CN115652344A - Method for preparing eight-membered selenium-containing benzo nitrogen heterocyclic compound - Google Patents

Abstract

The invention relates to a method for preparing an eight-membered selenium-containing benzoazacycle compound, which comprises the following steps: the method comprises the following steps of taking N- (butyl-3-alkene-1-yl) -4-methyl-N- (2- (1-phenyl vinyl) phenyl) benzene sulfonamide compound as a substrate, carrying out anodic oxidation on selenide under electrochemical driving to generate a seleno radical, and carrying out radical coupling-cyclization on the seleno radical and the substrate to obtain the octa-element selenium-containing benzo nitrogen heterocyclic compound. The method has the advantages of green and simple operation, no trace electrons replacing the added redox agent, no use of metal catalyst and the added redox agent, economical efficiency, simple and easy preparation of raw materials, wide substrate range and the like.

Description

A method for preparing eight-membered selenium-containing benzazine heterocyclic compound

technical field

The invention belongs to the field of chemical preparation, and in particular relates to a method for preparing an eight-membered selenium-containing benzazine heterocyclic compound.

Background technique

Selenium is one of the essential trace elements for the human body. It is known as the "kindling 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 in April 2018 stipulates that the reference intake of dietary nutrients for Chinese residents: the average daily selenium requirement for adults is 50-60 μg. In view of the important biological and pharmacological activities of selenium-containing heterocycles, as well as their important roles in antibacterial, anti-tumor, cardiovascular protection and immune regulation, the development of new methods for the efficient synthesis of selenium-containing heterocycles with novel structures is crucial for the development of selenium-containing products. , The establishment of selenium-containing drug molecular library and drug development has important research value and practical significance. On the other hand, nitrogen-containing heterocyclic rings are the key skeleton structures of many drug molecules, which have extensive and important biological activities and medicinal value. Therefore, the development of facile, efficient, and green methods to introduce selenium groups into nitrogen heterocycles has attracted extensive attention of chemists. At present, the selenium-containing N-heterocycles reported in the literature are limited to 5-membered or 6-membered heterocyclic ring systems; in contrast, reports on selenium-containing compounds containing medium-sized N-heterocycle structural units are still very rare. With the introduction of the concept of "green sustainable chemistry", electrochemical technology, as one of the green and sustainable synthesis methods, has opened up broad fields in the fields of difunctionalization of unsaturated bonds, cyclization, and direct functionalization of C-H bonds. Application prospect. Therefore, the effective construction of N-heterocycles by electrochemical techniques has always been a hot field of organic synthesis research. However, the development of a metal-free, oxidant-free, electrochemically driven method for the construction of eight-membered selenium-containing benzazene heterocycles has not been reported yet.

Contents of the invention

In view of the existing problems in the prior art, the present invention provides a method for preparing an eight-membered selenium-containing benzazene heterocyclic compound, which is a kind of N-(but-3-en-1-yl)-4- Methyl-N-(2-(1-phenylvinyl)phenyl)benzenesulfonamide compound is used as the substrate, and the selenyl ether is electrochemically driven to generate selenyl radicals after anodic oxidation, and the selenyl radicals and the substrate An effective method for obtaining eight-membered selenium-containing benzazenocyclic compounds after free radical coupling-cyclization.

The technical scheme that the present invention solves the problems of the technologies described above is as follows:

The invention provides a method for preparing an eight-membered selenium-containing benzazine heterocyclic compound, comprising the following steps: using N-(but-3-en-1-yl)-4-methyl-N-(2-(1 -Phenylvinyl)phenyl)benzenesulfonamide compound is used as the substrate, selenide is electrochemically driven to generate selenyl radicals after anodic oxidation, and selenyl radicals and substrates are obtained by free radical coupling-cyclization Eight-membered selenium-containing benzazepine heterocyclic compound.

The beneficial effects of adopting the above-mentioned technical solution include:

The invention generates selenium free radicals through electrocatalysis, and efficiently prepares a series of eight-membered selenium-containing benzazene heterocyclic compounds through free radical addition and tandem cyclization. Eight-membered selenium-containing benzazine heterocyclic compounds have a variety of biological activities.

The steps of the above method are green and simple to operate, using traceless electrons instead of external redox agents, avoiding the use of metal catalysts and external redox agents, and the steps are economical, the raw materials are simple and easy to prepare, the substrate range is wide, and the product can be enlarged. Preparation, cheap and easy-to-obtain substrate, green reaction without risk of explosion, no metal salt and easy post-treatment, etc.

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

The beneficial effects of adopting the above technical solution include: green and simple operation, use of traceless electrons instead of external redox agents, avoiding the use of metal catalysts and external redox agents.

Further, the following steps are included: adding N-(but-3-en-1-yl)-4-methyl-N-(2-(1-phenylvinyl)phenyl)benzenesulfonamide compound, selenide, ⁿ Bu ₄ NPF ₆ and DCM to give a mixture; the mixture was electrolyzed until N-(but-3-en-1-yl)-4-methyl-N-(2-(1-phenylethenyl)phenyl ) The benzenesulfonamide compound is completely consumed; after the reaction is completed, it is quenched and extracted; the organic solvent is concentrated; purified and eluted with an eluent to obtain an eight-membered selenium-containing benzazene heterocyclic compound.

Further, N-(but-3-en-1-yl)-4-methyl-N-(2-(1-phenylvinyl)phenyl)benzenesulfonamide compound, ⁿ Bu ₄ NPF ₆ and selenide The molar ratio is 1:(1-3):(1-1.2); N-(but-3-en-1-yl)-4-methyl-N-(2-(1-phenylethenyl) The molar volume ratio of phenyl)benzenesulfonamide compound and DCM is 0.2mmol:5mL.

The beneficial effects of adopting the above-mentioned technical solution include: adopting the above-mentioned ratio is beneficial to the progress of the reaction and improving the yield.

Preferably, N-(but-3-en-1-yl)-4-methyl-N-(2-(1-phenylethenyl)phenyl)benzenesulfonamide compound, ⁿ Bu ₄ NPF ₆ and selenium The molar ratio of ether is 1:2:(1-1.2), which can further increase the yield of the target product.

Further, after the completion of the reaction, the mixture was quenched with NaHCO ₃ and extracted with CH ₂ Cl ₂ ; then the organic solvent was concentrated in vacuo; the residue was purified by flash column chromatography using a mixed solvent of ethyl acetate and petroleum ether as eluent to obtain the octanary Selenium-containing benzoazepine heterocyclic compounds.

The beneficial effects of adopting the above-mentioned technical scheme include: quenching with NaHCO ₃ is beneficial to reduce the solubility of the product, extraction with CH ₂ Cl ₂ is beneficial to layering and thorough extraction of the product, and a mixed solvent of ethyl acetate and petroleum ether is used as the The eluent facilitates the removal of the eluent.

Further, under an air atmosphere, the mixture was electrolyzed at room temperature with a constant current of 2 mA using a Pt electrode.

The beneficial effects of adopting the above technical solution include: the yield can be further improved.

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

Wherein, R ¹ is independently selected from one of H, CH ₃ , Cl, and Br substituents; R ² is independently selected from o-CNPh, H, CH ₃ , OCH ₃ , F, Cl, and Br substituents A sort of.

Further, the N-(but-3-en-1-yl)-4-methyl-N-(2-(1-phenylvinyl)phenyl)benzenesulfonamide compound is selected from one of the following compounds or Several combinations: N-(but-3-en-1-yl)-4-methyl-N-(2-(1-phenylvinyl)phenyl)benzenesulfonamide, N-(butan-3 -en-1-yl)-4-methyl-N-(5-methyl-2-(1-phenylethenyl)phenyl)benzenesulfonamide, N-(but-3-en-1-yl )-N-(4-chloro-2-(1-phenylethenyl)phenyl)-4-methylbenzenesulfonamide, N-(4-bromo-2-(1-phenylethenyl)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-phenyl Vinyl)phenyl)benzenesulfonamide, N-(but-3-en-1-yl)-N-(4-chloro-2-(1-(p-tolyl)vinyl)phenyl)-4- Toluenesulfonamide, N-(but-3-en-1-yl)-N-(2'-cyano-3-(1-phenylethenyl)-[1,1'-biphenyl]- 4-yl)-4-methylbenzenesulfonamide.

Further, the selenide may be diselenide; preferably, the selenide is selected from diphenyl diselenide, 1,2-bis(2-methoxyphenyl) diselenide, 1,2- Bis(3-methoxyphenyl)diselenide, 1,2-bis(3-bromophenyl)diselenide, 1,2-bis(4-methylphenyl)diselenide, 1,2 -One of two (4-chlorophenyl) diselenide, 1,2-bis(3,5-dimethylphenyl) diselenide, 1,2-bis(2-naphthyl) diselenide species or several.

The invention provides an eight-membered selenium-containing benzazine heterocyclic compound, which has the following chemical formula:

Wherein, R ¹ is independently selected from one of H, CH ₃ , Cl, and Br substituents; R ² is independently selected from o-CNPh, H, CH ₃ , OCH ₃ , F, Cl, and Br substituents One; ^R3 is independently selected from benzene rings, naphthalene, and one or more substituted benzene rings containing halogen, methyl, and methoxy.

The beneficial effects of adopting the above technical solution include: the eight-membered selenium-containing benzazine heterocyclic compound prepared by the invention has various biological activities and has wide application prospects.

Description of drawings

Fig. 1 is a reaction mechanism diagram of the present invention for preparing eight-membered selenium-containing benzazine heterocyclic compounds.

Fig. 2 is the ¹ H NMR spectrum of compound 3a in Example 1. Fig. 3 is the ¹³ C NMR spectrum of compound 3a in Example 1.

Fig. 4 is the ¹ H NMR spectrum of compound 3b in Example 2. Fig. 5 is the ¹³ C NMR spectrum of compound 3b in Example 2.

Fig. 6 is the ¹ H NMR spectrum of compound 3c in Example 3. Fig. 7 is the ¹³ C NMR spectrum of compound 3c in Example 3.

Fig. 8 is the ¹ H NMR spectrum of compound 3d in Example 4. Fig. 9 is the ¹³ C NMR spectrum of compound 3d in Example 4.

Fig. 10 is the ¹ H NMR spectrum of compound 3e in Example 5. Fig. 11 is the ¹³ C NMR spectrum of compound 3e in Example 5.

Fig. 12 is the ¹ H NMR spectrum of compound 3f in Example 6. Fig. 13 is the ¹³ C NMR spectrum of compound 3f in Example 6.

Fig. 14 is the ¹ H NMR spectrum of compound 3g in Example 7. Fig. 15 is the ¹³ C NMR spectrum of compound 3g in Example 7.

Fig. 16 is the ¹ H NMR spectrum of compound 3h in Example 8. Fig. 17 is the ¹³ C NMR spectrum of compound 3h in Example 8.

Fig. 18 is the ¹ H NMR spectrum of compound 3i in Example 9. Fig. 19 is the ¹³ C NMR spectrum of compound 3i in Example 9.

Fig. 20 is the ¹ H NMR spectrum of compound 3j in Example 10. Fig. 21 is the ¹³ C NMR spectrum of compound 3j in Example 10.

Fig. 22 is the ¹ H NMR spectrum of compound 3k in Example 11. Fig. 23 is the ¹³ C NMR spectrum of compound 3k in Example 11.

Fig. 24 is the ¹ H NMR spectrum of compound 3l in Example 12. Fig. 25 is the ¹³ C NMR spectrum of compound 31 in Example 12.

Fig. 26 is the ¹ H NMR spectrum of compound 3m in Example 13. Fig. 27 is the ¹³ C NMR spectrum of compound 3m in Example 13. Fig. 28 is the ¹⁹ F NMR spectrum of compound 3m in Example 13.

Fig. 29 is the ¹ H NMR spectrum of compound 3n in Example 14. Fig. 30 is the ¹³ C NMR spectrum of compound 3n in Example 14.

Fig. 31 is the ¹ H NMR spectrum of compound 3o in Example 15. Fig. 32 is the ¹³ C NMR spectrum of compound 3o in Example 15.

Fig. 33 is the ¹ H NMR spectrum of compound 3p in Example 16. Fig. 34 is the ¹³ C NMR spectrum of compound 3p in Example 16.

Fig. 35 is the ¹ H NMR spectrum of compound 3q in Example 17. Fig. 36 is the ¹³ C NMR spectrum of compound 3q in Example 17.

Fig. 37 is the ¹ H NMR spectrum of compound 3r in Example 18. Fig. 38 is the ¹³ C NMR spectrum of compound 3r in Example 18.

Detailed ways

The principles and features of the present invention are described below in conjunction with the accompanying drawings, and the examples given are only used to explain the present invention, and are not intended to limit the scope of the present invention. The technical solution of the present invention is not limited to the following examples, but also includes any combination of the examples.

The invention provides an effective method for preparing an eight-membered selenium-containing benzazene heterocyclic compound by generating selenium free radicals through electrocatalysis and series cyclization through free radical addition.

The method for electrocatalytically preparing eight-membered selenium-containing benzazene heterocyclic compounds comprises the following steps: base) phenyl) benzenesulfonamide compound as the substrate, the selenide is electrochemically driven to generate selenium radicals after anodic oxidation, and the selenium radicals and the substrate are coupled with the substrate by radical coupling-cyclization to obtain the eight-membered selenium-containing Benzoazepine compounds.

Wherein, R ¹ is independently selected from one of H, CH ₃ , Cl, and Br substituents; R ² is independently selected from o-CNPh, H, CH ₃ , OCH ₃ , F, Cl, and Br substituents One; ^R3 is independently selected from benzene rings, naphthalene, and one or more substituted benzene rings containing halogen, methyl, and methoxy.

Specifically, the following method can be used to prepare an eight-membered selenium-containing benzazine heterocyclic compound:

At room temperature (generally 25°C), add N-(but-3-en-1-yl)-4-methyl-N-(2-(1-phenylethenyl)phenyl) to the reaction tube in sequence ) benzenesulfonamide compound 1, selenide 2, ^nBu ₄ NPF ₆ and dichloromethane DCM. Moles of N-(but-3-en-1-yl)-4-methyl-N-(2-(1-phenylvinyl)phenyl)benzenesulfonamide compound, ^nBu ₄ NPF ₆ and selenoether The ratio is 1:(1-3):(1-1.2), preferably, N-(but-3-en-1-yl)-4-methyl-N-(2-(1-phenylethenyl ) phenyl) benzenesulfonamide compound, ⁿ Bu ₄ NPF ₆ and selenide in a molar ratio of 1:2:(1-1.2); N-(but-3-en-1-yl)-4-methyl- The molar volume ratio of N-(2-(1-phenylvinyl)phenyl)benzenesulfonamide compound and DCM is 0.2mmol:5mL.

The mixture was electrolyzed at a constant current of 2 mA using a Pt electrode until the starting material 1 (i.e. N-(but-3-en-1-yl)-4-methyl-N-(2-(1- The phenylvinyl)phenyl)benzenesulfonamide compound 1) is completely consumed. After the reaction was complete, the mixture was quenched with saturated NaHCO ₃ (ie saturated sodium bicarbonate solution at room temperature, sat. aq. 15 mL) and extracted with CH ₂ Cl ₂ (3×5 mL). The organic solvent was then concentrated in vacuo. The residue was purified by flash column chromatography using a mixed solvent of ethyl acetate and petroleum ether as eluent to obtain the eight-membered selenium-containing benzazepine ring product 3. The volume ratio of petroleum ether and ethyl acetate used in the present invention can be 20:1, for example: the volume ratio of petroleum ether and ethyl acetate in Examples 1 to 19 can be 20:1.

As shown in Figure 1, with N-(but-3-en-1-yl)-4-methyl-N-(2-(1-phenylvinyl)phenyl)benzenesulfonamide 1a and diphenyl Diselenide is an example to further introduce the reaction mechanism of the present invention:

The diphenyl diselenide is oxidized at the anode to form a phenylselenyl radical, and the phenylselenyl radical attacks the double bond outside the butene in the substrate 1a to obtain a free radical intermediate. Intramolecular addition of radical intermediate A to another double bond affords radical intermediate B. Finally, radical intermediate B undergoes deprotonation to provide the final product. The reduction of dichloromethane at the cathode surface releases hydrogen gas.

The invention provides a method for electrocatalytically generating selenium free radicals under metal-free and oxidant-free conditions, and efficiently preparing a series of eight-membered selenium-containing benzazine heterocyclic compounds through free radical addition and series cyclization. The compound has a variety of biological activities. The above method has the advantages of economy, simple and easy preparation of raw materials, wide range of substrates, scalable preparation of products and the like.

ⁿ Bu ₄ NPF ₆ was purchased from Shanghai Pide Pharmaceuticals, and the column chromatography silica gel used in the flash column chromatography purification process was purchased from Yantai Xinnuo Chemical Co., Ltd., with parameters of 200-300 mesh.

Unless otherwise specified, the reagents of the present invention are conventional reagents in the art and can be obtained commercially. Unless otherwise specified, the experimental methods used in the present invention are conventional experimental methods in the art.

The following will be introduced through specific embodiments.

Example 1

In this example, the method for electrochemically driving the preparation of eight-membered selenium-containing benzazine heterocyclic compounds under metal-free and oxidant-free conditions is as follows:

At room temperature, N-(but-3-en-1-yl)-4-methyl-N-(2-(1-phenylvinyl)phenyl)benzenesulfonamide 1a ( 0.2mmol), diphenyldiselenide 2a (0.2mmol), ^nBu ₄ NPF ₆ (0.4mmol) and DCM (5mL), the reaction flask was equipped with two Pt electrodes (1cm×1cm). Electrolysis was performed at room temperature at 25° C. with a constant current of 2 mA until the starting material was completely consumed (monitored by TLC, approximately 12 h). After the reaction was complete, the mixture was quenched with NaHCO ₃ (sat.aq. 15 mL) and extracted with CH ₂ Cl ₂ (3×5 mL). The organic solvent was then concentrated in vacuo. The residue was purified by flash column chromatography using a mixed solvent of ethyl acetate and petroleum ether as eluent to obtain product 3a.

Spectrum results are shown in Figure 2 and Figure 3. The ¹ H NMR and ¹³ C NMR spectra of compound 3a revealed the compound structure. Specifically:

Rf (petroleum ether/ethyl acetate=10:1):0.23; Yellow liquid (66mg, yield 70%). ¹ H NMR (500MHz, CDCl ₃ ) δ7.63 (d, J=8.1Hz, 2H), 7.41 -7.34(m,4H),7.30-7.10(m,11H),6.92(d,J=7.3Hz,1H),5.97(d,J=8.7Hz,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, 6.4Hz, 1H), 1.84-1.74(m, 1H), 1.63 (d, J=13.5Hz, 1H); ¹³ C NMR (125MHz, CDCl ₃ ) δ143.17, 142.14, 142.01, 140.32, 138.48, 137.75, 133.18 (d, J=9.5Hz), 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.

Example 2

In this embodiment, the method for electrochemically driving the preparation of eight-membered selenium-containing benzazine heterocyclic compounds under metal-free and oxidant-free conditions is as follows:

At room temperature, N-(but-3-en-1-yl)-4-methyl-N-(2-(1-phenylvinyl)phenyl)benzenesulfonamide 1a ( 0.2mmol), 1,2-bis(2-methoxyphenyl)diselenide 2b (0.2mmol), ^nBu ₄ NPF ₆ (0.4mmol) and DCM (5mL), the reaction flask was equipped with two Pt Electrodes (1 cm x 1 cm). Electrolysis was performed at room temperature at 25° C. with a constant current of 2 mA until the starting material was completely consumed (monitored by TLC, approximately 12 h). After the reaction was complete, the mixture was quenched with NaHCO ₃ (sat.aq. 15 mL) and extracted with CH ₂ Cl ₂ (3×5 mL). The organic solvent was then concentrated in vacuo. 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.

Spectrum results are shown in Figure 4 and Figure 5. The ¹ H NMR and ¹³ C NMR spectra of compound 3b revealed the compound structure. Specifically:

Rf (petroleum ether/ethyl acetate=10:1):0.11; Yellow liquid (72mg, yield 61%). ¹ H NMR (500MHz, CDCl ₃ ) δ7.64 (d, J=8.1Hz, 2H), 7.37 (d, J=7.1Hz, 2H), 7.30-7.13(m, 9H), 7.11(dd, J=6.9, 2.2Hz, 1H), 6.96-6.90(m, 1H), 6.84-6.74(m, 2H ),5.99(d,J=8.7Hz,1H),4.24(dd,J=14.6,3.2Hz,1H),3.79(s,3H),3.06(dd,J=11.1,7.9Hz,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(125MHz,CDCl ₃ )δ157.88,143.15,142.10,141.95, 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.

Example 3

In this embodiment, the method for electrochemically driving the preparation of eight-membered selenium-containing benzazine heterocyclic compounds under metal-free and oxidant-free conditions is as follows:

At room temperature, N-(but-3-en-1-yl)-4-methyl-N-(2-(1-phenylvinyl)phenyl)benzenesulfonamide 1a ( 0.2mmol), 1,2-two (3-methoxyphenyl) diselenide 2c (1.2equiv, 0.24mmol), ^nBu ₄ NPF ₆ (0.4mmol) and DCM (5mL), the reaction bottle is equipped with Two Pt electrodes (1 cm x 1 cm). Electrolysis was performed at room temperature at 25° C. with a constant current of 2 mA until the starting material was completely consumed (monitored by TLC, approximately 12 h). After the reaction was complete, the mixture was quenched with NaHCO ₃ (sat.aq. 15 mL) and extracted with CH ₂ Cl ₂ (3×5 mL). The organic solvent was then concentrated in vacuo. The residue was purified by flash column chromatography using a mixed solvent of ethyl acetate and petroleum ether as eluent to obtain product 3c.

Spectrum results are shown in Figure 6 and Figure 7. The ¹ H NMR and ¹³ C NMR spectra of compound 3c revealed the compound structure. Specifically:

Rf (petroleum ether/ethyl acetate=10:1):0.11; Yellow liquid (72mg, yield 61%). ¹ H NMR (500MHz, CDCl ₃ ) δ7.64 (d, J=8.1Hz, 2H), 7.35 (d, J=7.1Hz, 2H), 7.29-7.18(m, 7H), 7.11(dd, J=6.9, 2.2Hz, 1H), 7.07(t, J=7.9Hz, 1H), 6.98-6.90( m,3H),6.71(dd,J=8.1,1.7Hz,1H),5.96(d,J=8.7Hz,1H),4.24(dd,J=14.6,3.5Hz,1H),3.72(s,3H ),3.09(dd,J＝11.4,8.5Hz,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=13.5Hz, 1H); ¹³ C NMR (125MHz, CDCl ₃ ) δ159.67, 143.17, 142.11, 141.97, 140.30, 138.50, 137.73, 133.01, 131.05, 130.95, 129.755, 129.489, 128. ,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.

Example 4

In this embodiment, the method for electrochemically driving the preparation of eight-membered selenium-containing benzazine heterocyclic compounds under metal-free and oxidant-free conditions is as follows:

At room temperature, N-(but-3-en-1-yl)-4-methyl-N-(2-(1-phenylvinyl)phenyl)benzenesulfonamide 1a ( 0.2mmol), 1,2-bis(3-bromophenyl)diselenide 2d (1.2equiv, 0.24mmol), ^nBu ₄ NPF ₆ (0.4mmol) and DCM (5mL), the reaction flask is equipped with two Pt electrode (1 cm x 1 cm). Electrolysis was performed at room temperature at 25° C. with a constant current of 2 mA until the starting material was completely consumed (monitored by TLC, approximately 12 h). After the reaction was complete, the mixture was quenched with NaHCO ₃ (sat.aq. 15 mL) and extracted with CH ₂ Cl ₂ (3×5 mL). The organic solvent was then concentrated in vacuo. The residue was purified by flash column chromatography using a mixed solvent of ethyl acetate and petroleum ether as eluent to obtain the product 3d.

Spectrum results are shown in Figure 8 and Figure 9. The ¹ H NMR and ¹³ C NMR spectra of compound 3d revealed the compound structure. Specifically:

Rf (petroleum ether/ethyl acetate=10:1):0.11; Yellow liquid (65mg, yield 51%). ¹ H NMR (500MHz, CDCl ₃ ) δ7.64 (d, J=8.1Hz, 2H), 7.52 (s,1H),7.36(d,J=7.1Hz,2H),7.33-7.19(m,9H),7.15-7.10(m,1H),7.03-6.90(m,2H),5.95(d,J =8.7Hz,1H),4.25(dd,J=14.6,3.6Hz,1H),3.08(dd,J=11.4,8.8Hz,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=16.3Hz,1H); ¹³ C NMR(125MHz,CDCl ₃ )δ143.20,142.01,141.85,140.25,138.74, 137.69,135.2222.66,131.96,131.43,130.90,130.27,130.00,129.45,128.56,128.34,127.72,122.75,5.93,33,35,35,35,35,35,35,35,35,35,35,35,35,35,35,35,35,35,35,35,35,5,85,5,85,5,5,5,5,5,5,5,5,5,5,5,5,5,5,5,5s,5.

Example 5

In this embodiment, the method for electrochemically driving the preparation of eight-membered selenium-containing benzazine heterocyclic compounds under metal-free and oxidant-free conditions is as follows:

At room temperature, N-(but-3-en-1-yl)-4-methyl-N-(2-(1-phenylvinyl)phenyl)benzenesulfonamide 1a ( 0.2mmol), 1,2-bis(4-methylphenyl) diselenide 2e (1.2equiv, 0.24mmol), ⁿ Bu ₄ NPF ₆ (0.4mmol) and DCM (5mL), the reaction flask is equipped with two Pt electrodes (1cm×1cm). Electrolysis was performed at room temperature at 25° C. with a constant current of 2 mA until the starting material was completely consumed (monitored by TLC, approximately 12 h). After the reaction was complete, the mixture was quenched with NaHCO ₃ (sat.aq. 15 mL) and extracted with CH ₂ Cl ₂ (3×5 mL). The organic solvent was then concentrated in vacuo. The residue was purified by flash column chromatography using a mixed solvent of ethyl acetate and petroleum ether as eluent to obtain the product 3e.

The spectrogram results are shown in Figure 10 and Figure 11. The ¹ H NMR and ¹³ C NMR spectra of compound 3e revealed the compound structure. Specifically:

Rf(petroleum ether/ethyl acetate＝10:1):0.17; Yellow liquid (82mg, yield 71%). ¹ H NMR (500MHz, CDCl ₃ )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=8.7 Hz, 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,CDCl ₃ )δ143.18,142.17,142.06,140.33,138.36, 137.77,137.09,133.76,133.33,130.97,129.83,129.46,128.85,128.62,128.58,128.18,127.98,127.75,127.22,125.90,50.98,38.54,36.09,33.71,21.57,21.12.；HRMS(ESI)calcd for C32H32NO2SSe [M+H]+:574.1313,found:574.1310.

Example 6

In this embodiment, the method for electrochemically driving the preparation of eight-membered selenium-containing benzazine heterocyclic compounds under metal-free and oxidant-free conditions is as follows:

At room temperature, N-(but-3-en-1-yl)-4-methyl-N-(2-(1-phenylvinyl)phenyl)benzenesulfonamide 1a ( 0.2mmol), 1,2-bis(4-chlorophenyl) diselenide 2f (1.2equiv, 0.24mmol), ^nBu ₄ NPF ₆ (0.4mmol) and DCM (5mL), the reaction flask is equipped with two Pt electrode (1 cm x 1 cm). Electrolysis was performed at room temperature at 25° C. with a constant current of 2 mA until the starting material was completely consumed (monitored by TLC, approximately 12 h). After the reaction was complete, the mixture was quenched with NaHCO ₃ (sat.aq. 15 mL) and extracted with CH ₂ Cl ₂ (3×5 mL). The organic solvent was then concentrated in vacuo. The residue was purified by flash column chromatography using a mixed solvent of ethyl acetate and petroleum ether as eluent to obtain the product 3f.

Spectrum results are shown in Figure 12 and Figure 13. The ¹ H NMR and ¹³ C NMR spectra of compound 3f revealed the structure of the compound. Specifically:

Rf (petroleum ether/ethyl acetate=10:1):0.14; Yellow liquid (76mg, yield 64%). ¹ H NMR (500MHz, CDCl ₃ ) 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,CDCl ₃ )δ143.21,142.04,141.88,140.27,138.60,137.70,134.73,133.28,132.85,130.85,129.47,129.13,128.95 128.54, 128.25, 128.01, 127.79, 127.71, 127.33, 50.93, 38.32, 35.94, 33.74, 21.55.

Example 7

In this embodiment, the method for electrochemically driving the preparation of eight-membered selenium-containing benzazine heterocyclic compounds under metal-free and oxidant-free conditions is as follows:

At room temperature, N-(but-3-en-1-yl)-4-methyl-N-(2-(1-phenylvinyl)phenyl)benzenesulfonamide 1a ( 0.2mmol), 1,2-two (3,5-dimethylphenyl) diselenide 2g (1.2equiv, 0.24mmol), ^nBu ₄ NPF ₆ (0.4mmol) and DCM (5mL), in the reaction bottle Equipped with two Pt electrodes (1 cm x 1 cm). Electrolysis was performed at room temperature at 25° C. with a constant current of 2 mA until the starting material was completely consumed (monitored by TLC, approximately 12 h). After the reaction was complete, the mixture was quenched with NaHCO ₃ (sat.aq. 15 mL) and extracted with CH ₂ Cl ₂ (3×5 mL). The organic solvent was then concentrated in vacuo. The residue was purified by flash column chromatography using a mixed solvent of ethyl acetate and petroleum ether as eluent to obtain the product 3g.

Spectrum results are shown in Figure 14 and Figure 15. The ¹ H NMR and ¹³ C NMR spectra of compound 3g revealed the structure of the compound. Specifically:

Rf(petroleum ether/ethyl acetate=10:1):0.23; Yellow solid (84mg, yield 71%):mp:67-68℃. ¹ H NMR(500MHz, CDCl ₃ )δ7.64(d,J= 8.1Hz, 2H), 7.35(d, J=7.0Hz, 2H), 7.29-7.17(m, 7H), 7.13(dd, J=7.1, 1.9Hz, 1H), 7.02(s, 2H), 6.96- 6.91(m,1H),6.80(s,1H),5.96(d,J=8.7Hz,1H),4.24(dd,J=14.6,3.5Hz,1H),3.06(dd,J=11.5,8.3Hz ,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 ＝13.5Hz,1H)； ¹³ C NMR(125MHz,CDCl ₃ )δ143.17,142.22,142.01,140.35,138.59,138.36,137.76,133.27,130.90,130.69,129.63,129.45,128.85,128.59,128.25,127.97,127.75, 127.21, 51.02, 38.74, 35.71, 33.65, 21.55, 21.15.

Example 8

In this embodiment, the method for electrochemically driving the preparation of eight-membered selenium-containing benzazine heterocyclic compounds under metal-free and oxidant-free conditions is as follows:

At room temperature, N-(but-3-en-1-yl)-4-methyl-N-(2-(1-phenylvinyl)phenyl)benzenesulfonamide 1a ( 0.2mmol), 1,2-bis(2-naphthyl)diselenide 2h (1.2equiv, 0.24mmol), ^nBu ₄ NPF ₆ (0.4mmol) and DCM (5mL), the reaction flask was equipped with two Pt Electrodes (1 cm x 1 cm). Electrolysis was performed at room temperature at 25° C. with a constant current of 2 mA until the starting material was completely consumed (monitored by TLC, approximately 12 h). After the reaction was complete, the mixture was quenched with NaHCO ₃ (sat.aq. 15 mL) and extracted with CH ₂ Cl ₂ (3×5 mL). The organic solvent was then concentrated in vacuo. The residue was purified by flash column chromatography using a mixed solvent of ethyl acetate and petroleum ether as eluent to obtain the product 3h.

The spectrogram results are shown in Figure 16 and Figure 17. The ¹ H NMR and ¹³ C NMR spectra of compound 3h revealed the structure of the compound. Specifically:

Rf(petroleum ether/ethyl acetate=10:1):0.11; Yellow solid (68mg, yield 56%):mp:182-183℃. ¹ H NMR(500MHz, CDCl ₃ )δ8.36(d,J= 8.0Hz, 1H), 7.78(d, J=7.3Hz, 1H), 7.72-7.59(m, 4H), 7.47(td, J=13.1, 6.6Hz, 2H), 7.36(d, J=6.9Hz, 2H),7.30-7.16(m,8H),7.05-6.98(m,1H),6.92-6.83(m,1H),5.99(d,J=8.6Hz,1H),4.19(dd,J=14.6, 3.4Hz, 1H), 3.08(dd, J＝11.4, 8.9Hz, 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); ¹³ C NMR(125MHz,CDCl ₃ )δ143.14,142.03,141.97,140.22,138.43,137.72,134.41,133.92,133.25,133.18,130.8 ,129.42,128.98,128.81,128.59,128.56,128.50,128.46,128.16,127.96,127.73,127.21,126.67,126.17,125.65,50.90,38.53,36.03,33.736.21

Example 9

In this embodiment, the method for electrochemically driving the preparation of eight-membered selenium-containing benzazine heterocyclic compounds under metal-free and oxidant-free conditions is as follows:

At room temperature, sequentially add N-(but-3-en-1-yl)-4-methyl-N-(5-methyl-2-(1-phenylethenyl)phenyl) Benzenesulfonamide 1b (0.2mmol), diphenyldiselenide 2a (0.2mmol), ^nBu ₄ NPF ₆ (0.4mmol) and DCM (5mL), the reaction bottle is equipped with two Pt electrodes (1cm×1cm) . Electrolysis was performed at room temperature at 25° C. with a constant current of 2 mA until the starting material was completely consumed (monitored by TLC, approximately 12 h). After the reaction was complete, the mixture was quenched with NaHCO ₃ (sat.aq. 15 mL) and extracted with CH ₂ Cl ₂ (3×5 mL). The organic solvent was then concentrated in vacuo. The residue was purified by flash column chromatography using a mixed solvent of ethyl acetate and petroleum ether as eluent to obtain the product 3i.

The spectrogram results are shown in Figure 18 and Figure 19. The ¹ H NMR and ¹³ C NMR spectra of compound 3i revealed the compound structure. Specifically:

Rf (petroleum ether/ethyl acetate=10:1):0.17; Yellow liquid (82mg, yield 72%). ¹ H NMR (500MHz, CDCl ₃ ) 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,1H),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,CDCl ₃ )δ143.19,142.17,140.14 ,138.96,138.46,137.76,133.16,132.84,130.64,130.06,129.36,129.16,129.03,128.58,127.99,127.84,127.20,126.96,50.82,358.65,135.72.8,21,3

Example 10

In this embodiment, the method for electrochemically driving the preparation of eight-membered selenium-containing benzazine heterocyclic compounds under metal-free and oxidant-free conditions is as follows:

At room temperature, add N-(but-3-en-1-yl)-N-(4-chloro-2-(1-phenylvinyl)phenyl)-4-methylbenzene Sulfonamide 1c (0.2mmol), diphenyldiselenide 2a (1.2equiv, 0.24mmol), ^nBu ₄ NPF ₆ (0.4mmol) and DCM (5mL), the reaction bottle is equipped with two Pt electrodes (1cm× 1cm). Electrolysis was performed at room temperature at 25° C. with a constant current of 2 mA until the starting material was completely consumed (monitored by TLC, approximately 12 h). After the reaction was complete, the mixture was quenched with NaHCO ₃ (sat.aq. 15 mL) and extracted with CH ₂ Cl ₂ (3×5 mL). The organic solvent was then concentrated in vacuo. The residue was purified by flash column chromatography using a mixed solvent of ethyl acetate and petroleum ether as eluent to obtain product 3j.

The spectrogram results are shown in Figure 20 and Figure 21. The ¹ H NMR and ¹³ C NMR spectra of compound 3J revealed the compound structure. Specifically:

Rf (petroleum ether/ethyl acetate=10:1): 0.14; Yellow solid (68mg, yield 57%): mp: 78-79℃. ¹ H NMR (500MHz, CDCl ₃ ) δ7.61 (d, J= 8.1Hz, 2H), 7.40-7.27(m, 7H), 7.23-7.14(m, 6H), 7.08(d, J=2.3Hz, 1H), 6.83(d, J=8.5Hz, 1H), 5.99( d,J=8.7Hz,1H),4.23(dd,J=14.6,3.7Hz,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(125MHz,CDCl ₃ )δ143.82,143.41,141.28,138.81,137.50,137.41,134.08,133.96,133.56 ,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.

Example 11

In this embodiment, the method for electrochemically driving the preparation of eight-membered selenium-containing benzazine heterocyclic compounds under metal-free and oxidant-free conditions is as follows:

At room temperature, sequentially add N-(4-bromo-2-(1-phenylvinyl)phenyl)-N-(but-3-en-1-yl)-4-methylbenzene Sulfonamide 1d (0.2mmol), diphenyldiselenide 2a (1.2equiv, 0.24mmol), ^nBu ₄ NPF ₆ (0.4mmol) and DCM (5mL), the reaction bottle is equipped with two Pt electrodes (1cm× 1cm). Electrolysis was performed at room temperature at 25° C. with a constant current of 2 mA until the starting material was completely consumed (monitored by TLC, approximately 12 h). After the reaction was complete, the mixture was quenched with NaHCO ₃ (sat.aq. 15 mL) and extracted with CH ₂ Cl ₂ (3×5 mL). The organic solvent was then concentrated in vacuo. The residue was purified by flash column chromatography using a mixed solvent of ethyl acetate and petroleum ether as eluent to obtain the product 3k.

The spectrogram results are shown in Figure 22 and Figure 23. The ¹ H NMR and ¹³ C NMR spectra of compound 3k revealed the compound structure. Specifically:

Rf (petroleum ether/ethyl acetate=10:1):0.14; Yellow liquid (74mg, yield 58%). ¹ H NMR (500MHz, CDCl ₃ ) δ7.62 (d, J=8.1Hz, 2H), 7.39 (dd, J=7.1,5.3Hz,4H),7.29-7.13(m,9H),7.08(dd,J=7.2,1.7Hz,1H),6.91-6.87(m,1H),5.97(d,J =8.7Hz,1H),4.23(dd,J=14.6,3.6Hz,1H),3.05(dd,J=11.5,8.8Hz,1H),2.96(dd,J=11.6,5.8Hz,1H),2.92 -2.84(m,1H),2.41(s,3H),2.01(dd,J=17.0,7.8Hz,1H),1.84(dt,J=10.4,8.5Hz,1H),1.63(d,J=13.7 Hz,1H)； ¹³ C NMR(125MHz,CDCl ₃ )δ143.29,141.67,140.89,140.32,137.64,137.44,133.74,133.23,131.07,130.74,130.18,129.77,129.49,129.12,129.04,128.60,128.36,127.65, 127.06, 121.38, 50.95, 38.66, 35.64, 33.79, 21.56.

Example 12

In this embodiment, the method for electrochemically driving the preparation of eight-membered selenium-containing benzazine heterocyclic compounds under metal-free and oxidant-free conditions is as follows:

At room temperature, sequentially add N-(but-3-en-1-yl)-4-methyl-N-(2-(1-(p-tolyl)vinyl)phenyl)benzenesulfonate to the reaction flask Amide 1e (0.2mmol), diphenyldiselenide 2a (1.2equiv, 0.24mmol), ^nBu ₄ NPF ₆ (0.4mmol) and DCM (5mL), the reaction bottle is equipped with two Pt electrodes (1cm×1cm ). Electrolysis was performed at room temperature at 25° C. with a constant current of 2 mA until the starting material was completely consumed (monitored by TLC, approximately 12 h). After the reaction was complete, the mixture was quenched with NaHCO ₃ (sat.aq. 15 mL) and extracted with CH ₂ Cl ₂ (3×5 mL). The organic solvent was then concentrated in vacuo. The residue was purified by flash column chromatography using a mixed solvent of ethyl acetate and petroleum ether as eluent to obtain the product 3l.

The spectrogram results are shown in Figure 24 and Figure 25. The ¹ H NMR and ¹³ C NMR spectra of compound 3l revealed the compound structure. Specifically:

Rf (petroleum ether/ethyl acetate=10:1):0.17; Yellow liquid (69mg, yield 60%). ¹ H NMR (500MHz, CDCl ₃ ) δ7.63 (d, J=8.1Hz, 2H), 7.40 (d,J=6.2Hz,2H),7.25-7.18(m,6H),7.18-7.12(m,4H),7.09(d,J=7.9Hz,2H),6.93(d,J=7.2Hz, 1H), 5.93(d, J=8.7Hz, 1H), 4.23(dd, J=14.6, 3.6Hz, 1H), 3.06(dd, J=11.4, 8.6Hz, 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＝18.7,9.4Hz,1H),1.62(d,J＝14.0Hz,1H) ； ¹³ C NMR(125MHz,CDCl ₃ )δ143.12,142.25,140.28,139.13,138.25,137.76,136.94,133.17,132.25,130.95,129.94,129.40,128.98,128.81,128.69,128.56,128.40,128.18,127.75,126.95, 50.95, 38.54, 35.80, 33.71, 21.53, 21.18.

Example 13

In this embodiment, the method for electrochemically driving the preparation of eight-membered selenium-containing benzazine heterocyclic compounds under metal-free and oxidant-free conditions is as follows:

At room temperature, sequentially add N-(but-3-en-1-yl)-4-methyl-N-(4-methyl-2-(1-phenylethenyl)phenyl) Benzenesulfonamide 1f (0.2mmol), diphenyldiselenide 2a (1.2equiv, 0.24mmol), ^nBu ₄ NPF ₆ (0.4mmol) and DCM (5mL), the reaction flask was equipped with two Pt electrodes (1cm ×1cm). Electrolysis was performed at room temperature at 25° C. with a constant current of 2 mA until the starting material was completely consumed (monitored by TLC, approximately 12 h). After the reaction was complete, the mixture was quenched with NaHCO ₃ (sat.aq. 15 mL) and extracted with CH ₂ Cl ₂ (3×5 mL). The organic solvent was then concentrated in vacuo. The residue was purified by flash column chromatography using a mixed solvent of ethyl acetate and petroleum ether as eluent to obtain the product 3m.

The spectrogram results are shown in Figure 26, Figure 27 and Figure 28. ¹ H NMR, ¹³ C NMR and ¹⁹ F NMR of compound 3m revealed the compound structure. Specifically:

Rf (petroleum ether/ethyl acetate=10:1):0.26; Yellow liquid (69mg, yield 58%). ¹ H NMR (500MHz, CDCl ₃ ) δ7.63 (d, J=8.0Hz, 2H), 7.38 (d,J=6.6Hz,2H),7.26-7.12(m,7H),7.11-7.05(m,3H),7.00-6.93(m,1H),6.65(dd,J=9.1,2.1Hz,1H ),5.92(d,J=8.7Hz,1H),4.19(dd,J=14.6,3.6Hz,1H),3.05(dd,J=11.4,8.6Hz,1H),2.95(dd,J=11.5, 6.0Hz,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=13.7Hz, 1H); ¹³ C NMR (125MHz, CDCl ₃ ) δ162.94, 160.95, 143.50, 141.28(d, J=9.2Hz), 138.94, 138.50(d, J=3.5Hz), 137.37(d, J=12.0Hz), 137.13, 133.22, 132.50, 132.13(d, J=8.8Hz), 129.76, 129.57, 129.01, 128.78, 128.34, 127.72, 127.04, 115.73(d, J=21.0Hz), 115.43(d, J=21.0Hz), 50.84, 38.54, 35.60, 33.67, 21.56, 21.19; ¹⁹ F NMR (471MHz, CDCl ₃ ) δ-112.12.

Example 14

In this embodiment, the method for electrochemically driving the preparation of eight-membered selenium-containing benzazine heterocyclic compounds under metal-free and oxidant-free conditions is as follows:

At room temperature, N-(but-3-en-1-yl)-N-(4-chloro-2-(1-(p-tolyl)vinyl)phenyl)-4- Toluenesulfonamide 1g (0.2mmol), diphenyldiselenide 2a ( _1.2equiv , 0.24mmol), ^nBu4NPF6 ( _0.4mmol ) and DCM (5mL), the reaction flask is equipped with two Pt electrodes (1cm×1cm). Electrolysis was performed at room temperature at 25° C. with a constant current of 2 mA until the starting material was completely consumed (monitored by TLC, approximately 12 h). After the reaction was complete, the mixture was quenched with NaHCO ₃ (sat.aq. 15 mL) and extracted with CH ₂ Cl ₂ (3×5 mL). The organic solvent was then concentrated in vacuo. The residue was purified by flash column chromatography using a mixed solvent of ethyl acetate and petroleum ether as eluent to obtain the product 3n.

The spectrogram results are shown in Figure 29 and Figure 30. The ¹ H NMR and ¹³ C NMR spectra of compound 3n revealed the compound structure. Specifically:

Rf (petroleum ether/ethyl acetate=10:1):0.23; Yellow liquid (75mg, yield 62%). ¹ H NMR (500MHz, CDCl ₃ ) δ7.60 (d, J=8.1Hz, 2H), 7.38 (d,J=6.5Hz,2H),7.25-7.21(m,2H),7.17(ddd,J=13.7,11.1,7.2Hz,6H),7.09(dd,J=12.2,5.1Hz,3H), 6.82(d, J=8.5Hz, 1H), 5.94(d, J=8.7Hz, 1H), 4.21(dd, J=14.6, 3.6Hz, 1H), 3.03-2.94(m, 2H), 2.86-2.77 (m,1H),2.38(s,3H),2.35(s,3H),1.95-1.85(m,1H),1.79-1.71(m,1H),1.63(d,J=16.1Hz,1H); ¹³ C NMR(125MHz,CDCl ₃ )δ143.96,143.39,138.80,138.46,137.44,137.28,133.92,133.54,133.24,130.76,129.88,129.52,129.23,129.00,128.97,128.87,128.38,127.69,127.20,50.96,38.23 ,35.43,33.56,21.55,21.21.

Example 15

In this embodiment, the method for electrochemically driving the preparation of eight-membered selenium-containing benzazine heterocyclic compounds under metal-free and oxidant-free conditions is as follows:

Add N-(but-3-en-1-yl)-N-(2'-cyano-3-(1-phenylethenyl)-[1,1'- Biphenyl]-4-yl)-4-methylbenzenesulfonamide 1h (0.2mmol), diphenyldiselenide 2a (1.2equiv, 0.24mmol), ^nBu ₄ NPF ₆ (0.4mmol) and DCM (5mL ), the reaction bottle is equipped with two Pt electrodes (1cm×1cm). Electrolysis was performed at room temperature at 25° C. with a constant current of 2 mA until the starting material was completely consumed (monitored by TLC, approximately 12 h). After the reaction was complete, the mixture was quenched with NaHCO ₃ (sat.aq. 15 mL) and extracted with CH ₂ Cl ₂ (3×5 mL). The organic solvent was then concentrated in vacuo. 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.

The spectrogram results are shown in Figure 31 and Figure 32. The ¹ H NMR and ¹³ C NMR spectra of compound 3o revealed the compound structure. Specifically:

Rf(petroleum ether/ethyl acetate＝10:1):0.06; Yellow liquid (70mg, yield 53%). ¹ H NMR (500MHz, CDCl ₃ )δ7.76 (d, J＝7.8Hz, 1H), 7.63 (dd, J=13.0,4.7Hz,3H),7.49(dt,J=12.0,8.1Hz,6H),7.41(d,J=7.2Hz,3H),7.20(ddd,J=16.4,15.2,7.6 Hz, 7H), 6.91(d, J=7.9Hz, 1H), 6.07(d, J=8.7Hz, 1H), 4.25(dd, J=14.6, 3.5Hz, 1H), 3.08(dd, J=11.5 ,8.8Hz,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); NMR(125MHz,CDCl ₃ )δ145.39,143.26,142.32,141.80,140.34,137.80,137.69,136.86,134.07,133.84,133.28,132.85,130.98,130.08,129.78,129.50,129.04,128.84,128.58,128.41,127.66,127.38 ,127.05,118.93,111.04,51.00,38.68,35.70,33.81,21.55.

Example 16

In this embodiment, the method for electrochemically driving the preparation of eight-membered selenium-containing benzazine heterocyclic compounds under metal-free and oxidant-free conditions is as follows:

At room temperature, sequentially add N-(4-chloro-2-(1-phenylvinyl)phenyl)-N-(but-3-en-1-yl)-4-methylbenzene Sulfonamide 1i (0.2mmol), diphenyldiselenide 2a (1.2equiv, 0.24mmol), ^nBu ₄ NPF ₆ (0.4mmol) and DCM (5mL), the reaction bottle is equipped with two Pt electrodes (1cm× 1cm). Electrolysis was performed at room temperature at 25° C. with a constant current of 2 mA until the starting material was completely consumed (monitored by TLC, approximately 12 h). After the reaction was complete, the mixture was quenched with NaHCO ₃ (sat.aq. 15 mL) and extracted with CH ₂ Cl ₂ (3×5 mL). The organic solvent was then concentrated in vacuo. The residue was purified by flash column chromatography using a mixed solvent of ethyl acetate and petroleum ether as eluent to obtain the product 3p.

The spectrogram results are shown in Figure 33 and Figure 34. ¹ H NMR and ¹³ C NMR spectra of compound 3p revealed the compound structure. Specifically:

Rf (petroleum ether/ethyl acetate=10:1): 0.14; Yellow liquid (68mg, yield 57%).1H NMR (500MHz, CDCl ₃ ) δ7.62 (d, J=8.2Hz, 2H), 7.39( dd,J=7.7,1.4Hz,2H),7.29-7.11(m,11H),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,CDCl ₃ )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.

Example 17

In this embodiment, the method for electrochemically driving the preparation of eight-membered selenium-containing benzazine heterocyclic compounds under metal-free and oxidant-free conditions is as follows:

At room temperature, sequentially add N-(but-3-en-1-yl)-4-methyl-N-(5-bromo-2-(1-phenylethenyl)phenyl)benzene Sulfonamide 1j (0.2mmol), diphenyldiselenide 2a (0.2mmol), ^nBu ₄ NPF ₆ (0.4mmol) and DCM (5mL), the reaction flask was equipped with two Pt electrodes (1cm×1cm). Electrolysis was performed at room temperature at 25° C. with a constant current of 2 mA until the starting material was completely consumed (monitored by TLC, approximately 12 h). After the reaction was complete, the mixture was quenched with NaHCO ₃ (sat.aq. 15 mL) and extracted with CH ₂ Cl ₂ (3×5 mL). The organic solvent was then concentrated in vacuo. The residue was purified by flash column chromatography using a mixed solvent of ethyl acetate and petroleum ether as eluent to obtain the product 3q.

The spectrogram results are shown in Figure 35 and Figure 36. The ¹ H NMR and ¹³ C NMR spectra of compound 3q revealed the compound structure. Specifically:

Rf (petroleum ether/ethyl acetate=10:1):0.23; Yellow liquid (69mg, yield 54%). ¹ H NMR (500MHz, CDCl ₃ ) δ7.63 (d, J=8.1Hz, 2H), 7.42 -7.36(m,3H),7.33(d,J＝6.9Hz,2H),7.30-7.23(m,5H),7.21-7.13(m,3H),7.05(s,1H),6.99(d,J =8.3Hz, 1H), 5.97(d, J=8.7Hz, 1H), 4.20(dd, J=14.6, 3.6Hz, 1H), 3.06(dd, J=11.4, 8.7Hz, 1H), 2.96(dd ,J=11.6,6.0Hz,1H),2.85(dd,J=19.7,7.6Hz,1H),2.42(s,3H),2.00-1.93(m,1H),1.82-1.71(m,1H), 1.64 (d, J=13.4Hz, 1H); ¹³ C NMR (125MHz, CDCl ₃ ) δ143.58, 141.46, 141.36, 141.26, 137.61, 137.19, 133.64, 133.28, 132.16, 131.76, 131.48, 129.656, 129.9 ,128.10,127.72,127.47,127.11,121.41,50.81,38.56,35.53,33.47,21.56.

Example 18

In this embodiment, the method for electrochemically driving the preparation of eight-membered selenium-containing benzazine heterocyclic compounds under metal-free and oxidant-free conditions is as follows:

At room temperature, add N-(but-3-en-1-yl)-N-(4-methoxy-2-(1-phenylvinyl)phenyl)-4-methyl phenylsulfonamide 1k (0.2mmol), diphenyldiselenide 2a (1.2equiv, 0.24mmol), ^nBu ₄ NPF ₆ (0.4mmol) and DCM (5mL), the reaction flask is equipped with two Pt electrodes ( 1cm×1cm). Electrolysis was performed at room temperature of 25° C. with a constant current of 2 mA until the starting material was completely consumed (monitored by TLC, approximately 12 h). After the reaction was complete, the mixture was quenched with NaHCO ₃ (sat.aq. 15 mL) and extracted with CH ₂ Cl ₂ (3×5 mL). The organic solvent was then concentrated in vacuo. The residue was purified by flash column chromatography using a mixed solvent of ethyl acetate and petroleum ether as eluent to obtain the product 3r.

The spectrogram results are shown in Figure 37 and Figure 38. The ¹ H NMR and ¹³ C NMR spectra of compound 3r revealed the compound structure. Specifically:

Rf(petroleum ether/ethyl acetate＝10:1):0.11; Yellow liquid (77mg, yield 65%). ¹ H NMR (500MHz, CDCl ₃ )δ7.62 (d, J＝8.1Hz, 2H), 7.44 -7.34(m,4H),7.30-7.12(m,8H),6.81(d,J=8.8Hz,1H),6.75(dd,J=8.8,2.9Hz,1H),6.59(d,J=2.8 Hz, 1H), 5.95(d, J=8.7Hz, 1H), 4.23(dd, J=14.5, 3.7Hz, 1H), 3.70(s, 3H), 3.06(dd, J=11.4, 8.6Hz, 1H ),2.96(dd,J＝11.5,6.0Hz,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)； ¹³ C NMR(125MHz,CDCl ₃ )δ158.83,143.23,143.08,141.71,138.45,137.77,133.27,133.20,133.14,129.94,129.49,129.41,128.98,128.55,127.98,127.69,127.23, 126.99, 115.09, 114.91, 55.51, 51.09, 38.53, 35.80, 33.85, 21.54.

Example 19

On the basis of Example 1, the type and amount of electrolyte, the type of solvent, and the electrolysis conditions were adjusted. The specific reaction system and screening results are shown in Table 1. It can be seen from Table 1 that different types of raw materials and electrolysis conditions have an impact on the yield of the target product, and the maximum yield of the target product using the reaction system of Item 8 can reach 70%.

Table 1

Entry Electrolyte Solvent(mL) electrode Yield(%) 1 ⁿBu₄NBF₄(2eq) DCE Pt(+)/Pt(-) 33 2 ⁿBu₄NI(2eq) DCE Pt(+)/Pt(-) 0 3 ⁿBu₄NPF₆(2eq) DCE Pt(+)/Pt(-) 57 4 ⁿBu₄NClO₄(2eq) DCE Pt(+)/Pt(-) 27 5 ⁿBu₄NPF₆(2eq) DMF Pt(+)/Pt(-) 0 6 ⁿBu₄NPF₆(2eq) THF Pt(+)/Pt(-) 0 7 ⁿBu₄NPF₆(2eq) MeOH Pt(+)/Pt(-) 0 8 ⁿBu₄NPF₆(2eq) DCM Pt(+)/Pt(-) 70 9 ⁿBu₄NPF₆(2eq) DCM C(+)/C(-) 0 10 ⁿBu₄NPF₆(2eq) DCM C(+)/Pt(-) 37 11 ⁿBu₄NPF₆(1eq) DCM Pt(+)/Pt(-) 63 12 ⁿBu₄NPF₆(3eq) DCM Pt(+)/Pt(-) 68

The above descriptions are only preferred embodiments of the present invention, and are not intended to limit the present invention. Any modifications, equivalent replacements, improvements, etc. made within the spirit and principles of the present invention shall be included in the protection of the present invention. within range.

Claims (10)

1. a method for preparing eight-membered selenium-containing benzazepine heterocycles, comprising the following steps: using N-(but-3-en-1-yl)-4-methyl-N-(2-(1- Phenyl vinyl) phenyl) benzene sulfonamide compound is used as the substrate, selenium ether is anodized under electrochemical drive to generate selenyl radicals, and selenyl radicals and substrates are coupled with substrates to obtain eight Selenium-containing benzoazepine heterocyclic compounds. 2. the method for preparing eight-membered selenium-containing benzazene heterocyclic compound according to claim 1, is characterized in that, N-(but-3-en-1-yl)-4-methyl-N-(2- The molar ratio of (1-phenylvinyl)phenyl)benzenesulfonamide compound to selenide is 1:(1-1.2). 3. according to claim 1, prepare the method for eight-membered selenium-containing benzazine heterocyclic compound, comprising the following steps: adding N-(but-3-en-1-yl)-4-methyl- N-(2-(1-phenylethenyl)phenyl)benzenesulfonamide compound, selenoether, ^nBu ₄ NPF ₆ and DCM to obtain a mixture; the mixture was electrolyzed until N-(but-3-ene-1 -yl)-4-methyl-N-(2-(1-phenylvinyl)phenyl)benzenesulfonamide compound is completely consumed; after the reaction is complete, it is quenched and extracted; the organic solvent is concentrated; purified, eluting with An eight-membered selenium-containing benzazene heterocyclic compound was obtained by elution with a solvent. 4. according to claim 3, prepare the method for eight-membered selenium-containing benzazine heterocyclic compound, it is characterized in that, N-(but-3-en-1-yl)-4-methyl-N-(2- The molar ratio of (1-phenylvinyl) phenyl) benzenesulfonamide compound, ⁿ Bu ₄ NPF ₆ and selenide is 1: (1-3): (1-1.2); N-(but-3-ene The molar volume ratio of -1-yl)-4-methyl-N-(2-(1-phenylvinyl)phenyl)benzenesulfonamide compound and DCM was 0.2 mmol: 5 mL. 5. according to claim 3, the method for preparing eight-membered selenium-containing benzazine heterocyclic compound is characterized in that, after the reaction is completed, the mixture is quenched with NaHCO ₃ and extracted with CH ₂ Cl ₂ ; then the organic solvent is concentrated in vacuo; The product was purified by flash column chromatography using a mixed solvent of ethyl acetate and petroleum ether as an eluent to obtain an eight-membered selenium-containing benzazepine heterocyclic compound. 6. The method for preparing an octa-membered selenium-containing benzazene heterocyclic compound according to claim 3, wherein a Pt electrode is used to electrolyze the mixture at room temperature with a constant current of 2 mA. 7. according to the method for preparing eight-membered selenium-containing benzazene heterocyclic compound according to any one of claims 1-6, it is characterized in that, N-(but-3-en-1-yl)-4-methyl- The structural formula of N-(2-(1-phenylvinyl) phenyl) benzenesulfonamide compound is shown in formula 1,

Wherein, R ¹ is independently selected from one of H, CH ₃ , Cl, and Br substituents; R ² is independently selected from o-CNPh, H, CH ₃ , OCH ₃ , F, Cl, and Br substituents A sort of. 8. according to claim 7, prepare the method for eight-membered selenium-containing benzazepine heterocyclic compound, it is characterized in that, N-(but-3-en-1-yl)-4-methyl-N-(2- (1-phenylvinyl) phenyl) benzenesulfonamide compound is selected from one or more combinations 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-methyl Benzenesulfonamide, 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-ene-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. 9. according to the method for preparing eight-membered selenium-containing benzazene heterocyclic compound according to any one of claims 1-6, it is characterized in that, described selenide is diselenide; Preferably, described selenide is selected from two Phenyl diselenide, 1,2-bis(2-methoxyphenyl) diselenide, 1,2-bis(3-methoxyphenyl) diselenide, 1,2-bis(3- Bromophenyl) diselenide, 1,2-bis(4-methylphenyl) diselenide, 1,2-bis(4-chlorophenyl) diselenide, 1,2-bis(3,5 -One or more of dimethylphenyl) diselenide and 1,2-bis(2-naphthyl) diselenide. 10. An eight-membered selenium-containing benzazine heterocyclic compound, characterized in that it has the following chemical formula:

Wherein, R ¹ is independently selected from one of H, CH ₃ , Cl, and Br substituents; R ² is independently selected from o-CNPh, H, CH ₃ , OCH ₃ , F, Cl, and Br substituents One; ^R3 is independently selected from benzene rings, naphthalene, and one or more substituted benzene rings containing halogen, methyl, and methoxy.

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