Method for constructing 6-chloro-4-phenylquinoline-2 (1H)-ketone compound by utilizing natural light to induce carbonylation reaction

Abstract

The invention relates to a method for constructing a 6-chloro-4-phenylquinoline-2 (1H)-ketone compound by utilizing natural light to induce carbonylation reaction. According to the method, 4-chloroaniline and phenylacetylene are taken as reaction raw materials, and the 6-chloro-4-phenylquinoline-2 (1H)-ketone compound is successfully constructed through two steps of aniline o-alkenylation reaction and natural light induced carbonylation reaction. The method has the characteristics of simple and easily available raw materials, simple synthesis steps, green and mild reaction conditions and simple operation process.

Description

Technical Field

[0001] The invention relates to the technical fields of medicine, clinic, cell biology and the like, and in particular to a new method for constructing 6-chloro-4-phenylquinoline-2(1H)-one by utilizing natural light-induced carbonylation reaction. Background Art

[0002] ‌6-Chloro-4-phenylquinoline-2(1H)-one, due to its unique chemical structure and biological activity, shows potential application value in the field of hepatitis B virus research and immune regulation. It is a relatively effective hepatitis B virus inhibitor and also provides new ideas and directions for future drug development and disease treatment‌.

[0003] Under this research background, we proposed a method to construct 6-chloro-4-phenylquinoline-2(1H)-one compounds by using natural light-induced carbonylation reaction. The synthetic route is as follows:

[0004]

[0005] The 6-chloro-4-phenylquinoline-2(1H)-one synthesized by the present invention has the following structural formula:

[0006]

[0007] The invention synthesizes 6-chloro-4-phenylquinoline-2(1H)-one by a two-step method of natural light-induced carbonylation reaction, providing a novel synthetic route for the synthesis of this type of compound. The raw materials involved in this route are cheap and easily available, the reaction conditions are green and mild, and the reaction route is simple. Summary of the invention

[0008] The present invention relates to a method for constructing a 6-chloro-4-phenylquinoline-2(1H)-one compound by using a natural light-induced carbonylation reaction. The method uses 4-chloroaniline and phenylacetylene as reaction raw materials to successfully construct a 6-chloro-4-phenylquinoline-2(1H)-one compound by two steps of aniline ortho-olefination and natural light carbonylation reaction. The method has the characteristics of simple and easy-to-obtain raw materials, concise synthesis steps, green and mild reaction conditions, and simple operation process.

[0009] The technical solution of the present invention is as follows.

[0010] 6-Chloro-4-phenylquinoline-2(1H)-one was synthesized by a two-step method using natural light-induced carbonylation reaction. The synthetic route is as follows:

[0011]

[0012] In the above method, the 6-chloro-4-phenylquinolin-2(1H)-one is prepared from compound 1 (4-chloroaniline) and compound 2 (phenylacetylene) through two reaction steps: ortho-olefination of aniline and carbonylation induced by natural light; the specific steps are as follows:

[0013] (1) Compound 1 (4-chloroaniline) is placed in a container, compound 2 (phenylacetylene) and magnesium bis(trifluoromethanesulfonyl)imide (II) are added, and solvent hexafluoroisopropanol is added and heated to 70 degrees Celsius and stirred for 24 hours. After the reaction is completed, the mixture is cooled to room temperature, and compound 3 (4-chloro-2-(1-phenylvinyl)aniline) is separated and purified to achieve the ortho-eneification process of aniline.

[0014] (2) Compound 3 (4-chloro-2-(1-phenylvinyl)aniline) was placed in a test tube, and a catalyst, additive, and solvent were added. A balloon filled with carbon monoxide gas was placed on the tube, and the reaction was stirred under natural light. After the reaction was completed, the balloon was removed, and the reaction solution was purified by column chromatography to obtain 6-chloro-4-phenylquinolin-2(1H)-one.

[0015] In the above method: the reaction container of the specific step (2) is a test tube; the metal palladium is palladium acetate, palladium trifluoroacetate, palladium chloride, tetrakis(triphenylphosphine)palladium; the additive is tetrabutylammonium bromide, tetrabutylammonium iodide, tetrabutylammonium hexafluorophosphate, tetraethylammonium bromide.

[0016] In the above method, the solvent in the specific step (2) is acetonitrile.

[0017] In the above method, the reaction temperature in the specific step (2) is room temperature.

[0018] Compared with the prior art, the advantages of the present invention are: the method has a novel synthesis method, and 6-chloro-4-phenylquinoline-2(1H)-one is successfully synthesized by utilizing natural light-induced carbonylation reaction, the reaction raw materials are simple and easy to obtain, the reaction conditions are mild, and it meets the development requirements of green chemistry. BRIEF DESCRIPTION OF THE DRAWINGS

[0019] Figure 1 is the H NMR spectrum of compound 3 (4-chloro-2-(1-phenylvinyl)aniline) obtained in Example 1;

[0020] Figure 2 is the carbon NMR spectrum of compound 3 (4-chloro-2-(1-phenylvinyl)aniline) obtained in Example 1;

[0021] Figure 3 is the hydrogen nuclear magnetic resonance spectrum of 6-chloro-4-phenylquinoline-2(1H)-one obtained in Example 2-12;

[0022] Figure 4is the carbon nuclear magnetic resonance spectrum of 6-chloro-4-phenylquinoline-2(1H)-one obtained in Example 2-12; DETAILED DESCRIPTION

[0023] The invention will be further described below through specific embodiments.

[0024] Example 1

[0025] Synthesis of compound 3 (4-chloro-2-(1-phenylvinyl)aniline)

[0026] In a 100 mL round-bottom flask, 3 mmol of 4-chloroaniline and 1 mmol of phenylacetylene were added, followed by 0.1 mmol of bis(trifluoromethanesulfonyl)imide magnesium (II), and the solvent hexafluoroisopropanol was added. The mixture was heated to 70 degrees Celsius and stirred for 24 hours. After the reaction was completed, the mixture was cooled to room temperature. After completion, the solvent was removed by vacuum rotary evaporation, and then separated and purified by column chromatography to obtain compound 3 (4-chloro-2-(1-phenylvinyl)aniline) with a yield of 80%.

[0027] The structural characterization data of compound 3 (4-chloro-2-(1-phenylvinyl)aniline) obtained in Example 1 are as follows: Figure 1 and Figure 2 )

[0028] 1 H NMR (500 MHz, CDCl3) δ 7.37 (dddd, J = 11.8, 5.5, 4.5, 3.0 Hz, 5H), 7.17-7.10 (m, 2H), 6.66-6.62 (m, 1H), 5.84 (d, J = 1.2 Hz, 1H), 5.39 (d, J =1.2 Hz, 1H).

[0029] 13 C NMR (125 MHz, CDCl3) δ 146.17, 142.63, 138.96, 130.30, 128.72,128.64, 128.56, 128.38, 126.61, 122.89, 116.81, 116.70.

[0030] The structure of the compound 3 (4-chloro-2-(1-phenylvinyl)aniline) obtained by inferring the above data is as follows:

[0031]

[0032] Example 2

[0033] Synthesis of 6-Chloro-4-phenylquinolin-2(1H)-one

[0034] Add 0.1 mmol of compound 3 (4-chloro-2-(1-phenylvinyl)aniline), 0.005 mmol of palladium acetate, 0.1 mmol of tetrabutylammonium bromide, and 0.1 mmol of acetic acid to a test tube, add 3 ml of acetonitrile as a solvent, put on a balloon containing carbon monoxide as a carbonyl source, and stir the reaction under natural light. After four hours, remove the balloon and slowly vent the unreacted carbon monoxide. The reaction solution is evaporated under reduced pressure to remove the solvent, and then separated and purified by column chromatography to obtain compound 6-chloro-4-phenylquinoline-2(1H)-one with a yield of 61%.

[0035] Example 3

[0036] Add 0.1 mmol of compound 3 (4-chloro-2-(1-phenylvinyl)aniline), 0.005 mmol of palladium trifluoroacetate, 0.1 mmol of tetrabutylammonium bromide, and 0.1 mmol of acetic acid to a test tube, add 3 ml of acetonitrile as a solvent, put on a balloon containing carbon monoxide as a carbonyl source, and stir the reaction under natural light. After four hours, remove the balloon and slowly vent the unreacted carbon monoxide. The reaction solution is evaporated under reduced pressure to remove the solvent, and then separated and purified by column chromatography to obtain compound 6-chloro-4-phenylquinoline-2(1H)-one with a yield of 30%.

[0037] Example 4

[0038] Add 0.1 mmol of compound 3 (4-chloro-2-(1-phenylvinyl)aniline), 0.005 mmol of palladium chloride, 0.1 mmol of tetrabutylammonium bromide, 0.1 mmol of acetic acid into a test tube, add 3 ml of acetonitrile as a solvent, put on a balloon containing carbon monoxide as a carbonyl source, and stir the reaction under natural light. After four hours, remove the balloon and slowly release the unreacted carbon monoxide. The reaction solution is evaporated under reduced pressure to remove the solvent, and then separated and purified by column chromatography to obtain compound 6-chloro-4-phenylquinoline-2(1H)-one with a yield of 0%.

[0039] Example 5

[0040] Add 0.1 mmol of compound 3 (4-chloro-2-(1-phenylvinyl)aniline), 0.005 mmol of tetrakis(triphenylphosphine)palladium, 0.1 mmol of tetrabutylammonium bromide, and 0.1 mmol of acetic acid to a test tube, add 3 ml of acetonitrile as a solvent, put on a balloon containing carbon monoxide as a carbonyl source, and stir the reaction under natural light. After four hours, remove the balloon and slowly vent the unreacted carbon monoxide. The reaction solution is evaporated under reduced pressure to remove the solvent, and then separated and purified by column chromatography to obtain compound 6-chloro-4-phenylquinoline-2(1H)-one with a yield of 47%.

[0041] Example 6

[0042] Add 0.1 mmol of compound 3 (4-chloro-2-(1-phenylvinyl)aniline), 0.005 mmol of palladium acetate, 0.1 mmol of tetrabutylammonium iodide, and 0.1 mmol of acetic acid to a test tube, add 3 ml of acetonitrile as a solvent, put on a balloon containing carbon monoxide as a carbonyl source, and stir the reaction under natural light. After four hours, remove the balloon and slowly vent the unreacted carbon monoxide. The reaction solution is evaporated under reduced pressure to remove the solvent, and then separated and purified by column chromatography to obtain compound 6-chloro-4-phenylquinoline-2(1H)-one with a yield of 58%.

[0043] Example 7

[0044] Add 0.1 mmol of compound 3 (4-chloro-2-(1-phenylvinyl)aniline), 0.005 mmol of palladium acetate, 0.1 mmol of tetrabutylammonium acetate, 0.1 mmol of acetic acid, 3 ml of acetonitrile as solvent, put on a balloon containing carbon monoxide as a carbonyl source, and stir the reaction under natural light. After four hours, remove the balloon and slowly release the unreacted carbon monoxide. The reaction solution is evaporated under reduced pressure to remove the solvent, and then separated and purified by column chromatography to obtain compound 6-chloro-4-phenylquinoline-2(1H)-one with a yield of 31%.

[0045] Example 8

[0046] Add 0.1 mmol of compound 3 (4-chloro-2-(1-phenylvinyl)aniline), 0.005 mmol of palladium acetate, 0.1 mmol of tetraethylammonium bromide, and 0.1 mmol of acetic acid to a test tube, add 3 ml of acetonitrile as a solvent, put on a balloon containing carbon monoxide as a carbonyl source, and stir the reaction under natural light. After four hours, remove the balloon and slowly vent the unreacted carbon monoxide. The reaction solution is evaporated under reduced pressure to remove the solvent, and then separated and purified by column chromatography to obtain compound 6-chloro-4-phenylquinoline-2(1H)-one with a yield of 60%.

[0047] The structural characterization data of 6-chloro-4-phenylquinoline-2(1H)-one obtained in Example 2-9 are as follows: (see Figure 3 and Figure 4 )

[0048] 1 H NMR (500 MHz, DMSO-d6) δ 12.06 (s, 1H), 7.59-7.55 (m, 2H), 7.53 (d,J = 6.9 Hz, 2H), 7.46 (dd, J = 7.5, 1.9 Hz, 2H), 7.41 (d, J = 8.8 Hz, 1H), 7.26 (d, J = 2.4 Hz, 1H), 6.46 (s, 1H).

[0049] 13 C NMR (125 MHz, DMSO-d6) δ 161.57, 150.89, 138.52, 136.48, 131.00,129.54, 129.36, 129.09, 126.29, 125.43, 122.88, 120.09, 118.25.

[0050] The structure of 6-chloro-4-phenylquinoline-2(1H)-one obtained based on the above data is as follows:

[0051] .

Claims

1. A method for constructing a 6-chloro-4-phenylquinoline-2(1H)-one compound by using natural light-induced carbonylation reaction, characterized in that: The synthetic route is as follows: .

2. The method for constructing a 6-chloro-4-phenylquinoline-2(1H)-one compound by utilizing natural light-induced carbonylation reaction according to claim 1, characterized in that: The 6-chloro-4-phenylquinolin-2(1H)-one is prepared from compound 1 (4-chloroaniline) and compound 2 (phenylacetylene) through two steps of ortho-olefination of aniline and carbonylation induced by natural light; the compound 1 is 4-chloroaniline and the compound 2 is phenylacetylene; The specific steps are as follows: (1) Compound 1 (4-chloroaniline) is placed in a container, compound 2 (phenylacetylene) and magnesium (II) bis(trifluoromethanesulfonyl)imide are added, and the mixture is heated to 70°C in a solvent of hexafluoroisopropanol and stirred for 24 hours. After the reaction is completed, the mixture is cooled to room temperature, and compound 3 (4-chloro-2-(1-phenylvinyl)aniline) is separated and purified to achieve the ortho-eneification process of aniline; (2) Compound 3 (4-chloro-2-(1-phenylvinyl)aniline) was placed in a test tube, and a catalyst, additive, and solvent were added. A balloon filled with carbon monoxide gas was placed on the tube, and the reaction was stirred under natural light. After the reaction was completed, the balloon was removed, and the reaction solution was purified by column chromatography to obtain 6-chloro-4-phenylquinolin-2(1H)-one.

3. The method for constructing a 6-chloro-4-phenylquinoline-2(1H)-one compound by utilizing natural light-induced carbonylation reaction according to claim 2, characterized in that: The reaction container of the specific step (2) is a test tube; the metal palladium is palladium acetate, palladium trifluoroacetate, palladium chloride, tetrakis(triphenylphosphine)palladium; and the additive is tetrabutylammonium bromide, tetrabutylammonium iodide, tetrabutylammonium hexafluorophosphate, and tetraethylammonium bromide.

4. The method for constructing a 6-chloro-4-phenylquinoline-2(1H)-one compound by utilizing natural light-induced carbonylation reaction according to claim 2, characterized in that: In the specific step (2), the solvent is acetonitrile.

5. The method for constructing a 6-chloro-4-phenylquinoline-2(1H)-one compound by utilizing natural light-induced carbonylation reaction according to claim 2, characterized in that: The reaction temperature in the specific step (2) is room temperature.

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