Synthesis method of triphenyl-4-(trifluoromethylbenzamide)butylphosphonium chloride and application of triphenyl-4-(trifluoromethylbenzamide)butylphosphonium chloride in antitumor drugs

Abstract

The invention relates to a synthesis method of triphenyl-4-(trifluoromethylbenzamide)butylphosphonium chloride and an application of triphenyl-4-(trifluoromethylbenzamide)butylphosphonium chloride inantitumor drugs, and belongs to the technical field of organic synthesis. The method comprises the following steps: taking o-trifluoromethylaniline, m-trifluoromethylaniline and p-trifluoromethylaniline as raw materials, chloroform as a solvent and sodium carbonate, triethylamine, pyridine and the like as an acid binding agent to be subjected to reaction with 4-chlorobutyryl chloride so as to obtain a first-grade product, and performing reflux on the obtained first-grade product and triphenylphosphine in the solvent to obtain the final product trifluoromethylbenzamide triphenyl quaternary phosphonium salt. The target product is not limited by the types of the acid binding agents and solvents, and defects of harsh synthesis conditions, uneasy control and low purity of the synthesized product in the prior art are overcome; besides, the step-by-step elution procedure is introduced into purification of the final product, the selected specific eluent ensures purity of the final product. Theraw materials are widely sourced, cheap and easily available, and the prepared quaternary phosphonium salt compound is low in toxicity and efficient, and triphenyl-4-(trifluoromethylbenzamide)butylphosphonium chloride can be applied to preparation of the antitumor drugs.

Description

technical field [0001] The invention belongs to the technical field of organic synthesis, and relates to the synthesis and application of a fluorine-containing phosphorus nitrogen compound (FPN). More specifically, the invention relates to a chlorinated triphenyl-4-(trifluoromethylbenzamide ) Synthetic method of butylphosphonium and its application in antineoplastic drugs. Background technique [0002] Malignant tumor is a common and frequently-occurring disease that seriously threatens human health. More than 7 million people die from malignant tumors every year in the world. Cancer is becoming the number one killer of human beings. Due to the characteristics of tumor cell proliferation and metastasis, radiotherapy, chemotherapy, and surgical treatment cannot achieve the goal of radical cure, and chemotherapy techniques generally have problems such as individual differences, side effects, and drug dependence, and the therapeutic effect has always reached Therefore, it is...

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Problems solved by technology

In 2007, Xiao Chunfen, Zhou Li, Kui Lanhua, and Lou Zhaowen published a basic research achievement "Synthesis and Characterization of Several Triphenyl-substituted Alkyl Quaternary Phosphonium Salts", using phenol as raw material and chloroalkanoyl chloride as linking group Synthesized 4 phenoxycarbonyl alkyl triphenyl quaternary phosphonium salts, but due to the cytotoxicity of the raw material phenol and the low purity of the obtained quaternary phosphonium salts, it is not suitable for use in antitumor drugs. In addition, the synthesis disclosed in this article The method needs to strictly control the reaction temperature at 0-5°C, and the synthesis conditions are harsh and difficult to control. Therefore, the method needs to be further optimized and improved.

But this synthetic method all has higher selectivity to the kind of acid-binding agent and solvent, and experimental result shows can not obtain expected reaction product without sodium carbonate, and the product purity of making is still not high

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