01/12/2023, 15:08 TEMPO

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Chemicals >> Oxidizing Agents

TEMPO, 2,2,6,6-Tetramethylpiperidinyloxy

2,2,6,6-Tetramethylpiperidinyloxy is a stable nitroxyl radical, which serves in oxidations as catalyst. By

substitution in position 4 (4-hydroxy-TEMPO, 4-acetamido-TEMPO) its reactivity can be steered.

For example, processes with oxygen and 5 mol-% TEMPO permit environmentally benign reactions as
alternatives to some oxidations, where so far e.g. chrome reagents were used.

Proposed mechanism for the oxidation of primary alcohols under basic conditions
M. Angelin, M. Hermansson, H. Dong, O. Ramström, Eur. J. Org. Chem., 2006, 4323-4326.

2-Azaadamantane N-Oxyl (AZADO), 9-Azabicyclo[3.3.1]nonane N-Oxyl (ABNO), 9-Azanoradamantane N-oxy

(Nor-AZADO) form a less hindered class of nitroxyl radicals and exhibit an enhanced reactivity compared with
TEMPO.

Recent Literature

Sodium hypochlorite pentahydrate crystals with very low NaOH and NaCl contents oxidize primary and
secondary alcohols to the corresponding aldehydes and ketones in the presence of TEMPO/Bu4NHSO4
without pH adjustment. This new oxidation method is also applicable to sterically hindered secondary
alcohols.
T. Okada, T. Asawa, Y. Sugiyama, M. Kirihara, T. Iwai, Y. Kimura, Synlett, 2014, 25, 596-598.

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Oxidation of primary and secondary alcohols, using catalytic amounts of TEMPO and tetra-n-butylammonium
bromide in combination with periodic acid and wet alumina in dichloromethane is compatible with a broad
range of functional groups and acid-sensitive protecting groups. The system also enables a chemoselective
oxidation of secondary alcohols in the presence of primary alcohols.
M. Attoui, J.-M. Vatèle, Synlett, 2014, 25, 2923-2927.

A convenient method enables the preparation of a silica gel supported TEMPO catalyst. The catalyst prepare
from [4-hydroxy-TEMPO + NaCl]/SiO2 was used for an aerobic oxidation of alcohols to carbonyls under mild
reaction conditions in the presence of Fe(NO3)3 • 9 H2O. Alcohols were converted to the corresponding
carbonyls in good to excellent yields. After a simple filtration, the catalyst can be reused at least six times.
N. Tamura, T. Aoyama, T. Takido, M. Kodomari, Synlett, 2012, 23, 1397-1407.

A rapid oxidation of primary and secondary alcohols using catalytic amounts of TEMPO and Yb(OTf)3 in
combination with a stoichiometric amount of iodosylbenzene afforded carbonyl compounds in excellent yields
without over-oxidation. Oxidation of primary alcohols in the presence of secondary alcohols proceeded with
good selectivity.
J.-M. Vatèle, Synlett, 2006, 2055-2058.

An aerobic oxidation of primary and secondary alcohols to aldehydes and ketones using TEMPO-CuCl as
catalyst in the ionic liquid [bmin][PF6] has been developed. The system needs no bubbling of O2 due to its
good solubility in the ionic liquid. The resulting aldehydes (with no traces of carboxylic acids) and ketones can
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be extracted with organic solvents. The ionic liquid can be reused after washing with water and drying under
high vacuum (8 runs for the oxidation of benzyl alcohol: yields of 72%, 70, 68, 70, 65, 64, 62, and 60).
I. A. Ansari, R. Gree, Org. Lett., 2001, 1507-1509.

A highly efficient 2,2,6,6-tetramethylpiperidin-1-yloxy (TEMPO) catalyzed reaction using recyclable 1-chloro-

1,2-benziodoxol-3(1H)-one as the terminal oxidant allows the conversion of various alcohols to their
corresponding carbonyl compounds in high to excellent yields at room temperature in ethyl acetate, which is
an environmentally friendly organic solvent.
X.-Q. Li, C. Zhang, Synthesis, 2009, 1163-1169.

The combination of TEMPO and CAN can be used for the aerobic oxidation of benzylic and allylic alcohols
into their corresponding carbonyl compounds. However, steric hindrance has been observed to impede the
reaction with some substituted allylic systems. The present method is superior to others currently available
due to its relatively short reaction times and excellent yields.
S. S. Kim, H. C. Jung, Synthesis, 2003, 2135-2137.

The reaction of KBrO3 and NH2OH • HCl in situ generates NOx and Br anion, which allows in the presence o
2,2,6,6-tetramethylpiperidine-N-oxide (TEMPO) an activation of dioxygen to oxidize various benzylic alcohols
quantitatively to their corresponding carbonyl compounds under mild conditions.
G. Yang, W. Wang, W. Zhu, C. An, X. Gao, M. Song, Synlett, 2010, 437-440.

TEMPO-derived reagents tagged with multiple perfluoroalkyl chains and triazole moieties promote the
oxidation of alcohols to aldehydes in organic solvent/water mixtures with reaction rates comparable to
homogeneous TEMPO reagents, but can be easily recovered by liquid/emulsion filtration.
A. Gheorghe, T. Chinnusamy, E. Cuevas-Yañez, P. Hilgers, O. Reiser, Org. Lett., 2008, 10, 4171-4174.

A. Gheorghe, T. Chinnusamy, E. Cuevas-Yañez, P. Hilgers, O. Reiser, Org. Lett., 2008, 10, 4171-4174.

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Silica-supported TEMPO is easily obtained in a one-step reductive amination procedure starting from a
commercially available aminopropyl-functionalized silica. This supported catalyst mediates the Anelli oxidatio
of various alcohols. The recyclability and stability of the applied silica-supported TEMPO have been studied.
T. Fey, H. Fischer, S. Bachmann, K. Albert, C. Bolm, J. Org. Chem., 2001, 66, 8154-8159.

A four-component system consisting of acetamido-TEMPO/Cu(ClO4)2/TMDP/DABCO in DMSO allows an

efficient room-temperature aerobic alcohol oxidation of various alcohols into their corresponding aldehydes o
ketones in good to excellent yields. The catalytic system can be recycled.
N. Jiang, A. J. Ragauskas, J. Org. Chem., 2006, 71, 7087-7090.

The system Cu(ClO4)2/acetamido-TEMPO/DMAP catalyses the room-temperature aerobic oxidation of

primary alcohols to aldehydes in the ionic liquid [bmpy]PF6. The catalysts can be recycled and reused.
N. Jiang, A. J. Ragauskas, Org. Lett., 2005, 7, 3689-3692.

An efficient oxidation of primary alcohols to the corresponding aldehydes can be carried out at room
temperature in DCM, using trichloroisocyanuric acid in the presence of catalytic TEMPO: aliphatic, benzylic,
and allylic alcohols, and β-amino alcohols are rapidly oxidized without no overoxidation to carboxylic acids.
The slow oxidation of secondary carbinols makes the reaction highly chemoselective.
L. De Luca, G. Giacomelli, A. Porcheddu, Org. Lett., 2001, 3, 3041-3043.

A highly efficient and mild procedure for the oxidation of different types of alcohols uses TEMPO as catalyst,
iodobenzene dichloride as stoichiometric oxidant, and pyridine as base. Oxidation of 1,2-diols gives α-hydrox
ketones or α-diketones depending on the amount of oxidant used. High yielding procedures for the
preparation of iodoarene dichlorides have been developed.
X.-F. Zhao, C. Zhang, Synthesis, 2007, 551-557.

A stable nitroxyl radical class of catalysts, 2-azaadamantane N-oxyl (AZADO) and 1-Me-AZADO, exhibit
superior catalytic proficiency to TEMPO, converting various sterically hindered alcohols to the corresponding

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carbonyl compounds in excellent yields.

M. Shibuya, M. Tomizawa, I. Suzuki, Y. Iwabuchi, J. Am. Chem. Soc., 2006, 128, 8412-8413.

A combination of FeCl3, L-valine and TEMPO oxidizes a wide range of primary/secondary benzyl, allylic, and
heterocyclic alcohols to aldehydes and ketones with good to excellent isolated yields in the presence of
oxygen.
G. Zhang, S. Li, J. Lei, G. Zhang, X. Xie, C. Ding, R. Liu, Synlett, 2016, 27, 956-960.

An iron-catalyzed α,β-dehydrogenation of carbonyl compounds converts a broad range of aldehydes,

ketones, lactones, lactams, amines, and alcohols to their α,β-unsaturated counterparts in a simple one-step
reaction with high yields.
X.-W. Zhang, G.-Q. Jiang, S.-H. Lei, X.-H. Shan, J.-P. Qu, Y.-B. Kang, Org. Lett., 2021, 23, 1611-1615.

An eco-friendly and mild aerobic oxidation of allylic alcohols using Fe(NO3)3·9H2O/TEMPO/NaCl as catalysts
under atmospheric pressure of oxygen at room temperature provides a convenient pathway to the synthesis
of stereodefined α,β-unsaturated enals or enones with the retention of the double-bond configuration.
J. Liu, S. Ma, Org. Lett., 2013, 15, 5150-5153.

A method for generating (E)-α,β-unsaturated aldehydes from Z- or E-allylic alcohols involves a Cu-catalyzed
oxidation followed by an organocatalytic Z/E-isomerization with N,N-dimethylaminopyridine (DMAP).
D. Könning, W. Hiller, M. Christmann, Org. Lett., 2012, 14, 5258-5261.

X.-F. Zhao, C. Zhang, Synthesis, 2007, 551-557.

The use of NaClO/TEMPO/Co(OAc)2 enabled a benzylic oxidation of alkyl arenes to yield various aromatic
aldehydes and ketones in very good yields. The reaction reactivity, selectivity, and scope of the reaction were

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investigated.
C. Jin, L. Zhang, W. Su, Synlett, 2011, 1435-1438.

A one-pot two-step sequence involving an oxidation/imine-iminium formation/reduction allowed the N-

alkylation of amines by alcohols. Optically active alcohols and amines can be converted without any
epimerization.
C. Guérin, V. Bellosta, G. Guillamot, J. Cossy, Org. Lett., 2011, 13, 3478-3481.

A sequential one-pot synthesis for the oxidation of primary and secondary tert-butyldimethylsilyl (TBDMS)
ethers, using the presence of PhIO or PhI(OAc)2 and catalytic amounts of metal triflates and TEMPO in THF
or acetonitrile tolerates acid-sensitive protecting groups and leaves tert-butyldiphenylsilyl ethers and phenolic
TBDMS groups untouched.
B. Barnych, J.-M. Vatèle, Synlett, 2011, 2048-2052.

Oxidation from alcohols to carboxylic acids are often conducted using at least a stoichiometric amount of an
expensive and toxic oxidant. An efficient and practical sustainable oxidation technology of alcohols using pure
O2 or even air as the oxidant in the presence of a catalytic amount each of Fe(NO3)3·9H2O/TEMPO/MCl
provides a series of carboxylic acids in high yields at room temperature.
X. Jiang, J. Zhang, S. Ma, J. Am. Chem. Soc., 2016, 138, 8344-8347.

Catalytic amounts of TEMPO and NaOCl enable a chemoselective oxidation of 1,2-diols to in the presence of
NaClO2 as terminal oxidant. The use of a two-phase condition suppresses the concomitant oxidative
cleavage. The observed selectivity seems to be derived from the precise solubility control of diols and hydrox
acids as well as the charge transfer complex TEMPO-ClO2, which dissolves into the organic layer.
K. Furukawa, M. Shibuya, Y. Yamamoto, Org. Lett., 2015, 17, 2282-2285.

A copper(II)-promoted denitrogenation/oxidation reaction of α-azido ketones and TEMPO as an oxidant

provides primary α-ketoamides. α-Azido ketones were denitrogenated in situ to form an imino ketone
intermediate, which underwent a radical addition process and radical migration to form α-ketoamides.
A.-J. Wang, C.-Y. She, Y.-D. Zhang, L.-H. Zhao, W.-M. Shu, W.-C. Yu, J. Org. Chem., 2022, 87, 16099-16105

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In a direct conversion of primary and secondary alcohols into the corresponding α-chloro aldehydes and α-
chloro ketones, trichloroisocyanuric acid serves both as stoichiometric oxidant and α-halogenating reagent.
For primary alcohols, TEMPO has to be added as an oxidation catalyst, and for the transformation of
secondary alcohols MeOH as an additive is essential to promote chlorination of the intermediary ketones.
Y. Jing, C. G. Daniliuc, A. Studer, Org. Lett., 2014, 16, 4932-4935.

In a direct conversion of primary and secondary alcohols into the corresponding α-chloro aldehydes and α-
chloro ketones, trichloroisocyanuric acid serves both as stoichiometric oxidant and α-halogenating reagent.
For primary alcohols, TEMPO has to be added as an oxidation catalyst, and for the transformation of
secondary alcohols MeOH as an additive is essential to promote chlorination of the intermediary ketones.
Y. Jing, C. G. Daniliuc, A. Studer, Org. Lett., 2014, 16, 4932-4935.

An oxidation/imine-iminium formation/reduction cascade using TEMPO-BAIB-HEH-Brønsted acid catalysis in

DMPU as solvent enables a mild and atom-economical nonepimerizing chemo- and enantioselective N-
alkylating procedure of amines with alcohols.
I. A. Khan, A. K. Saxena, J. Org. Chem., 2013, 78, 11656-11669.

A highly regio- and enantioselective hydroxyamination of aldehydes with in situ generated nitrosocarbonyl
compounds from hydroxamic acid derivatives was realized by combining TEMPO and BPO as oxidants in the
presence of a binaphthyl-modified amine catalyst.
T. Kano, F. Shirozu, K. Maruoka, J. Am. Chem. Soc., 2013, 135, 17735-17738.

Various alcohols were efficiently converted into the corresponding nitriles at room temperature by treatment
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with tert-butyl hypochlorite, diiodine, or 1,3-diiodo-5,5-dimethylhydantoin (DIH) in the presence of TEMPO,

followed by treatment with diiodine and aqueous ammonia. The nitriles were obtained in good yields and high
purities by a simple extraction of the reaction mixture with chloroform and subsequent removal of the solvent
H. Shimojo, K. Moriyama, H. Togo, Synthesis, 2013, 45, 2155-2156.

In the presence of a catalytic amount of 4-AcNH-TEMPO, NaNO2, and HNO3, benzaldehydes underwent
condensation with NH4OAc and a subsequent aerobic oxidation to produce nitriles selectively under O2.
Aerobic oxidative conversion of a primary alcohol is also achieved.
J.-H. Noh, J. Kim, J. Org. Chem., 2015, 80, 11624-11628.

Iron-catalyzed aerobic oxidative reactions of primary amines, secondary amines, benzylamines with anilines,
and alcohols with amines in the presence of air as the economic and safe oxidant, provide several direct,
practical, and greener approaches for the preparation of useful imines.
E. Zhang, H. Tian, S. Xu, X. Yu, Q. Xu, Org. Lett., 2013, 15, 2704-2707.

The combination of Fe(III), l-valine, and 4-OH-TEMPO catalyzes an oxidation of alcohols followed by
condensation with sulfinamide or sulfonamide in one pot to provide N-sulfinyl- and N-sulfonyl imines under
mild conditions in very good yields.
G. Zhang, Y. Xing, S. Xu, C. Ring, S. Shan, Synlett, 2018, 29, 1232-1238.

A Cu/TEMPO catalyst system exhibits both excellent reactivity and selectivity for the synthesis of
alkenylboronates from inexpensive alkenes and pinacol diboron. This approach enables a direct
functionalization of both aromatic and aliphatic terminal alkenes.
W. Lu, Z. Shen, Org. Lett., 2019, 21, 142-146.

A wide range of olefins with diverse functionalities has been nitrated in synthetically useful yields in a single
step under metal-free conditions. This transformation is operationally simple and exhibits excellent E-
selectivity. Furthermore, site selective nitration in a complex setup makes this method advantageous.
S. Maity, T. Naveen, U. Sharma, D. Maiti, Org. Lett., 2013, 15, 3384-3387.

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Ferric nitrate with catalytic TEMPO is a useful combination of reagents for regio- and stereoselective nitration
of various aromatic, aliphatic, and heteroaromatic olefins. This mild and operationally simple reaction provide
nitroolefins in preparatively useful yields with excellent E-selectivity.
T. Naveen, S. Maity, U. Sharma, D. Maiti, J. Org. Chem., 2013, 78, 5949-5954.

A Cu-catalyzed oxidative amidation-diketonization reaction of terminal alkynes leads to α-ketoamides. In this

copper-catalyzed radical process, O2 not only participates as the ideal oxidant but also undergoes dioxygen
activation under ambient conditions.
C. Zhang, N. Jiao, J. Am. Chem. Soc., 2010, 132, 28-29.

Passerini three-component reaction under catalytic aerobic conditions allows the conversion of alcohols
instead of aldehydes. The reaction of alcohols, isocyanides, and carboxylic acids in toluene in the presence o
a catalytic amount of cupric chloride, NaNO2, and TEMPO afforded, under an oxygen atmosphere, the P-3CR
adducts in good yields.
J. Brioche, G. Masson, J. Zhu, Org. Lett., 2010, 12, 1432-1435.

α-Oxidation of a variety of carboxylic acids, which preferentially undergo undesired decarboxylation under
radical conditions, proceeded efficiently under optimized conditions via a chemoselective enolization without
stoichiometric amounts of Brønsted base. The formed redox-active heterobimetallic enediolate efficiently
coupled with free radical TEMPO.
T. Tanaka, R. Yazaki, T. Ohshima, J. Am. Chem. Soc., 2020, 142, 4517-4524.

Flexible and chemoselective methods for the transition-metal-free oxidation of amides provide α-keto amides
and α-hydroxy amides. These highly valuable motifs are accessed in good to excellent yields and
stereoselectivities with high functional group tolerance.
A. de la Torre, D. Kaiser, N. Maulide, J. Am. Chem. Soc., 2017, 139, 6578-6581.

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A highly convenient organocatalytic method for the mono-oxidation of unprotected glycosides relies on the
chemoselective properties of TEMPO in combination with trichloroisocyanuric acid under very mild, basic
conditions. The resulting dialdo-glycosides are efficiently purified with the use of solid-phase imine capture.
M. Angelin, M. Hermansson, H. Dong, O. Ramström, Eur. J. Org. Chem., 2006, 4323-4326.

A mild, aerobic, catalytic synthesis of nitriles directly from alcohols and aqueous ammonia proceeds via a
dehydrogenation cascade mediated by catalytic CuI, bpy, and TEMPO in the presence of oxygen. The
substrate scope includes various functionalized aromatic and aliphatic alcohols. This protocol also enabled a
one-pot synthesis of various biaryl heterocycles directly from commercially available alcohols.
W. Yin, C. Wang, H. Huang, Org. Lett., 2013, 15, 1850-1853.

A direct conversion of a wide range of aliphatic, benzylic, heteroaromatic, allylic, and propargyl alcohols into
nitriles with 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO), iodosobenzene diacetate, and ammonium acetate
as a nitrogen source proceeds through an oxidation-imination-aldimine oxidation sequence in situ. Highly
chemoselective ammoxidation of primary alcohols in the presence of secondary alcohols was also achieved.
J.-M. Vatèle, Synlett, 2014, 25, 1275-1278.

An efficient and highly selective method for the oxidative conversion of primary amines to the corresponding
nitriles using trichloroisocyanuric acid in the presence of catalytic TEMPO provides a new entry to the
synthesis of various aliphatic, aromatic and heterocyclic nitriles in excellent yield.
F.-E. Chen, Y.-Y. Kuang, H.-F. Dai, L. Lu, M. Huo, Synthesis, 2003, 2629-2631.

Iodine was compared to other positive halogens as terminal oxidant in chemoselective oxidations of alcohols
using catalytic TEMPO and was shown to be superior in cases of electron-rich and heteroaromatic benzylic
alcohols.
R. A. Miller, R. S. Hoerrner, Org. Lett., 2003, 5, 285-287.

A novel, metal-free oxidation system for the catalytic synthesis of aldehydes and ketones using TEMPO and
quarternary ammonium salt as catalysts and Oxone as oxidant proved especially successful for the synthesis
of ketones. The mild conditions tolerate even sensitive silyl protective groups which can otherwise be cleaved
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in the presence of Oxone.

C. Bolm, A. S. Magnus, J. P. Hildebrand, Org. Lett., 2000, 2, 1173-1175.

C. Bolm, A. S. Magnus, J. P. Hildebrand, Org. Lett., 2000, 2, 1173-1175.

1 mol-% TEMPO and a catalytic amount of 1,3-dibromo-5,5-dimethylhydantoin and NaNO2 is a highly efficien
catalytic system for the aerobic oxidations of benzylic alcohols in water.
R. Liu, C. Dong, X. Liang, X. Wang, X. Hu, J. Org. Chem., 2005, 70, 239-244.

Benzylic ethers are oxidatively cleaved by 4-acetamido-2,2,6,6-tetramethylpiperidine-1-oxoammonium

tetrafluoroborate in wet MeCN at room temperature to give the corresponding aromatic aldehydes and
alcohols in high yield. Primary and secondary alkyl alcohols are further oxidized to give carboxylic acids and
ketones, respectively.
P. P. Pradhan, J. M. Bobbitt, W. F. Bailey, J. Org. Chem., 2009, 74, 9501-9504.

A smooth, organocatalytic one-pot oxidative cleavage of terminal 1,2-diols to one-carbon-unit-shorter

carboxylic acids is catalyzed by 1-Me-AZADO in the presence of a catalytica amount of NaOCl and NaClO2
under mild conditions. A broad range of substrates including carbohydrates and N-protected amino diols were
converted without epimerization.
M. Shibuya, R. Doi, T. Shibuta, S.-i. Uesugi, Y. Iwabuchi, Org. Lett., 2012, 14, 5006-5009.

A copper(II)-catalyzed intermolecular three-component oxyarylation of allenes using arylboronic acids as a

carbon source and TEMPO as an oxygen source proceeded under mild conditions with high regio- and
stereoselectivity and functional group tolerance.
T. Itoh, Y. Shimizu, M. Kanai, Org. Lett., 2014, 16, 2736-2739.

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In situ aerobic dual oxidation with asymmetric organocatalysis enables an enantioselective synthesis of α-
hydrazino aldehydes from alcohols and N-Boc hydrazine instead of the conventional combination of
aldehydes with azodicarboxylates. This reaction tolerates various substituents on the alcohol component and
features excellent enantiocontrol, cheap starting materials, operational simplicity, and scalability.
Z. Cui, D.-M. Du, Org. Lett., 2016, 18, 5616-5619.

Cu/nitroxyl catalysts promote a highly efficient and selective aerobic oxidative lactonization of diols under mild
reaction conditions using ambient air as the oxidant. A Cu/ABNO catalyst system shows excellent reactivity
with symmetrical diols and hindered unsymmetrical diols, whereas a Cu/TEMPO catalyst system displays
excellent chemo- and regioselectivity for the oxidation of less hindered unsymmetrical diols.
X. Xie, S. S. Stahl, J. Am. Chem. Soc., 2015, 137, 3767-3770.

Oxoammonium salts enable a practical and highly efficient oxidative rearrangement of tertiary allylic alcohols
to β-substituted α,β-unsaturated carbonyl compounds. Acyclic substrates as well as medium membered ring
substrates and macrocyclic substrates can be oxidized.
M. Shibuya, M. Tomizawa, Y. Iwabuchi, J. Org. Chem., 2008, 73, 4750-4752.

The use of cheap and innocuous reagents, such as NaClO2, NaOCl, and catalytic amounts of TEMPO
enables an environmentally friendly C(sp3)-H oxidation of piperazines and morpholines to 2,3-
diketopiperazines and 3-morpholinones, respectively. In addition, by using a stoichiometric amount of
TEMPO, 2-alkoxyamino-3-morpholinones can be prepared from morpholine derivatives.
D. Chamorro-Arenas, U. Osorio-Nieto, L. Quintero, L. Hernández-García, F. Sartillo-Piscil, J. Org. Chem.,
2018, 83, 15333-15346.

Microwave-promoted iminyl radical cyclizations can be terminated by trapping with TEMPO, affording
functionalized adducts without using toxic and hazardous reagents. The use of alkynes as radical acceptors

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delivers a range of 2-acylpyrroles in good yields.

Y. Cai, A. Jalan, A. R. Kubosumi, S. L. Castle, Org. Lett., 2015, 17, 488-491.

The use of TEMPO enables a novel, metal-free, and regioselective approach for the synthesis of isoxazolines
or cyclic nitrones substituted with methylene groups via tandem iminoxyl radical-promoted cyclization or
TEMPO-mediated Cope-like elimination, respectively.
F. Chen, X.-L. Yang, Z.-W. Wu, B. Han, J. Org. Chem., 2016, 81, 3042-3050.

The use of 2,2,6,6-tetramethylpiperidine-N-oxyl (TEMPO) as catalyst enables a Machetti-De Sarlo reaction of

nitroalkenes with alkynes/alkenes under sustainable conditions to afford a library of isoxazole/isoxaline
products.
M. Vadivelu, S. Sampath, K. Muthu, K. Karthikeyan, C. Praveen, J. Org. Chem., 2019, 84, 13636-13645.

The combination of gold catalysis and radical chemistry enables the synthesis of 5-oxazole ketones from
internal N-propargylamides in the presence of 4-MeO-TEMPO as an oxidant. The desired 5-oxazole ketones
were provided in good yields with an excellent functional group compatibility under mild conditions.
H. An, S. Mai, Q. Xuan, Y. Zhou, Q. Song, J. Org. Chem., 2019, 84, 401-408.

A simple and efficient cationic Fe(III)/TEMPO-catalyzed oxidative cyclization of aroyl hydrazones in the
presence of oxygen enables the synthesis of 2,5-disubstituted 1,3,4-oxadiazole derivatives in high yields. The
reaction offers a broad scope and good functional-group tolerance.
G. Zhang, Y. Yu, Y. Zhao, X. Xie, C. Ding, Synlett, 2017, 28, 1373-1377.

An operationally simple, regioselective reaction of ketones, aldehydes, or esters with amidines in the
presence of TEMPO and an in situ prepared recyclable iron(II)-complex provides various pyrimidine
derivatives with broad functional group tolerance. The reactions are likely to proceed through a TEMPO
complexation/enamine addition/transient α-occupation/β-TEMPO elimination/cyclization sequence.
X.-Q. Chu, W.-B. Cao, X.-P. Xu, S.-J. Ji, J. Org. Chem., 2017, 82, 1145-1154.

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A Cu-catalyzed and 4-HO-TEMPO-mediated [3 + 3] annulation of commercially available amidines with

saturated ketones enables an efficient and facile synthesis of structurally important pyrimidines via a cascade
reaction of oxidative dehydrogenation/annulation/oxidative aromatization.
J.-L. Zhang, M.-W. Wu, F. Chen, B. Han, J. Org. Chem., 2016, 81, 11994-12000.

Oxidative one-pot sequential reactions of inactivated saturated ketones with electron-deficient enamines
enable an efficient synthesis of 3-acylpyridines and pyridine-3-carboxylates. The reaction involve oxidative
dehydrogenation of the saturated ketone substrate, followed by [3+3] annulation with β-enaminone or β-
enaminoester via a cascade process, including Michael addition, aldol type condensation, and oxidative
aromatization.
G. Chen, Z. Wang, X. Zhang, X. Fan, J. Org. Chem., 2017, 82, 11230-11237.

An efficient oxidative protocol enables the synthesis of multisubstituted or fused tetracyclic benzimidazoles vi
a metal-free oxidative C-N coupling between the sp3 C-H and free N-H of readily available N1-benzyl/alkyl-
1,2-phenylenediamines in the presence of oxygen and TEMPO.
D. Xue, Y.-Q. Long, J. Org. Chem., 2014, 79, 4727-4734.

A visible-light-driven, intramolecular C(sp2)-H thiolation without addition of a photosensitizer, metal catalyst, o

base induces the cyclization of thiobenzanilides to benzothiazoles. The substrate undergoes a reverse
hydrogen-atom transfer (RHAT) in its excited state with TEMPO to form a sulfur radical, which adds to the
benzene ring followed by a rearomatization via RHAT.
Z.-M. Xu, H.-X. Li, D. J. Young, D.-L. Zhu, H.-Y. Li, J.-P. Lang, Org. Lett., 2019, 21, 237-241.

A one-pot method enables the synthesis of multisubstituted indolizines from α-halo carbonyl compounds,
pyridines, and electron-deficient alkenes via oxidative dehydrogenation under transition-metal-free conditions
using TEMPO as an oxidant. This protocol uses readily available starting materials in a convenient procedure
under mild reaction conditions.
F. Shi, Y. Zhang, Z. Lu, X. Zhu, W. Kan, X. Wang, H. Hu, Synthesis, 2016, 48, 413-420.
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A TEMPO oxoammonium salt mediates a metal-free oxidative dearomatization of indoles with aromatic
ketones in the presence of H2SO4 to provide 2,2-disubstituted indolin-3-ones in good yields. The
dearomatization proceeds smoothly and displays a broad substrate scope with respect to both indoles and
aromatic ketones.
J. Liu, J. Huang, K. Jia, T. Du, C. Zhao, R. Zhu, X. Liu, Synthesis, 2020, 52, 763-768.

CuCl/DABCO/4-HO-TEMPO as the catalysts and oxygen as the terminal oxidant enabled an efficient aerobic
oxidative synthesis of 2-substituted quinazolines and 4H-3,1-benzoxazines from the one-pot reaction of
aldehydes with 2-aminobenzylamines and 2-aminobenzyl alcohols, respectively.
B. Han, X.-L. Yang, C. Wang, Y.-W. Bai, T.-C. Pan, X. Chen, W. Yu, J. Org. Chem., 2012, 77, 1136-1142.

An efficient copper-catalyzed cascade reaction of (2-aminophenyl)methanols with aldehydes using the

combination of cerium nitrate hexahydrate and ammonium chloride leads to a wide range of 2-substituted
quinazolines in good yields. The method tolerates a various functional groups and represents a convenient
and practical strategy for synthesis of 2-substituted quinazoline derivatives.
Z. Chen, J. Chen, M. Liu, J. Ding, W. Gao, X. Huang, H. Wu, J. Org. Chem., 2013, 78, 11342-11348.

A fast and simple reaction of amidines gave benzimidazoles via iodine(III)-promoted oxidative C(sp3)-C(sp2)
bond formation in nonpolar solvents, whereas the use of polar solvents favoured a C(sp2)-N bond formation t
yield quinazolines. Further selective synthesis of quinazolines in polar solvent was realized using TEMPO as
catalyst and K2S2O8 as the oxidant. No metal, base, or other additives were needed.
J.-P. Lin, F.-H. Zhang, Y.-Q. Long, Org. Lett., 2014, 16, 2822-2825.

A one-pot dehydrogenative Povarov/oxidation tandem reaction of N-alkyl anilines with mono- and 1,2-
disubstituted aryl and alkyl olefins enables the synthesis of a various substituted quinolines. The simple
protocol uses cheap and benign iron(III)chloride as the Lewis acid catalyst and a TEMPO oxoammonium salt
as a nontoxic, mild, efficient oxidant.
H. Richter, O. G. Mancheño, Org. Lett., 2011, 13, 6066-6069.

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Using TEMPO as the oxidant and KOtBu as the base enables a metal-free, a simple and direct access to a
broad range of 2-arylquinolin-4(1H)-ones from readily available N-arylmethyl-2-aminophenylketones via
oxidative intramolecular Mannich reaction.
W. Hu, J.-P. Lin, L.-R. Song, Y.-Q. Long, Org. Lett., 2015, 17, 1268-1271.

Cross coupling of ortho-substituted aryl Grignard reagents with alkynyl Grignard reagents can be performed
without adding any transition metal in the presence of 2,2,6,6-tetramethylpiperidine-N-oxyl radical (TEMPO)
as an environmentally benign organic oxidant. Importantly, functional groups such as esters, amides, and
cyanides are tolerated.
M. S. Maji, S. Murarka, A. Studer, Org. Lett., 2010, 12, 3878-3881.

A method for aliphatic C-H bond oxidation of oximes and hydrazones mediated by 2,2,6,6-
tetramethylpiperidin-1-oxyl (TEMPO) enables the concise assembly of substituted isoxazole and pyrazole
skeletons.
X. Zu, Y.-F. Wang, W. Ren, F.-L. Zhang, S. Chiba, Org. Lett., 2013, 15, 3214-3214.

An easily prepared recyclable TEMPO derived sulfonic salt catalyst, and mineral acids (NaNO2 and HCl)
enable a selective aerobic oxidation of structurally diverse benzylic sp3 C-H bonds of ethers and alkylarenes
to provide synthetically and biologically valued isochromanones and xanthones in good yields.
Z. Zhang, Y. Gao, Y. Liu, J. Li, H. Xie, H. Li, W. Wang, Org. Lett., 2015, 17, 5492-5495.

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