Formaldehyde → 1,5-Dimethyl-4-hydroxymethyl-2-(4-trifluoromethylphenyl)imidazole

HRID 22243Notes

Reaction equation

HRID 22243 reaction equation
[CH3:1][N:2]1[C:6]([CH3:7])=[CH:5][N:4]=[C:3]1[C:8]1[CH:13]=[CH:12][C:11]([C:14]([F:17])([F:16])[F:15])=[CH:10][CH:9]=1.C=O.[C:20]([O-])(=[O:22])C.[Na+].[OH-].[Na+]>C(O)(=O)C>[CH3:1][N:2]1[C:6]([CH3:7])=[C:5]([CH2:20][OH:22])[N:4]=[C:3]1[C:8]1[CH:9]=[CH:10][C:11]([C:14]([F:16])([F:17])[F:15])=[CH:12][CH:13]=1

Participants

6

Reactant 4

HCID 712FormaldehydeHCID 14798Sodium HydroxideHCID 517045Sodium AcetateHCID 194303261,5-Dimethyl-2-(4-trifluoromethylphenyl)imidazole

Product 1

HCID 194302591,5-Dimethyl-4-hydroxymethyl-2-(4-trifluoromethylphenyl)imidazoleYield 59.3%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

A mixture of 1,5-dimethyl-2-(4-trifluoromethylphenyl)imidazole (0.6 g), aqueous formaldehyde (3.5 ml of 36%), sodium acetate (0.6 g), and acetic acid (0.5 ml) was refluxed for 24 hours. The mixture was cooled, and concentrated sodium hydroxide added until the mixture was just: basic, keeping the temperature at about 10° C. The mixture was extracted with methylene chloride, and solvent removed from the organic layer under reduced pressure. The residue was flash-chromatographed on silica gel, eluting with methylene chloride containing methanol (97/3), to yield 0.4 g of 1,5-dimethyl-4-hydroxymethyl-2-(4-trifluoromethyl-phenyl)imidazole, m.p. 152° C.

Workup

  1. temperaturewas refluxed for 24 hours
  2. temperatureThe mixture was cooled
  3. customat about 10° C
  4. extractionThe mixture was extracted with methylene chloride, and solvent
  5. customremoved from the organic layer under reduced pressure
  6. customThe residue was flash-chromatographed on silica gel
  7. washeluting with methylene chloride
  8. additioncontaining methanol (97/3)

Sources & evidence

ORD record
ord-66da34ae437d4783b183ef9f520b5cba
Source dataset
uspto-grants-1995_06
Patent number
US05428037

Reaction notes

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