Nucleophilic substitution at a saturated carbon atom

180 Pages·1963·56.038 MB·English

by  Clifford A. Bunton

REACTION MECHANISMS
IN
ORGANIC CHEMISTRY
A SERIES OF MONOGRAPHS EDITED BY
E. D. HUGHES, F.R.S. ■
P rofessor o f C hem istry
U n iversity College
L ondon
VOLUME I
ELSEVIER PUBLISHING COMPANY
AMSTERDAM / LONDON / NEW YORK
NUCLEOPHILIC SUBSTITUTION
AT A
SATURATED CARBON ATOM
BY
C.A.BUNTON,Ph .D.
R eader in C hem istry
U niversity College
L ondon
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PREFACE
In this monograph I have attempted to summarise my own views
on one branch of Physical-Organic Chemistry, and to discuss some
limited aspects of the subject. Workers in this field have been much
too energetic for any complete review to be possible.
I have deliberately restricted the field under discussion to nucleo
philic substitution at a saturated carbon atom in order to keep this
volume to a reasonable size. The price of this is the omission of such
related topics as substitution at formally unsaturated centres, and
at atoms other than carbon. Rearrangements and eliminations are
mentioned briefly because they throw considerable light upon the
properties of carbonium ion intermediates. The experimental
problems of determining reaction rate, and the related kinetic
parameters, have been omitted; they are not specific to this subject,
and are dealt with very adequately in existing works.
Physical-Organic Chemistry is a descriptive subject, and plagued
by the uncertainties and ambiguities of our terminology. This is a
great weakness, but one which is inescapable until theoretical
chemistry can treat adequately such an immensely complicated
problem as a chemical reaction in solution. For 25 years or more it
has been customary to place reactions into mechanistic categories,
usually in terms of their molecularities. I have generally followed
the original mechanistic classification of Hughes and Ingold, which
is based upon the concept of the duality of mechanism, although
I believe that we should use the terms “uni-” and “bi-molecular”
with considerable caution, particularly for solvolytic reactions and
for reactions in solvents of low dielectric constant. Thus a given
reaction may' show much of the behaviour typical of either
mechanistic model without it being possible to assign it un
ambiguously to either category. To the extent that I have abused,
or perhaps what is worse, ignored the views or nomenclatures of
VI PREFACE
other workers I make my apologies in advance. Progress in any
field results from the efforts of many individuals, and I have no
intention of trying to make distinctions between individual contri
butions. The literature has been covered up to the end of 1961.
A fascinating aspect of any study of reaction mechanism is that
it inevitably brings together a wide range of experimental methods.
Mechanistic studies of nucleophilic substitution have benefited
considerably from the use of the newer instrumental methods, but
much of the stimuli for the work came from observations on
reactions of naturally occurring compounds, in particular in the
sugar, terpene and steroid fields. One can hope that the stimuli are
in both directions.
I am particularly grateful to my old teachers. Professors Sir
Christopher Ingold, F.R.S., and E. D. Hughes, F.R.S. for their
stimulating influence.The latter and Drs. D. Banthorpe, A. Ledwith,
A. Maccoll and R. E. Robertson have read much or the whole of
the manuscript and their contributions have been invaluable.
Much of the preparation of this manuscript was done during a most
enjoyable visit to the Department of Chemistry, University of
California, Los Angeles, and I am happy to acknowledge the
generous hospitality of its members, and in particular many
entertaining discussions with Professors S. Winstein and D. J. Cram.
Discussion with Professor V. J. Shiner and R. W. Taft and Drs. G.
Kohnstam and R. E. Robertson were most helpful, and I am grateful
to Professor Taft and Drs, Kohnstam and Robertson for giving me
useful information in advance of its publication.
C. A. B.
CONTENTS
P r e f a c e . . . . . . . . . . . ..................................... v
Chapter 1.
N u c l e o ph il ic Su bs t it u t io n a n d t h e D u a l it y o f
M echanism . . . . . . .......................................... \
1. Duality of mechanism ...................................... 3
(a) Molecularity of the reaction 3 / (b) Driving forces for
substitution 4 t (c) Carbonium ions as reaction inter
mediates 5
2. Simple kinetic evidence for the duality of mechanism . . . 6
(a) Kinetic form of an SnI solvolysis 8 / (b) The Sn2C+
mechanism 9
3. Alternative classifications of nucleophilic substitutions .... 10
(a) Charge-type classification 11
4. Side reactions : .......................... 12
(a) Rearrangements 12 /(b) Elimination 13
5. The nature of a substitution process. ................................... 15
Chapter 2. 25
St r u c t u r a l E f f e c t s u po n R a t e o f Su bst it u t io n
1. Introduction. . . . . . . . . . . . . . . . . . . . 25
2. Bimolecular substitution. Alkyl groups . . . . . . . . . 27
(a) Steric and electronic effects 27 /(b) Cycloalkyl groups 31
3. Bimolecular substitution. Substituents other than alkyl . . 33
(a) Aryl groups 33 / (b) Allyl and ethynyl groups 34 / (c)
a-Carbonyl substituents 35 / (d) Other groups 38
4. a-Elimination . . . . \ . . .................................. 39
5. Unimolecular substitution. Alkyl groups. . . . . . . 39
(a) Electronic effects 40 / (b) Steric acceleration 40
6. Unimolecular substitution. Cycloalkyl groups ................... 42
(a) Bridgehead systems 42 / (b) Effect of ring size 43
7. Unimolecular substitution. Aryl groups . . . . . . . . . 45
(a) Baker-Nathan effect 47 / (b) Ortho-Alkyl groups and
steric inhibition of resonance 48
8. Unimolecular substitution. Allyl and ethynyl groups . . . 49
9. Unimolecular substitution. Halogeno ethers and thioethers . 50
10. Neighbouring group effect . . . . . . . . . . . . . . . 51
11. Non-classical carbonium ions . . . . . . . . . . . . . 59
(a) Homoallylic and homoaromatic conjugation 65
VIII CONTENTS
12. Secondary structural isotope effects............................ 67
13. Analysis of kinetic effects in terms of energies and entropies
of activation. ................................ 70
14. The displaced group X . . ................... , 72
15. The nucleophile Y . . . . . . . . . . . . . . . . . . 75
16. Summary . . . . . . . . ........................ . . 76
Chapter 3. 85
St e r e o c h e m is t r y ............................................................
1. The Walden Inversion . . ................................ 85
2. Stereochemistry of bimolecular nucleophilic substitution. , 86
3. Stereochemistry of unimolecular substitution ..................... 88
(a) Configuration-retaining groups absent 88 / (b) Solvent
effects upon the steric course of an Sn I solvolysis 90 / (c)
Nature of the carbonium ion 92 / (d) Effect of configuration-
retaining substituents 93
4. Replacements of OH and NH2 . . . . . . . . . . . . * 100
(a) Reactions of alcohols with halides of sulphur and phos
phorus 101 /(b) Reactions of alcohols with hydrogen halides
103 / (c) Deamination 103 i
Chapter 4. So l vent Ef f ec t s . ..............................................................Ill
1. Qualitative solvent theory........................ . Ill
(a) Specific interactions between solvent and reactants 113
2. Linear free energy relationships.................................................115
3. Correlation of rates with product composition in mixed
solvents. .................................... 118
4. Spectral measurements of solvent polarity . . . . . . . . . 119
5. Deuterium solvent isotope effects.................... 120
6. Special features of some solvents ................................ . . . 121
Chapter 5. Sal t Ef f ec t s f ....................... . . . . . . . . . . . 126
1. Aqueous and mixed aqueous-organic solvents.........................126
(a) Ionic strength effect 126 / (b) Common-ion retardation 129
2. Solvents of low dielectric constant........................ 132
(a) Ion-pairing and the reactivity of nucleophilic anions 133
3. Ion-pairs as reaction intermediates in Sn I reactions. . . . 135
(a) Reactions in aprotic solvents 136 / (b) Reactions in
hydroxylic solvents 138 / (c) Evidence from oxygen equi
libration studies 146
Chapter 6. ..................................................151
E l e c t r o ph il ic Ca t a l y s is
1. Catalysis by ions of silver and m ercury.................... 151
(a) Catalysis by silver ions 151 / (b) Catalysis by mercuric
ions 153
CONTENTS IX
2. Catalysis by proton acids . . ...................................................156
(a) Acid-catalysed hydrolysis of epoxides 157 / (b) Acid-
catalysed hydrolysis of alkyl fluorides 160 / (c) Acid catalysis
in aprotic solvents 161
......................................................................................... 164
A d d e n d u m
167
In d e x .
Chapter 1
NUCLEOPHILIC SUBSTITUTION AND THE
DUALITY OF MECHANISM
Nucleophilic substitutions at a saturated carbon atom are hetero-
lytic reactions in which a group X is displaced by a reagent Y with
transfer of a pair of electrons from Y to the reaction centre, and
from the reaction centre to X, e.g.,*
Y + -^cj—X — ► Y—C^- + x
In these reactions the reagent Y and the displaced ion or molecule
are nucleophiles, or Lewis bases. The terms solvolytic* * and non-
solvolytic reaction are used to differentiate between the situations
in which Y is, or is not, a solvent molecule.
This large class of substitution reactions, designated Sn, includes
many reactions of preparative organic chemistry, e.g., alkylations
by esters of strong acids, where the nucleophile may be a hydroxy-
compound, an amine or sulphide, or a carbanion. The substitution
may involve no net chemical change, e.g., we can observe the iso
topic exchange: _
i3ii + It—I ^ 1S1I—R + I
and its stereochemical consequences at an optically active centre.
The reactant may be an unstable intermediate; one of the steps in
the aqueous deamination of an aliphatic amine can be written as
the alkylation of water by an aliphatic diazonium ion, or by a
carbonium ion derived from it:
RNH, + HONO + H RN, + 2H,0
' RN, + HjO ROH + N, + H
* The development of these mechanistic ideas is discussed in ref. [1],
* * For a comprehensive review of solvolytic reactions see ref. [2aJ, and for a review of the chemistry
of carbonium ions see ref. [2bJ.
2 1
NUCLEOPHILIC SUBSTITUTION
Various pictures had long been formulated for substitutions at
a saturated carbon atom, (cf., ref. [1]). Formation of an addition
complex, followed by ejection of the displaced group was one sug
gested model; another involved synchronous addition of the reagent
and ejection of the displaced group. A somewhat different model
postulated a prior dissociation to a reactive intermediate which was
subsequently captured by the reagent. In general these earlier
theories were mutually exclusive, and because no single one could
be accommodated to all the results it became necessary to suppose
that the molecularity of a nucleophilic substitution depended in a
characteristic way upon the structures of the reactants and their
environment. Various examples of displaced and entering groups
are given below; the list is not intended to be exhaustive.
Displaced groups: \ ' ■ •».
+ + + +
Na, HRO, R-SOj-O, halide, R2S, R3N, (R0)aP0-0, RCOa
Entering groups:
R3C, H, CN, NOa, RO, RS, RCOa, SOa, ROH, R3N, RjjS, halide ions
This formulation of these reactions tells us little about their
mechanisms, and progress in this direction has followed intensive
experimental effort devoted largely to those reactions which were
amenable to kinetic study. For much of the early work the solvent
was water, or mixtures of water and organic solvents; this choice
of protic solvents of high dielectric constant simplified the in
vestigation in many ways. Solvents of low dielectric constant are
now being studied in detail, and more complicated behaviour,
governed in part by powerful electrostatic forces, is being observed.
This recent work is of great theoretical interest, and it also provides
useful pointers in the choice of experimental conditions for pre
parative reactions, e.g., dipolar aprotic solvents are proving to be
excellent media for displacements involving nucleophilic anions
(Chap. 4, sect. 6).
The initial phase of this investigation led directly to the concept
of the duality of mechanism, i.e., to the idea that it was possible.