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A kind of preparation method of fenbendazole

A technology of fenbendazole and preparation process, applied in the field of preparation of fenbendazole, can solve the problem of high production cost, achieve the effects of reduced production cost, mild reaction conditions, and avoidance of the use of thiophenol

Active Publication Date: 2022-07-12
JIANGSU BAOZONG & BAODA PHARMACHEM
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

In the stage of the cyclization reaction, S-methylisothiourea formate or O-methyl isothiourea formate is currently used as the cyclizing agent, and the production cost is relatively high.

Method used

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  • A kind of preparation method of fenbendazole

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0016] (1) Preparation of methyl cyanamide formate aqueous solution

[0017] 44.0g of cyanamide aqueous solution was cooled to 0-5°C, and 10.93g of methyl chloroformate and 16.03g of sodium hydroxide solution (30%) were added dropwise under stirring. The material was dripped at the same time or the methyl chloroformate was dripped slightly earlier than the sodium hydroxide solution. After the dropwise addition of both materials, the mixture was stirred at 0-5° C. for 2 hours to obtain 70.91 g of an aqueous methyl cyanamide formate solution with a concentration of 14.0%, which was stored at about 0° C. for low temperature for later use.

[0018] (2) Intermediate 1 (2,4-dibromonitrobenzene)

[0019] Dissolve 24.5g m-dibromobenzene into 49.0g concentrated sulfuric acid (98%) at room temperature, cool to 0-5°C, add 9.80g nitric acid (68%) dropwise, and control the temperature at 0-5°C during the dropping process. After the addition was complete, stir at 5-10°C for 2 hours. Afte...

Embodiment 2

[0029] (1) Preparation of methyl cyanamide formate aqueous solution

[0030] 220.0g of cyanamide aqueous solution was cooled to 0-5°C, and 54.65g of methyl chloroformate and 80.15g of sodium hydroxide solution (30%) were added dropwise under stirring. The material was dripped at the same time or the methyl chloroformate was dripped slightly earlier than the sodium hydroxide solution. After the dropwise addition of both materials, the mixture was stirred at 0-5° C. for 2 hours to obtain 355.0 g of an aqueous methyl cyanamide formate solution with a concentration of 14.0%, which was stored at about 0° C. for low temperature for later use.

[0031] (2) Intermediate 1 (2,4-dibromonitrobenzene)

[0032] Dissolve 122.5g m-dibromobenzene into 245.0g concentrated sulfuric acid (98%) at room temperature, cool to 0-5°C, add 49.0g nitric acid (68%) dropwise, control the temperature during the dropwise addition at 0-5°C, dropwise After the addition was complete, stir at 5-10°C for 2 hou...

Embodiment 3

[0042] (1) Preparation of methyl cyanamide formate aqueous solution

[0043] 440.0g of cyanamide aqueous solution was cooled to 0-5°C, and 109.3g of methyl chloroformate and 160.3g of sodium hydroxide solution (30%) were added dropwise under stirring. The material was dripped at the same time or the methyl chloroformate was dripped slightly earlier than the sodium hydroxide solution. After the dropwise addition of both materials, the mixture was stirred at 0-5° C. for 2 hours to obtain 708.0 g of an aqueous methyl cyanamide formate solution with a concentration of 14.0%, which was stored at about 0° C. for low temperature for later use.

[0044] (2) Intermediate 1 (2,4-dibromonitrobenzene)

[0045] Dissolve 245.0g m-dibromobenzene into 490.0g concentrated sulfuric acid (98%) at room temperature, cool to 0-5°C, add 98.0g nitric acid (68%) dropwise, control the temperature in the dropping process at 0-5°C, dropwise After the addition was complete, stir at 5-10°C for 2 hours. ...

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Abstract

The invention discloses a preparation method of fenbendazole. It is characterized in that: (1) using m-dibromobenzene as a starting material, through nitric acid / sulfuric acid system nitration reaction, to prepare intermediate 1 (2,4-dibromonitrobenzene); (2) using intermediate 1 as a raw material , through the ammoniation reaction that ammonia methanol solution participates in, prepares intermediate 2 (5-bromo-2-nitroaniline); (3) takes intermediate 2 and sodium thiophenolate solution as raw materials, through condensation reaction, prepares Intermediate 3 (4-phenylthio-2-nitroaniline); (4) Intermediate 3 is subjected to palladium-carbon catalytic hydrogenation reduction to generate intermediate 4 (4-phenylthio-1,2-phenylenediamine) (5) Intermediate 4 and methyl cyanamide formate aqueous solution, through cyclization reaction, generate product fenbendazole. The method is clean and environmentally friendly, with low production cost, product purity of more than 99.5%, and yield of not less than 84.0%.

Description

technical field [0001] The invention relates to the preparation of fenbendazole and an intermediate thereof, in particular to a preparation method of fenbendazole. Background technique [0002] Fenbendazole, also known as benzimidazole, chemical name is 5-phenylthiobenzimidazole-2-carbamic acid methyl ester, is a benzimidazole anthelmintic. It not only has high anthelmintic activity on gastrointestinal nematodes adults and larvae, but also has good effects on reticulate nematodes, fasciola and tapeworms, and has a strong insecticidal egg effect. It has the advantages of maggot spectrum light, low toxicity, good tolerance, wide safety range and good palatability. [0003] At present, m-dichlorobenzene is often used as the starting material in the selection of synthetic routes at home and abroad, and liquid ammonia needs to be selected as the ammoniation reagent during the ammoniation reaction. The reaction pressure needs to be above 8.0 MPa, and the temperature needs to be a...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07D235/32
CPCC07D235/32Y02P20/584
Inventor 陈荣张智红林楠
Owner JIANGSU BAOZONG & BAODA PHARMACHEM
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