Eco-Friendly Synthesis of Thiazole Derivatives Using Recyclable Cross-Linked Chitosan Hydrogel Biocatalyst Under Ultrasonic Irradiation as Anti-Hepatocarcinogenic Agents

Abstract

In the current study, pyromellitimide benzoyl thiourea cross-linked chitosan (PIBTU-CS) hydrogel, was evaluated as a green biocatalyst for the efficient synthesis of novel thiazole derivatives. The PIBTU-CS hydrogel showcased key advantages, such as an expanded surface area and superior thermal stability, establishing it as a potent eco-friendly catalyst. By employing PIBTU-CS alongside ultrasonic irradiation, we successfully synthesized a series of novel thiazoles through the reaction of 2-(4-((2-carbamothioylhydrazineylidene)methyl)phenoxy)-N-(4-chlorophenyl)acetamide with a variety of hydrazonoyl halides (6a–f) and α-haloketones (8a–c or 10a,b). A comparative analysis with TEA revealed that PIBTU-CS hydrogel consistently delivered significantly higher yields. This synthetic strategy provided several benefits, including mild reaction conditions, reduced reaction times, and consistently high yields. The robustness of PIBTU-CS was further underscored by its ability to be reused multiple times without a substantial reduction in catalytic efficiency. The structures of the synthesized thiazole derivatives were meticulously characterized using a range of analytical techniques, including IR, 1H-NMR, 13C-NMR, and mass spectrometry (MS), confirming their successful formation. These results underscore the potential of PIBTU-CS hydrogel as a sustainable and recyclable catalyst for the synthesis of heterocyclic compounds. Additionally, all synthesized products were tested for their anticancer activity against HepG2-1 cells, with several new compounds exhibiting good anticancer effects.