Dichloromethane → Butoconazole

HRID 1864768

Reaction equation

HRID 1864768 reaction equation
[S:1](Cl)(Cl)=O.[Cl:5][C:6]1[CH:11]=[CH:10][C:9]([CH2:12][CH2:13][CH:14](O)[CH2:15][N:16]2[CH:20]=[CH:19][N:18]=[CH:17]2)=[CH:8][CH:7]=1.[Cl:22][C:23]1[CH:28]=C[C:26](CCC(Cl)CN2C=CN=C2)=[CH:25][CH:24]=1.Cl[CH2:40][Cl:41]>ClCCCl.CN(C)C=O.ClC1C=CC=CC=1.C1(C)C=CC=CC=1>[Cl:5][C:6]1[CH:11]=[CH:10][C:9]([CH2:12][CH2:13][CH:14]([S:1][C:28]2[C:23]([Cl:22])=[CH:24][CH:25]=[CH:26][C:40]=2[Cl:41])[CH2:15][N:16]2[CH:20]=[CH:19][N:18]=[CH:17]2)=[CH:8][CH:7]=1

Participants

9

Reactant 4

HCID 6344DichloromethaneHCID 24386Thionyl Chloride2×HCID 109559944-(4-chlorophenyl)-1-(1H-imidazol-1-yl)-2-butanol2×HCID 124320341-[2-Chloro-4-(4-chlorophenyl)butyl]-1H-imidazole3×

Product 1

HCID 47472Butoconazole

Reagents, catalysts & solvents 4

HCID 111,2-DichloroethaneSolventHCID 1140TolueneSolventHCID 6228DimethylformamideSolvent2×HCID 7964ChlorobenzeneSolvent

Procedure

Next we studied alternative solvents to replace the thionyl chloride in solvent function in the reaction step converting (1-[4-(4-chlorophenyl)-2-hydroxy-n-butyl]-imidazole) (IV) into (1-[4-(4-chlorophenyl)-2-chloro-n-butyl]-imidazole) (V). In the inert solvents which could be taken into account such as dichloromethane, toluene, chlorobenzene and dimethylformamide, the chlorinating reaction yielded a sticky reaction mixture which couldn't be processed. We have surprisingly found, however that when (1-[4-(4-chlorophenyl)-2-hydroxy-n-butyl]-imidazole) (IV) is dissolved in 1,2-dichloroethane and reacted with approximately equimolar amount of thionyl chloride reagent in the presence of catalytic amount of dimethylformamide at 30-35° C. temperature, a crystal suspension is obtained which is easy-to-stir during the whole reaction time, resulting in that chlorination proceeds completely giving 1-[4-(4-chlorophenyl)-2-chloro-n-butyl]-imidazole (V) in quantitative yield. Being the compound sufficiently pure, it is not isolated, but separated by extraction and reacted directly with 2,6-dichlorothiophenol in methyl isobutyl ketone to give 1-[4-(4-chlorophenyl)-2-(2,6-dichlorophenylthio)-n-butyl]-imidazole (VI) (butoconazole).

Workup

  1. customin the reaction step
  2. customthe chlorinating reaction
  3. customyielded a sticky reaction mixture which
  4. customa crystal suspension is obtained which
  5. customresulting in that chlorination
  6. customit is not isolated
  7. customseparated by extraction
  8. customreacted directly with 2,6-dichlorothiophenol in methyl isobutyl ketone

Sources & evidence

ORD record
ord-c1c5b990d21044a397fe45fdc4b93b5e
Source dataset
uspto-grants-2009_12
Patent number
US07625935B2

Linked notes

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