Ethylvanillin → 3-Ethoxy-4-hydroxybenzoic acid

HRID 1990858Notes

Reaction equation

HRID 1990858 reaction equation
[OH-:1].[Na+].[CH2:3]([O:5][C:6]1[CH:7]=[C:8]([CH:11]=[CH:12][C:13]=1[OH:14])[CH:9]=[O:10])[CH3:4]>O.[N+]([O-])([O-])=O.[Ag+]>[CH2:3]([O:5][C:6]1[CH:7]=[C:8]([CH:11]=[CH:12][C:13]=1[OH:14])[C:9]([OH:1])=[O:10])[CH3:4]

Participants

5

Reactant 2

HCID 8467EthylvanillinHCID 14798Sodium Hydroxide2×

Product 1

HCID 950853-Ethoxy-4-hydroxybenzoic acidYield 27%

Reagents, catalysts & solvents 2

HCID 24470Silver NitrateCatalystHCID 962WaterSolvent

Procedure

A solution of silver nitrate (45.0 g, 265.0 mmol, 1.0 equiv) in water (230 mL) was treated with NaOH (10.6 g, 265 mmol, 1.0 equiv) and stirred for 20 min at rt. The formed precipitate was filtered off, washed with water (3×200 mL) and directly suspended in water (260 mL). To this suspension was added 3-ethoxy-4-hydroxy-benzaldehyde (20.0 g, 120.4 mmol, 0.45 equiv) and NaOH (26.5 g, 662.5 mmol, 2.5 equiv) the reaction mixture heated to reflux for 2 h. The reaction mixture was filtered, acidified to pH 2 by addition of sulfuric acid and the solution extracted with ethyl acetate (3×100 mL). The combined organic phases were dried over MgSO4, the solvent removed by evaporation under reduced pressure and the crude material purified over a plug of silica eluting with dichloromethane/methanol/acetic acid (97:2:1) to give 5.8 g (27%) of the title compound. 1H NMR (300 MHz, DMSO): δ 1.32 (t, J=7.0 Hz, 3H), 4.04 (q, J=7.0 Hz, 2H), 6.88 (d, J=8.0 Hz, 1H), 7.46 (s, 1H), 7.48 (d, J=8.0 Hz, 1H), 9.67 (br s, 1H), 12.42 (br s, 1H). 13C NMR (75 MHz, DMSO): δ 14.52, 63.93, 114.09, 115.11, 121.68, 123.49, 146.29, 151.32, 167.22. MS (ISN): 181.0 [M−H]−.

Workup

  1. filtrationThe formed precipitate was filtered off
  2. washwashed with water (3×200 mL)
  3. temperatureheated
  4. temperatureto reflux for 2 h
  5. filtrationThe reaction mixture was filtered
  6. additionacidified to pH 2 by addition of sulfuric acid
  7. extractionthe solution extracted with ethyl acetate (3×100 mL)
  8. dry with materialThe combined organic phases were dried over MgSO4
  9. customthe solvent removed by evaporation under reduced pressure
  10. customthe crude material purified over a plug of silica eluting with dichloromethane/methanol/acetic acid (97:2:1)

Sources & evidence

ORD record
ord-50a0fb3867604fbcb8f86d172a04ca1b
Source dataset
uspto-grants-2010_01
Patent number
US07645753B2

Reaction notes

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