Sulfuric Acid → 5-Fluoro-2-methylphenol

Participants

Reaction Conditions

Reaction Steps

7 mL of a hot solution of concentrated sulfuric acid in 21 mL of water was added to 5-fluoro-2-methylphenylamine (5 g, 40 mmol). The mixture was cooled in an ice bath for 30 minutes and treated with a solution of sodium nitrite (3.38 g, 48 mmol) in 10 mL of water over a period of 10 minutes. After stirring at 0° C. for 45 minutes, the reaction was diluted with 20 mL of cold water and treated with 0.3 g of urea. The resulting mixture was added to a stirred solution of 11 mL of concentrated sulfuric acid in 10 mL of water containing 15 g of anhydrous sodium sulfate at 130° C. over 10 minutes. After an additional 5 minutes at 130° C., the reaction was allowed to cool to room temperature and was extracted with three 100 mL portions of dichloromethane. The combined organic layers were washed with two 50 mL portions of water and concentrated in vacuo. The reddish oil was dissolved in 250 mL of diethyl ether and washed with three 50 mL portions of 10% aqueous sodium hydroxide. The combined aqueous sodium hydroxide extracts were washed with two 50 mL portions of diethyl ether. The basic layer was acidified with 1 N aqueous HCl and extracted with three 100 mL portions of dichloromethane. The combined dichloromethane layers were washed with two 50 mL portions of brine, dried over sodium sulfate, filtered, and concentrated in vacuo to give a light reddish liquid. The crude was purified by chromatography on SiO2 (10% ethyl acetate in hexanes) to give 5 g of 5-fluoro-2-methylphenol as a light brownish oil (99% yield).

Provenance & Evidence