14.27 : Nitriles to Ketones: Grignard Reaction

Organomagnesium halides, commonly known as Grignard reagents, convert nitriles to ketones and proceed through a nucleophilic acyl substitution. Nitriles react with a Grignard reagent, followed by an aqueous acid, to yield ketones. The reaction introduces a new carbon–carbon bond. The alkyl–magnesium bond in the Grignard reagent is highly polar, so the alkyl carbon develops a carbanionic character and acts as a nucleophile.

The mechanism begins with a nucleophilic attack by the Grignard reagent at the nitrile carbon to form an anion, also known as the salt of an imine. Next, the protonation of the anion with aqueous acid gives an imine as an intermediate, which is not isolated and enters the next step. In the last step, imine is hydrolyzed under acidic conditions to yield ketone as the final product.