Page 10 - Advanced Organic Chemistry Part A - Structure and Mechanisms, 5th ed (2007) - Carey _ Sundberg

x reactions, including hydrogenation, epoxidation of allylic alcohols, and dihydroxylation
of alkenes are discussed. Chapter 3 provides examples of structure-stability relation-
Introduction
ships derived from both experimental thermodynamics and computation. Most of the
chapter is about the effects of substituents on reaction rates and equilibria, how they are
measured, and what they tell us about reaction mechanisms. The electronic character of
the common functional groups is explored, as well as substituent effects on the stability
of carbocations, carbanions, radicals, and carbonyl addition intermediates. Other topics
in this chapter include the Hammett equation and related linear free-energy relation-
ships, catalysis, and solvent effects. Understanding how thermodynamic and kinetic
factors combine to influence reactivity and developing a sense of structural effects on
the energy of reactants, intermediates and transition structures render the outcome of
organic reactions more predictable.
Chapters 4 to 7 relate the patterns of addition, elimination, and substitution
reactions to the general principles developed in Chapters 1 to 3. A relatively small
number of reaction types account for a wide range of both simple and complex
reactions. The fundamental properties of carbocations, carbanions, and carbonyl
compounds determine the outcome of these reactions. Considerable information about
reactivity trends and stereoselectivity is presented, some of it in tables and schemes.
Although this material may seem overwhelming if viewed as individual pieces of infor-
mation, taken in the context of the general principles it fills in details and provides a
basis for recognizing the relative magnitude of various structural changes on reactivity.
The student should strive to develop a sufficiently broad perspective to generate an
intuitive sense of the effect of particular changes in structure.
Chapter 4 begins the discussion of specific reaction types with an examination of
nucleophilic substitution. Key structural, kinetic, and stereochemical features of substi-
tution reactions are described and related to reaction mechanisms. The limiting mecha-
nisms S 1 and S 2 are presented, as are the “merged” and “borderline” variants. The
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relationship between stereochemistry and mechanism is explored and specific examples
are given. Inversion is a virtually universal characteristic of the S 2 mechanism,
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whereas stereochemistry becomes much more dependent on the specific circumstances
for borderline and S 1 mechanisms. The properties of carbocations, their role in
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nucleophilic substitution, carbocation rearrangements, and the existence and relative
stability of bridged (nonclassical) carbocations are considered. The importance of
carbocations in many substitution reactions requires knowledge of their structure and
reactivity and the effect of substituents on stability. A fundamental characteristic of
carbocations is the tendency to rearrange to more stable structures. We consider the
mechanism of carbocation rearrangements, including the role of bridged ions. The case
of nonclassical carbocations, in which the bridged structure is the most stable form, is
also discussed.
Chapter 5 considers the relationship between mechanism and regio- and stereo-
selectivity. The reactivity patterns of electrophiles such as protic acids, halogens,
sulfur and selenium electrophiles, mercuric ion, and borane and its derivatives are
explored and compared. These reactions differ in the extent to which they proceed
through discrete carbocations or bridged intermediates and this distinction can explain
variations in regio- and stereochemistry. This chapter also describes the E1, E2, and
E1cb mechanisms for elimination and the idea that these represent specific cases
within a continuum of mechanisms. The concept of the variable mechanism can
explain trends in reactivity and regiochemistry in elimination reactions. Chapter 6
focuses on the fundamental properties and reactivity of carbon nucleophiles, including