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A kind of preparation method of mebendazole

A technology of mebendazole and trichlorotoluene, applied in the field of drug synthesis, can solve the problems of harsh reaction conditions, many processing steps, dangerous processes, etc., and achieve strong development space and competitiveness, mild reaction conditions, and low industrialization difficulty. Effect

Active Publication Date: 2022-03-25
SHANDONG GUOBANG PHARMA +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

Although this method reduces the impurity content, the reaction conditions are harsh, the equipment has higher requirements, and the reaction time is longer, the processing steps are more, and the operation is complicated, which is still unsatisfactory.
[0006] Moreover, the preparation methods disclosed in the above-mentioned patents all focus on improving the existing process, and do not fundamentally solve the problems of long reaction process and dangerous process.

Method used

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  • A kind of preparation method of mebendazole
  • A kind of preparation method of mebendazole
  • A kind of preparation method of mebendazole

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0028] Such as figure 1 Shown, a kind of preparation method of mebendazole is specifically:

[0029] 1. Acylation reaction: Take 4.18g (0.0307mol) of zinc chloride and 4.05g (0.2251mol) of water, stir and dissolve to obtain an aqueous solution of zinc chloride, then take 40g (0.2046mol) of trichlorotoluene into a four-necked flask, Raise the temperature to 70°C, start adding zinc chloride aqueous solution dropwise, control the dropping time for 1h, keep the temperature at 70°C during the dropping, and continue the heat preservation reaction for 1h after the dropping, and after the reaction is completed, distill under reduced pressure to obtain 27.61g (0.1964mol ) Benzoyl chloride, the molar yield is 96.00%, and the gas phase detection purity is 100%.

[0030] 2. Friedel-Crafts reaction: Take 39.44g (0.2063mol) carbendazim, 80g (1.3322mol) acetic acid, 31.43g (0.2357mol) anhydrous aluminum chloride into the flask, stir and cool down to 15°C, add dropwise to prepare in step 1 ...

Embodiment 2

[0035] Such as figure 1 Shown, a kind of preparation method of mebendazole is specifically:

[0036] 1. Acylation reaction: Take 2.79g (0.0205mol) of zinc chloride and 4.05g (0.2251mol) of water, stir and dissolve to obtain an aqueous solution of zinc chloride, then take 40g (0.2046mol) of trichlorotoluene into a four-necked flask, Raise the temperature to 70°C, start adding zinc chloride aqueous solution dropwise, control the dropping time for 1h, keep the temperature at 70°C during the dropping, and continue the heat preservation reaction for 1h after the dropping, after the reaction is completed, distill under reduced pressure to obtain 24.58g (0.1748mol ) Benzoyl chloride, the molar yield is 85.44%, and the gas phase detection purity is 100%.

[0037] 2. Friedel-Crafts reaction: Take 35.10g (0.1836mol) carbendazim, 80g (1.3322mol) acetic acid, 27.97g (0.2098mol) anhydrous aluminum chloride into the flask, stir and cool down to 15°C, add dropwise to prepare in step 1 The ...

Embodiment 3

[0039] Such as figure 1 Shown, a kind of preparation method of mebendazole is specifically:

[0040] 1. Acylation reaction: Take 5.58g (0.0409mol) of zinc chloride and 4.05g (0.2251mol) of water, stir and dissolve to obtain an aqueous solution of zinc chloride, then take 40g (0.2046mol) of trichlorotoluene into a four-necked flask, Raise the temperature to 70°C, start adding zinc chloride aqueous solution dropwise, control the dropping time for 1h, keep the temperature at 70°C during the dropping, and continue the heat preservation reaction for 1h after the dropping, after the reaction is completed, distill under reduced pressure to obtain 26.68g (0.1898mol ) Benzoyl chloride, the molar yield is 92.74%, and the gas phase detection purity is 100%.

[0041] 2. Friedel-Crafts reaction: Take 38.10g (0.1993mol) carbendazim, 80g (1.3322mol) acetic acid, 30.36g (0.2277mol) anhydrous aluminum chloride into the flask, stir and cool down to 15°C, add dropwise to prepare in step 1 The ...

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Abstract

The invention discloses a method for preparing mebendazole, which belongs to the technical field of drug synthesis. The preparation method includes an acylation reaction and a Friedel-Crafts reaction; wherein, in the acylation reaction, trichlorotoluene is heated to 50-90° C. and then chlorinated Zinc aqueous solution, after the dropwise addition, carry out insulation reaction. After the reaction is completed, benzoyl chloride is obtained by distillation under reduced pressure; the Friedel-Crafts reaction is to cool down after mixing and stirring carbendazim, solvent, and anhydrous aluminum chloride, and then add benzoyl chloride dropwise. After the dropwise addition, continue to stir and insulate the reaction, then distill under reduced pressure to obtain the product mebendazole; the present invention abandons the traditional method of first Friedel-Crafts and then forming a ring, and uses carbendazim as a reactant to directly synthesize mebendazole. The yield is high, and compared with the traditional process, it has the characteristics of simple process, mild conditions and high atom utilization rate.

Description

technical field [0001] The invention belongs to the technical field of medicine synthesis, and in particular relates to a preparation method of mebendazole. Background technique [0002] Mebendazole is a white, off-white or slightly yellow crystalline powder, belonging to the class of benzimidazole carbamates. It is an anthelmintic drug synthesized and put into clinical practice in the 1980s. Intestinal worms such as tapeworms and strongyloides are effective, and have the characteristics of broad spectrum, high efficiency and high safety. [0003] The synthesis method of mebendazole mainly uses p-chlorobenzoic acid as raw material, and obtains mebendazole after a series of steps of nitration, Friedel-Crafts, ammoniation, reduction, and condensation. This process has many reaction steps, low yield, and only Reaching 49.77%, and involving dangerous processes such as nitrification, ammonification and reduction, the safety is poor, the approval is difficult, and the industriali...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07D235/32
CPCC07D235/32
Inventor 李琦斌李芳陈士刚刘嘉俊吴青华
Owner SHANDONG GUOBANG PHARMA
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