Synthesis
At 0 °C, 2,5-dimethoxybenzaldehyde (1.0 g, 6.02 mmol) was dissolved in glacial acetic acid (7 mL) and a solution of bromine (0.34 mL, 6.62 mmol) in glacial acetic acid (3 mL) was slowly added. The reaction mixture was gradually warmed to room temperature and stirred continuously for 1 hour. Upon completion of the reaction, water (30 mL) was added to quench the reaction and the resulting white precipitate was collected by filtration. The precipitate was redissolved in water (30 mL) and dichloromethane (30 mL) for liquid-liquid separation. The aqueous phase was extracted with dichloromethane (3 x 25 mL), and all organic phases were combined, washed with brine (25 mL), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to give the crude product. The crude product was purified by silica gel column chromatography (eluent: 20% ethyl acetate/hexane) to afford 4-bromo-2,5-dimethoxybenzaldehyde as a light yellow solid (0.83 g, 3.37 mmol, 56% yield).
References
[1] Organic and Biomolecular Chemistry, 2013, vol. 11, # 35, p. 5782 - 5786
[2] Tetrahedron, 2011, vol. 67, # 21, p. 3904 - 3914
[3] Journal of the American Chemical Society, 2011, vol. 133, # 40, p. 15870 - 15873
[4] Synthetic Communications, 1998, vol. 28, # 24, p. 4629 - 4637
[5] Tetrahedron Letters, 2003, vol. 44, # 16, p. 3281 - 3284
