General procedure for the synthesis of 2-methoxy-4-bromoaniline and 2,4-dibromo-6-methoxyaniline from o-methoxyaniline: o-methoxyaniline (470 mg, 3.60 mmol) was dissolved in dichloromethane (8 mL) and cooled to -10 °C. 2,4,4,6-tetrabromocyclohexanedione (1.56 g, 3.60 mmol) was added slowly under stirring, keeping the reaction temperature below -5 °C. The reaction mixture was gradually warmed to room temperature and stirring was continued overnight. Upon completion of the reaction, the reaction mixture was washed sequentially with 2M sodium hydroxide solution (10 mL) and water (15 mL), then dried over magnesium sulfate, filtered and concentrated to dryness. The residue was separated by silica gel column chromatography (eluent: dichloromethane) and first eluted to give 2,4-dibromo-6-methoxyaniline (90 mg, 9% yield) as a dark brown liquid. Its 1H NMR (400 MHz, CDCl3) data were as follows: δ 3.84 (s, 3H, OCH3), 4.20 (br s, 2H, NH2), 6.83 (d, J = 2.1 Hz, 1H, ArH), 7.19 (d, J = 2.1 Hz, 1H, ArH), which is in accordance with the literature reports. Continued elution gave 4-bromo-2-methoxyaniline (579 mg, 83% yield) as a brown solid with a melting point of 57-59 °C (literature values: 56.5-58 °C and 60-61 °C). Its 1H NMR (400 MHz, CDCl3) data were as follows: δ 3.83 (s, 3H, OCH3), 3.85 (br s, 2H, NH2), 6.60 (d, J = 7.8 Hz, 2H, ArH), and 6.88-6.90 (m, 2H, ArH), which is in accordance with the literature reports. Ref: J.-M. Chretien, F. Zammattio, E. Le Grognec, M. Paris, B. Cahingt, G. Montavon, and J.-P. Quintard, J. Org. Chem. 70 (2005), pp. 2870-2873.
