At 0 °C, n-butyllithium (1.67 M hexane solution, 2.9 mL, 4.8 mmol) was slowly added dropwise to a solution of 1,3-dimethoxybenzene (0.55 g, 4.0 mmol) in tetrahydrofuran (5 mL). The reaction mixture was stirred continuously at 0 °C for 2 hours. Subsequently, N,N-dimethylformamide (0.34 mL, 4.4 mmol) was added to the mixture and stirring was continued for 2 hours at 0 °C. Upon completion of the reaction, ammonia solution (8 mL, 120 mmol) and iodine (1.12 g, 4.4 mmol) were added and the mixture was transferred to room temperature and stirred for 2 hours. The reaction mixture was quenched with saturated aqueous sodium sulfite solution (15 mL) and extracted several times with ether (3 x 20 mL). The organic layers were combined, washed with saturated saline and dried over anhydrous sodium sulfate to give the crude product 2,6-dimethoxybenzonitrile with a purity of over 80%. The crude product was purified by silica gel short-column chromatography (eluent: hexane/ethyl acetate=3:1) to afford pure 2,6-dimethoxybenzonitrile as a colorless solid in 91% yield.
