14.24 : Amides to Amines: LiAlH₄ Reduction

The reduction of amides to amines in the presence of strong reducing agents like lithium aluminum hydride proceeds through a nucleophilic acyl substitution.

Primary, secondary, and tertiary amides on reduction, yield primary, secondary, and tertiary amines, respectively.

The reaction requires two equivalents of the reducing agent, which acts as a source of hydride ions.

The mechanism begins with a nucleophilic attack by the hydride ion, a Lewis base, at the amide carbonyl carbon, forming a tetrahedral intermediate.

Next, the carbonyl oxygen reacts with aluminum hydride, now a Lewis acid, to form an oxygen–aluminum bond.

Further rearrangement of electron pairs results in the expulsion of an aluminate anion as a leaving group, giving an iminium ion intermediate.

Lastly, the iminium ion is attacked by a second hydride ion, forming amine as the final product. The net effect is converting the amide carbonyl group into a methylene group.

Notably, lactams also undergo reduction with lithium aluminum hydride to form cyclic amines.