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

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

Technical Field

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

Background

Selenium is one of the essential trace elements of human body, is known as 'fire of life', and enjoys the reputations of 'long life element', 'anticancer king' and the like. 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. Sanitation industry standard WS/T578.3 newly implemented in 2018 and 4 months-2017 dietary nutrient reference intake regulation of Chinese residents: the average selenium requirement of adult per day is 50-60 μ g. In view of the important biological and pharmacological activities of the selenium-containing heterocyclic compound and the important effects in the aspects of antibiosis, tumor resistance, cardiovascular protection and immunoregulation, a novel method for efficiently synthesizing the selenium-containing heterocycle with a novel structure is developed, and the method has important research values and practical significance for the development of selenium-containing products, the establishment of selenium-containing drug molecule libraries and the research and development of drugs. On the other hand, nitrogen-containing heterocycles are key framework structures of many drug molecules and have wide and important biological activities and medicinal values. Therefore, the development of a simple, efficient, green process for introducing seleno groups into azacycles has attracted a wide range of attention from chemists. At present, the selenium-containing N-heterocycles reported in the literature are limited to 5-or 6-membered heterocyclic ring systems; in contrast, reports of selenium-containing compounds containing medium-sized N-heterocyclic building blocks have been very rare. With the proposal of the concept of 'green sustainable chemistry', the electrochemical technology is one of green and sustainable synthesis methods, and opens up wide application prospects in the fields of double functionalization and cyclization of unsaturated bonds, direct functionalization of C-H bonds and the like. Therefore, the efficient construction of N-heterocycles using electrochemical techniques has been a popular area of organic synthesis research. However, no report is available on the development of a method for constructing an eight-membered selenium-containing benzoazacycle under electrochemical drive without metal or oxidant.

Disclosure of Invention

In view of the problems in the prior art, the invention provides a method for preparing an eight-membered selenium-containing benzoazacyclo compound, which is an effective method for preparing the eight-membered selenium-containing benzoazacyclo compound by taking N- (but-3-en-1-yl) -4-methyl-N- (2- (1-phenyl vinyl) phenyl) benzene sulfonamide compound as a substrate, generating a seleno radical through anodic oxidation of seleno ether under electrochemical driving, and coupling and cyclizing the seleno radical and the substrate through the free radical.

The technical scheme for solving the technical problems is as follows:

the invention provides a method for preparing an eight-membered selenium-containing benzoazacyclo 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 beneficial effects of adopting the technical scheme include:

the invention generates selenium radical free radical through electrocatalysis, and prepares a series of octatomic selenium-containing benzo nitrogen heterocyclic compounds efficiently through serial cyclization of free radical addition. The eight-membered selenium-containing benzoazacycle compounds have various biological activities.

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, economy, simple and easy preparation of raw materials, wide range of substrates, amplified preparation of products, cheap and easily obtained substrates, green reaction, no explosion risk, no metal salt, easy post-treatment and the like.

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

The beneficial effects of adopting the technical scheme include: the operation is green and simple, and traceless electrons are used for replacing an additional redox agent, so that the use of a metal catalyst and the additional redox agent is avoided.

Further, the method comprises the following steps: adding N- (but-3-en-1-yl) -4-methyl-N- (2- (1-phenyl vinyl) phenyl) benzene sulfonamide compound, selenoether, ⁿ Bu ₄ NPF ₆ And DCM to give 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 finished, quenching and extracting; concentrating the organic solvent; purifying and eluting with eluent to obtain the octavalent selenium-containing benzo nitrogen heterocyclic compound.

Further, N- (but-3-en-1-yl) -4-methyl-N- (2- (1-phenylethenyl) phenyl) benzenesulfonamide compounds, ⁿ Bu ₄ NPF ₆ And selenoether in a molar ratio of 1: (1-3): (1-1.2); the molar volume ratio of the N- (but-3-en-1-yl) -4-methyl-N- (2- (1-phenylvinyl) phenyl) benzenesulfonamide compound to DCM was 0.2mmol:5mL.

The beneficial effects of adopting the technical scheme include: the above ratio is favorable for the reaction and the yield is improved.

Preferably, N- (but-3-en-1-yl) -4-methyl-N- (2- (1-phenylvinyl) phenyl) benzenesulfonamide compounds, ⁿ Bu ₄ NPF ₆ And selenoether in a molar ratio of 1:2: (1-1.2), the yield of the desired product can be further improved.

Further, after the reaction was completed, the mixture was treated with NaHCO ₃ Quenching and use of CH ₂ Cl ₂ Extracting; then concentrating the organic solvent in vacuum; the residue was purified by flash column chromatography using a mixed solvent of ethyl acetate and petroleum ether as an eluent to give an eight-membered selenium-containing benzazepine compound.

The beneficial effects of adopting the technical scheme include: with NaHCO ₃ Quenching is advantageous to reduce the solubility of the product, using CH ₂ Cl ₂ The extraction is favorable for layering and thorough extraction of products, and the mixed solvent of ethyl acetate and petroleum ether is used as an eluent to be favorable for removing the eluent.

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

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

Further, the structural formula of the N- (butyl-3-alkene-1-yl) -4-methyl-N- (2- (1-phenyl vinyl) phenyl) benzene sulfonamide compound is shown as a formula 1,

wherein R is ¹ Independently selected from H, CH ₃ One of Cl and Br substituents; r is ² Independently selected from o-CNPh, H, CH ₃ 、OCH ₃ And one of F, cl and Br substituent.

Further, the N- (but-3-en-1-yl) -4-methyl-N- (2- (1-phenyl vinyl) phenyl) benzene sulfonamide compound is 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- (p-tolyl) vinyl) phenyl) benzenesulfonamide Benzenesulfonamide, N- (but-3-en-1-yl) -N- (2 '-cyano-3- (1-phenylvinyl) - [1,1' -biphenyl ] -4-yl) -4-methylbenzenesulfonamide.

Further, the selenoether may be diselenide; preferably, the selenide is one or more selected from diphenyl diselenide, 1, 2-di (2-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.

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

wherein R is ¹ Independently selected from H, CH ₃ One of Cl and Br substituents; r ² Independently selected from o-CNPh, H, CH ₃ 、OCH ₃ One of substituents of F, cl and Br; r is ³ Independently selected from benzene ring, naphthalene, benzene ring containing one or more of halogen, methyl and methoxyl.

The beneficial effects of adopting the technical scheme include: the octa-element selenium-containing benzo nitrogen heterocyclic compound prepared by the invention has various biological activities and wide application prospect.

Drawings

FIG. 1 is a reaction scheme for the preparation of eight-membered selenium-containing benzoazaheterocyclic compounds in accordance with the present invention.

FIG. 2 is a drawing of Compound 3a from example 1 ¹ H NMR spectrum. FIG. 3 is a photograph of Compound 3a of example 1 ¹³ C NMR spectrum.

FIG. 4 shows the preparation of compound 3b in example 2 ¹ H NMR spectrum. FIG. 5 is a drawing of Compound 3b from example 2 ¹³ C NMR spectrum.

FIG. 6 is a schematic representation of Compound 3c of example 3 ¹ H NMR spectrum. FIG. 7 is a drawing of Compound 3c from example 3 ¹³ C NMR spectrum.

FIG. 8 is a drawing of Compound 3d of example 4 ¹ H NMR spectrum. FIG. 9 is a drawing of Compound 3d of example 4 ¹³ C NMR spectrum.

FIG. 10 shows the preparation of Compound 3e in example 5 ¹ H NMR spectrum. FIG. 11 is a drawing of Compound 3e of example 5 ¹³ C NMR spectrum.

FIG. 12 is a drawing of Compound 3f of example 6 ¹ H NMR spectrum. FIG. 13 is a drawing of Compound 3f from example 6 ¹³ C NMR spectrum.

FIG. 14 shows 3g of the compound in example 7 ¹ H NMR spectrum. FIG. 15 is a drawing showing 3g of the compound in example 7 ¹³ C NMR spectrum.

FIG. 16 is a photograph of compound 3h of example 8 ¹ H NMR spectrum. FIG. 17 is of 3h for example 8 ¹³ C NMR spectrum.

FIG. 18 shows the preparation of Compound 3i in example 9 ¹ H NMR spectrum. FIG. 19 is a schematic representation of Compound 3i of example 9 ¹³ C NMR spectrum.

FIG. 20 is a drawing of Compound 3j from example 10 ¹ H NMR spectrum. FIG. 21 is a drawing of Compound 3j from example 10 ¹³ C NMR spectrum.

FIG. 22 is a photograph of Compound 3k in example 11 ¹ H NMR spectrum. FIG. 23 is a drawing of Compound 3k from example 11 ¹³ C NMR spectrum.

FIG. 24 is a drawing of 3l compound of example 12 ¹ H NMR spectrum. FIG. 25 is of 3l in example 12 ¹³ C NMR spectrum.

FIG. 26 is a drawing showing a scheme of preparation of compound 3m in example 13 ¹ H NMR spectrum. FIG. 27 is a drawing of compound 3m from example 13 ¹³ C NMR spectrum. FIG. 28 is a photograph of Compound 3m of example 13 ¹⁹ F NMR spectrum.

FIG. 29 is a drawing of Compound 3n from example 14 ¹ H NMR spectrum. FIG. 30 is a combination of example 14Of object 3n ¹³ C NMR spectrum.

FIG. 31 is a scheme showing that of Compound 3o in example 15 ¹ H NMR spectrum. FIG. 32 is a photograph of compound 3o from example 15 ¹³ C NMR spectrum.

FIG. 33 is a photograph of Compound 3p of example 16 ¹ H NMR spectrum. FIG. 34 is a drawing of Compound 3p from example 16 ¹³ C NMR spectrum.

FIG. 35 is a scheme showing that of Compound 3q in example 17 ¹ H NMR spectrum. FIG. 36 shows a modification of compound 3q of example 17 ¹³ C NMR spectrum.

FIG. 37 is a drawing of compound 3r from example 18 ¹ H NMR spectrum. FIG. 38 is a drawing of Compound 3r from example 18 ¹³ C NMR spectrum.

Detailed Description

The principles and features of this invention are described below in conjunction with the following drawings, which are set forth by way of illustration only and are not intended to limit the scope of the invention. The technical solution of the present invention is not limited to the following examples, but includes any combination between the examples.

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

The method for preparing the octa-element selenium-containing benzo nitrogen heterocyclic compound by electrocatalysis 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.

Wherein R is ¹ Independently selected from H, CH ₃ One of Cl and Br substituents; r ² Independently selected from o-CNPh, H, CH ₃ 、OCH ₃ One of substituents of F, cl and Br; r is ³ Independently selected from benzene ring, naphthalene, halogen, methylBenzene ring substituted by one or more of oxy.

Specifically, the following method can be used to prepare eight-membered selenium-containing benzoazacyclic compounds:

at room temperature (generally 25 ℃), adding N- (butyl-3-en-1-yl) -4-methyl-N- (2- (1-phenyl vinyl) phenyl) benzene sulfonamide compound 1, selenide 2, and, ⁿ Bu ₄ NPF ₆ And dichloromethane DCM. N- (but-3-en-1-yl) -4-methyl-N- (2- (1-phenylvinyl) phenyl) benzenesulfonamide compounds, ⁿ Bu ₄ NPF ₆ And selenoether in a molar ratio of 1: (1-3): (1-1.2), preferably, N- (but-3-en-1-yl) -4-methyl-N- (2- (1-phenylvinyl) phenyl) benzenesulfonamide compounds, ⁿ Bu ₄ NPF ₆ And selenoether in a molar ratio of 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 to DCM was 0.2mmol:5mL.

The mixture was electrolyzed using a Pt electrode at a constant current of 2mA until complete consumption of the starting material 1 (i.e., N- (but-3-en-1-yl) -4-methyl-N- (2- (1-phenylvinyl) phenyl) benzenesulfonamide compound 1) as monitored by TLC analysis. After the reaction was complete, the mixture was saturated with NaHCO ₃ (i.e., saturated sodium bicarbonate solution at room temperature, sat. Aq.15mL) and quenched with CH ₂ Cl ₂ (3X 5 mL) was extracted. 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 give eight-membered selenium-containing benzazepine product 3. The volume ratio of petroleum ether to ethyl acetate employed in the present invention may be 20: the volume ratio of petroleum ether to ethyl acetate in examples 1 to 19 may be 20.

As shown in FIG. 1, the reaction mechanism of the present invention is further illustrated by taking N- (but-3-en-1-yl) -4-methyl-N- (2- (1-phenylvinyl) phenyl) benzenesulfonamide 1a and diphenyl diselenide as examples:

the diphenyl diselenide is oxidized into a phenylseleno radical through anodic oxidation, and the phenylseleno radical attacks the double bond on the outer side of the butylene in the substrate 1a to obtain a radical intermediate. And performing intramolecular addition of the free radical intermediate A and another double bond to obtain a free radical intermediate B. Finally, the radical intermediate B is deprotonated to provide the final product. The methylene chloride is reduced on the surface of the cathode to release hydrogen.

The invention provides a method for efficiently preparing a series of eight-membered selenium-containing benzo nitrogen heterocyclic compounds by electrocatalysis to generate selenium radical free radicals and by addition of the free radicals in series cyclization under the conditions of no metal and no oxidant. The compound has various biological activities. The method has the advantages of economy, simple and easy preparation of raw materials, wide substrate range, capability of amplifying and preparing products and the like.

ⁿ Bu ₄ NPF ₆ Purchased from Shanghai Biao medicine, and column chromatography silica gel used in the purification process of rapid column chromatography is purchased from Nicotiana Xinno chemical Co., ltd, and the parameters are 200-300 meshes.

Unless otherwise specified, the reagents of the present invention are conventional in the art and are commercially available. Unless otherwise specified, the experimental methods adopted in the invention are all routine experimental methods in the field.

The following description is given by way of specific examples.

Example 1

In this example, the method for electrochemically driving the preparation of an eight-membered selenium-containing benzazepine compound in the absence of metal and oxidant is as follows:

at room temperature, sequentially adding N- (butyl-3-en-1-yl) -4-methyl-N- (2- (1-phenyl vinyl) phenyl) benzene sulfonamide 1a (0.2 mmol), diphenyl diselenide 2a (0.2 mmol) and sodium hydrogen sulfide into a reaction bottle, ⁿ Bu ₄ NPF ₆ (0.4 mmol) and DCM (5 mL) equipped with two Pt electrodes (1 cm. Times.1 cm). The electrolysis was carried out at 25 ℃ at room temperature, using a constant current of 2mA, until complete consumption of the starting material (TLC monitoring, about 12 h). After the reaction was complete, the mixture was washed with NaHCO ₃ (sat. Aq.15mL) and quenched with CH ₂ Cl ₂ (3X 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 a wash to give product 3a.

The results of the spectra are shown in FIGS. 2 and 3. Of compound 3a ¹ H NMR、 ¹³ The structure of the compound is known from the C NMR spectrum. Specifically, the method comprises the following steps:

rf (petroleum ether/ethyl acetate = 10): 0.23; yellow liquid (66 mg, 70% yield). 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＝14.6,3.6Hz,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

The method for electrochemically driving the preparation of the eight-membered selenium-containing benzoazacyclic compound in the absence of metal and oxidant in this example is as follows:

at room temperature, sequentially adding N- (butyl-3-en-1-yl) -4-methyl-N- (2- (1-phenyl vinyl) phenyl) benzene sulfonamide 1a (0.2 mmol), 1, 2-di (2-methoxyphenyl) diselenide 2b (0.2 mmol) and sodium hydrogen carbonate into a reaction bottle, ⁿ Bu ₄ NPF ₆ (0.4 mmol) and DCM (5 mL), equipped with two Pt electrodes (1 cm. Times.1 cm). The electrolysis was carried out at 25 ℃ and room temperature, using a constant current of 2mA, until complete consumption of the starting material (TLC monitoring, approx. 12 h). After the reaction was complete, the mixture was washed with NaHCO ₃ (sat. Aq.15mL) and CH ₂ Cl ₂ (3X 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 a wash to give product 3b.

The spectrogram results are shown in FIGS. 4 and 45, respectively. Of compound 3b ¹ H NMR、 ¹³ The structure of the compound is known from the C NMR spectrum. Specifically, the method comprises the following steps:

rf (petroleum ether/ethyl acetate = 10): 0.11; yellow liquid (72 mg, 61% yield). 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

The method for electrochemically driving and preparing the eight-membered selenium-containing benzoazacyclo compound under the condition of no metal and no oxidant in the embodiment is as follows:

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-methoxyphenyl) diselenide 2c (1.2equiv, 0.24mmol), and, ⁿ Bu ₄ NPF ₆ (0.4 mmol) and DCM (5 mL) equipped with two Pt electrodes (1 cm. Times.1 cm). The electrolysis was carried out at 25 ℃ and room temperature, using a constant current of 2mA, until complete consumption of the starting material (TLC monitoring, approx. 12 h). After the reaction was complete, the mixture was washed with NaHCO ₃ (sat. Aq.15mL) and CH ₂ Cl ₂ (3X 5 mL) was extracted. 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 a wash to give product 3c.

The results of the spectra are shown in FIGS. 6 and 7. Of compound 3c ¹ H NMR、 ¹³ The structure of the compound is known from the C NMR spectrum. Specifically, the method comprises the following steps:

rf (petroleum ether/ethyl acetate = 10): 0.11; yellow liquid (72 mg, 61% yield). 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 )δ159.67,143.17,142.11,141.97,140.30,138.50,137.73,133.01,131.05,130.95,129.75,129.44,128.87,128.59,128.54,128.23,127.97,127.74,127.24,125.11,118.29,112.67,55.25,50.98,38.68,35.68,33.69,21.54.

Example 4

The method for electrochemically driving and preparing the eight-membered selenium-containing benzoazacyclo compound under the condition of no metal and no oxidant in the embodiment is as follows:

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-bromophenyl) diselenide 2d (1.2equiv, 0.24mmol) and, ⁿ Bu ₄ NPF ₆ (0.4 mmol) and DCM (5 mL) equipped with two Pt electrodes (1 cm. Times.1 cm). The electrolysis was carried out at 25 ℃ at room temperature, using a constant current of 2mA, until complete consumption of the starting material (TLC monitoring, about 12 h). After the reaction was complete, the mixture was washed with NaHCO ₃ (sat. Aq.15mL) and quenched with CH ₂ Cl ₂ (3X 5 mL) was extracted. 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 a wash to give product 3d.

The results of the spectra are shown in FIGS. 8 and 9. Of Compound 3d ¹ H NMR、 ¹³ The structure of the compound is known from the C NMR spectrum. Specifically, the method comprises the following steps:

Rf(petroleum ether/ethyl acetate＝10:1):0.11; yellow liquid (65 mg, 51% yield). 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 )δ143.20,142.01,141.85,140.25,138.74,137.69,135.22,132.66,131.96,131.43,130.90,130.27,130.00,129.45,128.95,128.56,128.52,128.34,128.01,127.72,127.32,122.75,50.93,38.45,35.85,33.74,21.54.

Example 5

The method for electrochemically driving and preparing the eight-membered selenium-containing benzoazacyclo compound under the condition of no metal and no oxidant in the embodiment is as follows:

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) diselenide 2e (1.2equiv, 0.24mmol) and, ⁿ Bu ₄ NPF ₆ (0.4 mmol) and DCM (5 mL) equipped with two Pt electrodes (1 cm. Times.1 cm). The electrolysis was carried out at 25 ℃ and room temperature, using a constant current of 2mA, until complete consumption of the starting material (TLC monitoring, approx. 12 h). After the reaction is complete, the mixture is treated with NaHCO ₃ (sat. Aq.15mL) and quenched with CH ₂ Cl ₂ (3X 5 mL) was extracted. 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 a wash to give product 3e.

The results of the spectra are shown in FIGS. 10 and 11. Of Compound 3e ¹ H NMR、 ¹³ The structure of the compound is known from the C NMR spectrum. Specifically, the method comprises the following steps:

rf (petroleum ether/ethyl acetate =10: 1) 0.17; yellow liquid (82 mg, 71% yield). 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＝8.7Hz,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,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

The method for electrochemically driving and preparing the eight-membered selenium-containing benzoazacyclo compound under the condition of no metal and no oxidant in the embodiment is as follows:

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) diselenide 2f (1.2equiv, 0.24mmol), and, ⁿ Bu ₄ NPF ₆ (0.4 mmol) and DCM (5 mL), equipped with two Pt electrodes (1 cm. Times.1 cm). The electrolysis was carried out at 25 ℃ and room temperature, using a constant current of 2mA, until complete consumption of the starting material (TLC monitoring, approx. 12 h). After the reaction is complete, the mixture is treated with NaHCO ₃ (sat. Aq.15mL) and CH ₂ Cl ₂ (3X 5 mL) was extracted. 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 a wash to give product 3f.

The results of the spectra are shown in FIGS. 12 and 13. Of compound 3f ¹ H NMR、 ¹³ The structure of the compound is known from the C NMR spectrum. Specifically, the method comprises the following steps:

rf (petroleum ether/ethyl acetate =10: 1) 0.14; yellow liquid (76 mg, 64% yield). 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 )δ143.21,142.04,141.88,140.27,138.60,137.70,134.73,133.28,132.85,130.85,129.47,129.13,128.96,128.57,128.54,128.25,128.01,127.79,127.71,127.33,50.93,38.32,35.94,33.74,21.55.

Example 7

The method for electrochemically driving and preparing the eight-membered selenium-containing benzoazacyclo compound under the condition of no metal and no oxidant in the embodiment is as follows:

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) diselenide 2g (1.2equiv, 0.24mmol), and, ⁿ Bu ₄ NPF ₆ (0.4 mmol) and DCM (5 mL) equipped with two Pt electrodes (1 cm. Times.1 cm). The electrolysis was carried out at 25 ℃ at room temperature, using a constant current of 2mA, until complete consumption of the starting material (TLC monitoring, about 12 h). After the reaction is complete, the mixture is treated with NaHCO ₃ (sat. Aq.15mL) and CH ₂ Cl ₂ (3X 5 mL) was extracted. 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 a wash to give 3g of a product.

The results of the spectra are shown in FIGS. 14 and 15. Compound 3g of ¹ H NMR、 ¹³ The structure of the compound is known from the C NMR spectrum. Specifically, the method comprises the following steps:

rf (petroleum ether/ethyl acetate =10: 1) 0.23; yellow solid (84 mg, 71% yield) 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

The method for electrochemically driving and preparing the eight-membered selenium-containing benzoazacyclo compound under the condition of no metal and no oxidant in the embodiment is as follows:

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 (1.2equiv, 0.24mmol) and, ⁿ Bu ₄ NPF ₆ (0.4 mmol) and DCM (5 mL), equipped with two Pt electrodes (1 cm. Times.1 cm). The electrolysis was carried out at 25 ℃ and room temperature, using a constant current of 2mA, until complete consumption of the starting material (TLC monitoring, approx. 12 h). After the reaction was complete, the mixture was washed with NaHCO ₃ (sat. Aq.15mL) and quenched with CH ₂ Cl ₂ (3X 5 mL) was extracted. 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 a wash to give the product for 3h.

The results of the spectra are shown in FIGS. 16 and 17. Of the compound 3h ¹ H NMR、 ¹³ The structure of the compound is known from the C NMR spectrum. Specifically, the method comprises the following steps:

rf (petroleum ether/ethyl acetate = 10): 0.11; yellow solid (68 mg, 56% yield) 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 )δ143.14,142.03,141.97,140.22,138.43,137.72,134.41,133.92,133.25,133.19,130.88,129.42,128.98,128.81,128.59,128.56,128.50,128.46,128.16,127.96,127.73,127.21,126.67,126.17,125.65,50.90,38.53,36.03,33.76,21.53.

Example 9

The method for electrochemically driving and preparing the eight-membered selenium-containing benzoazacyclo compound under the condition of no metal and no oxidant in the embodiment is as follows:

at room temperature, sequentially adding N- (butyl-3-en-1-yl) -4-methyl-N- (5-methyl-2- (1-phenyl vinyl) phenyl) benzene sulfonamide 1b (0.2 mmol), diphenyl diselenide 2a (0.2 mmol), and, ⁿ Bu ₄ NPF ₆ (0.4 mmol) and DCM (5 mL) equipped with two Pt electrodes (1 cm. Times.1 cm). The electrolysis was carried out at 25 ℃ and room temperature, using a constant current of 2mA, until complete consumption of the starting material (TLC monitoring, approx. 12 h). After the reaction was complete, the mixture was washed with NaHCO ₃ (sat. Aq.15mL) and quenched with CH ₂ Cl ₂ (3X 5 mL) was extracted. 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 a wash to give product 3i.

The results of the spectra are shown in FIGS. 18 and 19. Of Compound 3i ¹ H NMR、 ¹³ The structure of the compound is known from the C NMR spectrum. Specifically, the method comprises the following steps:

rf (petroleum ether/ethyl acetate = 10): 0.17; yellow liquid (82 mg, 72% yield). 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 )δ143.19,142.17,140.14,138.96,138.46,137.76,133.16,132.84,130.64,130.06,129.36,129.16,129.03,128.58,127.99,127.84,127.20,126.96,50.82,38.65,35.84,33.78,21.57,21.02.

Example 10

The method for electrochemically driving and preparing the eight-membered selenium-containing benzoazacyclo compound under the condition of no metal and no oxidant in the embodiment is as follows:

at room temperature, N- (but-3-en-1-yl) -N- (4-chloro-2- (1-phenylvinyl) phenyl) -4-methylbenzenesulfonamide 1c (0.2 mmol), diphenyl diselenide 2a (1.2equiv, 0.24mmol) and sodium chloride were sequentially added to a reaction flask, ⁿ Bu ₄ NPF ₆ (0.4 mmol) and DCM (5 mL), equipped with two Pt electrodes (1 cm. Times.1 cm). The electrolysis was carried out at 25 ℃ and room temperature, using a constant current of 2mA, until complete consumption of the starting material (TLC monitoring, approx. 12 h). After the reaction is complete, the mixture is treated with NaHCO ₃ (sat. Aq.15mL) and CH ₂ Cl ₂ (3X 5 mL) was extracted. 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 a wash to give product 3j.

The results of the spectra are shown in FIGS. 20 and 21. Of Compound 3J ¹ H NMR、 ¹³ The structure of the compound is known from the C NMR spectrum. Specifically, the method comprises the following steps:

rf (petroleum ether/ethyl acetate = 10): 0.14; yellow solid (68 mg, 57% yield) 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

The method for electrochemically driving and preparing the eight-membered selenium-containing benzoazacyclo compound under the condition of no metal and no oxidant in the embodiment is as follows:

at room temperature, N- (4-bromo-2- (1-phenylethenyl) phenyl) -N- (but-3-en-1-yl) -4-methylbenzenesulfonamide 1d (0.2 mmol), diphenyl diselenide 2a (1.2equiv, 0.24mmol), and N- (4-bromo-2- (1-phenylethenyl) phenyl) -N- (but-3-en-1-yl) -4-methylbenzenesulfonamide were added to a reaction flask in this order, ⁿ Bu ₄ NPF ₆ (0.4 mmol) and DCM (5 mL), equipped with two Pt electrodes (1 cm. Times.1 cm). The electrolysis was carried out at 25 ℃ and room temperature, using a constant current of 2mA, until complete consumption of the starting material (TLC monitoring, approx. 12 h). After the reaction was complete, the mixture was washed with NaHCO ₃ (sat. Aq.15mL) and quenched with CH ₂ Cl ₂ (3X 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 a wash to give the product 3k.

The results of the spectra are shown in FIGS. 22 and 23. Of Compound 3k ¹ H NMR、 ¹³ The structure of the compound is known from the C NMR spectrum. Specifically, the method comprises the following steps:

rf (petroleum ether/ethyl acetate = 10): 0.14; yellow liquid (74 mg, 58% yield). 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＝13.7Hz,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

The method for electrochemically driving and preparing the eight-membered selenium-containing benzoazacyclo compound under the condition of no metal and no oxidant in the embodiment is as follows:

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 (1.2equiv, 0.24mmol), and water were sequentially added to a reaction flask, ⁿ Bu ₄ NPF ₆ (0.4 mmol) and DCM (5 mL) equipped with two Pt electrodes (1 cm. Times.1 cm). The electrolysis was carried out at 25 ℃ at room temperature, using a constant current of 2mA, until complete consumption of the starting material (TLC monitoring, about 12 h). After the reaction was complete, the mixture was washed with NaHCO ₃ (sat. Aq.15mL) and quenched with CH ₂ Cl ₂ (3X 5 mL) was extracted. 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 a wash to give 3l of the product.

The results of the spectra are shown in FIGS. 24 and 25. Of Compound 3l ¹ H NMR、 ¹³ The structure of the compound is known from the C NMR spectrum. Specifically, the method comprises the following steps:

rf (petroleum ether/ethyl acetate = 10): 0.17; yellow liquid (69 mg, 60% yield). 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

The method for electrochemically driving and preparing the eight-membered selenium-containing benzoazacyclo compound under the condition of no metal and no oxidant in the embodiment is as follows:

sequentially adding N- (butyl-3-en-1-yl) -4-methyl-N- (4-methyl-2- (1-benzene) into a reaction bottle at room temperatureMonovinyl) phenyl) benzenesulfonamide 1f (0.2 mmol), diphenyl diselenide 2a (1.2equiv, 0.24mmol), ⁿ Bu ₄ NPF ₆ (0.4 mmol) and DCM (5 mL) equipped with two Pt electrodes (1 cm. Times.1 cm). The electrolysis was carried out at 25 ℃ and room temperature, using a constant current of 2mA, until complete consumption of the starting material (TLC monitoring, approx. 12 h). After the reaction was complete, the mixture was washed with NaHCO ₃ (sat. Aq.15mL) and quenched with CH ₂ Cl ₂ (3X 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 a wash to give a product of 3m.

The results of the spectra are shown in fig. 26, 27 and 28. Of compound 3m ¹ H NMR、 ¹³ C NMR spectrum, ¹⁹ F NMR showed the structure of the compound. Specifically, the method comprises the following steps:

rf (petroleum ether/ethyl acetate = 10): 0.26; yellow liquid (69 mg, 58% yield). 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

The method for electrochemically driving the preparation of the eight-membered selenium-containing benzoazacyclic compound in the absence of metal and oxidant in this example is as follows:

at room temperatureTo a reaction flask were added in this order 1g (0.2 mmol) of N- (but-3-en-1-yl) -N- (4-chloro-2- (1- (p-tolyl) vinyl) phenyl) -4-methylbenzenesulfonamide, 1.2equiv (0.24mmol) of diphenyl diselenide, and, ⁿ Bu ₄ NPF ₆ (0.4 mmol) and DCM (5 mL), equipped with two Pt electrodes (1 cm. Times.1 cm). The electrolysis was carried out at 25 ℃ at room temperature, using a constant current of 2mA, until complete consumption of the starting material (TLC monitoring, about 12 h). After the reaction was complete, the mixture was washed with NaHCO ₃ (sat. Aq.15mL) and quenched with CH ₂ Cl ₂ (3X 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 a wash to give the product 3n.

The results of the spectra are shown in FIGS. 29 and 30. Of compound 3n ¹ H NMR、 ¹³ The structure of the compound is known from the C NMR spectrum. Specifically, the method comprises the following steps:

rf (petroleum ether/ethyl acetate = 10): 0.23; yellow liquid (75 mg, 62% yield). 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

The method for electrochemically driving and preparing the eight-membered selenium-containing benzoazacyclo compound under the condition of no metal and no oxidant in the embodiment is as follows:

sequentially adding N- (butyl-3-en-1-yl) -N- (2 '-cyano-3- (1-phenylvinyl) - [1,1' -biphenyl into a reaction bottle at room temperature]-4-1h (0.2 mmol) of 4-methylbenzenesulfonamide, 2a (1.2equiv, 0.24mmol) of diphenyl diselenide, ⁿ Bu ₄ NPF ₆ (0.4 mmol) and DCM (5 mL) equipped with two Pt electrodes (1 cm. Times.1 cm). The electrolysis was carried out at 25 ℃ and room temperature, using a constant current of 2mA, until complete consumption of the starting material (TLC monitoring, approx. 12 h). After the reaction was complete, the mixture was washed with NaHCO ₃ (sat. Aq.15mL) and CH ₂ Cl ₂ (3X 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 a wash to give product 3o.

The results of the spectra are shown in FIGS. 31 and 32. Of compound 3o ¹ H NMR、 ¹³ The structure of the compound is known from the C NMR spectrum. Specifically, the method comprises the following steps:

rf (petroleum ether/ethyl acetate =10: 1) 0.06; yellow liquid (70 mg, 53% yield). 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＝16.4,15.2,7.6Hz,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)； ¹³ C 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

The method for electrochemically driving and preparing the eight-membered selenium-containing benzoazacyclo compound under the condition of no metal and no oxidant in the embodiment is as follows:

to a reaction flask were added N- (4-chloro-2- (1-phenylethenyl) phenyl) -N- (but-3-en-1-yl) -4-methylbenzenesulfonamide 1i (0.2 mmol), diphenyldiselenide 2a (1.2equiv, 0.24 mmol) in this order at room temperaturemmol)、 ⁿ Bu ₄ NPF ₆ (0.4 mmol) and DCM (5 mL), equipped with two Pt electrodes (1 cm. Times.1 cm). The electrolysis was carried out at 25 ℃ and room temperature, using a constant current of 2mA, until complete consumption of the starting material (TLC monitoring, approx. 12 h). After the reaction is complete, the mixture is treated with NaHCO ₃ (sat. Aq.15mL) and CH ₂ Cl ₂ (3X 5 mL) was extracted. 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 a wash to give product 3p.

The results of the spectra are shown in FIGS. 33 and 34. Of Compound 3p ¹ H NMR、 ¹³ The structure of the compound is known from the C NMR spectrum. Specifically, the method comprises the following steps:

rf (petroleum ether/ethyl acetate =10: 1) 0.14; yellow liquid (68 mg, 57% yield). 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

The method for electrochemically driving the preparation of the eight-membered selenium-containing benzoazacyclic compound in the absence of metal and oxidant in this example is as follows:

at room temperature, sequentially adding N- (butyl-3-en-1-yl) -4-methyl-N- (5-bromo-2- (1-phenyl vinyl) phenyl) benzenesulfonamide 1j (0.2 mmol), diphenyl diselenide 2a (0.2 mmol) and sodium hydrogen sulfide into a reaction bottle, ⁿ Bu ₄ NPF ₆ (0.4 mmol) and DCM (5 mL) equipped with two Pt electrodes (1 cm. Times.1 cm). Is electrolyzed atAt 25 ℃ at room temperature, a constant current of 2mA was used until complete consumption of the starting material (TLC monitoring, approx. 12 h). After the reaction was complete, the mixture was washed with NaHCO ₃ (sat. Aq.15mL) and CH ₂ Cl ₂ (3X 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 a wash to give product 3q.

The results of the spectra are shown in FIGS. 35 and 36. Of compound 3q ¹ H NMR、 ¹³ The structure of the compound is known from the C NMR spectrum. Specifically, the method comprises the following steps:

rf (petroleum ether/ethyl acetate =10: 1) 0.23; yellow liquid (69 mg, 54% yield). 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 )δ143.58,141.46,141.36,141.26,137.61,137.19,133.64,133.28,132.16,131.76,131.48,129.65,129.56,129.03,128.53,128.10,127.72,127.47,127.11,121.41,50.81,38.56,35.53,33.47,21.56.

Example 18

The method for electrochemically driving and preparing the eight-membered selenium-containing benzoazacyclo compound under the condition of no metal and no oxidant in the embodiment is as follows:

at room temperature, N- (but-3-en-1-yl) -N- (4-methoxy-2- (1-phenylvinyl) phenyl) -4-methylbenzenesulfonamide 1k (0.2 mmol), diphenyl diselenide 2a (1.2equiv, 0.24mmol) and sodium chloride were sequentially added to a reaction flask, ⁿ Bu ₄ NPF ₆ (0.4 mmol) and DCM (5 mL), equipped with two Pt electrodes (1 cm. Times.1 cm). The electrolysis is carried out at 25 ℃ and room temperature, using a constant current of 2mA, until complete consumption of the starting material(s) (ii)TLC monitoring, about 12 h). After the reaction is complete, the mixture is treated with NaHCO ₃ (sat. Aq.15mL) and CH ₂ Cl ₂ (3X 5 mL) was extracted. 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 a wash to give product 3r.

The results of the spectra are shown in FIGS. 37 and 38. Of compound 3r ¹ H NMR、 ¹³ The structure of the compound is known from the C NMR spectrum. Specifically, the method comprises the following steps:

rf (petroleum ether/ethyl acetate =10: 1) 0.11; yellow liquid (77 mg, 65% yield). 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＝2.8Hz,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

The types and amounts of the electrolytes, the types of the solvents, and the electrolysis conditions were adjusted in addition to those of example 1, and specific reaction systems and screening results are shown in table 1. As can be seen from Table 1, the yield of the desired product was affected by the kinds of raw materials and electrolysis conditions, and the yield of the desired product was 70% at the maximum using the reaction system of item 8.

TABLE 1

Entry	electrolyte	Solvent(mL)	electrode	Yield(％)
					1	n Bu 4 NBF 4 (2eq)	DCE	Pt(+)/Pt(-)	33
2	n Bu 4 NI(2eq)	DCE	Pt(+)/Pt(-)	0
					3	n Bu 4 NPF 6 (2eq)	DCE	Pt(+)/Pt(-)	57
4	n Bu 4 NClO 4 (2eq)	DCE	Pt(+)/Pt(-)	27
					5	n Bu 4 NPF 6 (2eq)	DMF	Pt(+)/Pt(-)	0
6	n Bu 4 NPF 6 (2eq)	THF	Pt(+)/Pt(-)	0
					7	n Bu 4 NPF 6 (2eq)	MeOH	Pt(+)/Pt(-)	0
8	n Bu 4 NPF 6 (2eq)	DCM	Pt(+)/Pt(-)	70
					9	n Bu 4 NPF 6 (2eq)	DCM	C(+)/C(-)	0
10	n Bu 4 NPF 6 (2eq)	DCM	C(+)/Pt(-)	37
					11	n Bu 4 NPF 6 (1eq)	DCM	Pt(+)/Pt(-)	63
12	n Bu 4 NPF 6 (3eq)	DCM	Pt(+)/Pt(-)	68

The above description is only for the purpose of illustrating the preferred embodiments of the present invention and should not be taken as limiting the scope of the present invention, which is intended to cover any modifications, equivalents, improvements, etc. within the spirit and scope of the present invention.

Claims (10)

1. A method of preparing an eight-membered selenium-containing benzoazacyclic compound comprising the steps of: n- (butyl-3-alkene-1-yl) -4-methyl-N- (2- (1-phenyl vinyl) phenyl) benzene sulfonamide compound is used as a substrate, selenoether is subjected to anodic oxidation under electrochemical drive to generate seleno free radicals, and the seleno free radicals and the substrate are subjected to free radical coupling-cyclization to obtain the eight-membered selenium-containing benzo nitrogen heterocyclic compound.

2. The process for the preparation of an eight-membered selenium containing benzazepine compound according to claim 1, wherein the molar ratio of N- (but-3-en-1-yl) -4-methyl-N- (2- (1-phenylvinyl) phenyl) benzenesulfonamide compound to selenoether is 1: (1-1.2).

3. The method of preparing an eight-membered selenium-containing benzoazacycle compound of claim 1, comprising the steps of: adding N- (but-3-en-1-yl) -4-methyl-N- (2- (1-phenyl vinyl) phenyl) benzene sulfonamide compound, selenoether, ⁿ Bu ₄ NPF ₆ And DCM to give 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 finished, quenching and extracting; concentrating the organic solvent; purifying and eluting with eluent to obtain the octavalent selenium-containing benzo nitrogen heterocyclic compound.

4. The method of claim 3, wherein the N- (but-3-en-1-yl) -4-methyl-N- (2- (1-phenylvinyl) phenyl) benzenesulfonamide compound, ⁿ Bu ₄ NPF ₆ And selenoether in a molar ratio of 1: (1-3): (1-1.2); the molar volume ratio of N- (but-3-en-1-yl) -4-methyl-N- (2- (1-phenylvinyl) phenyl) benzenesulfonamide compound to DCM was 0.2mmol:5mL.

5. The method of claim 3, wherein after the reaction is complete, the mixture is treated with NaHCO ₃ Quenching and application of CH ₂ Cl ₂ Extracting; then concentrating the organic solvent in vacuum; the residue was purified by flash column chromatography using a mixed solvent of ethyl acetate and petroleum ether as eluent to give an eight-membered selenium-containing benzoazacyclo compound.

6. The method of claim 3, wherein the mixture is electrolyzed using a Pt electrode at room temperature at a constant current of 2 mA.

7. The method for preparing an eight-membered selenium-containing benzazepine compound according to any one of claims 1 to 6, wherein the structural formula of the N- (but-3-en-1-yl) -4-methyl-N- (2- (1-phenylvinyl) phenyl) benzenesulfonamide compound is represented by formula 1,

wherein R is ¹ Independently selected from H, CH ₃ One of Cl and Br substituents; r ² Independently selected from o-CNPh, H, CH ₃ 、OCH ₃ And one of F, cl and Br substituent.

8. The method of claim 7, wherein the N- (but-3-en-1-yl) -4-methyl-N- (2- (1-phenylvinyl) phenyl) benzenesulfonamide compound is 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- (p-tolyl) vinyl) phenyl) benzenesulfonamide Benzenesulfonamide, N- (but-3-en-1-yl) -N- (2 '-cyano-3- (1-phenylvinyl) - [1,1' -biphenyl ] -4-yl) -4-methylbenzenesulfonamide.

9. The process for preparing an eight-membered selenium containing benzoazacycle compound according to any of claims 1 to 6, wherein the selenoether is diselenide; preferably, the selenide is one or more selected from diphenyl diselenide, 1, 2-di (2-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.

10. An eight-membered selenium-containing benzoazacyclo compound, having the formula:

wherein R is ¹ Independently selected from H, CH ₃ One of Cl and Br substituents; r is ² Independently selected from o-CNPh, H, CH ₃ 、OCH ₃ One of substituents of F, cl and Br; r ³ Independently selected from benzene ring, naphthalene, benzene ring containing one or more of halogen, methyl and methoxyl.

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