A method for synthesizing selenocyanidin

Abstract

The invention discloses a free radical addition tandem cyclization reaction of N-aryl acryloylbenzamide or 2-aryl-N-acryloyl indole or N-methacryloyl-2-phenylbenzimidazole with potassium selenocyanate under visible light conditions, using cheap KSeCN as a selenocyanation reagent, potassium persulfate and the like as an oxidant, 2,4,6-triphenyl tetrafluoroborate and the like as a phase transfer catalysis and photocatalytic bifunctional catalyst to carry out a selenocyanation cyclization reaction. The reaction synthesizes selenocyanide isoquinoline-1,3 (2H, 4H)-diketone, indole [2,1-a] isoquinolinone and benzimidazole [2,1-a] isoquinoline-6 ​​(5H)-one in moderate to excellent yields under room temperature and visible light. The method has the advantages of mild reaction conditions, good substrate compatibility, large-scale synthesis, simple operation, cheap and easily available raw materials, simple preparation, and stable structure.

Description

Technical Field

[0001] The present invention discloses a tandem cyclization reaction of N-aryl acryloylbenzamide, 2-aryl-N-acryloyl indole, or N-methacryloyl-2-phenylbenzimidazole with potassium selenocyanate under green and environmentally friendly visible light conditions. This method for synthesizing a selenocyanated isoquinolinedione, indole[2,1-a]isoquinolinone, or benzimidazolo[2,1-a]isoquinolin-6(5H)-one compound provides a convenient route. The selenocyanation reaction is carried out using inexpensive KSeCN as a selenocyanation reagent, potassium persulfate as an oxidant, and 2,4,6-triphenyl tetrafluoroborate as a phase transfer catalyst and photocatalytic bifunctional catalyst. The selenocyanation reaction has a wide range of substrates. The advantages of the present invention include mild conditions, a green reaction without the need for a transition metal catalyst, and simple operation; cheap and readily available raw materials, a wide range of sources, simple preparation, and a stable structure. Background Art

[0002] Isoquinoline-1,3(2H,4H)-dione compounds and their derivatives are an important class of nitrogen-containing heterocyclic compounds, widely found in natural products, pharmaceutical molecules, and organic functional materials. These bioactive molecules include HIV-1 integrase inhibitors, aldose reductase inhibitors, progesterone receptor antagonists, and anti-tumor drugs. (Billamboz, M.; Bailly, F.; Lion, C.; Touati, N.; Vezin, H.; Calmels, C.; Andreola, ML; Christ, F., Debyser, Z.; and Cotelle, PJMed. Chem. 2011, 54, 1812-1824 .Mayer, SC; Banker, AL; Boschelli, F.; Li, D.; Johnson, M.; Kenny, CH; Krishnamurthy, G.; Kutterer, K.; Moy, F.; Petusky, S.; Ravi, M.; Tkach, D.; Tsouc, HR; and Wei,XXBioorg.Med.Chem.Lett.2008,18,3641-3645.Nakagawa,A.;Uno,S.;Makishima,M.;Miyachi,H.;and Hashimoto, Y.; Bioorg. Med. Chem. 2008, 16, 7046-7054. Billamboz, M.; Suchaud, V.; Bailly, F.; Lion, C.; Demeulemeester, J.; Calmels, C.; Andreola, ML; Christ, F.; Debyser, Z.; and Cotelle. P.; ACS Med. Chem. Lett. 2013, 4, 606-611.) Indolo[2,1-a]isoquinolinone compounds are widely present in biologically active and pharmaceutical molecules.(Kraus, G.A.; Gupta, V.; Kohut, M.; Singh, N.; Bioorg.Med.Chem.Lett., 2009, 19, 5539-5542. Alam, K.; Hong, S.W.; Oh, K.H.; Park, J.K.; Angew.Chem.Int.Ed., 2017, 56, 13387-13391. Goldbrunner, M.; Loidl, G.; Polossek, T.; Mannschreck, A.; Angerer, E.von; J.Med.Chem., 1997, 40, 3 524-3533.Ambros,R.;Schneider,MR;Angerer,S.von.;J.Med.Chem.,1990,33,153-160.Wang,S.;Wang,JS;Ying,J.;Wu,XFChin.Chem.Let t.,2023,34,107873.Zhai,SX;Qiub,SX;Yang,S.;Hua,BY;Niu,YS;Ha n,CC;Yu,YZ;Li,YC;Zhai,HB;Chin.Chem.Lett.,2022,33,276-279.)。

[0003] In the past decade, research on the construction of isoquinolinone skeletons using N-aryl acryloylbenzamides, 2-aryl-N-acryloylindoles, or N-methacryloyl-2-phenylbenzimidazole compounds as substrates through free radical addition and cyclization reactions has received widespread attention. Due to the unique chemical structure of N-aryl acryloylbenzamides, 2-aryl-N-acryloylindoles, or N-methacryloyl-2-phenylbenzimidazole compounds, they can produce free radicals to initiate rapid ring closure without polymerization, making them a method for synthesizing isoquinolinediones, 2-aryl-N-acryloylindoles, or benzimidazolo[2,1-a]isoquinolin-6(5H)-one compounds through free radical addition and cyclization. Traditional methods for synthesizing isoquinolinediones or indole[2,1-a]isoquinolinones or benzimidazolo[2,1-a]isoquinolin-6(5H)-one compounds (Tang, QJ; Xie, P.; Wang, J.; Lin, JJ; Feng, CL; Pittman Jr. CU; Zhou, AH; Tetrahedron., 2017, 73, 5436-5443. Huang, SH; Niu, PF; Su, YP; Hu, DC; and Huo, CD Org. Biomol. Chem., 2018, 16, 7748-7752. Chen, YJ; He, YH; Guan, Z.; Tetrahedron., 2019, 75, 3053-3061. Zou, GL; and Wang.XL; Org.Biomol.Chem., 2017, 15, 8748-8754. Pan, Y.; Beilstein J. Org. Chem. 2016, 12, 301-308. Li, J.; Wang, ZG; Wu, NJ; Gao, G.; and You, JS; Chem. Commun., 2014, 50, 15049-15051. Ge, YX; Tian, ​​YF; Wu, JL; Yan, QQ; Zheng, LP; Ren, YM; Zhao, JC; and Li, ZJ; Chem. Commun., 2020, 56, 12656-12659. Li, JZ; Mei, L.; Cai, XE; Zhang, CC; Cao, TT; Huang, XJ;Liu,YL;and Wei,WT;Adv.Synth.Catal.,2022,364,2080-2085.Cui,HH;Niu,CH;and Zhang.C.;J.Org.Chem.2021,86,15835-15844.Wei,YL;Chen,JQ;Sun,B.;and Xu, PF; Chem. Commun., 2019, 55, 5922-5925. Zeng, FL; Zhu, HL; Chen, XL; Qu, LB; and Yu, B.; Green Chem., 2021, 23, 3677-3682. Ma, N.; Guo, L.; Shen, Z. J.; Qi, D.; Yang, C.; and Xia, W. J. (Org. Biomol. Chem., 2022, 20, 1731-1737). The above methods generally have the disadvantages of requiring high temperatures, transition metal catalysts, expensive ligands, and a limited substrate range. The present invention efficiently synthesizes selenocyanate-substituted isoquinolinediones, indole[2,1-a]isoquinolinones, or benzimidazolo[2,1-a]isoquinolin-6(5H)-ones under visible light conditions using inexpensive and readily available N-arylacryloylbenzamides, 2-aryl-N-acryloylindoles, or N-methacryloyl-2-phenylbenzimidazole compounds as raw materials. The reaction is simple, environmentally friendly, and can be performed at room temperature without the need for transition metals. Summary of the Invention

[0004] The present invention aims to provide a method for preparing selenocyanidedione, indole[2,1-a]isoquinolinone, or benzimidazolo[2,1-a]isoquinolin-6(5H)-one compounds using readily available raw materials, simple operation, mild reaction conditions, and an environmentally friendly method using inexpensive KSeCN as a selenocyanidation reagent, potassium persulfate as an oxidant, and a photocatalytic bifunctional catalyst as a phase transfer catalyzer. To achieve the above objectives, the present invention provides the following technical solutions:

[0005] Under visible light conditions, N-aryl acryloylbenzamide, 2-aryl-N-acryloyl indole, or N-methacryloyl-2-phenylbenzimidazole compound (Ⅰ) reacts with potassium selenocyanate (Ⅱ) to undergo a free radical tandem cyclization reaction at room temperature (Scheme 1). After the reaction, the product is isolated and characterized using conventional separation and purification methods to obtain the corresponding selenocyanidedione, indole[2,1-a]isoquinolinone, or benzimidazolo[2,1-a]isoquinolin-6(5H)-one compound (Ⅲ).

[0006] The structure of selenocyanate-substituted isoquinolinediones or indole[2,1-a]isoquinolinones is as follows:

[0007]

[0008] R 1 、R 3 Each independently represents a substituent at one or more different positions of the benzene ring, such as the ortho position, meta position, or para position, or a substituent which is hydrogen, and the substituent R 1 is H, halogen, alkyl having 1 to 4 carbon atoms, alkoxy having 1 to 4 carbon atoms, fluoroalkyl C n F m H, n is 1-4, m is one or more of 1-4, the number of substituents is 1-5; halogen is one or more of F, Cl, Br or I; the substituent R 2 It is an alkyl group having 1 to 4 carbon atoms, an alkyl group having 15 to 20 carbon atoms, a cycloalkyl group having 3 to 7 carbon atoms, a phenyl group, or an aryl group containing a substituent, wherein the substituent is an alkyl group or a fluoroalkyl group having 1 to 4 carbon atoms, a fluoroalkyl group C n F m H, n is 1-4, m is one or more of 1-4; substituent R 3 It is one or more of H, CH3 or halogen, and halogen is one or more of F, Cl, Br or I. The number of substituents is 1-5.

[0009] Wherein, the reaction process is shown in the following reaction formula:

[0010]

[0011] The substituent R 1 and substituent R 3 Same as above;

[0012] The dotted line in N-aryl acryloylbenzamide or 2-aryl-N-acryloyl indole or N-methacryloyl-2-phenylbenzimidazole (I) indicates that there are three situations: there is no benzene ring or there is a benzene ring. When there is no benzene ring and X=O, n=1,2, etc., it is N-aryl acryloylbenzamide; when there is a benzene ring and X=C, n=0, it is 2-aryl-N-acryloyl indole; when there is no benzene ring above X and X=N, n=0, it is N-methacryloyl-2-phenylbenzimidazole; and selenium cyanide isoquinolinedione or indole [2 ,1-a]isoquinolinone or benzimidazolo[2,1-a]isoquinolin-6(5H)-one (III) The dotted line indicates that there are three types of compounds with or without a benzene ring. When there is no benzene ring and X=O, n=1,2,etc, it is a selenocyanidedisoquinolinedione. When there is a benzene ring and X=C, n=0, it is a selenocyanidedindolo[2,1-a]isoquinolinone compound. When there is no benzene ring above X and X=N, n=0, it is a selenocyanidedbenzimidazolo[2,1-a]isoquinolin-6(5H)-one compound.

[0013] As shown in the above reaction formula, the present invention uses blue light as a light source under room temperature conditions, uses N-aryl acryloylbenzamide or 2-aryl-N-acryloyl indole or N-methacryloyl-2-phenylbenzimidazole compound (Ⅰ) and potassium selenocyanate (Ⅱ) to achieve visible light-induced free radical cascade cyclization reaction at room temperature to generate selenocyanide isoquinolinedione or 2-indole [2,1-a] isoquinolinone or benzimidazolo [2,1-a] isoquinolin-6 (5H) -one compound (Ⅲ).

[0014] In the present invention, the reaction is carried out under irradiation of white light (6500K), purple light (400-405nm), blue light (460-465nm), green light (526-531nm) or red light (700-705nm), with 12W blue light (460-465nm) being optimal, and the reaction light source is 460-465nm blue light.

[0015] In the present invention, the reaction is performed in a solvent selected from one or more of acetonitrile, dichloromethane, water, dichloromethane / water (4:1-1:4 by volume), methanol, N,N-dimethylformamide, N-methylpyrrolidone, dimethyl sulfoxide, and 1,2-dichloroethane, with the reaction solvent being dichloromethane / water (1:1 by volume). The concentration of the N-(hetero)aryl acrylamide compound is 0.1-0.3 M, with an optimal concentration being 0.1 M.

[0016] In the present invention, in the reaction, the oxidant is any one or two of N-chlorosuccinimide, dibenzoyl peroxide, oxygen, potassium persulfate, tert-butyl perbenzoate, and di-tert-butyl peroxide, and the reaction oxidant is potassium persulfate; the concentration of the base in the solvent is 0.05-0.2M, preferably 0.125-0.2M, and most preferably 0.2M.

[0017] In the present invention, the reaction is carried out in the presence of a bifunctional catalyst, which is any one or two of PC1, PC2, PC3, and PC4, with PC2 being the preferred bifunctional catalyst. The optimal concentration of the bifunctional catalyst in the solvent is 0.001M.

[0018]

[0019] In the present invention, the preferred molar ratio of the N-aryl acryloylbenzamide, 2-aryl-N-acryloylindole, or N-methacryloyl-2-phenylbenzimidazole compound (I) to potassium selenocyanate (II) in the reaction is 1:1-1:3, with the most preferred molar ratio being 1:1.5. The concentration of the N-aryl acryloylbenzamide, 2-aryl-N-acryloylindole, or N-methacryloyl-2-phenylbenzimidazole compound in the reaction solvent is 0.1 M, and the concentration of potassium selenocyanate in the reaction solvent is 0.15 M.

[0020] In the present invention, the reaction time is 12-24 hours. Preferably, the reaction time is 12 hours.

[0021] The building-up reaction of the present invention comprises the following steps:

[0022] Synthesis of N-methacryloylbenzamide:

[0023]

[0024] According to the previous preparation literature report (J.Xu, Z.Yang, J.-W.Hua., Org.Chem.Front., 2020, 7, 3223-3228.), compound A was added to a primary amine (15mmol), Et3N (20mmol) and DCM (20mL) in a 100mL round-bottom flask, and the reaction mixture was cooled to 0°C, and then benzoyl chloride (10mmol) was slowly added dropwise. Stirred at room temperature for 4-6 hours, after which the reaction was completed under TLC monitoring, the organic phase was separated, dried over Na2SO4, and concentrated in vacuo. The resulting residue was purified by flash silica gel column chromatography (eluent: petroleum ether / ethyl acetate = 1: 1) in a yield of 93-95%.

[0025] To a 100 mL round-bottom flask, add N-methylbenzamide (10 mmol), DMAP (1 mmol), triethylamine (20 mmol), and dichloromethane (20 mL). The reaction mixture is cooled to 0°C, and methacryloyl chloride is slowly added. The mixture is then stirred at room temperature for 4-6 hours. The reaction is complete under TLC monitoring. The organic phase is separated, dried over Na2SO4, and concentrated in vacuo. The resulting residue is purified by flash silica gel column chromatography (eluent: petroleum ether / ethyl acetate = 3:1) to afford the desired product 1a in a yield of 74-85%.

[0026]

[0027] Or, Synthesis of Compound D:

[0028] According to the previous preparation literature report (Y.Yuan, Y.Zheng, B.Xu, et al., ACS Catal.2020, 10, 6676-6681.), a mixture of substituted phenylhydrazine hydrochloride (2.0mmol, 2.0equiv) and acetic acid was added to a 250mL round-bottom flask and stirred at 50°C under N2 atmosphere for 30 minutes, and then the substituted ketone (1.0mmol, 1.0equiv) was added to the solution, heated to 130°C, and the reaction mixture was cooled after 8 hours of reaction. Water was added and the mixture was stirred at 0°C to obtain a precipitate. The obtained crude solid indole compound D can then be used directly in the next step of synthesis after drying. Sometimes, the obtained crude solid should be purified by column chromatography to obtain indole compound D.

[0029] Synthesis of 2-aryl-N-acryloyl indole:

[0030] Following a modified literature procedure, a 100 mL round-bottom flask was charged with DCM (10 mL), indole D (5 mmol, 1 equiv), and DMAP (2.0 mmol, 0.4 equiv). Et3N (10 mmol, 2.0 equiv) was then added to the mixture at 0°C. Methacryloyl chloride (10 mmol, 2.0 equiv) was then slowly added dropwise to the solution, which was then warmed to room temperature and stirred for 2-3 days. The mixture was diluted with DCM (20 mL) and saturated NH4Cl solution (20 mL). The organic and aqueous layers were separated. The aqueous layer was extracted with DCM (20 mL x 3). The combined organic layers were washed with brine and dried over Na2SO4. After evaporation of the solvent, the crude product 1ad was purified by column chromatography on silica gel using petroleum ether / ethyl acetate as the eluent.

[0031] Or, Synthesis of Compound F

[0032]

[0033] According to the previous preparation literature report (Y.Yuan, Y.Zheng, B.Xu, et al., ACS Catal.2020, 10, 6676-6681.), para-substituted benzaldehyde (0.58mL, 5.0mmol) and NaHSO3 (5.73g, 55.0mmol) were mixed in H2O (20.0mL) in a round-bottom flask (50mL) equipped with a magnetic stirrer and added. When the mixture reached reflux temperature, o-phenylenediamine (0.54g, 5.0mmol) was added. The resulting mixture was stirred for 3 hours. After completion of the reaction, it was monitored by TLC analysis. After the reaction mixture was cooled to room temperature, it was vacuum filtered through a glass funnel. The residue was washed with water (20mL×2) and dried in an air-drying oven to obtain the corresponding product F.

[0034] Synthesis of N-Methacryloyl-2-phenylbenzimidazole

[0035] To a solution of F (0.63 g, 3 mmol) and DMAP (73 mg, 0.6 mmol) in DCM (6 ml) was added Et3N (0.83 mL, 6 mmol). Methacryloyl chloride (0.58 mL, 6 mmol) was slowly added dropwise to the solution at 0°C. The solution was warmed to room temperature and stirred at room temperature for 12 hours. According to TLC analysis, the reaction was complete, and water (20 mL) was added to the mixture, which was extracted with DCM (15 mL x 3). The organic solvent was then concentrated in vacuo. The residue was purified by flash column chromatography using ethyl acetate and petroleum ether as eluents to obtain 1ah. BRIEF DESCRIPTION OF THE DRAWINGS

[0036] Figure 1 The following are the hydrogen and carbon nuclear magnetic spectra of the nuclear magnetic resonance instrument of Example 1.

[0037] Figure 2 The following are the hydrogen and carbon nuclear magnetic resonance spectra of Example 6.

[0038] Figure 3 These are the hydrogen and carbon nuclear magnetic resonance spectra of Example 8.

[0039] Figure 4 These are the hydrogen and carbon nuclear magnetic resonance spectra of Example 17.

[0040] Figure 5 These are the hydrogen and carbon nuclear magnetic resonance spectra of Example 19.

[0041] Figure 6 These are the hydrogen and carbon nuclear magnetic resonance spectra of Example 22.

[0042] Figure 7These are the hydrogen and carbon nuclear magnetic resonance spectra of Example 24.

[0043] Figure 8 These are the hydrogen and carbon nuclear magnetic resonance spectra of Example 26.

[0044] Figure 9 These are the hydrogen and carbon nuclear magnetic resonance spectra of Example 27.

[0045] Figure 10 These are the hydrogen and carbon nuclear magnetic resonance spectra of Example 28.

[0046] Figure 11 These are the hydrogen and carbon nuclear magnetic resonance spectra of Example 31.

[0047] Figure 12 This is the nuclear magnetic resonance spectrum of Example 32.

[0048] Figure 13 The NMR spectra of 3a and 3c in the application examples are shown in FIG. DETAILED DESCRIPTION

[0049] The present invention is further described in detail with reference to the following specific examples, and the protection content of the present invention is not limited to the following examples. Without departing from the spirit and scope of the inventive concept, changes and advantages that can be thought of by those skilled in the art are included in the present invention, and are protected by the appended claims. The process, conditions, reagents, experimental methods, etc. for implementing the present invention, except for the contents specifically mentioned below, are common knowledge and common common sense in the art, and the present invention has no special restrictions. The data given in the following examples include specific operations and reaction conditions and products. The purity of the product is identified by nuclear magnetic resonance and high-resolution mass spectrometry.

[0050] The experimental raw materials in the present invention were prepared under the following conditions with different substituents:

[0051] Synthesis of N-methacryloylbenzamide:

[0052]

[0053] According to the previous preparation literature report (J.Xu, Z.Yang, J.-W.Hua., Org.Chem.Front., 2020, 7, 3223-3228.), compound A was added to a primary amine (15mmol), Et3N (20mmol) and DCM (20mL) in a 100mL round-bottom flask, and the reaction mixture was cooled to 0°C, and then benzoyl chloride (10mmol) was slowly added dropwise. Stirred at room temperature for 4-6 hours, after which the reaction was completed under TLC monitoring, the organic phase was separated, dried over Na2SO4, and concentrated in vacuo. The resulting residue was purified by flash silica gel column chromatography (eluent: petroleum ether / ethyl acetate = 1: 1) in a yield of 93-95%.

[0054] To a 100 mL round-bottom flask, add N-methylbenzamide (10 mmol), DMAP (1 mmol), triethylamine (20 mmol), and dichloromethane (20 mL). The reaction mixture is cooled to 0°C, and methacryloyl chloride is slowly added. The mixture is then stirred at room temperature for 4-6 hours. The reaction is complete under TLC monitoring. The organic phase is separated, dried over Na2SO4, and concentrated in vacuo. The resulting residue is purified by flash silica gel column chromatography (eluent: petroleum ether / ethyl acetate = 3:1) to afford the desired product 1a in a yield of 74-85%.

[0055]

[0056] Or, Synthesis of Compound D:

[0057] According to the previous preparation literature report (Y.Yuan, Y.Zheng, B.Xu, et al., ACS Catal.2020, 10, 6676-6681.), a mixture of substituted phenylhydrazine hydrochloride (2.0mmol, 2.0equiv) and acetic acid was added to a 250mL round-bottom flask and stirred at 50°C under N2 atmosphere for 30 minutes, and then the substituted ketone (1.0mmol, 1.0equiv) was added to the solution, heated to 130°C, and the reaction mixture was cooled after 8 hours of reaction. Water was added and the mixture was stirred at 0°C to obtain a precipitate. The obtained crude solid indole compound D can then be used directly in the next step of synthesis after drying. Sometimes, the obtained crude solid should be purified by column chromatography to obtain indole compound D.

[0058] Synthesis of 2-aryl-N-acryloyl indole:

[0059] Following a modified literature procedure, a 100 mL round-bottom flask was charged with DCM (10 mL), indole D (5 mmol, 1 equiv), and DMAP (2.0 mmol, 0.4 equiv). Et3N (10 mmol, 2.0 equiv) was then added to the mixture at 0°C. Methacryloyl chloride (10 mmol, 2.0 equiv) was then slowly added dropwise to the solution, which was then warmed to room temperature and stirred for 2-3 days. The mixture was diluted with DCM (20 mL) and saturated NH4Cl solution (20 mL). The organic and aqueous layers were separated. The aqueous layer was extracted with DCM (20 mL x 3). The combined organic layers were washed with brine and dried over Na2SO4. After evaporation of the solvent, the crude product 1ad was purified by column chromatography on silica gel using petroleum ether / ethyl acetate as the eluent.

[0060] Or, Synthesis of Compound F

[0061]

[0062] According to the previous preparation literature report (Y.Yuan, Y.Zheng, B.Xu, et al., ACS Catal.2020, 10, 6676-6681.), para-substituted benzaldehyde (0.58mL, 5.0mmol) and NaHSO3 (5.73g, 55.0mmol) were mixed in H2O (20.0mL) in a round-bottom flask (50mL) equipped with a magnetic stirrer and added. When the mixture reached reflux temperature, o-phenylenediamine (0.54g, 5.0mmol) was added. The resulting mixture was stirred for 3 hours. After completion of the reaction, it was monitored by TLC analysis. After the reaction mixture was cooled to room temperature, it was vacuum filtered through a glass funnel. The residue was washed with water (20mL×2) and dried in an air-drying oven to obtain the corresponding product F.

[0063] Synthesis of N-Methacryloyl-2-phenylbenzimidazole

[0064] To a solution of F (0.63 g, 3 mmol) and DMAP (73 mg, 0.6 mmol) in DCM (6 ml) was added Et3N (0.83 mL, 6 mmol). Methacryloyl chloride (0.58 mL, 6 mmol) was slowly added dropwise to the solution at 0°C. The solution was warmed to room temperature and stirred at room temperature for 12 hours. According to TLC analysis, the reaction was complete, and water (20 mL) was added to the mixture, which was extracted with DCM (15 mL x 3). The organic solvent was then concentrated in vacuo. The residue was purified by flash column chromatography using ethyl acetate and petroleum ether as eluents to obtain 1ah.

[0065] Example 1

[0066]

[0067] Such as the synthesis of N-methacryloylbenzamide:

[0068] According to the previous preparation literature report (J.Xu, Z.Yang, J.-W.Hua., Org.Chem.Front., 2020, 7, 3223-3228.), compound A (the raw material R1 substituent is H in Example 1) was added to a primary amine (15mmol), Et3N (20mmol) and DCM (20mL) in a 100mL round-bottom flask, and the reaction mixture was cooled to 0°C, and then benzoyl chloride (10mmol) was slowly added dropwise. It was stirred at room temperature for 4 hours, after which the reaction was completed under TLC monitoring, the organic phase was separated, dried over Na2SO4, and concentrated in vacuo. The resulting residue was purified by flash silica gel column chromatography (eluent: petroleum ether / ethyl acetate = 1: 1) in a yield of 93%.

[0069] To a 100 mL round-bottom flask, add N-methylbenzamide (10 mmol), DMAP (1 mmol), triethylamine (20 mmol), and dichloromethane (20 mL). The reaction mixture is cooled to 0°C, and methacryloyl chloride is slowly added. The mixture is then stirred at room temperature for 4-6 hours. The reaction is complete under TLC monitoring. The organic phase is separated, dried over Na2SO4, and concentrated in vacuo. The resulting residue is purified by flash silica gel column chromatography (eluent: petroleum ether / ethyl acetate = 3:1) to afford the desired product 1a in a 77% yield.

[0070] To a 10 mL quartz reaction tube equipped with a stirrer at room temperature and in air was added N-methylacryloylbenzamide 1a (40.6 mg, 0.2 mmol), potassium selenocyanate (43.2 mg, 0.3 mmol), potassium persulfate (54.6 mg, 0.2 mmol), 2,4,6-triphenyl tetrafluoroborate (PC4) (0.8 mg, 0.002 mmol), and a mixture of 1 mL of dichloromethane and 1 mL of water (1:1 volume ratio). The reaction was stirred for 12 hours under 12 W blue light (465 nm) as the light source. After completion of the reaction, the mixture was extracted with ethyl acetate (3 × 10 mL). The organic layers were combined, dried over Na2SO4, filtered, and the volatile components removed under reduced pressure. The product was then separated by silica gel column chromatography (eluent: petroleum ether / ethyl acetate, v / v = 3:1) to afford the desired product 1a as a yellow solid (54.8 mg, 89% yield). The target product was confirmed by nuclear magnetic resonance and high-resolution mass spectrometry. The parameters of the obtained product were 2,4-dimethyl-4-(selenocyanatomethyl)isoquinoline-1,3(2H,4H)-dione (2a): New compound. Yellow solid (54.8 mg, 89%); Mp: 96.4-96.9℃; 1 H NMR (600MHz, CDCl3) δ8.30(d,J=7.7Hz,1H),7.72(t,J=7.4Hz,1H),7.55(t,J=7.6Hz,1H),7.4 4(d,J=7.7Hz,1H),3.79(d,J=12.0Hz,1H),3.64(d,J=12.0Hz,1H),3.40(s,3H),1.78(s,3H). 13 C NMR(150MHz, CDCl3)δ175.51,163.66,140.22,134.83,129.76,128.90,125.29,124.81,101.91,47.90,38.09,30.04,27.60.HRMS(ESI)m / zCalcd for C 13 H 12 N2O2Se[M+H] + :309.0134,found:309.0136.

[0071] Example 2

[0072] The reaction steps and operating conditions were the same as in Example 1, except that the reaction was carried out in the absence of light. The reaction was stopped and the same post-treatment as above was performed, but the target product 2a was not obtained. This indicates that the reaction cannot proceed in the absence of light.

[0073] Example 3

[0074] The reaction steps and operating conditions were the same as in Example 1, except that the reaction was carried out in the absence of potassium persulfate. The reaction was terminated and the same post-treatment as above was performed to obtain the desired product 2a (22.18 mg, 36% yield). This demonstrates that potassium persulfate has a significant effect on the system.

[0075] Example 4

[0076] The reaction steps and operating conditions were the same as in Example 1, except that NaOCN was used instead of KSeCN. The reaction was stopped and the same post-treatment as above failed to yield the desired product 2a, indicating that KSeCN is a necessary condition.

[0077] Example 5

[0078] The reaction steps and operating conditions were the same as in Example 1, except that the reaction was carried out in the absence of PC4. The reaction was terminated and the same post-treatment as above was performed to obtain the desired product 2a (41.89 mg, 68% yield). This indicates that PC4 has a certain influence on the system.

[0079] Example 6

[0080]

[0081] The reaction steps and operating conditions are the same as those in Example 1, except that the R 1 Me, R 2 Me was used to obtain the raw material 1b with a yield of 78%. The difference between the reaction systems is that the raw material added to the reaction system is 1b (43.42 mg, 0.2 mmol) instead of the reaction substrate (1a). The reaction was stopped under blue light (465 nm) for 12 hours and then post-treated to obtain a yellow solid 2b (36.4 mg, 59% yield). Nuclear magnetic resonance spectroscopy and high-resolution mass spectrometry were used to confirm that it was the target product. The parameters of the obtained product were 2,4,8-trimethyl-4-(selenocyanatomethyl)isoquinoline-1,3(2H,4H)-dione (2b): New compound. Yellow solid (36.4 mg, 59%); Mp: 131.7-132.5℃; 1H NMR (600MHz, CDCl3) δ7.54(t,J=7.7Hz,1H),7.32(d,J=7.6Hz,1H),7.30(d,J=7.9Hz,1H) ,3.78(d,J=12.1Hz,1H),3.64(d,J=12.1Hz,1H),3.35(s,3H),2.78(s,3H),1.75(s,3H). 13 C NMR (150MHz, CDCl3) δ175.26,164.08,143.48,141.41,133.52,132.76,123.3 1,123.07,102.50,47.80,38.11,30.48,27.55,23.96.HRMS(ESI)m / zCalcdfor C 14 H 14 N2O2Se[M+H] + :323.0293,found:323.0289.

[0082] Example 7

[0083]

[0084] The reaction steps and operating conditions are the same as those in Example 1, except that the R 1 is para-substituted Me, R 2 Me was used to obtain the raw material 1c with a yield of 85%. The difference between the reaction systems is that the raw material added to the reaction system is 1c (43.42 mg, 0.2 mmol) instead of the reaction substrate (1a). The reaction was stopped under blue light (465 nm) for 12 hours and then post-treated to obtain a white solid 2c (45.8 mg, 74% yield). Nuclear magnetic resonance spectroscopy and high-resolution mass spectrometry were used to confirm the target product. The product parameters were 2,4,6-trimethyl-4-(selenocyanatomethyl)isoquinoline-1,3(2H,4H)-dione (2c): New compound. White solid (45.8 mg, 71%); Mp: 132.5-132.9℃; 1 H NMR (600MHz, CDCl3) δ8.13(d,J=8.0Hz,1H),7.31(d,J=8.0Hz,1H),7.21(s,1H),3.7 6(d,J=12.1Hz,1H),3.63(d,J=12.1Hz,1H),3.34(s,3H),2.45(s,3H),1.74(s,3H). 13C NMR(150MHz, CDCl3)δ175.62,163.55,145.87,140.13,129.74,129.60,125.72,122.09,102.21,47.63,37.88,29.90,27.39,22.02.HRMS(ESI)m / zCalcd forC 14 H 14 N2O2Se[M+H] + :323.0293,found:323.0289.

[0085] Example 8

[0086]

[0087] The reaction steps and operating conditions are the same as those in Example 1, except that the R 1 Me, R 2 The raw material 1d was obtained for Me with a yield of 78%. The difference in the reaction system was that the raw material added to the reaction system was 1d (43.42 mg, 0.2 mmol) instead of the reaction substrate (1a). The reaction was stopped under blue light (465 nm) for 12 hours and then post-treated to obtain yellow solids 2d and 2d' (47.35 mg, yield 74%). Nuclear magnetic resonance spectroscopy and high-resolution mass spectrometry were used to confirm that they were the target products. The parameters of the obtained products were 2,4,7-trimethyl-4-(selenocyanatomethyl)isoquinoline-1,3(2H,4H)-dione(2d)+2,4,5-trimethyl-4-(selenocyanatomethyl)isoquinoline-1,3(2H,4H)-dione(2d'): New compound. Yellow solid (47.35 mg, 74%); Mp: 118.0-119.0℃; 1H NMR (600MHz, CDCl3) δ8.24 (dd, J=7.8, 1.1Hz, 0.24H), 8.06 (d, J=0.8Hz, 1H), 7.50 (dd, J=8.0, 1.4Hz,1H),7.47(d,J=0.9Hz,0.14H),7.42(t,J=7.7Hz,0.27H),7.31(d,J=8.0Hz,1H),3.98( d,J=12.4Hz,0.24H),3.93(d,J=12.4Hz,0.24H),3.76(d,J=12.1Hz,1H),3.60(d,J=12.1Hz,1 H),3.37(s,0.72H),3.35(s,3H),2.62(s,0.72H),2.43(s,3H),1.86(s,0.72H),1.72(s,3H). 13 C NMR (150MHz, CDCl3) δ176.16,175.57,163.82,163.74,139.22,138.92,137.28,137.05,135.66,135.6,129.70,128.70,128.49,12 5.85,125.14,124.44,102.08,101.08,49.31,47.45,38.08,35.69,29.91,27.72,27.49,26.85,22.62,21.07.HRMS(ESI)m / zCalcd for C 14 H 14 N2O2Se[M+H] + :323.0293,found:323.0288.

[0088] Example 9

[0089]

[0090] The reaction steps and operating conditions are the same as those in Example 1, except that the R 1 is para-substituted Et, R 2The raw material 1e was obtained for Me with a yield of 79%. The difference in the reaction system was that the raw material added to the reaction system was 1e (46.2 mg, 0.2 mmol) instead of the reaction substrate (1a). The reaction was stopped under blue light (465 nm) for 12 hours and then post-treated to obtain a yellow solid 2e (48.4 mg, 72% yield). Nuclear magnetic resonance spectroscopy and high-resolution mass spectrometry were used to confirm that it was the target product. The parameters of the obtained product were 6-ethyl-2,4-dimethyl-4-(selenocyanatomethyl)isoquinoline-1,3(2H,4H)-dione (2e): New compound. Yellow solid (48.4 mg, 72%); Mp: 83.0-83.8℃; 1 H NMR (600MHz, CDCl3) δ8.19(d,J=8.0Hz,1H),7.36(dd,J=8.1,1.0Hz,1H),7.22(d,J=0.7Hz,1H),3.78(d,J=12. 1Hz,1H),3.65(d,J=12.1Hz,1H),3.37(s,3H),2.76(q,J=15.2,7.6Hz,2H),1.75(s,3H),1.29(t,J=7.6Hz,3H). 13 C NMR (150MHz, CDCl3) δ175.82,163.65,152.06,140.27,129.87,128.62,124.56 ,122.36,102.31,47.82,37.89,30.10,29.32,27.48,15.10(s).HRMS(ESI)m / z Calcd for C 15 H 16 N2O2Se[M+H] + :337.0450,found:337.0438.

[0091] Example 10

[0092]

[0093] The reaction steps and operating conditions are the same as those in Example 1, except that the R 1 Para-substituted n Pr, R 2The raw material 1f was obtained for Me with a yield of 75%. The difference in the reaction system is that the raw material added to the reaction system is 1f (58.3 mg, 0.2 mmol) instead of the reaction substrate (1a). The reaction was stopped under blue light (465 nm) for 12 hours and then post-treated to obtain a white solid 2f (52.4 mg, yield 75%). The target product was confirmed by nuclear magnetic resonance and high-resolution mass spectrometry. The obtained product parameters are 2,4-dimethyl-6-propyl-4-(selenocyanatomethyl)isoquinoline-1,3(2H,4H)-dione (2f): New compound. White solid (52.4 mg, 75%); Mp: 99.0-99.4℃; 1 H NMR (600MHz, CDCl3) δ8.18(d,J=8.0Hz,1H),7.34(dd,J=8.1,1.1Hz,1H),7.20(s,1H),3.77(d,J=12.0Hz,1H) ,3.65(d,J=12.0Hz,1H),3.37(s,3H),2.69(t,J=7.7Hz,2H),1.75(s,3H),1.69(m,2H),0.96(t,J=7.3Hz,3H). 13 C NMR (150MHz, CDCl3) δ175.82,163.66,150.65,140.23 129.78,129.19,125.09,122.38,102.35,47.74,38.39,37.94,30.09,27.49,24.25,13.90.HRMS(ESI)m / z Calcd for C 16 H 18 N2O2Se[M+H] + :351.0606,found:351.0602.

[0094] Example 11

[0095]

[0096] The reaction steps and operating conditions are the same as those in Example 1, except that the R 1 Para-substituted t Bu, R 21g of raw material was obtained for Me with a yield of 75%. The difference in the reaction system was that 1g (58.3mg, 0.2mmol) of raw material was added to the reaction system instead of the reaction substrate (1a). The reaction was stopped under blue light (465nm) for 12 hours and then post-treated to obtain 2g of yellow solid (66.9mg, yield 92%). Nuclear magnetic resonance spectroscopy and high-resolution mass spectrometry were used to confirm the target product. The product parameters were 6-(tert-butyl)-2,4-dimethyl-4-(selenocyanatomethyl)isoquinoline-1,3(2H,4H)-dioe (2g): New compound. White solid (52.4mg, 75%); Mp: 99.0-99.4℃; 1 H NMR (600MHz, CDCl3) δ8.18(d,J=8.0Hz,1H),7.34(dd,J=8.1,1.1Hz,1H),7.20(s,1H),3.77(d,J=12.0Hz,1H) ,3.65(d,J=12.0Hz,1H),3.37(s,3H),2.69(t,J=7.7Hz,2H),1.75(s,3H),1.69(m,2H),0.96(t,J=7.3Hz,3H). 13 C NMR (150MHz, CDCl3) δ175.82,163.66,150.65,140.23 129.78,129.19,125.09,122.38,102.35,47.74,38.39,37.94,30.09,27.49,24.25,13.90.HRMS(ESI)m / z Calcdfor C 16 H 18 N2O2Se[M+H] + :351.0606,found:351.0602.

[0097] Example 12

[0098]

[0099] The reaction steps and operating conditions are the same as those in Example 1, except that the R 1 OMe is para-substituted, R 2The raw material 1h was obtained for Me with a yield of 82%. The difference in the reaction system is that the raw material added to the reaction system is 1h (46.6 mg, 0.2 mmol) instead of the reaction substrate (1a). The reaction was stopped under blue light (465 nm) for 12 hours and then post-treated to obtain a yellow oily liquid 2h (45 mg, yield 67%). The target product was confirmed by nuclear magnetic resonance and high-resolution mass spectrometry. The obtained product parameters are 6-methoxy-2,4-dimethyl-4-(selenocyanatomethyl)isoquinoline-1,3(2H,4H)-dione (2h): New compound. Yellow oily liquid (45 mg, 67%); 1 H NMR (600MHz, CDCl3) δ8.20 (d, J=8.8Hz, 1H), 7.01 (dd, J=8.8, 2.3Hz, 1H), 6.85 (d, J=2.3Hz, 1H),3.89(s,3H),3.76(d,J=12.1Hz,1H),3.61(d,J=12.1Hz,1H),3.33(s,3H),1.73(s,3H). 13 C NMR(150MHz, CDCl3)δ175.57,164.66,163.19,142.41,131.95,117.43,114.53,110.51,102.31,55.86,47.90,37.81,29.99,27.34.HRMS(ESI)m / zCalcd forC 14 H 14 N2O3Se[M+H] + :339.0242,found:339.0238.

[0100] Example 13

[0101]

[0102] The reaction steps and operating conditions are the same as those in Example 1, except that the R 1 F, R is para-substituted 2The raw material 1i was obtained for Me with a yield of 76%. The difference in the reaction system was that the raw material added to the reaction system was 1i (46.6 mg, 0.2 mmol) instead of the reaction substrate (1a). The reaction was stopped under blue light (465 nm) for 12 hours and then post-treated to obtain a yellow solid 2i (45.9 mg, yield 71%). Nuclear magnetic resonance spectroscopy and high-resolution mass spectrometry were used to confirm that it was the target product. The product parameters were 6-fluoro-2,4-dimethyl-4-(selenocyanatomethyl)isoquinoline-1,3(2H,4H)-dione (2i): New compound. Yellow solid (45.9 mg, 71%); Mp: 147.5-147.9℃; 1 H NMR (600MHz, CDCl3) δ8.30 (dd, J=8.8, 5.8Hz, 1H), 7.21 (ddd, J=15.3, 7.9, 2.4Hz, 1H), 7.14 (dd ,J=9.1,2.4Hz,1H),3.74(d,J=12.3Hz,1H),3.58(d,J=12.3Hz,1H),3.36(s,3H),1.76(s,3H). 13 C NMR (150MHz, CDCl3) δ174.87, 166.59 (d, J = 257.3Hz), 162.67, 143.15 (d, J = 9Hz), 132.72 (d, J = 10.5Hz), 121 .26(d,J=1.5Hz),116.72(d,J=21Hz),112.61(d,J=24Hz),101.35,48.05(d,J=1.5Hz),37.93,29.69,27.52. 19 F NMR(565MHz,CDCl3)δ-23.55.HRMS(ESI)m / zCalcd for C 13 H 11 FN2O2Se[M+H] + :327.0043,found:327.0039.

[0103] Example 14

[0104]

[0105] The reaction steps and operating conditions are the same as those in Example 1, except that the R 1 is para-substituted Cl, R 2The raw material 1j was obtained for Me with a yield of 76%. The difference in the reaction system was that the raw material added to the reaction system was 1j (47.4 mg, 0.2 mmol) instead of the reaction substrate (1a). The reaction was stopped under blue light (465 nm) for 12 hours and then post-treated to obtain a yellow solid 2j (52.8 mg, yield 77%). Nuclear magnetic resonance spectroscopy and high-resolution mass spectrometry were used to confirm that it was the target product. The product parameters were 6-chloro-2,4-dimethyl-4-(selenocyanatomethyl)isoquinoline-1,3(2H,4H)-dione (2j): New compound. Yellow solid (52.8 mg, 77%); Mp: 178.4-178.7℃; 1 H NMR(600MHz, CDCl3) δ8.24(d,J=8.5Hz,1H),7.52(dd,J=8.5,1.9Hz,1H),7.42(d,J=1 .9Hz,1H),3.76(d,J=12.3Hz,1H),3.58(d,J=12.3Hz,1H),3.39(s,3H),1.78(s,3H). 13 C NMR(150MHz, CDCl3)δ174.80,162.86,141.87,141.53,131.31,129.52,125.74,123.32,101.36,48.00,37.94,29.82,27.68.HRMS(ESI)m / zCalcd forC 13 H 11 ClN2O2Se[M+H] + :342.9747,found:342.9742.

[0106] Example 15

[0107]

[0108] The reaction steps and operating conditions are the same as those in Example 1, except that the R 1 Br substituted at the phosphorus position, R 2The raw material 1k was obtained for Me with a yield of 78%. The difference in the reaction system was that the raw material added to the reaction system was 1k (56.2 mg, 0.2 mmol) instead of the reaction substrate (1a). The reaction was stopped under blue light (465 nm) for 12 hours and then post-treated to obtain a yellow solid 2k (12.1 mg, 16% yield). Nuclear magnetic resonance spectroscopy and high-resolution mass spectrometry were used to confirm that it was the target product. The product parameters were 8-bromo-2,4-dimethyl-4-(selenocyanatomethyl)isoquinoline-1,3(2H,4H)-dione (2k): New compound. Yellow solid (12.1 mg, 16%); Mp: 151.1-152.1℃; 1 H NMR (600MHz, CDCl3) δ7.85(d,J=7.9Hz,1H),7.50(t,J=7.9Hz,1H),7.44(d,J=7.8 Hz,1H),3.79(d,J=12.3Hz,1H),3.63(d,J=12.3Hz,1H),3.39(s,3H),1.77(s,3H). 13 C NMR(150MHz, CDCl3)δ174.39,161.63,143.17,136.64,134.31,124.99,124.87,123.40,102.13,48.68,37.58,30.63,28.20.HRMS(ESI)m / zCalcd for C 13 H 11 BrN2O2Se[M+H] + :386.9242,found:386.9232.

[0109] Example 16

[0110]

[0111] The reaction steps and operating conditions are the same as those in Example 1, except that the R 1 is para-substituted Br, R 2The raw material 1l was obtained for Me with a yield of 75%. The difference in the reaction system was that the raw material 1l (56.2 mg, 0.2 mmol) was added to the reaction system instead of the reaction substrate (1a). The reaction was stopped under blue light (465 nm) for 12 hours and then post-treated to obtain a yellow solid 2l (46 mg, yield 61%). The target product was confirmed by nuclear magnetic resonance and high-resolution mass spectrometry. The obtained product parameters were 6-bromo-2,4-dimethyl-4-(selenocyanatomethyl)isoquinoline-1,3(2H,4H)-dione (2l): New compound. Yellow solid (46 mg, 61%); Mp: 178.0-179.0℃; 1 H NMR (600MHz, CDCl3) δ8.15(d,J=8.4Hz,1H),7.68(dd,J=8.4,1.5Hz,1H),7.58(d,J=1 .4Hz,1H),3.76(d,J=12.3Hz,1H),3.58(d,J=12.3Hz,1H),3.38(s,3H),1.78(s,3H). 13 C NMR(150MHz, CDCl3)δ174.76,163.01,141.93,132.54,131.28,130.17,128.70,123.74,101.40,47.94,37.93,29.84,27.71.HRMS(ESI)m / zCalcd forC 13 H 11 BrN2O2Se[M+H] + :386.9242,found:386.9230.

[0112] Example 17

[0113]

[0114] The reaction steps and operating conditions are the same as those in Example 1, except that the R 1 is Br substituted at the meta position, R 2The raw material 1m was obtained for Me with a yield of 81%. The difference in the reaction system is that the raw material added to the reaction system is 1m (56.2 mg, 0.2 mmol) instead of the reaction substrate (1a). The reaction was stopped under blue light (465 nm) for 12 hours and the reaction was post-treated to obtain a yellow solid 2m (22.8 mg, yield 31%) and a yellow solid 2m' (19 mg, 26%). Nuclear magnetic resonance and high-resolution mass spectrometry were used to confirm that it was the target product. The parameters of the obtained product were 7-bromo-2,4-dimethyl-4-(selenocyanatomethyl)isoquinoline-1,3(2H,4H)-dione (2m): New compound. Yellow solid (22.8 mg, 31%); Mp: 133.9-134.4℃; 1 H NMR (600MHz, CDCl3) δ8.36 (d, J=2.1Hz, 1H), 7.76 (dd, J=8.4, 2.1Hz, 1H), 7.25 (d, J=8 .4Hz,1H),3.72(d,J=12.2Hz,1H),3.52(d,J=12.2Hz,1H),3.33(s,3H),1.69(s,3H). 13 C NMR(150MHz, CDCl3)δ174.93,162.47,138.96,137.76,132.52,127.12,126.56,123.13,101.58,47.94,37.69,30.02,27.81.HRMS(ESI)m / zCalcd for C 13 H 11 BrN2O2Se[M+H] + :386.9242,found:386.9230.

[0115] 5-bromo-2,4-dimethyl-4-(selenocyanatomethyl)isoquinoline-1,3(2H,4H)-dione(2m'):New compound.Yellowsolid(19mg,26%); Mp:86.8-87.6℃ 1 H NMR (600MHz, CDCl3) δ8.43 (dd, J=7.9, 1.3Hz, 1H), 7.93 (dd, J=7.9, 1.3Hz, 1H), 7.42 (t, J=7.9Hz,1H),4.67(d,J=12.7Hz,1H),3.96(d,J=12.7Hz,1H),3.42(s,3H),2.03(s,3H). 13C NMR(150MHz, CDCl3)δ175.18,162.56,141.70,137.29,130.20,130.01,128.08,121.47,99.78,50.51,34.44,27.99,26.14.HRMS(ESI)m / zCalcd for C 13 H 11 BrN2O2Se[M+H] + :386.9242,found:386.9233.

[0116] Example 18

[0117]

[0118] The reaction steps and operating conditions are the same as those in Example 1, except that the R 1 is a para-substituted CF3, R 2 The raw material 1n was obtained for Me with a yield of 76%. The difference in the reaction system was that the raw material added to the reaction system was 1n (54.22 mg, 0.2 mmol) instead of the reaction substrate (1a). The reaction was stopped under blue light (465 nm) for 12 hours and then post-treated to obtain a white solid 2n (43.3 mg, 58% yield). Nuclear magnetic resonance spectroscopy and high-resolution mass spectrometry were used to confirm that it was the target product. The product parameters were 2,4-dimethyl-4-(selenocyanatomethyl)-6-(trifluoromethyl)isoquinoline-1,3(2H,4H)-dione (2n): New compound. White solid (43.3 mg, 58%); Mp: 134.8-135.4℃; 1 H NMR (600MHz, CDCl3) δ8.44(d,J=8.2Hz,1H),7.80(d,J=8.3Hz,1H),7.69(s,1 H),3.80(d,J=12.4Hz,1H),3.63(d,J=12.4Hz,1H),3.41(s,3H),1.82(s,3H). 13 C NMR (150MHz, CDCl3) δ174.62, 162.59, 141.02, 136.27 (q, J = 33Hz), 130.61, 127.78, 125.73 ( q, J=3Hz), 123.21 (q, J=271.5Hz), 122.67 (q, J=4.5Hz), 100.94, 48.19, 37.89, 29.80, 27.80. 19F NMR(565MHz,CDCl3)δ14.69.HRMS(ESI)m / zCalcdfor C 14 H 11 FN2O2Se[M+H] + :377.0011,found:377.0003.

[0119] Example 19

[0120]

[0121] The reaction steps and operating conditions are the same as those in Example 1, except that the R 1 is disubstituted OMe, R 2 The raw material 1o was obtained for Me with a yield of 75%. The difference in the reaction system was that the raw material 1o (52.62 mg, 0.2 mmol) was added to the reaction system instead of the reaction substrate (1a). The reaction was stopped under blue light (465 nm) for 12 hours and then post-treated to obtain a white solid 2o (39.9 mg, 54% yield). Nuclear magnetic resonance spectroscopy and high-resolution mass spectrometry were used to confirm the target product. The obtained product parameters were 6,7-dimethoxy-2,4-dimethyl-4-(selenocyanatomethyl)isoquinoline-1,3(2H,4H)-dione (2o): New compound. White solid (39.9 mg, 54%); Mp: 153.9-154.4℃; 1 H NMR (600MHz, CDCl3) δ7.66(s,1H),6.76(s,1H),3.98(s,3H),3.95(s,3H),3.78(d,J=12.1Hz,1H),3.61(d,J=12.1Hz,1H),3.34(s,3H),1.72(s,3H). 13 C NMR (150MHz, CDCl3) δ175.87,163.33,154.69,149.49,134.21,117.62,110.54, 106.95,102.64,56.54,56.33,47.68,37.93,30.11,27.48.HRMS(ESI)m / zCalcd for C 15 H 16 N2O4Se[M+H] + :369.0348,found:369.0344.

[0122] Example 20

[0123]

[0124] The reaction steps and operating conditions are the same as those in Example 1, except that the R 1 is trisubstituted OMe, R 2 The raw material 1p was obtained for Me with a yield of 78%. The difference in the reaction system is that the raw material added to the reaction system is 1p (58.62 mg, 0.2 mmol) instead of the reaction substrate (1a). The reaction was stopped under blue light (465 nm) for 12 hours and then post-treated to obtain a white solid 2p (26.5 mg, yield 34%). Nuclear magnetic resonance spectroscopy and high-resolution mass spectrometry were used to confirm that it was the target product. The parameters of the obtained product were 5,6,7-trimethoxy-2,4-dimethyl-4-(selenocyanatomethyl)isoquinoline-1,3(2H,4H)-dione (2p): New compound. White solid (26.5 mg, 34%); Mp: 144.9-145.5℃; 1 H NMR (600MHz, CDCl3) δ7.61(s,1H),4.17(d,J=12.0Hz,1H),4.03(s,3H),3.94(s,3H),3.91(s,3H),3.78(d,J=12.0Hz,1H),3.35(s,3H),1.78(s,3H). 13 C NMR (150MHz, CDCl3) δ176.06,163.38,154.21,151.55,147.35,125.08,120.50,107 .05,100.90,61.16,60.83,56.24,48.25,36.65,27.59,27.19.HRMS(ESI)m / zCalcd for C 16 H 18 N2O5Se[M+H] + :399.0454,found:369.0452.

[0125] Example 21

[0126]

[0127] The reaction steps and operating conditions are the same as those in Example 1, except that the R 1 H, R 2The raw material 1q was obtained for Et with a yield of 83%. The difference in the reaction system is that the raw material 1q (43.42 mg, 0.2 mmol) was added to the reaction system instead of the reaction substrate (1a). The reaction was stopped under blue light (465 nm) for 12 hours and then post-processed to obtain a yellow oily liquid 2q (62.7 mg, yield 97%). Nuclear magnetic resonance spectroscopy and high-resolution mass spectrometry were used to confirm that it was the target product. The parameters of the obtained product were 2-ethyl-4-methyl-4-(selenocyanatomethyl)isoquinoline-1,3(2H,4H)-dione (2q): New compound. Yellow oily liquid (62.7 mg, 97%); 1 H NMR (600MHz, CDCl3) δ8.28(d,J=7.8Hz,1H),7.71(t,J=7.8Hz,1H),7.53(t,J=7.6Hz,1H),7.43(d,J=7.9Hz, 1H), 4.10-4.00 (m, 2H), 3.77 (d, J = 12.1Hz, 1H), 3.66 (d, J = 12.1Hz, 1H), 1.75 (s, 3H), 1.22 (t, J = 7.1Hz, 3H). 13 C NMR(150MHz, CDCl3)δ175.11,163.11,140.19,134.72,129.70,128.82,125.23,124.91,102.08,47.74,37.92,36.20,30.02,13.20.HRMS(ESI)m / zCalcd for C 14 H 14 N2O2Se[M+H] + :323.0293,found:323.0287.

[0128] Example 22

[0129]

[0130] The reaction steps and operating conditions are the same as those in Example 1, except that the R 1 H, R 2 for iThe raw material 1r was obtained from Pr with a yield of 76%. The difference in the reaction system was that the raw material added to the reaction system was 1r (46.23 mg, 0.2 mmol) instead of the reaction substrate (1a). The reaction was stopped under blue light (465 nm) for 12 hours and then post-treated to obtain a yellow solid 2l (46.4 mg, yield 69%). Nuclear magnetic resonance spectroscopy and high-resolution mass spectrometry were used to confirm that it was the target product. The product parameters were 2-isopropyl-4-methyl-4-(selenocyanatomethyl)isoquinoline-1,3(2H,4H)-dione (2r): White solid (26.5 mg, 34%); Mp: 144.9-145.5℃; 1 H NMR (600MHz, CDCl3) δ7.61(s,1H),4.17(d,J=12.0Hz,1H),4.03(s,3H),3.94(s,3H),3.91(s,3H),3.78(d,J=12.0Hz,1H),3.35(s,3H),1.78(s,3H). 13 C NMR (150MHz, CDCl3) δ176.06,163.38,154.21,151.55,147.35,125.08,120.50,107 .05,100.90,61.16,60.83,56.24,48.25,36.65,27.59,27.19.HRMS(ESI)m / zCalcd for C 16 H 18 N2O5Se[M+H] + :399.0454,found:369.0452.

[0131] Example 23

[0132]

[0133] The reaction steps and operating conditions are the same as those in Example 1, except that the R 1 H, R 2 for nThe raw material 1s was obtained with a yield of 81%. The difference in the reaction system was that the raw material added to the reaction system was 1s (49.03 mg, 0.2 mmol) instead of the reaction substrate (1a). The reaction was stopped under blue light (465 nm) for 12 hours and then post-treated to obtain a yellow solid 2s (44.4 mg, yield 63%). Nuclear magnetic resonance spectroscopy and high-resolution mass spectrometry were used to confirm that it was the target product. The parameters of the obtained product were 2-butyl-4-methyl-4-(selenocyanatomethyl)isoquinoline-1,3(2H,4H)-dione (2s): New compound. Yellow solid (44.4 mg, 63%); MP: 108.8-109.3℃; 1 H NMR (600MHz, CDCl3) δ8.25(dd,J=7.9,1.2Hz,1H),7.68(t,J=7.8Hz,1H),7.51(t,J=7.7Hz,1H),7.43(d,J=7.9Hz,1H),4.01-3. 92(m,2H),3.76(d,J=12.1Hz,1H),3.66(d,J=12.1Hz,1H),1.73(s,3H),1.57(quin,2H),1.35(quin,2H),0.92(t,J=7.4Hz,3H). 13 C NMR (150MHz, CDCl3) δ175.23,163.21,140.12,134.61,129.60,128.70,125.18,124 .77,102.08,47.71,40.69,37.73,30.03,29.91,20.20,13.77.HRMS(ESI)m / zCalcd forC 16 H 18 N2O2Se[M+H] + :351.0606,found:351.0600.

[0134] Example 24

[0135]

[0136] The reaction steps and operating conditions are the same as those in Example 1, except that the R 1 H, R 2 for tThe raw material 1t was obtained with a yield of 76%. The difference in the reaction system was that the raw material added to the reaction system was 1t (49.03 mg, 0.2 mmol) instead of the reaction substrate (1a). The reaction was stopped under blue light (465 nm) for 12 hours and then post-processed to obtain a yellow solid 2t (23.5 mg, yield 35%). Nuclear magnetic resonance spectroscopy and high-resolution mass spectrometry were used to confirm that it was the target product. The parameters of the obtained product were 2-(tert-butyl)-4-methyl-4-(selenocyanatomethyl)isoquinoline-1,3(2H,4H)-dione (2t): New compound. Yellow solid (23.5 mg, 35%); MP: 139.4-140.4℃; 1 H NMR (600MHz, CDCl3) δ6.90 (dd, J=10.4, 3.1Hz, 1H), 6.62-6.58 (m, 2H), 6.52 (dd, J=10.1 ,1.7Hz,1H),3.55(d,J=12.4Hz,1H),2.95(d,J=12.4Hz,1H),1.63(s,3H),1.56(s,9H). 13 C NMR(150MHz, CDCl3)δ183.49,179.99,172.44,141.48,141.02,134.73,133.54,103.01,60.39,58.57,52.75,32.57,28.15,22.54.HRMS(ESI)m / zCalcd for C 16 H 18 N2O2Se[M+H] + :351.0606,found:351.0602.

[0137] Example 25

[0138]

[0139] The reaction steps and operating conditions are the same as those in Example 1, except that the R 1 H, R 2The raw material 1u was obtained as hexadecyl with a yield of 77%. The difference in the reaction system is that the raw material 1u (82.67 mg, 0.2 mmol) was added to the reaction system instead of the reaction substrate (1a). The reaction was stopped under blue light (465 nm) for 12 hours and then post-treated to obtain a yellow oily liquid 2u (46.4 mg, 45% yield). Nuclear magnetic resonance spectroscopy and high-resolution mass spectrometry were used to confirm that it was the target product. The parameters of the obtained product were 2-hexadecyl-4-methyl-4-(selenocyanatomethyl)isoquinoline-1,3(2H,4H)-dione (2u): New compound. Yellow oily liquid (46.5 mg, 45%); 1 H NMR (600MHz, CDCl3) δ8.28(d,J=7.8Hz,1H),7.70(t,J=7.4Hz,1H),7.53(t,J=7.6Hz,1H),7.43(d,J=7.9Hz,1H),4.02-3.93(m,2H), 3.77(d,J=12.1Hz,1H),3.67(d,J=12.1Hz,1H),1.75(s,3H),1.64-1.58(m,2H),1.32(br,5H),1.24(br,21H),0.86(t,J=6.8Hz,3H). 13 C NMR (150MHz, CDCl3) δ175.34,163.27,140.18,134.68,129.74,128.79,125.21,124.88,102.15,47.79,41.04,37.78,3 1.99,30.15,29.76,29.74,29.73,29.70,29.64,29.60,29.43,29.33,27.94,27.05,22.76,14.20.HRMS(ESI)m / zCalcd forC 28 H 42 N2O2Se[M+H] + :519.2484,found:519.2477.

[0140] Example 26

[0141]

[0142] The reaction steps and operating conditions are the same as those in Example 1, except that the R 1 H, R 2The raw material 1v was obtained as a cyclopropyl with a yield of 82%. The difference in the reaction system is that the raw material added to the reaction system is 1v (45.82 mg, 0.2 mmol) instead of the reaction substrate (1a). The reaction was stopped under blue light (465 nm) for 12 hours and then post-treated to obtain a yellow solid 2v (37 mg, yield 55%). The target product was confirmed by nuclear magnetic resonance and high-resolution mass spectrometry. The obtained product parameters are 2-cyclopropyl-4-methyl-4-(selenocyanatomethyl)isoquinoline-1,3(2H,4H)-dione (2v): New compound. Yellow solid (37 mg, 55%); MP: 71.6-72.2℃; 1 HNMR (600MHz, CDCl3) δ8.24(dd,J=7.9,1.2Hz,1H),7.69(td,J=7.7,1.4Hz,1H),7.53-7.50(m,1H),7.41(d,J=7.9Hz,1H),3.74(d ,J=12.1Hz,1H),3.65(d,J=12.1Hz,1H),2.76-2.72(m,1H),1.70(s,3H),1.21-1.10(m,2H),0.81-0.76(m,1H),0.62-0.58(m,1H). 13 C NMR (150MHz, CDCl3) δ176.88,164.31,140.06,134.71,129.61,128.80,125.16 ,125.10,102.47,48.26,37.29,29.81,24.78,8.87,8.01.HRMS(ESI)m / zCalcd for C 15 H 14 N2O2Se[M+H] + :335.0293,found:335.0288.

[0143] Example 27

[0144]

[0145] The reaction steps and operating conditions are the same as those in Example 1, except that the R 1 H, R 2The raw material 1w was obtained as a cyclohexyl group with a yield of 80%. The difference in the reaction system is that the raw material 1w (54.23 mg, 0.2 mmol) was added to the reaction system instead of the reaction substrate (1a). The reaction was stopped under blue light (465 nm) for 12 hours and then post-treated to obtain a yellow oily liquid 2w (39.16 mg, yield 52%). The target product was confirmed by nuclear magnetic resonance and high-resolution mass spectrometry. The obtained product parameters are 2-cyclohexyl-4-methyl-4-(selenocyanatomethyl)isoquinoline-1,3(2H,4H)-dione (2w): New compound. Yellow oily liquid (39.16 mg, 52%); 1 H NMR (600MHz, CDCl3) δ8.24 (dd, J=7.9, 1.2Hz, 1H), 7.68 (td, J=7.6, 1.4Hz, 1H), 7.5 2-7.49(m,1H),7.40(d,J=7.9Hz,1H),4.72(tt,J=12.2,3.7Hz,1H),3.73(d,J=12. 0Hz,1H),3.66(d,J=12.0Hz,1H),2.37-2.28(m,2H),1.85-1.82(m,2H),1.72(s,3H ),1.67-1.65(m,2H),1.60(d,J=12.4Hz,1H),1.41-1.31(m,2H),1.27-1.19(m,1H). 13 C NMR (150MHz, CDCl3) δ176.24,163.67,140.01,134.49,129.82,128.69,125.36,124.81,10 2.94,54.67,48.24,37.34,30.12,29.45,28.57,26.44,26.35,25.33.HRMS(ESI)m / zCalcd for C 15 H 14 N2O2Se[M+H] + :377.0763,found:377.0749.

[0146] Example 28

[0147]

[0148] The reaction steps and operating conditions are the same as those in Example 1, except that the R 1 H, R 2The raw material 1x was obtained as benzyl with a yield of 82%. The difference in the reaction system is that the raw material 1x (55.83 mg, 0.2 mmol) was added to the reaction system instead of the reaction substrate (1a). The reaction was stopped under blue light (465 nm) for 12 hours and then post-treated to obtain a white solid 2x (63 mg, yield 82%). Nuclear magnetic resonance spectroscopy and high-resolution mass spectrometry were used to confirm that it was the target product. The parameters of the obtained product were 2-benzyl-4-methyl-4-(selenocyanatomethyl)isoquinoline-1,3(2H,4H)-dione (2x): New compound. White solid (63 mg, 82%); Mp: 131.7-132.3℃; 1 H NMR (600MHz, CDCl3) δ8.21(d,J=7.8Hz,1H),7.62(t,J=7.4Hz,1H),7.44(t,J=7.6Hz,1H),7.35(d,J=7.9Hz,1H),7.32(d,J=7.4 Hz,2H),7.21(t,J=7.3Hz,2H),7.16(t,J=6.8Hz,1H),5.10(s,2H),3.68(d,J=12.1Hz,1H),3.57(d,J=12.1Hz,1H),1.64(s,3H). 13 C NMR (150MHz, CDCl3) δ175.20,163.24,140.05,136.53,134.82,129.80,128.80,128.62,12 8.55,127.70,125.25,124.73,101.92,48.00,43.98,37.76,29.91.HRMS(ESI)m / zCalcdfor C 16 H 18 N2O2Se[M+H] + :385.0450,found:385.0441.

[0149] Example 29

[0150]

[0151] The reaction steps and operating conditions are the same as those in Example 1, except that the R 1 H, R 2The raw material 1y was obtained as a benzylmethyl compound with a yield of 79%. The difference in the reaction system was that the raw material 1y (58.63 mg, 0.2 mmol) was added to the reaction system instead of the reaction substrate (1a). The reaction was stopped under blue light (465 nm) for 12 hours and then post-processed to obtain a yellow oily liquid 2y (57.2 mg, 72% yield). Nuclear magnetic resonance spectroscopy and high-resolution mass spectrometry were used to confirm the target product. The obtained product parameters were 4-methyl-2-(1-phenylethyl)-4-(selenocyanatomethyl)isoquinoline-1,3(2H,4H)-dione (2y): New compound. Yellow oily liquid (57.2 mg, 72%, dr = 1:1); 1 H NMR (600MHz, CDCl3) δ8.19-8.16(m,1H),7.62-7.59(m,1H),7.45-7.41(m,1H),7.33(dd,J=7.7,4.9Hz,1H) ,7.29(d,J=7.9Hz,2H),7.23(td,J=7.5,3.4Hz,2H),7.16-7.13(m,1H),6.19(dd,J=7.0,2.5Hz,0.5H),6.17 (dd,J=7.0,2.5Hz,0.5H),,3.64(d,J=12.1Hz,0.5H),3.60(d,J=12.1Hz,0.5H),3.58(d,J=12.1Hz,0.5H), 3.53(d,J=12.1Hz,0.5H),1.79(d,J=7.4Hz,1.5H),1.78(d,J=7.4Hz,1.5H),1.69(s,1.5H),1.52(s,1.5H). 13 C NMR (151MHz, CDCl3) δ175.35,175.20,163.36,163.28,140.12,139.95,139.93, 139.77,134.69,134.68,129.96,129.88,128.77,128.26,128.23,127.21,127.1 9,126.94,126.91,125.16,125.13,125.09,124.98,102.26,102.18,51.03,51. 00,48.64,48.35,37.69,36.93,30.21,29.85,16.35,16.09.HRMS(ESI)m / zCalcd for C 20 H 18 N2O2Se[M+H] +:399.0606,found:399.0600.

[0152] Example 30

[0153]

[0154] The reaction steps and operating conditions are the same as those in Example 1, except that the R 1 H, R 2 The raw material 1z was obtained as a phenyl group with a yield of 83%. The difference in the reaction system is that the raw material added to the reaction system is 1z (53.02 mg, 0.2 mmol) instead of the reaction substrate (1a). The reaction was stopped under blue light (465 nm) for 12 hours and then post-treated to obtain a yellow solid 2z (32.5 mg, yield 44%). Nuclear magnetic resonance spectroscopy and high-resolution mass spectrometry were used to confirm that it was the target product. The parameters of the obtained product were 4-methyl-2-phenyl-4-(selenocyanatomethyl)isoquinoline-1,3(2H,4H)-dione (2z): New compound. Yellow solid (32.5 mg, 44%); Mp: 196.5-197.5℃; 1 HNMR (600MHz, CDCl3) δ8.34 (dd, J=7.9, 1.0Hz, 1H), 7.79 (td, J=7.7, 1.3Hz, 1H), 7.59 (t, J=7.7Hz, 1H), 7.53 (t, J=7. 2Hz, 3H), 7.47 (t, J = 7.3Hz, 1H), 7.21 (d, J = 7.4Hz, 2H), 3.82 (d, J = 12.2Hz, 1H), 3.77 (d, J = 12.2Hz, 1H), 1.90 (s, 3H). 13 C NMR (150MHz, CDCl3) δ175.68,163.57,140.27,135.22,134.81,130.18,129.60,129.1 8,129.09,128.35,125.45,124.98,101.97,48.68,37.78,30.41.HRMS(ESI)m / zCalcd for C 18 H 14 N2O2Se[M+H] + :371.0293,found:371.0287.

[0155] Example 31

[0156]

[0157] The reaction steps and operating conditions are the same as those in Example 1, except that the R 1 H, R 2 The raw material 1aa was obtained from p-methylbenzene with a yield of 76%. The difference in the reaction system was that the raw material 1aa (55.83 mg, 0.2 mmol) was added to the reaction system instead of the reaction substrate (1a). The reaction was stopped under blue light (465 nm) for 12 hours and then post-processed to obtain a yellow solid 2aa (29.9 mg, 38% yield). Nuclear magnetic resonance spectroscopy and high-resolution mass spectrometry were used to confirm the target product. The obtained product parameters were 4-methyl-4-(selenocyanatomethyl)-2-(p-tolyl)isoquinoline-1,3(2H,4H)-dione (2aa): New compound. Yellow solid (29.9 mg, 38%); Mp: 171.5-172.4℃; 1 H NMR (600MHz, CDCl3) δ8.33(dd,J=7.9,1.0Hz,1H),7.77(td,J=7.8,1.3Hz,1H),7.58(t,J=7.4Hz,1H),7.51(d,J=7.9Hz,1H ),7.32(d,J=8.0Hz,2H),7.10(d,J=8.2Hz,2H),3.80(d,J=12.2Hz,1H),3.76(d,J=12.2Hz,1H),2.42(s,3H),1.88(s,3H). 13 C NMR (150MHz, CDCl3) δ175.75,163.60,140.27,139.10,135.08,132.06,130.23,130.06,1 28.95,127.95,125.40,124.93,102.15,48.49,37.69,30.28,21.34.HRMS(ESI)m / zCalcd for C 19 H 16 N2O2Se[M+H] + :358.0450,found:358.0445.

[0158] Example 32

[0159]

[0160] The reaction steps and operating conditions are the same as those in Example 1, except that the R 1 H, R 2The raw material 1ab was obtained from trifluoromethylbenzene with a yield of 77%. The difference in the reaction system was that the raw material 1ab (66.61 mg, 0.2 mmol) was added to the reaction system instead of the reaction substrate (1a). The reaction was stopped under blue light (465 nm) for 12 hours and then post-processed to obtain a yellow solid 2ab (14.1 mg, 15% yield). Nuclear magnetic resonance spectroscopy and high-resolution mass spectrometry confirmed that it was the target product. The product parameters were 4-methyl-4-(selenocyanatomethyl)-2-(4-(trifluoromethyl)phenyl)isoquinoline-1,3(2H,4H)-dione (2ab): New compound. Yellow solid (14.1 mg, 15%); Mp: 153.2-154.1°C 1 H NMR (600MHz, CDCl3) δ8.34(d,J=7.1Hz,1H),7.82-7.78(m,3H),7.61(t,J=7.7Hz,1H),7.52(d,J =7.9Hz,1H),7.37(d,J=8.2Hz,2H),3.85(d,J=12.4Hz,1H),3.75(d,J=12.4Hz,1H),1.91(s,3H). 13 C NMR(150MHz,CDCl3)δ175.23,163.33,140.21,138.05,135.51,131.32(q,J=33Hz),13 0.20,129.23,126.69(q,J=3Hz),125.57,124.72,123.83(q,J=270Hz),122.92,101.27 48.94,37.89,30.41. 19 F NMR(565MHz,CDCl3)δ15.18.HRMS(ESI)m / zCalcd for C 19 H 16 N2O2Se[M+H] + :358.0450,found:358.0445.

[0161] Example 33

[0162]

[0163] According to the previous preparation literature report (Y.Yuan, Y.Zheng, B.Xu, et al., ACS Catal.2020, 10, 6676-6681.), a mixture of substituted phenylhydrazine hydrochloride (2.0mmol, 2.0equiv) (the raw material R3 substituent is H in 33 of this embodiment) and acetic acid was added to a 250mL round-bottom flask and stirred under N2 atmosphere at 50°C for 30 minutes, and then the substituted ketone (1.0mmol, 1.0equiv) was added to the solution, heated to 130°C, and the reaction mixture was cooled after 8 hours of reaction. Water was added and the mixture was stirred at 0°C to obtain a precipitate. Then, the obtained crude solid indole compound D can be directly used in the next step of synthesis after drying. Sometimes, the obtained crude solid should be purified by column chromatography to obtain indole compound D.

[0164] Synthesis of 2-aryl-N-acryloyl indole:

[0165] According to a modified literature procedure, DCM (10 mL), indole compound D (5 mmol, 1 equiv), and DMAP (2.0 mmol, 0.4 equiv) were added to a 100 mL round-bottom flask. Et3N (10 mmol, 2.0 equiv) was then added to the mixture at 0°C. Methacryloyl chloride (10 mmol, 2.0 equiv) was then slowly added dropwise to the solution, which was then warmed to room temperature and stirred for 2-3 days. The mixture was diluted with DCM (20 mL) and saturated NH4Cl solution (20 mL). The organic and aqueous layers were separated. The aqueous layer was extracted with DCM (20 mL x 3). The combined organic layers were washed with brine and dried over Na2SO4. After evaporation of the solvent, the crude product 1ac was purified by column chromatography on silica gel using petroleum ether / ethyl acetate as the eluent in a yield of 75%. The difference in the reaction system was that 1ac (67.43 mg, 0.2 mmol) was added instead of the reaction substrate (1a). The reaction was terminated under blue light (465 nm) for 12 hours and then post-processed to obtain a white solid 2ac (85.7 mg, 92% yield). Nuclear magnetic resonance spectroscopy and high-resolution mass spectrometry confirmed the target product. The product parameters were: 5-methyl-12-phenyl-5-(selenocyanatomethyl)indolo[2,1-a]isoquinolin-6(5H)-one (2ac): New compound. White solid (85.7 mg, 92%); Mp: 184.1-184.5°C; 1H NMR(600MHz, CDCl3)δ8.56(d,J=8.2Hz,1H),7.60-7.57(m,2H),7.55-7.52(m,3H),7.47(d,J=8.0Hz,1H),7.45-7.43(m,1H), 7.41(d,J=7.8Hz,1H),7.37-7.32(m,3H),7.12(t,J=7.6Hz,1H),3.92(d,J=11.9Hz,1H),3.82(d,J=11.9Hz,1H),1.88(s,3H). 13 CNMR (150MHz, CDCl3) δ171.76,135.72,134.17,133.480,132.37,130.11,129.48,129.14,128.82,128.49,128.05, 126.54,125.98,125.88,125.41,125.24,121.82,119.91,116.58,103.14,48.82,37.75,29.39.HRMS(ESI)m / zCalcd for C 25 H 18 N2OSe[M+H] + :443.0657,found:443.0653.

[0166] Example 34

[0167]

[0168] The reaction steps and operating conditions are the same as those of Example 33, except that the R 3 The reaction system was modified with a substituted dimethyl group to obtain the raw material 1ae with a yield of 76%. The difference in the reaction system was that the raw material added to the reaction system was 1ae (73.04 mg, 0.2 mmol) instead of the reaction substrate (1ac). The reaction was stopped under blue light (465 nm) for 12 hours and then post-treated to obtain a white solid 2ae (77.1 mg, 82% yield). Nuclear magnetic resonance spectroscopy and high-resolution mass spectrometry were used to confirm that it was the target product. The product parameters were 5,9,11-trimethyl-12-phenyl-5-(selenocyanatomethyl)indolo[2,1-a]isoquinolin-6(5H)-one (2ad): New compound. White solid (77.1 mg, 82%); Mp: 184.1-184.5℃; 1H NMR (600MHz, CDCl3) δ8.32(s,1H),7.58-7.55(m,1H),7.54-7.50(m,3H),7.44-7.42(m,1H),7.36(dd,J=7.9,0.7Hz,1H),7.30-7.27(m,1H),7.0 7(dd,J=8.2,1.1Hz,1H),7.04-7.01(m,1H),6.89(s,1H),3.89(d,J=11. 8Hz,1H),3.81(d,J=11.8Hz,1H),2.48(s,3H),1.92(s,3H),1.83(s,3H). 13 C NMR (150MHz, CDCl3) δ171.92,136.72,136.11,135.41,134.77,131.54,130.57,130.17,129.36,129.34,128.92,128.61,128.47, 128.32,128.03,127.60,125.83,125.72,125.61,122.80,114.73,103.47,48.68,37.83,29.59,21.88,19.78.HRMS(ESI)m / zCalcd forC 27 H 22 N2OSe[M+H] + :471.0970,found:471.0969.

[0169] Example 35

[0170]

[0171] The reaction steps and operating conditions are the same as those of Example 33, except that the R 3The reaction system was modified to obtain the raw material 1af with a yield of 76%. The difference between the two reaction systems was that the raw material added to the reaction system was 1af (74.22 mg, 0.2 mmol) instead of the reaction substrate (1ac). The reaction was stopped under blue light (465 nm) for 12 hours and then post-processed to obtain a white solid 2af (90.4 mg, 95% yield). The target product was confirmed by nuclear magnetic resonance and high-resolution mass spectrometry. The product parameters were 10-chloro-5-methyl-12-phenyl-5-(selenocyanatomethyl)indolo[2,1-a]isoquinolin-6(5H)-one (2ae): New compound. White solid (90.4 mg, 95%); Mp: 165.6-166.6℃; 1 H NMR (600MHz, CDCl3) δ8.47(d,J=8.7Hz,1H),7.58(t,J=7.0Hz,2H),7.55-7.52(m,1H),7.50(d,J=7.1Hz,2H),7.45(d,J=7.7Hz, 1H),7.41-7.35(m,3H),7.29(d,J=2.0Hz,1H),7.16-7.09(m,1H),3.90(d,J=11.9Hz,1H),3.80(d,J=11.9Hz,1H),1.87(s,3H). 13 C NMR (150MHz, CDCl3) δ171.69,135.89,133.82,132.89,132.51,131.07,130.13,130.08,129.68,129.58,128.81,1 28.24,126.59,126.16,126.02,125.09,120.92,119.58,117.71,102.67,48.94,37.90,29.45.HRMS(ESI)m / zCalcd for C 25 H 17 ClN2OSe[M+H] + :477.0267,found:477.0259.

[0172] Example 36

[0173]

[0174] The reaction steps and operating conditions are the same as those of Example 33, except that the R 3The reaction system was modified to obtain a disubstituted Cl, yielding 1ag (76%). The difference in the reaction system was that 1ag (81.01 mg, 0.2 mmol) was added to the reaction system instead of the reaction substrate (1ac). The reaction was stopped under blue light (465 nm) for 12 hours and then post-processed to obtain a white solid 2ag (33.6 mg, 33% yield). Nuclear magnetic resonance spectroscopy and high-resolution mass spectrometry confirmed the target product. The product parameters were: 8,9-dichloro-5-methyl-12-phenyl-5-(selenocyanatomethyl)indolo[2,1-a]isoquinolin-6(5H)-one (2af): New compound. Yellow oily liquid (33.6 mg, 33%). 1 H NMR (600MHz, CDCl3) δ7.58(t,J=6.7Hz,2H),7.54(dt,J=2.6,1.3Hz,1H),7.47(d,J=6.8Hz,2H),7 .42-7.38(m,4H),7.14-7.10(m,2H),3.88(d,J=12.2Hz,1H),3.77(d,J=12.2Hz,1H),1.96(s,3H). 13 C NMR (150MHz, CDCl3) δ172.11,136.49,134.62,133.15,132.93,132.54,131.25,130.33,130.07,129.75,129.61,1 28.80,128.20,127.10,125.99,125.96,125.45,120.53,118.84,103.20,50.68,36.88,28.83.HRMS(ESI)m / zCalcd for C 25 H 17 Cl2N2OSe[M+H] + :510.9877,found:510.9869.

[0175] Example 37

[0176]

[0177] According to the previous preparation literature report (Y.Yuan, Y.Zheng, B.Xu, et al., ACS Catal.2020, 10, 6676-6681.), in a round-bottom flask (50 mL) equipped with a magnetic stirrer, para-substituted benzaldehyde (the raw material R1 substituent in this example is H) (0.58 mL, 5.0 mmol) and NaHSO3 (5.73 g, 55.0 mmol) were mixed in H2O (20.0 mL) and added. When the mixture reached reflux temperature, o-phenylenediamine (0.54 g, 5.0 mmol) was added. The resulting mixture was stirred for 3 hours. After completion of the reaction, it was monitored by TLC analysis. After the reaction mixture was cooled to room temperature, it was vacuum filtered through a glass funnel. The residue was washed with water (20 mL × 2) and dried in an air-drying oven to obtain the corresponding product F.

[0178] Synthesis of N-Methacryloyl-2-phenylbenzimidazole

[0179] To a solution of F (0.63 g, 3 mmol) and DMAP (73 mg, 0.6 mmol) in DCM (6 ml) was added Et3N (0.83 mL, 6 mmol). At 0°C, methacryloyl chloride (0.58 mL, 6 mmol) was slowly added dropwise to the solution. The solution was warmed to room temperature and stirred at room temperature for 12 hours. According to TLC analysis, the reaction was complete, and water (20 mL) was added to the mixture, which was extracted with DCM (15 mL×3). The organic solvent was then concentrated in vacuo. The residue was purified by flash column chromatography using ethyl acetate and petroleum ether as eluents to obtain 1ah, i.e., the substituent R 1 The raw material 1ah was obtained with a yield of 79% for H. The difference in the reaction system is that the raw material added to the reaction system is 1ag (52.42 mg, 0.2 mmol) instead of the reaction substrate (1a). The reaction was stopped under blue light (465 nm) for 12 hours and then post-treated to obtain a white solid 2ah (30.8 mg, 33% yield). Nuclear magnetic resonance spectroscopy and high-resolution mass spectrometry were used to confirm that it was the target product. The parameters of the obtained product were 5-methyl-5-(selenocyanatomethyl)indolo[2,1-a]isoquinolin-6(5H)-one (2ag): New compound. White solid (30.8 mg, 53%); Mp: 116.9-117.3℃; 1H NMR (600MHz, CDCl3) δ8.53(d,J=7.6Hz,1H),8.31(d,J=7.2Hz,1H),7.84(d,J=7.3Hz,1H),7.65(t,J=7.2Hz, 1H),7.59(t,J=7.5Hz,1H),7.49-7.44(m,3H),3.92(d,J=12.3Hz,1H),3.78(d,J=12.3Hz,1H),1.88(s,3H). 13 C NMR (150MHz, CDCl3) δ171.47,149.19,144.24,138.31,132.60,131.21,129.32,126.76,126.58 ,126.21(d,J=6Hz),123.13,120.29,115.83,101.08,49.79,37.90,29.73.HRMS(ESI)m / zCalcd for C 18 H 13 N3OSe[M+H] + :368.0300,found:368.0300.

[0180] Example 38

[0181]

[0182] The reaction steps and operating conditions are the same as those of Example 37, except that R 1 The raw material 1ai was obtained for Me with a yield of 81%. The difference in the reaction system was that the raw material added to the reaction system was 1ai (55.23 mg, 0.2 mmol) instead of the reaction substrate (1ah). The reaction was stopped under blue light (465 nm) for 12 hours and then post-processed to obtain a white solid 2ah (30.8 mg, 33% yield). Nuclear magnetic resonance spectroscopy and high-resolution mass spectrometry were used to confirm the target product. The obtained product parameters were 5-methyl-5-(selenocyanatomethyl)indolo[2,1-a]isoquinolin-6(5H)-one (2ah): New compound. White solid (40.4 mg, 53%); Mp: 135.1-135.6℃; 1H NMR (600MHz, CDCl3) δ8.40(d,J=8.0Hz,1H),8.28(d,J=7.6Hz,1H),7.81(d,J=7.6Hz,1H),7.47-7.41(m,2H), 7.39(d,J=7.9Hz,1H),7.26(s,1H),3.91(d,J=12.2Hz,1H),3.78(d,J=12.2Hz,1H),2.50(s,3H),1.87(s,3H). 13 C NMR (150MHz, CDCl3) δ171.70,149.45,144.31,143.46,138.31,131.18,130.31,126.70 (d,J=4.5Hz) ,126.50,125.96,120.39,120.12,115.74,101.40,49.67,37.76,29.77,22.13.HRMS(ESI)m / zCalcd for C 19 H 15 N3OSe[M+H] + :382.0453,found:382.0453.

[0183] Example 39

[0184]

[0185] The reaction steps and operating conditions are the same as those in Example 37, except that the R 3 H, R 1 The raw material 1aj was obtained from F with a yield of 79%. The difference in the reaction system was that the raw material 1aj (56.02 mg, 0.2 mmol) was added to the reaction system instead of the reaction substrate (1ah). The reaction was stopped under blue light (465 nm) for 12 hours and then post-treated to obtain a white solid 2aj (24.6 mg, 32% yield). Nuclear magnetic resonance spectroscopy and high-resolution mass spectrometry were used to confirm the target product. The obtained product parameters were 3-fluoro-5-methyl-5-(selenocyanatomethyl)indolo[2,1-a]isoquinolin-6(5H)-one (2ai): New compound. White solid (24.6 mg, 32%); Mp: 139.2-139.7℃; 1H NMR (600MHz, CDCl3) δ8.54(dd,J=8.7,5.7Hz,1H),8.29(d,J=7.3Hz,1H),7.82(d,J=7.3Hz,1H),7.48-7.43(m,2H),7 .30(td,J=8.5,2.3Hz,1H),7.17(dd,J=9.2,2.3Hz,1H),3.87(d,J=12.5Hz,1H),3.71(d,J=12.5Hz,1H),1.89(s,3H). 13 C NMR (150MHz, CDCl3) δ170.85, 165.26 (d, J = 253.5Hz), 148.43, 144.16, 140.93 (d, J = 7.5Hz), 131.10, 129.33 (d, J = 9.0Hz), 126.67,126.26,120.24,119.66(d,J=3.0Hz),117.33(d,J=22.5),115.79,113.55(d,J=24),100.55,49.98,37.81,29.49. 19 F NMR(565MHz,CDCl3)δ-104.54.HRMS(ESI)m / zCalcd for C 18 H 12 FN3OSe[M+H] + :386.0202,found:386.0204.

[0186] Example 40

[0187]

[0188] The reaction steps and operating conditions are the same as those of Example 137, except that the R 3 H, R 1The raw material 1ak was obtained with a yield of 80% for Cl. The reaction system differed in that 1ak (59.4 mg, 0.2 mmol) was added instead of the reaction substrate (1ah). The reaction was terminated under blue light (465 nm) for 12 hours and then post-processed to obtain a white solid 2ak (32.1 mg, 40% yield). Nuclear magnetic resonance spectroscopy and high-resolution mass spectrometry confirmed the target product. The product parameters were: 3-chloro-5-methyl-5-(selenocyanatomethyl)indolo[2,1-a]isoquinolin-6(5H)-one (2ak): New compound. White solid (32.1 mg, 40%); Mp: 161.8-162.3°C; 1 H NMR (600MHz, CDCl3) δ8.46 (d, J=8.5Hz, 1H), 8.29-8.28 (m, 1H), 7.83-7.81 (m, 1H), 7.56 (dd, J=8 .4,1.9Hz,1H),7.49-7.44(m,3H),3.88(d,J=12.5Hz,1H),3.72(d,J=12.4Hz,1H),1.89(s,3H). 13 C NMR (150MHz, CDCl3) δ170.72,148.30,144.16,139.94,138.85,131.14,129.86,128.06,126.7 2,126.62,126.44,121.72,120.34,115.82,100.60,49.83,37.71,29.44.HRMS(ESI)m / zCalcd for C 18 H 12 ClN3OSe[M+H] + :401.9907,found:401.9906.

[0189] Application Examples

[0190]

[0191] In addition, a derivatization experiment of the target product 2a obtained in Example 1 was carried out to further demonstrate the synthetic application of this scheme. The product 2a (0.2 mmol), TMSCF3 (0.4 mmol) and Cs2CO3 (0.4 mmol) were reacted under a nitrogen atmosphere with acetonitrile as a solvent for 15 hours. The SeCN group was successfully converted into the isoquinolinedione 3a containing the SeCF3 group with a yield of 94% (detected by nuclear magnetic resonance and high-resolution mass spectrometry). Its lipophilicity and transmembrane permeability were significantly enhanced, thereby improving its biological activity (Q. Wang, Z. Qi, F. Xie and X. Li, Adv. Synth. Catal., 2015, 357, 355-360.). Trifluoromethylselenide (CF3Se) also shows valuable electronic properties, such as strong electron-withdrawing property (Hamiett constant σp = 0.45, σm = 0.44) (C. Hansch, A. Leo, S. Hunger, K. H. Kim, D. Nikaitani and E. J. Lien, J. Med. Chem., 1973, 16, 1207-1216; C. Hansch, A. Leo and R. W. Taft, Chem. Rev., 1991, 91, 165-195.), and the Hansch-Leo parameter (π = 1.29) recently measured by Billard reflects high lipophilicity (Q. Glenadel, E. Ismalaj and T. Billard, Eur. J. Org. Chem., 2017, 530–533.). In addition, product 2a (0.2 mmol), diethyl phosphate (0.4 mmol) and DBU (0.2 mmol) were reacted in toluene (2 mL) for 5 h to give 3b in quantitative yield (detected by nuclear magnetic resonance and high-resolution mass spectrometry).

[0192] The above descriptions are merely embodiments of the present invention and are not intended to limit the patent scope of the present invention. Any equivalent structure or equivalent process transformation made using the contents of the present invention's description and drawings, or directly or indirectly applied in other related technical fields, are also included in the patent protection scope of the present invention.

Claims

1. A method for synthesizing isoquinolinone selenocyanide, characterized in that: N- (Hetero)aryl acrylamide is used as a substrate, potassium selenocyanate and an oxidant potassium persulfate are added, and a bifunctional catalyst of photocatalysis and phase transfer catalysis is added in a solvent. Under visible light conditions, the substrate is induced to synthesize a selenocyanated isoquinolinone compound; the bifunctional catalyst is PC4, PC4 is ; Visible light is blue light at 460-465 nm; The N- (Hetero)aryl acrylamide is N -Aryl acryloyl benzamide or 2-aryl- N -acryloyl indole or N -methacryloyl-2-phenylbenzimidazole compound, the selenocyanided isoquinolinone compound is selenocyanided isoquinolinone or indole [2, 1-a] isoquinolinone or benzimidazole [2, 1-a] isoquinolin-6 (5 H )-ketone compounds; N -Aryl acryloyl benzamide structure is as follows: ； 2-aryl- N -Acryloyl indole structure is as follows: ； N- The structure of methacryloyl-2-arylbenzimidazole is as follows: ； Selenium cyanide isoquinolinone or indole [2,1-a] isoquinolinone or benzimidazolo [2,1-a] isoquinolin-6 (5 H )-ketone structure is as follows: ； Substituent R 1 is H, halogen, alkyl having 1 to 4 carbon atoms, alkoxy having 1 to 4 carbon atoms, fluoroalkyl C n F m H x , n is 1-4, m is 1-9, x is one or more of 0-8, the number of substituents is 1-5; halogen is one or more of F, Cl, Br or I; the substituent R 2 It is an alkyl group having 1 to 4 carbon atoms, an alkyl group having 15 to 20 carbon atoms, a cycloalkyl group having 3 to 7 carbon atoms, a phenyl group, or an aryl group containing a substituent, wherein the substituent in the aryl group containing a substituent is an alkyl group or a fluoroalkyl group having 1 to 4 carbon atoms. n F m H x , n is 1-4, m is 1-9, x is one or more of 0-8; the substituent R 3 It is one or more of H, CH3 or halogen, and halogen is one or more of F, Cl, Br or I. The number of substituents is 1-5.

2. The synthesis method according to claim 1, wherein: The solvents are acetonitrile, dichloromethane, water, dichloromethane / water (4:1-1:4 by volume), methanol, N,N -dimethylformamide, N,N -dimethylacetamide, N - one or more of methylpyrrolidone, dimethyl sulfoxide and 1,2-dichloroethane, N The concentration of the (hetero)aryl acrylamide compound in the solvent is 0.1-1 M.

3. The synthesis method according to claim 2, wherein: The solvent was dichloromethane / water at a volume ratio of 1:

1. N The concentration of the (hetero)aryl acrylamide compound in the solvent is 0.1-0.3 M.

4. The synthesis method according to claim 1, wherein: The reaction is carried out in the presence of an oxidant, which is potassium persulfate; the molar concentration of the oxidant in the solvent is 0.05-0.2 M.

5. The synthesis method according to claim 4, wherein: The molar concentration of the oxidant to the solvent is 0.125-0.2 M.

6. The synthesis method according to claim 1, wherein: The molar concentration of the bifunctional catalyst in the solvent is 0.001-0.004 M.

7. The synthesis method according to claim 1, wherein: substrate The molar ratio of the amount of potassium selenocyanate (II) is 1:1-1:

3.

8. The synthesis method according to claim 1, wherein: The reaction is carried out under air atmosphere for 6-36 hours.

Images