Theoretical study on the reaction mechanisms of the imide formation in an N-(O-carboxybenzoyl)-L-amino acid

Reaction mechanisms of the imide formation in an N-(o-carboxybenzoyl)-L-amino acid have been studied using density functional theory. Our results suggest that the reaction route initiated by protonation at the oxygen of the carboxyl group of the amino acid is favored, and those initiated by deprotonation at the oxygen of carboxyl group of phthalic acid and at amidic nitrogen from the reactant are minor pathways. These conclusions are in good agreement with the experimental facts that under highly acidic conditions (hydrogen ion concentration < -1), imide formation is the most favorable, while in the pH range 0-5, cyclization is not the dominant reaction. Our calculations also show that the carboxyl group of the amino acid is involved in the catalytic reaction in both the favored and minor pathways.