A method for electrochemically promoting the construction of N-sulfide-substituted sulfoximine derivatives

Abstract

The present invention discloses a method for electrochemically promoting the construction of N-sulfide-substituted sulfoximine derivatives. The synthesis method of the method is as follows: in a three-necked round-bottom flask, tetrabutylammonium iodide, sulfoximine compounds, disulfide compounds, tert-butyl alcohol, and a solvent are added, electrodes are inserted, and the reaction is stirred under power at room temperature. The crude product can be separated and purified to obtain N-sulfide-substituted sulfoximine derivatives. The present invention realizes an efficient coupling reaction of sulfoximine compounds and disulfide compounds under electrochemical conditions, and a series of functionalized N-sulfide sulfoximine derivatives can be constructed by simple operation. In addition, the reaction does not require the addition of a metal catalyst, an oxidant, and a base, and has good functional group tolerance.

Description

Technical Field

[0001] The invention belongs to the field of organic synthetic chemistry, and particularly relates to a method for electrochemically promoting the construction of N-thioether-substituted sulfoximine derivatives. Background Art

[0002] Organic electrochemical synthesis involves the synthesis of organic compounds by reactants gaining or losing electrons at electrodes. This method requires no additional redox reagents, operates under mild reaction conditions, and can control the reaction rate by adjusting the current. Consequently, the use of electrochemical organic synthesis to functionalize XH (X = C, N) bonds has garnered significant attention in recent years among organic researchers. Sulfoximines are important nitrogen-containing compounds, found in numerous drug molecules, and their functionalization is of significant research value in the discovery of lead compounds (Han, Y.; Xing, K.; Zhang, J.; Tong, T.; Shi, Y.; Cao, H.; Yu, H.; Zhang, Y.; Liu, D.; Zhao, L. Eur. J. Med. Chem. 2021, 209, 112885.). Electrochemical organic synthesis is an effective means of structurally modifying sulfoximine derivatives. After decades of development, the NH functionalization of sulfoximines under electrochemical conditions has made some progress. For example, in 2021, the Wang research group developed a coupling reaction of sulfoximines with diarylmethane compounds under electrochemical conditions (Kong, X.; Tian, ​​Y.; Chen, X.; Chen, Y.; Wang, WJ Org. Chem., 2021, 86, 13610-13617.), realizing the alkylation reaction of the NH bond. In the same year, the Mei research group realized the nickel-catalyzed electrochemical promotion of the coupling of sulfoximines with aryl halides for the first time (Liu, D.; Liu, Z.-R.; Ma, C.; Jiao, K.-J.; Wei, L.; Lefranc. J.; Herbert, S.; Mei, T.-S. Angew. Chem. Int. Ed., 2021, 60, 9444-9449.), this method has good functional group tolerance, and at the same time, this scheme provides a new strategy for the synthesis of related drug compounds; later, in order to solve the incompatibility problems of electron-rich aromatic halides and weakly nucleophilic anilines and sulfonamides, the Magnus research group realized a nickel electrocatalytic arylation reaction of aniline, sulfonamides, sulfoximine, carbonate and imine in 2021 (Zhu, C.; Kale, AP; Yue, H.; M, R. JACS Au., 2021, 1, 1057−1065.), and developed an efficient and universal nickel electrocatalytic scheme for the formation of different CN bonds.In 2022, the Huang group reported an electrochemical sulfamide oxygenation reaction of alkenes, NH-sulfoximines, and alcohols (Wan, J.-L.; Huang, J.-M.Org. Lett., 2022, 24, 8914-8919.), successfully introducing both sulfoximines and alcohols onto alkenes. In 2023, our group reported an electrochemically driven removal of the directing group of the S=N double bond of sulfoximines (Xiong Z, Nie H, Zhang S, Hu M, Qin C, Wang S, Ji F, Jiang G.J. Org. Chem. 2023, 88:4334-4344.). This method exhibits excellent site selectivity and enables the gram-scale preparation of multiple compounds in good yields. In general, the current research on the functionalization reaction of sulfoximine NH bonds under electrochemical conditions is very limited, and only arylation and alkylation reactions of NH bonds can be achieved. There have been no reports on the green sulfurization reaction of NH bonds based on electro-organic synthesis methodology.

[0003] Organosulfides have attracted significant attention from organic chemists due to their importance in organic synthesis and materials science (N. Amri and T. Wirth, Chem. Rec., 2021, 21, 2526–2537). Among them, the N-S bond is a crucial component of many important functional molecules (Ye Z, Zhang X, Ma W, Zhang F. Green Chem. 2023; 25: 2524). Sulfoximine, as an excellent nitrogen source, has important research value in the development of N-S bonds.In recent years, some progress has been made in constructing N-S bonds through sulfoximines (K. Akutagawa, N. Furukawa, S. Oae, Bull. Chem. Soc. Jpn. 1984, 57, 518–524.; C. Bohnen, C. Bolm, Org. Lett. 2015, 17, 3011–3013.; H. Wang, D. Zhang, M. Cao, C. Bolm, Synthesis. 2018, 51, 271–275.; H. Zhu, J. T. Yu, J. Cheng, Chem. Commun. 2016, 52, 11908–11911.; L. Yang, J. Feng, M. Qiao, Q. Zeng, Org. Chem. Front. 2018, 5, 24–28.; Y. Peng, Y. Lin, R. F. Nie, Y. Zheng, Y. Z. Liu, L. Guo, Y. Wu, Eur. J. Org. Chem. 2018, 6, 844–850; Y. Lin, L. Ü. Guanghui, Y. Liu, Y. Zheng, R. Nie, L. Guo, Y. Wu, Catal. Commun. 2018, 112, 68–73.; Y. Lin, Y. Liu, Y. Zheng, R. Nie, L. Guo, Y. Wu, ACS Sustainable Chem. Eng. 2018, 6, 13644–13649; D. Kong, D. Ma, P. Wu, C. Bolm, ACS Sustainable Chem. Eng. 2022, 10, 2863–2867; Kang, X.; Wang, H.; Zeng, Q. Transition-metal-free N-sulfenylation of sulfoximines with thiosulfonates under mild conditions. Eur. J. Org. Chem. 2022, 2022, e202201229.).For example, in 2016, the Cheng group used disulfide as a sulfur source to report a copper-catalyzed N-thioetherification sulfonamide oxime reaction and prepared different types of N-thioether-substituted sulfoximine derivatives. However, this method requires the use of metallic copper and base to initiate the reaction. In 2018, the Zeng group used thiophenol as a sulfur source to achieve a metal-free NH / SH dehydrogenation synthesis of N-sulfinyl imine and sulfinamide coupling reaction. Although this reaction has high atom economy, it requires the use of excess H2O2 as an oxidant. In the same year, the Wu group used 1-phenylsulfide to Using 2,5-pyrroline-2,5-dione as a sulfur source, a green and efficient synthesis of N-sulfenyl imines in water was achieved. This reaction can achieve cross-coupling reactions in water using Tween 80 as a catalyst. However, the reaction cannot be carried out using disulfide as a sulfur source, limiting the diversity of products. In 2022, Bolm's group used disulfide as a sulfur source and a ball mill as a reaction equipment to achieve a solvent-free N-sulfonylation reaction of sulfenyl imines and sulfonyl imines, synthesizing the first N-sulfenylation substrate of sulfonyl imines. However, this reaction requires precious metal catalysis. In summary, the currently reported synthetic strategies for N-sulfide-substituted sulfoximine derivatives have more or less some drawbacks, such as limited substrate sources, metal catalysis, multi-step transformations, strong oxidants, and strong bases. Therefore, the development of new green methods for N-sulfide-substituted sulfoximine derivatives is of great research value. Summary of the Invention

[0004] The purpose of the present invention is to provide a new method for electrochemically promoting the construction of N-sulfide-substituted sulfoximine derivatives in view of the shortcomings and deficiencies of the prior art.

[0005] The present invention utilizes disulfide compounds and sulfoximine compounds as substrates, tetrabutylammonium iodide as an electrolyte, tert-butyl alcohol as an additive, and acetonitrile as a solvent to generate a redox reaction under electrochemical conditions, achieving a highly efficient coupling reaction between sulfides and sulfoximines. This method, for the first time, demonstrates the electrochemical thioetherification of the NH bonds of imine-imine compounds. The reaction is mild and requires no external oxidants, reducing agents, strong acids, or strong bases. Furthermore, the reaction is short and easily scalable, demonstrating its potential for application.

[0006] The purpose of the present invention is achieved through the following technical solutions.

[0007] A method for electrochemically promoting the construction of N-sulfide-substituted sulfoximine derivatives comprises the following preparation process:

[0008] In a three-necked flask, a disulfide compound, a sulfoximine compound, an electrolyte, an additive, and an organic solvent were sequentially added, an electrode was inserted, and an electric current was applied at room temperature with a current of 7-13 mA. After the reaction, the mixture was filtered and extracted, and the organic phase was collected and rotary evaporated under reduced pressure to obtain a crude product. The crude product was separated and purified by column chromatography to obtain an N-sulfide-substituted sulfoximine derivative.

[0009] Furthermore, the preparation formula of N-sulfide substituted sulfoximine derivatives is shown below:

[0010]

[0011] In the formula, in the formula, R 1 is selected from the group consisting of phenyl, 2-chlorophenyl, 4-methylphenyl, 4-chlorophenyl, 4-nitrophenyl, 4-bromophenyl, 4-methoxyphenyl, 3-bromophenyl and piperidinyl; R 2 is one of phenyl, methyl, 4-bromophenyl, 4-methylphenyl, 4-chlorophenyl and cyclopropyl; R 3 It is one of phenyl, 2-fluorophenyl and 2-benzamidophenyl; the electrolyte is tetrabutylammonium iodide; the additive is tert-butanol; the organic solvent is one of methanol, acetone, furan, dichloromethane, DMSO, DMF, and acetonitrile; the electrodes are any two of graphite rod, graphite felt, meshed glassy carbon, platinum sheet, nickel sheet, and stainless steel as the positive and negative electrodes.

[0012] Furthermore, the molar ratio of the disulfide compound to the sulfoximine compound is 0.5-3:1, preferably 1:1;

[0013] Furthermore, the molar ratio of the sulfoximine compound to the electrolyte is 1:1-3, preferably 1:2;

[0014] Furthermore, the molar ratio of the sulfoximine compound to the additive is 1:1 to 3, preferably 1:1;

[0015] Furthermore, the organic solvent is methanol, acetone, furan, dichloromethane, DMSO, DMF, acetonitrile, preferably acetonitrile;

[0016] Furthermore, the reaction electrodes are any two of graphite rod, graphite felt, meshed glassy carbon, platinum sheet, nickel sheet, and stainless steel as the positive electrode and the negative electrode, preferably a carbon rod positive electrode and a platinum sheet negative electrode;

[0017] Furthermore, the reaction current is 7-13 mA, preferably 10 mA;

[0018] Furthermore, the reaction time is 0.5 to 10 hours, preferably 1 to 3 hours;

[0019] Furthermore, the crude product is separated by column chromatography, and the eluent is a mixed solvent of petroleum ether and ethyl acetate, with a mixing ratio of petroleum ether: ethyl acetate = 3~50:1, preferably a mixing ratio of petroleum ether: ethyl acetate = 3~25:1.

[0020] The principle of the present invention is as follows: first, tetrabutylammonium iodide generates iodine anions, which first lose electrons at the anode to generate iodine element, which reacts with diphenyl disulfide to generate the intermediate PhSI, which then undergoes homolysis to generate phenylthiol free radicals. Diphenyl disulfide can also directly generate phenylthiol free radicals. Sulfoximine loses H under the action of iodine anions and tert-butyl oxide anions. + , generating a sulfoximine anion. This anion loses electrons at the anode to generate a free radical, which then couples with a phenylthiol radical to generate the target compound. Simultaneously, sulfoximine can react with PhSI to generate an ionic sulfoximine intermediate, which further reacts to remove hydrogen iodide to generate the target compound. At the cathode, hydrogen protons gain electrons to generate hydrogen gas.

[0021] Compared with the prior art, the present invention has the following advantages and beneficial effects:

[0022] (1) The present invention realizes for the first time the efficient coupling reaction of imine-imine compounds with disulfide compounds under electrochemical conditions. The reaction conditions are mild and no external oxidants, reducing agents, strong acids, strong bases or the like are required. In addition, the reaction time is short and it is easy to scale up, which has potential application value. BRIEF DESCRIPTION OF THE DRAWINGS

[0023] Figure 1 、 Figure 2 These are the hydrogen and carbon spectra of the target product obtained in Example 1;

[0024] Figure 3 、 Figure 4 These are the hydrogen and carbon spectra of the target product obtained in Example 2;

[0025] Figure 5 、 Figure 6 These are the hydrogen and carbon spectra of the target product obtained in Example 3;

[0026] Figure 7 、 Figure 8 These are the hydrogen and carbon spectra of the target product obtained in Example 4; DETAILED DESCRIPTION

[0027] The present invention is further described below with reference to specific examples, but the protection scope and implementation modes of the present invention are not limited thereto.

[0028] Example 1

[0029] To a 10 mL three-necked round-bottom flask, diphenyl disulfide (0.1 mmol), S,S-diphenylsulfonyl imine (0.1 mmol), tetrabutylammonium iodide (0.2 mmol), acetonitrile (3 mL), and tert-butanol (0.1 mmol) were added in sequence. A platinum sheet was inserted as the negative electrode and a carbon rod as the positive electrode. The reaction was stirred at room temperature for 1.5 hours. After completion of the reaction, the mixture was filtered and evaporated under reduced pressure to obtain the crude product. The filtrate was extracted three times with ethyl acetate, and the organic phases were combined and dried over anhydrous magnesium sulfate. Finally, the product was separated and purified by column chromatography using a mixture of petroleum ether and ethyl acetate (petroleum ether:ethyl acetate = 10:1) as the eluent. The pure target product obtained was diphenyl[(phenylthio)imino]-λ 6 -Aminosulfamethoxazole, the yield is 80%.

[0030] The hydrogen and carbon spectra of the target product are as follows: Figure 1 and Figure 2 As shown, the structural characterization data are as follows:

[0031] 1 H NMR (500 MHz, CDCl3) δ 8.04 (d, J = 7.5 Hz, 4H), 7.62 – 7.42 (m,8H), 7.28 (t, J = 7.7 Hz, 2H), 7.10 (t, J = 7.3 Hz, 1H);

[0032] 13 C NMR (126 MHz, CDCl3) δ 142.06, 139.88, 133.19, 129.31, 128.45,128.42, 125.00, 123.91;

[0033] HRMS (ESI) m / z: calculated for C 18 H 16 NOS2[M+H] + 326.0668; found 326.0666.

[0034] The structure of the target compound is inferred from the above characterization data as follows:

[0035]

[0036] Example 2

[0037] To a 10 mL three-necked round-bottom flask, diphenyl disulfide (0.1 mmol), 1-chloro-2-(S-methylsulfonyl)benzene (0.1 mmol), tetrabutylammonium iodide (0.2 mmol), acetonitrile (3 mL), and tert-butanol (0.1 mmol) were added sequentially. A platinum sheet was inserted as the negative electrode and a carbon rod as the positive electrode. The reaction was stirred at room temperature for 1.0 hour. After completion of the reaction, the mixture was filtered and evaporated under reduced pressure to obtain the crude product. The filtrate was extracted three times with ethyl acetate, and the organic phases were combined and dried over anhydrous magnesium sulfate. Finally, the product was separated and purified by column chromatography using a mixture of petroleum ether and ethyl acetate (petroleum ether:ethyl acetate = 10:1) as the eluent. The pure target product obtained was (2-chlorophenyl)(methyl)((phenylthio)imino)-λ 6 -Aminosulfamethoxazole, the yield is 86%.

[0038] The hydrogen and carbon spectra of the target product are as follows: Figure 3 and Figure 4 As shown, the structural characterization data are as follows:

[0039] 1 H NMR (500 MHz, CDCl3) δ 8.10 (dd, J = 7.9, 1.6 Hz, 1H), 7.48 – 7.43 (m, 2H), 7.39 (td, J = 7.5, 7.0, 1.7 Hz, 1H), 7.31 – 7.25 (m, 2H), 7.14 (t, J = 7.7 Hz, 2H), 6.98 (t, J = 7.4 Hz, 1H), 3.40 (s, 3H);

[0040] 13 C NMR (126 MHz, CDCl3) δ 141.51, 135.82, 134.81, 132.92, 132.21,132.14, 128.45, 127.55, 125.33, 124.55, 42.07;

[0041] HRMS (ESI) m / z: calculated for C 13 H 12 NNaOS2[M+Na] + 319.9941; found319.9956.

[0042] The structure of the target compound is inferred from the above characterization data as follows:

[0043]

[0044] Example 3

[0045] To a 10 mL three-necked round-bottom flask, diphenyl disulfide (0.1 mmol), 1-(phenylsulfonylpiperidine) (0.1 mmol), tetrabutylammonium iodide (0.2 mmol), acetonitrile (3 mL), and tert-butanol (0.1 mmol) were added in sequence. A platinum sheet was inserted as the negative electrode and a carbon rod as the positive electrode. The reaction was stirred at room temperature for 1.5 hours. After the reaction, the mixture was filtered and the crude product was obtained by rotary evaporation under reduced pressure. The filtrate was extracted three times with ethyl acetate, and the organic phases were combined and dried over anhydrous magnesium sulfate. Finally, the product was separated and purified by column chromatography using a mixture of petroleum ether and ethyl acetate (petroleum ether:ethyl acetate = 10:1) as the eluent. The pure target product obtained was: N-[Oxo(phenyl)(piperidin-1-yl)-λ 6 -sulfylidene]-S-phenylthiohydroxylamine, the yield was 68%.

[0046] The hydrogen and carbon spectra of the target product are as follows: Figure 5 and Figure 6 As shown, the structural characterization data are as follows:

[0047] 1 H NMR (500 MHz, CDCl3) δ 7.86 (d, J = 7.7 Hz, 2H), 7.53 (t, J = 7.3Hz, 1H), 7.47 (t, J = 7.5 Hz, 2H), 7.36 (d, J = 7.8 Hz, 2H), 7.18 (t, J = 7.7Hz, 2H), 6.99 (t, J = 7.4 Hz, 1H), 2.97 (hept, J = 5.8, 5.2 Hz, 4H), 1.55 (p,J = 5.6 Hz, 4H), 1.36 (q, J = 6.3 Hz, 2H);

[0048] 13 C NMR (126 MHz, CDCl3) δ 142.08, 135.99, 132.67, 128.94, 128.47, 127.95, 124.84, 123.85, 47.54, 25.22, 23.61;

[0049] HRMS (ESI) m / z: calculated for C 17 H 20 N2NaOS2[M+Na] + 355.0909; found355.0910.

[0050] The structure of the target compound is inferred from the above characterization data as follows:

[0051]

[0052] Example 4

[0053] To a 10 mL three-necked round-bottom flask, 2,2'-difluorodiphenyl disulfide (0.1 mmol), S,S-biphenylsulfonyl imine (0.1 mmol), tetrabutylammonium iodide (0.2 mmol), acetonitrile (3 mL), and tert-butanol (0.1 mmol) were added in sequence. A platinum sheet was inserted as the negative electrode and a carbon rod as the positive electrode. The reaction was stirred at room temperature for 1.0 hour. After completion of the reaction, the mixture was filtered and evaporated under reduced pressure to obtain the crude product. The filtrate was extracted three times with ethyl acetate, and the organic phases were combined and dried over anhydrous magnesium sulfate. Finally, the product was separated and purified by column chromatography using a mixture of petroleum ether and ethyl acetate (petroleum ether:ethyl acetate = 10:1) as the eluent. The pure target product obtained was (((2-fluorophenyl)thio)imino)diphenyl-λ 6 -sulfamethoxazole, the yield is 90%.

[0054] The hydrogen and carbon spectra of the target product are as follows: Figure 7 and Figure 8 As shown, the structural characterization data are as follows:

[0055] 1 H NMR (500 MHz, CDCl3) δ 8.07 – 7.95 (m, 4H), 7.74 (td, J = 7.8, 1.9Hz, 1H), 7.60 – 7.46 (m, 6H), 7.15 – 7.02 (m, 2H), 6.96 – 6.85 (m, 1H);

[0056] 13 C NMR (126 MHz, CDCl3) δ 157.98, 156.06, 139.71, 133.28, 129.36,128.37, 126.19, 126.17, 126.04, 125.98, 124.38, 114.49, 114.33;

[0057] HRMS (ESI) m / z: calculated for C 18 H 15 FNOS2[M+H] + 344.0574; found 344.0571.

[0058] The structure of the target compound is inferred from the above characterization data as follows:

[0059]

[0060] Example 5

[0061] To a 10 mL three-necked round-bottom flask, diphenyl disulfide (0.1 mmol), (4-bromophenyl)(imino)(p-tolyl)-λ6-thiocanone (0.1 mmol), tetrabutylammonium iodide (0.2 mmol), acetonitrile (3 mL), and tert-butanol (0.1 mmol) were added in sequence. A platinum sheet was inserted as the negative electrode and a carbon rod as the positive electrode. The reaction was stirred at room temperature for 2.0 hours. After completion of the reaction, the mixture was filtered and evaporated under reduced pressure to obtain the crude product. The filtrate was extracted three times with ethyl acetate, and the organic phases were combined and dried over anhydrous magnesium sulfate. Finally, the product was separated and purified by column chromatography using a mixture of petroleum ether and ethyl acetate (petroleum ether:ethyl acetate = 10:1) as the eluent. The pure target product obtained was (4-bromophenyl)((phenylthio)imino)(p-tolyl)-λ6-thiocanone. 6 -sulfamethoxazole, with a yield of 60%.

[0062] The structural characterization data of the obtained target product are shown below:

[0063] 1 H NMR (500 MHz, CDCl3) δ 7.88 (dd, J = 23.1, 8.3 Hz, 4H), 7.64 (d, J= 8.5 Hz, 2H), 7.43 (d, J = 7.7 Hz, 2H), 7.35 – 7.26 (m, 4H), 7.11 (t, J =7.3 Hz, 1H), 2.43 (s, 3H);

[0064] 13 C NMR (126 MHz, CDCl3) δ 144.55, 141.90, 139.41, 136.38, 132.48,130.11, 129.84, 128.46, 128.44, 128.29, 125.07, 123.95, 21.52;

[0065] HRMS (ESI) m / z: calculated for C 19 H 17 BrNOS2[M+H] + 417.9929; found 417.9932.

[0066] The structure of the target compound is inferred from the above characterization data as follows:

[0067]

[0068] Example 6

[0069] In a 10 mL three-necked round-bottom flask, diphenyl disulfide (0.1 mmol), imino-p-tolyl-λ 6 α-sulfanilamide (0.1 mmol), tetrabutylammonium iodide (0.2 mmol), acetonitrile (3 mL), and tert-butanol (0.1 mmol) were added to a solution of 1% thiazolinone (0.1 mmol), 1% thiazolinone (0.2 mmol), 1% thiazolinone (0.2 mmol), 1% thiazolinone (0.2 mmol), 1% thiazolinone (0.1 ... 6 -sulfamethoxazole, with a yield of 72%.

[0070] The structural characterization data of the obtained target product are shown below:

[0071] 1 H NMR (500 MHz, CDCl3) δ 7.91 (d, J = 8.1 Hz, 4H), 7.45 (d, J = 7.8Hz, 2H), 7.33 – 7.25 (m, 6H), 7.09 (t, J = 7.4 Hz, 1H), 2.41 (s, 6H);

[0072] 13 C NMR (126 MHz, CDCl3) δ 144.01, 137.20, 129.93, 129.70, 128.36,127.79, 124.80, 123.77, 21.48;

[0073] HRMS (ESI) m / z: calculated for C 20 H 20 NOS2(M+H) + 354.0981; found 354.0983.

[0074] The structure of the target compound is inferred from the above characterization data as follows:

[0075]

[0076] Example 7

[0077] In a 10 mL three-necked round-bottom flask, diphenyl disulfide (0.1 mmol), bis(4-chlorophenyl)(imino)-λ 6 α-sulfamethoxazole (0.1 mmol), tetrabutylammonium iodide (0.2 mmol), acetonitrile (3 mL), and tert-butanol (0.1 mmol) were added to a solution of 1% sulfanilamide (0.1 mmol), 1% tetrabutylammonium iodide (0.2 mmol), acetonitrile (3 mL), and tert-butanol (0.1 mmol). A platinum sheet was inserted as the negative electrode and a carbon rod as the positive electrode. The reaction was stirred at room temperature for 2.0 hours. After the reaction was completed, the mixture was filtered and evaporated under reduced pressure to obtain the crude product. The filtrate was extracted three times with ethyl acetate, and the organic phases were combined and dried over anhydrous magnesium sulfate. Finally, the mixture was separated and purified by column chromatography using a mixed solvent of petroleum ether and ethyl acetate (petroleum ether:ethyl acetate = 10:1) as the eluent. The pure target product obtained was bis(4-chlorophenyl)((phenylthio)imino)-λ 6 -sulfamethoxazole, the yield was 76%.

[0078] The structural characterization data of the obtained target product are shown below:

[0079] 1 H NMR (500 MHz, CDCl3) δ 7.94 – 7.88 (m, 4H), 7.50 – 7.46 (m, 4H), 7.42 – 7.38 (m, 2H), 7.27 (t, J = 7.8 Hz, 2H), 7.10 (t, J = 7.4 Hz, 1H);

[0080] 13 C NMR (126 MHz, CDCl3) δ 141.43, 140.22, 138.08, 129.87, 129.71,128.53, 125.36, 124.18;

[0081] HRMS (ESI) m / z: calculated for C 18 H 14 Cl2NOS2[M+H] + 393.9888; found 393.9891.

[0082] The structure of the target compound is inferred from the above characterization data as follows:

[0083]

[0084] Example 8

[0085] To a 10 mL three-necked round-bottom flask, diphenyl disulfide, S-methylsulfonyliminobenzene (0.1 mmol), tetrabutylammonium iodide (0.2 mmol), acetonitrile (3 mL), and tert-butanol (0.1 mmol) were added in sequence. A platinum sheet was inserted as the negative electrode and a carbon rod as the positive electrode. The reaction was stirred at room temperature for 1.0 hour. After the reaction, the mixture was filtered and evaporated under reduced pressure to obtain the crude product. The filtrate was extracted three times with ethyl acetate, and the organic phases were combined and dried over anhydrous magnesium sulfate. Finally, the product was separated and purified by column chromatography using a mixture of petroleum ether and ethyl acetate (petroleum ether:ethyl acetate = 10:1) as the eluent. The pure target product obtained was methyl(phenyl)((phenylthio)imino)-λ 6 -sulfamethoxazole, the yield was 63%.

[0086] The structural characterization data of the obtained target product are shown below:

[0087] 1 H NMR (500 MHz, CDCl3) δ 7.98 (d, J = 7.3 Hz, 2H), 7.64 (dt, J =41.7, 7.4 Hz, 3H), 7.42 (d, J = 7.4 Hz, 2H), 7.29 (t, J = 7.8 Hz, 2H), 7.11(t, J = 7.3 Hz, 1H), 3.31 (s, 3H);

[0088] 13 C NMR (126 MHz, CDCl3) δ 142.06, 138.62, 133.70, 129.47, 128.47,128.38, 125.05, 123.76, 43.71;

[0089] HRMS (ESI) m / z: calculated for C 13 H 14 NOS2[M+H] + 264.0511; found 264.0515.

[0090] The structure of the target compound is inferred from the above characterization data as follows:

[0091]

[0092] Example 9

[0093] To a 10 mL three-necked round-bottom flask, diphenyl disulfide (0.1 mmol), 1-chloro-4-(S-methylsulfonylimino)benzene (0.1 mmol), tetrabutylammonium iodide (0.2 mmol), acetonitrile (3 mL), and tert-butanol (0.1 mmol) were added in sequence. A platinum sheet was inserted as the negative electrode and a carbon rod as the positive electrode. The reaction was stirred at room temperature for 1.0 hour. After completion of the reaction, the mixture was filtered and evaporated under reduced pressure to obtain the crude product. The filtrate was extracted three times with ethyl acetate, and the organic phases were combined and dried over anhydrous magnesium sulfate. Finally, the product was separated and purified by column chromatography using a mixture of petroleum ether and ethyl acetate (petroleum ether:ethyl acetate = 10:1) as the eluent. The pure target product obtained was (4-chlorophenyl)(methyl)(phenylthio)imino-λ 6 -sulfamethoxazole, the yield was 52%.

[0094] The structural characterization data of the obtained target product are shown below:

[0095] 1 H NMR (500 MHz, CDCl3) δ 7.89 (d, J = 7.9 Hz, 2H), 7.56 (d, J = 7.9Hz, 2H), 7.40 (d, J = 7.8 Hz, 2H), 7.29 (t, J = 7.4 Hz, 2H), 7.12 (t, J = 7.2Hz, 1H), 3.30 (s, 3H);

[0096] 13 C NMR (126 MHz, CDCl3) δ 141.77, 140.58, 137.19, 129.97, 129.83,128.59, 124.02, 43.89;

[0097] HRMS (ESI) m / z: calculated for C 13 H 12 ClNNaOS2 (M+Na) + 319.9941; found319.9940.

[0098] The structure of the target compound is inferred from the above characterization data as follows:

[0099]

[0100] Example 10

[0101] To a 10 mL three-necked round-bottom flask, diphenyl disulfide (0.1 mmol), 1-(S-methylsulfonylimino)-4-nitrobenzene (0.1 mmol), tetrabutylammonium iodide (0.2 mmol), acetonitrile (3 mL), and tert-butanol (0.1 mmol) were added in sequence. A platinum sheet was inserted as the negative electrode and a carbon rod as the positive electrode. The reaction was stirred at room temperature for 2.0 hours. After completion of the reaction, the mixture was filtered and evaporated under reduced pressure to obtain the crude product. The filtrate was extracted three times with ethyl acetate, and the organic phases were combined and dried over anhydrous magnesium sulfate. Finally, the product was separated and purified by column chromatography using a mixture of petroleum ether and ethyl acetate (petroleum ether:ethyl acetate = 10:1) as the eluent. The pure target product obtained was methyl(4-nitrophenyl)((phenylthio)imino)-λ 6 -sulfamethoxazole, with a yield of 40%.

[0102] The structural characterization data of the obtained target product are shown below:

[0103] 1 H NMR (500 MHz, CDCl3) δ 8.39 (d, J = 8.6 Hz, 2H), 8.12 (d, J = 8.6Hz, 2H), 7.36 (d, J = 7.5 Hz, 2H), 7.27 (t, J = 7.5 Hz, 2H), 7.12 (t, J = 7.2Hz, 1H), 3.35 (s, 3H);

[0104] 13 C NMR (126 MHz, CDCl3) δ 150.77, 144.80, 140.97, 129.93, 128.62,125.65, 124.49, 124.29, 43.61;

[0105] HRMS (ESI) m / z: calculated for C 13 H 12 N2NaO3S2[M+Na] + 331.0182; found331.0175.

[0106] The structure of the target compound is inferred from the above characterization data as follows:

[0107]

[0108] Example 11

[0109] To a 10 mL three-necked round-bottom flask, diphenyl disulfide (0.1 mmol), 1-bromo-4-(S-methylsulfonylimino)benzene (0.1 mmol), tetrabutylammonium iodide (0.2 mmol), acetonitrile (3 mL), and tert-butanol (0.1 mmol) were added in sequence. A platinum sheet was inserted as the negative electrode and a carbon rod as the positive electrode. The reaction was stirred at room temperature for 1.0 hour. After completion of the reaction, the mixture was filtered and evaporated under reduced pressure to obtain the crude product. The filtrate was extracted three times with ethyl acetate, and the organic phases were combined and dried over anhydrous magnesium sulfate. Finally, the product was separated and purified by column chromatography using a mixture of petroleum ether and ethyl acetate (petroleum ether:ethyl acetate = 10:1) as the eluent. The pure target product obtained was (4-bromophenyl)(methyl)((phenylthio)imino)-λ 6 -sulfamethoxazole, with a yield of 80%.

[0110] The structural characterization data of the obtained target product are shown below:

[0111] 1 H NMR (500 MHz, CDCl3) δ 7.79 (d, J = 8.4 Hz, 2H), 7.70 (d, J = 8.6Hz, 2H), 7.41 – 7.32 (m, 2H), 7.26 (t, J = 7.6 Hz, 2H), 7.13 – 7.06 (m, 1H),3.27 (s, 3H);

[0112] 13 C NMR (126 MHz, CDCl3) δ 141.66, 137.69, 132.74, 129.96, 129.08,128.51, 125.25, 123.97, 43.77;

[0113] HRMS (ESI) m / z: calculated for C 13 H 12 BrNNaOS2 [M+Na] + 363.9436; found363.9429.

[0114] The structure of the target compound is inferred from the above characterization data as follows:

[0115]

[0116] Example 12

[0117] To a 10 mL three-necked round-bottom flask, diphenyl disulfide (0.1 mmol), 1-methyl-4-(S-methylsulfonylimino)benzene (0.1 mmol), tetrabutylammonium iodide (0.2 mmol), acetonitrile (3 mL), and tert-butanol (0.1 mmol) were added in sequence. A platinum sheet was inserted as the negative electrode and a carbon rod as the positive electrode. The reaction was stirred at room temperature for 1.0 hour. After completion of the reaction, the mixture was filtered and the crude product was obtained by rotary evaporation under reduced pressure. The filtrate was extracted three times with ethyl acetate, and the organic phases were combined and dried over anhydrous magnesium sulfate. Finally, the product was separated and purified by column chromatography using a mixture of petroleum ether and ethyl acetate (petroleum ether:ethyl acetate = 10:1) as the eluent. The pure target product obtained was methyl((phenylthio)imino)(p-tolyl)-λ 6 -sulfamethoxazole, with a yield of 42%.

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

[0119] 1 H NMR (500 MHz, CDCl3) δ 7.91 – 7.78 (m, 2H), 7.40 (t, J = 9.2 Hz,4H), 7.31 – 7.26 (m, 2H), 7.10 (t, J = 7.4 Hz, 1H), 3.28 (s, 3H), 2.48 (s,3H);

[0120] 13 C NMR (126 MHz, CDCl3) δ 144.83, 142.32, 135.63, 130.19, 128.50,128.47, 125.00, 123.74, 43.91, 21.63;

[0121] HRMS (ESI) m / z: calculated for C 14 H 15 NNaOS2 [M+Na] + 300.0487; found300.0487.

[0122] The structure of the target compound is inferred from the above characterization data as follows:

[0123]

[0124] Example 13

[0125] To a 10 mL three-necked round-bottom flask, diphenyl disulfide (0.1 mmol), 1-methoxy-4-(S-methylsulfonylimino)benzene (0.1 mmol), tetrabutylammonium iodide (0.2 mmol), acetonitrile (3 mL), and tert-butanol (0.1 mmol) were added in sequence. A platinum sheet was inserted as the negative electrode and a carbon rod as the positive electrode. The reaction was stirred at room temperature for 1.0 hour. After completion of the reaction, the mixture was filtered and evaporated under reduced pressure to obtain the crude product. The filtrate was extracted three times with ethyl acetate, and the organic phases were combined and dried over anhydrous magnesium sulfate. Finally, the product was separated and purified by column chromatography using a mixture of petroleum ether and ethyl acetate (petroleum ether:ethyl acetate = 10:1) as the eluent. The pure target product obtained was (4-methoxyphenyl)(methyl)((phenylthio)imino)-λ 6 -sulfamethoxazole, with a yield of 60%.

[0126] The structural characterization data of the obtained target product are shown below:

[0127] 1 H NMR (500 MHz, CDCl3) δ 7.89 (d, J = 8.6 Hz, 2H), 7.41 (d, J = 8.1Hz, 2H), 7.28 (t, J = 7.5 Hz, 2H), 7.10 (t, J = 7.0 Hz, 1H), 7.05 (d, J = 8.6Hz, 2H), 3.90 (s, 3H), 3.28 (s, 3H);

[0128] 13 C NMR (126 MHz, CDCl3) δ 163.87, 142.38, 130.62, 129.73, 128.50,124.98, 123.72, 114.77, 55.76, 44.12;

[0129] HRMS (ESI) m / z: calculated for C 14 H 16 NO2S2 [M+H] + 294.0617; found 294.0605.

[0130] The structure of the target compound is inferred from the above characterization data as follows:

[0131]

[0132] Example 14

[0133] To a 10 mL three-necked round-bottom flask, diphenyl disulfide (0.1 mmol), (cyclopropanesulfonyl)benzene (0.1 mmol), tetrabutylammonium iodide (0.2 mmol), acetonitrile (3 mL), and tert-butanol (0.1 mmol) were added in sequence. A platinum sheet was inserted as the negative electrode and a carbon rod as the positive electrode. The reaction was stirred at room temperature for 1.5 hours. After the reaction, the mixture was filtered and the crude product was obtained by rotary evaporation under reduced pressure. The filtrate was extracted three times with ethyl acetate, and the organic phases were combined and dried over anhydrous magnesium sulfate. Finally, the product was separated and purified by column chromatography using a mixture of petroleum ether and ethyl acetate (petroleum ether:ethyl acetate = 10:1) as the eluent. The pure target product obtained was: cyclopropyl(phenyl)((phenylthio)imino)-λ 6 -sulfamethoxazole, the yield was 51%.

[0134] The structural characterization data of the obtained target product are shown below:

[0135] 1 H NMR (500 MHz, CDCl3) δ 7.92 (d, J = 7.7 Hz, 2H), 7.65 (t, J = 7.3Hz, 1H), 7.57 (t, J = 7.6 Hz, 2H), 7.39 (d, J = 7.8 Hz, 2H), 7.29 – 7.25 (m,2H), 7.09 (t, J = 7.4 Hz, 1H), 2.70 (tt, J = 8.0, 4.7 Hz, 1H), 1.74 – 1.66(m, 1H), 1.28 – 1.16 (m, 2H), 0.95 (qd, J = 8.0, 5.3 Hz, 1H);

[0136] 13 C NMR (126 MHz, CDCl3) δ 142.61, 139.12, 133.37, 129.38, 128.44,124.89, 123.69, 33.00, 6.71, 5.65;

[0137] HRMS (ESI) m / z: calculated for C 15 H 16 NOS2 [M+H] + 290.0668; found 290.0657.

[0138] The structure of the target compound is inferred from the above characterization data as follows:

[0139]

[0140] Example 15

[0141] In a 10 mL three-necked round-bottom flask, diphenyl disulfide (0.1 mmol), (3-bromophenyl)(imino)(methyl)-λ 6 -sulfamethoxazole (0.1 mmol), tetrabutylammonium iodide (0.2 mmol), acetonitrile (3 mL), and tert-butanol (0.1 mmol) were added to a solution of 1% sulfanilamide (0.1 mmol), 1% sulfanilamide (0.1 mmol), 1% sulfanilamide (0.2 ... 6 -sulfamethoxazole, with a yield of 81%.

[0142] The structural characterization data of the obtained target product are shown below:

[0143] 1 H NMR (500 MHz, CDCl3) δ 8.10 (d, J = 2.1 Hz, 1H), 7.90 – 7.86 (m,1H), 7.81 – 7.77 (m, 1H), 7.46 (t, J = 8.0 Hz, 1H), 7.40 (d, J = 7.8 Hz, 2H),7.31 – 7.28 (m, 2H), 7.13 (t, J = 7.4 Hz, 1H), 3.31 (s, 3H);

[0144] 13 C NMR (126 MHz, CDCl3) δ 141.59, 140.71, 136.80, 131.45, 130.93,128.60, 126.99, 125.43, 124.20, 123.55, 43.86;

[0145] HRMS (ESI) m / z: calculated for C 13 H 12 BrNNaOS2 [M+Na] + 363.9436; found363.9448.

[0146] The structure of the target compound is inferred from the above characterization data as follows:

[0147]

[0148] Example 16

[0149] In a 10 mL three-necked round-bottom flask, diphenyl disulfide (0.1 mmol), imino(4-nitrophenyl)(phenyl)-λ 6 α-sulfamethoxazole (0.1 mmol), tetrabutylammonium iodide (0.2 mmol), acetonitrile (3 mL), and tert-butanol (0.1 mmol) were added to a solution of 4-nitrophenyl (4-nitrophenyl)(phenyl)((phenylthio)imino)-λ-aminobenzoic acid (0.1 mmol). A platinum sheet was inserted as the negative electrode and a carbon rod as the positive electrode. The reaction was stirred at room temperature for 3 hours. After the reaction was completed, the mixture was filtered and evaporated under reduced pressure to obtain the crude product. The filtrate was extracted three times with ethyl acetate, and the organic phases were combined and dried over anhydrous magnesium sulfate. Finally, the mixture was separated and purified by column chromatography using a mixed solvent of petroleum ether and ethyl acetate (petroleum ether:ethyl acetate = 10:1) as the eluent. The pure target product obtained was (4-nitrophenyl)(phenyl)((phenylthio)imino)-λ-aminobenzoic acid (0.1 mmol). 6 -sulfamethoxazole, with a yield of 70%.

[0150] The structural characterization data of the obtained target product are shown below:

[0151] 1 H NMR (500 MHz, CDCl3) δ 8.36 – 8.30 (m, 2H), 8.21 – 8.15 (m, 2H), 8.08 (d, J = 7.8 Hz, 2H), 7.66 (t, J = 7.2 Hz, 1H), 7.59 (q, J = 7.6, 5.7 Hz,2H), 7.42 (d, J = 7.5 Hz, 2H), 7.29 (q, J = 7.5, 6.2 Hz, 2H), 7.14 (q, J =7.3, 6.1 Hz, 1H);

[0152] 13 C NMR (126 MHz, CDCl3) δ 150.27, 146.18, 141.14, 138.43, 134.02,129.77, 129.67, 128.73, 128.56, 125.53, 124.31;

[0153] HRMS (ESI) m / z: calculated for C 18 H 14 N2NaO3S2 [M+Na] + 393.0344; found393.0345.

[0154] The structure of the target compound is inferred from the above characterization data as follows:

[0155]

[0156] Example 17

[0157] In a 10 mL three-necked round-bottom flask, 2,2'-diphenyltetraamidodisulfide (0.1 mmol), 1-methyl-4-(S-methylsulfonylimino)benzene (0.1 mmol), tetrabutylammonium iodide (0.2 mmol), acetonitrile (3 mL), and tert-butanol (0.1 mmol) were added in sequence. A platinum sheet was inserted as the negative electrode and a carbon rod as the positive electrode. The reaction was stirred at room temperature for 2.0 hours. After completion of the reaction, the mixture was filtered and the crude product was obtained by rotary evaporation under reduced pressure. The filtrate was extracted three times with ethyl acetate, and the organic phases were combined and dried over anhydrous magnesium sulfate. Finally, the product was separated and purified by column chromatography using a mixture of petroleum ether and ethyl acetate (petroleum ether:ethyl acetate = 10:1) as the eluent. The pure target product obtained was: N-(2-(((methyl(oxo)(p-tolyl))-λ 6 -amino)thio)phenyl)benzamide in 70% yield.

[0158] The structural characterization data of the obtained target product are shown below:

[0159] 1 H NMR (500 MHz, CDCl3) δ 9.99 (s, 1H), 8.46 (d, J = 8.0 Hz, 1H), 8.06 (d, J = 6.9 Hz, 2H), 7.62 – 7.59 (m, 2H), 7.52 (t, J = 7.6 Hz, 1H), 7.45 (t,J = 7.7 Hz, 2H), 7.31 (t, J = 7.1 Hz, 2H), 7.20 (d, J = 7.8 Hz, 2H), 6.92 (t,J = 7.7 Hz, 1H), 3.14 (s, 3H), 2.39 (s, 3H);

[0160] 13 C NMR (126 MHz, CDCl3) δ 165.12, 144.96, 139.36, 134.96, 134.75,131.76, 131.28, 130.00, 129.69, 128.63, 128.29, 128.10, 127.46, 123.64,121.14, 43.54, 21.59;

[0161] HRMS (ESI) m / z: calculated for C 21 H 20 N2NaO2S2 [M+Na] + 419.0864; found419.0864.

[0162] The structure of the target compound is inferred from the above characterization data as follows:

[0163]

[0164] The above embodiments are partial implementation methods of the present invention. The specific implementation methods of the present invention are not affected by the above embodiments. Any other structural modifications and condition simplifications made without departing from the spirit and principles of the present invention should be equivalent replacement methods and are included in the protection scope of the present invention.

Claims

1. A method for electrochemically promoting the construction of N-sulfide-substituted sulfoximine derivatives, characterized in that: The following steps are included: In a three-necked flask, a disulfide compound, a sulfoximine compound, an electrolyte, an additive, and an organic solvent were sequentially added, an electrode was inserted, and an electric current was applied at room temperature with a current of 7-13 mA. After the reaction, the mixture was filtered and extracted, and the organic phase was collected and rotary evaporated under reduced pressure to obtain a crude product. The crude product was separated and purified by column chromatography to obtain an N-sulfide-substituted sulfoximine derivative. The above reaction is shown in the following formula: , where R 1 is selected from the group consisting of phenyl, 2-chlorophenyl, 4-methylphenyl, 4-chlorophenyl, 4-nitrophenyl, 4-bromophenyl, 4-methoxyphenyl, 3-bromophenyl and piperidinyl; R 2 is one of phenyl, methyl, 4-bromophenyl, 4-methylphenyl, 4-chlorophenyl and cyclopropyl; R 3 It is one of phenyl, 2-fluorophenyl and 2-benzamidophenyl; the electrolyte is tetrabutylammonium iodide; the additive is tert-butanol; the organic solvent is one of methanol, acetone, furan, dichloromethane, DMSO, DMF, and acetonitrile; the electrodes are any two of graphite rod, graphite felt, meshed glassy carbon, platinum sheet, nickel sheet, and stainless steel as the positive and negative electrodes.

2. The method for electrochemically promoting the construction of N-sulfide-substituted sulfoximine derivatives according to claim 1, characterized in that: The molar ratio of the disulfide compound to the sulfoximine compound is 0.5-3:

1.

3. The method for electrochemically promoting the construction of N-sulfide-substituted sulfoximine derivatives according to claim 1, characterized in that: The molar ratio of the sulfoximine compound to the electrolyte is 1:1-3.

4. The method for electrochemically promoting the construction of N-sulfide-substituted sulfoximine derivatives according to claim 1, characterized in that: The molar ratio of the sulfoximine compound to the additive is 1:1-3.

5. The method for electrochemically promoting the construction of N-sulfide-substituted sulfoximine derivatives according to claim 1, characterized in that: The reaction time is 0.5 to 10 hours.

6. The method for electrochemically promoting the construction of N-sulfide-substituted sulfoximine derivatives according to claim 1, characterized in that: The crude product is separated by column chromatography, and the eluent is a mixed solvent of petroleum ether and ethyl acetate, with a mixing ratio of petroleum ether to ethyl acetate of 3 to 50:1.

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