Table Of ContentORGANIC CHEMISTRY
A SERIES OF MONOGRAPHS
ALFRED T. BLOMQUIST, Editor
DeparfmenfolChemistry, Cornell UniversifY, ¡thaca,New York
1. Wolfgang Kirmse. CARBENE CHEMISTRY, 1964; 2nd Edition, In
preparation
2. Brandes H. Smith. BRIDGED AROMATIC COMPOUNDS, 1964
3. Michael Hanack. CONFORMATION THEORY, 1965
4. Donald J. Cram. FUNDAMENTAL OF CARBANION CHEMISTRY, 1965
5. KennethB. Wiberg (Editor). OXIDATION IN ORGANICCHEMISTRY, PARTA,
1965; PART B, In preparation
6. R. F. Hudson. STRUCTURE AND MECHANISM IN ORGANO-PHOSPHORUS
CHEMISTRY, 1965
7. A. William Johnson. YLID CHEMISTRY, 1966
8. Jan Hamer (Editor). 1,4-CYCLOADDITION REACTIONS, 1967
9. Henri Ulrich. CYCLOADDITION REACTIONS OF HETEROCUMULENES, 1967
10. M. P. Cava and M. J. Mitchell. CYCLOBUTADIENE AND RELATED COM
POUNDS, 1967
11. Reinhard W. Hoffman. DEHYDROBENZENE AND CYCLOALKYNES, 1967
12. Stanley R. Sandler and Wolf Karo. ORGANIC FUNCTIONAL GROUP
PREPARATIONS, VOLUME I, 1968; VOLUME 11, In preparation
13. Robert J. Cotter and Markus Matzner. RING-FoRMING POLYMERIZATIONS.,
PART A, 1969; PART B, In preparation
14. R. H. DeWolfe. CARBOXYLIC ORTHO ACID DERIVATIVES, 1970
15. R. Foster. ORGANIC CHARGE-TRANSFER COMPLEXES, 1969
16. James P. Snyder (Editor). NONBENZENOID AROMATICS, I, 1969
17. C. H. Rochester. ACIDITY FUNCTIONS, 1970
18. Richard J. Sundberg. THE CHEMISTRY OF INDOLES, 1970
19. A. R. Katritzky and J. M. Lagowski. CHEMISTRY OF THE HETEROCYCLIC
'N-OXIDES, 1970
20. Ivar Ugi (Editor). ISONITRILECHEMISTRY, 1971
21. G. Chiurdoglu (Editor). CONFORMATIONAL ANALYSIS, 1971
In preparation
GottfriedSchill. CATENANES, ROTAXANES, AND KNOTS
Isonitrile
Chemistry
Edited by
Ivar Ugi
Department of Chemistry
University of Southern California
Los Angeles, California
Academic Press 1971 New York and London
COPYRIGHT © 1971, BY ACADEMIC PRESS, INC.
ALL RIGHTS RESERVED
NO PART OF THIS BOOK MAY BE REPRODUCED IN ANY FORM,
BY PHOTOSTAT, MICROFILM, RETRIEVAL SYSTEM, OR ANY
OTHER MEANS, WITHOUT WRITTEN PERMISSION FROM
THE PUBLISHERS.
ACADEMIC PRESS, INC.
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United Kingdom Edition published by
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PRINTED IN THE UNITED STATES OF AMERICA
List of Contributors
Numbers in parentheses indicate the pages on which the authors' contributions begin.
JOSEPH CASANOVA, JR. (109), Department of Chemistry, California State College, Los
Angeles, California
G. GOKEL (9,133,145,201,235), Department of Chemistry, University of Southern California,
Los Angeles, California
J. A. GREEN II (/), Department of Chemistry, University of Southern California, Los
Angeles, California
P. T. HOFFMANN (/, 9, 133, 201), Department of Chemistry, University of Southern
California, Los Angeles, California; and Wissenschaftliches Hauptlaboratorium der
Farbenfabriken Bayer, Leverkusen, Germany
Y. ITO (65), Department of Synthetic Chemistry, Kyoto University, Kyoto, Japan
H. J. KABBE (93), Wissenschaftliches Hauptlaboratorium der Farbenfabriken Bayer, Lever-
kusen, Germany
H. KLEIMANN (201), Wissenschaftliches Hauptlaboratorium der Farbenfabriken Bayer,
Leverkusen, Germany
H. KLUSACEK (201), Department of Chemistry, University of Southern California, Los
Angeles, California; and Wissenschaftliches Hauptlaboratorium der Farbenfabriken
Bayer, Leverkusen, Germany
G. LUDKE (145, 201), Department of Chemistry, University of Southern California, Los
Angeles, California
KENNETH M. MALONEY (41), General Electric Lighting Research Laboratory, Cleveland,
Ohio
D. MARQUARDING (9, 133, 201), Department of Chemistry, University of Southern
California, Los Angeles, California; and Wissenschaftliches Hauptlaboratorium der Farben
fabriken Bayer, Leverkusen, Germany
B. S. RABINOVITCH (41), Fundamental Research Section, Battelle Memorial Institute,
Pacific Northwest Laboratories, Richland, Washington
T. SAEGUSA (65), Department of Synthetic Chemistry, Kyoto University, Kyoto, Japan
I. UGI (9, 133, 145, 201), Department of Chemistry, University of Southern California, Los
Angeles, California
ARND VOGLER (217), Lehrstuhl fur Spez. PhysikChemie, Technische Universitàt, Berlin,
Germany
ix
Preface
After M. Passerini's papers appeared in the early thirties, the end of the
classical era of isonitrile chemistry, very little was published in this field for
almost three decades. During the past decade, however, a renaissance has
occurred, numerous investigators have entered the field, the novel, intriguing
results are evolving at an impressive rate.
Isonitriles are now easy to prepare and are useful intermediates for the
synthesis of a wide variety of compounds. It can be predicted safely that in
the near future isonitriles will no longer be a class of esoteric compounds,
outside the mainstream of organic chemistry, but will be widely investigated
and used in syntheses. Few areas of chemistry of broad interest can be covered
in their entirety, comprehensively and in a unified manner. Isonitrile chemistry
is one of these rarities.
The chemistry of isonitriles is not just the chemistry of one of the many
functional classes of organic compounds; it is remarkably different from the
rest of organic chemistry because the isonitriles are the only class of stable
organic compounds containing formally divalent carbon. This divalent carbon
accounts for the wide variety of reactions, particularly the multicomponent
reactions. In fact, all reactions that lead to isonitriles and all subsequent
transformations are transitions of the isonitrile carbon from the formally
divalent state to the tetravalent state and vice versa, a transition which is
unique within the organic chemistry of stable compounds.
This work should prove useful to anyone requiring information on the
chemistry of isonitriles. It provides an introduction to as well as a com
prehensive coverage of isonitrile chemistry, from its beginnings, around the
middle of the last century, to 1970. The most recent developments in the
field are covered in an Addendum written with the generous help of an
impressive number of isonitrile chemists who responded to my request to
point out recent publications and to submit recent unpublished results.
This work is comprised of ten chapters, which correspond to the major
aspects of isonitrile chemistry, and an Addendum. An attempt has been made to
organize the book in the following manner: Chapter 1 deals with general
properties, Chapter 2 reviews isonitrile syntheses, Chapters 3 to 9 cover the
major reactions, and Chapter 10 is devoted to the coordination chemistry of
xi
xii Preface
isonitriles. The Addendum is a compilation of recent advances in the field.
In a few years there will probably be other major areas such as reactions of
isonitriles with organometallic reagents, radicals, and reactions via catalytic-
ally active complexes. These three fields can be anticipated on the basis of
the most recent advances, but there will surely be others.
A variety of industrial uses for isonitriles can also be foreseen because of
their biocidal properties as well as their utility in building up and/or cross-
linking macromolecular systems by multicomponent reactions of poly-
functional reactants. The increasingly important technological aspects of the
isonitriles are covered only where the applications involve their specific
chemical properties.
Isonitrile chemistry, by virtue of the unique valency status of the isonitrile
carbon, contrives many intriguing problems for the physical chemist. It
offers novel synthetic approaches (particularly because of the ability to
participate in multicomponent reactions) to a wide variety of nitrogen-con
taining organic compounds, most notably the peptide and related derivatives
of the α-amino acids. The reported biosynthesis of some isonitriles as well as
the pronounced effects of some isonitriles on living organisms provide a link
to biology and biochemistry. The coordination properties of isonitriles are
not only of interest to coordination chemists but also to those engaged in
homogeneous catalysis.
I gratefully acknowledge the fact that the present volume is the product
of the common effort of a great number of active isonitrile chemists, not only
of those who contributed as authors, but also of many colleagues who par
ticipated in helpful discussions, made stimulating suggestions, and pointed
out to the authors pertinent published and unpublished work.
I am further indebted to the Western Research Application Center
(WESRAC) for helping to scan the literature for recent publications.
Chapter 1
The Structure
of Isonitriles
J. A, Green II and P. T. Hoffmann
I. The History of the Structure of Isonitriles 1
II. Some Physicochemical Consequences of the Structure of the Isocyano Group . 4
References. 6
I. THE HISTORY OF THE STRUCTURE OF ISONITRILES
The history of isonitriles actually began several years before they were
identified as a discrete class of compounds. Several chemists, trying to prepare
alkyl cyanides from alkyl iodides and silver cyanide, isolated considerable
amounts of substances whose "horrifying" odor often led to termination of
the preparation.
In 1859, eight years before Gautier's work first appeared, Lieke42 reacted
allyl iodide and silver cyanide and obtained in reasonable yield a liquid with
a "penetrating" odor, which he believed to be allyl cyanide. He tried to
transform the presumed allyl cyanide into crotonic acid by acidic hydrolysis,
but was surprised to obtain only formic acid. Study of this "anomalous"
hydrolysis reaction was discontinued because of "continuing complaints in
the neighborhood about the vile odor." Lieke carried out all his experiments
outdoors because "opening a vessel containing the nitrile [sic] is sufficient to
taint the air in a room for days."
Several years later, Meyer48 described methyl- and ethyl "cyanide," which
he had obtained by alkylation of silver cyanide without realizing that he had
isolated the isonitriles. It was not until the fundamental work by Gautier12""20
that these unpleasant smelling compounds were known to be "isomers of the
ordinary nitriles."
At the same time, Hofmann31-34 synthesized several isonitriles, among
them phenyl isocyanide,* by reacting amines with chloroform and potassium
* In accordance with generally accepted usage, the term isonitriles is used for the general
class of compounds, whereas the term isocyanide is used for specific designations (e.g.,
ethyl isocyanide or alkyl isocyanide).
1
2 J. A. Green II and P. T. Hoffman
hydroxide. Gautier and Hofmann started a lengthy series of studies which
lasted the next few decades and which dealt with the peculiar bonding relation
ships in the new class of compounds.
Gautier saw isonitriles as "true homologs of hydrocyanic acid,"16 since,
like the acid, "they have the greatest of deleterious effects on an organism,"17
and by hydrolysis are converted into formic acid and "substituted ammonia."
Somewhat later, he observed that methyl and ethyl isonitrile, whose "detest
able odors were at the same time reminiscent of artichokes and phosphorus,"17
were perhaps not poisonous, since no ill effects resulted when he dropped
them into the eyes and mouth of a dog.*14
On the basis of his hydrolysis results, Gautier16 developed the first structural
formula for ethyl isonitrile (I):
C£)N
2 5
(I)
In contrast to the isomeric propionitrile (II), the "lone" carbon in isonitrile (I)
C2H5QN
(ID
is attached to the ethyl radical via the nitrogen atom. Since the terminal
carbon may be di- as well as tetravalent, he finally suggested two structural
formulas, III and IV, which were discussed further by Nef49 54 25 years later.
CH—N=C CH—N=C
2 5 2 5
(III) (IV)
Because of the inordinately large number of observed α-addition reactions
of the isonitrile carbon, Nef settled on the structural formula (V) which
emphasizes the unsaturated, formally divalent character of the terminal
carbon.49
CH—N=C=
2 5
(V)
* With a few exceptions, isonitriles exhibit no appreciable toxicity to mammals. As has
been found in the toxicological laboratories of Farbenfabriken Bayer A.G., Elberfeld,
Germany, oral and subcutaneous doses of 500-5000 mg/kg of most of the isonitriles can
be tolerated by mice, yet there are exceptions like 1,4-diisocyanobutane which is extremely
toxic (LDso.mice < 10 mg/kg).
1. The Structure of Isonitriles 3
In 1930, a third, polar structure (VI) was proposed by Lindemann and
Wiegrebe43 in analogy to the structure of carbon monoxide as postulated by
Langmuir40 and which best complied with the new octet rule. In support of
their proposed structure, they cited parachor measurements as evidence of
the triple bond. Indeed, parachor results predict no significant contribution
from resonance with a double bond structure, such as V.4,25
© Θ
R-N=C
(VI)
In the same year, Hammick and co-workers29 found the partial dipole
moment of the isonitrile-NC group to be opposite to that of the nitrile-CN
group. Further dipole measurements with 4-substituted phenyl isocyanides29,55
were consistent with the dipolar structure (VI) and support the linear C—Ν—C
linkage which such a structure implies.63 Sidgwick summarized these and
other early experiments in an excellent review of structural studies of iso
nitriles.62
Soon thereafter, Brockway5 presented electron diffraction data, later
corroborated by Gordy and Pauling,26 which supported a predominantly
triple-bonded structure.56
The early normal coordinate analyses of isonitrile vibrational spectra by
Lechner,41 and later by Badger and Bauer,1 yielded only limited information,
indicating an almost exclusively triple-bonded structure, although not ruling
out double-bond character entirely. As early as 1931, Dadieu7 had proposed
that the Raman band between 1960 and 2400 cm-1 in isonitrile spectra was
evidence for a triple bond.
Finally, two decades after the proposal of Lindemann and Wiegrebe,
extensive microwave studies provided perhaps the most conclusive evidence
for structure VI.6,37 These results prove the linearity of the C—Ν—C bond
system beyond doubt. Microwave dimensions for methyl isocyanide and the
isomeric acetonitrile are given in Table I.
TABLE I
MOLECULAR DIMENSIONS OF CHNC AND CHCN37
3 3
^CH(A) i/cc(À) C/-N(Â) ^N=C(CsN)(Â) <HCH
C
CHNC 1.094 — 1.427 1.167 109°46/
3
CHCN 1.092 1.460 — 1.158 109°8/
3
4 J. A. Green II and P. T. Hoffman
Thus, the early evidence fully established the triple-bond representation
(VI); the equivalent structural representation (VII) is now generally being
(VII)
used. The unique system of bonding orbitals of the isocyano group leads to a
number of consequences in the physicochemical properties of isonitriles,
which of course may serve as latter-day confirmation of the assigned structure.
II. SOME PHYSICOCHEMICAL CONSEQUENCES OF THE
STRUCTURE OF THE ISOCYANO GROUP
The strengths of the C=N bonds in isonitriles and nitriles are approxi
mately equal, as is indicated by the similar C=N stretch frequencies at ca.
2150 and 2250 cm-1, respectively.30 Force constants have been re
ported,8,38,41,44 the most recent and probably most accurate being those
reported by Duncan8: fc =16.7 mdyne/À and & =18.1 mdyne/Â. In
NC CN
addition, heat of formation calculations65 based on thermodynamic data11
yield similar values for the isocyano and cyano groups, i.e., AH = 88-98
f
kcal/mole.
In a comparative study of the structures of the cyano and isocyano groups,
Bak and co-workers2 have calculated electron densities using the nuclear
positions and dipole moments (μ = 3.92 D for CHCN and μ = 3.83 D for
3
CHNC).21 The centers of negative charge (r_) and positive charge (t )
3 6 e+
are at quite similar positions with regard to the nitrogen nucleus, suggesting
similar electron distributions between carbon and nitrogen, as shown in
Figs. 1 and 2.
Ν t t- C
6+ 6
0 0.387 0.474 1.160 À
C /+ *6- Ν
6
» — ι — ι — ι — ι.
1.160 0.580 0.445 0Â
Fig. 1. Charge distribution in isocyano and cyano groups.2
-N- R-
R C Ν or R C Ν
Fig. 2. Possible π-electron density curves for isocyano and cyano groups.2
