A method for photocatalytic synthesis of tetracyclic quinazolinones under metal-free conditions

Abstract

The present invention discloses a method for photocatalytic synthesis of tetracyclic quinazolinones under metal-free conditions. The synthesis process of this method is as follows: In a glass reaction vessel, different types of substrates N-acyl-N-(2-bromobenzyl)amino nitriles are added in proportion, with N,N-diisopropylethylamine as an additive and 2,4,5,6-tetrakis(diphenylamino)isophthalonitrile (4-DPAIPN) as a catalyst. Using acetonitrile as a solvent, under a nitrogen atmosphere, the reaction is irradiated with two blue LEDs (450 - 460 nm) at 68 oC for 8 hours. After the crude product is separated and purified by column chromatography, tetracyclic quinazolinone derivatives are obtained. The present invention uses cheap and readily available 2-bromobenzylamine as a raw material, avoiding the use of precious metal catalysts, toxic reagents, and expensive raw materials. In addition, this reaction is simple to operate, has mild conditions, and excellent separation yields.

Description

Technical Field

[0001] The present invention belongs to the field of organic synthetic chemistry, and particularly relates to a method for synthesizing tetracyclic quinazolinones. Background Art

[0002] The tetracyclic quinazolinone skeleton widely exists in natural products, such as luotonins A, B and E, mackinazolinone, rutaecarpine, and deoxyvasicinone, etc. They have broad-spectrum biological activities, including specific cytotoxicity and effective inhibition of proteases, and play an important role in drug research and development (J. Org. Chem. 2016, 81, 7276−7281). Therefore, the synthesis of heterocyclic compounds containing the tetracyclic pyrroloquinazolinone scaffold has attracted great attention of synthetic chemists. Initially, the construction of the tetracyclic quinazolinone scaffold mainly relied on [Pd]-catalyzed cyclization (Org. Lett. 2009, 11, 3582-3585; Org. Biomol. Chem. 2015, 13, 4422-4425). With the development of free radical reactions in organic chemistry, tetracyclic quinazolinone compounds were synthesized by intramolecular free radical cyclization of N-acyl-N-(2-iodobenzyl)amino nitrile catalyzed by n-Bu3SnH or under light irradiation conditions with [Ir] (J. Org. Chem. 2016, 81, 7276−7281; Angew. Chem. Int. Ed. 2007, 46, 576-579). However, these methods require the use of expensive 2-iodobenzylamine, [Pd], [Ir], and toxic n-Bu3SnH as raw materials or catalysts, which increase the operational difficulties and costs in the synthesis of such tetracyclic compounds. Most importantly, it limits their availability in the pharmaceutical field. Therefore, it is of great theoretical and practical significance to develop a simple and green method to synthesize tetracyclic quinazolinone compounds starting from inexpensive and readily available raw materials. Summary of the Invention

[0003] The object of the present invention is to solve the limitations of the current synthesis of tetracyclic quinazolinone compounds, and to develop a metal-free photocatalytic reaction for synthesizing tetracyclic quinazolinones. The strategy of reducing N-acyl-N-(2-bromobenzyl)amino nitrile to aryl radicals through a visible light continuous induced electron transfer mechanism (ConPET) is used to achieve debromination cyclization to prepare tetracyclic quinazolinone derivatives.

[0004] Idea of the present invention: Using N-acyl-N-(2-bromobenzyl)amino nitrile as the raw material, 2,4,5,6-tetrakis(diphenylamino)isophthalonitrile (4-DPAIPN) as the catalyst, N,N-diisopropylethylamine as the additive, and acetonitrile as the solvent, under a nitrogen atmosphere and blue light irradiation conditions, a reductive debromination and intramolecular tandem cyclization reaction occurs at 68 o °C to efficiently achieve the synthesis of tetracyclic quinazolinone compounds. The present invention uses the non-metal photocatalyst 4-DPAIPN, avoiding the use of metal catalysts, toxic reagents, and expensive 2-iodobenzylamine. In addition, this reaction has simple operation, mild conditions, excellent separation yields, and a wide substrate scope.

[0005] The object of the present invention is achieved through the following technical solutions.

[0006] A method for photocatalytic synthesis of tetracyclic quinazolinone under metal-free conditions, comprising the following operating steps:

[0007] In a glass reaction vessel, add N-acyl-N-(2-bromobenzyl)amino nitrile, catalyst, and additive in proportion. Using an organic solvent as the solvent, under a nitrogen atmosphere and blue light irradiation conditions, stir magnetically at 68 o °C for 8 hours, then cool to room temperature. The reaction solution is extracted with ethyl acetate multiple times, the organic phases are combined, and after rotary evaporation under reduced pressure, a crude product is obtained. Finally, the tetracyclic quinazolinone derivative is prepared by column chromatography separation and purification;

[0008] Furthermore, the chemical reaction equation for photocatalytic synthesis of tetracyclic quinazolinone under metal-free conditions is as follows:

[0009]

[0010] In the formula, R 1 is selected from one or more of hydrogen, 2-methyl, 3-methyl, 4-methyl, 4-tert-butyl, 4-methoxy, 3,4-dimethoxy, 3,4,5-trimethoxy, 4-ethoxy;

[0011] Furthermore, the additive is one or more of triethylamine and N,N-diisopropylethylamine, preferably N,N-diisopropylethylamine.

[0012] Furthermore, the molar ratio of the additive to the N-acyl-N-(2-bromobenzyl)amino nitrile derivative in the feed is 1 to 3:1, preferably 2:1.

[0013] Furthermore, the organic solvent is one or more of dichloromethane, methanol, acetonitrile, tetrahydrofuran, DMSO, toluene, 1,4-dioxane, and DMF, and preferably acetonitrile is used as the solvent.

[0014] Furthermore, the debromination cyclization reaction time of the N-acyl-N-(2-bromobenzyl)amino nitrile is between 6 and 10 hours, and the preferred reaction time is 8 hours.

[0015] Furthermore, the catalyst is one or more of 4-DPAIPN, 2,4,5,6-tetrakazolyl isophthalonitrile (4CzIPN), 2,4,5-trikazolyl-6-(N-methylaniline) isophthalonitrile (3CzMPAIPN), 2,4,5-trikazolyl-6-(N-methyl-o-toluidino) isophthalonitrile (o-Me-3CzMPAIPN), and preferably 4-DPAIPN.

[0016] Furthermore, the molar ratio of the catalyst to the N-acyl-N-(2-bromobenzyl)amino nitrile compound is 0.01-1:1, and the preferred ratio is 0.03:1.

[0017] Furthermore, the target product tetracyclic quinazolinone is separated and purified by column chromatography, and the eluent can be a mixed solvent of petroleum ether and ethyl acetate, and the volume ratio of ethyl acetate to petroleum ether is between 1:3 and 10. The preferred developing agent is petroleum ether:ethyl acetate = 5:1.

[0018] The principle of the present invention is: under visible light irradiation, 4-DPAIPN forms the excited state 4-DPAIPN * , and then through a single electron transfer mechanism, a long-lived radical anion 4-DPAIPN is formed •− . 4-DPAIPN •− is irradiated by light again to form the excited state 4-DPAIPN •−* , and then 4-DPAIPN •−* undergoes a single electron transfer process with the raw material N-acyl-N-(2-bromobenzyl)amino nitrile to break the Csp2-Br bond to form an aryl radical intermediate, and releases the ground state 4-DPAIPN for the next catalytic cycle. The aryl radical intermediate undergoes an intramolecular radical cascade cyclization reaction to obtain a tetracyclic quinazolinone compound.

[0019] Compared with the prior art, the present invention has the following advantages and beneficial effects:

[0020] (1) The present invention realizes the photocatalytic debromination cyclization reaction of the Csp2-Br bond in N-acyl-N-(2-bromobenzyl)amino nitrile under metal-free conditions. In addition, the absence of a metal photocatalyst, mild conditions, and simple operation are the main characteristics of this reaction;

[0021] (2) The present invention utilizes visible light to induce 4-DPAIPN to form an excited state, and efficiently realizes the synthesis of tetracyclic quinazolinone compounds through a continuous photoinduced electron transfer mechanism. Compared with the existing methods, it has higher step economy and avoids the use of toxic reagents, expensive raw materials and noble metal catalysts. BRIEF DESCRIPTION OF THE DRAWINGS

[0022] Figure 1 and Figure 2 are the hydrogen spectrum and carbon spectrum of the target product obtained in Example 1;

[0023] Figure 3 and Figure 4 are the hydrogen spectrum and carbon spectrum of the target product obtained in Example 2;

[0024] Figure 5 and Figure 6 are the hydrogen spectrum and carbon spectrum of the target product obtained in Example 3;

[0025] Figure 7 and Figure 8 are the hydrogen spectrum and carbon spectrum of the target product obtained in Example 4; DETAILED DESCRIPTION OF THE INVENTION

[0026] The present invention will be further described below through specific examples, but the protection scope and implementation manner of the present invention are not limited thereto.

[0027] Example 1

[0028] Take a quartz reaction tube for standby, and successively add the weighed N-acyl-N-(2-bromobenzyl)amino nitrile (0.2 mmol), N,N-diisopropylethylamine (0.4 mmol), 4-DPAIPN (0.006 mmol) and acetonitrile (1 mL). React at 68 °C for 8 hours under blue light irradiation. Monitor by TLC. After the reaction is completed, cool to room temperature. Extract the reaction solution with ethyl acetate in small portions and combine the organic phases. Dry with anhydrous magnesium sulfate, filter, and rotary evaporate under reduced pressure to obtain a crude product. Finally, purify it by passing through a silica gel column to obtain the final product isoindolo[1,2-b]quinazolinone with a yield of 83%.

[0029] The hydrogen spectrum and carbon spectrum of the obtained target product are as shown in Figure 1 and Figure 2 shown, and the structure characterization data are as follows:

[0030] 11H NMR (500 MHz, CDCl3) δ 8.40 (d, J = 7.9 Hz, 1H), 8.20 (d, J = 7.5Hz, 1H), 7.82 (dt, J = 15.0, 8.0 Hz, 2H), 7.72 – 7.56 (m, 3H), 7.52 (t, J =7.4 Hz, 1H), 5.19 (s, 2H) ppm.

[0031] 13 C{ 1 1H} NMR (125 MHz, CDCl3) δ 160.7, 155.0, 149.5, 139.6, 134.3,132.7, 132.4, 128.9, 127.4, 126.5, 126.4, 123.6, 123.5, 120.6, 49.8 ppm.

[0032] HRMS (ESI-TOF) [M+H] + calcd. for C 15 13 10 N2O 235.0866; found 235.0873.

[0033] Based on the above characterization data, the structure of the target compound is as follows:

[0034]

[0035] Example 2

[0036] Take a quartz reaction tube and add N-(2-bromobenzyl)-N-cyano-2-methylbenzamide (0.2 mmol), N,N-diisopropylethylamine (0.4 mmol), 4-DPAIPN (0.006 mmol) and acetonitrile (1 mL) in sequence. React at 68 °C for 8 hours under blue light irradiation. Monitor by TLC. After the reaction is completed, cool to room temperature. Extract the reaction solution with ethyl acetate in small portions multiple times. Combine the organic phases and dry over anhydrous magnesium sulfate. Filter and concentrate under reduced pressure to obtain the crude product. Finally, purify by silica gel column chromatography to obtain the final product iso-9-methylindolo[1,2-b]quinazolinone with a yield of 71%.

[0037] The 1H NMR and 13C NMR spectra of the obtained target product are as Figure 3 and Figure 4 shown. The structure characterization data are as follows:

[0038] 11H NMR (500 MHz, CDCl3) δ 8.15 (d, J = 7.6 Hz, 1H), 7.66 (d, J = 8.0Hz, 1H), 7.60 (dd, J = 15.5, 6.7 Hz, 4H), 7.24 (d, J = 8.8 Hz, 1H), 5.10 (d,J = 5.7 Hz, 2H), 2.95 (d, J = 5.6 Hz, 3H) ppm.

[0039] 13 C{ 1 1H} NMR (125 MHz, CDCl3) δ 161.4, 154.6, 151.1, 141.1, 139.7,133.3, 132.7, 132.2, 129.2, 128.8, 125.7, 123.5, 123.5, 119.1, 49.8, 23.1ppm.

[0040] HRMS (ESI-TOF) [M+H] + calcd. for C 16 13 12 H11N2O 249.1022; found 249.1032.

[0041] Based on the above characterization data, the structure of the target compound is as follows:

[0042]

[0043] Example 3

[0044] Take a quartz reaction tube and add N-(2-bromobenzyl)-N-cyano-3-methylbenzamide (0.2 mmol), N,N-diisopropylethylamine (0.4 mmol), 4-DPAIPN (0.006 mmol) and acetonitrile (1 mL) in sequence. React at 68 °C for 8 hours under blue light irradiation. Monitor by TLC. After the reaction is completed, cool to room temperature. Extract the reaction solution with ethyl acetate in small portions multiple times. Combine the organic phases and dry with anhydrous magnesium sulfate. Filter and rotary evaporate under reduced pressure to obtain the crude product. Finally, purify it by silica gel column chromatography to obtain the final product iso-8-methylindolo[1,2-b]quinazolinone with a yield of 42%.

[0045] The 1H NMR and 13C NMR of the obtained target product are as Figure 5 and Figure 6 shown, and the structure characterization data are as follows:

[0046] 11H NMR (500 MHz, CDCl3) δ 8.22 (d, J = 8.0 Hz, 1H), 8.18 (d, J = 7.6Hz, 1H), 7.62 (d, J = 8.8 Hz, 3H), 7.56 (dt, J = 8.0, 3.9 Hz, 1H), 7.37 (t, J= 7.6 Hz, 1H), 5.13 (s, 2H), 2.72 (s, 3H) ppm.

[0047] 13 C{ 1 1H} NMR (125 MHz, CDCl3) δ 161.0, 153.6, 148.1, 139.5, 136.0,134.8, 133.2, 132.0, 128.7, 125.8, 124.1, 123.5, 123.4, 120.5, 49.6, 17.6.ppm.

[0048] HRMS (ESI-TOF) [M+H] + calcd. for C 16 13 12 H11N2O 249.1022; found 249.1032.

[0049] Based on the above characterization data, the structure of the target compound is as follows:

[0050]

[0051] Example 4

[0052] A quartz reaction tube was prepared and weighed N-(2-bromobenzyl)-N-cyano-4-methylbenzamide (0.2 mmol), N,N-diisopropylethylamine (0.4 mmol), 4-DPAIPN (0.006 mmol) and acetonitrile (1 mL) were added in sequence. The reaction was carried out at 68 °C for 8 hours under blue light irradiation. Monitored by TLC. After the reaction was completed, it was cooled to room temperature. The reaction solution was extracted with ethyl acetate in small portions and combined. The organic phase was dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure to obtain a crude product. Finally, the final product iso-7-methylindolo[1,2-b]quinazolinone was purified by silica gel column chromatography with a yield of 59%.

[0053] The 1H NMR and 13C NMR of the obtained target product are as Figure 7 and Figure 8 shown, and the structure characterization data are as follows:

[0054] 11H NMR (500 MHz, CDCl3) δ 8.17 (d, J = 8.1 Hz, 2H), 7.73 (d, J = 8.3Hz, 1H), 7.66 – 7.55 (m, 4H), 5.16 (s, 2H), 2.52 (s, 3H) ppm.

[0055] 13 C{ 1 1H} NMR (125 MHz, CDCl3) δ 160.6, 155.0, 149.6, 145.2, 139.7,132.8, 132.2, 128.8, 128.0, 127.1, 126.3, 123.5, 123.5, 118.2, 49.7, 21.9ppm.

[0056] HRMS (ESI-TOF) [M+H] + calcd. for C 16 H 12 N2O 249.1022; found 249.1028.

[0057] Based on the above characterization data, the structure of the target compound is as follows:

[0058]

[0059] Example 5

[0060] Take a quartz reaction tube and add successively weighed N-(2-bromobenzyl)-N-cyano-4-tert-butylbenzamide (0.2 mmol), N,N-diisopropylethylamine (0.4 mmol), 4-DPAIPN (0.006 mmol) and acetonitrile (1 mL). React at 68 °C for 8 hours under blue light irradiation. Monitor by TLC. After the reaction is completed, cool to room temperature. Extract the reaction solution with ethyl acetate in small portions and combine the organic phases. Dry over anhydrous magnesium sulfate, filter, and concentrate under reduced pressure to obtain a crude product. Finally, purify by silica gel column chromatography to obtain the final product iso-7-tert-butylindolo[1,2-b]quinazolinone with a yield of 52%.

[0061] The structure characterization data of the obtained target product are as follows:

[0062] 11H NMR (500 MHz, CDCl3) δ 8.31 (d, J = 8.4 Hz, 1H), 8.20 (d, J = 7.6Hz, 1H), 7.85 (s, 1H), 7.64 (d, J = 4.2 Hz, 2H), 7.62 – 7.55 (m, 2H), 5.16(s, 2H), 1.43 (s, 9H) ppm.

[0063] 13 C{ 1 1H} NMR (125 MHz, CDCl3) δ 160.6, 158.4, 155.0, 149.5, 139.7,132.8, 132.3, 124.6, 123.7, 123.5, 123.4, 118.1, 49.7, 35.4, 31.1 ppm.

[0064] HRMS (ESI-TOF) [M+H] + calcd. for C 19 13 18 N2O 291.1492; found 291.1503.

[0065] Based on the above characterization data, the structure of the target compound is as follows:

[0066]

[0067] Example 6

[0068] Take a quartz reaction tube and add the weighed N-(2-bromobenzyl)-N-cyano-4-methoxybenzamide (0.2 mmol), N,N-diisopropylethylamine (0.4 mmol), 4-DPAIPN (0.006 mmol) and acetonitrile (1 mL) in sequence. React at 68 °C for 8 hours under blue light irradiation. Monitor by TLC. After the reaction is completed, cool to room temperature. Extract the reaction solution with ethyl acetate in small portions and combine the organic phases. Dry over anhydrous magnesium sulfate, filter, and rotary evaporate under reduced pressure to obtain the crude product. Finally, purify by silica gel column chromatography to obtain the final product iso-7-methoxyindolo[1,2-b]quinazolinone with a yield of 67%.

[0069] The structure characterization data of the obtained target product are as follows:

[0070] 11H NMR (500 MHz, CDCl3) δ 8.25 (d, J = 8.9 Hz, 1H), 8.15 (d, J = 7.7Hz, 1H), 7.62 (s, 2H), 7.59 – 7.53 (m, 1H), 7.20 (d, J = 2.6 Hz, 1H), 7.05(dd, J = 8.8, 2.5 Hz, 1H), 5.12 (s, 2H), 3.94 (s, 3H) ppm.

[0071] 13 C{ 1 1H} NMR (125 MHz, CDCl3) δ 164.5, 160.2, 155.6, 151.8, 139.8,132.7, 132.3 128.8, 127.9, 123.5, 123.4, 116.5, 114.1, 108.0, 55.7, 49.7 ppm.

[0072] HRMS (ESI-TOF) [M+H] + calcd. for C 16 13 12 N2O2 265.0972; found 265.0982.

[0073] Based on the above characterization data, the structure of the target compound is as follows:

[0074]

[0075] Example 7

[0076] Take a quartz reaction tube and add successively weighed N-(2-bromobenzyl)-N-cyano-3,4-dimethoxybenzamide (0.2 mmol), N,N-diisopropylethylamine (0.4 mmol), 4-DPAIPN (0.006 mmol) and acetonitrile (1 mL). React at 68 °C for 8 hours under blue light irradiation. Monitor by TLC. After the reaction is completed, cool to room temperature. Extract the reaction solution with ethyl acetate in small portions and combine the organic phases. Dry over anhydrous magnesium sulfate, filter, and concentrate under reduced pressure to obtain a crude product. Finally, purify by silica gel column chromatography to obtain the final product iso-7,8-dimethoxyindolo[1,2-b]quinazolinone with a yield of 54%.

[0077] The structure characterization data of the obtained target product are as follows:

[0078] 11H NMR (500 MHz, CDCl3) δ 8.13 (d, J = 7.6 Hz, 1H), 7.69 (s, 1H), 7.62(d, J = 4.9 Hz, 2H), 7.59 – 7.54 (m, 1H), 7.23 (s, 1H), 5.14 (s, 2H), 4.02(d, J = 2.6 Hz, 6H) ppm.

[0079] 13 C{ 1 1H} NMR (125 MHz, CDCl3) δ 160.0, 154.8, 153.9, 148.8, 145.7,139.4, 132.9, 131.9, 128.8, 123.5, 123.0, 113.9, 107.8, 105.5, 56.3, 49.8ppm.

[0080] HRMS (ESI-TOF) [M+H] + calcd. for C 17 13 14 H11N2O3 295.1077; found 249.295.1088.

[0081] Based on the above characterization data, the structure of the target compound is as follows:

[0082]

[0083] Example 8

[0084] Take a quartz reaction tube and add N-(2-bromobenzyl)-N-cyano-3,4,5-trimethoxybenzamide (0.2 mmol), N,N-diisopropylethylamine (0.4 mmol), 4-DPAIPN (0.006 mmol) and acetonitrile (1 mL) in sequence. React at 68 °C for 8 hours under blue light irradiation. Monitor by TLC. After the reaction is completed, cool to room temperature. Extract the reaction solution with ethyl acetate in small portions and combine the organic phases. Dry over anhydrous magnesium sulfate, filter, and concentrate under reduced pressure to obtain a crude product. Finally, purify by silica gel column chromatography to obtain the final product iso-6,7,8-trimethoxyindolo[1,2-b]quinazolinone with a yield of 35%.

[0085] The structure characterization data of the obtained target product are as follows:

[0086] 11H NMR (500 MHz, CDCl3) δ 8.24 (d, J = 7.6 Hz, 1H), 7.63 (d, J = 4.0Hz, 2H), 7.58 (s, 2H), 5.16 (s, 2H), 4.17 (s, 3H), 4.06 (s, 3H), 4.01 (s, 3H) ppm.

[0087] 13 C{ 1 1H} NMR (125 MHz, CDCl3) δ 160.2, 153.0, 152.5, 148.1, 147.8, 139.7, 139.3, 133.1, 131.9, 128.8, 123.6, 123.4, 116.8, 101.6, 62.4, 61.4, 56.3, 49.8 ppm.

[0088] HRMS (ESI-TOF) [M+H] + calcd. for C 18 1 16 H1N2O4 325.1183; found 325.1190.

[0089] Based on the above characterization data, the structure of the target compound is as follows:

[0090]

[0091] Example 9

[0092] Take a quartz reaction tube and add successively weighed N-(2-bromobenzyl)-N-cyano-4-ethoxybenzamide (0.2 mmol), N,N-diisopropylethylamine (0.4 mmol), 4-DPAIPN (0.006 mmol) and acetonitrile (1 mL). React at 68 °C for 8 hours under blue light irradiation. Monitor by TLC. After the reaction is completed, cool to room temperature. Extract the reaction solution with ethyl acetate in small portions and combine the organic phases. Dry over anhydrous magnesium sulfate, filter, and concentrate under reduced pressure to obtain a crude product. Finally, purify by silica gel column chromatography to obtain the final product iso-7-ethoxyindolo[1,2-b]quinazolinone with a yield of 73%.

[0093] The structure characterization data of the obtained target product are as follows:

[0094] 11H NMR (500 MHz, CDCl3) δ 8.26 (d, J = 8.8 Hz, 1H), 8.16 (d, J = 7.7Hz, 1H), 7.63 (s, 2H), 7.60 – 7.56 (m, 1H), 7.20 (d, J = 2.4 Hz, 1H), 7.05(dd, J = 8.9, 2.5 Hz, 1H), 5.13 (s, 2H), 4.19 (q, J = 7.0 Hz, 2H), 1.49 (t, J= 7.0 Hz, 3H) ppm.

[0095] 13 C{ 1 1H} NMR (125 MHz, CDCl3) δ 163.9, 160.3, 155.6, 151.8, 139.8,132.8, 132.3, 128.8, 127.9, 123.5, 123.4, 116.9, 114.0, 108.5, 64.0, 49.7,14.7 ppm.

[0096] HRMS (ESI-TOF) [M+H] + calcd. for C 17 1H 14 N2O2 279.1128; found 279.1138.

[0097] Based on the above characterization data, the structure of the target compound is as follows:

[0098]

[0099] The above embodiments are partial embodiments of the method of the present invention, but this does not limit the specific implementation manners of the present invention. Any substitution of substituents, change of the basic skeleton, and simplification of conditions made without departing from the spirit and principle of the present invention shall be attributed to equivalent substitution manners and are all included in the protection scope of the present invention.

Claims

1. A method for photocatalytic synthesis of tetracyclic quinazolinones under metal-free conditions, characterized in that, It comprises the following steps: In a glass reaction vessel, N-substituted or unsubstituted benzoyl-N-(2-bromobenzyl)amino nitrile, a catalyst, and an additive are added in proportion. Using an organic solvent as the solvent, under a nitrogen atmosphere, under blue light irradiation conditions at 68 o °C, stir magnetically for 8 hours, then cool to room temperature. The reaction solution is extracted with ethyl acetate multiple times, and the organic phases are combined. After rotary evaporation under reduced pressure, a crude product is obtained. Finally, the tetracyclic quinazolinone derivative is prepared by column chromatography separation and purification; the chemical reaction equation for synthesizing the tetracyclic quinazolinone is shown as follows: , where R 1 is selected from one or more of hydrogen, 2-methyl, 3-methyl, 4-methyl, 4-tert-butyl, 4-methoxy, 3,4-dimethoxy, 3,4,5-trimethoxy, 4-ethoxy; the additive is one or more of triethylamine and N,N-diisopropylethylamine; the catalyst is 4-DPAIPN.

2. The preparation method according to claim 1, characterized in that, The molar ratio of the additive to the N-substituted or unsubstituted benzoyl-N-(2-bromobenzyl)amino nitrile derivative is 2:

1.

3. The preparation method according to claim 1, characterized in that, The organic solvent is one or more of dichloromethane, methanol, acetonitrile, tetrahydrofuran, DMSO, toluene, 1,4-dioxane, and DMF.

4. The preparation method according to claim 1, characterized in that, The molar ratio of the catalyst to the N-substituted or unsubstituted benzoyl-N-(2-bromobenzyl)amino nitrile compound is 0.03:

1.

5. The preparation method according to claim 1, characterized in that, The reaction time of the method for photocatalytic synthesis of tetracyclic quinazolinone under metal-free conditions is 6 to 10 hours.

6. The preparation method according to claim 1, characterized in that, The target product, tetracyclic quinazolinone derivative, is purified by column chromatography, and the eluent is a mixed solvent of petroleum ether and ethyl acetate, and the mixing ratio is: petroleum ether:ethyl acetate = 10:1 to 3:1.

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