p-Fluoronitrobenzene → 2-n-Butyl-4-chloro-1-(4-nitrophenyl)imidazole-5-carboxaldehyde

HRID 653946Notes

Reaction equation

HRID 653946 reaction equation
[CH2:1]([C:5]1[NH:6][C:7]([CH:11]=[O:12])=[C:8]([Cl:10])[N:9]=1)[CH2:2][CH2:3][CH3:4].C[O-].[Na+].F[C:17]1[CH:22]=[CH:21][C:20]([N+:23]([O-:25])=[O:24])=[CH:19][CH:18]=1>CO>[CH2:1]([C:5]1[N:6]([C:17]2[CH:22]=[CH:21][C:20]([N+:23]([O-:25])=[O:24])=[CH:19][CH:18]=2)[C:7]([CH:11]=[O:12])=[C:8]([Cl:10])[N:9]=1)[CH2:2][CH2:3][CH3:4]

Participants

5

Reactant 3

HCID 9590p-Fluoronitrobenzene2×HCID 10942334Sodium MethoxideHCID 178418251HCID 178418251, compound

Product 1

HCID 545349642-n-Butyl-4-chloro-1-(4-nitrophenyl)imidazole-5-carboxaldehydeYield 30%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
100 °C

Procedure

2-n-Butyl-4-chloroimidazole-5-carboxaldehyde (10.00 g, 53.6 mmol, 1 eq.) was dissolved in a freshly prepared solution of sodium methoxide (1.23 g Na, 53.6 mmol, 1 eq.) in methanol (175 mL). The methanol was removed in vacuo and replaced with DMF (100 mL). 4-Fluoro-1-nitrobenzene (11.37 mL, 107.0 mmol, 2 eq.) was then added. The mixture was heated at 100° C. for 36 h. Two more equivalents of 4-fluoro-1-nitrobenzene were then added and the mixture heated at 100° C. for an additional 48 hours. The DMF was removed in vacuo and the residue partitioned between ethyl acetate and water. The aqueous phase was extracted twice more with ethyl acetate, the organic layers combined, dried (MgSO4) and the solvent removed in vacuo. Flash chromatography of the residue over silica gel in 9:1 toluene/ethyl acetate yielded 4.92 g (30%) of an amber oil. NMR (CDCl3): δ 9.74 (s, 1); 8.42 (d, 2H, J=9Hz); 7.46 (d, 2H, J=9Hz); 2.51 (t, 2H, J=7Hz); 1.67 (t of t, 2H, J=7,7Hz); 1.30 (t of q, 2H, J=7,7Hz); 0.84 (t, 3H, J=7Hz). Anal. calcd. for C14H14ClN3O3 : C, 54.64; H, 4.59; Cl, 11.52, N, 13.65. Found: C, 54.91; H, 4.67; Cl, 11.20; N, 13.62.

Workup

  1. customThe methanol was removed in vacuo
  2. temperaturethe mixture heated at 100° C. for an additional 48 hours
  3. customThe DMF was removed in vacuo
  4. customthe residue partitioned between ethyl acetate and water
  5. extractionThe aqueous phase was extracted twice more with ethyl acetate
  6. dry with materialdried (MgSO4)
  7. customthe solvent removed in vacuo

Sources & evidence

ORD record
ord-d42bfbd65d8445559f2b79c3f7267520
Source dataset
uspto-grants-1992_07
Patent number
US05128355

Reaction notes

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