Guaiacol → 4-Methoxy-1-methyl-2-phenoxybenzene

HRID 1416951Notes

Reaction equation

HRID 1416951 reaction equation
O[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[O:8][CH3:9].Br[C:11]1[CH:16]=[CH:15]C=[CH:13][CH:12]=1.[C:17]([O-:20])([O-])=O.[K+].[K+].N1C=CC=C[CH:24]=1>>[CH3:24][C:6]1[CH:5]=[CH:4][C:3]([O:8][CH3:9])=[CH:2][C:7]=1[O:20][C:17]1[CH:15]=[CH:16][CH:11]=[CH:12][CH:13]=1

Participants

5

Reactant 4

HCID 460GuaiacolHCID 1049PyridineHCID 7961Bromobenzene2×HCID 11430Potassium Carbonate

Product 1

HCID 537769894-Methoxy-1-methyl-2-phenoxybenzeneYield 51.7%

Conditions

Temperature
70 °C

Procedure

Into 50 mL pyridine, was added 4.14 g (30 mmoles) of the hydroxyanisole prepared above, 3.48 mL (33 mmoles) of bromobenzene, and 4.8 g (60 mmoles) of K2CO3. Under argon, the mixture was heated to 70° C., and 4.8 g (60 mmoles) of powdered CuO was added. The mixture was then heated for 16 hours at reflux with vigorous stirring. Additional CuO (4.8 g,60 mmoles) and bromobenzene (3.5 mL, 60 mmoles) were added, and the reaction mixture was heated 16 hours at reflux. After cooling and filtering, the reaction mixture was evaporated under vacuum. The residue was extracted between EtOAC and cold dilute HCl three times. The organic layer was dried over Na2SO4, filtered and evaporated under vacuum. The product was purified via silica gel flash chromatography (0 to 30% EtOAc in hexane), giving 3.32 g (51.7%) 4-methyl-3-phenoxyanisole as an oil.

Workup

  1. temperatureThe mixture was then heated for 16 hours
  2. temperatureat reflux with vigorous stirring
  3. temperaturethe reaction mixture was heated 16 hours
  4. temperatureat reflux
  5. temperatureAfter cooling
  6. filtrationfiltering
  7. customthe reaction mixture was evaporated under vacuum
  8. extractionThe residue was extracted between EtOAC and cold dilute HCl three times
  9. dry with materialThe organic layer was dried over Na2SO4
  10. filtrationfiltered
  11. customevaporated under vacuum
  12. customThe product was purified via silica gel flash chromatography (0 to 30% EtOAc in hexane)

Sources & evidence

ORD record
ord-6117db0522b249d0bdc4f03c6190eece
Source dataset
uspto-grants-1999_06
Patent number
US05916922

Reaction notes

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