Optimization of 2-amino-4-methyl-5-ethoxycarbonyl Thiazole Synthesis

The global rise of antibiotic resistance poses a major public health threat, highlighting the need for new antibacterial agents. Thiazoles have attracted attention because of their antibacterial, antifungal, and pharmaceutical potential. However, traditional thiazole synthesis methods, such as the Hantzsch synthesis (1887), typically yield only (18-20)%, while optimization strategies remain limited. Preliminary trials under conventional conditions yielded only 22.80%. This study aimed to optimize the synthesis of 2-amino-4-methyl-5-ethoxycarbonyl thiazole using Response Surface Methodology (RSM). Three factors – thiourea-to-ethyl acetoacetate molar ratio, reaction temperature, and reaction time – were investigated using Central Composite Design (CCD). The product was purified by solvent crystallization and characterized by UV- Vis, IR, 1H-NMR, and 13C-NMR spectroscopy. Under optimized conditions (molar ratio 1.23, 77 °C, 5.75 h), the yield reached (50.84 ± 1.65)%. These results demonstrate the effectiveness of RSM in improving thiazole synthesis.