Hydrogen Peroxide → 3-Isopropyl-4-methoxyphenol

HRID 393389Notes

Reaction equation

HRID 393389 reaction equation
OC([C:7]1[CH:12]=[CH:11][C:10]([O:13][CH3:14])=[C:9]([CH:15]([CH3:17])[CH3:16])[CH:8]=1)S(O)(=O)=O.[Na].O.C1(C)C=CC(S(O)(=O)=[O:27])=CC=1.OO.S(S([O-])=O)([O-])=O.[Na+].[Na+]>CO>[CH:15]([C:9]1[CH:8]=[C:7]([OH:27])[CH:12]=[CH:11][C:10]=1[O:13][CH3:14])([CH3:17])[CH3:16]

Participants

7

Reactant 5

HCID 784Hydrogen Peroxide2×HCID 24489Sodium DithioniteHCID 521998p-Toluenesulfonic acid monohydrateHCID 5360545SodiumHCID 9900401Hydroxy-(3-isopropyl-4-methoxyphenyl)methanesulfonic acid

Product 1

HCID 113326753-Isopropyl-4-methoxyphenolYield 66.7%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A 22 L three-necked round bottom flask equipped with mechanical agitation was charged with hydroxy-(3-isopropyl-4-methoxyphenyl)methanesulfonic acid, sodium salt (1300 g, 4.61 moles), p-toluenesulfonic acid monohydrate (908 g, 4.77 moles), and methanol (10.4 L), and the mixture was cooled to 0° to 5° C. Hydrogen peroxide (30% aqueous, 1.625 L, 16.12 moles) was added slowly to the reaction mixture over about 2 h. The reaction mixture was stirred overnight and allowed to return to room temperature. The completeness of the reaction was assayed by HPLC; if the reaction was incomplete, further hydrogen peroxide was added to the reaction mixture. The reaction mixture was cooled once more to 0° to 5° C. and then quenched by addition of an aqueous slurry of sodium dithionite (1860 g, 10.68 moles, stirred 1 h at room temperature in 6.5 L deionized water). After stirring at least 0.5 h, the reaction mixture was filtered, and the white solids were washed with ethyl acetate (8 L). The ethyl acetate and the aqueous filtrate were combined, agitated, and allowed to separate. Cyclohexane was added if necessary to facilitate separation. The organic phase was washed with sodium bicarbonate (4 L, 10% aqueous solution), then with saturated aqueous sodium chloride solution (4 L). The solvent was removed by vacuum distillation to afford 3-isopropyl-4-methoxyphenol (510 g, 66.7%).

Workup

  1. customA 22 L three-necked round bottom flask equipped with mechanical agitation
  2. temperaturethe mixture was cooled to 0° to 5° C
  3. customto return to room temperature
  4. temperatureThe reaction mixture was cooled once more to 0° to 5° C.
  5. stirringAfter stirring at least 0.5 h
  6. filtrationthe reaction mixture was filtered
  7. washthe white solids were washed with ethyl acetate (8 L)
  8. stirringagitated
  9. customto separate
  10. additionCyclohexane was added if necessary
  11. customseparation
  12. washThe organic phase was washed with sodium bicarbonate (4 L, 10% aqueous solution)
  13. customThe solvent was removed by vacuum distillation

Sources & evidence

ORD record
ord-0620eafdee744790bbfa016fb198488e
Source dataset
uspto-grants-2004_10
Patent number
US06806381B2

Reaction notes

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