Hydrochloric Acid → 2-Hydroxy-5-trifluoromethylbenzonitrile

Participants

Reaction Steps

Bromine (15.9 ml) was added to a solution of 4-trifluoromethylphenol (50 g) in dichloromethane (300 ml) at room temperature and the mixture was stirred for 38 hours. The reaction mixture was successively washed with aqueous sodium bisulfite solution and saturated saline solution, dried over anhydrous magnesium sulfate, and the solvent was distilled off to obtain crude 2-bromo-4-trifluoromethylphenol (78.5 g) as oil. N,N-dimethylformamide (250 ml) was added to the crude product and copper cyanide (I) (27.6 g), and the mixture was heated to reflux for 2 hours under Ar. This hot reaction mixture was poured into a solution of ferric chloride hexahydrate (137.5 g) and hydrochloric acid (35 ml) in water (400 ml), and the mixture was stirred for 30 minutes. The mixture was extracted with ethyl acetate, and the ethyl acetate was successively washed with dilute hydrochloric acid and saturated saline solution, and dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure. The residue was purified by column chromatography on silica gel eluting with ethyl acetate/hexane to obtain 2-cyano-4-trifluoromethylphenol (34.6 g, mp. 149.5°-151° C.).

Provenance & Evidence