31.33 Intramolecular cyclization during electroreduction of 1,3-dibenzoylpropanes.
As for the mechanism, two pathways were suggested: either the cyclization occurs on the level of
dianion of the parent compound III (Equations 31.1 through 31.4) [125,126] or on the level of radical
anion (Equations 31.1 and 31.4 through 31.6) [127].
III + e− ⇆ III− • (31.1)

(a)
2 III− • → III2− + III (31.2)
III2− → IV2− (cyclization) (31.3)
IV2− + 2 H+ → IV H2 (31.4)
(b)
III− • → IV− • (cyclization) (31.5)
IV− • + III− • → IV2− + III (31.6)
IV2− + 2 H+ → IV H2 (31.4)
More recently, the electroreduction of aryl 1,4-, 1,5-, or 1,6- (γ-, δ- or ε-) diketones in the presence
of CTMS was studied from the stereospecific electrosynthetic point of view and the formation
of unsymmetrical cyclic pinacols (vic-diols) via intramolecular head-to-head coupling with trans-
stereoselectivity was confirmed (Scheme 31.34). It is notable that in contrast to electroreduction, the
chemical reduction using TiCl4 –Zn yields prevalently cis-isomers [51,128].
An analogous reaction with γ-, δ-, ε-, and ζ-keto acylimidazoles [93], however, gives rise to cyclic
α-hydroxy ketones (instead of cyclic pinacols) due to the leaving imidazole anion (Scheme 31.35).
4. β-Keto Esters
In the electrochemical reduction of β-keto esters, the carbonyl is reduced first, therefore this topic
was inserted in the present chapter. This process, accompanied by the Tafel rearrangement, is
already a “classic” reaction [8]. The accepted reaction mechanism is the following [129]: under acidic
O OH OH
Ph Electroreduction Ph
X
O X X = (–CH2–)1–3
HO
O O
HO
Y Y
Electroreduction
CO-OEt CO-OEt
Y = (–CH2–)1–2
SchEME 31.34 Electrochemical reduction of aryl 1,4-, 1,5-, or 1,6- (γ-, δ- or ε-) diketones.
O OH
1) +2e –, CTMS/TEA O
Im 2) TBAF/THF
O – Cl–; – Im–
SchEME 31.35 Electrochemical reduction of γ-, δ-, ε- and ζ-keto acylimidazoles.
OH OH OH
O O O
OH O
+e– +H+ +e– +H+ O–Et
O-Et
O-Et –EtOH
R1 R2 R2 R1
R1 R2 R1 R2
V
O O
R2 O O
O-Et Reduction
R1 R2 R1 R2
VI R1
SchEME 31.36 Electrochemical reduction of β-keto esters accompanied by the Tafel rearrangement.
conditions, the carbonyl is reduced and protonated and the radical is coupled with the electrophilic
ester carbon, resulting in an intermediate cyclic pinacol that stabilizes to hydroxycyclopropanone.
The latter, after the ring opening, yields an α-diketone, whose stepwise reduction finally results in
the rearranged hydrocarbon (Scheme 31.36). The first part of the process—the pinacol formation—
seems to be similar to the crossed pinacol coupling [51]. For this rearrangement, the β-carbonyl must
be unconjugated (compound V). Esters like VI do not undergo this reaction and in acidic solution
they are reduced to a secondary alcohol.
When aromatic δ- and ε-keto esters are reduced, a similar intramolecular coupling proceeds,
however, due to the alkoxy leaving group; the final product is an α-hydroxy ketone [130].
At the end of this section, an interesting example of intermolecular coupling of reduced dik-
etones in nonaqueous DMF will be mentioned: Diaryl-1,2-diketones (e.g., benzil) are electro-
chemically reversibly reduced to the dianion that undergoes an intermolecular coupling with
carbonimidoyl dichlorides under the formation of the corresponding enediol iminocarbonates
(Scheme 31.37) [131]:
+ Cl
N
O O–
+2e– Cl
O O +2Cl–
O –O
N
SchEME 31.37 Intermolecular coupling of reduced diaryl-1,2-diketones (e.g., benzil) with carbonimidoyl
dichloride.
G. REDUCTIoN MECHaNISMS IN ANaLYTICaL AppLICaTIoNS

In Sections I.B through I.F, a number of model types of carbonyl compounds were selected and their
characteristic electrochemical reduction mechanisms were presented and discussed. On the other
hand, especially in electroanalysis, one can encounter important, biologically significant molecules
containing one or more carbonyl groups, often with rather complicated structure and nonfitting
unambiguously to one of the mentioned types. Nevertheless, even in these cases the reduction pro-
cesses were investigated and the respective mechanisms were put forward. Several recent examples
are presented in this section with the hope that the readers working with rather complex carbonyl-
containing molecules can find here a similarity or an inspiration. The structures are depicted later.
It is noteworthy that for trace analysis of reducible organic analytes, advanced polarographic and
voltammetric methods with mercury electrodes are steadily considered to be very suitable. Due to
their instantly renewable, absolutely smooth surface, they exhibit high reproducibility and sensitiv-
ity accompanied with simple preparation of samples (e.g., possibility of direct measurements of
even suspensions or biological samples without separation or other pretreatment). In addition to this,
small-size and low-cost instrumentation (often easily portable) are other advantages.
For detection and determination of the agrochemical chlorophacinone in formulations, grains
and vegetables a method based on differential pulse polarography (DPP) was developed. The suit-
able electrochemical response—DPP peak—was attributed to the simultaneous reduction of three
carbonyl groups [132].
A spectrum of electroanalytical methods like dc-polarography (DCP), cyclic voltammetry
(CV), DPP, controlled potential electrolysis (CPE), and millicoulometry was used for a study of the
cathodic reduction of iprodione. A single four-electron signal interpreted as a simultaneous reduc-
tion of two carbonyl groups was obtained and was used for analytical purposes [133].
Valone is a pesticide containing a carbonyl group whose determination in water is important.
CV and DPP study of fundamental electrochemical properties was performed and the signal at pH
4 was used for analytical application [134].
The antidepressant drug and smoking cessation aid bupropion hydrochloride (in fact its carbonyl
group) is best reduced in slightly acidic medium on mercury electrodes. The electrochemical prop-
erties and kinetic parameters were evaluated [135].
Electrochemical and spectrophotometric study of the contraceptive drug norethisterone at mer-
cury electrodes in aqueous solutions resulted not only in mechanistic considerations and deter-
mination of pKa, but particularly in its trace quantification in pharmaceutical formulations using
stripping methods and reaching a detection limit 1.5 × 10−9 mol L−1 [136].
Reducibility and catalytic activity of lovastatin were investigated by polarographic and voltam-
metric methods. The main reduction wave at −1.49 V (vs. SCE) was ascribed to a two-electron and
two-proton addition to the carbonyl group on the lactone ring. In the presence of a hydroperoxide,
a strong catalytic reduction wave appears that can be used in trace detection of lovastatin (up to
8 × 10−9 mol L−1) in pharmaceuticals, urine, and blood serum [137].
The main cathodic response of captopril (a medical against hypertension) is the two-electron
reduction of the carbonyl group at −0.9 V (vs. SCE). This signal was used for the development of a
DPP detection of captopril in tablets [138].
A new polarographic (DC, AC, NPP, and DPP) method of daunomycin detection in pure form,
vials, and in blood is presented, based on the cathodic peak of the quinone moiety. The analysis is
complicated by a strong adsorption [139].
The mechanism for reduction of isatic acid was investigated by DCP and pulse polarography,
linear sweep and CV, electrocapillary curves, chronocoulometry and bulk electrolysis with electro-
chemical and UV spectroscopic monitoring of the reaction. Three forms of isatic acid in aqueous
solution were detected, depending on pH: diprotonated, monoprotonated, and nonprotonated. The
reduction center is a carbonyl in all cases. In acidic media, adsorption was observed [140].
The mechanistic study of electroreduction of lichexanthone was performed in aprotic DMSO
at stationary as well as rotating glassy carbon disk electrodes. The reduction proceeds in two
one-electron steps to anion radical and dianion, the first is reversible. The slow follow-up chemical
reaction involves opening of the 4-pyrone ring at the oxygen heteroatom and necessary protonation.
The expected reduction of the carbonyl group does not take place [141].
An effect of substituents in position 7 on the reducibility of flavones was followed by NPP in
DMF/aqueous buffer mixture and the corresponding kinetic parameters were evaluated using the
Meites and Israel equation [142].
O Cl O
O Cl COOH
O H
N
Cl N NH2
O N
O isatic acid
O
HS O
chlorophacinone iprodione
O
HO O HO OH N
OH
O O
O O captopril
+2e– +2H+
O
H3C O H3C O
H3C CH3 H3C CH3
O
H3C H 3C O
lovastatin valone
O OH O
O R OH CH3
H OH
H H
O O O OH O O CH3
H 3C
flavone H H
O daunomycin OH
norethisterone
NH2
Me O OH Me O OH O
H
+2e– +2H+ N
Me-O O O-Me Me-O OH O-Me

lichexanthone
Cl bupropion
II. AzOMEThiNE COMPOUNDS

A. GENEraL MECHaNISTIC CoNSIDEraTIoNS
Azomethine compounds are molecules derived from carbonyls, where the oxygen is replaced by nitro-
gen. Since azomethines can be generally prepared by condensation of a carbonyl with an amine and the
reverse hydrolysis yielding the starting substances is also possible, the azomethine group can be con-
sidered as a direct carbonyl analog with many common features with parent carbonyl compounds and
simultaneously as a “krypto-” carbonyl, a precursor from which the carbonyl moiety can be released.
Unlike carbonyls with oxygen being always the terminal atom, the azomethine bond need not to
be only the terminal one, like in imines, but it is mostly incorporated in a chain or in a heterocycle.
Therefore, the spectrum of various azomethine compounds is broader: the azomethine nitrogen
can bear not only hydrogen, like in imines, but also carbon (Schiff bases, heterocycles), oxygen
as hydroxyl (oximes) or as alkoxy substituent (O-alkyl oximes), and another nitrogen (hydrazones,
azines), eventually other heteroatoms.
Similar to carbonyl compounds, the azomethine bond is polarized with the electrophilic center
attractive for nucleophiles (and electrons) at the carbon atom. However, the nitrogen with its non-
bonding electron pair is prone to protonation, which affects significantly the reduction mechanism.
Generally, two types of electroreduction mechanisms exist (Scheme 31.38): since the electron is the
elementary nucleophile, the electrochemical reduction of neutral, unprotonated azomethine (in basic or
aprotic media) starts by the electron transfer to the carbon atom under formation of a radical anion that
either abstracts a proton from the solvent and is further reduced to saturation of the azomethine bond
or that dimerizes [143–146]. On the other hand, in the case of protonated molecules, the first electron
transfer is aimed at the nitrogen atom, causing first the splitting of the bond between two heteroatoms.
In addition to this, a covalent addition of nucleophiles may play a significant role in reactivity
and reducibility of azomethine compounds. The most frequent nucleophile is the hydroxide anion
from water; hence, the discussion concerning the addition of nucleophiles will be devoted mainly to
hydration. Addition of water to imines or Schiff bases derived from aliphatic or alicyclic carbonyls
results in the corresponding carbinol amine, which is unstable and decomposes rapidly to the par-
ent carbonyl and amine (hydrolysis of imines). In the case of benzylidene Schiff bases, the stability
of the carbinol amine is higher due to the stabilizing aromatic system and depends on pH, benzal-
dehyde substituents, and structure of the amine [17]. However, carbinol amines are not reducible,
therefore their formation and decomposition cannot be directly followed electrochemically and the
proof of their existence must be done indirectly [147].
Covalent addition of water on the azomethine bond being a part of the unsubstituted N-heteroaromatic
ring does not proceed without activation, which means without increased polarization of the C=N
bond. This effect can be achieved either by substitution with an EWG in m-positions toward the
(–) Y Y Dimerization
N +e– –N
protonation (Y = O, N, C)
Aprotic
R1 (+) R2 basic R1 R2 reduction of C=N
+H+
+ Y Protonation
HN +2e– NH _
Protic
+ reduction of C=N (Y = O, N)
Y
R1 R2 R1 R2 hydrolysis
SchEME 31.38 Electrochemical reduction mechanisms of unprotonated and protonated azomethine bonds,
respectively.
heteroatom and/or by the second nitrogen in the ring (pyrimidine derivatives) or by another annealed
aromatic ring [148] The first two conditions are well fulfilled, for example, in the case of 5-nitropy-
rimidine or its 2-methyl and 2-benzyl derivatives where covalent addition of water was found [149].
All azomethine groups (under conditions where the protonation steps may occur, that means, not
only in aqueous solutions) are ultimately electrochemically reduced to amines. On the basis of the
consumption of electrons during the electroreduction process, the compounds bearing azomethine
bonds can be divided into three groups:
Imines (>C=N–H) and Schiff bases (>C=N–R) derived from the reaction of a carbonyl with
ammonia or primary amine are reduced by two electrons and two protons under saturation of the
C=N double bond.
Oximes (>C=N–OH or >C=N–OR) derived from the analogous reaction of carbonyl with
hydroxylamine (NH2–OH) or alkoxyamine (NH2–OR), and hydrazones (>C=N–NR2) derived from
hydrazine are reduced by four electrons and four protons since there are two reducible groups: the
azomethine bond and the bond between the two heteroatoms N–Y (Y=O, N). Important factors
influencing the reactivity of these azomethine compounds and stability of intermediates are (a)
electron affinity of the double bond (π-electron system); (b) leaving ability of the group Y−.
Azines (>C=N–N=C<) having two azomethine bonds are, consequently, totally reduced by six
electrons and six protons. An analogous behavior is reported in hydrazonates (>C=N–N=C (–O–R) R).
Besides this fundamental classification, the individual reduction processes may differ (a) by the
sequence of proton- and electron transfers; (b) by the order which group is reduced first: whether
the C=N bond or the N–O (N–N) bond between two heteroatoms. These differences in reduction
pathway depend naturally on the conditions (protic–aprotic solution and pH). Generally, azome-
thine compounds are reduced more easily than the parent carbonyls and antecedent protonation
facilitates the reduction.
Azomethine compounds—similar to the carbonyls—are frequently used, electrochemically
investigated and their electrochemical reduction reviewed (e.g., References 9,150–153). In this part,
a general overview is presented and supplemented by more recent achievements.
B. DErIVaTIVES oF AMMoNIa (IMINES, SCHIFF BaSES, IMINIUM CaTIoNS)

1. Protic Media
Imines derived from aliphatic ketones are reducible only in alkaline solution; otherwise, they
undergo a fast hydrolysis yielding the original carbonyl and ammonia. Preparative electroreduction
of such imines to corresponding amines can be therefore performed only in a “one-pot” experi-
ment, where the parent ketone reacts with the large excess of ammonia and the produced imine is
simultaneously electrochemically reduced to the amine product (Scheme 31.39, left) especially at
low temperature. The reduction potential of imine is less negative than that of the carbonyl.
When a higher concentration of the ketone is used for electroreduction of the in situ generated
imine, the product—amine—undergoes a “secondary” condensation with starting ketone yielding
a new Schiff base (Scheme 31.39, right) [154].
Aromatic imines are more stable (and thus reducible) even in neutral and acidic media. Besides
their formation from parent carbonyls, they are often encountered as reduction intermediates of
oximes, hydrazones, and azines (see Sections II.C–II.E).
O –H2O N-H NH2 + –H2O

+2e , +2H O
+ NH3 N
SchEME 31.39 “One-pot” condensation–reduction–condensation experiment resulting in an aliphatic

Schiff base.
H
+e– +H+ N
R2
+H+ +e– R1
H
N R1
N NH+ H
R2 R2 N
R2 R2
R1 R1 Dim.
R1
R2
N
H
R1
SchEME 31.40 Electrochemical reduction of preprotonated aromatic Schiff bases in acidic media.
Schiff bases, especially the aromatic ones, are in water much more stable than imines. Their
electrochemical reduction leads generally to a saturation of the azomethine double bond [155].
In acidic media, pre-protonated Schiff bases of aromatic carbonyls are reduced in two one-
electron waves that at higher pH merge into one (see Section I.A.1, Figure 31.1) [154,156]. The first
wave corresponds (similar to the case of carbonyls) to radical formation, which may either dimerize
(mechanism: CEDim) or be further reduced at the more negative potential in the second wave to
saturation (CEEC) [143] (Scheme 31.40).
2. Aprotic Media
In nonaqueous solvents, the azomethine compounds are more stable than in water. Their reduction
occurs at more negative potentials because the nitrogen atom is not pre-protonated.
Aliphatic ketimines and Schiff bases are typically reduced at rather highly negative potentials
by a single two-electron process to a saturated C–N bond, following the ECEC mechanism. The
primary imine radical anions are strong bases able to abstract proton(s) from the solvent and the
resulting protonated neutral radical is generally reduced more easily than the parent Schiff base
(Scheme 31.41, upper pathway) [144].
Aromatic Schiff bases, due to the stabilizing π-system, are reduced less negatively, their primary
radical anions are less basic and more stable, hence their reduction proceeds in two one-electron
waves according to an EEC mechanism (especially in DMF where activity of protons is lower than,
e.g., in AN; Scheme 31.41, lower pathway). Besides, the radical anion may undergo a dimerization.
Substituted iminium cations or protonated imines are reducible in a one-electron process in
aprotic media giving rise to radicals that are relatively stable (especially those derived from (di)
aryl ketones) and are able to dimerize [145]. The process is purely radical, without participation of
protons and occurs at the originally carbonyl carbon [146].
H
N
+SH +e–, +H+
R2
–S–
+e– R1
H
N N– Dimer N
R2 R2 +2H+ R2
R1 R1 +e– R1
–
– N
R2
R1
SchEME 31.41 Electrochemical reduction of ketimines in nonaqueous media.

Alkyl NH2 Alkyl N–H Alkyl N–H

Alkyl N–H
+2e–
+2e–
+2H+
+2H+
SchEME 31.42 Preferential reduction of the aromatic ring in the case of 9-, 10- or 9,10-anthryl(di)imines.
When comparing electrochemical reduction (in DMF) of aromatic ketimines derived from ben-
zene, naphthalene, and anthracene, the phenyl or 1-naphthyl ketimines are reduced in a standard way
at the azomethine bond giving rise to the corresponding amine, while the 9-, 10-, or 9,10-anthryl (di)
imines are reduced first at the aromatic ring under formation of the imine of 9,10-dihydroanthra-
cene (Scheme 31.42). The chemical reduction showed the same difference in products; the experi-
mental results were supported by quantum chemical calculations [157].
Aromatic imines, as direct analogs of quinones, where one or both C=O groups are replaced by
N-aryl imino moieties (quinone mono- and diimines), are reduced by two electrons resulting in satu-
ration of both C=N (C=O) bonds and aromatization of the ring [158]. More recently, a seminal study
appeared, where based on a large series of newly synthesized quinone mono- and diimines, the
structural influences on redox properties in aprotic as well as in protic media were systematically
investigated and discussed [159]. It was found that the nature of the substituent on the nitrogen atom
(N-phenyl-, N-phenylsulfonyl-, and N-benzoyl-) is the most significant indicator for nucleophilicity
of radical intermediates and products. In aprotic media, the quinone monoimine VII is reduced in
the standard way by two reversible one-electron steps followed by the abstraction of two protons
from the solvent giving rise to p-aminophenol. By addition of proton donors of various strength,
the nucleophilicity of the primary radical anion can be evaluated. In acidic solutions, a pre-pro-
tonation takes place, the iminium cation is reduced to the corresponding aminophenol, and this
process is chemically reversible. The redox properties of VII were compared with analogous series
of N-phenylsulfonyl- and N-benzoyl-imines and diimines with characteristic structures VIII–XII.
O O R5
O
R1 R5 R4 R1
R4 R1 R4
R3 R2 R3 R2 R3 R2
O S O
N O N N
N
N O O S O
R5 R4 R1
R5 R4 R1
VII
N R3 R2
R3 R2
R4 R1 R5 N
VIII O N R5
IX O S O
R3 R2
N
R5 X R5
R5
XI XII

Aromatic imines, with a good leaving group in the position 4 of the quinoid ring, have also simi-
lar character. In acetonitrile, the two-electron reduction causes splitting of the leaving group (in the
presented case trichloromethyl) and the ring becomes aromatic simultaneously with the saturation
of the azomethine bond. This reaction is significant mainly in organic electrosynthesis as a way to
N-tolylation of aromatic amines (Scheme 31.43) [160].
+2e– H
R(H) N R(H) N
–C Cl3
C Cl3
H3C CH3
SchEME 31.43 Electrochemical reduction of aromatic imines with a good leaving group in position 4 of
the quinoid ring.
In the case of newly synthesized aromatic Schiff bases combined with azobenzene XIII (exhib-
iting good antimicrobial activity), in DMF, the preferential reduction of the azomethine bond is
reported [161].
H3C–O O–Alk
N
N N
OH
XIII
Electrochemical reduction of the enol–imine compound XIV in DMF proceeds in two one-
electron quasireversible steps (to radical anion and dianion), according to expectations. The revers-
ibility is suppressed by the presence of two hydroxylic hydrogen atoms due to the intramolecular
hydrogen bonding and autoprotonation reaction [162].
H3C CH3
H O CH3
HO N
XIV
When aromatic Schiff bases (fluorinated benzylidene anilines) are reduced in aprotic conditions
in the presence of CO2, the primary radical anion reacts with the carbon dioxide under formation
of fluorine-containing amino acids and electrochemically activated insertion of carbon dioxide is
going on (Scheme 31.44). The originally reversible first wave becomes irreversible and increases,
whereas the second reduction step (to the dianion) disappears [163,164]. In the following, more
recent study, the crucial influence of ion-pairing (various solvents, various indifferent electrolytes)
on effectiveness is discussed [165].
F F F F
–
+e– CO2 H
N N– N +e–, +2H+ N
OOC OOC
R R R R
SchEME 31.44 Electrochemical reduction of fluorinated benzylidene anilines in aprotic conditions in the
presence of CO2.
O
+
R +2e– R R R
+CTMS H3C Im H3C –Im– CH3
_ O–
–TMS
Im O
–Cl– HN
N N N
TMS TMS
R R R R
SchEME 31.45 Coupling of a reduced diarylimine (Schiff base) with a ketone.
Another synthetic application of electrochemical imine reduction in aprotic media is based on cou-
pling of a reduced diarylimine (Schiff base) with a ketone (acylimidazole is very suitable since imidazole
is a good leaving group) in the presence of chlortrimethylsilane (CTMS). In this process, α-amino-α-
aryl ketones (C-acylated imines) are formed enabling synthesis of, for example, α-aryl glycine (Scheme
31.45, see Scheme 31.17) [166]. This type of reaction can be used also intramolecularly [167].
C. DErIVaTIVES oF HYDroXYLaMINE (OXIMES, O-ALkYLaTED

OXIMES, N-aLkYLaTED OXIMES–NITroNES)
1. Protic Media
Oximes are generally reduced to amines by four electrons. There were two theoretical possibilities
of the first reduction step: saturation of the C=N bond or splitting of the N–O bond. Lund suggested
already in the 1950s that in acidic or neutral aqueous media the first two-electron reduction pro-
ceeds at the N–O bond under formation of imine since the hypothetic corresponding hydroxylamine
is nonreducible under the given conditions [154].
The intermediate imine is then reduced in the second two-electron step to the final product—
amine, or, in the case of (di)alkylimine and/or in slightly acidic pH, the imine is simultaneously
hydrolyzed to the original carbonyl compound and ammonia. Which of these processes prevails
(electroreduction vs. hydrolysis) depends on the imine structure (aromatic imines are more stable
intermediates than aliphatic ones) and on conditions, particularly pH.
The reduction of the intermediate imine can occur either at less negative potentials than the starting
oxime and a single four-electron process is observed, or at more negative potentials and two 2-electron
waves are obtained (this is possible in strongly acidic media). In the latter case, the imine is relatively sta-
ble to be isolated and identified. This was achieved in the case of a cyclic oxime 4-(4′-methoxyphenyl)-2,
3-benzoxazin-1-one (Scheme 31.46) and 2,4-dihydroxybenzophenone oxime [168], when the existence of
both intermediate imines was experimentally proven. Later the presence of imines during the reduction
of a series of p-substituted aryl aldoximes and ketoximes was confirmed for those derivatives when the
p-substituent was an electron-donating group [169].
O-CH3 O-CH3 O-CH3
+H+ +2e–, +2H+
N NH+ NH2+
O O OH
O O O
SchEME 31.46 Electrochemical reduction of a cyclic oxime in strongly acidic media yielding a stable
protonated imine.
In acidic and neutral solutions, oximes—like other azomethines—exist in the protonated form,
hence depending on pH, the species being actually reduced differ. This feature is evident from
(a) the total number of observed reduction processes (waves) within the total pH range (at lower pH
the protonated positively charged molecule is reduced at less negative potentials than the neutral
species in basic solution), and (b) from the linear dependence of the reduction potential on pH, point-
ing to a pre-protonation reaction in the diffusion layer. There is a general rule (see Section II.A):
when the molecule itself prevailing at the given pH in the bulk of solution is reduced, no antecedent
proton transfer takes place and the reduction potential is independent of pH. Since the protonated
form is always reduced more easily, at slightly higher pH when the prevailing bulk form is already
nonreducible at the given potential, the molecules transported from the bulk are continuously pro-
tonated in the diffusion layer and immediately reduced. The depletion of the pre-protonated form
shifts the equilibrium to its side and therefore the full reduction may occur even 3–4 pH units above
the pKa. Since the supply with protonated form with increasing pH is more difficult, the reduction
potential is linearly shifted to more negative values. The slope of this dependence indicates among
others the number of protons involved.
At the oxime moiety, there are two sites of possible protonation (N and O), therefore both should
be considered. Based on the respective pKa, in strong acids a diprotonated form prevails in the
bulk, in slightly acidic media monoprotonated species dominate. In neutral to basic solution, the
uncharged original form of the molecule is typical, which in very alkaline environments dissociates
to the irreducible oximate anion.
The protonated oximes in acidic–neutral media are thus always reduced by four electrons to
amines, with imines as intermediates. In basic solutions, however, (and in aprotic solvents—see
Section II.C.2) the situation is different and the most electrophilic site on the unprotonated molecule
is the oxime carbon. Therefore, in the case of reduction of benzaldoxime in alkaline media, only
two-electron reduction occurs under the formation of benzyl hydroxylamine [170].
In a more recent study of electroreduction mechanism of a series of substituted benzaldehyde-
and acetophenone oximes [171], a diprotonation mechanism was suggested based on the shape
(slope) analysis of the E1/2 versus pH and ilim versus pH dependence. In the diprotonated structure
>C=NH+–OH2+, the positive charges at both heteroatoms focus the electron uptake to this site and
the cleavage of the N–O bond is facilitated by the good leaving group (OH2). This process occur-
ring at pH between 3 and 8 proceeds in close vicinity of the electrode. It is adsorption assisted and
analogous to the reduction mechanism of nitrones (N-alkylated oximes), where antecedent proton-
ation of the already positively charged molecule takes place. This represents another example of
the cleavage of the N–O bond with positive charges on both the nitrogen and the adjacent oxygen
atoms [172].
In the case of trifluoroacetophenone oxime, a strong hydration was found due to the strong elec-
tron-withdrawing effect of –CF3. Between pH 2 and 8, the reduction limiting current decreases to
about 2% of the original value recorded at pH < 2, pointing to the nearly exclusive presence of carbi-
nolamine, a species assumed to be the first unstable intermediate in reaction of carbonyl compounds
with amines (Scheme 31.47) [173].
The four-electron reduction pattern yielding the corresponding amine operates also in pyr-
idine-4-aldoxime [174] as well as in the series of methyl hetaryl (pyridin-2-yl, pyridazin-3-yl,
OH
N OH HN
+H2O
OH
CF3 CF3
SchEME 31.47 Hydration of trifluoroacetophenone oxime.

pyrimidin-2-yl, pyrimidin-4-yl, pyrazinyl) ketoximes [175]. Due to the presence of more hetero-
atoms, the acidobasic properties are more complex (pre-protonation, shift of reduction potentials,
formation of intramolecular hydrogen bonds etc.). Nevertheless, depending on pH, only three dif-
ferent acidobasic forms of hetaryl oximes (di-, mono-, and unprotonated) could be identified during
reduction of all studied derivatives. Within the whole pH scale, three 4-electron processes were
observed that replace each other with increasing pH [175]. In the case of the pyridine-4-aldoxime,
at potentials close to the electrolyte discharge, the second reduction process occurs assigned to the
reductive splitting of the amine [174]. Changes of the δE1/2/δpH and δilim /δpH dependences over the
whole pH region were presented and discussed in the context of protonation state, kinetics and (α. n)
values. Imines (even unstable in acidic solutions) as intermediates are expected at all pH.
In the diazine ketoximes, the second ring nitrogen (according to its position) facilitates reduction
of the oxime group in comparison to methylpyridin-2-yl ketoxime. Reducibility of the oximes corre-
lates with the enhancement of their hydrolytic activity towards organic esters (4-nitrophenyl acetate
served as a model). The reduction of the heteroaromatic ring in the diazine ketoximes proceeds at
more negative potentials than the reduction of the oxime group [175].
Nevertheless, one should keep in mind that pyridine-4-aldoxime XV can theoretically exist in
two tautomers: besides the classical oxime formula, the quinoid tautomer is also reported [176],
hence, the acidobasic properties as well as the reactivity of this compound can be more complicated.
In the electrochemical literature, however, no such discussion has been found.
OH O
N N
N N
XV H
Derivatives alkylated on the oxygen atom (O-alkyloximes) are another type of oximes. Their
reduction mechanism in buffered solutions was found to be analogous to that of other oximes. In
the case of the antibiotic cefetamet, a single four-electron process in acidic media is replaced by two
two-electron waves at pH 5–9 corresponding to a gradual reduction to the imine and amine, respec-
tively. The reason for the separation of potentials of the two processes was explained on the basis
of combination–superposition of two acid–base equilibria causing pre-protonation of the starting
oxime and intermediate imine, respectively [177].
HO O
NH2
H3C O
N O N
S
S N
H H
N
O
CH3
cefetamet
The oxime reduction can be complicated by the spontaneous hydrolysis of the imine or in the
presence of alcohol by its covalent addition to the intermediate imine. As a result, a decrease of
the limiting current is observed. It was demonstrated that at a given concentration of the alcohol,
the drop of current increases in the sequence MeOH < EtOH < i-PrOH < tert-BuOH, following the
increasing nucleophilicity of the alcohol [178].
2. Aprotic Media
Electrochemical reduction of benzaldehyde oximes in DMF in presence of a proton donor (e.g.,
phenol) proceeds as a totally four-electron process, resulting in the respective amine. In carefully
dried DMF, the presence of the intermediate anion radical PhCH=N− • after the rupture of the
N–O bond was suggested. Among the products, N,N′-dibenzylhydrazine and benzonitrile were
detected [179].
In the only, up to now published systematic study of the reduction mechanism of oximes in
dry DMF, six types of oximes were discussed [180]. In electroreduction of benzaldoximes, their
O-alkyl and O-acyl derivatives, the formation of benzonitrile as a product was confirmed. (This
finding is rather surprising since the conversion of benzaldoxime to benzonitrile is not a reduction.)
Two characteristic features were experimentally observed: (a) the CV curve starts with a small
irreversible reduction peak, which is “interrupted” by a well-developed reversible couple of peaks
of the stable product, identified as benzonitrile; (b) the charge consumption during preparative
electrolysis resulting in 60–80% yield of benzonitrile corresponds to n = 0.4–0.6 only. The forma-
tion of nitrile from benzaldoxime was explained by a combination of electroreduction and electro-
catalytic processes (Scheme 31.48) initiated by a one-electron reduction of the oxime followed by
the splitting of the N–O bond under the formation of the imine radical and a hydroxide anion as an
electrogenerated base (EGB). The OH− attacks the parent oxime resulting in elimination of water
giving rise to benzonitrile. The alternative pathway is the deprotonation of the imine radical and
the formed nitrile radical anion transfers the electron to the parent oxime or back to the electrode.
The reduction of O-alkyl and O-acyl derivatives follows an analogous pattern and differs only in
the base being split-off.
In acetophenone, fluorenone, and O-acyl fluorenone oximes, benzonitrile cannot be formed due
to the lacking hydrogen on the oxime carbon. Their preparative reduction in aprotic DMF yields the
corresponding imine that is hydrolyzed by the present base and/or during the work-up to acetophe-
none and fluorenone, respectively [180].
The electroreduction behavior observed for pyridine-4-aldoxime in DMF differs from that
described earlier in this section for benzaldoxime: in the cyclic voltammograms, no reversible peak
appeared that could be ascribed to the reduction of the pyridine-4-nitrile; on the other hand, the
final reduction product was identified as the amine derivative. The expected mechanism starts as in
the previous case by the uptake of the first electron and splitting the N–O bond to imine radical and
hydroxide anion. The latter, however, deprotonates the starting pyridine-4-aldoxime giving rise to
the oxime anion, which is reduced more negatively and abstracting protons from the solvent yields
the corresponding amine [181].
From the electrosynthetic point of view, an electroreductive intramolecular coupling of
O-methyloximes with aliphatic cyclic imides in 2-propanol afforded five-, six-, and seven-membered
cyclized products. These reactions provide a useful method to synthesize azabicyclo compounds
(Scheme 31.49) [182].
–
PhCH —
— N–OH + e PhCH — N–OH–° PhCH —
— N° + OH
–
OH– + PhCH —
— N–OH H2O + PhC N + OH–
PhCH —
— N° + OH– PhC N–° + H2O
PhC N–° + PhCH —

— N–OH PhC N + PhCH — N–OH–°
PhC N + e– PhC N–°
SchEME 31.48 Proposed mechanism of the formation of nitrile from benzaldoxime.

R H H O–Me
O
O N O–Me H N
Electroreduction Work-up
N i-PrOH
O–Me n N n
n N N
O O O
n = 1–3
SchEME 31.49 Electroreductive intramolecular coupling of O-methyl oximes with aliphatic cyclic imides
yielding azabicyclo compounds.
3. Mono- and Dioximes of α-Diketones

The presence of the electron-withdrawing carbonyl group in α-position with respect to an oxime
enhances the reducibility of the oxime function. A similar rule is valid also for O-substituted oximes =
oxime alkylethers, and monohydrazones of α-diketones. As a result, the oxime is reducible even at
pH 10.2 when the oxime is in its anionic form. The reduction process in aqueous media is going on
in a standard way, like in isolated oximes: a four-electron reduction results in an α-amino carbonyl
compound, which is at more negative potentials further reduced and ammonia is released [183,184].
It has been proposed that in aromatic species also the enaminol might be the possible alternative
intermediate [185,186].
This problem was later studied on the example of aryl-alkyl diketones and the regioselectivity
of the reduction was demonstrated using the comparison of behavior of two isomeric monooximes
of phenyl-methyl diketone. At pH lower than 5 in the time scale of seconds (under conditions of
d.c. polarography and CV), the 1-phenyl-1,2-propanedione-1-oxime (XVI) is reduced in a standard
way by four electrons to 1-phenyl-1-aminopropan-2-one. The isomeric 1-phenyl-1,2-propanedione-
2-oxime (XVII), however, does not yield the expected reducible α-aminoketone but a nonreducible
olefin derivative (oxidizable to ketoimine) [187]. In the time scale of tens of minutes (during con-
trolled potential electrolysis), the olefinic enaminol undergoes a slow conversion to the 1-phenyl-2-
aminopropan-1-one as the main, further reducible product. The optimized geometry showed that
the protonated imine of XVI is in cisoid nonplanar conformation and the LUMO is unsymmetrical,
localized mainly at the imine moiety. Hence, the imine group is rather isolated and the delocaliza-
tion with the carbonyl is limited. On the other hand, the protonated imine of XVII exists in transoid,
nearly planar conformation with the LUMO symmetrically spread over the two carbonyl functions.
This molecule (including the LUMO) closely resembles benzil that is reduced to the stable and fur-
ther nonreducible enediol. This comparison suggests the role of the molecule conformation in the
reduction mechanism of monooximes of α-diketone (Scheme 31.50) [188].
The vic-dioxime is reduced in acidic-neutral media in a six-electron wave under formation
of an ene-diamine further reducible at more negative potentials. The last reduction step is again
H3C H3C H3C
+2e– +2e–
O O O
+2H+ +2H+
–H2O
N OH NH NH2
XVI “cisoid”
OH
N HN H2N H2N
+2e– +2e–
CH3 CH3 +2H+ CH3 CH3
+2H+
–H2O
O O OH O
XVII “transoid”
SchEME 31.50 Role of the molecule conformation in the reduction mechanism of two isomeric monoox-
imes of α-diketone.
+6e– +2e–
N–OH NH2 NH O O
N +6H+ Slow Hydrolysis +2H+
–2H2O –NH3
N–OH NH2 NH2 NH2
+2e–
+2H+
–
NH2 +2e + NH2 Slow
NH O
+2H Hydrolysis
SchEME 31.51 Six-electron electrochemical reduction of the vic-dioxime in acidic–neutral media.
analogous to that of benzil. The stability of the ene-diamine, however, is limited, and it is slowly
transformed to the amine-imine undergoing hydrolysis to the α-aminoketone. From the latter,
ammonia is reductively split-off at even more negative potentials. Using controlled-potential
electrolysis at the first six-electron wave, the α-aminoketone was identified as the main product
(Scheme 31.51). Depending on the pH and structure (aromatic–aliphatic, aldimines–ketoimines),
the protonation and concurrent reactions (tautomeric changes, hydrolysis) proceed in various
p roportions [186,189].
D. DErIVaTIVES oF HYDraZINE (HYDraZoNES)

1. Protic Media
The reduction of some hydrazones may be influenced by tautomeric changes to “azo-” or “ene-
hydrazine” forms when the structure permits the hydrogen transfer (Scheme 31.52). The hydrazone
form is dominant in acidic and neutral media, the other tautomers are expected in basic solution
[190,191]. This can be the reason for the low reducibility of hydrazones in basic media.
Phenylhydrazones of aromatic carbonyl compounds are reduced in acidic media in a four-elec-
tron process: first, the protonated form of the central N–N bond is split by two electrons, to an
aniline derivative and a corresponding aromatic imine, which is subsequently reduced by other two
electrons under saturation of the azomethine bond (Scheme 31.53) [154]. When the amine nitrogen
is bearing an EWG, and, especially in basic media, the antecedent protonation becomes difficult.
Then the electron uptake occurs first and a two-electron reduction takes place yielding a hydrazine
derivative (Scheme 31.54). The same reaction pattern is followed by acylated hydrazones [192].
Phenylhydrazones derived from aliphatic carbonyl compounds are not reducible in aqueous solu-
tions, only their trialkylhydrazonium salts [9].
Hydrazones derived from aromatic aldehydes and ketones are reduced at pH 2 to about 8 in a
four-electron step. The observed linear pH-dependence of half-wave potentials of N,N,N-trialkyl
hydrazonium ions indicates a protonation of the azomethine nitrogen prior to the first electron
uptake. The reduced species is thus bearing two positive charges on adjacent nitrogen atoms.
R3 R3 R3
N N N
N N H HN H
R1 R1 R1
R2 R2 R2
azo- hydrazone ene-hydrazine
SchEME 31.52 Tautomeric equilibria of some hydrazones.

H+ +e– H
+H+
N N N
N Acidic soln. N N
R1 R2 R1 R2 R1 R2
+H+
+2e–, 2H+ +e–

H +
NH2 NH N H
– HN
N
R1 R1 R2 R1 R2
SchEME 31.53 Four-electron electrochemical reduction of phenylhydrazones in acidic media.
+e–, +H+ H
N N
N Basic soln. N
R1 EWG R1 EWG
+e–
H +H+ H H
– N N
N N
R1 EWG R1 EWG
SchEME 31.54 Two-electron electrochemical reduction of phenylhydrazones in basic media.
From the evaluation of other δE1/2/δpH dependencies in acidic-neutral media plotted for a series
of hydrazones and oximes follows that their electrochemical behavior is consistent with the forma-
tion of a dicationic form, present as a reducible intermediate at the surface of the mercury electrode
[193,194]. The proven presence of imines as intermediates represents a confirmation of the reduc-
tion pathway where the initial two-electron reductive cleavage of the N–N bond takes place [195].
In the case of hydrazones derived from α,β-unsaturated carbonyl compounds (e.g., of carvone or
cinnamaldehyde), in alkaline solutions the α,β-double bond is reduced first by two electrons under
formation of a saturated hydrazone [9,154].
2. Aprotic Media
For the reduction mechanism of aromatic hydrazones ArR1C=N–NR2R3 in aprotic media, the prin-
cipal question is whether one of the R-substituents is hydrogen. When R1, R2 and R3 are carbon
substituents (structure type XVIII), the reduction starts with a reversible one-electron step under
formation of a stable radical anion, especially in phenylhydrazones (Scheme 31.55, upper part). The
presence of protons results in splitting of the N–N bond to imine radical and amine anion and their
reduction/protonation yielding primary and secondary amines. In this sense, the process is analo-
gous to the reduction of aromatic vinyl halides [196] or aryl halides [197,198].
When R1 is a hydrogen (derivative of benzaldehyde), the N-dialkyl hydrazone is deprotonated by
an EGB, the amine anion (as a leaving group) is eliminated and a nitrile is formed (Scheme 31.55,
lower part) [199–201].
When R2 or R3 is a hydrogen, its acidity is high enough to protonate the primary radical anion.
The reduction becomes irreversible [202] due to the autoprotonation (father-son) mechanism [203]
and the C=N bond is reduced [204].
R3 R3
–
R3 –N HN
XVIII N R2 R2
N R2
N + NH2 +
XVIII Protonation
+e– R1 reduction R1
R1
R3
N N
N R2
R3
H
+ EGB– + –
N + H-EGB
R2
SchEME 31.55 Electrochemical reduction mechanism of aromatic hydrazones in aprotic media.
E. AZINES (CYCLIC, ACYCLIC)

1. Protic and Aprotic Media
Benzalazine (XIX) has two azomethine bonds; therefore, compared to hydrazones, two more elec-
trons (and protons) are needed for its electrochemical reduction. A six-electron reduction occurs in
acidic aqueous solution giving rise to two molecules of benzylamine. In basic solution, the reduc-
tion yields benzaldehyde benzylhydrazone after consumption of two electrons and two protons. The
latter is further reducible (by four electrons to benzylamine) only in acidic media [9].
The question remains, what is the initial reaction in acidic solution, or, in other words, whether
benzaldehyde benzylhydrazone is the first intermediate even in acidic media or if the first reduc-
tion step causes splitting of the N–N single bond. This discussion was reopened by the study of
2-benzoylpyridine azine [205] where the pathway involving azo- and hydrazine derivatives was
suggested.
Based on the analogy concerning the antecedent protonation of other azomethine compounds
(oximes, hydrazones) preferentially at the two adjacent heteroatoms, the most probable general
reduction mechanism of azines in acidic and neutral media starts with (di)protonation of the two
heteroatoms (stabilized at the electrode surface), followed by a two-electron reductive splitting
of the N–N bond (Scheme 31.56—see also Sections II.C and II.D on oximes and hydrazones).
This mechanism was supported in the study of electrochemical reduction of unsymmetrical azines
derived from aromatic and aliphatic carbonyls in aqueous acidic or neutral solutions [206]. It was
concluded that the central single N–N bond is split into two imines first. The following reduction
of the azomethine bond occurs, however, only at the aromatic imine (due to its higher stability)
under formation of the corresponding amine. The aliphatic imine, on the other hand, undergoes fast
hydrolysis, resulting in the parent dialkylketone and ammonia. Hence, in the latter case, only four
electrons were consumed for the total reductive degradation of the studied aryl-alkyl azine.
On the other hand, the preferential reduction of one of the azomethine bonds in alkaline solu-
tion is consistent with the reduction of the same type of azines in non-aqueous solvents (acetoni-
trile—AN, DMF). Under strictly aprotic conditions, benzalazine is reduced in two one-electron
reversible steps under the formation of radical anion and dianion where both electron transfers
are aimed to the unprotonated azomethine bonds [207]. The stability of the radical intermediate
allows to record its EPR spectrum due to the presence of the stabilizing aromatic system. The
primary radical anion of fluorenone azine is thus stable in DMF for months. In the presence of a
proton donor (e.g., hexafluoro-2-propanol), an analogous two-electron reduction like in alkaline
solution occurs where one azomethine bond is saturated giving rise to fluorenone fluorenylhydra-
zone [208,209].
+2H+ H+ +2e– HN
N N 2
N Acidic soln. N+
H
XIX
HN +4e_, +4H+ H2N

2 2
–
+e_ +H+, +e–, +H+
N N
N Basic soln. XIX N
H
– 2–
+e– +e–
N XIX …
N XIX
Aprotic
SchEME 31.56 Electrochemical reduction mechanism of azines.
It is evident that the presence of protons decides about the reduction mechanism of azines. The
reduction pathways of benzalazine-type compounds under various conditions are summarized in
Scheme 31.56.
Though the azine grouping >C=N–N=C< seems to be an electron delocalized conjugated
π-system analogous to 1,3-butadiene, it was found that in fact the single N–N bond as well as the
C=N double bonds are isolated and noncommunicating. The latter feature was detected in cyclic
azines (1,2,4-triazine derivatives XX and XXI) [210–212]. Unlike the acyclic azines, the first step
of electrochemical reduction of these molecules in aqueous media involved the saturation of the
1,6-C=N bond (proven by preparative electrolysis), at more negative potentials the 2,3-azomethine
bond was reduced without a ring opening. As a model compound, the 2,3-dihydroderivative was
chemically independently prepared and its 1,6-azomethine bond was electrochemically reduced.
Surprisingly, the reduction potential of the 1,6-C=N bond of these two compounds were identical.
That means that the reduction center at the 1,6-azomethine bond is not influenced by the presence or
absence of the neighbor double bond being in structural conjugation. Hence, the N–N bond should
block the electron delocalization in this heterocyclic azine [213].
NH2 NH2
O 4 N Me O N S-Me
5 3
N N
Ph 6 N 2 t-Bu N
1
XX XXI
To prove this phenomenon also in acyclic azines, the extent of electron delocalization in
symmetrical and unsymmetrical p-substituted benzalazines [214] and in a series of analogous
aryl-substituted acetophenone azines [207] was systematically studied using detailed interpretation
of electroreduction data of the mentioned compounds in AN and DMF. The results proved the exis-
tence of a reduction system containing two localized, noncommunicating redox centers. The N–N
O-R O-R
H H
+e– N– R1 +2H+, +e– N R1
R3 N R3 N
O-R (Aprotic) Solv-H
R2 R2
N R1
R3 N
O-R H O-R
R2 +H+
N+ R1 +2e–, +H+ HN R1
(Protic) R3 N R3 NH +
R2 R2
SchEME 31.57 Electrochemical reduction mechanism of hydrazonates.

bond should have thus a single bond character. The comparison of x-ray structural data of various
conjugated analogues of 1,3-butadiene revealed that whereas the bond order of the central C–C bond
in 1,3-butadiene is about 1.4, the bond order of the N–N bond in acyclic azines is below unity (0.9).
This surprisingly long N–N bond in azines is well consistent with the electrochemically observed
blocking of electron delocalization along this grouping [214,215]. This problem was treated theoreti-
cally and in the solid state by Glaser [216,217].
2. Hydrazonates
Hydrazonates are formally azines where the –O–R group represents one substituent on carbon
atom. Hydrazonates are reduced in aprotic media on a mercury electrode in two steps; the first one
is a reversible one-electron process, but affected by a rather fast homogeneous follow-up reaction,
since the ratio Ipa /Ipc is less than one, the second reduction step is irreversible. When an EWG group
is present as the substituents R1 or R2, a third reduction step appears at more negative potential.
Controlled-potential electrolysis in aprotic conditions at the potential of the first wave lead to satura-
tion of a C=N double bond (Scheme 31.57, upper part).
When a proton donor (phenol) is gradually added, a new, most positive and irreversible reduction
peak appears and increases on expense of the originally first one. This effect points to a pre-proton-
ation of one nitrogen atom leading to a change of mechanism where the protonated nitrogen atom
is the reduction center. The preparative electrolysis in presence of a proton donor then results in the
splitting of the N–N bond (Scheme 31.57, lower part). As a product, only imine (R1 = Me, R2 = Aryl)
could be isolated and identified, whereas the iminoether undergoes fast hydrolysis during the work-
up [218]. Hence, the reduction behavior of hydrazonates is in principle analogous to that of azines.
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32 Reductions of Carboxylic
Acids and Derivatives
Rolf Breinbauer and Martin Peters
CONTENTS
I. Introduction ......................................................................................................................... 1249
II. Cathodic Reduction of Carboxylic Acids ............................................................................ 1249
III. Cathodic Reduction of Esters and Peresters........................................................................ 1251
IV. Cathodic Reduction of Anhydrides and Acyl Halides ........................................................ 1255
V. Cathodic Reduction of Amides, Lactams, Imides, Imidates, and Hydrazides ................... 1256
VI. Cathodic Reduction of Nitriles and Acyl Cyanides ............................................................ 1260
VII. Cathodic Reduction of Thioesters and Thio-Derivatives .................................................... 1261
References .................................................................................................................................... 1262
I. INTRODUcTiON
This chapter is focused on the cathodic reduction of carboxylic acids and its derivatives. Included
are carboxylic acids, esters, peresters, lactones, and anhydrides. Because of covering the compound
class of acyl halides in Chapter 25, the acyl halides are only briefly discussed, to put them into
the context of other acyl derivatives. Also included are the cathodic reduction of amides, lactams,
imides, imidates, and hydrazides. Section VI is focused on the reduction of nitriles, but also iso-
cyanates, cyanohydrins, and cyanides are included. The chapter closes with a short discussion of
sulfur analogs of carboxylic acids, especially thioesters and their derivatives. Good reviews and
compilation of electrochemical research in the last century have been published recently [1–3].
Cathodic transformation of carboxylic acids and their derivatives are well known [4,5], and in the
last decade the mechanistic understanding about the electrode processes has been tremendously
improved, which has stimulated more applications [4–13].
II. CAThODic REDUcTiON Of CARBOxYLic AciDS

A considerable challenge in the reduction of carboxylic acids is to stop the reduction at the alde-
hyde oxidation level as these compounds can be easily reduced further to alcohols or even alkanes
(Scheme 32.1) [14–17]. The reduction of aliphatic acids and unactivated aromatic acids results in the
production of hydrogen gas and the carboxylate anion [4,18].
In aqueous solution, the aldehyde reaction product predominantly exists as the hydrate, which is
reduced at lower potentials than the carboxylic acid starting materials. For example, cinnamic acid
can be reduced to cinnamaldehyde using either Zn or amalgamated copper [19]. In a similar man-
ner, the reduction of oxalic acid leads to glyoxylic acid [20–22].
1249
R H
+2 e–
+2 H+
–H2O
O +e–, +H+ O +4e–, +4H+

+ H2 R OH
– –H2O
R O R OH
+6 e–
+6 H+
–2 H2O
CH3
R
SchEME 32.1 Possible reactions in the cathodic reduction of carboxylic acids. (From Wagenknecht, et al., in:
Lund, H., Hammerich, O., eds., Organic Electrochemistry; 4th edn., Marcel Dekker, Inc., New York, 2001,
pp. 453–470.)
Wagenknecht et al. have defined the following requirements that must be fulfilled for the reduc-
tion of a carboxyl group to take place [4]:
• The carboxyl group must be activated by an electron-withdrawing group.

• The carboxyl group must be the most easily reducible group in the molecule.
• The formed aldehyde must be protected against further reduction by formation of a nonre-
ducible derivative, such as a hydrate or hemiacetal, borate complex, or bisulfite adduct [4].
Ohmori et al. have devised a sophisticated strategy in which triphenylphosphine (1) as an additive
gets first oxidized at the anode, allowing the formation of acyloxytriphenylphosphonium ions (2),
which are simultaneously reduced at the cathode to triphenylphosphine oxide (3) and aldehyde
(Scheme 32.2) [23]. With keto acids and tributylphosphine (Bu3P) as substrates, the corresponding
α-hydroxycycloalkanones are produced in good yield [24].
Anode Cathode
+
+ RCOOH Ph3P O
Ph3P O
–e– 2 R
–e– –H+
+e–
Ph3P
1 O
Ph3P = O +
R
3
+e–
O +H+ O
R – R
H
SchEME 32.2 Triphenylphosphine (1) additive allows the selective reduction of carboxylic acids to
a ldehydes. (From Maeda, H. et al., Tetrahedron Lett., 33, 1347, 1992.)
Reductions of Carboxylic Acids and Derivatives 1251
OH
CO2H
Pb cathode
H2O/NH4OH/(NH4)2CO3
80%
CO2H CO2H
4 5
SchEME 32

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Organic Chemistry Hammerich

“Outstanding praise for previous editions…the single best general reference

Highlights from the Fifth Edition:

• Coverage of the electrochemistry of buckminsterfullerene and related

Completely revised and updated, Organic Electrochemistry, Fifth

Boca Raton London New York

CRC Press is an imprint of the

No claim to original U.S. Government works

International Standard Book Number-13: 978-1-4200-8402-3 (eBook - PDF)

SECTION I Fundamentals and Methods

Chapter 1 Basic Concepts ............................................................................................................. 3

Chapter 2 Techniques for Studies of Electrochemical Reactions in Solution.............................97

Chapter 3 In Situ Spectroelectrochemistry of Organic Compounds ........................................ 169

Chapter 4 Surface Techniques .................................................................................................. 191

Chapter 5 Application of Digital Simulation ............................................................................ 205

Chapter 6 Theoretical Calculation of Reduction Potentials...................................................... 229

SECTION II General Preparative Aspects

Chapter 7 Preparative Electrolysis on the Laboratory Scale .................................................... 263

Chapter 9 Combinatorial Electrochemistry and Miniaturization ............................................. 345

Chapter 10 Relations between Micro- and Macrophenomena.................................................... 371

SECTION III Electron Transfers and Concerted Processes

Chapter 12 Electrochemically Driven Supramolecular Devices ................................................ 433

Chapter 13 Proton-Coupled Electron Transfers .......................................................................... 481

Chapter 14 Dissociative Electron Transfers ................................................................................ 511

Chapter 15 Electron Transfer–Catalyzed Reactions ................................................................... 531

SECTION IV Organic Electrochemical Reaction Types

Chapter 16 Cleavages and Deprotections ................................................................................... 559

Chapter 17 Reductive Coupling .................................................................................................. 621

Chapter 18 Oxidative Coupling .................................................................................................. 705

Chapter 19 Oxidative Substitution and Addition Reactions ....................................................... 775

Chapter 20 Fluorination ..............................................................................................................807

SECTION V Electrochemical Conversions of Organic Compounds

Chapter 22 Aliphatic and Aromatic Hydrocarbons: Reduction .................................................. 861

Chapter 23 Oxidation of Hydrocarbons ...................................................................................... 891

Chapter 24 Activation of the Carbon–Halogen Bond ................................................................. 917

Chapter 25 Aliphatic and Aromatic Halides: Conversions ......................................................... 941

Chapter 26 Oxygen-Containing Compounds: Alcohols, Ethers, and Phenols ........................... 981

Chapter 27 Sulfur-, Selenium-, and Tellurium-Containing Compounds .................................. 1035

Chapter 28 Aliphatic Nitrogen–Containing Compounds: Amines, Amino Alcohols,

Chapter 29 Aromatic Nitrogen–Containing Compounds ..........................................................1121

Chapter 30 Reduction of Nitro Compounds and Related Substrates .........................................1149

Chapter 31 Reduction of Aldehydes, Ketones, and Azomethines ............................................ 1201

Chapter 32 Reductions of Carboxylic Acids and Derivatives................................................... 1249

Chapter 33 Oxidation of Carboxylic Acids and Derivatives .................................................... 1267

Chapter 34 Heterocyclic Compounds ....................................................................................... 1309

Chapter 35 Organoelemental Compounds ................................................................................ 1357

Chapter 36 Organometallic Compounds as Tools in Organic Electrosynthesis ....................... 1393

SECTION VI Stereochemical and Biological Aspects

Chapter 38 Stereochemistry of Organic Electrode Processes .................................................. 1461

Chapter 39 Electroenzymatic Synthesis ....................................................................................1511

Chapter 40 Electrochemical Modeling of Biological Processes ............................................... 1543

SECTION VII Surface Confined Systems

Chapter 42 Surface-Bound and Immobilized Molecules ......................................................... 1605

SECTION VIII Special Applications

Chapter 44 Electrocatalytic Hydrogenation .............................................................................. 1657

Index ............................................................................................................................................ 1673

• Chapter 3: In Situ Spectroelectrochemistry of Organic Compounds by Peter Rapta, Evgenia

• Chapter 24: Activation of the Carbon-Halogen Bond by Armando Gennaro, Abdirisak

• Old Chapter 4: Comparison Between Electrochemical Reactions and Chemical Oxidations

Fructuoso Barba Cyrille Costentin

Lourdes E. Echegoyen Junming Ho

William E. Geiger Anny Jutand

R. Daniel Little Osamu Onomura

SECTION V Electrochemical Conversions of Organic Compounds

α1O1 + α 2O2 + + ne β1R1 + β2 R 2 +

NA Aff Rgas ∆G 0R, rel

∆G 0O, rel Ogas + emet 2

RCO2H + H 2O RCO2 − + H3O + (Ka ) (1.29)

Ag + + 2NH 3 Ag(NH 3 )+ + NH 3 Ag(NH 3 )2 + (1.36)

6. Relationships between Thermodynamic Driving Force ΔE0

α1O1 + β2 R 2 β1R1 + α 2O2 (1.37)

α1O1 + β2 R 2 β1R1 + α 2O2 → (1.40)