Accelerated Synthesis of 4-Arylideneisoxazolones in Glycerol Medium

The isoxazole-5-one ring system is a central structure in many synthetic bioactive molecules, showing a wide range of biological activities, including antibacterial, antitumor, anticorrosion, antifungal, antituberculosis, and antioxidant. They are also applied as agrochemicals with potential fungicidal effects. Given various applications, these pharmaceutically and biologically significant heterocyclic compounds have attracted the attention of chemistry researchers. This study aimed to investigate the application of glycerol as a reaction medium for the three-component synthesis of arylidenisoxazol-5(4H)-one derivatives. The results of the optimized investigations revealed that 3.0 mL of glycerol is the best reaction medium. Evaluation of the effect of reaction temperature showed that the best temperature for this strategy is 60 °C. In the present environmentally friendly study, the desired heterocyclic compounds were quickly synthesized via a one-pot three-component reaction of two keto-esters with hydroxylamine hydrochloride and a number of aryl/heteroaryl aldehydes. This synthetic approach has significant merits, such as cost-effectiveness of the reaction medium, rapid green synthesis, operational simplicity, easy workup, avoiding chromatographic purification, sustainability, acceptable yields, and relatively inexpensive as well as commercially available starting materials.