Preparation of Amines

The alkylation of ammonia, Gabriel synthesis, reduction of nitriles, reduction of amides, reduction of nitrocompounds, and reductive amination of aldehydes and ketones are methods commonly used for preparing amines.

Alkylation of ammonia

The reaction of ammonia with an alkyl halide leads to the formation of a primary amine. The primary amine that is formed can also react with the alkyl halide, which leads to a disubstituted amine that can further react to form a trisubstituted amine. Therefore, the alkylation of ammonia leads to a mixture of products.

Reduction of alkylazides

You can best prepare a primary amine from its alkylazide by reduction or by the Gabriel synthesis.

In the Gabriel synthesis, potassium phthalimide is reacted with an alkyl halide to produce an N‐alkyl phthalimide. This N‐alkyl phthalimide can be hydrolyzed by aqueous acids or bases into the primary amine.

Reduction of nitriles

Nitriles can be reduced by lithium aluminum hydride (LiAIH 4) to primary amines.

Reduction of amides

Amides yield primary amines on reduction by lithium aluminum hydride, while N‐substituted and N, N‐disubstituted amides produce secondary and tertiary amines, respectively.

Because amides are easily prepared, their reduction is a preferred method for making all classes of amines.

Reduction of nitrocompounds

Aromatic amines are normally prepared by reduction of the corresponding aromatic nitrocompound.

Reductive amination of aldehydes and ketones

Aldehydes or ketones can be reduced by catalytic or chemical reductions in the presence of ammonia or primary or secondary amines, producing primary, secondary, or tertiary amines.

The reaction of a ketone with ammonia, followed by catalytic reduction or reduction by sodium cyanoborohydride, produces a 1° amine.

N‐substituted amines are produced by reaction of ketones with primary amines, followed by reduction.

N,N‐disubstituted amines can be produced by reaction of 2° amines with ketones followed by reduction.