Sulfuric Acid → 4-Fluoro-3-(trifluoromethyl)phenol

HRID 1834034Notes

Reaction equation

HRID 1834034 reaction equation
[F:1][C:2]1[CH:8]=[CH:7][C:5](N)=[CH:4][C:3]=1[C:9]([F:12])([F:11])[F:10].S(=O)(=O)(O)[OH:14].N([O-])=O.[Na+]>O>[F:1][C:2]1[CH:8]=[CH:7][C:5]([OH:14])=[CH:4][C:3]=1[C:9]([F:12])([F:11])[F:10]

Participants

5

Reactant 3

HCID 1118Sulfuric AcidHCID 753774-Fluoro-3-(trifluoromethyl)anilineHCID 23668193Sodium Nitrite

Product 1

HCID 6018544-Fluoro-3-(trifluoromethyl)phenolYield 52%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
65 °C

Procedure

70 g (0.39 mol) of 4-fluoro-3-trifluoromethylaniline, prepared according to G.C. Finger and colleagues, Journal of Med. Chem., 7, (1964), 572, are added a little at a time, while stirring, to 500 ml of a 2.5 N solution of sulphuric acid heated to a temperature of 65° C. The solution obtained is cooled to 0° C and 27 g of sodium nitrite dissolved in 45 ml of water are added whilst continuing the stirring and ensuring that the temperature does not exceed +5° C. After the end of the addition, the mixture is stirred for a further hour, during which it becomes perfectly clear. Thereafter, whilst carrying out a steam distillation, the cold solution of the diazonium salt is introduced dropwise into a mixture of 56g of copper sulphate, 21 g of urea, 70 ml of water and 2 ml of concentrated sulphuric acid. The speed of addition is regulated so that the phenol formed is immediately carried away. The distillate is cooled and is extracted repeatedly with ether. The ether solutions are combined and dried, the solvent is driven off and the residue is rectified. 37 g (yield: 52%) of 4-fluoro-3-trifluoromethyl-phenol, distilling at 84° C under 15 mm, are obtained.

Workup

  1. addition, 7, (1964), 572, are added a little at a time
  2. customThe solution obtained
  3. temperatureis cooled to 0° C
  4. additionare added
  5. customdoes not exceed +5° C
  6. additionAfter the end of the addition
  7. distillationa steam distillation
  8. additionthe cold solution of the diazonium salt is introduced dropwise into a mixture of 56g of copper sulphate, 21 g of urea, 70 ml of water and 2 ml of concentrated sulphuric acid
  9. additionThe speed of addition
  10. customformed
  11. temperatureThe distillate is cooled
  12. extractionis extracted repeatedly with ether
  13. customdried

Sources & evidence

ORD record
ord-6d9ba2edb46645a783bd249e5293bc9d
Source dataset
uspto-grants-1978_01
Patent number
US04067996

Reaction notes

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