Combined experimental and computational study of Al2O3 catalyzed transamidation of secondary amides with amines

Abstract

Amides are the most extensively used substances in both synthetic organic and bioorganic chemistry. Unfortunately, the traditional synthesis of amides suffers from some important drawbacks, including low atom efficiency, high catalyst loading, separation of products from the reaction mixture and production of byproducts. Al₂O₃ is an amphoteric catalyst that activates the carbonyl carbon of the secondary amide group and helps the C–N cleavage of the reactant amide group by attacking the N–H hydrogen. By using the concepts of amphoteric properties of Al₂O₃, amides were synthesized from secondary amides and amines in the presence of triethylamine solvent. Several aliphatic and aromatic amines were used for the transamidation of N-methylbenzamide in the presence of the Al₂O₃ catalyst. Moreover, using the Gaussian09 software at the DFT level, HUMO, LUMO and the intrinsic reaction coordinates (IRCs) have also been calculated to find out the transition state of the reaction and energy. In this study, five successful compounds were synthesized by the transamidation of secondary amides with amines using a reusable Al₂O₃ catalyst. The catalyst was reused several times with no significant loss in its catalytic activity. The products were purified by recrystallization and column chromatography techniques. This catalytic method is effective for the simultaneous activation of the carbonyl group and N–H bond by using the Al₂O₃ catalyst.