阅读说明：本技术 一种氯乙基亚砜类化合物的电化学合成方法 (Electrochemical synthesis method of chloroethyl sulfoxide compound ) 是由 黄嘉涛 凌飞 冯聪 钟为慧 于 2019-11-25 设计创作，主要内容包括：本发明公开了一种氯乙基亚砜类化合物的电化学合成方法。本发明的方法在不分立的电解槽中进行反应,将芳基硫酚类化合物、1,2-二氯乙烷以及电解质溶解在溶剂中得到反应溶液,反应溶液加入电解槽中,再将电极插入到反应溶液中,在合适的气体氛围中接通恒定电流搅拌反应,反应结束后,经柱层析分离,得到氯乙基亚砜。(The invention discloses an electrochemical synthesis method of chloroethyl sulfoxide compounds. The method comprises the steps of carrying out reaction in an undivided electrolytic tank, dissolving aryl thiophenol compounds, 1, 2-dichloroethane and electrolyte in a solvent to obtain a reaction solution, adding the reaction solution into the electrolytic tank, inserting an electrode into the reaction solution, connecting constant current in a proper gas atmosphere, stirring for reaction, and carrying out column chromatography separation after the reaction is finished to obtain chloroethyl sulfoxide.)

1. An electrochemical synthesis method of chloroethyl sulfoxide compounds is characterized in that the reaction is carried out in an undissociated electrolytic tank, aryl thiophenol compounds shown in formula (II), 1, 2-dichloroethane and electrolyte are dissolved in a solvent to obtain a reaction solution, the reaction solution is added into the electrolytic tank, an electrode is inserted into the reaction solution, constant current is conducted in a proper gas atmosphere for stirring reaction, and after the reaction is finished, column chromatography separation is carried out to obtain chloroethyl sulfoxide shown in formula (I); the reaction formula is as follows:

wherein R is selected from aryl and heteroaryl.

2. The method for electrochemically synthesizing a chloroethyl sulfoxide compound according to claim 1, wherein the positive electrode and the negative electrode are each selected from one of a platinum electrode, a nickel electrode, a graphite electrode, a glassy carbon electrode, and an RVC electrode.

3. The electrochemical synthesis method of chloroethyl sulfoxide compound according to claim 1, wherein the electrolyte is one or more of lithium perchlorate, tetrabutylammonium tetrafluoroborate, tetrabutylammonium hexafluorophosphate, tetrabutylammonium iodide, tetrabutylammonium bromide and tetrabutylammonium fluoride; wherein the amount of the electrolyte is 50 to 400 mol%, and more preferably 80 to 200 mol% of the aryl thiophenol compound.

4. The method for electrochemically synthesizing chloroethyl sulfoxides as claimed in claim 1, wherein the solvent is 1, 2-dichloroethane or a mixed solvent of 1, 2-dichloroethane, water, dichloromethane, acetonitrile, tetrahydrofuran.

5. The method for electrochemically synthesizing a chloroethyl sulfoxide compound according to claim 1, characterized in that the gas atmosphere is oxygen, air, nitrogen or argon.

6. The method for electrochemically synthesizing a chloroethyl sulfoxide compound according to claim 1, wherein the constant current is 5 to 100mA, preferably 10 to 60 mA.

7. The method for electrochemical synthesis of chloroethyl sulfoxide compounds according to claim 1, characterized in that the reaction temperature is 10-80 ℃, preferably 30-70 ℃.

8. The electrochemical synthesis method of chloroethyl sulfoxide compounds according to claim 1, characterized in that the reaction time is 1-24 hours, preferably 3-12 hours.

9. The method for electrochemically synthesizing chloroethyl sulfoxides as claimed in claim 1, wherein the concentration of the arylsulfophenol compound is 0.05 to 1mol/L, preferably 0.1 to 0.5 mol/L.

Technical Field

The invention belongs to the technical field of synthesis of pharmaceutical and chemical intermediates, and particularly relates to an electrochemical synthesis method of chloroethyl sulfoxide compounds.

Background

The sulfoxide and the derivatives thereof are used as very important intermediates and have important functions in the industries of medicine, chemical industry, pesticide, organic synthesis and the like. In particular, in the field of medicine, the well-known proton pump inhibitors for the treatment of gastric ulcers, omeprazole and lansoprazole, among others, also belong to the sulfoxide group of drugs. After the intensive research and structural modification of other sulfoxide compounds, a series of anti-tumor, anti-virus, anti-HIV and other medicines are also developed. Therefore, its efficient synthesis is one of the hot spots of the current research.

The conventional method for preparing sulfoxides is via thiol or thioether oxidation. For example, Brinksma project group 2001 reports a method for synthesizing sulfoxide under the catalysis of Mn (III) complex by taking benzyl sulfide as a raw material and hydrogen peroxide as an oxidant (Tetrahedron Letters,2001,42, 4049-. In 2005, the Velusamy project group reported a method for oxidizing sulfide into sulfoxide with copper (II) complex and hydrogen peroxide (Tetrahedron Letters,2005,46, 3819-3822), which can improve the selectivity and conversion rate of reaction after adding TEMPO in a mixed manner, and the copper (II) complex can be recycled. However, these methods are less sustainable because they require stoichiometric amounts of metal complexes as sacrificial acceptors for electrons.

In recent years, the selection of catalysts has shifted from metal complexes to nano-mesoporous materials. The Kiumars topic group uses SBA-15-PR-SO₃H(Catalysis Science&Technology,2011,1,389-393.), is used as a nano reactor to catalytically oxidize sulfide into sulfoxide at 40 ℃, and has good yield. The Nikoorazm group successfully used H in the absence of a solvent using Si-MCM-41 as a catalyst, which is a vo (IV) complex₂O₂Several types of aryl thiophenols and aliphatic thiols are oxidized to the corresponding sulfoxides.

Chloroethyl sulfoxide, an important intermediate raw material, was used to prepare sitafloxacin, a quinolone antibacterial drug (j. org. chem.2014,79,15,7226-. The common method for preparing chloroethyl sulfoxide is to generate thiophenol and 1-chloro-2-bromoethane through two-step reaction (EP2277872,2016, B1), and then to oxidize sulfide into chloroethyl sulfoxide by using nano-scale mesoporous sodium iron hydroxy phosphate loaded with gold and hydrogen peroxide in methanol solvent at 60 ℃ (Catalysis Science and Technology,2016,6-7, 2055-2059).

Disclosure of Invention

Aiming at the problems in the prior art, the invention aims to provide an electrochemical synthesis method of chloroethyl sulfoxide compounds, which is characterized in that thiophenol compounds, 1, 2-dichloroethane and electrolyte are dissolved in an organic solvent and subjected to oxidative coupling reaction under the action of current to generate chloroethyl sulfoxide.

The technical scheme adopted by the invention is as follows:

a synthetic method of chloroethyl sulfoxide compounds comprises the following steps: dissolving aryl thiophenol compound shown in formula (II), 1, 2-Dichloroethane (DCE) and electrolyte in a solvent to obtain a reaction solution, adding the reaction solution into an electrolytic bath, inserting an electrode into the reaction solution in a proper gas atmosphere, switching on constant current, stirring and reacting at a proper temperature, and after the reaction is finished, performing column chromatography separation to obtain chloroethyl sulfoxide shown in formula (I).

The reaction formula is as follows:

in the structural formulas I and II, R is selected from aryl and heteroaryl.

The anode and the cathode are respectively selected from one of a platinum electrode, a nickel electrode, a graphite electrode, a glassy carbon electrode and an RVC electrode.

The electrolyte is one or more of lithium perchlorate, tetrabutylammonium tetrafluoroborate, tetrabutylammonium hexafluorophosphate, tetrabutylammonium iodide, tetrabutylammonium bromide, tetrabutylammonium fluoride and the like; the amount of the electrolyte is 50 to 400 mol%, more preferably 80 to 200 mol%, based on the thiophenols.

The solvent is 1, 2-dichloroethane or a mixed solvent of the dichloroethane and water, dichloromethane, acetonitrile, tetrahydrofuran and the like.

The gas atmosphere is oxygen, air, nitrogen and argon.

The current is constant current, 5-100 mA, preferably 10-60 mA.

The reaction temperature of the preparation method is 10-80 ℃, and preferably 30-70 ℃.

The reaction time of the preparation method is 1-24 hours, and more preferably 3-12 hours.

The concentration of the substrate in the preparation method is 0.05-1 mol/L, and more preferably 0.1-0.5 mol/L.

Compared with the prior art, the invention has the following beneficial effects:

the preparation method disclosed by the invention does not need to use metal catalysis, an oxidant and an additive, but uses green energy for electrocatalytic oxidation, the reaction is completed in one step, the distribution is not needed, the preparation method is more green and environment-friendly, the raw materials are easy to obtain, the operation is simple, the reaction chemical selectivity is high, the environment is friendly, and the like, and the preparation method has the characteristics of higher implementation value and social and economic benefits.

Detailed Description

The invention is further described below with reference to specific examples, but is not limited to the embodiments described by the specific examples listed herein.