阅读说明：本技术 一种杂芳基硫醚的合成方法 (Synthetic method of heteroaryl thioether ) 是由 徐清 王�琦 章小兰 赵霖昱 于 2020-05-29 设计创作，主要内容包括：本发明公开了一种杂芳基硫醚的合成方法,其步骤为：在无催化剂、无溶剂、无添加剂等条件下,不使用常规有机硫化物如硫醇或硫酚,直接以卤代芳烃/2-溴吡啶、硫脲和取代苄基溴为原料一步选择性合成非对称杂芳基硫醚。该方法避免了毒性大、臭味重的有机硫化物如硫醇或硫酚的使用,缩短了合成步骤,从而提高了合成效率,且反应具有很好的选择性,可以优先得到非对称硫醚。(The invention discloses a method for synthesizing heteroaryl thioether, which comprises the following steps: under the conditions of no catalyst, no solvent, no additive and the like, the asymmetric heteroaryl thioether is directly selectively synthesized in one step by taking halogenated aromatic hydrocarbon/2-bromopyridine, thiourea and substituted benzyl bromide as raw materials without using conventional organic sulfides such as mercaptan or thiophenol. The method avoids the use of organic sulfides such as mercaptan or thiophenol with high toxicity and strong odor, shortens the synthesis steps, thereby improving the synthesis efficiency, has good selectivity of the reaction, and can preferentially obtain the asymmetric thioether.)

1. A method for synthesizing heteroaryl thioether is characterized by comprising the step of selectively synthesizing asymmetric heteroaryl thioether by using halogenated aromatic hydrocarbon/2-bromopyridine, thiourea and substituted benzyl bromide as reaction raw materials,

Method A

Method B

wherein FG is methyl or chlorine; r is phenyl, p-methylphenyl, p-nitrophenyl, p-chlorophenyl, cinnamyl, naphthyl, cyclopentyl, cyclohexyl or cycloheptyl.

2. The method of claim 1, wherein the reaction time is 2 to 24 hours and the reaction temperature is 80 to 170 ℃.

3. The process of claim 1 wherein the molar ratio of haloarene/2-bromopyridine, thiourea and substituted benzyl bromide is 1:1.2: 1.2.

4. The process of claim 1, wherein the reaction is carried out in the presence or absence of a solvent.

5. The process of claim 1, wherein the reaction is carried out under an inert gas blanket or under air.

Technical Field

The invention relates to a synthesis method of heteroaryl thioether, belonging to the technical field of synthesis of organic sulfur compounds.

Background

Organic sulfur compounds are a very important compound, are used as important intermediates for organic and pharmaceutical synthesis, and have important applications in the fields of catalysis, high molecular materials, natural products, pesticides and the like. In addition, various thioether structures are widely present in molecules having various biological and pharmaceutical activities, such as treating diseases such as inflammation, anti-depression, HIV, asthma and senile dementia.

However, in the former work, a catalyst, an auxiliary agent, an additive or the like needs to be added into the reaction system, and more waste is generated. Therefore, it is very significant for organic synthesis, biochemistry and medicinal chemists to find a new green and simple method for synthesizing asymmetric heteroaryl thioether compounds in one step by using stable and low-toxicity raw materials.

Disclosure of Invention

The invention aims to provide a method for preparing heteroaryl thioether by directly reacting benzyl bromide which is cheap and easy to obtain as an alkylating reagent and common thiourea as a sulfur source with 2-bromopyridine without any additional catalyst.

The technical scheme of the invention is as follows: a process for synthesizing the heteroaryl thioether includes such steps as selectively synthesizing the asymmetric heteroaryl thioether from haloarylhydrocarbon or 2-bromopyridine, thiourea (or selenourea) and substituted benzyl bromide,

Method A

Method B

wherein FG refers to a substituted functional group of halogenated aromatic hydrocarbon, preferably methyl and chlorine; r in the substituted benzyl bromide refers to a functional group such as phenyl, p-methylphenyl, p-nitrophenyl, p-chlorophenyl, cinnamyl, naphthyl, cyclopentyl, cyclohexyl, cycloheptyl and the like.

Preferably, the reaction time is 2-24 hours, and the reaction temperature is 80-170 ℃.

Preferably, the molar ratio of the halogenated aromatic hydrocarbon or the 2-bromopyridine to the thiourea to the substituted benzyl bromide is 1:1.2: 1.2.

Preferably, the reaction is carried out with or without a solvent.

Preferably, the reaction is carried out under an inert gas blanket or under air.

Compared with the prior art, the invention has the advantages that: the method avoids the use of organic sulfides with high toxicity and heavy odor, such as mercaptan or thiophenol, shortens the synthesis steps, thereby improving the synthesis efficiency, has good selectivity for the reaction, can preferentially obtain the asymmetric thioether, and does not need any additional catalyst, auxiliary agent or additive for the reaction.

The invention will be further described with reference to specific embodiments.

Detailed Description

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

A method for selectively synthesizing asymmetric heteroaryl thioether in one step by using 2-bromopyridine, thiourea and benzyl bromide as raw materials. The method avoids the use of organic sulfides such as mercaptan or thiophenol with high toxicity and strong odor, shortens the synthesis steps, thereby improving the synthesis efficiency, has good selectivity of the reaction, and can preferentially obtain the asymmetric thioether. The method has the advantages of simple reaction conditions, no need of inert gas protection, no need of solvent, easy operation and low requirements on the reaction conditions. The reaction time is 2-24 hours, and the reaction temperature is 80-170 ℃.