Formaldehyde → 2-Hydroxy-3,5-dimethylbenzaldehyde

HRID 854922Notes

Reaction equation

HRID 854922 reaction equation
[CH3:1][C:2]1[CH:7]=[C:6]([CH3:8])[CH:5]=[CH:4][C:3]=1[OH:9].CN(P(N(C)C)(N(C)C)=O)C.[CH2:21]=[O:22]>C1(C)C=CC=CC=1.C([Mg]Br)C>[OH:22][C:21]1[C:2]([CH3:1])=[CH:7][C:6]([CH3:8])=[CH:5][C:4]=1[CH:3]=[O:9]

Participants

6

Reactant 3

HCID 712FormaldehydeHCID 77712,4-DimethylphenolHCID 12679Hexamethylphosphoramide

Product 1

HCID 47702452-Hydroxy-3,5-dimethylbenzaldehydeYield 59%

Reagents, catalysts & solvents 2

HCID 178418443HCID 178418443, compoundCatalystHCID 1140TolueneSolvent

Procedure

To a solution of 2,4-dimethylphenol (24.9 g, 204 mmole) in anhydrous toluene (75 mL) at 0° C. was added HMPA (35 mL) and then a solution of ethylmagnesium bromide (61 mL-3 M in ethyl ether, 0.183 mmole), keeping the temperature <10° C. Then paraformaldehyde (13 g, 0.43 mole) was added and the cooling was removed. The ethyl ether was removed by distillation and the mixture was refluxed. The mixture was quenched with 10% HCl and EtOAc was added. The EtOAc solution was washed twice with H2O, twice with aqueous NH4Cl, dried over Na2SO4 and concentrated in vacuo. Purification by silica chromatography (98:2 hexanes:EtOAc) gave 17.9 g (59% yield) of the product as a yellow oil: ESHRMS m/z 147.0619 (M−H, C9H9O2, Calc'd 147.0603).

Workup

  1. customthe temperature <10° C
  2. customthe cooling was removed
  3. customThe ethyl ether was removed by distillation
  4. temperaturethe mixture was refluxed
  5. customThe mixture was quenched with 10% HCl and EtOAc
  6. additionwas added
  7. washThe EtOAc solution was washed twice with H2O, twice with aqueous NH4Cl
  8. dry with materialdried over Na2SO4
  9. concentrationconcentrated in vacuo
  10. customPurification by silica chromatography (98:2 hexanes:EtOAc)

Sources & evidence

ORD record
ord-2be9918480ce4678a5dcc36bf1bc4998
Source dataset
uspto-grants-2007_08
Patent number
US07259266B2

Reaction notes

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