Hydrochloric Acid → 2-Hydroxy-5-trifluoromethylbenzonitrile

HRID 326581Notes

Reaction equation

HRID 326581 reaction equation
BrBr.[F:3][C:4]([F:13])([F:12])[C:5]1[CH:10]=[CH:9][C:8]([OH:11])=[CH:7][CH:6]=1.[Cu](C#N)[C:15]#[N:16].Cl>ClCCl.O.CN(C)C=O>[C:15]([C:7]1[CH:6]=[C:5]([C:4]([F:12])([F:13])[F:3])[CH:10]=[CH:9][C:8]=1[OH:11])#[N:16]

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 24408BromineHCID 678744-(Trifluoromethyl)phenolHCID 178418260HCID 178418260, compound

Product 1

HCID 107262312-Hydroxy-5-trifluoromethylbenzonitrileYield 77.4%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

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.).

Workup

  1. washThe reaction mixture was successively washed with aqueous sodium bisulfite solution and saturated saline solution
  2. dry with materialdried over anhydrous magnesium sulfate
  3. distillationthe solvent was distilled off
  4. customto obtain crude 2-bromo-4-trifluoromethylphenol (78.5 g) as oil
  5. temperaturethe mixture was heated
  6. temperatureto reflux for 2 hours under Ar
  7. stirringthe mixture was stirred for 30 minutes
  8. extractionThe mixture was extracted with ethyl acetate
  9. washthe ethyl acetate was successively washed with dilute hydrochloric acid and saturated saline solution
  10. dry with materialdried over anhydrous magnesium sulfate
  11. distillationThe solvent was distilled off under reduced pressure
  12. customThe residue was purified by column chromatography on silica gel eluting with ethyl acetate/hexane

Sources & evidence

ORD record
ord-c17fbb12054940a89931d2daa176ac1d
Source dataset
uspto-grants-1993_12
Patent number
US05270308

Reaction notes

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