Methyl iodide → 1-methyl-4-phenyl-1H-imidazole

HRID 252626Notes

Reaction equation

HRID 252626 reaction equation
[H-].[Na+].[CH2:3]1COCC1.[C:8]1([C:14]2[N:15]=[CH:16][NH:17][CH:18]=2)[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1.CI>ClCCl>[CH3:3][N:17]1[CH:18]=[C:14]([C:8]2[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=2)[N:15]=[CH:16]1.[CH3:3][N:15]1[C:14]([C:8]2[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=2)=[CH:18][N:17]=[CH:16]1

Participants

7

Reactant 4

HCID 6328Methyl iodideHCID 8028TetrahydrofuranHCID 24758Sodium hydrideHCID 178418822HCID 178418822, compound

Product 2

HCID 27487821-methyl-4-phenyl-1H-imidazoleHCID 37463431-Methyl-5-phenyl-1H-imidazole

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a slurry of sodium hydride, 60% in mineral oil (1.2 g, 31 mmol) in 100 mL anhyd. THF at 0° C. was added 4-phenylimidazole (4.00 g, 28 mmol) in small portions under nitrogen. Upon complete addition, the reaction was homogeneous and orange. After 10 min, methyl iodide (2.1 ml, 33 mmol) was added and the reaction was allowed to warm to ambient temperature. After 2 h, the reaction was quenched with 10 mL water and concentrated in vacuo. The resulting liquid was partitioned between water/brine and DCM. The aqueous layer was extracted with DCM (4×). The combined organic extracts were dried over anhyd sodium sulfate, filtered, and concentrated in vacuo to give an orange solid. This was dissolved in dichloromethane and purified by silica gel chromatography, 120 g, 60 min, 0-50% 90/10 DCM/MeOH in DCM, to give 1-methyl-4-phenyl-1H-imidazole and 1-methyl-5-phenyl-1H-imidazole as off-white solids.

Workup

  1. additionUpon complete addition
  2. waitAfter 2 h
  3. customthe reaction was quenched with 10 mL water
  4. concentrationconcentrated in vacuo
  5. customThe resulting liquid was partitioned between water/brine and DCM
  6. extractionThe aqueous layer was extracted with DCM (4×)
  7. dry with materialThe combined organic extracts were dried over anhyd sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customto give an orange solid
  11. custompurified by silica gel chromatography, 120 g, 60 min, 0-50% 90/10 DCM/MeOH in DCM

Sources & evidence

ORD record
ord-63c9de5a516346e4b0c2d93c810b0c16
Source dataset
uspto-grants-2011_01
Patent number
US07868177B2

Reaction notes

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