2-Chloro-4-fluorobenzothiazole

154327-24-9

182344-56-5

General procedure for the synthesis of 2-chloro-4-fluorobenzothiazole from 2-mercapto-4-fluorobenzothiazole: General method GP3-1: 2-halo-substituted anilines (1.0 eq.) were dissolved in 10 volumes of anhydrous DMF under nitrogen protection with potassium ethylxanthate (1.2 eq. or 2.2 eq., 2.2 eq. was usually used) and the reaction was heated for 4 hr. at 100°C or 120°C. The reaction progress was monitored by TLC. Upon completion of the reaction, the mixture was cooled to room temperature, diluted with 10 volumes of water and neutralized with 1 M HCl solution to pH 5. The resulting precipitate was collected by filtration, washed with water, dried by rotary evaporator and then further dried under an oil pump. General method GP3-2: To a solution of 2-mercaptobenzothiazole in 10 volumes of anhydrous DCM was slowly added sulfuryl chloride (SO2Cl2, 1 volume) under cooling conditions in an ice bath. The reaction mixture was stirred at room temperature for 1 h. The reaction progress was monitored by TLC. After complete consumption of the ingredients, the reaction mixture was diluted with 30 volumes of ether and the reaction was quenched by careful addition of water. Stirring was continued for 1 hour to ensure complete consumption of thionyl chloride and product release. The organic layer was separated, neutralized with saturated NaHCO3 solution, dried over anhydrous Na2SO4 and finally purified by silica gel column chromatography to afford the pure 2-chloro-4-fluorobenzothiazole. The final structure of the product was confirmed by characterization by LC-MS and NMR.