General procedure for the synthesis of 1-(bromomethyl)-4-methoxy-2-nitrobenzene from 4-methyl-3-nitroanisole:
Intermediate 1: Synthesis of 1-(bromomethyl)-4-methoxy-2-nitrobenzene: To a solution of 4-methyl-3-nitroanisole (16.53 mL, 119.64 mmol, 1 eq.) in carbon tetrachloride (500 mL), N-bromosuccinimide (21.29 g, 119.64 mmol, 1 eq.) and azobisisobutyronitrile (392.9 mg , 2.39 mmol, 0.02 equiv). The reaction mixture was heated to reflux at 85 °C for 20 hours. After completion of the reaction, the solution was cooled to room temperature and filtered to remove the resulting succinimide precipitate. The filtrate was concentrated to give a yellow oil. The oily substance was allowed to crystallize overnight at -25°C. It was subsequently dissolved in ethyl acetate (15 mL), petroleum ether was added and allowed to stand at -25°C for 2 hours to promote recrystallization. The crystallized product was washed with petroleum ether and dried under vacuum to give 17.4 g (59% yield) of 1-(bromomethyl)-4-methoxy-2-nitrobenzene as a liquid.
Product Characterization:
1H NMR (DMSO-d6) δ 7.68 (d, J = 8 Hz, 1H), 7.56 (d, J = 3 Hz, 1H), 7.33 (dd, J = 8.0, 3.0 Hz, 1H), 4.89 (s, 2H), 3.87 (s, 3H).
HPLC (max plot) 99%; Rt 4.09 min.
