2-FLUORO-6-HYDROXYBENZONITRILE

94088-46-7

140675-43-0

General procedure for the synthesis of 2-fluoro-6-hydroxybenzonitrile from 2-fluoro-6-methoxybenzonitrile: 1. 151 g (1 mol) of 2-fluoro-6-methoxybenzonitrile and 346.5 g (3 mol) of aqueous pyridinium solution were added to a 2 liter flask. Hydrogen chloride gas was slowly passed into the flask under a protective atmosphere. 2. The reaction mixture was slowly heated to 190 °C and stirred at this temperature for 5 hours. 3. Upon completion of the reaction, the mixture was cooled to room temperature overnight with slow stirring. 4. 1000 ml of water was added to the cooled mixture, and the mixture was heated to 80 °C. 5. 1000 ml of methyl tert-butyl ether was added and mixed thoroughly to separate the organic and aqueous phases. The aqueous phase was back-extracted twice with 500 ml of methyl tert-butyl ether. 6. Combine all the methyl tert-butyl ether phases and wash once with 800 ml of 10% aqueous sodium hydroxide and once with 400 ml of water. 7. Combine the two aqueous phases and adjust the pH to 2 with concentrated hydrochloric acid, then extract three times with 500 ml of dichloromethane. 8. The organic phases were combined and washed once with 10% hydrochloric acid. 9. The organic phases were dried with anhydrous sodium sulfate. 10. Finally, the solvent was removed by distillation under vacuum to give 120 g (87% yield) of 2-fluoro-6-hydroxybenzonitrile with >99% purity, and the product was confirmed by GC and 1H NMR (D6-dimethylsulfoxide, δ=6.85 ppm (m,2H,aryl H), 7.55 ppm (q,1H,aryl H), 11.7 ppm (s,1H,OH)) structure.