Eco-Friendly Synthesis of 2,3-Disubstituted Thiazolidine-4-One Derivatives Via A Multicomponent Reaction with Microwave Irradiation in a Chiral Ionic Liquid Medium

Abstract

Thiazolidinone (TZD) derivatives, especially those containing a 1,3-thiazolidine-4-one core, are highly valued in drug design due to their broad spectrum of biological activities, including antimicrobial, antidiabetic, anticancer, and anti-inflammatory effects. These compounds are considered “privileged scaffolds” due to their potential in developing novel therapeutic agents. Traditional methods for synthesizing TZD derivatives involve condensation reactions that typically require toxic catalysts and organic solvents, often resulting in low yields. These drawbacks have spurred the development of more sustainable and efficient synthesis methods. Recent advancements focus on green and efficient techniques, such as microwave heating, solid-phase synthesis, and the use of ionic liquids (ILs). ILs, particularly chiral ionic liquids (CILs), offer significant benefits, including non-volatility, recyclability, and high thermal stability, making them ideal for multicomponent reactions. Their use improves both sustainability and reaction efficiency. In one recent study, a one-pot, three-component reaction was conducted with aromatic aldehyde, aromatic amine, and thioglycolic acid in the presence of the chiral ionic liquid 1-(S-2'-methyl butyl)-3-methyl imidazolium tetrafluoroborate [mbmi][BF₄]. This method, utilizing microwave irradiation, enabled the rapid and highly efficient synthesis (88–96% yield) of various 2-(3-halophenyl)-3-(methoxy-substituted phenyl) thiazolidine-4-one derivatives. Notably, several compounds, including 3d, 3e, 3g, 3h, and 3i, were synthesized for the first time, highlighting the effectiveness of CILs in the green synthesis of TZD derivatives.