Reactions that Yield Aliphatic Amines

Simple amines and ammonia are strong nucleophiles and will undergo an S_N2 reaction with alkyl halides (or alkyl groups with "good leaving groups") to give further substitution on the nitrogen. Ammonia reacts with alkyl halides to give a mixture, consisting largely of the corresponding primary and secondary amines, with a trace of tertiary and quarternary amines. Since a mixture is obtained, this is generally a poor method for the preparation of amines.

Better methods for the preparation of primary amines involve the reduction of an intermediate alkyl azide, or the Gabriel Synthesis, involving an intermediate phthalimide. In the first method, the alkyl halide reacts with azide anion in a simple S_N2 reaction to give the intermediate alkyl azide. This is generally not isolated, but is reduced immediately with LiAlH₄ to give the corresponding primary amine.

In the Gabriel Synthesis, phthalimide anion is reacted with the alkyl halide to give the intermediate N-substituted pthalimide. On acid hydrolysis, this gives pthalic acid and the corresponding primary amine.

Primary amines can also be prepared by the reduction of two other functional groups, nitriles and amides. The reduction of a nitrile by LiAlH₄ gives the primary amine, as shown below. Reduction of an amide can yield a primary, secondary or tertiary amine, depending on the amide.

Amines can also be prepared by the process of reductive amination of aldehydes and ketones. An aldehyde or ketone will react with ammonia to give an intermediate imine. Reduction of this imine with Raney Ni/H₂ gives the corresponding amine.

Primary and secondary amines can also be utilized in reductive amination reactions, typically using cyanoborohydride (NaBH₃CN) to trap the intermediate immonium ion.