Practical Considerations for the Formation of Acyl Imidazolides from Carboxylic Acids and N,N′-Carbonyldiimidazole: The Role of Acid Catalysis

The conversion of carboxylic acids to acyl imidazolides using N,N′-carbonyldiimidazole (CDI) is hampered by the presence of alkali salts of the carboxylic acid, resulting in incomplete reactions, which cannot be driven to completion with excess CDI. Addition of an exogenous proton source reverses this effect. Sparging of the reaction mixture with carbon dioxide is also effective, presumably due to the formation of the carbamic acid of imidazole, which acts as a proton source. These results suggest that acyl imidazolide formation is subject to acid catalysis. The acceleration of acyl imidazolide formation using triflic acid or imidazolium triflate, as catalyst, is demonstrated.