Ammonia → 5-[(1H-imidazol-1-yl)methyl]-2-nitrobenzeneamine

HRID 1091635Notes

Reaction equation

HRID 1091635 reaction equation
F[C:2]1[CH:3]=[C:4]([CH:11]=[CH:12][C:13]=1[N+:14]([O-:16])=[O:15])[CH2:5][N:6]1[CH:10]=[CH:9][N:8]=[CH:7]1.[NH3:17]>>[N:6]1([CH2:5][C:4]2[CH:11]=[CH:12][C:13]([N+:14]([O-:16])=[O:15])=[C:2]([NH2:17])[CH:3]=2)[CH:10]=[CH:9][N:8]=[CH:7]1

Participants

3

Reactant 2

HCID 222AmmoniaHCID 66593505HCID 66593505, compound

Product 1

HCID 665933535-[(1H-imidazol-1-yl)methyl]-2-nitrobenzeneamine

Conditions

Temperature
80 °C

Procedure

Potassium carbonate (1.18 g, 8.54 mmol) was added to a stirred solution of 4-(bromomethyl)-2-fluoro-1-nitrobenzene (2.0 g, 8.55 mmol) and imidazole (584 mg, 8.58 mmol) in acetonitrile (40 mL), the mixture stirred at room temperature for 3.5 h, the solvent removed under reduced pressure, and the residue partitioned between water and EA. The aqueous layer was extracted three times with EA, then the combined EA layers were extracted three times with 1M hydrochloric acid. The pH of the combined aqueous layers was adjusted to 8 with 5M aqueous sodium hydroxide, and the resulting milky solution was extracted three times with EA. The EA layers were combined, washed with brine, and dried over magnesium sulfate. Filtration and concentration gave 1-(3-fluoro-4-nitrobenzyl)-1H-imidazole (914 mg), which contained about 15% of a bis-alkylated imidazole byproduct. 1-(3-Fluoro-4-nitrobenzyl)-1H-imidazole (914 mg) was treated with an ethanolic ammonia solution (2M NH3, 55 mL) in a sealed tube heated to 80° C. for 2 days. After cooling, the solvent was removed to give 5-[(1H-imidazol-1-yl)methyl]-2-nitrobenzeneamine (1.0 g) as an orange solid. 5-[(1H-Imidazol-1-yl)methyl]-2-nitrobenzeneamine (1.0 g, 4.77 mmol) was dissolved in a 10% solution of dimethylformamide in ethanol (44 mL), and 10% palladium on carbon (130 mg, 0.12 mmol) was added. The solution was degassed and stirred under a hydrogen atmosphere using a balloon for 1 day. Following degassing, the solution was diluted with MeOH and filtered through diatomaceous earth, giving 4-[(1H-imidazol-1-yl)methyl]benzene-1,2-diamine (1.08 g) as a brown oil.

Workup

  1. temperatureAfter cooling
  2. customthe solvent was removed

Sources & evidence

ORD record
ord-f23df7871104488d996c59a33bdee4c6
Source dataset
uspto-grants-2012_03
Patent number
US08129396B2

Reaction notes

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