Hexamethylenetetramine → Methyl 4-formyl-3-hydroxybenzoate

HRID 491837Notes

Reaction equation

HRID 491837 reaction equation
[OH:1][C:2]1[CH:3]=[C:4]([CH:9]=[CH:10][CH:11]=1)[C:5]([O:7][CH3:8])=[O:6].C1N2CN3CN(C2)CN1C3.FC(F)(F)[C:24](O)=[O:25]>>[CH:24]([C:3]1[C:2]([OH:1])=[CH:11][CH:10]=[CH:9][C:4]=1[C:5]([O:7][CH3:8])=[O:6])=[O:25].[CH:24]([C:11]1[CH:10]=[CH:9][C:4]([C:5]([O:7][CH3:8])=[O:6])=[CH:3][C:2]=1[OH:1])=[O:25]

Participants

5

Reactant 3

HCID 4101HexamethylenetetramineHCID 6422Trifluoroacetic acidHCID 88068Methyl 3-Hydroxybenzoate

Product 2

HCID 14395860Methyl 4-formyl-3-hydroxybenzoateHCID 14774772Methyl 2-formyl-3-hydroxybenzoate

Procedure

Methyl 3-hydroxybenzoate (75.5 g) is dissolved in trifluoroacetic acid (2 L), thereto is added hexamethylenetetramine (141.4 g) at room temperature and the mixture is heated under reflux for 3 hours. The reaction solution is concentrated under reduced pressure, to the resulting residue is added water, the mixture is adjusted to pH 8 with potassium carbonate and sodium hydrogen carbonate, diluted with water and extracted with ethyl acetate. The organic layer is washed with saturated brine, dried over sodium sulfate and evaporated to remove the solvent under reduced pressure. The resulting residue is purified by silica gel column chromatography (eluent: hexane/ethyl acetate=8/1, 5/1 followed by 2/1) to give methyl 2-formyl-3-hydroxybenzoate (54.6 g) (ESI-MS m/z: 179[M−H]−) and methyl 4-formyl-3-hydroxybenzoate (4.4 g)

Workup

  1. temperaturethe mixture is heated
  2. temperatureunder reflux for 3 hours
  3. concentrationThe reaction solution is concentrated under reduced pressure, to the resulting residue
  4. additionis added water
  5. additiondiluted with water
  6. extractionextracted with ethyl acetate
  7. washThe organic layer is washed with saturated brine
  8. dry with materialdried over sodium sulfate
  9. customevaporated
  10. customto remove the solvent under reduced pressure
  11. customThe resulting residue is purified by silica gel column chromatography (eluent: hexane/ethyl acetate=8/1, 5/1 followed by 2/1)

Sources & evidence

ORD record
ord-05772cf270ab4c9ca8e5e42e4124fd47
Source dataset
uspto-grants-2009_05
Patent number
US07531537B2

Reaction notes

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