General procedure for the synthesis of 2,5-dimethylanisole from 2,5-dimethylphenol and dimethyl sulfate:
Step 1: 2,5-dimethylphenol (50 g, 410 mmol) and potassium carbonate (68 g, 490 mmol) were dissolved in acetone (600 mL) at room temperature, followed by the addition of dimethyl sulfate (31.02 g, 246 mmol). The reaction mixture was heated and refluxed for 9 h. The progress of the reaction was monitored by TLC and it was found that the starting material was still present. Dimethyl sulfate (31.02 g, 246 mmol) was added additionally and the reaction was continued to reflux for 9 hours. Upon completion of the reaction, the mixture was filtered and acetone was removed using a rotary evaporator. The resulting oil was stirred with 20% sodium hydroxide solution (100 mL) for 10 minutes. The organic layer was washed with water (2 x 500 mL) until the aqueous layer was neutral. The organic layer was dried over sodium sulfate and concentrated in vacuum to give 45.5 g of 2-methoxy-1,4-dimethylbenzene in 81% yield.
1H NMR (CDCl3) δ ppm: 2.2 (3H, s, CH3), 2.34 (3H, s, CH3), 3.82 (3H, s, OCH3), 6.65 (1H, s, Ar-H), 6.7 (1H, d, J = 7.2Hz, Ar-H), 7.03 (1H, d, J = 7.2Hz, Ar-H).
