Preparation method of albendazole

Abstract

The invention discloses a preparation method of albendazole, which comprises the following steps of: dissolving 4-propylthio-o-phenylenediamine in methanol, cooling, keeping the temperature at 0-5 DEGC, slowly dropwise adding cyanogen chloride for reaction under the condition of uniform stirring, and regulating and keeping the pH value at 4-5 in the process; heating to 35-45 DEG C after dropwiseadding is finished, carrying out heat preservation for 1-2 hours, then carrying out atmospheric distillation to recover methanol to obtain a solid-liquid mixed aqueous solution, and carrying out cooling, filtering and drying to obtain 6-propylthio-2-amino-1-hydrogen-benzo [d] imidazole; adding the obtained product into methanol, stirring, cooling, maintaining the temperature at 5-10 DEG C, slowlydropwise adding methyl chloroformate, and adjusting and maintaining the pH value at 6-7; after dropwise adding is finished, heating to 35-45 DEG C, keeping the temperature for 1-2 hours, distilling atnormal pressure to recover methanol, cooling to 15-20 DEG C, and performing filtering and drying to obtain an albendazole product. The method has the advantages of mild process conditions, low cost of used raw materials, water saving, strong reaction activity, good selectivity, high product yield and good product quality.

Description

technical field [0001] The invention belongs to the technical field of organic chemical synthesis, in particular to a preparation method of albendazole, a veterinary drug and a pharmaceutical raw material drug. Background technique [0002] Albendazole, alias albendazole, prothiocarbendazim, anti-dementia, Changchongqing, etc., chemical name 5-propylthio-benzimidazole-2-carbamate methyl ester, its structural formula is: [0003] [0004] Albendazole was developed by Smith Kline Bichem Company (predecessor of GlaxoSmithKline). It is a broad-spectrum thiabendazole anthelmintic drug, which can be used for humans and animals, and can inhibit the growth of parasites. grow and reproduce. At present, the preparation route of albendazole mainly used at home and abroad is the process route reported in U.S. Patent US4152522. In the back-stage process of its product synthesis, 4-propylthio-2-nitroaniline is used to obtain 4-Propylthio o-phenylenediamine, finally cyclized with meth...

AI Technical Summary

Problems solved by technology

However, there are deficiencies in this method. Methyl cyanamide is one of the earliest cyclizing agents. Due to the instability of methyl cyanamide (generally stored in aqueous solution in the form of sodium salt), the cyclization conditions are not easy. Mastery, the yield and quality of the product are often unstable

In order to stabilize methyl cyanamide, a lower concentration of raw materials (10%) is often used, resulting in a large amount of wastewater generated during the production process

[0005] There is an attempt in the literature to use N-(methylcarbonyl) methyl carbaimidate for improvement, but it is difficult to remove impurities detected in the product

There is also an attempt to use S-methyl-N in the literature, N-di(methylcarbonyl) isothiourea as a cyclizing agent and in the patent CN201410567647.2, an attempt to use O-methylisourea formate as a cyclizing agent, although To a certain extent, it solves the disadvantages of methyl cyanamide, but the cost is still relatively high

[0006] Also have bibliography report, use cheap pesticide carbendazim, be starting raw material, undergo chlorosulfonation, reduction, three-step reaction of thioetherification to synthesize albendazole, reaction steps is few, easy and simple to operate, production cost is low, but yield The relative reduction (60%) has caused problems such as high pressure on the treatment of three wastes

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