Synthesis
General method: GP3-1: 2,6-Difluoroaniline (1.0 eq.) was dissolved with potassium ethylxanthate (1.2 eq. or 2.2 eq., usually 2.2 eq. was used) in 10 volumes of anhydrous DMF and heated under nitrogen protection for 4 hrs. 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 in an oil pump.GP3-2: Thionyl chloride (SO2Cl2, 1 volume) was slowly added to 10 volumes of anhydrous DMF containing 2-mercaptobenzothiazole (obtained in step GP3-1) under the cooling conditions of an ice bath. step) in 10 volumes of anhydrous DCM solution. The reaction mixture was stirred at room temperature for 1 h. The reaction progress was monitored by TLC. After complete consumption of raw materials, 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 SO2Cl2 and release of the product. The organic layer was separated, neutralized with saturated NaHCO3 solution, dried over Na2SO4 and finally purified by silica gel column chromatography to afford the pure 2-mercapto-4-fluorobenzothiazole. The structure of the product was confirmed by LC-MS and NMR.
References
[1] Synthetic Communications, 2007, vol. 37, # 3, p. 369 - 376
[2] Bioorganic and Medicinal Chemistry, 2015, vol. 23, # 24, p. 7661 - 7670
[3] Advanced Synthesis and Catalysis, 2017, vol. 359, # 11, p. 1837 - 1843
[4] Journal of the American Chemical Society, 2013, vol. 135, # 41, p. 15579 - 15584
