ONE-POT MULTICOMPONENT COUPLING SYNTHESIS OF 2-AMINO-3-CYANO-4H-PYRAN DERIVATIVES USING DEEP EUTECTIC SOLVENTS (DES)

Abstract

Considering the importance of 2-Amino-3-cyano-4H-pyran derivatives and the need for the development of new environmental friendly synthetic methodologies, the combination of Multicomponent Coupling reactions (MCR) and Deep Eutectic solvents (DES) was the goal of our study in order to make the reaction more environmentally, as well as economically, viable. Moreover, a simple work up procedure was developed via recrystallization from ethanol or ethanol-water to avoid the use of expensive silica gel chromatography and exclude the massive use of organic chromatography eluents. Finally, this work avoids the use of toxic and expensive catalyst or solvents.

Interestingly, increasing the reaction scale from 1 mmol to 3 mmol improved the reaction isolated yield. A variety of substituted aromatic as well as heteroaromatic aldehydes were explored using the larger 3 mmol scale. Generally, electron withdrawing groups (EWG) on the aldehyde produced lower yields comparing with the electron donating groups (EDG). Lastly, an evaluation of the sequence addition off the reaction components was performed. The study shows that by mixing benzaldehyde, malononitrile, and adding dimedone after five minutes, in accordance with the Mantelingu procedure, the yield increases dramatically and the side reactions are limited.