White Paper In Situ Reaction Profiling

A Literature Review
Author: Alan Rein, Ph.D., METTLER TOLEDO

Understanding the kinetics and mechanisms of the individual reactions in a new synthetic
route is often required in order to advance novel chemistry. Scientists in academic and
industrial laboratories working on synthesizing new chemical entities use in situ FTIR
spectroscopy to more effectively obtain reaction rate information and to deduce reaction
mechanisms. This is well evidenced by the thousands of articles and citations published
over the past three decades that referenced the use of in situ FTIR spectroscopy for synthesis
research in various fields of chemistry. In this white paper, we will review some of the more
recent research that utilized this powerful technique to better understand chemical synthesis.

Contents
1 In Situ FTIR Analysis in Academic Research & Teaching
2 About this Literature Review
3 Polymerization Reactions
4 Catalyzed Reactions
5 Organic Synthesis
6 Inorganic/Organometallic Synthesis
 1 The Role of In Situ FTIR Spectroscopy
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in Academic Research and Teaching

Researchers and educators find in situ spectroscopy particularly useful for supporting improved understanding
of molecular structure, chemical synthesis, reaction mechanisms, and reaction kinetics for several over-arching
reasons:
• By eliminating the need to remove samples for analysis, in situ FTIR spectroscopy provides information on
key reaction species, including transient intermediates, under actual reaction conditions.
• In situ FTIR spectroscopy provides data-rich information to yield reaction rate information and kinetics more
quickly, easily, and accurately than classic, offline analytical methods.
• Mid-IR spectroscopy provides fundamental vibrational band assignments that provide specific information
on molecule structure, adding to the overall understanding of the reaction mechanism and pathway.

How In Situ FTIR Spectroscopy Works

absorbance

absorbance
time time

wavenumber wavenumber

The Sensor: In situ sampling
technology places the sensor directly
into the reaction for continuous,
real-time, mid-IR monitoring.
The Measurement: Spectra of
reactants, reagents, intermediates,
products, and byproducts are
continuously collected and presented
in absorbance vs. wavenumber vs.
time plot.
The Peaks: Software automatically
identifies isolated peaks of individual
reaction species. Absorbance vs. time
plots for each of the peaks provide
trends for each reaction species, which
can be used to determine kinetic and
mechanistic information.

A+B C D Temperature

Dosing
absorbance

Product

time
The Trends: Beer’s Law tells us that
absorbance is proportional to
concentration resulting in reaction
profiles which show key reaction
events – for example, initiation,
intermediate formation, and end-point.
time
The Chemistry: By observing how
trend plots for reaction species change
as conditions are varied, scientists can
determine which process parameters
deliver optimized reactions.

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METTLER TOLEDO
 2 About this Literature Review

Review Structure: Color indicates type of chemistry:

The purpose of this literature
Polymerization Reactions
review is to collect and share
Catalyzed Reactions
recent examples where in situ Organic Synthesis
FTIR spectroscopy has provided Inorganic/Organometallic Synthesis
pivotal information that supports
the creation of innovative Overview
chemical syntheses. For full
comprehension of the chemistry
and overall understanding of each Article Excerpt
piece of research, please refer to
the original articles cited herein.

All articles are used with the Article Data

permission of the cited publication.
For further use, contact the
publication directly.
Full citation for further reading

Recurring Themes

ReactIR™ In situ FTIR spectroscopy is widely used in academic research for the fundamental reason that it
enables real-time, in situ measurement of reaction species, under actual reaction conditions. ReactIR eliminates
the problems associated with sample removal for off-line measurements. The implications of this capability are
profound; the literature and breadth of applications reflect these general values:

In Research In Teaching
• Monitor key stages/conditions of a reaction or • Students gain hands-on experience in using
process including reaction start, induction period, spectroscopic data to derive chemical structure,
accumulation, stalling, upsets, steady state, and kinetics, and mechanistic information
endpoint • Supports a safer laboratory environment since
• Identify, track and profile key reactions species: potentially hazardous reactions no longer need to
reactants, reagents, intermediates, products, and be manually sampled for offline analysis
byproducts • Continuous measurement provides a 'molecular
• Detect, identify, and track transient intermediates video' of the reaction for immediate understanding
for mechanism and pathway studies, or to • Students who have experience with inline FTIR
understand the origin of byproducts spectroscopy have a career advantage since both
• Rapidly test the effect of variables on reaction major academic and industrial labs frequently use
performance this technology
• Obtain data-rich information for better and easier
kinetic rate calculations
• Deduce reaction mechanisms based on a more
complete understanding of molecular structure
and reaction rate information
• Measure reactions run in batch or continuous flow
• Handle reactions that are difficult, impossible, or
undesirable to extract samples – low temperature,
elevated/ pressure, viscous, toxic reagents,
highly energetic reactions, air/moisture sensitive
reactants, and reagents

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 3 Polymerization Reactions
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Real-time, in situ FTIR measurement has proven particularly valuable to provide insight into key kinetic,
mechanistic and chemical structure information in polymerization reactions. The technique has broad
applicability for the following reasons:

• Investigate broad range of polymerizations including homogeneous (e.g. free radical and condensation) and
heterogeneous (e.g. emulsion and microemulsion)
• Acquire data for reaction kinetics, monomer conversion rates, reactivity ratios, activation energies, role of
initiators, intermediates, and byproduct formation
• Track individual monomer conversion rates and overall polymer composition in copolymer and
multicomponent polymerizations.
• Understand mechanistic role of catalysts in polymerizations; determine catalyst active species and kinetics
• Monitor and proactively adjust reaction conditions as required to ensure compliance with intended end-
product specifications

To learn more about ReactIR, Reaction Analysis visit

www.mt.com/ReactIR

Featured Articles
1. Hydrocarbon-Soluble Piperazine-Containing Dilithium Anionic Initiator for High Cis-1,4 Isoprene
Polymerization, from the research group of Professor Timothy Long, Virginia Tech
2. Living Anionic Polymerization of 4-Diphenylphosphinostyrene for ABC Triblock Copolymers, from
the research group of Professor Timothy Long, Virginia Tech
3. Effects of Ether on the Cationic Polymerization of Isobutylene Catalyzed by AlCl3, from the
research group of Professor Yangcheng Lu, Tsinghua University
4. Single Component Polymerization of Diisocyanoacetates toward Polyimidazoles, from the research
group of Professor Anjun Qin, South China University of Technology and Professor Ben Zhong Tang,
The Hong Kong University of Science & Technology
5. Kinetic Studies of Copolymerization of Cyclohexene Oxide with CO2 by a Diamino-bis(phenolate)
Chromium(III) Complex, from the research group of Professor Christopher Kozak, Memorial University
of Newfoundland

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Overview
From the research group The synthesis of a novel piperazine-containing difunctional organolithium
of Professor Timothy Long, initiator for the living anionic polymerization of isoprene is described.
Virginia Tech: In situ FTIR tracks both monomer conversion, polymer formation and
reaction rates.

“In situ FTIR spectroscopy monitored the reaction, tracking the vinyl
CH2 out-of-plane wag vibration at 967 cm-1...Vinyl concentration
disappearance over time revealed the quantitative conversion to
the dilithium product within 3 h. In situ FTIR spectroscopy then
monitored sequential isoprene addition with the vinyl CH2 out-of-
plane wag vibration at 912 cm-1...Vinyl consumption occurred within
1.5 h and confirmed the anionic polymerization of isoprene with the
1,4-bis[4-(1-phenyl ethenyl) benzyl] piperazine dilithium initiator...In
situ FTIR spectroscopy studies elucidated the anionic polymerization
kinetics with isoprene and the novel dilithium initiator, and resulted
in a well-defined synthetic method for preparing polyisoprenes with
controlled molecular weights.”
Alison R. Schultz, Sachin
Bobade, Philip J. Scott, and
Timothy E. Long, “Hydrocarbon-
Soluble Piperazine-Containing
Dilithium Anionic Initiator
for High Cis-1,4 Isoprene
Polymerization”, Macromol.
Chem. Phys. 2018, 219,
1700201.

ReactIR tracks disappearance of vinyl group in A) 1,4-Bis[4-(1-phenylethenyl)benzyl]

piperazine (967 cm-1) and B) isoprene (912 cm-1).

Adapted with permission from Alison R. Schultz, Sachin Bobade, Philip J. Scott, and Timothy E. Long, “Hydrocarbon-Soluble Piperazine-
Containing Dilithium Anionic Initiator for High Cis-1,4 Isoprene Polymerization”, Macromol. Chem. Phys. 2018, 219, 1700201. Copyright
2019 John Wiley & Sons, Inc.

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From the research group
of Professor Timothy Long,
Virginia Tech:
Alison R Schultz, Mingtao
Chen, Gregory B Fahs, Robert
B Moore and Timothy E Long,
“Living Anionic Polymerization
of 4-Diphenylphosphinostyrene
for ABC Triblock Copolymers”,
Polym. Int. 2017, 66, 52–58.
Adapted with permission from Alison R Schultz, Mingtao Chen, Gregory B Fahs, Robert B Moore and Timothy E Long, “Living Anionic Po-
lymerization of 4-Diphenylphosphinostyrene for ABC Triblock Copolymers”, Polym. Int. 2017, 66, 52–58. Copyright 2019 John Wiley &
Sons, Inc.
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Overview
The synthesis of poly(S-b-I-b-DPPS) ABC triblock copolymers via living
anionic polymerization of 4-diphenylphosphinostyrene is described. In
situ FTIR tracked sequential monomer propagation, polymer formation
and provided kinetic information.
“In situ FTIR spectroscopy monitored the sequential addition
process, i.e. the vinyl CH2 out-of-plane wag mode for each monomer
(styrene, 908cm-1; isoprene, 912cm-1; DPPS, 918cm-1)… This
enabled real-time insight into the anionic polymerization of DPPS…
Vinyl concentration disappearance as a function of time elucidated
monomer propagation…The styrenic monomers exhibited faster
propagation times in comparison to isoprene, presumably due
to the lower activation energies required for producing the more
delocalized carbanion…Pseudo-first-order kinetic analysis of
monomer concentration (M/M0) versus time (s) provided additional
insight into the polymerization kinetics, revealing a similar observed
rate constant kobs for DPPS compared to styrene and isoprene. In
situ FTIR spectroscopy also defined suitable anionic polymerization
conditions for the synthesis of novel phosphorus-containing ABC
triblock copolymers.”
In the polymerization of poly(S-b-I-b-DPPS), ReactIR tracks the vinyl peak for monomers sty-
rene, 908 cm-1; isoprene, 912 cm-1; DPPS, 918 cm-1
 3
Overview
From the research group of
The interaction between AlCl3 and ether was shown to differ based on the
Professor Yangcheng Lu,
preparation method and also shown to have different mechanistic effects
Tsinghua University:
on isobutylene polymerization. In situ FTIR monitored various initiator
solutions and the effect on the polymerization mechanism.

“…we prepared different initiator solutions containing ether and

AlCl3 by changing the addition sequence of ingredients, studied
the interactions between ether and AlCl3 from the evolution of
the Fourier transform infrared (FTIR) spectra by comparison,
and investigated the catalytic performances of AlCl3 affected by
ether for isobutylene polymerization. We observed that different
preparation methods of initiator solutions could lead to two kinds
of interactions between ether and H2O/AlCl3 in hexane. The strong
interaction could stabilize carbenium ions and seriously decrease the
catalytic performance, whereas the weak interaction could promote
isomerization and proton elimination...a universal mechanism based
on the AlCl3-involved interactions in different solvents was proposed
Shan Zhu, Kai Wang, and
to understand the effects of ether on the cationic polymerization
Yangcheng Lu, “Effects of Ether
catalyzed by AlCl3.”
on the Cationic Polymerization
of Isobutylene Catalyzed by
AlCl3”, ACS Omega 2018, 3,
2033-2039.

Interactions between ether and AlCl3 in initiator solutions for isobutylene polymerization

Adapted with permission from Shan Zhu, Kai Wang, and Yangcheng Lu, “Effects of Ether on the Cationic Polymerization of Isobutylene
Catalyzed by AlCl3”, ACS Omega 2018, 3, 2033-2039.. Copyright 2019 American Chemical Society.

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From the research group of
Professor Anjun Qin, South
China University of Technology
and Professor Ben Zhong Tang,
The Hong Kong University of
Science & Technology:
Tianyu Cheng, Yizhao
Chen, Anjun Qin,and
Ben Zhong Tang, “Single
Component Polymerization
of Diisocyanoacetates
toward Polyimidazoles”,
Macromolecules 2018, 51 (15),
pp 5638–5645.
Overview
Diisocyanoacetates are polymerized to form polyimidazoles via a silver
acetate-catalyzed reaction. In situ FTIR tracked monomer conversion,
polymer formation and reaction completion
“…The stretching vibration of isocyano groups is observed at
2247 cm-1. This characteristic peak, however, disappeared in
the spectrum of PII (polymer), indicating that the isocyano group
of M2 (monomer) has been consumed by the polymerization
reaction. Moreover, the other obvious difference between the
FT-IR spectra of PII and M2 is the peaks at about 1700 cm-1
which belong to the stretching vibration of carbonyl groups. In the
spectrum of M2, only one peak was observed at near 1700 cm-1,
indicating that only one kind of carbonyl group existed. However,
in the spectrum of PII, two peaks were observed. These results
suggest that there are two kinds of carbonyl groups in the polymer
structure…we also used the ReactIR to monitor the IR absorption
peak change of the carbonyl group during the polymerization.
The peak at 1753 cm-1, which belongs to the absorption of
carbonyl group in the monomer, decreases dramatically at the
beginning of the polymerization, indicative of high efficiency
of this polymerization. Meanwhile, the new peak at 1740 cm-1
that belongs to the carbonyl group adjacent to the newly formed
imidazole ring in the polymer chain increases quickly. Those
characteristic peaks become unchanged after 4 h, suggestive of
the completion of reaction…”

ReactIR tracks the monomer (1753 cm-1) and polymer bands (1740 cm-1) as a function of
time, indicating reaction completion at 4 hours.

Adapted with permission from Tianyu Cheng, Yizhao Chen, Anjun Qin,and Ben Zhong Tang, “Single Component Polymerization of Diisocya-
noacetates toward Polyimidazoles”, Macromolecules 2018, 51 (15), pp 5638–5645. Copyright 2019 American Chemical Society.

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From the research group of
Professor Christopher Kozak,
Memorial University of
Newfoundland:
Kaijie Ni and Christopher
M. Kozak, “Kinetic Studies
of Copolymerization of
Cyclohexene Oxide with CO2
by a Diamino-bis(phenolate)
Chromium(III) Complex”, Inorg.
Chem. 2018, 57, 3097-3106.
Adapted with permission from Kaijie Ni and Christopher M. Kozak, “Kinetic Studies of Copolymerization of Cyclohexene Oxide with CO2 by a
Diamino-bis(phenolate) Chromium(III) Complex”, Inorg. Chem. 2018, 57, 3097-3106. Copyright 2019 American Chemical Society.
Overview
A diamino-bis(phenolate) complex of Cr(III) was synthesized and shown to
be highly effective for copolymerizing CO2 and cyclohexene oxide to form
polycarbonate polymers. In situ FTIR provided data to measure cocatalyst
effectiveness and the effect of altering reaction conditions on product and by-
product formation.
“We have developed a series of Cr(III) amino-bis(phenolato)
complexes…, which in the presence of DMAP, PPNCl, or PPNN3 as a
cocatalyst show good to excellent activity toward the copolymerization
of epoxide and CO2…The in situ infrared reaction profiles for the
formation of PCHC (poly(cyclohexene) carbonate) using 1 ((diamino-
bis(phenolate) chromium(III) complex, CrCl(THF)[L], 1, where
[L] = dimethylaminoethylamino-N,N-bis(2-methylene-4,6-tert-
butylphenolate)) with different cocatalysts are shown…The initial rates
calculated from the slope of absorbance vs time for the linear part
showed that ionic cocatalysts were more efficient than DMAP, and
PPNN3 exhibited the fastest rate…Effect of temperature on the formation
of PCHC was monitored by following the νCO of polycarbonate at 1750
cm-1 by in situ infrared spectroscopy…The rate of PCHC formation can
be observed to increase further with increased temperature…When the
temperature increased to 85 °C under the same catalyst loading and
CO2 pressure, a 5-fold increase in initial reaction rate compared to the
reaction at 60 °C was obtained; however, trans-cyclic carbonate was
observed, which was identified by a new absorbance at 1825 cm-1…”
Copolymerization of CO2 and cyclohexene oxide by diamino-bis(phenolate) chromium(III)
complex, CrCl(THF)[L], where [L] = dimethylaminoethylamino-N,N-bis(2-methylene-4,6-
tert-butylphenolate) using DMAP (4-dimethylaminopyridine) as a cocatalyst.
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 4 Catalyzed Reactions
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Kinetics and mechanisms of metal, organo- and enzymatic catalyzed reactions are among the most prolifically
investigated chemistries by in situ FTIR. The technique enables:

• Analysis of homogeneous and heterogeneous catalytic reactions under actual reaction conditions, including
at elevated pressure and temperature
• Detection and identification of key catalytic reaction species including intermediates
• Data-rich experiments that support Reaction Progress Kinetics Analysis (RPKA)
• Insight into metal-ligand bonding and structure
• Rapid development and testing of conditions for optimized reaction performance
• Rapid evaluation of catalyst performance for specific reaction
• Elimination of the introduction of air, moisture, or disturbing reaction resulting from sample extraction for
offline analysis
• Analysis of reactions containing highly reactive, corrosive, or toxic reactants and reagents

To learn more about ReactIR, Reaction Analysis visit

www.mt.com/ReactIR

Featured Articles
6. Kinetic Analysis of Copper(I)/Feringa-Phosphoramidite Catalyzed AlEt3 1,4-Addition to Cyclohex-
2-en-1-one, from the research group of Professor Simon Woodward, University of Nottingham;
Nottingham Trent University, and Key Organics Ltd
7. Efficient and Selective Iron-Complex-Catalyzed Hydroboration of Aldehydes, from the research
group of Professor Jason Hein, University of British Columbia and Professor R. Tom Baker, University
of Ottawa
8. Double Diastereoselective Approach to Chiral syn- and anti-1,3-Diol Analogues through
Consecutive Catalytic Asymmetric Borylations, from the research group of Professor Andrew
Whiting, Durham University
9. Guanidine-Catalyzed Reductive Amination of Carbon Dioxide with Silanes: Switching between
Pathways and Suppressing Catalyst Deactivation, from research groups at University of Leeds,
Universidad Autónoma Metropolitana-Iztapalapa, Imperial College London
10. Iridium-Catalyzed Asymmetric Transfer Hydrogenation of Alkynyl Ketones Using Sodium Formate
and Ethanol as Hydrogen Sources, from the research group of Professors Jian-Hua Xie and Qi-Lin
Zhou, Nankai University

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From the research group of
Professor Simon Woodward,
University of Nottingham;
Nottingham Trent University,
and Key Organics Ltd:
Darren Willcox, Ryan Nouch,
Alexander Kingsbury, David
Robinson, Joe V. Carey, Steve
Brough, and Simon Woodward,
“Kinetic Analysis of Copper(I)/
Feringa-Phosphoramidite
Catalyzed AlEt3 1,4-Addition
to Cyclohex-2-en-1-one”, ACS
Catal. 2017, 7, 6901-6908.
Adapted with permission from Darren Willcox, Ryan Nouch, Alexander Kingsbury, David Robinson, Joe V. Carey, Steve Brough, and Simon
Woodward, “Kinetic Analysis of Copper(I)/Feringa-Phosphoramidite Catalyzed AlEt 3 1,4-Addition to Cyclohex-2-en-1-one”, ACS Catal. 2017,
7, 6901-6908. Copyright 2019 American Chemical Society.
Overview
The kinetics of the reaction of cyclohex-2-en-1-one and AlEt3 catalyzed by
precatalytic Cu(OAc)2 in the presence of the (R,S,S)-Feringa ligand was
undertaken. After hydrolysis of the enolate, the resultant product ketone
had an 88 % ee. In situ FTIR tracked the formation of the adduct and
provided kinetic data on the order of the various reactants.
“ReactIR studies of mixtures of AlEt3 (A) and cyclohex-2-en-1-one
(CX) in Et2O indicate immediate formation of the Lewis acid-
base complex CX·A at -40 °C…Variation of the CX·A stoichiometry
indicates that the 1:1 Lewis acid-base complex CX·A is formed…
[CX·A]0 vs ln k1 plot provided a best-fit slope of 1.0, commensurate
with the enantioselective catalytic reaction being first order in
CX·A…post induction period, the enantioselective catalytic reaction
is best described by a [Cu]1.5 order term… both GC and ReactIR
data gave ligand reaction orders of 0.66 and -2.52 for the separate
ligand acceleration and retardation processes… The only difference
detected between the ReactIR and GC studies was that the greater
data density of the former allowed the detection that the retardation
process fits better to zero-order, rather than first order, kinetics."
ReactIR tracks key reaction species
and provides kinetic information
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Overview
From the research group A novel imine coupled Fe(II) complex, [Fe(N2S2)]2 was synthesized
of Professor Jason Hein, and then used for selective hydroboration catalysis of various aliphatic
University of British Columbia and aromatic aldehydes using pinacolborane (HBpin). In situ FTIR data
and Professor R. Tom Baker, showed that the iron catalyst is activated by reaction with the borane
University of Ottawa: compound.

“…When utilizing the RPKA method to extract information, analysis

of the data is simplified because the difference in initial concentration
of the two components is maintained for each experiment. However,
for hydroboration using Fe precatalyst 1' [Fe(N2S3)], analysis by
ReactIR revealed that in a typical experiment, the rate of consumption
of HBpin was greater than that for the aldehyde. This results in
incomplete reduction of the aldehyde at short reaction times, unless
more than 1 equiv of HBpin is present… we hypothesized that HBpin
was being utilized to activate the initial iron catalyst. … Kinetic
evidence for catalyst activation could be gleaned by carrying out
a series of reductions where aliquots of both aldehyde and HBpin
are added, allowing the reaction to proceed to completion between
each subsequent addition. These experiments revealed several key
Uttam K. Das, Carolyn S. features. First, conversion to product is lowest after the first equimolar
Higman, Bulat Gabidullin, addition of aldehyde and HBpin, and increases in all subsequent
Jason E. Hein, and R. Tom doses. In addition, the rate of reaction appears to increase after the
Baker, “Efficient and Selective first aliquot addition. This is observed from the reaction profile for the
Iron-Complex-Catalyzed concentration of HBpin for a series of sequential additions. These
Hydroboration of Aldehydes”, observations revealed conclusively that the iron catalyst needs to
ACS Catal. 2018, 8, 1076-1081. undergo irreversible activation through reaction with HBpin to form
the active complex. Furthermore, once activated, this catalyst is both
exceptionally active and very long-lived.“

ReactIR measurements indicate that for hydroboration using Fe precatalyst Fe(N2S3), HBpin
(pinacolborane ) was consumed at a greater rate than for the aldehyde. The researchers
proposed that HBpin activates the iron catalyst.

Adapted with permission from Uttam K. Das, Carolyn S. Higman, Bulat Gabidullin, Jason E. Hein, and R. Tom Baker, “Efficient and Selective
Iron-Complex-Catalyzed Hydroboration of Aldehydes”, ACS Catal. 2018, 8, 1076-1081. Copyright 2019 American Chemical Society.

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From the research group of
Professor Andrew Whiting,
Durham University:
Alba Pujol and Andrew Whiting,
“Double Diastereoselective
Approach to Chiral syn- and
anti-1,3-Diol Analogues
through Consecutive Catalytic
Asymmetric Borylations”, J. Org.
Chem. 2017, 82, 14, 7265-
7279.
Adapted with permission from Alba Pujol and Andrew Whiting, “Double Diastereoselective Approach to Chiral syn- and anti-1,3-Diol
Analogues through Consecutive Catalytic Asymmetric Borylations”, J. Org. Chem. 2017, 82, 14, 7265-7279. Copyright 2019 American
Chemical Society.
Overview
1,3-diborylated carboxylate esters with excellent control of the
stereochemistry of the two stereogenic centers was achieved via a second
borylation of the homoallylic boronate carboxylate esters. In situ FTIR
aided by enabling testing/optimizing reaction parameters.
“For the purpose of following the second boryl addition outlined to
the α,β-unsaturated ester of homoallylic boronate ester to give the
diborylated ester…, we examined the use of in situ IR spectroscopy
(ReactIR), providing an opportunity to examine different reaction
parameters, i.e., time, temperature, and ligand effects…it was
observed that the signal corresponding to the B-O stretch (1126
cm-1) decreased smoothly along with the consumption of the α,β-
unsaturated ester 5a (1720 cm-1) and formation of the product 6a
(1734 cm-1) over 3 h…pure product was obtained in a 47% yield;
a result which was comparable to that previously reported for the
first attempt in the case of the 16 h reaction, showing that longer
reaction times were not required for this transformation… it was
clear that the presence of a more bulky, bidentate and chiral (R)-(S)-
Josiphos ligand did not have a significant influence on the reaction
time. However, the initial consumption of B2pin2 was considerably
faster than in the racemic reaction using triphenylphosphine…
Nonetheless, the subsequent reaction proceeded similarly with high
conversion over approximately 3 h, confirming that the homoallylic
boronate carboxylate esters were suitable substrates for the β-boryl
addition reaction, providing access to diborylated ester”
ReactIR tracks the room temperature β-borylation reaction of homoallylic boronate ester
(5a). 6a is the diborylated product
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From research groups
at University of Leeds,
Universidad Autónoma
Metropolitana-Iztapalapa§,
Imperial College London:
Rachel L. Nicholls, James
A. McManus, Christopher
M. Rayner, José A. Morales-
Serna, Andrew J. P. White, and
Bao N. Nguyen, “Guanidine-
Catalyzed Reductive Amination
of Carbon Dioxide with Silanes:
Switching between Pathways
and Suppressing Catalyst
Deactivation”, ACS Catal. 2018,
8, 3678-3687.
Adapted with permission from Rachel L. Nicholls, James A. McManus, Christopher M. Rayner, José A. Morales-Serna, Andrew J. P. White,
and Bao N. Nguyen, “Guanidine-Catalyzed Reductive Amination of Carbon Dioxide with Silanes: Switching between Pathways and Sup-
pressing Catalyst Deactivation”, ACS Catal. 2018, 8, 3678-3687. Copyright 2019 American Chemical Society.
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Overview
Various catalytic pathways are proposed and tested for the guanidine-
catalyzed reductive functionalization of CO2 using silanes, resulting in the
formation of formamides, amines and aminals. FTIR aided in defining the
catalytic pathway.
“A mechanistic investigation into the guanidine catalyzed reductive
amination of CO2, using a combination of 1H, 29Si NMR, FT-IR, MS, and
GC profiling, is reported. Inexpensive and readily available N,N,N',N'-
tetramethylguanidine (TMG) was found to be an equally effective
catalyst compared to more elaborate cyclic guanidines. Different
catalytic pathways to formamide, aminal, and N-methylamine were
identified. A pathway to formamide product 2 dominates at 23 °C.
Increasing the reaction temperature to
60 °C enables a competitive, higher-energy pathway…which requires
direct reduction of CO2 with PhSiH3 to formoxysilane… Reduction of
aminal in the presence of CO2 and the catalyst, led to formation of a
1:1 ratio of 2 and 3. The catalyst itself can be formylated under the
reaction conditions, resulting in its deactivation. Thus, alkylated TMGs
were found to be more stable and more active catalysts than TMG,
leading to a successful organocatalyzed reductive functionalization of
CO2 with silane...
FT-IR analysis of the reaction between 1, CO2 and PhSiH3 (1.0 equiv)
at 23 °C showed formation of a silylcarbamate species (1698 cm-1,
1242 cm-1) in the first 10 min. This signal quickly disappeared
once TMG (5 mol %) was introduced…This led to the formation
of formamide 2 (1678 cm-1) within 120 min in 98% yield…The
silylcarbamate signal was assigned to Mor-D.”
ReactIR tracks the reaction of morpholine (1) with CO2 and PhSiH3. A silylcarbamate
species forms and then disappears when TMG is added, resulting in the formation of a
formamide.
 10
From the research group of
Professors Jian-Hua Xie and
Qi-Lin Zhou, Nankai University:
Yang-Ming Zhang, Ming-Lei
Yuan, Wei-Peng Liu, Jian-Hua
Xie, and Qi-Lin Zhou, “Iridium-
Catalyzed Asymmetric Transfer
Hydrogenation of Alkynyl
Ketones Using Sodium Formate
and Ethanol as Hydrogen
Sources”, Org. Lett. 2018, 20,
4486-4489.
Adapted with permission from Yang-Ming Zhang, Ming-Lei Yuan, Wei-Peng Liu, Jian-Hua Xie, and Qi-Lin Zhou, “Iridium-Catalyzed Asym-
metric Transfer Hydrogenation of Alkynyl Ketones Using Sodium Formate and Ethanol as Hydrogen Sources”, Org. Lett. 2018, 20, 4486-
4489. Copyright 2019 American Chemical Society.
Overview
The hydrogenation of alkynyl ketones to chiral propargylic alcohols via
a chiral spiro iridium catalyst and using sodium formate and ethanol
as the hydrogen sources is reported. In situ FTIR is used to track the
hydrogenation and revealed the hydride and proton sources.
“The asymmetric transfer hydrogenation of an alkynyl ketone (2d)
with HCO2Cs was tracked by in situ IR spectroscopy. We found that
the HCO2Cs was converted to cesium ethyl carbonate (EtOCO2Cs)
after providing hydrogen. In the reaction of 2d (1704 cm-1) with
1.2 equiv. of HCO2Cs (1602 cm-1) catalyzed by (S)-1b (chiral spiro
iridium catalyst), the peaks at 1704 (peak for 2d) and 1602 cm-1
decreased rapidly at the first stage and a new peak at 1640 cm-1,
which belongs to EtOCO2Cs, increased. After reaction for 3 h, the
peaks at 1704 and 1602 cm-1 disappeared, and the peak at 1640
cm-1 was a single major peak in the spectrum. In addition, no
obvious peak at 1743 cm-1, which belongs to ethyl acetate, was
observed in the reaction. These results indicate that the formate salt
and EtOH served as the hydride and proton sources, respectively, in
the reaction…"
ReactIR tracks the asymmetric hydrogenation of an alkynyl ketone (compound 2d in
illustration)
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METTLER TOLEDO
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 5 Organic Synthesis
White Paper

The variety and scope of reactions investigated by in situ FTIR spectroscopy straddles the range of classic
organic chemistry. The ability to obtain information on chemistry in real-time and without the need to remove
samples for offline measurement has proven very useful, both for batch and continuous flow chemistries.

• Track reactants, reagents, intermediates, products and by-products without disturbing reaction equilibrium
• Monitor key stages/conditions of a reaction or process including reaction start, induction period,
accumulation, stalling, upsets, steady state, endpoint
• Detect and identify reaction transient intermediates
• Obtain data-rich information for better kinetic rate calculations including Reaction Progress Kinetics Analysis
(RPKA)
• Handle reactions that are difficult, impossible or undesirable to extract samples – low temperature, high
temperature/pressure, viscous, toxic reagents, highly energetic reactions, air/moisture sensitive
• Rapidly test the effect of variables on reaction performance
• Safely analyze reactions that contain toxic chemicals or are highly energetic

To learn more about ReactIR, Reaction Analysis visit

www.mt.com/ReactIR

Featured Articles
11. Radical C-H Fluorination Using Unprotected Amino Acids as Radical Precursors, from the research
group of Professor Ryan Baxter, U.C. Merced
12. Favorskii-Type Rearrangement of the 4,5-Epoxymorphinan Skeleton, from the research group of
Professors Ken-ichi Tominaga, National Institute of Advanced Industrial Science and Technology, and
Hiroshi Nagase, University of Tsukuba
13. Metal-Free Synthesis of Unsymmetrical Ureas and Carbamates from CO2 and Amines via
Isocyanate Intermediates, from the research group of Professor Sophie Rousseaux, University of
Toronto
14. General Procedures for the Lithiation/Trapping of N‑Boc Piperazines, from the research group of
Professor Peter O’Brien, University of York
15. Metal-Free C-H Functionalization of Alkanes by Aryldiazoacetates, from the research group of
Professor Huw M. L. Davies, Emory University:

16 White Paper
METTLER TOLEDO
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Overview
From the research group of Using a silver catalyst and Selectfluor to generate aminoalkyl radicals
Professor Ryan Baxter, U.C. from unprotected amino acids, benzylic C-H fluorination is accomplished
Merced: via a radical process. In situ FTIR provided evidence for reaction
mechanism.

“Based simply on the analysis of reduction potentials, Selectfluor

should not be capable of generating Ag(II) from Ag(I)via single
electron transfer. To provide spectroscopic evidence for the formation
of Ag(III)-F, we studied the radical fluorination of substrate 10
by in situ ReactIR. We were surprised to find that no significant
change in Selectfluor concentration was observed when exposed to
stoichiometric AgNO3. Upon the addition of glycine to this reaction
mixture, a rapid decrease in Selectfluor concentration was observed,
suggesting that glycine plays an important role in the reaction
between Ag(I) and Selectfluor…This result led us to reconsider the
possibility of a Ag(I)/Ag(II) catalyst cycle for decarboxylation of
unprotected amino acids with Selectfluor.”
Alyssa M. Hua, Duy N. Mai,
Ramon Martinez, and Ryan D.
Baxter “Radical C-H Fluorination
Using Unprotected Amino Acids
as Radical Precursors”, Org.
Lett., 2017, 19 (11), pp 2949–
2952.

ReactIR tracks Selectfluor concentration in benzylic fluorination reaction

Adapted with permission from Alyssa M. Hua, Duy N. Mai, Ramon Martinez, and Ryan D. Baxter “Radical C-H Fluorination Using Unpro-
tected Amino Acids as Radical Precursors”, Org. Lett., 2017, 19 (11), pp 2949–2952. Copyright 2019 American Chemical Society.

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METTLER TOLEDO
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White Paper
12
From the research group
of Professors Ken-ichi
Tominaga, National Institute of
Advanced Industrial Science
and Technology, and Hiroshi
Nagase, University of Tsukuba:
Noriki Kutsumura, Yasuaki
Koyama, Yuko Suzuki, Ken-ichi
Tominaga, Naoshi Yamamoto,
Tsuyoshi Saitoh, Yasuyuki
Nagumo, and Hiroshi Nagase,
“Favorskii-Type Rearrangement
of the 4,5-Epoxymorphinan
Skeleton”, Org. Lett. 2018, 20,
1559-1562.
Adapted with permission from Noriki Kutsumura, Yasuaki Koyama, Yuko Suzuki, Ken-ichi Tominaga, Naoshi Yamamoto, Tsuyoshi Saitoh,
Yasuyuki Nagumo, and Hiroshi Nagase, “Favorskii-Type Rearrangement of the 4,5-Epoxymorphinan Skeleton”, Org. Lett. 2018, 20, 1559-
1562. Copyright 2019 American Chemical Society.
18 White Paper
METTLER TOLEDO
Overview
7-benzylidene naltrexone compounds were synthesized in high yield via
the aldol condensation of naltrexone. When 2-pyridinecarboxaldehyde
was used as a coupling partner, novel C-ring contracted morphinan
compounds were produced. In situ FTIR provided mechanistic information
and experimental support for DFT calculations.
“…supportive mechanistic information was also gained by using
the time-resolved in situ IR spectroscopy (ReactIR) of the reaction
progress…the methyl ester 3b (1728 cm-1) and the bicyclo[2.2.1]
lactone 10 (1789 cm-1) were produced when piperidine (1.0 equiv)
was added to a solution of 2b (1686 cm-1) in methanol (0.6 M) at
room temperature. Those IR absorption regions of 3b and 10 were
increased over time, whereas the α,β-unsaturated ketone stretch of
2b was decreased. It should be noted that the distinguishing small
peaks (1832, 1848, and 1874 cm-1), which would correspond to the
reported cyclopropanone absorption,10 were always identified during
the reaction. Additionally, we also carried out DFT calculations at
the B3LYP/6-31+G* level of theory for the hypothetical intermediate
D to support the validity of the IR absorption of the cyclopropanone
moiety on the 5-membered C-ring of these morphinan structures…
As a result, the calculations indicated that the estimates of the
carbonyl absorption of the intermediate D ranged from 1833 to
1856 cm-1; that is, the theoretical IR values were close to the actual
measured values. These results support the idea that 2b…was
transformed into the C-ring-contracted morphinans through the
Favorskii-type rearrangement.”
ReactIR supports the hypothesis that compound 2b was transformed via a Favorskii-type
rearrangement
 13
From the research group of
Professor Sophie Rousseaux,
University of Toronto:
Yiming Ren and Sophie A.
L. Rousseaux, “Metal-Free
Synthesis of Unsymmetrical
Ureas and Carbamates from
CO2 and Amines via Isocyanate
Intermediates”, J. Org. Chem.
2018, 83, 913-92.
Adapted with permission from Yiming Ren and Sophie A. L. Rousseaux, “Metal-Free Synthesis of Unsymmetrical Ureas and Carbamates
from CO2 and Amines via Isocyanate Intermediates”, J. Org. Chem. 2018, 83, 913-92. Copyright 2019 American Chemical Society.
Overview
Aryl isocyanates are synthesized from aryl amines under a CO2
atmosphere. Via a dehydration by sulfonium reagent, carbamic acid
intermediate forms the corresponding isocyanate. In situ FTIR tracks
key reaction intermediate and provides insight into optimizing reaction
conditions.
“In situ monitoring by IR spectroscopy clearly demonstrated the
formation of an isocyanate intermediate using both the TFAA and
oxalyl chloride mediated protocols. Upon transferring the solution of
the carbamic acid intermediate to the activated dimethylsulfonium
reagent at low temperature, a signal at 2265 cm-1 corresponding
to phenyl isocyanate appeared. This signal increased in strength
upon addition of Et3N to the reaction mixture, indicating complete
conversion to the isocyanate product. This signal disappeared upon
quenching the reaction with n-butylamine because the isocyanate
intermediate was consumed to generate the unsymmetrical urea.
Under our optimized conditions, a range of aryl and alkyl amines
could be converted to unsymmetrical ureas and carbamates in one
pot, via the isocyanate, by quenching the reactions with amines or
alcohols, respectively.”
ReactIR shows the presence of a band at 2265 cm-1 arising from the phenyl isocyanate
intermediate
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METTLER TOLEDO
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White Paper
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Overview
From the research group Using in situ FTIR spectroscopy to determine optimum lithiation times, two
of Professor Peter O’Brien, procedures were developed for the racemic lithiation/trapping of N-Boc
University of York: piperazines.

“The simplest piperazine lithiation protocol involves the use of …

James D. Firth, Peter O’Brien,
and Leigh Ferris “General
Procedures for the Lithiation/
Trapping of N‑Boc Piperazines”,
J. Org. Chem. 2017, 82, 7023-
7031.
orthogonally protected N-Boc-N-benzyl piperazine (1) and diamine-
free lithiation conditions… To assess the feasibility of such a
system, we employed the use of in situ IR spectroscopy to identify
the time taken for lithiation (by monitoring the change in νC=O). A
solution of 1 in THF at -78 °C showed a νC=O peak at 1696 cm-1.
Upon addition of sBuLi, lithiation of 1 proceeded to give lithiated
intermediate (νC=O peak at 1645 cm-1)… In contrast to our previous
in situ IR spectroscopic studies with s-BuLi/ diamines in Et2O, the
prelithiation species was not detected… in situ IR studies with the
previously reported N-Boc-N'-tert-butyl piperazine 12 showed that
diamine-free lithiation was much slower than with N-Boc-N'-benzyl
piperazine. Upon addition of s-BuLi to 12 in THF at -78 °C (νC=O
1694 cm-1), lithiation proceeded to give lithiated intermediate 13
(νC=O 1645 cm-1). However, after 2 h, the reaction was incomplete.
Conversely, lithiation using s-BuLi/TMEDA in Et2O at -78 °C was
much faster: 12 (νC=O 1700 cm-1) was converted into lithiated
intermediate 15 (νC=O 1644 cm-1) via prelithiation complex 14
(νC=O 1681 cm-1) within 15 min…"

Reaction time differences as a function of complexing agent

Adapted with permission from James D. Firth, Peter O’Brien, and Leigh Ferris “General Procedures for the Lithiation/Trapping of N‑Boc Pi-
perazines”, J. Org. Chem. 2017, 82, 7023-7031. Copyright 2019 American Chemical Society.

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From the research group of
Professor Huw M. L. Davies,
Emory University:
Cecilia Tortoreto, Daniel Rackl,
and Huw M. L. Davies, “Metal-
Free C-H Functionalization of
Alkanes by Aryldiazoacetates”,
Org. Lett. 2017, 19, 770-773.
Adapted with permission from Cecilia Tortoreto, Daniel Rackl, and Huw M. L. Davies, “Metal-Free C-H Functionalization of Alkanes by Aryl-
diazoacetates”, Org. Lett. 2017, 19, 770-773. Copyright 2019 American Chemical Society.
Overview
Carbene intermediates for C-H functionalization are generated by
thermally induced reactions of diazo compounds. In situ FTIR provided the
data to determine relative rates of C-H functionalization.
“In order to obtain further information about the relative rates of
C-H functionalization of cyclohexane, the reactions were followed
by in situ IR monitoring (ReactIR). Figure 1 (see below) compares
the rates of decomposition of the four substrates 1a-d. The signals
for the diazo functionality (at ~2090 cm-1) decreased over time,
following first-order kinetics. As seen previously in the thermal
cyclopropanation of aryldiazoacetates, the p-methoxy derivatives 1c
and 1d are more reactive than the p-bromo derivatives 1a and 1b.
The nature of the ester group also influences the thermal reaction,
as the trichloroethyl derivatives 1b and 1d are about 2 to 3 times
more reactive that the corresponding methyl esters 1a and 1c. Thus,
1c has a half-life of 92 min at 80 °C, whereas 1d has a half-life of
39 min. These results indicate that a significant background thermal
reaction would be a distinct possibility in attempted metal-catalyzed
reactions under extended forcing conditions.”
Reaction scheme and thermal decomposition rates as a function of substituent group from
ReactIR data
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 6 Inorganic/Organometallic Synthesis
White Paper

With the ability to measure chemical species in real time and under actual reaction conditions, in situ FTIR has
proven to be a valuable tool for investigating inorganic and organometallic compounds with respect to bonding,
structure and interaction with ligands.

• Obtain infrared data under experimental conditions including vacuum, elevated pressure, elevated, or low
temperature
• Eliminate experiment contaminants such as air and moisture
• Compact in situ FTIR operates in fume hood, reducing exposure to toxic or hazardous chemicals and gases
• Investigate metal-ligand interactions under varied experimental conditions
• Track association and disassociation of ligands
• From data rich, in situ experiments, get kinetic information such as rate constants; derive heats of enthalpy
and entropy
• Via mid-IR band positions, aid in determining bonding and structure
• Use experimentally measured bond frequencies for comparison/confirmation of DFT calculations

To learn more about ReactIR, Reaction Analysis visit

www.mt.com/ReactIR

Featured Articles
16. Twisting and Tilting 1,1'-Bis(dialkylphosphino)ferrocene Bound to Low Valent
Tricarbonylmaganese(I to -I), from Universität Stuttgart and J. Heyrovský Institute of Physical
Chemistry
17. Kinetics and Mechanism of Isocyanide-Promoted Carbene Insertion into the Aryl Substituent of an
N‑Heterocyclic Carbene Ligand in Ruthenium-Based Metathesis Catalysts, from the research group
of Professor Steven Diver, SUNY, Buffalo
18. Carbon Monoxide Induced Reductive Elimination of Disulfide in an N‑Heterocyclic Carbene (NHC)/
Thiolate Dinitrosyl Iron Complex (DNIC), rom the research group of Professor Marcetta Darensbourg,
Texas A&M University
19. Acrylic Acid Derivatives of Group 8 Metal Carbonyls: A Structural and Kinetic Study, from the
research group of Professor Donald Darensbourg, Texas A&M University
20. Bonding in Complexes of Bis(pentalene)dititanium, Ti2(C8H6)2, from the research group of Professor
Jennifer C. Green, University of Oxford and Professor F. Geoffrey N. Cloke, University of Sussex

22 White Paper
METTLER TOLEDO
 16
Research from Universität
Stuttgart; J. Heyrovský Institute
of Physical Chemistry:
K. Michael Schäfer, Leonie
Reinders, Jan Fiedler, and Mark
R. Ringenberg “Twisting and
Tilting 1,1'-Bis(dialkylphosphino)
ferrocene Bound to Low Valent
Tricarbonylmaganese(I to -I)”,
Inorg. Chem. 2017, 56, 14688-
14696.
Adapted with permission from K. Michael Schäfer, Leonie Reinders, Jan Fiedler, and Mark R. Ringenberg “Twisting and Tilting
1,1'-Bis(dialkylphosphino)ferrocene Bound to Low Valent Tricarbonylmaganese(I to -I)”, Inorg. Chem. 2017, 56, 14688-14696. Copyright
2019 American Chemical Society.
Overview
Two new tricarbonylmanganese complexes are synthesized. In situ
FTIR experiments were used to determine the reaction mechanism and
investigate the Fe→Mn interaction.
“In situ infrared spectroscopy was used to probe the formation of
the Fe→Mn interaction. A solution of 1H, (HMn(CO)3(dppf) where
dppf is 1,1′-bis(diphenylphosphino)ferrocene) in CH2Cl2 was treated
with 1.5 equiv of [(Et2O)2H][B(ArF)4] in CH2Cl2. Upon addition of
the acid, the bands at νCO = 1997 s, 1917 m, and 1904 m shift
to three new signals at νCO = 2037 m, 1979 m, and 1928 m
along with rapid evolution of a gas…The fac-(CO)3 signals were
replaced by new signals at νCO = 2044 w, 1970 sh, 1933 s, which
are the same as from isolated [1][B(ArF)4]. A similar behavior
was also observed when 2H, (HMn(CO)3(dippf) where dippf is
1,1′-bis(diisopropylphosphino)ferrocene) was treated with H[B(ArF)4],
although the reorganization of the open fac-(CO)3 to mer-(CO)3 and
the formation of the Fe→Mn interaction was significantly faster (ca.
5 min).
The mechanism for the formation of the Fe→Mn interaction was
determined by in situ IR measurements which show the formation of
an open coordination site at the tricarbonyl manganese (TCMn) site
followed by the formation of the Fe→Mn interaction. This process
was significantly faster (ca. 5 min) for [2]+ as compared to [1]+
(>24 h)…”
ReactIR measures the reaction of 2H with 1.5 equiv of H[B(ArF)4] as a function of time.
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METTLER TOLEDO
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White Paper
17
From the research group of
Professor Steven Diver, SUNY,
Buffalo:
Justin R. Griffiths, Elan J.
Hofman, Jerome B. Keister,
and Steven T. Diver, “Kinetics
and Mechanism of Isocyanide-
Promoted Carbene Insertion
into the Aryl Substituent of an
N‑Heterocyclic Carbene Ligand
in Ruthenium-Based Metathesis
Catalysts”, Organometallics
2017, 36, 3043-3052.
Adapted with permission from Justin R. Griffiths, Elan J. Hofman, Jerome B. Keister, and Steven T. Diver, “Kinetics and Mechanism of
Isocyanide-Promoted Carbene Insertion into the Aryl Substituent of an N‑Heterocyclic Carbene Ligand in Ruthenium-Based Metathesis
Catalysts”, Organometallics 2017, 36, 3043-3052. Copyright 2019 American Chemical Society.*
24 White Paper
METTLER TOLEDO
Overview
The kinetics of addition of L = alkyl and aryl isocyanides to Ru(H2IMes)
(CHPh)(PCy3)Cl2 (H2IMes = 1,3-dimesityl-4,5-dihydroimidazol-2-ylidene),
to form Ru{1-mesityl-3-(7'-Ph-2',4',6'-trimethylcycloheptatrienyl)-4,5-
dihydroimidazol-2-ylidene}L2(PCy3)Cl2, is investigated by in situ FTIR
spectroscopy.
“In situ IR spectroscopy was used to monitor…NC stretches in
the 2300-1900 cm-1 region…Disappearance of the absorption at
2129 cm-1 due to free isocyanide is accompanied by increases in
absorptions at 2060 and 2005 cm-1 due to the Buchner insertion
product…The isosbestic point at 2124 cm-1 indicates that only
reactants and a single product are present at any time… data
analysis was done at a stoichiometric 2:1 molar ratio of isocyanide
to carbene complex…plots of [CNR]-1 vs time are linear, indicating
that the reaction is second order overall, either first order in [CNR]
and first order in ruthenium carbene or second order in [CNR].
For alkyl isocyanides, the initial bis(isocyanide) intermediate
can be observed. For cyclohexyl isocyanide, the disappearance
of free isocyanide was accompanied by the appearance of two
new absorptions at 2062 and 2100 cm-1, due to the expected
bis(isocyanide) Buchner insertion product. However, this complex
is unstable and, with time, the tris(isocyanide) complex is formed…
absorbances at 2145 cm-1 due to cyclohexyl isocyanide, at 2100
cm-1 due to the bis(isocyanide) Buchner insertion product 7 g,
and at 2185 cm-1 due to the tris(isocyanide) complex 8 g (3:1
isocyanide to Ru molar ratio)…The experimentally determined rate
law is consistent with three mechanisms…we favor…reversible
coordination of one isocyanide, followed by rate-limiting benzylidene
addition to the mesityl group, with fast follow-up steps.”
ReactIR tracks cyclohexyl isocyanide (2145 cm-1), intermediate 7g (2100 cm-1), and prod-
uct 8g (2185 cm-1)
 18
From the research group
of Professor Marcetta
Darensbourg, Texas A&M
University:
Randara Pulukkody, Samuel
J. Kyran, Ryan D. Bethel,
Chung-Hung Hsieh, Michael B.
Hall, Donald J. Darensbourg,
and Marcetta Y. Darensbourg,
“Carbon Monoxide Induced
Reductive Elimination of
Disulfide in an N‑Heterocyclic
Carbene (NHC)/ Thiolate
Dinitrosyl Iron Complex (DNIC)”,
J. Am. Chem. Soc. 2013, 135,
8423-8430.
ReactIR profile of the reaction of complex 1 with carbon monoxide
at 60 °C in toluene
Adapted with permission from Randara Pulukkody, Samuel J. Kyran, Ryan D. Bethel, Chung-Hung Hsieh, Michael B. Hall, Donald J.
Darensbourg, and Marcetta Y. Darensbourg, “Carbon Monoxide Induced Reductive Elimination of Disulfide in an N‑Heterocyclic Carbene
(NHC)/ Thiolate Dinitrosyl Iron Complex (DNIC)”, J. Am. Chem. Soc. 2013, 135, 8423-8430. Copyright 2019 American Chemical Society.*
Overview
Referring to the significance of dinitrosyliron (DNIC) complexes as products
of degradation of iron-sulfur clusters in biological processes, the authors
investigate a {Fe(NO)2}9/{Fe(NO)2}10 reduction that proceeds under mild
conditions and is driven by a thiolate/disulfide oxidation. The mechanism
of this reaction and how CO initiates the disulfide elimination is revealed.
In situ FTIR measurements were carried out to define the kinetics and aid in
understanding the mechanism of the reaction.
“In the presence of CO, the oxidized, paramagnetic {Fe(NO)2}9 (complex
1) converts to the reduced, diamagnetic {Fe(NO)2}10 (complex 2)…
The spectral monitor indicated ν(NO) positions red-shifted by ~15 cm-1
and the appearance of a new CO band at 1986 cm-1, indicating the
formation of the reduced DNIC 2. The byproduct PhSSPh…is generated
by bimolecular reductive elimination from 1…
The rate of conversion of 1 to 2 is amenable to kinetic and mechanistic
studies. This was accomplished via in situ IR spectroscopy of toluene
solutions of 1, saturated with CO and maintained under an atmosphere
of CO…the mole ratio of CO to DNIC in solution is approximately one
to one, but, as the reaction is carried out under a CO atmosphere, the
concentration of CO is constant…the rate was determined to have a
first-order dependence with respect to the iron complex…In order to
establish the order of CO dependence…reaction rates were monitored at
CO pressures of 3.1 and 6.1 atm at 323 K. A plot of the kobs vs [CO]…
is linear with a y-intercept of zero implicating first-order dependence
on the concentration of CO. The complete rate expression is thus
bimolecular with a first-order rate dependence on both complex 1 and
CO…The activation parameters for the formation of complex 2 were
determined through an Eyring analysis and found to have values for
ΔH‡ of 7.80 ± 0.16 kcal/mol and a ΔS‡ of -45.0 ± 0.5 e.u. The ΔG‡ at
298.15 K can be calculated as 21.2 ± 0.2 kcal/mol. The small ΔH‡ and
large negative ΔS‡ values are indicative of an associative mechanism,
consistent with the second order rate expression.”
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METTLER TOLEDO
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White Paper
19
Overview
From the research group of The authors were involved in research to find metal complexes that will
Professor Donald Darensbourg, couple ethylene and CO2 to form an adduct of acrylic acid, and to develop
Texas A&M University a complete catalytic cycle to produce the acrylic acid. In this article, they
investigate the binding and removal of acrylic acid from iron tetracarbonyl
and zero valent ruthenium compounds. In situ FTIR studies reveal the
kinetics of the displacement reactions.

“The kinetic parameters for the displacement of acrylic acid from

(acrylic acid)Ru(CO)4 with triphenylphosphine were determined
using in situ infrared monitoring of the ligand substitution process
with an iC10 ReactIR instrument. Figure A (below) contains a
reaction profile illustrating the disappearance of the parent complex
with the concomitant appearance of the mono- and disubstituted
triphenylphosphine derivatives in CH2Cl2…

Bo Li, Samuel J. Kyran, Andrew
D. Yeung, Ashfaq A. Bengali,
Donald J. Darensbourg, “Acrylic
Acid Derivatives of Group 8
Metal Carbonyls: A Structural
and Kinetic Study”, Inorg. Chem.
2013, 52, 5438-5447.
The slight inhibition noted during the onset of the olefin substitution
process is thought to be due to adduct formation…there is a small
red shift observed in the νCO frequencies upon the addition of PPh3
to a solution of the ruthenium acrylic acid complex…deprotonation of
the (acrylic acid)Ru(CO)4 complex with 1 equiv of piperidine results
in a red shift of the νCO bonds of 15-20 cm-1. This in turn leads to a
significantly enhanced rate of olefin loss concomitantly without the
inhibition step.
We have examined this process in the iron analogue and its ester
derivative, (CH2=CHCOOMe)Fe(CO)4. Upon examining the displacement
of the acrylic acid ligand in (CH2=CHCOOH)Fe(CO)4 by PPh3 some
striking differences from the course of the ruthenium analogue are
noted. As seen in Figure B (below), it is apparent that the inhibition
step is more pronounced in this instance, and importantly, the product
distribution is quite different with the disubstituted phosphine complex
being the dominant product. In addition, the νCO infrared bands for the
PPh3 adduct are red-shifted significantly which allows for monitoring
the decrease in both iron carbonyl species with time…”

A. νCO profiles vs. time for (CH2=CHCOOH)Ru(CO)4 (red), (PPh3)Ru(CO)4 (green), and trans-
(PPh3)2Ru(CO)3 (black). B. νCO profiles vs. time for (CH2=CHCOOH)Fe(CO)4 (red), PPh3Fe(CO)4
(green), trans-(PPh3)2Fe(CO)3 (black), and Fe(CO)4(CH2=CHCOOH)·PPh3 (blue).

Adapted with permission from Bo Li, Samuel J. Kyran, Andrew D. Yeung, Ashfaq A. Bengali, Donald J. Darensbourg, “Acrylic Acid
Derivatives of Group 8 Metal Carbonyls: A Structural and Kinetic Study”, Inorg. Chem. 2013, 52, 5438-5447. Copyright 2019 American
Chemical Society.*

26 White Paper
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From the research group of
Professor Jennifer C. Green,
University of Oxford and
Professor F. Geoffrey N. Cloke,
University of Sussex:
Alexander F. R. Kilpatrick,
Jennifer C. Green, and F.
Geoffrey N. Cloke, “Bonding in
Complexes of Bis(pentalene)
dititanium, Ti2(C8H6)2”,
Organometallics 2015, 34,
4830-4843.
Adapted with permission from Alexander F. R. Kilpatrick, Jennifer C. Green, and F. Geoffrey N. Cloke, “Bonding in Complexes of
Bis(pentalene)dititanium, Ti2(C8H6)2”, Organometallics 2015, 34, 4830-4843. Copyright 2019 American Chemical Society.*
Overview
Bonding in novel double-sandwich compounds of titanium with the
silylated pentalene ligand 1,4-{SiiPr3}2C8H4 (Pn†) was investigated. In situ
FTIR studies were used to study the carbonylation of Ti2Pn†2 under actual
temperature and pressure conditions.
"The carbonylation of Ti2Pn†2 in methylcyclohexane solution at -55 °C
was studied by in situ IR spectroscopy, which showed initial growth of
an IR band at 1992 cm-1 that then decreased in intensity and leveled off
as a ν(CO) stretch at 1910 cm-1 grew in. This lower-energy ν(CO) stretch
became the major IR band at -55 °C once gas addition was complete.
At 26 °C under CO, the intensities of the two bands reversed, with
1992 cm-1 as the major ν(CO) stretching band. Removal of the CO
headspace in vacuo led to near complete removal in the lower-energy
ν(CO) stretch at 1910 cm-1. These results suggest that the band centered
at 1992 cm-1 is due to Ti2Pn†2(CO)2, which is the major product in the
initial stages of reaction and upon warming to 26 °C when CO becomes
less soluble. The IR band at 1910 cm-1 is assigned to the terminal ν(CO)
stretch in Ti2Pn†2(CO)3, which is the major product in solution under
excess CO at -55 °C but diminishes upon exposure to vacuum and
warming to room temperature…”
ReactIR spectra of carbonyl region of Ti2Pn†2 with CO at -55 °C.
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