阅读说明：本技术 一种钯催化合成4-取代喹啉衍生物的方法 (Method for synthesizing 4-substituted quinoline derivative under palladium catalysis ) 是由 *** 姚子健 薛原 于 2019-09-26 设计创作，主要内容包括：本发明属于合成化学技术领域,具体为一种钯催化合成4-取代喹啉衍生物的方法。本发明在乙酰丙酮钯为催化剂,有机膦为配体的条件下,将喹啉或其衍生物、卤代烃和Cs<Sub>2</Sub>CO<Sub>3</Sub>溶于有机溶剂,在60～80℃下反应5～8小时,分离纯化,即得4-取代喹啉衍生物。本发明合成工艺简单绿色,具有优良的选择性和较高产率,且具有广泛的底物范围,本发明在药物化学和生物化学等领域具有广泛的应用价值。(The invention belongs to the technical field of synthetic chemistry, and particularly relates to a method for synthesizing a 4-substituted quinoline derivative under the catalysis of palladium. In the invention, quinoline or derivatives thereof, halogenated hydrocarbon and Cs are reacted under the conditions that palladium acetylacetonate is used as a catalyst and organic phosphine is used as a ligand 2 CO 3 Dissolving in an organic solvent, reacting for 5-8 hours at 60-80 ℃, and separating and purifying to obtain the 4-substituted quinoline derivative. The invention has simple and green synthesis process, excellent selectivity, higher yield and wide substrate range, and has wide application value in the fields of medicinal chemistry, biochemistry and the like.)

1. A method for synthesizing a 4-substituted quinoline derivative under the catalysis of palladium is characterized by comprising the following steps:

under the condition of using palladium acetylacetonate as catalyst and using organic phosphine as ligand, quinoline or its derivative, halohydrocarbon and Cs₂CO₃Dissolving in an organic solvent, reacting for 5-8 h at 60-80 ℃, and separating and purifying to obtain the 4-substituted quinoline derivative.

2. The method of claim 1, wherein the palladium acetylacetonate, the organophosphine, the quinoline or its derivatives, the halogenated hydrocarbon and the Cs are selected from the group consisting of palladium acetylacetonate, an organic phosphine, and Cs₂CO₃Is 0.05: (0.10-0.12): 1.0: (1.1-1.2): 1.5.

3. the method for palladium-catalyzed synthesis of 4-substituted quinoline derivatives according to claim 1, wherein the separation and purification is performed by column chromatography, and the eluent is dichloromethane and petroleum ether at a volume ratio of 1: 6.

4. The method of claim 1, wherein the quinoline or the derivative thereof is selected from the group consisting of but not limited to quinoline, 6-methylquinoline, 8-methylquinoline, and 7-methoxyquinoline.

5. The method of claim 1, wherein the halogenated hydrocarbon includes, but is not limited to, methyl iodide, ethyl bromide, n-propyl bromide, benzyl chloride, iso-butyl bromide, and bromobenzene.

6. The method for palladium-catalyzed synthesis of 4-substituted quinoline derivatives as claimed in claim 1, wherein the organic phosphine includes but is not limited to triphenylphosphine PPh₃Trimethyl phosphine PMe₃Tricyclohexylphosphine PCy₃。

7. The method for palladium-catalyzed synthesis of 4-substituted quinoline derivatives according to claim 1, wherein the organic solvent is toluene or tetrahydrofuran.

Technical Field

The invention relates to the technical field of chemical synthesis, in particular to a method for synthesizing a 4-substituted quinoline derivative under the catalysis of palladium.

Background

Quinoline is an important chemical raw material and is widely used for industrial production of dyes, medicines, bactericides, herbicides and the like, for example, quinoline and derivatives thereof can be used for synthesizing medicaments for resisting malaria, hypertension and the like, and some derivatives containing quinoline rings also have biological activities of resisting tumors, resisting depression, resisting bacteria, diminishing inflammation, resisting hypertension and the like. Through further research, the quinoline has substituent groups on the quinoline ring, so that the activity of the quinoline can be greatly improved, but the traditional method for synthesizing the quinoline derivative has more steps, low yield and difficult separation.

Therefore, how to provide a method for realizing the selective coupling of quinoline and halogenated hydrocarbon by using a transition metal catalysis method so as to directly construct the 4-substituted quinoline derivative has very important research significance.

Disclosure of Invention

In view of the above, the invention provides a method for synthesizing a 4-substituted quinoline derivative under palladium catalysis, which has the advantages of simple and green synthesis process, excellent selectivity, high yield, wide substrate range and wide application value in the fields of pharmaceutical chemistry, biochemistry and the like.

In order to achieve the purpose, the invention adopts the following technical scheme:

a method for synthesizing 4-substituted quinoline derivatives by palladium catalysis comprises the following steps:

under the condition of using palladium acetylacetonate as catalyst and using organic phosphine as ligand, quinoline or its derivative, halohydrocarbon and Cs₂CO₃Dissolving in an organic solvent, reacting for 5-8 h at 60-80 ℃, and separating and purifying to obtain the 4-substituted quinoline derivative.

The beneficial effects of the above technical scheme are: the chemical reaction of the invention is carried out at room temperature, the conditions are simple, the operation is convenient, and if the temperature is too low, the yield of the product is reduced.

Preferably, in one of the above-mentioned methods for the palladium-catalyzed synthesis of a 4-substituted quinoline derivative, palladium acetylacetonate, an organic phosphine, quinoline or a derivative thereof, a halogenated hydrocarbon and Cs₂CO₃Is 0.05: (0.10-0.12): 1.0: (1.1-1.2): 1.5.

the beneficial effects of the above technical scheme are: the efficiency is highest under the condition of the molar ratio, and the waste of raw materials is not caused.

Preferably, in the above method for palladium-catalyzed synthesis of 4-substituted quinoline derivatives, the separation and purification is performed by column chromatography, and the eluent is dichloromethane and petroleum ether at a volume ratio of 1: 6.

Preferably, in one of the above methods for palladium-catalyzed synthesis of 4-substituted quinoline derivatives, the quinoline or its derivatives include, but are not limited to, quinoline, 6-methylquinoline, 8-methylquinoline, 7-methoxyquinoline.

Preferably, in one of the above methods for palladium-catalyzed synthesis of 4-substituted quinoline derivatives, the halogenated hydrocarbon includes, but is not limited to, methyl iodide, ethyl bromide, n-propyl bromide, benzyl chloride, iso-bromobutane, bromobenzene.

Preferably, in one of the above-described methods for the palladium-catalyzed synthesis of 4-substituted quinoline derivatives, the organophosphine includes, but is not limited to, triphenylphosphine, PPh₃Trimethyl phosphine PMe₃Tricyclohexylphosphine PCy₃。

Preferably, in the above method for palladium-catalyzed synthesis of a 4-substituted quinoline derivative, the organic solvent is toluene or tetrahydrofuran.

The beneficial effects of the above technical scheme are: the organic solvent is used for fully dissolving each substrate, so that the reaction is easier to carry out.

According to the technical scheme, compared with the prior art, the invention discloses a method for synthesizing the 4-substituted quinoline derivative under the catalysis of palladium, which has the following advantages:

(1) the synthetic method is simple and green, and the 4-substituted quinoline derivative is directly constructed by using cheap and easily-obtained raw materials of quinoline and halogenated hydrocarbon;

(2) the reaction condition is mild, and the selectivity is high;

(3) the invention uses cheap, easily obtained and stable palladium acetylacetonate Pd (acac)₂The catalyst is green and economical;

(4) the invention has good substrate universality, thereby being better convenient for application.

Detailed Description

The technical solutions in the embodiments of the present invention will be clearly and completely described below, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.