Background and overview[1][2]
4-Bromo-2,3-dimethylanisole is an organic chemical intermediate, generally obtained by bromination of 2,3-dimethylanisole. The bromination reagent can be bromine or NBS. .
Preparation[1-2]
Method 1,
Add a solution of Br2 (5.3g, 33.2mmol) in CCl4 (15mL) to the intermediate 2,3-dimethylanisole (4.1 g, 30.2 mmol) in DCM (100 mL) and the resulting solution was stirred for 1 h. The reaction mixture was concentrated and purified by chromatography to give 1.7 g (26%) of the intermediate 4-bromo-2,3-dimethylanisole. 1HNMR (DMSO-d6): 7.33 (d, J = 8Hz, 1H), 6.58 (d, J = 8Hz, 1H), 3.78 (s, 3H) , 2.36 (s, 3H), 2.19 (s, 3H).
Method 2: Add NBS (18.7g, 105mmol) to a 5mL CH3CN solution of 2,3-dimethylanisole (13.6g, 100mmol) at 0°C. . After the reaction was stirred at room temperature for 3 hours, the solvent was evaporated under reduced pressure and CCl4 was added. The solid was filtered, washed with CCl4, and the solvent was removed. The yield was 98% and it was a colorless oil. 1H NMR (CDCl3, MHz) δ = 7.36 (d, J = 8.8Hz, 1H), 6.61 (d, J = 8.8Hz, 1H), 3.81 (s, 3H), 2.39 (s, 3H), 2.23 (s, 3H); 13C NMR (CDCl3 ,100MHz) δ= 156.6,136.8,129.6,127.0,116.3,109.3,55.6,19.8,12.8; FTIR (KBr, neat, cm-1): ν3336,2935,1572 ,1460,1260,1106,796,585;HRMS (ESIMS, m/z) calculated value C9H12BrO [M + H] + 215.0066, measured value 215.0062.
Apply[1]
4-Bromo-2,3-dimethylanisole can be used as an intermediate to synthesize other compounds. For example, the intermediate 4-bromo-2,3-dimethylanisole (1.5g, 7mmol ) dissolved in AcOH (9.2mL) andin H2O (1.6mL). After cooling at 5°C, fuming HNO3 (0.49 mL) in AcOH (3.6 mL) was added dropwise. The mixture was stirred at 5°C for 15 minutes, H2O was added, and the mixture was extracted with DCM. The organic layer was washed with H2O, dried (Na2SO4), concentrated, and chromatographed (EA/hexane) Purification yielded 1.2 g (66%) of intermediate 37C. Calculated value of LC[m/z] C9H10BrNO3: 259.0; found value: 259.0. Found 261.1 [M + H] +,
Main reference materials
[1] PCT Int. Appl., 2018045246, 08 Mar 2018
[2] Organic Letters, 16(7), 1996-1999; 2014
