The general procedure for the synthesis of 2-methoxy-4-bromoaniline and 2,4-dibromo-6-methoxyaniline from o-methoxyaniline was as follows: o-methoxyaniline (470 mg, 3.60 mmol) was dissolved in dichloromethane (8 mL) and the solution was cooled to -10 °C. 2,4,4,6-tetrabromocyclohexanedione (1.56 g, 3.60 mmol) was slowly added to the stirred solution while keeping the temperature below -5 °C. Subsequently, the reaction mixture was allowed to warm slowly 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 evaporated to dryness. The residue was separated by silica gel column chromatography (eluent: dichloromethane), and 2,4-dibromo-6-methoxyaniline (90 mg, 9% yield) was first obtained 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). These spectral data are in agreement with 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), 6.88-6.90 (m, 2H, ArH). These spectral data are again in agreement with 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.
