4-Bromo-2-methyl-benzaldehyde

17100-58-2

24078-12-4

Procedure for the synthesis of 4-bromo-2-methylbenzaldehyde: Oxalyl chloride (249 mL, 497 mmol) was dissolved in dichloromethane (150 mL) under argon protection and cooled to -78 °C. A dichloromethane solution (75 mL) of dimethyl sulfoxide (DMSO, 42.4 mL, 597 mmol) was slowly added dropwise through a vent needle, taking care to control the rate of dropwise acceleration to avoid violent outgassing. After dropwise addition, the venting needle was removed and the reaction mixture continued to be stirred at -78 °C for 30 min. Subsequently, a dichloromethane solution (203 mL) of (4-bromo-2-methylphenyl)methanol (28A, 20.0 g, 99.0 mmol) was added and stirred for 30 min at -78 °C. Next, triethylamine (TEA, 166 mL, 1190 mmol) was slowly added dropwise and the reaction mixture was gradually warmed to room temperature and stirring was continued for 12 hours. After completion of the reaction, the organic layer was separated by diluting the reaction mixture with dichloromethane (30 mL) and water (20 mL). The aqueous layer was extracted with dichloromethane (3 x 50 mL), the organic phases were combined, washed sequentially with water and brine, dried over anhydrous magnesium sulfate, filtered and concentrated. Purification of the crude product by fast chromatography afforded the target compound 4-bromo-2-methylbenzaldehyde (28B, 15.4 g, 78 mmol, 78% yield) as a yellow oil.1H NMR (400 MHz, CDCl3) δ 10.22 (s, 1H), 7.66 (d, J = 8.28 Hz, 1H), 7.51 (dd, J = 8.28, 1.76 Hz, 1H). 1.76 Hz, 1H), 7.45 (s, 1H), 2.65 (s, 3H).