tert-Butyl isothiocyanate → 2-(tert-Butylamino)-5,6-dichloro-1H-benzimidazole

Participants

Reaction Conditions

Reaction Steps

4,5-Dichlorophenylene diamine (8.0 g, 45.2 mmol) (Aldrich, Milwaukee, Wis.) was combined with tert-butyl isothiocyanate (6.3 mL, 49.7 mmol) (Aldrich, Milwaukee, Wis.) in anhydrous pyridine (100 mL). The solution was heated at 80° C. for 1 h under nitrogen. 1-cyclohexyl-3-(2-morpholinoethyl)carbodiimide metho-ρ-toluene-sulphonate (24.9 g, 58.8 mmol) (Fluka Chemika) was added along with anhydrous pyridine (90 mL). This solution was heated at 90° C. for 2.5 h. The pyridine. was removed by rotoevaporation, and the residue was dissolved in ethyl acetate (300 μM) and extracted with water (4×100 mL). The ethyl acetate layer was treated with decolorizing carbon and washed through a silica gel filter pad (4×8 cm, 230-400 mesh) using ethyl acetate. The crude product was purifed on a silica gel column (5×16 cm, 230-400 mesh) using (1:4) ethyl acetate:hexane. Crude fractions were repurified on a second identical column using (1:3) ethyl acetate: hexane. Pure fractions from the two columns were combined to give a tan solid (3.13 g, 12.1 mmol, 27%); m.p. 219-221° C.; MS (API+): m/z (rel. intensity) 258 (100, M+1); 1H NMR (DMSO-d6) d 10.31 (s, 1H, NH), 7.31 (s, 2H, Ar-H), 6.61 (s, 1H, NH), 1.38 (s, 9H, t-butyl).

Provenance & Evidence