A Novel Approach for the Synthesis of 3,3′-((4-Methoxyphenyl)methylene)bis(4-hydroxyfuran-2(5H)-one) Employing Natural Deep Eutectic Solvents and Microwave Irradiation

Abstract

Tetronic acid, a five-membered heterocyclic moiety present in various natural products, has emerged as a significant building block for many pharmaceutically active compounds. In this study, a novel protocol for the synthesis of the bis-tetronic acid 3,3′-((4-methoxyphenyl)methylene)bis(4-hydroxyfuran-2(5H)-one) (3) via a domino Knoevenagel–Michael reaction is presented. The natural deep eutectic solvent L-proline/glycerol 1:2 molar ratio was utilized as a solvent and catalyst, while the reaction was further promoted via microwave irradiation, providing the desired product in high yield (83%). The solvent was successfully recycled and reused up to three times.