General procedure for the synthesis of 6-bromo-7-methylquinoline from 4-bromo-3-methylaniline and glycerol:
[0304] A mixture of 4-bromo-3-methylaniline (20 g, 107.5 mmol), ferric sulfate (6.6 g, 43.4 mmol), glycerol (40.8 g, 440 mmol) and nitrobenzene (8.12 g, 66 mmol) was mixed with concentrated sulfuric acid (23 ml) and slowly heated. After the initial vigorous reaction subsided, the reaction mixture was refluxed for 3 h. The excess nitrobenzene was subsequently removed by evaporation. The pH was adjusted to 7-8 by adding saturated aqueous sodium bicarbonate solution to the reaction mixture and then filtered. The filtrate was extracted with dichloromethane and the organic layers were combined and dried over anhydrous sodium sulfate. The dried organic phase was filtered and concentrated in vacuum and the resulting solid was purified by fast column chromatography. The purified yellow solid was further washed with petroleum ether to afford 7.5 g of 6-bromo-7-methylquinoline in 31% yield. The structure of the product was confirmed by 1H NMR (CDCl3): δ 2.60 (s, 3H), 7.36 (m, 1H), 7.96 (s, 1H), 8.04 (m, 2H), 8.89 (m, 1H).
