Synthesis method of 4-chloro-2-cyano benzene sulfonyl chloride

Abstract

The invention discloses a synthesis method of 4-chloro-2-cyano benzene sulfonyl chloride. The method comprises the following steps: reacting 2-fluoro-5-chloro benzonitrile with sodium sulfide nonahydrate to generate an intermediate 1; oxidizing the intermediate 1 with sodium hypochlorite to generate an intermediate 2; and reacting the intermediate 2 with thionyl chloride to generate 4-chloro-2-cyano benzene sulfonyl chloride. According to the synthetic route of 4-chloro-2-cyano benzene sulfonyl chloride, provided by the invention, a diazotization reaction is avoided, and the production safety is improved; the used raw materials are simple and low in toxicity, and only a small amount of waste water containing nitrogen and acetic acid can be generated; and the reaction only comprises three steps, the reaction time and post-treatment time of each step are short, the post-treatment is simple, the manufacturing cost is low, and the method is beneficial for industrial production.

Description

technical field [0001] The invention belongs to the technical field of organic synthesis, and in particular relates to a synthesis method of 4-chloro-2-cyanobenzenesulfonyl chloride. Background technique [0002] The document [CN201880075992.0] reports that the inventors have discovered a series of sulfonamide compounds with excellent ribonucleotide reductase inhibitory activity, as crystalline forms such as co-crystals and / or as salt forms, with low electrostatic It exists in a non-hygroscopic form, and its properties are stable. These sulfonamide compounds are potent and selective inhibitors of ribonucleotide reductase and can be used as antineoplastic or therapeutic agents in the treatment of other diseases associated with ribonucleotide reductase, 4-chloro-2 -Cyanobenzenesulfonyl chloride is an important intermediate for the synthesis of the above-mentioned sulfonamide compounds. [0003] Up to now, this intermediate has not been reported in the literature on the same ...

AI Technical Summary

Problems solved by technology

The diazotization reaction is a type of dangerous reaction in chemical production, which is prone to safety production accidents, and in pharmaceutical products, the diazotization reaction is a type of reaction that introduces genotoxic impurities (for example, the diazotization reaction can produce hydrazine The impurity R-N=N-R of the structure, this structure is the warning structure that produces genotoxicity, and pharmaceutical products need to pay close attention to), increased the workload of drug research process, so research provides a kind of can avoid diazotization reaction and synthesize 4-chloro The safe industrialized production method of -2-cyanobenzenesulfonyl chloride seems particularly urgent

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