Synthesis
The general procedure for the synthesis of 2-methyl-6-hydroxybenzothiazole from 6-methoxy-2-methylbenzothiazole is as follows: to a dichloromethane solution (10 ml) of 6-methoxy-2-methylbenzothiazole (500 mg, 2.79 mmol) was slowly added to a dichloromethane solution (8.4 ml, 8.40 mmol) of boron bromide (8.4 ml) at -78°C and under nitrogen protection . The reaction mixture was then warmed to 0°C and stirred continuously at this temperature for 1 hour. Upon completion of the reaction, the reaction was quenched by the addition of water to the reaction mixture, followed by extraction with dichloromethane. The combined organic phases were washed sequentially with saturated aqueous sodium bicarbonate and pure water, followed by drying with anhydrous sodium sulfate. The organic layer was concentrated under reduced pressure and the resulting crude product was purified by medium pressure preparative liquid chromatography (Yamazen Corporation, W-Prep 2XY) to give 2-methyl-6-hydroxybenzothiazole (103 mg, 22% yield) as a colorless oil. The structure of the product was confirmed by 1H-NMR (CDCl3, 400 MHz) and mass spectrometry (ESI): 1H-NMR δ 7.66 (1H, d, J = 8.8 Hz), 7.23 (1H, d, J = 2.4 Hz), 6.94 (1H, dd, J = 8.8 Hz, 2.4 Hz), 2.74 (3H, s); MS (ESI, m/z). 166 (M + H)+.
References
[1] Helvetica Chimica Acta, 1992, vol. 75, # 4, p. 1185 - 1197
[2] Patent: EP2258697, 2010, A1. Location in patent: Page/Page column 117
[3] Zhurnal Obshchei Khimii, 1949, vol. 19, p. 1158,1159, 1164; engl. Ausg. S. 1153, 1154,1159
[4] Sb. Statei Obshch. Khim., 1953, p. 1263,1264, 1266, 1271
[5] Chem.Abstr., 1955, p. 5443
