阅读说明：本技术 一种炔基砜类化合物及其制备方法和应用 (Alkynyl sulfone compound and preparation method and application thereof ) 是由 孟祥太 徐鹤华 傅元媛 王亚铭 张颖茵 陈登峰 黄申林 于 2020-07-30 设计创作，主要内容包括：本发明涉及化学合成技术领域,具体公开了一种炔基砜类化合物及其制备方法和应用,所述炔基砜类化合物包括以下的原料炔烃类化合物、亚磺酸钠类化合物、碘化钾、水以及有机溶剂。本发明提供的炔基砜类化合物以炔烃类化合物、亚磺酸钠类化合物、碘化钾、水以及有机溶剂作为原料,通过电解即可制备炔基砜类化合物,可以在温和无金属催化剂的条件下实现合成炔基砜类化合物,无需高温、富氧、恒压等条件,反应条件不苛刻,而且步骤简单,无需多步反应,简化了合成步骤,解决了现有炔基砜类化合物在制备中存在条件苛刻,而且步骤繁琐的问题；而提供的所述炔基砜类化合物的制备方法操作简单,产率高,具有较高的经济适用性。(The invention relates to the technical field of chemical synthesis, and particularly discloses an alkynyl sulfone compound and a preparation method and application thereof. The alkynyl sulfone compound provided by the invention takes an alkyne compound, a sodium sulfinate compound, potassium iodide, water and an organic solvent as raw materials, the alkynyl sulfone compound can be prepared by electrolysis, the alkynyl sulfone compound can be synthesized under the mild condition without a metal catalyst, the conditions of high temperature, oxygen enrichment, constant pressure and the like are not required, the reaction condition is not harsh, the steps are simple, the multi-step reaction is not required, the synthesis steps are simplified, and the problems that the existing alkynyl sulfone compound has harsh conditions and complicated steps in the preparation are solved; the preparation method of the alkynyl sulfone compound is simple to operate, high in yield and high in economic applicability.)

1. An alkynyl sulfone compound comprises the following raw materials: the catalyst comprises an alkyne compound, a sodium sulfinate compound, potassium iodide, water and an organic solvent, wherein the molar ratio of the alkyne compound to the sodium sulfinate compound is 1: 1-6.

2. The alkynyl sulfone compound of claim 1, wherein the molar ratio of the alkyne compound to the sodium sulfinate compound is 1: 2-4.

3. The alkynyl sulfone compound of claim 1, wherein the organic solvent is any one of acetonitrile, ethyl acetate or acetone.

4. The alkynyl sulfone compound of claim 1, wherein the alkyne compound and the organic solvent are added in an amount of 3-4mL of organic solvent per millimole of alkyne compound, and the alkyne compound and the water are added in an amount of 0.03-0.06mL of water per millimole of alkyne compound.

5. The alkynyl sulfone compound of claim 1, wherein the molar ratio of the alkyne compound to the potassium iodide is 1: 0.5-1.5.

6. The alkynyl sulfone compound of claim 1, wherein the alkyne compound is an alkyne compound containing phenyl and/or substituted phenyl, and the sodium sulfinate compound is a sodium sulfinate compound containing phenyl and/or substituted phenyl.

7. The alkynyl sulfone compound of claim 1, wherein the structure of the alkynyl sulfone compound is shown as formula I:

R in formula I²And R¹Are each independentlyAnd the number of carbons is 1 to 12.

8. A method for preparing an alkynyl sulfone compound as claimed in any one of claims 1 to 7, comprising the steps of: mixing an alkyne compound, a sodium sulfinate compound, potassium iodide, water and an organic solvent, and then carrying out electrolysis and separation to obtain the alkyne sulfone compound.

9. The method for preparing alkynyl sulfone compound of claim 8, wherein the electrolysis is performed at room temperature under a constant current of 5-15mA for 1-24h under stirring.

10. Use of a process for the preparation of an alkynyl sulfone compound as claimed in claim 8 or 9 in organic synthesis.

Technical Field

The invention relates to the technical field of chemical synthesis, in particular to an alkynyl sulfone compound and a preparation method and application thereof.

Background

The alkynyl sulfone compound (alkynyl sulfone) is a compound modified by sulfone containing an unsaturated C-C bond, can be converted into a key intermediate of other heterocyclic compounds, has various biological activities and photoconductivity, and has wide application in the fields of life sciences, organic synthesis, drug synthesis and the like.

Currently, there are many reports on the synthesis of alkynyl sulfones, and efficient oxidative cross-coupling reactions involving terminal alkynes remain challenging. However, the preparation methods of alkynyl sulfones in the prior art usually require the use of alkyl halides or alkynes as substrates and the use of excess amounts of oxidizing agents and metal cleaving agents. The part is to oxidize alkynyl sulfide by peroxide, and synthesize by oxidation selenium removal method or dehydrohalogenation method. And the other method adopts sulfonyl hydrazide and alkyne for electrochemical synthesis.

However, the above method for synthesizing an alkynyl sulfone compound has the following disadvantages in practical use: the existing alkynyl sulfone compound needs conditions of high temperature, oxygen enrichment, constant pressure and the like in preparation, so that the conditions are harsh, and the steps are complicated. Therefore, there is an urgent need to develop a more efficient synthesis method, which can realize synthesis under mild conditions without metal catalyst and simplify the synthesis steps.

Disclosure of Invention

The embodiment of the invention aims to provide an alkynyl sulfone compound, and aims to solve the problems that the existing alkynyl sulfone compound in the background technology has harsh conditions and complicated steps in preparation.

In order to achieve the above purpose, the embodiments of the present invention provide the following technical solutions:

an alkynyl sulfone compound comprises the following raw materials: alkyne compounds, sodium sulfinate compounds, potassium iodide (KI) and water (H)₂O) and an organic solvent, wherein the mol ratio of the alkyne compound to the sodium sulfinate compound is 1: 1-6.

As a further scheme of the invention: the mol ratio of the alkyne compound to the sodium sulfinate compound is 1: 2-4.

Preferably, the mol ratio of the alkyne compound to the sodium sulfinate compound is 1: 3.

As a still further scheme of the invention: the alkynyl sulfone compound is prepared by mixing an alkyne compound, a sodium sulfinate compound, potassium iodide, water and an organic solvent and electrolyzing.

As a still further scheme of the invention: the electrolysis condition is that the electrolysis is carried out for 1 to 24 hours at room temperature under the constant current of 5 to 15 mA.

As a still further scheme of the invention: the organic solvent is acetonitrile (CH)₃CN), ethyl acetate or acetone.

As a still further scheme of the invention: in the raw material, the addition amount of the alkyne compound and the organic solvent is 3-4mL of the organic solvent for each millimole of the alkyne compound.

Preferably, the alkyne compound and the organic solvent are added in the starting material in an amount of 3.3mL of acetonitrile per millimole of alkyne compound.

As a still further scheme of the invention: in the raw material, the mol ratio of the alkyne compound to the potassium iodide is 1: 0.5-1.5.

As a still further scheme of the invention: in the raw material, the addition amount of the alkyne compound and the water is 0.03-0.06mL of water per millimole of alkyne compound.

Preferably, the acetylenic compound and the water are added in the starting material in an amount of 0.033mL of water per millimole of acetylenic compound.

As a still further scheme of the invention: the alkyne compound is an alkyne compound containing phenyl and/or substituted phenyl. Specifically, the alkyne compound includes any one or more of a phenyl alkyne compound or a substituted phenyl alkyne compound.

As a still further scheme of the invention: the sodium sulfinate compound is a sodium sulfinate compound containing phenyl and/or substituted phenyl. Specifically, the sodium sulfinate compound comprises any one or more of sodium benzene sulfinate or sodium p-methyl benzene sulfinate.

Another object of the embodiments of the present invention is to provide a method for preparing an alkynyl sulfone compound, and in particular, to a method for preparing an alkynyl sulfone compound by diaphragm-free electrochemical synthesis using sodium sulfinate and alkyne as raw materials, wherein the method for preparing an alkynyl sulfone compound comprises the following steps: mixing an alkyne compound, a sodium sulfinate compound, potassium iodide, water and an organic solvent, and then carrying out electrolysis and separation to obtain a target product, namely the alkyne sulfone compound.

As a still further scheme of the invention: the electrolysis condition is that the electrolysis is carried out for 1 to 24 hours at room temperature under the constant current of 5 to 15 mA.

Preferably, the preparation method of the alkynyl sulfone compound is that the alkyne compound, the sodium sulfinate compound, the potassium iodide, the water and the acetonitrile are added into an undivided three-neck flask (25mL) which is dried in an oven and is provided with a stirring rod in advance and mixed to obtain a mixture, the three-neck flask is provided with a platinum electrode as an anode and a cathode, the mixture is stirred and electrolyzed at constant current of 10mA at room temperature for 7 hours, after the reaction is finished, the solvent is removed by rotary evaporation through a rotary evaporator, petroleum ether and ethyl acetate are used as eluent, and the pure product is obtained by flash chromatography on silica gel.

As a still further scheme of the invention: the rotary steaming has the rotation speed of 100-200rpm, the temperature of 25-30 ℃, the vacuum degree of 0.08-0.12Mpa and the treatment time of 3-5 min.

As a still further scheme of the invention: in the preparation method of the alkynyl sulfone compound, the chromatography is performed by adopting 100-mesh 300-mesh column chromatography silica gel, the developing agent of the column chromatography is petroleum ether and ethyl acetate, and the petroleum ether: the volume ratio of the ethyl acetate is 15-30: 1.

Another object of the embodiments of the present invention is to provide an alkynyl sulfone compound prepared by the above preparation method of an alkynyl sulfone compound.

As a still further scheme of the invention: the structure of the alkynyl sulfone compound is shown as a formula I:

wherein

R in formula I²And R¹Are independent groups, and the carbon number is 1-12.

Further, R²And R¹Are each independently a substituent group, in particular, R²And R¹Can be independently selected from aldehyde group, carbonyl group, ester group, nitro group, carboxyl group, substituted or unsubstituted C1-C12 alkyl group, substituted or unsubstituted C1-C12 aryl group, substituted or unsubstituted C1-C12 cycloalkyl group, substituted or unsubstituted C1-C12 alkoxy group, substituted or unsubstituted C1-C12 alkylamino group, substituted or unsubstituted C1-C12 alkylene group, substituted or unsubstituted C1-C12 alkynyl group, substituted or unsubstituted C1-C12 heterocyclic group, substituted or unsubstituted C1-C12 condensed ring group, or substituted or unsubstituted C1-C12 spiro ring group.

Of course, it should be noted that the alkynyl sulfones compounds are not limited to the structure shown in formula I, R²And R¹The substituent groups may be other substituents having 1 to 12 carbon atoms, and are not limited thereto.

Another object of the embodiments of the present invention is to provide an application of the above alkynyl sulfone compound in the preparation of a pharmaceutical intermediate and/or the preparation of a basic skeleton of a drug.

Another object of the embodiment of the present invention is to provide an application of the preparation method of the alkynyl sulfone compound in organic synthesis.

As a still further scheme of the invention: the application can be the application of the alkynyl sulfone compound and the derivative thereof in organic synthesis or drug synthesis, or the application can be the application of the alkynyl sulfone compound as a raw material for preparing drugs or organic materials, or the application can be the application of the alkynyl sulfone compound as a basic skeleton of various natural products such as drugs after subsequent derivation.

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

the alkynyl sulfone compound provided by the invention takes an alkyne compound, a sodium sulfinate compound, potassium iodide, water and an organic solvent as raw materials, the alkynyl sulfone compound can be prepared by electrolysis, the alkynyl sulfone compound can be synthesized under the mild condition without a metal catalyst, the conditions of high temperature, oxygen enrichment, constant pressure and the like are not required, the reaction condition is not harsh, the steps are simple, the multi-step reaction is not required, the synthesis steps are simplified, and the problems that the existing alkynyl sulfone compound has harsh conditions and complicated steps in the preparation are solved; the preparation method of the alkynyl sulfone compound is simple to operate, is a method for electrochemically synthesizing the alkynyl sulfone compound without a diaphragm, is particularly suitable for synthesizing some medicaments because the whole reaction is carried out in an organic solvent system, fundamentally eliminates the problems of metal residue and the like, and has high yield and higher economic applicability.

Drawings

In order to more clearly illustrate the technical solutions of the embodiments of the present invention, the drawings needed to be used in the description of the embodiments will be briefly introduced below, and it is obvious that the drawings in the following description are only some embodiments of the present invention, and it is obvious for those skilled in the art to obtain other drawings based on these drawings without inventive exercise. Wherein:

fig. 1 is a H-spectrum of a nuclear magnetic spectrum of the alkynyl sulfone compound prepared in example 1 of the present invention.

Fig. 2 is a H-spectrum of a nuclear magnetic spectrum of the alkynyl sulfone compound prepared in example 2 of the present invention.

Fig. 3 is a H-spectrum of a nuclear magnetic spectrum of the alkynyl sulfone compound prepared in example 3 of the present invention.

Fig. 4 is a H-spectrum of a nuclear magnetic spectrum of the alkynyl sulfone compound prepared in example 4 of the present invention.

Detailed Description

The invention is described in further detail below with reference to the figures and specific examples. The following examples will assist those skilled in the art in further understanding the invention, but are not intended to limit the invention in any way. It should be noted that those skilled in the art can easily and easily make a similar generalization without departing from the spirit of the present invention, and therefore the present invention is not limited to the specific embodiments disclosed below. All falling within the scope of the present invention.

Furthermore, reference herein to "one embodiment" or "an embodiment" means that a particular feature, structure, or characteristic described in connection with the embodiment is included in at least one implementation of the invention. The appearances of the phrase "in one embodiment" in various places in the specification are not necessarily all referring to the same embodiment, nor are separate or alternative embodiments mutually exclusive of other embodiments.