Question

A Mannich reaction puts a group on the $\mathrm{\alpha }$-carbon of a carbon acid. Propose a mechanism for the reaction.

Short answer

Mechanism of the given reaction

Step-by-step solution

Step-by-Step Solution Step 1: Mannich reaction

Mannich reaction is used to synthesize a beta amino carbonyl compound called Mannich base by the reaction of an enolizable carbonyl and a non-enolizable carbonyl compound.

The reaction also involves the use of ammonia, primary amine, or secondary amine.

Acids catalyze the reaction. It is an example of amino alkylation reactions and is initiated by the reaction of an amine with non-ionizable carbonyl like formaldehyde.

General mechanism of Mannich reaction

Mannich reaction is a condensation reaction initiated by the attack of nucleophilic nitrogen of the amine on the electrophilic carbon atom of non-ionizable carbonyl. The adduct thus formed abstracts the hydrogen ion from acid.

Water is a good leaving group and is therefore removed from the adduct. The electrophilic carbon atom is attacked by the enol formed from ionizable carbonyl. This produces the beta amino carbonyl compound.

Mechanism of the given reaction

The dimethyl amine reacts with formaldehyde to form the adduct in the given reaction. The adduct abstracts a proton from acid and removes water to form a C=N bond with nitrogen having a positive charge. This makes the carbon atom electrophilic.

The enol formed from cyclohexanone attacks the electrophilic carbon atom, removing a proton to form the final product.

Mechanism of the given reaction