CN109796403B

CN109796403B - Quinoline derivatives and preparation method thereof

Info

Publication number: CN109796403B
Application number: CN201910020065.5A
Authority: CN
Inventors: 秦锋; 张武
Original assignee: Anhui Normal University
Current assignee: Anhui Normal University
Priority date: 2019-01-09
Filing date: 2019-01-09
Publication date: 2021-09-28
Anticipated expiration: 2039-01-09
Also published as: CN109796403A

Abstract

The invention discloses a quinoline derivative and a preparation method thereof, wherein the preparation method comprises the following steps: (1) mixing an aromatic amine compound, a styrene compound, copper salt, persulfate and 1, 10-phenanthroline, adding an organic solvent, stirring and heating to obtain a product; (2) drying, separating and purifying the product to obtain the quinoline derivative. The method has the advantages of easily available raw materials, high efficiency and wide application.

Description

Quinoline derivatives and preparation method thereof

Technical Field

The invention relates to the field of organic synthesis, in particular to a quinoline derivative and a preparation method thereof.

Background

Quinoline compounds are widely present in natural products, and have good biological and physiological activities, so that the quinoline compounds are widely applied to the aspects of pharmaceutical industry and the like, particularly as important components of anticancer agents, antiviral agents, antimalarial agents and antituberculosis agents, and the research on a synthesis method of the quinoline compounds is necessary due to the important application value of the quinoline compounds in the field of medicines. The methods for synthesizing quinoline compounds reported in the literature mainly include the following methods:

reacting o-aminobenzyl alcohol with fatty alcohol to obtain a quinoline tired compound under the action of KOH;

this method, although simple in terms of conditions, requires the use of strong base KOH;

under the action of metal cobalt, adding bis (trifluoromethane sulfonyl) imide silver salt into acetanilide and diphenylacetylene, and reacting in DCE for 16 hours to obtain a product;

the substrate of the reaction has wide application range and high yield, but the reaction needs to use noble metal silver;

(III) benzophenone and aniline in FeCl₃Under the action of the (3), potassium persulfate is added and nitrogen is introduced, and the reaction is carried out in DMSO for 16 hours, so that a target product can be obtained, the yield can reach 80 percent, although the method has high yield and wide substrate application range, nitrogen is required to be introduced for protection, and the industrialization is difficult;

(IV) reacting for 12 h under the nitrogen condition by using an o-amino alkene compound as a substrate and metal palladium as a catalyst to obtain a quinoline product, wherein the method not only uses noble metal palladium, but also needs nitrogen protection, and has higher reaction cost, so the method is not suitable for industrial production;

(penta) aniline benzaldehyde benzophenone can obtain a product under the action of silver trifluoromethanesulfonate and trifluoromethanesulfonic acid, and the method is simple but needs to use silver salt and trifluoromethanesulfonic acid;

(VI) aniline and aromatic ketone compounds react for 36 hours under the action of methanesulfonic acid to obtain a target product quinoline compound, and although the reaction has cheap and easily obtained raw materials, the reaction time is long, and the yield is low;

(VII) the aromatic amine compound and the alkyne compound are heated and reacted for 12 hours in DMSO under the action of metal cobalt and silver, so that a target product can be obtained, the substrate adaptability of the reaction is wide, and the raw materials are cheap and easy to obtain and the yield is high;

in summary, the prior art has many methods for synthesizing quinoline derivatives, but some of the methods require complicated synthetic steps and have more side reactions and lower yield; some use highly toxic substrates or organic solvents easily cause environmental pollution; some of the catalyst uses noble metal palladium and the like, has high cost, is not suitable for industrial production and the like.

Therefore, the invention provides a quinoline derivative which is easy to obtain raw materials, environment-friendly, efficient, high in yield and suitable for industrial production and a preparation method thereof, and aims to solve the problem in urgent need.

Disclosure of Invention

The invention aims to provide a quinoline derivative and a preparation method thereof, and the method has the advantages of easily available raw materials, high efficiency and wide application.

In order to achieve the above object, the present invention provides a preparation method of a quinoline derivative, the preparation method comprising:

(1) mixing an aromatic amine compound, a styrene compound, copper salt, persulfate and 1, 10-phenanthroline, adding an organic solvent, stirring and heating to obtain a product;

(2) drying, separating and purifying the product to obtain the quinoline derivative.

The invention also provides a quinoline derivative prepared by the preparation method.

According to the technical scheme, the invention provides a quinoline derivative and a preparation method thereof, compared with the prior art, the 4-quinoline derivative is synthesized by reacting an aromatic amine compound with a styrene compound, firstly, an organic solvent is oxidized by persulfate to obtain an intermediate A, then, styrene and aniline react to obtain an intermediate B, the intermediate A and the intermediate B react to generate a six-membered ring, and finally, the 4-quinoline compound is generated under the action of an oxidant; the method has the following advantages: (1) the method is carried out in an air-gas environment, so that the cost is low; (2) noble metals such as palladium, ruthenium and the like are not used, and copper salts such as cuprous iodide and the like are used as catalysts, so that the cost is saved; (3) the reaction raw materials are cheap and easy to obtain; (4) the synthesis method has high efficiency and wide application range, and is suitable for reaction of various substrates.

Additional features and advantages of the invention will be set forth in the detailed description which follows.

Drawings

The accompanying drawings, which are included to provide a further understanding of the invention and are incorporated in and constitute a part of this specification, illustrate embodiments of the invention and together with the description serve to explain the principles of the invention and not to limit the invention. In the drawings:

FIG. 1 is a reaction equation of aromatic amine compound and styrene compound;

R¹selected from the group consisting of 4-F, 4-Cl, 4-Br, 4-COOMe, 4-NO₂Or 3, 4-dimethyl;

R²is H, 4-F, 4-OCH₃、4-C(CH₃)₃、2-CH₃Or 3-CH₃One of (1);

FIG. 3a is a diagram of 6-chloro-4-phenylquinoline prepared in example 2¹H NMR；

FIG. 3b is a diagram of 6-chloro-4-phenylquinoline prepared in example 2¹³C NMR；

FIG. 4a is a schematic representation of 6-bromo-4-phenylquinoline prepared in example 3¹H NMR；

FIG. 4b is a schematic representation of 6-bromo-4-phenylquinoline prepared in example 3¹³C NMR；

FIG. 5a is a drawing of methyl 6-carboxylate-4-phenylquinoline prepared in example 4¹H NMR；

FIG. 5b is a drawing of methyl 6-carboxylate-4-phenylquinoline prepared in example 4¹³C NMR；

FIG. 6a is a photograph of 6-nitro-4-phenylquinoline prepared in example 5¹H NMR；

FIG. 6b is a photograph of 6-nitro-4-phenylquinoline prepared in example 5¹³C NMR；

FIG. 7a is a photograph of 4- (4-tert-butylphenyl) -6-methyl-quinoline prepared according to example 6¹H NMR；

FIG. 7b is a photograph of 4- (4-tert-butylphenyl) -6-methyl-quinoline prepared according to example 6¹³C NMR；

FIG. 8a is a photograph of 4- (4-methoxyphenyl) -6-methyl-quinoline prepared in example 7¹H NMR；

FIG. 8b is a scheme showing the preparation of 4- (4-methoxyphenyl) -6-methyl-quinoline in example 7¹³C NMR；

FIG. 9a is a photograph of 4- (4-fluorophenyl) -6-methyl-quinoline prepared according to example 8¹H NMR；

FIG. 9b is a drawing of 4- (4-fluorophenyl) -6-methyl-quinoline prepared in example 8¹³C NMR；

FIG. 10a is a photograph of 6, 7-dimethyl-4-phenylquinoline prepared in example 9¹H NMR；

FIG. 10b is a drawing of 6, 7-dimethyl-4-phenylquinoline prepared in example 9¹³C NMR；

FIG. 11a is 4- (2-methylphenyl) -6-methyl-quinoline prepared according to example 10¹H NMR；

FIG. 11b is 4- (2-methylphenyl) -6-methyl-quinoline prepared in example 10¹³C NMR；

FIG. 12a is 4- (3-methylphenyl) -6-methyl-quinoline prepared according to example 11¹H NMR；

FIG. 12b is 4- (3-methylphenyl) -6-methyl-quinoline prepared in example 11¹³C NMR。

Detailed Description

The following detailed description of embodiments of the invention refers to the accompanying drawings. It should be understood that the detailed description and specific examples, while indicating the present invention, are given by way of illustration and explanation only, not limitation.

The invention provides a preparation method of quinoline derivatives, which comprises the following steps:

In a preferred embodiment of the present invention, in order to further improve the quality and yield of the product, the aromatic amine compound, the styrene compound, the copper salt, the persulfate and the 1, 10-phenanthroline are mixed in a molar ratio of 1:1.0-1.5:0.8-0.15: 1-2.

In a preferred embodiment of the invention, the quality of the product is further improvedThe amount and the yield of the aromatic amine compound are as follows:

；

wherein, R is¹Selected from 4-F, 4-Cl, 4-Br, 4-COOMe, 4-NO₂Or 3, 4-dimethyl;

in a preferred embodiment of the present invention, to further improve the quality and yield of the product, the styrenic compound has the formula:

；

wherein R is²Is H, 4-F, 4-OCH₃、4-C(CH₃)₃、2-CH₃Or 3-CH₃One kind of (1).

In a preferred embodiment of the present invention, the copper salt is one or more of cuprous iodide, cuprous bromide, cuprous chloride and cupric acetate in order to further improve the quality and yield of the product.

In a preferred embodiment of the present invention, the persulfate is potassium persulfate and/or ammonium persulfate in order to further improve the quality and yield of the product.

In a preferred embodiment of the present invention, the organic solvent is selected from one or more of DMF, DMSO and DMA in order to further improve the quality and yield of the product.

In a preferred embodiment of the present invention, to further improve the quality and yield of the product, the heating conditions comprise: the temperature is 100-120 ℃, and the time is 8-16 h.

In a preferred embodiment of the present invention, in order to further improve the quality and yield of the product, the step (2) further comprises: extracting the product with ethyl acetate, drying with anhydrous sodium sulfate, concentrating under reduced pressure to obtain crude product, and separating by column chromatography to obtain quinoline derivatives;

preferably, the developing solvent used for column chromatography separation comprises the following raw materials: petroleum ether and ethyl acetate;

preferably, the volume ratio of petroleum ether to ethyl acetate is 10: 0.9-1.1.

The invention also provides a quinoline derivative, which is prepared by the preparation method;

preferably, the quinoline derivatives have the structural formula:

；

wherein R is¹Selected from 4-F, 4-Cl, 4-Br, 4-COOMe, 4-NO₂Or 3, 4-dimethyl;

R²is H, 4-F, 4-OCH₃、4-C(CH₃)₃、2-CH₃Or 3-CH₃One kind of (1).

The following description will be made by specific examples.

Example 2

(1) 0.5 mmol of 4-chloroaniline and 0.6 mmol of styrene are taken and put into a reaction tube, and then 0.05 mmol of CuCl is added in turn₂、0.05 mmol 1,10-Phen、0.75 mmol K₂S₂O₈3 mL of DMSO, and stirring and reacting for 12 hours at 110 ℃;

(2) extracting the product with ethyl acetate, drying with anhydrous sodium sulfate, concentrating under reduced pressure to obtain crude product, and purifying the crude product with silica gel column chromatography (the volume ratio of the solvent is petroleum ether: ethyl acetate = 10: 1) to obtain yellow solid, i.e. 6-chloro-4-phenylquinoline with a yield of 38%; the nuclear magnetic resonance spectrum is shown in figure 3a and figure 3 b;

¹ (500 MHz, CDCl₃) δ ppm : 8.94 (d, J = 4.0 Hz, 1H), 8.13 (d, J = 9.0 Hz, 1H), 7.89 (d, J = 2 Hz, 1H), 7.69-7.66 (m, 1H), 7.58-7.48 (m, 6H), 7.37(d, J = 4.5 Hz, 1H);

¹³ (125 MHz, CDCl₃) δ ppm : 149.1, 146.8, 146.1, 136.3, 131.6, 130.5, 129.3, 128.4, 127.8, 127.7, 126.5, 123.7, 121.0

example 3

(1) 0.5 mmol of 4-bromoaniline and 0.6 mmol of the compound are takenmmol styrene is put in a reaction tube, and then 0.05 mmol CuI, 0.05 mmol 1,10-Phen, 3 mL DMF and 0.75 mmol K are added in sequence₂S₂O₈Stirring and reacting for 12 hours at 110 ℃;

(2) extracting the product with ethyl acetate, drying with anhydrous sodium sulfate, concentrating under reduced pressure to obtain crude product, and purifying the crude product with silica gel column chromatography (the volume ratio of the solvent is petroleum ether: ethyl acetate = 10: 1) to obtain yellow solid, i.e. 6-bromo-4-phenylquinoline with a yield of 49%; the nuclear magnetic resonance spectrum is shown in figure 4a and figure 4 b;

¹ (500 Hz, CDCl₃) δ ppm : 8.88 (s, 1H), 7.99 (d, J = 7.5 Hz, 2H), 7.73 (d, J =8.5 Hz, 1H), 7.49-7.41 (m, 6H), 7.30 (d, J = 3 Hz, 1H);

¹³ (125 MHz, CDCl₃) δ ppm : 149.2, 146.8, 146.3, 136.2, 131.9, 131.1, 130.6, 128.4, 127.8, 127.8, 127.0, 126.0。

example 4

(1) 0.5 mmol of 4-methyl formate aniline and 0.6 mmol of styrene are put into a reaction tube, and then 0.05 mmol of CuCl, 0.05 mmol of 1,10-Phen, 3 mL of DMSO and 0.75 mmol of K are sequentially added₂S₂O₈Stirring and reacting for 12 hours at 110 ℃;

(2) extracting the product with ethyl acetate, drying with anhydrous sodium sulfate, concentrating under reduced pressure to obtain crude product, and purifying the crude product with silica gel column chromatography (the solvent volume ratio is petroleum ether: ethyl acetate = 10: 1) to obtain yellow solid, namely 6-methyl formate-4-phenylquinoline, with the yield of 57%; the nuclear magnetic resonance spectrum is shown in figure 5a and figure 5 b;

¹ (500 Hz, CDCl₃) δ ppm : 8.98 (d, J = 4.5 Hz, 1H), 8.63 (d, J = 1.5 Hz, 1H), 8.27-8.25 (m, 1H), 8.19 (d, J = 8.5 Hz, 1H), 7.52-7.44 (m, 5H), 7.36 (d, J = 4.0 Hz, 1H), 3.86 (s, 3H);

¹³ (125 MHz, CDCl₃) δ ppm : 165.6, 150.5, 149.6, 148.9, 136.1, 128.6, 128.0, 127.9, 127.4, 127.3, 125.1, 121.1, 51.4.

example 5

(1) 0.5 mmol of 4-nitroaniline and 0.6 mmol of styrene are put into a reaction tube, and then 0.05 mmol of CuI, 0.05 mmol of 1,10-Phen, 3 mL of DMSO and 0.75 mmol (NH) are added in sequence₄）₂S₂O₈Stirring and reacting for 12 hours at 110 ℃;

(2) extracting the product with ethyl acetate, drying with anhydrous sodium sulfate, concentrating under reduced pressure to obtain crude product, and purifying the crude product with silica gel column chromatography (the volume ratio of the solvent is petroleum ether: ethyl acetate = 10: 1) to obtain yellow solid, i.e. 6-nitro-4-phenylquinoline with a yield of 52%; the nuclear magnetic resonance spectrum is shown in figure 6a and figure 6 b;

¹ (500 Hz, CDCl₃) δ ppm: 9.11 (d, J = 4.0 Hz, 1H), 8.89 (d, J = 2.0 Hz, 1H), 8.51-8.49 (m, 1H),8.34 (d, J = 9.5 Hz, 1H), 7.63-7.57 (m, 3H), 7.53-7.51 (m, 3H)；

¹³ (500 MHz, CDCl₃) δ ppm: 153.4, 151.3, 151.0, 146.2, 136.8, 132.1, 130.1, 129.9, 129.6, 126.3, 123.5, 123.3, 123.3。

example 6

(1) 0.5 mmol of 4-methylaniline and 0.6 mmol of 4-tert-butylstyrene are put into a reaction tube, and then 0.05 mmol of CuBr, 0.05 mmol of 1,10-Phen, 3 mL of DMSO and 0.75 mmol of K are sequentially added₂S₂O₈Stirring and reacting for 12 hours at 110 ℃;

(2) extracting the product with ethyl acetate, drying with anhydrous sodium sulfate, concentrating under reduced pressure to obtain crude product, and purifying the crude product with silica gel column chromatography (the volume ratio of the solvent is petroleum ether: ethyl acetate = 10: 1) to obtain white liquid, i.e. 4- (4-tert-butylphenyl) -6-methyl-quinoline with a yield of 73%; the nuclear magnetic resonance spectrum is shown in figure 7a and figure 7 b;

¹ (500 Hz, CDCl₃) δ ppm : 8.79 (d, J = 3.5 Hz, 1H), 8.07 (d, J = 8.5 Hz, 1H), 7.69 (s, 1H), 7.52-7.48 (m, 3H), 7.39 (d, J = 8.5 Hz, 1H), 7.26 (d, J = 4.5 Hz, 1H), 2.49 (s, 3H), 1.42 (s, 9H).

¹³ (125 MHz, CDCl₃) δ ppm: 148.4, 148.2, 147.4, 146.0, 137.1, 128.5, 128.2, 127.5, 127.4, 127.3, 125.2, 120.4, 119.7, 34.0, 30.1;

example 7

(1) 0.5 mmol of 4-methylaniline and 0.6 mmol of 4-methoxystyrene are put into a reaction tube, and then 0.05 mmol of CuI, 0.05 mmol of 1,10-Phen, 3 mL of DMSO and 0.75 mmol of K are sequentially added₂S₂O₈Stirring and reacting for 12 hours at 110 ℃;

(2) extracting the product with ethyl acetate, drying with anhydrous sodium sulfate, concentrating under reduced pressure to obtain crude product, and purifying the crude product with silica gel column chromatography (the volume ratio of the solvent is petroleum ether: ethyl acetate = 10: 1) to obtain yellow liquid, i.e. 4- (4-methoxyphenyl) -6-methyl-quinoline with a yield of 72%; the nuclear magnetic resonance spectrum is shown in figure 8a and figure 8 b;

¹(500 Hz, CDCl₃) δ ppm : 8.76 (d, J = 4.5 Hz, 1H), 7.99 (d, J = 8.5 Hz, 1H), 7.63 (s, 1H), 7.48-7.46 (m, 1H), 7.37-7.36 (m, 2H), 7.20-7.18 (m, 1H), 7.00-6.98 (m, 2H), 3.83 (s, 3H), 2.40 (m, 3H);

¹³ (125 MHz, CDCl₃) δ ppm: 157.8, 147.4, 147.1, 144.6, 138.2, 131.1, 129.2, 128.6, 128.3, 127.6, 121.7, 121.6, 103.6, 55.3。

example 8

(1) 0.5 mmol of 4-methylaniline and 0.6 mmol of 4-fluorostyrene are put into a reaction tube, and then 0.05 mmol of CuI, 0.05 mmol of 1,10-Phen, 3 mL of DMSO and 0.75 mmol of K are sequentially added₂S₂O₈Stirring and reacting for 12 hours at 110 ℃;

(2) extracting the product with ethyl acetate, drying with anhydrous sodium sulfate, concentrating under reduced pressure to obtain crude product, and purifying the crude product with silica gel column chromatography (the volume ratio of the solvent is petroleum ether: ethyl acetate = 10: 1) to obtain white solid, namely 4- (4-fluorophenyl) -6-methyl-quinoline, wherein the yield is 77%; the nuclear magnetic resonance spectrum is shown in figure 9a and figure 9 b;

¹ (500 Hz, CDCl₃) δ ppm : 8.88 (d, J = 4.5 Hz, 1H), 8.10 (d, J = 8.5 Hz, 1H), 7.61-7.57 (m, 2H),7.49-7.46 (m, 2H), 7.29-7.22 (m, 3H), 2.49 (s, 3H);

¹³ (125 MHz, CDCl₃) δ ppm: 163.0(d, J = 246.3Hz), 149.0, 147.1 (d, J = 33.8Hz), 136.9, 134.2 (d, J = 33.8Hz), 131.9, 131.3 (d, J = 33.8Hz), 129.6, 126.8, 124.4, 121.6, 22.0.

example 9

(1) Taking 0.5 mmol of 3, 4-dimethylaniline and 0.6 mmol of styrene, placing the materials in a reaction tube, and then sequentially adding 0.05 mmol of CuI, 0.05 mmol of 1,10-Phen, 3 mL of DMSO and 0.75 mmol of K2S2O8, and stirring the materials at 110 ℃ for reaction for 12 hours;

(2) extracting the product with ethyl acetate, drying with anhydrous sodium sulfate, concentrating under reduced pressure to obtain crude product, and purifying the crude product with silica gel column chromatography (the volume ratio of the solvent is petroleum ether: ethyl acetate = 10: 1) to obtain white solid, i.e. 4- (34-dimethylphenyl) -6-methyl-quinoline, with a yield of 53%; the nuclear magnetic resonance spectrum is shown in figure 10a and figure 10 b;

¹ (500 Hz, CDCl3) δ ppm : 8.77 (d, J = 5.5 Hz, 1H), 7.96 (s, 1H), 7.60 (s,1H), 7.50-7.43 (m, 5H), 7.23 (d, J = 2.0 Hz, 1H), 2.43 (s, 3H), 2.32 (s, 3H);

¹³ (125 MHz, CDCl3) δ ppm : 139.5, 136.8, 145.1, 136.2, 128.3, 127.5, 127.4, 127.4, 126.8, 124.2, 123.9, 119.6, 19.2, 19.2。

example 10

(1) Taking 0.5 mmol of 4-methylaniline and 0.6 mmol of 3-methylstyrene, placing the mixture in a reaction tube, and then sequentially adding 0.05 mmol of CuI, 0.05 mmol of 1,10-Phen, 3 mL of DMSO and 0.75 mmol of K2S2O8, and stirring the mixture at 110 ℃ for reaction for 12 hours;

(2) extracting the product with ethyl acetate, drying with anhydrous sodium sulfate, concentrating under reduced pressure to obtain crude product, and purifying the crude product with silica gel column chromatography (the volume ratio of the solvent is petroleum ether: ethyl acetate = 10: 1) to obtain white solid, i.e. 4- (3-methylphenyl) -6-methyl-quinoline with a yield of 37%; the nuclear magnetic resonance spectrum is shown in FIG. 11a and FIG. 11 b;

¹ (500 Hz, CDCl3) δ ppm : 8.79 (s, 1H), 8.03 (d, J = 8.4 Hz, 1H), 7.60 (s,1H), 7.49 (d, J = 8.4 Hz, 1H), 7.36-7.32 (m, 1H), 7.24-7.21 (m, 4H), 2.39 (s, 3H), 2.38 (s, 3H);

¹³ (125 MHz, CDCl3) δ ppm : 147.5, 145.7, 137.3, 137.0, 135.7, 130.8, 129.1, 128.1, 127.4, 125.6, 123.7, 120.3, 103.9, 20.8, 20.5。

example 11

(1) Taking 0.5 mmol of 4-methylaniline and 0.6 mmol of 2-methylstyrene, placing the materials in a reaction tube, and then sequentially adding 0.05 mmol of CuI, 0.05 mmol of 1,10-Phen, 3 mL of DMSO and 0.75 mmol of K2S2O8, and stirring the materials at 110 ℃ for reaction for 12 hours;

(2) extracting the product with ethyl acetate, drying with anhydrous sodium sulfate, concentrating under reduced pressure to obtain crude product, and purifying the crude product with silica gel column chromatography (the volume ratio of the solvent is petroleum ether: ethyl acetate = 10: 1) to obtain white solid, i.e. 4- (2-methylphenyl) -6-methyl-quinoline with a yield of 54%; the nuclear magnetic resonance spectrum is shown in FIG. 11a and FIG. 11 b;

¹ (500 Hz, CDCl3) δ ppm : 8.81 (d, J = 4.00 Hz, 1H), 8.04 (d, J = 8.8 Hz, 1H), 7.50-7.48 (m, 3H), 7.34-7.23 (m,3H), 7.19-7.12(m, 3H), 2.35 (s, 3H), 1.96 (d, 3H);

¹³ (100 MHz, CDCl3) δ ppm : 147.4, 147.3, 145.2, 135.8, 134.9, 130.8, 128.4, 127.3, 126.2, 124.6, 123.5, 120.4, 20.6, 18.8。

the preferred embodiments of the present invention have been described in detail with reference to the accompanying drawings, however, the present invention is not limited to the specific details of the above embodiments, and various simple modifications can be made to the technical solution of the present invention within the technical idea of the present invention, and these simple modifications are within the protective scope of the present invention.

It should be noted that the various technical features described in the above embodiments can be combined in any suitable manner without contradiction, and the invention is not described in any way for the possible combinations in order to avoid unnecessary repetition.

In addition, any combination of the various embodiments of the present invention is also possible, and the same should be considered as the disclosure of the present invention as long as it does not depart from the spirit of the present invention.

Claims

1. A preparation method of quinoline derivatives is characterized by comprising the following steps:

(1) mixing an aromatic amine compound, a styrene compound, copper salt, persulfate and 1, 10-phenanthroline, adding one or more of DMF (dimethyl formamide), DMSO (dimethyl sulfoxide) and DMA (direct memory access), stirring and heating to obtain a product;

(2) drying, separating and purifying the product to obtain quinoline derivatives;

wherein, the structural formula of the aromatic amine compound is as follows:

R¹selected from 4-Cl, 4-Br, 4-COOMe, 4-NO₂Or 3, 4-dimethyl; the structural formula of the styrene compound is as follows:

R²is H, 4-F, 4-OCH₃、4-C(CH₃)₃、2-CH₃Or 3-CH₃One of (1); the copper salt is one or more of cuprous iodide, cuprous bromide, cuprous chloride and cupric acetate; the persulfate is potassium persulfate and/or ammonium persulfate.

2. The preparation method according to claim 1, wherein the aromatic amine compound, the styrene compound, the copper salt, the persulfate and the 1, 10-phenanthroline are mixed in a molar ratio of 1:1.0-1.5:0.8-0.15: 1-2.

3. The production method according to claim 1, wherein the heating conditions include: the temperature is 100-120 ℃, and the time is 8-16 h.

4. The production method according to claim 1, wherein the step (2) further comprises: and extracting the product with ethyl acetate, drying the product with anhydrous sodium sulfate, concentrating the product under reduced pressure to obtain a crude product, and separating the crude product by column chromatography to obtain the quinoline derivative.

5. The preparation method of claim 4, wherein the raw materials of the developing solvent for column chromatographic separation comprise: petroleum ether and ethyl acetate.

6. The method according to claim 5, wherein the volume ratio of petroleum ether to ethyl acetate is 10: 0.9-1.1.