General procedure for the synthesis of 5-bromo-2-chlorotoluene from 2-methyl-4-bromoaniline: 11.7 g (63.2 mmol) of 2-methyl-4-bromoaniline was dissolved in 45 mL (6 mol/L) of hydrochloric acid solution and stirred thoroughly to form the hydrochloride salt. The resulting solution was cooled to 0°C in an ice-salt bath. Under the condition that the temperature was kept below 0°C, about 20% sodium nitrite solution (4.8 g, 69.5 mmol, 20 mL) was added slowly and dropwise. Subsequently, 12 mL of 1,4-dioxane was added and stirred well. The diazonium salt solution prepared above was slowly added to a hydrochloric acid solution (20 mL) of 3 mol/L cuprous chloride (6.7 g, 66.4 mmol) in an ice-water bath with vigorous stirring. After completion of the dropwise addition, the reaction mixture was stirred at room temperature for 0.5 h and then at 80 °C for 3 h. The reaction mixture was then stirred for 0.5 h at room temperature. After completion of the reaction, the mixture was cooled and extracted with dichloromethane (75 mL x 2). The organic phases were combined, washed sequentially with NaHCO3 solution (150 mL), water (150 mL), and saturated brine (100 mL x 2), and dried with anhydrous sodium sulfate overnight. Finally, the dried organic phase was concentrated under reduced pressure to afford 11.2 g (87% yield) of reddish brown liquid product.
