The Dakin-West reaction is a chemical reaction that transforms an amino-acid into a keto-amide using an acid anhydride and a base, typically pyridine. It is named for Henry Drysdale Dakin (1880-1952) and Randolph West (1890-1949). In 2016 Schreiner and coworkers reported the first asymmetric variant of this reaction employing short oligopeptides as catalysts.
With pyridine as a base and solvent, refluxing conditions are required. However, with the addition of 4-dimethylaminopyridine (DMAP) as a catalyst, the reaction can take place at room temperature.
With some acids, this reaction can take place even in the absence of an a-amino group.
This reaction should not be confused with the Dakin reaction.
The reaction mechanism involves the acylation and activation of the acid 1 to the mixed anhydride 3. The amide will serve as a nucleophile for the cyclization forming the azlactone 4. Deprotonation and acylation of the azlactone forms the key carbon-carbon bond. Subsequent ring-opening of 6 and decarboxylation give the final keto-amide product.
Modern variations on the Dakin-West reaction permit many enolizable carboxylic acids - not merely amino acids - to be converted to their corresponding methyl ketones. For example, b-aryl carboxylic acids can be efficiently converted to b-aryl ketones by treatment of an acetic anhydride solution of the acid with catalytic N-methylimidazole. This reactivity is attributed in part to generation of acetylimidazolium, a powerful cationic acetylating agent, in situ.