7-Fluoro-3H-benzothiazole-2-thione synthesis

Yield:154327-29-4 100%

Reaction Conditions:

in N,N-dimethyl-formamide; for 4 h;Inert atmosphere;Heating;

Steps:

GeneralProcedure of Method B for 2-chlorobenzothiazoles Synthesis (GP3)^7,8

General procedure: GP3-1: A solution of 2-halo substituted aniline (1.0 eq), potassium ethyl xanthate (1.2 eq or 2.2 eq,typically 2.2 eq) in 10 volume of anhydrous DMF was heated at 100 ⁰Cor 120 ⁰C for 4 hours under nitrogen. TLC monitored the progress ofreaction. After completion, the reaction mixture was cooled to room temperature,diluted with water (10 volume) and neutralized by 1 M HCl solution to pH 5. Theformed precipitate was collected by filtration, rinsed with water, firstlydried by rotavapor, and then dried by oil pump to afford 2-mercaptobenzothiazole.GP3-2: 2-mercaptobenzothiazole in 10 volume ofanhydrous DCM, was added by sulfuryl chloride (SO₂Cl₂, 1volume) under ice-cooled condition. The mixture was stirred at rt for 1 hour,which was monitored by TLC. After consumption of starting material, the mixturewas diluted by 30 volume of ether, following quenching carefully by addingwater. Stirring was kept for 1 hour to make sure the SO₂Cl₂was totally consumed and product was released. Organic layer was collected,neutralized by saturated NaHCO₃, dried over Na₂SO₄and purified by silica gel chromatograph to give the pure product, which wasfinally characterized by LC-MS and NMR.

References:

Lv, Fengping;Li, Zhi-Fang;Hu, Wenhao;Wu, Xiaohua [Bioorganic and Medicinal Chemistry,2015,vol. 23,# 24,p. 7661 - 7670] Location in patent:supporting information