2-Chlorothiazole

288-47-1

3034-52-4

General procedure for the synthesis of 2-chlorothiazole from thiazole: To an anhydrous THF (60 mL) solution of thiazole (5.0 g, 58.7 mmol) was added n-butyllithium (1.6 M hexane solution, 44 mL, 70.4 mmol) slowly and dropwise over a period of 20 min at -78 °C with stirring. The reaction mixture was kept at 0 °C for 15 min, followed by dropwise addition of anhydrous THF (40 mL) solution of 2,2,2-trichloroacetyl chloride (6.6 mL, 58.7 mmol) to the orange colored mixture. The reaction mixture was continued to be stirred at -78 °C for 30 min, after which the reaction was quenched with saturated ammonium chloride solution (100 mL). After extraction with ether (2 x 150 mL), the organic layers were combined, washed with brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The crude product was purified by silica gel column chromatography (0-20% ether/pentane gradient elution) to afford the target compound 2-chlorothiazole (4.95 g, isolated yield 71%).1H NMR (400 MHz, CDCl3) δ 7.50 (d, J=4.0 Hz, 1H), 7.15 (d, J=4.0 Hz, 1H).