Facile Green Synthesis of Functionalized Dihydropyrimidines in a Protic Deep Eutectic Solvent

Abstract

Background: The Biginelli reaction is a one-pot multicomponent reaction used in the synthesis of various types of pharmacologically-active molecules. However, the use of harsh reaction conditions and volatile organic solvents makes the reaction harmful to the environment.

Objective: Deep eutectic solvents (DES), eutectic mixtures which melt at ambient temperatures and possess similar properties to ionic liquids, are now being explored as greener alternatives to conventional solvents in organic synthesis because of their biodegradability and low toxicity.

Methods: A novel reaction medium, a protic DES consisting of a melt of urea and 2-amino-2-hydroxymethylpropane-1,3-diol hydrochloride (Tris-HCl) in a 2:1 molar ratio was synthesized and used in the synthesis of functionalized 3,4-dihydropyrimidin-2(1H)-ones (DHPMs) via a facile and green Biginelli reaction.

Results: The reaction was accomplished under mild and solvent-free conditions, producing DHPMs in excellent yields.

Conclusion: The environmentally-benign protic DES used in this study acted as both the reaction medium and reagent.