A method for constructing 6-chloro-4-phenylquinolin-2(1H)-one compound by using natural light to induce carbonylation reaction

Abstract

The application relates to a method for constructing a 6-chloro-4-phenylquinoline-2(1H)-ketone compound by using natural light to induce a carbonylation reaction. The method successfully constructs the 6-chloro-4-phenylquinoline-2(1H)-ketone compound by using 4-chloroaniline and phenylacetylene as reaction raw materials through aniline ortho-olefination reaction and natural light-induced carbonylation reaction. The method has the characteristics of simple and easily-obtained raw materials, simple synthesis steps, green and mild reaction conditions and simple operation process.

Description

TECHNICAL FIELD

[0001] The application relates to the technical fields of medicine, clinic, cell biology and the like, and particularly relates to a novel method for constructing 6-chloro-4-phenylquinoline-2(1H)-one by using natural light to induce a carbonylation reaction. BACKGROUND

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

[0003] Under the research background, a method for constructing 6-chloro-4-phenylquinoline-2(1H)-one compound by using natural light to induce a carbonylation reaction is provided, and a synthesis route is as follows:

[0004]

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

[0006]

[0007] The application synthesizes 6-chloro-4-phenylquinoline-2(1H)-one by using natural light to induce a carbonylation reaction in two steps, provides a novel synthesis route for the synthesis of the compound, the raw materials involved in the route are cheap and easy to obtain, the reaction conditions are green and mild, and the reaction route is simple. SUMMARY

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

[0009] The technical scheme of the application is as follows.

[0010] 6-chloro-4-phenylquinoline-2(1H)-one is synthesized by using natural light to induce a carbonylation reaction in two steps, and a synthesis 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 aniline ortho-alkenylation and natural light-induced carbonylation reaction; the specific steps are as follows:

[0013] (1) Put compound 1 (4-chloroaniline) into a container, add compound 2 (phenylacetylene), bis(trifluoromethylsulfonyl) imidazole magnesium (II), add a solvent hexafluoroisopropanol, heat to 70 degrees Celsius, stir for 24 hours, cool to room temperature after the reaction is completed, and separate and purify to obtain compound 3 (4-chloro-2-(1-phenylvinyl) aniline), to realize the aniline ortho-alkenylation process.

[0014] (2) Put compound 3 (4-chloro-2-(1-phenylvinyl) aniline) into a test tube, add a catalyst, an additive, a solvent, cover a balloon filled with carbon monoxide gas, stir and react under natural light, remove the balloon after the reaction is completed, and purify the reaction liquid 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, and tetrakis(triphenylphosphine) palladium; and the additive is tetrabutylammonium bromide, tetrabutylammonium iodide, tetrabutylammonium hexafluorophosphate, and 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 method has the advantages that the synthesis means is novel, 6-chloro-4-phenylquinolin-2(1H)-one is successfully synthesized by using natural light-induced carbonylation reaction, the reaction raw materials are simple and easy to obtain, the reaction conditions are mild, and the development requirements of green chemistry are met. BRIEF DESCRIPTION OF DRAWINGS

[0019] Figure 1 It is the nuclear magnetic resonance hydrogen spectrum of compound 3 (4-chloro-2-(1-phenylvinyl) aniline) obtained in Example 1.

[0020] Figure 2 It is the nuclear magnetic resonance carbon spectrum of compound 3 (4-chloro-2-(1-phenylvinyl) aniline) obtained in Example 1.

[0021] Figure 3 It is the nuclear magnetic resonance hydrogen spectrum of 6-chloro-4-phenylquinolin-2(1H)-one obtained in Examples 2-12.

[0022] Figure 4NMR carbon spectrum of 6-chloro-4-phenylquinolin-2(lH)-one obtained in Examples 2-12; DETAILED DESCRIPTION

[0023] The application will be further described in the following with specific examples.

[0024] Example 1

[0025] Synthesis of compound 3 (4-chloro-2-(l-styryl) aniline)

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

[0027] The structural characterization data of compound 3 (4-chloro-2-(l-styryl) aniline) obtained in Example 1 are as follows: (see 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 compound 3 (4-chloro-2-(l-styryl) aniline) obtained according to the above data is as follows:

[0031]

[0032] Example 2

[0033] Synthesis of 6-chloro-4-phenylquinolin-2(lH)-one

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

[0035] Example 3

[0036] In a test tube, add compound 3 (4-chloro-2-(1-styryl) aniline) 0.1 mmol, palladium acetate 0.005 mmol, tetrabutylammonium bromide 0.1 mmol, acetic acid 0.1 mmol, add acetonitrile 3 ml as solvent, cover with a balloon containing carbon monoxide as the carbonyl source, stir the reaction under natural light. After four hours, remove the balloon and slowly release the unreacted carbon monoxide. The reaction solution is reduced in pressure and rotary evaporated to remove the solvent, then purified by column chromatography to obtain compound 6-chloro-4-phenylquinolin-2(lH)-one, yield 61%.

[0037] Example 4

[0038] In a test tube, add compound 3 (4-chloro-2-(1-styryl) aniline) 0.1 mmol, palladium acetate 0.005 mmol, tetrabutylammonium bromide 0.1 mmol, acetic acid 0.1 mmol, add acetonitrile 3 ml as solvent, cover with a balloon containing carbon monoxide as the carbonyl source, stir the reaction under natural light. After four hours, remove the balloon and slowly release the unreacted carbon monoxide. The reaction solution is reduced in pressure and rotary evaporated to remove the solvent, then purified by column chromatography to obtain compound 6-chloro-4-phenylquinolin-2(lH)-one, yield 61%.

[0039] Example 5

[0040] In a test tube, add compound 3 (4-chloro-2-(1-styryl) aniline) 0.1 mmol, palladium acetate 0.005 mmol, tetrabutylammonium bromide 0.1 mmol, acetic acid 0.1 mmol, add acetonitrile 3 ml as solvent, cover with a balloon containing carbon monoxide as the carbonyl source, stir the reaction under natural light. After four hours, remove the balloon and slowly release the unreacted carbon monoxide. The reaction solution is reduced in pressure and rotary evaporated to remove the solvent, then purified by column chromatography to obtain compound 6-chloro-4-phenylquinolin-2(lH)-one, yield 61%.

[0041] Example 6

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

[0043] Example 7

[0044] In a test tube, add compound 3 (4-chloro-2-(1-styryl) aniline) 0.1 mmol, palladium acetate 0.005 mmol, tetrabutylammonium iodide 0.1 mmol, acetic acid 0.1 mmol, add acetonitrile 3 ml as solvent, cover with a balloon containing carbon monoxide as the carbonyl source, stir the reaction under natural light. After four hours, remove the balloon and slowly release the unreacted carbon monoxide. The reaction solution is reduced pressure rotary evaporation to remove the solvent, and then separated and purified by column chromatography to obtain compound 6-chloro-4-phenylquinolin-2(lH)-one, yield 31%.

[0045] Example 8

[0046] In a test tube, add compound 3 (4-chloro-2-(1-styryl) aniline) 0.1 mmol, palladium acetate 0.005 mmol, tetrabutylammonium iodide 0.1 mmol, acetic acid 0.1 mmol, add acetonitrile 3 ml as solvent, cover with a balloon containing carbon monoxide as the carbonyl source, stir the reaction under natural light. After four hours, remove the balloon and slowly release the unreacted carbon monoxide. The reaction solution is reduced pressure rotary evaporation to remove the solvent, and then separated and purified by column chromatography to obtain compound 6-chloro-4-phenylquinolin-2(lH)-one, yield 60%.

[0047] The structural characterization data of 6-chloro-4-phenylquinolin-2(lH)-one obtained in Examples 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 the resulting 6-chloro-4-phenylquinolin-2(lH)-one is deduced from the above data as follows:

[0051] .

Claims

1. A method for constructing 6-chloro-4-phenylquinolin-2(lH)-one compound by using natural light to induce carbonylation reaction, characterized in that, The synthetic route is as follows: ； The specific steps are as follows: (1) Put compound 1 into a container, add compound 2, magnesium (II) bis (trifluoromethylsulfonyl) imide, and a solvent hexafluoroisopropanol, heat to 70 degrees Celsius, stir for 24 hours, cool to room temperature after the reaction is completed, separate and purify to obtain compound 3; (2) Put compound 3 into a test tube, add a catalyst, an additive, a solvent, cover a balloon filled with carbon monoxide gas, stir under natural light, remove the balloon after the reaction is completed, and purify the reaction liquid by column chromatography to obtain 6-chloro-4-phenylquinolin-2(1H)-one; The reaction container of the specific step (2) is a test tube; the catalyst is palladium acetate, palladium trifluoroacetate, and palladium tetraphenylphosphine; the additive is tetrabutylammonium bromide, tetrabutylammonium iodide, tetrabutylammonium hexafluorophosphate, and tetraethylammonium bromide.

2. The method for constructing 6-chloro-4-phenylquinoline-2(lH)-one compound by using natural light to induce carbonylation reaction according to claim 1, characterized in that: The solvent in the step (2) is acetonitrile.

3. The method for constructing 6-chloro-4-phenylquinoline-2(lH)-one compound by using natural light to induce carbonylation reaction according to claim 1, characterized in that: The reaction temperature in the step (2) is room temperature.

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