Substituted benzimidazole, the production thereof and the use thereof as means against parasitic protozoa
A kind of benzimidazole, representative technology, is applied in the field of substituted benzimidazoles
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Embodiment 1
[0167] 3.3 g (10 mmol) of 4-bromo-2,6-di-trifluoromethylbenzimidazole was added to 100 ml of dichloromethane, and 1.73 ml (12.5 mmol) of triethylamine was added at 20°C. Then, 10 ml of dichloromethane containing 2.4 g (12.5 mmol) of 4-bromomethyl-5-methyl-1,3-dioxol-2-one was added dropwise at 20°C, and the mixture was refluxed for 24 hours . The dichloromethane solution was washed three times using 30 ml of water each time, dried over sodium sulfate and concentrated in vacuo. The residue was chromatographed on silica gel (35-70 μm) using cyclohexane / ethyl acetate (3:1). 1.5 g (34% of the theoretical yield) of the above compound was obtained. Melting point: 141-143°C.
[0168] Implement
Embodiment a
[0170] Add 1400g (6.7mol) of 2,3-tetrafluoro-1,4-benzodioxane and 7g (0.08mol) of FeS (powder), add dropwise at 20-30℃ in the course of about 4 hours 1190 g (7.4 mol) bromine, the mixture was stirred for about 20 hours until the end of gassing. Wash with aqueous sodium sulfite solution and dry over sodium sulfate. The residue is distilled in vacuum.
[0171] Yield: 1540 g (80% of theory), boiling point 10: 70-74°C (GC: 99%).
Embodiment b
[0173] Add 350g (1.2mol) 6-bromo-2,3-tetrafluoro-1,4-benzodioxane dropwise to 273ml (98% concentration) nitric acid and 293ml concentrated sulfuric acid at 20℃ within 75 minutes, the mixture Stir at 20°C for 1 hour and at 40°C for 3 hours. The batch was poured on ice, extracted with dichloromethane, the organic phase was washed with water and aqueous sodium bicarbonate solution and dried over sodium sulfate. The organic phase is evaporated and reacted further as a crude product.
[0174] Yield: 396 g (98% of theory), (crude product, GC: 99.1%), boiling point 16: 121-124°C, nD at 20°C: 1.5065.
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