Imidazole → 3-(1H-Imidazol-1-yl)phenol

HRID 1493953Notes

Reaction equation

HRID 1493953 reaction equation
[NH:1]1[CH:5]=[CH:4][N:3]=[CH:2]1.Br[C:7]1[CH:8]=[C:9]([O:13]C)[CH:10]=[CH:11][CH:12]=1.C(=O)([O-])[O-].[K+].[K+].C(OC(C)C)(C)C>CN1CCCC1=O.O.[OH-].[NH4+].C(O)C>[N:1]1([C:7]2[CH:8]=[C:9]([OH:13])[CH:10]=[CH:11][CH:12]=2)[CH:5]=[CH:4][N:3]=[CH:2]1

Participants

9

Reactant 4

HCID 795ImidazoleHCID 7914Diisopropyl EtherHCID 11430Potassium CarbonateHCID 169713-Bromoanisole

Product 1

HCID 104645913-(1H-Imidazol-1-yl)phenol

Reagents, catalysts & solvents 4

HCID 702EthanolSolventHCID 962WaterSolventHCID 13387N-methyl-2-pyrrolidoneSolventHCID 14923Ammonium HydroxideSolvent

Procedure

Imidazole (34 g, 0.5 mole), m-bromoanisole (51 ml, 0.4 mole), potassium carbonate (52 g), and cuprous chloride (2.4 g) in 300 ml N-methyl-2-pyrrolidone was heated at reflux for 4 hours. The cooled mixture was diluted with water and 100 ml concentrated ammonium hydroxide. The product was extracted into toluene-ethyl acetate (several times until TLC of aqueous layer showed only a trace amount of product). All the organic extracts were combined, filtered, extracted once with water and then three times with a total of 300 ml 48% hydrobromic acid. The hydrobromic acid extracts were combined and heated at reflux for 6 hours and then concentrated. The residue was redissolved in water and basified first with sodium hydroxide and at the end with sodium bicarbonate to get a final pH of 8. Some isopropyl ether was added to cause the product to crystallize. The solid was collected by filtration, washed with water, and dried at 80° C. in a vacuum oven to obtain 50.9 g (79.5% yield). A small portion of this solid was dissolved in absolute ethanol, filtered, concentrated, and recrystallized. The recrystallized material melted at 169°-170° C.

Workup

  1. temperatureat reflux for 4 hours
  2. extractionThe product was extracted into toluene-ethyl acetate (several times until TLC of aqueous layer
  3. filtrationfiltered
  4. extractionextracted once with water
  5. temperatureheated
  6. temperatureat reflux for 6 hours
  7. concentrationconcentrated
  8. dissolutionThe residue was redissolved in water and basified first with sodium hydroxide and at the end with sodium bicarbonate
  9. customto get a final pH of 8
  10. customto crystallize
  11. filtrationThe solid was collected by filtration
  12. washwashed with water
  13. customdried at 80° C. in a vacuum oven
  14. customto obtain 50.9 g (79.5% yield)
  15. filtrationfiltered
  16. concentrationconcentrated
  17. customrecrystallized

Sources & evidence

ORD record
ord-c5371ad37f1c4d269ff6247a8e7f2ee3
Source dataset
uspto-grants-1991_06
Patent number
US05025031

Reaction notes

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