Method for preparing modafinil by electrochemical reaction

Abstract

The invention belongs to the field of organic electrosynthesis green oxidation, and relates to a method for preparing modafinil by adopting electrochemical reaction. The preparation method comprises the following steps: mixing benzhydryl thioacetamide with water, an electrolyte and a solvent to obtain a mixed solution, and carrying out electrochemical reaction on the mixed solution under the electrolysis action of an electrode to obtain modafinil. Compared with the current mainstream thermochemical and photochemical oxidation processes, the strategy provided by the invention does not use hydrogen peroxide (H2O2) as an oxidizing agent, does not need to provide heating and pressure, does not need to use an expensive photocatalyst, avoids the cost and danger caused by the storage and transportation of the oxidizing agent, and is more green, mild, safe and firmer.

Description

Technical Field

[0001] This invention belongs to the field of organic electrosynthesis and green oxidation, and relates to a method for preparing modafinil by electrochemical reaction. Background Technology

[0002] Modafinil, with its excellent physical and chemical properties, readily participates in in vivo metabolic processes, exhibiting significant physiological activity and medicinal value. From a molecular manufacturing perspective, the mainstream process for the selective oxidation of sulfur atoms to sulfoxide groups in the modafinil molecular skeleton is currently achieved in an equivalent or excess acidic hydrogen peroxide (H2O2) solution. Numerous studies have reported on this process (Molecules 2012,17,10446-10458., J.Org.Chem.2015,80,2676-2699., Adv.Syn.&Cat.2015,357,3573-3586., ACS Catal.2020,10,245-252., GreenChem.,2017,19,629-633., Green Chem.,2022,24,2094-2103.). The thermochemical hydrogen peroxide (H2O2) oxidation process is difficult to control the selectivity of oxidation products and is prone to side reactions such as the peroxidation of sulfide to sulfone groups, which makes it difficult to separate the target product from the peroxidation byproducts. At the same time, the storage and transportation of acidic solution oxidants is also a safety production problem.

[0003] In recent years, as governments around the world have increasingly emphasized sustainable energy, recyclable resources, and a green and safe living environment, green chemical production processes have received much attention from scientific researchers, especially in using light energy and green electrocatalytic conversion technologies to replace and solve the problems of high pollution, high energy consumption, and high risk in the thermocatalytic chemical industry. Compared to the thermochemical oxidation process of hydrogen peroxide (H2O2), the photocatalytic green oxidation process of "modafinil" has milder reaction conditions, usually carried out at room temperature. It adds a catalytic amount of photocatalyst and uses clean oxygen as the oxygen source to achieve this catalytic oxidation process. However, this oxidation conversion process has engineering challenges that need to be solved, such as expensive and non-recyclable photocatalysts, low mass and heat transfer efficiency, long reaction time, and difficulty in scaling up the process (Adv.Syn.&Cat.2016,358,1654-1663.,Synlett 2025,36,1723-1728.,Inorg.Chem.2021,60,7008-7022.,ChemCatChem.2019,11,4916-4922.). Summary of the Invention

[0004] The technical problem to be solved by this invention is that the existing thermochemical and photochemical synthesis methods for modafinil have problems such as high reaction temperature, poor selectivity of reaction products, need to add additional oxidants, expensive photocatalysts, and long reaction time. This invention develops and studies a new process for preparing modafinil using green electrochemical batch and microchannel continuous flow oxidation. This method, under current and electrolyte conditions, does not require additional catalysts and oxidants, is simple and safe to operate, and achieves a green and efficient preparation process of modafinil under mild conditions.

[0005] To solve the above-mentioned technical problems, the technical solution adopted by the present invention is as follows:

[0006] This invention discloses a method for preparing modafinil by electrochemical reaction. Diphenylmethylthioacetamide is mixed with water, electrolyte and solvent, and the resulting mixture undergoes an electrochemical reaction under the action of electrode electrolysis to obtain modafinil.

[0007] The structural formula of the diphenylmethylthioacetamide is shown in Formula I, and the structural formula of the modafinil is shown in Formula II.

[0008]

[0009] In some embodiments, the electrolyte is tetraethylammonium chloride; the molar ratio of diphenylmethylthioacetamide to the electrolyte is 1.0:(1.5-2.0).

[0010] In some embodiments, the electrochemical reaction is carried out using a conventional electrochemical autoclave or an electrochemical microchannel continuous flow reactor.

[0011] In some embodiments, when the electrochemical reaction is carried out using a conventional electrochemical autoclave, the molar ratio of diphenylmethylthioacetamide to water is 1.0:(10.0 to 50.0).

[0012] In some embodiments, preferably, when the electrochemical reaction is carried out using a conventional electrochemical autoclave apparatus, the molar ratio of diphenylmethylthioacetamide to water is 1.0:(15.0–50.0), more preferably 1.0:(25.0–35.0).

[0013] In some embodiments, when the electrochemical reaction is carried out using a conventional electrochemical autoclave apparatus, the solvent is a mixed solvent of acetonitrile, ethanol, pyridine, 1,2-dichloroethane and acetonitrile in a volume ratio of (1.0–3.0):(1.0–9.0), a mixed solvent of tetrahydrofuran and acetonitrile in a volume ratio of (1.0–5.0):(1.0–9.0), or a mixed solvent of pyridine and acetonitrile in a volume ratio of (1.0–4.0):(3.0–6.0); and / or, the concentration of diphenylmethylthioacetamide in the mixture is 0.04 mmol / mL to 0.10 mmol / mL.

[0014] In some embodiments, preferably, when the electrochemical reaction is carried out using a conventional electrochemical autoclave apparatus, the solvent is a mixed solvent of acetonitrile, pyridine, tetrahydrofuran, and acetonitrile in a volume ratio of 2.0:5.0, or a mixed solvent of pyridine and acetonitrile in a volume ratio of (1.0–4.0):(3.0–6.0). More preferably, it is a mixed solvent of acetonitrile, pyridine, tetrahydrofuran, and acetonitrile in a volume ratio of 2.0:5.0, a mixed solvent of pyridine and acetonitrile in a volume ratio of 1.0:6.0, a mixed solvent of pyridine and acetonitrile in a volume ratio of 2.0:5.0, a mixed solvent of pyridine and acetonitrile in a volume ratio of 3.0:4.0, or a mixed solvent of pyridine and acetonitrile in a volume ratio of 4.0:3.0. Even more preferably, it is a mixed solvent of acetonitrile, pyridine, and acetonitrile in a volume ratio of 2.0:5.0, or a mixed solvent of pyridine and acetonitrile in a volume ratio of 3.0:4.0.

[0015] In some embodiments, preferably, the concentration of diphenylmethylthioacetamide in the mixture is 0.04 mmol / mL to 0.08 mmol / mL.

[0016] In some embodiments, when the electrochemical reaction is carried out using a conventional electrochemical reactor apparatus: the anode of the electrode is a carbon sheet, and the cathode of the electrode is a platinum sheet; and / or, the constant current in the electrochemical reaction is 2.0 mA to 8.0 mA; and / or, the reaction temperature of the electrochemical reaction is 0 °C to 40 °C; and / or, the reaction time of the electrochemical reaction is 8.0 hours to 10.5 hours; and / or, the electrochemical reaction is carried out under inert gas protection.

[0017] In some embodiments, preferably when the electrochemical reaction is carried out using a conventional electrochemical autoclave apparatus: the constant current in the electrochemical reaction is 2.0 mA to 5.0 mA, more preferably 5.0 mA.

[0018] In some embodiments, preferably, when the electrochemical reaction is carried out using a conventional electrochemical autoclave apparatus: the electrochemical reaction is carried out at a temperature of 0°C to room temperature, more preferably 0°C.

[0019] The inert gas is preferably nitrogen.

[0020] In some embodiments, when the electrochemical reaction is carried out using an electrochemical microchannel continuous flow reactor, the following steps are included:

[0021] Diphenylmethylthioacetamide is mixed with water, electrolyte, and solvent. The resulting mixture is pumped into the electrochemical microchannel continuous flow reactor of the electrochemical microchannel continuous flow reactor device, where it undergoes an electrochemical reaction under the action of electrode electrolysis to obtain modafinil.

[0022] In some embodiments, when the electrochemical reaction is carried out using an electrochemical microchannel continuous flow reactor: the solvent is acetonitrile, or a mixed solvent of acetonitrile and pyridine in a volume ratio of (25.0–40.0):(5.0–20.0); and / or, the molar ratio of diphenylmethylthioacetamide to water is 1.0:(55.0–280.0); and / or, the volume ratio of water to the solvent is (5.0–25.0):(25.0–45.0).

[0023] In some embodiments, preferably, when the electrochemical reaction is carried out using an electrochemical microchannel continuous flow reactor: the solvent is a mixed solvent of acetonitrile and pyridine in a volume ratio of (25.0–40.0):(5.0–20.0); more preferably, the solvent is a mixed solvent of acetonitrile and pyridine in a volume ratio of 40.0:5.0, a mixed solvent of acetonitrile and pyridine in a volume ratio of 35.0:10.0, a mixed solvent of acetonitrile and pyridine in a volume ratio of 30.0:15.0, or a mixed solvent of acetonitrile and pyridine in a volume ratio of 25.0:20.0; even more preferably, the solvent is a mixed solvent of acetonitrile and pyridine in a volume ratio of 40.0:5.0, a mixed solvent of acetonitrile and pyridine in a volume ratio of 35.0:10.0, or a mixed solvent of acetonitrile and pyridine in a volume ratio of 30.0:15.0.

[0024] In some embodiments, preferably, when the electrochemical reaction is carried out using an electrochemical microchannel continuous flow reactor: the molar ratio of diphenylmethylthioacetamide to water is 1.0:(55.0 to 115.0), more preferably 1.0:(55.0 to 60.0).

[0025] In some embodiments, preferably, when the electrochemical reaction is carried out using an electrochemical microchannel continuous flow reactor: the volume ratio of the water to the solvent is (5.0 to 10.0):(40.0 to 45.0), more preferably 5.0:45.0.

[0026] In some embodiments, when the electrochemical reaction is carried out using an electrochemical microchannel continuous flow reactor: the flow rate of the mixed liquid pumped into the electrochemical microchannel continuous flow reactor of the electrochemical microchannel continuous flow reactor is 0.1 mL / min to 0.5 mL / min; and / or, the residence time of the electrochemical reaction in the electrochemical microchannel continuous flow reactor is 10.0 min to 50.0 min; and / or, the anode of the electrode is a graphite plate or a platinum sheet, and the cathode is a graphite plate or a platinum sheet; and / or, the constant current in the electrochemical reaction is 40.0 mA to 200 mA; and / or, the reaction temperature of the electrochemical reaction is room temperature.

[0027] In some embodiments, preferably, when the electrochemical reaction is carried out using an electrochemical microchannel continuous flow reactor: the flow rate of the mixture pumped into the electrochemical microchannel continuous flow reactor of the electrochemical microchannel continuous flow reactor is 0.2 mL / min to 0.3 mL / min.

[0028] In some embodiments, preferably, when the electrochemical reaction is carried out using an electrochemical microchannel continuous flow reactor: the residence time of the electrochemical reaction in the electrochemical microchannel continuous flow reactor is 16.7 min to 25.0 min.

[0029] In some embodiments, preferably, when the electrochemical reaction is carried out using an electrochemical microchannel continuous flow reactor: the anode of the electrode is a platinum sheet and the cathode is a graphite plate, or the anode of the electrode is a platinum sheet and the cathode is a platinum sheet; more preferably, the anode of the electrode is a platinum sheet and the cathode is a graphite plate.

[0030] In some embodiments, preferably, when the electrochemical reaction is carried out using an electrochemical microchannel continuous flow reactor: the constant current in the electrochemical reaction is 120.0 mA to 160.0 mA.

[0031] In some embodiments, the electrochemical microchannel continuous flow reactor includes a connecting pipe, an injection pump, an electrochemical microchannel continuous flow reactor, an electrical box, and a receiver; wherein the injection pump, the electrochemical microchannel continuous flow reactor, and the receiver are connected in series via the connecting pipe; the electrical box applies current to both ends of the electrochemical microchannel continuous flow reactor, with the positive terminal of the electrical box connected to the anode terminal of the electrochemical microchannel continuous flow reactor, and the negative terminal of the electrical box connected to the cathode terminal of the electrochemical microchannel continuous flow reactor.

[0032] Beneficial effects:

[0033] (1) This invention discloses a green, efficient and safe organic electrochemical batch and microchannel continuous flow oxidation process to realize the electrochemical oxidation preparation of commercially available modafinil drug. The process is characterized by: using diphenylmethylthioacetamide as raw material, water as oxygen atom donor, and clean electrons as green and traceless oxidant to selectively oxidize and obtain modafinil drug in one step.

[0034] (2) The oxidation preparation process disclosed in this invention is carried out in a conventional unseparated electrolytic cell or in an electrochemical microchannel continuous flow reaction device, and the operation is simple and safe.

[0035] (3) The oxidation preparation process disclosed in this invention does not contain any exogenous oxidant. Based on the thermochemical hydrogen peroxide (H2O2) oxidation process and the photocatalytic oxygen (O2) oxidation process, this invention provides a supplementary scheme for electrochemical oxidation that can be referenced and is green and safe.

[0036] (4) This invention discloses a green oxidation process for modafinil using an electrochemical autoclave and microchannel continuous flow process. This process uses clean, green electrons as the oxidant, avoiding the use of external oxidants. Water (H2O) serves as the oxygen atom donor, and the additive pyridine can appropriately improve the reaction yield. The reaction operation is simple, and modafinil can be successfully obtained in medium to excellent yields. Compared with the current mainstream thermochemical and photochemical oxidation processes, this strategy does not use hydrogen peroxide (H2O2) as an oxidant, requires no heating or pressure, and does not require the use of expensive photocatalysts. It avoids the costs and dangers associated with oxidant storage and transportation. This electrochemical strategy is greener, milder, safer, and more robust.

[0037] (5) The present invention uses a green electrochemical oxidation reaction device, which is characterized by: high reaction efficiency, specific reaction selectivity, high raw material conversion rate, no by-products, and can achieve a high target product yield under mild reaction conditions, up to 83%.

[0038] (6) Compared with intermittent thermochemical and photochemical oxidation processes, the electrochemical microchannel continuous flow oxidation reaction device and process provided by the present invention do not require the participation of additional oxidants, which can greatly improve the reaction efficiency, shorten the process cycle, ensure safe operation, reduce process cost, and have the potential for pilot-scale reaction and industrial scale-up. Attached Figure Description

[0039] The present invention will be further described in detail below with reference to the accompanying drawings and specific embodiments, and the advantages of the present invention in the above and / or other aspects will become clearer.

[0040] Figure 1 This is a photograph of the electrochemical autoclave oxidation reactor used in the embodiments of the present invention.

[0041] Figure 2 This is a photograph of the electrochemical microchannel continuous flow reaction apparatus used in the embodiments of the present invention.

[0042] Figure 3 The modafinil structure prepared in the embodiments of the present invention is typical. 1 H NMR spectrum.

[0043] Figure 4 The modafinil structure prepared in the embodiments of the present invention is typical. 13 C10 NMR spectrum. Detailed Implementation

[0044] The present invention will be further described in detail below with reference to specific embodiments, but the scope of protection of the present invention is not limited thereto, and also includes other reactions derived from this technology.

[0045] The experimental methods mentioned in the following examples are all conventional methods, i.e., common and universal methods. Unless otherwise specified, all reagents and materials are commercially available.

[0046] Figure 1 This is a photograph of the electrochemical autoclave oxidation reactor used in the embodiments of the present invention.

[0047] Figure 2 This is a photograph of the electrochemical microchannel continuous flow reactor used in an embodiment of the present invention. The electrochemical microchannel continuous flow reactor includes connecting pipes, an injection pump, an electrochemical microchannel continuous flow reactor, an electrostatic precipitator, and a receiver; wherein the injection pump, the electrochemical microchannel continuous flow reactor, and the receiver are connected in series via connecting pipes; the anode of the electrochemical microchannel continuous flow reactor is a platinum sheet or a graphite plate, and the cathode is a graphite plate or a platinum sheet; the electrostatic precipitator applies current to both ends of the electrochemical microchannel continuous flow reactor, with the positive terminal of the electrostatic precipitator connected to the anode end of the electrochemical microchannel continuous flow reactor, and the negative terminal of the electrostatic precipitator connected to the cathode end of the electrochemical microchannel continuous flow reactor.

[0048] The connecting pipe is made of polytetrafluoroethylene.

[0049] The injection pump is model number RIFE TYD02-01.

[0050] The electrochemical microchannel continuous flow reactor has a retention volume of 5.0 mL, an inner diameter of 0.8 mm, and is model number Kaituo MFS-EC / 1X4-V5BE-202316.

[0051] The electrical box is model number Espressif MS-305DS.

[0052] Example 1: Optimization of the process for preparing modafinil using an electrochemical batch oxidation reaction

[0053]

[0054] Electrochemical autoclave oxidation reaction: Diphenylmethylthioacetamide (0.5 mmol, 128.7 mg, 1.0 equiv.), tetraethylammonium chloride (0.75 mmol, 124.3 mg, 1.5 equiv.), acetonitrile (10.0 mL), and water (90.0 μL, 10.0 equiv.) were added sequentially to a clean, dry, unseparated electrolytic cell. A carbon sheet was then used as the anode and a platinum sheet as the cathode. A constant current of 5.0 mA was applied at room temperature under a nitrogen atmosphere for 10.5 hours. After the reaction, the solvent was removed by rotary evaporation, and the product was separated by silica gel column chromatography with eluent to obtain modafinil, a white solid, in 41% yield.

[0055] The prepared modafinil structure is typical 1 H NMR spectrum as shown Figure 3 As shown, the prepared modafinil structure is typical. 13 The C NMR spectrum is as follows Figure 4 As shown.

[0056] Example 2: The experimental method in this example is the same as in Example 1, except that the amount of water used is increased to 135.0 μL.

[0057] In a clean, dry, unseparated electrolytic cell, diphenylmethylthioacetamide (0.5 mmol, 128.7 mg, 1.0 equiv.), tetraethylammonium chloride (0.75 mmol, 124.3 mg, 1.5 equiv.), acetonitrile (10.0 mL), and water (135.0 μL, 15.0 equiv.) were added sequentially. The electrolytic cell was then used with a carbon sheet as the anode and a platinum sheet as the cathode, and a constant current of 5.0 mA was applied at room temperature under a nitrogen atmosphere for 10.5 hours. After the reaction was complete, the solvent was removed by rotary evaporation, and the product was separated by silica gel column chromatography with eluent to obtain modafinil, a white solid, in 55% yield.

[0058] Example 3: The experimental method in this example is the same as in Example 1, except that the amount of water used is increased to 180.0 μL.

[0059] In a clean, dry, unseparated electrolytic cell, diphenylmethylthioacetamide (0.5 mmol, 128.7 mg, 1.0 equiv.), tetraethylammonium chloride (0.75 mmol, 124.3 mg, 1.5 equiv.), acetonitrile (10.0 mL), and water (180.0 μL, 20.0 equiv.) were added sequentially. The electrolytic cell was then used with a carbon sheet as the anode and a platinum sheet as the cathode, and a constant current of 5.0 mA was applied at room temperature under a nitrogen atmosphere for 10.5 hours. After the reaction was complete, the yield was determined by HPLC using biphenyl as an internal standard, yielding modafinil in 37% of the target product.

[0060] Example 4: The experimental method in this example is the same as in Example 1, except that the amount of water used is increased to 225.0 μL.

[0061] In a clean, dry, unseparated electrolytic cell, diphenylmethylthioacetamide (0.5 mmol, 128.7 mg, 1.0 equiv.), tetraethylammonium chloride electrolyte (0.75 mmol, 124.3 mg, 1.5 equiv.), acetonitrile solvent (10.0 mL), and water (225.0 μL, 25.0 equiv.) were added sequentially. The electrolytic cell was then used with a carbon sheet as the anode and a platinum sheet as the cathode, and a constant current of 5.0 mA was applied at room temperature under a nitrogen atmosphere for 10.5 hours. After the reaction was complete, the yield was determined by HPLC using biphenyl as an internal standard, yielding modafinil at 32%.

[0062] Example 5: The experimental method in this example is the same as in Example 1, except that the amount of water used is increased to 270.0 μL.

[0063] In a clean, dry, unseparated electrolytic cell, diphenylmethylthioacetamide (0.5 mmol, 128.7 mg, 1.0 equiv.), tetraethylammonium chloride (0.75 mmol, 124.3 mg, 1.5 equiv.), acetonitrile (10.0 mL), and water (270.0 μL, 30.0 equiv.) were added sequentially. The electrolytic cell was then used with a carbon sheet as the anode and a platinum sheet as the cathode, and a constant current of 5.0 mA was applied at room temperature under a nitrogen atmosphere for 10.5 hours. After the reaction was complete, the solvent was removed by rotary evaporation, and the product was separated by silica gel column chromatography with eluent to obtain modafinil, a white solid, in 32% yield.

[0064] Table 1. Effect of Oxygen Source Donor Water Addition Amount on the Reactor Electrochemical Green Oxidation Process

[0065] Example <![CDATA[H2O (equivalent)]]> Yield a (%) 1 10.0 <![CDATA[41 b ]]> 2 15.0 <![CDATA[55 b ]]> 3 20.0 37 4 25.0 32 5 30.0 <![CDATA[32 b ]]>

[0066] a) Yield was determined by HPLC, with biphenyl as the internal standard; b) Yield was the separation yield.

[0067] Example 6: The experimental method in this example is the same as in Example 2, except that a constant current of 2.0mA is applied.

[0068] In a clean, dry, unseparated electrolytic cell, diphenylmethylthioacetamide (0.5 mmol, 128.7 mg, 1.0 equiv.), tetraethylammonium chloride (0.75 mmol, 124.3 mg, 1.5 equiv.), acetonitrile (10.0 mL), and water (135.0 μL, 15.0 equiv.) were added sequentially. The electrolytic cell was then used with a carbon sheet as the anode and a platinum sheet as the cathode, and a constant current of 2.0 mA was applied at room temperature under a nitrogen atmosphere for 10.5 hours. After the reaction was complete, the solvent was removed by rotary evaporation, and the product was separated by silica gel column chromatography with eluent to obtain modafinil, a white solid, in 39% yield.

[0069] Example 7: The experimental method in this example is the same as in Example 2, except that a constant current of 8.0mA is applied.

[0070] In a clean, dry, unseparated electrolytic cell, diphenylmethylthioacetamide (0.5 mmol, 128.7 mg, 1.0 equiv.), tetraethylammonium chloride electrolyte (0.75 mmol, 124.3 mg, 1.5 equiv.), acetonitrile solvent (10.0 mL), and water (135.0 μL, 15.0 equiv.) were added sequentially. The electrolytic cell was then used with a carbon sheet as the anode and a platinum sheet as the cathode, and a constant current of 8.0 mA was applied at room temperature under a nitrogen atmosphere for 10.5 hours. After the reaction was complete, the yield was determined by HPLC using biphenyl as an internal standard, yielding modafinil in 30% of the target product.

[0071] Table 2. Effect of oxidation current on batch electrochemical green oxidation process

[0072] Example Current (mA) Yield a (%) 2 5.0 <![CDATA[55 b ]]> 6 2.0 <![CDATA[39 b ]]> 7 8.0 30

[0073] a) Yield was determined by HPLC, with biphenyl as the internal standard; b) Yield was the separation yield.

[0074] Example 8: The experimental method in this example is the same as in Example 2, except that the electrolyte is tetraethylammonium bromide.

[0075] In a clean, dry, unseparated electrolytic cell, diphenylmethylthioacetamide (0.5 mmol, 128.7 mg, 1.0 equiv.), tetraethylammonium bromide electrolyte (0.75 mmol, 157.5 mg, 1.5 equiv.), acetonitrile solvent (10.0 mL), and water (135.0 μL, 15.0 equiv.) were added sequentially. The electrolytic cell was then used with a carbon sheet as the anode and a platinum sheet as the cathode, and a constant current of 5.0 mA was applied at room temperature under a nitrogen atmosphere for 10.5 hours. After the reaction was completed, no target product was formed.

[0076] Example 9: The experimental method in this example is the same as in Example 2, except that the electrolyte is tetrabutylammonium hexafluorophosphate.

[0077] In a clean, dry, unseparated electrolytic cell, diphenylmethylthioacetamide (0.5 mmol, 128.7 mg, 1.0 equiv.), tetrabutylammonium hexafluorophosphate electrolyte (0.75 mmol, 290.6 mg, 1.5 equiv.), acetonitrile solvent (10.0 mL), and water (135.0 μL, 15.0 equiv.) were added sequentially. The electrolytic cell was then used with a carbon sheet as the anode and a platinum sheet as the cathode, and a constant current of 5.0 mA was applied at room temperature under a nitrogen atmosphere for 10.5 hours. After the reaction was completed, no target product was formed.

[0078] Example 10: The experimental method in this example is the same as in Example 2, except that the electrolyte is tetraethylammonium iodide.

[0079] In a clean, dry, unseparated electrolytic cell, diphenylmethylthioacetamide (0.5 mmol, 128.7 mg, 1.0 equiv.), tetraethylammonium iodide electrolyte (0.75 mmol, 192.9 mg, 1.5 equiv.), acetonitrile solvent (10.0 mL), and water (135.0 μL, 15.0 equiv.) were added sequentially. The electrolytic cell was then used with a carbon sheet as the anode and a platinum sheet as the cathode, and a constant current of 5.0 mA was applied at room temperature under a nitrogen atmosphere for 10.5 hours. After the reaction was completed, no target product was formed.

[0080] Example 11: The experimental method in this example is the same as in Example 2, except that the electrolyte is tetrabutylammonium acetate.

[0081] In a clean, dry, unseparated electrolytic cell, diphenylmethylthioacetamide (0.5 mmol, 128.7 mg, 1.0 equiv.), tetrabutylammonium acetate (0.75 mmol, 226.1 mg, 1.5 equiv.), acetonitrile (10.0 mL), and water (135.0 μL, 15.0 equiv.) were added sequentially. The electrolytic cell was then used with a carbon sheet as the anode and a platinum sheet as the cathode, and a constant current of 5.0 mA was applied at room temperature under a nitrogen atmosphere for 10.5 hours. After the reaction was completed, no target product was formed.

[0082] Example 12: The experimental method in this example is the same as in Example 2, except that the electrolyte is sodium bromide.

[0083] In a clean, dry, unseparated electrolytic cell, diphenylmethylthioacetamide (0.5 mmol, 128.7 mg, 1.0 equiv.), sodium bromide electrolyte (0.75 mmol, 77.2 mg, 1.5 equiv.), acetonitrile solvent (10.0 mL), and water (135.0 μL, 15.0 equiv.) were added sequentially. The electrolytic cell was then used with a carbon sheet as the anode and a platinum sheet as the cathode, and a constant current of 5.0 mA was applied at room temperature under a nitrogen atmosphere for 10.5 hours. After the reaction was completed, no target product was formed.

[0084] Table 3. Effect of electrolyte type on autoclave electrochemical green oxidation process

[0085] Example electrolytes Yield a (%) 2 Tetraethylammonium chloride <![CDATA[55 b ]]> 8 Tetraethylammonium bromide 0 9 Tetrabutylammonium hexafluorophosphate 0 10 Tetraethylammonium iodide 0 11 Tetrabutylacetic acid ammonium 0 12 Sodium bromide 0

[0086] a) Yield was determined by HPLC, with biphenyl as the internal standard; b) Yield was the separation yield.

[0087] Example 13: The experimental method in this example is the same as in Example 2, except that the amount of acetonitrile is 5.0 ml, the amount of water is 270.0 μL, and the reaction time is 9 hours.

[0088] In a clean, dry, unseparated electrolytic cell, diphenylmethylthioacetamide (0.5 mmol, 128.7 mg, 1.0 equiv.), tetraethylammonium chloride electrolyte (0.75 mmol, 124.3 mg, 1.5 equiv.), acetonitrile solvent (5.0 mL), and water (270.0 μL, 30.0 equiv.) were added sequentially. The electrolytic cell was then used with a carbon sheet as the anode and a platinum sheet as the cathode, and a constant current of 5.0 mA was applied at room temperature under a nitrogen atmosphere for 9 hours. After the reaction was complete, the solvent was removed by rotary evaporation, and the product was separated by silica gel column chromatography with eluent to obtain modafinil, a white solid, in 40% yield.

[0089] Example 14: The experimental method in this example is the same as in Example 2, except that the amount of acetonitrile is 7.0 ml, the amount of water is 270.0 μL, and the reaction time is 9 hours.

[0090] In a clean, dry, unseparated electrolytic cell, diphenylmethylthioacetamide (0.5 mmol, 128.7 mg, 1.0 equiv.), tetraethylammonium chloride electrolyte (0.75 mmol, 124.3 mg, 1.5 equiv.), acetonitrile solvent (7.0 mL), and water (270.0 μL, 30.0 equiv.) were added sequentially. The electrolytic cell was then used with a carbon sheet as the anode and a platinum sheet as the cathode, and a constant current of 5.0 mA was applied at room temperature under a nitrogen atmosphere for 9 hours. After the reaction was complete, the solvent was removed by rotary evaporation, and the product was separated by silica gel column chromatography with eluent to obtain modafinil, a white solid, in 44% yield.

[0091] Example 15: The experimental method in this example is the same as in Example 14, except that the reaction temperature is 40°C, the additive water is 135 μL, and the reaction time is 10.5 hours.

[0092] In a clean, dry, unseparated electrolytic cell, diphenylmethylthioacetamide (0.5 mmol, 128.7 mg, 1.0 equiv.), tetraethylammonium chloride (0.75 mmol, 124.3 mg, 1.5 equiv.), acetonitrile (7.0 mL), and water (135.0 μL, 15.0 equiv.) were added sequentially. The electrolytic cell was then used with a carbon sheet as the anode and a platinum sheet as the cathode. A constant current of 5.0 mA was applied at a reaction temperature of 40 °C under a nitrogen atmosphere for 10.5 hours. After the reaction was complete, the solvent was removed by rotary evaporation, and the product was separated by silica gel column chromatography with an eluent to obtain modafinil, a white solid, in 20% yield.

[0093] Example 16: The experimental method in this example is the same as in Example 14, except that the reaction temperature is 0°C, the additive water is 135.0 μL, and the reaction time is 8 hours.

[0094] In a clean, dry, unseparated electrolytic cell, diphenylmethylthioacetamide (0.5 mmol, 128.7 mg, 1.0 equiv.), tetraethylammonium chloride electrolyte (0.75 mmol, 124.3 mg, 1.5 equiv.), acetonitrile solvent (7.0 mL), and water (135.0 μL, 15.0 equiv.) were added sequentially. The electrolytic cell was then used with a carbon sheet as the anode and a platinum sheet as the cathode. A constant current of 5.0 mA was applied at a reaction temperature of 0 °C under a nitrogen atmosphere for 8 hours. After the reaction was complete, the solvent was removed by rotary evaporation, and the product was separated by silica gel column chromatography with eluent to obtain modafinil, a white solid, in 68% yield.

[0095] Example 17: The experimental method in this example is the same as in Example 16, except that the additive is sodium carbonate.

[0096] In a clean, dry, unseparated electrolytic cell, diphenylmethylthioacetamide (0.5 mmol, 128.7 mg, 1.0 equiv.), tetraethylammonium chloride (0.75 mmol, 124.3 mg, 1.5 equiv.), acetonitrile (7.0 mL), sodium carbonate (79.5 mg, 1.5 equiv.), and water (135.0 μL, 15.0 equiv.) were added sequentially. The electrolytic cell was then used with a carbon sheet as the anode and a platinum sheet as the cathode. A constant current of 5.0 mA was applied at a reaction temperature of 0 °C under a nitrogen atmosphere for 8 hours. After the reaction was complete, the solvent was removed by rotary evaporation, and the product was separated by silica gel column chromatography using an eluent to obtain modafinil, a white solid, in 23% yield.

[0097] Example 18: The experimental method in this example is the same as in Example 16, except that the additive is 1,8-diazabicyclo[5.4.0]undec-7-ene.

[0098] In a clean, dry, unseparated electrolytic cell, diphenylmethylthioacetamide (0.5 mmol, 128.7 mg, 1.0 equiv.), tetraethylammonium chloride (0.75 mmol, 124.3 mg, 1.5 equiv.), acetonitrile (7.0 mL), 1,8-diazabicyclo[5.4.0]undec-7-ene (115.7 mg, 1.5 equiv.), and water (135.0 μL, 15.0 equiv.) were added sequentially. The electrolytic cell was then used with a carbon sheet as the anode and a platinum sheet as the cathode. A constant current of 5.0 mA was applied at a reaction temperature of 0 °C under a nitrogen atmosphere for 8 hours. After the reaction was completed, no target product was formed.

[0099] Example 19: The experimental method in this example is the same as in Example 16, except that the additive is 1,1,1,3,3,3-hexafluoro-2-propanol.

[0100] In a clean, dry, unseparated electrolytic cell, diphenylmethylthioacetamide (0.5 mmol, 128.7 mg, 1.0 equiv.), tetraethylammonium chloride (0.75 mmol, 124.3 mg, 1.5 equiv.), acetonitrile (7.0 mL), 1,1,1,3,3,3-hexafluoro-2-propanol (126.0 mg, 1.5 equiv.), and water (135.0 μL, 15.0 equiv.) were added sequentially. The electrolytic cell was then used with a carbon sheet as the anode and a platinum sheet as the cathode. A constant current of 5.0 mA was applied at a reaction temperature of 0 °C under a nitrogen atmosphere for 8 hours. After the reaction was complete, the solvent was removed by rotary evaporation, and the product was separated by silica gel column chromatography with an eluent to obtain modafinil, a white solid, in 25% yield.

[0101] Example 20: The experimental method in this example is the same as in Example 16, except that the additive is potassium iodide.

[0102] In a clean, dry, unseparated electrolytic cell, diphenylmethylthioacetamide (0.5 mmol, 128.7 mg, 1.0 equiv.), tetraethylammonium chloride (0.75 mmol, 124.3 mg, 1.5 equiv.), potassium iodide (24.9 mg, 0.3 equiv.), acetonitrile (7.0 mL), and water (135.0 μL, 15.0 equiv.) were added sequentially. The electrolytic cell was then used with a carbon sheet as the anode and a platinum sheet as the cathode. A constant current of 5.0 mA was applied at a reaction temperature of 0 °C under a nitrogen atmosphere for 8 hours. After the reaction was completed, no target product was formed.

[0103] Example 21: The experimental method in this example is the same as in Example 16, except that the additive is ferrocene.

[0104] In a clean, dry, unseparated electrolytic cell, diphenylmethylthioacetamide (0.5 mmol, 128.7 mg, 1.0 equiv.), tetraethylammonium chloride (0.75 mmol, 124.3 mg, 1.5 equiv.), ferrocene (27.9 mg, 0.3 equiv.), acetonitrile (7.0 mL), and water (135.0 μL, 15.0 equiv.) were added sequentially. The electrolytic cell was then used with a carbon sheet as the anode and a platinum sheet as the cathode. A constant current of 5.0 mA was applied at a reaction temperature of 0 °C under a nitrogen atmosphere for 8 hours. After the reaction was complete, the solvent was removed by rotary evaporation, and the product was separated by silica gel column chromatography using an eluent to obtain modafinil, a white solid, in 40% yield.

[0105] Table 4. Effects of additives on batch electrochemical green oxidation process

[0106]

[0107]

[0108] The yield of a is the separation yield.

[0109] Example 22: The experimental method in this example is the same as in Example 16, except that the solvent is N,N-dimethylformamide.

[0110] In a clean, dry, unseparated electrolytic cell, diphenylmethylthioacetamide (0.5 mmol, 128.7 mg, 1.0 equiv.), tetraethylammonium chloride electrolyte (0.75 mmol, 124.3 mg, 1.5 equiv.), N,N-dimethylformamide solvent (7.0 mL), and water (135.0 μL, 15.0 equiv.) were added sequentially. The electrolytic cell was then used with a carbon sheet as the anode and a platinum sheet as the cathode. A constant current of 5.0 mA was applied at a reaction temperature of 0 °C under a nitrogen atmosphere for 8 hours. After the reaction was complete, the solvent was removed by rotary evaporation, and the product was separated by silica gel column chromatography using an eluent to obtain modafinil, a white solid, in 8% yield.

[0111] Example 23: The experimental method in this example is the same as in Example 16, except that the solvent is ethanol.

[0112] In a clean, dry, unseparated electrolytic cell, diphenylmethylthioacetamide (0.5 mmol, 128.7 mg, 1.0 equiv.), tetraethylammonium chloride electrolyte (0.75 mmol, 124.3 mg, 1.5 equiv.), ethanol (7.0 mL), and water (135.0 μL, 15.0 equiv.) were added sequentially. The electrolytic cell was then used with a carbon sheet as the anode and a platinum sheet as the cathode. A constant current of 5.0 mA was applied at a reaction temperature of 0 °C under a nitrogen atmosphere for 8 hours. After the reaction was complete, the solvent was removed by rotary evaporation, and the product was separated by silica gel column chromatography using an eluent to obtain modafinil, a white solid, in 31% yield.

[0113] Example 24: The experimental method in this example is the same as in Example 16, except that the solvent is dimethyl sulfoxide and the reaction is carried out at room temperature.

[0114] In a clean, dry, unseparated electrolytic cell, diphenylmethylthioacetamide (0.5 mmol, 128.7 mg, 1.0 equiv.), tetraethylammonium chloride (0.75 mmol, 124.3 mg, 1.5 equiv.), dimethyl sulfoxide (7.0 mL), and water (135.0 μL, 15.0 equiv.) were added sequentially. The electrolytic cell was then used with a carbon sheet as the anode and a platinum sheet as the cathode, and a constant current of 5.0 mA was applied at room temperature under a nitrogen atmosphere for 8 hours. After the reaction was complete, the solvent was removed by rotary evaporation, and the product was separated by silica gel column chromatography with eluent to obtain modafinil, a white solid, in 7% yield.

[0115] Example 25: The experimental method in this example is the same as in Example 16, except that the solvent is pyridine.

[0116] In a clean, dry, unseparated electrolytic cell, diphenylmethylthioacetamide (0.5 mmol, 128.7 mg, 1.0 equiv.), tetraethylammonium chloride electrolyte (0.75 mmol, 124.3 mg, 1.5 equiv.), pyridine solvent (7.0 mL), and water (135.0 μL, 15.0 equiv.) were added sequentially. The electrolytic cell was then used with a carbon sheet as the anode and a platinum sheet as the cathode. A constant current of 5.0 mA was applied at a reaction temperature of 0 °C under a nitrogen atmosphere for 8 hours. After the reaction was complete, the solvent was removed by rotary evaporation, and the product was separated by silica gel column chromatography using an eluent to obtain modafinil, a white solid, in 55% yield.

[0117] Table 5. Effect of solvent type on batch electrochemical green oxidation process

[0118] Example solvent Yield a (%) 16 Acetonitrile 68 22 N,N-Dimethylformamide 8 23 ethanol 31 24 Dimethyl sulfoxide 7 25 Pyridine 55

[0119] The yield of a is the separation yield.

[0120] Example 26: The experimental method in this example is the same as in Example 16, except that the solvent is 1,2-dichloroethane (2.0 mL) and acetonitrile (5.0 mL).

[0121] In a clean, dry, unseparated electrolytic cell, diphenylmethylthioacetamide (0.5 mmol, 128.7 mg, 1.0 equiv.), tetraethylammonium chloride electrolyte (0.75 mmol, 124.3 mg, 1.5 equiv.), 1,2-dichloroethane solvent (2.0 mL) and acetonitrile (5.0 mL), and water (135.0 μL, 15.0 equiv.) were added sequentially. The electrolytic cell was then used with a carbon sheet as the anode and a platinum sheet as the cathode. A constant current of 5.0 mA was applied at a reaction temperature of 0 °C under a nitrogen atmosphere for 8 hours. After the reaction was complete, the solvent was removed by rotary evaporation, and the product was separated by silica gel column chromatography using an eluent to obtain modafinil, a white solid, in 36% yield.

[0122] Example 27: The experimental method in this example is the same as in Example 16, except that the solvent is tetrahydrofuran (2.0 mL) and acetonitrile (5.0 mL).

[0123] In a clean, dry, unseparated electrolytic cell, diphenylmethylthioacetamide (0.5 mmol, 128.7 mg, 1.0 equiv.), tetraethylammonium chloride electrolyte (0.75 mmol, 124.3 mg, 1.5 equiv.), tetrahydrofuran solvent (2.0 mL), acetonitrile solvent (5.0 mL), and water solvent (135.0 μL, 15.0 equiv.) were added sequentially. The electrolytic cell was then used with a carbon sheet as the anode and a platinum sheet as the cathode. A constant current of 5.0 mA was applied at a reaction temperature of 0 °C under a nitrogen atmosphere for 8 hours. After the reaction was complete, the solvent was removed by rotary evaporation, and the product was separated by silica gel column chromatography using an eluent to obtain modafinil, a white solid, in 50% yield.

[0124] Example 28: The experimental method in this example is the same as in Example 16, except that the solvent is triethylamine (2.0 mL) and acetonitrile (5.0 mL).

[0125] In a clean, dry, unseparated electrolytic cell, diphenylmethylthioacetamide (0.5 mmol, 128.7 mg, 1.0 equiv.), tetraethylammonium chloride electrolyte (0.75 mmol, 124.3 mg, 1.5 equiv.), triethylamine (2.0 mL) and acetonitrile (5.0 mL) solvents, and water (135.0 μL, 15.0 equiv.) were added sequentially. Then, with a carbon sheet as the anode and a platinum sheet as the cathode, a constant current of 5.0 mA was applied to the electrolytic cell at a reaction temperature of 0 °C under a nitrogen atmosphere for 8 hours. After the reaction was completed, no target product was formed.

[0126] Example 29: The experimental method in this example is the same as in Example 16, except that the solvent is pyridine (1.0 mL) and acetonitrile (6.0 mL).

[0127] Electrochemical reaction in a batch: Diphenylmethylthioacetamide (0.5 mmol, 128.7 mg, 1.0 equiv.), tetraethylammonium chloride (0.75 mmol, 124.3 mg, 1.5 equiv.), pyridine (1.0 mL), acetonitrile (6.0 mL), and water (135.0 μL, 15.0 equiv.) were added sequentially to a clean, dry, unseparated electrolytic cell. A carbon sheet was then used as the anode and a platinum sheet as the cathode. A constant current of 5.0 mA was applied at a reaction temperature of 0 °C under a nitrogen atmosphere for 8 hours. After the reaction was complete, the solvent was removed by rotary evaporation, and the product was separated by silica gel column chromatography with an eluent to obtain modafinil, a white solid, in 58% yield.

[0128] Example 30: The experimental method in this example is the same as in Example 16, except that the solvent is pyridine (2.0 mL) and acetonitrile (5.0 mL).

[0129] In a clean, dry, unseparated electrolytic cell, diphenylmethylthioacetamide (0.5 mmol, 128.7 mg, 1.0 equiv.), tetraethylammonium chloride electrolyte (0.75 mmol, 124.3 mg, 1.5 equiv.), pyridine (2.0 mL) and acetonitrile (5.0 mL) solvents, and water (135.0 μL, 15.0 equiv.) were added sequentially. The electrolytic cell was then used with a carbon sheet as the anode and a platinum sheet as the cathode. A constant current of 5.0 mA was applied at a reaction temperature of 0 °C under a nitrogen atmosphere for 8 hours. After the reaction was complete, the solvent was removed by rotary evaporation, and the product was separated by silica gel column chromatography with an eluent to obtain modafinil, a white solid, in 80% yield.

[0130] Example 31: The experimental method in this example is the same as in Example 16, except that the solvent is pyridine (3.0 mL) and acetonitrile (4.0 mL).

[0131] In a clean, dry, unseparated electrolytic cell, diphenylmethylthioacetamide (0.5 mmol, 128.7 mg, 1.0 equiv.), tetraethylammonium chloride electrolyte (0.75 mmol, 124.3 mg, 1.5 equiv.), pyridine (3.0 mL) and acetonitrile (4.0 mL) solvents, and water (135.0 μL, 15.0 equiv.) were added sequentially. The electrolytic cell was then used with a carbon sheet as the anode and a platinum sheet as the cathode. A constant current of 5.0 mA was applied at a reaction temperature of 0 °C under a nitrogen atmosphere for 8 hours. After the reaction was complete, the solvent was removed by rotary evaporation, and the product was separated by silica gel column chromatography using an eluent to obtain modafinil, a white solid, in 78% yield.

[0132] Example 32: The experimental method in this example is the same as in Example 16, except that the solvent is pyridine (4.0 mL) and acetonitrile (3.0 mL).

[0133] In a clean, dry, unseparated electrolytic cell, diphenylmethylthioacetamide (0.5 mmol, 128.7 mg, 1.0 equiv.), tetraethylammonium chloride electrolyte (0.75 mmol, 124.3 mg, 1.5 equiv.), pyridine (4.0 mL) and acetonitrile (3.0 mL) solvents, and water (135.0 μL, 15.0 equiv.) were added sequentially. The electrolytic cell was then used with a carbon sheet as the anode and a platinum sheet as the cathode. A constant current of 5.0 mA was applied at a reaction temperature of 0 °C under a nitrogen atmosphere for 8 hours. After the reaction was complete, the solvent was removed by rotary evaporation, and the product was separated by silica gel column chromatography using an eluent to obtain modafinil, a white solid, in 54% yield.

[0134] Table 6. Effect of mixed solvent combinations on batch electrochemical green oxidation process

[0135] Example Mixed solvents Yield a (%) 16 Acetonitrile 68 26 1,2-Dichloroethane (2.0 mL) + Acetonitrile (5.0 mL) 36 27 Tetrahydrofuran (2.0 mL) + Acetonitrile (5.0 mL) 50 28 Triethylamine (2.0 mL) + Acetonitrile (5.0 mL) 0 29 Pyridine (1.0 mL) + Acetonitrile (6.0 mL) 58 30 Pyridine (2.0 mL) + Acetonitrile (5.0 mL) 80 31 Pyridine (3.0 mL) + Acetonitrile (4.0 mL) 78 32 Pyridine (4.0 mL) + Acetonitrile (3.0 mL) 54

[0136] The yield of a is the separation yield.

[0137] Example 33: The experimental method in this example is the same as in Example 30, except that the amount of water added is 225.0 μL, 25.0 equiv.

[0138] In a clean, dry, unseparated electrolytic cell, diphenylmethylthioacetamide (0.5 mmol, 128.7 mg, 1.0 equiv.), tetraethylammonium chloride electrolyte (0.75 mmol, 124.3 mg, 1.5 equiv.), pyridine (2.0 mL) and acetonitrile (5.0 mL) solvents, and water (225.0 μL, 25.0 equiv.) were added sequentially. The electrolytic cell was then used with a carbon sheet as the anode and a platinum sheet as the cathode. A constant current of 5.0 mA was applied at a reaction temperature of 0 °C under a nitrogen atmosphere for 8 hours. After the reaction was complete, the solvent was removed by rotary evaporation, and the product was separated by silica gel column chromatography using an eluent to obtain modafinil, a white solid, in 83% yield.

[0139] Example 34: The experimental method in this example is the same as in Example 30, except that the amount of water added is 315 μL, 35.0 equiv.

[0140] In a clean, dry, unseparated electrolytic cell, diphenylmethylthioacetamide (0.5 mmol, 128.7 mg, 1.0 equiv.), tetraethylammonium chloride electrolyte (0.75 mmol, 124.3 mg, 1.5 equiv.), pyridine (2.0 mL) and acetonitrile (5.0 mL) solvents, and water (315 μL, 35.0 equiv.) were added sequentially. The electrolytic cell was then used with a carbon sheet as the anode and a platinum sheet as the cathode. A constant current of 5.0 mA was applied at a reaction temperature of 0 °C under a nitrogen atmosphere for 8 hours. After the reaction was complete, the solvent was removed by rotary evaporation, and the product was separated by silica gel column chromatography using an eluent to obtain modafinil, a white solid, in 83% yield.

[0141] Example 35: The experimental method in this example is the same as in Example 30, except that the amount of water added is 450 μL, 50.0 equiv.

[0142] In a clean, dry, unseparated electrolytic cell, diphenylmethylthioacetamide (0.5 mmol, 128.7 mg, 1.0 equiv.), tetraethylammonium chloride electrolyte (0.75 mmol, 124.3 mg, 1.5 equiv.), pyridine (2.0 mL) and acetonitrile (5.0 mL) solvents, and water (450 μL, 50.0 equiv.) were added sequentially. The electrolytic cell was then used with a carbon sheet as the anode and a platinum sheet as the cathode. A constant current of 5.0 mA was applied at a reaction temperature of 0 °C under a nitrogen atmosphere for 8 hours. After the reaction was complete, the solvent was removed by rotary evaporation, and the product was separated by silica gel column chromatography using an eluent to obtain modafinil, a white solid, in 81% yield.

[0143] Table 7. Effect of water addition on the batch electrochemical green oxidation process

[0144] Example <![CDATA[H2O (equivalent)]]> Yield a (%) 30 15.0 80 33 25.0 83 34 35.0 83 35 50.0 81

[0145] The yield of a is the separation yield.

[0146] Example 36: Optimization of the process for preparing modafinil via continuous flow electrochemical microchannel oxidation reaction

[0147] Diphenylmethylthioacetamide (5.0 mmol, 1286.8 mg, 1.0 equiv.) and the electrolyte tetraethylammonium chloride (10.0 mmol, 1657.0 mg, 2.0 equiv.) were dissolved in a mixture of acetonitrile (45.0 mL) and water (5.0 mL, 278 mmol, 55.6 equiv.), and the mixture was shaken until completely dissolved. A plastic syringe was used to draw up the reaction solution. The syringe was fixed to an automatic syringe pump, and the flow rate was adjusted to 0.3 mL / min. The syringe outlet was connected to the inlet of a self-made electrochemical microchannel continuous flow reactor with a capacity of 5.0 mL. This self-made electrochemical microchannel continuous flow reactor used a graphite plate as the anode and a platinum plate as the cathode. A constant current of 40.0 mA was introduced into the electrochemical microchannel continuous flow reactor, and the electrochemical reaction was carried out at room temperature. The reaction retention time in the electrochemical microchannel continuous flow reactor was 16.7 min. The reaction solution was collected from the reactor outlet. After the reaction was stopped, the reaction yield was tested by HPLC with biphenyl as an internal standard. The yield was 3.0%.

[0148] Example 37: The experimental method in this example is the same as in Example 36, except that the current is 60.0mA.

[0149] Diphenylmethylthioacetamide (5.0 mmol, 1286.8 mg, 1.0 equiv.) and the electrolyte tetraethylammonium chloride (10.0 mmol, 1657.0 mg, 2.0 equiv.) were dissolved in a mixture of acetonitrile (45.0 mL) and water (5.0 mL, 278 mmol, 55.6 equiv.), and the mixture was shaken until completely dissolved. A plastic syringe was used to draw up the reaction solution. The syringe was fixed to an automatic syringe pump, and the flow rate was adjusted to 0.3 mL / min. The syringe outlet was connected to the inlet of a self-made electrochemical microchannel continuous flow reactor with a capacity of 5.0 mL. This self-made electrochemical microchannel continuous flow reactor used a graphite plate as the anode and a platinum plate as the cathode. A constant current of 60.0 mA was introduced into the electrochemical microchannel continuous flow reactor, and the electrochemical reaction was carried out at room temperature. The reaction retention time in the electrochemical microchannel continuous flow reactor was 16.7 min. The reaction solution was collected from the reactor outlet. After the reaction was stopped, the reaction yield was tested by HPLC with biphenyl as an internal standard. The yield was 4.0%.

[0150] Example 38: The experimental method in this example is the same as in Example 36, except that the current is 80.0mA.

[0151] Diphenylmethylthioacetamide (5.0 mmol, 1286.8 mg, 1.0 equiv.) and the electrolyte tetraethylammonium chloride (10.0 mmol, 1657.0 mg, 2.0 equiv.) were dissolved in a mixture of acetonitrile (45.0 mL) and water (5.0 mL, 278 mmol, 55.6 equiv.), and the mixture was shaken until completely dissolved. A plastic syringe was used to draw up the reaction solution. The syringe was fixed to an automatic syringe pump, and the flow rate was adjusted to 0.3 mL / min. The syringe outlet was connected to the inlet of a self-made electrochemical microchannel continuous flow reactor with a capacity of 5.0 mL. This self-made electrochemical microchannel continuous flow reactor used a graphite plate as the anode and a platinum plate as the cathode. A constant current of 80.0 mA was introduced into the electrochemical microchannel continuous flow reactor, and the electrochemical reaction was carried out at room temperature. The reaction retention time in the electrochemical microchannel continuous flow reactor was 16.7 min. The reaction solution was collected from the reactor outlet. After the reaction was stopped, the reaction yield was tested by HPLC with biphenyl as an internal standard. The yield was 7.0%.

[0152] Example 39: The experimental method in this example is the same as in Example 36, except that the current is 120.0mA.

[0153] Diphenylmethylthioacetamide (5.0 mmol, 1286.8 mg, 1.0 equiv.) and the electrolyte tetraethylammonium chloride (10.0 mmol, 1657.0 mg, 2.0 equiv.) were dissolved in a mixture of acetonitrile (45.0 mL) and water (5.0 mL, 278 mmol, 55.6 equiv.), and the mixture was shaken until completely dissolved. A plastic syringe was used to draw up the reaction solution. The syringe was fixed to an automatic syringe pump, and the flow rate was adjusted to 0.3 mL / min. The syringe outlet was connected to the inlet of a self-made electrochemical microchannel continuous flow reactor with a capacity of 5.0 mL. This self-made electrochemical microchannel continuous flow reactor used a graphite plate as the anode and a platinum plate as the cathode. A constant current of 120.0 mA was introduced into the electrochemical microchannel continuous flow reactor, and the electrochemical reaction was carried out at room temperature. The reaction retention time in the electrochemical microchannel continuous flow reactor was 16.7 min. The reaction solution was collected from the reactor outlet. After the reaction was stopped, the reaction yield was tested by HPLC with biphenyl as an internal standard. The yield was 9.0%.

[0154] Example 40: The experimental method in this example is the same as in Example 36, except that the current is 160.0mA.

[0155] Diphenylmethylthioacetamide (5.0 mmol, 1286.8 mg, 1.0 equiv.) and the electrolyte tetraethylammonium chloride (10.0 mmol, 1657.0 mg, 2.0 equiv.) were dissolved in a mixture of acetonitrile (45.0 mL) and water (5.0 mL, 278 mmol, 55.6 equiv.), and the mixture was shaken until completely dissolved. A plastic syringe was used to draw up the reaction solution. The syringe was fixed to an automatic syringe pump, and the flow rate was adjusted to 0.3 mL / min. The syringe outlet was connected to the inlet of a self-made electrochemical microchannel continuous flow reactor with a capacity of 5.0 mL. This self-made electrochemical microchannel continuous flow reactor used a graphite plate as the anode and a platinum plate as the cathode. A constant current of 160.0 mA was introduced into the electrochemical microchannel continuous flow reactor, and the electrochemical reaction was carried out at room temperature. The reaction retention time in the electrochemical microchannel continuous flow reactor was 16.7 min. The reaction solution was collected from the reactor outlet. After the reaction was stopped, the reaction yield was tested by HPLC with biphenyl as an internal standard. The yield was 9.0%.

[0156] Example 41: The experimental method in this example is the same as in Example 36, except that the current is 200.0mA.

[0157] Diphenylmethylthioacetamide (5.0 mmol, 1286.8 mg, 1.0 equiv.) and the electrolyte tetraethylammonium chloride (10.0 mmol, 1657.0 mg, 2.0 equiv.) were dissolved in a mixture of acetonitrile (45.0 mL) and water (5.0 mL, 278 mmol, 55.6 equiv.), and the mixture was shaken until completely dissolved. A plastic syringe was used to draw up the reaction solution. The syringe was fixed to an automatic syringe pump, and the flow rate was adjusted to 0.3 mL / min. The syringe outlet was connected to the inlet of a self-made electrochemical microchannel continuous flow reactor with a capacity of 5.0 mL. This self-made electrochemical microchannel continuous flow reactor used a graphite plate as the anode and a platinum plate as the cathode. A constant current of 200 mA was introduced into the electrochemical microchannel continuous flow reactor, and the electrochemical reaction was carried out at room temperature. The reaction retention time in the electrochemical microchannel continuous flow reactor was 16.7 min. The reaction solution was collected from the reactor outlet. After the reaction was stopped, the reaction yield was tested by HPLC with biphenyl as an internal standard. The yield was 8.0%.

[0158] Table 8. Effect of current magnitude on microchannel continuous flow electrochemical green oxidation process

[0159] Example Current (mA) Yield a (%) 36 40 3.0 37 60 4.0 38 80 7.0 39 120 9.0 40 160 9.0 41 200 8.0

[0160] The yield of a was determined by HPLC, with biphenyl as the internal standard.

[0161] Example 42: The experimental method in this example is the same as in Example 39, except that the pump flow rate is 0.1 mL / min.

[0162] Diphenylmethylthioacetamide (5.0 mmol, 1286.8 mg, 1.0 equiv.) and the electrolyte tetraethylammonium chloride (10.0 mmol, 1657.0 mg, 2.0 equiv.) were dissolved in a mixture of acetonitrile (45.0 mL) and water (5.0 mL, 278 mmol, 55.6 equiv.), and the mixture was shaken until completely dissolved. A plastic syringe was used to draw up the reaction solution. The syringe was fixed to an automatic syringe pump, and the flow rate was adjusted to 0.1 mL / min. The syringe outlet was connected to the inlet of a self-made electrochemical microchannel continuous flow reactor with a capacity of 5.0 mL. This self-made electrochemical microchannel continuous flow reactor used a graphite plate as the anode and a platinum plate as the cathode. A constant current of 120.0 mA was introduced into the electrochemical microchannel continuous flow reactor, and the electrochemical reaction was carried out at room temperature. The reaction retention time in the electrochemical microchannel continuous flow reactor was 50.0 min. The reaction solution was collected from the reactor outlet. After the reaction was stopped, the reaction yield was tested by HPLC with biphenyl as an internal standard. The yield was 7.0%.

[0163] Example 43: The experimental method in this example is the same as in Example 39, except that the pump flow rate is 0.2 mL / min.

[0164] Diphenylmethylthioacetamide (5.0 mmol, 1286.8 mg, 1.0 equiv.) and the electrolyte tetraethylammonium chloride (10.0 mmol, 1657.0 mg, 2.0 equiv.) were dissolved in a mixture of acetonitrile (45.0 mL) and water (5.0 mL, 278 mmol, 55.6 equiv.), and the mixture was shaken until completely dissolved. A plastic syringe was used to draw up the reaction solution. The syringe was fixed to an automatic syringe pump, and the flow rate was adjusted to 0.2 mL / min. The syringe outlet was connected to the inlet of a self-made electrochemical microchannel continuous flow reactor with a capacity of 5.0 mL. This self-made electrochemical microchannel continuous flow reactor used a graphite plate as the anode and a platinum plate as the cathode. A constant current of 120.0 mA was introduced into the electrochemical microchannel continuous flow reactor, and the electrochemical reaction was carried out at room temperature. The reaction retention time in the electrochemical microchannel continuous flow reactor was 25.0 min. The reaction solution was collected from the reactor outlet. After the reaction was stopped, the reaction yield was tested by HPLC with biphenyl as an internal standard. The yield was 12.0%.

[0165] Example 44: The experimental method in this example is the same as in Example 39, except that the pump flow rate is 0.4 mL / min.

[0166] Diphenylmethylthioacetamide (5.0 mmol, 1286.8 mg, 1.0 equiv.) and the electrolyte tetraethylammonium chloride (10.0 mmol, 1657.0 mg, 2.0 equiv.) were dissolved in a mixture of acetonitrile (45.0 mL) and water (5.0 mL, 278 mmol, 55.6 equiv.), and the mixture was shaken until completely dissolved. A plastic syringe was used to draw up the reaction solution. The syringe was fixed to an automatic syringe pump, and the flow rate was adjusted to 0.4 mL / min. The syringe outlet was connected to the inlet of a self-made electrochemical microchannel continuous flow reactor with a capacity of 5.0 mL. This self-made electrochemical microchannel continuous flow reactor used a graphite plate as the anode and a platinum plate as the cathode. A constant current of 120.0 mA was introduced into the electrochemical microchannel continuous flow reactor, and the electrochemical reaction was carried out at room temperature. The reaction retention time in the electrochemical microchannel continuous flow reactor was 12.5 min. The reaction solution was collected from the reactor outlet. After the reaction was stopped, the reaction yield was tested by HPLC with biphenyl as an internal standard. The yield was 7.0%.

[0167] Example 45: The experimental method in this example is the same as in Example 39, except that the pump flow rate is 0.5 mL / min.

[0168] Diphenylmethylthioacetamide (5.0 mmol, 1286.8 mg, 1.0 equiv.) and the electrolyte tetraethylammonium chloride (10.0 mmol, 1657.0 mg, 2.0 equiv.) were dissolved in a mixture of acetonitrile (45.0 mL) and water (5.0 mL, 278 mmol, 55.6 equiv.), and the mixture was shaken until completely dissolved. A plastic syringe was used to draw up the reaction solution. The syringe was fixed to an automatic syringe pump, and the flow rate was adjusted to 0.5 mL / min. The syringe outlet was connected to the inlet of a self-made electrochemical microchannel continuous flow reactor with a capacity of 5.0 mL. This self-made electrochemical microchannel continuous flow reactor used a graphite plate as the anode and a platinum plate as the cathode. A constant current of 120.0 mA was introduced into the electrochemical microchannel continuous flow reactor, and the electrochemical reaction was carried out at room temperature. The reaction retention time in the electrochemical microchannel continuous flow reactor was 10.0 min. The reaction solution was collected from the reactor outlet. After the reaction was stopped, the reaction yield was tested by HPLC with biphenyl as an internal standard. The yield was 6.0%.

[0169] Table 9. Effect of flow rate on microchannel continuous flow electrochemical green oxidation process

[0170] Example Flow rate (mL / min) Yield a (%) 39 0.3 9.0 42 0.1 7.0 43 0.2 12.0 44 0.4 7.0 45 0.5 6.0

[0171] The yield of a was determined by HPLC, with biphenyl as the internal standard.

[0172] Example 46: The experimental method in this example is the same as in Example 43, except that the ratio of acetonitrile to water is 8:2.

[0173] Diphenylmethylthioacetamide (5.0 mmol, 1286.8 mg, 1.0 equiv.) and the electrolyte tetraethylammonium chloride (10.0 mmol, 1657.0 mg, 2.0 equiv.) were dissolved in a mixture of acetonitrile (40.0 mL) and water (10.0 mL, 111.2 equiv.), and the mixture was shaken until completely dissolved. A plastic syringe was used to draw up the reaction solution. The syringe was fixed to an automatic syringe pump, and the flow rate was adjusted to 0.2 mL / min. The syringe outlet was connected to the inlet of a self-made electrochemical microchannel continuous flow reactor with a capacity of 5.0 mL. This self-made electrochemical microchannel continuous flow reactor used a graphite plate as the anode and a platinum plate as the cathode. A constant current of 120.0 mA was introduced into the electrochemical microchannel continuous flow reactor, and the electrochemical reaction was carried out at room temperature. The reaction retention time in the electrochemical microchannel continuous flow reactor was 25.0 min. The reaction solution was collected from the reactor outlet. After the reaction was stopped, the reaction yield was tested by HPLC with biphenyl as an internal standard. The yield was 11%.

[0174] Example 47: The experimental method in this example is the same as in Example 43, except that the ratio of acetonitrile to water is 7:3.

[0175] Diphenylmethylthioacetamide (5 mmol, 1286.8 mg, 1.0 equiv.) and the electrolyte tetraethylammonium chloride (10.0 mmol, 1657.0 mg, 2.0 equiv.) were dissolved in a mixture of acetonitrile (35.0 mL) and water (15.0 mL, 166.8 equiv.), and the mixture was shaken until completely dissolved. A plastic syringe was used to draw up the reaction solution. The syringe was fixed to an automatic syringe pump, and the flow rate was adjusted to 0.2 mL / min. The syringe outlet was connected to the inlet of a self-made electrochemical microchannel continuous flow reactor with a capacity of 5.0 mL. This self-made electrochemical microchannel continuous flow reactor used a graphite plate as the anode and a platinum plate as the cathode. A constant current of 120.0 mA was introduced into the electrochemical microchannel continuous flow reactor, and the electrochemical reaction was carried out at room temperature. The reaction retention time in the electrochemical microchannel continuous flow reactor was 25.0 min. The reaction solution was collected from the reactor outlet. After the reaction was stopped, the reaction yield was tested by HPLC with biphenyl as an internal standard. The yield was 9.0%.

[0176] Example 48: The experimental method in this example is the same as in Example 43, except that the ratio of acetonitrile to water is 6 to 4.

[0177] Diphenylmethylthioacetamide (5.0 mmol, 1286.8 mg, 1.0 equiv.) and the electrolyte tetraethylammonium chloride (10.0 mmol, 1657.0 mg, 2.0 equiv.) were dissolved in a mixture of acetonitrile (30.0 mL) and water (20.0 mL, 222.4 equiv.), and the mixture was shaken until completely dissolved. A plastic syringe was used to draw up the reaction solution. The syringe was fixed to an automatic syringe pump, and the flow rate was adjusted to 0.2 mL / min. The syringe outlet was connected to the inlet of a self-made electrochemical microchannel continuous flow reactor with a capacity of 5.0 mL. This self-made electrochemical microchannel continuous flow reactor used a graphite plate as the anode and a platinum plate as the cathode. A constant current of 120.0 mA was introduced into the electrochemical microchannel continuous flow reactor, and the electrochemical reaction was carried out at room temperature. The reaction retention time in the electrochemical microchannel continuous flow reactor was 25.0 min. The reaction solution was collected from the reactor outlet. After the reaction was stopped, the reaction yield was tested by HPLC with biphenyl as an internal standard. The yield was 9.0%.

[0178] Example 49: The experimental method in this example is the same as in Example 43, except that the ratio of acetonitrile to water is 5:5.

[0179] Diphenylmethylthioacetamide (5.0 mmol, 1286.8 mg, 1.0 equiv.) and the electrolyte tetraethylammonium chloride (10.0 mmol, 1657.0 mg, 2.0 equiv.) were dissolved in a mixture of acetonitrile (25.0 mL) and water (25.0 mL, 278.0 equiv.), and the mixture was shaken until completely dissolved. A plastic syringe was used to draw up the reaction solution. The syringe was fixed to an automatic syringe pump, and the flow rate was adjusted to 0.2 mL / min. The syringe outlet was connected to the inlet of a self-made electrochemical microchannel continuous flow reactor with a capacity of 5.0 mL. This self-made electrochemical microchannel continuous flow reactor used a graphite plate as the anode and a platinum plate as the cathode. A constant current of 120.0 mA was introduced into the electrochemical microchannel continuous flow reactor, and the electrochemical reaction was carried out at room temperature. The reaction retention time in the electrochemical microchannel continuous flow reactor was 25.0 min. The reaction solution was collected from the reactor outlet. After the reaction was stopped, the reaction yield was tested by HPLC with biphenyl as an internal standard. The yield was 9.0%.

[0180] Table 10. Effect of mixed solvent ratio on microchannel continuous flow electrochemical green oxidation process

[0181]

[0182]

[0183] The yield of a was determined by HPLC, with biphenyl as the internal standard.

[0184] Example 50: The method in this example is the same as in Example 43, except that the graphite plate is the cathode and the platinum plate is the anode.

[0185] Diphenylmethylthioacetamide (5.0 mmol, 1286.8 mg, 1.0 equiv.) and the electrolyte tetraethylammonium chloride (10.0 mmol, 1657.0 mg, 2.0 equiv.) were dissolved in a mixture of acetonitrile (45.0 mL) and water (5.0 mL, 278 mmol, 55.6 equiv.), and the mixture was shaken until completely dissolved. A plastic syringe was used to draw up the reaction solution. The syringe was fixed to an automatic syringe pump, and the flow rate was adjusted to 0.2 mL / min. The syringe outlet was connected to the inlet of a self-made electrochemical microchannel continuous flow reactor with a capacity of 5.0 mL. This self-made electrochemical microchannel continuous flow reactor used a graphite plate as the cathode and a platinum plate as the anode. A constant current of 120.0 mA was introduced into the electrochemical microchannel continuous flow reactor, and the electrochemical reaction was carried out at room temperature. The reaction retention time in the electrochemical microchannel continuous flow reactor was 25.0 min. The reaction solution was collected from the reactor outlet. After the reaction was stopped, the reaction yield was tested by HPLC with biphenyl as an internal standard. The yield was 26%.

[0186] Example 51: The method in this example is the same as in Example 43, except that the graphite plate is the cathode and the graphite plate is the anode.

[0187] Diphenylmethylthioacetamide (5.0 mmol, 1286.8 mg, 1.0 equiv.) and the electrolyte tetraethylammonium chloride (10.0 mmol, 1657.0 mg, 2.0 equiv.) were dissolved in a mixture of acetonitrile (45.0 mL) and water (5.0 mL, 278 mmol, 55.6 equiv.), and the mixture was shaken until completely dissolved. A plastic syringe was used to draw up the reaction solution. The syringe was fixed to an automatic syringe pump, and the flow rate was adjusted to 0.2 mL / min. The syringe outlet was connected to the inlet of a self-made electrochemical microchannel continuous flow reactor with a capacity of 5.0 mL. This self-made electrochemical microchannel continuous flow reactor used a graphite plate as the cathode and a graphite plate as the anode. A constant current of 120.0 mA was introduced into the electrochemical microchannel continuous flow reactor, and the electrochemical reaction was carried out at room temperature. The reaction retention time in the electrochemical microchannel continuous flow reactor was 25.0 min. The reaction solution was collected from the reactor outlet. After the reaction was stopped, the reaction yield was tested by HPLC with biphenyl as an internal standard. The yield was 14%.

[0188] Example 52: The experimental method in this example is the same as in Example 43, except that the platinum plate is used as the cathode and the platinum plate is used as the anode.

[0189] Diphenylmethylthioacetamide (5.0 mmol, 1286.8 mg, 1.0 equiv.) and the electrolyte tetraethylammonium chloride (10.0 mmol, 1657.0 mg, 2.0 equiv.) were dissolved in a mixture of acetonitrile (45.0 mL) and water (5.0 mL, 278 mmol, 55.6 equiv.), and the mixture was shaken until completely dissolved. A plastic syringe was used to draw up the reaction solution. The syringe was fixed to an automatic syringe pump, and the flow rate was adjusted to 0.2 mL / min. The syringe outlet was connected to the inlet of a self-made electrochemical microchannel continuous flow reactor with a capacity of 5.0 mL. This self-made electrochemical microchannel continuous flow reactor used a platinum plate as the cathode and a platinum plate as the anode. A constant current of 120.0 mA was introduced into the electrochemical microchannel continuous flow reactor, and the electrochemical reaction was carried out at room temperature. The reaction retention time in the electrochemical microchannel continuous flow reactor was 25.0 min. The reaction solution was collected from the reactor outlet. After the reaction was stopped, the reaction yield was tested by HPLC with biphenyl as an internal standard. The yield was 26%.

[0190] Table 11. Influence of electrode materials on microchannel continuous flow electrochemical green oxidation process

[0191] Example Electrode materials (anode / cathode) Yield a (%) 43 C(+) / Pt(-) 12.0 50 Pt(+) / C(-) 26.0 51 C(+) / C(-) 14.0 52 Pt(+) / Pt(-) 26.0

[0192] The yield of a was determined by HPLC, with biphenyl as the internal standard.

[0193] Example 53: The experimental method in this example is the same as in Example 50, except that the ratio of pyridine, acetonitrile and water added is 1:8:1.

[0194] Diphenylmethylthioacetamide (5.0 mmol, 1286.8 mg, 1.0 equiv.) and the electrolyte tetraethylammonium chloride (10.0 mmol, 1657.0 mg, 2.0 equiv.) were dissolved in a mixed solvent of acetonitrile (40.0 mL), pyridine (5.0 mL), and water (5.0 mL, 278 mmol, 55.6 equiv.), and the mixture was shaken until completely dissolved. A plastic syringe was used to draw up the reaction solution. The syringe was fixed to an automatic syringe pump, and the flow rate was adjusted to 0.2 mL / min. The syringe outlet was connected to the inlet of a self-made electrochemical microchannel continuous flow reactor with a capacity of 5.0 mL. This self-made electrochemical microchannel continuous flow reactor used a graphite plate as the cathode and a platinum plate as the anode. A constant current of 120.0 mA was introduced into the electrochemical microchannel continuous flow reactor, and the electrochemical reaction was carried out at room temperature. The reaction retention time in the electrochemical microchannel continuous flow reactor was 25.0 min. The reaction solution was collected from the reactor outlet. After the reaction was stopped, the reaction yield was tested by HPLC with biphenyl as an internal standard. The yield was 49%, and the separation yield was 41%.

[0195] Example 54: The experimental method in this example is the same as in Example 50, except that the ratio of pyridine, acetonitrile and water is 2:7:1.

[0196] Diphenylmethylthioacetamide (5.0 mmol, 1286.8 mg, 1.0 equiv.) and the electrolyte tetraethylammonium chloride (10.0 mmol, 1657.0 mg, 2.0 equiv.) were dissolved in a mixture of acetonitrile (35.0 mL), pyridine (10.0 mL), and water (5.0 mL, 278 mmol, 55.6 equiv.), and the mixture was shaken until completely dissolved. A plastic syringe was used to draw up the reaction solution. The syringe was fixed to an automatic syringe pump, and the flow rate was adjusted to 0.2 mL / min. The syringe outlet was connected to the inlet of a self-made electrochemical microchannel continuous flow reactor with a capacity of 5.0 mL. This self-made electrochemical microchannel continuous flow reactor used a graphite plate as the cathode and a platinum plate as the anode. A constant current of 120.0 mA was introduced into the electrochemical microchannel continuous flow reactor, and the electrochemical reaction was carried out at room temperature. The reaction retention time in the electrochemical microchannel continuous flow reactor was 25.0 min. The reaction solution was collected from the reactor outlet. After the reaction was stopped, the reaction yield was tested by HPLC with biphenyl as an internal standard. The yield was 52%.

[0197] Example 55: The experimental method in this example is the same as in Example 50, except that the ratio of pyridine, acetonitrile and water added is 3:6:1.

[0198] Diphenylmethylthioacetamide (5.0 mmol, 1286.8 mg, 1.0 equiv.) and the electrolyte tetraethylammonium chloride (10.0 mmol, 1657.0 mg, 2.0 equiv.) were dissolved in a mixture of acetonitrile (30.0 mL), pyridine (15.0 mL), and water (5.0 mL, 278 mmol, 55.6 equiv.), and the mixture was shaken until completely dissolved. A plastic syringe was used to draw up the reaction solution. The syringe was fixed to an automatic syringe pump, and the flow rate was adjusted to 0.2 mL / min. The syringe outlet was connected to the inlet of a self-made electrochemical microchannel continuous flow reactor with a capacity of 5.0 mL. This self-made electrochemical microchannel continuous flow reactor used a graphite plate as the cathode and a platinum plate as the anode. A constant current of 120.0 mA was introduced into the electrochemical microchannel continuous flow reactor, and the electrochemical reaction was carried out at room temperature. The reaction retention time in the electrochemical microchannel continuous flow reactor was 25.0 min. The reaction solution was collected from the reactor outlet. After the reaction was stopped, the reaction yield was tested by HPLC with biphenyl as an internal standard. The yield was 52%.

[0199] Example 56: The experimental method in this example is the same as in Example 50, except that the ratio of pyridine, acetonitrile and water added is 4:5:1.

[0200] Diphenylmethylthioacetamide (5.0 mmol, 1286.8 mg, 1.0 equiv.) and the electrolyte tetraethylammonium chloride (10.0 mmol, 1657.0 mg, 2.0 equiv.) were dissolved in a mixture of acetonitrile (25.0 mL), pyridine (20.0 mL), and water (5.0 mL, 278 mmol, 55.6 equiv.), and the mixture was shaken until completely dissolved. A plastic syringe was used to draw up the reaction solution. The syringe was fixed to an automatic syringe pump, and the flow rate was adjusted to 0.2 mL / min. The syringe outlet was connected to the inlet of a self-made electrochemical microchannel continuous flow reactor with a capacity of 5.0 mL. This self-made electrochemical microchannel continuous flow reactor used a graphite plate as the cathode and a platinum plate as the anode. A constant current of 120.0 mA was introduced into the electrochemical microchannel continuous flow reactor, and the electrochemical reaction was carried out at room temperature. The reaction retention time in the electrochemical microchannel continuous flow reactor was 25.0 min. The reaction solution was collected from the reactor outlet. After the reaction was stopped, the reaction yield was tested by HPLC with biphenyl as an internal standard. The yield was 37%.

[0201] Table 12. Effect of Pyridine Addition on Microchannel Continuous Flow Electrochemical Green Oxidation Process

[0202] Example Volume ratio of pyridine, acetonitrile and water Yield a (%) 50 0:9:1 26 53 1:8:1 <![CDATA[49(41 b )]]> 54 2:7:1 52 55 3:6:1 52 56 4:5:1 37

[0203] a) Yield was determined by HPLC, with biphenyl as the internal standard; b) Yield was separated by column chromatography.

[0204] Comparative Example 1: Thermochemical Oxidation Method 1

[0205] The prior art, as reported in the paper (Molecules 2012, 17, 10446-10458), describes the oxidation reaction of diphenylmethylthioacetamide to modafinil. Compared with the method of this invention, the prior art requires the use of an equivalent amount of 30% hydrogen peroxide as an oxidant, acetic acid as a solvent and catalyst, and a reaction at 40°C for 16 hours to obtain modafinil in a yield of 67%.

[0206] Comparative Example 2: Thermochemical Oxidation Method 2

[0207] The existing technology reported in the paper (ACS Catal. 2020, 10, 245-252.) for the oxidation reaction of diphenylmethylthioacetamide to modafinil, compared with the method of the present invention, requires an allourea catalyst (5 mol%), an equivalent amount of hydrogen peroxide as an oxidant, and an excess of anhydrous magnesium sulfate as an additive, forming a catalytic system.

[0208] Comparative Example 3: Photochemical Oxidation Method 1

[0209] Compared with the method of this invention, the existing technology reported in the paper (Inorg.Chem.2021,60,7008-7022.) for the oxidation reaction of diphenylmethylthioacetamide to modafinil requires a catalytic system with the noble metal ruthenium (Ru) catalyst and oxygen as the oxygen source.

[0210] Comparative Example 4: Photochemical Oxidation Method 2

[0211] The existing technology, as reported in the paper (Synlett 2025, 36, 1723-1728), for the oxidation reaction of diphenylmethylthioacetamide to modafinil, requires eosin dye (4 mol%) as a photocatalyst and air as the source of oxygen atoms, compared with the method of this invention.

[0212] Table 13. Comparison of various oxidation processes for preparing modafinil

[0213]

[0214]

[0215] This invention provides a method for preparing modafinil using an electrochemical reaction. 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 for preparing modafinil using an electrochemical reaction, characterized in that, Diphenylmethylthioacetamide is mixed with water, electrolyte, and solvent. The resulting mixture undergoes an electrochemical reaction under electrode electrolysis to obtain modafinil. The structural formula of the diphenylmethylthioacetamide is shown in Formula I, and the structural formula of the modafinil is shown in Formula II.

2. The method according to claim 1, characterized in that, The electrolyte is tetraethylammonium chloride; the molar ratio of diphenylmethylthioacetamide to the electrolyte is 1.0:(1.5-2.0).

3. The method according to claim 1, characterized in that, The electrochemical reaction is carried out using a conventional electrochemical autoclave or an electrochemical microchannel continuous flow reactor.

4. The method according to claim 3, characterized in that, When the electrochemical reaction is carried out using a conventional electrochemical autoclave, the molar ratio of diphenylmethylthioacetamide to water is 1.0:(10.0~50.0).

5. The method according to claim 3, characterized in that, When the electrochemical reaction is carried out using a conventional electrochemical autoclave apparatus, the solvent is a mixed solvent of acetonitrile, ethanol, pyridine, 1,2-dichloroethane and acetonitrile in a volume ratio of (1.0–3.0):(1.0–9.0), a mixed solvent of tetrahydrofuran and acetonitrile in a volume ratio of (1.0–5.0):(1.0–9.0), or a mixed solvent of pyridine and acetonitrile in a volume ratio of (1.0–4.0):(3.0–6.0); and / or, the concentration of diphenylmethylthioacetamide in the mixture is 0.04 mmol / mL to 0.10 mmol / mL.

6. The method according to claim 3, characterized in that, When the electrochemical reaction is carried out using a conventional electrochemical reactor apparatus: the anode of the electrode is a carbon sheet, and the cathode of the electrode is a platinum sheet; and / or, the constant current in the electrochemical reaction is 2.0 mA to 8.0 mA; and / or, the reaction temperature of the electrochemical reaction is 0 °C to 40 °C; and / or, the reaction time of the electrochemical reaction is 8.0 hours to 10.5 hours; and / or, the electrochemical reaction is carried out under inert gas protection.

7. The method according to claim 3, characterized in that, When the electrochemical reaction is carried out using an electrochemical microchannel continuous flow reactor, the following steps are included: Diphenylmethylthioacetamide is mixed with water, electrolyte, and solvent. The resulting mixture is pumped into the electrochemical microchannel continuous flow reactor of the electrochemical microchannel continuous flow reactor device, where it undergoes an electrochemical reaction under the action of electrode electrolysis to obtain modafinil.

8. The method according to claim 7, characterized in that, The solvent is acetonitrile, or a mixed solvent of acetonitrile and pyridine in a volume ratio of (25.0–40.0):(5.0–20.0); and / or, the molar ratio of the diphenylmethylthioacetamide to water is 1.0:(55.0–280.0); and / or, the volume ratio of the water to the solvent is (5.0–25.0):(25.0–45.0).

9. The method according to claim 7, characterized in that, The flow rate of the mixed liquid pumped into the electrochemical microchannel continuous flow reactor of the electrochemical microchannel continuous flow reactor is 0.1 mL / min to 0.5 mL / min; and / or, the residence time of the electrochemical reaction in the electrochemical microchannel continuous flow reactor is 10.0 min to 50.0 min; and / or, the anode of the electrode is a graphite plate or a platinum sheet, and the cathode is a graphite plate or a platinum sheet; and / or, the constant current in the electrochemical reaction is 40.0 mA to 200 mA; and / or, the reaction temperature of the electrochemical reaction is room temperature.

10. The method according to claim 7, characterized in that, The electrochemical microchannel continuous flow reactor includes a connecting pipe, an injection pump, an electrochemical microchannel continuous flow reactor, an electrical box, and a receiver; wherein the injection pump, the electrochemical microchannel continuous flow reactor, and the receiver are connected in series via the connecting pipe; the electrical box applies current to both ends of the electrochemical microchannel continuous flow reactor, with the positive terminal of the electrical box connected to the anode terminal of the electrochemical microchannel continuous flow reactor, and the negative terminal of the electrical box connected to the cathode terminal of the electrochemical microchannel continuous flow reactor.

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