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Method A - bromine and hydrogen peroxide in acetic acid
2 ArH + Br2 + H2O2 → 2 ArBr + 2 H2O
To ice-cooled and stirred mixture of 138 g 1,4-dimethoxybenzene (DMB) and 600 ml acetic acid was carefully added a solution of 26 ml bromine in 50 ml acetic acid during 20 min. Then 52 ml of 30% hydrogen peroxide were dropwise added during 30 min. Ice bath was then removed and stirring was continued for 30 min. Then the mixture was poured into 3 l water and dark red liquid product was extracted with CH2Cl2. Work-up and yield - see Method B.
Method B - hydrobromic acid and hydrogen peroxide in dichloromethane/water
ArH + HBr + H2O2 → ArBr + 2 H2O
To water-cooled and stirred mixture of 138 g 1,4-DMB, 200 ml CH2Cl2, 150 ml water and 115 ml 48% hydrobromic acid were dropwise added 110 ml of 30% hydrogen peroxide during 1 h. The reaction mixture was stirred for 1 day (TLC control) and then filtered through Celite to allow separation of layers. Water layer was extracted with 50 ml CH2Cl2, organic extracts were dried over Na2SO4 and evaporated in vacuo to give 193 g of dark red liquid (1). Crude product was distilled at 0.2 kPa with aid of 15 cm Vigreux column - 30 g of forerun were collected at 55-90°C (2) and then 144 g (66% yield) of pure product at 90-100°C (3).
ArH + CH2O + HCl → ArCH2Cl + H2O
To vigorously stirred mixture of 130g 2-Bromo-1,4-Dimethoxybenzene, 58 ml 35% HCl, 24 g 1,3,5-trioxane (1) and 130 mg cetyltrimethylammonium bromide (2) in 500 ml RBF was introduced gaseous HCl (about 17 g was necessary) at 80°C (oil bath) during 2 h (3). The hot mixture was then poured into 1000 mL ice/water while stirring with a glass rod to avoid the crude product forming lumps. Filtration, several washings with cold water and drying over KOH pellets in vacuum dessicator provided 156 g of light yellow crude product (4). One crystallization from minimum amount of dry acetone gave 81 g (51% yield) of white crystals (5). The pure material melts at 110°C6.
4-Br-2,5-diMeO-BnCl:
1H-NMR (CDCl3, 400MHz) 7.10 (s,1H), 6.95 (s,1H), 4.61 (s,2H), 3.87 (s,3H), 3.84 (s,3H).
13C-NMR (CDCl3, 100MHz) 151.4 (s), 149.9 (s), 125.6 (s), 116.4 (d), 114.1 (d), 112.0 (s), 56.9 (q), 56.4 (q), 41.1 (t).
6-Br-2,5-diMeO-BnCl:
1H-NMR (CDCl3, 400MHz) 6.86 (s,1H), 6.84 (s,1H), 5.47 (s,2H), 3.86 (s,6H).
2CB freebase
1H NMR (CDCl3,400MHz) 7.02 (s,1H), 6.74 (s,1H), 3.84 (s,3H), 3.77 (s,3H), 2.90 (t,J=6.9Hz,2H), 2.72 (t,J=6.9Hz,2H), 1.35 (broad s,2H)
13C NMR (CDCl3,100MHz) 151.9 (s), 149.6 (s), 128.3 (s), 115.7 (d), 114.8(d), 108.8 (s), 56.9 (q), 56.0 (q), 42.1 (t), 34.9 (t)
2CB hydrochloride
1H NMR (D2O,400MHz) 7.14 (s,1H), 6.88 (s,1H), 3.78 (s,3H), 3.74 (s,3H), 3.17 (t,J=6.9Hz,2H), 2.88 (t,J=6.9Hz,2H)
2C-B freebase FTIR2: 1039, 1210, 1381 and 1491 cm-1.
![]() Mass Spectrum of 2C-B3 |