The general procedure for the synthesis of 2-mercapto-4-(4-pyridinyl)thiazole from 2-bromo-1-(pyridin-4-yl)ethanone and ammonium dithiocarbamate was as follows: to 1000 ml of water, 60 g of 4-acetylpyridine was added, the temperature was maintained at 10-15 °C, followed by the slow addition of 101 g of hydrobromic acid. Gradually 87.9 g of bromine was added dropwise at the same temperature and the reaction was kept for 1 hour after the dropwise addition. The reaction system was then warmed up to 30-35 °C and the reaction was continued for 4 h. The progress of the reaction was monitored by HPLC until the feedstock was completely consumed. Upon completion of the reaction, the reaction solution was cooled to 0 °C, 66 g of ammonium dithiocarbamate was added and the reaction was kept at 0 °C for 1 hour. After that, the reaction system was slowly warmed up to 20-25°C and the reaction was continued for 4 hours. At the end of the reaction, the solid was collected by filtration to give 81.7 g of crude 2-mercapto-4-(pyridin-4-yl)thiazole. The crude product was refluxed in water for 2 h. After cooling and filtration, 80.2 g of purified 2-mercapto-4-(pyridin-4-yl)thiazole was obtained in 82.6% yield, and the product was a light yellow solid with 99.7% HPLC purity.
