- Preparation method of flubendazole
-
The invention relates to a preparation method of flubendazole. The preparation method comprises the following steps: dropwise adding thionyl chloride into a reaction system taking 4-chloro-3-nitrobenzoic acid and o-dichlorobenzene as solvents, wherein DMF (Dimethyl Formamide) is used as a reaction catalyst; then dropwise adding an acylated reaction solution into a fluorobenzene and aluminum trichloride system and carrying out Friedel-Crafts reaction; adding ammonia water, methane and a Friedel-Crafts product into a closed reactor for carrying out amination reaction; adding aminate, the methaneand a palladium carbon catalyst into a high-pressure hydrogenation reactor for reducing; adding a cyclization agent into a reduced reaction solution from which a catalyst is removed for cyclizing; finally, dropwise adding hydrogen peroxide into the cyclized reaction solution for oxidizing. The preparation method disclosed by the invention has the advantages that firstly, during cyclization reaction, an intermediate has an passivation action of carbonyl, so that the cyclization reaction is smoother and reaction time is greatly shortened; secondly, nitro is reduced by adopting a hydroreductionmethod which has better economic and environment-friendly properties compared with a traditional sulfuration alkaline method; thirdly, the cyclization agent adopts lower-price methyl cyanocarbamate,so that production cost is reduced.
- -
-
-
- Synthesis and anthelminthic acitivity of alkyl-(5-acyl-1-benzimidazol-2-yl) carbamates
-
A series of alkyl-(5-acyl-l-H-benzimidazol-2-yl)-carbamates were prepared and screened for anthelminthic activity. Some of them were found to be fully active at low, atoxic oral dose levels against gastro-intestinal nematodes. The activity against Syphacia muris and Strongyloides ratta is indicated. From these studies methyl (5-benzoyl-1-H-benzimidazol-2-yl) carbamate (mebendazole) and methyl [5-(4-fluorobenzoyl)-1-H-benzimidazol-2-yl]carbamate (flubendazole) were selected for detailed investigation.
- Raeymackers,Van Gelder,Roevens,Janssen
-
p. 586 - 594
(2007/10/05)
-