Formaldehyde → 1H-Imidazole-5-methanol, 2-butyl-1-[(2-chlorophenyl)methyl]-

HRID 273831Notes

Reaction equation

HRID 273831 reaction equation
[CH2:1]([C:5]1[N:6]([CH2:10][C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=2[Cl:17])[CH:7]=[CH:8][N:9]=1)[CH2:2][CH2:3][CH3:4].C=O.[C:20]([O-])(=[O:22])C.[Na+]>C(O)(=O)C>[CH2:1]([C:5]1[N:6]([CH2:10][C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=2[Cl:17])[C:7]([CH2:20][OH:22])=[CH:8][N:9]=1)[CH2:2][CH2:3][CH3:4]

Participants

5

Reactant 3

HCID 712FormaldehydeHCID 517045Sodium AcetateHCID 103773571H-Imidazole, 2-butyl-1-[(2-chlorophenyl)methyl]-

Product 1

HCID 100164181H-Imidazole-5-methanol, 2-butyl-1-[(2-chlorophenyl)methyl]-Yield 41.1%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

A mixture of 2-n-butyl-1-(2-chlorophenyl)methyl-1H-imidazole (95.5 g, 0.384 mol), 37% formaldehyde (500 mL), sodium acetate (80 g) and acetic acid (60 mL) was heated to reflux for 40 hours under argon. The reaction was concentrated in vacuo, and the residue was stirred with 500 mL of 20% sodium hydroxide solution for 4 hours, diluted with water and extracted with methylene chloride. The extract was washed, dried, and concentrated. The crude product (117 g) was flash chromatographed over 600 g of silica gel with a gradient of ethyl acetate to 10% of methanol in ethyl acetate to give 8.3 g of starting material, 24.5 g of a mixture of starting material and product, and 44 g (41%) of 2-n-butyl-1-(2-chlorophenyl)methyl-5-hydroxymethyl-1H-imidazole; mp 86°-88° C. (from ethyl acetate). Further elution provided the bis (4,5-hydroxymethyl) derivative; mp 138°-140° C. (from ethyl acetate).

Workup

  1. temperaturewas heated
  2. temperatureto reflux for 40 hours under argon
  3. concentrationThe reaction was concentrated in vacuo
  4. additiondiluted with water
  5. extractionextracted with methylene chloride
  6. washThe extract was washed
  7. customdried
  8. concentrationconcentrated
  9. customchromatographed over 600 g of silica gel with a gradient of ethyl acetate to 10% of methanol in ethyl acetate

Sources & evidence

ORD record
ord-b1aa0d4b18c7406fb2832a51fcd7b34a
Source dataset
uspto-grants-1995_02
Patent number
US05387601

Reaction notes

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