14.27:
Nitriles to Ketones: Grignard Reaction
Nitriles can be converted to ketones in the presence of organomagnesium halides, known as Grignard reagents.
The reaction proceeds via a nucleophilic acyl substitution, introducing a new carbon–carbon bond.
Notably, the alkyl–magnesium bond in the Grignard reagent is highly polar. As a result, the alkyl carbon develops a carbanionic character and acts as a nucleophile in the reaction.
The first step of the mechanism begins with a nucleophilic attack by the Grignard reagent at the nitrile carbon, forming an anion.
The second step involves protonation of the anion with an aqueous acid to form an imine as an intermediate.
Since the imine intermediate is not isolated, it enters the next step, where the imine is hydrolyzed under acidic conditions to yield ketone as the final product.
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.
