阅读说明：本技术 一种氧化深度可控硫醚氧化方法 (Oxidation depth controllable thioether oxidation method ) 是由 张旭 周瑞 俞磊 沈德智 王俊坤 仇从光 范中明 于 2021-06-16 设计创作，主要内容包括：本发明涉及一种氧化深度可控硫醚氧化方法,在5℃～80℃下,乙腈溶剂中,使用过氧化氢为氧化剂、苯亚硒酸/硝酸铝复合催化剂体系催化氧化硫醚,其中过氧化氢与硫醚摩尔比为50％～400％:1,苯亚硒酸与硫醚摩尔比为2％～8％:1,硝酸铝与硫醚摩尔比为0.4～2.0％:1。在该条件下,硫醚可被氧化为亚砜或砜,而控制氧化深度的关键在于过氧化氢用量。使用等当量(即100％硫醚摩尔量)或不足量的过氧化氢,只有亚砜产生,使用过量过氧化氢,可以将硫醚充分氧化为砜。与现有技术相比：该方法催化剂体系简单,反应过程简便易操作并且清洁,有很好的应用价值。(The invention relates to a thioether oxidation method with controllable oxidation depth, which is characterized in that thioether is catalytically oxidized by using hydrogen peroxide as an oxidant and a selenious acid/aluminum nitrate composite catalyst system in an acetonitrile solvent at the temperature of 5-80 ℃, wherein the molar ratio of hydrogen peroxide to thioether is 50-400 percent to 1, the molar ratio of selenious acid to thioether is 2-8 percent to 1, and the molar ratio of aluminum nitrate to thioether is 0.4-2.0 percent to 1. Under these conditions, the thioether can be oxidized to the sulfoxide or sulfone, and the key to controlling the depth of oxidation is the amount of hydrogen peroxide used. Using an equivalent (i.e., 100% thioether molar amount) or insufficient amount of hydrogen peroxide, only sulfoxide is produced, and using an excess of hydrogen peroxide, thioether can be fully oxidized to sulfone. Compared with the prior art: the method has the advantages of simple catalyst system, simple and convenient reaction process, easy operation and cleanness, and good application value.)

1. An oxidation depth controllable thioether oxidation method is characterized in that thioether is catalytically oxidized by using hydrogen peroxide as an oxidant and a selenious acid/aluminum nitrate composite catalyst system in an acetonitrile solvent at the temperature of 5-80 ℃, wherein the molar ratio of hydrogen peroxide to thioether is 50-400% to 1, the molar ratio of selenious acid to thioether is 2-8% to 1, and the molar ratio of aluminum nitrate to thioether is 0.4-2.0% to 1.

2. The process of claim 1, wherein the reaction temperature is between about 5 ℃ and about 40 ℃.

3. The method as claimed in claim 1, wherein the reaction uses hydrogen peroxide as the oxidant, and the molar ratio of hydrogen peroxide to thioether is 100% -300%: 1.

4. The method as claimed in claim 1, wherein selenious acid is used as the catalyst in the reaction, and the molar ratio of selenious acid to thioether is 5%: 1.

5. The method as claimed in claim 1, wherein aluminum nitrate is used as the catalyst in the reaction, and the molar ratio of aluminum nitrate to thioether is 1.2%: 1.

Technical Field

The invention relates to the technical field of material chemical industry, in particular to a thioether oxidation method with controllable oxidation depth.

Background

Sulfoxides and sulfones are important organic intermediates in the pharmaceutical industry and in the materials and chemicals industry. Because the low-valence sulfur compound has higher nucleophilicity, the low-valence sulfur compound can generate thioether through simple nucleophilic substitution reaction with cheap halide, and the preparation of sulfoxide or sulfone through oxidation reaction by taking the easily obtained thioether as a raw material is an important method. However, the difficulty in achieving this approach is in reaction selectivity control. In addition, the development of a clean oxidation process, which is convenient for industrial production, is also an important development trend. For the pharmaceutical industry, it is significant to develop a synthesis method without transition metal catalysis due to the residual and strict requirements of transition metal in the quality control of the product.

In recent years, selenium-catalyzed reactions have been developed vigorously. Because the selenium catalytic reaction process is clean and the tolerance of the pharmaceutical industry to selenium residues is relatively high, the development of related drug intermediate synthesis technology around the selenium catalytic reaction has good practical significance. The subject group has conducted long-term and continuous studies on this. Recently, research on selenium catalysis technology has gradually developed into multi-component catalysis, and the synergistic effect of a plurality of catalytic components is utilized to improve the activity of a catalytic system, so that a plurality of oxidation processes which are difficult to achieve by a conventional method can be realized. For example, oxidative deoximation using molecular oxygen as an oxidant can be achieved by using selenium-iron bimetallic concerted catalysis (adv. Synth. Cat. 2019,361, 603-610), while selenium-copper bimetallic concerted catalysis can catalyze carbonyl ortho C-H bond oxidation-functionalization (Chin. J. chem.2020,38, 1045-. The invention develops a method for catalyzing thioether oxidation by using a selenious acid/aluminum nitrate composite catalytic system. Unlike previous work, the co-catalytic system does not contain transition metals. The technology is successfully applied to selective oxidation of thioether, can selectively and controllably prepare sulfoxide or sulfone under clean and mild conditions, and has good application value.

Disclosure of Invention

The invention aims to provide a thioether oxidation method with controllable oxidation depth. The invention uses clean hydrogen peroxide as an oxidant, uses a unique selenious acid/aluminum nitrate system as a composite catalyst, can realize the control of the reaction oxidation depth by adjusting the dosage of the hydrogen peroxide, and selectively generates sulfoxide or sulfone.

In order to solve the technical problems, the technical scheme provided by the invention is as follows: thioether is catalytically oxidized by using hydrogen peroxide as an oxidant and a selenious acid/aluminum nitrate composite catalyst system in an acetonitrile solvent at the temperature of 5-80 ℃, wherein the molar ratio of hydrogen peroxide to thioether is 50-400% to 1, the molar ratio of selenious acid to thioether is 2-8% to 1, and the molar ratio of aluminum nitrate to thioether is 0.4-2.0% to 1. Under these conditions, the thioether can be oxidized to the sulfoxide or sulfone, and the key to controlling the depth of oxidation is the amount of hydrogen peroxide used. Using an equivalent (i.e., 100% thioether molar amount) or insufficient amount of hydrogen peroxide, only sulfoxide is produced, and using an excess of hydrogen peroxide, thioether can be fully oxidized to sulfone.

Further, the reaction temperature is between 5 ℃ and 80 ℃, preferably between 5 ℃ and 40 ℃, and the specific temperature depends on the thioether substrate used in the reaction.

Furthermore, the reaction uses hydrogen peroxide as an oxidant, and the molar ratio of the hydrogen peroxide to the thioether is 50-400% to 1, preferably 100-300% to 1. The amount of hydrogen peroxide used determines the depth of the reaction. The reaction can be controlled in the step of producing sulfoxide by using hydrogen peroxide with the molar quantity of thioether being less than 100%. When hydrogen peroxide is used in an amount of 200% or more by mole of the thioether, sulfone is selectively produced.

Furthermore, the reaction uses selenious acid benzene as a catalyst, the molar ratio of the dosage to the thioether is 2% -8% to 1, preferably 5% to 1, and the reactant can be fully converted by using the selenium catalyst with the dosage.

Further, aluminum nitrate is used as a catalyst in the reaction, and the molar ratio of the aluminum nitrate to the thioether is 0.4-2.0: 1, wherein 1.2: 1 is preferred. The use of the aluminum nitrate in the amount can fully exert the oxygen carrying function of nitrate radical and the Lewis acidity of aluminum ions.

Compared with the prior art, the invention has the advantages that:

1. the reaction process is clean;

2. the selenious acid/aluminum nitrate is a brand new composite catalyst system, and is different from selenium-iron and selenium-copper in that nitrate radicals are used as oxygen-carrying enhancing components, so that transition metals are avoided, and the catalyst system is more suitable for the field of drug synthesis. The aluminum ions play a unique regulating role in the selenium catalytic reaction.

Detailed Description

The following examples illustrate the invention in more detail, but do not limit the invention further.

A thioether oxidation method with controllable oxidation depth. The process can selectively oxidize the thioether to a sulfoxide or sulfone. The reaction process is clean, the reaction condition is mild, and the method is suitable for large-scale application.

Example 1

1mmol of thioanisole, 0.012mmol of aluminum nitrate nonahydrate, 0.05mmol of selenious acid benzene and 2mL of acetonitrile are added into a reaction tube, 1mmol of hydrogen peroxide (30% by mass) is added dropwise under stirring, the mixture is stirred for 40min at normal temperature (25 ℃), and TLC (developing agent: V petroleum ether: V ethyl acetate: 5:1) is used for tracking the reaction until the reaction is finished. After the reaction, the reaction mixture was separated by thin layer chromatography (developing solvent: V petroleum ether: V ethyl acetate: 1) to obtain a pale yellow liquid (119.0mg, yield 85%).

Example 2

The reaction was carried out under the same conditions as in example 1 at different reaction temperatures, and the influence of the temperature on the reaction yield was examined. The results are shown in Table 1.

TABLE 1 Effect of different temperatures on the reaction

As can be seen from the above, the optimum reaction temperature for the oxidation of methylthiophenyl ether to sulfoxide is 25 ℃, i.e., at room temperature.

Example 3

Other conditions copper example 1 was reacted using different amounts of hydrogen peroxide, and the results are shown in table 2.

TABLE 2 Effect of different amounts of Hydrogen peroxide on the reaction

From the above, it was found that the reaction selectively produces sulfoxide using hydrogen peroxide in which the molar amount of thioether is 100% or less. When the amount of hydrogen peroxide is more than 200% by mole based on the amount of the thioether, the sulfone is selectively formed. At this time, thin layer chromatography analysis showed no sulfoxide formation. The selective control of the reaction results very well.

Example 4

Other conditions copper example 1, with different amounts of selenious acid catalyzed the reaction, the results are shown in table 3.

TABLE 3 Effect of different selenious acid amounts on the reaction

From the above, the reaction yield can be maximized by using selenious acid containing 5 mol% of thioether. Further increase the dosage of the selenium catalyst, which is not beneficial to improving the reaction yield.

Example 5

Other conditions copper example 1, with varying amounts of aluminum nitrate to catalyze the reaction, the results are shown in table 4.

TABLE 4 Effect of different amounts of aluminum nitrate on the reaction

From the above, the reaction yield was maximized by using aluminum nitrate in which the molar amount of thioether was 1.2%. The aluminum nitrate is insufficient, the activity of a catalytic system is insufficient, and the yield of the sulfoxide is reduced. An excess of aluminum nitrate interferes with the reaction, resulting in a sharp drop in yield.

Example 6

The above reaction was subjected to substrate extension, and the results are shown in Table 5

TABLE 5 substrate application development

From the above, it can be seen that the method can realize selective oxidation of various thioethers under relatively mild conditions to prepare sulfoxides or sulfones.

The above description is only a preferred embodiment of the present invention, and should not be taken as limiting the invention in any way, and any person skilled in the art can make any simple modification, equivalent replacement, and improvement on the above embodiment without departing from the technical spirit of the present invention, and still fall within the protection scope of the technical solution of the present invention.