Ultrasound and ZnCl₂ Promoted Synthesis of Phthaloyl Derivatives of α-Amino Carboxamides

A new, one-step and racemization-free synthesis of phthaloyl derivatives of α-amino carboxamides is described. Under ultrasound, α-amino carboxamides and dipeptide derivatives react with monomethyl phthalate in the presence of BOP, ZnCl₂ and i-Pr₂NEt to afford the corresponding N ^α -phthaloyl α-amino carboxamides or dipeptides in good to excellent yields. Cyclization of the intermediate N ^α -[(o-methoxycarbonyl)benzoyl]amino carboxamides to the desired products was very slow when the reaction was conducted either in the absence of ZnCl₂ and/or without sonication, but the process was greatly accelerated when both ZnCl₂ and ultrasound were used.

phthaloyl protection - zinc chloride - sonochemistry - α-amino carboxamides - monomethylphthalate - cyclization - peptides