阅读说明：本技术 一种α-甲亚砜基甲酯类化合物及其制备方法 (α -methyl sulfoxide methyl ester compound and preparation method thereof ) 是由 徐翔民 王慧 李宾杰 贾磊 宋新 仝蓓蓓 张孝彦 张豫徽 牛聪 曹永睇 张宏祥 于 2020-04-11 设计创作，主要内容包括：本发明公开了一种α-甲亚砜基甲酯类化合物及其制备方法,将具有结构(I)的芳基卤溶解在结构(II)的二甲亚砜溶剂中,向上述混合物中加入钯碳催化剂及碱,再通入二氧化碳加压加热反应即可得到具有结构(III)的α-甲亚砜基甲酯类化合物：<Image he="128" wi="538" file="DEST_PATH_IMAGE001.GIF" imgContent="drawing" imgFormat="GIF" orientation="portrait" inline="no"></Image>本发明公开的合成方法首次以二甲亚砜同时作为硫源和溶剂,在零价钯的催化下发生氧化加成、配体交换、还原消除、异构化等过程通过在加热即可实现目标物的构建。此方法涉及的反应成本低、条件相对温和、操作简便。(The invention discloses an α -methyl sulfoxide methyl ester compound and a preparation method thereof, aryl halide with a structure (I) is dissolved in a dimethyl sulfoxide solvent with a structure (II), a palladium-carbon catalyst and alkali are added into the mixture, and carbon dioxide is introduced for pressurized heating reaction to obtain the α -methyl sulfoxide methyl ester compound with a structure (III): the synthesis method disclosed by the invention can realize the construction of the target object by taking dimethyl sulfoxide as a sulfur source and a solvent at the same time and carrying out processes of oxidation addition, ligand exchange, reduction elimination, isomerization and the like under the catalysis of zero-valent palladium and heating. The method has the advantages of low reaction cost, relatively mild conditions and simple operation.)

1. An α -methylsulfonyl methyl ester compound is characterized by having the following structure:

r is hydrogen, 3-nitro, 2-nitro, 4-trifluoromethyl, 4-chlorine, 4-fluorine, 4-methyl, 2-methyl, 3-methoxyl, 4-cyano, 4-acetamido or 4-acetyl.

2. The method for preparing α -methylsulfonyl methyl ester compounds according to claim 1, wherein aryl halide with the structure (I) is dissolved in dimethyl sulfoxide solvent with the structure (II), palladium carbon catalyst and alkali are added into the mixture, and carbon dioxide is introduced to carry out pressurized heating reaction to obtain α -methylsulfonyl methyl ester compounds with the structure (III):

。

3. the preparation method of α -methylsulfonylmethyl ester compound as claimed in claim 2, wherein X is bromine or iodine.

4. The method for preparing α -methylsulfonylmethyl ester compound as claimed in claim 2, wherein the base is potassium phosphate, sodium carbonate, cesium carbonate, potassium tert-butoxide, sodium hydroxide or sodium ethoxide.

5. The preparation method of α -methylsulfonylmethyl ester compound as claimed in claim 2, wherein the molar ratio of aryl halide to palladium-carbon catalyst is 20: 1-10: 1.

6. The preparation method of α -methylsulfonylmethyl ester compound as claimed in claim 2, wherein the reaction temperature is 110%^oC—140^oC。

7. The preparation method of α -methylsulfonylmethyl ester compound as claimed in claim 2, wherein the pressure of the carbon dioxide is 10-15 atm.

Technical Field

The invention particularly relates to an α -methyl sulfoxide methyl ester compound and a preparation method thereof, and relates to the field of chemical synthesis.

Background

α -methyl sulfoxide methyl ester compounds are special sulfur and ester compounds containing dominant groups of sulfoxide groups, have unique biological and chemical activities, and can be used as potential lead medical compounds, some reports have been reported to synthesize thioether and sulfone compounds by using dimethyl sulfoxide as a sulfur source (org. L ett. 2010, 12, 1644; chem. Commun.2012, 48, 7513; chem. Commun. 2017, 53, 5346; org. L ett. 2017, 19, 5798), and no method is disclosed for synthesizing α -methyl sulfoxide methyl ester compounds at present.

Disclosure of Invention

In order to overcome the defects in the prior art, the invention provides a method for synthesizing α -methyl sulfoxide methyl ester compound smoothly under the action of alkaline additive by using palladium-carbon as catalyst and cheap aryl halide, carbon dioxide and dimethyl sulfoxide as raw materials.

The purpose of the invention is realized as follows:

an α -methylsulfonyl methyl ester compound is characterized by having the following structure:

r is hydrogen, 3-nitro, 2-nitro, 4-trifluoromethyl, 4-chlorine, 4-fluorine, 4-methyl, 2-methyl, 3-methoxyl, 4-cyano, 4-acetamido or 4-acetyl.

Dissolving aryl halide with a structure (I) in a dimethyl sulfoxide solvent with a structure (II), adding a palladium-carbon catalyst and alkali into the mixture, and introducing carbon dioxide to perform pressurized heating reaction to obtain α -methyl sulfoxide methyl ester compounds with a structure (III):

x is bromine or iodine;

the alkali is potassium phosphate, sodium carbonate, cesium carbonate, potassium tert-butoxide, sodium hydroxide or sodium ethoxide;

the molar ratio of the aryl halide to the palladium-carbon catalyst is 20: 1-10: 1;

the reaction temperature is 110 DEG C^oC—140^oC；

The pressure of the carbon dioxide is 10-15 atmospheric pressures.

The method has the beneficial effects that the α -methyl sulfoxide methyl ester compound is constructed by coupling aryl halide, dimethyl sulfoxide and carbon dioxide under the catalysis of palladium for the first time, and a novel α -methyl sulfoxide methyl ester compound and a preparation method thereof are provided for the field of the existing chemical synthesis.

Drawings

FIG. 1 is a nuclear magnetic resonance hydrogen spectrum of α -methylsulfoxidate prepared in examples 1,2 and 3 of the present invention;

FIG. 2 shows the NMR carbon spectrum of α -methylsulfoxidate prepared in examples 1,2 and 3 of the present invention.

Detailed Description

The invention is further described with reference to the following drawings and specific embodiments:

an α -methylsulfonyl methyl ester compound is characterized by having the following structure:

r is hydrogen, 3-nitro, 2-nitro, 4-trifluoromethyl, 4-chlorine, 4-fluorine, 4-methyl, 2-methyl, 3-methoxyl, 4-cyano, 4-acetamido or 4-acetyl.

Dissolving aryl halide with a structure (I) in a dimethyl sulfoxide solvent with a structure (II), adding a palladium-carbon catalyst and alkali into the mixture, and introducing carbon dioxide to perform pressurized heating reaction to obtain α -methyl sulfoxide methyl ester compounds with a structure (III):

x is bromine or iodine;

the alkali is potassium phosphate, sodium carbonate, cesium carbonate, potassium tert-butoxide, sodium hydroxide or sodium ethoxide;

the molar ratio of the aryl halide to the palladium-carbon catalyst is 20: 1-10: 1;

the reaction temperature is 110 DEG C^oC—140^oC；

The pressure of the carbon dioxide is 10-15 atmospheric pressures.