A method for synthesizing N-sulfonyl sulfoximine derivatives

Abstract

The invention discloses a method for synthesizing an N-sulfonyl sulfoximine derivative, which comprises the following steps: adding a copper catalyst, a sulfoximine compound, DABSO, a tetrafluoroborate diazonium compound, a base and a solvent to a glass reaction vessel, protecting with nitrogen, stirring and reacting at 80° C. for 12 hours, and separating and purifying the crude reaction product to obtain an N-sulfonyl sulfoximine compound. The invention develops a coupling reaction of a sulfoximine derivative with DABSO and a tetrafluoroborate diazonium derivative, and a series of functionalized N-sulfonyl sulfoximine derivatives can be constructed by simple operation, which has a high degree of step economy and atom economy. In addition, the main advantages of the reaction are that the raw materials are simple and easy to obtain, the selectivity is single, the functional group tolerance is good, and the yield is high.

Description

Technical Field

[0001] The invention belongs to the field of organic synthetic chemistry, and specifically relates to a method for synthesizing an N-sulfonyl sulfoximine derivative. Background Art

[0002] Sulfoximine derivatives are an important class of organosulfur compounds that exist in various drug molecules, agrochemicals, and bioactive natural products, exhibiting many unique properties, such as good water solubility, chemical and biological importance, and excellent directing and coordination capabilities. Therefore, organic researchers have made a lot of efforts to achieve the functionalization reaction of sulfoximines. Among them, copper-catalyzed NH functionalization has become an efficient means to synthesize highly functionalized sulfoximines. For example, Liu and colleagues reported a CuTc-catalyzed sulfoximine free radical alkylation reaction in 2021 to obtain α-chiral primary amine derivatives. (Y. Zhang, X. Dong, J. Cheng, N. Yang, L. Wang, F. Wang, C. Luan, J. Liu, Z. Li, Q. Gu, X. Liu, J. Am. Chem. Soc., 2021, 143, 15413-15419.); Recently, the Jia research group discovered the copper-catalyzed photoredox Chan-Lam coupling reaction of free diaryl sulfoximines to obtain N-aryl sulfoximines. (C. Wang, H. Zhang, L. A. Wells, T. Liu, T. Meng, Q. Liu, P. Walsh, M. Kozlowski, T. Jia, Nature communications, 2021, 12, 1, 1-11.) In addition, Dong, Chen, Kandasamy, Varma and other research groups have achieved the synthesis of highly functionalized sulfoximine derivatives using aromatic sulfinates, aldehydes, dialkyl phosphites and diaryliodonium salts as reaction substrates.(B. Vaddula, J. Leazer, R. Varma, Adv. Synth. Catal., 2012, 354, 986-990; L. Wang, D. Priebbenow, L. Zou, C. Bolm, Adv. Synth. Catal., 2013 ,355,1490-1494; R.Pirwerdjan,D.Priebbenow,P.Becker,P.Lamers,C.Bolm,Org.Lett.,2013,15,21,5397-5399;Y.Jiang,Y.You,W.Dong , Z. Peng, Y. Zhang, D. An, J. Org. Chem., 2017, 82, 5810-5818; S. Gupta, S. Baranwal, P. Chaudhary, J. Kandasamy, Org. Chem. Front., 2019, 6, 2260-2265; C. Wu, R. Huang, M. Zhang, Z. Chen, J. Org. Chem., 2020, 85, 841-850.), Despite such great achievements, the research on the functionalization of NH sulfoximines by SO2 insertion has not been realized.

[0003] Recently, the use of 1,4-diazabicyclo[2.2.2]octane-sulfur dioxide (DABSO) as a substitute for sulfur dioxide to synthesize valuable sulfonyl functional molecules has attracted widespread attention. In this context, the Santos, Mello, Willis, Wu, Manolikakes and other groups have discovered many valuable strategies in this field and developed a series of sulfur dioxide insertion reactions. (R.Mao,D.Zheng,H.Xia,J.Wu,Org.Chem.Front.,2016,3,693-696;K.Sun,Z.Shi,Z.Liu,B.Luan,J.Zhu,Y.Xue,Org.Lett.,2018,20,6687-6690;J.Zhang,W.Xie,S.Ye ,J.Wu,Org.Chem.Front.,2019,6,2254-2259; T.Zhu,J.Wu,Org.Lett.,2020,22,7094-7097;M.Kumar,R.Ahmed,M.Singh,S.Sharm,T.Thatikonda,PPSingh,J.Org.Chem ., 2020, 85, 716-725; Q. Tang, X. Yin, RR Kuchukulla, Q. Zeng, Chem. Rec., 2021, 21, 893-905.) For example, in 2016, Wu's group reported a simple metal-free catalyzed sulfonylation / cyclization reaction of aromatic propiolates (D. Zheng, J. Yu, J. Wu, Angew. Chem. Int. Ed., 2016, 55, 11925-11929.). In addition, Willis and his team described an efficient and general method for the synthesis of multifunctional olefin sulfonyl fluorides (TS Lou, SW Bagley, MC Willis, Angew. Chem. Int. Ed., 2019, 58, 18859-18863). The latest research hotspots of SO2 insertion are mainly focused on the field of free radicals. A series of free radical precursors including phenyl propiolate, electron-deficient olefins, alkenyl boronic acid, and indolyl alkynone have been successfully used to capture SO2 and induce the formation of sulfonyl radical intermediates. Based on this research background, it is of great research value to fix SO2 by sulfoximine as a substrate to prepare a series of sulfonylated sulfoximine derivatives. Summary of the invention

[0004] The object of the present invention is to provide a novel method for synthesizing N-sulfonyl sulfoximine derivatives by inserting SO2 into sulfoximine in view of the shortcomings and deficiencies of the prior art.

[0005] The idea of ​​the present invention is to use sulfoximine compounds, DABSO and tetrafluoroborate diazonium salt compounds as raw materials, add copper catalyst, base and solvent, stir and react at 80°C for 12 hours under nitrogen protection, and a series of functionalized N-sulfonylsulfoximine derivatives can be constructed. This strategy is simple to operate and can complete the conversion in one step. In addition, the main advantages of this reaction are that the raw materials are simple and easy to obtain, the selectivity is single, the functional group tolerance is good, and the reaction yield is high.

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

[0007] A method for synthesizing an N-sulfonyl sulfoximine derivative comprises the following preparation process:

[0008] In a glass reaction container, a copper catalyst, a sulfoximine compound, DABSO, a tetrafluoroborate diazonium salt compound, a base and a solvent are added, and the mixture is stirred and reacted at 80° C. for 12 hours under nitrogen protection. The crude reaction product can be separated and purified to obtain an N-sulfonyl sulfoximine compound.

[0009] Further, the preparation formula of N-sulfonyl sulfoximine derivatives is shown below:

[0010]

[0011] In the formula, R 1 is selected from the group consisting of hydrogen, 4-methyl, 4-methoxy, 4-fluoro, 4-chloro, 4-bromo, 4-iodo, 4-cyano, 4-ester, 4-acetyl, 3-fluoro, 3-chloro, 3-bromo, 2-fluoro, 2-chloro, and 2-bromo; R is selected from the group consisting of methyl, ethyl, benzyl, and cyclopropyl; R 2 It is one of 2-methyl-4-methoxy, 2-bromo-4-methoxy, 3-chloro-4-methoxy, 3-bromo-4-methoxy, and 3-iodo-4-methoxy;

[0012] Further, the copper catalyst is one or more of cuprous bromide, copper trifluoromethanesulfonate, cupric chloride, and cuprous cyanide, preferably cuprous bromide;

[0013] Furthermore, the molar ratio of the copper catalyst to the sulfoximine compound is 0.1:1;

[0014] Furthermore, the molar ratio of the sulfoximine derivative to DABSO and diazonium tetrafluoroborate salt compound is 1:2:2;

[0015] Further, the base is one or more of cesium pivalate, cesium carbonate, sodium trifluoromethanesulfonate, sodium carbonate, potassium carbonate, and sodium acetate, preferably potassium carbonate;

[0016] Furthermore, the molar ratio of the base to the sulfoximine compound is 1.0-2.0:1, preferably 1:1;

[0017] Further, the solvent is ethylene dichloride, and its volume is 2 mL;

[0018] Further, the stirring temperature of the reaction is 70-80°C, preferably 80°C;

[0019] Further, the stirring time of the reaction is 12 to 24 hours, preferably 12 hours;

[0020] Furthermore, the crude product is separated by column chromatography using ethyl acetate and petroleum ether as eluents, the volume ratio of ethyl acetate to petroleum ether being 1:1 to 3, and a mixed solvent having a volume ratio (ethyl acetate: petroleum ether) of 1:1 is preferred.

[0021] The principle of the present invention is as follows: first, DABSO and aryl diazonium tetrafluoroborate form a complex through electrostatic interaction, and then N2, SO2, radical cations and aryl radicals are obtained through NS bond rupture and single electron transfer. Secondly, the aryl radical and SO2 combine to provide a sulfonyl group, and DABCO is produced by single electron reduction of the radical cation by Cu(I). Subsequently, the Cu(II) catalyst interacts with sulfoximine to produce a complex, and then the sulfonyl group is subjected to oxidative addition and then reduced elimination to obtain an N-sulfonyl sulfoximine derivative.

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

[0023] (1) The present invention realizes the efficient coupling reaction of copper-catalyzed sulfoximine derivatives with DABSO and tetrafluoroborate diazonium salt compounds, and constructs a series of N-sulfonyl sulfoximine derivatives that are difficult to prepare. The reaction has the characteristics of good functional group tolerance, high yield and simple operation;

[0024] (2) The method of the present invention for preparing N-sulfonyl sulfoximine derivatives can be completed through a one-step reaction, has high step economy, and is therefore expected to be applied to industrial production. BRIEF DESCRIPTION OF THE DRAWINGS

[0025] Figure 1 , Figure 2 are the hydrogen spectrum and carbon spectrum of the target product obtained in Example 1;

[0026] Figure 3 , Figure 4 are the hydrogen spectrum and carbon spectrum of the target product obtained in Example 2;

[0027] Figure 5 , Figure 6 are the hydrogen spectrum and carbon spectrum of the target product obtained in Example 3;

[0028] Figure 7 , Figure 8 are the hydrogen spectrum and carbon spectrum of the target product obtained in Example 4;

[0029] Fig. 9 , Fig.10 are the hydrogen spectrum and carbon spectrum of the target product obtained in Example 5;

[0030] Fig.11 , Fig.12 are the hydrogen spectrum and carbon spectrum of the target product obtained in Example 6;

[0031] Fig.13 , Fig.14 are the hydrogen spectrum and carbon spectrum of the target product obtained in Example 7; DETAILED DESCRIPTION

[0032] The present invention is further described below by means of specific examples, but the protection scope and implementation modes of the present invention are not limited thereto.

[0033] Example 1

[0034] 0.1 mmol of imino(methyl)(phenyl)-λ 6 -thioketone, 0.2 mmol DABSO, 0.2 mmol tetrafluoroborate diazonium salt derivative, 0.1 mmol potassium carbonate and 0.01 mmol cuprous bromide, followed by the addition of 2 ml dichloroethane, nitrogen protection, stirring at 80 ° C for 12 hours, stopping the reaction, cooling to room temperature and filtering, the filtrate was extracted with ethyl acetate three times, the organic phases were combined and dried over anhydrous magnesium sulfate, filtered, and the crude product was obtained by vacuum rotary evaporation, and finally separated and purified by column chromatography, the column chromatography eluent used was a mixed solvent of petroleum ether and ethyl acetate (petroleum ether: ethyl acetate = 1:1). Pure 4-methoxy-N-(methyl (oxo) (phenyl)-λ 6 -sulfonamido)benzenesulfonamide in a yield of 76%.

[0035] The hydrogen and carbon spectra of the obtained target product are as follows Figure 1 and Figure 2 The structural characterization data are shown below:

[0036] 1 H NMR(500MHz,Chloroform-d)δ8.03(d,J=7.5Hz,2H),7.92(d,J=8.9Hz,2H),7.72(t,J =7.4Hz,1H),7.62(t,J=7.8Hz,2H),6.95(d,J=8.9Hz,2H),3.86(s,3H),3.44(s,3H);

[0037] 13 C NMR (125MHz, Chloroform-d) δ162.54,138.40,135.46,134.39,129.73,128.77,127.51,113.82,55.55,46.65;

[0038] HRMS(ESI)m / z:calcd for C 14 H 15 NO4S2[M+Na] + 348.0335; found 348.0338.

[0039] The structure of the target compound is inferred from the above characterization data as follows:

[0040]

[0041] Example 2

[0042] 0.1 mmol of imino(4-methoxyphenyl)(methyl)-λ 6 -thioketone, 0.2 mmol DABSO, 0.2 mmol tetrafluoroborate diazonium salt derivative, 0.1 mmol potassium carbonate, 0.01 mmol cuprous bromide, then add 2 ml dichloroethane, nitrogen protection, stir and react at 80 ° C for 12 hours, stop the reaction, cool to room temperature and filter, extract the filtrate with ethyl acetate three times, combine the organic phases and dry with anhydrous magnesium sulfate, filter, and evaporate under reduced pressure to obtain a crude product, which is finally separated and purified by column chromatography, and the column chromatography eluent used is a mixed solvent of petroleum ether and ethyl acetate (petroleum ether: ethyl acetate = 1:1). Pure 4-methoxy-N-((4-methoxyphenyl)(methyl)(oxo)-λ 6 -sulfonamido)benzenesulfonamide with a yield of 81%.

[0043] The hydrogen and carbon spectra of the obtained target product are as follows Figure 3 and Figure 4 The structural characterization data are shown below:

[0044] 1 H NMR(500MHz,Chloroform-d)δ7.93(dd,J=13.4,8.9Hz,4H),7.06(d,J=8.9Hz,2H),6.94(d,J=8.8Hz,2H),3.91(s,3H),3.86(s,3H),3.41(s,3H);

[0045] 13C NMR (125MHz, Chloroform-d) δ164.34,162.47,135.62,129.79,129.29,128.74,114.93,113.78,55.87,55.53,47.11;

[0046] HRMS(ESI)m / z:calcd for C 15 H 17 NO5S2[M+Na] + 378.0440; found 378.0444.

[0047] The structure of the target compound is inferred from the above characterization data as follows:

[0048]

[0049] Example 3

[0050] 0.1 mmol (4-fluorophenyl)(imino)(methyl)-λ 6 -thioketone, 0.2 mmol DABSO, 0.2 mmol tetrafluoroborate diazonium salt derivative, 0.1 mmol potassium carbonate, 0.01 mmol cuprous bromide, then add 2 ml dichloroethane, nitrogen protection, stir and react at 80 ° C for 12 hours, stop the reaction, cool to room temperature and filter, extract the filtrate with ethyl acetate three times, combine the organic phases and dry with anhydrous magnesium sulfate, filter, and evaporate under reduced pressure to obtain a crude product, which is finally separated and purified by column chromatography, and the column chromatography eluent used is a mixed solvent of petroleum ether and ethyl acetate (petroleum ether: ethyl acetate = 1:1). Pure N-((4-fluorophenyl)(methyl)(oxo)-λ 6 -sulfonamido)-4-methoxybenzenesulfonamide, the yield was 69%.

[0051] The hydrogen and carbon spectra of the obtained target product are as follows Figure 5 and Figure 6 The structural characterization data are shown below:

[0052] 1 H NMR (500MHz, Chloroform-d) δ8.08–8.03(m,2H),7.91(d,J=8.8Hz,2H),7.31(d,J=8.4Hz,2H),6.96(d,J=8.8Hz,2H),3.87(s,3H),3.44(s,3H);

[0053] 13C NMR (125MHz, Chloroform-d) δ165.21,162.65,135.30,134.29,130.63,130.55,128.79,117.25,117.07,113.87,55.57,46.87;

[0054] HRMS(ESI)m / z:calcd for C 14 H 14 FNO4S2[M+Na] + 366.0240; found 366.0251.

[0055] The structure of the target compound is inferred from the above characterization data as follows:

[0056]

[0057] Example 4

[0058] 0.1 mmol (4-chlorophenyl)(imino)(methyl)-λ 6 -thioketone, 0.2 mmol DABSO, 0.2 mmol tetrafluoroborate diazonium salt derivative, 0.1 mmol potassium carbonate, 0.01 mmol cuprous bromide, then add 2 ml dichloroethane, nitrogen protection, stir and react at 80 ° C for 12 hours, stop the reaction, cool to room temperature and filter, extract the filtrate with ethyl acetate three times, combine the organic phases and dry with anhydrous magnesium sulfate, filter, and evaporate under reduced pressure to obtain a crude product, and finally separate and purify by column chromatography, the column chromatography eluent used is a mixed solvent of petroleum ether and ethyl acetate (petroleum ether: ethyl acetate = 1:1). Pure N-((4-chlorophenyl)(methyl)(oxo)-λ 6 -sulfonamido)-4-methoxybenzenesulfonamide with a yield of 74%.

[0059] The hydrogen and carbon spectra of the obtained target product are as follows Figure 7 and Figure 8 The structural characterization data are shown below:

[0060] 1 H NMR (500MHz, Chloroform-d) δ7.97(d,J=8.6Hz,2H),7.90(d,J=8.8Hz,2H),7.59(d,J=8.6Hz,2H),6.95(d,J=8.8Hz,2H),3.87(s,3H),3.42(s,3H);

[0061] 13C NMR (125MHz, Chloroform-d) δ162.66,141.39,136.87,135.19,130.06,129.08,128.78,113.86,55.57,46.67;

[0062] HRMS(ESI)m / z:calcd for C 14 H 14 ClNO4S2[M+Na] + 381.9945; found 381.9952.

[0063] The structure of the target compound is inferred from the above characterization data as follows:

[0064]

[0065] Example 5

[0066] 0.1 mmol (4-bromophenyl)(imino)(methyl)-λ 6 -thioketone, 0.2 mmol DABSO, 0.2 mmol tetrafluoroborate diazonium salt derivative, 0.1 mmol potassium carbonate, 0.01 mmol cuprous bromide, then add 2 ml dichloroethane, nitrogen protection, stir and react at 80 ° C for 12 hours, stop the reaction, cool to room temperature and filter, extract the filtrate with ethyl acetate three times, combine the organic phases and dry with anhydrous magnesium sulfate, filter, and evaporate under reduced pressure to obtain a crude product, which is finally separated and purified by column chromatography, and the column chromatography eluent used is a mixed solvent of petroleum ether and ethyl acetate (petroleum ether: ethyl acetate = 1:1). Pure N-((4-bromophenyl)(methyl)(oxo)-λ 6 -sulfonamido)-4-methoxybenzenesulfonamide with a yield of 67%.

[0067] The hydrogen and carbon spectra of the obtained target product are as follows Fig. 9 and Fig.10 The structural characterization data are shown below:

[0068] 1 H NMR (500MHz, Chloroform-d) δ7.89(dd,J=8.6,4.1Hz,4H),7.76(d,J=8.5Hz,2H),6.95(d,J=8.8Hz,2H),3.87(s,3H),3.42(s,3H);

[0069] 13C NMR (125MHz, Chloroform-d) δ162.68,137.45,135.17,133.07,129.99,129.13,128.80,113.88,55.58,46.62;

[0070] HRMS(ESI)m / z:calcd for C 14 H 14 BrNO4S2[M+Na] + 425.9440; found 425.9442.

[0071] The structure of the target compound is inferred from the above characterization data as follows:

[0072]

[0073] Example 6

[0074] 0.1 mmol (4-iodophenyl)(imino)(methyl)-λ 6 -thioketone, 0.2 mmol DABSO, 0.2 mmol tetrafluoroborate diazonium salt derivative, 0.1 mmol potassium carbonate, 0.01 mmol cuprous bromide, then add 2 ml dichloroethane, nitrogen protection, stir and react at 80 ° C for 12 hours, stop the reaction, cool to room temperature and filter, extract the filtrate with ethyl acetate three times, combine the organic phases and dry with anhydrous magnesium sulfate, filter, and evaporate under reduced pressure to obtain a crude product, which is finally separated and purified by column chromatography, and the column chromatography eluent used is a mixed solvent of petroleum ether and ethyl acetate (petroleum ether: ethyl acetate = 1:1). Pure N-((4-iodophenyl)(methyl)(oxo)-λ 6 -sulfonamido)-4-methoxybenzenesulfonamide, the yield was 58%.

[0075] The hydrogen and carbon spectra of the obtained target product are as follows Fig.11 and Fig.12 The structural characterization data are shown below:

[0076] 1 H NMR (500MHz, Chloroform-d) δ7.98(d,J=8.4Hz,2H),7.89(d,J=8.8Hz,2H),7.72(d,J=8.5Hz,2H),6.95(d,J=8.8Hz,2H),3.87(s,3H),3.41(s,3H);

[0077] 13C NMR (125MHz, Chloroform-d) δ162.67,139.03,138.18,135.18,128.88,128.80,113.87,102.62,55.59,46.56;

[0078] HRMS(ESI)m / z:calcd for C 14 H 14 INO4S2[M+Na] + 473.9301; found 473.9304.

[0079] The structure of the target compound is inferred from the above characterization data as follows:

[0080]

[0081] Example 7

[0082] 0.1 mmol 4-(S-methylsulfonylimino)benzonitrile, 0.2 mmol DABSO, 0.2 mmol tetrafluoroborate diazonium salt derivative, 0.1 mmol potassium carbonate, 0.01 mmol cuprous bromide were added to the sealed tube in sequence, followed by 2 ml dichloroethane, nitrogen protection, stirring and reacting at 80°C for 12 hours, stopping the reaction, cooling to room temperature and filtering, extracting the filtrate with ethyl acetate three times, combining the organic phases and drying with anhydrous magnesium sulfate, filtering, and vacuum rotary evaporation to obtain a crude product, which was finally separated and purified by column chromatography, and the column chromatography eluent used was a mixed solvent of petroleum ether and ethyl acetate (petroleum ether: ethyl acetate = 1:1). Pure N-((4-cyanophenyl)(methyl)(oxo)-λ 6 -sulfonamido)-4-methoxybenzenesulfonamide with a yield of 62%.

[0083] The hydrogen and carbon spectra of the obtained target product are as follows Fig.13 and Fig.14 The structural characterization data are shown below:

[0084] 1 H NMR (500MHz, Chloroform-d) δ8.18(d,J=8.4Hz,2H),7.91(dd,J=18.9,8.6Hz,4H),6.97(d,J=8.9Hz,2H),3.88(s,3H),3.43(s,3H);

[0085] 13C NMR (125MHz, Chloroform-d) δ162.86,143.00,134.84,133.42,128.84,128.49,118.25,116.80,113.96,55.61,46.22;

[0086] HRMS(ESI)m / z:calcd for C 15 H 14 N2O4S2[M+H] + 351.0468; found 351.0478.

[0087] The structure of the target compound is inferred from the above characterization data as follows:

[0088]

[0089] Example 8

[0090] 0.1 mmol 4-(S-methylsulfonylimino)benzoic acid, 0.2 mmol DABSO, 0.2 mmol tetrafluoroborate diazonium salt derivative, 0.1 mmol potassium carbonate, 0.01 mmol cuprous bromide were added to the sealed tube in sequence, followed by 2 ml dichloroethane, nitrogen protection, stirring and reacting at 80°C for 12 hours, stopping the reaction, cooling to room temperature and filtering, extracting the filtrate with ethyl acetate three times, combining the organic phases and drying with anhydrous magnesium sulfate, filtering, and vacuum rotary evaporation to obtain a crude product, which was finally separated and purified by column chromatography, and the column chromatography eluent used was a mixed solvent of petroleum ether and ethyl acetate (petroleum ether: ethyl acetate = 1:1). Pure 4-(N-((4-methoxyphenyl)sulfonyl)-S-methylsulfonylimino)benzoic acid methyl ester was obtained with a yield of 65%.

[0091] The structural characterization data of the obtained target product are shown below:

[0092] 1 H NMR(500MHz,Chloroform-d)δ8.25(d,J=8.5Hz,2H),8.10(d,J=8.5Hz,2H),7.89 (d,J=8.8Hz,2H),6.94(d,J=8.8Hz,2H),3.99(s,3H),3.86(s,3H),3.44(s,3H);

[0093] 13 C NMR (125MHz, Chloroform-d) δ165.21,162.69,142.36,135.47,135.14,130.79,128.80,127.75,113.89,55.57,52.90,46.36;

[0094] HRMS(ESI)m / z:calcd for C 16 H 17 NO6S2[M+Na] + 406.0389; found 406.0389.

[0095] The structure of the target compound is inferred from the above characterization data as follows:

[0096]

[0097] Example 9

[0098] 0.1 mmol (4-acetylphenyl)(imino)(methyl)-λ 6 -thioketone, 0.2 mmol DABSO, 0.2 mmol tetrafluoroborate diazonium salt derivative, 0.1 mmol potassium carbonate, 0.01 mmol cuprous bromide, then add 2 ml dichloroethane, nitrogen protection, stir and react at 80 ° C for 12 hours, stop the reaction, cool to room temperature and filter, extract the filtrate with ethyl acetate three times, combine the organic phases and dry with anhydrous magnesium sulfate, filter, and evaporate under reduced pressure to obtain a crude product, and finally separate and purify by column chromatography, the column chromatography eluent used is a mixed solvent of petroleum ether and ethyl acetate (petroleum ether: ethyl acetate = 1:1). Pure N-((4-acetylphenyl)(methyl)(oxo)-λ 6 -sulfonamido)-4-methoxybenzenesulfonamide with a yield of 70%.

[0099] The structural characterization data of the obtained target product are shown below:

[0100] 1 H NMR (500MHz, Chloroform-d) δ8.14(t,J=6.3Hz,4H),7.90(d,J=8.8Hz,2H),6.95(d,J=8.8Hz,2H),3.87(s,3H),3.44(s,3H),2.69(s,3H);

[0101] 13 C NMR (125MHz, Chloroform-d) δ196.46,162.71,142.35,141.37,135.13,129.38,128.81,128.09,113.90,55.58,46.34,26.99;

[0102] HRMS(ESI)m / z:calcd for C 16 H 17 NO5S2[M+Na]+ 390.0440; found 390.0442.

[0103] The structure of the target compound is inferred from the above characterization data as follows:

[0104]

[0105] Example 10

[0106] 0.1 mmol of ethyl(imino)(phenyl)-λ 6 -thioketone, 0.2 mmol DABSO, 0.2 mmol tetrafluoroborate diazonium salt derivative, 0.1 mmol potassium carbonate, 0.01 mmol cuprous bromide, then add 2 ml dichloroethane, nitrogen protection, stir and react at 80 ° C for 12 hours, stop the reaction, cool to room temperature and filter, extract the filtrate with ethyl acetate three times, combine the organic phases and dry with anhydrous magnesium sulfate, filter, and evaporate under reduced pressure to obtain a crude product, and finally separate and purify by column chromatography, the column chromatography eluent used is a mixed solvent of petroleum ether and ethyl acetate (petroleum ether: ethyl acetate = 1:1). Pure N-(ethyl (oxy) (phenyl)-λ 6 -sulfonamido)-4-methoxybenzenesulfonamide with a yield of 72%.

[0107] The structural characterization data of the obtained target product are shown below:

[0108] 1 H NMR(500MHz,Chloroform-d)δ7.99(d,J=7.5Hz,2H),7.91(d,J=8.9Hz,2H),7.72(t,J=7.4Hz,1H),7 .62(t,J=7.8Hz,2H),6.93(d,J=8.9Hz,2H),3.86(s,3H),3.59–3.51(m,2H),1.28(t,J=7.3Hz,3H);

[0109] 13 C NMR (125MHz, Chloroform-d) δ162.46,135.94,135.72,134.34,129.60,128.75,128.47,113.76,55.53,52.84,7.45;

[0110] HRMS(ESI)m / z:calcd for C 15 H 17 NO4S2[M+Na] + 362.0491; found 362.0500.

[0111] The structure of the target compound is inferred from the above characterization data as follows:

[0112]

[0113] Embodiment 11

[0114] 0.1 mmol of benzyl(imino)(phenyl)-λ 6 -thioketone, 0.2 mmol DABSO, 0.2 mmol tetrafluoroborate diazonium salt derivative, 0.1 mmol potassium carbonate, 0.01 mmol cuprous bromide, then add 2 ml dichloroethane, nitrogen protection, stir and react at 80°C for 12 hours, stop the reaction, cool to room temperature and filter, extract the filtrate with ethyl acetate three times, combine the organic phases and dry with anhydrous magnesium sulfate, filter, and evaporate under reduced pressure to obtain a crude product, which is finally separated and purified by column chromatography, and the column chromatography eluent used is a mixed solvent of petroleum ether and ethyl acetate (petroleum ether: ethyl acetate = 1:1). Pure N-(benzyl(oxo)(phenyl)-λ6-sulfonamido)-4-methoxybenzenesulfonamide is obtained with a yield of 68%.

[0115] The structural characterization data of the obtained target product are shown below:

[0116] 1 H NMR(500MHz,Chloroform-d)δ7.94(d,J=8.9Hz,2H),7.64(d,J=8.1Hz,3H),7.45(t,J=7.9Hz,2H),7.33(d,J=7 .5Hz,1H),7.23(t,J=7.6Hz,2H),7.02(d,J=7.3Hz,2H),6.94(d,J=8.9Hz,2H),4.90–4.77(m,2H),3.86(s,3H);

[0117] 13 C NMR (125MHz, Chloroform-d) δ162.49,135.76,134.83,134.31,131.41,129.41,129.08,128.85,128.78,128.63,126.64,113.79,64.67,55.54;

[0118] HRMS(ESI)m / z:calcd for C 20 H 19 NO4S2[M+Na] + 424.0648; found 424.0647.

[0119] The structure of the target compound is inferred from the above characterization data as follows:

[0120]

[0121] Example 12

[0122] 0.1 mmol of cyclopropyl(imino)(phenyl)-λ 6 -thioketone, 0.2 mmol DABSO, 0.2 mmol tetrafluoroborate diazonium salt derivative, 0.1 mmol potassium carbonate, 0.01 mmol cuprous bromide, then add 2 ml dichloroethane, nitrogen protection, stir and react at 80 ° C for 12 hours, stop the reaction, cool to room temperature and filter, extract the filtrate with ethyl acetate three times, combine the organic phases and dry with anhydrous magnesium sulfate, filter, and evaporate under reduced pressure to obtain a crude product, and finally separate and purify by column chromatography, the column chromatography eluent used is a mixed solvent of petroleum ether and ethyl acetate (petroleum ether: ethyl acetate = 1:1). Pure N-(cyclopropyl(oxo)(phenyl)-λ 6 -sulfonamido)-4-methoxybenzenesulfonamide, the yield was 61%.

[0123] The structural characterization data of the obtained target product are shown below:

[0124] 1 H NMR(500MHz,Chloroform-d)δ7.96(d,J=7.7Hz,2H),7.86(d,J=8.5Hz,2H),7.69(t,J=7.1Hz,1H),7.59 (t,J=7.5Hz,2H),6.92(d,J=8.5Hz,2H),3.86(s,3H),2.74(s,1H),1.24(d,J=29.6Hz,3H),1.02(s,1H);

[0125] 13 C NMR (125MHz, Chloroform-d) δ162.42,138.76,135.73,133.99,129.56,128.73,127.78,113.73,55.55,35.16,7.41,6.34;

[0126] HRMS(ESI)m / z:calcd for C 16 H 17 NO4S2[M+Na] + 374.0491; found 374.0494.

[0127] The structure of the target compound is inferred from the above characterization data as follows:

[0128]

[0129] Embodiment 13

[0130] 0.1 mmol of imino(methyl)(thiophene-3-yl)-λ 6 -thioketone, 0.2 mmol DABSO, 0.2 mmol tetrafluoroborate diazonium salt derivative, 0.1 mmol potassium carbonate, 0.01 mmol cuprous bromide, then add 2 ml dichloroethane, nitrogen protection, stir and react at 80 ° C for 12 hours, stop the reaction, cool to room temperature and filter, extract the filtrate with ethyl acetate three times, combine the organic phases and dry with anhydrous magnesium sulfate, filter, and evaporate under reduced pressure to obtain a crude product, which is finally separated and purified by column chromatography, and the column chromatography eluent used is a mixed solvent of petroleum ether and ethyl acetate (petroleum ether: ethyl acetate = 1:1). Pure 4-methoxy-N-(methyl(oxo)(thiophen-3-yl)-λ 6 -sulfonamido)benzenesulfonamide in 45% yield.

[0131] The structural characterization data of the obtained target product are shown below:

[0132] 1 H NMR (500MHz, Chloroform-d) δ8.22(s,1H),7.91(d,J=8.8Hz,2H),7.52(s,1H),7.46(d,J=5.1Hz,1H),6.95(d,J=8.8Hz,2H),3.87(s,3H),3.48(s,3H);

[0133] 13 C NMR (125MHz, Chloroform-d) δ162.57,137.89,135.35,133.32,129.14,128.77,125.50,113.83,55.56,47.07;

[0134] HRMS(ESI)m / z:calcd for C 12 H 13 NO4S3[M+Na] + 353.9899; found 353.9900.

[0135] The structure of the target compound is inferred from the above characterization data as follows:

[0136]

[0137] Embodiment 14

[0138] 0.1 mmol (3-fluorophenyl)(imino)(methyl)-λ 6 -thioketone, 0.2 mmol DABSO, 0.2 mmol tetrafluoroborate diazonium salt derivative, 0.1 mmol potassium carbonate, 0.01 mmol cuprous bromide, then add 2 ml dichloroethane, nitrogen protection, stir and react at 80 ° C for 12 hours, stop the reaction, cool to room temperature and filter, extract the filtrate with ethyl acetate three times, combine the organic phases and dry with anhydrous magnesium sulfate, filter, and evaporate under reduced pressure to obtain a crude product, which is finally separated and purified by column chromatography, and the column chromatography eluent used is a mixed solvent of petroleum ether and ethyl acetate (petroleum ether: ethyl acetate = 1:1). Pure N-((3-fluorophenyl)(methyl)(oxo)-λ 6 -sulfonamido)-4-methoxybenzenesulfonamide, the yield was 66%.

[0139] The structural characterization data of the obtained target product are shown below:

[0140] 1 H NMR(500MHz,Chloroform-d)δ7.91(d,J=8.9Hz,2H),7.84(d,J=7.9Hz,1H),7.73(d,J=7.7Hz,1 H),7.65–7.60(m,1H),7.42(t,J=8.1Hz,1H),6.96(d,J=8.9Hz,2H),3.87(s,3H),3.44(s,3H);

[0141] 13 C NMR (125MHz, Chloroform-d) δ163.59,162.70,140.53,135.16,131.68,128.82,123.44,121.86,115.26,113.89,55.58,46.51;

[0142] HRMS(ESI)m / z:calcd for C 14 H 14 FNO4S2[M+Na] + 366.0240; found 366.0244.

[0143] The structure of the target compound is inferred from the above characterization data as follows:

[0144]

[0145] 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 that do not deviate 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 synthesizing an N-sulfonyl sulfoximine derivative, characterized in that: The following steps are included: In a glass reaction container, a copper catalyst, a sulfoximine compound, DABSO, a tetrafluoroborate diazonium salt derivative, a base and a solvent are added, and the mixture is stirred and reacted at 80° C. for 12 hours under nitrogen protection. The crude product can be separated and purified to obtain an N-sulfonyl sulfoximine compound; The above reaction is shown in the following formula: In the formula, R 1 is selected from the group consisting of hydrogen, 4-methyl, 4-methoxy, 4-fluoro, 4-chloro, 4-bromo, 4-iodo, 4-cyano, 4-ester, 4-acetyl, 3-fluoro, 3-chloro, 3-bromo, 2-fluoro, 2-chloro, and 2-bromo; R is selected from the group consisting of methyl, ethyl, benzyl, and cyclopropyl; R 2 It is one of 2-methyl-4-methoxy, 2-bromo-4-methoxy, 3-chloro-4-methoxy, 3-bromo-4-methoxy, and 3-iodo-4-methoxy; the copper catalyst is one or more of cuprous bromide and cuprous cyanide; the solvent is ethylene dichloride; and the base is one or more of cesium pivalate, cesium carbonate, sodium trifluoromethanesulfonate, sodium carbonate, potassium carbonate, and sodium acetate.

2. The method for synthesizing an N-sulfonyl sulfoximine derivative according to claim 1, characterized in that: The molar ratio of the copper catalyst to the sulfoximine compound is 0.1:

1.

3. The method for synthesizing an N-sulfonyl sulfoximine derivative according to claim 1, characterized in that: The molar ratio of the sulfoximine derivative to DABSO and the tetrafluoroborate diazonium salt compound is 1:2:

2.

4. The method for synthesizing an N-sulfonyl sulfoximine derivative according to claim 1, characterized in that: The molar ratio of the base to the sulfoximine compound is 1.0-2.0:

1.

5. The method for synthesizing an N-sulfonyl sulfoximine derivative according to claim 1, characterized in that: The crude product is separated by column chromatography using ethyl acetate and petroleum ether as eluents.

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