2-Chloro-6-cyanobenzothiazole

19759-66-1

80945-83-1

Step A: Synthesis of 2-chlorobenzothiazole-6-carbonitrile; To a mixture of 4-aminobenzyl cyanide (23.6 g, 0.2 mol) and ammonium thiocyanate (30.4 g, 0.4 mol) was added glacial acetic acid (600 mL) and the resulting solution was cooled to 13.5 °C in an ice bath. The mixture of bromine and glacial acetic acid was slowly added dropwise. The reaction mixture was continuously stirred at 13.5 °C for 1 hour and then filtered. The filter cake was washed with glacial acetic acid (6 x 100 mL) and subsequently stirred in hot water (1000 mL). After filtration, the pH of the filtrate was adjusted with saturated sodium carbonate solution to 7. The precipitate was separated and dried to give 19.5 g (56% yield) of 2-aminobenzothiazole-6-carbonitrile. A mixture of concentrated hydrochloric acid (113 mL) and water (52 mL) was heated to 90 °C and 2-aminobenzothiazole-6-carbonitrile (19 g, 0.108 mol) was added. The mixture was cooled to -5 °C in an ice bath and a solution of sodium nitrite (7.72 g, 0.112 mol) in water (20 mL) was added slowly dropwise, controlling the reaction temperature below 0 °C. After the dropwise addition was completed, stirring was continued for 0.5 h. Subsequently, a solution of copper(II) chloride (16 g) in water (108 mL) was added slowly dropwise. After completion of the dropwise addition, stir for 10 minutes and remove the ice bath. Stirring was continued for 2 h. The mixture was cooled to room temperature and filtered. The solid was washed to neutrality with water and dried to give 12.8 g (61% yield) of 2-chlorobenzothiazole-6-carbonitrile.1H-NMR data: δ 8.14 (s, 1H), 8.03 (d, 1H), 7.75 (d, 1H).