Synthesis
General procedure for the synthesis of 2-bromothiazole from 2-aminothiazole: 2-aminothiazole (0.25 mol) and 150 mL of 45% sulfuric acid were added to a 500 mL reaction flask, and stirred until the 2-aminothiazole was completely dissolved. The reaction mixture was cooled to 2 °C and 50 mL of 65% concentrated nitric acid was added slowly and dropwise, controlling the reaction temperature to not exceed 10 °C. Subsequently, 50 mL of 5 mol/L sodium nitrite solution was added slowly dropwise, and after the dropwise addition was completed, stirring was continued for 1 hour to keep the reaction temperature below 7 °C. The reaction mixture was dripped into a 200 mL solution containing 74 g of sodium bromide and 40 g of copper sulfate through a dropping funnel for the bromination reaction, controlling the temperature at 6 °C, and the dropping time was about 1.5 hours. After the reaction was completed, N2 gas was removed. After cooling, the pH of the reaction mixture was adjusted to 6-7 with 20% NaOH solution, followed by hydrodistillation to collect the aqueous solution containing 2-bromothiazole. After drying with magnesium sulfate, vacuum distillation was carried out to collect the fraction with a boiling point of 71~73 °C/2.4 kPa to give 35.2 g of 2-bromothiazole in 85.8% yield. In this reaction, keeping the reaction temperature in the range of 0~10 °C not only accelerated the reaction rate, but also reduced the occurrence of side reactions, thus significantly increasing the reaction yield.
References
[1] Synthesis, 2012, vol. 44, # 7, p. 1026 - 1029
[2] Patent: CN105348216, 2016, A. Location in patent: Paragraph 0048; 0049
[3] Recueil des Travaux Chimiques des Pays-Bas, 1934, vol. 53, p. 77,78
[4] Recueil des Travaux Chimiques des Pays-Bas, 1962, vol. 81, p. 554 - 564
[5] Patent: WO2016/55947, 2016, A1. Location in patent: Page/Page column 142
