4-Bromoanisole → 4-(2-Methyl-1H-imidazol-1-YL)phenol

HRID 327650Notes

Reaction equation

HRID 327650 reaction equation
[CH3:1][C:2]1[NH:3][CH:4]=[CH:5][N:6]=1.Br[C:8]1[CH:13]=[CH:12][C:11]([O:14]C)=[CH:10][CH:9]=1.C(=O)([O-])[O-].[K+].[K+]>CN1CCCC1=O>[CH3:1][C:2]1[N:3]([C:8]2[CH:13]=[CH:12][C:11]([OH:14])=[CH:10][CH:9]=2)[CH:4]=[CH:5][N:6]=1

Participants

5

Reactant 3

HCID 77304-BromoanisoleHCID 11430Potassium CarbonateHCID 127492-Methylimidazole

Product 1

HCID 112522894-(2-Methyl-1H-imidazol-1-YL)phenolYield 28.6%

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

To a 3-neck, 1-liter, round-bottom flask was added 2-methylimidazole (41.0 g, 0.50 mole), 4-bromoanisole (100 g, 0.53 mole) and potassium carbonate (96.0 g, 0.70 mole) in N-methyl-2-pyrrolidinone (300 ml). A small amount of cuprous chloride (2.5 g) was added. The stirred reaction mixture was heated at reflux temperature for 24 hr and then the N-methyl-2-pyrrolidinone and excess bromoanisole gently distilled. The black pot residue was partitioned between toluene and water and a black solid removed by filtration. The toluene layer was extracted with 48% hydrobromic acid (2×200 ml) and the hydrobromic acid solution was heated at reflux temperature 3 hr then stirred at room temperature overnight. The solution was then concentrated, diluted with water (500 ml) and made basic with sodium hydroxide and sodium bicarbonate solutions. The white solid which precipitated was collected and cried and a small amount recrystallized from methanol/isopropyl alcohol. The total yield was 24.88g (28.6% yield), mp 205°-208° C.

Workup

  1. customThe stirred reaction mixture
  2. temperaturewas heated
  3. temperatureat reflux temperature for 24 hr
  4. distillationthe N-methyl-2-pyrrolidinone and excess bromoanisole gently distilled
  5. customThe black pot residue was partitioned between toluene and water
  6. customa black solid removed by filtration
  7. extractionThe toluene layer was extracted with 48% hydrobromic acid (2×200 ml)
  8. temperaturethe hydrobromic acid solution was heated
  9. temperatureat reflux temperature 3 hr
  10. concentrationThe solution was then concentrated
  11. additiondiluted with water (500 ml)
  12. customThe white solid which precipitated
  13. customwas collected
  14. customa small amount recrystallized from methanol/isopropyl alcohol

Sources & evidence

ORD record
ord-3bc743c2abe24214a723de24591bed5d
Source dataset
uspto-grants-1993_12
Patent number
US05273993

Reaction notes

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