Imidazole → Bifonazole

HRID 2216952Notes

Reaction equation

HRID 2216952 reaction equation
[NH:1]1[CH:5]=[CH:4][N:3]=[CH:2]1.S(Cl)(Cl)=O.S(C1NC=CN=1)(C1NC=CN=1)=O.[C:22]1([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1.[C:34]1([CH2:40]O)[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1>C(#N)C>[CH:25]1[CH:24]=[CH:23][C:22]([C:28]2[CH:29]=[CH:30][C:31]([CH:40]([N:1]3[CH:2]=[N:3][CH:4]=[CH:5]3)[C:34]3[CH:35]=[CH:36][CH:37]=[CH:38][CH:39]=3)=[CH:32][CH:33]=2)=[CH:27][CH:26]=1

Participants

6

Reactant 4

HCID 795ImidazoleHCID 24386Thionyl ChlorideHCID 21946057ThionyldiimidazoleHCID 21946058Biphenyl phenyl-carbinol

Product 1

HCID 2378BifonazoleYield 56%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

The second and third stage of synthesis consists of making imidazole react with thionyl chloride, using acetonitrile as solvent; the operation is performed at 10° C. To the resulting thionylbisimidazole solution, biphenyl-phenyl-carbinol is added in a 1:4 molar relation to the thionyl. After fifteen hours at room temperature, the solvent is removed by vacuum distillation. The remaining is dissolved in chloroform and washed with water, the organic phase is dried over sodium sulfate; after filtering, the solvent is vacuum distilled. The resulting solid is purified by recrystallization in acetonitrile. Bifonazole is obtained in 56% yield in relation to the theoretical.

Workup

  1. customThe second and third stage of synthesis
  2. customis performed at 10° C
  3. waitAfter fifteen hours at room temperature
  4. customthe solvent is removed by vacuum distillation
  5. dissolutionThe remaining is dissolved in chloroform
  6. washwashed with water
  7. dry with materialthe organic phase is dried over sodium sulfate
  8. filtrationafter filtering
  9. distillationdistilled
  10. customThe resulting solid is purified by recrystallization in acetonitrile

Sources & evidence

ORD record
ord-f0a60934002844bb9e6a83d537e80381
Source dataset
uspto-grants-2006_09
Patent number
US07112681B2

Reaction notes

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