Recent Approaches in the Synthesis of 5-Arylidene-2,4-thiazolidinedioneDerivatives Using Knoevenagel Condensation

Abstract: 5-Arylidene-2,4-thiazolidinedione (5-A-TZD) is an emerging precursor molecule in medicinal chemistry for discovering multifunctional therapeutic agents. For synthesizing this precursor molecule, Knoevenagel Condensation (KC) is one of the most excellent tools in modern organic chemistry. The 5-A-TZD framework has a variety of therapeutic functions such as antidiabetic, anticancer, antimicrobial, and anti-inflammatory. As a result, several approaches and methods of KC have been established for the synthesis of this multifunctional precursor. However, the use of highly corrosive catalysts, prolonged reaction times, by-products formation, and poor product yields are the main drawbacks in 5-A-TZDs synthesis via KC. Therefore, several authors have been successfully established fast, effective, and environmentally sustainable protocols of KC using organic catalysts, inorganic catalysts, heterogeneous solid catalysts, ionic liquids (ILs), and bio-catalysts to synthesize 5-A-TZD derivatives with high conversion yield and selectivity. In this review, we have summarized the recent approaches for synthesizing 5-A-TZDs via KC and their therapeutic application as a precursor molecule in medicinal chemistry.