57310-39-1

2-Bromo-1-chloro-4-methyl-benzene is a useful synthetic intermediate. It can be used to synthesize N-heterocycle-fused phenanthridines via palladium-catalyzed tandem N-H/C-H arylation of aryl-N-heteroarenes with dihaloarenes. It can also be used to synthesize substituted fluorenes.

General procedure for the synthesis of 4-chloro-3-bromotoluene from 2-bromo-4-methylaniline: tert-butyl nitrite (48 mmol, 6.34 mL) and anhydrous copper(II) chloride (60 mmol, 8.07 g) were mixed at 65 °C in anhydrous acetonitrile (100 mL). 2-Bromo-4-methylaniline (30 mmol) was slowly added under vigorous stirring for 30 min. Subsequently, the reaction mixture was continued to be stirred at 65 °C for 2 hours. After completion of the reaction, the mixture was cooled, poured into 20% hydrochloric acid (400 mL) and extracted with ether (3 x 120 mL). The organic phases were combined, washed with brine (100 mL), dried over anhydrous Na2SO4 and the solvent was subsequently evaporated. The crude product was purified by fast column chromatography.

[1] Bioorganic and Medicinal Chemistry Letters, 2016, vol. 26, # 22, p. 5568 - 5572