Nucleophilic Substitution

Abstract

Nucleophilic substitution reactions of alkyl halides are related to elimination reactions in that the halogen acts as a leaving group on carbon and is lost as an anion. The carbon–halo-gen bond of the alkyl halide is broken heterolytically: the two electrons in that bond are lost with the leaving group. Ϫ Y R X R Y ϩ X Ϫ R X X ϭ I, Br, Cl, F ␦ϩ ␦Ϫ The carbon−halogen bond in an alkyl halide is polar and is cleaved on attack by a nucleophile so that the two electrons in the bond are retained by the halogen The most frequently encountered nucleophiles are anions, which are used as their lithium, sodium, or potassium salts. If we use M to represent lithium, sodium, or potassium, some representative nucleophilic reagents are MOR MOCR O X MSH MCN MN 3 (a metal alkoxide, a source of the nucleophilic anion) RO Ϫ (a metal hydrogen sulfide, a source of the nucleophilic anion) HS Ϫ (a metal cyanide, a source of the nucleophilic anion) CPN Ϫ (a metal azide, a source of the nucleophilic anion NoeNoeN Ϫ Ϫ ϩ) (a metal carboxylate, a source of the nucleophilic anion RC±O O X) Ϫ Table 8.1 illustrates an application of each of these to a functional group transforma-tion. The anionic portion of the salt substitutes for the halogen of an alkyl halide. The metal cation portion becomes a lithium, sodium, or potassium halide. Nucleophilic reagent M ϩ Ϫ Y ϩ R X Alkyl halide R Y Product of nucleophilic substitution ϩ X Ϫ M ϩ Metal halide Notice that all the examples in Table 8.1 involve alkyl halides, that is, compounds in which the halogen is attached to an sp 3 -hybridized carbon. Alkenyl halides and aryl hali-des, compounds in which the halogen is attached to sp 2 -hybridized carbons, are essentially Alkenyl halides are also referred to as vinylic halides. TABLE 8.1 Functional Group Transformation via Nucleophilic Substitution Nucleophile and comments General equation and specific example Alkoxide ion: The oxygen atom of a metal alkoxide is nucleophilic and replaces the halogen of an alkyl halide. The product is an ether. RO + R' X ROR' + X Alkoxide ion Alkyl halide Ether Halide ion ONa + Br O isobutyl alcohol Ethyl isobutyl ether (66%) Sodium isobutoxide Ethyl bromide Continued 8.1 Functional Group Transformation by Nucleophilic Substitution 307