Example 1: Preparation of 4-bromo-1,2-dimethoxybenzene from veratrole ether
(1) An acetic acid solution (1.6 L) of veratrole ether (142 g, 1.03 mol) and ammonium bromide (110 g, 1.12 mol, 1.10 eq.) was added to a 3.0 L reactor.
(2) Aqueous hydrogen peroxide solution (30%, 180 mL, 1.76 mol, 1.67 eq.) was slowly added dropwise to the reaction mixture and the reaction system was continuously stirred at room temperature.
(3) After 20 hours of reaction, the reaction was quenched with saturated sodium bicarbonate solution and the reaction mixture was extracted with dichloromethane (3 x 200 mL).
(4) The organic phases were combined, washed sequentially with water (2 x 200 mL) and saturated saline (200 mL), and dried over anhydrous sodium sulfate.
(5) Concentrate the organic phase under reduced pressure to obtain a yellow crude product.
(6) The crude product was purified by decompression distillation and the fraction with boiling point 128-133 °C/10 mbar was collected to obtain 4-bromo-1,2-dimethoxybenzene (202.7 g, 91% yield).
(7) The structure of the product was confirmed by NMR hydrogen (400 MHz, DMSO-d6) and carbon (100 MHz, DMSO-d6) spectra: 1H NMR δ: 7.50 (d, J=8.4 Hz, 1H), 6.90 (d, J=2.0 Hz, 1H), 6.80 (dd, J=8.4, 2.0 Hz, 1H), 3.85 (s, 3H ), 3.80 (s, 3H); 13C NMR δ: 150.3, 148.8, 123.5, 115.3, 113.8, 112.3, 56.2, 56.0.
