Chlorodifluoromethane → 3-Difluoromethoxy-4-methoxy-benzaldehyde

HRID 635832Notes

Reaction equation

HRID 635832 reaction equation
Cl[CH:2]([F:4])[F:3].[O:5]=[CH:6][C:7]1[CH:15]=[CH:14][C:11]([O:12][CH3:13])=[C:9]([OH:10])[CH:8]=1.[OH-].[Na+]>[Cl-].C([N+](C)(C)C)C1C=CC=CC=1.O1CCOCC1>[F:3][CH:2]([F:4])[O:10][C:9]1[CH:8]=[C:7]([CH:15]=[CH:14][C:11]=1[O:12][CH3:13])[CH:6]=[O:5]

Participants

6

Reactant 3

HCID 6372ChlorodifluoromethaneHCID 12127IsovanillinHCID 14798Sodium Hydroxide

Product 1

HCID 38668403-Difluoromethoxy-4-methoxy-benzaldehyde

Reagents, catalysts & solvents 2

HCID 5963Benzyltrimethylammonium chlorideCatalystHCID 312751,4-DioxaneSolvent

Procedure

With vigorous stirring, chlorodifluoromethane is introduced into a mixture of 200 g of isovanillin, 6.7 g of benzyltrimethylammonium chloride, 314 g of 50% strength aqueous sodium hydroxide solution and 2 l of dioxane for approximately 2 h. The mixture is subsequently partitioned between ice-water and ethyl acetate, the organic phase is separated off, the aqueous phase is extracted twice with ethyl acetate and the combined organic phases are dried over magnesium sulfate and concentrated under reduced pressure. To remove unreacted isovanillin, the oil is chromatographed over neutral silica gel using toluene. Evaporation of the eluate gives 249 g of 3-difluoromethoxy-4-methoxybenzaldehyde as an oil.

Workup

  1. customThe mixture is subsequently partitioned between ice-water and ethyl acetate
  2. customthe organic phase is separated off
  3. extractionthe aqueous phase is extracted twice with ethyl acetate
  4. dry with materialthe combined organic phases are dried over magnesium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customTo remove unreacted isovanillin
  7. customthe oil is chromatographed over neutral silica gel
  8. customEvaporation of the eluate

Sources & evidence

ORD record
ord-e0d9fd8c93de45e687e9307811c48182
Source dataset
uspto-grants-2001_02
Patent number
US06191138B1

Reaction notes

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