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Synthesis method of 3-(halogenated phenoxy) benzene sulfonyl chloride derivative

A technology of benzenesulfonyl chloride derivatives and halogenated phenoxy groups, which is applied in the field of synthesis of 3-benzenesulfonyl chloride derivatives, can solve the problems of polluted environment, high corrosion, high toxicity of benzenesulfonyl chloride reagents, etc., and achieves reaction selection High performance, strong operability, and the effect of reducing synthesis cost

Pending Publication Date: 2021-10-29
上海毕得医药科技股份有限公司
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  • Abstract
  • Description
  • Claims
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Problems solved by technology

[0005] In order to solve the problems of high toxicity, high corrosion and high environmental pollution of reagents used in the existing 3-(halogenated phenoxy) benzenesulfonyl chloride derivative synthesis technology, the invention provides a 3-(halogenated phenoxy ) Synthetic method of benzenesulfonyl chloride derivatives, the synthetic method has simple steps, cheap and easy-to-obtain raw materials, mild reaction conditions, and environmental protection

Method used

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  • Synthesis method of 3-(halogenated phenoxy) benzene sulfonyl chloride derivative
  • Synthesis method of 3-(halogenated phenoxy) benzene sulfonyl chloride derivative
  • Synthesis method of 3-(halogenated phenoxy) benzene sulfonyl chloride derivative

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preparation example Construction

[0048] The synthetic method of 3-(halogenated phenoxy) benzenesulfonyl chloride derivatives of the present invention comprises: cheap and easy-to-get p-halogenoiodobenzene compound and m-hydroxyaniline are raw materials, carry out Ullmann method in the presence of copper catalyst and ligand Coupling reaction obtains halogenated 3-phenoxyaniline intermediate, which, under the action of diazo reagent, reacts with sodium thiosulfate and benzyl chloride to realize benzyl thiolation to obtain benzyl (3-(4 -Chlorophenoxy)phenyl)sulfane intermediate, and finally treated with oxidative chlorination reagent to obtain the target compound.

[0049] A kind of synthetic method of 3-(halogenated phenoxy group) benzenesulfonyl chloride derivative, its synthetic route is as shown in formula (I):

[0050]

[0051] Wherein, X is fluorine, chlorine or bromine.

[0052] The synthetic method of described 3-(halogenated phenoxy) benzenesulfonyl chloride derivatives comprises the following steps...

Embodiment 1-17

[0082] Embodiments 1-17 describe the present invention in further detail through the synthesis of 3-(4-chlorophenoxy)benzene-1-sulfonyl chloride, which includes the following steps:

[0083] The first step: the preparation of compound 33-(4-chlorophenoxy)aniline;

[0084] The second step: the preparation of compound 41-(4-chlorophenoxy)-3-iodobenzene;

[0085] The third step: the preparation of compound 53-(4-chlorophenoxy)benzene-1-sulfonyl chloride.

Embodiment 1

[0087] The preparation of step (1) 3-(4-chlorophenoxy)aniline, its synthetic route is as follows:

[0088]

[0089]2,9-diphenyl-1,10-phenanthroline (2.77g, 8.34mmol, 0.1eq), p-chloroiodobenzene (20g, 83.40mmol, 1.0eq), m-hydroxyaniline (10.98g, 100.60mmol , 1.2eq), join in the dimethylsulfoxide of 170ml, then add tripotassium phosphate (35.6g, 167.7mmol, 2.0eq), then add copper powder (0.25g, 167.7mmol, 0.05eq), inert gas protection, React overnight at 80°C. The reaction was monitored by TLC until the reaction was complete, washed into ice water, extracted with ethyl acetate, mixed and passed through the column to obtain 15.19 g of compound 3 with a yield of 81.41% and a purity of 98.21%.

[0090] The preparation of step (2) 1-(4-chlorophenoxy group)-3-iodobenzene, its synthetic route is as follows:

[0091]

[0092] Sodium thiosulfate pentahydrate (118.62g, 477.96mmol, 7eq), benzyl chloride (60.5g, 477.96mmol, 7eq), anhydrous copper sulfate (1.09g, 6.83mmol, 0.1eq), 2...

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Abstract

The invention discloses a synthesis method of a 3-(halogenated phenoxy) benzene sulfonyl chloride derivative. The synthesis method comprises the following steps of: by taking a p-halogen iodobenzene compound and m-hydroxyaniline which are cheap and easy to obtain as raw materials, carrying out Ullmann coupling reaction in the presence of a copper catalyst and a ligand to obtain halogenated 3-phenoxy aniline; making the intermediate react with sodium thiosulfate and benzyl chloride under the action of a diazo reagent to realize benzyl sulfhydrylation to obtain benzyl (3-(4-chlorophenoxy) phenyl) sulfane; and finally treating the benzyl (3-(4-chlorophenoxy) phenyl) sulfane by using an oxidation chlorination reagent to obtain a target compound. According to the method of the invention, through optimal design of a synthesis route, the synthesis cost of the route is reduced while the synthesis steps are shortened; and in the reaction, the operability is strong, the reaction selectivity is high, high-toxicity, high-corrosivity and high-environment-staining reagents are not used, so that the method is more suitable for large-scale expanded production.

Description

technical field [0001] The invention relates to the field of pharmaceutical intermediates, in particular to a method for synthesizing 3-(halophenoxy)benzenesulfonyl chloride derivatives. Background technique [0002] 3-(halogenated phenoxy) benzenesulfonyl chloride derivatives, which have both aryl ether and sulfonyl chloride structures, can be used as intermediate building blocks for inhibitors of matrix metalloproteinases, and can be used to treat And related diseases, such as tissue ulcers, periodontal disease and aortic aneurysm disease. [0003] In the prior art, the synthesis of 3-(halogenated phenoxy)benzenesulfonyl chloride derivatives is generally sulfonated first and then chlorinated, so strong acids and strong oxidizing reagents such as chlorosulfonic acid and thionyl chloride are used , the reaction is not conducive to environmental protection, and at the same time, it is highly corrosive to the experimental equipment, and the synthesis method is cumbersome to o...

Claims

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Application Information

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IPC IPC(8): C07C303/16C07C309/87
CPCC07C213/06C07C319/14C07C303/16C07C217/90C07C323/20C07C309/87Y02P20/55
Inventor 王治国周永加郦荣浩罗春艳
Owner 上海毕得医药科技股份有限公司
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