A method for preparing an eight-membered selenium-containing benzazepine compound

Abstract

The application relates to a method for preparing an eight-membered selenium-containing benzazepine compound, which comprises the following steps: taking an N-(but-3-en-1-yl)-4-methyl-N-(2-(1-phenylvinyl)phenyl)benzenesulfonamide compound as a substrate, generating a selenyl radical through anodic oxidation of a selenide under electrochemical driving, and obtaining the eight-membered selenium-containing benzazepine compound through radical coupling-cyclization of the selenyl radical and the substrate. The method steps have the advantages of green simple operation, use of traceless electrons instead of an external oxidizing and reducing agent, avoidance of use of a metal catalyst and an external oxidizing and reducing agent, economy, simple and easy-to-prepare raw materials, wide substrate range and the like.

Description

TECHNICAL FIELD

[0001] The present application belongs to the field of chemical preparation, and particularly relates to a method for preparing an eight-membered selenium-containing benzoazepine compound. BACKGROUND

[0002] Selenium is one of the essential trace elements for human body, and is known as "the spark of life", and enjoys the reputation of "longevity element" and "king of anti-cancer". Due to the redox and soft and hard proton properties of selenium, selenium participates in a series of important metabolic activities in the human body. The newly implemented health industry standard WS / T 578.3-2017 Chinese Residents Dietary Nutrient Reference Intake stipulates that the average daily selenium requirement of adults is 50-60 μg. In view of the important biological and pharmacological activities of selenium-containing heterocyclic compounds, and the important role in antibacterial, antitumor, cardiovascular protection and immunomodulation, developing a new method for efficiently synthesizing novel selenium-containing heterocyclic compounds has important research value and practical significance for the development of selenium-containing products, the establishment of selenium-containing drug molecule library and drug research and development. On the other hand, nitrogen-containing heterocycles are the key skeleton structures of many drug molecules, and have wide and important biological activities and medicinal value. Therefore, developing a simple, efficient and green method to introduce selenium group into nitrogen heterocycles has attracted widespread attention from chemists. At present, the reported selenium-containing N-heterocycles are limited to 5-membered or 6-membered heterocyclic systems; in contrast, the reports of selenium-containing compounds containing medium-sized N-heterocyclic structural units are still very rare. With the concept of "green and sustainable chemistry", electrochemical technology as one of the green and sustainable synthetic methods has opened up a broad application prospect in the field of bifunctionalization of unsaturated bonds, cyclization and direct functionalization of C-H bonds. Therefore, the effective construction of N-heterocycles using electrochemical technology has been a popular field of organic synthesis research. However, there is no report on a method for constructing an eight-membered selenium-containing benzoazepine ring driven by electrochemistry without metal and oxidant. SUMMARY

[0003] In view of the problems existing in the prior art, the present application provides a method for preparing an eight-membered selenium-containing benzoazepine compound, which is an effective method for obtaining an eight-membered selenium-containing benzoazepine compound by using N-(but-3-en-1-yl)-4-methyl-N-(2-(1-phenylvinyl)phenyl)benzenesulfonamide compound as a substrate, generating selenium radical by anodic oxidation of selenium ether under electrochemical driving, and obtaining the eight-membered selenium-containing benzoazepine compound by radical coupling-cyclization of the selenium radical and the substrate.

[0004] The technical solution of the present application to solve the above technical problems is as follows:

[0005] The application provides a method for preparing an eight-membered selenium-containing benzazepine compound, which comprises the following steps: taking N-(but-3-en-1-yl)-4-methyl-N-(2-(1-phenylvinyl)phenyl)benzenesulfonamide compound as a substrate, generating a selenyl radical under electrochemical driving after anodic oxidation of a selenide ether, and obtaining the eight-membered selenium-containing benzazepine compound through radical coupling-cyclization of the selenyl radical and the substrate.

[0006] The beneficial effects of adopting the above technical solution include:

[0007] The application generates a selenyl radical through electrocatalysis, and efficiently prepares a series of eight-membered selenium-containing benzazepine compounds through radical addition-cyclization.

[0008] The above method has the advantages of green and simple operation, use of traceless electrons instead of an external oxidizing and reducing agent, avoidance of the use of metal catalysts and an external oxidizing and reducing agent, economy, simple and easy-to-prepare raw materials, wide substrate range, product scalability, low cost of substrates, green reaction, no explosion risk, and easy post-treatment without metal salts.

[0009] Further, the molar ratio of the N-(but-3-en-1-yl)-4-methyl-N-(2-(1-phenylvinyl)phenyl)benzenesulfonamide compound to the selenide ether is 1:(1-1.2).

[0010] The beneficial effects of adopting the above technical solution include: green and simple operation, use of traceless electrons instead of an external oxidizing and reducing agent, and avoidance of the use of metal catalysts and an external oxidizing and reducing agent.

[0011] Further, the method comprises the following steps: adding the N-(but-3-en-1-yl)-4-methyl-N-(2-(1-phenylvinyl)phenyl)benzenesulfonamide compound, the selenide ether, n Bu4NPF6 and DCM to obtain a mixture; electrolyzing the mixture until the N-(but-3-en-1-yl)-4-methyl-N-(2-(1-phenylvinyl)phenyl)benzenesulfonamide compound is completely consumed; after the reaction is completed, quenching, extraction; concentrating the organic solvent; and purifying, eluting with an eluent to obtain the eight-membered selenium-containing benzazepine compound.

[0012] Further, the molar ratio of the N-(but-3-en-1-yl)-4-methyl-N-(2-(1-phenylvinyl)phenyl)benzenesulfonamide compound, n The molar ratio of the N-(but-3-en-1-yl)-4-methyl-N-(2-(1-phenylvinyl)phenyl)benzenesulfonamide compound to the selenide ether is 1:(1-1.2); and the molar volume ratio of the N-(but-3-en-1-yl)-4-methyl-N-(2-(1-phenylvinyl)phenyl)benzenesulfonamide compound to DCM is 0.2 mmol:5 mL.

[0013] The beneficial effects of the above technical solutions include: the above-mentioned ratio is conducive to the reaction and improves the yield.

[0014] Preferably, the N-(but-3-en-1-yl)-4-methyl-N-(2-(1-phenylvinyl)phenyl)benzenesulfonamide compound, n The molar ratio of Bu4NPF6 and selenoether is 1:2:(1-1.2), which can further improve the yield of the target product.

[0015] Further, after the reaction is completed, the mixture is quenched with NaHCO3 and extracted with CH2Cl2; then the organic solvent is concentrated under vacuum; the residue is purified by flash column chromatography, and a mixture of ethyl acetate and petroleum ether is used as the eluent to obtain an eight-membered selenium-containing benzazepine compound.

[0016] The beneficial effects of the above technical solutions include: quenching with NaHCO3 is conducive to reducing the solubility of the product, extracting with CH2Cl2 is conducive to layering and complete extraction of the product, and using a mixture of ethyl acetate and petroleum ether as the eluent is conducive to the removal of the eluent.

[0017] Further, under an air atmosphere, the mixture is electrolyzed at room temperature under a constant current of 2mA using a Pt electrode.

[0018] The beneficial effects of the above technical solutions include: which can further improve the yield.

[0019] Further, the structural formula of the N-(but-3-en-1-yl)-4-methyl-N-(2-(1-phenylvinyl)phenyl)benzenesulfonamide compound is shown as formula 1,

[0020]

[0021] wherein R 1 independently selected from one of H, CH3, Cl, Br substituents; R 2 independently selected from one of o-CNPh, H, CH3, OCH3, F, Cl, Br substituents.

[0022] Further, the N-(but-3-en-1-yl)-4-methyl-N-(2-(1-phenylvinyl)phenyl)benzenesulfonamide compound is selected from one or a combination of several of the following: N-(but-3-en-1-yl)-4-methyl-N-(2-(1-phenylvinyl)phenyl)benzenesulfonamide, N-(but-3-en-1-yl)-4-methyl-N-(5-methyl-2-(1-phenylvinyl)phenyl)benzenesulfonamide, N-(but-3-en-1-yl)-N-(4-chloro-2-(1-phenylvinyl)phenyl)-4-methylbenzenesulfonamide, N-(4-bromo-2-(1-phenylvinyl)phenyl)-N-(but-3-en-1-yl)-4-methylbenzenesulfonamide, N-(but-3-en-1-yl)-4-methyl-N-(2-(1-(p-tolyl)vinyl)phenyl)benzenesulfonamide, N-(but-3-en-1-yl)-4-methyl-N-(4-methyl-2-(1-phenylvinyl)phenyl)benzenesulfonamide, N-(but-3-en-1-yl)-N-(4-chloro-2-(1-(p-tolyl)vinyl)phenyl)-4-methylbenzenesulfonamide, N-(but-3-en-1-yl)-N-(2'-cyano-3-(1-phenylvinyl)-[1,1'-biphenyl]-4-yl)-4-methylbenzenesulfonamide.

[0023] Further, the selenium ether can be a diselenide; preferably, the selenium ether is selected from one or several of diphenyl diselenide, 1,2-di(2-methoxyphenyl)diselenide, 1,2-di(3-methoxyphenyl)diselenide, 1,2-di(3-bromophenyl)diselenide, 1,2-di(4-methylphenyl)diselenide, 1,2-di(4-chlorophenyl)diselenide, 1,2-di(3,5-dimethylphenyl)diselenide, 1,2-di(2-naphthyl)diselenide.

[0024] The present application provides an eight-membered selenium-containing benzoazepine compound, having the following chemical formula:

[0025]

[0026] wherein, R 1 independently selected from one of H, CH3, Cl, Br substituents; R 2 independently selected from one of o-CNPh, H, CH3, OCH3, F, Cl, Br substituents; R 3 independently selected from one or several of benzene ring, naphthalene, benzene ring containing halogen, methyl, methoxy.

[0027] The beneficial effects of adopting the above technical solutions include: the eight-membered selenium-containing benzoazepine compound prepared by the present application has multiple biological activities and has wide application prospects. BRIEF DESCRIPTION OF DRAWINGS

[0028] Figure 1 Reaction mechanism diagram for the preparation of eight-membered selenium-containing benzazepine compounds of the present invention.

[0029] Figure 2 is compound 3a of Example 1 1 H NMR spectrum. Figure 3 is compound 3a of Example 1 13 C NMR spectrum.

[0030] Figure 4 is compound 3b of Example 2 1 H NMR spectrum. Figure 5 is compound 3b of Example 2 13 C NMR spectrum.

[0031] Figure 6 is compound 3c of Example 3 1 H NMR spectrum. Figure 7 is compound 3c of Example 3 13 C NMR spectrum.

[0032] Figure 8 is compound 3d of Example 4 1 H NMR spectrum. Figure 9 is compound 3d of Example 4 13 C NMR spectrum.

[0033] Figure 10 is compound 3e of Example 5 1 H NMR spectrum. Figure 11 is compound 3e of Example 5 13 C NMR spectrum.

[0034] Figure 12 is compound 3f of Example 6 1 H NMR spectrum. Figure 13 is compound 3f of Example 6 13 C NMR spectrum.

[0035] Figure 14 is compound 3g of Example 7 1 H NMR spectrum. Figure 15 is compound 3g of Example 7 13 C NMR spectrum.

[0036] Figure 16 is compound 3h of Example 8 1 H NMR spectrum. Figure 17 is compound 3h of Example 8 13 C NMR spectrum.

[0037] Figure 18 is compound 3i in Example 9 1 H NMR spectrum. Figure 19 is compound 3i in Example 9 13 C NMR spectrum.

[0038] Figure 20 is compound 3j in Example 10 1 H NMR spectrum. Figure 21 is compound 3j in Example 10 13 C NMR spectrum.

[0039] Figure 22 is compound 3k in Example 11 1 H NMR spectrum. Figure 23 is compound 3k in Example 11 13 C NMR spectrum.

[0040] Figure 24 is compound 3l in Example 12 1 H NMR spectrum. Figure 25 is compound 3l in Example 12 13 C NMR spectrum.

[0041] Figure 26 is compound 3m in Example 13 1 H NMR spectrum. Figure 27 is compound 3m in Example 13 13 C NMR spectrum. Figure 28 is compound 3m in Example 13 19 F NMR spectrum.

[0042] Figure 29 is compound 3n in Example 14 1 H NMR spectrum. Figure 30 is compound 3n in Example 14 13 C NMR spectrum.

[0043] Figure 31 is compound 3o in Example 15 1 H NMR spectrum. Figure 32 is compound 3o in Example 15 13 C NMR spectrum.

[0044] Figure 33 is compound 3p in Example 16 1 H NMR spectrum. Figure 34 is compound 3p in Example 16 13 C NMR spectrum.

[0045] Figure 35 is compound 3q in Example 17 1 H NMR spectrum. Figure 36 is compound 3q in Example 17 13 C NMR spectrum.

[0046] Figure 37 is compound 3r in Example 18 1 H NMR spectrum. Figure 38 is compound 3r in Example 18 13 C NMR spectrum. DETAILED DESCRIPTION

[0047] The principles and features of the present application are described below in conjunction with the accompanying drawings, which are only used to explain the present application and are not intended to limit the scope of the present application. The technical solutions of the present application are not limited to the following examples, and any combination of the examples is also included.

[0048] The present application provides an effective method for preparing an eight-membered selenium-containing benzazepine compound by electrocatalytically generating a selenium-based radical and through radical addition-cyclization.

[0049] The method for preparing an eight-membered selenium-containing benzazepine compound by electrocatalysis comprises the following steps: taking N-(but-3-en-1-yl)-4-methyl-N-(2-(1-phenylvinyl)phenyl)benzenesulfonamide compound as a substrate, generating a selenium-based radical through anodic oxidation of a selenide under electrochemical driving, and obtaining an eight-membered selenium-containing benzazepine compound through radical coupling-cyclization of the selenium-based radical and the substrate.

[0050]

[0051] wherein, R 1 independently selected from one of H, CH3, Cl, Br; R 2 independently selected from one of o-CNPh, H, CH3, OCH3, F, Cl, Br; R 3 independently selected from one or more of a benzene ring, a naphthalene ring, a benzene ring containing one or more of halogen, methyl, methoxy.

[0052] Specifically, the following method can be used to prepare an eight-membered selenium-containing benzazepine compound:

[0053] At room temperature (generally 25°C), N-(but-3-en-1-yl)-4-methyl-N-(2-(1-phenylvinyl)phenyl)benzenesulfonamide compound 1, selenide 2, n Bu4NPF6 and dichloromethane DCM are sequentially added to the reaction tube. N-(but-3-en-1-yl)-4-methyl-N-(2-(1-phenylvinyl)phenyl)benzenesulfonamide compound,n The molar ratio of Bu4NPF6and selenoether is 1 : (1-3) : (1-1.2), preferably, the N-(but-3-en-1-yl)-4-methyl-N-(2-(1-phenylvinyl)phenyl)benzenesulfonamide compound, n The molar ratio of Bu4NPF6and selenoether is 1 : 2 : (1-1.2); the molar volume ratio of the N-(but-3-en-1-yl)-4-methyl-N-(2-(1-phenylvinyl)phenyl)benzenesulfonamide compound and DCM is 0.2 mmol: 5 mL.

[0054] The mixture was electrolyzed with a Pt electrode at a constant current of 2 mA until the starting material 1 (i.e. the N-(but-3-en-1-yl)-4-methyl-N-(2-(1-phenylvinyl)phenyl)benzenesulfonamide compound 1) was completely consumed as monitored by TLC analysis. After the reaction was completed, the mixture was quenched with saturated NaHCO3 (i.e. saturated sodium bicarbonate solution at room temperature, sat. aq. 15 mL) and extracted with CH2Cl2 (3 x 5 mL). The organic solvent was then concentrated in vacuo. The residue was purified by flash column chromatography eluting with a mixture of ethyl acetate and petroleum ether as eluent to give the eight-membered selenium-containing benzoazepine product 3. The volume ratio of petroleum ether to ethyl acetate used in the present application can be 20:1, for example: the volume ratio of petroleum ether to ethyl acetate used in Example 1 to Example 19 can be 20:1.

[0055] As shown in Figure 1 The reaction mechanism of the present application is further introduced by taking N-(but-3-en-1-yl)-4-methyl-N-(2-(1-phenylvinyl)phenyl)benzenesulfonamide 1a and diphenyl diselenide as an example:

[0056] Diphenyl diselenide is oxidized to a phenylselenyl radical at the anode, which attacks the buten outer double bond of the substrate 1a to give a radical intermediate. The intramolecular addition of the radical intermediate A to another double bond gives a radical intermediate B. Finally, the deprotonation of the radical intermediate B provides the final product. The reduction of dichloromethane releases hydrogen gas at the cathode surface.

[0057] The present application provides a method for efficiently preparing a series of eight-membered selenium-containing benzoazepine compounds by electrocatalytic generation of selenium-based radicals under metal-free and oxidant-free conditions, and radical addition tandem cyclization. The compounds have a variety of biological activities. The above method has the advantages of economy, simple and easy-to-prepare raw materials, wide substrate range, and scalable product preparation.

[0058] n Bu4NPF6was purchased from Shanghai Bide Pharmaceutical, and the column chromatography silica gel used in the process of flash column chromatography purification was purchased from Yantai Xinuo Chemical Co., Ltd., with parameters of 200-300 mesh.

[0059] Unless otherwise specified, all reagents used in this invention are conventional reagents in the art and can be obtained commercially. Unless otherwise specified, all experimental methods used in this invention are conventional experimental methods in the art.

[0060] The following is a description through specific embodiments.

[0061] Example 1

[0062] In this embodiment, the method for electrochemically driven preparation of eight-membered selenium-containing benzo[a] nitrogen heterocyclic compounds under metal-free and oxidant-free conditions is as follows:

[0063] At room temperature, N-(but-3-en-1-yl)-4-methyl-N-(2-(1-phenylvinyl)phenyl)benzenesulfonamide 1a (0.2 mmol), diphenyldiselenes 2a (0.2 mmol), were added sequentially to the reaction flask. n Bu4NPF6 (0.4 mmol) and DCM (5 mL) were used in a reaction flask equipped with two Pt electrodes (1 cm × 1 cm). Electrolysis was carried out at room temperature (25 °C) using a constant current of 2 mA until the starting material was completely consumed (TLC monitoring, approximately 12 h). After the reaction was complete, the mixture was quenched with NaHCO3 (sat. aq. 15 mL) and extracted with CH2Cl2 (3 × 5 mL). The organic solvent was then concentrated under vacuum. The residue was purified by rapid column chromatography, using a mixture of ethyl acetate and petroleum ether as eluent to give product 3a.

[0064]

[0065] Spectral results as follows Figure 2 and Figure 3 As shown. Compound 3a 1 H NMR, 13 The structure of the compound was determined by C10 NMR spectroscopy. Specifically:

[0066] Rf (petroleum ether / ethyl acetate=10:1): 0.23; Yellow liquid (66 mg, yield 70%). 1H NMR (500 MHz, CDC13) δ 7.63 (d, J = 8.1 Hz, 2H), 7.41 - 7.34 (m, 4H), 7.30 - 7.10 (m, 11H), 6.92 (d, J = 7.3 Hz, 1H), 5.97 (d, J = 8.7 Hz, 1H), 4.24 (dd, J = 14.6, 3.6 Hz, 1H), 3.09 - 3.03 (m, 1H), 2.98 - 2.86 (m, 2H), 2.39 (s, 3H), 2.02 (dd, J = 14.9, 6.4 Hz, 1H), 1.84 - 1.74 (m, 1H), 1.63 (d, J = 13.5 Hz, 1H); 13 C NMR (125 MHz, CDC13) δ 143.17, 142.14, 142.01, 140.32, 138.48, 137.75, 133.18 (d, J = 9.5 Hz), 130.95, 129.88, 129.44, 129.24, 129.00, 128.88, 128.61, 128.56, 128.23, 127.98, 127.74, 127.24, 127.00, 50.97, 38.56, 35.80, 33.74, 21.55.

[0067] Example 2

[0068] The method of electrochemically driven preparation of eight-membered selenium-containing benzazepine compounds without metal and oxidant in this example is as follows:

[0069] At room temperature, N-(but-3-en-1-yl)-4-methyl-N-(2-(1-phenylvinyl)phenyl)benzenesulfonamide 1a (0.2 mmol), 1,2-di(2-methoxyphenyl)diselenide 2b (0.2 mmol), Bu4NPF6 (0.4 mmol) and DCM (5 mL) were added into the reaction bottle successively, which was equipped with two Pt electrodes (1 cm x 1 cm). The electrolysis was carried out at room temperature of 25 °C using a constant current of 2 mA until the complete consumption of the starting material (TLC monitoring, about 12 h). After the reaction was completed, the mixture was quenched with NaHCO3 (sat. aq. 15 mL) and extracted with CH2Cl2 (3 x 5 mL). Then the organic solvent was concentrated in vacuum. The residue was purified by flash column chromatography using a mixed solvent of ethyl acetate and petroleum ether as eluent to obtain the product 3b. n Bu4NPF6 (0.4 mmol) and DCM (5 mL) were added into the reaction bottle successively, which was equipped with two Pt electrodes (1 cm x 1 cm). The electrolysis was carried out at room temperature of 25 °C using a constant current of 2 mA until the complete consumption of the starting material (TLC monitoring, about 12 h). After the reaction was completed, the mixture was quenched with NaHCO3 (sat. aq. 15 mL) and extracted with CH2Cl2 (3 x 5 mL). Then the organic solvent was concentrated in vacuum. The residue was purified by flash column chromatography using a mixed solvent of ethyl acetate and petroleum ether as eluent to obtain the product 3b.

[0070]

[0071] The spectral results are shown in Figure 4 and Figure 5 The spectral results are shown in 1H NMR, 13 C NMR spectrum to determine the structure of the compound. Specifically:

[0072] Rf(petroleum ether / ethyl acetate = 10:1): 0.11; Yellow liquid (72 mg, yield 61%). 1 H NMR (500 MHz, CDC13) δ 7.64 (d, J = 8.1 Hz, 2H), 7.37 (d, J = 7.1 Hz, 2H), 7.30 - 7.13 (m, 9H), 7.11 (dd, J = 6.9, 2.2 Hz, 1H), 6.96 - 6.90 (m, 1H), 6.84 - 6.74 (m, 2H), 5.99 (d, J = 8.7 Hz, 1H), 4.24 (dd, J = 14.6, 3.2 Hz, 1H), 3.79 (s, 3H), 3.06 (dd, J = 11.1, 7.9 Hz, 1H), 2.97 - 2.87 (m, 2H), 2.39 (s, 3H), 2.10 - 2.01 (m, 1H), 1.84 - 1.67 (m, 2H); 13 C NMR (125 MHz, CDC13) δ 157.88, 143.15, 142.10, 141.95, 140.33, 138.38, 137.75, 133.07, 131.91, 130.96, 129.43, 128.88, 128.61, 128.57, 128.24, 127.96, 127.86, 127.74, 127.22, 121.36, 119.37, 110.40, 55.78, 51.02, 38.63, 33.66, 33.07, 21.54.

[0073] Example 3

[0074] The method for preparing octa-membered selenium-containing benzazepine compounds electrochemically driven under the conditions of no metal and no oxidant in this example is as follows:

[0075] At room temperature, N-(but-3-en-1-yl)-4-methyl-N-(2-(1-phenylvinyl)phenyl)benzenesulfonamide 1a (0.2 mmol), 1,2-di(3-methoxyphenyl)diselenide 2c (1.2 equiv, 0.24 mmol), potassium carbonate (1.2 equiv, 0.24 mmol) and 1,4-dioxane (2 mL) were sequentially added into a reaction bottle. nBu4NPF6(0.4 mmol) and DCM (5 mL), reaction flask equipped with two Pt electrodes (1 cm x 1 cm). The electrolysis was carried out at 25 °C room temperature using a constant current of 2 mA until complete consumption of the starting material (TLC monitoring, ca. 12 h). After completion of the reaction, the mixture was quenched with NaHCO3(sat. aq. 15 mL) and extracted with CH2Cl2(3 x 5 mL). The organic solvents were then concentrated in vacuo. The residue was purified by flash column chromatography using a mixture of ethyl acetate and petroleum ether as eluent to give the product 3c.

[0076]

[0077] The spectroscopic results are shown in Figure 6 and Figure 7 . The structure of compound 3c was confirmed by 1 H NMR, 13 C NMR spectra. In particular:

[0078] Rf(petroleum ether / ethyl acetate = 10:1): 0.11; Yellow liquid (72 mg, yield 61%). 1 H NMR (500 MHz, CDC13) δ 7.64 (d, J = 8.1 Hz, 2H), 7.35 (d, J = 7.1 Hz, 2H), 7.29 - 7.18 (m, 7H), 7.11 (dd, J = 6.9, 2.2 Hz, 1H), 7.07 (t, J = 7.9 Hz, 1H), 6.98 - 6.90 (m, 3H), 6.71 (dd, J = 8.1, 1.7 Hz, 1H), 5.96 (d, J = 8.7 Hz, 1H), 4.24 (dd, J = 14.6, 3.5 Hz, 1H), 3.72 (s, 3H), 3.09 (dd, J = 11.4, 8.5 Hz, 1H), 3.01 - 2.87 (m, 2H), 2.40 (s, 3H), 2.08 - 1.98 (m, 1H), 1.85 - 1.75 (m, 1H), 1.65 (d, J = 13.5 Hz, 1H); 13 C NMR (125 MHz, CDC13) δ 159.67, 143.17, 142.11, 141.97, 140.30, 138.50, 137.73, 133.01, 131.05, 130.95, 129.75, 129.44, 128.87, 128.59, 128.54, 128.23, 127.97, 127.74, 127.24, 125.11, 118.29, 112.67, 55.25, 50.98, 38.68, 35.68, 33.69, 21.54.

[0079] Example 4

[0080] The method of preparing octa-se-containing benzoazepine compounds electrochemically driven under the condition of no metal and no oxidant in this example is as follows:

[0081] To the reaction flask, N-(but-3-en-1-yl)-4-methyl-N-(2-(1-phenylvinyl)phenyl)benzenesulfonamide 1a (0.2 mmol), 1,2-di(3-bromophenyl)diselenide 2d (1.2 equiv, 0.24 mmol), Bu4NPF6 (0.4 mmol) and DCM (5 mL) were added successively at room temperature. The reaction flask was equipped with two Pt electrodes (1 cm x 1 cm). The electrolysis was carried out at room temperature (25 °C) using a constant current of 2 mA until the complete consumption of the starting material (TLC monitoring, ca. 12 h). After the completion of the reaction, the mixture was quenched with NaHCO3 (sat. aq. 15 mL) and extracted with CH2Cl2 (3 x 5 mL). The organic solvent was then concentrated in vacuo. The residue was purified by flash column chromatography using a mixture of ethyl acetate and petroleum ether as eluent to give the product 3d. n Bu4NPF6 (0.4 mmol) and DCM (5 mL). The reaction flask was equipped with two Pt electrodes (1 cm x 1 cm). The electrolysis was carried out at room temperature (25 °C) using a constant current of 2 mA until the complete consumption of the starting material (TLC monitoring, ca. 12 h). After the completion of the reaction, the mixture was quenched with NaHCO3 (sat. aq. 15 mL) and extracted with CH2Cl2 (3 x 5 mL). The organic solvent was then concentrated in vacuo. The residue was purified by flash column chromatography using a mixture of ethyl acetate and petroleum ether as eluent to give the product 3d.

[0082]

[0083] The spectral results are shown in Figure 8 and Figure 9 . The structure of compound 3d was confirmed by 1 H NMR, 13 C NMR spectra. In particular:

[0084] Rf(petroleum ether / ethyl acetate = 10:1): 0.11; Yellow liquid (65 mg, yield 51%). 1 H NMR (500 MHz, CDC13) δ 7.64 (d, J = 8.1 Hz, 2H), 7.52 (s, 1H), 7.36 (d, J = 7.1 Hz, 2H), 7.33 - 7.19 (m, 9H), 7.15 - 7.10 (m, 1H), 7.03 - 6.90 (m, 2H), 5.95 (d, J = 8.7 Hz, 1H), 4.25 (dd, J = 14.6, 3.6 Hz, 1H), 3.08 (dd, J = 11.4, 8.8 Hz, 1H), 3.00 - 2.86 (m, 2H), 2.40 (s, 3H), 2.04 - 1.95 (m, 1H), 1.87 - 1.77 (m, 1H), 1.66 (d, J = 16.3 Hz, 1H); 13C NMR (125MHz, CDCl3) δ143.20,142.01,141.85,140.25,138.74,137.69,135.22,132.66,131.96,131.43,130.90,130.27 ,130.00,129.45,128.95,128.56,128.52,128.34,128.01,127.72,127.32,122.75,50.93,38.45,35.85,33.74,21.54.

[0085] Example 5

[0086] The method for electrochemically-driven preparation of eight-membered selenium-containing benzo[a] nitrogen heterocyclic compounds under metal-free and oxidant-free conditions in this embodiment is as follows:

[0087] At room temperature, N-(but-3-en-1-yl)-4-methyl-N-(2-(1-phenylvinyl)phenyl)benzenesulfonamide 1a (0.2 mmol), 1,2-bis(4-methylphenyl)diselenoether 2e (1.2 equiv, 0.24 mmol), were added sequentially to the reaction flask. n Bu4NPF6 (0.4 mmol) and DCM (5 mL) were used in a reaction flask equipped with two Pt electrodes (1 cm × 1 cm). Electrolysis was carried out at room temperature (25 °C) using a constant current of 2 mA until the starting material was completely consumed (TLC monitoring, approximately 12 h). After the reaction was complete, the mixture was quenched with NaHCO3 (sat. aq. 15 mL) and extracted with CH2Cl2 (3 × 5 mL). The organic solvent was then concentrated under vacuum. The residue was purified by rapid column chromatography, using a mixture of ethyl acetate and petroleum ether as eluent to give product 3e.

[0088]

[0089] Spectral results as follows Figure 10 and Figure 11 As shown. Compound 3e 1 H NMR, 13 The structure of the compound was determined by C10 NMR spectroscopy. Specifically:

[0090] Rf (petroleum ether / ethyl acetate=10:1): 0.17; Yellow liquid (82 mg, yield 71%). 1H NMR(500MHz, CDCl3)δ7.63(d,J=8.1Hz,2H),7.35(d,J=7.1Hz,2H),7.30-7.17 (m,9H),7.11(dd,J=7.1,1.6Hz,1H),6.98-6.88(m,3H),5.96(d,J=8.7Hz,1H), 4.22(dd,J=14.6,3.6Hz,1H),3.01(dd,J=11.4,8.7Hz,1H),2.94-2.85(m,2H) ,2.38(s,3H),2.26(s,3H),2.02-1.95(m,1H),1.81-1.73(m,1H),1.62(s,1H); 13 C NMR (125MHz, CDCl3) δ143.18,142.17,142.06,140.33,138.36,137.77,137.09,133.76,133.33,130.97,129.83,129.46,12 8.85,128.62,128.58,128.18,127.98,127.75,127.22,125.90,50.98,38.54,36.09,33.71,21.57,21.12.; HRMS(ESI)calcd for C32H32NO2SSe[M+H]+:574.1313,found:574.1310.

[0091] Example 6

[0092] The method for electrochemically-driven preparation of eight-membered selenium-containing benzo[a] nitrogen heterocyclic compounds under metal-free and oxidant-free conditions in this embodiment is as follows:

[0093] At room temperature, N-(but-3-en-1-yl)-4-methyl-N-(2-(1-phenylvinyl)phenyl)benzenesulfonamide 1a (0.2 mmol), 1,2-bis(4-chlorophenyl)diselenoether 2f (1.2 equiv, 0.24 mmol), were added sequentially to the reaction flask. n Bu4NPF6 (0.4 mmol) and DCM (5 mL) were used in a reaction flask equipped with two Pt electrodes (1 cm × 1 cm). Electrolysis was carried out at room temperature (25 °C) using a constant current of 2 mA until the starting material was completely consumed (TLC monitoring, approximately 12 h). After the reaction was complete, the mixture was quenched with NaHCO3 (sat. aq. 15 mL) and extracted with CH2Cl2 (3 × 5 mL). The organic solvent was then concentrated under vacuum. The residue was purified by rapid column chromatography, using a mixture of ethyl acetate and petroleum ether as eluent to give product 3f.

[0094]

[0095] Spectral results as follows Figure 12 and Figure 13 As shown. Compound 3f 1 H NMR, 13 The structure of the compound was determined by C10 NMR spectroscopy. Specifically:

[0096] Rf (petroleum ether / ethyl acetate=10:1): 0.14; Yellow liquid (76 mg, yield 64%). 1 H NMR (500MHz, CDCl3) δ7.63(d,J=8.1Hz,2H),7.38-7.18(m,11H),7.09(d,J=8.4Hz,3H),6.90(d,J=7.4Hz,1H),5.94(d,J=8.7Hz,1H),4.23 (dd,J=14.6,3.7Hz,1H),3.02(dd,J=11.4,9.0Hz,1H),2.96-2.82(m,2H),2.39(s,3H),2.01-1.92(m,1H),1.85-1.75(m,1H),1.61(s,1H); 13 C NMR (125MHz, CDCl3) δ143.21,142.04,141.88,140.27,138.60,137.70,134.73,133.28,132.85,130.85,129.47 ,129.13,128.96,128.57,128.54,128.25,128.01,127.79,127.71,127.33,50.93,38.32,35.94,33.74,21.55.

[0097] Example 7

[0098] The method for electrochemically-driven preparation of eight-membered selenium-containing benzo[a] nitrogen heterocyclic compounds under metal-free and oxidant-free conditions in this embodiment is as follows:

[0099] At room temperature, N-(but-3-en-1-yl)-4-methyl-N-(2-(1-phenylvinyl)phenyl)benzenesulfonamide 1a (0.2 mmol), 1,2-bis(3,5-dimethylphenyl)diselenoether 2 g (1.2 equiv, 0.24 mmol) were added sequentially to the reaction flask. nBu4NPF6(0.4 mmol) and DCM (5 mL), reaction flask equipped with two Pt electrodes (1 cm x 1 cm). The electrolysis was carried out at 25 °C room temperature using a constant current of 2 mA until complete consumption of the starting material (TLC monitoring, ca. 12 h). After completion of the reaction, the mixture was quenched with NaHCO3(sat. aq. 15 mL) and extracted with CH2Cl2(3 x 5 mL). The organic solvents were then concentrated in vacuo. The residue was purified by flash column chromatography using a mixture of ethyl acetate and petroleum ether as eluent to give the product 3g.

[0100]

[0101] The spectroscopic results are shown in Figure 14 and Figure 15 . The structure of compound 3g was confirmed by 1 H NMR, 13 C NMR spectra. In particular:

[0102] Rf(petroleum ether / ethyl acetate = 10:1): 0.23; Yellow solid (84 mg, yield 71%): mp: 67-68 °C. 1 H NMR (500 MHz, CDC13) δ 7.64 (d, J = 8.1 Hz, 2H), 7.35 (d, J = 7.0 Hz, 2H), 7.29 - 7.17 (m, 7H), 7.13 (dd, J = 7.1, 1.9 Hz, 1H), 7.02 (s, 2H), 6.96 - 6.91 (m, 1H), 6.80 (s, 1H), 5.96 (d, J = 8.7 Hz, 1H), 4.24 (dd, J = 14.6, 3.5 Hz, 1H), 3.06 (dd, J = 11.5, 8.3 Hz, 1H), 2.95 - 2.85 (m, 2H), 2.39 (s, 3H), 2.20 (s, 6H), 2.08 - 2.00 (m, 1H), 1.83 - 1.73 (m, 1H), 1.65 (d, J = 13.5 Hz, 1H); 13 C NMR (125 MHz, CDC13) δ 143.17, 142.22, 142.01, 140.35, 138.59, 138.36, 137.76, 133.27, 130.90, 130.69, 129.63, 129.45, 128.85, 128.59, 128.25, 127.97, 127.75, 127.21, 51.02, 38.74, 35.71, 33.65, 21.55, 21.15.

[0103] Example 8

[0104] The method of electrochemically driven preparation of eight-membered selenium-containing benzazepine compounds without metal and oxidant in this embodiment is as follows:

[0105] At room temperature, N-(but-3-en-1-yl)-4-methyl-N-(2-(1-phenylvinyl)phenyl)benzenesulfonamide 1a (0.2 mmol), 1,2-di(2-naphthyl)diselenide 2h (1.2 equiv, 0.24 mmol), Bu4NPF6(0.4 mmol) and DCM (5 mL) were added into the reaction flask, which was equipped with two Pt electrodes (1 cm x 1 cm). The electrolysis was carried out at room temperature of 25 °C using a constant current of 2 mA until the complete consumption of the starting material (TLC monitoring, about 12 h). After the reaction was completed, the mixture was quenched with NaHCO3(sat. aq. 15 mL) and extracted with CH2Cl2(3 x 5 mL). Then the organic solvent was concentrated in vacuo. The residue was purified by flash column chromatography using a mixture of ethyl acetate and petroleum ether as eluent to give the product 3h. n Bu4NPF6(0.4 mmol) and DCM (5 mL), which was equipped with two Pt electrodes (1 cm x 1 cm). The electrolysis was carried out at room temperature of 25 °C using a constant current of 2 mA until the complete consumption of the starting material (TLC monitoring, about 12 h). After the reaction was completed, the mixture was quenched with NaHCO3(sat. aq. 15 mL) and extracted with CH2Cl2(3 x 5 mL). Then the organic solvent was concentrated in vacuo. The residue was purified by flash column chromatography using a mixture of ethyl acetate and petroleum ether as eluent to give the product 3h.

[0106]

[0107] The spectral results are shown in Figure 16 and Figure 17 . The structure of compound 3h is known from 1 H NMR, 13 C NMR spectra. Specifically:

[0108] Rf(petroleum ether / ethyl acetate = 10:1): 0.11; Yellow solid (68 mg, yield 56%): mp: 182-183 °C. 1 H NMR (500 MHz, CDC13) δ 8.36 (d, J = 8.0 Hz, 1H), 7.78 (d, J = 7.3 Hz, 1H), 7.72 - 7.59 (m, 4H), 7.47 (td, J = 13.1, 6.6 Hz, 2H), 7.36 (d, J = 6.9 Hz, 2H), 7.30 - 7.16 (m, 8H), 7.05 - 6.98 (m, 1H), 6.92 - 6.83 (m, 1H), 5.99 (d, J = 8.6 Hz, 1H), 4.19 (dd, J = 14.6, 3.4 Hz, 1H), 3.08 (dd, J = 11.4, 8.9 Hz, 1H), 3.01 - 2.94 (m, 1H), 2.88 - 2.80 (m, 1H), 2.39 (s, 3H), 1.98 - 1.89 (m, 1H), 1.82 - 1.73 (m, 1H), 1.61 (s, 1H); 13C NMR (125MHz, CDCl3) δ143.14,142.03,141.97,140.22,138.43,137.72,134.41,133.92,133.25,133.19,130.88,129.42,128.98,12 8.81,128.59,128.56,128.50,128.46,128.16,127.96,127.73,127.21,126.67,126.17,125.65,50.90,38.53,36.03,33.76,21.53.

[0109] Example 9

[0110] The method for electrochemically-driven preparation of eight-membered selenium-containing benzo[a] nitrogen heterocyclic compounds under metal-free and oxidant-free conditions in this embodiment is as follows:

[0111] At room temperature, N-(but-3-en-1-yl)-4-methyl-N-(5-methyl-2-(1-phenylvinyl)phenyl)benzenesulfonamide 1b (0.2 mmol), diphenyldiselenes 2a (0.2 mmol), and [other ingredients] were added sequentially to the reaction flask. n Bu4NPF6 (0.4 mmol) and DCM (5 mL) were used in a reaction flask equipped with two Pt electrodes (1 cm × 1 cm). Electrolysis was carried out at room temperature (25 °C) using a constant current of 2 mA until the starting material was completely consumed (TLC monitoring, approximately 12 h). After the reaction was complete, the mixture was quenched with NaHCO3 (sat. aq. 15 mL) and extracted with CH2Cl2 (3 × 5 mL). The organic solvent was then concentrated under vacuum. The residue was purified by rapid column chromatography, using a mixture of ethyl acetate and petroleum ether as eluent to give product 3i.

[0112]

[0113] Spectral results as follows Figure 18 and Figure 19 As shown. Compound 3i 1 H NMR, 13 The structure of the compound was determined by C10 NMR spectroscopy. Specifically:

[0114] Rf (petroleum ether / ethyl acetate=10:1): 0.17; Yellow liquid (82 mg, yield 72%). 1H NMR (500MHz, CDCl3) δ7.62 (d, J = 8.1Hz, 2H), 7.43-7.32 (m, 4H), 7.28-7.12 (m, 8H ),7.06(d,J=7.8Hz,1H),6.99(d,J=7.9Hz,1H),6.76(s,1H),5.91(d,J=8.6Hz,1 H),4.20(dd,J=14.6,3.4Hz,1H),3.05(dd,J=11.3,8.7Hz,1H),2.96-2.86(m,2H ),2.37(s,3H),2.26(s,3H),2.07-1.99(m,1H),1.77-1.67(m,1H),1.61(s,1H); 13 C NMR (125MHz, CDCl3) δ143.19,142.17,140.14,138.96,138.46,137.76,133.16,132.84,130.64,130.06,12 9.36,129.16,129.03,128.58,127.99,127.84,127.20,126.96,50.82,38.65,35.84,33.78,21.57,21.02.

[0115] Example 10

[0116] The method for electrochemically-driven preparation of eight-membered selenium-containing benzo[a] nitrogen heterocyclic compounds under metal-free and oxidant-free conditions in this embodiment is as follows:

[0117] At room temperature, N-(but-3-en-1-yl)-N-(4-chloro-2-(1-phenylvinyl)phenyl)-4-methylbenzenesulfonamide 1c (0.2 mmol), diphenyldiselenes 2a (1.2 equiv, 0.24 mmol), were added sequentially to the reaction flask. n Bu4NPF6 (0.4 mmol) and DCM (5 mL) were used in a reaction flask equipped with two Pt electrodes (1 cm × 1 cm). Electrolysis was carried out at room temperature (25 °C) using a constant current of 2 mA until the starting material was completely consumed (TLC monitoring, approximately 12 h). After the reaction was complete, the mixture was quenched with NaHCO3 (sat. aq. 15 mL) and extracted with CH2Cl2 (3 × 5 mL). The organic solvent was then concentrated under vacuum. The residue was purified by rapid column chromatography, using a mixture of ethyl acetate and petroleum ether as eluent to give product 3j.

[0118]

[0119] Spectral results as follows Figure 20 and Figure 21 As shown. Compound 3J1 H NMR, 13 C NMR spectrum to determine the structure of the compound. Specifically:

[0120] Rf(petroleum ether / ethyl acetate = 10:1): 0.14; Yellow solid (68 mg, yield 57%): mp: 78-79 °C. 1 H NMR (500 MHz, CDC13) δ 7.61 (d, J = 8.1 Hz, 2H), 7.40-7.27 (m, 7H), 7.23-7.14 (m, 6H), 7.08 (d, J = 2.3 Hz, 1H), 6.83 (d, J = 8.5 Hz, 1H), 5.99 (d, J = 8.7 Hz, 1H), 4.23 (dd, J = 14.6, 3.7 Hz, 1H), 3.05-2.93 (m, 2H), 2.89-2.79 (m, 1H), 2.40 (s, 3H), 1.96-1.87 (m, 1H), 1.83-1.73 (m, 1H), 1.63 (s, 1H); 13 C NMR (125 MHz, CDC13) δ 143.82, 143.41, 141.28, 138.81, 137.50, 137.41, 134.08, 133.96, 133.56, 130.75, 129.85, 129.53, 129.16, 129.00, 128.54, 128.15, 127.68, 127.51, 127.23, 50.96, 38.25, 35.39, 33.56, 21.54.

[0121] Example 11

[0122] The method for preparing octa-membered selenium-containing benzazepine compounds electrochemically driven under the conditions of no metal and no oxidant in this example is as follows:

[0123] At room temperature, N-(4-bromo-2-(1-phenylvinyl)phenyl)-N-(but-3-en-1-yl)-4- methylbenzenesulfonamide 1d (0.2 mmol), diphenyl diselenide 2a (1.2 equiv, 0.24 mmol), potassium carbonate (1.2 equiv, 0.24 mmol) and 1,4-dioxane (2 mL) were sequentially added into a reaction bottle. nBu4NPF6(0.4 mmol) and DCM (5 mL), reaction flask equipped with two Pt electrodes (1 cm x 1 cm). The electrolysis was carried out at 25 °C room temperature using a constant current of 2 mA until complete consumption of the starting material (TLC monitoring, ca. 12 h). After completion of the reaction, the mixture was quenched with NaHC03(sat. aq. 15 mL) and extracted with CH2CI2(3 x 5 mL). The organic solvents were then concentrated in vacuo. The residue was purified by flash column chromatography using a mixture of ethyl acetate and petroleum ether as eluent to give the product 3k.

[0124]

[0125] The results of the spectroscopic analysis are shown in Figure 22 and Figure 23 . The structure of compound 3k was confirmed by 1 H NMR, 13 C NMR spectroscopy. In particular:

[0126] Rf(petroleum ether / ethyl acetate = 10: 1): 0.14; Yellow liquid (74 mg, yield 58%). 1 H NMR (500 MHz, CDC13) δ 7.62 (d, J = 8.1 Hz, 2H), 7.39 (dd, J = 7.1, 5.3 Hz, 4H), 7.29 - 7.13 (m, 9H), 7.08 (dd, J = 7.2, 1.7 Hz, 1H), 6.91 - 6.87 (m, 1H), 5.97 (d, J = 8.7 Hz, 1H), 4.23 (dd, J = 14.6, 3.6 Hz, 1H), 3.05 (dd, J = 11.5, 8.8 Hz, 1H), 2.96 (dd, J = 11.6, 5.8 Hz, 1H), 2.92 - 2.84 (m, 1H), 2.41 (s, 3H), 2.01 (dd, J = 17.0, 7.8 Hz, 1H), 1.84 (dt, J = 10.4, 8.5 Hz, 1H), 1.63 (d, J = 13.7 Hz, 1H); 13 C NMR (125 MHz, CDC13) δ 143.29, 141.67, 140.89, 140.32, 137.64, 137.44, 133.74, 133.23, 131.07, 130.74, 130.18, 129.77, 129.49, 129.12, 129.04, 128.60, 128.36, 127.65, 127.06, 121.38, 50.95, 38.66, 35.64, 33.79, 21.56.

[0127] Example 12

[0128] The method of electrochemically driven preparation of eight-membered selenium-containing benzazepine compounds without metal and oxidant in this example is as follows:

[0129] At room temperature, N-(but-3-en-1-yl)-4-methyl-N-(2-(1-(p-tolyl)vinyl)phenyl)benzenesulfonamide 1e (0.2 mmol), diphenyl diselenide 2a (1.2 equiv, 0.24 mmol), Bu4NPF6(0.4 mmol) and DCM (5 mL) were added into the reaction flask, which was equipped with two Pt electrodes (1 cm x 1 cm). The electrolysis was carried out at room temperature (25 °C) using a constant current of 2 mA until the complete consumption of the starting material (TLC monitoring, about 12 h). After the reaction was completed, the mixture was quenched with NaHCO3(sat. aq. 15 mL) and extracted with CH2Cl2(3 x 5 mL). The organic solvent was then concentrated in vacuo. The residue was purified by flash column chromatography using a mixture of ethyl acetate and petroleum ether as eluent to give the product 3l. n Bu4NPF6(0.4 mmol) and DCM (5 mL), which was equipped with two Pt electrodes (1 cm x 1 cm). The electrolysis was carried out at room temperature (25 °C) using a constant current of 2 mA until the complete consumption of the starting material (TLC monitoring, about 12 h). After the reaction was completed, the mixture was quenched with NaHCO3(sat. aq. 15 mL) and extracted with CH2Cl2(3 x 5 mL). The organic solvent was then concentrated in vacuo. The residue was purified by flash column chromatography using a mixture of ethyl acetate and petroleum ether as eluent to give the product 3l.

[0130]

[0131] The spectral results are shown in Figure 24 and Figure 25 . The structure of compound 3l was confirmed by 1 H NMR, 13 C NMR spectra. Specifically:

[0132] Rf(petroleum ether / ethyl acetate = 10:1): 0.17; Yellow liquid (69 mg, yield 60%). 1 H NMR (500 MHz, CDC13) δ 7.63 (d, J = 8.1 Hz, 2H), 7.40 (d, J = 6.2 Hz, 2H), 7.25 - 7.18 (m, 6H), 7.18 - 7.12 (m, 4H), 7.09 (d, J = 7.9 Hz, 2H), 6.93 (d, J = 7.2 Hz, 1H), 5.93 (d, J = 8.7 Hz, 1H), 4.23 (dd, J = 14.6, 3.6 Hz, 1H), 3.06 (dd, J = 11.4, 8.6 Hz, 1H), 2.98 - 2.85 (m, 2H), 2.40 (s, 3H), 2.34 (s, 3H), 2.05 - 1.96 (m, 1H), 1.77 (dt, J = 18.7, 9.4 Hz, 1H), 1.62 (d, J = 14.0 Hz, 1H); 13C NMR (125MHz, CDCl3) δ143.12,142.25,140.28,139.13,138.25,137.76,136.94,133.17,132.25,130.95,129.94,12 9.40,128.98,128.81,128.69,128.56,128.40,128.18,127.75,126.95,50.95,38.54,35.80,33.71,21.53,21.18.

[0133] Example 13

[0134] The method for electrochemically-driven preparation of eight-membered selenium-containing benzo[a] nitrogen heterocyclic compounds under metal-free and oxidant-free conditions in this embodiment is as follows:

[0135] At room temperature, N-(but-3-en-1-yl)-4-methyl-N-(4-methyl-2-(1-phenylvinyl)phenyl)benzenesulfonamide 1f (0.2 mmol), diphenyldiselenes 2a (1.2 equiv, 0.24 mmol), were added sequentially to the reaction flask. n Bu4NPF6 (0.4 mmol) and DCM (5 mL) were used in a reaction flask equipped with two Pt electrodes (1 cm × 1 cm). Electrolysis was carried out at room temperature (25 °C) using a constant current of 2 mA until the starting material was completely consumed (TLC monitoring, approximately 12 h). After the reaction was complete, the mixture was quenched with NaHCO3 (sat. aq. 15 mL) and extracted with CH2Cl2 (3 × 5 mL). The organic solvent was then concentrated under vacuum. The residue was purified by rapid column chromatography, using a mixture of ethyl acetate and petroleum ether as eluent to give product 3 mL.

[0136]

[0137] Spectral results as follows Figure 26 , Figure 27 and Figure 28 As shown. Compound 3m 1 H NMR, 13 C NMR spectrum, 19 The structure of the compound was determined by F NMR. Specifically:

[0138] Rf (petroleum ether / ethyl acetate=10:1): 0.26; Yellow liquid (69 mg, yield 58%). 1H NMR (500 MHz, CDC13) δ 7.63 (d, J = 8.0 Hz, 2H), 7.38 (d, J = 6.6 Hz, 2H), 7.26 - 7.12 (m, 7H), 7.11 - 7.05 (m, 3H), 7.00 - 6.93 (m, 1H), 6.65 (dd, J = 9.1, 2.1 Hz, 1H), 5.92 (d, J = 8.7 Hz, 1H), 4.19 (dd, J = 14.6, 3.6 Hz, 1H), 3.05 (dd, J = 11.4, 8.6 Hz, 1H), 2.95 (dd, J = 11.5, 6.0 Hz, 1H), 2.89 - 2.81 (m, 1H), 2.40 (s, 3H), 2.34 (s, 3H), 2.00 - 1.90 (m, 1H), 1.80 - 1.70 (m, 1H), 1.64 (d, J = 13.7 Hz, 1H); 13 C NMR (125 MHz, CDC13) δ 162.94, 160.95, 143.50, 141.28 (d, J = 9.2 Hz), 138.94, 138.50 (d, J = 3.5 Hz), 137.37 (d, J = 12.0 Hz), 137.13, 133.22, 132.50, 132.13 (d, J = 8.8 Hz), 129.76, 129.57, 129.01, 128.78, 128.34, 127.72, 127.04, 115.73 (d, J = 21.0 Hz), 115.43 (d, J = 21.0 Hz), 50.84, 38.54, 35.60, 33.67, 21.56, 21.19; 19 F NMR (471 MHz, CDC13) δ -112.12.

[0139] Example 14

[0140] The method of electrochemically driving the preparation of eight-membered selenium-containing benzazepine compounds without metal and oxidant in this embodiment is as follows:

[0141] At room temperature, N-(but-3-en-1-yl)-N-(4-chloro-2-(1-(p-tolyl)vinyl)phenyl)-4- methylbenzenesulfonamide 1g (0.2 mmol), diphenyl diselenide 2a (1.2 equiv, 0.24 mmol), potassium carbonate (1.2 equiv, 0.24 mmol) and 1,4-dioxane (2 mL) were sequentially added into a reaction bottle. nBu4NPF6(0.4 mmol) and DCM (5 mL), reaction flask equipped with two Pt electrodes (1 cm x 1 cm). The electrolysis was carried out at 25 °C room temperature using a constant current of 2 mA until complete consumption of the starting material (TLC monitoring, ca. 12 h). After completion of the reaction, the mixture was quenched with NaHC03(sat. aq. 15 mL) and extracted with CH2CI2(3 x 5 mL). The organic solvents were then concentrated in vacuo. The residue was purified by flash column chromatography using a mixture of ethyl acetate and petroleum ether as eluent to give the product 3n.

[0142]

[0143] The spectroscopic results are shown in Figure 29 and Figure 30 . The structure of compound 3n was confirmed by 1 H NMR, 13 C NMR spectra. In particular:

[0144] Rf(petroleum ether / ethyl acetate = 10:1): 0.23; Yellow liquid (75 mg, yield 62%). 1 H NMR (500 MHz, CDCI3) δ 7.60 (d, J = 8.1 Hz, 2H), 7.38 (d, J = 6.5 Hz, 2H), 7.25 - 7.21 (m, 2H), 7.17 (ddd, J = 13.7, 11.1, 7.2 Hz, 6H), 7.09 (dd, J = 12.2, 5.1 Hz, 3H), 6.82 (d, J = 8.5 Hz, 1 H), 5.94 (d, J = 8.7 Hz, 1 H), 4.21 (dd, J = 14.6, 3.6 Hz, 1 H), 3.03 - 2.94 (m, 2H), 2.86 - 2.77 (m, 1 H), 2.38 (s, 3H), 2.35 (s, 3H), 1.95 - 1.85 (m, 1 H), 1.79 - 1.71 (m, 1 H), 1.63 (d, J = 16.1 Hz, 1 H); 13 C NMR (125 MHz, CDCI3) δ 143.96, 143.39, 138.80, 138.46, 137.44, 137.28, 133.92, 133.54, 133.24, 130.76, 129.88, 129.52, 129.23, 129.00, 128.97, 128.87, 128.38, 127.69, 127.20, 50.96, 38.23, 35.43, 33.56, 21.55, 21.21.

[0145] Example 15

[0146] The method of electrochemically driving the preparation of eight-membered selenium-containing benzazepine compounds without metal and oxidant in this embodiment is as follows:

[0147] At room temperature, N-(but-3-en-1-yl)-N-(2'-cyano-3-(1-phenylvinyl)-[1,1'-biphenyl]-4-yl)-4-methylbenzenesulfonamide 1h (0.2 mmol), diphenyl diselenide 2a (1.2 equiv, 0.24 mmol), Bu4NPF6(0.4 mmol) and DCM (5 mL) were added into the reaction bottle successively, which was equipped with two Pt electrodes (1 cm x 1 cm). The electrolysis was carried out at room temperature of 25 °C using a constant current of 2 mA until the complete consumption of the starting material (TLC monitoring, about 12 h). After the reaction was completed, the mixture was quenched with NaHCO3(sat. aq. 15 mL) and extracted with CH2Cl2(3 x 5 mL). Then the organic solvent was concentrated in vacuum. The residue was purified by flash column chromatography using a mixed solvent of ethyl acetate and petroleum ether as eluent to obtain the product 3o. n Bu4NPF6(0.4 mmol) and DCM (5 mL), which was equipped with two Pt electrodes (1 cm x 1 cm). The electrolysis was carried out at room temperature of 25 °C using a constant current of 2 mA until the complete consumption of the starting material (TLC monitoring, about 12 h). After the reaction was completed, the mixture was quenched with NaHCO3(sat. aq. 15 mL) and extracted with CH2Cl2(3 x 5 mL). Then the organic solvent was concentrated in vacuum. The residue was purified by flash column chromatography using a mixed solvent of ethyl acetate and petroleum ether as eluent to obtain the product 3o.

[0148]

[0149] The spectrum results are shown in Figure 31 and Figure 32 . The structure of compound 3o is known from 1 H NMR, 13 C NMR spectrum. Specifically:

[0150] Rf(petroleum ether / ethyl acetate = 10:1): 0.06; Yellow liquid (70 mg, yield 53%). 1 H NMR (500 MHz, CDC13) δ 7.76 (d, J = 7.8 Hz, 1H), 7.63 (dd, J = 13.0, 4.7 Hz, 3H), 7.49 (dt, J = 12.0, 8.1 Hz, 6H), 7.41 (d, J = 7.2 Hz, 3H), 7.20 (ddd, J = 16.4, 15.2, 7.6 Hz, 7H), 6.91 (d, J = 7.9 Hz, 1H), 6.07 (d, J = 8.7 Hz, 1H), 4.25 (dd, J = 14.6, 3.5 Hz, 1H), 3.08 (dd, J = 11.5, 8.8 Hz, 1H), 3.01 - 2.88 (m, 2H), 2.40 (s, 3H), 2.08 - 2.02 (m, 1H), 1.88 - 1.81 (m, 1H), 1.66 (s, 1H); 13C NMR (125 MHz, CDC13) δ 145.39, 143.26, 142.32, 141.80, 140.34, 137.80, 137.69, 136.86, 134.07, 133.84, 133.28, 132.85, 130.98, 130.08, 129.78, 129.50, 129.04, 128.84, 128.58, 128.41, 127.66, 127.38, 127.05, 118.93, 111.04, 51.00, 38.68, 35.70, 33.81, 21.55.

[0151] Example 16

[0152] The method of electrochemically driving the preparation of eight-membered selenium-containing benzazepine compounds without metal and oxidant in this example is as follows:

[0153] At room temperature, N-(4-chloro-2-(1-phenylvinyl)phenyl)-N-(but-3-en-1-yl)-4- methylbenzenesulfonamide 1i (0.2 mmol), diphenyl diselenide 2a (1.2 equiv, 0.24 mmol), K2CO3 (1.2 equiv, 0.24 mmol) and DCM (5 mL) were added into a reaction flask equipped with two Pt electrodes (1 cm x 1 cm). The electrolysis was carried out at room temperature (25 °C) using a constant current of 2 mA until the complete consumption of the starting material (TLC monitoring, about 12 h). After the reaction was completed, the mixture was quenched with NaHCO3 (sat. aq. 15 mL) and extracted with CH2Cl2 (3 x 5 mL). Then the organic solvent was concentrated in vacuo. The residue was purified by flash column chromatography using a mixture of ethyl acetate and petroleum ether as eluent to give the product 3p. n Bu4NPF6 (0.4 mmol) and DCM (5 mL), and the reaction flask was equipped with two Pt electrodes (1 cm x 1 cm). The electrolysis was carried out at room temperature (25 °C) using a constant current of 2 mA until the complete consumption of the starting material (TLC monitoring, about 12 h). After the reaction was completed, the mixture was quenched with NaHCO3 (sat. aq. 15 mL) and extracted with CH2Cl2 (3 x 5 mL). Then the organic solvent was concentrated in vacuo. The residue was purified by flash column chromatography using a mixture of ethyl acetate and petroleum ether as eluent to give the product 3p.

[0154]

[0155] The spectral results are shown in Figure 33 and Figure 34 . The structure of compound 3p was determined by 1 H NMR, 13 C NMR spectra. Specifically:

[0156] Rf (petroleum ether / ethyl acetate=10:1):0.14; Yellow liquid (68mg, yield 57%).1H NMR(500MHz, CDCl3)δ7.62(d,J=8.2Hz,2H),7.39(dd,J=7.7,1.4Hz,2H),7.29-7.11(m,1 1H),7.08(dd,J=7.3,1.8Hz,1H),6.89(dd,J=7.6,1.2Hz,1H),5.96(d,J=8.7Hz,1H),4.23 (dd,J=14.6,3.5Hz,1H),3.05(dd,J=11.6,8.8Hz,1H),2.96(dd,J=11.6,5.8Hz,1H),2.92 -2.84(m,1H),2.40(s,3H),2.05-1.96(m,1H),1.88-1.79(m,1H),1.63(d,J=13.5Hz,1H); 13 C NMR (125MHz, CDCl3) δ143.29,141.76,140.46,140.31,137.66,137.40,133.69,133.23,133.10,130.75,129.85 ,129.78,129.50,129.10,129.04,128.59,128.36,128.12,127.65,127.06,50.96,38.64,35.67,33.81,21.55.

[0157] Example 17

[0158] The method for electrochemically-driven preparation of eight-membered selenium-containing benzo[a] nitrogen heterocyclic compounds under metal-free and oxidant-free conditions in this embodiment is as follows:

[0159] At room temperature, N-(but-3-en-1-yl)-4-methyl-N-(5-bromo-2-(1-phenylvinyl)phenyl)benzenesulfonamide 1j (0.2 mmol), diphenyldiselenes 2a (0.2 mmol), were added sequentially to the reaction flask. n Bu4NPF6 (0.4 mmol) and DCM (5 mL) were used in a reaction flask equipped with two Pt electrodes (1 cm × 1 cm). Electrolysis was carried out at room temperature (25 °C) using a constant current of 2 mA until the starting material was completely consumed (TLC monitoring, approximately 12 h). After the reaction was complete, the mixture was quenched with NaHCO3 (sat. aq. 15 mL) and extracted with CH2Cl2 (3 × 5 mL). The organic solvent was then concentrated under vacuum. The residue was purified by rapid column chromatography, using a mixture of ethyl acetate and petroleum ether as eluent to give product 3q.

[0160]

[0161] The results of the spectra are shown in Figure 35 and Figure 36 The structure of compound 3q was confirmed by 1 H NMR, 13 C NMR spectra. In particular:

[0162] Rf(petroleum ether / ethyl acetate = 10:1): 0.23; Yellow liquid (69 mg, yield 54%). 1 H NMR (500 MHz, CDC13) δ 7.63 (d, J = 8.1 Hz, 2H), 7.42 - 7.36 (m, 3H), 7.33 (d, J = 6.9 Hz, 2H), 7.30 - 7.23 (m, 5H), 7.21 - 7.13 (m, 3H), 7.05 (s, 1H), 6.99 (d, J = 8.3 Hz, 1H), 5.97 (d, J = 8.7 Hz, 1H), 4.20 (dd, J = 14.6, 3.6 Hz, 1H), 3.06 (dd, J = 11.4, 8.7 Hz, 1H), 2.96 (dd, J = 11.6, 6.0 Hz, 1H), 2.85 (dd, J = 19.7, 7.6 Hz, 1H), 2.42 (s, 3H), 2.00 - 1.93 (m, 1H), 1.82 - 1.71 (m, 1H), 1.64 (d, J = 13.4 Hz, 1H); 13 C NMR (125 MHz, CDC13) δ 143.58, 141.46, 141.36, 141.26, 137.61, 137.19, 133.64, 133.28, 132.16, 131.76, 131.48, 129.65, 129.56, 129.03, 128.53, 128.10, 127.72, 127.47, 127.11, 121.41, 50.81, 38.56, 35.53, 33.47, 21.56.

[0163] Example 18

[0164] The method of electrochemically driving the preparation of eight-membered selenium-containing benzazepine compounds without metal and oxidant in this example is as follows:

[0165] To a reaction flask equipped with a magnetic bar, N-(but-3-en-1-yl)-N-(4-methoxy-2-(1- phenylvinyl)phenyl)-4-methylbenzenesulfonamide 1k (0.2 mmol), diphenyl diselenide 2a (1.2 equiv, 0.24 mmol), Bu4NPF6(0.4 mmol) and DCM (5 mL) were added successively at room temperature. The reaction flask was equipped with two Pt electrodes (1 cm x 1 cm). The electrolysis was carried out at room temperature (25 °C) using a constant current of 2 mA until complete consumption of the starting material (TLC monitoring, ca. 12 h). After completion of the reaction, the mixture was quenched with NaHCO3(sat. aq. 15 mL) and extracted with CH2Cl2(3 x 5 mL). The organic solvents were then concentrated in vacuo. The residue was purified by flash column chromatography using a mixture of ethyl acetate and petroleum ether as eluent to give the product 3r. n Bu4NPF6(0.4 mmol) and DCM (5 mL), the reaction flask was equipped with two Pt electrodes (1 cm x 1 cm). The electrolysis was carried out at room temperature (25 °C) using a constant current of 2 mA until complete consumption of the starting material (TLC monitoring, ca. 12 h). After completion of the reaction, the mixture was quenched with NaHCO3(sat. aq. 15 mL) and extracted with CH2Cl2(3 x 5 mL). The organic solvents were then concentrated in vacuo. The residue was purified by flash column chromatography using a mixture of ethyl acetate and petroleum ether as eluent to give the product 3r.

[0166]

[0167] The spectroscopic results are shown in Figure 37 and Figure 38 . The structure of compound 3r was confirmed by 1 H NMR, 13 C NMR spectroscopy. In particular:

[0168] Rf(petroleum ether / ethyl acetate = 10:1): 0.11; Yellow liquid (77 mg, yield 65%). 1 H NMR (500 MHz, CDC13) δ 7.62 (d, J = 8.1 Hz, 2H), 7.44 - 7.34 (m, 4H), 7.30 - 7.12 (m, 8H), 6.81 (d, J = 8.8 Hz, 1H), 6.75 (dd, J = 8.8, 2.9 Hz, 1H), 6.59 (d, J = 2.8 Hz, 1H), 5.95 (d, J = 8.7 Hz, 1H), 4.23 (dd, J = 14.5, 3.7 Hz, 1H), 3.70 (s, 3H), 3.06 (dd, J = 11.4, 8.6 Hz, 1H), 2.96 (dd, J = 11.5, 6.0 Hz, 1H), 2.90 - 2.82 (m, 1H), 2.39 (s, 3H), 2.10 - 2.02 (m, 1H), 1.83 - 1.73 (m, 1H), 1.64 (s, 1H); 13C NMR (125 MHz, CDC13) δ 158.83, 143.23, 143.08, 141.71, 138.45, 137.77, 133.27, 133.20, 133.14, 129.94, 129.49, 129.41, 128.98, 128.55, 127.98, 127.69, 127.23, 126.99, 115.09, 114.91, 55.51, 51.09, 38.53, 35.80, 33.85, 21.54.

[0169] Example 19

[0170] The kind and amount of electrolyte, the kind of solvent and electrolysis conditions were adjusted based on Example 1. The specific reaction system and screening results are shown in Table 1. From Table 1, it can be seen that different raw material types and electrolysis conditions have an effect on the yield of the target product. The yield of the target product in the reaction system of item 8 can reach 70%.

[0171] Table 1

[0172] Entry electrolyte Solvent(mL) electrode Yield(%) 1 n Bu4NBF4(2 eq) ​ DCE Pt(+) / Pt(-) 33 2 n Bu4NI (2 eq) ​ DCE Pt(+) / Pt(-) 0 3 n Bu4NPF6(2 eq) ​ DCE Pt(+) / Pt(-) 57 4 n Bu4NClO4(2 eq) ​ DCE Pt(+) / Pt(-) 27 5 n Bu4NPF6(2 eq) ​ DMF Pt(+) / Pt(-) 0 6 n Bu4NPF6(2 eq) ​ THF Pt(+) / Pt(-) 0 7 n Bu4NPF6(2 eq) ​ MeOH Pt(+) / Pt(-) 0 8 n Bu4NPF6(2 eq) ​ DCM Pt(+) / Pt(-) 70 9 n Bu4NPF6(2 eq) ​ DCM C(+) / C(-) 0 10 n Bu4NPF6(2 eq) ​ DCM C(+) / Pt(-) 37 11 n Bu4NPF6(1 eq) ​ DCM Pt(+) / Pt(-) 63 12 n Bu4NPF6(3 eq) ​ DCM Pt(+) / Pt(-) 68

[0173] The above description is merely preferred embodiments of the present application, and is not intended to limit the present application. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present application shall be included in the protection scope of the present application.

Claims

1. A method for preparing an eight-membered selenium-containing benzo[a]azine heterocyclic compound, comprising the following steps: by N -(but-3-en-1-yl)-4-methyl- N Using a 2-(1-phenylvinyl)phenyl)benzenesulfonamide compound as a substrate, selenium ether is anoly oxidized under electrochemical drive to generate selenium radicals. The selenium radicals and the substrate are coupled and cyclized to obtain an eight-membered selenium-containing benzo[a] nitrogen heterocyclic compound. N -(but-3-en-1-yl)-4-methyl- N The molar ratio of the 2-(1-phenylvinyl)phenyl)benzenesulfonamide compound to the selenium ether is 1:(1-1.2). Electrolysis using Pt electrodes with a constant current of 2mA; N -(but-3-en-1-yl)-4-methyl- N The structural formula of the -(2-(1-phenylvinyl)phenyl)benzenesulfonamide compound is shown in Formula 1. , Among them, R 1 Independently selected from one of the substituents H, CH3, Cl, and Br; R 2 Independent selection o One of the following substituents: -CNPh, H, CH3, OCH3, F, Cl, Br; The structural formula of selenium ether is shown in Formula 2, where Formula 2 is R 3 SeSeR 3 Among them, R 3 Independently selected from benzene rings, naphthalene, and containing one or more substituted benzene rings of halogen, methyl, and methoxy groups; The general formula for the reaction is shown below: 。 2. The method for preparing an eight-membered selenium-containing benzo[a]azine heterocyclic compound according to claim 1, characterized in that, Includes the following steps: join in N -(but-3-en-1-yl)-4-methyl- N 2-(1-Phenylacetyl)phenyl)benzenesulfonamide compounds, selenium ethers, n Bu4NPF6 and DCM were reacted to obtain a mixture; the mixture was then electrolyzed until... N -(but-3-en-1-yl)-4-methyl- N The 2-(1-phenylvinyl)phenyl)benzenesulfonamide compound was completely consumed; after the reaction was complete, the reaction was quenched and extracted; the organic solvent was concentrated. Purification was performed, and the compound was eluted with an eluent to obtain an eight-membered selenium-containing benzo[a]azine heterocyclic compound.

3. The method for preparing an eight-membered selenium-containing benzo[a]azine heterocyclic compound according to claim 2, characterized in that, N -(but-3-en-1-yl)-4-methyl- N 2-(1-Phenylacetyl)phenyl)benzenesulfonamide compounds, n The molar ratio of Bu4NPF6 to selenide is 1:(1-3):(1-1.2). N -(but-3-en-1-yl)-4-methyl- N The molar volume ratio of 2-(1-phenylvinyl)phenyl)benzenesulfonamide compound to DCM was 0.2 mmol: 5 mL.

4. The method for preparing an eight-membered selenium-containing benzo[a]azine heterocyclic compound according to claim 2, characterized in that, After the reaction was complete, the mixture was quenched with NaHCO3 and extracted with CH2Cl2; then the organic solvent was concentrated under vacuum; the residue was purified by rapid column chromatography, and the eight-membered selenium-containing benzo[a]azine heterocyclic compound was obtained by using a mixed solvent of ethyl acetate and petroleum ether as the eluent.

5. The method for preparing an eight-membered selenium-containing benzo[a]azine heterocyclic compound according to claim 2, characterized in that, The mixture was electrolyzed at a constant current of 2mA at room temperature using Pt electrodes.

6. The method for preparing an eight-membered selenium-containing benzo[a]azine heterocyclic compound according to any one of claims 1-5, characterized in that, N -(but-3-en-1-yl)-4-methyl- N -(2-(1-phenylvinyl)phenyl)benzenesulfonamide compounds are selected from one or more of the following compounds: N -(but-3-en-1-yl)-4-methyl- N -(2-(1-phenylvinyl)phenyl)benzenesulfonamide, N -(but-3-en-1-yl)-4-methyl- N -(5-methyl-2-(1-phenylvinyl)phenyl)benzenesulfonamide, N -(but-3-en-1-yl)- N -(4-chloro-2-(1-phenylvinyl)phenyl)-4-methylbenzenesulfonamide, N -(4-bromo-2-(1-phenylvinyl)phenyl)- N -(but-3-en-1-yl)-4-methylbenzenesulfonamide, N -(but-3-en-1-yl)-4-methyl- N -(2-(1-(p-tolyl)vinyl)phenyl)benzenesulfonamide, N -(but-3-en-1-yl)-4-methyl- N -(4-methyl-2-(1-phenylvinyl)phenyl)benzenesulfonamide, N -(but-3-en-1-yl)- N -(4-chloro-2-(1-(p-tolyl)vinyl)phenyl)-4-methylbenzenesulfonamide, N -(but-3-en-1-yl)- N -(2'-cyano-3-(1-phenylvinyl)-[1,1'-biphenyl]-4-yl)-4-methylbenzenesulfonamide.

7. The method for preparing an eight-membered selenium-containing benzo[a]azine heterocyclic compound according to claim 1, characterized in that, The selenide is selected from one or more of diphenyl diselenide, 1,2-di(2-methoxyphenyl)diselenide, 1,2-di(3-methoxyphenyl)diselenide, 1,2-di(3-bromophenyl)diselenide, 1,2-di(4-methylphenyl)diselenide, 1,2-di(4-chlorophenyl)diselenide, 1,2-di(3,5-dimethylphenyl)diselenide, and 1,2-di(2-naphthyl)diselenide.

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