A method for preparing 3-imine isoindolone via visible light-induced debromination cyclization reaction

Abstract

This invention discloses a method for preparing 3-imine isoyindolone via visible light-induced debromination cyclization reaction. The synthesis process is as follows: In a glass reaction vessel, different types of substrates, N-benzyl-N-cyano-2-bromobenzamide, are added in proportion, with N,N-diisopropylethylamine as an additive, 4-DPAIPN as a photocatalyst, and acetonitrile as a solvent. Under a nitrogen atmosphere, the reaction is carried out at 68°C. o The reaction was irradiated with two blue LEDs (450-460 nm) at C for 8 hours. The crude product was purified by column chromatography to obtain a 3-imine isoindole ketone derivative. This invention uses the metal-free photocatalyst 4-DPAIPN, avoiding the use of noble metal catalysts and reducing agents. In addition, the reaction is simple to operate, has mild conditions, and has a wide range of applicable substrates.

Description

Technical Field

[0001] This invention belongs to the field of organic synthetic chemistry, and specifically relates to a new method for preparing 3-imine isoindoleone by debromination cyclization reaction. Background Technology

[0002] 3-Imineisoindolones, structurally belonging to N-heterocyclic compounds, are key skeletons in many natural and non-natural products, possessing a wide range of biological and pharmaceutical properties (Pharm. Res. 1987, 4, 21; J. Med. Chem. 1992, 35, 4613; Bioorg. Med. Chem. 2011, 19, 3965.). Furthermore, they can serve as useful synthetic intermediates for the rapid construction of other important bioactive molecules (J. Org. Chem. 2004, 69, 3538; J. Org. Chem. 2005, 70, 7744; Chem. Commun. 2014, 50, 1074; Org. Biomol. Chem. 2014, 12, 8223.). Therefore, the development of efficient methods for the synthesis of 3-imineisoindolones has attracted great interest from organic synthetic chemists.

[0003] Currently, there are three main methods for constructing 3-imine isoindole ketones. The first method involves cyanotyping the C2 position of benzamide in the presence of metal catalysts such as [Rh], [Cu], [Pd], and [Ni]. Subsequently, the NH group of the amide attacks the cyano group, resulting in intramolecular cyclization to form 3-imine isoindole ketones (Asian J. Org. Chem. 2015, 4, 1250; Tetrahedron Lett. 2021, 72, 153062; Chem. Sci. 2015, 6, 5595; Adv. Synth. Catal. 2014, 356, 2609; Org. Lett. 2018, 20, 3206.). The second method involves the coupling of acyl chloride and N-cyanoarylamine under alkaline conditions to generate N-cyano-N-arylbenzamide, followed by intramolecular cyclization via CH bond activation catalysis by a copper complex to yield 3-imine isoindole ketones (Scientificreports, 2022, 12, 6724). The third method utilizes tributyltin hydride (Bu3SnH) and azobisisobutyronitrile (AIBN) to induce amide-imine radical cyclization of N-benzyl-N-cyano-2-iodobenzamide to generate 3-imine isoindole ketones (Chem. Eur. J. 2008, 14, 1238). Although these reported methods can construct 3-imine isoindole ketones relatively well, they require the use of metal catalysts and the highly toxic radical inducing agent Bu3SnH. The presence of trace amounts of metal catalyst residues in the products and the use of toxic reagents hindering industrial production severely limit their application in drug research. Therefore, developing a simple, green, and environmentally friendly method to synthesize the 3-imine isoindole ketone skeleton has both theoretical and practical significance. Summary of the Invention

[0004] The purpose of this invention is to overcome the limitations of current methods for synthesizing 3-imine isoyindolones and to develop a visible light-induced debromination cyclization reaction that induces the formation of the highly reducing species 4-DPAIPN from 2,4,5,6-tetraphenylamine isophthalonitrile (4-DPAIPN) under visible light. •−* Csp of N-benzyl-N-cyano-2-bromobenzamide 2 The strategy of reducing the -Br bond to an aryl radical enables the cyclization of amide-imine radicals to prepare 3-imine isoindole ketone derivatives.

[0005] The concept of this invention is as follows: using N-benzyl-N-cyano-2-bromobenzamide as a raw material, 4-DPAIPN as a photocatalyst, N,N-diisopropylethylamine as an additive, acetonitrile as a solvent, and under a nitrogen atmosphere and blue light irradiation for 68 hours...o The synthesis of 3-imine isoindoleone compounds is achieved efficiently through reductive debromination and intramolecular tandem cyclization reactions at C. This invention utilizes the non-metallic photocatalyst 4-DPAIPN, avoiding the use of metal catalysts and toxic reagents. Furthermore, the reaction is simple to operate, operates under mild conditions, yields excellent separation, and has a wide range of applicable substrates.

[0006] The objective of this invention is achieved through the following technical solution.

[0007] A method for preparing 3-imine isoyindolone via visible light-induced debromination cyclization reaction comprises the following steps:

[0008] In a glass reaction vessel, N-benzyl-N-cyano-2-bromobenzamide, a catalyst, and additives were added in proportion, using an organic solvent, and the mixture was subjected to blue light irradiation for 65°C. o The mixture was magnetically stirred for 8 hours, then cooled to room temperature. The reaction solution was extracted multiple times with ethyl acetate. The organic phases were combined, and the crude product was obtained by rotary evaporation under reduced pressure. Finally, the 3-imine isoindole ketone derivative was obtained by column chromatography for separation and purification.

[0009] Furthermore, the debromination cyclization chemical reaction equation for N-benzyl-N-cyano-2-bromobenzamide is shown below:

[0010]

[0011] In the formula, Ar is selected from one or more of phenyl, 4-tert-butylphenyl, 4-methylphenyl, 3-methylphenyl, 2-methylphenyl, 3,4-methylenedioxyphenyl, 3,4-dimethoxyphenyl, 4-ethoxyphenyl, 2-fluorophenyl, 3-fluorophenyl, 2-chlorophenyl, 2-bromophenyl, and 4-bromophenyl;

[0012] Furthermore, the additive is one or more of triethylamine and N,N-diisopropylethylamine, preferably N,N-diisopropylethylamine.

[0013] Furthermore, the molar ratio of the additive to the N-benzyl-N-cyano-2-bromobenzamide derivative is 1 to 3:1, preferably 2:1.

[0014] Furthermore, the organic solvent is one or more of dichloromethane, methanol, acetonitrile, tetrahydrofuran, DMSO, toluene, 1,4-dioxane, and DMF, with acetonitrile being the preferred solvent.

[0015] Furthermore, the dehalogenation cyclization reaction time of the N-benzyl-N-cyano-2-bromobenzamide is between 6 and 10 hours, preferably 8 hours.

[0016] Further, the catalyst is one or more of 4-DPAIPN, 2,4,5,6-tetracarbazole isophthalonitrile (4CzIPN), 2,4,5-tricarbazole-6-(N-methylaniline) isophthalonitrile (3CzMPAIPN), and 2,4,5-tricarbazole-6-(N-methylo-o-methylaniline) isophthalonitrile (o-Me-3CzMPAIPN), preferably 4-DPAIPN.

[0017] Furthermore, the molar ratio of the catalyst to the N-benzyl-N-cyano-2-bromobenzamide compound is 0.01 to 1:1, preferably 0.03:1.

[0018] Furthermore, the target product 3-imine isoindole is separated and purified by column chromatography. The eluent can be a mixed solvent of petroleum ether and ethyl acetate, with a volume ratio of ethyl acetate to petroleum ether between 1:3 and 10. Preferably, the developing solvent is petroleum ether:ethyl acetate = 5:1.

[0019] The principle of this invention is as follows: under visible light irradiation, 4-DPAIPN forms an excited state of 4-DPAIPN. * Subsequently, a long-lived free radical anion 4-DPAIPN is formed through a single-electron transfer mechanism. •− 4-DPAIPN •− 4-DPAIPN forms an excited state after being exposed to light again. •−* Then 4-DPAIPN •−* Csp is achieved through a single-electron transfer process with the raw material N-benzyl-N-cyano-2-bromobenzamide. 2 The -Br bond breaks to form an aryl radical intermediate, releasing ground-state 4-DPAIPN for the next catalytic cycle. The aryl radical intermediate undergoes intramolecular radical tandem cyclization to yield a 3-imine isoindole ketone compound.

[0020] Compared with the prior art, the present invention has the following advantages and beneficial effects:

[0021] (1) This invention realizes the photocatalytic preparation of 3-imine isoindole ketone compounds under metal-free conditions. In addition, the main features of this reaction are that it does not require metallizing agents, the conditions are mild, the substrate range is wide, and the operation is simple;

[0022] (2) This invention utilizes visible light to induce 4-DPAIPN photocatalysts to form strongly reducing species for Csp 2 -Br bond reduction efficiently achieves the debromination and cyclization reaction of N-benzyl-N-cyano-2-bromobenzamide. Compared with existing methods, it has higher step economy and avoids the use of precious metal catalysts and reducing agents. Attached Figure Description

[0023] Figure 1 , Figure 2 These are the proton and carbon spectra of the target product obtained in Example 1;

[0024] Figure 3 , Figure 4 These are the proton and carbon spectra of the target product obtained in Example 2;

[0025] Figure 5 , Figure 6 These are the proton and carbon spectra of the target product obtained in Example 3;

[0026] Figure 7 , Figure 8 These are the proton and carbon spectra of the target product obtained in Example 4; Detailed Implementation

[0027] The present invention will be further described below through specific embodiments, but the scope of protection and implementation of the present invention are not limited thereto.

[0028] Example 1

[0029] A quartz reaction tube was prepared for use. Weighed N-benzyl-N-cyano-2-bromobenzamide (0.2 mmol), N,N-diisopropylethylamine (0.4 mmol), 4-DPAIPN (0.006 mmol), and acetonitrile (1 mL) were added sequentially. The reaction was carried out under blue light at 68°C for 8 hours, monitored by TCL. After the reaction was completed, the mixture was cooled to room temperature. The reaction solution was extracted with ethyl acetate in small batches. The organic phases were combined and dried over anhydrous magnesium sulfate. After filtration, the crude product was obtained by rotary evaporation under reduced pressure. Finally, the crude product 2-benzyl-3-imine isoindoleone was purified by silica gel column chromatography with a yield of 40%.

[0030] The proton and carbon spectra of the obtained target product are as follows: Figure 1 and Figure 2 As shown, the structural characterization data is as follows:

[0031] 1 H NMR (500 MHz, CDCl3) δ 7.88 (d, J = 6.8 Hz, 1H), 7.79 (d, J = 6.9Hz, 1H), 7.67 (p, J = 7.4 Hz, 2H), 7.42 (d, J = 7.5 Hz, 2H), 7.31 (t, J = 7.5Hz, 2H), 7.24 (d, J = 7.6 Hz, 1H), 5.03 (s, 2H) ppm.

[0032] 13 C{ 1H} NMR (125 MHz, CDCl3) δ 167.8, 156.8, 137.9, 136.7, 133.1,132.4, 131.0, 128.6, 128.1, 127.6, 123.4, 121.2, 41.9 ppm.

[0033] HRMS (ESI-TOF) [M+H] + calcd. for C 15 H 12 N₂O 237.1022; found 237.1029.

[0034] Based on the above characterization data, the structure of the target compound is inferred as follows:

[0035]

[0036] Example 2

[0037] A quartz reaction tube was prepared for use. Weighed N-benzyl-N-cyano-2-bromobenzamide (0.2 mmol), N,N-diisopropylethylamine (0.4 mmol), 4-DPAIPN (0.006 mmol), and acetonitrile (1 mL) were added sequentially. The reaction was carried out under blue light at 68°C for 8 hours, monitored by TCL. After the reaction was completed, the mixture was cooled to room temperature. The reaction solution was extracted with ethyl acetate in small batches. The organic phases were combined and dried over anhydrous magnesium sulfate. After filtration, the crude product was obtained by rotary evaporation under reduced pressure. Finally, the crude product 2-(4-tert-butylbenzyl)-3-imine isoindoleone was purified by silica gel column chromatography with a yield of 19%.

[0038] The proton and carbon spectra of the obtained target product are as follows: Figure 3 and Figure 4 As shown, the structural characterization data is as follows:

[0039] 1 H NMR (500 MHz, CDCl3) δ 7.87 (d, J = 6.7 Hz, 1H), 7.82 (d, J = 5.9Hz, 1H), 7.67 (p, J = 7.4 Hz, 2H), 7.37 (d, J = 8.0 Hz, 2H), 7.33 (d, J = 6.7Hz, 2H), 5.01 (s, 2H), 1.28 (s, 9H) ppm.

[0040] 13 C{ 1H} NMR (125 MHz, CDCl3) δ 167.7, 163.5, 150.6, 133.3, 132.6,131.0, 127.9, 126.3, 124.1, 121.7, 119.4, 115.8, 41.7, 34.5, 31.3 ppm.

[0041] HRMS (ESI-TOF) [M+H] + calcd. for C 19 H 20 N₂O 293.1648; found 293.1658.

[0042] Based on the above characterization data, the structure of the target compound is inferred as follows:

[0043]

[0044] Example 3

[0045] A quartz reaction tube was prepared for use. Weighed N-benzyl-N-cyano-2-bromobenzamide (0.2 mmol), N,N-diisopropylethylamine (0.4 mmol), 4-DPAIPN (0.006 mmol), and acetonitrile (1 mL) were added sequentially. The reaction was carried out under blue light at 68°C for 8 hours, monitored by TCL. After the reaction was completed, the mixture was cooled to room temperature. The reaction solution was extracted with ethyl acetate in small batches. The organic phases were combined and dried over anhydrous magnesium sulfate. After filtration, the crude product was obtained by rotary evaporation under reduced pressure. Finally, the crude product 2-(4-methylbenzyl)-3-imine isoindoleone was purified by silica gel column chromatography with a yield of 23%.

[0046] The proton and carbon spectra of the obtained target product are as follows: Figure 5 and Figure 6 As shown, the structural characterization data is as follows:

[0047] 1 H NMR (500 MHz, CDCl3) δ 7.87 (d, J = 7.0 Hz, 1H), 7.75 (d, J = 7.2Hz, 1H), 7.66 (p, J = 7.3 Hz, 2H), 7.31 (d, J = 7.7 Hz, 2H), 7.11 (d, J = 7.7Hz, 2H), 4.98 (s, 2H), 2.30 (s, 3H) ppm.

[0048] 13 C{ 1H} NMR (125 MHz, CDCl3) δ 167.8, 160.0, 137.3, 133.9, 133.7,133.0, 132.3, 131.0, 129.3, 128.1, 123.3, 121.0, 41.6, 21.1 ppm.

[0049] HRMS (ESI-TOF) [M+H] + calcd. for C 16 H 14 N₂O 251.1179; found 251.1180.

[0050] Based on the above characterization data, the structure of the target compound is inferred as follows:

[0051]

[0052] Example 4

[0053] A quartz reaction tube was prepared for use. Weighed N-benzyl-N-cyano-2-bromobenzamide (0.2 mmol), N,N-diisopropylethylamine (0.4 mmol), 4-DPAIPN (0.006 mmol), and acetonitrile (1 mL) were added sequentially. The reaction was carried out under blue light at 68°C for 8 hours, monitored by TCL. After the reaction was completed, the mixture was cooled to room temperature. The reaction solution was extracted with ethyl acetate in small batches. The organic phases were combined and dried over anhydrous magnesium sulfate. After filtration, the crude product was obtained by rotary evaporation under reduced pressure. Finally, the crude product 2-(3-methylbenzyl)-3-imine isoindoleone was purified by silica gel column chromatography with a yield of 19%.

[0054] The proton and carbon spectra of the obtained target product are as follows: Figure 7 and Figure 8 As shown, the structural characterization data is as follows:

[0055] 1 H NMR (500 MHz, CDCl3) δ 7.88 (d, J = 6.6 Hz, 1H), 7.80 (d, J = 7.0Hz, 1H), 7.68 (p, J = 7.4 Hz, 2H), 7.21 (d, J = 11.0 Hz, 3H), 7.06 (d, J =6.8 Hz, 1H), 4.99 (s, 2H), 2.31 (s, 3H) ppm.

[0056] 13 C{ 1H} NMR (125 MHz, CDCl3) δ 167.7, 158.2, 138.4, 136.6, 136.4,133.2, 132.5, 130.9, 128.7, 128.5, 128.4, 125.1, 123.5, 121.4, 42.0, 21.4ppm.

[0057] HRMS (ESI-TOF) [M+H] + calcd. for C 16 H 14 N₂O 251.1179; found 251.1180.

[0058] Based on the above characterization data, the structure of the target compound is inferred as follows:

[0059]

[0060] Example 5

[0061] A quartz reaction tube was prepared for use. Weighed N-benzyl-N-cyano-2-bromobenzamide (0.2 mmol), N,N-diisopropylethylamine (0.4 mmol), 4-DPAIPN (0.006 mmol), and acetonitrile (1 mL) were added sequentially. The reaction was carried out under blue light at 68°C for 8 hours, monitored by TCL. After the reaction was completed, the mixture was cooled to room temperature. The reaction solution was extracted with ethyl acetate in small batches. The organic phases were combined and dried over anhydrous magnesium sulfate. After filtration, the crude product was obtained by rotary evaporation under reduced pressure. Finally, the crude product 2-(2-methylbenzyl)-3-imine isoindoleone was purified by silica gel column chromatography with a yield of 55%.

[0062] The structural characterization data of the obtained target product are shown below:

[0063] 1 H NMR (500 MHz, CDCl3) δ 7.90 (d, J = 7.2 Hz, 1H), 7.82 (d, J = 7.3Hz, 1H), 7.73 – 7.66 (m, 2H), 7.17 (s, 2H), 7.11 (s, 2H), 5.02 (s, 2H), 2.46(s, 3H) ppm.

[0064] 13 C{ 1H} NMR (125 MHz, CDCl3) δ 167.8, 160.1, 135.7, 134.0, 133.2,132.0, 131.0, 130.5, 127.7, 127.4, 126.7, 126.1, 123. 5, 121.2, 39.7, 19.4ppm.

[0065] HRMS (ESI-TOF) [M+H] + calcd. for C 16 H 14 N₂O 251.1179; found 251.1180.

[0066] Based on the above characterization data, the structure of the target compound is inferred as follows:

[0067]

[0068] Example 6

[0069] A quartz reaction tube was prepared for use. Weighed N-benzyl-N-cyano-2-bromobenzamide (0.2 mmol), N,N-diisopropylethylamine (0.4 mmol), 4-DPAIPN (0.006 mmol), and acetonitrile (1 mL) were added sequentially. The reaction was carried out under blue light at 68°C for 8 hours, monitored by TCL. After the reaction was completed, the mixture was cooled to room temperature. The reaction solution was extracted with ethyl acetate in small batches. The organic phases were combined and dried over anhydrous magnesium sulfate. After filtration, the crude product was obtained by rotary evaporation under reduced pressure. Finally, the crude product 2-(3,4-methylenedioxybenzyl)-3-imine isoindoleone was purified by silica gel column chromatography with a yield of 23%.

[0070] The structural characterization data of the obtained target product are shown below:

[0071] 1 H NMR (500 MHz, CDCl3) δ 7.87 (d, J = 6.5 Hz, 1H), 7.76 (d, J = 7.1Hz, 1H), 7.67 (p, J = 7.4 Hz, 2H), 6.93 (d, J = 11.4 Hz, 2H), 6.74 (d, J =7.9 Hz, 1H), 5.91 (s, 2H), 4.93 (s, 2H) ppm.

[0072] 13 C{ 1H} NMR (125 MHz, CDCl3) δ 167.7, 160.2, 147.8, 147.0, 133.1,132.4, 130.9, 130.6, 123.4, 121.7, 121.1, 108.9, 108.2, 101.0, 41.7, 29.7ppm.

[0073] HRMS (ESI-TOF) [M+H] + calcd. for C 16 H 12 N2O3 281.0921; found 281.0920.

[0074] Based on the above characterization data, the structure of the target compound is inferred as follows:

[0075]

[0076] Example 7

[0077] A quartz reaction tube was prepared for use. Weighed N-benzyl-N-cyano-2-bromobenzamide (0.2 mmol), N,N-diisopropylethylamine (0.4 mmol), 4-DPAIPN (0.006 mmol), and acetonitrile (1 mL) were added sequentially. The reaction was carried out under blue light at 68°C for 8 hours, monitored by TCL. After the reaction was completed, the mixture was cooled to room temperature. The reaction solution was extracted with ethyl acetate in small batches. The organic phases were combined and dried over anhydrous magnesium sulfate. After filtration, the crude product was obtained by rotary evaporation under reduced pressure. Finally, the crude product 2-(3,4-dimethoxybenzyl)-3-imine isoindoleone was purified by silica gel column chromatography with a yield of 31%.

[0078] The structural characterization data of the obtained target product are shown below:

[0079] 1 H NMR (500 MHz, CDCl3) δ 7.86 (s, 1H), 7.75 (d, J = 7.2 Hz, 1H), 7.66(p, J = 7.4 Hz, 2H), 7.05 – 6.98 (m, 2H), 6.79 (d, J = 8.2 Hz, 1H), 4.95 (s,2H), 3.84 (d, J = 10.1 Hz, 6H) ppm.

[0080] 13 C{ 1H} NMR (125 MHz, CDCl3) δ 167.8, 160.2, 149.0, 148.5, 133.0,132.3, 131.0, 129.4, 123.4, 121.0, 120.8, 111.8, 111.0, 55.9, 41.7ppm.

[0081] HRMS (ESI-TOF) [M+H] + calcd. for C 17 H 16 N2O3 297.1234; found 297.1242.

[0082] Based on the above characterization data, the structure of the target compound is inferred as follows:

[0083]

[0084] Example 8

[0085] A quartz reaction tube was prepared for use. Weighed N-benzyl-N-cyano-2-bromobenzamide (0.2 mmol), N,N-diisopropylethylamine (0.4 mmol), 4-DPAIPN (0.006 mmol), and acetonitrile (1 mL) were added sequentially. The reaction was carried out under blue light at 68°C for 8 hours, monitored by TCL. After the reaction was completed, the mixture was cooled to room temperature. The reaction solution was extracted with ethyl acetate in small batches. The organic phases were combined and dried over anhydrous magnesium sulfate. After filtration, the crude product was obtained by rotary evaporation under reduced pressure. Finally, the crude product 2-(4-ethoxybenzyl)-3-imine isoindoleone was purified by silica gel column chromatography with a yield of 55%.

[0086] The structural characterization data of the obtained target product are shown below:

[0087] 1 H NMR (500 MHz, CDCl3) δ 7.86 (d, J = 6.9 Hz, 1H), 7.78 (d, J = 7.0Hz, 1H), 7.66 (p, J = 7.4 Hz, 2H), 7.36 (d, J = 8.1 Hz, 2H), 6.82 (d, J = 8.2Hz, 2H), 4.96 (s, 2H), 3.99 (q, J = 7.0 Hz, 2H), 1.38 (t, J = 7.0 Hz, 3H)ppm.

[0088] 13 C{ 1H} NMR (125 MHz, CDCl3) δ 167.7, 160.9, 158.5, 133.1, 132.5,131.0, 129.6, 128.7, 123.4, 121.3, 121.3, 114.6, 63.4, 41.5, 14.8 ppm.

[0089] HRMS (ESI-TOF) [M+H] + calcd. for C 17 H 16 N2O2 281.1285; found 281.1284.

[0090] Based on the above characterization data, the structure of the target compound is inferred as follows:

[0091]

[0092] Example 9

[0093] A quartz reaction tube was prepared for use. Weighed N-benzyl-N-cyano-2-bromobenzamide (0.2 mmol), N,N-diisopropylethylamine (0.4 mmol), 4-DPAIPN (0.006 mmol), and acetonitrile (1 mL) were added sequentially. The reaction was carried out under blue light at 68°C for 8 hours, monitored by TCL. After the reaction was completed, the mixture was cooled to room temperature. The reaction solution was extracted with ethyl acetate in small batches. The organic phases were combined and dried over anhydrous magnesium sulfate. After filtration, the crude product was obtained by rotary evaporation under reduced pressure. Finally, the crude product 2-(2-fluorobenzyl)-3-imine isoindoleone was purified by silica gel column chromatography with a yield of 44%.

[0094] The structural characterization data of the obtained target product are shown below:

[0095] 1 H NMR (500 MHz, CDCl3) δ 7.88 (s, 1H), 7.81 (s, 1H), 7.76 – 7.62 (m,2H), 7.29 (t, J = 7.6 Hz, 1H), 7.24 (d, J = 20.9 Hz, 1H), 7.06 (t, J = 7.6Hz, 2H), 5.09 (s, 2H). ppm.

[0096] 13 C{ 1H} NMR (125 MHz, CDCl3) δ 167.7, 160.5 (d, J = 246.9 Hz), 156.1,133.2, 132.4, 131.0, 130.9, 129.6 (d, J = 3.7 Hz), 129.3 (d, J = 8.3 Hz), 124.3 (d, J = 3.8 Hz), 123.52, 123.49, 121.3, 115.5 (d, J = 21.5 Hz), 35.5ppm.

[0097] HRMS (ESI-TOF) [M+H] + calcd. for C 15 H 11 FN2O 255.0928; found 255.0937.

[0098] Based on the above characterization data, the structure of the target compound is inferred as follows:

[0099]

[0100] Example 10

[0101] A quartz reaction tube was prepared for use. Weighed N-benzyl-N-cyano-2-bromobenzamide (0.2 mmol), N,N-diisopropylethylamine (0.4 mmol), 4-DPAIPN (0.006 mmol), and acetonitrile (1 mL) were added sequentially. The reaction was carried out under blue light at 68°C for 8 hours, monitored by TCL. After the reaction was completed, the mixture was cooled to room temperature. The reaction solution was extracted with ethyl acetate in small batches. The organic phases were combined and dried over anhydrous magnesium sulfate. After filtration, the crude product was obtained by rotary evaporation under reduced pressure. Finally, the crude product 2-(3-fluorobenzyl)-3-imine isoindoleone was purified by silica gel column chromatography with a yield of 40%.

[0102] The structural characterization data of the obtained target product are shown below:

[0103] 1H NMR (500 MHz, CDCl3) δ 7.89 (d, J = 7.1 Hz, 1H), 7.78 (d, J = 7.2Hz, 1H), 7.69 (p, J = 7.4, 7.0 Hz, 2H), 7.27 (d, J = 9.5 Hz, 1H), 7.20 (d, J= 7.7 Hz, 1H), 7.12 (d, J = 9.6 Hz, 1H), 6.94 (t, J = 7.1 Hz, 1H), 5.02 (s,2H) ppm.

[0104] 13 C{ 1 H} NMR (125 MHz, CDCl3) δ 167.7, 162.9 (d, J = 246.4 Hz), 160.2,147.6 (d, J = 64.4 Hz), 134.1, 133.2, 132.5, 130.9, 130.1 (d, J = 7.9 Hz), 123.7, 123.5, 121.1, 115.1 (d, J = 22.2 Hz), 114.5 (d, J = 21.1 Hz), 41.4ppm.

[0105] HRMS (ESI-TOF) [M+H] + calcd. for C 15 H 11 FN2O 255.0928; found 255.0934.

[0106] Based on the above characterization data, the structure of the target compound is inferred as follows:

[0107]

[0108] Example 11

[0109] A quartz reaction tube was prepared for use. Weighed N-benzyl-N-cyano-2-bromobenzamide (0.2 mmol), N,N-diisopropylethylamine (0.4 mmol), 4-DPAIPN (0.006 mmol), and acetonitrile (1 mL) were added sequentially. The reaction was carried out under blue light at 68°C for 8 hours, monitored by TCL. After the reaction was completed, the mixture was cooled to room temperature. The reaction solution was extracted with ethyl acetate in small batches. The organic phases were combined and dried over anhydrous magnesium sulfate. After filtration, the crude product was obtained by rotary evaporation under reduced pressure. Finally, the crude product 2-(2-chlorobenzyl)-3-imine isoindoleone was purified by silica gel column chromatography with a yield of 25%.

[0110] The structural characterization data of the obtained target product are shown below:

[0111] 1 H NMR (500 MHz, CDCl3) δ 7.92 (d, J = 6.9 Hz, 1H), 7.83 (d, J = 7.6Hz, 1H), 7.71 (dt, J = 15.2, 7.4 Hz, 2H), 7.39 (d, J = 7.7 Hz, 1H), 7.22 –7.14 (m, 2H), 7.10 (d, J = 7.0 Hz, 1H), 5.13 (s, 2H) ppm.

[0112] 13 C{ 1 H} NMR (125 MHz, CDCl3) δ 167.7, 157.6, 139.1, 133.7, 133.3,132.7, 132.5, 130.9, 129.6, 128.6, 127.7, 127.0, 123.5, 121.3, 39.5ppm.

[0113] HRMS (ESI-TOF) [M+H] + calcd. for C 15 H 11 ClN2O 271.0633; found 271.0637.

[0114] Based on the above characterization data, the structure of the target compound is inferred as follows:

[0115]

[0116] Example 12

[0117] A quartz reaction tube was prepared for use. Weighed N-benzyl-N-cyano-2-bromobenzamide (0.2 mmol), N,N-diisopropylethylamine (0.4 mmol), 4-DPAIPN (0.006 mmol), and acetonitrile (1 mL) were added sequentially. The reaction was carried out under blue light at 68°C for 8 hours, monitored by TCL. After the reaction was completed, the mixture was cooled to room temperature. The reaction solution was extracted with ethyl acetate in small batches. The organic phases were combined and dried over anhydrous magnesium sulfate. After filtration, the crude product was obtained by rotary evaporation under reduced pressure. Finally, the crude product 2-(2-bromobenzyl)-3-imine isoindoleone was purified by silica gel column chromatography with a yield of 58%.

[0118] The structural characterization data of the obtained target product are shown below:

[0119] 1 H NMR (500 MHz, CDCl3) δ 7.92 (d, J = 7.2 Hz, 1H), 7.83 (d, J = 7.2Hz, 1H), 7.71 (dt, J = 15.4, 7.3 Hz, 2H), 7.57 (d, J = 7.9 Hz, 1H), 7.20 (t,J = 7.5 Hz, 1H), 7.11 (t, J = 6.9 Hz, 1H), 7.04 (d, J = 7.7 Hz, 1H), 5.10 (s,2H) ppm.

[0120] 13 C{ 1 H} NMR (125 MHz, CDCl3) δ 167.7, 159.5, 135.1, 134.2, 133.3,132.9, 132.5, 130.9, 128.8, 127.6, 127.4, 123.5, 122.5, 121.3, 42.0ppm.

[0121] HRMS (ESI-TOF) [M+H] + calcd. for C 15 H 11 BrN2O 315.0128; found 315.0130.

[0122] Based on the above characterization data, the structure of the target compound is inferred as follows:

[0123]

[0124] Example 13

[0125] A quartz reaction tube was prepared for use. Weighed N-benzyl-N-cyano-2-bromobenzamide (0.2 mmol), N,N-diisopropylethylamine (0.4 mmol), 4-DPAIPN (0.006 mmol), and acetonitrile (1 mL) were added sequentially. The reaction was carried out under blue light at 68°C for 8 hours, monitored by TCL. After the reaction was completed, the mixture was cooled to room temperature. The reaction solution was extracted with ethyl acetate in small batches. The organic phases were combined and dried over anhydrous magnesium sulfate. After filtration, the crude product was obtained by rotary evaporation under reduced pressure. Finally, the crude product 2-(4-bromobenzyl)-3-imine isoindoleone was purified by silica gel column chromatography with a yield of 55%.

[0126] The structural characterization data of the obtained target product are shown below:

[0127] 1 HNMR (500 MHz, CDCl3) δ 7.87 (d, J = 7.1 Hz, 1H), 7.74 (d, J = 7.5Hz, 1H), 7.67 (p, J = 7.3 Hz, 2H), 7.42 (d, J = 8.7 Hz, 2H), 7.31 (d, J = 7.8Hz, 2H), 4.97 (s, 2H) ppm.

[0128] 13 C{ 1 H} NMR (125 MHz, CDCl3) δ 167.8, 160.1, 134.1, 133.1, 132.4,131.7, 130.9, 130.4, 130.0, 123.5, 121.6, 120.9, 41.3 ppm.

[0129] HRMS (ESI-TOF) [M+H] + calcd. for C 15 H 11 BrN2O 315.0128; found 315.0134.

[0130] Based on the above characterization data, the structure of the target compound is inferred as follows:

[0131]

[0132] The above embodiments are some examples of the method of the present invention, but they do not limit the specific implementation of the present invention. Any substitution of substituents, changes in the basic skeleton, or simplification of conditions made without departing from the spirit and principle of the present invention should be classified as equivalent substitution methods and are included within the protection scope of the present invention.

Claims

1. A method for preparing 3-imine isoyindolone derivatives via visible light-induced debromination cyclization reaction, characterized in that, It includes the following steps: In a glass reaction vessel, N-(substituted benzyl)-N-cyano-2-bromobenzamide 1 was added in proportion, 4-DPAIPN was used as the catalyst, and one of triethylamine or N,N-diisopropylethylamine was added as the additive. Acetonitrile was used as the solvent. The mixture was magnetically stirred at 68 °C for 8 hours under blue light irradiation, and then cooled to room temperature. The reaction solution was extracted multiple times with ethyl acetate, and the organic phases were combined. The crude product was obtained by rotary evaporation under reduced pressure. Finally, the crude product was purified by column chromatography to obtain 3-imine isoindole ketone derivative 2. The chemical reaction equation for the debromination and cyclization of raw material 1 is shown below: ， In the formula, Ar is selected from phenyl, 4-tert-butylphenyl, 4-methylphenyl, 3-methylphenyl, 2-methylphenyl, 3,4-methylenedioxyphenyl, 3,4-dimethoxyphenyl, 4-ethoxyphenyl, 2-fluorophenyl, 3-fluorophenyl, 2-chlorophenyl, 2-bromophenyl, and 4-bromophenyl; The structural formula of catalyst 4-DPAIPN is shown below: 。 2. The preparation method according to claim 1, characterized in that, The molar ratio of the additive to raw material 1 is 1 to 3:

1.

3. The preparation method according to claim 1, characterized in that, The molar ratio of the catalyst to raw material 1 is 0.01 to 1:

1.

4. The preparation method according to claim 1, characterized in that, The target product, 3-imine isoindole ketone derivative, was purified by column chromatography. The eluent was a mixture of petroleum ether and ethyl acetate in a ratio of 10:1 to 3:1.

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