Imidazole → Clotrimazole

HRID 1855873Notes

Reaction equation

HRID 1855873 reaction equation
P([O-])(OC1C=CC=CC=1)OC1C=CC=CC=1.[NH:17]1[CH:21]=[CH:20][N:19]=[CH:18]1.[Cl:22][C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=1[C:29]([C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1)([C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1)O.[OH-].[Na+]>C(C(C)=O)C(C)C>[Cl:22][C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=1[C:29]([C:31]1[CH:32]=[CH:33][CH:34]=[CH:35][CH:36]=1)([C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1)[N:17]1[CH:21]=[CH:20][N:19]=[CH:18]1

Participants

6

Reactant 4

HCID 795ImidazoleHCID 14798Sodium HydroxideHCID 298659(2-Chlorophenyl)diphenylmethanolHCID 23418553Diphenoxyphosphanolate

Product 1

HCID 2812ClotrimazoleYield 100.1%

Reagents, catalysts & solvents 1

HCID 7909Methyl Isobutyl KetoneSolvent

Conditions

Temperature
85 °C

Procedure

A mixture of methyl isobutyl ketone (60 ml), diphenyl phosphite (13.1 g), imidazole (5.44 g) and o-chlorophenyldiphenylmethanol (11.78 g) obtained in Example 1 (B) was heated at 85° C. for 4 hours. To the reaction mixture, a 10% aqueous sodium hydroxide solution (110 g) was added, and the mixture was refluxed for 1 hour. After cooling to room temperature, the organic layer was separated, washed with water and concentrated to dryness under reduced pressure to give 13.8 g of 1-(o-chlorophenyldiphenylmethyl)imidazole. Yield, 100%. M.P., 138°-142° C. Recrystallization from methyl isobutyl ketone gave 12.3 g of the pure compound. Yield, 89%. M.P., 142°-143° C.

Workup

  1. temperaturethe mixture was refluxed for 1 hour
  2. temperatureAfter cooling to room temperature
  3. customthe organic layer was separated
  4. washwashed with water
  5. concentrationconcentrated to dryness under reduced pressure

Sources & evidence

ORD record
ord-3518856595a347a6b53d91badf1f63d2
Source dataset
uspto-grants-1980_08
Patent number
US04216333

Reaction notes

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