Table Of ContentNitrones, Nitronates and
Nitroxides
THE CHEMISTRY OF FUNCTIONAL GROUPS
A series of advanced treatises under the general editorship of
Professor Saul Patai
The chemistry of alkenes (2 volumes)
The chemistry of the carbonyl group (2 volumes)
The chemistry of the ether linkage
The chemistry of the amino group
The chemistry of the nitro and nitroso groups (2 parts)
The chemistry of carboxylic acids and esters
The chemistry of the carbon-nitrogen double bond
The chemistry of amides
The chemistry of the cyano group
The chemistry of the hydroxyl group (2 parts)
The chemistry of the azido group
The chemistry of the acyl halides
The chemistry of the carbon-halogen bond (2 parts)
The chemistry of the quinonoid compounds (2 volumes, 4 parts)
The chemistry of the thiol group (2 parts)
The chemistry of the hydrazo, azo and azoxy groups (2 parts)
The chemistry of amidines and imidates
The chemistry of cyanates and their thio derivatives (2 parts)
The chemistry of diazonium and diazo groups (2 parts)
The chemistry of the carbon-carbon triple bond (2 parts)
The chemistry of ketenes, allenes and related compounds (2 parts)
The chemistry of the sulphonium group (2 parts)
Supplement A: The chemistry of double-bonded functional groups (2 parts)
Supplement B: The chemistry of acid derivatives (2 parts)
Supplement C: The chemistry of triple-bonded functional groups (2 parts)
Supplement D: The chemistry of halides, pseudo-halides and azides (2 parts)
Supplement E: The chemistry of ethers, crown ethers, hydroxyl groups
and their sulphur analogues (2 parts)
Supplement F: The chemistry of amino, nitroso and nitro compounds
and their derivatives (2 parts)
The chemistry of the metal-carbon bond (4 volumes)
The chemistry of peroxides
The chemistry of organic selenium and tellurium compounds (2 volumes)
The chemistry of the cyclopropyl group (2 parts)
The chemistry of sulphones and sulphoxides
Updates
The chemistry of a-haloketones, a-haloaldehydes and a-haloimines
Crown ethers (in press)
The formation of carbon-halogen bonds (in press)
Nitrones, nitronates and
n it roxides
BY
ELI BREUER
The Hebrew University of Jerusalem
HANSG UNTERA URICH
Phillips-Universitat Marburg
ARNOLDN IELSEN
Michelson Laboratory, China Lake, Calfornia
Edited by
SAULP ATAI
and
Zvr RAPPOPORT
The Hebrew University of Jerusalem
Updates from the Chemistry of Functional Groups
1989
JOHN WTLEY & SONS
CHICHESTER * NEW YORK BRISBANE * TORONTO . SINGAPORE
An Interscience Publication
r(
Copyright 0 1989 by John Wiley & Sons Ltd
All rights reserved.
No part of this book may be reproduced by any means, or transmitted, or translated into a machine
language without the written permission of the publisher
Library of Congress of Cataloging-in-Publication Data:
Breuer, Eli.
Nitrones, nitronates, and nitroxides/by Eli Breuer, Hans Gunter
Aurich, Arnold Nielsen; edited by Saul Patai and Zvi Rappoport.
p. cm.-(The Chemistry of functional groups)
‘An Interscience publication.’
ISBN 0 471 91709 5
I. Nitroxides. 1. Aurich. Hans Gunter, 1932-
11. Nielsen, Arnold. 111. Title. IV. Series.
QD305.NSB83 1989 88- 17388
546.71 I-dc19 CI P
British Library Cataloguing in Publication Data:
Breuer, Eli
Nitrones. Nitronates and Nitroxides.
(The chemistry of functional groups).
I. Nitroxides. Chemical reactions.
Catalysis
1. Title 11. Aurich, Hans Gunter
111. Nielsen, Arnold IV. Series
546. 711595
ISBN 0 471 91709 5
Typeset by Thomson Press (India) Limited, New Delhi and
Printed in Great Britain by the Bath Press.
List of contributors
H. G. Aurich Fachbereich Chemie, Phillips-Universitat Marburg, Marburg,
FRG.
E. Breuer School of Pharmacy, Faculty of Medicine, The Hebrew Univers-
ity of Jerusalem, Jerusalem 91904, Israel.
A. T. Nielsen Michelson Laboratory, Naval Weapon Center, China I.ake,
California, USA.
V
Contents
1. Nitronic acids and esters I
A. T. Nielsen
Nitrones and nitronic acid derivatives: their structure and their 139
2.
roles in synthesis
E. Breuer
3. Nitrones and nitronic acid derivatives: an update 245
E. Breuer
4. Nitroxides 31 3
H. G. Aurich
Appendix to 'Nitroxides' 371
5.
H. G. Aurich
Author index 401
Subject index 429
vii
Foreword
This is the second volume published in the new series entitled ‘Updates from the Chemistry
of Functional Groups’.
As in the other volumes of this series, our intention is to present selected chapters in the
original form in which they were published, together with an extensive updating of the
subject, if possible by the authors of the original chapters.
The present volume contains the chapter ‘Nitronic acids and esters’ by A. T. Nielsen,
first published in 1969 in The chemistry ofthe nitro and nitroso groups, edited by H. Feuer.
This is followed by the chapter ‘Nitrones and nitronic acid derivatives: their structure and
their roles in synthesis’ by E. Breuer, published originally in Supplement F: The chemistry
ofamino, nitroso and nitro compounds und their derivatives (Ed. S. Patai, 1982). Both the
chapters mentioned above are updated by E. Breuer in Chapter 3 of the present book,
which contains also some sections on material which has not been discussed previously in
the main series.
This is followed by the chapter on ‘Nitroxides’ by H. G. Aurich, originally also
published in Supplement F, and by an ‘Appendix to Nitroxides’ (Chapter 5), again written
by H. G. Aurich.
An additional volume in the same series, now in the press will deal in a similar manner
with crown ethers, based on the original chapters published in 1980 in Supplement E. and
updated to account for the rapid development of this subject. Several other volumes are in
the course of active preparation.
We will be grateful to readers who would call our attention to mistakes and/or
omissions in this and other volumes of the series.
JERUSALEM SAUL PATAl
October 1988 ZVI RAPPOPORT
ix
Nitrones, Nitronates and Nitroxides
Edited by S. Patai and 2.R appoport
@ 1989 John Wiley & Sons Ltd
CHAPTER 1
Nitronic acids and esters
ARNOLD T. NIELSEN
Michelson Laboratory, Naval Weapons Center,
China Lake, California
I. INTRODUCTION. . 2
11. ACI-NITROT AUTOMERIS. M . 4
A. Introduction . 4
B. Tautomerization of Nitronic Acids to Nitroalkanes . . 5
C. Proton Removal from Nitroalkanes . . . 16
D. Ionization Constants of Nitronic Acids and Nitroalkanes . . 24
m.N ITRONICA CIDS . . . . . . . 28
A. Preparation of Nitronic Acids . 28
B. Physical Properties of Nitronic Acids . . 34
C. Reactions of Nitronic Acids . . 36
1. .4ddition reactions of nitronic acids . . . 36
a. Nucleophilic addition . . . . 36
b. Electrophilic addition . . . . 45
2. Oxidation and reduction reactions . . 50
3. Reactions of a-halonitronic acids . . 56
4. Reactions of ketonitronic acids . . 58
IV. NITRONICA CIDE STERS . . 69
A. Preparation of Nitronic Acid Esters . . . 69
1. Acyclic nitronic acid esters . . 69
2. Cyclic nitronic acid esters . . . . 82
B. Physical Properties of Nitronic Acid Esters . . 87
C. Reactions of Nitronic Acid Esters . . . . 89
I. Hydrolysis of nitronic esters . . . . 89
2. Oxidation and reduction reactions of nitronic acid esters . 95
3. 1,J-Dipolar addition reactions of nitronic acid esters . . 105
V. NITRONIAC CIDD ERIVATIVOEST HERT HAENS TERS . . 111
A. Nitronic Acid Salts . . 111
B. Nitronic Acid Anhydrides . . . . 113
C. Nitronic Acid Halides . . . . . . 120
D. Nitronic Acid Amides . . 121
I
2 Arnold T. Nielsen
VI. ANALYITCAL METHODFSO R NITRONIC ACIDS . 122
VII. REFERENCES . . 125
1. INTRODUCTION
The nitronic acids, or aci-nitro compounds, R1R2C;N02H, are an
important group of organic acids. They may be characterized as
rather unstable substances and good oxidizing agents, as are their
esters. Most are relatively weak acids ( pK,lc' 2-6) resembling
carboxylic acids in acid strength. They are somcwhat unique among
organic acids of this strength in that their chemistry is closely linked
with that of a stable tautomeric form, tlie parent nitroalkane. 'The
nitro and aci forms share a common anion. This relationship,
fundamental to nitronic acid chemistry, is illustrated with plienyl-
nitromethane1.2~3T. he equilibria of equation ( 1) illustrate the
phenomenon of aci-nitro tautomerism.
0- OH
'0 0
R.p. looo (8 mrn) M.P. a4O
Phenylnitromethane Phcnylmrthanenitronic acid
Phenylmct1i;rnrnirronnte
Nitro compound Sitronate anion Nitronic acid (mif orm)
The nomenclature of nitronic acids lias often been a matter of
di~cussion4.T~.h e term nitronic acid (nifronsiilue) was introduced by
Bamberger,. However, use of the prefix nci before the nitro com-
pound name, a concept introdLiced by Hantzsch a few years later',
achieved much wider use for many years. Thc general term nci was
taken to mean the tautomeric, more acidic form of a pseudo acid. A
pseudo acid is one whose proton is rcmo\.ed slowly'; a nitroalkane is
a pseudo acid8. The prefix ZJO', and sometimes incorrectly pseudo,
before the nitro compound name to indicate the nitronic acid form
were widely employed for many years (isonitro listings are found in
Chemical Abstracls through 1916).
The nitronic acid naming sj-stem is now more widely acceptcd"lO.
As pointed out originally by Bamberger,, and later by Has5, it
follows more closely the systematic naming of other organic acids and
derivatives. It also clearly recognizes the identity of these substances
as genuine organic acids. The naming of dcri\.ntives such as salts,
esters, and anhydrides follows systematically. 'The nci-nitro term
I. Nitronic Acids and Esters 3
employed only as a prefixl1*l2d oes not readily adapt itself to naming
these derivatives.
The nitronic acid function is =N02H; as a suffix it is called
nitronic acid. If a prefix is required aci-nitro may be used11r12. For
example, butane-2-nitronic acid = 2-aci-nitrobutane. However, the
prefix nomenclature should be avoided with nitronic acids, as it is
with carboxylic acids.
It is suggested that the two possible types of nitronic acids,
RCH=NO,H and R1R2CH=N02H, derived from primary and
secondary nitroalkanes, be designated primary and secondary nitronic
acids, respectively. Some examples of nitronic acid nomenclature
follow.
CH,CH=SO,H Ethanenitronic acid (p~imary)
(CH,I,C~-N O,H Propane-2-nitronic acid (secondury)
rr-C3H,CH=S0,-Naf Sodium butane-1-nitronate
C,H,CH-SO,CH, Methyl phenylmethanenitronate
0
N0,Et Ethyl cyclohexanenitronate
CH,CH---NOCOCH, '4cetic ethanenitronic anhydride
1
0
CH,-- hlethanenitronyl chloride
~SCI
1
0
The first preparation of a nitronic acid was apparently made by
Konowalow ( 1893) who isolated diphenylmethanenitronic acid,
l3
mp 90", and described it as a very unstable substance, decomposing
at room temperature. The phenomenon of aci-nitro tautomerism in
solution was discovered by Holleman (1895) who observed
14,
conductometrically the isomerization of 3-nitrophenylmethane-
nitronic acid into the nitro form. Hantzsch (1896)' was first to
preparc both forms of a single nitro compound (phenylnitromethane
and phenylniethanenitronic acid) and to recognize their tautomeric
relationship.
The first preparation of a nitronic ester appears to be that of Nef
( 1894) who synthesized, isolated, and recognized the unstable
15,
substance H,NCOC(CN) -=NO,C,H,.
The question of nitronic acid structure was incompletely resolved
and a subject of some debate and discussion for nearly 50 years after
the disco\.ery of these substances. The now accepted structure 1 was
originally proposed by Nef15 and employed by Bamberger'j. An
alternate oxazirane structure (2) was proposed by Hantzsch'.
