CN115819341A

CN115819341A - Synthesis method of benzoquinoline compound containing alkyl and aryl

Info

Publication number: CN115819341A
Application number: CN202211485455.8A
Authority: CN
Inventors: 高庆贺; 尹延彦; 贾岩龙; 李莹莹; 武利强; 高一乔; 宋宇; 郭一美
Original assignee: Xinxiang Medical University
Current assignee: Xinxiang Medical University
Priority date: 2022-11-24
Filing date: 2022-11-24
Publication date: 2023-03-21

Abstract

The invention discloses a synthetic method of alkyl and aryl containing benzoquinoline compounds, belonging to the technical field of organic synthesis. The technical scheme provided by the invention has the key points that: a synthetic method of benzoquinoline compounds containing alkyl and aryl is characterized by comprising the following specific steps: dissolving an aromatic aldehyde compound 1, a beta-naphthylamine compound 2 and a tertiary aliphatic amine compound 3 in a solvent, adding an iodine reagent and an oxidant, and reacting at 110-130 ℃ to obtain a target product, namely an alkyl and aryl benzoquinoline compound. The method has the advantages of simple and efficient synthetic process, capability of directly preparing the benzoquinoline compound by one-pot series reaction without transition metal catalysis, cheap and easily-obtained raw material catalyst, mild reaction conditions, simple and convenient operation, suitability for commercial and large-scale industrial production, wide substrate application range and skillful introduction of alkyl substituent by taking the tertiary aliphatic amine compound as the raw material.

Description

Synthesis method of benzoquinoline compound containing alkyl and aryl

Technical Field

The invention belongs to the technical field of organic synthesis, and particularly relates to a synthesis method of alkyl and aryl containing benzoquinoline compounds.

Background

Researches show that the benzoquinoline derivative is an important pharmacological alkaloid in natural products. Benzoquinolines have been extensively studied in pharmaceutical chemistry because of their various biological activities, including anticancer, antibacterial, anti-inflammatory and antimalarial. The method for preparing the benzoquinoline derivative comprises the traditional Skraup reaction, the Doebner-Miller reaction, the Combes reaction and the Povarov reaction as well as the transition metal catalyzed beta-naphthylamine cross coupling reaction, but the synthesis methods have the defects of harsh reaction conditions, more byproducts, difficult product separation, stronger limitation of substrates for reaction, limited synthesis of the benzoquinoline derivative of a substituent group and difficult synthesis of the benzoquinoline derivative with the substitution of a beta position and a gamma position. More importantly, as the synthesis technology develops to mature, the alkylation modified benzoquinoline can improve the lipophilicity of the whole molecule in the field of new drug research and development, so the structure of the benzoquinoline which is subjected to alkylation modification at the beta position is gradually emphasized and hoped. However, from the viewpoint of synthesis, the difficulty of introducing an alkyl group into the β site is relatively high, and the relative synthesis cost is also relatively high. Therefore, research and development of the alkyl-containing benzoquinoline derivative which is synthesized by taking cheap and safe reagents as raw materials through simple and convenient operation steps have certain theoretical significance and important application value.

Disclosure of Invention

The invention provides a synthesis method of alkyl and aryl containing benzoquinoline compounds, which starts from simple and easily obtained raw materials, prepares the alkyl and aryl containing benzoquinoline compounds in one step through one-pot series reaction, has the advantages of convenient operation of synthesis process, mild reaction conditions, cheap and easily obtained raw material catalyst, suitability for commercial and large-scale industrial production and the like, and has potential application value in the aspect of medicine.

The invention adopts the following technical scheme for solving the technical problems, and the synthesis method of the benzoquinoline compound containing alkyl and aryl is characterized by comprising the following specific steps: dissolving an aromatic aldehyde compound 1, a beta-naphthylamine compound 2 and a tertiary aliphatic amine compound 3 in a solvent, adding an iodine reagent and an oxidant, and reacting at 110-130 ℃ to obtain a target product, namely an alkyl and aryl containing benzoquinoline compound 4, wherein the reaction equation in the synthesis method is as follows:

wherein R is ¹ Is phenyl, substituted phenyl, 2-naphthyl, 1-naphthyl, furyl, thienyl, pyridyl, quinolyl, benzofuryl, benzothienyl or indolyl, the substituent on the phenyl ring of the substituted phenyl is methyl, tert-butyl, methoxy, thiomethyl, fluorine, chlorine, bromine, trifluoromethyl, cyano, carbomethoxy or nitro, R is ² Is bromine, methoxy, carbomethoxy or amino, R ³ Is hydrogen, methyl, n-propyl, isopropyl, n-butyl, n-pentyl, n-hexyl, n-heptyl, n-octyl, n-nonyl or n-decyl, R ⁴ Ethyl, N-propyl, N-pentyl, isopentyl, N-hexyl, N-heptyl, N-octyl, N-nonyl, N-decyl, N-undecyl or N-dodecyl, the iodine reagent is ammonium iodide or elemental iodine, the oxidant is di-tert-butyl peroxide (DTBP), dicumyl peroxide (DCP), potassium persulfate or air, and the solvent is chlorobenzene, toluene, 1,4-dioxane, acetonitrile, N-methyl-2-pyrrolidone, dimethyl sulfoxide or 1,2-dichloroethane.

Further preferably, the feeding molar ratio of the aromatic aldehyde compound 1, the beta-naphthylamine compound 2, the tertiary aliphatic amine compound 3, the iodine reagent and the oxidant is 1.

Further preferably, the synthesized target product contains alkyl and aryl benzoquinoline compounds and the corresponding yield is as follows:

compared with the prior art, the invention has the following advantages: 1. the synthesis process is a one-pot series reaction without transition metal catalysis, and the process is simple and efficient; 2. the raw material catalyst is cheap and easy to obtain, the reaction condition is mild, the operation is simple and convenient, and the method is suitable for commercial and large-scale industrial production; 3. the application range of the substrate is wide; 4. the tertiary aliphatic amine compound is taken as a raw material, and alkyl substituent groups can be skillfully introduced into a target product. Therefore, the invention provides a novel method which is economical, practical, simple and efficient for synthesizing the alkyl-and aryl-containing benzoquinoline compounds.

Detailed Description

The present invention is described in further detail below with reference to examples, but it should not be construed that the scope of the above subject matter of the present invention is limited to the following examples, and that all the technologies realized based on the above subject matter of the present invention belong to the scope of the present invention.

Example 1

Benzaldehyde 1a (53mg, 0.5mmol), β -naphthylamine 2a (71.5mg, 0.5mmol), triethylamine 3a (151.5mg, 1.5mmol), ammonium iodide (108.7 mg, 0.75mmol), di-t-butylperoxide (146mg, 1mmol) and chlorobenzene (2 mL) were added to a 35mL sealed tube, followed by stirring in a 120 ℃ metal bath for 8 hours. The reaction was quenched with 50mL of water, extracted with ethyl acetate (50 mL. Times.3), and the organic phase was then quenched with 10% by weight Na ₂ S ₂ O ₃ The solution and the saturated brine were successively washed, and dried over anhydrous sodium sulfate. Filtration, spin-drying and silica gel column separation (petroleum ether/ethyl acetate = 100/1) gave product 4a (117mg, 92%) as a yellow solid. The compoundThe characterization data of (A) are as follows: ¹ H NMR(400MHz,CDCl ₃ ):δ(ppm)8.93(d,J＝8.8Hz,1H),8.57(d,J＝8.0Hz,1H),8.23–8.16(m,2H),8.07(d,J＝9.2Hz,1H),8.00–7.94(m,2H),7.93–7.89(m,1H),7.69–7.59(m,2H),7.57–7.50(m,2H),7.49–7.43(m,1H)； ¹³ C NMR(100MHz,CDCl ₃ ):δ(ppm)156.8,148.1,139.4,131.6,131.4,130.9,129.6,129.2,128.8,128.7,128.6,127.4,127.1,127.0,124.1,122.6,118.7；HRMS(ESI):m/z[M+H] ⁺ calcd for C ₁₉ H ₁₄ N:256.1121；found:256.1123。

example 2

1a (53mg, 0.5mmol), 2a (71.5mg, 0.5mmol), 3a (151.5mg, 1.5mmol), elemental iodine (190.5mg, 0.75mmol), di-t-butyl peroxide (146mg, 1mmol), and chlorobenzene (2 mL) were added to a 35mL sealed tube, followed by stirring for 8h in a 120 ℃ metal bath. The reaction was quenched with 50mL of water, extracted with ethyl acetate (50 mL. Times.3), and the organic phase was then quenched with 10% by weight Na ₂ S ₂ O ₃ The solution was washed with saturated brine, and dried over anhydrous sodium sulfate. Filtration, spin-drying, and separation on silica gel column (petroleum ether/ethyl acetate = 100/1) gave the desired product 4a (52.3 mg, 41%).

Example 3

1a (53mg, 0.5 mmol), 2a (71.5 mg,0.5 mmol), 3a (151.5 mg,1.5 mmol), ammonium iodide (108.7 mg, 0.75mmol), dicumyl peroxide (270mg, 1mmol) and chlorobenzene (2 mL) were added to a 35mL sealed tube, followed by stirring at 120 ℃ for 8h. The reaction was quenched with 50mL of water, extracted with ethyl acetate (50 mL. Times.3), and the organic phase was then quenched with 10% by weight Na ₂ S ₂ O ₃ The solution and the saturated brine were successively washed, and dried over anhydrous sodium sulfate. Filtration, spin-drying, and separation on silica gel column (petroleum ether/ethyl acetate = 100/1) gave the desired product 4a (99.5mg, 78%).

Example 4

1a (53mg, 0.5 mmol), 2a (71.5 mg,0.5 mmol), 3a (151.5 mg,1.5 mmol), ammonium iodide (108.7 mg, 0.75mmol), potassium persulfate (270mg, 1mmol) and chlorobenzene (2 mL) were added to a 35mL sealed tube, followed by stirring at 120 ℃ for 8h. The reaction was quenched with 50mL of water, extracted with ethyl acetate (50 mL. Times.3),then the organic phase is treated with Na with a mass concentration of 10% ₂ S ₂ O ₃ The solution was washed with saturated brine, and dried over anhydrous sodium sulfate. Filtration, spin-drying and silica gel column separation (petroleum ether/ethyl acetate = 100/1) gave the desired product 4a (57.4 mg, 45%).

Example 5

A35 mL reaction flask was charged with 1a (53mg, 0.5mmol), 2a (71.5mg, 0.5mmol), 3a (151.5mg, 1.5mmol), ammonium iodide (108.7mg, 0.75mmol), and chlorobenzene (2 mL), and then placed in a 120 ℃ metal bath and stirred open for 8h. The reaction was quenched with 50mL of water, extracted with ethyl acetate (50 mL. Times.3), and the organic phase was then quenched with 10% by weight Na ₂ S ₂ O ₃ The solution was washed with saturated brine, and dried over anhydrous sodium sulfate. Filtration, spin-drying and silica gel column separation (petroleum ether/ethyl acetate = 100/1) gave the desired product 4a (75mg, 59%).

Example 6

1a (53mg, 0.5 mmol), 2a (71.5 mg,0.5 mmol), 3a (151.5 mg,1.5 mmol), ammonium iodide (108.7 mg, 0.75mmol), di-t-butyl peroxide (146mg, 1mmol) and toluene (2 mL) were added to a 35mL sealed tube, followed by stirring for 8h in a 120 ℃ metal bath. The reaction was quenched with 50mL of water, extracted with ethyl acetate (50 mL. Times.3), and the organic phase was then quenched with 10% by weight Na ₂ S ₂ O ₃ The solution was washed with saturated brine, and dried over anhydrous sodium sulfate. Filtration, spin-drying and silica gel column separation (petroleum ether/ethyl acetate = 100/1) gave the desired product 4a (111mg, 87%).

Example 7

1a (53mg, 0.5 mmol), 2a (71.5 mg,0.5 mmol), 3a (151.5 mg,1.5 mmol), ammonium iodide (108.7 mg, 0.75mmol), di-t-butyl peroxide (146mg, 1mmol) and 1,4-dioxane (2 mL) were added to a 35mL sealed tube, followed by stirring in a 120 ℃ metal bath for 8h. The reaction was quenched with 50mL of water, extracted with ethyl acetate (50 mL. Times.3), and the organic phase was then quenched with 10% by weight Na ₂ S ₂ O ₃ The solution was washed with saturated brine, and dried over anhydrous sodium sulfate. Filtration, spin-drying and silica gel column separation (petroleum ether/ethyl acetate = 100/1) gave the desired product 4a (100.7mg, 79%).

Example 8

1a (53mg, 0.5 mmol), 2a (71.5 mg,0.5 mmol), 3a (151.5 mg,1.5 mmol), ammonium iodide (108.7 mg, 0.75mmol), di-t-butyl peroxide (146mg, 1mmol) and acetonitrile (2 mL) were added to a 35mL sealed tube, which was then stirred in a 120 ℃ metal bath for 8h. The reaction was quenched with 50mL of water, extracted with ethyl acetate (50 mL. Times.3), and the organic phase was then quenched with 10% by weight Na ₂ S ₂ O ₃ The solution and the saturated brine were successively washed, and dried over anhydrous sodium sulfate. Filtration, spin-drying, and separation on silica gel column (petroleum ether/ethyl acetate = 100/1) gave the desired product 4a (53.5mg, 42%).

Example 9

1a (53mg, 0.5 mmol), 2a (71.5 mg,0.5 mmol), 3a (151.5 mg,1.5 mmol), ammonium iodide (108.7 mg, 0.75mmol), di-t-butyl peroxide (146mg, 1mmol) and N-methyl-2-pyrrolidone (2 mL) were added to a 35mL sealed tube, followed by stirring at 120 ℃ for 8h. The reaction was quenched with 50mL of water, extracted with ethyl acetate (50 mL. Times.3), and the organic phase was then quenched with 10% by weight Na ₂ S ₂ O ₃ The solution was washed with saturated brine, and dried over anhydrous sodium sulfate. Filtration, spin-drying, and separation on silica gel column (petroleum ether/ethyl acetate = 100/1) gave the desired product 4a (62.5mg, 49%).

Example 10

1a (53mg, 0.5mmol), 2a (71.5mg, 0.5mmol), 3a (151.5mg, 1.5mmol), ammonium iodide (108.7mg, 0.75mmol), di-t-butyl peroxide (146mg, 1mmol) and dimethyl sulfoxide (2 mL) were added to a 35mL sealed tube, followed by stirring in a 120 ℃ metal bath for 8h. The reaction was quenched with 50mL of water, extracted with ethyl acetate (50 mL. Times.3), and the organic phase was then quenched with 10% by weight Na ₂ S ₂ O ₃ The solution and the saturated brine were successively washed, and dried over anhydrous sodium sulfate. Filtration, spin-drying, and separation on silica gel column (petroleum ether/ethyl acetate = 100/1) gave the desired product 4a (68.5mg, 54%).

Example 11

1a (53mg, 0.5mmol), 2a (71.5mg, 0.5mmol), 3a (151.5mg, 1.5mmol), ammonium iodide (108.7mg, 0.75mmol), di-t-butyl peroxide were added to a 35mL sealed tube(146mg, 1mmol) and 1,2-dichloroethane (2 mL) were then placed in a 120 ℃ metal bath and stirred for 8h. The reaction was quenched with 50mL of water, extracted with ethyl acetate (50 mL. Times.3), and the organic phase was then quenched with 10% by weight Na ₂ S ₂ O ₃ The solution and the saturated brine were successively washed, and dried over anhydrous sodium sulfate. Filtration, spin-drying, and separation on silica gel column (petroleum ether/ethyl acetate = 100/1) gave the desired product 4a (107mg, 84%).

Example 12

1a (53mg, 0.5 mmol), 2a (71.5 mg,0.5 mmol), 3a (151.5 mg,1.5 mmol), ammonium iodide (108.7 mg, 0.75mmol), di-t-butyl peroxide (146mg, 1mmol) and 1,2-dichloroethane (2 mL) were added to a 35mL sealed tube, followed by stirring in a 110 ℃ metal bath for 8h. The reaction was quenched with 50mL of water, extracted with ethyl acetate (50 mL. Times.3), and the organic phase was then quenched with 10% by weight Na ₂ S ₂ O ₃ The solution was washed with saturated brine, and dried over anhydrous sodium sulfate. Filtration, spin-drying, and separation on silica gel column (petroleum ether/ethyl acetate = 100/1) gave the desired product 4a (104.5mg, 82%).

Example 13

1a (53mg, 0.5 mmol), 2a (71.5 mg,0.5 mmol), 3a (151.5 mg,1.5 mmol), ammonium iodide (108.7 mg, 0.75mmol), di-t-butyl peroxide (146mg, 1mmol) and 1,2-dichloroethane (2 mL) were added to a 35mL sealed tube, followed by stirring at 130 ℃ for 8h. The reaction was quenched with 50mL of water, extracted with ethyl acetate (50 mL. Times.3), and the organic phase was then quenched with 10% by weight Na ₂ S ₂ O ₃ The solution was washed with saturated brine, and dried over anhydrous sodium sulfate. Filtration, spin-drying and silica gel column separation (petroleum ether/ethyl acetate = 100/1) gave the desired product 4a (117mg, 92%).

Example 14

1b (60mg, 0.5mmol), 2a (71.5mg, 0.5mmol), 3a (151.5mg, 1.5mmol), ammonium iodide (108.7mg, 0.75mmol), di-tert-butylperoxide (146mg, 1mmol) and chlorobenzene (2 mL) were added to a 35mL sealed tube,then placed in a metal bath at 120 ℃ and stirred for 8h. The reaction was quenched with 50mL of water, extracted with ethyl acetate (50 mL. Times.3), and the organic phase was then quenched with 10% by weight Na ₂ S ₂ O ₃ The solution was washed with saturated brine, and dried over anhydrous sodium sulfate. Filtration, spin-drying and separation on silica gel column (petroleum ether/ethyl acetate = 100/1) gave product 4b as a yellow solid (122mg, 91%). The characterization data for this compound are as follows: ¹ H NMR(400MHz,CDCl ₃ ):δ(ppm)8.91(d,J＝8.4Hz,1H),8.57(d,J＝8.0Hz,1H),8.12–8.08(m,2H),8.06(d,J＝8.8Hz,1H),7.99–7.94(m,2H),7.92(dd,J＝7.6,1.2Hz,1H),7.69–7.59(m,2H),7.33(d,J＝8.0Hz,2H),2.43(s,3H)； ¹³ C NMR(100MHz,CDCl ₃ ):δ(ppm)156.8,148.1,139.3,136.6,131.5,131.3,130.8,129.6(2),129.5(6),128.6(4),128.5(9),127.2,126.9(7),126.9(5),123.9,122.5,118.5,21.3；HRMS(ESI):m/z[M+H] ⁺ calcd for C ₂₀ H ₁₆ N:270.1277；found:270.1279。

example 15

1c (81mg, 0.5 mmol), 2a (71.5 mg,0.5 mmol), 3a (151.5 mg,1.5 mmol), ammonium iodide (108.7 mg, 0.75mmol), di-t-butyl peroxide (146mg, 1mmol) and chlorobenzene (2 mL) were added to a 35mL sealed tube, followed by stirring at 120 ℃ for 8h. The reaction was quenched with 50mL of water, extracted with ethyl acetate (50 mL. Times.3), and the organic phase was then quenched with 10% by weight Na ₂ S ₂ O ₃ The solution was washed with saturated brine, and dried over anhydrous sodium sulfate. Filtration, spin-drying and silica gel column separation (petroleum ether/ethyl acetate = 100/1) gave product 4c as a yellow solid (146mg, 94%). The characterization data for this compound are as follows: ¹ H NMR(400MHz,CDCl ₃ ):δ(ppm)8.96(d,J＝8.8Hz,1H),8.61(d,J＝8.0Hz,1H),8.15–8.11(m,2H),8.07(d,J＝8.8Hz,1H),8.01–7.97(m,2H),7.93(dd,J＝8.0,1.2Hz,1H),7.71–7.60(m,2H),7.58–7.54(m,2H),1.39(s,9H)； ¹³ C NMR(100MHz,CDCl ₃ ):δ(ppm)156.8,152.4,148.2,136.6,131.5,131.3,130.8,129.6,128.6(4),128.6(2),127.1,127.0,126.9,125.8,123.9,122.5,118.7,34.7,31.3；HRMS(ESI):m/z[M+H] ⁺ calcd for C ₂₃ H ₂₂ N:312.1747；found:312.1748。

example 16

1d (68mg, 0.5mmol), 2a (71.5mg, 0.5mmol), 3a (151.5mg, 1.5mmol), ammonium iodide (108.7mg, 0.75mmol), di-t-butylperoxide (146mg, 1mmol) and chlorobenzene (2 mL) were added to a 35mL sealed tube, followed by stirring in a 120 ℃ metal bath for 8 hours. The reaction was quenched with 50mL of water, extracted with ethyl acetate (50 mL. Times.3), and the organic phase was then quenched with 10% by weight Na ₂ S ₂ O ₃ The solution was washed with saturated brine, and dried over anhydrous sodium sulfate. Filtration, spin-drying and silica gel column separation (petroleum ether/ethyl acetate = 100/1) gave the product 4d as a yellow solid (127mg, 89%). The characterization data for this compound are as follows: ¹ H NMR(400MHz,CDCl ₃ ):δ(ppm)8.92(d,J＝8.8Hz,1H),8.58(d,J＝8.4Hz,1H),8.19–8.15(m,2H),8.05(d,J＝9.2Hz,1H),7.98(d,J＝9.2Hz,1H),7.95–7.91(m,2H),7.70–7.60(m,2H),7.07–7.03(m,2H),3.88(s,3H)； ¹³ C NMR(100MHz,CDCl ₃ ):δ(ppm)160.7,156.4,148.1,131.9,131.5,131.4,130.8,129.7,128.6(9),128.6(6),128.5,127.0,126.9,123.6,122.5,118.2,114.2,55.4.HRMS(ESI):m/z[M+H] ⁺ calcd for C ₂₀ H ₁₆ NO:286.1226；found:286.1226。

example 17

1e (76mg, 0.5 mmol), 2a (71.5 mg,0.5 mmol), 3a (151.5 mg,1.5 mmol), ammonium iodide (108.7 mg, 0.75mmol), di-t-butyl peroxide (146mg, 1mmol) and chlorobenzene (2 mL) were added to a 35mL sealed tube, followed by stirring at 120 ℃ in a metal bath for 8h. The reaction was quenched with 50mL of water, extracted with ethyl acetate (50 mL. Times.3), and the organic phase was then quenched with 10% by weight Na ₂ S ₂ O ₃ The solution was washed with saturated brine, and dried over anhydrous sodium sulfate. Filtration, spin-drying and separation on silica gel column (petroleum ether/ethyl acetate = 100/1) gave product 4e as a yellow solid (107mg, 71%). The characterization data for this compound are as follows: ¹ H NMR(400MHz,CDCl ₃ ):δ(ppm)8.96(d,J＝8.8Hz,1H),8.60(d,J＝8.0Hz,1H),8.17–8.13(m,2H),8.05(d,J＝9.2Hz,1H),7.98(dd,J＝8.8,7.2Hz,2H),7.94(dd,J＝8.0,1.2Hz,1H),7.71–7.61(m,2H),7.42–7.37(m,2H),2.55(s,3H)； ¹³ C NMR(100MHz,CDCl ₃ ):δ(ppm)156.1,148.2,140.2,136.0,131.6,131.5,131.0,129.6,128.7,128.5,127.6,127.0,126.4,124.0,122.6,118.3,15.5；HRMS(ESI):m/z[M+H] ⁺ calcd for C ₂₀ H ₁₆ NS:302.0998；found:302.0998。

example 18

1f (62mg, 0.5 mmol), 2a (71.5 mg,0.5 mmol), 3a (151.5 mg,1.5 mmol), ammonium iodide (108.7 mg, 0.75mmol), di-t-butyl peroxide (146mg, 1mmol) and chlorobenzene (2 mL) were added to a 35mL sealed tube, followed by stirring at 120 ℃ for 8h. The reaction was quenched with 50mL of water, extracted with ethyl acetate (50 mL. Times.3), and the organic phase was then quenched with 10% by weight Na ₂ S ₂ O ₃ The solution was washed with saturated brine, and dried over anhydrous sodium sulfate. Filtration, spin-drying and separation on silica gel column (petroleum ether/ethyl acetate = 100/1) gave product 4f as a yellow solid (108mg, 79%). The characterization data for this compound are as follows: ¹ H NMR(400MHz,CDCl ₃ ):δ(ppm)8.96(d,J＝8.8Hz,1H),8.60(d,J＝8.0Hz,1H),8.22–8.16(m,2H),8.02(q,J＝9.2Hz,2H),7.96–7.92(m,2H),7.72–7.62(m,2H),7.24–7.18(m,2H)； ¹³ C NMR(100MHz,CDCl ₃ ):δ(ppm)165.0,162.5,155.7,148.1,135.6,135.5,131.6(1),131.5(8),131.1,129.5,129.3,129.2,128.7,128.4,127.1(4),127.1(1),124.0,122.6,118.4,115.9,115.7；HRMS(ESI):m/z[M+H] ⁺ calcd for C ₁₉ H ₁₃ FN:274.1027；found:274.1026。

example 19

1g (70.3mg, 0.5mmol), 2a (71.5mg, 0.5mmol), 3a (151.5mg, 1.5mmol), ammonium iodide (108.7mg, 0.75mmol), di-t-butyl peroxide (146mg, 1mmol) and chlorobenzene (2 mL) were added to a 35mL sealed tube, followed by stirring at 120 ℃ for 8 hours. The reaction was quenched with 50mL of water, extracted with ethyl acetate (50 mL. Times.3), and the organic phase was then quenched with 10% by weight Na ₂ S ₂ O ₃ The solution was washed with saturated brine, and dried over anhydrous sodium sulfate. Filtration, spin-drying and separation on silica gel column (petroleum ether/ethyl acetate = 100/1) gave 4g (129mg, 89%) of the product as a yellow solid. The characterization data for this compound are as follows: ¹ H NMR(400MHz,CDCl ₃ ):δ(ppm)8.94(d,J＝8.8Hz,1H),8.58(d,J＝8.0Hz,1H),8.17–8.11(m,2H),8.01(q,J＝9.2Hz,2H),7.93(d,J＝8.8Hz,2H),7.71–7.62(m,2H),7.52–7.46(m,2H)； ¹³ C NMR(100MHz,CDCl ₃ ):δ(ppm)155.4,148.2,137.8,135.4,131.7,131.6,131.2,129.5,129.0,128.7,128.6,128.4,127.2,127.1,124.2,122.6,118.3；HRMS(ESI):m/z[M+H] ⁺ calcd for C ₁₉ H ₁₃ ClN:290.0731；found:290.0730。

example 20

1h (92.5mg, 0.5mmol), 2a (71.5mg, 0.5mmol), 3a (151.5mg, 1.5mmol), ammonium iodide (108.7mg, 0.75mmol), di-t-butyl peroxide (146mg, 1mmol) and chlorobenzene (2 mL) were added to a 35mL sealed tube, followed by stirring at 120 ℃ for 8h. The reaction was quenched with 50mL of water, extracted with ethyl acetate (50 mL. Times.3), and the organic phase was then quenched with 10% by weight Na ₂ S ₂ O ₃ The solution and the saturated brine were successively washed, and dried over anhydrous sodium sulfate. Filtration, spin-drying and silica gel column separation (petroleum ether/ethyl acetate = 100/1) gave the product as a yellow solid for 4h (140mg, 84%). Characterization number of the CompoundThe following is provided: ¹ H NMR(400MHz,CDCl ₃ ):δ(ppm)8.98(d,J＝8.8Hz,1H),8.61(d,J＝8.0Hz,1H),8.11–8.07(m,2H),8.02(q,J＝8.8Hz,2H),7.98–7.93(m,2H),7.73–7.68(m,1H),7.68–7.63(m,3H)； ¹³ C NMR(100MHz,CDCl ₃ ):δ(ppm)155.5,148.2,138.2,132.0,131.6(8),131.6(5),131.2,129.5,128.9,128.7,128.4,127.3,127.2,124.3,123.8,122.6,118.3；HRMS(ESI):m/z[M+H] ⁺ calcd for C ₁₉ H ₁₃ BrN:334.0226；found:334.0226。

example 21

1i (87mg, 0.5mmol), 2a (71.5mg, 0.5mmol), 3a (151.5mg, 1.5mmol), ammonium iodide (108.7mg, 0.75mmol), di-t-butylperoxide (146mg, 1mmol) and chlorobenzene (2 mL) were added to a 35mL sealed tube, followed by stirring for 8 hours in a 120 ℃ metal bath. The reaction was quenched with 50mL of water, extracted with ethyl acetate (50 mL. Times.3), and the organic phase was then quenched with 10% by weight Na ₂ S ₂ O ₃ The solution was washed with saturated brine, and dried over anhydrous sodium sulfate. Filtration, spin-drying and separation on silica gel column (petroleum ether/ethyl acetate = 100/1) gave the product 4i (143.7mg, 89%) as a yellow solid. The characterization data for this compound are as follows: ¹ H NMR(400MHz,CDCl ₃ ):δ(ppm)8.98(d,J＝8.4Hz,1H),8.60(d,J＝8.0Hz,1H),8.30(d,J＝8.0Hz,2H),8.07–7.97(m,3H),7.96–7.92(m,1H),7.78(d,J＝8.4Hz,2H),7.73–7.63(m,2H)； ¹³ C NMR(100MHz,CDCl ₃ ):δ(ppm)155.1,148.2,142.6,131.8,131.7,131.4,131.1,130.8,129.4,128.8,128.4,127.6,127.4,127.2,125.7(9),125.7(6),125.7(2),125.6(8),125.5,124.6,122.8,122.7,118.7；HRMS(ESI):m/z[M+H] ⁺ calcd for C ₂₀ H ₁₃ F ₃ N:324.0995；found:324.0994。

example 22

1j (65.5mg, 0.5mmol), 2a (71.5mg, 0.5mmol), 3a (151.5mg, 1.5mmol), ammonium iodide (108.7mg, 0.75mmol), di-t-butyl peroxide (146mg, 1mmol) and chlorobenzene (2 mL) were added to a 35mL sealed tube, followed by stirring at 120 ℃ for 8 hours. The reaction was quenched with 50mL of water, extracted with ethyl acetate (50 mL. Times.3), and the organic phase was then quenched with 10% by weight Na ₂ S ₂ O ₃ The solution was washed with saturated brine, and dried over anhydrous sodium sulfate. Filtration, spin-drying and separation on silica gel column (petroleum ether/ethyl acetate = 100/1) gave product 4j (105mg, 75%) as a yellow solid. The characterization data for this compound are as follows: ¹ H NMR(400MHz,CDCl ₃ ):δ(ppm)9.03(d,J＝8.8Hz,1H),8.63(d,J＝8.0Hz,1H),8.35–8.30(m,2H),8.08–8.00(m,3H),7.96(dd,J＝7.6,1.6Hz,1H),7.84–7.79(m,2H),7.75–7.66(m,2H)； ¹³ C NMR(100MHz,CDCl ₃ ):δ(ppm)154.3,148.2,143.4,132.6,131.9,131.8,131.6,129.3,128.8,128.3,127.9,127.6,127.3,124.8,122.8,118.9,118.6,112.6；HRMS(ESI):m/z[M+H] ⁺ calcd for C ₂₀ H ₁₃ N ₂ :281.1073；found:281.1073。

example 23

1k (82mg, 0.5 mmol), 2a (71.5 mg,0.5 mmol), 3a (151.5 mg,1.5 mmol), ammonium iodide (108.7 mg, 0.75mmol), di-t-butyl peroxide (146mg, 1mmol) and chlorobenzene (2 mL) were added to a 35mL sealed tube, followed by stirring at 120 ℃ for 8 hours. The reaction was quenched with 50mL of water, extracted with ethyl acetate (50 mL. Times.3), and the organic phase was then quenched with 10% by weight Na ₂ S ₂ O ₃ The solution and the saturated brine were successively washed, and dried over anhydrous sodium sulfate. Filtration, spin-drying and silica gel column separation (petroleum ether/ethyl acetate = 30/1) gave the product 4k (116mg, 74%) as a yellow solid. The characterization data for this compound are as follows: ¹ H NMR(400MHz,CDCl ₃ ):δ(ppm)8.99(d,J＝8.4Hz,1H),8.62(d,J＝8.0Hz,1H),8.30–8.26(m,2H),8.21–8.18(m,2H),8.08–8.00(m,3H),7.94(dd,J＝8.0,1.2Hz,1H),7.73–7.63(m,2H),3.96(s,3H)； ¹³ C NMR(100MHz,CDCl ₃ ):δ(ppm)166.9,155.4,148.2,143.5,131.8,131.6,131.3,130.5,130.1,129.4,128.7,128.5,127.4,127.3,127.2,124.6,122.7,118.9,52.2；HRMS(ESI):m/z[M+H] ⁺ calcd for C ₂₁ H ₁₆ NO ₂ :314.1176；found:314.1174。

example 24

1l (60mg, 0.5 mmol), 2a (71.5 mg,0.5 mmol), 3a (151.5 mg,1.5 mmol), ammonium iodide (108.7 mg, 0.75mmol), di-t-butyl peroxide (146mg, 1mmol) and chlorobenzene (2 mL) were added to a 35mL sealed tube, followed by stirring at 120 ℃ for 8 hours. The reaction was quenched with 50mL of water, extracted with ethyl acetate (50 mL. Times.3), and the organic phase was then quenched with 10% by weight Na ₂ S ₂ O ₃ The solution was washed with saturated brine, and dried over anhydrous sodium sulfate. Filtration, spin-drying and separation on silica gel column (petroleum ether/ethyl acetate = 100/1) gave 4l (114mg, 85%) of the product as a yellow solid. The characterization data for this compound are as follows: ¹ H NMR(400MHz,CDCl ₃ ):δ(ppm)8.96(d,J＝8.8Hz,1H),8.60(d,J＝8.0Hz,1H),8.10–8.04(m,2H),8.01–7.91(m,4H),7.71–7.61(m,2H),7.42(t,J＝7.6Hz,1H),7.28(d,J＝7.6Hz,1H),2.49(s,3H)； ¹³ C NMR(100MHz,CDCl ₃ ):δ(ppm)157.0,148.1,139.3,138.5,131.6,131.4,130.9,130.0,129.6,128.7(3),128.6(7),128.6,128.1,127.0(4),127.0(2),124.5,124.1,122.6,118.9,21.6；HRMS(ESI):m/z[M+H] ⁺ calcd for C ₂₀ H ₁₆ N:270.1277；found:270.1278。

example 25

1m (75.5mg, 0.5mmol), 2a (71.5mg, 0.5mmol), 3a (151.5mg, 1.5mmol), ammonium iodide (108.7mg, 0.75mmol), di-t-butyl peroxide (146mg, 1mmol) and chlorobenzene (2 mL) were added to a 35mL sealed tube, and then stirred in a 120 ℃ metal bathAnd 8h. The reaction was quenched with 50mL of water, extracted with ethyl acetate (50 mL. Times.3), and the organic phase was then quenched with 10% by weight Na ₂ S ₂ O ₃ The solution was washed with saturated brine, and dried over anhydrous sodium sulfate. Filtration, spin-drying and silica gel column separation (petroleum ether/ethyl acetate = 50/1) gave the product 4m as a yellow solid (104mg, 69%). The characterization data for this compound are as follows: ¹ HNMR(400MHz,CDCl ₃ ):δ(ppm)9.06(t,J＝2.0Hz,1H),9.01(d,J＝8.4Hz,1H),8.61(d,J＝8.0Hz,1H),8.58–8.53(m,1H),8.31–8.26(m,1H),8.07–8.00(m,3H),7.95(dd,J＝8.0,1.2Hz,1H),7.74–7.65(m,3H)； ¹³ C NMR(100MHz,CDCl ₃ ):δ(ppm)153.8,148.8,148.2,141.0,133.1,131.9,131.8,131.6,129.7,129.3,128.8,128.3,127.6,127.3,124.8,123.7,122.8,122.2,118.2；HRMS(ESI):m/z[M+H] ⁺ calcd for C ₁₉ H ₁₃ N ₂ O ₂ :301.0972；found:301.0973。

example 26

1n (60mg, 0.5 mmol), 2a (71.5 mg,0.5 mmol), 3a (151.5 mg,1.5 mmol), ammonium iodide (108.7 mg, 0.75mmol), di-t-butyl peroxide (146mg, 1mmol) and chlorobenzene (2 mL) were added to a 35mL sealed tube, followed by stirring at 120 ℃ for 8h. The reaction was quenched with 50mL of water, extracted with ethyl acetate (50 mL. Times.3), and the organic phase was then quenched with 10% by weight Na ₂ S ₂ O ₃ The solution was washed with saturated brine, and dried over anhydrous sodium sulfate. Filtration, spin-drying and separation on silica gel column (petroleum ether/ethyl acetate = 100/1) gave the product 4n as a yellow solid (75mg, 56%). The characterization data for this compound are as follows: ¹ H NMR(400MHz,CDCl ₃ ):δ(ppm)9.01(d,J＝8.4Hz,1H),8.67(d,J＝8.0Hz,1H),8.04(q,J＝9.2Hz,2H),7.96(dd,J＝8.0,1.2Hz,1H),7.75–7.69(m,2H),7.69–7.64(m,1H),7.58–7.54(m,1H),7.37–7.32(m,3H),2.46(s,3H)； ¹³ C NMR(100MHz,CDCl ₃ )δ(ppm):159.7,147.8,140.5,136.1,131.7,130.9(4),130.8(8),130.8,129.8,129.6,128.7,128.5,128.4,127.2,127.1,126.0,123.7,122.6,122.3,20.4；HRMS(ESI):m/z[M+H] ⁺ calcd for C ₂₀ H ₁₆ N:270.1277；found:270.1275。

example 27

1o (67mg, 0.5 mmol), 2a (71.5 mg,0.5 mmol), 3a (151.5 mg,1.5 mmol), ammonium iodide (108.7 mg, 0.75mmol), di-t-butyl peroxide (146mg, 1mmol) and chlorobenzene (2 mL) were added to a 35mL sealed tube, followed by stirring at 120 ℃ for 8h. The reaction was quenched with 50mL of water, extracted with ethyl acetate (50 mL. Times.3), and the organic phase was then quenched with 10% by weight Na ₂ S ₂ O ₃ The solution was washed with saturated brine, and dried over anhydrous sodium sulfate. Filtration, spin-drying and silica gel column separation (petroleum ether/ethyl acetate = 100/1) gave the product 4o as a yellow solid (133mg, 94%). The characterization data for this compound are as follows: ¹ H NMR(400MHz,CDCl ₃ ):δ(ppm)8.88(d,J＝8.8Hz,1H),8.55(d,J＝8.0Hz,1H),8.06(d,J＝8.8Hz,1H),8.01(s,1H),7.98–7.92(m,2H),7.91–7.87(mi,2H),7.66–7.57(m,2H),7.27(d,J＝8.0Hz,1H),2.38(s,3H),2.33(s,3H)； ¹³ C NMR(100MHz,CDCl ₃ ):δ(ppm)156.9,148.1,138.0,137.0,136.9,131.5,131.3,130.8,130.1,129.6,128.6(1),128.5(8),128.5,126.9(2),126.8(8),124.7,123.8,122.5,118.6,20.0,19.7；HRMS(ESI):m/z[M+H] ⁺ calcd for C ₂₁ H ₁₈ N:284.1434；found:284.1436。

example 28

1p (87.5mg, 0.5mmol), 2a (71.5mg, 0.5mmol), 3a (151.5mg, 1.5mmol), ammonium iodide (108.7mg, 0.75mmol), di-t-butyl peroxide (146mg, 1mmol) and chlorobenzene (2 mL) were added to a 35mL sealed tube, followed by stirring at 120 ℃ for 8 hours. The reaction was quenched with 50mL of water, extracted with ethyl acetate (50 mL. Times.3), and the organic phase was then quenched with 10% by weight Na ₂ S ₂ O ₃ The solution was washed with saturated brine, and dried over anhydrous sodium sulfate. Filtration, spin-drying and separation on silica gel column (petroleum ether/ethyl acetate = 100/1) gave the product 4p as a yellow solid (87.5mg, 54%). The characterization data for this compound are as follows: ¹ H NMR(400MHz,CDCl ₃ ):δ(ppm)9.02(d,J＝8.4Hz,1H),8.66(d,J＝7.6Hz,1H),8.06–8.01(m,2H),7.97(dd,J＝8.0,1.2Hz,1H),7.92(d,J＝8.4Hz,1H),7.76–7.71(m,2H),7.70–7.66(m,1H),7.55(d,J＝2.0Hz,1H),7.42(dd,J＝8.0,2.0Hz,1H)； ¹³ C NMR(100MHz,CDCl ₃ ):δ(ppm)155.5,148.1,137.9,135.1,133.1,132.7,131.8,131.3,130.6,129.9,129.4,128.8,128.2,127.5(4),127.4(8),127.3,124.4,122.8,122.6；HRMS(ESI):m/z[M+H] ⁺ calcd for C ₁₉ H ₁₂ C _l2 N:324.0341；found:324.0341。

example 29

1q (98mg, 0.5 mmol), 2a (71.5 mg,0.5 mmol), 3a (151.5 mg,1.5 mmol), ammonium iodide (108.7 mg, 0.75mmol), di-t-butyl peroxide (146mg, 1mmol) and chlorobenzene (2 mL) were added to a 35mL sealed tube, followed by stirring for 8h in a 120 ℃ metal bath. The reaction was quenched with 50mL of water, extracted with ethyl acetate (50 mL. Times.3), and the organic phase was then quenched with 10% by weight Na ₂ S ₂ O ₃ The solution was washed with saturated brine, and dried over anhydrous sodium sulfate. Filtration, spin-drying and silica gel column separation (petroleum ether/ethyl acetate = 12/1) gave 4q (145mg, 84%) of the product as a yellow solid. The characterization data for this compound are as follows: ¹ H NMR(400MHz,CDCl ₃ ):δ(ppm)8.99(d,J＝8.8Hz,1H),8.63(d,J＝8.4Hz,1H),8.08(d,J＝8.8Hz,1H),8.01(d,J＝9.2Hz,1H),7.97(d,J＝8.8Hz,1H),7.95(dd,J＝8.0,1.2Hz,1H),7.73–7.63(m,2H),7.45(s,2H),4.03(s,6H),3.94(s,3H)； ¹³ C NMR(100MHz,CDCl ₃ ):δ(ppm)156.4,153.6,148.1,139.3,135.1,131.6,131.5,131.0,129.6,128.7,128.5,127.1(1),127.0(9),124.0,122.6,118.6,104.6,61.0,56.3；HRMS(ESI):m/z[M+H] ⁺ calcd for C ₂₂ H ₂₀ NO ₃ :346.1438；found:346.1437。

example 30

1r (78mg, 0.5 mmol), 2a (71.5 mg,0.5 mmol), 3a (151.5 mg,1.5 mmol), ammonium iodide (108.7 mg, 0.75mmol), di-t-butyl peroxide (146mg, 1mmol) and chlorobenzene (2 mL) were added to a 35mL sealed tube, followed by stirring at 120 ℃ for 8h. The reaction was quenched with 50mL of water, extracted with ethyl acetate (50 mL. Times.3), and the organic phase was then quenched with 10% by weight Na ₂ S ₂ O ₃ The solution and the saturated brine were successively washed, and dried over anhydrous sodium sulfate. Filtration, spin-drying and silica gel column separation (petroleum ether/ethyl acetate = 50/1) gave the product 4r as a yellow solid (113mg, 74%). The characterization data for this compound are as follows: ¹ H NMR(400MHz,CDCl ₃ ):δ(ppm)9.03(d,J＝8.4Hz,1H),8.68(d,J＝1.2Hz,1H),8.65(d,J＝8.4Hz,1H),8.40(dd,J＝8.4,2.0Hz,1H),8.17(d,J＝8.4Hz,1H),8.13(d,J＝9.2Hz,1H),8.04–7.99(m,3H),7.96(dd,J＝7.6,1.2Hz,1H),7.92–7.88(m,1H),7.73–7.63(m,2H),7.56–7.51(m,2H)； ¹³ C NMR(100MHz,CDCl ₃ ):δ(ppm)156.7,148.3,136.7,133.8,133.5,131.7,131.5,131.1,129.6,128.8,128.7,128.6(0),128.5(8),127.7,127.1(4),127.0(9),126.9,126.7,126.3,124.9,124.2,122.7,119.0；HRMS(ESI):m/z[M+H] ⁺ calcd for C ₂₃ H ₁₆ N:306.1277；found:306.1278。

example 31

1s (78mg, 0.5 mmol), 2a (71.5 mg,0.5 mmol), 3a (151.5 mg,1.5 mmol), ammonium iodide (108.7 mg, 0.75mmol), di-t-butyl peroxide (146mg, 1mmol) and chlorobenzene (2 mL) were added to a 35mL sealed tube, followed by stirring at 120 ℃ for 8h. The reaction was quenched with 50mL of water, extracted with ethyl acetate (50 mL. Times.3), and the organic phase was then quenched with 10% by weight Na ₂ S ₂ O ₃ The solution and the saturated brine were successively washed, and dried over anhydrous sodium sulfate. Filtration, spin-drying, and separation on silica gel column (petroleum ether/ethyl acetate = 50/1) gave the product as a yellow solid 4s (120.5mg, 79%). The characterization data for this compound are as follows: ¹ H NMR(400MHz,CDCl ₃ ):δ(ppm)9.05(d,J＝8.4Hz,1H),8.68(d,J＝8.0Hz,1H),8.19(d,J＝8.0Hz,1H),8.12(d,J＝8.8Hz,1H),8.04(d,J＝8.8Hz,1H),7.99–7.92(m,3H),7.85(d,J＝8.8Hz,1H),7.77–7.70(m,2H),7.69–7.65(m,1H),7.61(dd,J＝8.0,7.2Hz,1H),7.54–7.45(m,2H)； ¹³ C NMR(100MHz,CDCl ₃ ):δ(ppm)158.9,148.0,138.5,134.0,131.7,131.3,131.1,131.0,129.6,129.1,128.7,128.5,128.4,127.8,127.2(4),127.1(5),126.6,125.9,125.7,125.4,124.0,123.2,122.7；HRMS(ESI):m/z[M+H] ⁺ calcd for C ₂₃ H ₁₆ N:306.1277；found:306.1275。

example 32

1t (48mg, 0.5 mmol), 2a (71.5mg, 0.5mmol), 3a (151.5mg, 1.5mmol), ammonium iodide (108.7mg, 0.75mmol), di-t-butyl peroxide (146mg, 1mmol) and chlorobenzene (2 mL) were added to a 35mL sealed tube, followed by stirring at 120 ℃ for 8 hours. The reaction was quenched with 50mL of water, extracted with ethyl acetate (50 mL. Times.3), and the organic phase was then quenched with 10% by weight Na ₂ S ₂ O ₃ The solution was washed with saturated brine, and dried over anhydrous sodium sulfate. Filtration, spin-drying and separation on silica gel column (petroleum ether/ethyl acetate = 100/1) gave 4t (48mg, 39%) of the product as a yellow solid. The characterization data for this compound are as follows: ¹ H NMR(400MHz,CDCl ₃ ):δ(ppm)8.97(d,J＝8.8Hz,1H),8.61(d,J＝8.0Hz,1H),8.06–7.97(m,3H),7.94(dd,J＝7.6,1.2Hz,1H),7.72–7.68(m,1H),7.67–7.62(m,2H),7.25(s,1H),6.61(dd,J＝3.6,2.0Hz,1H)； ¹³ C NMR(100MHz,CDCl ₃ ):δ(ppm)153.6,148.7,148.1,144.0,131.6,131.4,131.2,129.6,128.7,128.2,127.1(3),127.1(0),124.0,122.5,117.3,112.2,109.8；HRMS(ESI):m/z[M+H] ⁺ calcd for C ₁₇ H ₁₂ NO:246.0913；found:246.0913。

example 33

1u (56mg, 0.5 mmol), 2a (71.5 mg,0.5 mmol), 3a (151.5 mg,1.5 mmol), ammonium iodide (108.7 mg, 0.75mmol), di-t-butyl peroxide (146mg, 1mmol) and chlorobenzene (2 mL) were added to a 35mL sealed tube, followed by stirring at 120 ℃ for 8h. The reaction was quenched with 50mL of water, extracted with ethyl acetate (50 mL. Times.3), and the organic phase was then quenched with 10% by weight Na ₂ S ₂ O ₃ The solution was washed with saturated brine, and dried over anhydrous sodium sulfate. Filtration, spin-drying and silica gel column separation (petroleum ether/ethyl acetate = 100/1) gave the product 4u (99mg, 76%) as a yellow solid. The characterization data for this compound are as follows: ¹ H NMR(400MHz,CDCl ₃ ):δ(ppm)8.88(d,J＝8.4Hz,1H),8.56(d,J＝8.4Hz,1H),8.01–7.95(m,2H),7.93–7.88(m,2H),7.74(dd,J＝3.6,1.2Hz,1H),7.69–7.59(m,2H),7.47(dd,J＝4.8,1.2Hz,1H),7.16(dd,J＝4.8,3.6Hz,1H)； ¹³ C NMR(100MHz,CDCl ₃ ):δ(ppm)152.0,148.0,145.1,131.5,131.3,131.1,129.6,128.7,128.3,128.2,128.1,127.1,127.0,125.5,124.0,122.5,117.4；HRMS(ESI):m/z[M+H] ⁺ calcd for C ₁₇ H ₁₂ NS:262.0685；found:262.0686。

example 34

1v (53.5mg, 0.5mmol), 2a (71.5mg, 0.5mmol), 3a (151.5mg, 1.5mmol), ammonium iodide (108.7mg, 0.75mmol), di-t-butyl peroxide (146mg, 1mmol) and chlorobenzene (2 mL) were added to a 35mL sealed tube, followed by stirring at 120 ℃ for 8 hours. The reaction was quenched with 50mL of water, extracted with ethyl acetate (50 mL. Times.3), and the organic phase was then quenched with 10% by weight Na ₂ S ₂ O ₃ The solution was washed with saturated brine, and dried over anhydrous sodium sulfate. Filtering, spin-drying, and passing through siliconGel column separation (petroleum ether/ethyl acetate = 5/1) yielded 4v (104mg, 81%) of the product as a yellow solid. The characterization data for this compound are as follows: ¹ H NMR(400MHz,CDCl ₃ ):δ(ppm)9.41–9.36(m,1H),8.98(d,J＝8.8Hz,1H),8.70(dd,J＝4.8,1.6Hz,1H),8.60(d,J＝8.4Hz,1H),8.53(dt,J＝8.0,2.0Hz,1H),8.06–7.97(m,3H),7.95–7.91(m,1H),7.72–7.63(m,2H),7.48–7.43(m,1H)； ¹³ C NMR(100MHz,CDCl ₃ ):δ(ppm)154.0,150.1,148.7,148.3,134.8,134.7,131.7(3),131.7(0),131.3,129.4,128.7,128.3,127.4,127.2,124.5,123.7,122.7,118.4；HRMS(ESI):m/z[M+H] ⁺ calcd for C ₁₈ H ₁₃ N ₂ :257.1073；found:257.1073。

example 35

1w (78.5mg, 0.5mmol), 2a (71.5mg, 0.5mmol), 3a (151.5mg, 1.5mmol), ammonium iodide (108.7mg, 0.75mmol), di-t-butyl peroxide (146mg, 1mmol) and chlorobenzene (2 mL) were added to a 35mL sealed tube, followed by stirring at 120 ℃ for 8 hours. The reaction was quenched with 50mL of water, extracted with ethyl acetate (50 mL. Times.3), and the organic phase was then quenched with 10% by weight Na ₂ S ₂ O ₃ The solution was washed with saturated brine, and dried over anhydrous sodium sulfate. Filtration, spin-drying and silica gel column separation (petroleum ether/ethyl acetate = 5/1) gave the product 4w (121mg, 79%) as a yellow solid. The characterization data for this compound are as follows: ¹ HNMR(400MHz,CDCl ₃ ):δ(ppm)9.00(d,J＝8.4Hz,1H),8.95(dd,J＝4.0,1.6Hz,1H),8.65–8.59(m,3H),8.27(t,J＝9.0Hz,2H),8.14–8.09(m,2H),8.02(d,J＝9.2Hz,1H),7.97–7.93(m,1H),7.72–7.63(m,2H),7.44(q,J＝4.0Hz,1H)； ¹³ C NMR(100MHz,CDCl ₃ ):δ(ppm)155.7,151.0,148.7,148.3,137.3,136.8,131.7(1),131.6(6),131.2,130.0,129.5,128.7,128.6,128.5,128.3,127.3,127.2,126.6,124.3,122.7,121.5,118.8；HRMS(ESI):m/z[M+H] ⁺ calcd for C ₂₂ H ₁₅ N ₂ :307.1230；found:307.1231。

example 36

1X (78.5mg, 0.5mmol), 2a (71.5mg, 0.5mmol), 3a (151.5mg, 1.5mmol), ammonium iodide (108.7mg, 0.75mmol), di-t-butyl peroxide (146mg, 1mmol) and chlorobenzene (2 mL) were added to a 35mL sealed tube, followed by stirring at 120 ℃ for 8 hours. The reaction was quenched with 50mL of water, extracted with ethyl acetate (50 mL. Times.3), and the organic phase was then quenched with 10% by weight Na ₂ S ₂ O ₃ The solution was washed with saturated brine, and dried over anhydrous sodium sulfate. Filtration, spin-drying, and silica gel column separation (petroleum ether/ethyl acetate = 5/1) gave the product 4x (96.4 mg, 63%) as a yellow solid. The characterization data for this compound are as follows: ¹ H NMR(400MHz,CDCl ₃ ):δ(ppm)9.15(d,J＝8.8Hz,1H),9.08(d,J＝4.4Hz,1H),8.72(d,J＝8.0Hz,1H),8.26–8.22(m,2H),8.13–8.07(m,2H),8.01(dd,J＝8.0,1.2Hz,1H),7.90(d,J＝8.4Hz,1H),7.80–7.76(m,2H),7.75–7.70(m,1H),7.68(d,J＝4.4Hz,1H),7.60–7.55(m,1H)； ¹³ C NMR(100MHz,CDCl ₃ ):δ(ppm)156.1,150.1,148.9,148.1,146.3,131.9,131.7,131.5,129.9,129.5,129.4,128.8,128.2,127.7,127.4,127.2,126.1,125.8,124.7,122.8,122.5,121.7；HRMS(ESI):m/z[M+H] ⁺ calcd for C ₂₂ H ₁₅ N ₂ :307.1230；found:307.1232。

example 37

1y (73mg, 0.5 mmol), 2a (71.5 mg,0.5 mmol), 3a (151.5 mg,1.5 mmol), ammonium iodide (108.7 mg, 0.75mmol), di-t-butyl peroxide (146mg, 1mmol) and chlorobenzene (2 mL) were added to a 35mL sealed tube, followed by stirring at 120 ℃ for 8h. The reaction was quenched with 50mL of water, extracted with ethyl acetate (50 mL. Times.3), and the organic phase was then quenched with 10% by weight Na ₂ S ₂ O ₃ The solution was washed with saturated brine, and dried over anhydrous sodium sulfate. Filtering, spin-drying, separating with silica gel column (petroleum)Ether/ethyl acetate = 100/1) to yield 4y (99mg, 67%) as a yellow solid. The characterization data for this compound are as follows: ¹ H NMR(400MHz,CDCl ₃ ):δ(ppm)8.96(d,J＝8.8Hz,1H),8.58(d,J＝8.4Hz,1H),8.13–8.10(m,1H),8.07(d,J＝9.2Hz,1H),7.99(d,J＝9.2Hz,1H),7.94–7.90(m,1H),7.70–7.60(m,5H),7.39–7.34(m,1H),7.30–7.26(m,1H)； ¹³ C NMR(100MHz,CDCl ₃ ):δ(ppm)155.5,155.1,148.5,148.2,131.7,131.4(0),131.3(6),129.5,128.8,128.7,128.2,127.3,127.2,125.4,124.7,123.2,122.7,121.7,118.0,111.7,105.8；HRMS(ESI):m/z[M+H] ⁺ calcd for C ₂₁ H ₁₄ NO:296.1070；found:296.1069。

example 38

1z (81mg, 0.5 mmol), 2a (71.5 mg,0.5 mmol), 3a (151.5 mg,1.5 mmol), ammonium iodide (108.7 mg, 0.75mmol), di-t-butyl peroxide (146mg, 1mmol) and chlorobenzene (2 mL) were added to a 35mL sealed tube, followed by stirring at 120 ℃ for 8h. The reaction was quenched with 50mL of water, extracted with ethyl acetate (50 mL. Times.3), and the organic phase was then quenched with 10% by weight Na ₂ S ₂ O ₃ The solution was washed with saturated brine, and dried over anhydrous sodium sulfate. Filtration, spin-drying and silica gel column separation (petroleum ether/ethyl acetate = 100/1) gave the product 4z as a yellow solid (124.4 mg, 80%). The characterization data for this compound are as follows: ¹ H NMR(400MHz,CDCl ₃ ):δ(ppm)8.96(d,J＝8.4Hz,1H),8.84(d,J＝7.6Hz,1H),8.61(d,J＝8.0Hz,1H),8.11(d,J＝8.8Hz,1H),8.01(d,J＝9.2Hz,1H),7.96–7.91(m,4H),7.72–7.62(m,2H),7.51(ddd,J＝8.4,7.2,1.2Hz,1H),7.45–7.41(m,1H)； ¹³ C NMR(100MHz,CDCl ₃ ):δ(ppm)154.1,148.0,140.9,137.4,136.4,131.6,131.3,131.0,129.6,128.7,128.4,127.3,127.1(2),127.1(0),124.8(0),124.7(8),124.7,123.8,122.6(4),122.5(6),120.7；HRMS(ESI):m/z[M+H] ⁺ calcd for C ₂₁ H ₁₄ NS:312.0841；found:312.0842。

example 39

1aa (79.5mg, 0.5mmol), 2a (71.5mg, 0.5mmol), 3a (151.5mg, 1.5mmol), ammonium iodide (108.7mg, 0.75mmol), di-t-butyl peroxide (146mg, 1mmol) and chlorobenzene (2 mL) were added to a 35mL sealed tube, followed by stirring at 120 ℃ for 8 hours. The reaction was quenched with 50mL of water, extracted with ethyl acetate (50 mL. Times.3), and the organic phase was then quenched with 10% by weight Na ₂ S ₂ O ₃ The solution was washed with saturated brine, and dried over anhydrous sodium sulfate. Filtration, spin-drying, and separation on silica gel column (petroleum ether/ethyl acetate = 30/1) gave the product 4aa (88mg, 57%) as a yellow solid. The characterization data for this compound are as follows: ¹ HNMR(400MHz,CDCl ₃ ):δ(ppm)8.90(d,J＝8.8Hz,1H),8.73–8.68(m,1H),8.59(d,J＝8.4Hz,1H),8.08(d,J＝9.2Hz,1H),7.99–7.92(m,3H),7.83(s,1H),7.70–7.65(m,1H),7.63–7.58(m,1H),7.42–7.38(m,1H),7.36–7.31(m,2H),3.90(s,3H)； ¹³ CNMR(100MHz,CDCl ₃ ):δ(ppm)154.8,148.3,137.9,131.3,130.7,130.5,129.9,129.7,128.6(4),128.5(6),126.8,126.4,126.3,122.6,122.4,122.3,122.0,120.9,119.0,116.0,109.5,33.2；HRMS(ESI):m/z[M+H] ⁺ calcd for C ₂₂ H ₁₇ N ₂ :309.1386；found:309.1388。

example 40

1a (53mg, 0.5 mmol), 2b (111mg, 0.5 mmol), 3a (151.5 mg,1.5 mmol), ammonium iodide (108.7 mg, 0.75mmol), di-t-butyl peroxide (146mg, 1mmol) and chlorobenzene (2 mL) were added to a 35mL sealed tube, which was then stirred in a 120 ℃ metal bath for 8h. The reaction was quenched with 50mL of water, extracted with ethyl acetate (50 mL. Times.3), and the organic phase was then quenched with 10% by weight Na ₂ S ₂ O ₃ The solution was washed with saturated brine, and dried over anhydrous sodium sulfate. Filtering, spin-drying, and separating with silica gel column (petroleum ether/ethyl acetate = 100/1) to obtain yellowSolid product 4ab (142mg, 85%). The characterization data for this compound are as follows: ¹ H NMR(400MHz,CDCl ₃ ):δ(ppm)8.87(d,J＝8.8Hz,1H),8.42(d,J＝8.8Hz,1H),8.21–8.18(m,2H),8.11–8.02(m,2H),7.99(d,J＝8.4Hz,1H),7.87(d,J＝9.2Hz,1H),7.74(dd,J＝8.8,2.0Hz,1H),7.58–7.50(m,2H),7.50–7.45(m,1H)； ¹³ C NMR(100MHz,CDCl ₃ ):δ(ppm)157.2,148.0,139.2,133.0,131.3,130.8,130.2,129.9,129.7,129.4,128.9,128.2,127.4,124.3,123.8,121.1,119.1；HRMS(ESI):m/z[M+H] ⁺ calcd for C ₁₉ H ₁₃ BrN:334.0226；found:334.0229。

EXAMPLE 41

1a (53mg, 0.5 mmol), 2c (86mg, 0.5 mmol), 3a (151.5 mg,1.5 mmol), ammonium iodide (108.7 mg, 0.75mmol), di-t-butyl peroxide (146mg, 1mmol) and chlorobenzene (2 mL) were added to a 35mL sealed tube, which was then stirred in a 120 ℃ metal bath for 8h. The reaction was quenched with 50mL of water, extracted with ethyl acetate (50 mL. Times.3), and the organic phase was then quenched with 10% by weight Na ₂ S ₂ O ₃ The solution was washed with saturated brine, and dried over anhydrous sodium sulfate. Filtration, spin-drying and separation on silica gel column (petroleum ether/ethyl acetate = 100/1) gave the product 4ac (135mg, 95%) as a yellow solid. The characterization data for this compound are as follows: ¹ H NMR(400MHz,CDCl ₃ ):δ(ppm)8.79(d,J＝8.8Hz,1H),8.43(d,J＝8.8Hz,1H),8.19–8.15(m,2H),8.04(d,J＝9.2Hz,1H),7.92–7.84(m,2H),7.55–7.49(m,2H),7.47–7.42(m,1H),7.30–7.25(m,2H),3.94(s,3H)； ¹³ C NMR(100MHz,CDCl ₃ ):δ(ppm)158.7,155.8,147.2,139.5,133.0,130.9,130.4,129.1,129.0,128.8,127.3,124.2,124.1,123.7,118.8,117.7,108.6,55.4；HRMS(ESI):m/z[M+H] ⁺ calcd for C ₂₀ H ₁₆ NO:286.1226；found:286.1228。

example 42

1a (53mg, 0.5 mmol), 2d (100.5 mg,0.5 mmol), 3a (151.5 mg,1.5 mmol), ammonium iodide (108.7 mg, 0.75mmol), di-t-butyl peroxide (146mg, 1mmol) and chlorobenzene (2 mL) were added to a 35mL sealed tube, followed by stirring for 8h in a 120 ℃ metal bath. The reaction was quenched with 50mL of water, extracted with ethyl acetate (50 mL. Times.3), and the organic phase was then quenched with 10% by weight Na ₂ S ₂ O ₃ The solution was washed with saturated brine, and dried over anhydrous sodium sulfate. Filtration, spin-drying and separation on silica gel column (petroleum ether/ethyl acetate = 100/1) gave the product 4ad (130mg, 83%) as a yellow solid. The characterization data for this compound are as follows: ¹ H NMR(400MHz,CDCl ₃ ):δ(ppm)8.94(d,J＝8.8Hz,1H),8.62(d,J＝1.6Hz,1H),8.60(d,J＝8.8Hz,1H),8.26(dd,J＝8.8,1.6Hz,1H),8.22–8.19(m,2H),8.10(d,J＝9.2Hz,1H),8.03(d,J＝9.2Hz,1H),8.00(d,J＝8.8Hz,1H),7.57–7.52(m,2H),7.51–7.46(m,1H),4.00(s,3H)； ¹³ C NMR(100MHz,CDCl ₃ ):δ(ppm)166.9,157.7,148.9,139.1,132.6,132.0,131.2,130.9(5),130.8(7),129.5(2),129.4(8),128.9,128.4,127.5,126.8,123.5,122.8,119.0,52.3；HRMS(ESI):m/z[M+H] ⁺ calcd for C ₂₁ H ₁₆ NO ₂ :314.1176；found:314.1179。

example 43

1a (53mg, 0.5 mmol), 2e (79mg, 0.5 mmol), 3a (151.5 mg,1.5 mmol), ammonium iodide (108.7 mg, 0.75mmol), di-t-butyl peroxide (146mg, 1mmol) and chlorobenzene (2 mL) were added to a 35mL sealed tube, which was then stirred in a 120 ℃ metal bath for 8h. The reaction was quenched with 50mL of water, extracted with ethyl acetate (50 mL. Times.3), and the organic phase was then quenched with 10% by weight Na ₂ S ₂ O ₃ The solution was washed with saturated brine, and dried over anhydrous sodium sulfate. Filtration, spin-drying and separation on silica gel column (petroleum ether/ethyl acetate = 100/1) gave the product 4ae as a yellow solid (84mg, 62%). The characterization data for this compound are as follows: ¹ H NMR(400MHz,CDCl ₃ ):δ(ppm)8.83(d,J＝8.8Hz,1H),8.41(d,J＝8.4Hz,1H),8.21–8.15(m,2H),7.98(d,J＝9.2Hz,1H),7.95(d,J＝8.4Hz,1H),7.79(d,J＝9.2Hz,1H),7.53(t,J＝7.6Hz,2H),7.47–7.42(m,1H),7.13–7.07(m,2H),3.98(s,2H)；13C NMR(100MHz,CDCl3):δ(ppm)155.3,146.9,145.6,139.7,133.3,130.5,130.1,129.0,128.9,128.8,127.2,124.6,124.0,122.2,118.8,117.3,111.1；HRMS(ESI):m/z[M+H]+calcd for C19H15N2:271.1230；found:271.1233。

example 44

1a (53mg, 0.5mmol), 2a (71.5mg, 0.5mmol), 3b (214.5mg, 1.5mmol), ammonium iodide (108.7mg, 0.75mmol), di-tert-butyl peroxide (146mg, 1mmol) and chlorobenzene (2 mL) were added to a 35mL sealed tube, followed by stirring for 8h in a 120 ℃ metal bath. The reaction was quenched with 50mL of water, extracted with ethyl acetate (50 mL. Times.3), and the organic phase was then quenched with 10% by weight Na ₂ S ₂ O ₃ The solution was washed with saturated brine, and dried over anhydrous sodium sulfate. Filtration, spin-drying and silica gel column separation (petroleum ether/ethyl acetate = 100/1) gave the product 4af (117mg, 87%) as a yellow solid. The characterization data for this compound are as follows: ¹ HNMR(400MHz,CDCl ₃ ):δ(ppm)8.70(s,1H),8.55(d,J＝8.0Hz,1H),8.00(d,J＝9.2Hz,1H),7.89–7.85(m,2H),7.65–7.60(m,3H),7.60–7.56(m,1H),7.51–7.46(m,2H),7.44–7.40(m,1H),2.52(s,3H)；13C NMR(100MHz,CDCl3):δ(ppm)159.2,146.1,140.6,132.1,131.6,129.9,129.1,129.0,128.9,128.5,128.2,128.1,128.0,126.9,126.7,124.2,122.5,20.8；HRMS(ESI):m/z[M+H]+calcd for C20H16N:270.1277；found:270.1279。

example 45

1a (53mg, 0.5mmol), 2a (71.5mg, 0.5mmol), 3c (341mg, 1.5mmol), ammonium iodide (108.7mg, 0.75mmol), di-t-butyl peroxide (146mg, 1mmol) and chlorobenzene were added to a 35mL sealed tube(2 mL) and then placed in a 120 ℃ metal bath and stirred for 8h. The reaction was quenched with 50mL of water, extracted with ethyl acetate (50 mL. Times.3), and the organic phase was then quenched with 10% by weight Na ₂ S ₂ O ₃ The solution was washed with saturated brine, and dried over anhydrous sodium sulfate. Filtration, spin-drying and separation on silica gel column (petroleum ether/ethyl acetate = 100/1) gave the product 4ag (117.3mg, 79%) as a yellow solid. The characterization data for this compound are as follows: ¹ H NMR(400MHz,CDCl ₃ ):δ(ppm)8.83(s,1H),8.67(d,J＝8.0Hz,1H),8.03(d,J＝8.8Hz,1H),7.96–7.91(m,2H),7.72–7.61(m,2H),7.61–7.57(m,2H),7.53–7.47(m,2H),7.47–7.42(m,1H),2.86(t,J＝7.6Hz,2H),1.70–1.60(m,2H),0.90(t,J＝7.2Hz,3H)； ¹³ CNMR(100MHz,CDCl ₃ ):δ(ppm)159.7,146.0,140.8,133.8,131.7,131.2,130.1,129.3,128.9,128.7,128.3,128.2,128.0,127.0,126.8,124.4,122.6,35.1,24.2,13.9；HRMS(ESI):m/z[M+H] ⁺ calcd for C ₂₂ H ₂₀ N:298.1590；found:298.1591。

example 46

1a (53mg, 0.5 mmol), 2a (71.5 mg,0.5 mmol), 3d (341mg, 1.5 mmol), ammonium iodide (108.7 mg, 0.75mmol), di-t-butyl peroxide (146mg, 1mmol) and chlorobenzene (2 mL) were added to a 35mL sealed tube, which was then stirred in a 120 ℃ metal bath for 8h. The reaction was quenched with 50mL of water, extracted with ethyl acetate (50 mL. Times.3), and the organic phase was then quenched with 10% by weight Na ₂ S ₂ O ₃ The solution was washed with saturated brine, and dried over anhydrous sodium sulfate. Filtration, spin-drying, and separation on silica gel column (petroleum ether/ethyl acetate = 100/1) gave the product 4ah (96.5mg, 65%) as a yellow solid. The characterization data for this compound are as follows: ¹ H NMR(400MHz,CDCl ₃ ):δ(ppm)8.94(s,1H),8.71(d,J＝8.0Hz,1H),8.02(d,J＝8.8Hz,1H),7.96–7.91(m,2H),7.74–7.69(m,1H),7.67–7.62(m,1H),7.59–7.55(m,2H),7.53–7.48(m,2H),7.48–7.43(m,1H),3.40–3.30(m,1H),1.34(d,J＝6.8Hz,6H)； ¹³ CNMR(100MHz,CDCl ₃ ):δ(ppm)159.2,145.8,140.8,140.2,131.7,130.2,129.4,128.9,128.7,128.3,128.2,128.0,127.9,127.0,126.8,124.6,122.6,29.4,24.4；HRMS(ESI):m/z[M+H] ⁺ calcd for C ₂₂ H ₂₀ N:298.1590；found:298.1587。

example 47

1a (53mg, 0.5 mmol), 2a (71.5 mg,0.5 mmol), 3e (404mg, 1.5 mmol), ammonium iodide (108.7 mg, 0.75mmol), di-t-butyl peroxide (146mg, 1mmol) and chlorobenzene (2 mL) were added to a 35mL sealed tube, followed by stirring for 8h in a 120 ℃ metal bath. The reaction was quenched with 50mL of water, extracted with ethyl acetate (50 mL. Times.3), and the organic phase was then quenched with 10% by weight Na ₂ S ₂ O ₃ The solution was washed with saturated brine, and dried over anhydrous sodium sulfate. Filtration, spin-drying and silica gel column separation (petroleum ether/ethyl acetate = 100/1) gave the product 4ai as a yellow solid (132mg, 85%). The characterization data for this compound are as follows: ¹ H NMR(400MHz,CDCl ₃ ):δ(ppm)8.82(s,1H),8.67(d,J＝8.0Hz,1H),8.02(d,J＝9.2Hz,1H),7.95–7.90(m,2H),7.72–7.67(m,1H),7.66–7.61(m,1H),7.61–7.57(m,2H),7.53–7.47(m,2H),7.47–7.42(m,1H),2.88(t,J＝7.6Hz 2H),1.64–1.56(m,2H),1.35–1.26(m,2H),0.85(t,J＝7.6Hz,3H)； ¹³ C NMR(100MHz,CDCl ₃ ):δ(ppm)159.6,146.0,140.8,134.1,131.7,131.1,130.1,129.3,128.9,128.7,128.3,128.2,128.0,127.0,126.8,124.4,122.6,33.3,32.8,22.4,13.8；HRMS(ESI):m/z[M+H] ⁺ calcd for C ₂₃ H ₂₂ N:312.1747；found:312.1746。

example 48

1a (53mg, 0.5 mmol), 2a (71.5 mg,0.5 mmol), 3f (467mg, 1.5 mmol), ammonium iodide (108.7 mg, 0.75mmol), di-t-butyl peroxide (146mg, 1mmol) and chlorobenzene (2 mL) were added to a 35mL sealed tube, which was then placed in a 120 ℃ metal bathStirring for 8h. The reaction was quenched with 50mL of water, extracted with ethyl acetate (50 mL. Times.3), and the organic phase was then quenched with 10% by weight Na ₂ S ₂ O ₃ The solution and the saturated brine were successively washed, and dried over anhydrous sodium sulfate. Filtration, spin-drying and separation on silica gel column (petroleum ether/ethyl acetate = 100/1) gave the product 4aj (120mg, 74%) as a yellow solid. The characterization data for this compound are as follows: ¹ H NMR(400MHz,CDCl ₃ ):δ(ppm)8.83(s,1H),8.67(d,J＝8.4Hz,1H),8.03(d,J＝9.2Hz,1H),7.94(d,J＝9.2Hz,2H),7.72–7.62(m,2H),7.61–7.57(m,2H),7.53–7.47(m,2H),7.47–7.42(m,1H),2.87(t,J＝8.0Hz,2H),1.66–1.57(m,2H),1.29–1.22(m,4H),0.83(t,J＝7.2Hz,3H)； ¹³ C NMR(100MHz,CDCl ₃ ):δ(ppm)159.7,146.0,140.8,134.1,131.7,131.2,130.1,129.3,128.9,128.7,128.3,128.2,128.0,127.0,126.8,124.4,122.6,33.1,31.5,30.8,22.3,13.9；HRMS(ESI):m/z[M+H] ⁺ calcd for C ₂₄ H ₂₄ N:326.1903；found:326.1904。

example 49

1a (53mg, 0.5 mmol), 2a (71.5 mg,0.5 mmol), 3g (530.5 mg,1.5 mmol), ammonium iodide (108.7 mg, 0.75mmol), di-t-butyl peroxide (146mg, 1mmol) and chlorobenzene (2 mL) were added to a 35mL sealed tube, followed by stirring at 120 ℃ for 8h. The reaction was quenched with 50mL of water, extracted with ethyl acetate (50 mL. Times.3), and the organic phase was then quenched with 10% by weight Na ₂ S ₂ O ₃ The solution was washed with saturated brine, and dried over anhydrous sodium sulfate. Filtration, spin-drying and separation on silica gel column (petroleum ether/ethyl acetate = 100/1) gave the product 4ak (152.5mg, 90%) as a yellow solid. The characterization data for this compound are as follows: ¹ H NMR(400MHz,CDCl ₃ ):δ(ppm)8.80(s,1H),8.64(d,J＝8.0Hz,1H),8.02(d,J＝9.2Hz,1H),7.93–7.88(m,2H),7.70–7.65(m,1H),7.63–7.57(m,3H),7.52–7.46(m,2H),7.46–7.41(m,1H),2.85(t,J＝8.0Hz,2H),1.63–1.55(m,2H),1.30–1.18(m,6H),0.83(t,J＝6.8Hz,3H)； ¹³ C NMR(100MHz,CDCl ₃ ):δ(ppm)159.6,145.9,140.8,134.1,131.7,131.1,130.0,129.3,128.9,128.6,128.2,128.1,128.0,127.0,126.8,124.3,122.6,33.0,31.4,31.0,29.0,22.4,14.0；HRMS(ESI):m/z[M+H] ⁺ calcd for C ₂₅ H ₂₆ N:340.2060；found:340.2062。

example 50

1a (53mg, 0.5 mmol), 2a (71.5 mg,0.5 mmol), 3h (593.6 mg,1.5 mmol), ammonium iodide (108.7 mg, 0.75mmol), di-t-butyl peroxide (146mg, 1mmol) and chlorobenzene (2 mL) were added to a 35mL sealed tube, followed by stirring for 8h in a 120 ℃ metal bath. The reaction was quenched with 50mL of water, extracted with ethyl acetate (50 mL. Times.3), and the organic phase was then quenched with 10% by weight Na ₂ S ₂ O ₃ The solution was washed with saturated brine, and dried over anhydrous sodium sulfate. Filtration, spin-drying, and separation on silica gel column (petroleum ether/ethyl acetate = 100/1) gave 4al (123.5mg, 70%) as a yellow solid product. The characterization data for this compound are as follows: ¹ H NMR(400MHz,CDCl ₃ ):δ(ppm)8.83(s,1H),8.68(d,J＝8.0Hz,1H),8.03(d,J＝8.8Hz,1H),7.94(d,J＝8.8Hz,2H),7.73–7.68(m,1H),7.67–7.62(m,1H),7.61–7.57(m,2H),7.53–7.47(m,2H),7.47–7.42(m,1H),2.88(t,J＝7.6Hz,2H),1.65–1.57(m,2H),1.30–1.17(m,8H),0.85(t,J＝7.2Hz,3H)； ¹³ C NMR(100MHz,CDCl ₃ ):δ(ppm)159.6,146.0,140.8,134.2,131.7,131.2,130.1,129.3,128.9,128.7,128.3,128.2,128.0,127.0,126.8,124.4,122.6,33.1,31.6,31.1,29.3,28.9,22.6,14.1；HRMS(ESI):m/z[M+H] ⁺ calcd for C ₂₆ H ₂₈ N:354.2216；found:354.2212。

example 51

1a (53mg, 0.5mmol), 2a (71.5mg, 0.5mmol), 3i (656.7mg, 1.5mmol), ammonium iodide (108.7mg, 0.75mmol), di-t-butylperoxyThe oxide (146mg, 1mmol) and chlorobenzene (2 mL) were then placed in a 120 ℃ metal bath and stirred for 8h. The reaction was quenched with 50mL of water, extracted with ethyl acetate (50 mL. Times.3), and the organic phase was then quenched with 10% by weight Na ₂ S ₂ O ₃ The solution was washed with saturated brine, and dried over anhydrous sodium sulfate. Filtration, spin-drying, and separation on silica gel column (petroleum ether/ethyl acetate = 100/1) gave the product 4am as a yellow solid (156mg, 85%). The characterization data for this compound are as follows: ¹ H NMR(400MHz,CDCl ₃ ):δ(ppm)8.82(s,1H),8.67(d,J＝8.0Hz,1H),8.02(d,J＝9.2Hz,1H),7.93(d,J＝9.2Hz,2H),7.72–7.67(m,1H),7.66–7.61(m,1H),7.61–7.57(m,2H),7.52–7.47(m,2H),7.47–7.42(m,1H),2.87(t,J＝8.0Hz,2H),1.65–1.56(m,2H),1.28–1.17(m,10H),0.86(t,J＝7.2Hz,3H)； ¹³ C NMR(100MHz,CDCl ₃ ):δ(ppm)159.7,146.0,140.8,134.1,131.8,131.1,130.1,129.3,128.9,128.7,128.3,128.2,128.0,127.0,126.8,124.4,122.6,33.1,31.8,31.1,29.3,29.2,29.1,22.6,14.1；HRMS(ESI):m/z[M+H] ⁺ calcd for C ₂₇ H ₃₀ N:368.2373；found:368.2373。

example 52

1a (53mg, 0.5 mmol), 2a (71.5 mg,0.5 mmol), 3j (720mg, 1.5 mmol), ammonium iodide (108.7mg, 0.75mmol), di-t-butyl peroxide (146mg, 1mmol), and chlorobenzene (2 mL) were added to a 35mL sealed tube, followed by stirring at 120 ℃ for 8 hours. The reaction was quenched with 50mL of water, extracted with ethyl acetate (50 mL. Times.3), and the organic phase was then quenched with 10% by weight Na ₂ S ₂ O ₃ The solution was washed with saturated brine, and dried over anhydrous sodium sulfate. Filtration, spin-drying and separation on silica gel column (petroleum ether/ethyl acetate = 100/1) gave the product 4an as a yellow solid (137mg, 72%). The characterization data for this compound are as follows: ¹ H NMR(400MHz,CDCl ₃ ):δ(ppm)8.84(s,1H),8.68(d,J＝8.0Hz,1H),8.03(d,J＝9.2Hz,1H),7.94(d,J＝8.8Hz,2H),7.73–7.69(m,1H),7.67–7.63(m,1H),7.62–7.57(m,2H),7.53–7.48(m,2H),7.47–7.42(m,1H),2.88(t,J＝8.0Hz,2H),1.63–1.56(m,2H),1.30–1.19(m,12H),0.87(t,J＝7.2Hz,3H)； ¹³ C NMR(100MHz,CDCl ₃ ):δ(ppm)159.7,146.0,140.8,134.2,131.8,131.2,130.1,129.3,128.9,128.7,128.3,128.2,128.0,127.0,126.8,124.4,122.6,33.1,31.8,31.1,29.4,29.33,29.26,29.2,22.6,14.1；HRMS(ESI):m/z[M+H] ⁺ calcd for C ₂₈ H ₃₂ N:382.2529；found:382.2527。

example 53

1a (53mg, 0.5mmol), 2a (71.5mg, 0.5mmol), 3k (783mg, 1.5mmol), ammonium iodide (108.7mg, 0.75mmol), di-tert-butyl peroxide (146mg, 1mmol) and chlorobenzene (2 mL) were added to a 35mL sealed tube, followed by stirring at 120 ℃ for 8 hours. The reaction was quenched with 50mL of water, extracted with ethyl acetate (50 mL. Times.3), and the organic phase was then quenched with 10% by weight Na ₂ S ₂ O ₃ The solution and the saturated brine were successively washed, and dried over anhydrous sodium sulfate. Filtration, spin-drying and separation on silica gel column (petroleum ether/ethyl acetate = 100/1) gave the product 4ao as a yellow solid (134mg, 68%). The characterization data for this compound are as follows: ¹ H NMR(400MHz,CDCl ₃ ):δ(ppm)8.82(s,1H),8.67(d,J＝8.0Hz,1H),8.02(d,J＝9.2Hz,1H),7.93(d,J＝9.2Hz,2H),7.72–7.67(m,1H),7.66–7.62(m,1H),7.61–7.57(m,2H),7.52–7.47(m,2H),7.46–7.41(m,1H),2.87(t,J＝8.0Hz,2H),1.65–1.56(m,2H),1.29–1.20(m,14H),0.87(t,J＝6.8Hz,3H)； ¹³ C NMR(100MHz,CDCl ₃ ):δ(ppm)159.7,146.0,140.8,134.1,131.8,131.2,130.1,129.3,128.9,128.7,128.3,128.2,128.0,127.0,126.8,124.4,122.6,33.1,31.9,31.1,29.5,29.4,29.32,29.27,29.2,22.6,14.1；HRMS(ESI):m/z[M+H] ⁺ calcd for C ₂₉ H ₃₄ N:396.2686；found:396.2686。

the foregoing embodiments illustrate the principles, principal features and advantages of the invention, and it will be understood by those skilled in the art that the invention is not limited to the foregoing embodiments, which are merely illustrative of the principles of the invention, and that various changes and modifications may be made therein without departing from the scope of the principles of the invention.

Claims

1. A synthetic method of benzoquinoline compounds containing alkyl and aryl is characterized by comprising the following specific steps: dissolving an aromatic aldehyde compound 1, a beta-naphthylamine compound 2 and a tertiary aliphatic amine compound 3 in a solvent, adding an iodine reagent and an oxidant, and reacting at 110-130 ℃ to obtain a target product, namely an alkyl and aryl containing benzoquinoline compound 4, wherein the reaction equation in the synthesis method is as follows:

2. The method for synthesizing alkyl-and aryl-containing benzoquinolines as claimed in claim 1, wherein: the feeding molar ratio of the aromatic aldehyde compound 1, the beta-naphthylamine compound 2, the tertiary aliphatic amine compound 3, the iodine reagent and the oxidant is 1.

3. The method for synthesizing compounds containing alkyl and aryl benzoquinolines as claimed in claim 1, wherein the synthesized target product compounds containing alkyl and aryl benzoquinolines and the corresponding yield is: