The general procedure for the synthesis of 2-(bromomethyl)benzothiazole using 2-hydroxymethylbenzothiazole as starting material was as follows: 2-hydroxymethylbenzothiazole (1.00 g, 6.05 mmol) was dissolved in an appropriate amount of CH2Cl2 according to Attardo's method 1. Phosphorus tribromide (1.15 mL, 12.1 mmol) was slowly added dropwise to the above solution under argon protection. The reaction mixture was stirred at room temperature for 2 hours. Upon completion of the reaction, the solvent was removed by distillation under reduced pressure. The resulting crude product was purified by silica gel column chromatography (eluent ratio hexane:ethyl acetate = 5:1) to afford 2-(bromomethyl)benzothiazole (786 mg, 57% yield) as a brown solid. The structure of the product was confirmed by the following characterization data: 1H NMR (300 MHz, CDCl3) δ 4.81 (s, 2H), 7.42 (td, 1H, J = 8.1 Hz, 1.1 Hz), 7.50 (td, 1H, J = 8.1 Hz, 1.1 Hz), 7.87 (dd, 1H, J = 8.1 Hz, 1.1 Hz), 8.02 ( dd, 1H, J = 8.1 Hz, 1.1 Hz); 13C NMR (75 MHz, CDCl3) δ 27.1, 121.8, 123.5, 125.9, 126.5, 136.2, 152.8, 166.2; mass spectrometry (EI) showed molecular ion peaks at m/z 227, 229 (M+); and thin-layer chromatography (TLC) showed Rf value of 0.60 (unfolding agent ratio of hexane:ethyl acetate=5:1).
