A method for synthesizing alkyl and aryl containing benzoquinolines

Abstract

The application discloses a synthesis method of an alkyl and aryl containing benzoquinoline compound and belongs to the technical field of organic synthesis. The technical scheme of the application is characterized by the following specific steps: aromatic aldehyde compound 1, beta-naphthylamine compound 2 and tertiary aliphatic amine compound 3 are dissolved in a solvent, iodine reagent and an oxidizing agent are then added, and the target product, the alkyl and aryl containing benzoquinoline compound, is prepared by reacting at 110-130 DEG C. The synthesis process is simple and efficient, the benzoquinoline compound is directly prepared by one-pot cascade reaction without transition metal catalysis, the raw material catalyst is cheap and easy to obtain, the reaction condition is mild, the operation is simple, the method is suitable for commercial and large-scale industrial production, the substrate is widely applicable, and the alkyl substituent group is ingeniously introduced by using the tertiary aliphatic amine compound as the raw material.

Description

TECHNICAL FIELD

[0001] The present application belongs to the technical field of organic synthesis, and particularly relates to a synthesis method of an alkyl and aryl containing benzoquinoline compound. BACKGROUND

[0002] Research shows that benzoquinoline derivatives are an important pharmacological alkaloid in natural products. Due to the multiple biological activities such as anticancer, antibacterial, anti-inflammatory and antimalarial, benzoquinoline compounds are widely studied in medicinal chemistry. The methods for preparing benzoquinoline derivatives include traditional Skraup reaction, Doebner-Miller reaction, Combes reaction and Povarov reaction, and transition metal catalyzed β-naphthylamine cross-coupling reaction, but these synthesis methods have many shortcomings, such as harsh reaction conditions, many by-products, difficult product separation, strong substrate limitation, limited synthesis of substituted benzoquinoline derivatives, and difficulty in synthesizing β and γ substituted benzoquinoline derivatives. More importantly, with the development of synthesis technology becoming mature, for the field of new drug research and development, the alkylation modification of benzoquinoline can improve the lipophilicity of the whole molecule, so the structure of the benzoquinoline class modified by alkylation at the β position is gradually valued and expected. However, from the perspective of synthesis, it is relatively difficult to introduce an alkyl group at the β position, and the relative synthesis cost is also relatively high. Therefore, research and development of a synthesis method of an alkyl and aryl containing benzoquinoline compound using cheap and safe reagents as raw materials and through a simple operation step not only has certain theoretical significance, but also has important application value. SUMMARY

[0003] The technical problem solved by the present application is to provide a synthesis method of an alkyl and aryl containing benzoquinoline compound, which is prepared from simple and readily available raw materials through one-pot tandem reaction to obtain the alkyl and aryl containing benzoquinoline compound, has the advantages of convenient synthesis process operation, mild reaction conditions, cheap and readily available raw material catalyst, suitability for commercialization and large-scale industrial production, and has potential application value in the field of medicine.

[0004] The present application adopts the following technical solution to solve the above technical problem, a synthesis method of an alkyl and aryl containing benzoquinoline compound, characterized in that the specific steps are as follows: dissolving an aromatic aldehyde compound 1, a β-naphthylamine compound 2 and a tertiary aliphatic amine compound 3 in a solvent, then adding an iodine reagent and an oxidizing agent, and then reacting at 110-130 DEG C to obtain the target product, an alkyl and aryl containing benzoquinoline compound 4, and the reaction equation in the synthesis method is as follows:

[0005]

[0006] wherein R 1R is hydrogen, methyl, n-propyl, i-propyl, n-butyl, n-pentyl, n-hexyl, n-heptyl, n-octyl, n-nonyl or n-decyl, R is bromine, methoxy, methoxycarbonyl or amino, R is hydrogen, methyl, n-propyl, i-propyl, n-butyl, n-pentyl, n-hexyl, n-heptyl, n-octyl, n-nonyl or n-decyl, R is ethyl, n-propyl, n-pentyl, i-pentyl, 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. 2 R is hydrogen, methyl, n-propyl, i-propyl, n-butyl, n-pentyl, n-hexyl, n-heptyl, n-octyl, n-nonyl or n-decyl, R is bromine, methoxy, methoxycarbonyl or amino, R is hydrogen, methyl, n-propyl, i-propyl, n-butyl, n-pentyl, n-hexyl, n-heptyl, n-octyl, n-nonyl or n-decyl, R is ethyl, n-propyl, n-pentyl, i-pentyl, 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. 3 R is hydrogen, methyl, n-propyl, i-propyl, n-butyl, n-pentyl, n-hexyl, n-heptyl, n-octyl, n-nonyl or n-decyl, R is bromine, methoxy, methoxycarbonyl or amino, R is hydrogen, methyl, n-propyl, i-propyl, n-butyl, n-pentyl, n-hexyl, n-heptyl, n-octyl, n-nonyl or n-decyl, R is ethyl, n-propyl, n-pentyl, i-pentyl, 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. 4 R is hydrogen, methyl, n-propyl, i-propyl, n-butyl, n-pentyl, n-hexyl, n-heptyl, n-octyl, n-nonyl or n-decyl, R is bromine, methoxy, methoxycarbonyl or amino, R is hydrogen, methyl, n-propyl, i-propyl, n-butyl, n-pentyl, n-hexyl, n-heptyl, n-octyl, n-nonyl or n-decyl, R is ethyl, n-propyl, n-pentyl, i-pentyl, 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.

[0007] Further preferably, the feeding molar ratio of the aromatic aldehyde compound 1, the β-naphthylamine compound 2, the tertiary aliphatic amine compound 3, the iodine reagent and the oxidant is 1:1:3:1.5:2, and the feeding ratio of the aromatic aldehyde compound 1 and the solvent is 1 mmol:4 mL.

[0008] Further preferably, the target product synthesized is an alkyl- and aryl-containing benzoquinoline compound, and the corresponding yield is:

[0009]

[0010] Compared with the prior art, the present application has the following advantages: 1. The synthesis process is a one-pot tandem reaction without transition metal catalysis, which is simple and efficient; 2. The raw material catalyst is cheap and easy to obtain, the reaction conditions are mild, the operation is simple, and it is suitable for commercial and large-scale industrial production; 3. The application range of the substrate is wide; 4. The tertiary aliphatic amine compound can be used as a raw material to introduce an alkyl substituent group into the target product. Therefore, the present application provides an economical, practical and simple and efficient new method for synthesizing alkyl- and aryl-containing benzoquinoline compounds. DETAILED DESCRIPTION

[0011] The above content of the present application is further described in detail through the following examples, but this should not be understood as limiting the scope of the above subject matter of the present application to the following examples. Any technology realized based on the above content of the present application belongs to the scope of the present application.

[0012] Example 1

[0013]

[0014] In a 35 mL sealed tube, benzaldehyde 1a (53 mg, 0.5 mmol), β-naphthylamine 2a (71.5 mg, 0.5 mmol), triethylamine 3a (151.5 mg, 1.5 mmol), ammonium iodide (108.7 mg, 0.75 mmol), di-tert-butyl peroxide (146 mg, 1 mmol) and chlorobenzene (2 mL) were added, then placed in a 120 °C metal bath and stirred for 8 h. The reaction was quenched by adding 50 mL of water, extracted with ethyl acetate (50 mL x 3), then the organic phase was washed with 10% Na2S2O3solution and saturated brine successively, dried over anhydrous sodium sulfate. Filtration, rotary evaporation, and separation on a silica gel column (petroleum ether / ethyl acetate = 100 / 1) gave the yellow solid product 4a (117 mg, 92%). The characterization data of this compound are as follows: 1 H NMR (400 MHz, CDC13): δ (ppm) 8.93 (d, J = 8.8 Hz, 1H), 8.57 (d, J = 8.0 Hz, 1H), 8.23-8.16 (m, 2H), 8.07 (d, J = 9.2 Hz, 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 (100 MHz, CDC13): 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.

[0015] Example 2

[0016] In a 35 mL sealed tube, 1a (53 mg, 0.5 mmol), 2a (71.5 mg, 0.5 mmol), 3a (151.5 mg, 1.5 mmol), iodine (190.5 mg, 0.75 mmol), di-tert-butyl peroxide (146 mg, 1 mmol) and chlorobenzene (2 mL) were added, and then stirred in a 120 °C metal bath for 8 h. The reaction was quenched by adding 50 mL of water, extracted with ethyl acetate (50 mL x 3), and then the organic phase was washed with 10% Na2S2O3 solution and saturated brine in turn, and dried over anhydrous sodium sulfate. Filtration, rotary evaporation, and silica gel column separation (petroleum ether / ethyl acetate = 100 / 1) gave the target product 4a (52.3 mg, 41%).

[0017] Example 3

[0018] In a 35 mL sealed tube, 1a (53 mg, 0.5 mmol), 2a (71.5 mg, 0.5 mmol), 3a (151.5 mg, 1.5 mmol), ammonium iodide (108.7 mg, 0.75 mmol), diisopropylbenzene peroxide (270 mg, 1 mmol) and chlorobenzene (2 mL) were added, and then stirred in a 120 °C metal bath for 8 h. The reaction was quenched by adding 50 mL of water, extracted with ethyl acetate (50 mL x 3), and then the organic phase was washed with 10% Na2S2O3 solution and saturated brine in turn, and dried over anhydrous sodium sulfate. Filtration, rotary evaporation, and silica gel column separation (petroleum ether / ethyl acetate = 100 / 1) gave the target product 4a (99.5 mg, 78%).

[0019] Example 4

[0020] In a 35 mL sealed tube, 1a (53 mg, 0.5 mmol), 2a (71.5 mg, 0.5 mmol), 3a (151.5 mg, 1.5 mmol), ammonium iodide (108.7 mg, 0.75 mmol), potassium persulfate (270 mg, 1 mmol) and chlorobenzene (2 mL) were added, and then stirred in a 120 °C metal bath for 8 h. The reaction was quenched by adding 50 mL of water, extracted with ethyl acetate (50 mL x 3), and then the organic phase was washed with 10% Na2S2O3 solution and saturated brine in turn, and dried over anhydrous sodium sulfate. Filtration, rotary evaporation, and silica gel column separation (petroleum ether / ethyl acetate = 100 / 1) gave the target product 4a (57.4 mg, 45%).

[0021] Example 5

[0022] In a 35 mL reaction flask, 1a (53 mg, 0.5 mmol), 2a (71.5 mg, 0.5 mmol), 3a (151.5 mg, 1.5 mmol), ammonium iodide (108.7 mg, 0.75 mmol) and chlorobenzene (2 mL) were added, and then stirred in an open 120 °C metal bath for 8 h. The reaction was quenched by adding 50 mL of water, extracted with ethyl acetate (50 mL x 3), and then the organic phase was washed with 10% Na2S2O3 solution and saturated brine in turn, and dried over anhydrous sodium sulfate. Filtration, rotary evaporation, and silica gel column separation (petroleum ether / ethyl acetate = 100 / 1) gave the target product 4a (75 mg, 59%).

[0023] Example 6

[0024] In a 35 mL sealed tube, 1a (53 mg, 0.5 mmol), 2a (71.5 mg, 0.5 mmol), 3a (151.5 mg, 1.5 mmol), ammonium iodide (108.7 mg, 0.75 mmol), di-tert-butyl peroxide (146 mg, 1 mmol) and toluene (2 mL) were added, and then stirred in a 120 °C metal bath for 8 h. The reaction was quenched by adding 50 mL of water, extracted with ethyl acetate (50 mL x 3), and then the organic phase was washed with 10% Na2S2O3 solution and saturated brine in turn, and dried over anhydrous sodium sulfate. Filtration, rotary evaporation, and silica gel column separation (petroleum ether / ethyl acetate = 100 / 1) gave the target product 4a (111 mg, 87%).

[0025] Example 7

[0026] In a 35 mL sealed tube, 1a (53 mg, 0.5 mmol), 2a (71.5 mg, 0.5 mmol), 3a (151.5 mg, 1.5 mmol), ammonium iodide (108.7 mg, 0.75 mmol), di-tert-butyl peroxide (146 mg, 1 mmol) and 1,4-dioxane (2 mL) were added, and then stirred in a 120 °C metal bath for 8 h. The reaction was quenched by adding 50 mL of water, extracted with ethyl acetate (50 mL x 3), and then the organic phase was washed with 10% Na2S2O3 solution and saturated brine in turn, and dried over anhydrous sodium sulfate. Filtration, rotary evaporation, and silica gel column separation (petroleum ether / ethyl acetate = 100 / 1) gave the target product 4a (100.7 mg, 79%).

[0027] Example 8

[0028] In a 35 mL sealed tube, 1a (53 mg, 0.5 mmol), 2a (71.5 mg, 0.5 mmol), 3a (151.5 mg, 1.5 mmol), ammonium iodide (108.7 mg, 0.75 mmol), di-tert-butyl peroxide (146 mg, 1 mmol) and acetonitrile (2 mL) were added, and then stirred in a 120 °C metal bath for 8 h. The reaction was quenched by adding 50 mL of water, extracted with ethyl acetate (50 mL x 3), and then the organic phase was washed with 10% Na2S2O3 solution and saturated brine in turn, and dried over anhydrous sodium sulfate. Filtration, rotary evaporation, and silica gel column separation (petroleum ether / ethyl acetate = 100 / 1) gave the target product 4a (53.5 mg, 42%).

[0029] Example 9

[0030] In a 35 mL sealed tube, 1a (53 mg, 0.5 mmol), 2a (71.5 mg, 0.5 mmol), 3a (151.5 mg, 1.5 mmol), ammonium iodide (108.7 mg, 0.75 mmol), di-tert-butyl peroxide (146 mg, 1 mmol) and N-methyl-2-pyrrolidone (2 mL) were added, and then stirred in a 120 °C metal bath for 8 h. The reaction was quenched by adding 50 mL of water, extracted with ethyl acetate (50 mL x 3), and then the organic phase was washed with 10% Na2S2O3 solution and saturated brine in turn, and dried over anhydrous sodium sulfate. Filtration, rotary evaporation, and silica gel column separation (petroleum ether / ethyl acetate = 100 / 1) gave the target product 4a (62.5 mg, 49%).

[0031] Example 10

[0032] In a 35 mL sealed tube, 1a (53 mg, 0.5 mmol), 2a (71.5 mg, 0.5 mmol), 3a (151.5 mg, 1.5 mmol), ammonium iodide (108.7 mg, 0.75 mmol), di-tert-butyl peroxide (146 mg, 1 mmol) and dimethyl sulfoxide (2 mL) were added, and then stirred in a 120 °C metal bath for 8 h. The reaction was quenched by adding 50 mL of water, extracted with ethyl acetate (50 mL x 3), and then the organic phase was washed with 10% Na2S2O3 solution and saturated brine in turn, and dried over anhydrous sodium sulfate. Filtration, rotary evaporation, and silica gel column separation (petroleum ether / ethyl acetate = 100 / 1) gave the target product 4a (68.5 mg, 54%).

[0033] Example 11

[0034] In a 35 mL sealed tube, 1a (53 mg, 0.5 mmol), 2a (71.5 mg, 0.5 mmol), 3a (151.5 mg, 1.5 mmol), ammonium iodide (108.7 mg, 0.75 mmol), di-tert-butyl peroxide (146 mg, 1 mmol) and 1,2-dichloroethane (2 mL) were added, and then placed in a 120 °C metal bath for stirring for 8 h. The reaction was quenched by adding 50 mL of water, extracted with ethyl acetate (50 mL x 3), and then the organic phase was washed with 10% Na2S2O3solution and saturated brine in turn, and dried over anhydrous sodium sulfate. Filtration, rotary evaporation, and silica gel column separation (petroleum ether / ethyl acetate = 100 / 1) gave the target product 4a (107 mg, 84%).

[0035] Example 12

[0036] In a 35 mL sealed tube, 1a (53 mg, 0.5 mmol), 2a (71.5 mg, 0.5 mmol), 3a (151.5 mg, 1.5 mmol), ammonium iodide (108.7 mg, 0.75 mmol), di-tert-butyl peroxide (146 mg, 1 mmol) and 1,2-dichloroethane (2 mL) were added, and then placed in a 110 °C metal bath for stirring for 8 h. The reaction was quenched by adding 50 mL of water, extracted with ethyl acetate (50 mL x 3), and then the organic phase was washed with 10% Na2S2O3solution and saturated brine in turn, and dried over anhydrous sodium sulfate. Filtration, rotary evaporation, and silica gel column separation (petroleum ether / ethyl acetate = 100 / 1) gave the target product 4a (104.5 mg, 82%).

[0037] Example 13

[0038] In a 35 mL sealed tube, 1a (53 mg, 0.5 mmol), 2a (71.5 mg, 0.5 mmol), 3a (151.5 mg, 1.5 mmol), ammonium iodide (108.7 mg, 0.75 mmol), di-tert-butyl peroxide (146 mg, 1 mmol) and 1,2-dichloroethane (2 mL) were added, and then placed in a 130 °C metal bath for stirring for 8 h. The reaction was quenched by adding 50 mL of water, extracted with ethyl acetate (50 mL x 3), and then the organic phase was washed with 10% Na2S2O3solution and saturated brine in turn, and dried over anhydrous sodium sulfate. Filtration, rotary evaporation, and silica gel column separation (petroleum ether / ethyl acetate = 100 / 1) gave the target product 4a (117 mg, 92%).

[0039] Example 14

[0040]

[0041] In a 35 mL sealed tube was added 1b (60 mg, 0.5 mmol), 2a (71.5 mg, 0.5 mmol), 3a (151.5 mg, 1.5 mmol), ammonium iodide (108.7 mg, 0.75 mmol), di-tert-butyl peroxide (146 mg, 1 mmol) and chlorobenzene (2 mL), then placed in a 120 °C metal bath and stirred for 8 h. The reaction was quenched by adding 50 mL water, extracted with ethyl acetate (50 mL x 3), then the organic phase was washed with 10% Na2S2O3solution and saturated brine successively, dried over anhydrous sodium sulfate. Filtration, rotary evaporation, separation on silica gel column (petroleum ether / ethyl acetate = 100 / 1) gave the product 4b (122 mg, 91%) as a yellow solid. The characterization data of this compound are as follows: 1 H NMR (400 MHz, CDC13): δ (ppm) 8.91 (d, J = 8.4 Hz, 1H), 8.57 (d, J = 8.0 Hz, 1H), 8.12 - 8.08 (m, 2H), 8.06 (d, J = 8.8 Hz, 1H), 7.99 - 7.94 (m, 2H), 7.92 (dd, J = 7.6, 1.2 Hz, 1H), 7.69 - 7.59 (m, 2H), 7.33 (d, J = 8.0 Hz, 2H), 2.43 (s, 3H); 13 C NMR (100 MHz, CDC13): 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.

[0042] Example 15

[0043]

[0044] In a 35 mL sealed tube, 1c (81 mg, 0.5 mmol), 2a (71.5 mg, 0.5 mmol), 3a (151.5 mg, 1.5 mmol), ammonium iodide (108.7 mg, 0.75 mmol), di-tert-butyl peroxide (146 mg, 1 mmol) and chlorobenzene (2 mL) were added, and then placed in a 120 °C metal bath for stirring for 8 h. The reaction was quenched by adding 50 mL of water, extracted with ethyl acetate (50 mL x 3), and then the organic phase was washed with 10% Na2S2O3solution and saturated brine successively, and dried over anhydrous sodium sulfate. Filtration, rotary evaporation, and separation on a silica gel column (petroleum ether / ethyl acetate = 100 / 1) gave the product 4c (146 mg, 94%) as a yellow solid. The characterization data of this compound are as follows: 1 H NMR (400 MHz, CDC13): δ (ppm) 8.96 (d, J = 8.8 Hz, 1H), 8.61 (d, J = 8.0 Hz, 1H), 8.15-8.11 (m, 2H), 8.07 (d, J = 8.8 Hz, 1H), 8.01-7.97 (m, 2H), 7.93 (dd, J = 8.0, 1.2 Hz, 1H), 7.71-7.60 (m, 2H), 7.58-7.54 (m, 2H), 1.39 (s, 9H); 13 C NMR (100 MHz, CDC13): 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.

[0045] Example 16

[0046]

[0047] In a 35 mL sealed tube, 1d (68 mg, 0.5 mmol), 2a (71.5 mg, 0.5 mmol), 3a (151.5 mg, 1.5 mmol), ammonium iodide (108.7 mg, 0.75 mmol), di-tert-butyl peroxide (146 mg, 1 mmol) and chlorobenzene (2 mL) were added, then placed in a 120 °C metal bath and stirred for 8 h. The reaction was quenched by adding 50 mL of water, extracted with ethyl acetate (50 mL x 3), then the organic phase was washed with 10% Na2S2O3solution and saturated brine successively, dried over anhydrous sodium sulfate. Filtration, rotary evaporation, and separation on a silica gel column (petroleum ether / ethyl acetate = 100 / 1) gave the yellow solid product 4d (127 mg, 89%). The characterization data of this compound are as follows: 1 H NMR (400 MHz, CDC13): δ (ppm) 8.92 (d, J = 8.8 Hz, 1H), 8.58 (d, J = 8.4 Hz, 1H), 8.19-8.15 (m, 2H), 8.05 (d, J = 9.2 Hz, 1H), 7.98 (d, J = 9.2 Hz, 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 (100 MHz, CDC13): 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.

[0048] Example 17

[0049]

[0050] In a 35 mL sealed tube was added 1e (76 mg, 0.5 mmol), 2a (71.5 mg, 0.5 mmol), 3a (151.5 mg, 1.5 mmol), ammonium iodide (108.7 mg, 0.75 mmol), di-tert-butyl peroxide (146 mg, 1 mmol) and chlorobenzene (2 mL), then placed in a 120 °C metal bath and stirred for 8 h. The reaction was quenched by adding 50 mL of water, extracted with ethyl acetate (50 mL x 3), then the organic phase was washed with 10% Na2S2O3solution and saturated brine successively, dried over anhydrous sodium sulfate. Filtration, rotary evaporation, and separation on a silica gel column (petroleum ether / ethyl acetate = 100 / 1) gave the yellow solid product 4e (107 mg, 71%). The characterization data of this compound are as follows: 1 H NMR (400 MHz, CDC13): δ (ppm) 8.96 (d, J = 8.8 Hz, 1H), 8.60 (d, J = 8.0 Hz, 1H), 8.17 - 8.13 (m, 2H), 8.05 (d, J = 9.2 Hz, 1H), 7.98 (dd, J = 8.8, 7.2 Hz, 2H), 7.94 (dd, J = 8.0, 1.2 Hz, 1H), 7.71 - 7.61 (m, 2H), 7.42 - 7.37 (m, 2H), 2.55 (s, 3H); 13 C NMR (100 MHz, CDC13): 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.

[0051] Example 18

[0052]

[0053] In a 35 mL sealed tube, 1f (62 mg, 0.5 mmol), 2a (71.5 mg, 0.5 mmol), 3a (151.5 mg, 1.5 mmol), ammonium iodide (108.7 mg, 0.75 mmol), di-tert-butyl peroxide (146 mg, 1 mmol) and chlorobenzene (2 mL) were added, and then placed in a 120 °C metal bath for stirring for 8 h. The reaction was quenched by adding 50 mL of water, extracted with ethyl acetate (50 mL x 3), and then the organic phase was washed with 10% Na2S2O3solution and saturated brine successively, and dried over anhydrous sodium sulfate. Filtration, rotary evaporation, and separation on a silica gel column (petroleum ether / ethyl acetate = 100 / 1) gave the yellow solid product 4f (108 mg, 79%). The characterization data of this compound are as follows: 1 H NMR (400 MHz, CDC13): δ (ppm) 8.96 (d, J = 8.8 Hz, 1H), 8.60 (d, J = 8.0 Hz, 1H), 8.22-8.16 (m, 2H), 8.02 (q, J = 9.2 Hz, 2H), 7.96-7.92 (m, 2H), 7.72-7.62 (m, 2H), 7.24-7.18 (m, 2H); 13 C NMR (100 MHz, CDC13): 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.

[0054] Example 19

[0055]

[0056] In a 35 mL sealed tube, 1 g (70.3 mg, 0.5 mmol), 2a (71.5 mg, 0.5 mmol), 3a (151.5 mg, 1.5 mmol), ammonium iodide (108.7 mg, 0.75 mmol), di-tert-butyl peroxide (146 mg, 1 mmol) and chlorobenzene (2 mL) were added, and then placed in a 120 °C metal bath for stirring for 8 h. The reaction was quenched by adding 50 mL of water, extracted with ethyl acetate (50 mL x 3), and then the organic phase was washed with 10% Na2S2O3solution and saturated brine successively, and dried over anhydrous sodium sulfate. Filtration, rotary evaporation, and separation on a silica gel column (petroleum ether / ethyl acetate = 100 / 1) gave the yellow solid product 4g (129 mg, 89%). The characterization data of this compound are as follows: 1 H NMR (400 MHz, CDC13): δ (ppm) 8.94 (d, J = 8.8 Hz, 1H), 8.58 (d, J = 8.0 Hz, 1H), 8.17-8.11 (m, 2H), 8.01 (q, J = 9.2 Hz, 2H), 7.93 (d, J = 8.8 Hz, 2H), 7.71-7.62 (m, 2H), 7.52-7.46 (m, 2H); 13 C NMR (100 MHz, CDC13): 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.

[0057] Example 20

[0058]

[0059] In a 35 mL sealed tube, 1h (92.5 mg, 0.5 mmol), 2a (71.5 mg, 0.5 mmol), 3a (151.5 mg, 1.5 mmol), ammonium iodide (108.7 mg, 0.75 mmol), di-tert-butyl peroxide (146 mg, 1 mmol) and chlorobenzene (2 mL) were added, and then placed in a 120 °C metal bath for stirring for 8 h. The reaction was quenched by adding 50 mL of water, extracted with ethyl acetate (50 mL x 3), and then the organic phase was washed with 10% Na2S2O3solution and saturated brine successively, and dried over anhydrous sodium sulfate. Filtration, rotary evaporation, and separation on a silica gel column (petroleum ether / ethyl acetate = 100 / 1) gave the yellow solid product 4h (140 mg, 84%). The characterization data of this compound are as follows: 1 H NMR (400 MHz, CDC13): δ (ppm) 8.98 (d, J = 8.8 Hz, 1H), 8.61 (d, J = 8.0 Hz, 1H), 8.11 - 8.07 (m, 2H), 8.02 (q, J = 8.8 Hz, 2H), 7.98 - 7.93 (m, 2H), 7.73 - 7.68 (m, 1H), 7.68 - 7.63 (m, 3H); 13 C NMR (100 MHz, CDC13): 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.

[0060] Example 21

[0061]

[0062] In a 35 mL sealed tube was added 1i (87 mg, 0.5 mmol), 2a (71.5 mg, 0.5 mmol), 3a (151.5 mg, 1.5 mmol), ammonium iodide (108.7 mg, 0.75 mmol), di-tert-butyl peroxide (146 mg, 1 mmol) and chlorobenzene (2 mL), then placed in a 120 °C metal bath and stirred for 8 h. The reaction was quenched by adding 50 mL of water, extracted with ethyl acetate (50 mL x 3), then the organic phase was washed with 10% Na2S2O3solution and saturated brine successively, dried over anhydrous sodium sulfate. Filtration, rotary evaporation, and separation on a silica gel column (petroleum ether / ethyl acetate = 100 / 1) gave the product 4i (143.7 mg, 89%) as a yellow solid. The characterization data of this compound are as follows: 1 H NMR (400 MHz, CDC13): δ (ppm) 8.98 (d, J = 8.4 Hz, 1H), 8.60 (d, J = 8.0 Hz, 1H), 8.30 (d, J = 8.0 Hz, 2H), 8.07 - 7.97 (m, 3H), 7.96 - 7.92 (m, 1H), 7.78 (d, J = 8.4 Hz, 2H), 7.73 - 7.63 (m, 2H); 13 C NMR (100 MHz, CDC13): 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 F3N: 324.0995; found: 324.0994.

[0063] Example 22

[0064]

[0065] In a 35 mL sealed tube, 1j (65.5 mg, 0.5 mmol), 2a (71.5 mg, 0.5 mmol), 3a (151.5 mg, 1.5 mmol), ammonium iodide (108.7 mg, 0.75 mmol), di-tert-butyl peroxide (146 mg, 1 mmol) and chlorobenzene (2 mL) were added, and then placed in a 120 °C metal bath for stirring for 8 h. The reaction was quenched by adding 50 mL of water, extracted with ethyl acetate (50 mL x 3), and then the organic phase was washed with 10% Na2S2O3solution and saturated brine successively, and dried over anhydrous sodium sulfate. Filtration, rotary evaporation, and separation on a silica gel column (petroleum ether / ethyl acetate = 100 / 1) gave the yellow solid product 4j (105 mg, 75%). The characterization data of the compound are as follows: 1 H NMR (400 MHz, CDC13): δ (ppm) 9.03 (d, J = 8.8 Hz, 1H), 8.63 (d, J = 8.0 Hz, 1H), 8.35-8.30 (m, 2H), 8.08-8.00 (m, 3H), 7.96 (dd, J = 7.6, 1.6 Hz, 1H), 7.84-7.79 (m, 2H), 7.75-7.66 (m, 2H); 13 C NMR (100 MHz, CDC13): 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 N2: 281.1073; found: 281.1073.

[0066] Example 23

[0067]

[0068] In a 35 mL sealed tube, 1k (82 mg, 0.5 mmol), 2a (71.5 mg, 0.5 mmol), 3a (151.5 mg, 1.5 mmol), ammonium iodide (108.7 mg, 0.75 mmol), di-tert-butyl peroxide (146 mg, 1 mmol) and chlorobenzene (2 mL) were added, and then the mixture was stirred in a 120 °C metal bath for 8 h. The reaction was quenched by adding 50 mL of water, extracted with ethyl acetate (50 mL x 3), and then the organic phase was washed with 10% Na2S2O3solution and saturated brine successively, and dried over anhydrous sodium sulfate. Filtration, rotary evaporation, and silica gel column separation (petroleum ether / ethyl acetate = 30 / 1) gave the yellow solid product 4k (116 mg, 74%). The characterization data of the compound are as follows: 1 H NMR (400 MHz, CDC13): δ (ppm) 8.99 (d, J = 8.4 Hz, 1H), 8.62 (d, J = 8.0 Hz, 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, 1.2 Hz, 1H), 7.73-7.63 (m, 2H), 3.96 (s, 3H); 13 C NMR (100 MHz, CDC13): 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 NO2: 314.1176; found: 314.1174.

[0069] Example 24

[0070]

[0071] In a 35 mL sealed tube, 1i (60 mg, 0.5 mmol), 2a (71.5 mg, 0.5 mmol), 3a (151.5 mg, 1.5 mmol), ammonium iodide (108.7 mg, 0.75 mmol), di-tert-butyl peroxide (146 mg, 1 mmol) and chlorobenzene (2 mL) were added, and then placed in a 120 °C metal bath to stir for 8 h. The reaction was quenched by adding 50 mL of water, extracted with ethyl acetate (50 mL x 3), and then the organic phase was washed with 10% Na2S2O3solution and saturated brine successively, and dried over anhydrous sodium sulfate. Filtration, rotary evaporation, and separation on a silica gel column (petroleum ether / ethyl acetate = 100 / 1) gave the yellow solid product 4i (114 mg, 85%). The characterization data of this compound are as follows: 1 H NMR (400 MHz, CDC13): δ (ppm) 8.96 (d, J = 8.8 Hz, 1H), 8.60 (d, J = 8.0 Hz, 1H), 8.10-8.04 (m, 2H), 8.01-7.91 (m, 4H), 7.71-7.61 (m, 2H), 7.42 (t, J = 7.6 Hz, 1H), 7.28 (d, J = 7.6 Hz, 1H), 2.49 (s, 3H); 13 C NMR (100 MHz, CDC13): 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.

[0072] Example 25

[0073]

[0074] In a 35 mL sealed tube, 1 m (75.5 mg, 0.5 mmol), 2a (71.5 mg, 0.5 mmol), 3a (151.5 mg, 1.5 mmol), ammonium iodide (108.7 mg, 0.75 mmol), di-tert-butyl peroxide (146 mg, 1 mmol) and chlorobenzene (2 mL) were added, and then placed in a 120 °C metal bath for stirring for 8 h. The reaction was quenched by adding 50 mL of water, extracted with ethyl acetate (50 mL x 3), and then the organic phase was washed with 10% Na2S2O3solution and saturated brine in turn, and dried over anhydrous sodium sulfate. Filtration, rotary evaporation, and separation on a silica gel column (petroleum ether / ethyl acetate = 50 / 1) gave the yellow solid product 4m (104 mg, 69%). The characterization data of the compound are as follows: 1 HNMR (400 MHz, CDC13): δ (ppm) 9.06 (t, J = 2.0 Hz, 1H), 9.01 (d, J = 8.4 Hz, 1H), 8.61 (d, J = 8.0 Hz, 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, 1.2 Hz, 1H), 7.74-7.65 (m, 3H); 13 C NMR (100 MHz, CDC13): 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 N2O2: 301.0972; found: 301.0973.

[0075] Example 26

[0076]

[0077] In a 35 mL sealed tube was added 1n (60 mg, 0.5 mmol), 2a (71.5 mg, 0.5 mmol), 3a (151.5 mg, 1.5 mmol), ammonium iodide (108.7 mg, 0.75 mmol), di-tert-butyl peroxide (146 mg, 1 mmol) and chlorobenzene (2 mL), then placed in a 120 °C metal bath and stirred for 8 h. The reaction was quenched by adding 50 mL water, extracted with ethyl acetate (50 mL x 3), then the organic phase was washed with 10% Na2S2O3solution and saturated brine successively, dried over anhydrous sodium sulfate. Filtration, rotary evaporation, and separation on a silica gel column (petroleum ether / ethyl acetate = 100 / 1) gave the yellow solid product 4n (75 mg, 56%). The characterization data of this compound are as follows: 1 H NMR (400 MHz, CDC13): δ (ppm) 9.01 (d, J = 8.4 Hz, 1H), 8.67 (d, J = 8.0 Hz, 1H), 8.04 (q, J = 9.2 Hz, 2H), 7.96 (dd, J = 8.0, 1.2 Hz, 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 (100 MHz, CDC13) 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.

[0078] Example 27

[0079]

[0080] In a 35 mL sealed tube, 1o (67 mg, 0.5 mmol), 2a (71.5 mg, 0.5 mmol), 3a (151.5 mg, 1.5 mmol), ammonium iodide (108.7 mg, 0.75 mmol), di-tert-butyl peroxide (146 mg, 1 mmol) and chlorobenzene (2 mL) were added, and then placed in a 120 °C metal bath for stirring for 8 h. The reaction was quenched by adding 50 mL of water, extracted with ethyl acetate (50 mL x 3), and then the organic phase was washed with 10% Na2S2O3solution and saturated brine successively, and dried over anhydrous sodium sulfate. Filtration, rotary evaporation, and separation on a silica gel column (petroleum ether / ethyl acetate = 100 / 1) gave the yellow solid product 4o (133 mg, 94%). The characterization data of this compound are as follows: 1 H NMR (400 MHz, CDC13): δ (ppm) 8.88 (d, J = 8.8 Hz, 1H), 8.55 (d, J = 8.0 Hz, 1H), 8.06 (d, J = 8.8 Hz, 1H), 8.01 (s, 1H), 7.98-7.92 (m, 2H), 7.91-7.87 (m, 2H), 7.66-7.57 (m, 2H), 7.27 (d, J = 8.0 Hz, 1H), 2.38 (s, 3H), 2.33 (s, 3H); 13 C NMR (100 MHz, CDC13): 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.

[0081] Example 28

[0082]

[0083] In a 35 mL sealed tube, 1p (87.5 mg, 0.5 mmol), 2a (71.5 mg, 0.5 mmol), 3a (151.5 mg, 1.5 mmol), ammonium iodide (108.7 mg, 0.75 mmol), di-tert-butyl peroxide (146 mg, 1 mmol) and chlorobenzene (2 mL) were added, and then placed in a 120 °C metal bath for stirring for 8 h. The reaction was quenched by adding 50 mL of water, extracted with ethyl acetate (50 mL x 3), and then the organic phase was washed with 10% Na2S2O3solution and saturated brine successively, and dried over anhydrous sodium sulfate. Filtration, rotary evaporation, and separation on a silica gel column (petroleum ether / ethyl acetate = 100 / 1) gave the yellow solid product 4p (87.5 mg, 54%). The characterization data of the compound are as follows: 1 H NMR (400 MHz, CDCl3): δ (ppm) 9.02 (d, J = 8.4 Hz, 1H), 8.66 (d, J = 7.6 Hz, 1H), 8.06-8.01 (m, 2H), 7.97 (dd, J = 8.0, 1.2 Hz, 1H), 7.92 (d, J = 8.4 Hz, 1H), 7.76-7.71 (m, 2H), 7.70-7.66 (m, 1H), 7.55 (d, J = 2.0 Hz, 1H), 7.42 (dd, J = 8.0, 2.0 Hz, 1H); 13 C NMR (100 MHz, CDCl3): 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.

[0084] Example 29

[0085]

[0086] In a 35 mL sealed tube was added 1q (98 mg, 0.5 mmol), 2a (71.5 mg, 0.5 mmol), 3a (151.5 mg, 1.5 mmol), ammonium iodide (108.7 mg, 0.75 mmol), di-tert-butyl peroxide (146 mg, 1 mmol) and chlorobenzene (2 mL), then placed in a 120 °C metal bath and stirred for 8 h. The reaction was quenched by adding 50 mL water, extracted with ethyl acetate (50 mL x 3), then the organic phase was washed with 10% Na2S2O3solution and saturated brine successively, dried over anhydrous sodium sulfate. Filtration, rotary evaporation, separation on silica gel column (petroleum ether / ethyl acetate = 12 / 1) to give the yellow solid product 4q (145 mg, 84%). The characterization data of this compound are as follows: 1 H NMR (400 MHz, CDC13): δ (ppm) 8.99 (d, J = 8.8 Hz, 1H), 8.63 (d, J = 8.4 Hz, 1H), 8.08 (d, J = 8.8 Hz, 1H), 8.01 (d, J = 9.2 Hz, 1H), 7.97 (d, J = 8.8 Hz, 1H), 7.95 (dd, J = 8.0, 1.2 Hz, 1H), 7.73 - 7.63 (m, 2H), 7.45 (s, 2H), 4.03 (s, 6H), 3.94 (s, 3H); 13 C NMR (100 MHz, CDC13): 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 NO3: 346.1438; found: 346.1437.

[0087] Example 30

[0088]

[0089] In a 35 mL sealed tube, 1r (78 mg, 0.5 mmol), 2a (71.5 mg, 0.5 mmol), 3a (151.5 mg, 1.5 mmol), ammonium iodide (108.7 mg, 0.75 mmol), di-tert-butyl peroxide (146 mg, 1 mmol) and chlorobenzene (2 mL) were added, and then placed in a 120 °C metal bath for stirring for 8 h. The reaction was quenched by adding 50 mL of water, extracted with ethyl acetate (50 mL x 3), and then the organic phase was washed successively with 10% Na2S2O3solution and saturated brine, and dried over anhydrous sodium sulfate. Filtration, rotary evaporation, and separation on a silica gel column (petroleum ether / ethyl acetate = 50 / 1) gave the yellow solid product 4r (113 mg, 74%). The characterization data of this compound are as follows: 1 H NMR (400 MHz, CDC13): δ (ppm) 9.03 (d, J = 8.4 Hz, 1H), 8.68 (d, J = 1.2 Hz, 1H), 8.65 (d, J = 8.4 Hz, 1H), 8.40 (dd, J = 8.4, 2.0 Hz, 1H), 8.17 (d, J = 8.4 Hz, 1H), 8.13 (d, J = 9.2 Hz, 1H), 8.04 - 7.99 (m, 3H), 7.96 (dd, J = 7.6, 1.2 Hz, 1H), 7.92 - 7.88 (m, 1H), 7.73 - 7.63 (m, 2H), 7.56 - 7.51 (m, 2H); 13 C NMR (100 MHz, CDC13): 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.

[0090] Example 31

[0091]

[0092] In a 35 mL sealed tube, 1s (78 mg, 0.5 mmol), 2a (71.5 mg, 0.5 mmol), 3a (151.5 mg, 1.5 mmol), ammonium iodide (108.7 mg, 0.75 mmol), di-tert-butyl peroxide (146 mg, 1 mmol) and chlorobenzene (2 mL) were added, and then placed in a 120 °C metal bath for stirring for 8 h. The reaction was quenched by adding 50 mL of water, extracted with ethyl acetate (50 mL x 3), and then the organic phase was washed successively with 10% Na2S2O3solution and saturated brine, and dried over anhydrous sodium sulfate. Filtration, rotary evaporation, and separation on a silica gel column (petroleum ether / ethyl acetate = 50 / 1) gave the yellow solid product 4s (120.5 mg, 79%). The characterization data of the compound are as follows: 1 H NMR (400 MHz, CDC13): δ (ppm) 9.05 (d, J = 8.4 Hz, 1H), 8.68 (d, J = 8.0 Hz, 1H), 8.19 (d, J = 8.0 Hz, 1H), 8.12 (d, J = 8.8 Hz, 1H), 8.04 (d, J = 8.8 Hz, 1H), 7.99-7.92 (m, 3H), 7.85 (d, J = 8.8 Hz, 1H), 7.77-7.70 (m, 2H), 7.69-7.65 (m, 1H), 7.61 (dd, J = 8.0, 7.2 Hz, 1H), 7.54-7.45 (m, 2H); 13 C NMR (100 MHz, CDC13): 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.

[0093] Example 32

[0094]

[0095] In a 35 mL sealed tube, 1t (48 mg, 0.5 mmol), 2a (71.5 mg, 0.5 mmol), 3a (151.5 mg, 1.5 mmol), ammonium iodide (108.7 mg, 0.75 mmol), di-tert-butyl peroxide (146 mg, 1 mmol) and chlorobenzene (2 mL) were added, and then placed in a 120 °C metal bath for stirring for 8 h. The reaction was quenched by adding 50 mL of water, extracted with ethyl acetate (50 mL x 3), and then the organic phase was washed with 10% Na2S2O3solution and saturated brine successively, and dried over anhydrous sodium sulfate. Filtration, rotary evaporation, and separation on a silica gel column (petroleum ether / ethyl acetate = 100 / 1) gave the yellow solid product 4t (48 mg, 39%). The characterization data of this compound are as follows: 1 H NMR (400 MHz, CDCl3): δ (ppm) 8.97 (d, J = 8.8 Hz, 1H), 8.61 (d, J = 8.0 Hz, 1H), 8.06-7.97 (m, 3H), 7.94 (dd, J = 7.6, 1.2 Hz, 1H), 7.72-7.68 (m, 1H), 7.67-7.62 (m, 2H), 7.25 (s, 1H), 6.61 (dd, J = 3.6, 2.0 Hz, 1H); 13 C NMR (100 MHz, CDCl3): 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.

[0096] Example 33

[0097]

[0098] In a 35 mL sealed tube, 1u (56 mg, 0.5 mmol), 2a (71.5 mg, 0.5 mmol), 3a (151.5 mg, 1.5 mmol), ammonium iodide (108.7 mg, 0.75 mmol), di-tert-butyl peroxide (146 mg, 1 mmol) and chlorobenzene (2 mL) were added, and then placed in a 120 °C metal bath for stirring for 8 h. The reaction was quenched by adding 50 mL of water, extracted with ethyl acetate (50 mL x 3), and then the organic phase was washed with 10% Na2S2O3solution and saturated brine successively, and dried over anhydrous sodium sulfate. Filtration, rotary evaporation, and separation on a silica gel column (petroleum ether / ethyl acetate = 100 / 1) gave the yellow solid product 4u (99 mg, 76%). The characterization data of this compound are as follows: 1 H NMR (400 MHz, CDC13): δ (ppm) 8.88 (d, J = 8.4 Hz, 1H), 8.56 (d, J = 8.4 Hz, 1H), 8.01 - 7.95 (m, 2H), 7.93 - 7.88 (m, 2H), 7.74 (dd, J = 3.6, 1.2 Hz, 1H), 7.69 - 7.59 (m, 2H), 7.47 (dd, J = 4.8, 1.2 Hz, 1H), 7.16 (dd, J = 4.8, 3.6 Hz, 1H); 13 C NMR (100 MHz, CDC13): 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.

[0099] Example 34

[0100]

[0101] In a 35 mL sealed tube, 1v (53.5 mg, 0.5 mmol), 2a (71.5 mg, 0.5 mmol), 3a (151.5 mg, 1.5 mmol), ammonium iodide (108.7 mg, 0.75 mmol), di-tert-butyl peroxide (146 mg, 1 mmol) and chlorobenzene (2 mL) were added, and then placed in a 120 °C metal bath for stirring for 8 h. The reaction was quenched by adding 50 mL of water, extracted with ethyl acetate (50 mL x 3), and then the organic phase was washed with 10% Na2S2O3solution and saturated brine successively, and dried over anhydrous sodium sulfate. Filtration, rotary evaporation, and separation on a silica gel column (petroleum ether / ethyl acetate = 5 / 1) gave the yellow solid product 4v (104 mg, 81%). The characterization data of this compound are as follows: 1 H NMR (400 MHz, CDCl3): δ (ppm) 9.41-9.36 (m, 1H), 8.98 (d, J = 8.8 Hz, 1H), 8.70 (dd, J = 4.8, 1.6 Hz, 1H), 8.60 (d, J = 8.4 Hz, 1H), 8.53 (dt, J = 8.0, 2.0 Hz, 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 (100 MHz, CDCl3): 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 N2: 257.1073; found: 257.1073.

[0102] Example 35

[0103]

[0104] In a 35 mL sealed tube, 1w (78.5 mg, 0.5 mmol), 2a (71.5 mg, 0.5 mmol), 3a (151.5 mg, 1.5 mmol), ammonium iodide (108.7 mg, 0.75 mmol), di-tert-butyl peroxide (146 mg, 1 mmol) and chlorobenzene (2 mL) were added, and then placed in a 120 °C metal bath for stirring for 8 h. The reaction was quenched by adding 50 mL of water, extracted with ethyl acetate (50 mL x 3), and then the organic phase was washed with 10% Na2S2O3solution and saturated brine successively, and dried over anhydrous sodium sulfate. Filtration, rotary evaporation, and separation on a silica gel column (petroleum ether / ethyl acetate = 5 / 1) gave the yellow solid product 4w (121 mg, 79%). The characterization data of this compound are as follows: 1 HNMR (400 MHz, CDC13): δ (ppm) 9.00 (d, J = 8.4 Hz, 1H), 8.95 (dd, J = 4.0, 1.6 Hz, 1H), 8.65 - 8.59 (m, 3H), 8.27 (t, J = 9.0 Hz, 2H), 8.14 - 8.09 (m, 2H), 8.02 (d, J = 9.2 Hz, 1H), 7.97 - 7.93 (m, 1H), 7.72 - 7.63 (m, 2H), 7.44 (q, J = 4.0 Hz, 1H); 13 C NMR (100 MHz, CDC13): 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 N2: 307.1230; found: 307.1231.

[0105] Example 36

[0106]

[0107] In a 35 mL sealed tube, 1x (78.5 mg, 0.5 mmol), 2a (71.5 mg, 0.5 mmol), 3a (151.5 mg, 1.5 mmol), ammonium iodide (108.7 mg, 0.75 mmol), di-tert-butyl peroxide (146 mg, 1 mmol) and chlorobenzene (2 mL) were added, then placed in a 120 °C metal bath for stirring for 8 h. The reaction was quenched by adding 50 mL of water, extracted with ethyl acetate (50 mL x 3), then the organic phase was washed with 10% Na2S2O3solution and saturated brine successively, dried over anhydrous sodium sulfate. Filtration, rotary evaporation, and separation on a silica gel column (petroleum ether / ethyl acetate = 5 / 1) gave the yellow solid product 4x (96.4 mg, 63%). The characterization data of this compound are as follows: 1 H NMR (400 MHz, CDC13): δ (ppm) 9.15 (d, J = 8.8 Hz, 1H), 9.08 (d, J = 4.4 Hz, 1H), 8.72 (d, J = 8.0 Hz, 1H), 8.26-8.22 (m, 2H), 8.13-8.07 (m, 2H), 8.01 (dd, J = 8.0, 1.2 Hz, 1H), 7.90 (d, J = 8.4 Hz, 1H), 7.80-7.76 (m, 2H), 7.75-7.70 (m, 1H), 7.68 (d, J = 4.4 Hz, 1H), 7.60-7.55 (m, 1H); 13 C NMR (100 MHz, CDC13): 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 N2: 307.1230; found: 307.1232.

[0108] Example 37

[0109]

[0110] In a 35 mL sealed tube, 1y (73 mg, 0.5 mmol), 2a (71.5 mg, 0.5 mmol), 3a (151.5 mg, 1.5 mmol), ammonium iodide (108.7 mg, 0.75 mmol), di-tert-butyl peroxide (146 mg, 1 mmol) and chlorobenzene (2 mL) were added, and then placed in a 120 °C metal bath for stirring for 8 h. The reaction was quenched by adding 50 mL of water, extracted with ethyl acetate (50 mL x 3), and then the organic phase was washed with 10% Na2S2O3solution and saturated brine successively, and dried over anhydrous sodium sulfate. Filtration, rotary evaporation, and separation on a silica gel column (petroleum ether / ethyl acetate = 100 / 1) gave the yellow solid product 4y (99 mg, 67%). The characterization data of this compound are as follows: 1 H NMR (400 MHz, CDC13): δ (ppm) 8.96 (d, J = 8.8 Hz, 1H), 8.58 (d, J = 8.4 Hz, 1H), 8.13-8.10 (m, 1H), 8.07 (d, J = 9.2 Hz, 1H), 7.99 (d, J = 9.2 Hz, 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 (100 MHz, CDC13): 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.

[0111] Example 38

[0112]

[0113] In a 35 mL sealed tube, 1z (81 mg, 0.5 mmol), 2a (71.5 mg, 0.5 mmol), 3a (151.5 mg, 1.5 mmol), ammonium iodide (108.7 mg, 0.75 mmol), di-tert-butyl peroxide (146 mg, 1 mmol) and chlorobenzene (2 mL) were added, and then placed in a 120 °C metal bath for stirring for 8 h. The reaction was quenched by adding 50 mL of water, extracted with ethyl acetate (50 mL x 3), and then the organic phase was washed with 10% Na2S2O3solution and saturated brine successively, and dried over anhydrous sodium sulfate. Filtration, rotary evaporation, and separation on a silica gel column (petroleum ether / ethyl acetate = 100 / 1) gave the yellow solid product 4z (124.4 mg, 80%). The characterization data of this compound are as follows: 1 H NMR (400 MHz, CDC13): δ (ppm) 8.96 (d, J = 8.4 Hz, 1H), 8.84 (d, J = 7.6 Hz, 1H), 8.61 (d, J = 8.0 Hz, 1H), 8.11 (d, J = 8.8 Hz, 1H), 8.01 (d, J = 9.2 Hz, 1H), 7.96-7.91 (m, 4H), 7.72-7.62 (m, 2H), 7.51 (ddd, J = 8.4, 7.2, 1.2 Hz, 1H), 7.45-7.41 (m, 1H); 13 C NMR (100 MHz, CDC13): 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.

[0114] Example 39

[0115]

[0116] In a 35 mL sealed tube, 1aa (79.5 mg, 0.5 mmol), 2a (71.5 mg, 0.5 mmol), 3a (151.5 mg, 1.5 mmol), ammonium iodide (108.7 mg, 0.75 mmol), di-tert-butyl peroxide (146 mg, 1 mmol) and chlorobenzene (2 mL) were added, and then placed in a 120 °C metal bath for stirring for 8 h. The reaction was quenched by adding 50 mL of water, extracted with ethyl acetate (50 mL x 3), and then the organic phase was washed with 10% Na2S2O3solution and saturated brine successively, and dried over anhydrous sodium sulfate. Filtration, rotary evaporation, and separation on a silica gel column (petroleum ether / ethyl acetate = 30 / 1) gave the yellow solid product 4aa (88 mg, 57%). The characterization data of this compound are as follows: 1 HNMR (400 MHz, CDC13): δ (ppm) 8.90 (d, J = 8.8 Hz, 1H), 8.73-8.68 (m, 1H), 8.59 (d, J = 8.4 Hz, 1H), 8.08 (d, J = 9.2 Hz, 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 (100 MHz, CDC13): 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 N2: 309.1386; found: 309.1388.

[0117] Example 40

[0118]

[0119] In a 35 mL sealed tube, 1a (53 mg, 0.5 mmol), 2b (111 mg, 0.5 mmol), 3a (151.5 mg, 1.5 mmol), ammonium iodide (108.7 mg, 0.75 mmol), di-tert-butyl peroxide (146 mg, 1 mmol) and chlorobenzene (2 mL) were added, and then placed in a 120 °C metal bath for stirring for 8 h. The reaction was quenched by adding 50 mL of water, extracted with ethyl acetate (50 mL x 3), and then the organic phase was washed with 10% Na2S2O3solution and saturated brine successively, and dried over anhydrous sodium sulfate. Filtration, rotary evaporation, and separation on a silica gel column (petroleum ether / ethyl acetate = 100 / 1) gave the yellow solid product 4ab (142 mg, 85%). The characterization data of this compound are as follows: 1 H NMR (400 MHz, CDC13): δ (ppm) 8.87 (d, J = 8.8 Hz, 1H), 8.42 (d, J = 8.8 Hz, 1H), 8.21 - 8.18 (m, 2H), 8.11 - 8.02 (m, 2H), 7.99 (d, J = 8.4 Hz, 1H), 7.87 (d, J = 9.2 Hz, 1H), 7.74 (dd, J = 8.8, 2.0 Hz, 1H), 7.58 - 7.50 (m, 2H), 7.50 - 7.45 (m, 1H); 13 C NMR (100 MHz, CDC13): 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.

[0120] Example 41

[0121]

[0122] In a 35 mL sealed tube, 1a (53 mg, 0.5 mmol), 2c (86 mg, 0.5 mmol), 3a (151.5 mg, 1.5 mmol), ammonium iodide (108.7 mg, 0.75 mmol), di-tert-butyl peroxide (146 mg, 1 mmol) and chlorobenzene (2 mL) were added, and then placed in a 120 °C metal bath for stirring for 8 h. The reaction was quenched by adding 50 mL of water, extracted with ethyl acetate (50 mL x 3), and then the organic phase was washed with 10% Na2S2O3solution and saturated brine successively, and dried over anhydrous sodium sulfate. Filtration, rotary evaporation, and separation on a silica gel column (petroleum ether / ethyl acetate = 100 / 1) gave the yellow solid product 4ac (135 mg, 95%). The characterization data of this compound are as follows: 1 H NMR (400 MHz, CDC13): δ (ppm) 8.79 (d, J = 8.8 Hz, 1H), 8.43 (d, J = 8.8 Hz, 1H), 8.19-8.15 (m, 2H), 8.04 (d, J = 9.2 Hz, 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 (100 MHz, CDC13): 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.

[0123] Example 42

[0124]

[0125] In a 35 mL sealed tube was added 1a (53 mg, 0.5 mmol), 2d (100.5 mg, 0.5 mmol), 3a (151.5 mg, 1.5 mmol), ammonium iodide (108.7 mg, 0.75 mmol), di-tert-butyl peroxide (146 mg, 1 mmol) and chlorobenzene (2 mL), then placed in a 120 °C metal bath and stirred for 8 h. The reaction was quenched by adding 50 mL of water, extracted with ethyl acetate (50 mL x 3), then the organic phase was washed with 10% Na2S2O3solution and saturated brine successively, dried over anhydrous sodium sulfate. Filtration, rotary evaporation, and separation on a silica gel column (petroleum ether / ethyl acetate = 100 / 1) gave the yellow solid product 4ad (130 mg, 83%). The characterization data of this compound are as follows: 1 H NMR (400 MHz, CDC13): δ (ppm) 8.94 (d, J = 8.8 Hz, 1H), 8.62 (d, J = 1.6 Hz, 1H), 8.60 (d, J = 8.8 Hz, 1H), 8.26 (dd, J = 8.8, 1.6 Hz, 1H), 8.22 - 8.19 (m, 2H), 8.10 (d, J = 9.2 Hz, 1H), 8.03 (d, J = 9.2 Hz, 1H), 8.00 (d, J = 8.8 Hz, 1H), 7.57 - 7.52 (m, 2H), 7.51 - 7.46 (m, 1H), 4.00 (s, 3H); 13 C NMR (100 MHz, CDC13): 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 NO2: 314.1176; found: 314.1179.

[0126] Example 43

[0127]

[0128] In a 35 mL sealed tube was added 1a (53 mg, 0.5 mmol), 2e (79 mg, 0.5 mmol), 3a (151.5 mg, 1.5 mmol), ammonium iodide (108.7 mg, 0.75 mmol), di-tert-butyl peroxide (146 mg, 1 mmol) and chlorobenzene (2 mL), then placed in a 120 °C metal bath and stirred for 8 h. The reaction was quenched by adding 50 mL of water, extracted with ethyl acetate (50 mL x 3), then the organic phase was washed with 10% Na2S2O3solution and saturated brine successively, dried over anhydrous sodium sulfate. Filtration, rotary evaporation, and separation on a silica gel column (petroleum ether / ethyl acetate = 100 / 1) gave the yellow solid product 4ae (84 mg, 62%). The characterization data of this compound are as follows: 1 H NMR (400 MHz, CDCl3): δ (ppm) 8.83 (d, J = 8.8 Hz, 1H), 8.41 (d, J = 8.4 Hz, 1H), 8.21-8.15 (m, 2H), 7.98 (d, J = 9.2 Hz, 1H), 7.95 (d, J = 8.4 Hz, 1H), 7.79 (d, J = 9.2 Hz, 1H), 7.53 (t, J = 7.6 Hz, 2H), 7.47-7.42 (m, 1H), 7.13-7.07 (m, 2H), 3.98 (s, 2H);13C NMR (100 MHz, 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.

[0129] Example 44

[0130]

[0131] In a 35 mL sealed tube was added 1a (53 mg, 0.5 mmol), 2a (71.5 mg, 0.5 mmol), 3b (214.5 mg, 1.5 mmol), ammonium iodide (108.7 mg, 0.75 mmol), di-tert-butyl peroxide (146 mg, 1 mmol) and chlorobenzene (2 mL), then placed in a 120 °C metal bath and stirred for 8 h. The reaction was quenched by adding 50 mL of water, extracted with ethyl acetate (50 mL x 3), then the organic phase was washed with 10% Na2S2O3solution and saturated brine successively, dried over anhydrous sodium sulfate. Filtration, rotary evaporation, and separation on a silica gel column (petroleum ether / ethyl acetate = 100 / 1) gave the yellow solid product 4af (117 mg, 87%). The characterization data of this compound are as follows: 1 HNMR (400 MHz, CDC13): δ (ppm) 8.70 (s, 1H), 8.55 (d, J = 8.0 Hz, 1H), 8.00 (d, J = 9.2 Hz, 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 (100 MHz, CDC13): 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.

[0132] Example 45

[0133]

[0134] In a 35 mL sealed tube, 1a (53 mg, 0.5 mmol), 2a (71.5 mg, 0.5 mmol), 3c (341 mg, 1.5 mmol), ammonium iodide (108.7 mg, 0.75 mmol), di-tert-butyl peroxide (146 mg, 1 mmol) and chlorobenzene (2 mL) were added, and then placed in a 120 °C metal bath for stirring for 8 h. The reaction was quenched by adding 50 mL of water, extracted with ethyl acetate (50 mL x 3), and then the organic phase was washed with 10% Na2S2O3solution and saturated brine successively, and dried over anhydrous sodium sulfate. Filtration, rotary evaporation, and separation on a silica gel column (petroleum ether / ethyl acetate = 100 / 1) gave the yellow solid product 4ag (117.3 mg, 79%). The characterization data of the compound are as follows: 1 H NMR (400 MHz, CDC13): δ (ppm) 8.83 (s, 1H), 8.67 (d, J = 8.0 Hz, 1H), 8.03 (d, J = 8.8 Hz, 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 = 7.6 Hz, 2H), 1.70-1.60 (m, 2H), 0.90 (t, J = 7.2 Hz, 3H); 13 CNMR (100 MHz, CDC13): 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.

[0135] Example 46

[0136]

[0137] In a 35 mL sealed tube was added 1a (53 mg, 0.5 mmol), 2a (71.5 mg, 0.5 mmol), 3d (341 mg, 1.5 mmol), ammonium iodide (108.7 mg, 0.75 mmol), di-tert-butyl peroxide (146 mg, 1 mmol) and chlorobenzene (2 mL), then placed in a 120 °C metal bath and stirred for 8 h. The reaction was quenched by adding 50 mL of water, extracted with ethyl acetate (50 mL x 3), then the organic phase was washed with 10% Na2S2O3solution and saturated brine successively, dried over anhydrous sodium sulfate. Filtration, rotary evaporation, and separation on a silica gel column (petroleum ether / ethyl acetate = 100 / 1) gave the yellow solid product 4ah (96.5 mg, 65%). The characterization data of this compound are as follows: 1 H NMR (400 MHz, CDC13): δ (ppm) 8.94 (s, 1H), 8.71 (d, J = 8.0 Hz, 1H), 8.02 (d, J = 8.8 Hz, 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 = 6.8 Hz, 6H); 13 CNMR (100 MHz, CDC13): 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.

[0138] Example 47

[0139]

[0140] In a 35 mL sealed tube, 1a (53 mg, 0.5 mmol), 2a (71.5 mg, 0.5 mmol), 3e (404 mg, 1.5 mmol), ammonium iodide (108.7 mg, 0.75 mmol), di-tert-butyl peroxide (146 mg, 1 mmol) and chlorobenzene (2 mL) were added, and then placed in a 120 °C metal bath for stirring for 8 h. The reaction was quenched by adding 50 mL of water, extracted with ethyl acetate (50 mL x 3), and then the organic phase was washed successively with 10% Na2S2O3solution and saturated brine, and dried over anhydrous sodium sulfate. Filtration, rotary evaporation, and separation on a silica gel column (petroleum ether / ethyl acetate = 100 / 1) gave the yellow solid product 4ai (132 mg, 85%). The characterization data of this compound are as follows: 1 H NMR (400 MHz, CDCl3): δ (ppm) 8.82 (s, 1H), 8.67 (d, J = 8.0 Hz, 1H), 8.02 (d, J = 9.2 Hz, 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 = 7.6 Hz 2H), 1.64-1.56 (m, 2H), 1.35-1.26 (m, 2H), 0.85 (t, J = 7.6 Hz, 3H); 13 C NMR (100 MHz, CDCl3): 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.

[0141] Example 48

[0142]

[0143] In a 35 mL sealed tube was added 1a (53 mg, 0.5 mmol), 2a (71.5 mg, 0.5 mmol), 3f (467 mg, 1.5 mmol), ammonium iodide (108.7 mg, 0.75 mmol), di-tert-butyl peroxide (146 mg, 1 mmol) and chlorobenzene (2 mL), then placed in a 120 °C metal bath and stirred for 8 h. The reaction was quenched by adding 50 mL of water, extracted with ethyl acetate (50 mL x 3), then the organic phase was washed with 10% Na2S2O3solution and saturated brine successively, dried over anhydrous sodium sulfate. Filtration, rotary evaporation, and separation on a silica gel column (petroleum ether / ethyl acetate = 100 / 1) gave the yellow solid product 4aj (120 mg, 74%). The characterization data of this compound are as follows: 1 H NMR (400 MHz, CDC13): δ (ppm) 8.83 (s, 1H), 8.67 (d, J = 8.4 Hz, 1H), 8.03 (d, J = 9.2 Hz, 1H), 7.94 (d, J = 9.2 Hz, 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 = 8.0 Hz, 2H), 1.66 - 1.57 (m, 2H), 1.29 - 1.22 (m, 4H), 0.83 (t, J = 7.2 Hz, 3H); 13 C NMR (100 MHz, CDC13): 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.

[0144] Example 49

[0145]

[0146] In a 35 mL sealed tube was added 1a (53 mg, 0.5 mmol), 2a (71.5 mg, 0.5 mmol), 3g (530.5 mg, 1.5 mmol), ammonium iodide (108.7 mg, 0.75 mmol), di-tert-butyl peroxide (146 mg, 1 mmol) and chlorobenzene (2 mL), then placed in a 120 °C metal bath and stirred for 8 h. The reaction was quenched by adding 50 mL of water, extracted with ethyl acetate (50 mL x 3), then the organic phase was washed with 10% Na2S2O3solution and saturated brine successively, dried over anhydrous sodium sulfate. Filtration, rotary evaporation, and separation on a silica gel column (petroleum ether / ethyl acetate = 100 / 1) gave the yellow solid product 4ak (152.5 mg, 90%). The characterization data of this compound are as follows: 1 H NMR (400 MHz, CDC13): δ (ppm) 8.80 (s, 1H), 8.64 (d, J = 8.0 Hz, 1H), 8.02 (d, J = 9.2 Hz, 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 = 8.0 Hz, 2H), 1.63-1.55 (m, 2H), 1.30-1.18 (m, 6H), 0.83 (t, J = 6.8 Hz, 3H); 13 C NMR (100 MHz, CDC13): 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.

[0147] Example 50

[0148]

[0149] In a 35 mL sealed tube, 1a (53 mg, 0.5 mmol), 2a (71.5 mg, 0.5 mmol), 3h (593.6 mg, 1.5 mmol), ammonium iodide (108.7 mg, 0.75 mmol), di-tert-butyl peroxide (146 mg, 1 mmol) and chlorobenzene (2 mL) were added, and then placed in a 120 °C metal bath for stirring for 8 h. The reaction was quenched by adding 50 mL of water, extracted with ethyl acetate (50 mL x 3), and then the organic phase was washed successively with 10% Na2S2O3solution and saturated brine, and dried over anhydrous sodium sulfate. Filtration, rotary evaporation, and separation on a silica gel column (petroleum ether / ethyl acetate = 100 / 1) gave the yellow solid product 4al (123.5 mg, 70%). The characterization data of the compound are as follows: 1 H NMR (400 MHz, CDC13): δ (ppm) 8.83 (s, 1H), 8.68 (d, J = 8.0 Hz, 1H), 8.03 (d, J = 8.8 Hz, 1H), 7.94 (d, J = 8.8 Hz, 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 = 7.6 Hz, 2H), 1.65-1.57 (m, 2H), 1.30-1.17 (m, 8H), 0.85 (t, J = 7.2 Hz, 3H); 13 C NMR (100 MHz, CDC13): 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.

[0150] Example 51

[0151]

[0152] In a 35 mL sealed tube, 1a (53 mg, 0.5 mmol), 2a (71.5 mg, 0.5 mmol), 3i (656.7 mg, 1.5 mmol), ammonium iodide (108.7 mg, 0.75 mmol), di-tert-butyl peroxide (146 mg, 1 mmol) and chlorobenzene (2 mL) were added, and then placed in a 120 °C metal bath for stirring for 8 h. The reaction was quenched by adding 50 mL of water, extracted with ethyl acetate (50 mL x 3), and then the organic phase was washed successively with 10% Na2S2O3solution and saturated brine, and dried over anhydrous sodium sulfate. Filtration, rotary evaporation, and separation on a silica gel column (petroleum ether / ethyl acetate = 100 / 1) gave the yellow solid product 4am (156 mg, 85%). The characterization data of the compound are as follows: 1 H NMR (400 MHz, CDC13): δ (ppm) 8.82 (s, 1H), 8.67 (d, J = 8.0 Hz, 1H), 8.02 (d, J = 9.2 Hz, 1H), 7.93 (d, J = 9.2 Hz, 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 = 8.0 Hz, 2H), 1.65-1.56 (m, 2H), 1.28-1.17 (m, 10H), 0.86 (t, J = 7.2 Hz, 3H); 13 C NMR (100 MHz, CDC13): 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.

[0153] Example 52

[0154]

[0155] In a 35 mL sealed tube, 1a (53 mg, 0.5 mmol), 2a (71.5 mg, 0.5 mmol), 3j (720 mg, 1.5 mmol), ammonium iodide (108.7 mg, 0.75 mmol), di-tert-butyl peroxide (146 mg, 1 mmol) and chlorobenzene (2 mL) were added, and then placed in a 120 °C metal bath for stirring for 8 h. The reaction was quenched by adding 50 mL of water, extracted with ethyl acetate (50 mL x 3), and then the organic phase was washed successively with 10% Na2S2O3solution and saturated brine, and dried over anhydrous sodium sulfate. Filtration, rotary evaporation, and separation on a silica gel column (petroleum ether / ethyl acetate = 100 / 1) gave the yellow solid product 4an (137 mg, 72%). The characterization data of the compound are as follows: 1 H NMR (400 MHz, CDC13): δ (ppm) 8.84 (s, 1H), 8.68 (d, J = 8.0 Hz, 1H), 8.03 (d, J = 9.2 Hz, 1H), 7.94 (d, J = 8.8 Hz, 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 = 8.0 Hz, 2H), 1.63-1.56 (m, 2H), 1.30-1.19 (m, 12H), 0.87 (t, J = 7.2 Hz, 3H); 13 C NMR (100 MHz, CDC13): 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.

[0156] Example 53

[0157]

[0158] In a 35 mL sealed tube, 1a (53 mg, 0.5 mmol), 2a (71.5 mg, 0.5 mmol), 3k (783 mg, 1.5 mmol), ammonium iodide (108.7 mg, 0.75 mmol), di-tert-butyl peroxide (146 mg, 1 mmol) and chlorobenzene (2 mL) were added, and then placed in a 120 °C metal bath for stirring for 8 h. The reaction was quenched by adding 50 mL of water, extracted with ethyl acetate (50 mL x 3), and then the organic phase was washed successively with a 10% Na2S2O3 solution and saturated brine, and dried over anhydrous sodium sulfate. Filtration, rotary evaporation, and silica gel column separation (petroleum ether / ethyl acetate = 100 / 1) gave the yellow solid product 4ao (134 mg, 68%). The characterization data of the compound are as follows: 1 H NMR (400 MHz, CDC13): δ (ppm) 8.82 (s, 1H), 8.67 (d, J = 8.0 Hz, 1H), 8.02 (d, J = 9.2 Hz, 1H), 7.93 (d, J = 9.2 Hz, 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 = 8.0 Hz, 2H), 1.65-1.56 (m, 2H), 1.29-1.20 (m, 14H), 0.87 (t, J = 6.8 Hz, 3H); 13 C NMR (100 MHz, CDC13): 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.

[0159] The above examples describe the basic principles, main features and advantages of the present application. Those skilled in the art should understand that the present application is not limited to the above examples. The above examples and descriptions in the specification are only to illustrate the principles of the present application. Without departing from the principles of the present application, various changes and improvements can be made to the present application, and these changes and improvements all fall within the scope of protection of the present application.

Claims

1. A method for synthesizing alkyl and aryl containing benzoquinolines, characterized by The specific steps are: dissolving aromatic aldehyde compound 1, β-naphthylamine compound 2 and tertiary aliphatic amine compound 3 in a solvent, then adding iodine reagent and oxidant, and then reacting at 110-130 DEG C to obtain the target product, i.e. alkyl and aryl containing benzochinoline compound 4, and the reaction equation in the synthesis method is as follows: wherein R 1 is phenyl, substituted phenyl, 2-naphthyl, 1-naphthyl, furanyl, thienyl, pyridyl, quinolyl, benzofuranyl, benzothienyl or indolyl, the substituents on the phenyl ring of the substituted phenyl being methyl, tert-butyl, methoxy, thiomethyl, fluorine, chlorine, bromine, trifluoromethyl, cyano, carbo methoxy or nitro, R 2 is bromine, methoxy, carbo methoxy or amino, R 3 is hydrogen, methyl, n-propyl, i-propyl, n-butyl, n-pentyl, n-hexyl, n-heptyl, n-octyl, n-nonyl or n-decyl, R 4 is ethyl, n-propyl, n-pentyl, i-pentyl, 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 oxidizing agent 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.

2. The method of synthesis of alkyl and aryl benzoguinolines according to claim 1, wherein: The molar ratio of the aromatic aldehyde compound 1, β-naphthylamine compound 2, tertiary aliphatic amine compound 3, iodine reagent and oxidant is 1:1:3:1.5:2, and the feeding ratio of the aromatic aldehyde compound 1 and the solvent is 1 mmol:4 mL.

3. The synthesis method of the alkyl and aryl containing benzochinoline compound according to claim 1, wherein the target product, i.e. alkyl and aryl containing benzochinoline compound, and the corresponding yield are as follows:

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