Acyl imidazole formation
Abstract
The synthesis of a N-acylimidazole is a well-established strategy for activating the carbonyl function of the carboxylic acid toward further transformations. This activation opens access to a variety of derivatives, including ester, amide etc. The reaction involves the activating reagent carbonyldiimidazole (CDI) and a carboxylic acid.
Keywords
Carboxylic acid, CDI, N-acylimidazole
Category
Carboxylic acid
Mechanism
First, one of the aromatic imine-type nitrogen of the CDI deprotonates the carboxylic acid. The resulting carboxylate then attacks the electrophilic carbonyl carbon of CDI, releasing one molecule of imidazole and forming the corresponding carbamic–carboxylic anhydride. This intermediate undergoes nucleophilic addition-elimination by the imidazole leading to a carbamate anion and N-acylimidazolium. After equilibrium, the corresponding N-acylimidazole and carbamate are obtained. This latter undergoes a decarboxylation step to give carbon dioxide and imidazole as by-products.
Recent review
Mino, T.; Sakamoto, S.; Hamachi, I. Recent applications of N-acyl imidazole chemistry in chemical biology. Biosci. Biotechnol. Biochem. 2021, 85, 53-60.