Methanol → 3-[3-(Trifluoromethyl)phenoxy]phenol

HRID 973896Notes

Reaction equation

HRID 973896 reaction equation
CO.[Na].[C:4]1([CH:11]=[CH:10][CH:9]=[C:7]([OH:8])[CH:6]=1)[OH:5].[F:12][C:13]([F:29])([F:28])[C:14]1[CH:15]=[C:16]([CH:25]=[CH:26][CH:27]=1)OC1C=C(Br)C=CC=1>N1C=CC=CC=1>[F:12][C:13]([F:29])([F:28])[C:14]1[CH:27]=[C:26]([CH:25]=[CH:16][CH:15]=1)[O:5][C:4]1[CH:6]=[C:7]([OH:8])[CH:9]=[CH:10][CH:11]=1

Participants

6

Reactant 4

HCID 887MethanolHCID 5054ResorcinolHCID 5360545SodiumHCID 10686936HCID 10686936, compound

Product 1

HCID 156677683-[3-(Trifluoromethyl)phenoxy]phenolYield 67.9%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

All apparatus is rigorously dried and flushed with nitrogen before use. The reaction is performed in a 500 mL 3-necked flask equipped with a mechanical stirrer, a reflux condenser topped with a nitrogen inlet tube and a stopper. The flask is charged with methanol (100 mL) and sodium (10.0 g, 0.43 mol). After all of the sodium has been consumed the methanol is distilled from the flask, and the last traces are removed by azeotropic distillation with benzene. Pyridine (250 mL) and resorcinol (35.0 g, 0.32 mol) are added to the reaction mixture, followed by 3-(3-trifluoromethyl phenoxy)bromobenzene (50.0 g, 0.22 mol) and cuprous chloride (20.0 g, 0.20 mol), and the mixture is left to stir at reflux for 24 hours. Capillary GC analysis shows that ca. 87% of the mixture is the desired monoalkylation product, the rest being dialkylation product. The mixture is cooled and filtered with the aid of ether (200 mL). The ethereal phase is washed successively with water (250 mL), 5% HCl (2×250 mL), saturated NaHCO3 (200 mL) and brine (200 mL). Then it is dried with MgSO4, and the solvents are removed on the rotary evaporator to leave 38 g of a dark oily residue. Purification is accomplished by fractional distillation in vacuo. The second fraction (distilling at 132° C. @ 1.5 mm) consisted of pure monoalkylation product (colorless oil, 25.20 g, 44.6% yield). The dialkylation product is not isolated.

Workup

  1. customAll apparatus is rigorously dried
  2. customflushed with nitrogen before use
  3. customThe reaction is performed in a 500 mL 3-necked flask
  4. customequipped with a mechanical stirrer, a reflux condenser
  5. customtopped with a nitrogen inlet tube
  6. customAfter all of the sodium has been consumed the methanol
  7. distillationis distilled from the flask
  8. customthe last traces are removed by azeotropic distillation with benzene
  9. waitthe mixture is left
  10. temperatureat reflux for 24 hours
  11. temperatureThe mixture is cooled
  12. filtrationfiltered with the aid of ether (200 mL)
  13. washThe ethereal phase is washed successively with water (250 mL), 5% HCl (2×250 mL), saturated NaHCO3 (200 mL) and brine (200 mL)
  14. dry with materialThen it is dried with MgSO4
  15. customthe solvents are removed on the rotary evaporator

Sources & evidence

ORD record
ord-cdd9e8cc8f0c41a5b8a49b23f0e05ecb
Source dataset
uspto-grants-1991_11
Patent number
US05066409

Reaction notes

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