583-71-1

68-12-2

5724-56-1

22884-95-3

General method: n-Butyllithium (1.67 M hexane solution, 3.3 mL, 5.5 mmol) was slowly added dropwise to a tetrahydrofuran (THF, 5 mL) solution of 4-bromo-1,2-xylene (855 mg, 5.0 mmol) at -70 °C. After the dropwise addition was completed, the reaction mixture was kept stirred at -70 °C for 30 min. Subsequently, the reaction system was slowly warmed to 0 °C and stirring was continued for 5 min. Next, N,N-dimethylformamide (DMF, 0.43 mL, 5.5 mmol) was added to the reaction mixture and the reaction mixture was stirred at 0 °C. After 1 h, ammonia solution (10 mL, 150 mmol) and iodine (I2, 1.40 g, 5.5 mmol) were sequentially added to the reaction system and the reaction mixture was then transferred to room temperature and stirred for 2 h. The reaction was completed with the addition of saturated iminosilicate (I2, 1.40 g, 5.5 mmol). Upon completion of the reaction, the reaction was quenched with saturated aqueous sodium sulfite (Na2SO3) solution (15 mL), followed by extraction of the reaction mixture with ether (Et2O, 3 x 20 mL). The organic layers were combined, washed with saturated saline and dried over anhydrous sodium sulfate (Na2SO4). The solvent was removed by distillation under reduced pressure to give the crude product, 4-methylbenzyl cyanide, with a purity of more than 80%. The crude product was purified by silica gel short-column chromatography (eluent: hexane/ethyl acetate = 9:1) to give pure 4-methylbenzonitrile in 80% yield as a colorless solid.