阅读说明：本技术 一种2-(2-氨基苯基)喹啉类化合物的合成方法 (Synthetic method of 2- (2-aminophenyl) quinoline compound ) 是由 范学森 杨玉洁 贾瑞雪 张新迎 于 2020-07-07 设计创作，主要内容包括：一种2-(2-氨基苯基)喹啉类化合物的合成方法,属于有机合成技术领域。该合成方法采用如下操作：将2-炔基苯胺类化合物1、催化剂、添加剂和六氟异丙醇混合,在含氧气体氛围或惰性气体氛围下加热反应,分别得到2-(2-氨基苯基)喹啉类化合物2或2-(2-氨基苯基)喹啉类化合物3。该合成方法通过两分子2-炔基苯胺之间的串联反应,通过改变反应的气氛,可以选择性地一步合成出不同种类的2-(2-氨基苯基)喹啉类化合物。该方法具有原料简单易得、操作简便、条件温和、底物适用范围广等优点,具有潜在的工业应用前景。(A method for synthesizing 2- (2-aminophenyl) quinoline compounds, belonging to the technical field of organic synthesis. The synthesis method adopts the following operations: mixing the 2-alkynyl aniline compound 1, a catalyst, an additive and hexafluoroisopropanol, and heating and reacting in an oxygen-containing gas atmosphere or an inert gas atmosphere to respectively obtain the 2- (2-aminophenyl) quinoline compound 2 or the 2- (2-aminophenyl) quinoline compound 3. The synthesis method can selectively synthesize different types of 2- (2-aminophenyl) quinoline compounds in one step by the series reaction between two molecules of 2-alkynyl aniline and changing the reaction atmosphere. The method has the advantages of simple and easily obtained raw materials, simple and convenient operation, mild conditions, wide substrate application range and the like, and has potential industrial application prospect.)

1. A synthetic method of a 2- (2-aminophenyl) quinoline compound is characterized by comprising the following operations: mixing the 2-alkynyl aniline compound 1, a catalyst, an additive and hexafluoroisopropanol, and heating and reacting in an oxygen-containing gas atmosphere or an inert gas atmosphere to respectively obtain a 2- (2-aminophenyl) quinoline compound 2 or a 2- (2-aminophenyl) quinoline compound 3, wherein the reaction equation is as follows:

wherein: r¹Is hydrogen, halogen, trifluoromethyl, C_1-4Alkyl or C_1-4Alkoxy radical, R²Is cyclopropyl, thienyl, phenyl or substituted phenyl, and the substituent on the benzene ring of the substituted phenyl is halogen, trifluoromethyl, C_1-4Alkyl or C_1-4An alkoxy group.

2. The method for synthesizing 2- (2-aminophenyl) quinolines according to claim 1, wherein: the catalyst is copper sulfate, trifluoromethanesulfonic acid ketone, bismuth trifluoromethanesulfonate, lithium trifluoromethanesulfonate or bismuth acetate.

3. The method for synthesizing 2- (2-aminophenyl) quinolines according to claim 1, wherein: the additive is trifluoroacetic acid, 2,4, 6-trimethyl benzoic acid or 1-adamantane carboxylic acid.

4. The method for synthesizing 2- (2-aminophenyl) quinolines according to claim 1, wherein: the catalyst is selected from bismuth trifluoromethanesulfonate or ketone trifluoromethanesulfonate, and the additive is selected from 2,4, 6-trimethyl benzoic acid or 1-adamantanecarboxylic acid.

5. The method for synthesizing 2- (2-aminophenyl) quinolines according to claim 1, wherein: the oxygen-containing gas atmosphere is selected from oxygen or air, and the inert gas atmosphere is nitrogen or argon.

6. The method for synthesizing 2- (2-aminophenyl) quinolines as claimed in claim 5, wherein: the oxygen-containing gas atmosphere is favorable for the generation of the 2- (2-aminophenyl) quinoline compounds 2, and the inert gas atmosphere is favorable for the generation of the 2- (2-aminophenyl) quinoline compounds 3.

7. The method for synthesizing 2- (2-aminophenyl) quinolines according to claim 1, wherein: the feeding molar ratio of the 2-alkynyl aniline compound 1 to the additive to the catalyst is 1:0.25-2: 0.05-0.15.

8. The method for synthesizing 2- (2-aminophenyl) quinolines according to any one of claims 1 to 7, characterized in that: the heating reaction temperature is 60-120 ℃.

Technical Field

The invention belongs to the technical field of organic synthesis, and particularly relates to a synthetic method of a 2- (2-aminophenyl) quinoline compound.

Background

Quinoline is an important nitrogen-containing heterocyclic ring, and a plurality of compounds containing a quinoline framework have good pharmacological activities of resisting malaria, resisting inflammation, resisting schizophrenia and the like. The quinoline derivative can also form a complex with metal, and shows good electrochemical performance. Based on the characteristics, the functional group quinoline derivatives are widely applied to the fields of medicines, fine chemicals and the like.

At present, some reliable methods have been developed for synthesizing 2- (2-aminophenyl) quinoline compounds, but the methods still have the problems of difficult obtainment of raw materials, harsh reaction conditions, complicated synthesis steps, low atom economy and the like.

Therefore, a green and efficient novel method for synthesizing the 2- (2-aminophenyl) quinoline compound by starting from simple and easily-obtained raw materials and through simple and convenient operation steps is researched and developed, and the method has very important theoretical significance and practical prospect.

Disclosure of Invention

The invention solves the technical problem of providing a synthetic method of 2- (2-aminophenyl) quinoline compounds, and the synthetic method synthesizes the 2- (2-aminophenyl) quinoline compounds in one step through the series reaction between two molecules of 2-alkynyl aniline. The method has the advantages of simple and easily obtained raw materials, simple and convenient operation, mild conditions, wide substrate application range and the like, and has potential industrial application prospect.

The invention adopts the following technical scheme for solving the technical problems, and the synthesis method of the 2- (2-aminophenyl) quinoline compound comprises the following operations: mixing the 2-alkynyl aniline compound 1, a catalyst, an additive and Hexafluoroisopropanol (HFIP), and heating and reacting in an oxygen-containing gas atmosphere or an inert gas atmosphere to respectively obtain a 2- (2-aminophenyl) quinoline compound 2 or a 2- (2-aminophenyl) quinoline compound 3, wherein the reaction equation is as follows:

wherein: r¹Is hydrogen, halogen, trifluoromethyl, C_1-4Alkyl or C_1-4Alkoxy radical, R²Is cyclopropyl, thienyl, phenyl or substituted phenyl, and the substituent on the benzene ring of the substituted phenyl is halogen, trifluoromethyl, C_1-4Alkyl or C_1-4An alkoxy group.

Further, in the technical scheme, the catalyst is copper sulfate and trifluoromethanesulfonic acid ketone { Cu (OTf)₂Bismuth trifluoromethanesulfonate { Bi (OTf)₃Lithium trifluoromethanesulfonate (LiOTf) or bismuth acetate { Bi (OAc)₃}。

Further, in the above technical scheme, the additive is trifluoroacetic acid (TFA), 2,4, 6-trimethylbenzoic acid (MesCOOH) or 1-adamantanecarboxylic acid (1-AdCOOH).

Further, in the above-mentioned embodiment, the reaction atmosphere is an oxygen-containing gas atmosphere (for example, in oxygen or air) or an inert gas atmosphere (for example, in nitrogen or argon) which is advantageous for the production of the 2- (2-aminophenyl) quinoline compound 2, and the inert gas atmosphere (for example, in oxygen or air) which is advantageous for the production of the 2- (2-aminophenyl) quinoline compound 3.

Further, in the technical scheme, the feeding molar ratio of the 2-alkynyl aniline compound 1 to the additive to the catalyst is 1:0.25-2: 0.05-0.15.

Further, in the above technical scheme, the heating reaction temperature is 60-120 ℃.

The invention has the beneficial effects that:

compared with the prior art, the invention has the following advantages: 1) the synthetic process is simple and efficient, and the 2- (2-aminophenyl) quinoline compound is obtained in one step by the series reaction between two molecules starting from the 2-alkynyl aniline compound; 2) different 2- (2-aminophenyl) quinoline compounds can be selectively synthesized by changing the reaction atmosphere; 3) the raw materials are cheap and easy to obtain, the reaction conditions are mild, the operation is simple and convenient, the application range of the substrate is wide, the atom economy is high, and the requirements of green chemistry are met. Therefore, the invention provides a novel efficient and practical method for synthesizing the 2- (2-aminophenyl) quinoline compound.

Drawings

FIG. 1 is a single crystal X-ray diffraction pattern (30% ellipsoid) for Compound 2d of example 3.

Detailed Description

The present invention is described in further detail below with reference to examples, but it should not be construed that the scope of the above subject matter of the present invention is limited to the following examples, and that all the technologies realized based on the above subject matter of the present invention belong to the scope of the present invention.