Water → 2-Hydroxy-5-trifluoromethylbenzaldehyde

Participants

Reaction Steps

Hexamethylenetetramine (47.5 g) was added portionwise to a stirred solution of 4-trifluoromethylphenol (50 g) in trifluoroacetic acid (680 ml) and the mixture was heated at reflux temperature for 24 hours. After cooling, water (355 ml) was added followed by aqueous sulphuric acid (50% v/v, 190 ml) and the reaction was stirred at ambient temperature for 4 hours. The acidic aqueous phase was extracted with diethyl ether (3×500 ml). The combined organic extracts were washed with hydrochloric acid (5M, 3×500 ml) then water (500 ml) and dried over magnesium sulphate. The solvent was removed under reduced pressure and the residue purified by column chromatography on silica eluting with a 4:1 mixture of petroleum ether (b.p. 40-60° C.) and ethyl acetate. The appropriate fractions were combined and the solvent removed under reduced pressure to give 5-trifluoromethyl-2-hydroxybenzaldehyde (25 g) as a light pink solid.

Provenance & Evidence