Benzyl Chloride → 1-Benzyl-4-methyl-1H-benzimidazole

HRID 1926474Notes

Reaction equation

HRID 1926474 reaction equation
[CH3:1][C:2]1[C:10]2[N:9]=[CH:8][NH:7][C:6]=2[CH:5]=[CH:4][CH:3]=1.C(=O)([O-])[O-].[K+].[K+].[CH2:17](Cl)[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1>CN(C)C=O>[CH2:17]([N:7]1[C:6]2[CH:5]=[CH:4][CH:3]=[C:2]([CH3:1])[C:10]=2[N:9]=[CH:8]1)[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1

Participants

5

Reactant 3

HCID 7503Benzyl Chloride2×HCID 11430Potassium CarbonateHCID 15193414-Methylbenzimidazole

Product 1

HCID 149330241-Benzyl-4-methyl-1H-benzimidazole

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
6 °C

Procedure

To a flask were added 1.0 g 4-methyl-1H-benzimidazole, 1.6 g potassium carbonate, 25 ml N,N-dimethylformamide and the mixture was stirred under nitrogen. 1.4 g Benzyl chloride were added and the mixture was heated to 6° C. for 16 hours. Another 0.4 g of benzyl chloride were added and the reaction was heated to 70 C for 24 hours. The reaction was cooled to 50 C and quenched with 50 ml water and extracted with ethyl acetate. After washing with water, the solvent was removed and the product was purified by column chromatography using a gradient from 40% ethyl acetate in hexane to 75% ethyl acetate in hexane. Following removal of the solvent, the partially crystallized product was dissolved in 20 ml acetonitrile and treated with 0.1 g activated carbon. After refluxing for 20 minutes, the mixture was filtered through celite and the solvent was removed leaving a yellow oil which crystallized on standing, 1.0 g.

Workup

  1. temperaturethe reaction was heated to 70 C for 24 hours
  2. temperatureThe reaction was cooled to 50 C
  3. customquenched with 50 ml water
  4. extractionextracted with ethyl acetate
  5. washAfter washing with water
  6. customthe solvent was removed
  7. customthe product was purified by column chromatography
  8. customremoval of the solvent
  9. dissolutionthe partially crystallized product was dissolved in 20 ml acetonitrile
  10. additiontreated with 0.1 g
  11. temperatureAfter refluxing for 20 minutes
  12. filtrationthe mixture was filtered through celite
  13. customthe solvent was removed
  14. customleaving a yellow oil which
  15. customcrystallized

Sources & evidence

ORD record
ord-a414ecc3c475431b8c100d565e706580
Source dataset
uspto-grants-2012_05
Patent number
US08182718B2

Reaction notes

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