A method for synthesizing a sulfimide-substituted quinoxaline ketone compound

Abstract

The application discloses a synthesis method of a sulfimide substituted quinoxaline ketone compound, and a preparation flow of the method is as follows: quinoxaline ketone derivatives, sulfimide derivatives, electrolytes and solvents are sequentially added into a three-necked flask, a working electrode is inserted, and conversion can be completed by stirring and electrically conducting at room temperature for 5 hours. The reaction avoids the use of toxic redox agents and metal catalysts, and has excellent atom economy. In addition, the reaction has good substrate universality, and substrates substituted by electron-donating groups and electron-withdrawing groups can be compatible with the reaction system. It is worth mentioning that the operation is simple, the reaction is carried out in an air atmosphere, and the reaction is easy to scale up, which lays a solid foundation for industrial application of the conversion.

Description

Technical Field

[0001] This invention belongs to the field of organic synthetic chemistry, and specifically relates to a method for synthesizing sulfinimide-substituted quinoxalone compounds. Background Technology

[0002] Structural modification of small organic molecules can greatly facilitate the discovery of lead compounds. However, bioactive molecules often contain numerous CH bonds, and selectively activating high-energy CH bonds to achieve structural modification of functional molecules presents a significant challenge. In recent decades, with the development of organometallic chemistry, significant progress has been made in using CH bond functionalization reactions to achieve structural modification of functional molecules. However, these reactions often require the addition of metal catalysts or equivalent redox agents, which have certain drawbacks in terms of economy and environmental friendliness (SK Sinha, P. Ghosh, S. Jain, S. Maiti, SA Al-Thabati, AA Alshehri, M. Mokhtar, D. Maiti. Chem. Soc. Rev., 2023, 52, 7461-7503; R. Bisht, C. Haldar, MMM Hassan, ME Hoque, J.Chaturedi, B. Chattopadhyay. Chem. Soc. Rev., 2022, 51, 5042-5100). Electro-organic synthesis chemistry offers an effective method for solving such problems. By using electrodes instead of traditional redox agents, it not only enhances the environmental friendliness of the reaction but also enables the catalytic cycling of metal catalysts under certain conditions (Y. Yuan, A. Lei. Acc.Chem. Res. 2019, 52, 3309-3324; PRD Murray, JH Cox, ND Chiappini, CB Roos, EA McLoughlin, BG Hejna et al. Chem. Rev. 2022, 122, 2017-2291).

[0003] Quinoxalones are widely found in natural products and active pharmaceutical molecules, but the methods for synthesizing these compounds are very limited. To enrich the molecular library of quinoxalones, structural modification of quinoxalones through CH bond functionalization is an effective method. Among these, the electrochemically promoted C3-H functionalization of quinoxalinones has attracted more attention from organic chemistry researchers due to its outstanding environmental friendliness. For example, in 2021, Wang's group achieved the C3-H amination of quinoxalinones under electrochemical conditions, synthesizing a series of highly functionalized nitrogen-containing compounds (K. Niu, L. Ding, P. Zhou, Y. Hao, Y. Liu, H. Song, Q. Wang. Green Chem., 2021, 23, 32463249); in 2023, Sun's group achieved efficient coupling of quinoxalinones with ether compounds using indirect oxidation, preparing different types of alkylated products (H. Li, C. Qiang, Y. Liao, Q. Chu, P. Liu, P. Sun. Adv. Synth. Catal., 2023, 365, 1-7). It is worth noting that the coupling reaction of quinoxalinones with sulfinimides under electrochemical conditions has not yet been studied.

[0004] Based on the above research background, we have achieved an electrochemically promoted hydrogenotropic coupling reaction between quinoxalinone and sulfinylimide, and efficiently prepared a series of sulfinylimide-substituted quinoxalinone compounds, providing a new method for the structural modification of quinoxalinone. Summary of the Invention

[0005] The purpose of this invention is to address the shortcomings and deficiencies of the prior art by providing a method for synthesizing sulfinimide-substituted quinoxalone compounds.

[0006] The present invention utilizes quinoxalinone derivatives and sulfinimide derivatives as raw materials, tetrabutylammonium hexafluorophosphate as the electrolyte, and acetonitrile as the solvent. The conversion is achieved by stirring the reaction at room temperature for 5 hours. This reaction avoids the use of toxic redox agents and metal catalysts, while also exhibiting excellent atom economy. Furthermore, the reaction demonstrates good substrate universality, compatible with both electron-donating and electron-withdrawing substituted substrates. Notably, the ease of operation, air-atmosphere reaction, and scale-up characteristics provide a solid foundation for the industrial application of this conversion.

[0007] The objective of this invention is achieved through the following technical solution.

[0008] A method for synthesizing sulfinimide-substituted quinoxalone compounds, comprising the following preparation process:

[0009] In a three-necked glass flask, a quinoxalone derivative, a sulfinylimide derivative, an electrolyte, and a solvent are added sequentially. A working electrode is inserted, and the reaction is carried out at room temperature with stirring for 5 hours to complete the conversion. The crude product is obtained by rotary evaporation under reduced pressure, and the sulfinylimide-substituted quinoxalone compound is then separated and purified by column chromatography.

[0010] Furthermore, the preparation equation for sulfinimide-substituted quinoxalone compounds is shown below:

[0011]

[0012] In the formula, R 1 Selected from one of hydrogen, 6,7-dichloro, 7-nitro, and 6,7-dimethyl; R 2 Selected from one of hydrogen, methyl, ethyl, and allyl; R 3 Selected from one of 4-methylphenyl, 4-chlorophenyl, phenyl, 4-methoxyphenyl, and benzyl; R 4 It is selected from one of phenyl, methyl, ethyl and cyclopropyl.

[0013] Furthermore, the molar ratio of the quinoxalone derivative to sulfinimide is 1:0.5~4, preferably 1:3.

[0014] Furthermore, the feed ratio of the quinoxaloolone derivative to the electrolyte is 1:0.2~3, preferably 1:2.

[0015] Furthermore, the current is 1 to 10 mA, preferably 4 mA.

[0016] Furthermore, the electrolyte is one of tetrabutylammonium hexafluorophosphate, tetrabutylammonium bromide, tetrabutylammonium acetate, potassium hexafluorophosphate, and tetraethylammonium trifluoromethanesulfonate, preferably tetrabutylammonium hexafluorophosphate.

[0017] Further, the solvent is one of 1,2-dichloroethane, acetonitrile, dichloromethane, acetone and methanol, with acetonitrile being the preferred solvent.

[0018] Furthermore, the anode is one of glassy carbon, carbon rod, graphite felt, carbon plate, and platinum sheet, preferably a carbon plate.

[0019] Furthermore, the cathode is one of stainless steel sheet, carbon rod, nickel sheet, carbon plate and platinum sheet, preferably stainless steel sheet.

[0020] Furthermore, the crude product is separated by column chromatography, using a mixed solvent of petroleum ether and ethyl acetate as the eluent, with a mixing ratio of petroleum ether to ethyl acetate of 1 to 50:1. A gradient elution of 6:1 to 2:1 is preferred.

[0021] The principle of this invention is as follows: First, quinoxalone is anolyzed, losing one electron and one proton hydrogen to form a free radical intermediate. Then, the free radical intermediate abstracts hydrogen from the NH bond of sulfinimide to form an active intermediate sulfinimide nitrogen free radical. The nitrogen free radical reacts with quinoxalone in a free radical addition reaction to transform into a free radical cation. Finally, through continuous oxidation and proton hydrogen removal, the final target product, sulfinimide-substituted quinoxalone compound, is formed. At the same time, a hydrogen evolution reaction occurs at the cathode.

[0022] Compared with the prior art, the present invention has the following advantages and beneficial effects:

[0023] (1) This invention successfully achieved the coupling reaction of quinoxalinone and sulfinylimide under electrochemical conditions, preparing a series of sulfinylimide-substituted quinoxalinone compounds. This reaction avoids the use of toxic redox agents and metal catalysts, while possessing excellent atom economy. Furthermore, the reaction exhibits good substrate universality, with both electron-donating and electron-withdrawing substituted substrates compatible with the reaction system. It is worth mentioning that the simple operation, air-atmosphere reaction, and ease of scale-up provide a solid foundation for the industrial application of this conversion. Attached Figure Description

[0024] Figure 1 , Figure 2 These are the proton and carbon spectra of the target product obtained in Example 1;

[0025] Figure 3 , Figure 4 These are the proton and carbon spectra of the target product obtained in Example 2;

[0026] Figure 5 , Figure 6 These are the proton and carbon spectra of the target product obtained in Example 3;

[0027] Figure 7 , Figure 8 These are the proton and carbon spectra of the target product obtained in Example 4;

[0028] Figure 9 , Figure 10 These are the proton and carbon spectra of the target product obtained in Example 5; Detailed Implementation

[0029] The present invention will be further described below through specific embodiments, but the scope of protection and implementation of the present invention are not limited thereto.

[0030] Example 1

[0031] Prepare a three-necked flask and add weighed 1-methylquinoxaloline-2(1H)-one (0.2 mmol), S,S-diphenylsulfinimide (0.6 mmol), tetrabutylhexafluorophosphate (0.4 mmol), and acetonitrile (4 mL) in sequence. Assemble the reaction apparatus by inserting a carbon plate as the anode and a stainless steel sheet as the cathode. Stir the reaction at room temperature with a current of 4 mA for 5 hours, and monitor the reaction with a TCL. After the reaction is complete, filter with dichloromethane and remove the organic solvent by vacuum distillation to obtain the crude product. Extract the crude product with dichloromethane in small amounts several times, combine the organic phases, and dry with anhydrous sodium sulfate. After filtration, rotary evaporate under reduced pressure to obtain the preliminarily purified crude product. Finally, purify the crude product by column chromatography with a separation yield of 74%.

[0032] Gram-scale preparation:

[0033] Prepare a three-necked flask and add the weighed 1-methylquinoxaloline-2(1H)-one (5 mmol), S,S-diphenylsulfinylimide (15 mmol), tetrabutylhexafluorophosphate (10 mmol), and acetonitrile (100 mL) in sequence. Assemble the reaction apparatus by inserting a carbon plate as the anode and a stainless steel sheet as the cathode. Heat the mixture in an oil bath to 60°C and stir with an electric current of 4 mA for 90 hours, monitoring with a TCL. After the reaction is complete, cool to room temperature, filter with dichloromethane, and remove the organic solvent by vacuum distillation to obtain the crude product. Extract the crude product with dichloromethane in small batches several times, combine the organic phases, and dry with anhydrous sodium sulfate. After filtration, rotary evaporation under reduced pressure yields a preliminarily purified crude product. Finally, purify the crude product by column chromatography with a yield of 72%.

[0034] The proton and carbon spectra of the obtained target product are as follows: Figure 1 and Figure 2 As shown, the structural characterization data is as follows:

[0035] 1 H NMR (500 MHz, Chloroform-d) δ 8.17-8.10 (d, J = 34.1 Hz, 4H), 7.55-7.47 (m, 6H), 7.36-7.33 (d, J = 17.5 Hz, 1H), 7.29-7.26 (t, J = 14.5 Hz,1H), 7.16-7.11 (m, 2H), 3.72-3.66 (s, J = 30.4 Hz, 3H).

[0036] 13C NMR (125 MHz, Chloroform-d) δ 153.56, 152.35, 140.29, 132.91,132.49, 131.63, 129.30, 128.23, 127.65, 126.43, 123.34, 113.26, 29.54.

[0037] Based on the above characterization data, the structure of the target compound is inferred as follows:

[0038]

[0039] Example 2

[0040] Prepare a three-necked flask and add weighed 1-ethylquinoxaline-2(1H)-one (0.2 mmol), S,S-diphenylsulfinimide (0.6 mmol), tetrabutylhexafluorophosphate (0.4 mmol), and acetonitrile (4 mL) in sequence. Assemble the reaction apparatus by inserting a carbon plate as the anode and a stainless steel sheet as the cathode. Stir the reaction at room temperature with a current of 4 mA for 5 hours, and monitor the reaction with a TCL. After the reaction is complete, filter with dichloromethane and remove the organic solvent by vacuum distillation to obtain the crude product. Extract the crude product with dichloromethane in small amounts several times, combine the organic phases, and dry with anhydrous sodium sulfate. After filtration, rotary evaporate under reduced pressure to obtain the preliminarily purified crude product. Finally, purify the crude product by column chromatography with a separation yield of 78%.

[0041] The proton and carbon spectra of the obtained target product are as follows: Figure 3 and Figure 4 As shown, the structural characterization data is as follows:

[0042] 1 H NMR (500 MHz, Chloroform-d) δ 8.19-8.11 (d, J = 50.4 Hz, 4H), 7.56-7.46 (m, 6H), 7.40-7.34 (d, J = 29.5 Hz, 1H), 7.31-7.26 (m, 1H), 7.21-7.15 (d, J = 30.3 Hz, 1H), 7.15-7.09 (t, J = 30.3 Hz, 1H), 4.36-4.27 (q, J =45.3 Hz, 2H), 1.40-1.32 (t, J = 40.6 Hz, 2H).

[0043] 13C NMR (125 MHz, Chloroform-d) δ 153.00, 152.31, 140.28, 132.91,130.47, 129.27, 128.26, 127.88, 126.45, 123.15, 113.11, 37.72, 12.41.

[0044] Based on the above characterization data, the structure of the target compound is inferred as follows:

[0045]

[0046] Example 3

[0047] Prepare a three-necked flask and add weighed 6,7-dichloroquinoxalin-2(1H)-one (0.2 mmol), S,S-diphenylsulfinimide (0.6 mmol), tetrabutylhexafluorophosphate (0.4 mmol), and acetonitrile (4 mL) in sequence. Assemble the reaction apparatus by inserting a carbon plate as the anode and a stainless steel sheet as the cathode. Stir the reaction at room temperature with a current of 4 mA for 5 hours, and monitor the reaction with a TCL. After the reaction is complete, filter with dichloromethane and remove the organic solvent by vacuum distillation to obtain the crude product. Extract the crude product with dichloromethane in small amounts several times, combine the organic phases, and dry with anhydrous sodium sulfate. After filtration, rotary evaporate under reduced pressure to obtain the preliminarily purified crude product. Finally, purify the crude product by column chromatography with a separation yield of 78%.

[0048] The proton and carbon spectra of the obtained target product are as follows: Figure 5 and Figure 6 As shown, the structural characterization data is as follows:

[0049] 1 H NMR (500 MHz, Chloroform-d) δ 8.19-8.08 (m, 4H), 7.59-7.48 (m,6H), 7.39-7.32 (t, J = 33.4 Hz, 1H), 7.25-7.21 (d, J = 20.4 Hz, 1H), 4.30-4.19 (q, J = 54.6 Hz, 2H), 1.40-1.31 (t, J = 45.3 Hz, 3H).

[0050] 13C NMR (125 MHz, Chloroform-d) δ 153.18, 152.57, 139.75, 133.20,132.17, 129.91, 129.74, 129.42, 128.35, 128.15, 126.60, 38.12, 12.28.

[0051] Based on the above characterization data, the structure of the target compound is inferred as follows:

[0052]

[0053] Example 4

[0054] Prepare a three-necked flask and add weighed 7-nitroquinoxaloline-2(1H)-one (0.2 mmol), S,S-diphenylsulfinimide (0.6 mmol), tetrabutylhexafluorophosphate (0.4 mmol), and acetonitrile (4 mL) in sequence. Assemble the reaction apparatus by inserting a carbon plate as the anode and a stainless steel sheet as the cathode. Stir the reaction at room temperature with a current of 4 mA for 5 hours, and monitor the reaction with a TCL. After the reaction is complete, filter with dichloromethane and remove the organic solvent by vacuum distillation to obtain the crude product. Extract the crude product with dichloromethane in small amounts several times, combine the organic phases, and dry with anhydrous sodium sulfate. After filtration, rotary evaporate under reduced pressure to obtain the preliminarily purified crude product. Finally, purify the crude product by column chromatography with a separation yield of 65%.

[0055] The proton and carbon spectra of the obtained target product are as follows: Figure 7 and Figure 8 As shown, the structural characterization data is as follows:

[0056] 1 H NMR (500 MHz, Chloroform-d) δ 8.19-8.10 (m, 6H), 7.61-7.52 (m,6H), 7.27(s, 1H), 4.35 (q, J = 25.3 Hz, 2H), 1.39 (t, J = 25.4 Hz, 3H).

[0057] 13 C NMR (125 MHz, Chloroform-d) δ 153.79, 143.14, 139.59, 135.32,133.34, 132.36, 129.50, 128.16, 123.10 121.00, 113.47, 38.43, 12.39.

[0058] Based on the above characterization data, the structure of the target compound is inferred as follows:

[0059]

[0060] Example 5

[0061] Prepare a three-necked flask and add weighed 6,7-dimethylquinoxalin-2(1H)-one (0.2 mmol), S,S-diphenylsulfinimide (0.6 mmol), tetrabutylhexafluorophosphate (0.4 mmol), and acetonitrile (4 mL) in sequence. Assemble the reaction apparatus by inserting a carbon plate as the anode and a stainless steel sheet as the cathode. Stir the reaction at room temperature with a current of 4 mA for 5 hours, and monitor the reaction with a TCL. After the reaction is complete, filter with dichloromethane and remove the organic solvent by vacuum distillation to obtain the crude product. Extract the crude product with dichloromethane in small amounts several times, combine the organic phases, and dry with anhydrous sodium sulfate. After filtration, rotary evaporate under reduced pressure to obtain the preliminarily purified crude product. Finally, purify the crude product by column chromatography with a separation yield of 76%.

[0062] The proton and carbon spectra of the obtained target product are as follows: Figure 9 and Figure 10 As shown, the structural characterization data is as follows:

[0063] 1 H NMR (500 MHz, Chloroform-d) δ 8.16 (d, J = 30.2 Hz 4H), 7.55-7.42(m, 6H), 7.14 (s, 1H), 6.94 (s, 1H), 4.29 (q, J = 45.3 Hz, 2H), 2.31 (s, 3H), 2.21 (s, 3H), 1.35 (t, J = 35.6 Hz, 3H).

[0064] 13 C NMR (125MHz, Chloroform-d) δ 153.00, 151.66, 140.49, 135.73,132.81, 131.86, 129.25, 130.93, 128.26, 113.74, 37.59, 20.29, 19.06, 12.46.

[0065] Based on the above characterization data, the structure of the target compound is inferred as follows:

[0066]

[0067] Example 6

[0068] Prepare a three-necked flask and add weighed 1-allylquinoxalin-2(1H)-one (0.2 mmol), S,S-diphenylsulfinimide (0.6 mmol), tetrabutylhexafluorophosphate (0.4 mmol), and acetonitrile (4 mL) in sequence. Assemble the reaction apparatus by inserting a carbon plate as the anode and a stainless steel sheet as the cathode. Stir the reaction at room temperature with a current of 4 mA for 5 hours, and monitor the reaction with a TCL. After the reaction is complete, filter with dichloromethane and remove the organic solvent by vacuum distillation to obtain the crude product. Extract the crude product with dichloromethane in small amounts several times, combine the organic phases, and dry with anhydrous sodium sulfate. After filtration, rotary evaporate under reduced pressure to obtain the preliminarily purified crude product. Finally, purify the crude product by column chromatography with a separation yield of 72%.

[0069] The structural characterization data of the obtained target product are shown below:

[0070] 1 H NMR (500 MHz, Chloroform-d) δ 8.16 (d, J = 30.5 Hz, 4H), 7.46 (m,7H), 7.37 (d, J = 23.5 Hz, 1H), 7.24 (t, J = 15 Hz, 1H), 7.14-7.10 (m, 2H), 5.97-5,88 (m, 1H), 5.25-5.21 (d, J = 20.5 Hz, 1H), 5.19-5.14 (d, J = 20.8 Hz, 1H), 4.93-4.88 (d, J = 25.3 Hz, 2H).

[0071] 13 C NMR (125 MHz, Chloroform-d) δ 153.17, 152.27, 140.19, 132.96,130.87, 130.78, 129.29, 128.28, 127.67, 126.38, 123.33, 117.93, 113.81,44.97.

[0072] Based on the above characterization data, the structure of the target compound is inferred as follows:

[0073]

[0074] Example 7

[0075] Prepare a three-necked flask and add the weighed quinoxaline-2(1H)-one (0.2 mmol), S,S-diphenylsulfinimide (0.6 mmol), tetrabutylhexafluorophosphate (0.4 mmol), and acetonitrile (4 mL) in sequence. Assemble the reaction apparatus by inserting a carbon plate as the anode and a stainless steel sheet as the cathode. Heat the mixture in an oil bath to 60°C and stir with an electric current of 4 mA for 5 hours. Monitor the reaction with a TCL. After the reaction is complete, cool to room temperature, filter with dichloromethane, and remove the organic solvent by vacuum distillation to obtain the crude product. Extract the crude product with dichloromethane in small batches several times. Combine the organic phases and dry with anhydrous sodium sulfate. After filtration, evaporate under reduced pressure to obtain the preliminarily purified crude product. Finally, purify the crude product by column chromatography with a separation yield of 45%.

[0076] The structural characterization data of the obtained target product are shown below:

[0077] 1 H NMR (500 MHz, DMSO-d6) δ 12.28 (s, 1H), 8.12 (d, J = 6.8 Hz, 4H), 7.65 – 7.30 (m, 6H), 7.22-7.18 (m, 1H), 7.13 (d, J = 8.0 Hz, 1H), 7.09-7.02(m, 2H), 5.30 (d, J = 10.4 Hz, 1H), 5.19 (d, J = 17.2 Hz, 1H), 4.96-4.92 (m,2H), 3.58 (s, 3H), 2.59 (s, 3H).

[0078] 13 C NMR (126 MHz, DMSO-d6) δ 153.1, 152.8, 139.7, 133.4, 131.3, 130.3,129.7, 127.8, 126.3, 125.6, 122.8, 114.7.

[0079] Based on the above characterization data, the structure of the target compound is inferred as follows:

[0080]

[0081] Example 8

[0082] Prepare a three-necked flask and add the weighed 1-ethylquinoxaline-2(1H)-one (0.2 mmol), S-phenyl-S-(4-methylphenyl)sulfinimide (0.6 mmol), tetrabutylhexafluorophosphate (0.4 mmol), and acetonitrile (4 mL) in sequence. Assemble the reaction apparatus by inserting a carbon plate as the anode and a stainless steel sheet as the cathode. Heat the mixture in an oil bath to 60 degrees Celsius and stir with an electric current of 4 mA for 5 hours. Monitor the reaction with a TCL. After the reaction is complete, cool to room temperature, filter with dichloromethane, and remove the organic solvent by vacuum distillation to obtain the crude product. Extract the crude product with dichloromethane in small batches several times. Combine the organic phases and dry with anhydrous sodium sulfate. After filtration, evaporate under reduced pressure to obtain the preliminarily purified crude product. Finally, purify the crude product by column chromatography with a separation yield of 65%.

[0083] The structural characterization data of the obtained target product are shown below:

[0084] 1 H NMR (500 MHz, Chloroform-d) δ 15.07 (s, 1H), 7.77 (d, J = 8.1 Hz,2H), 7.59 (s, 1H), 7.39-7.36 (m, 1H), 7.29 (t, J = 8.8 Hz, 2H), 7.21 (d, J =8.1 Hz, 2H), 4.32 (q, J = 6.9 Hz, 2H), 2.67 (s, 3H), 2.36 (s, 3H), 1.40 (t, J= 7.1 Hz, 3H).

[0085] 13 C NMR (126 MHz, Chloroform-d) δ 153.05, 152.41, 143.88, 140.59,137.10, 132.83, 132.75, 130.45, 129.94, 129.19, 128.31, 128.14, 127.91,126.34, 123.09, 113.10, 37.67, 21.54, 12.41.

[0086] Based on the above characterization data, the structure of the target compound is inferred as follows:

[0087]

[0088] Example 9

[0089] Prepare a three-necked flask and add the weighed 1-ethylquinoxaline-2(1H)-one (0.2 mmol), S-phenyl-S-(4-chlorophenyl)sulfinimide (0.6 mmol), tetrabutylhexafluorophosphate (0.4 mmol), and acetonitrile (4 mL) in sequence. Assemble the reaction apparatus by inserting a carbon plate as the anode and a stainless steel sheet as the cathode. Heat the mixture in an oil bath to 60 degrees Celsius and stir with an electric current of 4 mA for 5 hours. Monitor the reaction with a TCL. After the reaction is complete, cool to room temperature, filter with dichloromethane, and remove the organic solvent by vacuum distillation to obtain the crude product. Extract the crude product with dichloromethane in small amounts several times, combine the organic phases, and dry with anhydrous sodium sulfate. After filtration, evaporate under reduced pressure to obtain the preliminarily purified crude product. Finally, purify the crude product by column chromatography with a separation yield of 74%.

[0090] The structural characterization data of the obtained target product are shown below:

[0091] 1 H NMR (500 MHz, Chloroform-d) δ 8.15 (d, J = 11.5 Hz 2H), 8.08 (d, J= 12.1 Hz, 2H), 7.56-7,48 (m, 3H), 7.45 (d, J = 9.2 Hz 2H), 7.29 (d, J = 8.8Hz, 1H), 7.18 (d, J = 8.1 Hz, 1H), 7.13 (d J = 9.6 Hz, 1H), 4.1 (q, J = 35.7Hz 2H), 1.36 (t, J = 15.5 Hz 3H).

[0092] 13 C NMR (125 MHz, Chloroform-d) δ 152.93, 152.13, 139.90, 139.56,138.93, 133.18, 132.69, 130.50, 129.72, 129.57, 129.42, 128.22, 127.95,126.66, 123.23, 37.75, 12.41.

[0093] Based on the above characterization data, the structure of the target compound is inferred as follows:

[0094]

[0095] Example 10

[0096] Prepare a three-necked flask and add weighed 1-ethylquinoxaloline-2(1H)-one (0.2 mmol), S-methyl-S-phenylsulfinimide (0.6 mmol), potassium hexafluorophosphate (0.4 mmol), and acetonitrile (4 mL) in sequence. Assemble the reaction apparatus by inserting a carbon plate as the anode and a stainless steel sheet as the cathode. Heat the mixture in an oil bath to 60 degrees Celsius and stir with an electric current of 4 mA for 5 hours. Monitor the reaction with a TCL. After the reaction is complete, cool to room temperature, filter with dichloromethane, and remove the organic solvent by vacuum distillation to obtain the crude product. Extract the crude product with dichloromethane in small amounts several times, combine the organic phases, and dry with anhydrous sodium sulfate. After filtration, evaporate under reduced pressure to obtain the preliminarily purified crude product. Finally, purify the crude product by column chromatography with a separation yield of 67%.

[0097] The structural characterization data of the obtained target product are shown below:

[0098] 1 H NMR (500 MHz, Chloroform-d) δ 8.10 (d, J = 7.4 Hz, 2H), 7.62 (t, J= 13.5 Hz, 1H), 7.56 (t, J = 7.7 Hz, 2H), 7.36 (d, J = 7.1 Hz, 1H), 7.27 (t,J = 7.0 Hz, 1H), 7.17 (d, J = 7.4 Hz,, 1H), 7.12 (t, J = 7.7 Hz,, 1H), 4.29(m, 2H), 3.50(s, 3H), 1.33(t, J = 10.2 Hz, 3H).

[0099] 13 C NMR (126 MHz, Chloroform-d) δ 152.81, 152.58, 139.41, 133.28,132.62, 130.34, 129.44, 127.67, 127.55, 126.35, 123.15, 113.14, 45.24, 37.63,12.37.

[0100] Based on the above characterization data, the structure of the target compound is inferred as follows:

[0101]

[0102] Example 11

[0103] Prepare a three-necked flask and add the weighed 1-ethylquinoxalin-2(1H)-one (0.2 mmol), S-methyl-S-(4-methoxyphenyl)sulfinimide (0.6 mmol), tetrabutylhexafluorophosphate (0.4 mmol), and acetonitrile (4 mL) in sequence. Assemble the reaction apparatus by inserting a carbon plate as the anode and a stainless steel sheet as the cathode. Heat the mixture in an oil bath to 60°C and stir with an electric current of 4 mA for 5 hours. Monitor the reaction with a TCL. After the reaction is complete, cool to room temperature, filter with dichloromethane, and remove the organic solvent by vacuum distillation to obtain the crude product. Extract the crude product with dichloromethane in small batches several times. Combine the organic phases and dry with anhydrous sodium sulfate. After filtration, evaporate under reduced pressure to obtain the preliminarily purified crude product. Finally, purify the crude product by column chromatography with a separation yield of 76%.

[0104] The structural characterization data of the obtained target product are shown below:

[0105] 1 H NMR (500 MHz, Chloroform-d) δ 7.65 (d, J = 7.7 Hz, 1H), 7.61 (s,1H), 7.46 (t, J = 7.5 Hz, 1H), 7.38 (d, J = 7.7 Hz, 1H), 7.28 (t, J = 8.4 Hz,1H), 7.18 (d, J = 9.0 Hz, 1H), 7.14 (t, J = 10.6 Hz, 2H), 4.30 (t, J = 8.3Hz, 2H), 3.87 (s, 3H), 3.48 (s, 3H), 1.34 (t, J = 7.8 Hz, 3H).

[0106] 13 C NMR (126 MHz, Chloroform-d) δ 160.23, 152.83, 152.55, 140.70,132.66, 130.49, 130.38, 127.75, 126.37, 123.17, 119.70, 119.61, 113.15,112.17, 55.83, 45.38, 37.66, 12.39.

[0107] Based on the above characterization data, the structure of the target compound is inferred as follows:

[0108]

[0109] Example 12

[0110] Prepare a three-necked flask and add the weighed 1-ethylquinoxaline-2(1H)-one (0.2 mmol), S-methyl-S-(4-chlorophenyl)sulfinimide (0.6 mmol), tetrabutylhexafluorophosphate (0.4 mmol), and acetonitrile (4 mL) in sequence. Assemble the reaction apparatus by inserting a carbon plate as the anode and a stainless steel sheet as the cathode. Heat the mixture in an oil bath to 60 degrees Celsius and stir with an electric current of 4 mA for 5 hours. Monitor the reaction with a TCL. After the reaction is complete, cool to room temperature, filter with dichloromethane, and remove the organic solvent by vacuum distillation to obtain the crude product. Extract the crude product with dichloromethane in small amounts several times, combine the organic phases, and dry with anhydrous sodium sulfate. After filtration, rotary evaporate under reduced pressure to obtain the preliminarily purified crude product. Finally, purify the crude product by column chromatography with a separation yield of 75%.

[0111] The structural characterization data of the obtained target product are shown below:

[0112] 1 H NMR (500 MHz, Chloroform-d) δ 8.04 (d, J = 9.2, 2H), 7.54 (d, J =9.6, 2H), 7.38 (d, J = 8.8 Hz, 1H), 7.30 (t, J = 11.2 Hz, 1H), 7.19 (d, J =7.4 Hz, 1H), 7.16 (t, J = 6.7 Hz, 1H), 4.31 (m, 2H), 3.49 (s, 3H), 1.35 (t, J= 9.5 Hz, 3H).

[0113] 13 C NMR (126 MHz, Chloroform-d) δ 152.80, 152.37, 139.97, 138.03,132.55, 130.44, 129.77, 129.13, 127.77, 126.61, 123.29, 113.23, 97.75, 45.39,37.73, 12.38.

[0114] Based on the above characterization data, the structure of the target compound is inferred as follows:

[0115]

[0116] Example 13

[0117] Prepare a three-necked flask and add the weighed 1-ethylquinoxalin-2(1H)-one (0.2 mmol), S-ethyl-S-phenylsulfinimide (0.6 mmol), tetrabutylhexafluorophosphate (0.4 mmol), and acetonitrile (4 mL) in sequence. Assemble the reaction apparatus by inserting a carbon plate as the anode and a stainless steel sheet as the cathode. Heat the oil bath to 60 degrees Celsius and stir the reaction with an electric current of 4 mA for 5 hours. Monitor the reaction with a TCL. After the reaction is complete, cool to room temperature, filter with dichloromethane, and remove the organic solvent by vacuum distillation to obtain the crude product. Extract the crude product with dichloromethane in small amounts several times, combine the organic phases, and dry with anhydrous sodium sulfate. After filtration, evaporate under reduced pressure to obtain the preliminarily purified crude product. Finally, purify the crude product by column chromatography with a separation yield of 57%.

[0118] The structural characterization data of the obtained target product are shown below:

[0119] 1 H NMR (500 MHz, Chloroform-d) δ 8.04 (d, J = 8.7 Hz, 2H), 7.61 (q, J= 7.7 Hz, 1H), 7.56 (t, J = 10.2 Hz, 2H), 7.36 (d, J = 9.5 Hz, 1H), 7.27 (t,J = 9.8 Hz, 1H), 7.18 (d, J = 7.7 Hz, 1H), 7.13 (t, J = 8.7 Hz, 1H), 4.30 (q,J = 8.4 Hz, 2H), 1.36-1.30 (m, 6H).

[0120] 13 C NMR (125 MHz, Chloroform-d) δ 152.89, 152.65, 137.02, 133.23,132.70, 130.34, 129.36, 128.35, 127.68, 126.26, 123.15, 113.12, 51.16, 37.68,12.38, 7.23.

[0121] Based on the above characterization data, the structure of the target compound is inferred as follows:

[0122]

[0123] Example 14

[0124] Prepare a three-necked flask and add the weighed 1-ethylquinoxaline-2(1H)-one (0.2 mmol), S-cyclopropyl-S-phenylsulfinimide (0.6 mmol), tetrabutylhexafluorophosphate (0.4 mmol), and acetonitrile (4 mL) in sequence. Assemble the reaction apparatus by inserting a carbon plate as the anode and a stainless steel sheet as the cathode. Heat the mixture in an oil bath to 60 degrees Celsius and stir with an electric current of 4 mA for 5 hours. Monitor the reaction with a TCL. After the reaction is complete, cool to room temperature, filter with dichloromethane, and remove the organic solvent by vacuum distillation to obtain the crude product. Extract the crude product with dichloromethane in small batches several times. Combine the organic phases and dry with anhydrous sodium sulfate. After filtration, evaporate under reduced pressure to obtain the preliminarily purified crude product. Finally, purify the crude product by column chromatography with a separation yield of 68%.

[0125] The structural characterization data of the obtained target product are shown below:

[0126] 1 H NMR (500 MHz, Chloroform-d) δ 8.03 (d, J = 6.7 Hz, 2H), 7.58 (t, J= 8.4 Hz, 1H), 7.53 (t, J = 11.2 Hz, 2H), 7.33 (d, J = 8.2 Hz, 1H), 7.26 (t,J = 6.7 Hz, 1H), 7.15 (d, J = 7.7 Hz, 1H), 7.11 (t, J = 7.1 Hz, 1H), 4.28 (q,J = 7.5 Hz, 2H), 2.9 (t, J = 7.5 Hz, 1H), 1.81 (t, J = 7.9 Hz, 1H), 1.33 (t,J = 10.4 Hz, 3H), 1.27 (d, J = 9.2 Hz, 2H), 0.98 (t, J = 7.2 Hz, 1H).

[0127] 13 C NMR (125 MHz, Chloroform-d) δ 152.83, 152.51, 130.65, 132.85,132.70, 130.37, 129.27, 127.66, 127.64, 126.22, 123.09, 113.09, 37.26, 34.00,12.39, 7.13, 5.31.

[0128] Based on the above characterization data, the structure of the target compound is inferred as follows:

[0129]

[0130] Example 15

[0131] Prepare a three-necked flask and add the weighed 1-ethylquinoxalin-2(1H)-one (0.2 mmol), S-benzyl-S-phenylsulfinimide (0.6 mmol), tetrabutylhexafluorophosphate (0.4 mmol), and acetonitrile (4 mL) in sequence. Assemble the reaction apparatus by inserting a carbon plate as the anode and a stainless steel sheet as the cathode. Heat the mixture in an oil bath to 60 degrees Celsius and stir with an electric current of 4 mA for 5 hours. Monitor the reaction with a TCL. After the reaction is complete, cool to room temperature, filter with dichloromethane, and remove the organic solvent by vacuum distillation to obtain the crude product. Extract the crude product with dichloromethane in small batches several times. Combine the organic phases and dry with anhydrous sodium sulfate. After filtration, evaporate under reduced pressure to obtain the preliminarily purified crude product. Finally, purify the crude product by column chromatography with a separation yield of 76%.

[0132] The structural characterization data of the obtained target product are shown below:

[0133] 1 H NMR (500 MHz, Chloroform-d) δ 7.76 (d, J = 9.7 Hz, 2H), 7.55 (t, J= 8.8 Hz, 1H), 7.46 (t, J = 11.2 Hz, 1H), 7.41 (t, J = 10.9 Hz, 2H), 7.32-7.27 (m, 2H), 7.22-7.14 (m, 4H), 6.99 (d, J = 7.8 Hz, 2H), 4.99 (q, J = 7.5Hz, 2H), 6.99 (d, J = 8.8 Hz, 2H), 4.32 (d, J = 9.8 Hz, 2H), 1.36 (t, J =10.3 Hz, 3H).

[0134] 13 C NMR (126 MHz, Chloroform-d) δ 152.96, 152.90, 136.27, 133.32,133.15, 132.76, 131.30, 131.06, 130.48, 128.95, 128.93, 128.86, 128.81,128.78, 128.47, 127.81, 127.62, 126.37, 123.21, 113.19, 62.65, 37.70, 12.43.

[0135] Based on the above characterization data, the structure of the target compound is inferred as follows:

[0136]

[0137] The above embodiments are some examples of the method of the present invention, but they do not limit the specific implementation of the present invention. Any substitution of substituents, changes in the basic skeleton, or simplification of conditions made without departing from the spirit and principle of the present invention should be classified as equivalent substitution methods and are included within the protection scope of the present invention.

Claims

1. A method for synthesizing sulfinimide-substituted quinoxalone compounds, characterized in that, It includes the following steps: In a three-necked glass flask, quinoxalone derivatives, sulfinimide derivatives, electrolytes and solvents are added sequentially. A working electrode is inserted, and the mixture is stirred for 5 hours at room temperature with a current of 1-10 mA to complete the conversion. The crude product is obtained by rotary evaporation under reduced pressure. Sulfinimide-substituted quinoxalone compounds can be obtained by separation and purification by column chromatography. The above reaction is shown in the following equation: In the formula, R 1 Selected from one of hydrogen, 6,7-dichloro, 7-nitro, and 6,7-dimethyl; R 2 Selected from one of hydrogen, methyl, ethyl, and allyl; R 3 Selected from one of 4-methylphenyl, 4-chlorophenyl, phenyl, 4-methoxyphenyl, and benzyl; R 4 The anode is selected from one of phenyl, methyl, ethyl, and cyclopropyl; the cathode is selected from one of glassy carbon, carbon rod, graphite felt, carbon plate, and platinum sheet; the cathode is selected from one of stainless steel sheet, carbon rod, nickel sheet, carbon plate, and platinum sheet; the electrolyte is selected from one of tetrabutylammonium hexafluorophosphate, tetrabutylammonium bromide, tetrabutylammonium acetate, potassium hexafluorophosphate, and tetraethylammonium trifluoromethanesulfonate; the solvent is selected from one of 1,2-dichloroethane, acetonitrile, dichloromethane, acetone, and methanol.

2. The method for synthesizing a sulfinylimide-substituted quinoxalone compound according to claim 1, characterized in that, The molar ratio of the quinoxalone derivative to the sulfinimide derivative is 1:0.5~4.

3. The method for synthesizing a sulfinylimide-substituted quinoxalone compound according to claim 1, characterized in that, The feeding ratio of quinoxalone derivative to electrolyte is 1:0.2~3.

4. The method for synthesizing a sulfinylimide-substituted quinoxalone compound according to claim 1, characterized in that, The crude product was separated and purified by column chromatography, using a mixture of petroleum ether and ethyl acetate as the eluent, with a mixing ratio of petroleum ether to ethyl acetate of 1 to 50:1.

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