Formaldehyde → Benzoic acid, 3-formyl-4-hydroxy-, methyl ester

HRID 419301Notes

Reaction equation

HRID 419301 reaction equation
[OH:1][C:2]1[CH:11]=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[CH:4][CH:3]=1.[Cl-].[Mg+2].[Cl-].[CH2:15]=[O:16]>C(#N)C>[CH:15]([C:11]1[CH:10]=[C:5]([CH:4]=[CH:3][C:2]=1[OH:1])[C:6]([O:8][CH3:9])=[O:7])=[O:16]

Participants

5

Reactant 3

HCID 712FormaldehydeHCID 7456MethylparabenHCID 5360315Magnesium Chloride

Product 1

HCID 212595Benzoic acid, 3-formyl-4-hydroxy-, methyl esterYield 58%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

Methyl 4-hydroxybenzoate (3.00 g, 19.7 mmol) and magnesium chloride (2.81 g, 29.5 mmol) were stirred in 100 mL of acetonitrile. TEA (10.3 mL, 73.9 mmol) was added via syringe. Paraformaldehyde (12.0 g, 133 mmol) was added in a single portion and the reaction was heated to reflux. The reaction was stirred at reflux for 24 hours and cooled to rt. The reaction was quenched by the addition of approximately 100 mL of 1N HCl and poured into EtOAc. The layers were separated, and the organic layer was washed with brine. The combined aqueous layers were extracted with EtOAc. The combined organic layers were dried over MgSO4, filtered, and concentrated in vacuo. The crude product was purified by flash chromatography. The clean fractions (by TLC) were concentrated in vacuo to afford 2.06 g (58%) of the desired product. 1H NMR (400 MHz, DMSO-d6): δ 11.54 (s, 1H), 10.27 (s, 1H), 8.21 (d, J=2.4 Hz, 1H), 8.03 (dd, J=8.8, 2.4 Hz, 1H), 7.07 (d, J=8.8 Hz, 1H), 3.79 (s, 3H).

Workup

  1. temperaturethe reaction was heated to reflux
  2. temperatureat reflux for 24 hours
  3. customThe reaction was quenched by the addition of approximately 100 mL of 1N HCl
  4. additionpoured into EtOAc
  5. customThe layers were separated
  6. washthe organic layer was washed with brine
  7. extractionThe combined aqueous layers were extracted with EtOAc
  8. dry with materialThe combined organic layers were dried over MgSO4
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customThe crude product was purified by flash chromatography
  12. concentrationThe clean fractions (by TLC) were concentrated in vacuo

Sources & evidence

ORD record
ord-4328506a50644f84bcc64273818ca09d
Source dataset
uspto-grants-2012_01
Patent number
US08093239B2

Reaction notes

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