Sulfonamide compound and preparation method thereof

Abstract

The invention relates to the technical field of preparation of compounds, in particular to a sulfenamide compound and a preparation method thereof. Compared with the prior art, a mild electrochemical method is adopted for preparing the sulfenamide compound forming the N-S bond, in the reaction process, halide salt serving as electrolyte is subjected to oxidation reaction at an anode to obtain free radicals, and after decarburization of an amine compound is promoted by the free radicals and alkali together, the free radicals react with disulfide or mercaptan to form the sulfenamide compound forming the N-S bond; the method disclosed by the invention has the advantages of good substrate compatibility and functional group tolerance, no need of additional addition of an oxidizing agent and a transition metal catalyst, simple reaction post-treatment operation and the like, is convenient to operate, high in atom utilization rate and mild in reaction condition, meets related requirements of green chemistry, and has a good development prospect.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of compound preparation, and particularly relates to a sulfenamide compound and a preparation method thereof. BACKGROUND

[0002] Sulfenamide compounds are substances with diversified pharmacological properties and therapeutic potential, and are widely used in the fields of biomedical research and drug development. In particular, sulfenamides with arylpiperazine or piperidine structures have high antihypertensive or diuretic activity. Due to the unique structure and properties of the N-S bond in sulfenamide compounds, they can not only be used as important functional groups in the synthesis of natural products, but also be used as intermediates in the preparation of rubber vulcanization accelerators and other fine chemical products in industry.

[0003] There are many reported methods for constructing N-S bonds, such as: (1) metal-catalyzed reactions: Franklin et al. reported a method for synthesizing sulfenamide derivatives from disulfides and secondary amines catalyzed by silver nitrate. The metal salt is dissolved in methanol, then disulfide and excess amine are added, and the product is obtained after removing the metal thiolate. The reaction has a wide application range, but it requires the use of expensive silver salts and the operation is complex, and it is not suitable for long-chain alkyl mercaptans and some heterocyclic aryl mercaptans.

[0004]

[0005] Lee et al. reported a coupling reaction catalyzed by CuI and TBD to synthesize a series of N-formyl sulfenamide compounds from N-formyl amine and thiol. The reaction needs to be carried out in an O2 atmosphere, and the yield of some substrates is low.

[0006]

[0007] Dou et al. reported a cobalt-catalyzed aqueous reaction for constructing S-N bonds. Sulfenamide compounds are generated from thiol and amine as raw materials and CoPcS as catalyst. O2 oxidizes Co (II) to form Co (III), and thiol reduces Co (III) to generate sulfur radicals, which then react with amine to generate sulfenamide compounds.

[0008]

[0009] (2) Electrochemical catalytic reaction: He et al. developed a method for electrochemical cross-coupling to synthesize sulfenamide compounds from benzene thiol and amine compounds. Some heterocyclic thiols cannot be used, and the yield of primary amine as a substrate is low and the post-treatment is difficult.

[0010]

[0011] Tang et al. reported an electrochemical promoted reaction of thiols and amines to form sulfenamides. However, there are some problems in the reaction process, such as electrode corrosion and desulfurization of substrates.

[0012]

[0013] (3) Oxidation reaction: Yang et al. reported a method of TEMPO catalytic oxidation to construct S-N bond. With TEMPO as catalyst and O2 as oxidant, sulfenamide was generated by the reaction of mercaptobenzothiazole and amine.

[0014]

[0015] This method uses oxygen as oxidant, which is in line with the concept of green chemistry, but is limited to the reaction of unsubstituted 2-mercaptobenzothiazole substrates.

[0016] Yang et al. reported a method of elemental iodine catalysis to construct S-N bond. With green PEG-400 as solvent, I2 as catalyst and hydrogen peroxide as oxidant, N-sulfinyl sulfoximine was generated by the coupling of sulfoximine and thiol.

[0017]

[0018] This method uses hydrogen peroxide as oxidant, which is under heating conditions, and has certain risk. At the same time, the byproduct of the reaction is corrosive hydriodic acid.

[0019] (4) Other reactions: Masao et al. reported a method of synthesizing N-thio reagent intermediates by amine hydrolysis reaction, and preparing sulfenamide by two-step reaction. Some N-thio compounds are unstable, and need to be carried out under high temperature or reflux conditions.

[0020] Liu et al. reported a photo-oxidation and reduction coupling reaction using thiol and azo compound such as diethyl azodicarboxylate as raw material, but the structure of azodicarboxylate substrate is limited.

[0021] Most of these methods are only suitable for succinimide or benzothiazole thiol substrates. And usually some dangerous chemicals are used as raw materials, there are problems such as the use of transition metal catalysts, the need for additional photo catalysts. In addition, for post-processing operation, column chromatography or thin layer chromatography is usually needed to further purify the crude product. Therefore, it is of great theoretical significance and application value to develop a method of metal-free, environmentally friendly and efficient synthesis of sulfenamide compounds. SUMMARY

[0022] In order to overcome the above technical defects, the purpose of the present application is to provide a low-cost, easy-to-operate, non-heavy metal participation, mild reaction conditions, and easy-to-promote industrial production of sulfenamide compounds and preparation method.

[0023] In order to achieve the above-mentioned purpose, the technical scheme adopted by the present application is as follows: On the one hand, a sulfenamide or a pharmaceutically acceptable salt thereof represented by formula I is provided, Formula I Wherein, R1 is selected from phenyl, phenyl containing 1-5 substituents, wherein the substituents can be independently selected from hydrogen atom, halogen atom, C1-C5 alkyl, C1-3 alkoxy, C1-C5 haloalkoxy, C1-C5 haloalkyl, nitro, cyano, ester group, heteroaryl containing 5-6 ring atoms, C5-C15 straight chain or branched alkane; R2 is independently selected from C1-C10 alkyl, aldehyde group; R3 is independently selected from one of C1-C10 alkyl; Or R2 and R3 form a saturated or unsaturated heterocyclic group with the N atom to which they are attached.

[0024] Further, R1 is a benzene ring, phenyl containing 1-2 substituents, wherein the substituents can be independently selected from H, F, Cl, Br, para-methyl monosubstituted, meta-methyl monosubstituted, ortho-methyl monosubstituted, disubstituted methyl, -CF3, -C(CH3)3, -C(CH3)2, -C2H5, -OCF3, -OCF3, -NO2, -COOCH3; R2 and R3 are independently selected from one of C1-C5 alkyl.

[0025] Further, R1 is a benzene ring, phenyl containing 1-2 substituents, wherein the substituents can be independently selected from H, F, Cl, Br, para-methyl monosubstituted, meta-methyl monosubstituted, ortho-methyl monosubstituted, disubstituted methyl, -CF3, -C(CH3)3, -C(CH3)2, -C2H5, -OCF3, -OCF3, -NO2, -COOCH3; R2 and R3 form a saturated ring group containing 6 ring atoms with the N atom to which they are attached, and the group also includes O, N, S heteroatoms.

[0026] Further, R1 is a heteroaryl containing 5-6 ring atoms, wherein the heteroatom is selected from one of O, N, S heteroatom; R2 and R3 are independently selected from one of C1-C5 alkyl.

[0027] Further, R1 is a C5-C15 straight chain; R2and R3are independently selected from one of C1-C5 alkyl.

[0028] Further, the sulfenamide of formula I is specifically: , , , , , , , , , , , , , , , , , , , , , , , , , , , , .

[0029] In a second aspect, a method for electrochemically synthesizing a sulfenamide is provided. In the method, an organic solution of a thiol compound of formula II, an amine compound of formula IV, a base, and an electrolyte salt is used as an electrolyte, and a direct current is passed through the electrolyte to form a sulfenamide compound with an N-S bond. Formula II, wherein R is selected from H, F, Cl, Br, para-methyl monosubstitution, meta-methyl monosubstitution, ortho-methyl monosubstitution, disubstitution methyl, -CF3, -C(CH3)3, -C(CH3)2, -C2H5, -OCF3, -OCF3, -NO2, -COOCH3; Formula IV, wherein R2is independently selected from C1-C10 alkyl, aldehyde group; R3is independently selected from one of C1-C10 alkyl; or R2and R3form a saturated or unsaturated heterocyclic group with the N atom to which they are attached.

[0030] In a second aspect, there is provided a method for electrochemically synthesizing a sulfenamide, in which a solution of a disulfide compound of Formula III, an amine compound of Formula IV, a base and an electrolyte salt in an organic solvent is used as an electrolyte, a direct current is passed through the electrolyte, and an electrochemical reaction is performed to form a sulfenamide compound with an N-S bond. Formula III, wherein R is selected from H, F, Cl, Br, para-methyl monosubstituted, meta-methyl monosubstituted, ortho-methyl monosubstituted, disubstituted methyl, -CF3, -C(CH3)3, -C(CH3)2, -C2H5, -OCF3, -OCF3, -NO2, -COOCH3; Formula IV, wherein R2 is independently selected from C1-C10 alkyl, aldehyde group; R3 is independently selected from one of C1-C10 alkyl; or R2 and R3 form a saturated or unsaturated heterocyclic group with the N atom to which they are attached.

[0031] Further, the amine compound is selected from one of DMF, N,N-dimethylformamide, 4-morpholine formaldehyde, N-methylformamide, N-ethylformamide; and / or, the electrolyte salt is selected from one or more of sodium iodide, potassium iodide, Me4NI, NH4I, Et4NI, n Bu4NI, n Bu4NBr; and / or, the base is selected from one or more of K2CO3, Na2CO3, KHCO3, (NH4)2CO3, Cs2CO3, NaOH, NH4Cl, AcONa, t BuOK.

[0032] Further, the molar ratio of the disulfide compound, the base and the electrolyte salt is 1:(1-3):(0.5-1.5), or 1:(1-2.5):(1-1.5), or 1:(1.5-2.5):(1-1.2), or 1:2:1.

[0033] Further, the electrochemical reaction condition is that the electrochemical electrode comprises one or a combination of two of nickel, copper, gold, zinc, platinum, graphite carbon; or the anode is a graphite carbon electrode and the cathode is a platinum electrode; or the anode is a platinum electrode and the cathode is a platinum electrode; and / or, a rated current of 20-40 mA is passed through in an air atmosphere, and the reaction is stirred; and / or, The reaction temperature is 30-60℃, or 40-60℃, or 45-55℃, or 45-50℃, or 50℃; and / or, the reaction time is 1-5h, or 1.5-4h, or 2-4h, or 2-3.5h, or 3h.

[0034] Beneficial effects: compared with the prior art, the present application adopts a mild electrochemical method to prepare a sulfoximine compound with N-S bond, in the reaction process, the halide salt as the electrolyte is oxidized at the anode to obtain a free radical, then the amine compound is de-carbonated with the aid of a base, and then reacts with a disulfide or a thiol to form a sulfoximine compound with N-S bond; the present application exhibits good substrate compatibility and functional group tolerance, without the need for additional oxidants and transition metal catalysts, and the post-reaction operation is simple, etc., overcoming the problems of difficult to obtain raw materials alkylamine, complicated post-treatment operation, low substrate universality, the need for metal catalysts or special catalyst preparation, etc., and has the advantages of convenient operation, high atom utilization rate, mild reaction conditions, meeting the relevant requirements of green chemistry, and good development prospect. BRIEF DESCRIPTION OF DRAWINGS

[0035] Figure 1 The reaction scheme of the sulfoximine compound of the present application is shown in the following figure: Figure 2 The H NMR chart of the product obtained in Example 5 is shown in the following figure: 1 H NMR chart; Figure 3 The C NMR chart of the product obtained in Example 5 is shown in the following figure: 13 C NMR chart; Figure 4 The H NMR chart of the product obtained in Example 7 is shown in the following figure: 1 H NMR chart; Figure 5 The C NMR chart of the product obtained in Example 7 is shown in the following figure: 13 C NMR chart. DETAILED DESCRIPTION

[0036] In order for those skilled in the art to better understand the technical solutions of the present application, the present application will be described in detail below in conjunction with specific embodiments. The experimental methods not specified in the following examples are usually carried out according to conventional conditions or according to the conditions recommended by the manufacturers. Unless otherwise specified, the percentages and parts are calculated by weight. Unless otherwise defined, all professional and scientific terms used herein have the same meaning as understood by those skilled in the art. In addition, any method and material similar or equivalent to those described can be applied in the present application. The preferred implementation methods and materials described herein are only for demonstration.

[0037] The endpoints of the ranges and any values disclosed herein are not limited to the precise values recited as the exact dimensions are not critical to the invention. Any numeric range recited is intended to include all values from the lower value to the upper value, inclusive of both values, and to sub-ranges falling within the specified range. In this context, individual points within a range should be considered as being included within that range, and individual points can be combined to form new ranges, which are to be considered as being included within the present disclosure.

[0038] Based on a large number of experimental summary and reference to previous literature reports, the present application proposes the following reaction mechanism: At the anode, on the one hand, iodine ions lose electrons to become iodine radicals, which co-catalyze the dehydrogenation of N, N-dimethylformamide to generate HI and carbonyl radicals, and then decarboxylate to generate N, N-dimethyl radicals; on the other hand, mercaptans ionize and lose electrons to oxidize to generate sulfur radicals, which rapidly couple with iodine radicals to generate a sulfur-iodine compound intermediate, or starting from a disulfide compound, directly react with iodine to generate a sulfur-iodine compound intermediate. The intermediate reacts with N, N-dimethyl radicals to generate the target product, and the iodine radicals are removed to continue the catalytic reaction. At the cathode, hydrogen ions gain electrons to reduce to generate hydrogen (see Figure 1 ).

[0039] In some specific embodiments, a method for electrochemically synthesizing sulfenamide is provided. Under the condition of electricity, an organic solution of mercaptan compound, amine compound, base and electrolyte salt is used as electrolyte, direct current is passed in, and electrochemical reaction is carried out to form sulfenamide compound with N-S bond. The specific reaction formula is as follows:

[0040] In the formula, R1 is selected from H, F, Cl, Br, para-methyl monosubstituted, meta-methyl monosubstituted, ortho-methyl monosubstituted, disubstituted methyl, -CF3, -C(CH3)3, -C(CH3)2, -C2H5, -OCF3, -OCF3, -NO2, -COOCH3; R2 is independently selected from C1-C10 alkyl, aldehyde group; R3 is independently selected from one of C1-C10 alkyl; Or R2 and R3 form a saturated or unsaturated heterocyclic group with the N atom to which they are attached.

[0041] Based on the present application, benzyl mercaptan without substituent and with electron-donating group has good to excellent yield. The yield of o-methyl and 2,6-dimethyl benzyl mercaptan is reduced due to steric hindrance effect, and the yield is 82% and 72% respectively. The yield of p-methoxy benzyl mercaptan with strong electron-donating group is as high as 95%, which has very excellent applicability.

[0042] When using phenylthiols with strong electron withdrawing groups, the yield decreased, with p-trifluoromethylphenylthiol and p-trifluoromethoxyphenylthiol having yields of 56% and 73% respectively. The yield of p-nitrophenylthiol reached 90% after secondary optimization of the reaction conditions. Phenylthiols with halogen functional groups had good yields. The addition of the corresponding halogenated zinc salt and control of the reaction time can inhibit the dehalogenation of the reaction.

[0043] Naphthalene thiol was also well applicable in this reaction, with a yield of 90%. The yield of o-methylformate phenylthiol was only 36%, which can be considered as the dual effect of strong electron withdrawing groups and steric hindrance. Long-chain alkyl mercaptans and some heterocyclic thiols that are not applicable in traditional classical reactions also achieved good to excellent yields.

[0044] In some embodiments of this implementation, the amine compound is selected from one of DMF, N,N-dimethylformamide, 4-morpholine formaldehyde, N-methylformamide, and N-ethylformamide.

[0045] As a preferred embodiment, the amine compound is selected from DMF.

[0046] In some embodiments of this implementation, the electrolyte salt is selected from one or more of sodium iodide, potassium iodide, Me4NI, NH4I, Et4NI, n Bu4NI, n Bu4NBr.

[0047] As a preferred embodiment, the electrolyte salt is selected from sodium iodide and potassium iodide.

[0048] In some embodiments of this implementation, the base is selected from one or more of K2CO3, Na2CO3, KHCO3, (NH4)2CO3, Cs2CO3, NaOH, NH4Cl, AcONa, t BuOK.

[0049] In some embodiments of this implementation, the molar ratio of the disulfide compound, the base, and the electrolyte salt is 1:(1-3):(0.5-1.5), or 1:(1-2.5):(1-1.5), or 1:(1.5-2.5):(1-1.2).

[0050] As a preferred embodiment, the molar ratio of the disulfide compound, the base, and the electrolyte salt is 1:2:1.

[0051] In some embodiments of this implementation, DMF is not only used as a solvent in the reaction, but also as an important raw material involved in the reaction. Therefore, a solvent dosage of 2.5 mL is used to ensure the immersion of the electrode in each experiment.

[0052] In some embodiments of the embodiment, the electrochemical electrode comprises one or a combination of nickel, copper, gold, zinc, platinum, and graphite carbon; or the anode is a graphite carbon electrode and the cathode is a platinum electrode. As a preferred embodiment, the electrochemical electrode is a platinum electrode as the anode and a platinum electrode as the cathode to form a two-electrode system. In some embodiments of the embodiment, the electrochemical reaction is carried out in an air atmosphere, a rated current of 20-40 mA is passed, and the reaction is stirred; the rated current is selected from 20 mA, 25 mA, 30 mA, 35 mA, and 40 mA, and other specific point values within the numerical range can also be selected, which will not be repeated here.

[0053] As a preferred embodiment, the rated current is 30 mA.

[0054] In some embodiments of the embodiment, the reaction temperature is 30-60 ℃, or 40-60 ℃, or 45-55 ℃, or 45-50 ℃; other specific point values within the numerical range can also be selected, which will not be repeated here.

[0055] As a preferred embodiment, the reaction temperature is 50 ℃.

[0056] In some embodiments of the embodiment, the reaction time is 1-5 h, or 1.5-4 h, or 2-4 h, or 2-3.5 h; other specific point values within the numerical range can also be selected, which will not be repeated here.

[0057] As a preferred embodiment, the reaction time is 3 h.

[0058] In a second aspect, a method for electrochemically synthesizing a sulfenamide is provided. In the method, a direct current is passed through an organic solution of a disulfide compound, an amine compound, a base, and an electrolyte salt as an electrolyte under an electric condition to perform an electrochemical reaction and form a sulfenamide compound with an N-S bond. The specific reaction formula is as follows:

[0059] wherein R1 is selected from H, F, Cl, Br, para-methyl monosubstituted, meta-methyl monosubstituted, ortho-methyl monosubstituted, disubstituted methyl, -CF3, -C(CH3)3, -C(CH3)2, -C2H5, -OCF3, -OCF3, -NO2, -COOCH3; R2 is independently selected from C1-C10 alkyl and aldehyde group; R3 is independently selected from one of C1-C10 alkyl; or R2 and R3 form a saturated or unsaturated heterocyclic group with the N atom to which they are attached.

[0060] Based on the present application, diphenyl disulfide compounds with electron-donating groups and electron-withdrawing groups have achieved good to excellent yield. In diphenyl disulfide compounds with nitro groups, the yield change is as expected. The strong electron-withdrawing cyano and amide groups also have very excellent performance. Heterocyclic mercaptans and alkyl mercaptans perform well with a yield of medium to good, 74% and 51%.

[0061] In some embodiments of the present application, the amine compound is selected from one of DMF, N,N -dimethylformamide, 4-morpholine formaldehyde, N-methyl formamide, N-ethyl formamide.

[0062] As a preferred embodiment, the amine compound is selected from DMF.

[0063] In some embodiments of the present application, the electrolyte salt is selected from one or more of sodium iodide, potassium iodide, Me4NI, NH4I, Et4NI, n Bu4NI, n Bu4NBr.

[0064] As a preferred embodiment, the electrolyte salt is selected from sodium iodide, potassium iodide.

[0065] In some embodiments of the present application, the base is selected from one or more of K2CO3, Na2CO3, KHCO3, (NH4)2CO3, Cs2CO3, NaOH, NH4Cl, AcONa, t BuOK.

[0066] In some embodiments of the present application, the molar ratio of disulfide compound, base and electrolyte salt is 1: (1-3): (0.5-1.5), or 1: (1-2.5): (1-1.5), or 1: (1.5-2.5): (1-1.2).

[0067] As a preferred embodiment, the molar ratio of disulfide compound, base and electrolyte salt is 1:2:1.

[0068] In some embodiments of the present application, DMF is not only used as a solvent for the reaction, but also as an important raw material for the reaction. Therefore, 2.5 mL of solvent is used to ensure the immersion of the electrode in each experiment.

[0069] In some embodiments of the present application, the electrochemical electrode includes one or a combination of nickel, copper, gold, zinc, platinum, graphite carbon; or the anode is a graphite carbon electrode and the cathode is a platinum electrode. As a preferred embodiment, the electrochemical electrode is a platinum electrode anode and a platinum electrode cathode to form a double electrode system. In some embodiments of this embodiment, the electrochemical reaction is carried out in an air atmosphere, a rated current of 20-40 mA is passed, and the reaction is stirred; the rated current is selected from 20 mA, 25 mA, 30 mA, 35 mA, and 40 mA, and other specific point values in this numerical range can also be selected, which will not be repeated here.

[0070] As a preferred embodiment, the rated current is 30 mA.

[0071] In some embodiments of this embodiment, the reaction temperature is 30-60 ℃, or 40-60 ℃, or 45-55 ℃, or 45-50 ℃; other specific point values in this numerical range can also be selected, which will not be repeated here.

[0072] As a preferred embodiment, the reaction temperature is 50 ℃.

[0073] And / or, the reaction time is 1-5 h, or 1.5-4 h, or 2-4 h, or 2-3.5 h, and other specific point values in this numerical range can also be selected, which will not be repeated here.

[0074] As a preferred embodiment, the reaction time is 3 h.

[0075] The technical solutions of the present application are further described in detail below in combination with specific embodiments and drawings. It should be understood that the following embodiments are only used to explain the present application and do not limit the present application.

[0076] Example 1 Synthesis of N,N-dimethyl-S-phenylthiohydroxylamine In a 10 mL test tube, add thiophenol (22.0 mg, 0.2 mmol), potassium iodide (33.2 mg, 0.2 mmol,), potassium carbonate (13.8 mg, 0.1 mmol), DMF (2.5 mL), add the test tube and place it in a 50 ℃ oil bath, pass a constant current of 30 mA under magnetic stirring for 3 hours. After the reaction is completed, add a small amount of salt water to quench the reaction after cooling to room temperature, take out the electrode and rinse with a small amount of DMF. Then extract the mixture with n-hexane (3 mL x 5), wash the organic phase with saturated ice salt water (10 mL x 3). Then transfer the organic phase to a clean conical flask, add an appropriate amount of anhydrous Na2SO4 to dry, filter to remove the solid and then vacuum reduce pressure rotary evaporation to obtain a relatively pure product, yellow oil, yield 90% (27.5 mg). 1H NMR (400 MHz, Chloroform-d) δ 7.43 (d, J = 7.3 Hz, 2H),7.36 (t, J = 7.5 Hz, 2H), 7.27 (t, J = 7.6 Hz, 1H), 2.75 (s, 6H); 13 C NMR (101MHz, Chloroform-d) δ 135.6, 130.3, 128.7, 127.6, 48.6.

[0077] Example 2 Synthesis of N,N-dimethyl-S-(p-tolyl) thiohydroxylamine In a 10 mL test tube, add 4-methylbenzenethiol (24.8 mg, 0.2 mmol), potassium iodide (33.2 mg, 0.2 mmol,), potassium carbonate (13.8 mg, 0.1 mmol), DMF (2.5 mL), add the test tube and put it in a 50 °C oil bath pot, pass electricity constant current 30 mA under magnetic stirring for 3 hours. After the reaction is completed, add a small amount of brine to quench the reaction after cooling to room temperature, take out the electrode and rinse with a small amount of DMF. Then extract the mixture with n-hexane (3 mL x 5), combine the small polarity solution of n-hexane layer, wash the organic phase with saturated ice brine (10 mL x 3). Then transfer the organic phase to a clean conical flask, add an appropriate amount of anhydrous Na2SO4 to dry, filter out the solid and vacuum reduce pressure rotary evaporation to obtain a relatively pure product, yellow oil, yield 86% (28.7 mg). 1 H NMR (400 MHz, Chloroform-d) δ 7.38 (d, J = 8.0Hz, 2H), 7.18 (d, J = 7.9 Hz, 2H), 2.68 (s, 6H), 2.36 (s, 3H); 13 C NMR (101MHz, Chloroform-d) δ 138.6, 132.9, 129.9, 129.4, 48.4, 21.4.

[0078] Example 3 Synthesis of N,N-dimethyl-S-(m-tolyl) thiohydroxylamine In a 10 mL test tube, add 3-methylbenzenethiol (24.8 mg, 0.2 mmol), potassium iodide (33.2 mg, 0.2 mmol,), potassium carbonate (13.8 mg, 0.1 mmol), DMF (2.5 mL), add to the test tube and place it in a 50 °C oil bath, pass a constant current of 30 mA under magnetic stirring for 3 hours. After the reaction is complete, cool it to room temperature, add a small amount of brine to quench the reaction, remove the electrode and rinse it with a small amount of DMF. Then extract the mixture with n-hexane (3 mL x 5), wash the organic phase with saturated ice brine (10 mL x 3). Then transfer the organic phase to a clean conical flask, add an appropriate amount of anhydrous Na2SO4 to dry it, filter off the solid and vacuum reduce pressure rotary evaporation to obtain a relatively pure product, yellow oil, yield 90% (30.1 mg). 1 H NMR (400 MHz, Chloroform-d) δ 7.24 (d, J = 2.9Hz, 3H), 7.11-7.07 (m, 1H), 2.75 (s, 6H), 2.36 (s, 3H); 13 C NMR (101 MHz,Chloroform-d) δ 138.5, 135.3, 130.8, 128.5, 128.4, 127.4, 48.6, 21.6.

[0079] Example 4 Synthesis of N,N-dimethyl-S-(o-tolyl) thiohydroxylamine In a 10 mL test tube, add 3-methylbenzenethiol (24.8 mg, 0.2 mmol), potassium iodide (33.2 mg, 0.2 mmol,), potassium carbonate (13.8 mg, 0.1 mmol), DMF (2.5 mL), add to the test tube and place it in a 50 °C oil bath, pass a constant current of 30 mA under magnetic stirring for 3 hours. After the reaction is complete, cool it to room temperature, add a small amount of brine to quench the reaction, remove the electrode and rinse it with a small amount of DMF. Then extract the mixture with n-hexane (3 mL x 5), wash the organic phase with saturated ice brine (10 mL x 3). Then transfer the organic phase to a clean conical flask, add an appropriate amount of anhydrous Na2SO4 to dry it, filter off the solid and vacuum reduce pressure rotary evaporation to obtain a relatively pure product, yellow oil, yield 90% (30.1 mg). 1H NMR (400 MHz, Chloroform-d) δ 7.50 (d, J = 7.7 Hz, 1H), 7.21 (t, J = 8.2 Hz, 1H), 7.16-7.08 (m, 2H), 2.82 (s, 6H), 2.26 (s, 1=3H); 13 C NMR (101 MHz, Chloroform-d) δ 137.5, 134.9, 130.4, 126.8, 126.1, 126.0, 48.6, 19.5.

[0080] Example 5 Synthesis of S-(3,5 -dimethylphenyl)-N,N -dimethylthiohydroxylamine In a 10 mL test tube, add 3,5 -dimethylbenzenethiol (27.7 mg, 0.2 mmol), potassium iodide (33.2 mg, 0.2 mmol,), potassium carbonate (13.8 mg, 0.1 mmol), DMF (2.5 mL), add the test tube and put it in a 50 °C oil bath pot, pass electricity constant current 30 mA under magnetic stirring for 3 hours. After the reaction is completed, add a small amount of brine to quench the reaction after cooling to room temperature, take out the electrode and rinse with a small amount of DMF. Then extract the mixture with n-hexane (3 mL x 5), wash the organic phase with saturated ice brine (10 mL x 3). Then transfer the organic phase to a clean conical flask, add an appropriate amount of anhydrous Na2SO4 to dry, filter out the solid and vacuum reduce pressure rotary evaporation to obtain a relatively pure product, yellow oil, yield 92% (33.3 mg). 1 H NMR (400 MHz, Chloroform-d) δ 7.05 (s, 2H), 6.91 (s, 1H), 2.75 (s, 6H), 2.32 (s, 6H); 13 C NMR (101 MHz, Chloroform-d) δ 138.3, 135.1, 129.4, 127.9, 48.6, 21.4.

[0081] Example 6 Synthesis of S-(2,6 -dimethylphenyl)-N,N -dimethylthiohydroxylamine In a 10 mL test tube, add 2,6-dimethylbenzenethiol (27.7 mg, 0.2 mmol), potassium iodide (33.2 mg, 0.2 mmol,), potassium carbonate (13.8 mg, 0.1 mmol), DMF (2.5 mL), add to the test tube and place it in a 50 °C oil bath, pass a constant current of 30 mA under magnetic stirring for 3 hours. After the reaction is complete, cool to room temperature, add a small amount of salt water to quench the reaction, remove the electrode and rinse with a small amount of DMF. Then extract the mixture with n-hexane (3 mL x 5), combine the small polarity solution of the n-hexane layer, and wash the organic phase with saturated ice salt water (10 mL x 3). Then transfer the organic phase to a clean conical flask, add an appropriate amount of anhydrous Na2SO4 to dry, filter off the solid and vacuum reduce pressure rotary evaporation to obtain a relatively pure product, yellow oil, yield 72% (26.1 mg). 1 H NMR (400 MHz, Chloroform-d) δ 7.18-7.12 (m,3H), 2.66 (s, 6H), 2.60 (s, 6H); 13 C NMR (101 MHz, Chloroform-d) δ 143.8,133.2, 129.5, 128.3, 49.0, 22.5.

[0082] Example 7 Synthesis of S-(4-tert-Butylphenyl)-N,N-dimethylthiohydroxylamine In a 10 mL test tube, add 2,6-dimethylbenzenethiol (27.7 mg, 0.2 mmol), potassium iodide (33.2 mg, 0.2 mmol,), potassium carbonate (13.8 mg, 0.1 mmol), DMF (2.5 mL), add to the test tube and place it in a 50 °C oil bath, pass a constant current of 30 mA under magnetic stirring for 3 hours. After the reaction is complete, cool to room temperature, add a small amount of salt water to quench the reaction, remove the electrode and rinse with a small amount of DMF. Then extract the mixture with n-hexane (3 mL x 5), combine the small polarity solution of the n-hexane layer, and wash the organic phase with saturated ice salt water (10 mL x 3). Then transfer the organic phase to a clean conical flask, add an appropriate amount of anhydrous Na2SO4 to dry, filter off the solid and vacuum reduce pressure rotary evaporation to obtain a relatively pure product, yellow oil, yield 72% (26.1 mg). 1 H NMR (400 MHz, Chloroform-d) δ 7.40 (s, 4H),2.71 (s, 6H), 1.33 (s, 9H); 13C NMR (101 MHz, Chloroform-d) δ 151.4, 131.9, 130.7, 125.7, 48.5, 34.7, 31.4.

[0083] Example 8 Synthesis of S-(4-ethylphenyl)-N,N-dimethylthiohydroxylamine In a 10 mL test tube, add 4-ethylphenylthiol (27.7 mg, 0.2 mmol), potassium iodide (33.2 mg, 0.2 mmol,), potassium carbonate (13.8 mg, 0.1 mmol), DMF (2.5 mL), add the test tube and place it in a 50 °C oil bath pan, pass a constant current of 30 mA under magnetic stirring for 3 hours. After the reaction is complete, cool to room temperature, add a small amount of brine to quench the reaction, remove the electrode and rinse with a small amount of DMF. Then extract the mixture with n-hexane (3 mL x 5), combine the n-hexane layer with small polarity, wash the organic phase with saturated ice brine (10 mL x 3). Then transfer the organic phase to a clean conical flask, add an appropriate amount of anhydrous Na2S04 to dry, filter off the solid and vacuum reduce pressure rotary evaporation to obtain a relatively pure product, yellow oil, yield 85% (30..8 mg). 1 H NMR (400 MHz, Chloroform-d) δ 7.40 (d, J = 8.1 Hz, 2H), 7.21 (d, J = 8.0 Hz, 2H), 2.69 (s, 6H), 2.68-2.61 (m, 2H), 1.25 (t, J = 7.6 Hz, 3H); 13 C NMR (101 MHz, Chloroform-d) δ 144.8, 132.8, 130.4, 128.3, 48.4, 28.7, 15.6.

[0084] Example 9 Synthesis of S-(4-isopropylphenyl)-N,N-dimethylthiohydroxylamine In a 10 mL test tube, add 4-isopropylbenzenethiol (30.5 mg, 0.2 mmol), potassium iodide (33.2 mg, 0.2 mmol,), potassium carbonate (13.8 mg, 0.1 mmol), DMF (2.5 mL), add to the test tube and place it in a 50 °C oil bath, pass a constant current of 30 mA under magnetic stirring for 3 hours. After the reaction is complete, cool to room temperature, add a small amount of salt water to quench the reaction, remove the electrode and rinse with a small amount of DMF. Then extract the mixture with n-hexane (3 mL x 5), combine the n-hexane layer of small polarity solution, wash the organic phase with saturated ice salt water (10 mL x 3). Then transfer the organic phase to a clean conical flask, add an appropriate amount of anhydrous Na2SO4 to dry, filter off the solid and vacuum reduce pressure rotary evaporation to obtain a relatively pure product, yellow oil, yield 95% (37.1 mg). 1 H NMR (400 MHz, Chloroform-d) δ 7.41 (d, J =8.1 Hz, 2H), 7.23 (d, J = 8.0 Hz, 2H), 2.92 (p, J = 6.9 Hz, 1H), 2.70 (s,6H), 1.26 (d, J = 6.9 Hz, 6H); 13 C NMR (101 MHz, Chloroform-d) δ 149.3, 132.6,130.7, 126.8, 48.5, 34.0, 24.0.

[0085] Example 10 Synthesis of S-(4-methoxyphenyl)-N,N-dimethylthiohydroxylamine In a 10 mL test tube, add 4-isopropylbenzenethiol (30.5 mg, 0.2 mmol), potassium iodide (33.2 mg, 0.2 mmol,), potassium carbonate (13.8 mg, 0.1 mmol), DMF (2.5 mL), add to the test tube and place it in a 50 °C oil bath, pass a constant current of 30 mA under magnetic stirring for 3 hours. After the reaction is complete, cool to room temperature, add a small amount of salt water to quench the reaction, remove the electrode and rinse with a small amount of DMF. Then extract the mixture with n-hexane (3 mL x 5), combine the n-hexane layer of small polarity solution, wash the organic phase with saturated ice salt water (10 mL x 3). Then transfer the organic phase to a clean conical flask, add an appropriate amount of anhydrous Na2SO4 to dry, filter off the solid and vacuum reduce pressure rotary evaporation to obtain a relatively pure product, yellow oil, yield 95% (37.1 mg). 1H NMR (400 MHz, Chloroform-d) δ 7.49 (d, J =8.2 Hz, 2H), 6.92 (d, J = 8.2 Hz, 2H), 3.84 (s, 3H), 2.61 (s, 6H); 13 C NMR (101 MHz, Chloroform-d) δ 160.8, 137.2, 122.3, 114.1, 55.4, 48.1.

[0086] Example 11 Synthesis of N,N-Dimethyl-S-(4-trifluoromethylphenyl)thiohydroxylamine In a 10 mL test tube, add 4-trifluoromethylphenylthiol (35.6 mg, 0.2 mmol), potassium iodide (33.2 mg, 0.2 mmol,), potassium carbonate (13.8 mg, 0.1 mmol), DMF (2.5 mL), add the test tube and put it in a 50 °C oil bath pot, pass electricity constant current 30 mA under magnetic stirring for 3 hours. After the reaction is completed, add a small amount of brine to quench the reaction after cooling to room temperature, take out the electrode and rinse with a small amount of DMF. Then extract the mixture with n-hexane (3 mL x 5), wash the organic phase with saturated ice brine (10 mL x 3). Then transfer the organic phase to a clean conical flask, add an appropriate amount of anhydrous Na2SO4 to dry, filter out the solid and then vacuum reduce pressure rotary evaporation to obtain a relatively pure product, yellow oil, yield 856% (24.8 mg). 1 H NMR (400 MHz, Chloroform-d) δ 7.55 (d, J =8.2 Hz, 2H), 7.38 (d, J = 8.1 Hz, 2H), 2.86 (s, 6H); 13 C NMR (101 MHz, Chloroform-d) δ 168.9, 138.4, 133.9, 128.4, 119.9, 48.3, 24.7; 19 F NMR (376MHz, Chloroform-d)δ-62.2.

[0087] Example 12 Synthesis of S-(4-trifluoromethoxyphenyl)-N,N-dimethylthiohydroxylamine In a 10 mL test tube, add 4-trifluoromethoxythiophenol (38.8 mg, 0.2 mmol), potassium iodide (33.2 mg, 0.2 mmol,), potassium carbonate (13.8 mg, 0.1 mmol), DMF (2.5 mL), add to the test tube and place it in a 50 °C oil bath, pass a constant current of 30 mA under magnetic stirring for 3 hours. After the reaction is complete, cool to room temperature, add a small amount of salt water to quench the reaction, remove the electrode and rinse with a small amount of DMF. Then extract the mixture with n-hexane (3 mL x 5), combine the small polarity solution of the n-hexane layer, and wash the organic phase with saturated ice salt water (10 mL x 3). Then transfer the organic phase to a clean conical flask, add an appropriate amount of anhydrous Na2SO4 to dry, filter off the solid and vacuum reduce pressure rotary evaporation to obtain a relatively pure product, yellow oil, yield 73% (34.6 mg). 1 H NMR (400 MHz, Chloroform-d) δ 7.42(d, J = 7.5 Hz, 2H), 7.20 (d, J = 8.1 Hz, 2H), 2.77 (s, 6H); 13 C NMR (101 MHz,Chloroform-d) δ 148.5, 135.2, 130.7, 130.6, 128.7, 121.9, 121.3, 119.3, 48.5,22.8(t, J = 898.9 Hz); 19 F NMR (376 MHz, Chloroform-d) δ -57.9.

[0088] Example 13 (New compound) Synthesis of S-(4-nitrophenyl)-N,N-dimethylthiohydroxylamine In a 10 mL test tube, add 4-trifluoromethoxythiophenol (38.8 mg, 0.2 mmol), potassium iodide (33.2 mg, 0.2 mmol,), potassium carbonate (13.8 mg, 0.1 mmol), DMF (2.5 mL), add to the test tube and place it in a 50 °C oil bath, pass a constant current of 30 mA under magnetic stirring for 3 hours. After the reaction is complete, cool to room temperature, add a small amount of salt water to quench the reaction, remove the electrode and rinse with a small amount of DMF. Then extract the mixture with n-hexane (3 mL x 5), combine the small polarity solution of the n-hexane layer, and wash the organic phase with saturated ice salt water (10 mL x 3). Then transfer the organic phase to a clean conical flask, add an appropriate amount of anhydrous Na2SO4 to dry, filter off the solid and vacuum reduce pressure rotary evaporation to obtain a relatively pure product, yellow oil, yield 73% (34.6 mg).1 H NMR (400 MHz, Chloroform-d) δ 8.16 (d, J = 8.7 Hz, 2H), 7.35 (d, J = 8.7 Hz, 2H), 2.91 (s, 6H); 13 C NMR (101 MHz, Chloroform-d) δ 152.1, 133.3, 124.2, 122.4, 48.6.

[0089] Synthesis of S-(4-fluorophenyl)-N,N-dimethylthiohydroxylamine In a 10 mL test tube, add 4-fluorothiophenol (25.6 mg, 0.2 mmol), potassium iodide (33.2 mg, 0.2 mmol,), potassium carbonate (13.8 mg, 0.1 mmol), DMF (2.5 mL), add the test tube and put it in a 50 °C oil bath pot, pass electricity constant current 30 mA under magnetic stirring for 3 hours. After the reaction is completed, add a small amount of brine to quench the reaction after cooling to room temperature, take out the electrode and rinse with a small amount of DMF. Then extract the mixture with n-hexane (3 mL x 5), wash the organic phase with saturated ice brine (10 mL x 3). Then transfer the organic phase to a clean conical flask, add an appropriate amount of anhydrous Na2SO4 to dry, filter out the solid and then vacuum reduce pressure rotary evaporation to obtain a relatively pure product, yellow oil, yield 62% (21.2 mg). 1 H NMR (400 MHz, Chloroform-d) δ 7.47 (dd, J = 8.3,5.7 Hz, 2H), 7.08 (t, J = 8.6 Hz, 2H), 2.67 (s, 6H); 13 C NMR (101 MHz, Chloroform-d) δ 163.1 (d, J = 248.3 Hz), 134.9 (d, J = 8.3 Hz), 128.7 (d, J = 3.9 Hz), 115.8 (d, J = 21.7 Hz), 48.3; 19 F NMR (376 MHz, Chloroform-d) δ -113.0.

[0090] Synthesis of S-(4-chlorophenyl)-N,N-dimethylthiohydroxylamine In a 10 mL test tube, add 4-chlorothiophenol (28.9 mg, 0.2 mmol), potassium iodide (33.2 mg, 0.2 mmol,), potassium carbonate (13.8 mg, 0.1 mmol), DMF (2.5 mL), add to the test tube and place it in a 50 °C oil bath, pass a constant current of 30 mA under magnetic stirring for 3 hours. After the reaction is complete, cool it to room temperature, add a small amount of salt water to quench the reaction, remove the electrode and rinse it with a small amount of DMF. Then extract the mixture with n-hexane (3 mL x 5), combine the n-hexane layer of small polarity, wash the organic phase with saturated ice salt water (10 mL x 3). Then transfer the organic phase to a clean conical flask, add an appropriate amount of anhydrous Na2S04 to dry, filter off the solid and vacuum reduce pressure rotary evaporation to obtain a relatively pure product, yellow oil, yield 88% (32.9 mg). 1 H NMR (400 MHz, Chloroform-d) δ 7.36-7.31 (m, 4H), 2.74 (s, 6H); 13 C NMR (101 MHz, Chloroform-d) δ 134.4, 133.5, 131.2, 128.9, 48.5.

[0091] Example 16 Synthesis of S-(4-bromophenyl)-N,N-dimethylthiohydroxylamine In a 10 mL test tube, add 4-chlorothiophenol (28.9 mg, 0.2 mmol), potassium iodide (33.2 mg, 0.2 mmol,), potassium carbonate (13.8 mg, 0.1 mmol), DMF (2.5 mL), add to the test tube and place it in a 50 °C oil bath, pass a constant current of 30 mA under magnetic stirring for 3 hours. After the reaction is complete, cool it to room temperature, add a small amount of salt water to quench the reaction, remove the electrode and rinse it with a small amount of DMF. Then extract the mixture with n-hexane (3 mL x 5), combine the n-hexane layer of small polarity, wash the organic phase with saturated ice salt water (10 mL x 3). Then transfer the organic phase to a clean conical flask, add an appropriate amount of anhydrous Na2S04 to dry, filter off the solid and vacuum reduce pressure rotary evaporation to obtain a relatively pure product, yellow oil, yield 88% (32.9 mg). 1 H NMR (400 MHz, Chloroform-d) δ 7.36-7.31 (m, 4H), 2.74 (s, 6H); 13C NMR (101 MHz, Chloroform-d) δ 135.6, 131.8, 130.9, 121.3, 48.5.

[0092] Example 17 Synthesis of N,N-dimethyl-S-(naphthalen-2-yl)thiohydroxylamine In a 10 mL test tube, add 2-naphthalenethiol (32.1 mg, 0.2 mmol), potassium iodide (33.2 mg, 0.2 mmol,), potassium carbonate (13.8 mg, 0.1 mmol), DMF (2.5 mL), add the test tube and put it in a 50 °C oil bath pot, pass electricity constant current 30 mA for 3 hours under magnetic stirring. After the reaction is completed, add a small amount of brine to quench the reaction after cooling to room temperature, take out the electrode and rinse with a small amount of DMF. Then extract the mixture with n-hexane (3 mL x 5), combine the small polarity solution of n-hexane layer, wash the organic phase with saturated ice brine (10 mL x 3). Then transfer the organic phase to a clean conical flask, add an appropriate amount of anhydrous Na2SO4 to dry, filter out the solid and vacuum reduce pressure rotary evaporation to obtain a relatively pure product, colorless oil, yield 70% (36.6 mg). 1 H NMR (400 MHz, Chloroform-d) δ 7.89 (s, 1H),7.83-7.79 (m, 3H), 7.51-7.44 (m, 3H), 2.82 (s, 6H); 13 C NMR (101 MHz, Chloroform-d) δ 133.7, 133.6, 132.7, 128.3, 128.2, 127.9, 127.8, 127.6, 126.6, 126.2, 48.6.

[0093] Example 18 Synthesis of methyl 2-[(dimethylamino)sulfanyl]benzoate In a 10 mL test tube, add 2 - mercaptobenzoic acid methyl ester (33.6 mg, 0.2 mmol), potassium iodide (33.2 mg, 0.2 mmol,), potassium carbonate (13.8 mg, 0.1 mmol), DMF (2.5 mL), add to the test tube and place it in a 50 °C oil bath, pass a constant current of 30 mA under magnetic stirring for 3 hours. After the reaction is complete, cool it to room temperature, add a small amount of brine to quench the reaction, remove the electrode and rinse it with a small amount of DMF. Then extract the mixture with n-hexane (3 mL x 5), combine the n-hexane layer of small polarity solution, wash the organic phase with saturated ice brine (10 mL x 3). Then transfer the organic phase to a clean conical flask, add an appropriate amount of anhydrous Na2S04 to dry, filter out the solid and then vacuum reduce pressure rotary evaporation to obtain a relatively pure product, yellow oil, yield 36% (15.2 mg). 1 H NMR (400 MHz, Chloroform-d) δ 8.01(dd, J=1.2, 8.0Hz, 1H), 7.83 (d, J = 7.7 Hz, 1H), 7.53 (t, J = 7.7 Hz, 1H),7.14 (t, J = 7.5 Hz, 1H), 3.90 (s, 3H), 2.88 (s, 6H); 13 C NMR (101 MHz,Chloroform-d) δ 167.0, 148.8, 132.8, 131.4, 123.6, 123.2, 122.9, 52.2, 47.9。

[0094] Example 19 Synthesis of N,N-dimethyl-S-(pyridin-4-yl)thiohydroxylamine In a 10 mL test tube, add 2 - mercaptobenzoic acid methyl ester (33.6 mg, 0.2 mmol), potassium iodide (33.2 mg, 0.2 mmol,), potassium carbonate (13.8 mg, 0.1 mmol), DMF (2.5 mL), add to the test tube and place it in a 50 °C oil bath, pass a constant current of 30 mA under magnetic stirring for 3 hours. After the reaction is complete, cool it to room temperature, add a small amount of brine to quench the reaction, remove the electrode and rinse it with a small amount of DMF. Then extract the mixture with n-hexane (3 mL x 5), combine the n-hexane layer of small polarity solution, wash the organic phase with saturated ice brine (10 mL x 3). Then transfer the organic phase to a clean conical flask, add an appropriate amount of anhydrous Na2S04 to dry, filter out the solid and then vacuum reduce pressure rotary evaporation to obtain a relatively pure product, yellow oil, yield 36% (15.2 mg). 1H NMR (400 MHz, Chloroform-d) δ 8.41 (d, J = 5.9 Hz, 2H), 7.15 (d, J = 6.0 Hz, 2H), 2.91 (s, 6H); 13 C NMR (101 MHz, Chloroform-d) δ 153.8, 149.3, 117.1, 48.5.

[0095] Example 20 Synthesis of N,N-dimethyl-S-(pyridin-2-yl)thiohydroxylamine In a 10 mL test tube, add 2-pyridinethiol (22.2 mg, 0.2 mmol), potassium iodide (33.2 mg, 0.2 mmol,), potassium carbonate (13.8 mg, 0.1 mmol), DMF (2.5 mL), add the test tube and place it in a 50 °C oil bath pan, pass a constant current of 30 mA under magnetic stirring for 3 hours. After the reaction is complete, cool to room temperature, add a small amount of brine to quench the reaction, remove the electrode and rinse with a small amount of DMF. Then extract the mixture with n-hexane (3 mL x 5), combine the small polar solution of n-hexane layer, and wash the organic phase with saturated ice brine (10 mL x 3). Then transfer the organic phase to a clean conical flask, add an appropriate amount of anhydrous Na2SO4 to dry, filter off the solid and vacuum reduce pressure rotary evaporation to obtain a relatively pure product, colorless oil, yield 74% (22.8 mg). 1 H NMR (400 MHz, Chloroform-d) δ 8.43 (d, J = 4.1 Hz, 1H), 7.59 (ddd, J = 8.2, 7.4, 1.8 Hz, 1H), 7.35 (dt, J = 8.1, 1.1 Hz, 1H), 6.96 (ddd, J = 7.5, 4.9, 1.1 Hz, 1H), 2.98 (s, 6H); 13 C NMR (101 MHz, Chloroform-d) δ 165.4, 149.5, 136.5, 119.3, 118.2, 48.6.

[0096] Example 21 Synthesis of N,N-dimethyl-S-(pyrimidin-2-yl)thiohydroxylamine In a 10 mL test tube, add 2-pyrimidinethiol (22.4 mg, 0.2 mmol), potassium iodide (33.2 mg, 0.2 mmol,), potassium carbonate (13.8 mg, 0.1 mmol), DMF (2.5 mL), add to the test tube and place it in a 50 °C oil bath, pass a constant current of 30 mA under magnetic stirring for 3 hours. After the reaction is complete, cool to room temperature, add a small amount of brine to quench the reaction, remove the electrode and rinse with a small amount of DMF. Then extract the mixture with n-hexane (3 mL x 5), combine the n-hexane layer of small polarity solution, wash the organic phase with saturated ice brine (10 mL x 3). Then transfer the organic phase to a clean conical flask, add an appropriate amount of anhydrous Na2S04 to dry, filter off the solid and vacuum reduce pressure rotary evaporation to obtain a relatively pure product, colorless oil, yield 58% (18.0 mg). 1 H NMR (400 MHz, Chloroform-d) δ 8.54 (d, J = 4.7Hz, 2H), 6.93 (t, J = 4.7 Hz, 1H), 3.12 (s, 6H); 13 C NMR (101 MHz, Chloroform-d) δ 177.3, 157.1, 116.6, 47.5.

[0097] Example 22 Synthesis of N,N-dimethyl-S-(pyrazin-2-yl)thiohydroxylamine In a 10 mL test tube, add 2-pyrimidinethiol (22.4 mg, 0.2 mmol), potassium iodide (33.2 mg, 0.2 mmol,), potassium carbonate (13.8 mg, 0.1 mmol), DMF (2.5 mL), add to the test tube and place it in a 50 °C oil bath, pass a constant current of 30 mA under magnetic stirring for 3 hours. After the reaction is complete, cool to room temperature, add a small amount of brine to quench the reaction, remove the electrode and rinse with a small amount of DMF. Then extract the mixture with n-hexane (3 mL x 5), combine the n-hexane layer of small polarity solution, wash the organic phase with saturated ice brine (10 mL x 3). Then transfer the organic phase to a clean conical flask, add an appropriate amount of anhydrous Na2S04 to dry, filter off the solid and vacuum reduce pressure rotary evaporation to obtain a relatively pure product, colorless oil, yield 58% (18.0 mg). 1H NMR (400 MHz, Chloroform-d) δ 8.56 (d, J = 1.3 Hz, 1H), 8.40-8.34 (m, 1H), 8.23 (d, J = 2.5 Hz, 1H), 3.01 (s, 6H); 13 C NMR (101 MHz, Chloroform-d) δ 49.1, 31.7, 30.8, 29.0, 28.5, 22.7, 14.2.

[0098] Example 23 Synthesis of S-hexyl-N,N-dimethylthiohydroxylamine In a 10 mL test tube, add hexanethiol (23.7 mg, 0.2 mmol), potassium iodide (33.2 mg, 0.2 mmol,), potassium carbonate (13.8 mg, 0.1 mmol), DMF (2.5 mL), add the test tube and put it in a 50 °C oil bath pot, pass electricity constant current 30 mA under magnetic stirring for 3 hours. After the reaction is completed, add a small amount of brine to quench the reaction after cooling to room temperature, take out the electrode and rinse with a small amount of DMF. Then extract the mixture with n-hexane (3 mL x 5), wash the organic phase with saturated ice brine (10 mL x 3). Then transfer the organic phase to a clean conical flask, add an appropriate amount of anhydrous Na2SO4 to dry, filter off the solid and vacuum reduce pressure rotary evaporation to obtain a relatively pure product, yellow oil, yield 51% (15.1 mg). 1 H NMR (400 MHz, Chloroform-d) δ 2.74-2.70 (m, 8H), 1.56 (p, J = 7.9, 7.5 Hz, 2H), 1.39 (dt, J = 14.5, 7.1 Hz, 2H), 1.30 (s, 4H), 0.89 (t, J = 6.6 Hz, 3H); 13 C NMR (101 MHz, Chloroform-d) δ 49.1, 31.7, 30.8, 29.0, 28.5, 22.7, 14.2.

[0099] Example 24 Synthesis of S-hexadecyl-N,N-dimethylthiohydroxylamine In a 10 mL test tube, add hexadecanethiol (51.7 mg, 0.2 mmol), potassium iodide (33.2 mg, 0.2 mmol,), potassium carbonate (13.8 mg, 0.1 mmol), DMF (2.5 mL), add the test tube and put it in a 50 °C oil bath, pass a constant current of 30 mA for 3 hours with magnetic stirring. After the reaction is complete, add a small amount of brine to quench the reaction after cooling to room temperature, remove the electrode and rinse with a small amount of DMF. Then extract the mixture with n-hexane (3 mL x 5), wash the organic phase with saturated ice brine (10 mL x 3). Then transfer the organic phase to a clean conical flask, add an appropriate amount of anhydrous Na2SO4 to dry, filter off the solid and vacuum reduce pressure rotary evaporation to obtain a relatively pure product, brown oil, yield 83% (47.7 mg). 1 H NMR (400 MHz, Chloroform-d) δ 2.75-2.72 (m, 6H),2.72-2.65 (m, 3H), 1.67 (dt, J = 14.6, 7.0 Hz, 2H), 1.56 (p, J = 7.6, 7.2 Hz,2H), 1.43-1.34 (m, 3H), 1.26 (s, 18H), 0.91-0.83 (m, 5H); 13 C NMR (101 MHz, Chloroform-d) δ 49.1, 39.4, 32.1, 30.9, 29.9, 29.8, 29.8, 29.7, 29.5, 29.5, 29.4, 29.4, 29.3, 28.7, 28.6, 22.9, 14.3.

[0100] Example 25 Synthesis of N,N-dimethyl-S-(3-nitrophenyl)thiohydroxylamine In a 10 mL test tube, add 1-(3 -nitrophenyl)-2 -phenyldisulfide (31.0 mg, 0.1 mmol), potassium iodide (33.2 mg, 0.2 mmol,), potassium carbonate (13.8 mg, 0.1 mmol), DMF (2.5 mL), add to the test tube and place it in a 50 °C oil bath, pass a constant current of 30 mA under magnetic stirring for 3 hours. Upon completion of the reaction, cool to room temperature, add a small amount of brine to quench the reaction, remove the electrode and rinse with a small amount of DMF. Then extract the mixture with n-hexane (3 mL x 5), combine the n-hexane layer of small polarity, wash the organic phase with saturated ice brine (10 mL x 3). Then transfer the organic phase to a clean conical flask, add an appropriate amount of anhydrous Na2S04 to dry, filter out the solid and then vacuum reduce pressure rotary evaporation to obtain a relatively pure product, yellow oil, yield 78% (31.0 mg). 1 H NMR (400 MHz, Chloroform-d) δ 8.18 (s, 1H), 8.01-7.98 (m, 1H), 7.56 (d, J = 7.8 Hz, 1H), 7.48 (t, J = 7.9Hz, 1H), 2.89 (s, 6H); 13 C NMR (101 MHz, Chloroform-d) δ 148.9, 143.1, 130.7,129.5, 120.6, 119.7, 48.7.

[0101] Example 26 Synthesis of N,N-dimethyl-S-(2-nitrophenyl)thiohydroxylamine In a 10 mL test tube, add 1-(3 -nitrophenyl)-2 -phenyldisulfide (31.0 mg, 0.1 mmol), potassium iodide (33.2 mg, 0.2 mmol,), potassium carbonate (13.8 mg, 0.1 mmol), DMF (2.5 mL), add to the test tube and place it in a 50 °C oil bath, pass a constant current of 30 mA under magnetic stirring for 3 hours. Upon completion of the reaction, cool to room temperature, add a small amount of brine to quench the reaction, remove the electrode and rinse with a small amount of DMF. Then extract the mixture with n-hexane (3 mL x 5), combine the n-hexane layer of small polarity, wash the organic phase with saturated ice brine (10 mL x 3). Then transfer the organic phase to a clean conical flask, add an appropriate amount of anhydrous Na2S04 to dry, filter out the solid and then vacuum reduce pressure rotary evaporation to obtain a relatively pure product, yellow oil, yield 78% (31.0 mg). 1H NMR (400 MHz, Chloroform-d) δ 8.29 (d, J = 8.3 Hz, 1H), 7.92 (d, J = 8.3 Hz, 1H), 7.65 (t, J = 7.7 Hz, 1H),7.27-7.23 (m, 1H), 2.92 (s, 6H); 13 C NMR (101 MHz, Chloroform-d) δ 145.6, 142.1, 134.0, 126.1, 124.6, 124.5, 47.4.

[0102] Example 2 Synthesis of 4-((dimethylamino)thio)benzonitrile In a 10 mL test tube, add 4-(phenyldithio)benzonitrile (24.3 mg, 0.1 mmol), potassium iodide (33.2 mg, 0.2 mmol,), potassium carbonate (13.8 mg, 0.1 mmol), DMF (2.5 mL), add the test tube and put it in a 50 °C oil bath pot, pass electricity constant current 30 mA for 3 hours under magnetic stirring. After the reaction is completed, add a small amount of brine to quench the reaction after cooling to room temperature, take out the electrode and rinse with a small amount of DMF. Then extract the mixture with n-hexane (3 mL x 5), wash the organic phase with saturated ice brine (10 mL x 3). Then transfer the organic phase to a clean conical flask, add an appropriate amount of anhydrous Na2SO4 to dry, filter out the solid and then vacuum reduce pressure rotary evaporation to obtain a relatively pure product, yellow oil, yield 90% (32.1 mg). 1 H NMR (400 MHz, Chloroform-d) δ 7.56(d, J = 8.4 Hz, 2H), 7.33 (d, J = 8.4 Hz, 2H), 2.89 (s, 6H); 13 C NMR (101 MHz, Chloroform-d) δ 149.0, 132.3, 123.2, 119.3, 107.9, 48.5.

[0103] Example 2 Synthesis of 4-((dimethylamino)thio)benzonitrile In a 10 mL test tube, add N-[4-(phenyldithio)phenyl]benzamide (33.7 mg, 0.1 mmol), potassium iodide (33.2 mg, 0.2 mmol,), potassium carbonate (13.8 mg, 0.1 mmol), DMF (2.5 mL), add the test tube and put it in a 50 °C oil bath, pass a constant current of 30 mA for 3 hours with magnetic stirring. After the reaction is complete, add a small amount of brine to quench the reaction after cooling to room temperature, remove the electrode and rinse with a small amount of DMF. Then extract the mixture with n-hexane (3 mL x 5), combine the n-hexane layer with small polarity, wash the organic phase with saturated ice brine (10 mL x 3). Then transfer the organic phase to a clean conical flask, add an appropriate amount of anhydrous Na2SO4 to dry, filter off the solid and vacuum reduce pressure rotary evaporation to obtain a relatively pure product, purple oil, yield 86% (46.8 mg). 1 H NMR (400 MHz, Chloroform-d) δ 9.95 (s, 1H), 8.66 (d, J = 7.6 Hz, 1H), 7.97 (d, J = 7.0 Hz, 2H), 7.68-7.43 (m, 5H), 7.13 (t, J = 7.5 Hz, 1H), 2.62 (s, 6H); 13 C NMR (101 MHz,Chloroform-d) δ 165.0, 140.9, 136.2, 134.9, 132.1, 131.7, 129.0, 127.2,123.6, 120.6, 120.0, 48.2。

[0104] Example 29 Synthesis of N,N-diethyl-S-phenyl thiohydroxylamine In a 10 mL test tube, diphenyl disulfide (21.8 mg, 0.1 mmol), potassium iodide (33.2 mg, 0.2 mmol, ), potassium carbonate (13.8 mg, 0.1 mmol), N,N -dimethylformamide (2.5 mL) were added into the test tube and placed in a 50 °C oil bath, and a constant current of 30 mA was applied for 3 h with magnetic stirring. After the reaction was completed, a small amount of salt water was added to quench the reaction after cooling to room temperature, the electrode was removed and rinsed with a small amount of DMF. Then the mixture was extracted with n-hexane (3 mL x 5), and the n-hexane layer was combined and washed with saturated ice salt water (10 mL x 3). Then the organic phase was transferred to a clean conical flask, dried with an appropriate amount of anhydrous Na2SO4, filtered to remove the solid, and vacuum reduced pressure rotary evaporation to obtain a relatively pure product, colorless oil, yield 82% (29.7 mg). 1 H NMR (400 MHz, Chloroform-d) δ 7.30 (dt, J = 14.8, 7.5 Hz, 4H), 7.12 (t, J = 7.0 Hz, 1H), 2.99 (q, J = 7.0Hz, 4H), 1.18 (t, J = 7.1 Hz, 6H); 13 C NMR (101 MHz, Chloroform-d) δ 141.2,128.6, 125.5, 125.2, 52.2, 13.8.

[0105] Comparative Example The thiophenol compounds and disulfide compounds (0.1 mmol) shown in Table 1 were added to a 10 mL test tube, respectively, and potassium iodide (33.2 mg, 0.2 mmol, ), potassium carbonate (13.8 mg, 0.1 mmol), N,N -dimethylformamide (2.5 mL) were added in turn, and placed in a 50 °C oil bath, and a constant current of 30 mA was applied for 3 h with magnetic stirring. After the reaction was completed, a small amount of salt water was added to quench the reaction after cooling to room temperature, the electrode was removed and rinsed with a small amount of DMF. Then the mixture was extracted with n-hexane (3 mL x 5), and the n-hexane layer was combined and washed with saturated ice salt water (10 mL x 3). Then the organic phase was transferred to a clean conical flask, dried with an appropriate amount of anhydrous Na2SO4, filtered to remove the solid, and vacuum reduced pressure rotary evaporation to obtain a relatively pure product, and the yield is shown in the following table.

[0106] Table 1

[0107] It can be seen that for benzyl mercaptan, benzoxazole mercaptan, benzothiazole mercaptan, phenyl selenol and phenyl mercaptan with active hydrogen, etc. are not applicable under the reaction condition; the rules exhibited by the expansion of the substrate of disulfide compounds are basically consistent with those of phenyl mercaptan compounds, and dibenzyl disulfide, asymmetric disulfide and disulfide compounds with active hydrogen, etc. have no yield under the reaction condition.

[0108] Finally, it should be noted that the above description is only a preferred embodiment of the present application, and those skilled in the art can make various similar expressions under the inspiration of the present application without violating the purpose of the present application and the claims, and such changes fall within the protection scope of the present application.

Claims

1. A sulfenamide of the formula I, or a pharmaceutically acceptable salt thereof, Formula I wherein R1 is selected from the group consisting of phenyl, phenyl with 1-5 substituents, wherein the substituents are independently selected from the group consisting of hydrogen atom, halogen atom, C1-C5 alkyl, C1-3 alkoxy, C1-C5 haloalkoxy, C1-C5 haloalkyl, nitro, cyano, ester, heteroaryl with 5-6 ring atoms, C5-C15 straight chain or branched alkane; R2 is independently selected from the group consisting of C1-C10 alkyl, aldehyde; R3 is independently selected from the group consisting of one of C1-C10 alkyl; or R2 and R3 form a saturated or unsaturated heterocyclic group with the N atom to which they are attached.

2. The sulfenamide of claim 1, or a pharmaceutically acceptable salt thereof, wherein, R1 is phenyl with 1-2 substituents, wherein the substituents are independently selected from the group consisting of H, F, Cl, Br, para-methyl monosubstitution, meta-methyl monosubstitution, ortho-methyl monosubstitution, disubstitution methyl, -CF3, -C(CH3)3, -C(CH3)2, -C2H5, -OCF3, -OCF3, -NO2, -COOCH3; R2 and R3 are independently selected from the group consisting of one of C1-C5 alkyl; or, R2 and R3 form a saturated ring group with the N atom to which they are attached, the group further comprising a heteroatom selected from the group consisting of O, N, S.

3. The sulfenamide of claim 1, or a pharmaceutically acceptable salt thereof, wherein, R1 is heteroaryl with 5-6 ring atoms, wherein the heteroatoms are selected from the group consisting of one of O, N, S. R2 and R3 are independently selected from the group consisting of one of C1-C5 alkyl. R1 is C5-C15 straight chain; 4. The sulfenamide of claim 1, or a pharmaceutically acceptable salt thereof, wherein, R2 and R3 are independently selected from the group consisting of one of C1-C5 alkyl. The sulfenamide of the formula I is specifically:

5. The sulfenamide of claim 1, or a pharmaceutically acceptable salt thereof, wherein, Under the condition of electricity, the organic solution of the thiol compound of the formula II, the amine compound of the formula IV, a base and an electrolyte salt as an electrolyte, direct current is passed to carry out electrochemical reaction to form the sulfenamide compound with N-S bond; 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 。 6. A method of electrochemically synthesizing a sulfenamide, characterized by: R1 is selected from the group consisting of H, F, Cl, Br, para-methyl monosubstitution, meta-methyl monosubstitution, ortho-methyl monosubstitution, disubstitution methyl, -CF3, -C(CH3)3, -C(CH3)2, -C2H5, -OCF3, Formula II, -OCF3, -NO2, -COOCH3; R2 is independently selected from the group consisting of C1-C10 alkyl, aldehyde; Formula IV, R3 is independently selected from the group consisting of one of C1-C10 alkyl; or R2 and R3 form a saturated or unsaturated heterocyclic group with the N atom to which they are attached. Under the condition of electricity, the organic solution of the disulfide compound of the formula III, the amine compound of the formula IV, a base and an electrolyte salt as an electrolyte, direct current is passed to carry out electrochemical reaction to form the sulfenamide compound with N-S bond; 7. A method of electrochemically synthesizing a sulfenamide, characterized by: R1 is selected from the group consisting of H, F, Cl, Br, para-methyl monosubstitution, meta-methyl monosubstitution, ortho-methyl monosubstitution, disubstitution methyl, -CF3, -C(CH3)3, -C(CH3)2, -C2H5, -OCF3, Formula III, -OCF3, -NO2, -COOCH3; R2 is independently selected from the group consisting of C1-C10 alkyl, aldehyde; Formula IV, R3 is independently selected from the group consisting of one of C1-C10 alkyl; ​ or R2 and R3 form, together with the N atom to which they are attached, a saturated or unsaturated heterocyclic radical.

8. The method according to claim 6 or 7, characterized in that, The amine compound is selected from one of DMF, N,N-dimethylformamide, 4-morpholine formaldehyde, N-methyl formamide, N-ethyl formamide; and / or the electrolyte salt is selected from one or more of sodium iodide, potassium iodide, Me4NI, NH4I, Et4NI, n Bu4NI, n Bu4NBr. and / or the base is selected from K2CO3, Na2CO3, KHCO3, (NH4)2CO3, Cs2CO3, NaOH, NH4CI, AcONa, t one or more of BuLi, BuMgCl, Bu2Mg, Bu2MgLi, Bu2MgCl, Bu2MgBr, Bu2MgI, Bu3Mg2, Bu3Mg, Bu3MgCl, Bu3MgBr, Bu3MgI, Bu4 9. The method according to claim 6 or 7, characterized in that, The molar ratio of the disulfide compound, the base and the electrolyte salt is 1:(1-3):(0.5-1.5), or 1:(1-2.5):(1-1.5), or 1:(1.5-2.5):(1-1.2), or 1:2:

1.

10. The method of claim 6 or 7, wherein, The electrochemical reaction condition is: The electrochemical electrode comprises one or a combination of two of nickel, copper, gold, zinc, platinum, graphite carbon; or the anode is a graphite carbon electrode and the cathode is a platinum electrode; or the anode is a platinum electrode and the cathode is a platinum electrode; and / or, In an air atmosphere, a rated current of 20-40 mA is introduced, and the reaction is stirred; and / or, The reaction temperature is 30-60 ℃, or 40-60 ℃, or 45-55 ℃, or 45-50 ℃, or 50 ℃; and / or, the reaction time is 1-5 h, or 1.5-4 h, or 2-4 h, or 2-3.5 h, or 3 h.

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