Electrochemical method for synthesizing diphenylhydrazine from nitrosobenzene compounds

Abstract

The application discloses an electrochemical method for synthesizing diphenylhydrazine from nitrosobenzene compounds, which comprises the following steps: mixing nitrosobenzene compounds, electrolyte and proton-type additives according to a molar ratio of 1:(0.5-1.0):(13-104) in a solvent, setting positive and negative electrodes, and performing reaction under the condition of power supply, and obtaining diphenylhydrazine after purification treatment. The application uses nitrosobenzene compounds with different structures as raw materials, uses clean electric energy as driving force, and uses low-reactivity organic nitrosobenzene compound reagents, thereby significantly improving the substrate application range and functional group tolerance, and having the advantages of simple and easily-obtained reagents, simple operation, high yield, environmental friendliness and the like.

Description

Technical Field

[0001] This invention relates to the synthesis of organic compounds, and more specifically, to an electrochemical method for synthesizing diphenylhydrazine from nitrosobenzene compounds. Background Technology

[0002] Diphenylhydrazine, a highly reactive nitrogen compound, primarily serves the synthesis of antipyretic analgesics and the development of high-performance dyes through benzidine rearrangement and redox reactions. Benzidine rearrangement: Under strong acid conditions, it rearranges to 4,4'-benzidine, historically the most important route for synthesizing azo dyes. Dehydrogenation: It is readily redox-reduced back to azobenzene, often acting as an electron / hydrogen donor or acceptor in organic synthesis. Substitution reaction: Its NH bond is nucleophilic, reacting with acyl chlorides or anhydrides to introduce functional groups into diphenylhydrazine. In the pharmaceutical field, diphenylhydrazine is a crucial intermediate in the synthesis of pyrazolone nonsteroidal anti-inflammatory drugs (NSAIDs), mainly used to treat arthritis and acute gout. It was once a primary first-line drug for rheumatism, with its synthesis heavily reliant on its stability. However, due to its potential hematopoietic toxicity, it is currently mainly used as a second-line drug or in veterinary medicine.

[0003] Therefore, diphenylhydrazine compounds are considered important organic precursors, attracting extensive research from chemists. The methods reported in the literature are as follows: (1) Nitrobenzene compounds can be reduced to diphenylhydrazine under catalytic conditions. For example, nitrobenzene compounds can be synthesized into diphenylhydrazine by chemiselective catalytic hydrogenation using gold nanoparticles supported on hexagonal boron nitride nanosheets (Au / h-BN) as catalyst, isopropanol as hydrogen source, and KOH as promoter at 90℃ under nitrogen atmosphere. (Liu Q, Xu Y, QiuX, et al. Journal of Catalysis, 2019, 370: 55-60.). Nitrobenzene compounds can be selectively reduced to diphenylhydrazine at room temperature in 50% ethanol aqueous solution with sodium borohydride as reducing agent under the action of supported gold nanoparticle catalyst (AuNPs@PS). (Hong JE, Jung Y, Park Y, et al. ACS omega, 2020, 5(13): 7576-7583.). Diphenylhydrazine can be obtained under visible light irradiation using CoP@CdS as a catalyst, ammonium formate as an electron donor, and water as a solvent, by controlling the reaction time (to a relatively short time). (Xu Y, Chen Y, Fu W F. ACS omega, 2018, 3(2): 1904-1911.). Nitrobenzene is reduced in two steps in an aqueous solution with an alkali metal catalyst and other organic solvents to obtain diphenylhydrazine (CN1032657A).

[0004] While these reactions have successfully achieved the reduction of nitrobenzene compounds, they suffer from poor catalyst selectivity. Existing catalysts may only be suitable for specific types of nitrobenzene compounds, exhibiting poor catalytic performance for structurally complex substrates. The method proposed in patent (CN1032657A) not only uses expensive quinone catalysts but also strong bases, making post-processing complex, environmentally unfriendly, and resulting in high reaction costs.

[0005] (2) Azobenzene compounds undergo reduction reactions under catalytic conditions to generate diphenylhydrazine. For example, azobenzene compounds, under the action of 4-cyanopyridine catalyst and with pinacol diboronate as a reducing agent, can selectively generate diphenylhydrazine by homolytic cleavage of B–B bonds in pentane solvent at 70 °C to form a boron radical intermediate (Wang G, Zhang H, Zhao J, et al. Angewandte Chemie, 2016, 128(20): 6089-6093.). Azobenzene, as a substrate, can generate diphenylhydrazine by transfer hydrogenation reaction in THF solvent at 35–50 °C under the catalysis of Bi(I) complex and with ammoniaborane as a hydrogen source (Wang F, Planas O, Cornella J. Journal of the American Chemical Society, 2019, 141(10): 4235-4240.). Copper oxide nanoparticles were used as a heterogeneous catalyst to selectively reduce azobenzene to diphenylhydrazine under mild conditions of 40 °C using ammonia borane as the hydrogen source (Thakur SD, Gupta S, Dey S, et al. Chemistry–A European Journal, 2025, 31(23): e202404196.). Using tris(8-hydroxyquinoline) phosphite as a catalyst precursor and ammonia borane as the hydrogen source, azobenzene was reduced to diphenylhydrazine in tetrahydrofuran solvent at 60 °C for 24 hours (Chacón‐Terán MA, Rodríguez‐Lugo RE, Wolf R, et al. European Journal of Inorganic Chemistry, 2019, 2019(39-40): 4336-4344.). Using IPrAgCl as a catalyst and benzenesilane as a reducing agent in isopropanol solvent, azobenzene was selectively reduced to diphenylhydrazine at room temperature for 24 hours (Han B, Jiao H, Chen R, et al. Organic Chemistry Frontiers, 2023, 10(9):2287-2293.). Using p-toluenethiophenol as a hydrogen donor, Eosin Y as a catalyst, and acetonitrile as a solvent, azobenzene was reduced to diphenylhydrazine at room temperature under visible light (22W energy-saving lamp) irradiation for 20 hours (Wang X, Wang X, Xia C, et al. Green Chemistry, 2019, 21(15): 4189-4193.).

[0006] These reactions have successfully reduced azobenzene compounds to diphenylhydrazine, but they suffer from poor catalyst selectivity. Existing catalysts may only be effective for specific types of azobenzene compounds, and their catalytic performance is poor for structurally complex substrates. Moreover, they almost always require heating, and without heating, the reaction time is very long. Summary of the Invention

[0007] To address the aforementioned problems, this invention provides an electrochemical reaction method for synthesizing diphenylhydrazine from nitrosobenzene compounds. This method is simple to operate and environmentally friendly, enabling the efficient synthesis of a series of diphenylhydrazine products in a one-pot process. Through an electrochemical reduction strategy, the reaction process can be precisely controlled, achieving not only high yields of the target product but also effectively suppressing excessive reduction and the formation of aniline byproducts. The reaction time is short, completing in just 3-5 hours, and it is insensitive to air and water.

[0008] To achieve the above objectives, the present invention provides an electrochemical method for synthesizing diphenylhydrazine from nitrosobenzene compounds, characterized by comprising the following steps: Nitrosaminoglycans, electrolytes, and protonated additives were mixed in a molar ratio of 1:(0.5~1.0):(13~104) in a solvent. Positive and negative electrodes were set up, and the reaction was carried out under energized conditions. After the reaction was completed, the mixture was purified to obtain diphenylhydrazine. The general formula for nitrosobenzene compounds is: , The structural formula of the product obtained from the reaction is: ; In the formula, R is any one of hydrogen, alkyl, alkoxy, halogen, and aryl.

[0009] Based on electrochemical reaction conditions, this invention generates ions on the electrode surface through direct reduction, obtains intermediate free radicals through free radical condensation, and further reduces them at the cathode to obtain the target compound. The unique electronic environment also helps to study the electron transfer process in free radical reactions.

[0010] The specific mechanism may be as follows: a portion of nitrosobenzene (NO) is reduced at the cathode to phenylhydroxylamine (NHOH). The remaining portion of nitrosobenzene condenses with phenylhydroxylamine to form azobenzene oxide (containing a -N=NO- structure). Azobenzene oxide is then reduced ([H]) to remove an oxygen atom, yielding azobenzene (-N=N-). Azobenzene can be further reduced to diphenylhydrazine (-NH-NH-).

[0011] Specifically, the nitrosobenzene compound is any one of the following compounds: , , , , , , , , , , , , , , , , .

[0012] Preferably, the electrolyte is one of tetrabutylammonium tetrafluoroborate and tetrabutylammonium hexafluorophosphate.

[0013] Preferably, the solvent is one of acetonitrile, tetrahydrofuran, dichloromethane, and acetone.

[0014] Preferably, the protonated additive is one of isopropanol, phenylboronic acid, ammonium chloride, and acetic acid.

[0015] Preferably, the volume ratio of the solvent to the additive is 4:1 to 1:1.

[0016] Preferably, the positive and negative electrode materials are each an independent noble metal, transition metal, or carbon material.

[0017] More preferably, the positive and negative electrodes are one of Zn(+) / Pt(-) and Zn(+) / NiF(-).

[0018] Preferably, the molar ratio of the nitrosobenzene compound, the electrolyte, and the additive is 1:0.5:26.

[0019] Preferably, the current is 15~20 mA, the temperature is 25~35℃, and the reaction time is 3~5 hours.

[0020] Specifically, the purification process includes: washing with sodium thiosulfate solution, extraction with dichloromethane, washing with brine, drying with anhydrous sodium sulfate, concentration under reduced pressure, and column chromatography.

[0021] Through the above technical solution, the present invention achieves the following beneficial effects: The preparation method of this invention is simple and environmentally friendly, yielding a series of reduction products of nitrosylbenzene compounds in high yields through a one-pot reaction. This method utilizes clean electrical energy as the driving force and employs less reactive and more stable organic nitrosylbenzene reagents, thus significantly improving the substrate applicability and functional group tolerance. It offers advantages such as readily available reagents, simple operation, high yield, and environmental friendliness, providing a green and efficient new route for the reduction of nitrosylbenzene compounds and broadening the scope of nitrosylbenzene reduction reactions. Detailed Implementation

[0022] The specific embodiments of the present invention will be described in detail below with reference to examples. It should be understood that the specific embodiments described herein are for illustration and explanation only and are not intended to limit the present invention.

[0023] In the following embodiments, unless otherwise specified, the methods described are conventional methods. The raw materials were partly obtained from publicly available commercial sources and partly prepared using known methods. In the column chromatography steps of the following embodiments, the chromatography column packing material used was 200-300 mesh silica gel with dimensions of 2 cm in diameter × 30 cm in height.

[0024] Example 1 The synthetic route for a reduction product of nitrosylbenzene, as shown in formula III-aa, is as follows:

[0025] The above reaction equation represents the synthesis of nitrosobenzene by reduction: Nitrosaminoglycans (54.7 mg, 0.5 mmol), tetrabutylammonium hexafluorophosphate (98.8 mg, 0.25 mmol), Zn(+) / Pt(-) were added sequentially to the reactor, along with 4 mL of acetonitrile and 1 mL of isopropanol. The reaction solution was reacted at room temperature for 4 h with an electric current of 15 mA. After the reaction was completed, the solution was washed with sodium thiosulfate solution, extracted with dichloromethane, washed with brine, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and separated by column chromatography to obtain 45.14 mg of the orange-yellow solid product III-aa (diphenylhydrazine, 98% yield).

[0026] The structural verification results are as follows: 1 H NMR (400 MHz, CDCl3) δ 7.14 - 7.09 (m, 4H), 6.76 -6.72 (m, 6H), 5.46 (s, 2H). 13 C NMR (100 MHz, CDCl3) δ 148.9, 129.4, 120.0, 112.4.

[0027] The synthesized compound, as identified by structural analysis, is the target compound III-aa, a diphenylhydrazine.

[0028] Other conditions are the same as in Example 1, but the effect of current intensity on yield is studied, and the results are shown in the table below:

[0029] Other conditions were the same as in Example 1, but the effect of solvent type on yield was studied. The results are shown in the table below:

[0030] Other conditions were the same as in Example 1, but the effect of solvent ratio on yield was studied, and the results are shown in the table below:

[0031] Other conditions were the same as in Example 1, but the effect of electrolyte type on yield was studied. The results are shown in the table below:

[0032] Other conditions were the same as in Example 1, but the effect of reaction time on yield was studied, and the results are shown in the table below:

[0033] Other conditions were the same as in Example 1, but the effect of reaction temperature on the yield was studied. The results are shown in the table below:

[0034] Other conditions were the same as in Example 1, but the effect of additives on the yield was studied, and the results are shown in the table below:

[0035] Other conditions were the same as in Example 1, but the effect of gas on the yield was studied, and the results are shown in the table below:

[0036] Other conditions were the same as in Example 1, but the effect of the electrode on the yield was studied, and the results are shown in the table below:

[0037] Example 2 The synthetic route for a reduction product of p-methylnitrosobenzene, as shown in Formula III-ba, is as follows:

[0038] The above reaction equation represents the synthesis of p-methylnitrosobenzene by reduction: p-Methylnitrosobenzene (79.2 mg, 0.5 mmol), tetrabutylammonium hexafluorophosphate (98.8 mg, 0.25 mmol), Zn(+) / Pt(-) were used as positive and negative electrodes, 4 mL of acetonitrile, and 1 mL of isopropanol were added sequentially to the reactor. The reaction solution was reacted at room temperature with an electric current of 15 mA for 4 h. After the reaction was completed, the solution was washed with sodium thiosulfate solution, extracted with dichloromethane, washed with brine, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and separated by column chromatography to obtain 47.76 mg of 1,2-bis(4-methylphenyl)hydrazine (III-ba), 90% yield.

[0039] The structural verification results are as follows: 1H NMR (400 MHz, CDCl3) δ 7.05 (d, J = 8.4 Hz, 4H), 6.78 (d, J = 8.4 Hz, 4H), 5.55 (s, 2H), 2.30 (s, 6H). 13 C NMR (100 MHz, CDCl3) δ146.8, 129.9, 129.1, 112.5, 20.6.

[0040] The synthesized compound, as identified by structural analysis, is 1,2-bis(4-methylphenyl)hydrazine, as shown in the target compound III-ba.

[0041] Example 3 The synthetic route for the reduction product of m-methylnitrosobenzene, as shown in Formula III-ca, is as follows:

[0042] The above reaction equation represents the synthesis of m-methylnitrosobenzene by reduction: m-Methylnitrosobenzene (72.1 mg, 0.5 mmol), tetrabutylammonium hexafluorophosphate (98.8 mg, 0.25 mmol), Zn(+) / Pt(-) were used as positive and negative electrodes, 4 mL of acetonitrile and 1 mL of isopropanol were added sequentially to the reactor. The reaction solution was reacted at room temperature with an electric current of 15 mA for 4 h. After the reaction was completed, the solution was washed with sodium thiosulfate solution, extracted with dichloromethane, washed with brine, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and separated by column chromatography to obtain 46.17 mg of the orange-yellow solid product III-ca (1,2-bis(3-methylphenyl)hydrazine), 87% yield.

[0043] The structural verification results are as follows: 1 H NMR (400 MHz, CDCl3) δ 7.09 (t, J = 7.6 Hz, 2H), 6.65 – 6.60 (m, 6H), 5.46 (s, 2H), 2.26 (s, 6H). 13 C NMR (100 MHz, CDCl3) δ149.1, 139.3, 129.2, 120.7, 113.0, 109.5, 21.6.

[0044] The synthesized compound, as identified by structural analysis, is 1,2-bis(3-methylphenyl)hydrazine, as shown in the target compound III-ca.

[0045] Example 4 The synthetic route for the reduction product of o-methylnitrosobenzene, as shown in Formula III-da, is as follows:

[0046] The above reaction equation represents the synthesis of o-methylnitrosobenzene by reduction: o-Methylnitrosobenzene (54.7 mg, 0.5 mmol), tetrabutylammonium hexafluorophosphate (98.8 mg, 0.25 mmol), Zn(+) / Pt(-) were used as positive and negative electrodes, 4 mL of acetonitrile and 1 mL of isopropanol were added sequentially to the reactor. The reaction solution was reacted at room temperature with an electric current of 15 mA for 4 h. After the reaction was completed, the solution was washed with sodium thiosulfate solution, extracted with dichloromethane, washed with brine, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and separated by column chromatography to obtain 48.82 mg of 1,2-bis(2-methylphenyl)hydrazine (III-da), 92% yield.

[0047] The structural verification results are as follows: 1 H NMR (400 MHz, CDCl3) δ 7.17 - 7.09 (m, 4H), 6.94(d, J = 8.0 Hz, 2H), 6.83 (t, J = 7.3 Hz, 2H), 5.55 (s, 2H), 2.30 (s, 6H). 13 C NMR (100 MHz, CDCl3) δ 146.3, 130.5, 127.3, 121.2, 119.4, 111.0, 17.2.

[0048] The synthesized compound, as identified by structural analysis, is 1,2-bis(2-methylphenyl)hydrazine, as shown in the target compound III-da.

[0049] Example 5 The synthetic route for the reduction product of p-fluoronitrosobenzene, as shown in Formula III-ea, is as follows:

[0050] The above reaction equation is for the synthesis of p-fluoronitrosobenzene by reduction: p-Fluoronide (78.2 mg, 0.5 mmol), tetrabutylammonium hexafluorophosphate (98.8 mg, 0.25 mmol), Zn(+) / Pt(-) were used as positive and negative electrodes, 4 mL of acetonitrile, and 1 mL of isopropanol were added sequentially to the reactor. The reaction solution was reacted at room temperature with an electric current of 15 mA for 4 h. After the reaction was completed, the solution was washed with sodium thiosulfate solution, extracted with dichloromethane, washed with brine, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and separated by column chromatography to obtain 47.90 mg of 1,2-bis(4-fluorophenyl)hydrazine (III-ea), with an 87% yield.

[0051] The structural verification results are as follows: 1 H NMR (400 MHz, CDCl3) δ 6.95 - 6.90 (m, 4H), 6.80 -6.77 (m, 4H), 5.55 (s, 2H). 13 C NMR (100 MHz, CDCl3) δ 158.4 (d, J = 235.8 Hz), 145.0 (d, J = 2.1 Hz), 116.1 (d, J = 22.5 Hz), 113.5 (d, J = 7.5 Hz).

[0052] The synthesized compound, as identified by structural analysis, is 1,2-bis(4-fluorophenyl)hydrazine, as shown in the target compound III-ea.

[0053] Example 6 The synthetic route for the reduction product of p-chloronitrosobenzene, as shown in Formula III-fa, is as follows:

[0054] The above reaction equation represents the synthesis of p-chloronitrosobenzene by reduction: p-Chlorotoxybenzene (88.5 mg, 0.5 mmol), tetrabutylammonium hexafluorophosphate (98.8 mg, 0.25 mmol), Zn(+) / Pt(-) were used as positive and negative electrodes, 4 mL of acetonitrile, and 1 mL of isopropanol were added sequentially to the reactor. The reaction solution was reacted at room temperature with an electric current of 15 mA for 4 h. After the reaction was completed, the solution was washed with sodium thiosulfate solution, extracted with dichloromethane, washed with brine, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and separated by column chromatography to obtain 50.42 mg of 1,2-bis(4-chlorophenyl)hydrazine (III-fa), an orange-yellow solid product (80% yield).

[0055] The structural verification results are as follows: 1H NMR (400 MHz, CDCl3) δ 7.17 (d, J = 8.8 Hz, 4H), 6.76 (d, J = 8.8 Hz, 4H), 5.63 (s, 2H). 13 C NMR (100 MHz, CDCl3) δ 147.1, 129.4, 124.8, 113.6.

[0056] The synthesized compound, as identified by structural analysis, is 1,2-bis(4-chlorophenyl)hydrazine, as shown in the target compound III-fa.

[0057] Example 7 The synthetic route for the reduction product of o-fluoronitrosobenzene, as shown in Formula III-ga, is as follows:

[0058] The above reaction equation is for the synthesis of o-fluoronitrosobenzene by reduction: o-fluoronitrosobenzene (75.7 mg, 0.5 mmol), tetrabutylammonium hexafluorophosphate (98.8 mg, 0.25 mmol), Zn(+) / Pt(-) were used as positive and negative electrodes, 4 mL of acetonitrile and 1 mL of isopropanol were added sequentially to the reactor. The reaction solution was reacted at room temperature with an electric current of 15 mA for 4 h. After the reaction was completed, the solution was washed with sodium thiosulfate solution, extracted with dichloromethane, washed with brine, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and separated by column chromatography to obtain 49.54 mg of 1,2-bis(2-fluorophenyl)hydrazine (III-ga), 90% yield.

[0059] The structural verification results are as follows: 1 H NMR (400 MHz, CDCl3) δ 7.07- 6.98 (m, 6H), 6.82 -6.77 (m, 2H), 5.86 (s, 2H). 13 C NMR (100 MHz, CDCl3) δ 151.9 (d, J = 237.9 Hz), 136.6 (d, J = 9.8 Hz), 124.9 (d, J = 3.5 Hz), 119.8 (d, J = 7.0 Hz), 115.1 (d, J =17.8 Hz), 113.8 (d, J = 2.8 Hz).

[0060] The synthesized compound, as identified by structural analysis, is 1,2-bisphenyl(2-fluorophenyl)hydrazine, as shown in the target compound III-ga.

[0061] Example 8 The synthetic route for the reduction product of p-tert-butylnitrosobenzene, as shown in Formula III-ha, is as follows:

[0062] The above reaction equation is for the synthesis of p-tert-butylnitrosobenzene by reduction: p-tert-butylnitrosobenzene (102.0 mg, 0.5 mmol), tetrabutylammonium hexafluorophosphate (98.8 mg, 0.25 mmol), Zn(+) / Pt(-) were used as positive and negative electrodes, 4 mL of acetonitrile, and 1 mL of isopropanol were added sequentially to the reactor. The reaction solution was reacted at room temperature with an electric current of 15 mA for 4 h. After the reaction was completed, the solution was washed with sodium thiosulfate solution, extracted with dichloromethane, washed with brine, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and separated by column chromatography to obtain 65.21 mg of 1,2-bis[4-(1,1-dimethylphenyl)phenyl]hydrazine (as shown in III-ha), 88% yield.

[0063] The structural verification results are as follows: 1 H NMR (400 MHz, CDCl3) δ 7.22 (d, J = 8.8 Hz, 4H), 6.79 (d, J = 8.8 Hz, 4H), 5.46 (s, 2H), 1.26 (s, 18H). 13 C NMR (100 MHz, CDCl3)δ 146.8, 142.7, 126.2, 112.2, 34.1, 31.6.

[0064] The synthesized compound, as identified by structural analysis, is 1,2-bis[4-(1,1-dimethylphenyl)phenyl]hydrazine, as shown in the target compound III-ha.

[0065] Example 9 The synthetic route for the reduction product of 3,5-dimethylnitrosobenzene, as shown in Formula III-ia, is as follows:

[0066] The above reaction equation represents the synthesis of 3,5-dimethylnitrosobenzene by reduction: 3,5-Dimethylnitrosobenzene (84.5 mg, 0.5 mmol), tetrabutylammonium hexafluorophosphate (98.8 mg, 0.25 mmol), Zn(+) / Pt(-) were used as positive and negative electrodes, 4 mL of acetonitrile, and 1 mL of isopropanol were added sequentially to the reactor. The reaction solution was reacted at room temperature with an electric current of 15 mA for 4 h. After the reaction was completed, the solution was washed with sodium thiosulfate solution, extracted with dichloromethane, washed with brine, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and separated by column chromatography to obtain 54.67 mg of 1,2-bis(3,5-dimethylphenyl)hydrazine (III-ia), a yellow oily product, with a yield of 91%.

[0067] The structural verification results are as follows: 1 H NMR (400 MHz, CDCl3) δ 6.47 (s, 2H), 6.45 (s, 4H), 5.38 (s, 2H), 2.22 (s, 12H). 13 C NMR (100 MHz, CDCl3) δ 149.3, 139.2, 121.8, 110.2, 21.5.

[0068] The synthesized compound, as identified by structural analysis, is 1,2-bis(3,5-dimethylphenyl)hydrazine, as shown in the target compound III-ia.

[0069] Example 10 The synthetic route for the reduction product of o-chloronitrosobenzene, as shown in Formula III-ja, is as follows:

[0070] The above reaction equation represents the synthesis of o-chloronitrosobenzene by reduction: o-N-chloronitrosobenzene (88.5 mg, 0.5 mmol), tetrabutylammonium hexafluorophosphate (98.8 mg, 0.25 mmol), Zn(+) / Pt(-) were used as positive and negative electrodes, 4 mL of acetonitrile and 1 mL of isopropanol were added sequentially to the reactor. The reaction solution was reacted at room temperature with an electric current of 15 mA for 4 h. After the reaction was completed, the solution was washed with sodium thiosulfate solution, extracted with dichloromethane, washed with brine, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and separated by column chromatography to obtain 56.32 mg of 1,2-bis(2-chlorophenyl)hydrazine (III-ja), 89% yield.

[0071] The structural verification results are as follows: 1H NMR (400 MHz, CDCl3) δ 7.34 (d, J = 8.0 Hz, 2H), 7.17 (t, J = 7.6 Hz, 2H), 6.99 (d, J = 8.0 Hz, 2H), 6.83 (t, J = 8.0 Hz, 2H), 6.22 (s, 2H). 13 C NMR (100 MHz, CDCl3) δ 143.9, 129.4, 128.1, 120.3, 118.0,113.0.

[0072] The synthesized compound, as identified by structural analysis, is 1,2-bis(2-chlorophenyl)hydrazine, as shown in the target compound III-ja.

[0073] Example 11 The synthetic route for the reduction product of p-ethylnitrosobenzene, as shown in Formula III-ka, is as follows:

[0074] The above reaction equation is for the synthesis of p-ethylnitrosobenzene by reduction: p-Ethylnitrosobenzene (85.7 mg, 0.5 mmol), tetrabutylammonium hexafluorophosphate (98.8 mg, 0.25 mmol), Zn(+) / Pt(-) were used as positive and negative electrodes, 4 mL of acetonitrile, and 1 mL of isopropanol were added sequentially to the reactor. The reaction solution was reacted at room temperature with an electric current of 15 mA for 4 h. After the reaction was completed, the solution was washed with sodium thiosulfate solution, extracted with dichloromethane, washed with brine, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and separated by column chromatography to obtain 54.08 mg of 1,2-bis(4-ethylphenyl)hydrazine (as shown in III-ka), 90% yield.

[0075] The structural verification results are as follows: 1 H NMR (400 MHz, CDCl3) δ 6.94 (d, J = 8.4 Hz, 4H), 6.59 (d, J = 8.2 Hz, 4H), 3.50 (s, 2H), 2.51 (q, J = 7.6 Hz, 4H), 1.16 (t, J= 7.6 Hz, 6H). 13 C NMR (100 MHz, CDCl3) δ 224.3, 143.8, 134.3, 128.3, 115.3, 28.1, 16.0.

[0076] The synthesized compound, as identified by structural analysis, is 1,2-bis(4-ethylphenyl)hydrazine, as shown in the target compound III-ka.

[0077] Example 12 The synthetic route for the reduction product of p-methoxynitrosobenzene, as shown in Formula III-la, is as follows:

[0078] The above reaction equation represents the synthesis of p-methoxynitrosobenzene by reduction: p-Methoxynitrosobenzene (85.7 mg, 0.5 mmol), tetrabutylammonium hexafluorophosphate (98.8 mg, 0.25 mmol), Zn(+) / Pt(-) were used as positive and negative electrodes, 4 mL of acetonitrile, and 1 mL of isopropanol were added sequentially to the reactor. The reaction solution was reacted at room temperature with an electric current of 15 mA for 4 h. After the reaction was completed, the solution was washed with sodium thiosulfate solution, extracted with dichloromethane, washed with brine, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and separated by column chromatography to obtain 52.52 mg of 1,2-bis(4-methoxyphenyl)hydrazine (III-la), with a yield of 86%, as shown in the figure.

[0079] The structural verification results are as follows: 1 H NMR (400 MHz, CDCl3) δ 7.75 (d, J = 8.5 Hz, 4H), 6.73 (d, J = 8.5 Hz, 4H), 6.39 (s, 2H), 2.41 (s, 6H). 13 C NMR (100 MHz, CDCl3)δ 196.2, 151.8, 130.0, 129.1, 111.0, 25.9.

[0080] The synthesized compound, as identified by structural analysis, is 1,2-bis(4-methoxyphenyl)hydrazine, as shown in target compound III-la.

[0081] Example 13 The synthetic route for the reduction product of p-tert-butylnitrosobenzene, as shown in Formula III-ma, is as follows:

[0082] The above reaction equation is for the synthesis of p-tert-butylnitrosobenzene by reduction: p-tert-butylnitrosobenzene (102.0 mg, 0.5 mmol), tetrabutylammonium hexafluorophosphate (98.8 mg, 0.25 mmol), Zn(+) / Pt(-) were used as positive and negative electrodes, 4 mL of acetonitrile, and 1 mL of isopropanol were added sequentially to the reactor. The reaction solution was reacted at room temperature with an electric current of 15 mA for 4 h. After the reaction was completed, the solution was washed with sodium thiosulfate solution, extracted with dichloromethane, washed with brine, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and separated by column chromatography to obtain 68.18 mg of 1,2-bis(4-tert-butylphenyl)hydrazine (III-ma), 92% yield.

[0083] The structural verification results are as follows: 1 H NMR (400 MHz, CDCl3) δ 7.22 (d, J = 8.8 Hz, 4H), 6.79 (d, J = 8.8 Hz, 4H), 5.46 (s, 2H), 1.26 (s, 18H). 13 C NMR (100 MHz, CDCl3)δ 146.8, 142.7, 126.2, 112.2, 34.1, 31.6.

[0084] The synthesized compound, as identified by structural analysis, is 1,2-bis(4-tert-butylphenyl)hydrazine, as shown in the target compound III-ma.

[0085] Example 14 The synthetic route for the reduction product of p-cyanonitrobenzene, as shown in Formula III-na, is as follows:

[0086] The above reaction equation is for the synthesis of p-cyanonitrobenzene by reduction: p-Cyanonitrobenzene (82.6 mg, 0.5 mmol), tetrabutylammonium hexafluorophosphate (98.8 mg, 0.25 mmol), Zn(+) / Pt(-) were used as positive and negative electrodes, 4 mL of acetonitrile, and 1 mL of isopropanol were added sequentially to the reactor. The reaction solution was reacted at room temperature with an electric current of 15 mA for 4 h. After the reaction was completed, the solution was washed with sodium thiosulfate solution, extracted with dichloromethane, washed with brine, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and separated by column chromatography to obtain 52.71 mg of 1,2-bis(4-cyanophenyl)hydrazine (III-na), 90% yield.

[0087] The structural verification results are as follows: 1H NMR (400 MHz, DMSO-d6) δ 8.76 (s, 2H), 7.57 (d, J= 8.4 Hz, 4H), 6.79 (d, J = 8.8 Hz, 4H). 13 C NMR (100 MHz, DMSO-d6) δ 153.1, 134.1, 120.4, 111.8, 99.3.

[0088] The synthesized compound, as identified by structural analysis, is 1,2-bis(4-cyanophenyl)hydrazine, as shown in the target compound III-na.

[0089] Example 15 The synthetic route for the reduction product of p-nitrosobenzene, as shown in Formula III-oa, is as follows:

[0090] The above reaction equation represents the synthesis of p-nitrosobenzene by reduction: p-Nitronitrosobenzene (95.1 mg, 0.5 mmol), tetrabutylammonium hexafluorophosphate (98.8 mg, 0.25 mmol), Zn(+) / Pt(-) were used as positive and negative electrodes, 4 mL of acetonitrile, and 1 mL of isopropanol were added sequentially to the reactor. The reaction solution was reacted at room temperature with an electric current of 15 mA for 4 h. After the reaction was completed, the solution was washed with sodium thiosulfate solution, extracted with dichloromethane, washed with brine, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and separated by column chromatography to obtain 56.22 mg of 1,2-bis(4-nitrophenyl)hydrazine (as shown in III-oa), 82% yield.

[0091] The structural verification results are as follows: 1 H NMR (400 MHz, DMSO-d6) δ 10.99 (s, 2H), 8.48 (d,J = 8.8 Hz, 4H), 8.18 (d,J = 9.2 Hz, 4H). 13 C NMR (100 MHz, DMSO-d6) δ 164.2, 149.1, 138.3, 129.1, 124.0.

[0092] The synthesized compound, as identified by structural analysis, is 1,2-bis(4-nitrophenyl)hydrazine, as shown in the target compound III-oa.

[0093] Example 16 The synthetic route for the reduction product of p-acetoketylnitrosobenzene, as shown in Formula III-pa, is as follows:

[0094] The above reaction equation represents the synthesis of p-acetophenone-nitrosobenzene by reduction: p-Ethylene nitrosobenzene (93.2 mg, 0.5 mmol), tetrabutylammonium hexafluorophosphate (98.8 mg, 0.25 mmol), Zn(+) / Pt(-) were used as positive and negative electrodes, 4 mL of acetonitrile, and 1 mL of isopropanol were added sequentially to the reactor. The reaction solution was reacted at room temperature with an electric current of 15 mA for 4 h. After the reaction was completed, the solution was washed with sodium thiosulfate solution, extracted with dichloromethane, washed with brine, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and separated by column chromatography to obtain 53.66 mg of 1,2-bis(2-chlorophenyl)hydrazine (as shown in III-pa), 80% yield.

[0095] The structural verification results are as follows: 1 H NMR (400 MHz, CDCl3) δ 7.79 (d, J = 8.4 Hz, 4 H), 6.64 (d, J = 8.4 Hz, 4 H), 4.29 (s, 2 H), 2.48 (s, 6 H). 13 C NMR (100 MHz, CDCl3) δ 196.7, 151.5, 130.8, 127.4, 113.6, 26.0.

[0096] The synthesized compound, as identified by structural analysis, is 1,2-bis(4-ethylketonephenyl)hydrazine, as shown in the target compound III-pa.

[0097] The preferred embodiments of the present invention have been described in detail above. However, the present invention is not limited to the specific details in the above embodiments. Within the scope of the technical concept of the present invention, various simple modifications can be made to the technical solution of the present invention, and these simple modifications all fall within the protection scope of the present invention.

[0098] It should also be noted that the various specific technical features described in the above specific embodiments can be combined in any suitable manner without contradiction. In order to avoid unnecessary repetition, the present invention will not describe the various possible combinations separately.

[0099] Furthermore, various different embodiments of the present invention can be combined in any way, as long as they do not violate the spirit of the present invention, they should also be regarded as the content disclosed by the present invention.

Claims

1. An electrochemical method for synthesizing diphenylhydrazine from nitrosobenzene compounds, characterized in that, Includes the following steps: Nitrosaminoglycans, electrolytes, and protonated additives were mixed in a molar ratio of 1:(0.5~1.0):(13~104) in a solvent. Positive and negative electrodes were set up, and the reaction was carried out under energized conditions. After the reaction was completed, the mixture was purified to obtain diphenylhydrazine. The general formula for nitrosobenzene compounds is: , The structural formula of the product obtained from the reaction is: ; In the formula, R is any one of hydrogen, alkyl, alkoxy, halogen, and aryl.

2. The method according to claim 1, characterized in that, The nitrosobenzene compound is any one of the following compounds: 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 。 3. The method according to claim 1, characterized in that, The electrolyte is one of tetrabutylammonium tetrafluoroborate and tetrabutylammonium hexafluorophosphate.

4. The method according to claim 1, characterized in that, The proton-type additive is one of isopropanol, phenylboronic acid, ammonium chloride, and acetic acid.

5. The method according to claim 1, characterized in that, The solvent is one of acetonitrile, tetrahydrofuran, dichloromethane, and acetone.

6. The method according to claim 1, characterized in that, The volume ratio of the solvent to the additive is 4:1 to 1:

1.

7. The method according to claim 1, characterized in that, The positive and negative electrode materials are each an independent noble metal, transition metal, or carbon material.

8. The method according to claim 7, characterized in that, The positive and negative electrodes are one of Zn(+) / Pt(-) and Zn(+) / NiF(-).

9. The method according to claim 1, characterized in that, The molar ratio of the nitrosobenzene compound, electrolyte, and additive is 1:0.5:

26.

10. The method according to any one of claims 1 to 9, characterized in that, The current is 15~20 mA, the temperature is 25~35℃, and the reaction time is 3~5 hours.

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