A method for direct amination of aromatic alkane carbon-hydrogen bonds via electrochemical catalysis

Abstract

This invention belongs to the field of fine organic synthesis, specifically relating to an electrochemically catalytic method for the direct amination of aromatic hydrocarbon carbon-hydrogen bonds. This invention efficiently converts primary or secondary aromatic hydrocarbons into corresponding amination products in a single reaction. Compared with commonly used methods, this method has significant advantages: (1) it uses widely available and inexpensive primary or secondary aromatic hydrocarbons as starting materials; (2) it requires no metal catalysts, no exogenous oxidants or bases, and uses electrons as a clean oxidation medium, eliminating the need for traditional exogenous oxidants, reducing costs and environmental pollution; (3) it achieves the activation of inert carbon-hydrogen bonds under mild reaction conditions; (4) the reaction uses sulfonylimide substrates as nitrogen sources to introduce amino groups, enabling the target product to be obtained with relatively ideal separation yields and rich product structures.

Description

TECHNICAL FIELD

[0001] The present application belongs to the field of fine organic synthesis, and particularly relates to a method for electrochemically catalyzing direct amination of aromatic alkane C-H bond. BACKGROUND

[0002] C-H bond is widely present in various organic compound molecules, and is the most basic and core chemical bond in organic molecules. Traditional valence bond construction strategy often needs pre-functionalization of raw materials, and then functional group transformation is used to realize structural diversity derivation. C-H bond activation strategy is to directly use inert C-H bond for functional group transformation, thereby avoiding the cumbersome multi-step pre-functionalization process, which is a very attractive synthesis strategy in the field of synthetic chemistry. It is quite challenging to realize inert C-H activation functionalization under mild conditions: C-H bond energy is high and is not easy to be catalytically activated, C-H bond polarity is small and is not easy to be recognized and acted by catalyst. At present, under the metal catalytic system, C-H bond activation strategy has been used to construct C-C bond, C-O bond, C-N bond, C-X bond and the like.

[0003] Nitrogen-containing groups exist in various drug molecule skeletons, and they can be converted into other functional groups by various chemical or biological catalytic methods. Most amine compounds are widely used in the field of medicine and health due to their good biological and drug activity, such as anti-breast cancer drug letrozole; and some amine-containing small molecules are also monomers of functional materials, such as nylon. At present, amine products are mainly constructed by substitution reaction of alkyl halide and N-containing nucleophile under alkaline conditions. The problems of this method are: the reaction needs to be carried out under alkaline conditions, and the substrate application is not wide due to the poor functional group compatibility of the reaction; at present, most N-alkylation reactions use alkyl halide as raw material, which is obtained by pre-halogenation of alkane, increasing the reaction steps and the atom economy and yield are not high; alkyl halide is easy to eliminate to produce olefin by-product under alkaline conditions, resulting in low yield of N-alkylation reaction. The direct N-H / C-H coupling process of amine and alkane under the participation of oxidant is an ideal and green high-efficiency strategy for constructing various amine compounds, but at present, the N-alkylation reaction by this strategy often needs excess chemical oxidant and it is difficult to control the reaction regioselectivity.

[0004] Currently, the construction of C–N bond relies on pre-functionalized substrates such as aryl halides, alkyl halides, aryl pseudohalides, alkyl pseudohalides, etc. under transition metal catalysts, palladium, rhodium, copper, etc. to achieve C–H bond activation amination reaction to form new C–N bond. For example: in 2012, Professor Gwilherm Evano's group reported a method of copper-mediated imine and terminal alkyne oxidative cross-coupling to efficiently construct C(sp)–N. A series of azido alkenes and dienes containing nitrogen precursors were synthesized by this method (Org. Lett., 2012, 14, 6–9.). Professor Buchwald of Massachusetts Institute of Technology and Professor Hartwig of University of California, Berkeley made important contributions to the construction of C(sp 2 )–N bond: Buchwald-Hartwig amination reaction provides an efficient and general method for the construction of C–N bond, which helps the efficient synthesis of active nitrogen-containing drug molecules and material monomers. Compared with C(sp 2 )–H bond amination reaction, C(sp 3 )–H bond amination reaction is more challenging. Currently, chemists still rely on traditional synthetic methods: nucleophilic substitution reaction between nitrogen nucleophile and alkyl halide. In terms of metal catalysis: in 2019, Prof. Warren used Cu catalyst to realize the coupling reaction of highly selective primary and secondary alkane C–H bond with ammonia. The catalyst showed high selectivity in the activation of primary and secondary C–H bond in the amidation reaction of linear and cyclic alkanes with aryl azide (Angew. Chem. Int. Ed. 2019, 58, 3421–3425.). In terms of photocatalysis, in 2023, Abigail G. Doyle reported a visible light redox catalytic method, which can realize the nucleophilic amination process of primary and secondary benzyl C(sp 3 )–H bond through hydrogen atom transfer (HAT) and oxidative radical-polar crossover strategy. In terms of electrocatalysis, in 2021, Professor Xu Haichao's group of Xiamen University reported a site-selective electrochemical amination reaction, which can realize the amination reaction of benzyl C–H bond through electrochemical selective oxidation without external oxidants or metal catalysts (Angew. Chem. Int. Ed. 2021, 60, 2943-2947.). Currently, transition metal-catalyzed C(sp 2-H) / C-N bond construction has been mature, the reaction mechanism is clear, the catalytic system is efficient, and is widely used in academic and industrial fields. However, with the development of green chemistry and the pursuit of clean and efficient use of energy, metal-free catalysis, ligand-free participation, mild conditions, green and high regioselectivity C-N bond formation reactions are still a hot topic in the field of chemistry. Under this background, the present application realizes the dehydrogenation cross-coupling reaction of cheap aryl alkane primary or secondary C-H and o-phenylthioimide N-H bond, which provides a new way and method for the construction of C(sp 3 -H) / C-N bond and C(sp 2 -H) / C-N bond construction provides a new way and method. The present application develops a green electrochemical oxidation dehydrogenation strategy to realize the activation of C-H bond and functionalization to construct C-N bond under mild conditions, which is high in atom economy, good in yield and mild in conditions, and is used for efficient and green preparation of nitrogen-containing drug small molecules. SUMMARY

[0005] The technical problems to be solved by the present application are as follows: ① the use of large polar high-boiling solvents; ② the need for equivalent strong base to participate, which causes the limitation of substrate application; ③ the need for pre-functionalization preparation of halogenated hydrocarbon raw materials, and the catalytic process cannot directly use alkanes; ④ high reaction temperature and long reaction time, etc. The present application provides a method for direct amination reaction of aromatic alkane carbon hydrogen bond.

[0006] In order to solve the above technical problems, the present application discloses a method for direct amination reaction of aromatic alkane carbon hydrogen bond. The present application provides a green and efficient preparation method for direct amination product of aromatic alkane carbon hydrogen bond. The present application uses electrochemical oxidation instead of transition metal catalysis strategy to realize the activation of carbon hydrogen bond of aromatic alkane and successfully construct C-N bond, and prepares a series of primary or secondary aromatic alkane inert C-H amination products. The method disclosed by the present application is a new method for constructing C-N coupling reaction of primary or secondary aromatic alkane C-H under metal-free mild conditions by electrochemical oxidation activation. The method uses cheap and easily available primary or secondary aromatic alkane instead of traditional halogenated hydrocarbon as raw material, sulfonimide substrate as ammonia source, without transition metal catalyst, base and organic ligand, and uses clean electron as oxidant to realize green and efficient aromatic alkane electrochemical oxidation carbon hydrogen bond amination product.

[0007] The specific technical solutions are as follows:

[0008] A method for direct amination reaction of aromatic alkane carbon hydrogen bond by electrochemical oxidation, wherein aromatic alkane compounds and sulfonimide compounds are subjected to electrochemical reaction in the presence of electrolyte to obtain amination product;

[0009] wherein the aromatic alkane compound has a structure as shown in Formula I, the sulfonamide compound has a structure as shown in Formula II or III, and the aminated product has a structure as shown in Formula IV or V.

[0010]

[0011] Preferably, the aromatic alkane compound having a structure as shown in Formula I and the sulfonamide compound having a structure as shown in Formula II are subjected to electrochemical reaction in the presence of an electrolyte to obtain the aminated product having a structure as shown in Formula IV; and the aromatic alkane compound having a structure as shown in Formula I and the sulfonamide compound having a structure as shown in Formula III are subjected to electrochemical reaction in the presence of an electrolyte to obtain the aminated product having a structure as shown in Formula V.

[0012] wherein R 1 is selected from any one of a hydrogen atom, an alkyl group, an alkoxy group, a fluoroalkyl group, a halogen, an ester group, a cyano group, a nitro group, a phenyl group, a substituted phenyl group, a furanyl group, a substituted furanyl group, a pyrrolyl group, a substituted pyrrolyl group, a thienyl group, and a substituted thienyl group;

[0013] R 2 , R 3 , R 4 , R 5 , and R 6 are each independently selected from any one of a hydrogen atom, an alkyl group, an alkoxy group, a fluoroalkyl group, a halogen, an acyl group, an ester group, a vinyl group, a phenyl group, a substituted phenyl group, a furanyl group, a substituted furanyl group, a pyrrolyl group, a substituted pyrrolyl group, a thienyl group, and a substituted thienyl group;

[0014] When R 6 is selected from a hydrogen atom, the aromatic alkane is a primary aromatic alkane; and when R 6 is selected from any one of an alkyl group, an alkoxy group, a fluoroalkyl group, a halogen, an acyl group, an ester group, a vinyl group, a phenyl group, a substituted phenyl group, a furanyl group, a substituted furanyl group, a pyrrolyl group, a substituted pyrrolyl group, a thienyl group, and a substituted thienyl group, the aromatic alkane is a secondary aromatic alkane. Preferably, R 1 is selected from any one of a hydrogen atom, an alkyl group, an alkoxy group, a fluoroalkyl group, a halogen, a phenyl group, a cyano group, and an ester group; R 2 , R 3 , R 4 , and R 5 are each independently selected from any one of an alkyl group, an alkoxy group, a phenyl group, a substituted phenyl group, and a thienyl group. R 6 is selected from any one of a hydrogen atom, an alkyl group, a vinyl group, a phenyl group, and a substituted phenyl group.

[0015] Preferably, the primary aromatic alkane includes any one of I-1 to I-12:

[0016]

[0017] Preferably, the secondary aromatic alkane includes any one of I-13 to I-31:

[0018]

[0019]

[0020] Preferably, the sulfonamide compound is selected from any one of II-1 to II-5, III-1, and III-2:

[0021]

[0022] Preferably, the amination product of the primary aromatic alkane includes any one of IV-1 to IV-15, V-1, or V-2:

[0023]

[0024]

[0025] Preferably, the amination product of the secondary aromatic alkane includes any one of IV-16 to IV-36:

[0026]

[0027]

[0028] wherein the molar ratio of the aromatic alkane compound to the sulfonamide compound is 4 to 6:1. Preferably, 4:1.

[0029] wherein the electrolyte includes any one of potassium bromide, ammonium bromide, tetraethylammonium bromide, tetrabutylammonium bromide, potassium iodide, or sodium bromide. Preferably, the electrolyte includes any one of sodium bromide, ammonium bromide, or potassium bromide. Further preferably, sodium bromide.

[0030] wherein the molar ratio of the electrolyte to the aromatic alkane compound is 1:2 to 4.

[0031] wherein the cathode material and the anode material of the electrochemical reaction are any one of carbon rod or platinum sheet. Preferably, the platinum sheet is the anode and the carbon rod is the cathode.

[0032] wherein the electrochemical reaction has a reaction current of 10 to 30 mA, preferably 20 mA. The reaction temperature is 60 to 80 °C, and the reaction time is 3 to 8 h. Preferably, the reaction is carried out at 80 °C for 5 h.

[0033] The electrochemical reaction includes a reaction solvent, which is acetonitrile. 0.1–0.4 mmol of an aromatic alkane compound is added per mL of acetonitrile. Preferably, 0.2–0.4 mmol of an aromatic alkane compound is added per mL of acetonitrile.

[0034] Preferably, the method uses inexpensive aromatic alkanes as raw materials, sulfonyl imide substrates as ammonia sources, clean electrons as oxidants, platinum sheets as anodes and carbon rods as cathodes, and sodium bromide (NaBr) as electrolyte. No external catalysts or oxidants are required, the reaction temperature is 80°C, no acid or alkali reagents are used, and the yield is moderate to excellent, successfully constructing high-value-added products from alkane C-H bond activated amination. More preferably, the electrochemical oxidation reaction involves dissolving aromatic alkanes, sulfonyl imide ammonia sources, and sodium bromide electrolyte in acetonitrile in an unseparated electrolytic cell, using platinum sheets as anodes and carbon rods as cathodes, under air conditions, at a reaction temperature of 80°C and a current of 20 mA for 5 hours, to obtain alkane C-H bond activated amination products. More preferably, the concentration of aromatic alkanes in the acetonitrile reaction solution is 0.2 mmol / mL.

[0035] Beneficial effects:

[0036] Currently, transition metal-catalyzed oxidation reactions for constructing C–N couplings face challenges such as poor regioselectivity, complex catalytic systems, large catalyst quantities, expensive raw materials, numerous byproducts, and low catalyst activity. To address these challenges, this invention provides an electrochemical oxidation strategy for the direct amination of C-H bonds in inert primary or secondary aromatic alkanes. This invention requires no catalyst or base, uses NaBr as the electrolyte, a platinum sheet as the anode and a carbon rod as the cathode, operates at a reaction temperature of 80°C, has a wide range of applications, and achieves efficient preparation of 17 direct oxidation amination products of benign C-H bonds in primary aromatic alkanes and 21 direct amination products of C-H bonds in secondary aromatic alkanes under mild reaction conditions. The yields are moderate to excellent, providing a simplified approach for the green preparation of small-molecule active pharmaceutical ingredients and offering a new strategy for the high-value utilization of inexpensive alkanes. Compared with the currently widely used substitution reactions using halogenated hydrocarbons as raw materials in strong bases and polar high-boiling solvents, this invention has better substrate universality, higher yield and atom economy, simpler oxidation process and lower energy consumption, thus reducing the production cost of such products and promoting the development of green processes.

[0037] This method improves reaction efficiency, ensures a clean and green reaction process, enhances reaction safety, minimizes environmental impact, and simplifies post-processing. Compared with existing technologies, the advantages of this invention are reflected in:

[0038] (1) The present application uses electrochemical oxidation process as reaction driving force, uses green electrons as oxidant, does not need to add metal catalyst and alkali, does not need to use the equivalent oxidant (such as TEMPO, KMnO4, BQ, etc.) widely used at present, and the reaction system is neutral, and the post-processing is simple.

[0039] (2) The present application directly uses primary or secondary aromatic alkane compounds as raw materials, is cheap and easy to obtain, the reaction system is simple and green, has little harm to the environment, replaces the widely used halogenated alkanes at present. Meanwhile, the high-value conversion and utilization of cheap alkanes can be realized.

[0040] (3) The present application is carried out in an electrolytic cell, is simple and safe to operate, has high mass transfer efficiency and short reaction time.

[0041] (4) Based on the present application, green and efficient preparation of multiple alkane direct oxidation amination compounds is realized, the yield is medium to excellent, which shows that the present application has wide applicability and universality for popularization and application.

[0042] The present application has mild reaction conditions, is easy to control, has high atom economy, is green, environmentally friendly, efficient and energy-saving in the reaction process. The prepared product has high economic value and application potential, and is expected to be widely used in the fields of green organic synthesis method and bioactive molecule creation. BRIEF DESCRIPTION OF DRAWINGS

[0043] The above and / or other aspects of the present application will become apparent from the following detailed description of the application taken in conjunction with the accompanying drawings.

[0044] Figure 1 The reaction general formula of the present application is shown in the following formula.

[0045] Figure 2 The general electrochemical reaction device used in the present application is shown in the following formula.

[0046] Figure 3 The gram-level reaction device is shown in the following formula.

[0047] Figure 4 The gram-level reaction product is shown in the following formula. DETAILED DESCRIPTION

[0048] The present application will be further described in detail in combination with specific examples, but the protection scope of the present application is not limited to this, and other oxidation amination reactions and corresponding skeleton products derived based on this technology are also included. The experimental methods mentioned in the following examples are all conventional methods, that is, common and general methods. The reagents and materials, if not specially mentioned, can be purchased from commercial channels.

[0049] The reaction general formula in the following examples is shown in the following formula. Figure 1 The electrochemical reaction device is shown in the following formula.Figure 2 as shown.

[0050] In the following examples, examples 1-35 are electrocatalytic amination of primary aromatic alkane to generate primary carbon-hydrogen bond amination products, and examples 36-71 are electrocatalytic amination of secondary aromatic alkane to generate secondary carbon-hydrogen bond amination products.

[0051] Example 1

[0052]

[0053] An open electrolysis cell (30 mL scale) was charged with o-phenylthiohydroxamic acid (0.5 mmol, 91.6 mg), electrolyte potassium bromide (1 mmol, 119.0 mg), acetonitrile (ACN, 10 mL), p-methylanisole (2 mmol, 244.3 mg) under air atmosphere. A carbon sheet (10 mm x 10 mm x 1 mm) was used as cathode and a platinum sheet (10 mm x 10 mm x 0.1 mm) as anode. A current of 20 mA was applied and the reaction temperature was set at 80 °C. The reaction was monitored by TLC and after completion of the reaction, the solvent was distilled off under reduced pressure and the target product, 2-(4-methoxybenzyl)benzo[d]isothiazol-3(2H)-one 1,1-dioxide, was isolated as a white solid in 16% yield using column chromatography (petroleum ether / ethyl acetate = 5 / 1).

[0054] Specific NMR data are as follows: 1 H NMR (400 MHz, CDC13): δ 8.04 (dd, J = 6.8, 1.3 Hz, 1H), 7.92 (dd, J = 6.9, 1.3 Hz, 1H), 7.87 - 7.79 (m, 2H), 7.45 (d, J = 8.7 Hz, 2H), 6.88 (d, J = 8.7 Hz, 2H), 4.85 (s, 2H), 3.79 (s, 3H); 13 C NMR (101 MHz, CDC13): δ 159.6, 158.9, 137.7, 134.8, 134.3, 130.4, 127.4, 126.6, 125.2, 121.0, 114.1, 55.3, 42.3.

[0055] Example 2

[0056] The experimental procedure was the same as Example 1, except that the electrolyte was ammonium bromide. An open electrolysis cell (30 mL scale) was charged with o- phenylthiohydroximic imide (0.5 mmol, 91.6 mg), ammonium bromide (1 mmol, 97.9 mg), acetonitrile (10 mL), p-methylanisole (2 mmol, 244.3 mg) under air atmosphere. A carbon sheet (10 mm x 10 mm x 1 mm) was used as the cathode and a platinum sheet (10 mm x 10 mm x 0.1 mm) as the anode. A current of 20 mA was applied and the reaction temperature was 80 °C. The reaction was allowed to proceed for 5 h. The progress of the reaction was monitored by TLC. After the reaction was completed, the solvent was removed by distillation under reduced pressure to obtain the crude product. The crude product was purified by column chromatography (petroleum ether / ethyl acetate = 5 / 1) to obtain the target product: 2-(4-methoxybenzyl)benzo[d]isothiazol-3(2H)-one 1,1-dioxide, white solid, the isolated yield was 34%.

[0057] Example 3

[0058] The experimental procedure was the same as Example 1, except that the electrolyte was tetraethylammonium bromide (Et4NBr).

[0059] An open electrolysis cell (30 mL scale) was charged with o-phenylthiohydroximic imide (0.5 mmol, 91.6 mg), tetraethylammonium bromide (1 mmol, 210.2 mg), acetonitrile (10 mL), p-methylanisole (2 mmol, 244.3 mg) under air atmosphere. A carbon sheet (10 mm x 10 mm x 1 mm) was used as the cathode and a platinum sheet (10 mm x 10 mm x 0.1 mm) as the anode. A current of 20 mA was applied and the reaction temperature was 80 °C. The reaction was allowed to proceed for 5 h. The progress of the reaction was monitored by TLC. It was found that the target product was not generated.

[0060] Example 4

[0061] The experimental procedure was the same as Example 1, except that the electrolyte was tetrabutylammonium bromide (TBABr).

[0062] An open electrolysis cell (30 mL scale) was charged with o-phenylthiohydroximic imide (0.5 mmol, 91.6 mg), tetrabutylammonium bromide (1 mmol, 322.4 mg), acetonitrile (10 mL), p-methylanisole (2 mmol, 244.3 mg, 252.1 μL) under air atmosphere. A carbon sheet (10 mm x 10 mm x 1 mm) was used as the cathode and a platinum sheet (10 mm x 10 mm x 0.1 mm) as the anode. A current of 20 mA was applied and the reaction temperature was 80 °C. The reaction was allowed to proceed for 5 h. The progress of the reaction was monitored by TLC. It was found that the target product was not generated.

[0063] Example 5

[0064] The experimental method is the same as example 1, except that the electrolyte is potassium iodide.

[0065] In an open electrolysis cell (30 mL scale) under air atmosphere, o- phenylthiohydroximic imide (0.5 mmol, 91.6 mg), potassium iodide (1 mmol, 166.0 mg), acetonitrile (10 mL), p-methylanisole (2 mmol, 244.3 mg) were added. A carbon sheet (10 mm x 10 mm x 1 mm) was used as cathode and a platinum sheet (10 mm x 10 mm x 0.1 mm) as anode. A current of 20 mA was applied and the reaction temperature was 80 °C. The reaction was carried out for 5 h. TLC was used to monitor the reaction and no target product was found.

[0066] Example 6

[0067] The experimental method is the same as example 1, except that the electrolyte is sodium bromide. In an open electrolysis cell (30 mL scale) under air atmosphere, o- phenylthiohydroximic imide (0.5 mmol, 91.6 mg), sodium bromide (1 mmol, 102.9 mg), acetonitrile (10 mL), p-methylanisole (2 mmol, 244.3 mg) were added. A carbon sheet (10 mm x 10 mm x 1 mm) was used as cathode and a platinum sheet (10 mm x 10 mm x 0.1 mm) as anode. A current of 20 mA was applied and the reaction temperature was 80 °C. The reaction was carried out for 5 h. TLC was used to monitor the reaction and no target product was found.

[0068] The product yield obtained under the reaction conditions described in examples 1-6 is shown in Table 1.

[0069] Table 1 Influence of different electrolyte types on product yield under the reaction conditions described in examples 1-6

[0070]

[0071] Note: In Table 1 a The product yield was obtained by actual separation; b The product yield was obtained by TLC spotting observation.

[0072] Example 7

[0073] The experimental method is the same as example 6, except that both the anode and cathode materials are platinum sheet electrodes.

[0074] An open electrolysis cell (30 mL scale) was charged with o-phenylthiohydroximic imide (0.5 mmol, 91.6 mg), sodium bromide (1 mmol, 102.9 mg), acetonitrile (10 mL), p-methylanisole (2 mmol, 244.3 mg) under air atmosphere. Platinum plate (10 mm x 10 mm x 0.1 mm) was used as cathode and carbon plate (10 mm x 10 mm x 1 mm) as anode. A current of 20 mA was applied and the reaction temperature was set at 80 °C. The reaction was monitored by TLC and was completed in 5 h. After the reaction was completed, the solvent was distilled off under reduced pressure to obtain the crude product which was separated by column chromatography (petroleum ether / ethyl acetate = 5 / 1) to obtain the target product: 2-(4-methoxybenzyl)benzo[d]isothiazol-3(2H)-one 1,1-dioxide as a white solid with an isolated yield of 38%.

[0075] Example 8

[0076] The experimental procedure was the same as in Example 6 except that the anode was carbon plate and the cathode was platinum plate.

[0077] An open electrolysis cell (30 mL scale) was charged with o-phenylthiohydroximic imide (0.5 mmol, 91.6 mg), sodium bromide (1 mmol, 102.9 mg), acetonitrile (10 mL), p-methylanisole (2 mmol, 244.3 mg) under air atmosphere. Platinum plate (10 mm x 10 mm x 0.1 mm) was used as cathode and carbon plate (10 mm x 10 mm x 1 mm) as anode. A current of 20 mA was applied and the reaction temperature was set at 80 °C. The reaction was monitored by TLC and was completed in 5 h. After the reaction was completed, the solvent was distilled off under reduced pressure to obtain the crude product which was separated by column chromatography (petroleum ether / ethyl acetate = 5 / 1) to obtain the target product: 2-(4-methoxybenzyl)benzo[d]isothiazol-3(2H)-one 1,1-dioxide with an isolated yield of 12%.

[0078] The product yields obtained under the reaction conditions described in Examples 6-8 are shown in Table 2.

[0079] Table 2: Effect of different electrode materials on product yield under the reaction conditions described in Examples 6-8

[0080] Reaction conditions Example 7 Example 8 Example 6 Materials (anode / cathode) Pt disc / Pt disc Carbon rod / Pt disc Pt disc / Carbon rod Yield a (%)]] 38.0 12.0 76.0

[0081] Note: In Table 2 a The product yield was obtained from actual separation.

[0082] Example 9

[0083] The experimental procedure was same as example 6 except that the current was 15 mA. In an open electrolysis cell (30 mL scale) was placed o-phenylthiohydroximic imide (0.5 mmol, 91.6 mg), sodium bromide (1 mmol, 102.9 mg), acetonitrile (10 mL), p-methylanisole (2 mmol, 244.3 mg, 252.1 μL) under air atmosphere. A carbon sheet (10 mm x 10 mm x 1 mm) was used as cathode and platinum sheet (10 mm x 10 mm x 0.1 mm) as anode. A current of 15 mA was applied and the reaction temperature was 80 °C. The reaction was carried out for 5 h. The progress of the reaction was monitored by TLC. After completion of the reaction, the solvent was distilled off under reduced pressure to obtain the crude product. The crude product was purified by column chromatography (petroleum ether / ethyl acetate = 5 / 1) to obtain the desired product: 2-(4-methoxybenzyl)benzo[d]isothiazol-3(2H)-one 1,1-dioxide as a white solid with 14% isolated yield.

[0084] Example 10

[0085] The experimental procedure was same as example 6 except that the current was 25 mA.

[0086] In an open electrolysis cell (30 mL scale) was placed o-phenylthiohydroximic imide (0.5 mmol, 91.6 mg), sodium bromide (1 mmol, 102.9 mg), acetonitrile (10 mL), p-methylanisole (2 mmol, 244.3 mg) under air atmosphere. A carbon sheet (10 mm x 10 mm x 1 mm) was used as cathode and platinum sheet (10 mm x 10 mm x 0.1 mm) as anode. A current of 25 mA was applied and the reaction temperature was 80 °C. The reaction was carried out for 5 h. The progress of the reaction was monitored by TLC. After completion of the reaction, the solvent was distilled off under reduced pressure to obtain the crude product. The crude product was purified by column chromatography (petroleum ether / ethyl acetate = 5 / 1) to obtain the desired product: 2-(4-methoxybenzyl)benzo[d]isothiazol-3(2H)-one 1,1-dioxide as a white solid with 73% isolated yield. The product yield obtained under the reaction conditions described in examples 9-10 is shown in table 3.

[0087] Table 3: Effect of different current on product yield under the reaction conditions described in examples 9-10

[0088] Example 9 Example 10 Example 6 Current (mA) 15 25 20 Yield a (%)]] 14.0 73.0 76.0

[0089] Note: In table 3 a Product yield obtained from actual isolation.

[0090] Example 11

[0091] The experimental procedure was same as example 6 except that the reaction time was 3h. In an open electrolysis cell (30 mL scale) was placed o-phenylthiohydroximic imide (0.5 mmol, 91.6 mg), sodium bromide (1 mmol, 102.9 mg), acetonitrile (10 mL), p-methylanisole (2 mmol, 244.3 mg) under air atmosphere. A carbon sheet (10 mm x 10 mm x 1 mm) was used as cathode and platinum sheet (10 mm x 10 mm x 0.1 mm) as anode. A current of 20 mA was applied and the reaction temperature was maintained at 80 °C for 3h. The progress of the reaction was monitored by TLC. After completion of the reaction, the solvent was distilled off under reduced pressure to obtain the crude product which was purified by column chromatography (petroleum ether / ethyl acetate = 5 / 1) to obtain the desired product: 2-(4-methoxybenzyl)benzo[d]isothiazol-3(2H)-one 1,1-dioxide as white solid with 64% isolated yield.

[0092] Example 12

[0093] The experimental procedure was same as example 6 except that the reaction time was 10h. In an open electrolysis cell (30 mL scale) was placed o-phenylthiohydroximic imide (0.5 mmol, 91.6 mg), sodium bromide (1 mmol, 102.9 mg), acetonitrile (10 mL), p-methylanisole (2 mmol, 244.3 mg) under air atmosphere. A carbon sheet (10 mm x 10 mm x 1 mm) was used as cathode and platinum sheet (10 mm x 10 mm x 0.1 mm) as anode. A current of 20 mA was applied and the reaction temperature was maintained at 80 °C for 10h. The progress of the reaction was monitored by TLC. After completion of the reaction, the solvent was distilled off under reduced pressure to obtain the crude product which was purified by column chromatography (petroleum ether / ethyl acetate = 5 / 1) to obtain the desired product: 2-(4-methoxybenzyl)benzo[d]isothiazol-3(2H)-one 1,1-dioxide as white solid with 12% isolated yield. The results are shown in Table 4.

[0094] Table 4: Effect of different reaction time on product yield under reaction conditions described in example 11-12

[0095] Example 11 Example 12 Example 6 Time (h) 3 10 5 Yield a (%)]] 64.0 12.0 76.0

[0096] Note: In Table 4 a Product yield obtained from actual isolation.

[0097] Example 13

[0098] The experimental method is the same as that of Example 6, except that the solvent is N,N-dimethylformamide (DMF). In an open electrolysis cell (30 mL scale) was added o-phenylthiohydroximic imide (0.5 mmol, 91.6 mg), sodium bromide (1 mmol, 102.9 mg), DMF (10 mL), p-methyl anisole (2 mmol, 244.3 mg) under air atmosphere. A carbon sheet (10 mm x 10 mm x 1 mm) was used as cathode and platinum sheet (10 mm x 10 mm x 0.1 mm) as anode. A current of 20 mA was applied and the reaction temperature was 80 °C. The reaction was carried out for 5 h. TLC was used to monitor the reaction and no target product was found.

[0099] Example 14

[0100] The experimental method is the same as that of Example 6, except that the solvent is 1,2-dichloroethane (DCE).

[0101] In an open electrolysis cell (30 mL scale) was added o-phenylthiohydroximic imide (0.5 mmol, 91.6 mg), sodium bromide (1 mmol, 102.9 mg), DCE (10 mL), p-methyl anisole (2 mmol, 244.3 mg, 252.1 μL) under air atmosphere. A carbon sheet (10 mm x 10 mm x 1 mm) was used as cathode and platinum sheet (10 mm x 10 mm x 0.1 mm) as anode. A current of 20 mA was applied and the reaction temperature was 80 °C. The reaction was carried out for 5 h. TLC was used to monitor the reaction and no target product was found. The product yield obtained under the reaction conditions described in Examples 13-14 is shown in Table 5.

[0102] Table 5 Effect of different solvent types on product yield under the reaction conditions described in Examples 13-14

[0103] Example 13 Example 14 Example 6 Solvent (10 mL) DMF DCE ACN Yield a (%)]] 0 b ]] 0 b ]] 76.0

[0104] Note: In Table 5 a The product yield was obtained by actual separation; b The product yield was obtained by TLC spotting observation.

[0105] Example 15

[0106] The experimental method is the same as that of Example 6, except that the reaction temperature is room temperature.

[0107] An open electrolysis cell (30 mL scale) was charged with o-phenylthiohydroximic imide (0.5 mmol, 91.6 mg), sodium bromide (1 mmol, 102.9 mg), acetonitrile (10 mL), p-methylanisole (2 mmol, 244.3 mg) under air atmosphere. A carbon sheet (10 mm x 10 mm x 1 mm) was used as cathode and a platinum sheet (10 mm x 10 mm x 0.1 mm) as anode. A current of 20 mA was applied and the reaction was carried out at room temperature for 5 h. The reaction was monitored by TLC during the reaction. After completion of the reaction, the solvent was distilled off under reduced pressure to obtain the crude product, which was purified by column chromatography (petroleum ether / ethyl acetate = 5 / 1) to obtain the desired product: 2-(4-methoxybenzyl)benzo[d]isothiazol-3(2H)-one 1,1-dioxide as a white solid with an isolated yield of 11%.

[0108] Example 16

[0109] The experimental procedure was same as Example 6 except that the reaction was carried out at 40 °C. An open electrolysis cell (30 mL scale) was charged with o-phenylthiohydroximic imide (0.5 mmol, 91.6 mg), sodium bromide (1 mmol, 102.9 mg), acetonitrile (10 mL), p-methylanisole (2 mmol, 244.3 mg) under air atmosphere. A carbon sheet (10 mm x 10 mm x 1 mm) was used as cathode and a platinum sheet (10 mm x 10 mm x 0.1 mm) as anode. A current of 20 mA was applied and the reaction was carried out at 40 °C for 5 h. The reaction was monitored by TLC during the reaction. After completion of the reaction, the solvent was distilled off under reduced pressure to obtain the crude product, which was purified by column chromatography (petroleum ether / ethyl acetate = 5 / 1) to obtain the desired product: 2-(4-methoxybenzyl)benzo[d]isothiazol-3(2H)-one 1,1-dioxide as a white solid with an isolated yield of 18%.

[0110] Example 17

[0111] The experimental procedure was same as Example 6 except that the reaction was carried out at 60 °C.

[0112] An open electrolysis cell (30 mL scale) was charged with o-phenylthiohydroxamic acid (0.5 mmol, 91.6 mg), sodium bromide (1 mmol, 102.9 mg), acetonitrile (10 mL), p-methylanisole (2 mmol, 244.3 mg) under air atmosphere. A carbon sheet (10 mm x 10 mm x 1 mm) was used as cathode and a platinum sheet (10 mm x 10 mm x 0.1 mm) as anode. A current of 20 mA was applied and the reaction temperature was set at 60 °C. The reaction was monitored by TLC and was completed after 5 h. The solvent was removed under reduced pressure to give the crude product which was purified by column chromatography (petroleum ether / ethyl acetate = 5 / 1) to give the target product: 2-(4-methoxybenzyl)benzo[d]isothiazol-3(2H)-one 1,1-dioxide as a white solid with an isolated yield of 34%.

[0113] The product yields obtained under the reaction conditions described in Examples 15-17 are shown in Table 6.

[0114] Table 6. Effect of different reaction temperatures on product yields under the reaction conditions described in Examples 15-17

[0115] Example 15 Example 16 Example 17 Example 6 Reaction temperature (°C) Room temperature 40 60 80 Yield a (%)]] 11.0 18.0 34.0 76.0

[0116] Note: In Table 6 a The product yields were obtained from actual isolation.

[0117] Example 18

[0118] The procedure of Example 6 was followed, except that 1,8-diazabicycloundec-7-ene (DBU) (1 mmol) was added as an organic base. An open electrolysis cell (30 mL scale) was charged with o-phenylthiohydroxamic acid (0.5 mmol, 91.6 mg), sodium bromide (1 mmol, 102.9 mg), acetonitrile (10 mL), p-methylanisole (2 mmol, 244.3 mg), DBU (1 mmol, 152.4 mg) under air atmosphere. A carbon sheet (10 mm x 10 mm x 1 mm) was used as cathode and a platinum sheet (10 mm x 10 mm x 0.1 mm) as anode. A current of 20 mA was applied and the reaction temperature was set at 80 °C. The reaction was monitored by TLC and was completed after 5 h. The solvent was removed under reduced pressure to give the crude product which was purified by column chromatography (petroleum ether / ethyl acetate = 5 / 1) to give the target product: 2-(4-methoxybenzyl)benzo[d]isothiazol-3(2H)-one 1,1-dioxide as a white solid with an isolated yield of 18%.

[0119] Example 19

[0120] The experimental method is the same as Example 6, except that Na2C03 (1 mmol) is added as an inorganic base. In an open electrolysis cell (30 mL scale) under air atmosphere, o- phenylthiohydroximic imide (0.5 mmol, 91.6 mg), sodium bromide (1 mmol, 102.9 mg), Na2C03 (1 mmol, 104.0 mg), acetonitrile (10 mL), p-methylanisole (2 mmol, 244.3 mg) are added. A carbon sheet (10 mm x 10 mm x 1 mm) is used as the cathode and a platinum sheet (10 mm x 10 mm x 0.1 mm) as the anode. A current of 20 mA is applied and the reaction temperature is 80 °C. The reaction is allowed to proceed for 5 h. The progress of the reaction is monitored by TLC. After the reaction is complete, the solvent is distilled off under reduced pressure to obtain the crude product, which is separated by column chromatography (petroleum ether / ethyl acetate = 5 / 1) to obtain the target product: 2-(4-methoxybenzyl)benzo[d]isothiazol-3(2H)-one-1,1-dioxide, white solid, with an isolated yield of 26%. The product yields obtained under the reaction conditions described in Examples 18-19 are shown in Table 7.

[0121] Table 7. Effect of different base addition on product yield under the reaction conditions described in Examples 18-19

[0122] Example 18 Example 19 Example 6 Base (1.0 mmol) DBU Na2CO3 - Yield a (%)]] 18.0 26.0 76.0

[0123] Note: In Table 7 a The product yield is obtained from actual separation.

[0124] Example 20

[0125]

[0126] In an open electrolysis cell (30 mL scale) under air atmosphere, o- phenylthiohydroximic imide (0.5 mmol, 91.6 mg), sodium bromide (1 mmol, 102.9 mg), acetonitrile (10 mL), 4-tert-butyltoluene (2 mmol, 296.5 mg) are added. A carbon sheet (10 mm x 10 mm x 1 mm) is used as the cathode and a platinum sheet (10 mm x 10 mm x 0.1 mm) as the anode. A current of 20 mA is applied and the reaction temperature is 80 °C. The reaction is allowed to proceed for 5 h. The progress of the reaction is monitored by TLC. After the reaction is complete, the solvent is distilled off under reduced pressure to obtain the crude product, which is separated by column chromatography (petroleum ether / ethyl acetate = 5 / 1) to obtain the target product: 2-(4-tert-butylbenzyl)benzo[d]isothiazol-3(2H)-one-1,1-dioxide, white solid, with an isolated yield of 49%. The specific NMR data are as follows: 1HNMR (400 MHz, CDC13): δ 8.07 - 8.03 (m, 1H), 7.93 (dd, J = 6.9, 1.3 Hz, 1H), 7.88 - 7.79 (m, 2H), 7.45 (d, J = 8.4 Hz, 2H), 7.41 - 7.34 (d, J = 8.4 Hz, 2H), 4.88 (s, 2H), 1.30 (s, 9H); 13 C NMR (101 MHz, CDC13): δ 158.9, 151.2, 137.7, 134.8, 134.3, 131.4, 128.6, 127.4, 125.7, 125.2, 121.0, 42.4, 34.6, 31.3.

[0127] Example 21

[0128]

[0129] An open electrolysis cell (30 mL scale) was charged with o-phenylthiohydroximic acid (0.5 mmol, 91.6 mg), sodium bromide (1 mmol, 102.9 mg), acetonitrile (10 mL), p-chloromethylbenzene (2 mmol, 253.2 mg) under air atmosphere. A carbon sheet (10 mm x 10 mm x 1 mm) was used as cathode and platinum sheet (10 mm x 10 mm x 0.1 mm) as anode. A current of 20 mA was applied and the reaction temperature was set at 80 °C. The reaction was monitored by TLC during the reaction. After completion of the reaction, the solvent was distilled off under reduced pressure to obtain the crude product which was purified by column chromatography (petroleum ether / ethyl acetate = 5 / 1) to obtain the target product: 2-(4-chlorobenzyl)benzo[d]isothiazol-3(2H)-one 1,1-dioxide as a white solid in 57% isolated yield.

[0130] Specific NMR data are as follows:

[0131] 1 H NMR (400 MHz, CDC13): δ 7.99 (d, J = 6.6 Hz, 1H), 7.87 (d, J = 7.2 Hz, 1H), 7.84 - 7.74 (m, 2H), 7.41 - 7.35 (m, 2H), 7.29 - 7.22 (m, 2H), 4.80 (s, 2H). 13 C NMR (101 MHz, CDC13): δ 158.9, 137.7, 135.0, 134.5, 134.3, 133.0, 130.2, 128.9, 127.2, 125.3, 121.1, 42.0.

[0132] Example 22

[0133]

[0134] An open electrolysis cell (30 mL scale) was charged with o-phenylthiohydroximic imide (0.5 mmol, 91.6 mg), sodium bromide (1 mmol, 102.9 mg), acetonitrile (10 mL), 4-bromotoluene (2 mmol, 342.1 mg) under air atmosphere. A carbon sheet (10 mm x 10 mm x 1 mm) was used as cathode and platinum sheet (10 mm x 10 mm x 0.1 mm) as anode. A current of 20 mA was applied and the reaction temperature was set at 80 °C for 5 h. The reaction was monitored by TLC during the reaction. After completion, the solvent was distilled off under reduced pressure to obtain the crude product which was purified by column chromatography (petroleum ether / ethyl acetate = 5 / 1) to obtain the desired product: 2-(4-bromobenzyl)benzo[d]isothiazol-3(2H)-one 1,1-dioxide as a white solid in 48% isolated yield.

[0135] Specific NMR data are as follows:

[0136] 1 H NMR (400 MHz, CDC13): δ 7.99 (dd, J = 6.6, 1.0 Hz, 1H), 7.87 (dd, J = 7.0, 1.2 Hz, 1H), 7.79 (dtd, J = 17.6, 7.4, 1.3 Hz, 2H), 7.44 - 7.39 (m, 2H), 7.35 - 7.30 (m, 2H), 4.78 (s, 2H); 13 C NMR (101 MHz, CDC13): δ 158.9, 137.7, 135.0, 134.5, 133.5, 131.9, 130.5, 128.8, 127.2, 125.3, 121.1, 42.0.

[0137] Example 23

[0138]

[0139] An open electrolysis cell (30 mL scale) was charged with o-phenylthiohydroximic imide (0.5 mmol, 91.6 mg), sodium bromide (1 mmol, 102.9 mg), acetonitrile (10 mL), 4-bromotoluene (2 mmol, 342.1 mg) under air atmosphere. A carbon sheet (10 mm x 10 mm x 1 mm) was used as cathode and platinum sheet (10 mm x 10 mm x 0.1 mm) as anode. A current of 20 mA was applied and the reaction temperature was set at 80 °C for 5 h. The reaction was monitored by TLC during the reaction. After completion, the solvent was distilled off under reduced pressure to obtain the crude product which was purified by column chromatography (petroleum ether / ethyl acetate = 5 / 1) to obtain the desired product: 2-(4-bromobenzyl)benzo[d]isothiazol-3(2H)-one 1,1-dioxide as a white solid in 48% isolated yield.

[0140] Specific NMR data are as follows:

[0141] 1 H NMR (400 MHz, CDC13): δ 8.05 (d, J = 7.0 Hz, 1H), 7.92 (d, J = 6.7 Hz, 1H), 7.83 (dtd, J = 17.0, 7.4, 1.3 Hz, 2H), 7.40 (d, J = 8.1 Hz, 2H), 7.16 (d, J = 7.8 Hz, 2H), 4.87 (s, 2H), 2.33 (s, 3H); 13 C NMR (101 MHz, CDC13): δ 158.9, 138.1, 137.8, 134.8, 134.3, 131.5, 129.4, 128.8, 127.4, 125.2, 121.0, 42.5, 21.2.

[0142] Example 24

[0143]

[0144] An open electrolysis cell (30 mL scale) was charged with o-phenylthiohydroximic acid (0.5 mmol, 91.6 mg), sodium bromide (1 mmol, 102.9 mg), acetonitrile (10 mL), 3-methylbenzoic acid methyl ester (2 mmol, 300.3 mg) under air atmosphere. A carbon sheet (10 mm x 10 mm x 1 mm) was used as cathode and platinum sheet (10 mm x 10 mm x 0.1 mm) as anode. A current of 20 mA was applied and the reaction temperature was set at 80 °C. The reaction was monitored by TLC and after completion of the reaction, the solvent was distilled off under reduced pressure to obtain the crude product which was purified by column chromatography (petroleum ether / ethyl acetate = 5 / 1) to obtain the target product: 3-[(1,1-dioxido-3-oxobenzo[d]isothiazol-2(3H)-yl)methyl]benzoic acid methyl ester as a white solid with an isolated yield of 32%. Specific NMR data are as follows:

[0145] 1 H NMR (400 MHz, CDC13): δ 8.18 (s, 1H), 8.07 (dd, J = 7.0, 1.5 Hz, 1H), 8.00 (d, J = 7.8 Hz, 1H), 7.94 (d, J = 7.2 Hz, 1H), 7.86 (dtd, J = 17.2, 7.4, 1.3 Hz, 2H), 7.71 (d, J = 7.7 Hz, 1H), 7.45 (t, J = 7.7 Hz, 1H), 4.96 (s, 2H), 3.91 (s, 3H); 13C NMR (101 MHz, CDC13): δ 166.7, 158.9, 137.7, 135.0, 134.9, 134.5, 133.1, 130.7, 129.8, 129.6, 128.9, 127.2, 125.4, 121.1, 52.3, 42.3.

[0146] Example 25

[0147]

[0148] An open electrolysis cell (30 mL scale) was charged with o-phenylthiohydroximic acid (0.5 mmol, 91.6 mg), sodium bromide (1 mmol, 102.9 mg), acetonitrile (10 mL), 2-fluorotoluene (2 mmol, 220.3 mg) under air atmosphere. A carbon sheet (10 mm x 10 mm x 1 mm) was used as cathode and a platinum sheet (10 mm x 10 mm x 0.1 mm) as anode. A current of 20 mA was applied and the reaction temperature was set to 80 °C. The reaction was monitored by TLC and after completion of the reaction, the solvent was distilled off under reduced pressure to obtain the crude product which was purified by column chromatography (petroleum ether / ethyl acetate = 5 / 1) to obtain the target product: 2-(2-fluorobenzyl)benzo[d]isothiazol-3(2H)-one 1,1-dioxide as a white solid in 29% isolated yield.

[0149] Specific NMR data are as follows:

[0150] 1 H NMR (400 MHz, CDC13): δ 8.11 - 8.07 (m, 1H), 7.94 (dd, J = 6.9, 1.4 Hz, 1H), 7.86 (dtd, J = 16.3, 7.4, 1.3 Hz, 2H), 7.48 (td, J = 7.6, 1.5 Hz, 1H), 7.31 (tdd, J = 7.3, 5.3, 1.7 Hz, 1H), 7.17 - 7.05 (m, 2H), 5.02 (d, J = 1.1 Hz, 2H); 13 C NMR (101 MHz, CDC13) 13C NMR (101 MHz, CDC13) δ 162.0, 159.5, 158.8, 137.8, 134.9, 134.4, 130.4 (d, J = 3.1 Hz), 130.2 (d, J = 8.0 Hz), 127.2, 125.4, 124.4 (d, J = 4.1 Hz), 121.6 (d, J = 14.0 Hz), 121.1, 115.6 (d, J = 21.1 Hz), 36.0 (d, J = 21.1 Hz); 19 F NMR (376 MHz, CDC13): δ -117.13.

[0151] Example 26

[0152]

[0153] An open electrolysis cell (30 mL scale) was charged with o-phenylthiohydroximic acid (0.5 mmol, 91.6 mg), o-xylene (2 mmol, 212.3 mg), sodium bromide (1 mmol, 102.9 mg), acetonitrile (10 mL), o-xylene (2 mmol, 212.3 mg) under air atmosphere. A carbon sheet (10 mm x 10 mm x 1 mm) was used as cathode and platinum sheet (10 mm x 10 mm x 0.1 mm) as anode. A current of 20 mA was applied and the reaction temperature was set at 80 °C for 5 h. The reaction was monitored by TLC during the reaction. After completion, the solvent was distilled off under reduced pressure to obtain the crude product which was purified by column chromatography (petroleum ether / ethyl acetate = 5 / 1) to obtain the target product: 2-(2-methylbenzyl)benzo[d]isothiazol-3(2H)-one 1,1-dioxide as a white solid with 60% isolated yield. The specific NMR data are as follows:

[0154] 1 H NMR (400 MHz, CDC13): δ 8.11 - 8.07 (m, 1H), 7.93 (dd, J = 6.7, 1.6 Hz, 1H), 7.86 (dtd, J = 14.4, 7.4, 1.4 Hz, 2H), 7.42 (dd, J = 7.8, 1.9 Hz, 1H), 7.25 - 7.16 (m, 3H), 4.96 (s, 2H), 2.47 (s, 3H); 13 C NMR (101 MHz, CDC13): δ 159.0, 137.9, 136.3, 134.9, 134.4, 132.1, 130.5, 128.7, 128.4, 127.3, 126.3, 125.3, 121.0, 40.6, 19.3.

[0155] Example 27

[0156]

[0157] An open electrolysis cell (30 mL scale) was charged with o-phenylthiohydroximic imide (0.5 mmol, 91.6 mg), sodium bromide (1 mmol, 102.9 mg), acetonitrile (10 mL), 2,3-dichlorotoluene (2 mmol, 322.1 mg) under air atmosphere. A carbon sheet (10 mm x 10 mm x 1 mm) was used as cathode and platinum sheet (10 mm x 10 mm x 0.1 mm) as anode. A current of 20 mA was applied and the reaction temperature was 80 °C for 5 h. The reaction was monitored by TLC during the reaction. After completion of the reaction, the solvent was distilled off under reduced pressure to obtain the crude product which was purified by column chromatography (petroleum ether / ethyl acetate = 5 / 1) to obtain the target product: 2-(2,3-dichlorobenzyl)benzo[d]isothiazol-3(2H)-one 1,1-dioxide as a white solid with 42% isolated yield. The specific NMR data are as follows:

[0158] The specific NMR data are as follows:

[0159] 1 H NMR (400 MHz, CDC13): δ 8.06 (d, J = 6.8 Hz, 1H), 7.93 (d, J = 6.8 Hz, 1H), 7.84 (dtd, J = 16.3, 7.4, 1.2 Hz, 2H), 7.11 (s, 2H), 6.94 (s, 1H), 4.84 (s, 2H), 2.30 (s, 6H); 13 C NMR (101 MHz, CDC13): δ 156.0, 138.3, 137.8, 134.8, 134.4, 130.0, 127.4, 126.4, 125.3, 121.0, 42.6, 21.3.

[0160] Example 28

[0161]

[0162] An open electrolysis cell (30 mL scale) was charged with o-phenylthiohydroximic imide (0.5 mmol, 91.6 mg), sodium bromide (1 mmol, 102.9 mg), acetonitrile (10 mL), 2,3-dichlorotoluene (2 mmol, 322.1 mg) under air atmosphere. A carbon sheet (10 mm x 10 mm x 1 mm) was used as cathode and platinum sheet (10 mm x 10 mm x 0.1 mm) as anode. A current of 20 mA was applied and the reaction temperature was 80 °C for 5 h. The reaction was monitored by TLC during the reaction. After completion of the reaction, the solvent was distilled off under reduced pressure to obtain the crude product which was purified by column chromatography (petroleum ether / ethyl acetate = 5 / 1) to obtain the target product: 2-(2,3-dichlorobenzyl)benzo[d]isothiazol-3(2H)-one 1,1-dioxide as a white solid with 42% isolated yield. The specific NMR data are as follows:

[0163] 1 H NMR (400 MHz, CDC13): δ 8.12 (d, J = 6.7 Hz, 1H), 7.99 - 7.85 (m, 3H), 7.44 (d, J = 8.0 Hz, 1H), 7.34 (d, J = 8.4 Hz, 1H), 7.19 (t, J = 7.9 Hz, 1H), 5.10 (s, 2H); 13 C NMR (101 MHz, CDC13): δ 158.9, 137.8, 135.1, 134.6, 134.2, 133.5, 131.5, 130.2, 127.5, 127.0, 125.5, 121.2, 40.7.

[0164] Example 29

[0165]

[0166] An open electrolysis cell (30 mL scale) was charged with o-phenylthiohydroximic acid (0.5 mmol, 91.6 mg), sodium bromide (1 mmol, 102.9 mg), acetonitrile (10 mL), 2,6-dimethylanisole (2 mmol, 272.4 mg) under air atmosphere. A carbon sheet (10 mm x 10 mm x 1 mm) was used as cathode and a platinum sheet (10 mm x 10 mm x 0.1 mm) as anode. A current of 20 mA was applied and the reaction temperature was set to 80 °C. The reaction was monitored by TLC and after completion of the reaction, the solvent was distilled off under reduced pressure to obtain the crude product which was purified by column chromatography (petroleum ether / ethyl acetate = 5 / 1) to obtain the target product: 2-(2-methoxy-3-methylbenzyl)benzo[d]isothiazol-3(2H)-one 1,1-dioxide as a white solid with an isolated yield of 33%. The specific NMR data are as follows:

[0167] 1 H NMR (400 MHz, CDC13): δ 8.08 (dd, J = 6.9, 1.7 Hz, 1H), 7.93 (dd, J = 6.8, 1.4 Hz, 1H), 7.89 - 7.79 (m, 2H), 7.24 (s, 1H), 7.14 (d, J = 7.1 Hz, 1H), 6.99 (t, J = 7.6 Hz, 1H), 5.03 (s, 2H), 3.87 (s, 3H), 2.33 (s, 3H); 13 C NMR (101 MHz, CDC13): δ 159.0, 156.6, 138.0, 134.8, 134.3, 131.6, 131.2, 127.4, 127.4, 127.0, 125.3, 124.2, 121.0, 60.6, 37.6, 16.1.

[0168] Example 30

[0169]

[0170] Under air atmosphere, o-phenylthioimide (0.5 mmol, 91.6 mg), sodium bromide (1 mmol, 102.9 mg), acetonitrile (10 mL), and 2,6-dimethoxytoluene (2 mmol, 304.2 mg) were added to an open electrolytic cell (30 mL). A carbon sheet (10 mm × 10 mm × 1 mm) was used as the cathode, and a platinum sheet (10 mm × 10 mm × 0.1 mm) as the anode. A current of 20 mA was applied, and the reaction temperature was 80 °C for 5 h. The product was monitored by TLC during the reaction. After the reaction was complete, the solvent was distilled off under reduced pressure to obtain the crude product. The crude product was then separated by column chromatography (petroleum ether / ethyl acetate = 5 / 1) to obtain the target product: 2-(2,6-dimethoxybenzyl)benzo[d]isothiazolyl-3(2H)-one-1,1-dioxide, a white solid, with a separation yield of 60%. Specific NMR data are as follows:

[0171] 1 H NMR (400MHz, CDCl3): δ8.07–8.03(m,1H),7.85–7.73(m,2H),7.30–7.23(m,2H),6.56(d,J=8.4Hz,2H),5.13(s,2H),3.87(s,6H); 13 C NMR (101MHz, CDCl3): δ159.3,158.5,138.2,134.4,133.9,130.2,127.5,125.0,120.5,110.1,103.6,55.9,32.1.

[0172] Example 31

[0173]

[0174] Under air atmosphere, N-acetyl-p-toluenesulfonamide (0.5 mmol, 106.6 mg), sodium bromide (1 mmol, 102.9 mg), acetonitrile (10 mL), and p-methyl anisole (2 mmol, 244.1 mg) were added to an open electrolytic cell (30 mL). A carbon sheet (10 mm × 10 mm × 1 mm) was used as the cathode and a platinum sheet (10 mm × 10 mm × 0.1 mm) as the anode. A current of 20 mA was applied, and the reaction temperature was 80 °C for 5 h. The product was monitored by TLC during the reaction. After the reaction was completed, the solvent was distilled off under reduced pressure to obtain the crude product, which was then separated by column chromatography (petroleum ether / ethyl acetate = 5 / 1) to obtain the target product: N-(4-methoxybenzyl)-N-toluenesulfonylacetamide, a white solid, with a separation yield of 42%.

[0175] The specific NMR data are as follows:

[0176] 1 H NMR (400MHz, CDCl3): δ7.59(d,J=8.3Hz,2H),7.34(d,J=8.6Hz,2H),7.26(d,J=8.0 Hz,2H),6.86(d,J=8.6Hz,2H),5.02(s,2H),3.81(s,3H),2.42(s,3H),2.27(s,3H); 13 C NMR (101MHz, CDCl3): δ170.4,159.2,144.8,136.7,129.8,128.9,127.7,113.9,55.3,49.0,29.71,25.0,21.6.

[0177] Example 32

[0178]

[0179] Under air atmosphere, N-(tert-butyloxycarbonyl)-p-toluenesulfonamide (0.5 mmol, 135.7 mg), sodium bromide (1 mmol, 102.9 mg), acetonitrile (10 mL), and p-toluenesulfonate (2 mmol, 244.3 mg) were added to an open electrolytic cell (30 mL). A carbon sheet (10 mm × 10 mm × 1 mm) was used as the cathode, and a platinum sheet (10 mm × 10 mm × 0.1 mm) as the anode. A current of 20 mA was applied, and the reaction temperature was 80 °C for 5 h. The product was monitored by TLC during the reaction. After the reaction was complete, the solvent was distilled off under reduced pressure to obtain the crude product, which was then separated by column chromatography (petroleum ether / ethyl acetate = 5 / 1) to obtain the target product: tert-butyl-N-(4-methoxybenzyl)-N-p-toluenesulfonyl carbamate, a green liquid, with a separation yield of 61%. Specific NMR data are as follows:

[0180] 1 H NMR (400MHz, CDCl3): δ7.54(d,J=8.3Hz,2H),7.38(d,J=8.7Hz,2H),7.20(d,J=8.1 Hz,2H),6.87(d,J=8.7Hz,2H),4.98(s,2H),3.82(s,3H),2.40(s,3H),1.31(s,9H); 13 C NMR (101MHz, CDCl3): δ159.2,151.2,144.0,137.3,129.9,129.6,129.1,127.9,113.8,84.4,55.3,49.1,27.9,21.6.

[0181] Example 33

[0182]

[0183] Under air atmosphere, N-(4-methylbenzyl)benzamide (0.5 mmol, 137.7 mg), sodium bromide (1 mmol, 102.9 mg), acetonitrile (10 mL), and p-toluene (2 mmol, 244.3 mg) were added to an open electrolytic cell (30 mL). A carbon sheet (10 mm × 10 mm × 1 mm) was used as the cathode, and a platinum sheet (10 mm × 10 mm × 0.1 mm) as the anode. A current of 20 mA was applied, and the reaction temperature was 80 °C for 5 h. The product was monitored by TLC during the reaction. After the reaction was complete, the solvent was distilled off under reduced pressure to obtain the crude product, which was then separated by column chromatography (petroleum ether / ethyl acetate = 5 / 1) to obtain the target product: N-(4-methoxybenzyl)-N-p-toluenesulfonylbenzamide, a yellow solid, with a separation yield of 40%. Specific NMR data are as follows:

[0184] 1 H NMR (400MHz, CDCl3): δ7.58(d,J=8.3Hz,2H),7.44(d,J=8.3Hz,3H),7.38–7.30(m,2H),7.22(d,J =8.1Hz,2H),7.13(d,J=8.7Hz,2H),6.78(d,J=8.7Hz,2H),4.92(s,2H),3.78(s,3H),2.41(s,3H); 13 C NMR (101MHz, CDCl3): δ171.6,159.2,144.6,136.1,135.1,131.7,129.6,129.4,128.5,128.3,128.3,128.2,113.9,55.3,50.7,21.7.

[0185] Example 34

[0186]

[0187] Under air atmosphere, bis(benzenesulfonyl)imide (0.5 mmol, 148.7 mg), sodium bromide (1 mmol, 102.9 mg), acetonitrile (10 mL), and p-methyl anisole (2 mmol, 244.3 mg) were added to an open electrolytic cell (30 mL). A carbon sheet (10 mm × 10 mm × 1 mm) was used as the cathode, and a platinum sheet (10 mm × 10 mm × 0.1 mm) as the anode. A current of 20 mA was applied, and the reaction temperature was 80 °C for 5 h. The product was monitored by TLC during the reaction. After the reaction was complete, the solvent was distilled off under reduced pressure to obtain the crude product, which was then separated by column chromatography (petroleum ether / ethyl acetate = 5 / 1) to obtain the target product: N-(4-methoxybenzyl)-N-benzenesulfonylbenzenesulfonamide, a white solid, with a separation yield of 81%. Specific NMR data are as follows: 1 H NMR (400MHz, CDCl3): δ7.79 (d, J = 7.1Hz, 4H), 7.57 (t, J = 7.4Hz, 2H), 7.43 (t, J = 7. 9Hz, 4H), 7.32 (d, J = 8.6Hz, 2H), 6.77 (d, J = 8.7Hz, 2H), 4.88 (s, 2H), 3.80 (s, 3H); 13 C NMR (101MHz, CDCl3): δ159.6,140.2,133.6,130.8,128.8,128.1,126.6,113.8,55.4,52.1.

[0188] Example 35

[0189]

[0190] Under air atmosphere, N-(benzenesulfonyl)thiophene-2-sulfonamide (0.5 mmol, 151.7 mg), sodium bromide (1 mmol, 102.9 mg), acetonitrile (10 mL), and p-methyl anisole (2 mmol, 244.3 mg) were added to an open electrolytic cell (30 mL). A carbon sheet (10 mm × 10 mm × 1 mm) was used as the cathode, and a platinum sheet (10 mm × 10 mm × 0.1 mm) as the anode. A current of 20 mA was applied, and the reaction temperature was 80 °C for 5 h. The product was monitored by TLC during the reaction. After the reaction was complete, the solvent was distilled off under reduced pressure to obtain the crude product, which was then separated by column chromatography (petroleum ether / ethyl acetate = 5 / 1) to obtain the target product: N-(4-methoxybenzyl)-N-benzenesulfonylthiophene-2-sulfonamide, a yellow solid, with a separation yield of 53%. Specific NMR data are as follows:

[0191] 1 H NMR (400MHz, CDCl3): δ7.78–7.72(m,2H),7.62(d,J=4.4Hz,2H),7.57(t,J=7.5Hz,1H),7.43(t,J=7. 9Hz,2H),7.35(d,J=8.7Hz,2H),7.06–7.01(m,1H),6.80(d,J=8.7Hz,2H),4.90(s,2H),3.81(s,3H); 13 C NMR (101MHz, CDCl3): δ159.6,140.2,140.1,134.8,133.9,133.6,130.8,128.8,128.1,127.2,126.5,113.8,55.4,52.2.

[0192] Example 36

[0193]

[0194] In a clean, dry, unseparated glass electrolytic cell, o-phenylthioimide (0.5 mmol, 91.6 mg), sodium bromide electrolyte (1.0 mmol, 102.9 mg), acetonitrile solvent (10 mL), and diphenylmethane (2.0 mmol, 336.0 μL) were added sequentially. The electrolytic cell was then operated with a platinum sheet as the anode and a carbon rod as the cathode, and a constant current of 20 mA was applied at 80 °C. The reaction was stirred for 5 hours. After the reaction, the solvent was removed by rotary evaporation, and the product 2-diphenylmethylbenzo[d]isothiazol-3(2H)-one-1,1-dioxide was obtained by column chromatography (petroleum ether / ethyl acetate = 5 / 1), a white powder, 151.8 mg, yield 87.0%. Specific NMR data are as follows: 1H NMR (400MHz, CDCl3): δ8.00(dd,J=6.9,0.8Hz,1H),7.93–7.89(m,1H),7.88–7.79(m,2H),7.47–7.41(m,4H),7.40–7.30(m,6H),6.51(s,1H); 13 C NMR (101 MHz, CDCl3): δ 158.4, 137.7, 136.5, 134.8, 134.3, 129.0, 128.5, 128.3, 127.1, 125.3, 120.9, 60.4. The results were consistent with previously reported data (R I. Robinson, R Fryatt, C Wilson, S Woodward Sulfonamide Ligands Attained Through Opening of Saccharin Derivatives. Eur. J. Org. Chem. 2006, 19, 4483–4489).

[0195] Unless otherwise specified, the electrode materials described in Examples 36 to 70 have the following specifications: carbon sheet 10mm×10mm×1mm, platinum sheet 10mm×10mm×0.1mm.

[0196] Example 37

[0197] The experimental method in this embodiment is the same as in embodiment 36, except that the electrolyte is tetrabutylammonium acetate (TBAOAc).

[0198] In a clean, dry, unseparated glass electrolytic cell, o-phenylthioimide (0.5 mmol, 91.6 mg), electrolyte tetrabutylammonium acetate (1.0 mmol, 301.5 mg), solvent acetonitrile (10 mL), and diphenylmethane (2.0 mmol, 336.0 μL) were added sequentially. Then, with a platinum sheet as the anode and a carbon rod as the cathode, a constant current of 20 mA was applied at 80 °C, and the reaction was stirred for 5 hours. The reaction solution was not detected by TLC, and the product 2-diphenylmethylbenzo[d]isothiazol-3(2H)-one-1,1-dioxide was not detected.

[0199] Example 38

[0200] The experimental method in this embodiment is the same as in Example 36, except that the electrolyte is tetrabutylammonium bromide (TBABr).

[0201] In a clean, dry, unseparated glass electrolytic cell, o-phenylthioimide (0.5 mmol, 91.6 mg), electrolyte tetrabutylammonium bromide (1.0 mmol, 322.4 mg), solvent acetonitrile (10 mL), and diphenylmethane (2.0 mmol, 336.0 μL) were added sequentially. Then, with a platinum sheet as the anode and a carbon rod as the cathode, a constant current of 20 mA was applied at 80 °C, and the reaction was stirred for 5 hours. The reaction solution was not detected by TLC, and the product 2-diphenylmethylbenzo[d]isothiazol-3(2H)-one-1,1-dioxide was not detected.

[0202] Example 39

[0203] The experimental method in this embodiment is the same as in Example 36, except that the electrolyte is tetrabutylammonium hydroxide (TBAOH).

[0204] In a clean, dry, unseparated glass electrolytic cell, o-phenylthioimide (0.5 mmol, 91.6 mg), electrolyte tetrabutylammonium hydroxide (1.0 mmol, 260.3 μL), solvent acetonitrile (10 mL), and diphenylmethane (2.0 mmol, 336.0 μL) were added sequentially. Then, with a platinum sheet as the anode and a carbon rod as the cathode, a constant current of 20 mA was passed through the electrolytic cell at 80 °C, and the reaction was stirred for 5 hours. The reaction solution was analyzed by TLC to detect only trace amounts of the product 2-diphenylmethylbenzo[d]isothiazolyl-3(2H)-one-1,1-dioxide.

[0205] Example 40

[0206] The experimental method in this embodiment is the same as in Example 36, except that the electrolyte is potassium bromide.

[0207] In a clean, dry, unseparated glass electrolytic cell, o-phenylthioimide (0.5 mmol, 91.6 mg), potassium bromide electrolyte (1.0 mmol, 119.0 mg), acetonitrile solvent (10 mL), and diphenylmethane (2.0 mmol, 336.0 μL) were added sequentially. The electrolytic cell was then operated with a platinum sheet as the anode and a carbon rod as the cathode, and a constant current of 20 mA was applied at 80 °C. The mixture was stirred for 5 hours. After the reaction was complete, the solvent was removed by rotary evaporation, and the product 2-diphenylmethylbenzo[d]isothiazolyl-3(2H)-one-1,1-dioxide was obtained by column chromatography (petroleum ether / ethyl acetate = 5 / 1), as a white powder, 26.4 mg, yield 15.1%.

[0208] Example 41

[0209] The experimental method in this embodiment is the same as in Example 36, except that the electrolyte is ammonium bromide.

[0210] In a clean, dry, unseparated glass electrolytic cell, o-phenylthioimide (0.5 mmol, 91.6 mg), ammonium bromide electrolyte (1.0 mmol, 97.9 mg), acetonitrile solvent (10 mL), and diphenylmethane (2.0 mmol, 336.0 μL) were added sequentially. The electrolytic cell was then operated with a platinum sheet as the anode and a carbon rod as the cathode, and a constant current of 20 mA was applied at 80 °C. The reaction was stirred for 5 hours. After the reaction, the solvent was removed by rotary evaporation, and the product 2-diphenylmethylbenzo[d]isothiazolyl-3(2H)-one-1,1-dioxide was obtained by column chromatography (petroleum ether / ethyl acetate = 5 / 1), a white powder, 60.7 mg, yield 34.5%. The yields of the products obtained under the reaction conditions described in Examples 36–41 are shown in Table 8.

[0211] Table 8 shows the effect of different electrolyte types on product yield under the reaction conditions described in Examples 36-41.

[0212]

[0213] Note: In Table 8 a Product yield was obtained from actual separation; b Product yield was obtained by TLC spot plate observation.

[0214] Example 42

[0215] The experimental method in this embodiment is the same as in Example 36, except that the solvent is DCE. In a clean, dry, unseparated glass electrolytic cell, o-phenylthioimide (0.5 mmol, 91.6 mg), sodium bromide electrolyte (1.0 mmol, 102.9 mg), 10 mL of DCE solvent, and diphenylmethane (2.0 mmol, 336.0 μL) were added sequentially. Then, with a platinum sheet as the anode and a carbon rod as the cathode, a constant current of 20 mA was applied at 80°C, and the reaction was stirred for 5 hours. No product 2-diphenylmethylbenzo[d]isothiazol-3(2H)-one-1,1-dioxide was detected by TLC.

[0216] Example 43

[0217] The experimental method in this embodiment is the same as in Example 36, except that the solvent is DMF. In a clean, dry, unseparated glass electrolytic cell, o-phenylthioimide (0.5 mmol, 91.6 mg), sodium bromide electrolyte (1.0 mmol, 102.9 mg), DMF solvent (10 mL), and diphenylmethane (2.0 mmol, 336.0 μL) were added sequentially. Then, with a platinum sheet as the anode and a carbon rod as the cathode, a constant current of 20 mA was applied at 80°C, and the reaction was stirred for 5 hours. No product 2-diphenylmethylbenzo[d]isothiazol-3(2H)-one-1,1-dioxide was detected by TLC.

[0218] The product yields obtained under the reaction conditions described in Examples 42 and 43 are shown in Table 9.

[0219] Table 9 shows the effect of different solvent types on product yield under the reaction conditions described in Examples 42-43.

[0220] Example 42 Example 43 Example 36 Solvent (10 mL) DCE DMF ACN Yield a (%)]] 0 b ]] 0 b ]] 87.0

[0221] Note: In Table 9 a Product yield was obtained from actual separation; b Product yield was obtained by TLC spot plate observation.

[0222] Example 44

[0223] The experimental method in this embodiment is the same as that in Example 36, except that the reaction temperature is room temperature.

[0224] In a clean, dry, unseparated glass electrolytic cell, o-phenylthioimide (0.5 mmol, 91.6 mg), sodium bromide electrolyte (1.0 mmol, 102.9 mg), acetonitrile solvent (10 mL), and diphenylmethane (2.0 mmol, 336.0 μL) were added sequentially. The electrolytic cell was then operated with a platinum sheet as the anode and a carbon rod as the cathode. A constant current of 20 mA was applied at room temperature, and the reaction was stirred for 5 hours. After the reaction, the solvent was removed by rotary evaporation, and the product 2-diphenylmethylbenzo[d]isothiazolyl-3(2H)-one-1,1-dioxide was obtained by column chromatography (petroleum ether / ethyl acetate = 5 / 1), a white powder, 16.1 mg, yield 9.2%.

[0225] Example 45

[0226] The experimental method in this embodiment is the same as in Example 36, except that the reaction temperature is 40°C.

[0227] In a clean, dry, unseparated glass electrolytic cell, o-phenylthioimide (0.5 mmol, 91.6 mg), sodium bromide electrolyte (1.0 mmol, 102.9 mg), acetonitrile solvent (10 mL), and diphenylmethane (2.0 mmol, 336.0 μL) were added sequentially. The electrolytic cell was then operated with a platinum sheet as the anode and a carbon rod as the cathode, and a constant current of 20 mA was applied at 40 °C. The mixture was stirred for 5 hours. After the reaction was complete, the solvent was removed by rotary evaporation, and the product 2-diphenylmethylbenzo[d]isothiazolyl-3(2H)-one-1,1-dioxide was obtained by column chromatography (petroleum ether / ethyl acetate = 5 / 1), as a white powder, 31.4 mg, yield 18.0%.

[0228] Example 46

[0229] The experimental method in this embodiment is the same as in Example 36, except that the reaction temperature is 60°C.

[0230] In a clean, dry, unseparated glass electrolytic cell, o-phenylthioimide (0.5 mmol, 91.6 mg), sodium bromide electrolyte (1.0 mmol, 102.9 mg), acetonitrile solvent (10 mL), and diphenylmethane (2.0 mmol, 336.0 μL) were added sequentially. The electrolytic cell was then operated with a platinum sheet as the anode and a carbon rod as the cathode, and a constant current of 20 mA was applied at 60 °C. The mixture was stirred for 5 hours. After the reaction, the solvent was removed by rotary evaporation, and the product 2-diphenylmethylbenzo[d]isothiazolyl-3(2H)-one-1,1-dioxide was obtained by column chromatography (petroleum ether / ethyl acetate = 5 / 1), a white powder, 59.3 mg, yield 34.0%.

[0231] The product yields obtained under the reaction conditions described in Examples 44-46 are shown in Table 10.

[0232] Table 10 shows the effect of different reaction temperatures on product yield under the reaction conditions described in Examples 44-46.

[0233] Example 44 Example 45 Example 46 Example 36 Reaction temperature (°C) Room temperature 40 60 80 Yield a (%)]] 9.2 18.0 34.0 87.0

[0234] Note: In Table 10 a Product yield was obtained from actual separation.

[0235] Example 47

[0236] The experimental method in this embodiment is the same as in embodiment 36, except that the constant current is 15mA.

[0237] In a clean, dry, unseparated glass electrolytic cell, o-phenylthioimide (0.5 mmol, 91.6 mg), sodium bromide electrolyte (1.0 mmol, 102.9 mg), acetonitrile solvent (10 mL), and diphenylmethane (2.0 mmol, 336.0 μL) were added sequentially. The electrolytic cell was then operated with a platinum sheet as the anode and a carbon rod as the cathode, and a constant current of 15 mA was applied at 80 °C. The mixture was stirred for 5 hours. After the reaction, the solvent was removed by rotary evaporation, and the product 2-diphenylmethylbenzo[d]isothiazolyl-3(2H)-one-1,1-dioxide was obtained by column chromatography (petroleum ether / ethyl acetate = 5 / 1), as a white powder, 24.4 mg, yield 14.0%.

[0238] Example 48

[0239] The experimental method in this embodiment is the same as in embodiment 36, except that the constant current is 25mA.

[0240] In a clean, dry, unseparated glass electrolytic cell, o-phenylthioimide (0.5 mmol, 91.6 mg), sodium bromide electrolyte (1.0 mmol, 102.9 mg), acetonitrile solvent (10 mL), and diphenylmethane (2.0 mmol, 336.0 μL) were added sequentially. The electrolytic cell was then operated with a platinum sheet as the anode and a carbon rod as the cathode, and a constant current of 25 mA was applied at 80 °C. The mixture was stirred for 5 hours. After the reaction, the solvent was removed by rotary evaporation, and the product 2-diphenylmethylbenzo[d]isothiazolyl-3(2H)-one-1,1-dioxide was obtained by column chromatography (petroleum ether / ethyl acetate = 5 / 1), a white powder, 127.4 mg, yield 73.0%.

[0241] The product yields obtained under the reaction conditions described in Examples 47 and 48 are shown in Table 11.

[0242] Table 11 shows the effect of different current magnitudes on product yield under the reaction conditions described in Examples 47-48.

[0243] Example 47 Example 48 Example 36 Current (mA) 15 25 20 Yield a (%)]] 14.0 73.0 87.0

[0244] Note: In Table 11 a Product yield was obtained from actual separation.

[0245] Example 49

[0246] The experimental method in this embodiment is the same as in Example 36, except that both the cathode and anode are platinum sheet electrodes. In a clean, dry, unseparated glass electrolytic cell, o-phenylthioimide (0.5 mmol, 91.6 mg), sodium bromide electrolyte (1.0 mmol, 102.9 mg), acetonitrile solvent (10 mL), and diphenylmethane (2.0 mmol, 336.0 μL) were added sequentially. Then, with platinum sheet as the anode and cathode, a constant current of 20 mA was applied at 80 °C, and the reaction was stirred for 5 hours. After the reaction, the solvent was removed by rotary evaporation, and the product 2-diphenylmethylbenzo[d]isothiazolyl-3(2H)-one-1,1-dioxide was obtained by column chromatography (petroleum ether / ethyl acetate = 5 / 1), a white powder, 66.3 mg, yield 38.0%.

[0247] Example 50

[0248] The experimental method in this embodiment is the same as in Example 36, except that a carbon rod is used as the anode and a platinum sheet as the cathode. In a clean, dry, unseparated electrolytic cell, o-phenylthioimide (0.5 mmol, 91.6 mg), sodium bromide electrolyte (1.0 mmol, 102.9 mg), acetonitrile solvent (10 mL), and diphenylmethane (2.0 mmol, 336.0 μL) were added sequentially. Then, with the carbon rod as the anode and the platinum sheet as the cathode, a constant current of 20 mA was applied at 80°C, and the reaction was stirred for 5 hours. After the reaction, the solvent was removed by rotary evaporation, and the product 2-diphenylmethylbenzo[d]isothiazolyl-3(2H)-one-1,1-dioxide was obtained by column chromatography (petroleum ether / ethyl acetate = 5 / 1), a white powder, 20.9 mg, with a yield of 12.0%. The yields of the products obtained under the reaction conditions described in Examples 49-50 are shown in Table 12.

[0249] Table 12 shows the effect of different electrode materials on product yield under the reaction conditions described in Examples 49-50.

[0250] Example 49 Example 50 Example 36 Materials (anode / cathode) Pt disc / Pt disc Carbon rod / Pt disc Pt disc / Carbon rod Yield a (%)]] 38.0 12.0 87.0

[0251] Note: In Table 12 a Product yield was obtained from actual separation.

[0252] Example 51

[0253]

[0254] The experimental method in this embodiment is the same as in Example 36, except that the substrate is 4-fluorodiphenylmethane. In a clean, dry, unseparated glass electrolytic cell, o-phenylthioimide (0.5 mmol, 91.6 mg), sodium bromide electrolyte (1.0 mmol, 102.9 mg), acetonitrile solvent (10 mL), and 4-fluorodiphenylmethane (2.0 mmol, 372.2 mg) were added sequentially. Then, with a platinum sheet as the anode and a carbon rod as the cathode, a constant current of 20 mA was applied at 80°C, and the reaction was stirred for 5 hours. After the reaction, the solvent was removed by rotary evaporation, and the product 2-[(4-fluorophenyl)(phenyl)methyl]benzo[d]isothiazolyl-3(2H)-one-1,1-dioxide, a white powder, was obtained by column chromatography (petroleum ether / ethyl acetate = 5 / 1), yielding 151.7 mg (82.6%).

[0255] The specific NMR data are as follows: 1 H NMR (400MHz, CDCl3): δ8.00(d,J=7.0Hz,1H),7.92(d,J=7.1Hz,1H),7.89–7.79 (m,2H),7.48–7.41(m,4H),7.41–7.33(m,3H),7.10–7.01(m,2H),6.48(s,1H); 13 C NMR (101MHz, CDCl3): δ163.8,161.4,158.4,137.7,136.4,134.9,134.4,132.4 ,131.1,131.1,128.7,128.6,128.4,127.0,125.3,120.9,115.5,115.3,59.7; 19 FNMR (376MHz, CDCl3): δ-113.6.

[0256] Example 52

[0257]

[0258] The experimental method in this embodiment is the same as in Example 36, except that the substrate is 4-chlorodiphenylmethane. In a clean, dry, unseparated glass electrolytic cell, o-phenylthioimide (0.5 mmol, 91.6 mg), sodium bromide electrolyte (1.0 mmol, 102.9 mg), acetonitrile solvent (10 mL), and 4-chlorodiphenylmethane (2.0 mmol, 404.1 mg) were added sequentially. Then, with a platinum sheet as the anode and a carbon rod as the cathode, a constant current of 20 mA was applied at 80°C, and the reaction was stirred for 5 hours. After the reaction, the solvent was removed by rotary evaporation, and the product 2-[(4-chlorophenyl)(phenyl)methyl]benzo[d]isothiazolyl-3(2H)-one-1,1-dioxide, a white powder, was obtained by column chromatography (petroleum ether / ethyl acetate = 5 / 1), yielding 141.1 mg, a yield of 73.5%.

[0259] The specific NMR data are as follows: 1 H NMR (400MHz, CDCl3): δ8.00 (d, J = 7.5Hz, 1H), 7.94–7.79 (m, 3H), 7.46–7.30 (m, 9H), 6.46 (s, 1H); 13 C NMR (101MHz, CDCl3): δ158.4,137.6,136.0,135.2,134.9,134.4,134.3,130.5,128.9,128.7,128.6,128.5,127.0,125.3,121.0,59.7.

[0260] Example 53

[0261]

[0262] The experimental method in this embodiment is the same as in Example 36, except that the substrate is 4-bromodiphenylmethane. In a clean, dry, unseparated glass electrolytic cell, o-phenylthioimide (0.5 mmol, 91.6 mg), sodium bromide electrolyte (1.0 mmol, 102.9 mg), acetonitrile solvent (10 mL), and 4-bromodiphenylmethane (2.0 mmol, 492.0 mg) were added sequentially. Then, with a platinum sheet as the anode and a carbon rod as the cathode, a constant current of 20 mA was applied at 80°C, and the reaction was stirred for 5 hours. After the reaction, the solvent was removed by rotary evaporation, and the product 2-[(4-bromophenyl)(phenyl)methyl]benzo[d]isothiazolyl-3(2H)-one-1,1-dioxide, a white powder, was obtained by column chromatography (petroleum ether / ethyl acetate = 5 / 1), yielding 160.6 mg (75.0%).

[0263] The specific NMR data are as follows: 1H NMR (400MHz, CDCl3): δ8.00(d,J=7.4Hz,1H),7.93–7.80(m,3H),7.49(d,J=8.5Hz, 2H),7.43–7.42(d,J=6.2Hz,2H),7.37–7.32(dd,J=12.1,7.7Hz,5H),6.44(s,1H); 13 C NMR (101MHz, CDCl3): δ158.4,137.6,135.9,135.8,134.9,134.4,131.7,130.8,128.9,128.6,128.5,127.0,125.3,122.5,121.9,59.2.

[0264] Example 54

[0265]

[0266] The experimental method in this embodiment is the same as in Example 36, except that the substrate is 4-methoxydiphenylmethane. In a clean, dry, unseparated glass electrolytic cell, o-phenylthioimide (0.5 mmol, 91.6 mg), sodium bromide electrolyte (1.0 mmol, 102.9 mg), acetonitrile solvent (10 mL), and 4-methoxydiphenylmethane (2.0 mmol, 396.2 mg) were added sequentially. Then, with a platinum sheet as the anode and a carbon rod as the cathode, a constant current of 20 mA was applied at 80°C, and the reaction was stirred for 5 hours. After the reaction, the solvent was removed by rotary evaporation, and the product 2-[(4-methoxyphenyl)(phenyl)methyl]benzo[d]isothiazolyl-3(2H)-one-1,1-dioxide, a yellow oil, was obtained by column chromatography (petroleum ether / ethyl acetate = 5 / 1), yielding 145.1 mg of the product (76.5%).

[0267] The specific NMR data are as follows: 1 H NMR (400MHz, CDCl3): δ7.99(d,J=6.9Hz,1H),7.90(d,J=7.2Hz,1H),7.83(dt,J=21.2,7.4Hz ,2H),7.48–7.40(m,3H),7.40–7.31(m,4H),6.89(d,J=8.8Hz,2H),6.47(s,1H),3.80(s,3H); 13 C NMR (101MHz, CDCl3): δ159.5,158.4,137.8,137.0,134.7,134.3,130.7,128.5,128.5,128.4,128.1,127.2,125.2,120.9,113.8,60.1,55.3.

[0268] Example 55

[0269]

[0270] The experimental method in this embodiment is the same as in Example 36, except that the substrate is 4-phenyldiphenylmethane. In a clean, dry, unseparated glass electrolytic cell, o-phenylthioimide (0.5 mmol, 91.6 mg), sodium bromide electrolyte (1.0 mmol, 102.9 mg), acetonitrile solvent (10 mL), and 4-phenyldiphenylmethane (2.0 mmol, 488.2 mg) were added sequentially. Then, with a platinum sheet as the anode and a carbon rod as the cathode, a constant current of 20 mA was applied at 80°C, and the reaction was stirred for 5 hours. After the reaction, the solvent was removed by rotary evaporation, and the product 2-[(1,1'-biphenyl)(4-phenyl)methyl]benzo[d]isothiazolyl-3(2H)-one-1,1-dioxide, a yellow powder, was obtained by column chromatography (petroleum ether / ethyl acetate = 5 / 1), yielding 180.3 mg (84.7%).

[0271] The specific NMR data are as follows: 1 H NMR (400MHz, CDCl3): δ8.02(d,J=7.1Hz,1H),7.93(d,J=7.5Hz,1H),7.84(dt,J=21.5, 7.5Hz,2H),7.59(d,J=8.5Hz,4H),7.56–7.47(m,4H),7.46–7.31(m,6H),6.54(s,1H); 13 C NMR (101MHz, CDCl3): δ158.5,141.1,140.6,137.7,136.5,135.6,134.8,13 4.3,129.4,129.1,128.8,128.5,128.3,127.5,127.2,125.3,120.9,60.1.

[0272] Example 56

[0273]

[0274] The experimental method in this embodiment is the same as in Example 36, except that the substrate is 4-tert-butyldiphenylmethane. In a clean, dry, unseparated glass electrolytic cell, o-phenylthioimide (0.5 mmol, 91.6 mg), sodium bromide electrolyte (1.0 mmol, 102.9 mg), acetonitrile solvent (10 mL), and 4-tert-butyldiphenylmethane (2.0 mmol, 448.2 mg) were added sequentially. Then, with a platinum sheet as the anode and a carbon rod as the cathode, a constant current of 20 mA was applied at 80°C, and the reaction was stirred for 5 hours. After the reaction, the solvent was removed by rotary evaporation, and the product 2-[(4-tert-butylphenyl)(phenyl)methyl]benzo[d]isothiazolyl-3(2H)-one-1,1-dioxide, a yellow powder, was obtained by column chromatography (petroleum ether / ethyl acetate = 5 / 1), yielding 130.3 mg, a yield of 64.6%.

[0275] The specific NMR data are as follows: 1 H NMR (400MHz, CDCl3): δ7.86(d,J=7.3Hz,1H),7.78(d,J=7.5Hz,1H),7.67(dt,J=20 .9,7.1Hz,2H),7.37(d,J=7.0Hz,2H),7.31–7.20(m,7H),6.38(s,1H),1.21(s,9H); 13 C NMR (101MHz, CDCl3): δ158.4,151.1,137.7,136.8,134.8,134.3,133.5,1 29.0,128.8,128.5,128.2,127.2,125.4,125.3,120.9,60.1,34.6,31.4.

[0276] Example 57

[0277]

[0278] The experimental method in this embodiment is the same as in Example 36, except that the substrate is 1-benzyl-3-methylbenzene. In a clean, dry, unseparated electrolytic cell, o-benzylthionimide (0.5 mmol, 91.6 mg), sodium bromide electrolyte (1.0 mmol, 102.9 mg), acetonitrile solvent (10 mL), and 1-benzyl-3-methylbenzene (2.0 mmol, 364.2 mg) were added sequentially. Then, with a platinum sheet as the anode and a carbon rod as the cathode, a constant current of 20 mA was applied at 80°C, and the reaction was stirred for 5 hours. After the reaction, the solvent was removed by rotary evaporation, and the product 2-[(3-methylphenyl)(phenyl)methyl]benzo[d]isothiazolyl-3(2H)-one-1,1-dioxide, a white powder, was obtained by column chromatography (petroleum ether / ethyl acetate = 5 / 1), yielding 130.8 mg (72.0%).

[0279] The specific NMR data are as follows: 1 H NMR (400MHz, CDCl3): δ7.99 (dd, J=7.3, 1.3Hz, 1H), 7.91 (d, J=7.0Hz, 1H), 7.82 (dtd, J=20.9, 7.4, 1.3Hz, 2H), 7 .45(dd,J=7.4,1.6Hz,2H),7.39–7.32(m,3H),7.26–7.25(m,3H),7.17–7.11(m,1H),6.47(s,1H),2.33(s,3H); 13 C NMR (101MHz, CDCl3): δ158.5,138.2,137.7,136.7,136.6,134.8,134.3,129. 6,129.1,129.1,128.5,128.4,128.3,127.1,126.1,125.3,120.9,60.5,21.6.

[0280] Example 58

[0281]

[0282] The experimental method in this embodiment is the same as in Example 36, except that the substrate is 4,4'-dimethyldiphenylmethane. Electrochemical anodic oxidation reaction: o-phenylthioimide (0.5 mmol, 91.6 mg), sodium bromide electrolyte (1.0 mmol, 102.9 mg), acetonitrile solvent (10 mL), and 4,4'-dimethyldiphenylmethane (2.0 mmol, 392.2 mg) were added sequentially to a clean, dry, unseparated glass electrolytic cell. A platinum sheet was then used as the anode and a carbon rod as the cathode. A constant current of 20 mA was applied at 80°C, and the reaction was stirred for 5 hours. After the reaction, the solvent was removed by rotary evaporation, and the product 2-(di-p-tolylmethyl)benzo[d]isothiazolyl-3(2H)-one-1,1-dioxide, a white powder, was obtained by column chromatography (petroleum ether / ethyl acetate = 5 / 1), yielding 100.6 mg, a yield of 53.3%.

[0283] The specific NMR data are as follows: 1 H NMR (400MHz, CDCl3): δ7.99(d,J=7.1Hz,1H),7.90(d,J=7.9Hz,1H),7.81(dtd,J=20.9, 7.4,1.2Hz,2H),7.36(d,J=8.1Hz,4H),7.17(d,J=8.0Hz,4H),6.46(s,1H),2.35(s,6H); 13C NMR (101MHz, CDCl3): δ169.4,158.5,150.4,137.7,136.2,134.7,134.3,129.0,127.3,125.1,121.6,120.8,52.5,21.1,17.7.

[0284] Example 59

[0285]

[0286] The experimental method in this embodiment is the same as in Example 36, except that the substrate is 4-fluoroethylbenzene. In a clean, dry, unseparated glass electrolytic cell, o-phenylthioimide (0.5 mmol, 91.6 mg), sodium bromide electrolyte (1.0 mmol, 102.9 mg), acetonitrile solvent (10 mL), and 4-fluoroethylbenzene (2.0 mmol, 248.2 mg) were added sequentially. Then, with a platinum sheet as the anode and a carbon rod as the cathode, a constant current of 20 mA was applied at 80°C, and the reaction was stirred for 5 hours. After the reaction, the solvent was removed by rotary evaporation, and the product 2-[1-(4-fluorophenyl)ethyl]benzisisothiazol-3(2H)-one-1,1-dioxide, a white powder, was obtained by column chromatography (petroleum ether / ethyl acetate = 5 / 1), yielding 30.5 mg (20.0%).

[0287] The specific NMR data are as follows: 1 H NMR (400MHz, CDCl3): δ7.97(d,J=6.9Hz,1H),7.89(d,J=6.9Hz,1H),7.81(dtd,J=20.5,7.4,1.3Hz,2H) ,7.58(ddt,J=8.2,5.0,3.0Hz,2H),7.04(t,J=8.7Hz,2H),5.43(q,J=7.3Hz,1H),2.01(d,J=7.3Hz,3H); 13 C NMR (101MHz, CDCl3): δ163.7,161.2,148.1,137.7,134.7,134.3,129.6,127.3,125.1,120.8,115.4,52.4,17.8; 19 F NMR (376MHz, CDCl3): δ-113.9.

[0288] Example 60

[0289]

[0290] The experimental method in this embodiment is the same as in Example 36, except that the substrate is 4-bromoethylbenzene. In a clean, dry, unseparated glass electrolytic cell, o-phenylthioimide (0.5 mmol, 91.6 mg), sodium bromide electrolyte (1.0 mmol, 102.9 mg), acetonitrile solvent (10 mL), and 4-bromoethylbenzene (2.0 mmol, 368.0 mg) were added sequentially. Then, with a platinum sheet as the anode and a carbon rod as the cathode, a constant current of 20 mA was applied at 80°C, and the reaction was stirred for 5 hours. After the reaction, the solvent was removed by rotary evaporation, and the product 2-[1-(4-bromophenyl)ethyl]benzisisothiazol-3(2H)-one-1,1-dioxide, a white powder, was obtained by column chromatography (petroleum ether / ethyl acetate = 5 / 1), yielding 49.9 mg, a yield of 27.3%.

[0291] The specific NMR data are as follows: 1 H NMR (400MHz, CDCl3): δ7.87(d,J=8.3Hz,1H),7.80–7.73(m,2H),7.72–7.66(m,1H),7.5 4(d,J=8.5Hz,2H),7.36(d,J=8.5Hz,2H),6.25(q,J=6.5Hz,1H),1.80(d,J=6.6Hz,3H); 13 C NMR (101MHz, CDCl3): δ168.3,143.5,138.1,134.2,133.4,132.0,128.3,127.2,123.3,123.1,121.9,80.1,21.5.

[0292] Example 61

[0293]

[0294] The experimental method in this embodiment is the same as in Example 36, except that the substrate is 4-ethyl anisole. In a clean, dry, unseparated glass electrolytic cell, o-phenylthioimide (0.5 mmol, 91.6 mg), sodium bromide electrolyte (1.0 mmol, 102.9 mg), acetonitrile solvent (10 mL), and 4-ethyl anisole (2.0 mmol, 272.2 mg) were added sequentially. Then, with a platinum sheet as the anode and a carbon rod as the cathode, a constant current of 20 mA was applied at 80°C, and the reaction was stirred for 5 hours. After the reaction, the solvent was removed by rotary evaporation, and the product 2-(1-(4-methoxyphenyl)ethyl)benzo[d]isothiazol-3(2H)-one 1,1-dioxide, a white powder, was obtained by column chromatography (petroleum ether / ethyl acetate = 5 / 1), yielding 137.4 mg (86.5%).

[0295] The specific NMR data are as follows: 1H NMR (400MHz, CDCl3): δ7.96 (dd, J=6.7, 0.9Hz, 1H), 7.88 (dd, J=6.9, 0.9Hz, 1H), 7.82 (td, J=7.5, 1.3Hz, 1H), 7.77 (td ,J=7.4,1.4Hz,1H),7.57–7.46(m,2H),6.91–6.85(m,2H),5.42(q,J=7.3Hz,1H),3.79(s,3H),2.00(d,J=7.3Hz,3H); 13 C NMR (101MHz, CDCl3): δ159.4,158.5,137.8,134.6,134.2,130.6,129.2,127.4,125.0,120.6,113.8,55.3,52.7,17.8.

[0296] Example 62

[0297]

[0298] The experimental method in this embodiment differs from that in Example 36 except that the substrate used is 4-ethylphenidate. In a clean, dry, unseparated glass electrolytic cell, o-phenylthioimide (0.5 mmol, 91.6 mg), sodium bromide electrolyte (1.0 mmol, 102.9 mg), acetonitrile solvent (10 mL), and 4-ethylphenidate (2.0 mmol, 300.2 μL) were added sequentially. Then, with a platinum sheet as the anode and a carbon rod as the cathode, a constant current of 20 mA was applied at 80 °C, and the reaction was stirred for 5 hours. After the reaction, the solvent was removed by rotary evaporation, and the product 2-(1-(4-ethoxyphenyl)ethyl)benzo[d]isothiazol-3(2H)-one 1,1-dioxide, a yellow powder, was obtained by column chromatography (petroleum ether / ethyl acetate = 5 / 1), yielding 121.6 mg (73.4%).

[0299] The specific NMR data are as follows: 1 H NMR (400MHz, CDCl3): δ7.96(dd,J=6.7,0.9Hz,1H),7.89–7.86(m,1H),7.84–7.75(m,2H),7.52–7.50(m,2H),6.88– 6.86(m,2H),5.34(q,J=7.3Hz,1H),3.94(qd,J=7.0,3.0Hz,2H),1.93(d,J=7.3Hz,2H),1.32(t,J=7.0,2.1Hz,3H); 13CNMR (101MHz, CDCl3): δ158.8,158.5,137.8,134.6,134.2,130.4,129.1,127.4,125.0,120.7,114.3,63.4,52.7,17.8,14.8.

[0300] Example 63

[0301]

[0302] The experimental method in this embodiment is the same as in Example 36, except that the substrate is 4-ethylbiphenyl. In a clean, dry, unseparated glass electrolytic cell, o-phenylthioimide (0.5 mmol, 91.6 mg), sodium bromide electrolyte (1.0 mmol, 102.9 mg), acetonitrile solvent (10 mL), and 4-ethylbiphenyl (2.0 mmol, 364.5 mg) were added sequentially. Then, with a platinum sheet as the anode and a carbon rod as the cathode, a constant current of 20 mA was applied at 80°C, and the reaction was stirred for 5 hours. After the reaction, the solvent was removed by rotary evaporation, and the product 2-[1-(1,1'-biphenyl)-4-ethyl]benzo[d]isothiazolyl-3(2H)-one-1,1-dioxide, a white powder, was obtained by column chromatography (petroleum ether / ethyl acetate = 5 / 1), yielding 116.8 mg, a yield of 64.3%.

[0303] The specific NMR data are as follows: 1 H NMR (400MHz, CDCl3): δ7.91(d,J=8.0Hz,1H),7.83(d,J=7.7Hz,1H),7.74(dtd,J=21.2,7.5,1.2Hz,2H),7.62–7.57( m,2H),7.54–7.46(m,4H),7.35(t,J=7.5Hz,2H),7.26(t,J=6.1Hz,1H),5.42(q,J=7.2Hz,1H),1.99(d,J=7.3Hz,3H); 13 C NMR (101MHz, CDCl3): δ158.6,141.1,140.6,137.8,137.7,134.7,134.3,128.8,128.1,127.4,127.2,127.2,125.1,120.8,52.8,17.7.

[0304] Example 64

[0305]

[0306] The experimental method in this embodiment is the same as in Example 36, except that the substrate is 4-methylethylbenzene. In a clean, dry, unseparated glass electrolytic cell, o-phenylthioimide (0.5 mmol, 91.6 mg), sodium bromide electrolyte (1.0 mmol, 102.9 mg), acetonitrile solvent (10 mL), and 4-methylethylbenzene (2.0 mmol, 240.2 mg) were added sequentially. Then, with a platinum sheet as the anode and a carbon rod as the cathode, a constant current of 20 mA was applied at 80°C, and the reaction was stirred for 5 hours. After the reaction, the solvent was removed by rotary evaporation, and the product 2-(1-(p-tolyl)ethyl)benzo[d]isothiazolyl-3(2H)-one-1,1-dioxide was obtained by column chromatography (petroleum ether / ethyl acetate = 5 / 1), a white powder, 46.1 mg, yield 30.6%.

[0307] The specific NMR data are as follows: 1 H NMR (400MHz, CDCl3): δ7.96(d,J=7.1Hz,1H),7.88(d,J=7.0Hz,1H),7.80(dtd,J=20.6,7.4,1.3Hz,2H), 7.48(d,J=8.1Hz,2H),7.17(d,J=7.9Hz,2H),5.43(q,J=7.2Hz,1H),2.33(s,3H),2.01(d,J=7.3Hz,3H); 13 C NMR (101MHz, CDCl3): δ158.5,138.0,137.8,135.6,134.6,134.2,129.2,127.6,127.4,125.0,120.7,52.9,21.2,17.7.

[0308] Example 65

[0309]

[0310] The experimental method in this embodiment is the same as in Example 36, except that the substrate is methyl 4-ethylbenzoate. In a clean, dry, unseparated glass electrolytic cell, o-benzothioimide (0.5 mmol, 91.6 mg), sodium bromide electrolyte (1.0 mmol, 102.9 mg), acetonitrile solvent (10 mL), and methyl 4-ethylbenzoate (2.0 mmol, 328.2 mg) were added sequentially. Then, with a platinum sheet as the anode and a carbon rod as the cathode, a constant current of 20 mA was applied at 80°C, and the reaction was stirred for 5 hours. After the reaction, the solvent was removed by rotary evaporation, and the product methyl 4-[1-(1,1-dioxide-3-oxobenzo[d]isothiazo-2(3H)-yl)ethyl]benzoate was obtained by column chromatography (petroleum ether / ethyl acetate = 5 / 1), as a yellow powder, 43.2 mg, yield 25.0%.

[0311] The specific NMR data are as follows: 1 H NMR (400MHz, CDCl3): δ7.93–7.87(m,1H),7.82(d,J=6.9Hz,1H),7.74(dtd,J=20.2,7.4,1.3Hz,2H ),7.58–7.52(m,2H),7.04–6.97(m,2H),5.36(q,J=7.3Hz,1H),2.21(s,3H),1.95(d,J=7.3Hz,3H). 13 C NMR (101MHz, CDCl3): δ169.4,158.5,150.4,137.7,136.2,134.7,134.3,129.0,127.3,125.1,121.6,120.8,52.5,21.1,17.7.

[0312] Example 66

[0313]

[0314] The experimental method in this embodiment is the same as in Example 36, except that the substrate is 3-ethylbenzonitrile. In a clean, dry, unseparated glass electrolytic cell, o-benzothioimide (0.5 mmol, 91.6 mg), sodium bromide electrolyte (1.0 mmol, 102.9 mg), acetonitrile solvent (10 mL), and 3-ethylbenzonitrile (2.0 mmol, 262.4 mg) were added sequentially. Then, with a platinum sheet as the anode and a carbon rod as the cathode, a constant current of 20 mA was applied at 80°C, and the reaction was stirred for 5 hours. After the reaction, the solvent was removed by rotary evaporation, and the product 3-[1-(1,1-dioxo-3-oxobenzo[d]isothiazo-2(3H)-yl)ethyl]benzonitrile was obtained by column chromatography (petroleum ether / ethyl acetate = 5 / 1), as a yellow powder, 45.6 mg, yield 29.2%.

[0315] The specific NMR data are as follows: 1 H NMR (400MHz, CDCl3): δ7.99(d,J=7.8Hz,1H),7.94–7.90(m,1H),7.90–7.85(m,2H),7.84–7.79(m,2 H),7.60(dt,J=7.7,1.4Hz,1H),7.47(t,J=7.8Hz,1H),5.43(q,J=7.3Hz,1H),2.03(d,J=7.3Hz,3H); 13C NMR (101MHz, CDCl3): δ158.5,140.4,137.6,135.0,134.5,132.1,131.9,131.3,129.4,127.0,125.2,120.9,118.6,112.8,52.0,17.4.

[0316] Example 67

[0317]

[0318] The experimental method in this embodiment is the same as in Example 36, except that the substrate is artemisinin. In a clean, dry, unseparated glass electrolytic cell, o-phenylthioimide (0.5 mmol, 91.6 mg), sodium bromide electrolyte (1.0 mmol, 102.9 mg), acetonitrile solvent (10 mL), and artemisinin (2.0 mmol, 296.2 mg) were added sequentially. Then, with a platinum sheet as the anode and a carbon rod as the cathode, a constant current of 20 mA was applied at 80°C, and the reaction was stirred for 5 hours. After the reaction, the solvent was removed by rotary evaporation, and the product 2-[1-(4-methoxyphenyl)allyl]benzo[d]isothiazolyl-3(2H)-one-1,1-dioxide, a white powder, was obtained by column chromatography (petroleum ether / ethyl acetate = 5 / 1), yielding 58.5 mg (35.5%).

[0319] The specific NMR data are as follows: 1 H NMR (400MHz, CDCl3): δ8.07(d,J=7.4Hz,1H),7.93(d,J=7.4Hz,1H),7.85(dt,J=15.1,7.1Hz,2H),7.33(d,J=8.6Hz, 2H), 6.84 (d, J = 8.7Hz, 2H), 6.73 (d, J = 15.7Hz, 1H), 6.19 (dt, J = 15.7, 6.8Hz, 1H), 4.52 (d, J = 6.7Hz, 2H), 3.80 (s, 3H); 13 C NMR (101MHz, CDCl3): δ159.6,158.7,137.8,134.9,134.8,134.3,128.8,128.0,127.5,125.2,121.0,119.2,114.0,55.3,41.2.

[0320] Example 68

[0321]

[0322] The experimental method in this embodiment is the same as in Example 36, except that the substrate is salsa musk. In a clean, dry, unseparated glass electrolytic cell, o-phenylthioimide (0.5 mmol, 91.6 mg), sodium bromide electrolyte (1.0 mmol, 102.9 mg), acetonitrile solvent (10 mL), and salsa musk (2.0 mmol, 488.7 mg) were added sequentially. Then, with a platinum sheet as the anode and a carbon rod as the cathode, a constant current of 20 mA was applied at 80°C, and the reaction was stirred for 5 hours. After the reaction, the solvent was removed by rotary evaporation, and the product was separated by column chromatography (petroleum ether / ethyl acetate = 5 / 1) to obtain 2-(7-acetyl-5-(tert-butyl)-3,3-dimethyl-2,3-dihydro-1H-inden-1-yl)benzo[d]isothiazolyl-3(2H)-one-1,1-dioxide, a yellow powder, 70.9 mg, yield 33.3%.

[0323] The specific NMR data are as follows: 1 H NMR (400MHz, CDCl3): δ8.12–8.06(m,1H),7.83–7.73(m,3H),7.68(d,J=1.7Hz,1H),7.41(d,J=1. 7Hz,1H),6.50(dd,J=8.9,7.2Hz,1H),2.65–2.50(m,2H),2.49(s,3H),1.39(s,9H),1.25(s,6H); 13 C NMR (101MHz, CDCl3): δ199.9,158.5,154.8,153.0,138.1,136.0,134.4,134.0,131.3,1 27.1,125.3,125.1,123.3,120.2,56.6,46.9,42.2,35.0,31.4,31.3,29.7,29.2,27.7.

[0324] Example 69

[0325]

[0326] The experimental method in this embodiment is the same as in Example 36, except that the substrates are 4-ethyl anisole and N-acetyl-p-toluenesulfonamide. In a clean, dry, unseparated glass electrolytic cell, N-acetyl-p-toluenesulfonamide (0.5 mmol, 106.6 mg), sodium bromide electrolyte (1.0 mmol, 102.9 mg), acetonitrile solvent (10 mL), and 4-ethyl anisole (2.0 mmol, 272.2 mg) were added sequentially. Then, with a platinum sheet as the anode and a carbon rod as the cathode, a constant current of 20 mA was applied at 80°C, and the reaction was stirred for 5 hours. After the reaction, the solvent was removed by rotary evaporation, and the product N-[1-(4-methoxyphenyl)ethyl]-N-(p-toluenesulfonyl)acetamide, a colorless oily liquid, was obtained by column chromatography (petroleum ether / ethyl acetate = 5 / 1), yielding 57.8 mg, a yield of 33.3%.

[0327] The specific NMR data are as follows: 1 H NMR (400MHz, CDCl3): δ7.69(d,J=8.4Hz,2H),7.32–7.27(m,4H),6.83(d,J=8.8Hz,2H) , δ5.74(q,J=7.1Hz,1H),3.79(s,3H),2.44(s,3H),2.20(s,3H),1.80(d,J=7.1Hz,3H); 13 C NMR (101MHz, CDCl3): δ170.4,158.8,144.8,137.0,131.9,129.8,128.6,127.9,113.6,56.3,55.3,26.4,21.6,18.1.

[0328] Example 70

[0329]

[0330] The experimental method in this embodiment is the same as in Example 36, except that the substrates are 4-ethyl anisole and N-(tert-butyloxycarbonyl)-p-toluenesulfonamide. In a clean, dry, unseparated glass electrolytic cell, N-(tert-butyloxycarbonyl)-p-toluenesulfonamide (0.5 mmol, 135.7 mg), sodium bromide electrolyte (1.0 mmol, 102.9 mg), acetonitrile solvent (10 mL), and 4-ethyl anisole (2.0 mmol, 272.2 mg) were added sequentially. The electrolytic cell was then operated with a platinum sheet as the anode and a carbon rod as the cathode, and a constant current of 20 mA was applied at 80°C. The reaction was stirred for 5 hours. After the reaction, the solvent was removed by rotary evaporation, and the product was separated by column chromatography (petroleum ether / ethyl acetate = 5 / 1) to obtain tert-butyl N-(p-toluenesulfonyl)-N-[1-(4-methoxyphenyl)ethyl]carbamate, a yellow oily liquid, 97.9 mg, yield 48.3%.

[0331] The specific NMR data are as follows: 1 H NMR (400MHz, CDCl3): δ7.78(d,J=8.3Hz,2H),7.30(d,J=8.1Hz,2H),7.24(d,J=8.5Hz,2H),6.84(d, J=8.8Hz,2H),5.74(q,J=7.0Hz,1H),3.80(s,3H),2.44(s,3H),1.86(d,J=7.0Hz,3H),1.18(s,9H); 13 C NMR (101MHz, CDCl3): δ158.6,150.7,144.0,137.4,133.0,129.3,128.1,128.1,113.5,83.9,55.7,55.3,27.8,21.6,18.7.

[0332] Example 71

[0333] To verify the scale-up effect of the amination reaction described in this invention, a gram-scale reaction was performed in this embodiment, using the following reaction apparatus: Figure 3 As shown, o-phenylthioimide (6 mmol, 1.10 g), sodium bromide (6.0 mmol, 0.62 g), acetonitrile (60 mL), and diphenylmethane (24.0 mmol, 4.0 mL) were added sequentially to a 100 mL three-necked flask. The mixture was then electrolyzed in a platinum anode and a carbon rod cathode at 80 °C with a constant current of 20 mA. The reaction was stirred for 24 hours. After the reaction, the solvent was removed by rotary evaporation, and the product 2-diphenylmethylbenzo[d]isothiazol-3(2H)-one-1,1-dioxide was obtained by column chromatography (petroleum ether / ethyl acetate = 5 / 1), a white powder, 1.18 g, yield 53.3%. The product is as follows: Figure 4 As shown.

[0334] This invention provides an electrochemical direct oxidative dehydrogenation amination reaction using alkanes as raw materials under mild conditions without the participation of metal catalysts and bases, and successfully prepares a variety of aromatic alkane amination products based on this reaction.

[0335] This invention provides a method and approach for the direct amination of aromatic alkane carbon-hydrogen bonds via electrochemical catalysis. Many methods and approaches exist for implementing this technical solution; the above description is merely a preferred embodiment of the invention. It should be noted that those skilled in the art can make various improvements and modifications without departing from the principles of this invention, and these improvements and modifications should also be considered within the scope of protection of this invention. All components not explicitly stated in this embodiment can be implemented using existing technologies.

Claims

1. A method of electrochemically catalyzing the direct amination of aromatic alkane C-H bonds, characterized in that, An aromatic alkane compound and a sulfonimide compound are subjected to an electrochemical reaction in the presence of an electrolyte to obtain an aminated product; The aromatic alkane compound has a structural formula as shown in Formula I, the sulfonimide compound has a structural formula as shown in Formula II or Formula III, and the aminated product has a structural formula as shown in Formula IV or Formula V; wherein, R 1 any one selected from the group consisting of a hydrogen atom, an alkyl group, an alkoxy group, a fluoroalkyl group, a halogen, an ester group, a cyano group, a nitro group, a phenyl group, a substituted phenyl group, a furanyl group, a substituted furanyl group, a pyrrolyl group, a substituted pyrrolyl group, a thienyl group, or a substituted thienyl group; R 2 , R 3 , R 4 , R 5 , and R 6 are each independently selected from any one of a hydrogen atom, an alkyl group, an alkoxy group, a fluoroalkyl group, a halogen, an acyl group, an ester group, a vinyl group, a phenyl group, a substituted phenyl group, a furanyl group, a substituted furanyl group, a pyrrolyl group, a substituted pyrrolyl group, a thienyl group, and a substituted thienyl group; when R 6 selected from any one of hydrogen atom, alkyl, alkoxy, fluoroalkyl, halogen, acyl, ester, vinyl, phenyl, substituted phenyl, furanyl, substituted furanyl, pyrrolyl, substituted pyrrolyl, and thienyl, the aromatic alkane is a secondary aromatic alkane; and when R 6 selected from any one of hydrogen atom, alkyl, alkoxy, fluoroalkyl, halogen, acyl, ester, vinyl, phenyl, substituted phenyl, furanyl, substituted furanyl, pyrrolyl, substituted pyrrolyl, and thienyl, the aromatic alkane is a secondary aromatic alkane; and when R The electrolyte comprises any one of potassium bromide, ammonium bromide or sodium bromide. The cathode material of the electrochemical reaction is any one of a carbon rod or a platinum sheet, and the anode material is any one of a carbon rod or a platinum sheet. The electrochemical reaction has a reaction current of 10-30 mA. The electrochemical reaction is performed in a reaction solvent, and the reaction solvent is acetonitrile.

2. The method of claim 1, wherein, The R mentioned 1 It is selected from any one of hydrogen atom, alkyl, alkoxy, fluoroalkyl, halogen, phenyl, cyano and ester group; R 2 , R 3 , R 4 , and R 5 are each independently selected from any one of alkyl, alkoxy, phenyl, substituted phenyl, and thienyl; The R 6 is selected from any one of a hydrogen atom, an alkyl group, a vinyl group, a phenyl group or a substituted phenyl group.

3. The method of claim 1, wherein, The molar ratio of the aromatic alkane compound to the sulfonimide compound is 4-6:

1.

4. The method of claim 1, wherein, The molar ratio of the electrolyte to the aromatic alkane compound is 1:2-4.

5. The method of claim 1, wherein, The electrochemical reaction has a reaction temperature of 60-80 ℃ and a reaction time of 3-8 h.

6. The method of claim 1, wherein, 0.1-0.4 mmol of the aromatic alkane compound is added per mL of acetonitrile.

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