A sustainable approach for the Erlenmeyer synthesis of azlactones in deep eutectic solvents

Abstract

Deep eutectic solvents (DESs) have emerged as promising alternatives to hazardous catalysts and solvents in various chemical transformations. This study presents a facile, green, and simple approach for the synthesis of azlactones using a novel DES system. The reaction between hippuric acid and substituted heterocyclic/aromatic aldehydes in the DES medium efficiently yields 4-arylidene-2-phenyl-5(4H)-oxazolones with excellent purity and high yields in short reaction times. The novel DES consists of lithium perchlorate (LiClO₄) as the hydrogen bond acceptor and urea as the hydrogen bond donor. This solvent system is cheap, commercially available, and easy to prepare through a simple, straightforward method. This strategy offers several key advantages, including mild reaction conditions, avoiding harsh reagents and extreme temperatures, and a simple, efficient work-up, minimizing purification steps. It ensures a high-yield economy, consistently achieving 73–97 % yields, while being environmentally friendly, offering a sustainable and non-toxic alternative. The approach demonstrates broad applicability, including pharmaceutically relevant molecules, and enhances DES reusability, improving cost-effectiveness and sustainability.