Chloroacetone → HCID 59324083, compound

Participants

Reaction Steps

10 g (79 mmol) of commercially available 1,2-diamino-4-fluorobenzene 1b were suspended in CS2 (500 mL), then NEt3 (2 eq, 22 ml) were added dropwise and the mixture stirred at r.t. for 2 h. The resulting dithiocarbamate salt was then filtered off, washed with Et2O and used without further purifications (24 g, yellow powder, 99%). 24 g (79 mmol) of dithiocarbamate salt were suspended in MeCN (500 mL), then commercially available chloroacetone (1.1 eq, 7.14 mL) was added dropwise and the mixture stirred at r.t. for 12 h. The solvent was then removed and HCl 37% (21 mL) was added under vigorous stirring. After 15 min, water (150 mL) was added and the mixture extracted 3×150 mL of CH2Cl2. The organic layer was washed 3×400 mL of water, dried with MgSO4 and evaporated under reduced pressure. 3-(2-Amino-4-fluorophenyl)-4-methyl-1,3-thiazole-2(3H)-thione 2b was obtained by crystallisation from CH2Cl2 as yellow crystals (12.1 g, 68%). Mp=138° C.; 1H NMR (300 MHz, CDCl3) δ=1.95 (3H, d, J=1.2, CH3), 3.80 (2H, brs, NH2), 6.37 (1H, q, J=1.2, H5), 6.57-6.99 (3H, m, Ar); 13C NMR (75 MHz, CDCl3) δ=15.44, 103.9 (d, J=26), 106.4 (d, J=24), 106.6, 119.3 (d, J=3), 130.0 (d, J=11), 144.6 (d, J=12), 163.8 (d, J=248), 189.2; HRMS m/z C10H10N2FS2 [M+H]+ calcd: 241.0264, found: 241.0262. The structure of 3-(2-amino-4-fluorophenyl)-4-methyl-1,3-thiazole-2(3H)-thione was fully established by X-ray single crystal analysis.

Provenance & Evidence