3-Bromo-4-(trifluoromethoxy)benzaldehyde

Synthesis

659-28-9

85366-66-1

The general procedure for the synthesis of 3-bromo-4-(trifluoromethoxy)benzaldehyde from 4-trifluoromethoxybenzaldehyde was as follows: 68 g (0.36 mol) of 4-trifluoromethoxybenzaldehyde was dissolved in a mixture of 100 ml of dichloromethane, 100 ml of trifluoroacetic acid and 50 ml of concentrated sulfuric acid. The reaction mixture was stirred at room temperature and 130 g (0.72 mol) of N-bromosuccinimide was slowly added over 7 hours. After the addition was completed, the reaction mixture continued to be stirred at room temperature for 2 days. At the end of the reaction, the reaction mixture was poured into 1.2 liters of ice-water mixture. The aqueous phase was extracted three times with 500 ml of dichloromethane, the organic phases were combined and neutralized with 500 ml of saturated sodium bicarbonate solution. Subsequently, the organic phase was dried with anhydrous sodium sulfate. After filtration to remove the desiccant, the organic solvent was removed by rotary evaporator under reduced pressure. To the residue, 500 ml of mixed n-pentane/ether (1:1) solvent was added and the precipitated succinimide was removed by filtration. The organic solvent was again removed by distillation under reduced pressure and the residue was purified by silica gel column chromatography (250 g, particle size 0.04-0.063 mm, Merck) using ethyl acetate/n-heptane (1:4) as mobile phase. Finally, 14 g of the target product was obtained. The product structure was confirmed by 1H-NMR (d6-DMSO, 600 MHz, δ ppm): 7.77 (d, J = 8.1 Hz, 1H), 8.05 (dd, J = 8.1 Hz, 1.7 Hz, 1H), 8.34 (d, J = 1.7 Hz, 1H), 10.01 (br s, 1H).

References