8: Nucleophilic Substitution and Elimination Reactions

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Nucleophilic substitution is a fundamental class of reactions in which an electron rich nucleophile selectively bonds with or attacks the positive or partially positive charge of an atom or a group of atoms to replace a so-called leaving group.

8.1: Prelude to Nucleophilic Substitution and Elimination Reactions
Substitution reactions involve the replacement of one atom or group by another. The halogenation of alkanes is one important type of substitution reaction, which proceeds by radical-chain mechanisms in which the bonds are broken and formed by atoms or radicals as reactive intermediates. This mode of bond-breaking is called homolytic bond cleavage. There are many reactions, often in solution, that do not involve atoms or radicals, but rather involve ions. They occur by heterolytic cleavage.
8.2: Classification of Reagents as Electrophiles and Nucleophiles. Acids and Bases
To understand ionic reactions, we need to be able to recognize whether a particular reagent will act to acquire an electron pair or to donate an electron pair. Reagents that acquire an electron pair in chemical reactions are said to be electrophilic ("electron-loving"). We can picture this in a general way as a heterolytic bond breaking of compound X:Y by an electrophile E such that E becomes bonded to Y by the electron pair of the XY bo
8.3: Thermochemistry of Substitution Reactions
Ionic or polar reactions of alkyl halides rarely are observed in the vapor phase because the energy required to dissociate a carbon-halogen bond heterolytically is almost prohibitively high. The reason is that ions are much more stable in water than in the gas phase; for example, the transfer of a chloride ion from the gas to water is exothermic with large ionic solvation energies.
8.4: General Considerations of Substitution Reactions
We now wish to discuss displacements by nucleophilic reagents (Y:) on alkyl derivatives (RX). These are ionic or polar reactions involving attack by a nucleophile at a carbon. Reactions of this type are very useful and can lead to compounds in which the new bond to carbon in the alkyl group. Nucleophilic substitutions are especially important for alkyl halides, but they should not be considered to be confined to alkyl halides.
8.5: Mechanisms of Nucleophilic Substitution Reactions
Two simple mechanisms can be written for the reaction of chloromethane with hydroxide ion in aqueous solution that differ in the timing of bond breaking relative to bond making. In the first mechanism, A , the overall reaction is the result of two steps, the first of which involves a slow dissociation of chloromethane to solvated methyl carbocation and solvated chloride ion. The second step involves a fast reaction between the carbocation and hydroxide ion (or water) to yield methanol.
8.6: Stereochemistry of \(S_N2\) Reactions
There are two simple ways in which the SN2 reaction of methyl chloride could occur with hydroxide ion; they differ in the direction of approach of the reagents. The hydroxide ion could attack chloromethane at the front side of the carbon where the chlorine is attached or, alternatively, the hydroxide ion could approach the carbon on the side opposite from the chlorine in what is called the back-side approach. The stereochemical consequences of front- and back-side displacements are different.
8.7: Stereochemistry of \(S_N1\) Reactions
Theoretically, if an SN1 reaction is carried out with a single pure enantiomer since a carbocation is most stable in the planar configuration and hence should lead to exactly equal amounts of the two enantiomers, regardless of the chiral configuration of the starting material. However, the extent of configuration change that actually results in an SN1 reaction depends upon the degree of "shielding" of the front side of the reacting carbon by the leaving group and its associated solvent molecule
8.8: Structural and Solvent Effects in \(S_N\) Reactions
We shall consider first the relationship between the structures of alkyl derivatives and their reaction rates toward a given nucleophile. This will be followed by a discussion of the relative reactivities of various nucleophiles toward a given alkyl derivative. Finally, we shall comment in more detail on the role of the solvent in nucleophilic substitution reactions.
8.9: The E2 Reaction
The conditions used for substitution reactions by the SN2 mechanism very often lead to elimination.
8.10: The E1 Reaction
Many secondary and tertiary halides undergo E1 elimination in competition with the SN1 reaction in neutral or acidic solutions. The SN1 and E1 reactions have a common rate-determining step, namely, slow ionization of the halide.
8.11: Elimination Reactions
8.E: Nucleophilic Substitution and Elimination Reactions (Exercises)
These are the homework exercises to accompany Chapter 8 of the Textmap for Basic Principles of Organic Chemistry (Roberts and Caserio).

Contributors and Attributions

John D. Robert and Marjorie C. Caserio (1977) Basic Principles of Organic Chemistry, second edition. W. A. Benjamin, Inc. , Menlo Park, CA. ISBN 0-8053-8329-8. This content is copyrighted under the following conditions, "You are granted permission for individual, educational, research and non-commercial reproduction, distribution, display and performance of this work in any format."