A kind of synthetic method of mebendazole medicine intermediate o-chloroaniline

Abstract

The invention discloses a mebendazole drug intermediate o-chloroaniline synthesis method. The method is free of an additive. The method comprises that a sodium bromide solution and neodymium chloride undergo a reaction, a 2, 2, 2-trifluoroethylmethyl ether solution and o-nitrochlorobenzene are added into the reaction product and undergo a reflux reaction, an oxalic acid solution is added into the reaction product and undergo a reaction, the reaction product is cooled, filtered and repeatedly washed, and the washed product is subjected to reduced pressure distillation in a nitrogen protective atmosphere and re-crystallization so that o-chloroaniline crystals are produced. The whole reaction time can be controlled in 8h and a yield is high. The invention provides a novel synthesis route and lays a good basis for further improving a reaction yield.

Description

technical field [0001] The invention relates to a method for preparing a pharmaceutical intermediate, which belongs to the field of organic synthesis, and in particular to a method for synthesizing o-chloroaniline, a drug intermediate of mebendazole. Background technique [0002] Mebendazole is a derivative of benzimidazole. This type of drug has a strong affinity for the β-tubulin of the worm body, and can bind to it at a very low concentration, thereby inhibiting the polymerization of microtubules and causing the epidermis of the worm body. Or the disappearance of intestinal cells, reducing digestion and reducing the absorption of nutrients such as glucose, leading to the death of the parasite. The drug can also inhibit fumarate reductase in mitochondria, reduce glucose transport, and uncouple oxidative phosphorylation, thereby affecting ATP production. Both in vivo and in vitro tests have proved that it can directly inhibit the intake of glucose by nematodes, leading to ...

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Problems solved by technology

[0003] Luo Xiongjun (Luo Xiongjun, Yan Xinhuan, Sun Junqing, Wang Wenjing, Yang Jianfeng. Study on Amorphous Pd-B / Al_2O_3 Catalyst for Hydrogenation of o-Chloronitrobenzene to Synthesis of O-Chloroaniline[J]. Journal of Chemical Engineering of Universities, 2006,03:476 -480.) The Pd-B / Al2O3 amorphous catalyst was prepared by chemical reduction method, and it was used for the liquid-phase hydrogenation reaction of o-chloronitrobenzene to synthesize o-chloroaniline. Although the yield of this synthesis method is very high, it can reach 99%. , but during the preparation of the catalyst, the raw materials need to be soaked overnight, the reaction time is very long, reaching more than 18 hours, and the dehalogenation rate is 2%, which still needs to be improved

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