Method for electrochemical synthesis of quinolinone compound
Through electrochemical synthesis methods, quinolinone compounds are synthesized in electrolytic reactions using specific compounds and catalysts, which solves the limitations and environmentally friendly problems of the synthesis methods in the prior art, and achieves efficient and environmentally friendly quinolinone compounds synthesis.
Patent Information
- Application Number
- CN202510063404.3
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-01-15
- Publication Date
- 2025-04-18
AI Technical Summary
The existing quinolinone synthesis methods have limitations, such as localization of olefins or alkynes used for reactions, requiring additional stoichiometric oxidants, producing toxic and harmful waste, low atomic utilization, etc.
Using electrochemical synthesis method, a compound containing a disubstituted alkyne fragment and an α-electron-electroleum substituted amide fragment in the molecule is used as raw materials, and an electrolytic reaction is carried out under the protection of an inert gas by combining a ferrocene catalyst, a support electrolyte, a base and a solvent. Quinolinone compounds are obtained by extraction, drying, filtration, concentration and purification.
The efficient synthesis of quinolinone compounds has been achieved, the scope of synthesis has been broadened, the generation of waste has been reduced, the atomic utilization has been improved, and the method is environmentally friendly and green.
Smart Images
Figure CN119843293A_ABST
Abstract
Description
Technical Field
[0001] The invention belongs to the field of chemical synthesis, and in particular relates to a method for electrochemically synthesizing quinolinone compounds. Background Art
[0002] Quinolinone compounds are a widely used organic chemical raw material that can be used to manufacture medicines, chemical agricultural products, artificial substitutes for natural products, dyes and fragrances.
[0003] At present, the main method for synthesizing such compounds is intramolecular cyclization reaction, including the cyclization reaction of β-ketoamide and aromatic hydrocarbons catalyzed by strong acid or ferric oxide, the cyclization reaction of β-carbonylamide and olefin or alkyne catalyzed by transition metal / oxidant, the cyclization reaction of β-carbonylamide and alkyne catalyzed by organic amine, etc. However, these methods have their own shortcomings, such as the olefins or alkynes used for the reaction are limited to diaryl substituents, the need for additional stoichiometric oxidants, the generation of toxic and harmful wastes, and low atomic utilization. Summary of the invention
[0004] Purpose of the invention: The technical problem to be solved by the present invention is to provide a more environmentally friendly synthesis method in view of the deficiencies of the prior art, so as to solve the shortcomings of the current technical means, broaden the synthesis range of quinolinone compounds, reduce the generation of waste, and improve the atomic utilization rate.
[0005] In order to achieve the above object, the technical solution adopted by the present invention is as follows: A method for electrochemically synthesizing quinolinone compounds, which uses a compound containing both a disubstituted alkyne fragment and an α-electron-withdrawing group-substituted amide fragment in the molecule as a raw material, and electrolyzes it in an electrolytic cell under the protection of an inert gas with a ferrocene catalyst, a supporting electrolyte, a base and a solvent. After the reaction is completed, the reaction solution is extracted, and the organic phases are combined, dried, filtered, concentrated and purified to obtain the compound.
[0006] The above reaction is shown in the following formula: .
[0007] Specifically, in the compound, the disubstituted alkyne fragment contained in the molecule is an aryl alkyl alkyne or a diaryl alkyne, and the α-electron withdrawing group substituted amide fragment contained in the molecule is selected from any one of α-cyanoamide, α-esteramide, and α-ketoamide.
[0008] Specifically, the base is selected from any one of sodium carbonate, potassium carbonate and cesium carbonate, preferably potassium carbonate; the solvent is selected from any one of methanol and ethanol, preferably methanol.
[0009] Specifically, the feed ratio of the raw material compound, the ferrocene catalyst, the supporting electrolyte and the base is 100:5~20:10~50:100~200, preferably 100:10:20:100.
[0010] Specifically, the inert gas is any one of nitrogen and argon, preferably argon.
[0011] Specifically, the electrolytic cell is a single-chamber electrolytic cell, wherein the anode material is selected from any one of porous glass carbon material, graphite carbon sheet, and platinum sheet, preferably porous glass carbon material; the cathode material is any one of platinum sheet, nickel sheet, and stainless steel sheet, preferably platinum sheet.
[0012] Specifically, the electrolysis reaction is carried out in a constant current mode, using a HSPY-600 DC power supply, with an operating current of 5-10 mA, preferably 7.5 mA; the electrolysis reaction time is 90-120 minutes, preferably 100 minutes; the reaction is carried out by heating the solvent under reflux, with a heating temperature of 50-70°C, preferably 70°C.
[0013] Specifically, the extraction is to add water and dichloromethane to the reaction solution, the volume ratio of water to dichloromethane is 1-3:1, preferably 2:1; the volume ratio of the extract composed of water and dichloromethane to the reaction solution is 1:1-3, preferably 1:2.
[0014] Specifically, the concentration is carried out under reduced pressure.
[0015] Specifically, the purification adopts silica gel column chromatography. Beneficial Effects
[0016] (1) The present invention successfully prepared quinolinone compounds by electrochemical synthesis for the first time.
[0017] (2) The electrochemical synthesis method of quinolinone compounds in the present invention can be applied to arylalkyl internal alkyne raw materials, which is not achievable with the prior art.
[0018] (3) The electrochemical synthesis method of quinolinone compounds in the present invention has the characteristics of high conversion efficiency, wide application range, mild reaction conditions, and easy gram-scale synthesis.
[0019] (4) The electrochemical synthesis method of quinolinone compounds of the present invention does not require the addition of a stoichiometric oxidant and does not generate waste pollutants. It is green and environmentally friendly and has high atom economy. BRIEF DESCRIPTION OF THE DRAWINGS
[0020] The present invention will be further described in detail below in conjunction with the accompanying drawings and specific embodiments, and the above and / or other advantages of the present invention will become more clear.
[0021] Figure 1 This is the NMR spectrum of quinolinone compound 1 prepared in Example 1.
[0022] Figure 2 This is the NMR spectrum of quinolinone compound 2 prepared in Example 2.
[0023] Figure 3 This is the NMR spectrum of quinolinone compound 3 prepared in Example 3.
[0024] Figure 4 This is the NMR spectrum of quinolinone compound 4 prepared in Example 4.
[0025] Figure 5 This is the NMR spectrum of quinolinone compound 5 prepared in Example 5.
[0026] Figure 6 This is the NMR spectrum of quinolinone compound 6 prepared in Example 6.
[0027] Figure 7 This is the NMR spectrum of quinolinone compound 7 prepared in Example 7.
[0028] Figure 8 This is the NMR spectrum of quinolinone compound 8 prepared in Example 8.
[0029] Fig. 9 This is the NMR spectrum of quinolinone compound 9 prepared in Example 9.
[0030] Fig.10 This is the NMR spectrum of the quinolinone compound 10 prepared in Example 10.
[0031] Fig.11 This is the NMR spectrum of quinolinone compound 11 prepared in Example 11.
[0032] Fig.12 This is the NMR spectrum of quinolinone compound 12 prepared in Example 12.
[0033] Fig.13 This is the NMR spectrum of quinolinone compound 13 prepared in Example 13.
[0034] Fig.14 This is the NMR spectrum of quinolinone compound 14 prepared in Example 14.
[0035] Fig.15 This is the NMR spectrum of quinolinone compound 15 prepared in Example 15.
[0036] Fig.16 This is the NMR spectrum of quinolinone compound 16 prepared in Example 16.
[0037] Fig.17 This is the NMR spectrum of quinolinone compound 17 prepared in Example 17.
[0038] Fig.18 This is the NMR spectrum of quinolinone compound 18 prepared in Example 18.
[0039] Fig.19 This is the NMR spectrum of quinolinone compound 19 prepared in Example 19.
[0040] Fig. 20 This is the NMR spectrum of quinolinone compound 20 prepared in Example 20.
[0041] Fig.21 This is the NMR spectrum of quinolinone compound 21 prepared in Example 21.
[0042] Fig. 22 This is the NMR spectrum of quinolinone compound 22 prepared in Example 22.
[0043] Fig.23 This is the NMR spectrum of quinolinone compound 23 prepared in Example 23.
[0044] Fig.24 This is the NMR spectrum of quinolinone compound 24 prepared in Example 24.
[0045] Fig.25 This is the NMR spectrum of quinolinone compound 25 prepared in Example 25.
[0046] Fig.26 This is the NMR spectrum of quinolinone compound 26 prepared in Example 26.
[0047] Fig. 27 This is the NMR spectrum of quinolinone compound 27 prepared in Example 27.
[0048] Fig.28 This is the NMR spectrum of quinolinone compound 28 prepared in Example 28. DETAILED DESCRIPTION
[0049] The present invention can be better understood with reference to the following examples.
[0050] Example 1: Electrochemical synthesis of quinolinone compound 1.
[0051] .
[0052] The raw materials S1 (50.8 mg), ferrocene (3.7 mg), potassium carbonate (27.6 mg), and (C2H5)4NPF6 (11 mg) were added to a single-chamber electrolytic cell equipped with a magnetic stirrer, and a porous glassy carbon anode and a platinum cathode were assembled. Argon was repeatedly pumped and filled three times, and methanol (5 ml) was added through a syringe. Then, the reaction was heated to reflux at 70 °C for 100 minutes under a constant current condition of 7.5 mA. After the reaction, water and dichloromethane were added to extract the reaction solution, and the organic phases were combined, dried, filtered, concentrated under reduced pressure, and purified by silica gel column chromatography to obtain quinolinone compound 1 with a yield of 42.7 mg (yield 84%).
[0053] The NMR data of the obtained product are as follows, and the spectrum is attached. Figure 1 : 1 H NMR (400 MHz, CDCl3) δ 7.91 (dd, J = 8.3, 1.5 Hz, 1H), 7.70 (ddd, J =8.6, 7.1, 1.4 Hz, 1H), 7.42 (d, J = 8.6 Hz, 1H), 7.32 (t, J = 7.7 Hz, 1H), 3.76(s, 3H), 3.17 (s, 2H), 1.07 (s, 9H). 13 C NMR (101 MHz, CDCl3) δ 159.0, 158.4,140.6, 133.8, 128.5, 122.6, 120.2, 116.3, 115.2, 108.9, 43.4, 35.3, 31.0,30.3. The high-resolution mass spectrometry data are as follows: C 16 H 18 N2O [M + Na] + Theoretical value 277.1311, tested value 277.1317.
[0054] Example 2: Electrochemical synthesis of quinolinone compound 2.
[0055] .
[0056] The raw materials S2 (56.0 mg), ferrocene (3.7 mg), potassium carbonate (27.6 mg), and (C2H5)4NPF6 (11 mg) were added to a single-chamber electrolytic cell equipped with a magnetic stirrer, and a porous glassy carbon anode and a platinum cathode were assembled. Argon was repeatedly pumped and filled three times, and methanol (5 ml) was added through a syringe. Then, the reaction was heated to reflux at 70 °C for 100 minutes under a constant current condition of 7.5 mA. After the reaction, water and dichloromethane were added to extract the reaction solution, and the organic phases were combined, dried, filtered, concentrated under reduced pressure, and purified by silica gel column chromatography to obtain quinolinone compound 2 with a yield of 42.6 mg (yield 76%).
[0057] The NMR data of the obtained product are as follows, and the spectrum is attached. Figure 2 : 1 H NMR (400 MHz, CDCl3) δ 7.82 (dd, J = 8.2, 1.4 Hz, 1H), 7.71 (ddd, J =8.6, 7.2, 1.4 Hz, 1H), 7.42 (d, J = 8.6 Hz, 1H), 7.35 (ddd, J = 8.2, 7.1, 1.1 Hz,1H), 3.74 (s, 3H), 3.05 (d, J = 6.8 Hz, 2H), 1.78 – 1.69 (m, 5H), 1.66 – 1.58 (m, 1H), 1.27 – 1.14 (m, 5H). 13 C NMR (101 MHz, CDCl3) δ 159.3, 158.8, 140.6,133.8, 127.0, 123.1, 119.2, 115.6, 115.3, 107.5, 39.7, 39.6, 33.5, 30.2,26.3, 26.1. The high-resolution mass spectrometry data are as follows: C 18 H 20 N2O [M + Na] + Theoretical value 303.1468, tested value 303.1463.
[0058] Example 3: Electrochemical synthesis of quinolinone compound 3.
[0059] .
[0060] The raw materials S3 (50.8 mg), ferrocene (3.7 mg), potassium carbonate (27.6 mg), and (C2H5)4NPF6 (11 mg) were added to a single-chamber electrolytic cell equipped with a magnetic stirrer, equipped with a porous glassy carbon anode and a platinum cathode, and argon was repeatedly pumped and filled three times. Methanol (5 ml) was added through a syringe, and then heated to reflux at 70 °C for 100 minutes under a constant current condition of 7.5 mA. After the reaction, water and dichloromethane were added to extract the reaction solution, and the organic phases were combined, dried, filtered, concentrated under reduced pressure, and purified by silica gel column chromatography to obtain quinolinone compound 3 with a yield of 21.6 mg (yield 45%).
[0061] The NMR data of the obtained product are as follows, and the spectrum is attached. Figure 3 : 1 H NMR (400 MHz, CDCl3) δ 7.84 (dd, J = 8.2, 1.5 Hz, 1H), 7.71 (ddd, J =8.6, 7.1, 1.5 Hz, 1H), 7.42 (dd, J = 8.7, 1.1 Hz, 1H), 7.35 (ddd, J 0.92 (t, J = 7.2 Hz, 3H). 13 C NMR (101 MHz, CDCl3) δ 160.9, 159.0, 140.9, 133.9, 126.8, 123.2, 118.9, 115.4, 115.2, 106.8, 32.2, 32.1, 30.3, 22.6, 14.1. The high-resolution mass spectrometry data are as follows: C 16 H 18 N2O [M + Na] + Theoretical value 277.1311, tested value 277.1317.
[0062] Example 4: Electrochemical synthesis of quinolinone compound 4.
[0063] .
[0064] The raw materials S4 (54.8 mg), ferrocene (3.7 mg), potassium carbonate (27.6 mg), and (C2H5)4NPF6 (11 mg) were added to a single-chamber electrolytic cell equipped with a magnetic stirrer, and a porous glassy carbon anode and a platinum cathode were assembled. Argon was repeatedly pumped and filled three times, and methanol (5 ml) was added through a syringe. Then, the reaction was heated to reflux at 70 °C for 100 minutes under a constant current condition of 7.5 mA. After the reaction, water and dichloromethane were added to extract the reaction solution, and the organic phases were combined, dried, filtered, concentrated under reduced pressure, and purified by silica gel column chromatography to obtain quinolinone compound 4 with a yield of 39.5 mg (yield 72%).
[0065] The NMR data of the obtained product are as follows, and the spectrum is attached. Figure 4 : 1 H NMR (500 MHz, CDCl3) δ 7.84 (dd, J = 8.2, 1.4 Hz, 1H), 7.66 (ddd, J =8.6, 7.1, 1.5 Hz, 1H), 7.41 (dd, J = 8.7, 0.9 Hz, 1H), 7.31 – 7.20 (m, 6H), 4.53 (s, 2H), 3.76 (s, 3H). 13 C NMR (126 MHz, CDCl3) δ 158.9, 157.7, 141.0,136.5, 134.0, 129.2, 128.3, 127.8, 127.4, 123.3, 119.0, 115.4, 115.3, 108.3,37.8, 30.3. The high-resolution mass spectrometry data are as follows: C 18 H 14 N2O [M + Na] + Theoretical value 297.0998, tested value 297.1003.
[0066] Example 5: Electrochemical synthesis of quinolinone compound 5.
[0067] .
[0068] The raw materials S5 (60.8 mg), ferrocene (3.7 mg), potassium carbonate (27.6 mg), and (C2H5)4NPF6 (11 mg) were added to a single-chamber electrolytic cell equipped with a magnetic stirrer, and a porous glassy carbon anode and a platinum cathode were assembled. Argon was repeatedly pumped and filled three times, and methanol (5 ml) was added through a syringe. Then, the reaction was heated to reflux at 70 °C for 100 minutes under a constant current condition of 7.5 mA. After the reaction, water and dichloromethane were added to extract the reaction solution, and the organic phases were combined, dried, filtered, concentrated under reduced pressure, and purified by silica gel column chromatography to obtain quinolinone compound 5 with a yield of 51.9 mg (yield 85%).
[0069] The NMR data of the obtained product are as follows, and the spectrum is attached. Figure 5 : 1 H NMR (400 MHz, CDCl3) δ 7.86 (dd, J = 8.2, 1.4 Hz, 1H), 7.66 (ddd, J =8.7, 7.2, 1.5 Hz, 1H), 7.40 (d, J = 8.6 Hz, 1H), 7.29 – 7.22 (m, 1H), 7.20 –7.14 (m, 2H), 6.84 – 6.78 (m, 2H), 4.46 (s, 2H), 3.75 (s, 3H), 3.75 (s, 3H). 13 C NMR (101 MHz, CDCl3) δ 158.9, 158.1, 141.0, 133.9, 129.4, 128.5, 127.8,123.3, 119.0, 115.4, 115.3, 114.6, 108.1, 55.5, 37.0, 30.3. The high-resolution mass spectrometry data are as follows: C 19 H 16 N2O2[M + Na] + Theoretical value 327.1104, tested value 327.1113.
[0070] Example 6: Electrochemical synthesis of quinolinone compound 6.
[0071] .
[0072] The raw materials S6 (66.0 mg), ferrocene (3.7 mg), potassium carbonate (27.6 mg), and (C2H5)4NPF6 (11 mg) were added to a single-chamber electrolytic cell equipped with a magnetic stirrer, and a porous glassy carbon anode and a platinum cathode were assembled. Argon was repeatedly pumped and filled three times, and methanol (5 ml) was added through a syringe. Then, the mixture was heated to reflux at 70 °C for 100 minutes under a constant current condition of 7.5 mA. After the reaction, water and dichloromethane were added to extract the reaction solution, and the organic phases were combined, dried, filtered, concentrated under reduced pressure, and purified by silica gel column chromatography to obtain quinolinone compound 6 with a yield of 40.1 mg (yield 61%).
[0073] The NMR data of the obtained product are as follows, and the spectrum is attached. Figure 6 : 1 H NMR (400 MHz, CDCl3) δ 7.90 (dd, J = 8.2, 1.5 Hz, 1H), 7.72 – 7.64(m, 1H), 7.42 (d, J = 8.6 Hz, 1H), 7.34 – 7.27 (m, 3H), 7.20 (d, J = 8.1 Hz, 2H), 4.51 (s, 2H), 3.77 (s, 3H), 1.28 (s, 9H). 13 C NMR (101 MHz, CDCl3) δ 159.0,158.0, 150.4, 141.0, 133.9, 133.4, 128.0, 127.9, 126.1, 123.3, 119.1, 115.4,115.3, 108.2, 37.3, 34.6, 31.5, 30.3. The high-resolution mass spectrometry data are as follows: C 22 H 22 N2O [M + Na] + Theoretical value is 353.1624, tested value is 353.1632.
[0074] Example 7: Electrochemical synthesis of quinolinone compound 7.
[0075] .
[0076] The raw materials S7 (71.6 mg), ferrocene (3.7 mg), potassium carbonate (27.6 mg), and (C2H5)4NPF6 (11 mg) were added to a single-chamber electrolytic cell equipped with a magnetic stirrer, and a porous glassy carbon anode and a platinum cathode were assembled. Argon was repeatedly pumped and filled three times, and methanol (5 ml) was added through a syringe. Then, the reaction was heated to reflux at 70 °C for 100 minutes under a constant current condition of 7.5 mA. After the reaction, water and dichloromethane were added to extract the reaction solution, and the organic phases were combined, dried, filtered, concentrated under reduced pressure, and purified by silica gel column chromatography to obtain quinolinone compound 7 with a yield of 63.2 mg (yield 88%).
[0077] The NMR data of the obtained product are as follows, and the spectrum is attached. Figure 7 : 1 H NMR (400 MHz, CDCl3) δ 7.80 (dd, J = 8.2, 1.4 Hz, 1H), 7.70 (ddd, J =8.5, 7.1, 1.4 Hz, 1H), 7.44 (d, J = 8.6 Hz, 1H), 7.32 – 7.24 (m, 3H), 7.14 (d, J = 8.3 Hz, 2H), 4.53 (s, 2H), 3.77 (s, 3H). 13 C NMR (101 MHz, CDCl3) δ 158.7,157.0, 148.5 (q, J = 1.9 Hz), 141.1, 135.1, 134.2, 129.7, 127.5, 123.5, 121.7,120.6 (q, J = 257.4 Hz) 118.8, 115.5, 115.3, 108.5, 37.0, 30.4. 19 F NMR (376 MHz, CDCl3) δ -57.9. The high-resolution mass spectrometry data are as follows: C 19 H 13 F3N2O2[M + Na] + Theoretical value is 381.0821, tested value is 381.0833.
[0078] Example 8: Electrochemical synthesis of quinolinone compound 8.
[0079] .
[0080] The raw materials S8 (59.8 mg), ferrocene (3.7 mg), potassium carbonate (27.6 mg), and (C2H5)4NPF6 (11 mg) were added to a single-chamber electrolytic cell equipped with a magnetic stirrer, and a porous glassy carbon anode and a platinum cathode were assembled. Argon was repeatedly pumped and filled three times, and methanol (5 ml) was added through a syringe. Then, the mixture was heated to reflux at 70 °C for 100 minutes under a constant current condition of 7.5 mA. After the reaction, water and dichloromethane were added to extract the reaction solution, and the organic phases were combined, dried, filtered, concentrated under reduced pressure, and purified by silica gel column chromatography to obtain quinolinone compound 8 with a yield of 48.3 mg (yield 81%).
[0081] The NMR data of the obtained product are as follows, and the spectrum is attached. Figure 8 : 1 H NMR (400 MHz, CDCl3) δ 7.75 – 7.66 (m, 2H), 7.60 (d, J = 7.9 Hz, 2H),7.45 (d, J = 8.8 Hz, 1H), 7.36 (d, J = 8.0 Hz, 2H), 7.30 – 7.24 (m, 2H), 4.59 (s, 2H), 3.78 (s, 3H). 13 C NMR (101 MHz, CDCl3) δ 158.6, 155.9, 141.8, 141.2,134.4, 133.1, 129.1, 127.3, 123.6, 118.6, 118.5, 115.6, 115.1, 111.7, 108.9,37.6, 30.5. The high-resolution mass spectrometry data are as follows: C 19 H 13 N3O [M + Na] + Theoretical value: 322.0951, tested value: 322.0959.
[0082] Example 9: Electrochemical synthesis of quinolinone compound 9.
[0083] .
[0084] The raw materials S9 (66.4 mg), ferrocene (3.7 mg), potassium carbonate (27.6 mg), and (C2H5)4NPF6 (11 mg) were added to a single-chamber electrolytic cell equipped with a magnetic stirrer, and a porous glassy carbon anode and a platinum cathode were assembled. Argon was repeatedly pumped and filled three times, and methanol (5 ml) was added through a syringe. Then, the reaction was heated to reflux at 70 °C for 100 minutes under a constant current condition of 7.5 mA. After the reaction, water and dichloromethane were added to extract the reaction solution, and the organic phases were combined, dried, filtered, concentrated under reduced pressure, and purified by silica gel column chromatography to obtain quinolinone compound 9 with a yield of 52.1 mg (yield 78%).
[0085] The NMR data of the obtained product are as follows, and the spectrum is attached. Fig. 9 : 1 H NMR (400 MHz, CDCl3) δ 7.98 – 7.93 (m, 2H), 7.75 (dd, J = 8.2, 1.4Hz, 1H), 7.68 (ddd, J = 8.7, 7.2, 1.5 Hz, 1H), 7.43 (d, J = 8.5 Hz, 1H), 7.31 (d, J = 8.1 Hz, 2H), 7.27 – 7.20 (m, 1H), 4.58 (s, 2H), 3.88 (s, 3H), 3.77 (s, 3H). 13 C NMR (101 MHz, CDCl3) δ 166.8, 158.7, 156.7, 141.6, 141.1, 134.2,130.5, 129.5, 128.4, 127.6, 123.4, 118.8, 115.5, 115.2, 108.7, 52.4, 37.8,30.4. The high-resolution mass spectrometry data are as follows: C 20 H 16 N2O3[M + Na] + Theoretical value 355.1053, tested value 355.1061.
[0086] Example 10: Electrochemical synthesis of quinolinone compound 10.
[0087] .
[0088] The raw materials S10 (60.8 mg), ferrocene (3.7 mg), potassium carbonate (27.6 mg), and (C2H5)4NPF6 (11 mg) were added to a single-chamber electrolytic cell equipped with a magnetic stirrer, and a porous glassy carbon anode and a platinum cathode were assembled. Argon was repeatedly pumped and filled three times, and methanol (5 ml) was added through a syringe. Then, the reaction was heated to reflux at 70 °C for 100 minutes under a constant current condition of 7.5 mA. After the reaction, water and dichloromethane were added to extract the reaction solution, and the organic phases were combined, dried, filtered, concentrated under reduced pressure, and purified by silica gel column chromatography to obtain quinolinone compound 10 with a yield of 48.3 mg (yield 79%).
[0089] The NMR data of the obtained product are as follows, and the spectrum is attached. Fig.10 : 1 H NMR (400 MHz, CDCl3) δ 7.84 (dd, J = 8.2, 1.4 Hz, 1H), 7.66 (ddd, J =8.6, 7.2, 1.4 Hz, 1H), 7.41 (dd, J = 8.6, 1.0 Hz, 1H), 7.27 – 7.22 (m, 1H),7.20 (t, J = 7.9 Hz, 1H), 6.82 (d, J = 8.0 Hz, 1H), 6.76 (dd, J = 11.1, 2.5 Hz,2H), 4.50 (s, 2H), 3.76 (s, 3H), 3.75 (s, 3H). 13 C NMR (101 MHz, CDCl3) δ160.2, 158.9, 157.5, 141.0, 138.0, 134.0, 130.2, 127.8, 123.3, 120.7, 119.0,115.4, 115.3, 114.5, 112.4, 108.4, 55.4, 37.8, 30.3. The high-resolution mass spectrometry data are as follows: C 19 H 16 N2O2[M + Na] + Theoretical value 327.1104, tested value 327.1113.
[0090] Example 11: Electrochemical synthesis of quinolinone compound 11.
[0091] .
[0092] The raw materials S11 (70.6 mg), ferrocene (3.7 mg), potassium carbonate (27.6 mg), and (C2H5)4NPF6 (11 mg) were added to a single-chamber electrolytic cell equipped with a magnetic stirrer, equipped with a porous glassy carbon anode and a platinum cathode, and argon was repeatedly pumped and filled three times. Methanol (5 ml) was added through a syringe, and then heated to reflux at 70 °C for 100 minutes under a constant current condition of 7.5 mA. After the reaction, water and dichloromethane were added to extract the reaction solution, and the organic phases were combined, dried, filtered, concentrated under reduced pressure, and purified by silica gel column chromatography to obtain quinolinone compound 11 with a yield of 50.1 mg (yield 71%).
[0093] The NMR data of the obtained product are as follows, and the spectrum is attached. Fig.11 : 1 H NMR (400 MHz, CDCl3) δ 7.76 (dd, J = 8.2, 1.4 Hz, 1H), 7.69 (ddd, J =8.7, 7.2, 1.5 Hz, 1H), 7.43 (dd, J = 8.7, 1.0 Hz, 1H), 7.39 – 7.34 (m, 2H), 7.29 – 7.24 (m, 1H), 7.19 – 7.14 (m, 2H), 4.50 (s, 2H), 3.77 (s, 3H). 13 C NMR (101 MHz, CDCl3) δ 158.7, 156.6, 141.1, 138.6, 134.2, 131.2, 130.8, 130.7,127.5, 127.0, 123.5, 123.3, 118.8, 115.5, 115.2, 108.7, 37.3, 30.4. The high-resolution mass spectrometry data are as follows: C 18 H 13 BrN2O [M + Na] + Theoretical values are 375.0103, 377.0083. Test values are 375.0111, 377.0092.
[0094] Example 12: Electrochemical synthesis of quinolinone compound 12.
[0095] .
[0096] The raw materials S12 (58.4 mg), ferrocene (3.7 mg), potassium carbonate (27.6 mg), and (C2H5)4NPF6 (11 mg) were added to a single-chamber electrolytic cell equipped with a magnetic stirrer, and a porous glassy carbon anode and a platinum cathode were assembled. Argon was repeatedly pumped and filled three times, and methanol (5 ml) was added through a syringe. Then, the reaction was heated to reflux at 70 °C for 100 minutes under a constant current condition of 7.5 mA. After the reaction, water and dichloromethane were added to extract the reaction solution, and the organic phases were combined, dried, filtered, concentrated under reduced pressure, and purified by silica gel column chromatography to obtain quinolinone compound 12 with a yield of 53.3 mg (yield 91%).
[0097] The NMR data of the obtained product are as follows, and the spectrum is attached. Fig.12 : 1 H NMR (400 MHz, CDCl3) δ 7.79 (dd, J = 8.2, 1.4 Hz, 1H), 7.70 (ddd, J =8.6, 7.1, 1.4 Hz, 1H), 7.45 (d, J = 8.6 Hz, 1H), 7.31 – 7.23 (m, 2H), 7.05 (d, J = 7.7 Hz, 1H), 6.97 – 6.89 (m, 2H), 4.53 (s, 2H), 3.78 (s, 3H). 13 C NMR (101MHz, CDCl3) δ 164.4, 162.0, 158.7, 156.8, 141.0, 138.8 (d, J = 7.4 Hz), 134.2,130.8 (d, J = 8.3 Hz), 127.6, 124.1 (d, J = 3.1 Hz), 123.5, 118.8, 115.4, 115.3(d, J = 21.5 Hz), 114.5 (d, J = 21.0 Hz), 108.5, 37.4, 30.4. 19 F NMR (376 MHz, CDCl3) δ -112.0. The high-resolution mass spectrometry data are as follows: C 18 H 13 FN2O [M + Na] +Theoretical value 315.0904, tested value 315.0909.
[0098] Example 13: Electrochemical synthesis of quinolinone compound 13.
[0099] .
[0100] The raw materials S13 (60.8 mg), ferrocene (3.7 mg), potassium carbonate (27.6 mg), and (C2H5)4NPF6 (11 mg) were added to a single-chamber electrolytic cell equipped with a magnetic stirrer, and a porous glassy carbon anode and a platinum cathode were assembled. Argon was repeatedly pumped and filled three times, and methanol (5 ml) was added through a syringe. Then, the reaction was heated to reflux at 70 °C for 100 minutes under a constant current condition of 7.5 mA. After the reaction, water and dichloromethane were added to extract the reaction solution, and the organic phases were combined, dried, filtered, concentrated under reduced pressure, and purified by silica gel column chromatography to obtain quinolinone compound 13 with a yield of 43.2 mg (yield 71%).
[0101] The NMR data of the obtained product are as follows, and the spectrum is attached. Fig.13 : 1 H NMR (400 MHz, CDCl3) δ 7.81 (dd, J = 8.2, 1.5 Hz, 1H), 7.63 (ddd, J =8.6, 7.1, 1.5 Hz, 1H), 7.39 (d, J = 8.5 Hz, 1H), 7.24 – 7.15 (m, 2H), 6.91 (d, J = 8.0 Hz, 2H), 6.80 (td, J = 7.5, 1.1 Hz, 1H), 4.51 (s, 2H), 3.94 (s, 3H), 3.77(s, 3H). 13 C NMR (101 MHz, CDCl3) δ 159.0, 158.7, 156.7, 140.8, 133.8, 129.0,128.6, 127.9, 125.1, 123.3, 121.0, 119.3, 115.4, 115.1, 110.8, 108.8, 55.7,31.8, 30.3. The high-resolution mass spectrometry data are as follows: C 19 H 16 N2O2[M + Na] +Theoretical value 327.1104, tested value 327.1108.
[0102] Example 14: Electrochemical synthesis of quinolinone compound 14.
[0103] .
[0104] The raw materials S14 (64.8 mg), ferrocene (3.7 mg), potassium carbonate (27.6 mg), and (C2H5)4NPF6 (11 mg) were added to a single-chamber electrolytic cell equipped with a magnetic stirrer, and a porous glassy carbon anode and a platinum cathode were assembled. Argon was repeatedly pumped and filled three times, and methanol (5 ml) was added through a syringe. Then, the mixture was heated to reflux at 70 °C for 100 minutes under a constant current of 7.5 mA. After the reaction, water and dichloromethane were added to extract the reaction solution, and the organic phases were combined, dried, filtered, concentrated under reduced pressure, and purified by silica gel column chromatography to obtain quinolinone compound 14 with a yield of 51.3 mg (yield 79%).
[0105] The NMR data of the obtained product are as follows, and the spectrum is attached. Fig.14 : 1 H NMR (400 MHz, CDCl3) δ 7.87 (dd, J = 8.2, 1.5 Hz, 1H), 7.81 – 7.76(m, 2H), 7.75 – 7.70 (m, 1H), 7.67 – 7.60 (m, 2H), 7.48 – 7.37 (m, 4H), 7.21(ddd, J = 8.2, 7.1, 1.1 Hz, 1H), 4.69 (s, 2H), 3.78 (s, 3H). 13 C NMR (101 MHz, CDCl3) δ 158.9, 157.5, 141.0, 134.0, 134.0, 133.7, 132.6, 129.1, 127.9, 127.0, 126.7, 126.3, 126.3, 123.4, 119.0, 115.4, 115.3, 108.5, 38.1, 30.4. The high-resolution mass spectrometry data are as follows: C 22 H 16 N2O [M + Na] + Theoretical value 347.1155, tested value 347.1160.
[0106] Example 15: Electrochemical synthesis of quinolinone compound 15.
[0107] .
[0108] The raw materials S15 (56.0 mg), ferrocene (3.7 mg), potassium carbonate (27.6 mg), and (C2H5)4NPF6 (11 mg) were added to a single-chamber electrolytic cell equipped with a magnetic stirrer, and a porous glassy carbon anode and a platinum cathode were assembled. Argon was repeatedly pumped and filled three times, and methanol (5 ml) was added through a syringe. Then, the reaction was heated to reflux at 70 °C for 100 minutes under a constant current condition of 7.5 mA. After the reaction, water and dichloromethane were added to extract the reaction solution, and the organic phases were combined, dried, filtered, concentrated under reduced pressure, and purified by silica gel column chromatography to obtain quinolinone compound 15 with a yield of 40.2 mg (yield 72%).
[0109] The NMR data of the obtained product are as follows, and the spectrum is attached. Fig.15 : 1 H NMR (400 MHz, CDCl3) δ 7.91 (dd, J = 8.2, 1.5 Hz, 1H), 7.69 (ddd, J =8.6, 7.2, 1.5 Hz, 1H), 7.42 (dd, J = 8.6, 1.1 Hz, 1H), 7.30 (ddd, J = 8.3, 7.2,1.1 Hz, 1H), 7.28 – 7.25 (m, 2H), 7.08 – 7.05 (m, 1H), 7.02 (dd, J = 5.0, 1.4Hz, 1H), 4.51 (s, 2H), 3.76 (s, 3H). 13 C NMR (101 MHz, CDCl3) δ 158.9, 157.5,141.1, 136.1, 134.1, 127.7, 127.5, 126.7, 123.4, 122.7, 118.8, 115.4, 115.3,107.6, 32.8, 30.4. The high-resolution mass spectrometry data are as follows: C 16 H 12 N2OS [M + Na] + Theoretical value 303.0563, tested value 303.0566.
[0110] Example 16: Electrochemical synthesis of quinolinone compound 16.
[0111] .
[0112] The raw materials S16 (83.8 mg), ferrocene (3.7 mg), potassium carbonate (27.6 mg), and (C2H5)4NPF6 (11 mg) were added to a single-chamber electrolytic cell equipped with a magnetic stirrer, and a porous glassy carbon anode and a platinum cathode were assembled. Argon was repeatedly pumped and filled three times, and methanol (5 ml) was added through a syringe. Then, the reaction was heated to reflux at 70 °C for 100 minutes under a constant current condition of 7.5 mA. After the reaction, water and dichloromethane were added to extract the reaction solution, and the organic phases were combined, dried, filtered, concentrated under reduced pressure, and purified by silica gel column chromatography to obtain quinolinone compound 16 with a yield of 60.8 mg (yield 73%).
[0113] The NMR data of the obtained product are as follows, and the spectrum is attached. Fig.16 : 1 H NMR (400 MHz, CDCl3) δ 7.84 (dd, J = 8.3, 1.5 Hz, 1H), 7.66 (ddd, J =8.6, 7.2, 1.5 Hz, 1H), 7.41 (dd, J = 8.6, 1.0 Hz, 1H), 7.24 (dd, J = 8.1, 6.3 Hz, 5H), 4.68 (s, 2H), 4.51 (s, 2H), 3.76 (s, 3H), 0.91 (s, 9H), 0.07 (s, 6H). 13 CNMR (101 MHz, CDCl3) δ 158.8, 157.7, 140.9, 140.7, 134.9, 133.8, 128.1,127.8, 126.8, 123.2, 118.9, 115.3, 115.2, 108.2, 64.6, 37.5, 30.3, 26.1,18.5, -5.2. The high-resolution mass spectrometry data are as follows: C 25 H 30 N2O2Si [M + Na] + Theoretical value 441.1969, tested value 441.1969.
[0114] Example 17: Electrochemical synthesis of quinolinone compound 17.
[0115] .
[0116] The raw materials S17 (111.4 mg), ferrocene (3.7 mg), potassium carbonate (27.6 mg), and (C2H5)4NPF6 (11 mg) were added to a single-chamber electrolytic cell equipped with a magnetic stirrer, equipped with a porous glassy carbon anode and a platinum cathode, and argon was repeatedly pumped and filled three times. Methanol (5 ml) was added through a syringe, and then heated to reflux at 70 °C for 100 minutes under a constant current condition of 7.5 mA. After the reaction, water and dichloromethane were added to extract the reaction solution, and the organic phases were combined, dried, filtered, concentrated under reduced pressure, and purified by silica gel column chromatography to obtain quinolinone compound 17 with a yield of 83.0 mg (yield 74%).
[0117] The NMR data of the obtained product are as follows, and the spectrum is attached. Fig.17 : 1 H NMR (500 MHz, CDCl3) δ 7.84 (dd, J = 8.2, 1.5 Hz, 1H), 7.67 (ddd, J =8.7, 7.2, 1.5 Hz, 1H), 7.49 – 7.45 (m, 2H), 7.43 (dd, J = 8.6, 1.0 Hz, 1H),7.34 – 7.30 (m, 2H), 7.28 – 7.23 (m, 2H), 7.22 (d, J = 8.1 Hz, 2H), 7.11 (d, J =8.1 Hz, 2H), 4.96 (s, 2H), 4.52 (s, 2H), 3.75 (s, 3H), 2.36 (s, 3H), 1.28 (s,9H). 13 C NMR (126 MHz, CDCl3) δ 158.7, 157.5, 151.1, 144.3, 140.9, 136.9,136.7, 135.8, 133.9, 129.2, 129.0, 128.4, 128.0, 127.6, 123.3, 118.8, 115.3(2C), 108.2, 84.7, 49.3, 37.4, 30.2, 27.9, 21.6. The high-resolution mass spectrometry data are as follows: C 31 H 31N3O5S [M + Na] + Theoretical value is 580.1877, tested value is 580.1886.
[0118] Example 18: Electrochemical synthesis of quinolinone compound 18.
[0119] .
[0120] The raw materials S18 (55.6 mg), ferrocene (3.7 mg), potassium carbonate (27.6 mg), and (C2H5)4NPF6 (11 mg) were added to a single-chamber electrolytic cell equipped with a magnetic stirrer, and a porous glassy carbon anode and a platinum cathode were assembled. Argon was repeatedly pumped and filled three times, and methanol (5 ml) was added through a syringe. Then, the mixture was heated to reflux at 70 °C for 100 minutes under a constant current condition of 7.5 mA. After the reaction, water and dichloromethane were added to extract the reaction solution, and the organic phases were combined, dried, filtered, concentrated under reduced pressure, and purified by silica gel column chromatography to obtain quinolinone compound 18 with a yield of 46.2 mg (yield 83%).
[0121] The NMR data of the obtained product are as follows, and the spectrum is attached. Fig.18 : 1 H NMR (400 MHz, CDCl3) δ 7.86 (dd, J = 8.2, 1.5 Hz, 1H), 7.69 (ddd, J =8.6, 7.2, 1.5 Hz, 1H), 7.41 (dd, J = 8.6, 1.0 Hz, 1H), 7.30 (ddd, J = 8.2, 7.1,1.1 Hz, 1H), 5.38 (dp, J = 3.8, 1.8 Hz, 1H), 3.78 (s, 2H), 3.74 (s, 3H), 2.05 –1.99 (m, 2H), 1.94 (dtp, J = 6.6, 4.6, 2.3 Hz, 2H), 1.65 – 1.58 (m, 2H), 1.54 –1.48 (m, 2H). 13C NMR (101 MHz, CDCl3) δ 158.9, 158.0, 140.6, 133.8 (2C), 127.6, 125.2, 123.1, 119.5, 115.3, 115.1, 108.2, 40.1, 30.2, 29.0, 25.4,22.9, 22.1. The high-resolution mass spectrometry data are as follows: C 18 H 18 N2O [M + Na] + Theoretical value 301.1311, tested value 301.1317.
[0122] Example 19: Electrochemical synthesis of quinolinone compound 19.
[0123] .
[0124] The raw materials S19 (57.6 mg), ferrocene (3.7 mg), potassium carbonate (27.6 mg), and (C2H5)4NPF6 (11 mg) were added to a single-chamber electrolytic cell equipped with a magnetic stirrer, and a porous glassy carbon anode and a platinum cathode were assembled. Argon was repeatedly pumped and filled three times, and methanol (5 ml) was added through a syringe. Then, the mixture was heated to reflux at 70 °C for 100 minutes under a constant current condition of 7.5 mA. After the reaction, water and dichloromethane were added to extract the reaction solution, and the organic phases were combined, dried, filtered, concentrated under reduced pressure, and purified by silica gel column chromatography to obtain quinolinone compound 19 with a yield of 33.2 mg (yield 58%).
[0125] The NMR data of the obtained product are as follows, and the spectrum is attached. Fig.19 : 1 H NMR (400 MHz, CDCl3) δ 7.63 – 7.60 (m, 1H), 7.48 (dd, J = 8.7, 2.0Hz, 1H), 7.33 – 7.27 (m, 3H), 7.27 – 7.20 (m, 4H), 4.52 (s, 2H), 3.75 (s,3H), 2.37 (s, 3H). 13 C NMR (101 MHz, CDCl3) δ 158.8, 157.3, 139.1, 136.5,135.2, 132.9, 129.2, 128.3, 127.4, 127.3, 119.0, 115.4, 115.2, 108.2, 37.7,30.3,21.0. The high-resolution mass spectrometry data are as follows: C 19 H 16 N2O [M + Na] + Theoretical value 311.1155, tested value 311.1162.
[0126] Example 20: Electrochemical synthesis of quinolinone compound 20.
[0127] .
[0128] The raw materials S20 (66.0 mg), ferrocene (3.7 mg), potassium carbonate (27.6 mg), and (C2H5)4NPF6 (11 mg) were added to a single-chamber electrolytic cell equipped with a magnetic stirrer, equipped with a porous glassy carbon anode and a platinum cathode, and argon was repeatedly pumped and filled three times. Methanol (5 ml) was added through a syringe, and then heated to reflux at 70 °C for 100 minutes under a constant current condition of 7.5 mA. After the reaction, water and dichloromethane were added to extract the reaction solution, and the organic phases were combined, dried, filtered, concentrated under reduced pressure, and purified by silica gel column chromatography to obtain quinolinone compound 20 with a yield of 53.2 mg (yield 81%).
[0129] The NMR data of the obtained product are as follows, and the spectrum is attached. Fig. 20 : 1 H NMR (400 MHz, CDCl3) δ 7.80 (d, J = 2.2 Hz, 1H), 7.70 (dd, J = 8.9, 2.2Hz, 1H), 7.34 (d, J = 8.9 Hz, 1H), 7.31 – 7.25 (m, 4H), 7.21 (ddd, J = 8.7, 5.0,3.8 Hz, 1H), 4.54 (s, 2H), 3.74 (s, 3H), 1.25 (s, 9H). 13 C NMR (101 MHz, CDCl3)δ 158.8, 157.9, 146.0, 138.9, 136.8, 131.8, 129.1, 128.3, 127.3, 124.0,118.3, 115.6, 115.0, 107.8, 38.2, 34.6, 31.2, 30.2. The high-resolution mass spectrometry data are as follows: C 22 H 22N2O [M + Na] + Theoretical value is 353.1624, tested value is 353.1636.
[0130] Example 21: Electrochemical synthesis of quinolinone compound 21.
[0131] .
[0132] The raw materials S21 (61.8 mg), ferrocene (3.7 mg), potassium carbonate (27.6 mg), and (C2H5)4NPF6 (11 mg) were added to a single-chamber electrolytic cell equipped with a magnetic stirrer, equipped with a porous glassy carbon anode and a platinum cathode, and argon was repeatedly pumped and filled three times. Methanol (5 ml) was added through a syringe, and then heated to reflux at 70 °C for 100 minutes under a constant current condition of 7.5 mA. After the reaction, water and dichloromethane were added to extract the reaction solution, and the organic phases were combined, dried, filtered, concentrated under reduced pressure, and purified by silica gel column chromatography to obtain quinolinone compound 21 with a yield of 48.0 mg (yield 78%).
[0133] The NMR data of the obtained product are as follows, and the spectrum is attached. Fig.21 : 1 H NMR (400 MHz, CDCl3) δ 7.81 (d, J = 2.3 Hz, 1H), 7.61 (dd, J = 9.1, 2.4Hz, 1H), 7.38 – 7.30 (m, 3H), 7.29 – 7.23 (m, 3H), 4.50 (s, 2H), 3.75 (s, 3H). 13 C NMR (101 MHz, CDCl3) δ 158.5, 156.6, 139.5, 135.9, 133.9, 129.4,129.1, 128.3, 127.7, 127.0, 120.1, 116.8, 115.0, 109.5, 37.8, 30.6. The high-resolution mass spectrometry data are as follows: C 18 H 13 ClN2O [M + Na] + Theoretical value: 331.0609, tested value: 331.0617.
[0134] Example 22: Electrochemical synthesis of quinolinone compound 22.
[0135] .
[0136] The raw materials S22 (70.6 mg), ferrocene (3.7 mg), potassium carbonate (27.6 mg), and (C2H5)4NPF6 (11 mg) were added to a single-chamber electrolytic cell equipped with a magnetic stirrer, equipped with a porous glassy carbon anode and a platinum cathode, and argon was repeatedly pumped and filled three times. Methanol (5 ml) was added through a syringe, and then heated to reflux at 70 °C for 100 minutes under a constant current condition of 7.5 mA. After the reaction, water and dichloromethane were added to extract the reaction solution, and the organic phases were combined, dried, filtered, concentrated under reduced pressure, and purified by silica gel column chromatography to obtain quinolinone compound 22 with a yield of 55.1 mg (yield 78%).
[0137] The NMR data of the obtained product are as follows, and the spectrum is attached. Fig. 22 : 1 H NMR (400 MHz, CDCl3) δ 7.97 (d, J = 2.2 Hz, 1H), 7.75 (dd, J = 9.0, 2.2Hz, 1H), 7.33 (d, J = 7.2 Hz, 2H), 7.30 – 7.24 (m, 4H), 4.50 (s, 2H), 3.76 (s, 3H). 13 C NMR (101 MHz, CDCl3) δ 158.4, 156.5, 139.9, 136.5, 135.8, 130.0,129.4, 128.3, 127.7, 120.4, 116.9, 116.4, 114.9, 109.4, 37.7, 30.5. The high-resolution mass spectrometry data are as follows: C 18 H 13 BrN2O [M + Na] + Theoretical values are 375.0103, 377.0083. Test values are 375.0110, 377.0092.
[0138] Example 23: Electrochemical synthesis of quinolinone compound 23.
[0139] .
[0140] The raw materials S23 (64.8 mg), ferrocene (3.7 mg), potassium carbonate (27.6 mg), and (C2H5)4NPF6 (11 mg) were added to a single-chamber electrolytic cell equipped with a magnetic stirrer, equipped with a porous glassy carbon anode and a platinum cathode, and argon was repeatedly pumped and filled three times. Methanol (5 ml) was added through a syringe, and then heated to reflux at 70 °C for 100 minutes under a constant current condition of 7.5 mA. After the reaction, water and dichloromethane were added to extract the reaction solution, and the organic phases were combined, dried, filtered, concentrated under reduced pressure, and purified by silica gel column chromatography to obtain quinolinone compound 23 with a yield of 30.5 mg (yield 47%).
[0141] The NMR data of the obtained product are as follows, and the spectrum is attached. Fig.23 : 1 H NMR (400 MHz, CDCl3) δ 8.41 (d, J = 8.7 Hz, 1H), 7.86 (dd, J = 8.1, 1.4Hz, 1H), 7.71 (d, J = 8.8 Hz, 1H), 7.68 – 7.63 (m, 1H), 7.61 – 7.56 (m, 2H), 7.32 – 7.25 (m, 4H), 7.23 (td, J = 6.5, 5.7, 2.5 Hz, 1H), 4.59 (s, 2H), 4.09 (s, 3H). 13 C NMR (101 MHz, CDCl3) δ 161.5, 157.4, 142.2, 136.7, 136.5, 129.3,129.2, 128.8, 128.3, 127.4, 126.5, 125.9, 124.9, 123.6, 122.2, 117.2, 115.5,106.9, 41.5, 38.2. The high-resolution mass spectrometry data are as follows: C 22 H 16 N2O [M + Na] + Theoretical value 347.1155, tested value 347.1166.
[0142] Example 24: Electrochemical synthesis of quinolinone compound 24.
[0143] .
[0144] The raw materials S24 (66.0 mg), ferrocene (3.7 mg), potassium carbonate (27.6 mg), and (C2H5)4NPF6 (11 mg) were added to a single-chamber electrolytic cell equipped with a magnetic stirrer, and a porous glassy carbon anode and a platinum cathode were assembled. Argon was repeatedly pumped and filled three times, and methanol (5 ml) was added through a syringe. Then, the reaction was heated to reflux at 70 °C under a constant current of 7.5 mA for 100 minutes. After the reaction, water and dichloromethane were added to extract the reaction solution, and the organic phases were combined, dried, filtered, concentrated under reduced pressure, and purified by silica gel column chromatography to obtain quinolinone compound 24 with a yield of 49.1 mg (yield 74%).
[0145] The NMR data of the obtained product are as follows, and the spectrum is attached. Fig.24 : 1 H NMR (400 MHz, CDCl3) δ 7.85 (dd, J = 8.2, 1.6 Hz, 1H), 7.48 (tt, J =8.4, 1.4 Hz, 1H), 7.28 (d, J = 8.7 Hz, 1H), 7.25 – 7.21 (m, 2H), 7.21 – 7.14(m, 4H), 5.50 (s, 2H), 3.14 (s, 2H), 1.04 (s, 9H). 13 C NMR (101 MHz, CDCl3) δ159.2, 159.0, 140.0, 135.6, 133.7, 129.1, 128.6, 127.8, 126.9, 122.6, 120.4,116.3, 116.0, 108.8, 46.9, 43.5, 35.3, 31.0. The high-resolution mass spectrometry data are as follows: C 22 H 22 N2O [M + Na] + Theoretical value is 353.1624, tested value is 353.1635.
[0146] Example 25: Electrochemical synthesis of quinolinone compound 25.
[0147] .
[0148] The raw materials S25 (72.0 mg), ferrocene (3.7 mg), potassium carbonate (27.6 mg), and (C2H5)4NPF6 (11 mg) were added to a single-chamber electrolytic cell equipped with a magnetic stirrer, and a porous glassy carbon anode and a platinum cathode were assembled. Argon was repeatedly pumped and filled three times, and methanol (5 ml) was added through a syringe. Then, the reaction was heated to reflux at 70 °C under a constant current of 7.5 mA for 100 minutes. After the reaction, water and dichloromethane were added to extract the reaction solution, and the organic phases were combined, dried, filtered, concentrated under reduced pressure, and purified by silica gel column chromatography to obtain quinolinone compound 25 with a yield of 55.0 mg (yield 76%).
[0149] The raw materials S25 (2.88 g), ferrocene (0.15 g), potassium carbonate (1.10 g), and (C2H5)4NPF6 (0.44 g) were added to a single-chamber electrolytic cell equipped with a magnetic stirrer, and a porous glassy carbon (5.0 cm×5.0 cm×1.2 cm) anode and a platinum sheet (5.0 cm×5.0 cm×0.1 cm) cathode were assembled. Argon was repeatedly pumped and filled three times, and methanol (200 ml) was added through a syringe. Then, the mixture was heated to reflux at 70 °C under a constant current of 187.5 mA for 2.3 hours in a sealed state. After the reaction, water and dichloromethane were added to extract the reaction solution, and the organic phases were combined, dried, filtered, concentrated under reduced pressure, and purified by silica gel column chromatography to obtain quinolinone compound 25 with a yield of 2.05 g (yield 71%).
[0150] The NMR data of the obtained product are as follows, and the spectrum is attached. Fig.25 : 1 H NMR (400 MHz, CDCl3) δ 7.92 (dd, J = 8.2, 1.4 Hz, 1H), 7.58 (ddd, J =8.7, 7.3, 1.4 Hz, 1H), 7.42 (d, J = 8.7 Hz, 1H), 7.32 – 7.25 (m, 1H), 7.22 (d, J = 8.4 Hz, 2H), 6.85 (d, J = 8.5 Hz, 2H), 5.52 (s, 2H), 3.77 (s, 3H), 3.21 (s, 2H), 1.12 (s, 9H). 13C NMR (101 MHz, CDCl3) δ 159.2, 158.9, 140.0, 133.7,128.5, 128.4, 127.6, 122.6, 120.4, 116.3, 116.0, 114.5, 108.8, 55.4, 46.4,43.5, 35.3, 31.0. The high-resolution mass spectrometry data are as follows: C 23 H 24 N2O2[M + Na] + Theoretical value is 383.1730, tested value is 383.1738.
[0151] Example 26: Electrochemical synthesis of quinolinone compound 26.
[0152] .
[0153] The raw materials S26 (64.4 mg), ferrocene (3.7 mg), potassium carbonate (27.6 mg), and (C2H5)4NPF6 (11 mg) were added to a single-chamber electrolytic cell equipped with a magnetic stirrer, equipped with a porous glassy carbon anode and a platinum cathode, and argon was repeatedly pumped and filled three times. Methanol (5 ml) was added through a syringe, and then heated to reflux at 70 °C for 100 minutes under a constant current condition of 7.5 mA. After the reaction, water and dichloromethane were added to extract the reaction solution, and the organic phases were combined, dried, filtered, concentrated under reduced pressure, and purified by silica gel column chromatography to obtain quinolinone compound 26 with a yield of 48.3 mg (yield 75%).
[0154] The NMR data of the obtained product are as follows, and the spectrum is attached. Fig.26 : 1 H NMR (400 MHz, CDCl3) δ 7.91 (dd, J = 8.3, 1.5 Hz, 1H), 7.68 (ddd, J =8.6, 7.1, 1.4 Hz, 1H), 7.43 – 7.36 (m, 1H), 7.29 (ddd, J = 8.2, 7.1, 1.0 Hz,1H), 5.89 – 5.71 (m, 1H), 5.09 – 4.91 (m, 2H), 4.37 – 4.23 (m, 2H), 3.16 (s,2H), 2.15 (q, J= 7.1 Hz, 2H), 1.83 – 1.71 (m, 2H), 1.57 (p, J = 7.5 Hz, 2H),1.08 (s, 9H). 13 C NMR (101 MHz, CDCl3) δ 158.6, 158.2, 139.8, 138.3, 133.5,128.6, 122.2, 120.3, 116.2, 115.2, 115.1, 108.9, 43.4, 43.2, 35.2, 33.4,30.9, 26.8, 26.3. The high-resolution mass spectrometry data are as follows: C 21 H 26 N2O [M + Na] + Theoretical value 345.1937, tested value 345.1940.
[0155] Example 27: Electrochemical synthesis of quinolinone compound 27.
[0156] .
[0157] The raw materials S27 (61.4 mg), ferrocene (3.7 mg), potassium carbonate (27.6 mg), and (C2H5)4NPF6 (11 mg) were added to a single-chamber electrolytic cell equipped with a magnetic stirrer, and a porous glassy carbon anode and a platinum cathode were assembled. Argon was repeatedly pumped and filled three times, and methanol (5 ml) was added through a syringe. Then, the reaction was heated to reflux at 70 °C for 100 minutes under a constant current condition of 7.5 mA. After the reaction, water and dichloromethane were added to extract the reaction solution, and the organic phases were combined, dried, filtered, concentrated under reduced pressure, and purified by silica gel column chromatography to obtain quinolinone compound 27 with a yield of 47.9 mg (yield 78%).
[0158] The NMR data of the obtained product are as follows, and the spectrum is attached. Fig. 27 : 1 H NMR (400 MHz, CDCl3) δ 7.70 (dd, J = 8.1, 1.4 Hz, 1H), 7.54 (ddd, J =8.6, 7.2, 1.4 Hz, 1H), 7.37 (d, J = 8.6 Hz, 1H), 7.27 (d, J = 4.4 Hz, 4H), 7.20(p, J= 4.2 Hz, 1H), 7.17 – 7.11 (m, 1H), 4.21 (s, 2H), 3.91 (s, 3H), 3.75 (s, 3H). 13 C NMR (101 MHz, CDCl3) δ 167.3, 159.4, 145.2, 140.1, 137.7, 131.5,129.0, 128.5, 128.0, 127.2, 126.9, 122.7, 119.7, 114.8, 52.9, 36.5, 29.8. The high-resolution mass spectrometry data are as follows: C 19 H 17 NO3[M + Na] + Theoretical value 330.1101, tested value 330.1106.
[0159] Example 28: Electrochemical synthesis of quinolinone compound 28.
[0160] .
[0161] The raw materials S28 (54.2 mg), ferrocene (3.7 mg), potassium carbonate (27.6 mg), and (C2H5)4NPF6 (11 mg) were added to a single-chamber electrolytic cell equipped with a magnetic stirrer, and a porous glassy carbon anode and a platinum cathode were assembled. Argon was repeatedly pumped and filled three times, and methanol (5 ml) was added through a syringe. Then, the mixture was heated to reflux at 70 °C for 100 minutes under a constant current condition of 7.5 mA. After the reaction, water and dichloromethane were added to extract the reaction solution, and the organic phases were combined, dried, filtered, concentrated under reduced pressure, and purified by silica gel column chromatography to obtain quinolinone compound 28 with a yield of 48.5 mg (yield 89%).
[0162] The NMR data of the obtained product are as follows, and the spectrum is attached. Fig.28 : 1 H NMR (400 MHz, CDCl3) δ 7.84 (dt, J = 8.1, 1.4 Hz, 1H), 7.58 – 7.51(m, 1H), 7.41 – 7.36 (m, 1H), 7.25 – 7.20 (m, 1H), 3.73 (s, 3H), 2.76 (s,2H), 0.99 (s, 9H). 13C NMR (101 MHz, CDCl3) δ 162.0, 148.3, 140.2, 130.3,126.5, 123.2, 122.0, 121.6, 114.7, 44.1, 32.7, 30.4, 29.8, 29.5. The high-resolution mass spectrometry data are as follows: C 17 H 21 NO2[M + Na] + Theoretical value 294.1465, tested value 294.1432.
[0163] The present invention provides a method and method for electrochemically synthesizing quinolinone compounds. There are many methods and approaches to implement the technical solution. The above is only a preferred embodiment of the present invention. It should be pointed out that for ordinary technicians in this technical field, several improvements and modifications can be made without departing from the principle of the present invention. These improvements and modifications should also be considered as the scope of protection of the present invention. All components not specified in this embodiment can be implemented by existing technologies.
Claims
1. A method for electrochemically synthesizing quinolinone compounds, characterized in that: A compound containing both a disubstituted alkyne fragment and an α-electron-withdrawing group-substituted amide fragment in the molecule is used as a raw material, and an electrolytic reaction is carried out in an electrolytic cell under the protection of an inert gas with a ferrocene catalyst, a supporting electrolyte, a base and a solvent. After the reaction is completed, the reaction solution is extracted, and the organic phases are combined, dried, filtered, concentrated and purified to obtain the product.
2. The method for electrochemically synthesizing quinolinone compounds according to claim 1, characterized in that: In the raw material compound, the disubstituted alkyne fragment contained in the molecule is an aryl alkyl alkyne or a diaryl alkyne, and the α-electron withdrawing group substituted amide fragment contained in the molecule is selected from any one of α-cyanoamide, α-esteramide and α-ketoamide.
3. The method for electrochemically synthesizing quinolinone compounds according to claim 1, characterized in that: The base is selected from any one of sodium carbonate, potassium carbonate and cesium carbonate; the solvent is selected from any one of methanol and ethanol.
4. The method for electrochemically synthesizing quinolinone compounds according to claim 1, characterized in that: The feed ratio of the compound raw material, the ferrocene catalyst, the supporting electrolyte and the base is 100:5-20:10-50:100-200.
5. The method for electrochemically synthesizing quinolinone compounds according to claim 1, characterized in that: The inert gas is any one of nitrogen and argon.
6. The method for electrochemically synthesizing quinolinone compounds according to claim 1, characterized in that: The electrolytic cell is a single-chamber electrolytic cell, wherein the anode material is selected from any one of porous glassy carbon material, graphite carbon sheet, and platinum sheet, and the cathode material is any one of platinum sheet, nickel sheet, and stainless steel sheet.
7. The method for electrochemically synthesizing quinolinone compounds according to claim 1, characterized in that: The electrolysis reaction is carried out in a constant current mode, the working current is 5-10 mA, the electrolysis reaction time is 90-120 minutes, and the solvent is heated and refluxed during the reaction, and the heating temperature is 50-70°C.
8. The method for electrochemically synthesizing quinolinone compounds according to claim 1, characterized in that: The extraction is performed by adding water and dichloromethane to the reaction solution, wherein the volume ratio of water to dichloromethane is 1-3:1, and the volume ratio of the extract composed of water and dichloromethane to the reaction solution is 1:1-3.
9. The method for electrochemically synthesizing quinolinone compounds according to claim 1, characterized in that: The concentration is carried out under reduced pressure.
10. The method for electrochemically synthesizing quinolinone compounds according to claim 1, characterized in that: The purification is carried out by silica gel column chromatography.