Method for catalytic synthesis of sulfoximine guanidine compound by cobalt dichloride

Abstract

The invention discloses a method for catalytic synthesis of sulfoximine guanidine compounds by cobalt dichloride, which realizes efficient preparation of the sulfoximine guanidine compounds by taking cobalt dichloride as a catalyst and through free radical coupling reaction of sulfoximine compounds, isonitrile compounds and sulfonyl azide compounds. The method can effectively protect high-valence thioguanidyl, has the advantages of mild reaction conditions, high synthesis efficiency and strong substrate universality, and has extremely high practical application value.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of organic synthesis, and particularly relates to a method for synthesizing sulfoximine guanidine compounds catalyzed by cobalt dichloride. BACKGROUND

[0002] Guanidino group is a kind of pharmacophore with extremely high application value in the field of biological medicine, which has excellent biological activity and unique pharmacological effect, and is widely distributed in various natural active molecules and artificially synthesized bioactive compounds, such as arginine in natural amino acids, guanine in nucleic acid components, and sulfaguanidine, a commonly used antibacterial drug in clinic. Guanidino group has strong alkalinity and can exist stably in the form of protonated cation in a physiological pH environment. This charged characteristic enables it to realize efficient binding with biological targets such as enzymes and receptors through ionic interaction, which is the key structural basis for guanidine compounds to exhibit a wide range of biological activities, and provides important molecular skeleton support for the research and development of drugs for anti-infection, anti-tumor, immune regulation and other types of drugs.

[0003] Traditional guanidine compound synthesis methods mainly include liquid phase synthesis and solid phase synthesis. These methods generally have many limitations: first, the reaction conditions are harsh, often requiring extreme environments such as high temperature, high pressure or strong oxidizing agents / reducing agents, which not only consumes more energy, but also easily leads to an increase in by-products; second, the synthesis steps are complicated, most routes require multiple protection and deprotection operations, which prolongs the synthesis cycle and reduces the overall yield; third, the substrate range is limited, and the compatibility of substrates with complex functional groups or special structures is poor, which is difficult to meet the diversified needs of drug research and development; fourth, the catalysts used are mostly noble metal catalysts, which are expensive and difficult to obtain, and are not conducive to large-scale production.

[0004] Sulfoximine guanidine compounds have both sulfoximine structural characteristics and guanidino biological activity, but their synthesis process not only faces the common problems of traditional guanidine synthesis, such as harsh conditions, complicated steps, narrow substrate range, and expensive catalysts, but also has the special problem of easily damaged high-valent sulfur guanidine group, which seriously hinders its research and application. Therefore, developing a synthesis method for sulfoximine guanidine compounds that is mild in conditions, efficient in reaction, strong in substrate adaptability, and can effectively protect the high-valent sulfur guanidine group has become a technical problem to be solved in the fields of biological medicine and organic synthesis. SUMMARY

[0005] The present application aims to solve the above technical problems, and provides a method for synthesizing sulfoximine guanidine compounds catalyzed by cobalt dichloride, which uses cobalt dichloride (CoCl2) as a catalyst to realize efficient preparation of sulfoximine guanidine compounds through free radical coupling reaction of sulfoximine compounds, isonitrile compounds and sulfonyl azide compounds.

[0006] The above object of the present application is achieved by the following technical solutions.

[0007] A method for synthesizing a sulfoximine guanidine compound catalyzed by cobalt dichloride, comprising the following steps:

[0008] In an organic solvent, a sulfoximine compound, an isonitrile compound and a sulfonyl azide compound are used as reaction substrates, and a free radical coupling reaction occurs under the catalysis of cobalt dichloride (CoCl2), to obtain the sulfoximine guanidine compound.

[0009] The sulfoximine compound has the following structural formula: ; wherein R1 is selected from one or more of hydrogen, fluorine, chlorine, bromine, methyl, methoxy, cyano, nitro, pyridyl and benzyl; and R2 is methyl, phenyl, cyclopropane or allyl.

[0010] The isonitrile compound has the following structural formula: ; wherein R3 is tert-butyl, cyclohexyl, adamantyl, 3,4-dimethylphenyl, p-chlorophenyl, p-ethoxyphenyl, m-fluorophenyl or p-methylphenylsulfonylmethyl.

[0011] The sulfonyl azide compound has the following structural formula: ; wherein R4 is selected from one or more of hydrogen, fluorine, bromine, chlorine, methyl, 2,4,6-methyl, n-butyl, tert-butyl, methoxy, nitro, cyano, ethyl, trifluoromethyl, benzyl, pyridyl, cyclohexyl, naphthyl, quinolinyl, 2,3-dihydro-1H-inden-5-yl and 2,3-dihydrobenzo[b][1,4]dioxane-6-yl.

[0012] The cobalt dichloride used in the present application is an air-stable crystalline water-free catalyst, which can maintain catalytic activity without inert gas protection, greatly simplifying the operation process and reducing costs compared to traditional noble metal catalytic systems which require nitrogen / argon protection.

[0013] Further, the organic solvent is selected from one or more of acetonitrile (MeCN), dimethyl sulfoxide (DMSO), N,N-dimethylformamide (DMF), dichloromethane (DCM) and N-methyl pyrrolidone (NMP).

[0014] Further, the sulfoximine compound is S,S-diphenylsulfoximine, S-methyl-S-phenyl sulfoximine, 4-(S-methylsulfonylimidoyl)benzonitrile, imino(methyl)(4-nitrophenyl)-λ 6- Sulfone, S-(4-methylphenyl)-S-phenylsulfoximine, S-methyl-S-(4- fluorophenyl)sulfoximine, S-methyl-S-(4-chlorophenyl)sulfoximine, S-methyl-S-(4- bromophenyl)sulfoximine, S-methyl-S-(4-methoxyphenyl)sulfoximine, S-methyl-S-(4- methylphenyl)sulfoximine, S-methyl-S-(2-pyridyl)sulfoximine, (2-hydroxyethyl)(imino)(phenyl)- lambda 6 - Sulfone, S-(4-methylphenyl)-S-phenylsulfoximine, S-methyl-S-(4- fluorophenyl)sulfoximine, S-methyl-S-(4-chlorophenyl)sulfoximine, S-methyl-S-(4- bromophenyl)sulfoximine, S-methyl-S-(4-methoxyphenyl)sulfoximine, S-methyl-S-(4- methylphenyl)sulfoximine, S-methyl-S-(2-pyridyl)sulfoximine, (2-hydroxyethyl)(imino)(phenyl)- lambda 6 - Sulfone, S-(4-methylphenyl)-S-phenylsulfoximine, S-methyl-S-(4- fluorophenyl)sulfoximine, S-methyl-S-(4-chlorophenyl)sulfoximine, S-methyl-S-(4- bromophenyl)sulfoximine, S-methyl-S-(4-methoxyphenyl)sulfoximine, S-methyl-S-(4- methylphenyl)sulfoximine, S-methyl-S-(2-pyridyl)sulfoximine, (2-hydroxyethyl)(imino)(phenyl)- lambda

[0015] Further, the isocyanide compound is tert-butyl isocyanide, p-tolylsulfonylmethyl isocyanide, 4-nitrophenyl isocyanide, 4-chlorophenyl isocyanide, 3-fluorophenyl isocyanide, 4- ethoxyphenyl isocyanate, 1-adamantyl isocyanide, cyclohexyl isocyanide, 3,4-dimethylphenyl isocyanate, or 2-isocyano-1,1'-biphenyl.

[0016] Further, the sulfonyl azide compound is phenylsulfonyl azide, p-tolylsulfonyl azide, p- ethylphenylsulfonyl azide, p-tert-butylphenylsulfonyl azide, p-n-butylphenylsulfonyl azide, 2,4,6- trimethylphenylsulfonyl azide, p-methoxyphenylsulfonyl azide, p-nitrophenylsulfonyl azide, p- trifluoromethylphenylsulfonyl azide, p-cyanophenylsulfonyl azide, p-chlorophenylsulfonyl azide, p- bromophenylsulfonyl azide, 3-fluorophenylsulfonyl azide, phenylmethanesulfonyl azide, cyclohexylsulfonyl azide, [1,1'-biphenyl]-4-sulfonyl azide, naphthalene-2-sulfonyl azide, naphthalene-1- sulfonyl azide, quinoline-8-sulfonyl azide, pyridine-3-sulfonyl azide, 2,3-dihydro-1H-indene-5- sulfonyl azide, or 2,3-dihydrobenzo[b][1,4]dioxan-6-sulfonyl azide.

[0017] Further, the molar ratio of the cobalt dichloride, the sulfoximine compound, the isocyanide compound, and the sulfonyl azide compound is (0.05-0.1):(1-1.2):(1.2-1.5):(1.5-2).

[0018] In one embodiment of the present application, the molar ratio of the cobalt dichloride and the sulfoximine compound is (0.05-0.1):1.

[0019] In one embodiment of the present application, the molar ratio of the isocyanide compound and the sulfoximine compound is (1.2-1.5):1.

[0020] In an embodiment of the present application, the molar ratio of the sulfonyl azide compound to the sulfoximine compound is (1.2-1.5):1.

[0021] Further, the free radical coupling reaction is carried out in an air atmosphere.

[0022] Further, the temperature of the free radical coupling reaction is 70-90 ℃.

[0023] Further, the time of the free radical coupling reaction is 6-8 h.

[0024] Further, after the free radical coupling reaction is completed, one or more of the following steps are further included: filtering, concentrating and purifying.

[0025] In an embodiment of the present application, the sulfoximine guanidine compound is (E)-N-(N'-(tert-butyl)-N-(oxodiphenyl-λ 6 The sulfoximine guanidine compound has a complete high-valence sulfur guanidine group structure and excellent biological activity adaptability.

[0026] The above technical solution of the present application has the following beneficial effects compared with the prior art:

[0027] The present application provides a method for synthesizing a sulfoximine guanidine compound catalyzed by cobalt dichloride, which uses air-stable cobalt dichloride as a catalyst to drive the free radical coupling reaction of a sulfoximine compound, an isocyanide compound and a sulfonyl azide compound, and successfully prepares the sulfoximine guanidine compound. This method not only realizes the efficient construction of the target product, but also effectively protects the high-valence sulfur guanidine group, and has the significant advantages of mild reaction conditions, high synthesis efficiency, strong substrate universality, and high practical application value. BRIEF DESCRIPTION OF DRAWINGS

[0028] Figure 1 A reaction catalytic cycle diagram for synthesizing a sulfoximine guanidine compound catalyzed by cobalt dichloride. DETAILED DESCRIPTION

[0029] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this application belongs. The terminology used in the description herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the application. As used herein, the term "and / or" includes any and all combinations of one or more of the associated listed items.

[0030] The present application provides a method for synthesizing a sulfoximine guanidine compound catalyzed by cobalt dichloride, which includes the following steps:

[0031] The sulfoximine guanidine compound is obtained by a free radical coupling reaction of a sulfoximine compound, an isonitrile compound and a sulfonyl azide compound in an organic solvent under the catalysis of cobalt dichloride (CoCl2).

[0032] In an embodiment of the present application, the catalytic cycle of the reaction for synthesizing the sulfoximine guanidine compound catalyzed by cobalt dichloride is shown as follows: Figure 1 First, cobalt dichloride (CoCl2) coordinates with acetonitrile (MeCN) to form an active species A ([CoCl2(MeCN)2]), and then an isonitrile compound (R3-NC) is combined with the cobalt center to form an intermediate B ([CoCl2(R3-NC)2]) through ligand exchange; under the activation of the cobalt species, a sulfonyl azide compound undergoes N2 dissociation to form a cobalt(III)-nitrene intermediate C, which is converted into a species E through a transition state D by intramolecular rearrangement; then, a sulfoximine compound coordinates with the species E to form an intermediate F, and the intermediate F further reacts with the isonitrile compound to regenerate the intermediate B (complete catalytic cycle) and obtain an intermediate G; finally, the intermediate G is dehydrogenated and aromatized to form the target product, the sulfoximine guanidine compound H.

[0033] In an embodiment of the present application, the reaction equation for synthesizing the sulfoximine guanidine compound catalyzed by cobalt dichloride is as follows:

[0034] ;

[0035] wherein R1 is selected from one or more of hydrogen, fluorine, chlorine, bromine, methyl, methoxy, cyano, nitro, pyridyl and benzyl; R2 is methyl, phenyl, cyclopropane or allyl; R3 is tert-butyl, cyclohexyl, adamantyl, 3,4-dimethylphenyl, p-chlorophenyl, p-ethoxyphenyl, m-fluorophenyl or p-methylphenylsulfonylmethyl; and R4 is selected from one or more of hydrogen, fluorine, bromine, chlorine, methyl, 2,4,6-methyl, n-butyl, tert-butyl, methoxy, nitro, cyano, ethyl, trifluoromethyl, benzyl, pyridyl, cyclohexyl, naphthyl, quinolyl, 2,3-dihydro-1H-inden-5-yl and 2,3-dihydrobenzo[b][1,4]dioxan-6-yl.

[0036] In an embodiment of the present application, the sulfoximine compound is prepared by the following method:

[0037] The sulfide (1.0 eq), iodobenzenedicarboxylic acid (2.5 eq) and ammonium carbamate (2.0 eq) are added to a flask equipped with a stirrer. Methanol (MeOH, 0.5 mol) is added, and the reaction is stirred at 25°C for 3 hours, and the solvent is removed under reduced pressure. The sulfoximine compound is purified by flash chromatography, and the yield is 80%-95%.

[0038] Specifically, the reaction equation for synthesizing the sulfoximine compound is as follows:

[0039] ;

[0040] wherein R1 is selected from one or more of hydrogen, fluorine, chlorine, bromine, methyl, methoxy, cyano, nitro, pyridyl, and benzyl; and R2 is methyl, phenyl, cyclopropane, or allyl.

[0041] In one embodiment of the present application, the isonitrile compound is prepared by the following method:

[0042] (1) The amino compound (1 equivalent) and a mixed solution of diethyl ether (Et2O) and n-hexane (1:1) are added into a sealed tube and cooled to 0 °C. Methyl acetoacetate prepared by reacting acetic anhydride (Ac2O, 2.5 equivalents) and formic acid (HCOOH, 2.5 equivalents) in a heating module at 55 °C for 2 hours is added dropwise into the solution of the amino compound at 0 °C, and the mixture is warmed to room temperature and stirred for 0.5 hours. Then, the mixture is quenched with saturated aqueous sodium bicarbonate solution and extracted with dichloromethane three times. The combined organic extracts are dried with anhydrous Na2SO4, filtered, concentrated under vacuum, and subjected to the next step without purification.

[0043] (2) Tetrahydrofuran (THF), triethylamine (Et3N, 4.0 equivalents), and the product of the previous step are added under a nitrogen atmosphere and cooled to 0 °C. Phosphorus oxychloride (POCl3, 1.5 equivalents) is added dropwise, and the mixture is stirred at 0 °C for 1 hour. Then, the mixture is quenched with saturated aqueous NaHCO3 solution and stirred for 1 hour, extracted with dichloromethane three times. The combined organic extracts are dried with anhydrous Na2SO4, filtered, and subjected to a series of operations such as concentration under reduced pressure and silica gel column chromatography to obtain the isonitrile compound with a yield of 80-89%.

[0044] Specifically, the reaction equation for synthesizing the isonitrile compound is as follows:

[0045] ;

[0046] wherein R3 is tert-butyl, cyclohexyl, adamantyl, 3,4-dimethylphenyl, p-chlorophenyl, p-ethoxyphenyl, m-fluorophenyl, or p-methylphenylsulfonylmethyl.

[0047] In one embodiment of the present application, the sulfonyl azide compound is prepared by the following method:

[0048] The substituted sulfonyl hydrazide (1 eq.) was stirred in acetonitrile at room temperature and tert-butyl nitrite (TBN, 2 eq.) was added. The progress of the reaction was monitored by TLC. After completion of the reaction, it was extracted with dichloromethane three times and the solvent was removed under reduced pressure. The sulfonyl azide compound was purified by flash chromatography with 85-92% yield.

[0049] Specifically, the reaction equation for synthesizing the sulfonyl azide compound is as follows:

[0050] ;

[0051] wherein R4 is selected from one or more of hydrogen, fluorine, bromine, chlorine, methyl, 2,4,6-methyl, n-butyl, t-butyl, methoxy, nitro, cyano, ethyl, trifluoromethyl, benzyl, pyridyl, cyclohexyl, naphthyl, quinolyl, 2,3-dihydro-lH-inden-5-yl and 2,3-dihydrobenzo[b][l,4]dioxan-6-yl.

[0052] The present application is further described below in conjunction with the accompanying drawings and specific examples so that those skilled in the art can better understand and implement the present application, but the examples are not intended to limit the present application.

[0053] The experimental methods used in the following examples are conventional methods unless otherwise specified, and the materials, reagents, etc. used are commercially available unless otherwise specified.

[0054] Example 1

[0055] A method for catalytically synthesizing (E)-N-(N'-(tert-butyl)-N-(oxodiphenyl-λ 6 - thioimino)ureido)-4-methylbenzenesulfonamide with cobalt dichloride includes the following steps:

[0056] ;

[0057] In air, S,S-diphenylsulfinimidamide (109 mg, 0.5 mmol), tert-butyl isocyanide (65 μL, 0.6 mmol), p-toluenesulfonyl azide (120 μL, 0.75 mmol) and cobalt dichloride (3 mg, 0.025 mmol) were charged into a dried screw-capped 20 mL vial with a magnetic stir bar, and acetonitrile (3 mL) was added. The reaction mixture was heated at 80 °C (metal bath heater) and stirred for 6 h. The crude reaction product was diluted with dichloromethane (20 mL) and washed with water (20 mL x 3). The organic layer was dried over Na2S04, filtered and concentrated. The residue was purified by flash chromatography (eluent: petroleum ether / ethyl acetate = 2 / 1) to give the product (E)-N-(N'-(tert-butyl)-N-(methyl(oxo(diphenyl-λ 6 - sulfenylimido)ureido)-4-methylbenzenesulfonamide as a white solid in 88% yield.

[0058] The product was dissolved in deuterated chloroform (CDC13) (about 0.4 mL), sealed, and measured at room temperature on a BRUKER AVANCE III HD-400 liquid superconducting nuclear magnetic resonance spectrometer, and the characterization data were: 1 H NMR (400 MHz, CDC13) δ 7.83 (d, J = 8.0 Hz, 4H), 7.68 (s, 1H), 7.60 - 7.37 (m, 6H), 7.29 (d, J = 7.9 Hz, 2H), 7.00 (d, J = 7.9 Hz, 2H), 2.31 (s, 3H), 1.46 (s, 9H); 13 C NMR (101 MHz, CDC13) δ 157.4, 141.24, 140.7, 140.1, 133.2, 129.5, 128.8, 127.2, 125.7, 52.5, 29.6, 21.4.

[0059] Example 2

[0060] A method for the cobalt dichloride catalyzed synthesis of (E)-N-(N'-(tert-butyl)-N-(methyl(oxo(diphenyl-λ 6 - sulfenylimido)ureido)-4-methylbenzenesulfonamide, comprising the following steps:

[0061] In air, S-methyl-S-phenyl sulfoxide imine (77.5 mg, 0.5 mmol), tert-butylisocyanate (65 μL, 0.6 mmol), p-toluenesulfonyl azide (120 μL, 0.75 mmol), and cobalt dichloride (3 mg, 0.025 mmol) were placed into a dried 20 mL vial with a screw cap and a magnetic stir bar, and acetonitrile (3 mL) was added. The reaction mixture was heated at 80 °C (metal bath heater) and stirred for 6 h. The crude reaction mixture was diluted with dichloromethane (20 mL) and washed with water (20 mL × 3). The organic layer was dried over Na₂SO₄, filtered, and concentrated. The residue was purified by rapid chromatography (eluent: petroleum ether / ethyl acetate = 2 / 1) to give a white solid product (E)-N-(N'-(tert-butyl)-N-(methyl(oxy)(phenyl)-λ) 6 (-thioimino)ureo)-4-methylbenzenesulfonamide, yield 83%.

[0062] The product was dissolved in CDCl3 (approximately 0.4 mL), sealed in a tube, and analyzed at room temperature using a BRUKER AVANCEIII HD-400 liquid superconducting nuclear magnetic resonance spectrometer. The characterization data are as follows: 1 H NMR (400 MHz, CDCl3) δ 7.86 – 7.78(m, 2H), 7.66 – 7.59 (m, 1H), 7.57 (s, 1H), 7.54 – 7.45 (m, 4H), 7.10 (d, J =8.0 Hz, 2H), 3.35 (s, 3H), 2.35 (s, 3H), 1.37 (s, 9H); 13 C NMR (101 MHz, CDCl3)δ 157.3, 141.4, 140.8, 139.0, 133.6, 130.4, 129.6, 128.9, 126.8, 125.8, 52.5, 45.4, 29.5, 21.4.

[0063] Example 3

[0064] A cobalt dichloride-catalyzed synthesis of (E)-N-(N'-(tert-butyl)-N-(oxy(phenyl)(p-methylphenyl)-λ) 6 A method for (-thioimino)ureo)-4-methylbenzenesulfonamide includes the following steps:

[0065] In air, S-(4-methylphenyl)-S-phenyl sulfoxide imine (115.5 mg, 0.5 mmol), tert-butylisocyanate (65 μL, 0.6 mmol), p-toluenesulfonyl azide (120 μL, 0.75 mmol), and cobalt dichloride (3 mg, 0.025 mmol) were placed into a dried 20 mL vial with a screw cap and a magnetic stir bar, and acetonitrile (3 mL) was added. The reaction mixture was heated at 80 °C (metal bath heater) and stirred for 6 h. The crude reaction mixture was diluted with dichloromethane (20 mL) and washed with water (20 mL × 3). The organic layer was dried over Na₂SO₄, filtered, and concentrated. The residue was purified by rapid chromatography (eluent: petroleum ether / ethyl acetate = 2 / 1) to give a white solid product (E)-N-(N'-(tert-butyl)-N-(oxy(phenyl)(p-methylphenyl)-λ) 6 (-thioimino)ureo)-4-methylbenzenesulfonamide, yield 92%.

[0066] The product was dissolved in CDCl3 (approximately 0.4 mL), sealed in a tube, and analyzed at room temperature using a BRUKER AVANCEIII HD-400 liquid superconducting nuclear magnetic resonance spectrometer. The characterization data are as follows: 1 H NMR (400 MHz, CDCl3) δ 7.83 (d, J =7.8 Hz, 2H), 7.72 (d, J = 8.0 Hz, 2H), 7.66 (s, 1H), 7.51 (t, J = 7.1 Hz,1H), 7.43 (t, J = 7.6 Hz, 2H), 7.35 (d, J = 7.9 Hz, 2H), 7.22 (d, J = 8.1 Hz, 2H), 7.03 (d, J = 7.9 Hz, 2H), 2.37 (s, 3H), 2.35 (s, 3H), 1.48 (s, 9H); 13 CNMR (101 MHz, CDCl3) δ 157.3, 144.0, 141.1, 140.6, 132.9, 130.1, 129.4,128.7, 127.4, 127.2, 125.9, 52.5, 29.7, 21.6, 21.4.

[0067] Example 4

[0068] A cobalt dichloride-catalyzed synthesis of (E)-N-(N'-(tert-butyl)-N-((4-fluorophenyl)(methyl)(oxy)-λ 6 A method for (-thioimino)ureo)-4-methylbenzenesulfonamide includes the following steps:

[0069] In air, S-methyl-S-(4-fluorophenyl)sulfinylimide (86.5 mg, 0.5 mmol), tert-butylisocyanate (65 μL, 0.6 mmol), p-toluenesulfonyl azide (120 μL, 0.75 mmol), and cobalt dichloride (3 mg, 0.025 mmol) were placed into a dried 20 mL vial with a screw cap and a magnetic stir bar, and acetonitrile (3 mL) was added. The reaction mixture was heated at 80 °C (metal bath heater) and stirred for 6 h. The crude reaction mixture was diluted with dichloromethane (20 mL) and washed with water (20 mL × 3). The organic layer was dried over Na₂SO₄, filtered, and concentrated. The residue was purified by rapid chromatography (eluent: petroleum ether / ethyl acetate = 2 / 1) to give a white solid product (E)-N-(N'-(tert-butyl)-N-((4-fluorophenyl)(methyl)(oxy)-λ) 6 (-thioimino)ureo)-4-methylbenzenesulfonamide, yield 91%.

[0070] The product was dissolved in CDCl3 (approximately 0.4 mL), sealed in a tube, and analyzed at room temperature using a BRUKER AVANCEIII HD-400 liquid superconducting nuclear magnetic resonance spectrometer. The characterization data are as follows: 1 H NMR (400 MHz, CDCl3) δ 7.68 (ddt, J= 6.9, 4.9, 2.2 Hz, 2H), 7.55 (s, 1H), 7.48 – 7.30 (m, 2H), 7.01 (ddd, J =11.5, 6.8, 2.2 Hz, 4H), 3.23 (d, J = 2.1 Hz, 3H), 2.29 (d, J = 1.8 Hz, 3H), 1.31 (d, J = 1.8 Hz, 9H); 13 C NMR (101 MHz, CDCl3) δ 166.8, 164.2, 156.9,141.6, 140.8, 134.8 (d, J = 3.2 Hz), 129.6, 129.6, 128.9, 125.7, 52.5, 45.6,29.5, 21.4; 19 F NMR (376 MHz, CDCl3) δ -103.74.

[0071] Example 5

[0072] A cobalt dichloride-catalyzed synthesis of (E)-N-(N'-(tert-butyl)-N-((4-methoxyphenyl)(methyl)(oxy)-λ6 A method for (-thioimino)ureo)-4-methylbenzenesulfonamide includes the following steps:

[0073] In air, S-methyl-S-(4-methoxyphenyl)sulfinylimide (92.5 mg, 0.5 mmol), tert-butylisocyanate (65 μL, 0.6 mmol), p-toluenesulfonyl azide (120 μL, 0.75 mmol), and cobalt dichloride (3 mg, 0.025 mmol) were placed into a dried 20 mL vial with a screw cap and a magnetic stir bar, and acetonitrile (3 mL) was added. The reaction mixture was heated at 80 °C (metal bath heater) and stirred for 6 h. The crude reaction mixture was diluted with dichloromethane (20 mL) and washed with water (20 mL × 3). The organic layer was dried over Na₂SO₄, filtered, and concentrated. The residue was purified by rapid chromatography (eluent: petroleum ether / ethyl acetate = 2 / 1) to give a white solid product (E)-N-(N'-(tert-butyl)-N-((4-methoxyphenyl)(methyl)(oxy)-λ) 6 (-thioimino)ureo)-4-methylbenzenesulfonamide, yield 89%.

[0074] The product was dissolved in CDCl3 (approximately 0.4 mL), sealed in a tube, and analyzed at room temperature using a BRUKER AVANCEIII HD-400 liquid superconducting nuclear magnetic resonance spectrometer. The characterization data are as follows: 1 H NMR (400 MHz, CDCl3) δ 7.69 (d, J =8.6 Hz, 2H), 7.56 (s, 1H), 7.50 (d, J = 7.9 Hz, 2H), 7.07 (d, J = 7.9 Hz, 2H), 6.90 (d, J = 8.8 Hz, 2H), 3.83 (s, 3H), 3.31 (s, 3H), 2.32 (s, 3H), 1.33 (s, 9H); 13 C NMR (101 MHz, CDCl3) δ 163.6, 157.3, 141.4, 140.9, 130.1, 128.9, 128.8, 125.8, 114.8, 55.8, 52.4, 45.8, 29.5, 21.4.

[0075] Example 6

[0076] A cobalt dichloride-catalyzed synthesis of (E)-N-(N'-(tert-butyl)-N-(methyl(oxy)(p-tolyl)-λ 6 A method for (-thioimino)ureo)-4-methylbenzenesulfonamide includes the following steps:

[0077] In air, S-methyl-S-(4-methylphenyl)sulfinylimide (84.5 mg, 0.5 mmol), tert-butylisocyanate (65 μL, 0.6 mmol), p-toluenesulfonyl azide (120 μL, 0.75 mmol), and cobalt dichloride (3 mg, 0.025 mmol) were placed into a dried 20 mL vial with a screw cap and a magnetic stir bar, and acetonitrile (3 mL) was added. The reaction mixture was heated at 80 °C (metal bath heater) and stirred for 6 h. The crude reaction mixture was diluted with dichloromethane (20 mL) and washed with water (20 mL × 3). The organic layer was dried over Na₂SO₄, filtered, and concentrated. The residue was purified by rapid chromatography (eluent: petroleum ether / ethyl acetate = 2 / 1) to give a white solid product (E)-N-(N'-(tert-butyl)-N-(methyl(oxy)(p-tolyl)-λ) 6 -Thioimino)ureo)-4-methylbenzenesulfonamide, yield 96%.

[0078] The product was dissolved in CDCl3 (approximately 0.4 mL), sealed in a tube, and analyzed at room temperature using a BRUKER AVANCEIII HD-400 liquid superconducting nuclear magnetic resonance spectrometer. The characterization data are as follows: 1 H NMR (400 MHz, CDCl3) δ 7.58 (d, J =8.4 Hz, 2H), 7.49 (s, 1H), 7.38 (d, J = 8.1 Hz, 2H), 7.17 (d, J = 8.1 Hz, 2H), 7.00 (d, J = 7.9 Hz, 2H), 3.23 (s, 3H), 2.32 (s, 3H), 2.26 (s, 3H), 1.28 (s, 9H); 13 C NMR (101 MHz, CDCl3) δ 157.3, 144.5, 141.3, 140.9, 135.9, 130.1,128.8, 126.8, 125.8, 52.4, 45.5, 29.4, 21.6, 21.4.

[0079] Example 7

[0080] A cobalt dichloride-catalyzed synthesis of (E)-N-(N'-(tert-butyl)-N-(methyl(oxy)(2-pyridyl)-λ 6 A method for (-thioimino)ureo)-4-methylbenzenesulfonamide includes the following steps:

[0081] In air, S-methyl-S-(2-pyridyl)sulfinylimide (78 mg, 0.5 mmol), tert-butylisocyanate (65 μL, 0.6 mmol), p-toluenesulfonyl azide (120 μL, 0.75 mmol), and cobalt dichloride (3 mg, 0.025 mmol) were placed into a dried 20 mL vial with a screw cap and a magnetic stir bar, and acetonitrile (3 mL) was added. The reaction mixture was heated at 80 °C (metal bath heater) and stirred for 6 h. The crude reaction mixture was diluted with dichloromethane (20 mL) and washed with water (20 mL × 3). The organic layer was dried over Na₂SO₄, filtered, and concentrated. The residue was purified by rapid chromatography (eluent: petroleum ether / ethyl acetate = 2 / 1) to give a white solid product (E)-N-(N'-(tert-butyl)-N-(methyl(oxy)(2-pyridyl)-λ) 6 (-thioimino)ureo)-4-methylbenzenesulfonamide, yield 80%.

[0082] The product was dissolved in CDCl3 (approximately 0.4 mL), sealed in a tube, and analyzed at room temperature using a BRUKER AVANCEIII HD-400 liquid superconducting nuclear magnetic resonance spectrometer. The characterization data are as follows: 1 H NMR (400 MHz, CDCl3) δ 8.55 – 8.50(m, 1H), 8.10 (dt, J = 8.0, 1.1 Hz, 1H), 7.82 (td, J = 7.8, 1.7 Hz, 1H), 7.44(d, J = 8.0 Hz, 4H), 7.09 (d, J = 7.9 Hz, 2H), 3.38 (s, 3H), 2.34 (s, 3H), 1.34 (s, 9H); 13 C NMR (101 MHz, CDCl3) δ 156.9, 149.4, 141.4, 140.9, 137.9, 128.8, 127.0, 125.8, 123.8, 52.6, 40.6, 29.4, 21.4.

[0083] Example 8

[0084] A cobalt dichloride-catalyzed synthesis of (E)-N-(N'-(tert-butyl)-N-(cyclopropyl(oxidized)(phenyl)-λ) 6 A method for (-thioimino)ureo)-4-methylbenzenesulfonamide includes the following steps:

[0085] In air, S-cyclopropyl-S-phenyl-sulfonyl oxime (90.5 mg, 0.5 mmol), tert-butylisocyanate (65 μL, 0.6 mmol), p-toluenesulfonyl azide (120 μL, 0.75 mmol), and cobalt dichloride (3 mg, 0.025 mmol) were placed into a dried 20 mL vial with a screw cap and a magnetic stir bar, and acetonitrile (3 mL) was added. The reaction mixture was heated at 80 °C (metal bath heater) and stirred for 6 h. The crude reaction mixture was diluted with dichloromethane (20 mL) and washed with water (20 mL × 3). The organic layer was dried over Na₂SO₄, filtered, and concentrated. The residue was purified by rapid chromatography (eluent: petroleum ether / ethyl acetate = 2 / 1) to give a white solid product (E)-N-(N'-(tert-butyl)-N-(cyclopropyl(oxidized)(phenyl)-λ) 6 (-thioimino)ureo)-4-methylbenzenesulfonamide, yield 88%.

[0086] The product was dissolved in CDCl3 (approximately 0.4 mL), sealed in a tube, and analyzed at room temperature using a BRUKER AVANCEIII HD-400 liquid superconducting nuclear magnetic resonance spectrometer. The characterization data are as follows: 1 H NMR (400 MHz, CDCl3) δ 7.71 (d, J =7.8 Hz, 2H), 7.55 (dd, J = 15.4, 8.0 Hz, 2H), 7.43 (t, J = 7.7 Hz, 2H), 7.31 (d, J = 7.7 Hz, 2H), 7.02 (d, J = 7.9 Hz, 2H), 2.67 (td, J = 7.8, 3.9 Hz,1H), 2.34 (s, 3H), 1.51 (dd, J = 8.8, 4.3 Hz, 1H), 1.39 (s, 9H), 1.20 (dd, J= 10.2, 5.0 Hz, 2H), 0.98 (dd, J = 7.7, 4.3 Hz, 1H); 13 C NMR (101 MHz, CDCl3) δ157.0, 141.1, 140.8, 139.4, 132.9, 129.4, 128.7, 126.9, 125.7, 52.4, 34.1, 29.5, 21.4.

[0087] Example 9

[0088] A cobalt dichloride-catalyzed synthesis of (E)-N-(N'-(tert-butyl)-N-(dibenzyl(oxy)-λ) 6A method for (-thioimino)ureo)-4-methylbenzenesulfonamide includes the following steps:

[0089] In air, S,S-bis(benzyl)-sulfonamide (122.5 mg, 0.5 mmol), tert-butylisocyanate (65 μL, 0.6 mmol), p-toluenesulfonyl azide (120 μL, 0.75 mmol), and cobalt dichloride (3 mg, 0.025 mmol) were placed into a dried 20 mL vial with a screw cap and a magnetic stir bar, and acetonitrile (3 mL) was added. The reaction mixture was heated at 80 °C (metal bath heater) and stirred for 6 h. The crude reaction mixture was diluted with dichloromethane (20 mL) and washed with water (20 mL × 3). The organic layer was dried over Na₂SO₄, filtered, and concentrated. The residue was purified by rapid chromatography (eluent: petroleum ether / ethyl acetate = 2 / 1) to give a white solid product (E)-N-(N'-(tert-butyl)-N-(dibenzyl(oxy)-λ) 6 (-thioimino)ureo)-4-methylbenzenesulfonamide, yield 90%.

[0090] The product was dissolved in CDCl3 (approximately 0.4 mL), sealed in a tube, and analyzed at room temperature using a BRUKER AVANCEIII HD-400 liquid superconducting nuclear magnetic resonance spectrometer. The characterization data are as follows: 1 H NMR (400 MHz, CDCl3) δ 7.90 (d, J =8.3 Hz, 2H), 7.59 (s, 1H), 7.33 – 7.25 (m, 8H), 7.21 (dt, J = 6.8, 1.6 Hz,4H), 4.76 (d, J = 13.3 Hz, 2H), 4.64 (d, J = 13.3 Hz, 2H), 2.35 (s, 3H), 1.09 (s, 9H); 13 C NMR (101 MHz, CDCl3) δ 155.8, 142.2, 141.0, 131.5, 129.4, 129.3, 128.8, 126.3, 126.0, 57.5, 52.4, 29.0, 21.5.

[0091] Example 10

[0092] A cobalt dichloride-catalyzed synthesis of (E)-N-(N'-(4-chlorophenyl)-N-(oxodiphenyl-λ) 6 A method for (-thioimino)aminourea)-4-methylbenzenesulfonamide includes the following steps:

[0093] In air, S,S-diphenylsulfinylimide (109 mg, 0.5 mmol), 4-chlorophenyl isocyanate (82.2 mg, 0.6 mmol), p-toluenesulfonyl azide (120 μL, 0.75 mmol), and cobalt dichloride (3 mg, 0.025 mmol) were placed into a dried 20 mL vial with a screw cap and a magnetic stir bar, and acetonitrile (3 mL) was added. The reaction mixture was heated at 80 °C (metal bath heater) and stirred for 6 h. The crude reaction mixture was diluted with dichloromethane (20 mL) and washed with water (20 mL × 3). The organic layer was dried over Na₂SO₄, filtered, and concentrated. The residue was purified by rapid chromatography (eluent: petroleum ether / ethyl acetate = 2 / 1) to give a white solid product (E)-N-(N'-(4-chlorophenyl)-N-(oxodiphenyl-λ) 6 -Thioimino)aminourea)-4-methylbenzenesulfonamide, yield 86%.

[0094] The product was dissolved in CDCl3 (approximately 0.4 mL), sealed in a tube, and analyzed at room temperature using a BRUKER AVANCEIII HD-400 liquid superconducting nuclear magnetic resonance spectrometer. The characterization data are as follows: 1 H NMR (400 MHz, CDCl3) δ 9.45 (s,1H), 7.80 (d, J = 7.8 Hz, 4H), 7.52 (t, J = 7.4 Hz, 2H), 7.47 – 7.36 (m, 8H),7.32 (d, J = 8.9 Hz, 2H), 7.07 (d, J = 8.0 Hz, 2H), 2.36 (s, 3H); 13 C NMR (101MHz, CDCl3) δ 155.3, 141.7, 139.4, 136.2, 133.4, 130.7, 129.5, 129.0, 128.8,127.5, 125.9, 124.9, 21.5.

[0095] Example 11

[0096] A cobalt dichloride-catalyzed synthesis of (E)-N-(N'-(3-fluorophenyl)-N-(oxodiphenyl-λ) 6 A method for (-thioimino)ureo)-4-methylbenzenesulfonamide includes the following steps:

[0097] In air, S,S-diphenylsulfinylimide (109 mg, 0.5 mmol), 3-fluorophenyl isocyanate (72.6 mg, 0.6 mmol), p-toluenesulfonyl azide (120 μL, 0.75 mmol), and cobalt dichloride (3 mg, 0.025 mmol) were placed into a dried 20 mL vial with a screw cap and a magnetic stir bar, and acetonitrile (3 mL) was added. The reaction mixture was heated at 80 °C (metal bath heater) and stirred for 6 h. The crude reaction mixture was diluted with dichloromethane (20 mL) and washed with water (20 mL × 3). The organic layer was dried over Na₂SO₄, filtered, and concentrated. The residue was purified by rapid chromatography (eluent: petroleum ether / ethyl acetate = 2 / 1) to give a white solid product (E)-N-(N'-(3-fluorophenyl)-N-(oxodiphenyl-λ) 6 (-thioimino)ureo)-4-methylbenzenesulfonamide, yield 74%.

[0098] The product was dissolved in CDCl3 (approximately 0.4 mL), sealed in a tube, and analyzed at room temperature using a BRUKER AVANCEIII HD-400 liquid superconducting nuclear magnetic resonance spectrometer. The characterization data are as follows: 1 H NMR (400 MHz, CDCl3) δ 9.56 (s,1H), 7.83 (d, J = 7.8 Hz, 4H), 7.52 (t, J = 7.4 Hz, 2H), 7.42 (t, J = 7.8 Hz,6H), 7.38 – 7.27 (m, 2H), 7.15 – 7.03 (m, 3H), 6.89 (td, J = 8.3, 2.5 Hz, 1H), 2.35 (s, 3H); 13 C NMR (101 MHz, CDCl3) δ 161.5, 155.1, 141.8, 140.2,139.3, 139.2, 139.1, 133.4, 130.0, 129.9, 129.5, 129.0, 127.5, 125.8, 118.7,112.0, 111.8, 110.8, 110.6, 21.4; 19 F NMR (376 MHz, CDCl3) δ -111.87.

[0099] Example 12

[0100] A cobalt dichloride-catalyzed synthesis of (E)-N-(N'-(4-ethoxyphenyl)-N-(oxodiphenyl-λ) 6A method for (-thioimino)ureo)-4-methylbenzenesulfonamide includes the following steps:

[0101] In air, S,S-diphenylsulfinylimide (109 mg, 0.5 mmol), 4-ethoxyphenyl isocyanate (88.2 mg, 0.6 mmol), p-toluenesulfonyl azide (120 μL, 0.75 mmol), and cobalt dichloride (3 mg, 0.025 mmol) were placed into a dried 20 mL vial with a screw cap and a magnetic stir bar, and acetonitrile (3 mL) was added. The reaction mixture was heated at 80 °C (metal bath heater) and stirred for 6 h. The crude reaction mixture was diluted with dichloromethane (20 mL) and washed with water (20 mL × 3). The organic layer was dried over Na₂SO₄, filtered, and concentrated. The residue was purified by rapid chromatography (eluent: petroleum ether / ethyl acetate = 2 / 1) to give a white solid product (E)-N-(N'-(4-ethoxyphenyl)-N-(oxodiphenyl-λ) 6 -Thioimino)ureo)-4-methylbenzenesulfonamide, yield 87%.

[0102] The product was dissolved in CDCl3 (approximately 0.4 mL), sealed in a tube, and analyzed at room temperature using a BRUKER AVANCEIII HD-400 liquid superconducting nuclear magnetic resonance spectrometer. The characterization data are as follows: 1 H NMR (400 MHz, CDCl3) δ 9.29 (s,1H), 7.75 (d, J = 7.8 Hz, 4H), 7.48 (t, J = 7.4 Hz, 2H), 7.38 (q, J = 7.8 Hz,6H), 7.33 – 7.27 (m, 2H), 7.04 (d, J = 7.9 Hz, 2H), 6.90 (d, J = 8.5 Hz, 2H), 4.04 (q, J = 7.0 Hz, 2H), 2.34 (s, 3H), 1.42 (t, J = 7.0 Hz, 3H); 13 C NMR (101MHz, CDCl3) δ 156.9, 156.2, 141.6, 140.5, 139.6, 133.2, 130.3, 129.5, 128.9,127.6, 125.9, 125.8, 114.5, 63.8, 21.4.

[0103] Example 13

[0104] A cobalt dichloride-catalyzed synthesis of 4-methyl-N-((E)-N'-((3aS,5R,7aR)-octahydro-2H-2,5-methyleneinden-2-yl)-N-(oxodiphenyl-λ) 6 The method for thioimino)ureo)benzenesulfonamide includes the following steps:

[0105] In air, S,S-diphenylsulfinylimide (109 mg, 0.5 mmol), 1-adamantaneisocyanate (96.7 mg, 0.6 mmol), p-toluenesulfonyl azide (120 μL, 0.75 mmol), and cobalt dichloride (3 mg, 0.025 mmol) were placed into a dried 20 mL vial with a screw cap and a magnetic stir bar, and acetonitrile (3 mL) was added. The reaction mixture was heated at 80 °C (metal bath heater) and stirred for 6 h. The crude reaction mixture was diluted with dichloromethane (20 mL) and washed with water (20 mL × 3). The organic layer was dried over Na₂SO₄, filtered, and concentrated. The residue was purified by rapid chromatography (eluent: petroleum ether / ethyl acetate = 2 / 1) to give a white solid product, 4-methyl-N-((E)-N'-((3aS,5R,7aR)-octahydro-2H-2,5-methyleneinden-2-yl)-N-(oxodiphenyl-λ) 6 -Thioimino)ureo)benzenesulfonamide, yield 85%.

[0106] The product was dissolved in CDCl3 (approximately 0.4 mL), sealed in a tube, and analyzed at room temperature using a BRUKER AVANCEIII HD-400 liquid superconducting nuclear magnetic resonance spectrometer. The characterization data are as follows: 1 H NMR (400 MHz, CDCl3) δ 7.85 (d, J =7.8 Hz, 4H), 7.52 (dd, J = 18.3, 10.8 Hz, 4H), 7.42 (t, J = 7.7 Hz, 4H), 7.32(d, J = 7.9 Hz, 2H), 7.01 (d, J = 7.9 Hz, 2H), 2.33 (s, 4H), 2.13 (s, 9H), 1.68 (t, J = 10.0 Hz, 6H); 13 C NMR (101 MHz, CDCl3) δ 156.8, 141.1, 140.8,140.3, 133.0, 129.4, 128.7, 127.4, 125.8, 53.1, 42.2, 36.3, 29.5, 21.4.

[0107] Example 14

[0108] A cobalt dichloride-catalyzed synthesis of (E)-N-(N'-(3,4-dimethylphenyl)-N-(oxodiphenyl-λ) 6 A method for (-thioimino)ureo)-4-methylbenzenesulfonamide includes the following steps:

[0109] In air, S,S-diphenylsulfinylimide (109 mg, 0.5 mmol), 3,4-dimethylphenyl isocyanate (78.6 mg, 0.6 mmol), p-toluenesulfonyl azide (120 μL, 0.75 mmol), and cobalt dichloride (3 mg, 0.025 mmol) were placed into a dried 20 mL vial with a screw cap and a magnetic stir bar, and acetonitrile (3 mL) was added. The reaction mixture was heated at 80 °C (metal bath heater) and stirred for 6 h. The crude reaction mixture was diluted with dichloromethane (20 mL) and washed with water (20 mL × 3). The organic layer was dried over Na₂SO₄, filtered, and concentrated. The residue was purified by rapid chromatography (eluent: petroleum ether / ethyl acetate = 2 / 1) to give a white solid product (E)-N-(N'-(3,4-dimethylphenyl)-N-(oxodiphenyl-λ) 6 (-thioimino)ureo)-4-methylbenzenesulfonamide, yield 90%.

[0110] The product was dissolved in CDCl3 (approximately 0.4 mL), sealed in a tube, and analyzed at room temperature using a BRUKER AVANCEIII HD-400 liquid superconducting nuclear magnetic resonance spectrometer. The characterization data are as follows: 1 H NMR (400 MHz, CDCl3) δ 9.42 (s,1H), 7.82 (d, J = 7.9 Hz, 4H), 7.54 – 7.48 (m, 2H), 7.40 (t, J = 7.7 Hz, 6H), 7.24 (d, J = 2.2 Hz, 1H), 7.18 (dd, J = 8.1, 2.3 Hz, 1H), 7.13 (d, J = 8.1Hz, 1H), 7.06 (d, J = 8.0 Hz, 2H), 2.35 (s, 3H), 2.27 (s, 6H); 13 C NMR (101MHz, CDCl3) δ 141.5, 140.6, 139.7, 137.1, 135.3, 133.8, 133.2, 129.8, 129.4,128.9, 127.7, 125.9, 124.8, 121.0, 21.5, 19.86, 19.31.

[0111] Example 15

[0112] A cobalt dichloride-catalyzed synthesis of (E)-N-(N'-([1,1'-biphenyl]-2-yl)-N-(oxodiphenyl-λ) 6 A method for (-thioimino)ureo)-4-methylbenzenesulfonamide includes the following steps:

[0113] In air, S,S-diphenylsulfinylimide (109 mg, 0.5 mmol), 2-isocyano-1,1'-biphenyl (107.4 mg, 0.6 mmol), p-toluenesulfonyl azide (120 μL, 0.75 mmol), and cobalt dichloride (3 mg, 0.025 mmol) were placed into a dried 20 mL vial with a screw cap and a magnetic stir bar, and acetonitrile (3 mL) was added. The reaction mixture was heated at 80 °C (metal bath heater) and stirred for 6 h. The crude reaction mixture was diluted with dichloromethane (20 mL) and washed with water (20 mL × 3). The organic layer was dried over Na₂SO₄, filtered, and concentrated. The residue was purified by rapid chromatography (eluent: petroleum ether / ethyl acetate = 2 / 1) to give a white solid product (E)-N-(N'-([1,1'-biphenyl]-2-yl)-N-(oxodiphenyl-λ) 6 (-thioimino)ureo)-4-methylbenzenesulfonamide, yield 80%.

[0114] The product was dissolved in CDCl3 (approximately 0.4 mL), sealed in a tube, and analyzed at room temperature using a BRUKER AVANCEIII HD-400 liquid superconducting nuclear magnetic resonance spectrometer. The characterization data are as follows: 1 H NMR (400 MHz, CDCl3) δ 9.29 (s,1H), 7.60 – 7.14 (m, 21H), 6.98 (d, J = 7.8 Hz, 2H), 2.36 (s, 3H); 13 C NMR (101MHz, CDCl3) δ 141.3, 140.6, 139.5, 138.7, 134.8, 132.9, 130.5, 129.2, 129.2,128.8, 128.7, 128.0, 127.6, 127.4, 125.9, 21.5.

[0115] Example 16

[0116] A cobalt dichloride-catalyzed synthesis of (E)-N-(N'-cyclohexyl-N-(oxodiphenyl-λ) 6 A method for (-thionyl)aminomidinyl)-4-methylbenzenesulfonamide includes the following steps:

[0117] In air, S,S-diphenylsulfinylimide (109 mg, 0.5 mmol), cyclohexylisocyanate (75 μL, 0.6 mmol), p-toluenesulfonyl azide (120 μL, 0.75 mmol), and cobalt dichloride (3 mg, 0.025 mmol) were placed into a dried 20 mL vial with a screw cap and a magnetic stir bar, and acetonitrile (3 mL) was added. The reaction mixture was heated at 80 °C (metal bath heater) and stirred for 6 h. The crude reaction mixture was diluted with dichloromethane (20 mL) and washed with water (20 mL × 3). The organic layer was dried over Na₂SO₄, filtered, and concentrated. The residue was purified by rapid chromatography (eluent: petroleum ether / ethyl acetate = 2 / 1) to give a white solid product (E)-N-(N'-cyclohexyl-N-(oxodiphenyl-λ) 6 (-thioimino)aminoamidinyl)-4-methylbenzenesulfonamide, yield 82%.

[0118] The product was dissolved in CDCl3 (approximately 0.4 mL), sealed in a tube, and analyzed at room temperature using a BRUKER AVANCEIII HD-400 liquid superconducting nuclear magnetic resonance spectrometer. The characterization data are as follows: 1 H NMR (400 MHz, CDCl3) δ 7.83 (d, J =7.8 Hz, 4H), 7.52 (q, J = 11.0, 7.1 Hz, 3H), 7.43 (d, J = 7.7 Hz, 4H), 7.33(d, J = 7.8 Hz, 2H), 7.01 (d, J = 7.9 Hz, 2H), 3.92 (d, J = 9.8 Hz, 1H), 2.33(s, 3H), 2.00 (d, J = 11.4 Hz, 2H), 1.75 (d, J = 11.1 Hz, 2H), 1.61 (d, J =12.9 Hz, 1H), 1.37 (d, J = 9.7 Hz, 5H); 13 C NMR (101 MHz, CDCl3) δ 156.9,141.1, 140.8, 140.1, 133.0, 129.4, 128.7, 127.5, 125.8, 51.7, 33.1, 25.5,24.5, 21.4.

[0119] Example 17

[0120] A cobalt dichloride-catalyzed synthesis of (E)-4-methyl-N-(N-(oxodiphenyl-λ) 6A method for (-thioimino)-N'-(p-toluenesulfonylmethyl)ureo)benzenesulfonamide includes the following steps:

[0121] In air, S,S-diphenylsulfinylimide (109 mg, 0.5 mmol), p-toluenesulfonylmethylisocyanate (92 μL, 0.6 mmol), p-toluenesulfonyl azide (120 μL, 0.75 mmol), and cobalt dichloride (3 mg, 0.025 mmol) were placed into a dried 20 mL vial with a screw cap and a magnetic stir bar, and acetonitrile (3 mL) was added. The reaction mixture was heated at 80 °C (metal bath heater) and stirred for 6 h. The crude reaction mixture was diluted with dichloromethane (20 mL) and washed with water (20 mL × 3). The organic layer was dried over Na₂SO₄, filtered, and concentrated. The residue was purified by rapid chromatography (eluent: petroleum ether / ethyl acetate = 2 / 1) to give a white solid product (E)-4-methyl-N-(N-(oxodiphenyl-λ) 6 -Thioimino)-N'-(p-toluenesulfonylmethyl)ureo)benzenesulfonamide, yield 79%.

[0122] The product was dissolved in CDCl3 (approximately 0.4 mL), sealed in a tube, and analyzed at room temperature using a BRUKER AVANCEIII HD-400 liquid superconducting nuclear magnetic resonance spectrometer. The characterization data are as follows: 1 H NMR (400 MHz, CDCl3) δ 8.15 (t, J =6.8 Hz, 1H), 7.93 (dd, J = 7.6, 1.7 Hz, 4H), 7.70 (d, J = 8.2 Hz, 2H), 7.57 –7.51 (m, 2H), 7.45 (dd, J = 8.5, 6.9 Hz, 4H), 7.35 – 7.25 (m, 5H), 7.08 (d, J= 8.0 Hz, 2H), 4.90 (d, J = 6.9 Hz, 2H), 2.41 (d, J = 15.9 Hz, 6H); 13 C NMR(101 MHz, CDCl3) δ 156.9, 145.6, 141.8, 139.9, 139.3, 134.0, 133.3, 130.2,129.5, 128.9, 128.8, 127.6, 125.9, 63.6, 21.8, 21.5.

[0123] Example 18

[0124] A cobalt dichloride-catalyzed synthesis of (E)-N-(N'-(tert-butyl)-N-(oxodiphenyl-λ) 6 The method for thioimino)ureo)benzenesulfonamide includes the following steps:

[0125] In air, S,S-diphenylsulfinylimide (109 mg, 0.5 mmol), tert-butylisocyanate (65 μL, 0.6 mmol), phenylsulfonyl azide (137.3 mg, 0.75 mmol), and cobalt dichloride (3 mg, 0.025 mmol) were placed into a dried 20 mL vial with a screw cap and a magnetic stir bar, and acetonitrile (3 mL) was added. The reaction mixture was heated at 80 °C (metal bath heater) and stirred for 6 h. The crude reaction mixture was diluted with dichloromethane (20 mL) and washed with water (20 mL × 3). The organic layer was dried over Na₂SO₄, filtered, and concentrated. The residue was purified by rapid chromatography (eluent: petroleum ether / ethyl acetate = 2 / 1) to give a white solid product (E)-N-(N'-(tert-butyl)-N-(oxodiphenyl-λ) 6 -Thioimino)ureo)benzenesulfonamide, yield 83%.

[0126] The product was dissolved in CDCl3 (approximately 0.4 mL), sealed in a tube, and analyzed at room temperature using a BRUKER AVANCEIII HD-400 liquid superconducting nuclear magnetic resonance spectrometer. The characterization data are as follows: 1 H NMR (400 MHz, CDCl3) δ 7.83 (d, J =7.8 Hz, 4H), 7.66 (s, 1H), 7.50 (t, J = 7.4 Hz, 2H), 7.42 (t, J = 7.5 Hz, 6H), 7.34 (t, J = 7.5 Hz, 1H), 7.21 (t, J = 7.6 Hz, 2H), 1.47 (s, 9H); 13 C NMR (101 MHz, CDCl3) δ 157.4, 143.544, 140.2, 133.2, 130.9, 129.5, 128.2, 127.3, 125.8, 52.6, 29.7.

[0127] Example 19

[0128] A cobalt dichloride-catalyzed synthesis of (E)-4-(tert-butyl)-N-(N'-(tert-butyl)-N-(oxodiphenyl-λ) 6 The method for thioimino)ureo)benzenesulfonamide includes the following steps:

[0129] In air, S,S-diphenylsulfinylimide (109 mg, 0.5 mmol), tert-butylisocyanate (65 μL, 0.6 mmol), p-tert-butylbenzenesulfonyl azide (179.3 mg, 0.75 mmol), and cobalt dichloride (3 mg, 0.025 mmol) were placed into a dried 20 mL vial with a screw cap and a magnetic stir bar, and acetonitrile (3 mL) was added. The reaction mixture was heated at 80 °C (metal bath heater) and stirred for 6 h. The crude reaction mixture was diluted with dichloromethane (20 mL) and washed with water (20 mL × 3). The organic layer was dried over Na₂SO₄, filtered, and concentrated. The residue was purified by rapid chromatography (eluent: petroleum ether / ethyl acetate = 2 / 1) to give a white solid product (E)-4-(tert-butyl)-N-(N'-(tert-butyl)-N-(oxodiphenyl-λ) 6 -Thioimino)ureo)benzenesulfonamide, yield 82%.

[0130] The product was dissolved in CDCl3 (approximately 0.4 mL), sealed in a tube, and analyzed at room temperature using a BRUKER AVANCEIII HD-400 liquid superconducting nuclear magnetic resonance spectrometer. The characterization data are as follows: 1 H NMR (400 MHz, CDCl3) δ 7.81 (d, J =7.9 Hz, 4H), 7.70 (s, 1H), 7.46 (t, J = 7.4 Hz, 2H), 7.36 (dd, J = 20.1, 7.9Hz, 6H), 7.19 (d, J = 8.2 Hz, 2H), 1.45 (s, 9H), 1.26 (s, 9H); 13 C NMR (101MHz, CDCl3) δ 157.3, 154.1, 140.7, 140.1, 133.1, 129.5, 127.3, 125.5, 125.1,52.5, 34.8, 31.2, 29.7.

[0131] Example 20

[0132] A method for synthesizing (E)-N-(N'-(tert-butyl)-N-(diphenyloxythioimino)ureo)-2,4,6-trimethylbenzenesulfonamide catalyzed by cobalt dichloride includes the following steps:

[0133] In air, S,S-diphenylsulfinylimide (109 mg, 0.5 mmol), tert-butylisocyanate (65 μL, 0.6 mmol), 2,4,6-trimethylphenylsulfonyl azide (168.9 mg, 0.75 mmol), and cobalt dichloride (3 mg, 0.025 mmol) were placed into a dried 20 mL vial with a screw cap and a magnetic stir bar, and acetonitrile (3 mL) was added. The reaction mixture was heated at 80 °C (metal bath heater) and stirred for 6 h. The crude reaction mixture was diluted with dichloromethane (20 mL) and washed with water (20 mL × 3). The organic layer was dried over Na₂SO₄, filtered, and concentrated. The residue was purified by rapid chromatography (eluent: petroleum ether / ethyl acetate = 2 / 1) to give a white solid product (E)-N-(N'-(tert-butyl)-N-(diphenyloxythioimino)ureido)-2,4,6-trimethylbenzenesulfonamide in 80% yield.

[0134] The product was dissolved in CDCl3 (approximately 0.4 mL), sealed in a tube, and analyzed at room temperature using a BRUKER AVANCEIII HD-400 liquid superconducting nuclear magnetic resonance spectrometer. The characterization data are as follows: 1 H NMR (400 MHz, CDCl3) δ 7.75 (d, J =7.8 Hz, 4H), 7.61 (s, 1H), 7.36 (d, J = 7.1 Hz, 2H), 7.30 (t, J = 7.6 Hz,5H), 6.67 (s, 2H), 2.41 (s, 7H), 2.21 (s, 3H), 1.50 (s, 9H); 13 C NMR (101 MHz, CDCl3) δ 156.3, 140.1, 139.8, 137.8, 132.8, 131.0, 129.2, 129.2, 127.9, 127.0, 52.5, 29.8, 22.7, 20.8.

[0135] Example 21

[0136] A cobalt dichloride-catalyzed synthesis of (E)-N-(N'-(tert-butyl)-N-(oxodiphenyl-λ) 6 A method for using (-thioimino)ureo)-4-nitrobenzenesulfonamide includes the following steps:

[0137] In air, S,S-diphenylsulfinylimide (109 mg, 0.5 mmol), tert-butylisocyanate (65 μL, 0.6 mmol), p-nitrobenzenesulfonyl azide (171 mg, 0.75 mmol), and cobalt dichloride (3 mg, 0.025 mmol) were placed into a dried 20 mL vial with a screw cap and a magnetic stir bar, and acetonitrile (3 mL) was added. The reaction mixture was heated at 80 °C (metal bath heater) and stirred for 6 h. The crude reaction mixture was diluted with dichloromethane (20 mL) and washed with water (20 mL × 3). The organic layer was dried over Na₂SO₄, filtered, and concentrated. The residue was purified by rapid chromatography (eluent: petroleum ether / ethyl acetate = 2 / 1) to give a white solid product (E)-N-(N'-(tert-butyl)-N-(oxodiphenyl-λ) 6 -Thioimino)ureo)-4-nitrobenzenesulfonamide, yield 70%.

[0138] The product was dissolved in CDCl3 (approximately 0.4 mL), sealed in a tube, and analyzed at room temperature using a BRUKER AVANCEIII HD-400 liquid superconducting nuclear magnetic resonance spectrometer. The characterization data are as follows: 1 H NMR (400 MHz, CDCl3) δ 8.07 (d, J =8.5 Hz, 2H), 7.84 (dd, J = 7.5, 1.8 Hz, 4H), 7.70 – 7.64 (m, 3H), 7.53 (t, J= 7.4 Hz, 2H), 7.46 (t, J = 7.6 Hz, 4H), 1.50 (s, 9H); 13 C NMR (101 MHz, CDCl3)δ 157.4, 149.5, 148.9, 139.9, 133.3, 129.6, 127.2, 126.9, 123.6, 52.9, 29.6.

[0139] Example 22

[0140] A cobalt dichloride-catalyzed synthesis of (E)-N-(N'-(tert-butyl)-N-(oxodiphenyl-λ) 6 A method for sulfonamide (-thioimino)ureo)-4-(trifluoromethyl)benzenesulfonamide includes the following steps:

[0141] In air, S,S-diphenylsulfinylimide (109 mg, 0.5 mmol), tert-butylisocyanate (65 μL, 0.6 mmol), p-trifluoromethylbenzenesulfonyl azide (188.2 mg, 0.75 mmol), and cobalt dichloride (3 mg, 0.025 mmol) were placed into a dried 20 mL vial with a screw cap and a magnetic stir bar, and acetonitrile (3 mL) was added. The reaction mixture was heated at 80 °C (metal bath heater) and stirred for 6 h. The crude reaction mixture was diluted with dichloromethane (20 mL) and washed with water (20 mL × 3). The organic layer was dried over Na₂SO₄, filtered, and concentrated. The residue was purified by rapid chromatography (eluent: petroleum ether / ethyl acetate = 2 / 1) to give a white solid product (E)-N-(N'-(tert-butyl)-N-(oxodiphenyl-λ) 6 -Thioimino)ureo)-4-(trifluoromethyl)benzenesulfonamide, yield 90%.

[0142] The product was dissolved in CDCl3 (approximately 0.4 mL), sealed in a tube, and analyzed at room temperature using a BRUKER AVANCEIII HD-400 liquid superconducting nuclear magnetic resonance spectrometer. The characterization data are as follows: 1 H NMR (400 MHz, CDCl3) δ 7.80 (d, J =7.9 Hz, 4H), 7.74 (s, 1H), 7.56 (d, J = 8.2 Hz, 2H), 7.46 (dd, J = 8.0, 3.6Hz, 4H), 7.39 (t, J = 7.7 Hz, 4H), 1.48 (s, 9H); 13 C NMR (101 MHz, CDCl3) δ157.4, 147.2, 139.9, 133.3, 129.6, 127.2, 126.2, 125.4, 125.3, 124.9, 122.2,52.8, 29.6; 19 F NMR (376 MHz, CDCl3) δ -62.83.

[0143] Example 23

[0144] A cobalt dichloride-catalyzed synthesis of (E)-N-(N'-(tert-butyl)-N-(oxodiphenyl-λ) 6 A method for thioimino)ureo)naphthalene-2-sulfonamide includes the following steps:

[0145] In air, S,S-diphenylsulfinylimide (109 mg, 0.5 mmol), tert-butylisocyanate (65 μL, 0.6 mmol), naphthalene-2-sulfonyl azide (137.3 mg, 0.75 mmol), and cobalt dichloride (3 mg, 0.025 mmol) were placed into a dried 20 mL vial with a screw cap and a magnetic stir bar, and acetonitrile (3 mL) was added. The reaction mixture was heated at 80 °C (metal bath heater) and stirred for 6 h. The crude reaction mixture was diluted with dichloromethane (20 mL) and washed with water (20 mL × 3). The organic layer was dried over Na₂SO₄, filtered, and concentrated. The residue was purified by rapid chromatography (eluent: petroleum ether / ethyl acetate = 2 / 1) to give a white solid product (E)-N-(N'-(tert-butyl)-N-(oxodiphenyl-λ) 6 -Thioimino)ureo)naphthalene-2-sulfonamide, yield 94%.

[0146] The product was dissolved in CDCl3 (approximately 0.4 mL), sealed in a tube, and analyzed at room temperature using a BRUKER AVANCEIII HD-400 liquid superconducting nuclear magnetic resonance spectrometer. The characterization data are as follows: 1 H NMR (400 MHz, CDCl3) δ 8.11 (s,1H), 7.85 – 7.77 (m, 7H), 7.67 (d, J = 8.7 Hz, 1H), 7.54 (ddd, J = 7.6, 5.6,1.6 Hz, 3H), 7.42 (dd, J = 8.5, 1.9 Hz, 1H), 7.32 (d, J = 7.3 Hz, 5H), 1.51(s, 9H); 13 C NMR (101 MHz, CDCl3) δ 157.4, 140.7, 140.1, 134.2, 133.0, 132.1,129.4, 129.1, 128.4, 127.8, 127.7, 127.2, 126.8, 126.0, 122.3, 52.7, 29.7.

[0147] Example 24

[0148] A cobalt dichloride-catalyzed synthesis of (E)-N-(N'-(tert-butyl)-N-(oxodiphenyl-λ) 6 A method for 3-sulfonamides (-thioimino)ureo)pyridine-3-sulfonamides includes the following steps:

[0149] In air, S,S-diphenylsulfinylimide (109 mg, 0.5 mmol), tert-butylisocyanate (65 μL, 0.6 mmol), pyridine-3-sulfonyl azide (138 mg, 0.75 mmol), and cobalt dichloride (3 mg, 0.025 mmol) were placed into a dried 20 mL vial with a screw cap and a magnetic stir bar, and acetonitrile (3 mL) was added. The reaction mixture was heated at 80 °C (metal bath heater) and stirred for 6 h. The crude reaction mixture was diluted with dichloromethane (20 mL) and washed with water (20 mL × 3). The organic layer was dried over Na₂SO₄, filtered, and concentrated. The residue was purified by rapid chromatography (eluent: petroleum ether / ethyl acetate = 2 / 1) to give a white solid product (E)-N-(N'-(tert-butyl)-N-(oxodiphenyl-λ) 6 -Thioimino)ureo)pyridine-3-sulfonamide, yield 80%.

[0150] The product was dissolved in CDCl3 (approximately 0.4 mL), sealed in a tube, and analyzed at room temperature using a BRUKER AVANCEIII HD-400 liquid superconducting nuclear magnetic resonance spectrometer. The characterization data are as follows: 1 H NMR (400 MHz, CDCl3) δ 8.65 (d, J =2.3 Hz, 1H), 8.55 (d, J = 4.8 Hz, 1H), 7.83 – 7.77 (m, 4H), 7.71 – 7.64 (m,2H), 7.52 – 7.46 (m, 2H), 7.41 (t, J = 7.6 Hz, 4H), 7.14 (dd, J = 8.0, 4.8Hz, 1H), 1.47 (s, 9H); 13 C NMR (101 MHz, CDCl3) δ 157.4, 151.5, 146.8, 139.9, 133.4, 133.3, 129.6, 127.2, 123.1, 52.8, 29.6.

[0151] Example 25

[0152] A cobalt dichloride-catalyzed synthesis of (E)-N-(N'-(tert-butyl)-N-(oxodiphenyl-λ) 6 A method for using (-thioimino)ureo)-2,3-dihydro-1H-indene-5-sulfonamide, comprising the following steps:

[0153] In air, S,S-diphenylsulfinylimide (109 mg, 0.5 mmol), tert-butylisocyanate (65 μL, 0.6 mmol), 2,3-dihydro-1H-indene-5-sulfonyl azide (167.3 mg, 0.75 mmol), and cobalt dichloride (3 mg, 0.025 mmol) were placed into a dried 20 mL vial with a screw cap and a magnetic stir bar, and acetonitrile (3 mL) was added. The reaction mixture was heated at 80 °C (metal bath heater) and stirred for 6 h. The crude reaction mixture was diluted with dichloromethane (20 mL) and washed with water (20 mL × 3). The organic layer was dried over Na₂SO₄, filtered, and concentrated. The residue was purified by rapid chromatography (eluent: petroleum ether / ethyl acetate = 2 / 1) to give a white solid product (E)-N-(N'-(tert-butyl)-N-(oxodiphenyl-λ) 6 (-thioimino)ureo)-2,3-dihydro-1H-indene-5-sulfonamide, yield 81%.

[0154] The product was dissolved in CDCl3 (approximately 0.4 mL), sealed in a tube, and analyzed at room temperature using a BRUKER AVANCEIII HD-400 liquid superconducting nuclear magnetic resonance spectrometer. The characterization data are as follows: 1 H NMR (400 MHz, CDCl3) δ 7.78 (d, J =7.8 Hz, 4H), 7.65 (s, 1H), 7.44 (t, J = 7.4 Hz, 3H), 7.35 (t, J = 7.7 Hz,4H), 7.16 (d, J = 6.8 Hz, 2H), 6.99 (d, J = 7.9 Hz, 1H), 2.77 (dt, J = 25.4,7.4 Hz, 5H), 1.98 (p, J = 7.4 Hz, 2H), 1.42 (s, 9H); 13 C NMR (101 MHz, CDCl3) δ157.2, 147.6, 144.1, 141.5, 140.1, 133.1, 129.4, 127.2, 123.9, 123.8, 121.7,52.5, 32.7, 32.6, 29.7, 25.4.

[0155] Comparative Example 1

[0156] In air, tert-butyl(imino)(methyl)-λ 6- Sulfonone (67.54 mg, 0.5 mmol), tert-butylisocyanate (65 μL, 0.6 mmol), p-toluenesulfonyl azide (120 μL, 0.75 mmol), and cobalt dichloride (3 mg, 0.025 mmol) were dispensed into a dried 20 mL vial with a screw cap and a magnetic stir bar, and acetonitrile (3 mL) was added. The reaction mixture was heated at 80 °C (metal bath heater) and stirred for 6 h. The crude reaction product was diluted with dichloromethane (20 mL) and washed with water (20 mL × 3). The organic layer was dried over Na2SO4, filtered, and concentrated. The residue was purified by rapid chromatography (eluent: petroleum ether / ethyl acetate = 2 / 1), and no sulfoxide-imine guanidine compounds were obtained.

[0157] Comparative Example 1 used tert-butyl(imino)(methyl)-λ 6 Although sulfinones belong to the sulfur-containing imine class of compounds, their tert-butyl-substituted sulfur-nitrogen skeletons suffer from excessive steric hindrance, and lack conjugated or heterocyclic functional groups in the substrates of this invention that can stabilize free radical intermediates, they cannot be used in Co... 2+ Under catalysis, it completes a three-component free radical coupling with isonitriles and sulfonyl azides.

[0158] Comparative Example 2

[0159] In air, S,S-diphenylsulfinylimide (109 mg, 0.5 mmol), tert-butylisocyanate (65 μL, 0.6 mmol), morpholine-4-sulfonyl azide (144.02 mg, 0.75 mmol), and cobalt dichloride (3 mg, 0.025 mmol) were placed into a dried 20 mL vial with a screw cap and a magnetic stir bar, and acetonitrile (3 mL) was added. The reaction mixture was heated at 80 °C (metal bath heater) and stirred for 6 h. The crude reaction product was diluted with dichloromethane (20 mL) and washed with water (20 mL × 3). The organic layer was dried over Na₂SO₄, filtered, and concentrated. The residue was purified by rapid chromatography (eluent: petroleum ether / ethyl acetate = 2 / 1), and no sulfoxide-imide guanidine compounds were obtained.

[0160] Morpholine-4-sulfonyl azide belongs to the heterocyclic sulfonyl azide family. The strong electron-donating effect of its morpholine ring leads to a significant decrease in the reactivity of the azide group, making it unable to react with Co. 2+ Under coordination, the free radicals are successfully broken down to generate nitrogen radicals and sulfonyl radicals, thus preventing the subsequent radical addition and guanidine cyclization steps from being initiated.

[0161] Obviously, the above embodiments of the present invention are merely examples for clearly illustrating the present invention, and are not intended to limit the implementation of the present invention. Those skilled in the art should understand that other variations or modifications can be made based on the above description. It is neither necessary nor possible to exhaustively describe all embodiments here. Any modifications, equivalent substitutions, and improvements made within the spirit and principles of the present invention should be included within the scope of protection of the claims of the present invention.

Claims

1. A method for the synthesis of sulfoximine guanidine compounds catalyzed by cobalt dichloride, characterized in that, The method comprises the following steps: The free radical coupling reaction of a sulfoximine compound, an isocyanide compound and a sulfonyl azide compound is carried out in an organic solvent under the catalysis of cobalt dichloride to obtain the sulfoximine guanidine compound. The structural formula of the sulfoximine compound is: ; wherein R1 is selected from one or more of hydrogen, fluorine, chlorine, bromine, methyl, methoxy, cyano, nitro, pyridyl, and benzyl; and R2 is methyl, phenyl, cyclopropane, or allyl. The isonitrile compound has a structural formula as shown in the following formula: ; wherein R3 is a tert-butyl group, a cyclohexyl group, an adamantyl group, a 3,4-dimethylphenyl group, a p-chlorophenyl group, a p-ethoxyphenyl group, a m-fluorophenyl group, or a p-methylphenylsulfonylmethyl group. The sulfuryl azide compound has a structural formula of: ; wherein R4 is selected from one or more of hydrogen, fluorine, bromine, chlorine, methyl, 2,4,6-methyl, n-butyl, t-butyl, methoxy, nitro, cyano, ethyl, trifluoromethyl, benzyl, pyridyl, cyclohexyl, naphthyl, quinolyl, 2,3-dihydro-1H-inden-5-yl, and 2,3-dihydrobenzo[b][1,4]dioxan-6-yl.

2. The method of claim 1, wherein, The organic solvent is selected from one or more of acetonitrile, dimethyl sulfoxide, N,N-dimethylformamide, dichloromethane and N-methyl pyrrolidone.

3. The method of claim 1, wherein, S,S-diphenylsulfoximine, S-methyl-S-phenylsulfoximine, 4-(S-methylsulfonimidoyl)benzonitrile, imino(methyl)(4-nitrophenyl)-lambda 6 - sulfoximines, S-(4-methylphenyl)-S-phenylsulfoximine, S-methyl-S-(4- fluorophenyl)sulfoximine, S-methyl-S-(4-chlorophenyl)sulfoximine, S-methyl-S-(4- bromophenyl)sulfoximine, S-methyl-S-(4-methoxyphenyl)sulfoximine, S-methyl-S-(4- methylphenyl)sulfoximine, S-methyl-S-(2-pyridyl)sulfoximine, (2-hydroxyethyl)(imino)(phenyl)-lambda 6 - sulfoximines, S-(4-methylphenyl)-S-phenylsulfoximine, S-methyl-S-(4- fluorophenyl)sulfoximine, S-methyl-S-(4-chlorophenyl)sulfoximine, S-methyl-S-(4- bromophenyl)sulfoximine, S-methyl-S-(4-methoxyphenyl)sulfoximine, S-methyl-S-(4- methylphenyl)sulfoximine, S-methyl-S-(2-pyridyl)sulfoximine, (2-hydroxyethyl)(imino)(phenyl)-lambda 6 - sulfoximines, S-(4-methylphenyl)-S-phenylsulfoximine, S-methyl-S-(4- fluorophenyl)sulfoximine, S-methyl-S-(4-chlorophenyl)sulfoximine, S-methyl-S-(4- bromophenyl)sulfoximine, S-methyl-S-(4-methoxyphenyl)sulfoximine, S-methyl-S-(4- methylphenyl)sulfoximine, S-methyl-S-(2-pyridyl)sulfoximine, (2-hydroxyethyl)(imino)(phenyl)-lambda 4. The method of claim 1, wherein, The isocyanide compound is t-butyl isocyanide, p-methylbenzenesulfonyl methyl isocyanide, 4-nitrophenyl isocyanide, 4-chlorophenyl isocyanide, 3-fluorophenyl isocyanide, 4-ethoxyphenyl isocyanate, 1-adamantane isocyanide, cyclohexyl isocyanide, 3,4-dimethylphenyl isocyanate or 2-isocyano-1,1'-biphenyl.

5. The method of claim 1, wherein, The sulfonyl azide compound is phenylsulfonyl azide, p-toluenesulfonyl azide, p-ethylbenzenesulfonyl azide, p-t-butylbenzenesulfonyl azide, p-n-butylbenzenesulfonyl azide, 2,4,6-trimethylphenylsulfonyl azide, p-methoxybenzenesulfonyl azide, p-nitrobenzenesulfonyl azide, p-trifluoromethylbenzenesulfonyl azide, p-cyanobenzenesulfonyl azide, p-chlorobenzenesulfonyl azide, p-bromobenzenesulfonyl azide, 3-fluorobenzenesulfonyl azide, phenylmethanesulfonyl azide, cyclohexylsulfonyl azide, [1,1'-biphenyl]-4-sulfonyl azide, naphthalene-2-sulfonyl azide, naphthalene-1-sulfonyl azide, quinoline-8-sulfonyl azide, pyridine-3-sulfonyl azide, 2,3-dihydro-1H-indene-5-sulfonyl azide or 2,3-dihydrobenzo[b][1,4]dioxane-6-sulfonyl azide.

6. The method of claim 1, wherein, The molar ratio of the cobalt dichloride, the sulfoximine compound, the isocyanide compound and the sulfonyl azide compound is (0.05-0.1):(1-1.2):(1.2-1.5):(1.5-2).

7. The method of claim 1, wherein, The free radical coupling reaction is carried out in an air atmosphere.

8. The method of claim 1, wherein, The temperature of the free radical coupling reaction is 70-90 ℃.

9. The method of claim 1, wherein, The time of the free radical coupling reaction is 6-8 h.

10. The method of claim 1, wherein, After the free radical coupling reaction is completed, one or more of the following steps is further included: filtration, concentration and purification.

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