阅读说明：本技术 一种芳烯基硫醚类化合物及其制备方法 (Aryl alkenyl thioether compound and preparation method thereof ) 是由 刘世文 于 2020-07-23 设计创作，主要内容包括：本发明公开了一种芳烯基硫醚类化合物及其制备方法,其中,包括如下化学式及其可接受的盐、互变异构体、立体异构体和所有比例的混合物：<Image he="214" wi="365" file="DDA0002598968450000011.GIF" imgContent="drawing" imgFormat="GIF" orientation="portrait" inline="no"></Image>其中R<Sub>1</Sub>为氢原子、烷基、甲氧基、卤素取代基、氰基、硝基、醛基、酯基中的一种；R<Sub>2</Sub>为烷基或苯基；R<Sub>3</Sub>为氢原子、烷基、卤素原子等。本发明提供了一种含硫化合物的能力,操作简单、步骤简洁、底物适用范围广,后处理简单,溶剂也可以回收再利用。(The invention discloses an aryl alkenyl thioether compound and a preparation method thereof, wherein the aryl alkenyl thioether compound comprises the following chemical formula and acceptable salts, tautomers, stereoisomers and mixtures in all proportions thereof: wherein R is 1 Is one of hydrogen atom, alkyl, methoxy, halogen substituent, cyano, nitro, aldehyde group and ester group; r 2 Is alkyl or phenyl; r 3 Hydrogen atom, alkyl group, halogen atom, etc. The invention provides the capability of the sulfur-containing compound, and has the advantages of simple operation, concise steps, wide substrate application range, simple post-treatment and capability of recycling the solvent.)

1. An arylalkenyl thioether compound, which is characterized in that: including the following formulae and acceptable salts, tautomers, stereoisomers and mixtures thereof in all ratios:

wherein

R₁Is one of hydrogen atom, alkyl, methoxy, halogen substituent, cyano, nitro, aldehyde group and ester group;

R₂is alkyl or phenyl;

R₃hydrogen atom, alkyl group, halogen atom, etc.

2. The arylalkenyl thioether compound according to claim 1, wherein: the R is₁Is alkyl, halogen, alkoxy, nitro, carbonyl, cyanoThiophene and furan group.

3. A preparation method of an aryl alkenyl thioether compound is characterized by comprising the following steps: the method comprises the following steps:

dissolving: dissolving alkyne, ammonium thiocyanate and N-aryl (alkyl) sulfenyl succinimide in an organic solvent;

heating: the dissolving system is heated and reacted for a period of time;

and (4) purification, namely separating and purifying after removing the solvent to obtain a product.

4. The process for producing an arylalkenyl thioether compound according to claim 3, wherein: the mol ratio of alkyne, ammonium thiocyanate and N-aryl (alkyl) sulfenyl succinimide in the dissolution is 1: 1.0-5.0: 1.0-3.

5. The process for producing an arylalkenyl thioether compound according to claim 3 or 4, wherein: the molar ratio of alkyne, ammonium thiocyanate and N-aryl (alkyl) sulfenyl succinimide in the dissolution is 1.0:2.0: 1.2.

6. The process for producing an arylalkenyl thioether compound according to claim 3, wherein: the organic solvent in the dissolving process is one or more of hexafluoroisopropanol, trifluoroethanol and acetic acid.

7. The process for producing an arylalkenyl thioether compound according to claim 3, wherein: the weight volume ratio of the dissolved ammonium thiocyanate to the organic solvent is 1 g to 50 ml-100 ml.

8. The process for producing an arylalkenyl thioether compound according to claim 3, wherein: the heating temperature is 50-120 ℃ and the heating time is 4-48 h.

9. The process for producing an arylalkenyl thioether compound according to claim 3 or 8, wherein: the heating temperature in the heating is 80 ℃, and the heating time is 12 h.

10. The process for producing an arylalkenyl thioether compound according to claim 3, wherein: in the purification, after removing the organic solvent, adding water, stirring for 3-5min, extracting by using ethyl acetate, drying the organic phase, and then carrying out column chromatography to obtain the product.

Technical Field

The invention relates to the technical field of compound preparation, in particular to an aryl thioether compound and a preparation method thereof.

Background

In the process of compound synthesis and drug synthesis, the physicochemical and biological properties of drugs can be effectively adjusted by introducing sulfur atoms or sulfur-containing groups into compound molecules and drug molecules, so that sulfur-containing compounds are extremely important organic synthesis intermediates in the fields of synthetic chemistry and pharmaceutical chemistry, for example, sulfur-containing cyano compounds are important organic synthesis intermediates, and can be further converted into trifluoromethylthio, thiol, thioether, disulfide, sulfur-containing heterocycle, thioamide and the like.

At present, the preparation of sulfur-containing compounds is mostly related to methods for synthesizing aryl or alkyl thiocyanates, but the methods for synthesizing alkenyl thiocyanates are not common, and particularly, a method for introducing two sulfur-containing groups into a molecule in one step does not have a corresponding synthesis method.

Disclosure of Invention

This section is for the purpose of summarizing some aspects of embodiments of the invention and to briefly introduce some preferred embodiments. In this section, as well as in the abstract and the title of the invention of this application, simplifications or omissions may be made to avoid obscuring the purpose of the section, the abstract and the title, and such simplifications or omissions are not intended to limit the scope of the invention.

The present invention has been made in view of the problems involved in the synthesis of sulfur-containing compounds.

Therefore, one of the objectives of the present invention is to overcome the disadvantages of the existing synthesis of sulfur-containing compounds, and to provide an arylalkenyl sulfide compound, which comprises the following chemical formula and acceptable salts, tautomers, stereoisomers and mixtures thereof in all ratios:

wherein

R₁Is one of hydrogen atom, alkyl, methoxy, halogen substituent, cyano, nitro, aldehyde group and ester group;

R₂is alkyl or phenyl;

R₃hydrogen atom, alkyl group, halogen atom, etc.

To solve the above technical problem, according to an aspect of the present invention, the present invention provides the following technical solutions: an arylalkenyl thioether compound, wherein R is₁Is one of alkyl, halogen, alkoxy, nitro, carbonyl, cyano, thiophene and furan groups.

The invention also aims to provide a preparation method of the arylalkenyl thioether compound, which comprises the following steps:

dissolving: dissolving alkyne, ammonium oxysulfate and N-aryl (alkyl) sulfenyl succinimide in an organic solvent;

heating: the dissolving system is heated and reacted for a period of time;

and (4) purification, namely separating and purifying after removing the solvent to obtain a product.

To solve the above technical problem, according to an aspect of the present invention, the present invention provides the following technical solutions: a preparation method of an arylalkenyl thioether compound is disclosed, wherein the molar ratio of alkyne, ammonium thiocyanate and N-aryl (alkyl) sulfenyl succinimide is 1: 1.0-5.0: 1.0-3.

To solve the above technical problem, according to an aspect of the present invention, the present invention provides the following technical solutions: the preparation process of aryl alkenyl thioether compound has the molar ratio of alkyne, ammonium thiocyanate and N-aryl (alkyl) sulfenyl succinimide of 1.0 to 2.0 to 1.2.

To solve the above technical problem, according to an aspect of the present invention, the present invention provides the following technical solutions: a method for preparing aryl alkenyl thioether compounds, wherein the organic solvent is one or more of hexafluoroisopropanol, trifluoroethanol and acetic acid.

To solve the above technical problem, according to an aspect of the present invention, the present invention provides the following technical solutions: a preparation method of aryl alkenyl thioether compounds is provided, wherein the weight volume ratio of ammonium thiocyanate to organic solvent is 1 g: 50 ml-100 ml.

To solve the above technical problem, according to an aspect of the present invention, the present invention provides the following technical solutions: a method for preparing aryl alkenyl thioether compounds, wherein the heating temperature is 50-120 deg.C, and the heating time is 4-48 h.

To solve the above technical problem, according to an aspect of the present invention, the present invention provides the following technical solutions: a preparation method of an arylalkenyl thioether compound is disclosed, wherein the heating temperature is 80 ℃, and the heating time is 12 hours.

To solve the above technical problem, according to an aspect of the present invention, the present invention provides the following technical solutions: a method for preparing aryl alkenyl thioether compounds comprises removing organic solvent, adding water, stirring for 3-5min, extracting with ethyl acetate, drying organic phase, and performing column chromatography to obtain the final product.

The invention provides an aryl thioether compound and a preparation method thereof, wherein the obtained product is (E) - (2-thiocyano) aryl thioether compound, which is a multifunctional group substituted olefin, is also an important organic synthesis intermediate, contains thiocyano and can be further converted into trifluoromethylthio, thioether, sulfur-containing heterocycle and the like, and is an intermediate product with a plurality of subsequent target sulfur-containing compounds, in the preparation process, the high-regioselectivity thiocyano/vulcanization bifunctional reaction of alkyne substrates is realized in one step by an atom-economical one-pot method, and compared with a common compound synthesis method, the method has the advantages of few steps, simplicity in operation, mild reaction, good selectivity, high yield, wide substrate application range, easiness in aftertreatment, and capability of recycling and reusing the solvent, and is suitable for large-scale mass synthesis.

Drawings

FIG. 1 is a NMR spectrum of a compound (E) -2- (4-fluorophenyl) -2-thiocyanoalkenyl-1- (4-methoxy) phenylsulfide;

FIG. 2 is a NMR carbon spectrum of the compound (E) -2- (4-fluorophenyl) -2-thiocyanoalkenyl-1- (4-methoxy) phenylsulfide;

FIG. 3 is a NMR spectrum of the compound (E) -2- (4-fluorophenyl) -2-thiocyanoalkenyl-1- (4-methoxy) phenylsulfide;

Detailed Description

In order to make the aforementioned objects, features and advantages of the present invention more comprehensible, specific embodiments thereof are described in detail below with reference to examples of the specification.

In the following description, numerous specific details are set forth in order to provide a thorough understanding of the present invention, but the present invention may be practiced in other ways than those specifically described and will be readily apparent to those of ordinary skill in the art without departing from the spirit of the present invention, and therefore the present invention is not limited to the specific embodiments disclosed below.

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.

The synthesis equation for the preparation of (E) - (2-thiocyano) aralkenyl sulfide compounds in the present invention is as follows:

the molecular formula of the obtained product, including one of (E) -2- (4-fluorophenyl) -2-thiocyano alkenyl-1- (4-methoxy) diphenyl sulfide, is shown as follows: