Imidazole → Clotrimazole

HRID 1855871Notes

Reaction equation

HRID 1855871 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 76.8%

Reagents, catalysts & solvents 1

HCID 7909Methyl Isobutyl KetoneSolvent

Procedure

A mixture of methyl isobutyl ketone (150 ml), diphenyl phosphite (32.8 g), imidazole (13.6 g) and o-chlorophenyldiphenylmethanol (29.5 g) obtained in Example 1 (A) was refluxed for 4 hours. A 10% aqueous sodium hydroxide solution (250 ml) was added thereto and the resultant mixture was refluxed for 1 hour. After cooling to room temperature, the organic layer was separated, washed with water, and evaporated to give a crystalline mass. Recrystallization from methyl isobutyl ketone gave 26.5 g of 1-(o-chlorophenyldiphenylmethyl)imidazole. Yield, 77%. M.P., 142°-143° C.

Workup

  1. temperaturewas refluxed for 4 hours
  2. customthe organic layer was separated
  3. washwashed with water
  4. customevaporated
  5. customto give a crystalline mass
  6. customRecrystallization from methyl isobutyl ketone

Sources & evidence

ORD record
ord-5a571d45dfe0491386501cc0eb5bd547
Source dataset
uspto-grants-1980_08
Patent number
US04216333

Reaction notes

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