Methanol → 1-Phenyl-1H-imidazole-4-carboxylic acid

HRID 1093807Notes

Reaction equation

HRID 1093807 reaction equation
O[Li].O.C[O:5][C:6]([C:8]1[N:9]=[CH:10][N:11]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[CH:12]=1)=[O:7].CO.O>C1COCC1>[C:13]1([N:11]2[CH:12]=[C:8]([C:6]([OH:7])=[O:5])[N:9]=[CH:10]2)[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=1

Participants

6

Reactant 4

HCID 887MethanolHCID 962WaterHCID 168937Lithium hydroxide, monohydrateHCID 10750619Methyl 1-phenyl-1H-imidazole-4-carboxylate

Product 1

HCID 234450471-Phenyl-1H-imidazole-4-carboxylic acidYield 87%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A stirred solution of 1H-imidazole-4-carboxylic acid (0.5 g, 0.00446 mmol), concentrated sulfuric acid (0.5 mL) and MeOH (20 mL) was heated to reflux overnight. The reaction mixture was concentrated under reduced pressure. The residue was diluted with cold water, extracted with ethyl acetate and washed the organic layer with sodium bicarbonate. The organic layer was dried over sodium sulfate and concentrated under reduced pressure to afford 325 mg (58% Yield) of 1H-imidazole-4-carboxylic acid methyl ester. A mixture of 1H-imidazole-4-carboxylic acid methyl ester (225 mg, 1.8 mmol), cuprous oxide (225 mg, 1.8 mmol), iodobenzene (736 mg, 3.6 mmol), 1,10-phenanthroline (320 mg, 1.8 mmol) and cesium carbonate (1.74 g, 5.3 mmol) in DMSO (2 mL) in a seal tube was subjected to reaction in a microwave reactor (time: 5 min, temp: 90° C., power: zero) The reaction mixture was filtered through celite and the filtrate collected was concentrated under reduced pressure. The residue was diluted with cold water, extracted with ethyl acetate, dried over sodium sulfate and concentrated under reduced pressure to afford the residue. Purification by column chromatography (using 60-120 silica gel and 50% ethyl acetate in hexane as eluent) to afford 200 mg (55% Yield) of 1-phenyl-1H-imidazole-4-carboxylic acid methyl ester. LiOH.H2O (143 mg, 3.4 mmol) was added to a stirred solution of 1-phenyl-1H-imidazole-4-carboxylic acid methyl ester (231 mg, 1.1 mmol) in a mixture of THF (3 mL), MeOH (1 mL), H2O (1 mL) and stirring was continued at ambient temperature for 3 hrs. The reaction mixture was concentrated under reduced pressure. Cold water was then added and acidified it with 10% aqueous HCl, the solid was collected to afford 180 mg (83.7% Yield) of 1-phenyl-1H-imidazole-4-carboxylic acid.

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. additionCold water was then added
  3. customthe solid was collected

Sources & evidence

ORD record
ord-20777e4cc94b4ab387008243d837325d
Source dataset
uspto-grants-2012_03
Patent number
US08129376B2

Reaction notes

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