The general procedure for the synthesis of 4-bromo-5-methyl-2-nitrophenol from 6-nitro-m-cresol was as follows: a solution of bromine (4.04 mL, 78 mmol) in acetic acid (10 mL) was slowly added dropwise to a stirred solution of 5-methyl-2-nitrophenol (6.0 g, 39.2 mmol) in acetic acid (60 mL) at 0 °C for a controlled time of 30 min. After the dropwise addition was completed, the reaction mixture was continued to be stirred at room temperature for 2 hours. Upon completion of the reaction, the solvent was removed by distillation under reduced pressure and the resulting residue was dissolved in ethyl acetate (300 mL). Subsequently, the organic phase was washed sequentially with saturated sodium thiosulfate solution (2 x 50 mL), water (50 mL) and saturated brine (50 mL). The washed organic layer was dried with anhydrous sodium sulfate and filtered to remove the desiccant. The filtrate was concentrated by rotary evaporation to afford the title compound 4-bromo-5-methyl-2-nitrophenol in yellow solid form 9.0 g in 99% yield. The structure of the product was analyzed by 1HNMR (400 MHz, CDCl3) δ 10.46 (s, 1H), 8.29 (s, 1H), 7.08 (s, 1H), 2.46 (s, 3H) and GC-MS (m/z) 232,234 [M+. Br79,81] confirmed.
