Organic Synthesis

Amines and ammonia are generally sufficiently nucleophilic to undergo direct alkylation, often under mild conditions. The reactions are complicated by the tendency of the product (a primary amine, secondary, or tertiary amine) to react with the alkylating agent. For example, reaction of 1-bromooctane with ammonia yields almost equal amounts of the primary amine and the secondary amine. Therefore, for laboratory purposes, N-alkylation is often limited to the synthesis of tertiary amines. An exception is the amination of alpha-halo carboxylic acids that do permit synthesis of primary amines with ammonia. Intramolecular reactions of haloamines X-(CH₂)n-NH₂ give cyclic aziridines, azetidines and pyrrolidines.

N-alkylation is a general and useful route to quaternary ammonium salts from tertiary amines, because overalkylation is not possible.

Use of the Gabriel synthesis is a safe route to a primary amine from an alkyl halide.

Examples of N-alkylation with alkyl halides are the syntheses of benzylaniline, 1-benzylindole, and azetidine. Another example is found in the derivatization of cyclen. Industrially, ethylenediamine is produced by alkylation of ammonia with 1,2-dichloroethane.