Phenol → 2-Fluoro-5-methoxyphenol

HRID 1684079Notes

Reaction equation

HRID 1684079 reaction equation
[C:1]1([OH:7])C=CC=CC=1.[F:8][C:9]1[CH:17]=[CH:16][CH:15]=[CH:14][C:10]=1NOC.S(=O)(=O)(O)[OH:19].N([O-])=O.[Na+].NC(N)=O>O>[F:8][C:9]1[CH:17]=[CH:16][C:15]([O:7][CH3:1])=[CH:14][C:10]=1[OH:19]

Participants

7

Reactant 5

HCID 996PhenolHCID 1118Sulfuric AcidHCID 1176UreaHCID 23668193Sodium NitriteHCID 569737372-Fluoro-methoxyaniline

Product 1

HCID 141189572-Fluoro-5-methoxyphenol

Reagents, catalysts & solvents 1

HCID 962WaterSolvent3×

Conditions

Temperature
150 °C

Procedure

The method used to prepare the phenol is basically the procedure reported by Claudi et. al. [med. Chem. 33, 2408-2412 (1990) with modification according to Lambooy [J. Amer. Chem. Soc. 72, 5327-5328 (1950)]. In a three-necked round-bottom flask (1000 mL), equipped with dropping-funnel and a magnetic stirrer, 2-fluoro-methoxyaniline (11.3 g, 80 mmol ), concentrated sulfuric acid (35 mL) and water (200 mL) were mixed and then cooled to 3°-5° C. A solution of sodium nitrite (6.07 g; 88 mmol) in water (20 mL) was added dropwise to the stirred mixture above at 2°-4° C. When the addition was completed the solution was stirred for five minutes and then urea (0.48 g) was added followed by water (100 mL). Meanwhile an apparatus was prepared consisting of a three-necked round-bottom flask (1000 mL), a thermometer, an electrical heating mantle, a steam distillation apparatus, and long (40 cm) water-jacketed condensor on top of which a 500 mL dropping funnel was attached. In the flask CuSO4 ×5H2O (56 g), concentrated sulfuric acid (160 mL) and water (160 mL) were placed. The mixture was heated to 150° C., the diazonium salt solution, cooled all the time by adding small chunks of the ice to it, was added dropwise from the dropping funnel, and a current of steam was passed through the system to remove the phenol. The distillate was extracted with ether (3×400 mL) and the combined ether extracts were dried (MgSO4), filtered and concentrated in vacuo. The crude phenol was purified on a silica column eluted with ether/n-hexane (15:85) to afford 4.03 g of the title compound as a crystalline solid. Mp. 25°-26° C.

Workup

  1. customIn a three-necked round-bottom flask (1000 mL), equipped with dropping-funnel and a magnetic stirrer
  2. temperaturecooled to 3°-5° C
  3. additionWhen the addition
  4. customMeanwhile an apparatus was prepared
  5. customconsisting of a three-necked round-bottom flask
  6. distillation(1000 mL), a thermometer, an electrical heating mantle, a steam distillation apparatus, and long (40 cm) water-jacketed condensor on top of which a 500 mL
  7. temperaturethe diazonium salt solution, cooled all the time
  8. additionby adding small chunks of the ice to it
  9. additionwas added dropwise from the dropping funnel
  10. customto remove the phenol
  11. extractionThe distillate was extracted with ether (3×400 mL)
  12. dry with materialthe combined ether extracts were dried (MgSO4)
  13. filtrationfiltered
  14. concentrationconcentrated in vacuo
  15. customThe crude phenol was purified on a silica column
  16. washeluted with ether/n-hexane (15:85)

Sources & evidence

ORD record
ord-ca39671fe94a47f69cc1bfb927a00954
Source dataset
uspto-grants-1997_06
Patent number
US05639772

Reaction notes

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