Page 408 - Advanced Organic Chemistry Part A - Structure and Mechanisms, 5th ed (2007) - Carey _ Sundberg

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Nucleophilic Substitution

Introduction

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Nucleophilic substitution at tetravalent sp carbon is a fundamental reaction of
broad synthetic utility and has been the subject of detailed mechanistic study. An
interpretation that laid the basis for current understanding was developed in England by
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C. K. Ingold and E. D. Hughes in the 1930s. Organic chemists have continued to study
substitution reactions; much detailed information about these reactions is available
and a broad mechanistic interpretation of nucleophilic substitution has been developed
from the accumulated data. At the same time, the area of nucleophilic substitution also
illustrates the fact that while a broad conceptual framework can outline the general
features to be expected for a given system, finer details reveal distinctive aspects that
are characteristic of specific systems. As the chapter unfolds, the reader will come to
appreciate both the breadth of the general concepts and the special characteristics of
some of the individual systems.

4.1. Mechanisms for Nucleophilic Substitution

Nucleophilic substitution reactions may involve several different combinations of
charged and uncharged species as reactants. The equations in Scheme 4.1 illustrate the
four most common charge types. The most common reactants are neutral halides or
sulfonates, as illustrated in Parts A and B of the scheme. These compounds can react
with either neutral or anionic nucleophiles. When the nucleophile is the solvent, as in
Entries 2 and 3, the reaction is called a solvolysis. Reactions with anionic nucleophiles,
as in Entries 4 to 6, are used to introduce a variety of substituents such as cyanide
and azide. Entries 7 and 10 show reactions that involve sulfonium ions, in which a
neutral sulfide is the leaving group. Entry 8 involves generation of the diphenylmethyl
diazonium ion by protonation of diphenyldiazomethane. In this reaction, the leaving

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C. K. Ingold, Structure and Mechanism in Organic Chemistry, 2nd Edition, Cornell University Press,
Ithaca, NY, 1969.
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