Table Of ContentSMALL RING HETEROCYCLES - 2
PART
This is the Forry-Second Volume in the Series
THE CHEMISTRY OF HETEROCYCLIC
COMPOUNDS
~-
THE CHEMISTRY OF HETEROCYCLIC COMPOUNDS
A SERIES OF MONOGRAPHS
ARNOLD WEISSBERGER EDWARD C. TAYLOR
AND
Editors
SMALL RING
HETEROCYCLES-
Part 2
Azet idines, Lactams, Diazet idines,
J-
and Diaziridines
Edited by
Alfred Hassner
DEPARTMENT OF CHEMISTRY
STATE UNIVERSITY OF NEW YORK AT BINCHAMTON
AN INTERSCIENCE@ PUBLICATION
JOHN WILEY AND SONS
NEWYORK * CHICHESTER BRISBANE TORONTO SINGAPORE
An Interscience@ Publication
Copyright 0 1983 by John Wiley & Sons, lnc.
All rghts reserved. Published simultaneously in Canada.
Reproduction or translation of any part of this work
beyond that permitted by Section 107 or 108 of the
1976 United States Copyright Act without the permission
of the copyright owner is unlawful. Requests for
permission or further information should be addressed to
the Permissions Department, John Wiley &
Sons, Inc.
Librov of Congress Cotaloging in Publicotion &to:
Main entry under title:
heterocycles.
Small ring
(The Chemistry of heterocyclic compounds, ISSN 0069
3154;v.42,pt. 1- )
“An Interscience publication”.
Includes indexes.
1. Heterocyclic compounds. 2. Ring formation
(Chemistry) I. Hassner, Alfred, 1930- .
11. Series: Chemistry of Heterocyclic compounds;
v. 42, pt. 1, etc.
QD4OO.SS115 547l.59 82-4790
0-47145625-1
ISBN
ISBN 13: 078-0-471-05625-6
10 9 8 7 6 5 4 3 2 1
To my wife Cyd
The Chemistry of Heterocyclic Compounds
The chemistry of heterocyclic compounds is one of the most complex branches
of organic chemistry. It is equally interesting for its theoretical implications, for
the diversity of its synthetic procedures, and for the physiological and industrial
significance of heterocyclic compounds.
A field of such importance and intrinsic difficulty should be made as readily
accessible possible, and the lack of a modem detailed and comprehensive
as
presentation of heterocyclic chemistry is therefore keenly felt. It is the intention of
the present series to fill this gap by expert presentations of the various branches
of heterocyclic chemistry. The subdivisions have been designed to cover the field
in its entirety by monographs which reflect the importance and the interrelations
of the various compounds, and accommodate the specific interests of the authors.
In order to continue to make heterocyclic chemistry as readily accessible as
possible new editions are planned for those areas where the respective volumes in
the first edition have become obsolete by overwhelming progress. If, however, the
changes are not too great so that the first editions can be brought up-to-date by
supplementary volumes, supplements to the respective volumes will be published
in the first edition.
WEISSBERGER
ARNOLD
Research Laboratories
Eastman Kodak Company
Rochester, New York
EDWARDC . TAYLOR
Princeton University
Princeton, New Jersey
vii
The chemistry of small ring compounds (three- and four-membered rings) has played
a considerable role in the development of modem organic chemistry. Foremost
among these reactive molecules are the small ring heterocycles. The presence of one
or more heteroatoms in these strained rings imparts a measurable dipole moment to
such molecules. It also adds a new dimension of intrinsic difficulty concerning the
synthesis and stability of such heterocyclic analogs of cyclopropanes and cyclo-
butanes. If one considers the compressed bond angles (near 60" in three-membered
rings and near 90" in four-membered rings), the mere synthetic challenge, especially
for the unsaturated analogs of these heterocycles, seems enormous. Indeed, the
small ring heterocycles possess much greater reactivity toward a variety of reagents
than do their five- or six-membered ring analogs.
The overwhelming amount of recent research literature in this field has made it
necessary to divide this treatise on small ring heterocycles into several parts, with
three- and four-membered rings sometimes interspersed. The current volume con-
stitutes Part 2 in the series.
Part 1 includes the three-membered rings containing one nitrogen or sulfur; thus
it consists of chapters on Aziridines, Azirines, and Three-Membered Rings Contain-
ing Sulfur, which includes niiranes, Thiirenes, well as their respective Oxides,
as
Dioxides. and Onuim salts.
Part 2 contains four chapters. Three of these cover the chemistry of four-
membered containing nitrogen, namely Azetidines (and Azetines), PLactams,
rings
and Four-Membered Rings Containing Two Nitrogens (Diazetidines and Diazetines).
To tie in with the latter subject, a chaptei on three-membered rings containing two
nitrogens (Diaziridines, Diazirines, Dioziridinones) is included.
It is only since the mid-1960s that an explosive expansion in the chemistry of
some of these heterocycles has taken place. In 1964, when the first review of this
series on three- and four-membered heterocycles, edited by Weissberger, was
published, azetines were unknown, while p-lactams and diazetidines were covered as
part of the azetidines (trimethyleneimines) chapter and little was known about
diaziridines. Most of these topics are now covered in separate chapters of the
current volume.
The recent interest in 0-lactams, largely due to the pharmacological properties
of penam (e.g., penicillin) and cepham (e.g., cephalosporin) antibiotics, has neces.
sitated a chapter devoted to synthesis of 0-lactams (azetidinones), separate from the
azetidine chapter. Even so, coverage here had to be limited to general synthetic
approaches to the 0-lactam ring system. 0-lactam antibiotics rightfully require
Since
a separate volume, only a few illustrative references to their synthesis are included.
There has been a great deal of recent progress on regio- and stereoselectivity,
as
well as on photochemistry of these three and four-membered rings. What is even
intriguing is their use as synthons for other functional groups as well as for larger
ix
X Preface
ring heterocycles. Furthermore, there has been increasing interest in the biological
properties and polymerization behavior of such molecules.
An effort was made to briefly present the general state of the art and to empha-
size research results of the past 15-20 years. Such an undertaking makes it necessary
to be more selective than all-inclusive. Often it became more realistic to build on
existing reviews of the subject.
Editing this volume is especially meaningful to me, because I had the privilege
of being involved firsthand in the exciting explorations of some of these hetero-
cycles during the past years.
20
I am indebted to the authors of the chapters for their splendid cooperation and
patience and to my secretary, Joyce Scotto, for her invaluable help.
Most of all, this book is devoted to my family, whose love has sustained me
through this effort, and to the loving memory of my daughter, Erica, cruelly torn
from us at a tender age.
ALFREDH ASSNER
Binghamton, New York
February I983
Contents
1. AZETIDINES 1
James A. Moore and
Rita Seelig Ayers
2. THE OF THE PLACTAM FUNCTION 219
SYNTHESIS
Gaty A. Koppel
3. FOURMEMBERED RINGS CONTAINING NITROGEN
TWO
HETEROATOMS
443
Reinhatd Richter and
Henri Ulrich
4. DIAZIRIDINES, 3H-DIAZIRINES, DIAZIRIDINONES, AND
DIAZIRIDLNIMINES 547
Harold W. Heine
Author Index 629
Subject Index 651
xi
Chemistry of Heterocyclic Compounds, Volume4 2
Edited by Alfred Hassner
Copyright 0 1983 by John Wiley & Sons, Ltd.
CHAPTER I
A ze t idi nes
JAMES A . MOORE
Department of Gemistry. University of Dehwre. Newark. Dehware
RITA SEELIG AYERS
. . ..
E I du Pont de Nemours and Co Centmi Research and Development Department.
Experimental Station. Wilmington.D ehwre
I . Introduction . . . . . . . . . . . . . . . . . . . . 3
I1. Physical Properties . . . . . . . . . . . . . . . . . . 4
1 . Thermodynamic Data and Basicity . . . . . . . . . . . . . 4
.
2 Vacuum Ultraviolet and Photoelectron Spectra . . . . . . . . . 5
3 . Infrared and Raman Data . . . . . . . . . . . . . . . 5
4 . Spectra . . . . . . . . . . . . . . . . . . . 6
NMR
5 . Diffraction Data and Molecular Structure . . . . . . . . . . . 7
6 . Spectra . . . . . . . . . . . . . . . . . . . 8
Mass
. ESR Spectra . . . . . . . . . . . . . . . . . . .
7 9
ill . Synthesis of the Azetidine Ring . . . . . . . . . . . . . . 10
1. Formation of the N-C, Bond . . . . . . . . . . . . . . 10
A . Secondary Azetidines . . . . . . . . . . . . . . . 11
B . N-Alkylazetidines . . . . . . . . . . . . . . . . 12
C. Quaternary Azetidinium Compounds . . . . . . . . . . . 14
D . NArylazetidines . . . . . . . . . . . . . . . . . 15
E. N-Sulfonylazetidines . . . . . . . . . . . . . . . 16
F . N-Alkyl-3-azetidinols and Azetidinones . . . . . . . . . . 17
C . N-Alkylazetidine-2-carboxylatesa nd Related Compounds . . . . . 19
H . N.Akyl.2-aryl.3.acyIazetidines . . . . . . . . . . . . . 20
2 . Formation of the C,-C, Bond . . . . . . . . . . . . . . 21
A . Photochemical Cyclization . . . . . . . . . . . . . . 21
B . Other Methods . . . . . . . . . . . . . . . . . 22
3 . Cycloaddition . . . . . . . . . . . . . . . . . . . 22
A. Thermal [2+2] Cycloaddition . . . . . . . . . . . . . 23
B . Photochemical [2+2] Cycloaddition . . . . . . . . . . . 25
C . [ 3+1) Cycloaddition . . . . . . . . . . . . . . . 28
4 . Formation of Azetidines from Other Ring Systems . . . . . . . . 30
1
