Efficient synthesis of pyrano[3,2-c]pyridines via a green and catalyst-free method at ambient temperature, and related DFT calculations

Abstract

Twelve medicinally important pyrano[3,2-c]pyridine derivatives were precipitated, with high yields, from ethanol solutions of malononitrile and (E)-3,5-bis(benzylidene)-4-piperidones at ambient temperature, requiring almost no work-up. Natural bond order calculations at the B3LYP/6-31+G* level indicate that electron-withdrawing groups on the phenyl rings deplete electron density on β-atoms (with respect to the carbonyl groups) of the piperidones, leading to higher yields of the corresponding products with shorter reaction times. This green methodology appears in a clear contrast to all previous reports, where either a catalyst and/or microwave was employed. So, simplicity and short reaction time, non-toxicity of the solvent, as well as economic feasibility are major advantages of this chemically waste-free process.