One-pot synthesis of phthalimides from phthalic acids and amines using cyanuric chloride and N,N-dimethylformamide as a cyclodehydrating agent under milder reaction conditions

Abstract

A new, one-pot, two-step, and efficient method has been developed to synthesize phthalimide and its derivatives directly from phthalic acids with an iminium cation as the cyclodehydrating agent, which in turn is generated from a mixture of cyanuric chloride and N,N-dimethylformamide and amines under milder reaction conditions. This method is a simple, cost effective, and uses inexpensive and commercially available reagents and catalysts. Broad functional group tolerance of the process led to the synthesis of many phthalimides in good to excellent isolated yields (up to 98 %). This method also afforded the thalidomide drug intermediate. The plausible reaction mechanism has been also reported.