A method for electrochemical synthesis of quinazolinone derivatives

Abstract

The present invention relates to the field of organic synthesis technology, and more particularly to an electrochemical synthesis method for quinazolinone derivatives. In the present invention, an isatoic anhydride compound, a styrene compound, a methylamine hydrochloride compound, an electrolyte, and an organic solvent are mixed to obtain a reaction solution. The reaction solution is then energized to induce an electrochemical reaction, thereby obtaining the quinazolinone derivative. This method does not require the use of metal catalysts or strong oxidants, and reaction media such as the electrolyte and solvent are recyclable. It has the advantages of readily available raw materials, simple operation, and environmental friendliness.

Description

Technical Field

[0001] The present invention relates to the technical field of organic synthesis, in particular to an electrochemical synthesis method of quinazolinone derivatives. Background Art

[0002] Quinazolinones belong to a family of nitrogen-containing aromatic compounds that can be used in the chemical synthesis of various useful therapeutic drugs. Quinazolinones have been reported to have targeted effects in anticancer, anti-inflammatory, osteoporosis treatment, anticonvulsant, antifungal, diuretic, antibacterial, antihypertensive, and hypolipidemic activities. Traditional methods for synthesizing quinazolinone derivatives include the reductive cyclization of complex aromatic azides, the cyclization of anthranilic acid derivatives, and intramolecular Mit-Sunobu reactions. However, these methods all suffer from harsh reaction conditions.

[0003] In order to reduce the requirements for reaction conditions, catalytic means are often used in the existing technology to synthesize quinazolinone derivatives. The main synthesis methods include: metal-catalyzed activation of benzylic C-H bonds, metal-catalyzed N-arylation cyclization, photoinduced free radical tandem cyclization, microwave-assisted intramolecular Friedel-Crafts type cyclization, electrochemical N-O bond cleavage and free radical synthesis. Representative synthesis methods include:

[0004] In 2018, Gong's group developed an electrochemical dehydrogenation method to synthesize quinazolinone derivatives under metal-free and oxidant-free conditions by combining acid catalysis and TEMPO catalysis for cyclization reaction (Cao, L.; Huo, H.; Zeng, H.; Yu, Y.; Lu, D.; Gong, Y., One-Pot Synthesis of Quinazolin-4(3H)-ones through Anodic Oxidation and the Related Mechanistic Studies. Advanced Synthesis & Catalysis. 2018, 360, 4764-4773.). In 2018, Ke Fang's team disclosed an effective method for synthesizing quinazolinone derivatives through the efficient coupling reaction of amidine with substituted 2-halogenated benzoic acid under microwave irradiation in water (Ke, F.; Liu, C.; Zhang, P.; Xu, J.; Chen, X., Efficient and selective microwave-assisted copper-catalyzed synthesis of quinazolinone derivatives inaqueous. Synthetic Communications. 2018, 48, 3089-3098.).

[0005] In 2019, Seohoo Lee's research team used DABCO as an alkaline catalyst and potassium persulfate as an added condition to use DMSO as a source of methyl groups for intramolecular oxidation to form rings, and assisted the generation of a series of quinazolinone derivatives (Lee, S.; Sim, J.; Jo, H.; Viji, M.; Srinu, L.; Lee, K.; Lee, H.; Manjunatha, V.; Jung, J.-K., Transition metal-free synthesis of quinazolinones using dimethyl sulfoxide as a synthon. Organic & Biomolecular Chemistry. 2019, 17, 8067-8070.). In 2020, Wang Ning et al. reported a Rh-catalyzed synthesis of a series of monofluoroolefin quinazolinone derivatives using 2-arylquinazolinone as the reaction substrate and 2,2-difluorovinyl tosylate as the monofluoro reagent (Wang, N.; Yang, Q.; Deng, Z.; Mao, X.; Peng, Y., Rhodium-Catalyzed Merging of 2-Arylquinazolinone and 2,2-DifluorovinylTosylate: Diverse Synthesis of Monofluoroolefin Quinazolinone Derivatives. ACSOmega. 2020, 5, 14635-14644.).

[0006] In 2021, Yi Lin et al. synthesized representative quinazolinone derivatives through the metal-free nitrogen heterocycle of isocyanate and secondary amine amide, with the assistance of 2-bromopyridine as a base catalyst, and activated N-aryl amide and isocyanate with trifluoroanhydride (Tf2O), realizing the one-pot synthesis of 2,3-dialkyl-substituted quinazolinones (Lin, Y.; He, S.-F.; Geng, H.; Xiao, Y.-C.; Ji, K.-L.; Zheng, J.-F.; Huang, P.-Q., Chemoselective Reactions of Isocyanates with Secondary Amides: One-Pot Construction of 2,3-Dialkyl-Substituted Quinazolinones. The Journal of Organic Chemistry. 2021, 86, 5345-5353.).

[0007] However, these methods still face challenges such as high catalyst costs, environmental pollution from heavy metal catalysts, stringent reaction temperatures for one-pot methods, and generally low yields for microwave methods. Therefore, developing green, economical, simple, efficient, and widely adaptable methods for synthesizing quinazolinone derivatives is of great significance. Summary of the Invention

[0008] The object of the present invention is to provide an electrochemical synthesis method for quinazolinone derivatives, which can achieve simple operation and efficient reaction for preparing quinazolinone derivatives.

[0009] In order to achieve the above-mentioned object of the invention, the present invention provides the following technical solutions:

[0010] A method for electrochemically synthesizing a quinazolinone derivative comprises the following steps:

[0011] mixing an isatoic anhydride compound, a styrene compound, a methylamine hydrochloride compound, an electrolyte and an organic solvent to obtain a reaction solution;

[0012] applying electricity to the reaction solution to perform an electrochemical reaction to obtain a quinazolinone derivative;

[0013] The structure of the isatoic anhydride compound is

[0014] The structure of the styrene compound is

[0015] The structure of the methylamine hydrochloride compound is

[0016] The structure of the quinazolinone derivative is

[0017] Among them, R 1 Contains at least one of hydrogen, an alkyl group having 1 to 3 carbon atoms, a halogen, or an alkoxy group having 1 to 3 carbon atoms;

[0018] R 2 Contains phenyl, furyl, pyridyl, thienyl or substituted phenyl, wherein the substituent of the substituted phenyl contains alkyl having 1 to 3 carbon atoms, alkoxy having 1 to 3 carbon atoms or halogen;

[0019] R 3 Contains an alkyl group having 1 to 3 carbon atoms, a benzene ring or a substituted phenyl group; the substituent of the substituted phenyl group contains an alkyl group having 1 to 3 carbon atoms, an alkoxy group having 1 to 3 carbon atoms, a cycloalkyl group having 3 to 5 carbon atoms or a halogen;

[0020] The organic solvent comprises methanol.

[0021] Optionally, the isatoic anhydride compound of the structure shown in Formula II comprises isatoic anhydride, 6-chloroisatoic anhydride, 6-methylisatoic anhydride or 5-bromoisatoic anhydride; the molar ratio of the isatoic anhydride compound, styrene compound, methylamine hydrochloride compound and electrolyte is 0.5-1:1-5:1-2.5:1-2.

[0022] Optionally, the styrene compound of the structure shown in Formula III includes styrene, p-methylstyrene, 2-vinylnaphthalene, 2-vinylthiophene, p-fluorostyrene, p-methoxystyrene or 3,4-dimethoxystyrene.

[0023] Optionally, the methylamine hydrochloride compound of the structure shown in Formula IV comprises methylamine hydrochloride, ethylamine hydrochloride, cyclopropylamine hydrochloride, aniline hydrochloride, p-methoxyaniline hydrochloride or p-fluoroaniline hydrochloride.

[0024] Optionally, the electrolyte comprises at least one of tetrabutylammonium chloride, tetrabutylammonium perchlorate, potassium hexafluorophosphate, tetrabutylammonium bromide or tetrabutylammonium tetrafluoroborate.

[0025] Optionally, the organic solvent further comprises at least one of acetonitrile, water, acetone or dimethyl sulfoxide; and the concentration of the isatoic anhydride compound in the reaction solution is 0.0833 to 0.1667 mol / L.

[0026] Optionally, the electrochemical reaction has a current of 5 to 10 mA, a temperature of 60 to 90° C., and a time of 8 to 24 hours.

[0027] In the electrochemical synthesis method described herein, a styrene compound is oxidized at the anode to form the corresponding free radical cation, which then reacts with methanol via 1,2 addition to form (1,2-dimethoxyethyl)benzene. Subsequently, (dimethoxymethyl)benzene undergoes anodic reoxidation and C-C bond cleavage to form (dimethoxymethyl)benzene, which is hydrolyzed in a solvent to form benzaldehyde. Isatoic anhydride compounds and methylamine from methylamine hydrochloride compounds undergo decarboxylation to form an o-aminobenzamide analog. This is then dehydrated and N-benzylated with benzaldehyde to form N-benzylated o-aminobenzamide, which then undergoes cyclodehydrogenation to produce the product quinazolinone. Simultaneously, hydrogen ions are reduced to hydrogen at the cathode. The method, which eliminates the need for metal catalysts or strong oxidants, utilizes only an electrically induced, cyclic catalytic amount of anhydride to oxidize the substrate, achieving catalytic dehydrogenation. Hydrogen and carbon dioxide are produced as byproducts. The reaction medium can be recycled and reused, resulting in virtually zero waste, three wastes, and environmentally friendly emissions. The method is environmentally friendly, with readily available raw materials, simple operation, and environmental friendliness, offering significant practical value and socioeconomic benefits. DETAILED DESCRIPTION

[0028] The present invention provides an electrochemical synthesis method for quinazolinone derivatives, comprising the following steps:

[0029] mixing an isatoic anhydride compound, a styrene compound, a methylamine hydrochloride compound, an electrolyte and an organic solvent to obtain a reaction solution;

[0030] applying electricity to the reaction solution to perform an electrochemical reaction to obtain a quinazolinone derivative;

[0031] The structure of the isatoic anhydride compound is

[0032] The structure of the styrene compound is

[0033] The structure of the methylamine hydrochloride compound is

[0034] The structure of the quinazolinone derivative is

[0035] Among them, R 1 Contains at least one of hydrogen, an alkyl group having 1 to 3 carbon atoms, a halogen, or an alkoxy group having 1 to 3 carbon atoms;

[0036] R 2 Contains phenyl, furyl, pyridyl, thienyl or substituted phenyl, wherein the substituent of the substituted phenyl contains alkyl having 1 to 3 carbon atoms, alkoxy having 1 to 3 carbon atoms or halogen;

[0037] R 3 Contains an alkyl group having 1 to 3 carbon atoms, a benzene ring or a substituted phenyl group; the substituent of the substituted phenyl group contains an alkyl group having 1 to 3 carbon atoms, an alkoxy group having 1 to 3 carbon atoms, a cycloalkyl group having 3 to 5 carbon atoms or a halogen; the substituent position of the substituted phenyl group contains at least one of the 2nd, 3rd or 4th positions of the benzene ring;

[0038] The organic solvent comprises methanol.

[0039] In the present invention, the isatoic anhydride compound of the structure shown in Formula II preferably comprises isatoic anhydride, 6-chloroisatoic anhydride, 6-methylisatoic anhydride or 5-bromoisatoic anhydride; the molar ratio of the isatoic anhydride compound, styrene compound, methylamine hydrochloride compound and electrolyte is preferably 0.5-1:1-5:1-2.5:1-2, and more preferably 0.75-1:2-4.5:1.5-2:1-1.5.

[0040] In the present invention, the styrene compound of the structure represented by formula III preferably comprises styrene, p-methylstyrene, 2-vinylnaphthalene, 2-vinylthiophene, p-fluorostyrene, p-methoxystyrene or 3,4-dimethoxystyrene.

[0041] In the present invention, the methylamine hydrochloride compound of the structure shown in formula IV preferably comprises methylamine hydrochloride, ethylamine hydrochloride, cyclopropylamine hydrochloride, aniline hydrochloride, p-methoxyaniline hydrochloride or p-fluoroaniline hydrochloride.

[0042] In the present invention, the electrolyte preferably comprises at least one of tetrabutylammonium chloride, tetrabutylammonium perchlorate, potassium hexafluorophosphate, tetrabutylammonium bromide or tetrabutylammonium tetrafluoroborate.

[0043] In the present invention, the organic solvent preferably further comprises at least one of acetonitrile, water, acetone or dimethyl sulfoxide; when the organic solvent is more than one of the above, the ratio between the organic solvents is not particularly limited and can be determined according to actual conditions; the concentration of the isatoic anhydride compound in the reaction solution is preferably 0.0833 mol / L to 0.1667 mol / L.

[0044] In the present invention, the energization is preferably to insert the positive electrode material and the negative electrode material into the reaction solution. The positive electrode material is preferably graphite felt, carbon rod electrode, platinum electrode, and more preferably graphite felt; the negative electrode material is preferably platinum electrode, nickel electrode or foam nickel electrode.

[0045] In the present invention, the general reaction formula of the electrochemical reaction is:

[0046]

[0047] In the present invention, the current of the electrochemical reaction is preferably 5-10 mA, more preferably 5-8 mA; the temperature is preferably 60-90° C., more preferably 70-80° C.; the time is preferably 8-24 h, more preferably 12-19 h, and even more preferably 14-18 h.

[0048] In the present invention, after the electrochemical reaction is completed, the method preferably includes cooling the reaction liquid, washing the positive electrode material and combining the washing liquid, performing microwave ultrasound on the electrode material in the combined washing liquid to obtain an electrode washing liquid, combining the cooled reaction liquid and the electrode washing liquid, and then performing reduced pressure distillation to evaporate the solvent to obtain a concentrate; eluting the concentrate with an eluent, and then separating by silica gel column chromatography to obtain a quinazolinone derivative.

[0049] The positive electrode material is preferably washed three times with ethyl acetate, and the amount of ethyl acetate used in the washing process is adjusted according to actual needs;

[0050] The microwave ultrasound conditions are not particularly limited and can be adjusted according to actual conditions.

[0051] The conditions for the reduced pressure distillation are not particularly limited and can be adjusted according to actual conditions;

[0052] The eluent is preferably a mixture of petroleum ether and ethyl acetate, and the ratio and amount of petroleum ether and ethyl acetate in the eluent are adjusted according to actual needs.

[0053] In the present invention, the quinazolinone derivatives are preferably 3-methyl-2-phenylquinazolin-4(3H)-one (Ia), 6-chloro-3-methyl-2-phenylquinazolin-4(3H)-one (Ib), 3,6-dimethyl-2-phenylquinazolin-4(3H)-one (Ic), 5-bromo-3-methyl-2-phenylquinazolin-4(3H)-one (Id), 3-methyl-2-(p-tolyl)quinazolin-4(3H)-one (Ie), 3-methyl-2-(naphthalen-2-yl)quinazolin-4(3H)-one (If), 3-methyl-2-(p-tolyl)quinazolin-4(3H)-one (Ie), 3-methyl-2-(naphthalen-2-yl)quinazolin-4(3H)-one (If), 3-methyl-2-(p-tolyl)quinazolin-4(3H)-one (If), 3-methyl-2-(p-tolyl)quinazolin-4(3H)-one (If), 3-methyl-2-(p-tolyl)quinazolin-4(3H)-one (Ig ... -methyl-2-(thiophen-2-yl)quinazolin-4(3H)-one (Ig), 2-(4-fluorophenyl)-3-methylquinazolin-4(3H)-one (Ih), 2-(4-methoxyphenyl)-3-methylquinazolin-4(3H)-one (Ii), 3-(4-methoxyphenyl)-2-phenylquinazolin-4(3H)-one (Ij), 2-(3,4-dimethoxyphenyl)-3-methylquinazolin-4(3H)-one (Il) or 3-(4-fluorophenyl)-2-phenylquinazolin-4(3H)-one (Im).

[0054] The technical solutions provided by the present invention are described in detail below with reference to the embodiments, but they should not be construed as limiting the scope of protection of the present invention.

[0055] Example 1

[0056] Isatoic anhydride (IIa, 81.6 mg, 0.5 mmol), styrene (IIIa, 260.4 mg, 2.5 mmol), methylamine hydrochloride (IVa, 84.4 mg, 1.25 mmol), tetrabutylammonium chloride (138.9 mg, 0.5 mmol), acetonitrile (3 mL), and methanol (3 mL) were added to a reaction tube, and a graphite felt electrode and a platinum electrode were inserted. Then, an electric current was passed, and the current was adjusted to a constant current of 5 mA. The reaction was stirred at 80°C for 12 h. After the reaction was completed by monitoring with TLC, heating was stopped and the reaction solution was cooled to room temperature.

[0057] The graphite felt electrode was washed three times with dichloromethane, and the washing solutions obtained after washing were combined. The graphite felt electrode was immersed in the washing solutions and subjected to microwave ultrasound for 5 minutes to obtain an electrode washing solution. The cooled reaction solution and the electrode washing solution were combined and then subjected to reduced pressure distillation to remove the solvent to obtain a concentrate. The concentrate was eluted with a mixture of petroleum ether and ethyl acetate in a volume ratio of 15:1 as an eluent, and then separated by silica gel column chromatography to obtain 94.5 mg of a white solid with a yield of 80%. The white solid was 3-methyl-2-phenylquinazolin-4(3H)-one (Ia), and its structural formula is:

[0058]

[0059] The 3-methyl-2-phenylquinazolin-4(3H)-one (Ia) was subjected to hydrogen and carbon spectrum detection:

[0060] 1 H NMR (600MHz, Chloroform-d) δ8.34 (dt, J=7.8, 1.2Hz, 1H), 7.80-7.75 (m, 2H), 7.58 (dq, J=6.6, 3.6, 2.4Hz, 2H), 7.55-7.49 (m, 4H), 3.51 (s, 3H). 13 C NMR(150MHz,Chloroform-d)δ163.0,156.5,147.6,135.6,134.6,130.4,129.2,128.3,127.8,127.3,127.0,120.8,34.6.HRMS(ESI)calcd for C 15 H 13 N2O[M+H] + :237.1023,found:237.1036.

[0061] Example 2

[0062] Isatoic anhydride (IIa, 81.6 mg, 0.5 mmol), styrene (IIIa, 260.4 mg, 2.5 mmol), methylamine hydrochloride (IVa, 84.4 mg, 1.25 mmol), tetrabutylammonium perchlorate (170.96 mg, 0.5 mmol), acetonitrile (3 mL), and methanol (3 mL) were added to a reaction tube, and a graphite felt electrode and a platinum electrode were inserted. The current was adjusted to a constant current of 5 mA, and the reaction was stirred at 80°C for 14 h. After the reaction was completed, the heating was stopped and the reaction solution was cooled to room temperature.

[0063] The graphite felt electrode was washed three times with dichloromethane, and the washing liquids obtained after washing were combined. The graphite felt electrode was immersed in the washing liquid and subjected to microwave ultrasound for 5 minutes to obtain an electrode washing liquid. The cooled reaction liquid and the electrode washing liquid were combined and then subjected to reduced pressure distillation to evaporate the solvent to obtain a concentrate. The concentrate was eluted with a mixture of petroleum ether and ethyl acetate in a volume ratio of 15:1 as an eluent, and then separated by silica gel column chromatography to obtain 70.88 mg of a white solid with a yield of 60%. The white solid was detected by hydrogen spectrum and carbon spectrum, and the results were as follows:

[0064] 1H NMR (600MHz, Chloroform-d) δ8.34 (dt, J=7.8, 1.2Hz, 1H), 7.80-7.75 (m, 2H), 7.58 (dq, J=6.6, 3.6, 2.4Hz, 2H), 7.55-7.49 (m, 4H), 3.51 (s, 3H). 13 C NMR(150MHz,Chloroform-d)δ163.0,156.5,147.6,135.6,134.6,130.4,129.2,128.3,127.8,127.3,127.0,120.8,34.6.HRMS(ESI)calcd for C 15 H 13 N2O[M+H] + :237.1023,found:237.1036.

[0065] The obtained white solid is 3-methyl-2-phenylquinazolin-4(3H)-one (Ia).

[0066] Example 3

[0067] Isatoic anhydride (IIa, 81.6 mg, 0.5 mmol), styrene (IIIa, 260.4 mg, 2.5 mmol), methylamine hydrochloride (IVa, 84.4 mg, 1.25 mmol), potassium hexafluorophosphate (92 mg, 0.5 mmol), acetonitrile (3 mL), and methanol (3 mL) were added to a reaction tube, and a graphite felt electrode and a platinum electrode were inserted. The current was adjusted to a constant current of 5 mA, and the reaction was stirred at 80°C for 18 h. After the reaction was completed, the heating was stopped and the reaction solution was cooled to room temperature.

[0068] The graphite felt electrode was washed three times with dichloromethane, and the washing liquids obtained after washing were combined. The graphite felt electrode was immersed in the washing liquid and subjected to microwave ultrasound for 5 minutes to obtain an electrode washing liquid. The cooled reaction liquid and the electrode washing liquid were combined and then subjected to reduced pressure distillation to evaporate the solvent to obtain a concentrate. The concentrate was eluted with a mixture of petroleum ether and ethyl acetate in a volume ratio of 15:1 as an eluent, and then separated by silica gel column chromatography to obtain 79.15 mg of a white solid with a yield of 67%. The white solid was detected by hydrogen spectrum and carbon spectrum, and the results were as follows:

[0069] 1 H NMR (600MHz, Chloroform-d) δ8.34 (dt, J=7.8, 1.2Hz, 1H), 7.80-7.75 (m, 2H), 7.58 (dq, J=6.6, 3.6, 2.4Hz, 2H), 7.55-7.49 (m, 4H), 3.51 (s, 3H).13 C NMR(150MHz,Chloroform-d)δ163.0,156.5,147.6,135.6,134.6,130.4,129.2,128.3,127.8,127.3,127.0,120.8,34.6.HRMS(ESI)calcd for C 15 H 13 N2O[M+H] + :237.1023,found:237.1036.

[0070] The obtained white solid is 3-methyl-2-phenylquinazolin-4(3H)-one (Ia).

[0071] Example 4

[0072] Isatoic anhydride (IIa, 81.6 mg, 0.5 mmol), styrene (IIIa, 260.4 mg, 2.5 mmol), methylamine hydrochloride (IVa, 84.4 mg, 1.25 mmol), tetrabutylammonium bromide (161.2 mg, 0.5 mmol), acetonitrile (3 mL), and methanol (3 mL) were added to a reaction tube, and a graphite felt electrode and a platinum electrode were inserted. The current was adjusted to a constant current of 5 mA, and the reaction was stirred at 80°C for 14 h. After the reaction was completed by monitoring with TLC, heating was stopped and the reaction solution was cooled to room temperature.

[0073] The graphite felt electrode was washed three times with dichloromethane, and the washing liquids obtained after washing were combined. The graphite felt electrode was immersed in the washing liquid and subjected to microwave ultrasound for 5 minutes to obtain an electrode washing liquid. The cooled reaction liquid and the electrode washing liquid were combined and then subjected to reduced pressure distillation to evaporate the solvent to obtain a concentrate. The concentrate was eluted with a mixture of petroleum ether and ethyl acetate in a volume ratio of 15:1 as an eluent, and then separated by silica gel column chromatography to obtain 53.16 mg of a white solid with a yield of 45%. The white solid was detected by hydrogen spectrum and carbon spectrum, and the results were as follows:

[0074] 1 H NMR (600MHz, Chloroform-d) δ8.34 (dt, J=7.8, 1.2Hz, 1H), 7.80-7.75 (m, 2H), 7.58 (dq, J=6.6, 3.6, 2.4Hz, 2H), 7.55-7.49 (m, 4H), 3.51 (s, 3H). 13C NMR(150MHz,Chloroform-d)δ163.0,156.5,147.6,135.6,134.6,130.4,129.2,128.3,127.8,127.3,127.0,120.8,34.6.HRMS(ESI)calcd for C 15 H 13 N2O[M+H] + :237.1023,found:237.1036.

[0075] The obtained white solid is 3-methyl-2-phenylquinazolin-4(3H)-one (Ia).

[0076] Example 5

[0077] Isatoic anhydride (IIa, 81.6 mg, 0.5 mmol), styrene (IIIa, 260.4 mg, 2.5 mmol), methylamine hydrochloride (IVa, 84.4 mg, 1.25 mmol), tetrabutylammonium chloride (138.9 mg, 0.5 mmol), acetonitrile (3 mL), and methanol (3 mL) were added to a reaction tube, and a graphite felt electrode and a nickel electrode were inserted. The current was adjusted to a constant current of 5 mA, and the reaction was stirred at 80°C for 12 h. After the reaction was completed, the heating was stopped and the reaction solution was cooled to room temperature.

[0078] The graphite felt electrode was washed three times with dichloromethane, and the washing liquids obtained after washing were combined. The graphite felt electrode was immersed in the washing liquid and subjected to microwave ultrasound for 5 minutes to obtain an electrode washing liquid. The cooled reaction liquid and the electrode washing liquid were combined and then subjected to reduced pressure distillation to evaporate the solvent to obtain a concentrate. The concentrate was eluted with a mixture of petroleum ether and ethyl acetate in a volume ratio of 15:1 as an eluent, and then separated by silica gel column chromatography to obtain 69.06 mg of a white solid with a yield of 50%. The white solid was detected by hydrogen spectrum and carbon spectrum, and the results were as follows:

[0079] 1 H NMR (600MHz, Chloroform-d) δ8.34 (dt, J=7.8, 1.2Hz, 1H), 7.80-7.75 (m, 2H), 7.58 (dq, J=6.6, 3.6, 2.4Hz, 2H), 7.55-7.49 (m, 4H), 3.51 (s, 3H). 13 C NMR(150MHz,Chloroform-d)δ163.0,156.5,147.6,135.6,134.6,130.4,129.2,128.3,127.8,127.3,127.0,120.8,34.6.HRMS(ESI)calcd for C15 H 13 N2O[M+H] + :237.1023,found:237.1036.

[0080] The obtained white solid is 3-methyl-2-phenylquinazolin-4(3H)-one (Ia).

[0081] Example 6

[0082] Isatoic anhydride (IIa, 81.6 mg, 0.5 mmol), styrene (IIIa, 260.4 mg, 2.5 mmol), methylamine hydrochloride (IVa, 84.4 mg, 1.25 mmol), tetrabutylammonium chloride (138.9 mg, 0.5 mmol), acetonitrile (3 mL), and methanol (3 mL) were added to a reaction tube, and a graphite felt electrode and a platinum electrode were inserted. The current was adjusted to a constant current of 6 mA, and the reaction was stirred at 80°C for 18 h. After the reaction was completed, the heating was stopped and the reaction solution was cooled to room temperature.

[0083] The graphite felt electrode was washed three times with dichloromethane, and the washing liquids obtained after washing were combined. The graphite felt electrode was immersed in the washing liquid and subjected to microwave ultrasound for 5 minutes to obtain an electrode washing liquid. The cooled reaction liquid and the electrode washing liquid were combined and then subjected to reduced pressure distillation to evaporate the solvent to obtain a concentrate. The concentrate was eluted with a mixture of petroleum ether and ethyl acetate in a volume ratio of 15:1 as an eluent, and then separated by silica gel column chromatography to obtain 64.98 mg of a white solid with a yield of 55%. The white solid was detected by hydrogen spectrum and carbon spectrum, and the results were as follows:

[0084] 1 H NMR (600MHz, Chloroform-d) δ8.34 (dt, J=7.8, 1.2Hz, 1H), 7.80-7.75 (m, 2H), 7.58 (dq, J=6.6, 3.6, 2.4Hz, 2H), 7.55-7.49 (m, 4H), 3.51 (s, 3H). 13 C NMR(150MHz,Chloroform-d)δ163.0,156.5,147.6,135.6,134.6,130.4,129.2,128.3,127.8,127.3,127.0,120.8,34.6.HRMS(ESI)calcd for C 15 H 13 N2O[M+H] + :237.1023,found:237.1036.

[0085] The obtained white solid is 3-methyl-2-phenylquinazolin-4(3H)-one (Ia).

[0086] Example 7

[0087] Isatoic anhydride (IIa, 81.6 mg, 0.5 mmol), styrene (IIIa, 260.4 mg, 2.5 mmol), methylamine hydrochloride (IVa, 84.4 mg, 1.25 mmol), tetrabutylammonium chloride (138.9 mg, 0.5 mmol), acetonitrile (3 mL), and methanol (3 mL) were added to a reaction tube, and a graphite felt electrode and a platinum electrode were inserted. The current was adjusted to a constant current of 8 mA, and the reaction was stirred at 80°C for 8 h. After the reaction was completed, the heating was stopped and the reaction solution was cooled to room temperature.

[0088] The graphite felt electrode was washed three times with dichloromethane, and the washing liquids obtained after washing were combined. The graphite felt electrode was immersed in the washing liquid and subjected to microwave ultrasound for 5 minutes to obtain an electrode washing liquid. The cooled reaction liquid and the electrode washing liquid were combined and then subjected to reduced pressure distillation to evaporate the solvent to obtain a concentrate. The concentrate was eluted with a mixture of petroleum ether and ethyl acetate in a volume ratio of 15:1 as an eluent, and then separated by silica gel column chromatography to obtain 56.70 mg of a white solid with a yield of 48%. The white solid was detected by hydrogen spectrum and carbon spectrum, and the results were as follows:

[0089] 1 H NMR (600MHz, Chloroform-d) δ8.34 (dt, J=7.8, 1.2Hz, 1H), 7.80-7.75 (m, 2H), 7.58 (dq, J=6.6, 3.6, 2.4Hz, 2H), 7.55-7.49 (m, 4H), 3.51 (s, 3H). 13 C NMR(150MHz,Chloroform-d)δ163.0,156.5,147.6,135.6,134.6,130.4,129.2,128.3,127.8,127.3,127.0,120.8,34.6.HRMS(ESI)calcd for C 15 H 13 N2O[M+H] + :237.1023,found:237.1036.

[0090] The obtained white solid is 3-methyl-2-phenylquinazolin-4(3H)-one (Ia).

[0091] Example 8

[0092] Isatoic anhydride (IIa, 81.6 mg, 0.5 mmol), styrene (IIIa, 260.4 mg, 2.5 mmol), methylamine hydrochloride (IVa, 84.4 mg, 1.25 mmol), tetrabutylammonium chloride (138.9 mg, 0.5 mmol), water (3 mL), and methanol (3 mL) were added to a reaction tube, and a graphite felt electrode and a platinum electrode were inserted. The current was adjusted to a constant current of 5 mA, and the reaction was stirred at 80°C for 19 h. After the reaction was completed by TLC monitoring, heating was stopped and the reaction solution was cooled to room temperature.

[0093] The graphite felt electrode was washed three times with dichloromethane, and the washing liquids obtained after washing were combined. The graphite felt electrode was immersed in the washing liquid and subjected to microwave ultrasound for 5 minutes to obtain an electrode washing liquid. The cooled reaction liquid and the electrode washing liquid were combined and then subjected to reduced pressure distillation to evaporate the solvent to obtain a concentrate. The concentrate was eluted with a mixture of petroleum ether and ethyl acetate in a volume ratio of 15:1 as an eluent, and then separated by silica gel column chromatography to obtain 85.05 mg of a white solid with a yield of 72%. The white solid was detected by hydrogen spectrum and carbon spectrum, and the results were as follows:

[0094] 1 H NMR (600MHz, Chloroform-d) δ8.34 (dt, J=7.8, 1.2Hz, 1H), 7.80-7.75 (m, 2H), 7.58 (dq, J=6.6, 3.6, 2.4Hz, 2H), 7.55-7.49 (m, 4H), 3.51 (s, 3H). 13 C NMR(150MHz,Chloroform-d)δ163.0,156.5,147.6,135.6,134.6,130.4,129.2,128.3,127.8,127.3,127.0,120.8,34.6.HRMS(ESI)calcd for C 15 H 13 N2O[M+H] + :237.1023,found:237.1036.

[0095] The obtained white solid is 3-methyl-2-phenylquinazolin-4(3H)-one (Ia).

[0096] Example 9

[0097] Isatoic anhydride (IIa, 81.6 mg, 0.5 mmol), styrene (IIIa, 260.4 mg, 2.5 mmol), methylamine hydrochloride (IVa, 84.4 mg, 1.25 mmol), tetrabutylammonium chloride (138.9 mg, 0.5 mmol), acetonitrile (2 mL), water (2 mL), and methanol (2 mL) were added to a reaction tube, and a graphite felt electrode and a platinum electrode were inserted. The current was adjusted to a constant current of 5 mA, and the reaction was stirred at 80°C for 19 h. After the reaction was completed by monitoring with TLC, heating was stopped and the reaction solution was cooled to room temperature.

[0098] The graphite felt electrode was washed three times with dichloromethane, and the washing liquids obtained after washing were combined. The graphite felt electrode was immersed in the washing liquid and subjected to microwave ultrasound for 5 minutes to obtain an electrode washing liquid. The cooled reaction liquid and the electrode washing liquid were combined and then subjected to reduced pressure distillation to evaporate the solvent to obtain a concentrate. The concentrate was eluted with a mixture of petroleum ether and ethyl acetate in a volume ratio of 15:1 as an eluent, and then separated by silica gel column chromatography to obtain 77.97 mg of a white solid with a yield of 66%. The white solid was detected by hydrogen spectrum and carbon spectrum, and the results were as follows:

[0099] 1 H NMR (600MHz, Chloroform-d) δ8.34 (dt, J=7.8, 1.2Hz, 1H), 7.80-7.75 (m, 2H), 7.58 (dq, J=6.6, 3.6, 2.4Hz, 2H), 7.55-7.49 (m, 4H), 3.51 (s, 3H). 13 C NMR(150MHz,Chloroform-d)δ163.0,156.5,147.6,135.6,134.6,130.4,129.2,128.3,127.8,127.3,127.0,120.8,34.6.HRMS(ESI)calcd for C 15 H 13 N2O[M+H] + :237.1023,found:237.1036.

[0100] The obtained white solid is 3-methyl-2-phenylquinazolin-4(3H)-one (Ia).

[0101] Example 10

[0102] 6-Chlorosaicin anhydride (IIb, 150.5 mg, 0.5 mmol), styrene (IIIa, 260.4 mg, 2.5 mmol), methylamine hydrochloride (IVa, 84.4 mg, 1.25 mmol), tetrabutylammonium chloride (138.9 mg, 0.5 mmol), acetonitrile (3 mL), and methanol (3 mL) were added to a reaction tube, and a graphite felt electrode and a platinum electrode were inserted. The current was adjusted to a constant current of 5 mA, and the reaction was stirred at 80°C for 19 h. After the reaction was completed by TLC monitoring, heating was stopped and the reaction solution was cooled to room temperature.

[0103] The graphite felt electrode was washed three times with dichloromethane, and the washing solutions obtained after washing were combined. The graphite felt electrode was immersed in the washing solutions and subjected to microwave ultrasound for 5 minutes to obtain an electrode washing solution. The cooled reaction solution and the electrode washing solution were combined and then subjected to reduced pressure distillation to remove the solvent to obtain a concentrate. The concentrate was eluted with a mixture of petroleum ether and ethyl acetate in a volume ratio of 15:1 as an eluent, and then separated by silica gel column chromatography to obtain 67 mg of a white solid with a yield of 50%. The white solid was 6-chloro-3-methyl-2-phenylquinazolin-4(3H)-one (Ib), and its structural formula is:

[0104]

[0105] The 6-chloro-3-methyl-2-phenylquinazolin-4(3H)-one (Ib) was subjected to hydrogen and carbon spectrum detection:

[0106] 1 H NMR (600MHz, Chloroform-d) δ8.34(d,J=7.8Hz,1H),7.78(d,J=7.8Hz,2H),7.58(s,2H),7.54(s,3H),3.51(s,3H). 13 C NMR(150MHz,Chloroform-d)δ162.8,156.4,147.1,134.6,130.4,129.1,128.2,127.5,127.3,126.9,120.6,34.5.HRMS(ESI)calcd forC 15 H 11 ClN2O[M+H] + :271.0633,found:271.0632.

[0107] Example 11

[0108] 6-Methylisatoic anhydride (IIc, 88.58 mg, 0.5 mmol), styrene (IIIa, 260.4 mg, 2.5 mmol), methylamine hydrochloride (IVa, 84.4 mg, 1.25 mmol), tetrabutylammonium chloride (138.9 mg, 0.5 mmol), acetonitrile (3 mL), and methanol (3 mL) were added to a reaction tube, and a graphite felt electrode and a platinum electrode were inserted. The current was adjusted to a constant current of 5 mA, and the reaction was stirred at 80°C for 19 h. After the reaction was completed, the heating was stopped and the reaction solution was cooled to room temperature.

[0109] The graphite felt electrode was washed three times with dichloromethane. The washing solutions obtained after washing were combined and the graphite felt electrode was immersed in the washing solutions and subjected to microwave ultrasound for 5 minutes to obtain an electrode washing solution. The cooled reaction solution and the electrode washing solution were combined and then subjected to reduced pressure distillation to remove the solvent to obtain a concentrate. The concentrate was eluted with a mixture of petroleum ether and ethyl acetate in a volume ratio of 15:1 as an eluent, and then separated by silica gel column chromatography to obtain 83.85 mg of a white solid with a yield of 67%. The white solid was 3,6-dimethyl-2-phenylquinazolin-4(3H)-one (Ic), and its structural formula is:

[0110]

[0111] The 3,6-dimethyl-2-phenylquinazolin-4(3H)-one (Ic) was subjected to hydrogen and carbon spectrum detection:

[0112] 1 H NMR (600MHz, Chloroform-d) δ8.12(s,1H),7.66(d,J=8.4Hz,1H),7.58-7.55(m,3H),7.52(dd,J=4.8,2.4Hz,3H),3.49(s,3H),2.51(s,3H). 13 CNMR(150MHz,Chloroform-d)δ162.7,155.4,145.2,137.2,135.8,135.4,130.0,128.9,128.1,127.2,126.0,120.2,34.3,21.4.HRMS(ESI)calcd for C 16 H 14 N2O[M+H] + :251.1179,found:251.1175.

[0113] Example 12

[0114] 5-Bromoisatoic anhydride (IId, 121 mg, 0.5 mmol), styrene (IIIa, 260.4 mg, 2.5 mmol), methylamine hydrochloride (IVa, 84.4 mg, 1.25 mmol), tetrabutylammonium chloride (138.9 mg, 0.5 mmol), acetonitrile (3 mL), and methanol (3 mL) were added to a reaction tube, and a graphite felt electrode and a platinum electrode were inserted. The current was adjusted to a constant current of 5 mA, and the reaction was stirred at 80°C for 19 h. After the reaction was completed by TLC monitoring, heating was stopped and the reaction solution was cooled to room temperature.

[0115] The graphite felt electrode was washed three times with dichloromethane. The washing solutions obtained after washing were combined and the graphite felt electrode was immersed in the washing solutions and subjected to microwave ultrasound for 5 minutes to obtain an electrode washing solution. The cooled reaction solution and the electrode washing solution were combined and then subjected to reduced pressure distillation to remove the solvent to obtain a concentrate. The concentrate was eluted with a mixture of petroleum ether and ethyl acetate in a volume ratio of 15:1 as an eluent, and then separated by silica gel column chromatography to obtain 94 mg of a white solid with a yield of 60%. The white solid was 5-bromo-3-methyl-2-phenylquinazolin-4(3H)-one (Id), whose structural formula is:

[0116]

[0117] The 5-bromo-3-methyl-2-phenylquinazolin-4(3H)-one (Id) was subjected to hydrogen and carbon spectrum detection:

[0118] 1 H NMR (600MHz, Chloroform-d) δ8.09(d,J=8.4Hz,1H),7.74(d,J=7.8Hz,1H),7.71(d,J=8.4Hz,1H),7.58-7.56(m,2H),7.54(d,J=2.4Hz,3H),3.48(s,3H). 13 C NMR(150MHz,Chloroform-d)δ171.1,160.8,156.7,149.5,134.0,133.5,130.4,130.1,128.9,128.0,121.4,118.6,34.7.HRMS(ESI)calcd for C 15 H 12 BrN2O[M+H]+:315.0128,found:315.0134.

[0119] Example 13

[0120] Isatoic anhydride (IIa, 81.56 mg, 0.5 mmol), p-methylstyrene (IIIe, 295.45 mg, 2.5 mmol), methylamine hydrochloride (IVa, 84.4 mg, 1.25 mmol), tetrabutylammonium chloride (138.9 mg, 0.5 mmol), acetonitrile (3 mL), and methanol (3 mL) were added to a reaction tube, and a graphite felt electrode and a platinum electrode were inserted. The current was adjusted to a constant current of 5 mA, and the reaction was stirred at 80°C for 19 h. After the reaction was completed by TLC monitoring, heating was stopped and the reaction solution was cooled to room temperature.

[0121] The graphite felt electrode was washed three times with dichloromethane, and the washing liquids obtained after washing were combined. The graphite felt electrode was immersed in the washing liquid and subjected to microwave ultrasound for 5 minutes to obtain an electrode washing liquid. The cooled reaction solution and the electrode washing liquid were combined and then subjected to reduced pressure distillation to evaporate the solvent to obtain a concentrate. The concentrate was eluted with a mixture of petroleum ether and ethyl acetate in a volume ratio of 15:1 as an eluent, and then separated by silica gel column chromatography to obtain 62.5 mg of a white solid with a yield of 50%. The white solid was 3-methyl-2-(p-tolyl)quinazolin-4(3H)-one (Ie), and its structural formula is:

[0122]

[0123] The 3-methyl-2-(p-tolyl)quinazolin-4(3H)-one (Ie) was subjected to hydrogen and carbon spectrum detection:

[0124] 1 H NMR(600MHz,Chloroform-d)δ8.25(d,J=7.8Hz,1H),7.70-7.65(m,2H),7.44-7.4 1(m,1H),7.39(d,J=7.8Hz,2H),7.25(d,J=7.8Hz,2H),3.44(s,3H),2.36(s,3H). 13 CNMR(150MHz,Chloroform-d)δ170.9,163.1,156.7,147.6,144.6,140.7,134.6,129.8,128.3,127.2,127.0,120.8.HRMS(ESI)calcd for C 16 H 14 N2O[M+H]+:251.1179,found:251.1185.

[0125] Example 14

[0126] Isatoic anhydride (IIa, 81.56 mg, 0.5 mmol), 2-vinylnaphthalene (IIIf, 365.6 mg, 2.5 mmol), methylamine hydrochloride (IVa, 84.4 mg, 1.25 mmol), tetrabutylammonium chloride (138.9 mg, 0.5 mmol), acetonitrile (3 mL), and methanol (3 mL) were added to a reaction tube, and a graphite felt electrode and a platinum electrode were inserted. The current was adjusted to a constant current of 5 mA, and the reaction was stirred at 80°C for 19 h. After the reaction was completed by TLC monitoring, heating was stopped and the reaction solution was cooled to room temperature.

[0127] The graphite felt electrode was washed three times with dichloromethane, and the washing liquids obtained after washing were combined. The graphite felt electrode was immersed in the washing liquid and subjected to microwave ultrasound for 5 minutes to obtain an electrode washing liquid. The cooled reaction liquid and the electrode washing liquid were combined and then subjected to reduced pressure distillation to evaporate the solvent to obtain a concentrate. The concentrate was eluted with a mixture of petroleum ether and ethyl acetate in a volume ratio of 15:1 as an eluent, and then separated by silica gel column chromatography to obtain 114 mg of a white solid with a yield of 80%. The white solid was 3-methyl-2-(naphthalen-2-yl)quinazolin-4(3H)-one (If), and its structural formula is:

[0128]

[0129] The 3-methyl-2-(naphthalen-2-yl)quinazolin-4(3H)-one (If) was subjected to hydrogen and carbon spectrum detection:

[0130] 1 H NMR(600MHz,Chloroform-d)δ8.36(d,J=8.4Hz,1H),8.09(s,1H),7.98(d,J=8.4Hz,1H),7.92(t,J=8.4 Hz,2H),7.78(s,2H),7.59(q,J=7.8,6.0Hz,2H),7.52(t,J=7.2Hz,1H),7.48-7.41(m,1H),3.53(s,3H). 13 C NMR(150MHz,Chloroform-d)δ162.7,156.2,147.3,134.4,133.7,132.9,128.7,128.6,128 .2,127.9,127.5,127.4,127.1,127.0,126.7,125.1,124.7,120.5,34.4.HRMS(ESI)calcd for C 19 H 15 N2O[M+H]+:287.1179,found:287.1183.

[0131] Example 15

[0132] Isatoic anhydride (IIa, 86.56 mg, 0.5 mmol), 2-vinylthiophene (IIIg, 160.26 mg, 2.5 mmol), methylamine hydrochloride (IVa, 84.4 mg, 1.25 mmol), tetrabutylammonium chloride (138.9 mg, 0.5 mmol), acetonitrile (3 mL), and methanol (3 mL) were added to a reaction tube, and a graphite felt electrode and a platinum electrode were inserted. The current was adjusted to a constant current of 5 mA, and the reaction was stirred at 80°C for 19 h. After the reaction was completed by monitoring with TLC, heating was stopped and the reaction solution was cooled to room temperature.

[0133] The graphite felt electrode was washed three times with dichloromethane, and the washing solutions obtained after washing were combined. The graphite felt electrode was immersed in the washing solutions and subjected to microwave ultrasound for 5 minutes to obtain an electrode washing solution. The cooled reaction solution and the electrode washing solution were combined and then subjected to reduced pressure distillation to remove the solvent to obtain a concentrate. The concentrate was eluted with a mixture of petroleum ether and ethyl acetate in a volume ratio of 15:1 as an eluent, and then separated by silica gel column chromatography to obtain 109 mg of a white solid with a yield of 90%. The white solid was 3-methyl-2-(thiophen-2-yl)quinazolin-4(3H)-one (1 g), and its structural formula is:

[0134]

[0135] The 3-methyl-2-(thiophen-2-yl)quinazolin-4(3H)-one (1g) was subjected to hydrogen and carbon spectrum detection:

[0136] 1 H NMR(600MHz,Chloroform-d)δ8.30(dd,J=7.8,1.8Hz,1H),7.77-7.72(m,2H),7.56(dd,J=5.4,1.2Hz ,1H),7.54-7.52(m,1H),7.48(ddd,J=8.4,6.6,1.8Hz,1H),7.17(dd,J=5.4,3.6Hz,1H),3.77(s,3H). 13 C NMR(150MHz,Chloroform-d)δ162.73,150.10,147.15,136.98,134.37,129.84,129.47,127.46,127.41,127.05,126.76,120.12,34.14.HRMS(ESI)calcd for C 13 H 11 N2OS[M+H]+:243.0587,found:243.0592.

[0137] Example 16

[0138] Isatoic anhydride (IIa, 81.56 mg, 0.5 mmol), p-fluorostyrene (IIIh, 305.35 mg, 2.5 mmol), methylamine hydrochloride (IVa, 84.4 mg, 1.25 mmol), tetrabutylammonium chloride (138.9 mg, 0.5 mmol), acetonitrile (3 mL), and methanol (3 mL) were added to a reaction tube, and a graphite felt electrode and a platinum electrode were inserted. The current was adjusted to a constant current of 5 mA, and the reaction was stirred at 80°C for 19 h. After the reaction was completed by monitoring with TLC, heating was stopped and the reaction solution was cooled to room temperature.

[0139] The graphite felt electrode was washed three times with dichloromethane, and the washing liquids obtained after washing were combined. The graphite felt electrode was immersed in the washing liquid and subjected to microwave ultrasound for 5 minutes to obtain an electrode washing liquid. The cooled reaction solution and the electrode washing liquid were combined and then subjected to reduced pressure distillation to evaporate the solvent to obtain a concentrate. The concentrate was eluted with a mixture of petroleum ether and ethyl acetate in a volume ratio of 15:1 as an eluent, and then separated by silica gel column chromatography to obtain 57 mg of a white solid with a yield of 45%. The white solid was 2-(4-fluorophenyl)-3-methylquinazolin-4(3H)-one (Ih), and its structural formula is:

[0140]

[0141] The 2-(4-fluorophenyl)-3-methylquinazolin-4(3H)-one (Ih) was subjected to hydrogen and carbon spectrum detection:

[0142] 1 H NMR (600MHz, Chloroform-d) δ8.36-8.30(m,1H),7.80-7.72(m,2H),7.63-7.57(m,2H),7.52(t,J=1.8Hz,1H),7.23(t,J=8.4Hz,2H),3.51(s,3H). 13 C NMR(150MHz,Chloroform-d)δ164.8,163.2,163.0,155.6,147.4,134.8,133.0(d,J=9.4Hz),131.7,130 .7(d,J=8.7Hz),127.7,127.1,120.8,116.5(d,J=22.1Hz),116.0(d,J=21.9Hz),34.7.HRMS(ESI)calcd for C 15 H 12 FN2O[M+H]+:255.0929,found:255.0936.

[0143] Example 17

[0144] Isatoic anhydride (IIa, 81.56 mg, 0.5 mmol), p-methoxystyrene (IIIi, 335.45 mg, 2.5 mmol), methylamine hydrochloride (IVa, 84.4 mg, 1.25 mmol), tetrabutylammonium chloride (138.9 mg, 0.5 mmol), acetonitrile (3 mL), and methanol (3 mL) were added to a reaction tube, and a graphite felt electrode and a platinum electrode were inserted. The current was adjusted to a constant current of 5 mA, and the reaction was stirred at 80°C for 19 h. After the reaction was completed, the heating was stopped and the reaction solution was cooled to room temperature.

[0145] The graphite felt electrode was washed three times with dichloromethane, and the washing liquids obtained after washing were combined. The graphite felt electrode was immersed in the washing liquid and subjected to microwave ultrasound for 5 minutes to obtain an electrode washing liquid. The cooled reaction solution and the electrode washing liquid were combined and then subjected to reduced pressure distillation to evaporate the solvent to obtain a concentrate. The concentrate was eluted with a mixture of petroleum ether and ethyl acetate in a volume ratio of 15:1 as an eluent, and then separated by silica gel column chromatography to obtain 106.52 mg of a white solid with a yield of 80%. The white solid was 2-(4-methoxyphenyl)-3-methylquinazolin-4(3H)-one (Ii), and its structural formula is:

[0146]

[0147] The 2-(4-methoxyphenyl)-3-methylquinazolin-4(3H)-one (Ii) was subjected to hydrogen and carbon spectrum detection:

[0148] 1 H NMR(600MHz,Chloroform-d)δ8.25-8.22(m,1H),7.68-7.64(m,2H),7.46(d,J=8.6Hz, 2H),7.41(td,J=6.9,6.1,1.7Hz,1H),6.95(d,J=8.3Hz,2H),3.80(s,3H),3.45(s,3H). 13 C NMR(150MHz,Chloroform-d)δ162.8,160.8,155.9,147.3,134.1,129.7,127.6,127.3,126.7,126.5,120.3,114.1,55.4,34.4.HRMS(ESI)calcd for C 16 H 15 N2O2[M+H]+:267.1129,found:267.1134.

[0149] Example 18

[0150] Isatoic anhydride (IIa, 81.56 mg, 0.5 mmol), styrene (IIIa, 260.4 mg, 2.5 mmol), p-anisidine hydrochloride (IVj, 199.52 mg, 1.25 mmol), tetrabutylammonium chloride (138.9 mg, 0.5 mmol), acetonitrile (3 mL), and methanol (3 mL) were added to a reaction tube, and a graphite felt electrode and a platinum electrode were inserted. The current was adjusted to a constant current of 5 mA, and the reaction was stirred at 80°C for 19 h. After the reaction was completed by monitoring with TLC, heating was stopped and the reaction solution was cooled to room temperature.

[0151] The graphite felt electrode was washed three times with dichloromethane, and the washing solutions obtained after washing were combined. The graphite felt electrode was immersed in the washing solutions and subjected to microwave ultrasound for 5 minutes to obtain an electrode washing solution. The cooled reaction solution and the electrode washing solution were combined and then subjected to reduced pressure distillation to remove the solvent to obtain a concentrate. The concentrate was eluted with a mixture of petroleum ether and ethyl acetate in a volume ratio of 10:1 as an eluent, and then separated by silica gel column chromatography to obtain 37.56 mg of a white solid with a yield of 61%. The white solid was 3-(4-methoxyphenyl)-2-phenylquinazolin-4(3H)-one (Ij), and its structural formula is:

[0152]

[0153] The 3-(4-methoxyphenyl)-2-phenylquinazolin-4(3H)-one (Ij) was subjected to hydrogen and carbon spectrum detection:

[0154] 1 H NMR(600MHz,Chloroform-d)δ8.36(d,J=8.4Hz,1H),7.83(dd,J=18.0,8.4Hz,2H),7.54(d,J =7.8Hz,1H),7.35(d,J=7.8Hz,2H),7.32-7.20(m,4H),7.05(d,J=8.4Hz,2H),6.82(d,J=8.4H z,1H),3.77(s,3H).13CNMR(150MHz,Chloroform-d)δ162.5,159.2,155.6,147.3,134.7,13 0.0,129.3,129.0,128.1,127.6,127.3,127.2,126.9,120.9,114.3,55.4.HRMS(ESI+)calcd for C21H17N2O2[M+H]+329.1285.Found 329.1289.

[0155] Example 19

[0156] Isatoic anhydride (IIa, 81.56 mg, 0.5 mmol), 1,2-dimethoxy-4-vinylbenzene (IIIl, 410.51 mg, 2.5 mmol), methylamine hydrochloride (IVa, 84.4 mg, 1.25 mmol), tetrabutylammonium chloride (138.9 mg, 0.5 mmol), acetonitrile (3 mL), and methanol (3 mL) were added to a reaction tube, and a graphite felt electrode and a platinum electrode were inserted. The current was adjusted to a constant current of 5 mA, and the reaction was stirred at 80°C for 19 h. After the reaction was completed by TLC monitoring, heating was stopped and the reaction solution was cooled to room temperature.

[0157] The graphite felt electrode was washed three times with dichloromethane, and the washing liquids obtained after washing were combined. The graphite felt electrode was immersed in the washing liquid and subjected to microwave ultrasound for 5 minutes to obtain an electrode washing liquid. The cooled reaction liquid and the electrode washing liquid were combined and then subjected to reduced pressure distillation to evaporate the solvent to obtain a concentrate. The concentrate was eluted with a mixture of petroleum ether and ethyl acetate in a volume ratio of 10:1 as an eluent, and then separated by silica gel column chromatography to obtain 69.63 mg of a white solid with a yield of 47%. The white solid was 2-(3,4-dimethoxyphenyl)-3-methylquinazolin-4(3H)-one (Il), and its structural formula is:

[0158]

[0159] The 2-(3,4-dimethoxyphenyl)-3-methylquinazolin-4(3H)-one (I1) was subjected to hydrogen and carbon spectrum detection:

[0160] 1 H NMR(600MHz,Chloroform-d)δ8.32(dd,J=8.4,3.0Hz,1H),7.76(t,J=4.2Hz,2H),7.50(dt,J=8.4,4.2Hz,1H),7. 15(dt,J=8.4,2.4Hz,1H),7.12(d,J=1.8Hz,1H),6.99(dd,J=8.4,2.4Hz,1H),3.96(d,J=3.6Hz,6H),3.54(s,3H). 13 C NMR(150MHz,Chloroform-d)δ162.9,156.0,150.6,149.2,134.3,127.3,126.9,126.7,121.1,120.4,111.3,111.1,56.1,34.5.HRMS(ESI)calcd for C 17 H 17 N2O3[M+H]+:297.1234,found:297.1241.

[0161] Example 20

[0162] Isatoic anhydride (IIa, 81.56 mg, 0.5 mmol), styrene (IIIa, 260.4 mg, 2.5 mmol), p-fluoroaniline hydrochloride (IVm, 229.0 mg, 1.25 mmol), tetrabutylammonium chloride (138.9 mg, 0.5 mmol), acetonitrile (3 mL), and methanol (3 mL) were added to a reaction tube, and a graphite felt electrode and a platinum electrode were inserted. The current was adjusted to a constant current of 5 mA, and the reaction was stirred at 80°C for 19 h. After the reaction was completed by TLC monitoring, heating was stopped and the reaction solution was cooled to room temperature.

[0163] The graphite felt electrode was washed three times with dichloromethane, and the washing solutions obtained after washing were combined. The graphite felt electrode was immersed in the washing solutions and subjected to microwave ultrasound for 5 minutes to obtain an electrode washing solution. The cooled reaction solution and the electrode washing solution were combined and then subjected to reduced pressure distillation to remove the solvent to obtain a concentrate. The concentrate was eluted with a mixture of petroleum ether and ethyl acetate in a volume ratio of 10:1 as an eluent, and then separated by silica gel column chromatography to obtain 56.94 mg of a white solid with a yield of 36%. The white solid was 3-(4-fluorophenyl)-2-phenylquinazolin-4(3H)-one (Im), and its structural formula is:

[0164]

[0165] The 3-(4-fluorophenyl)-2-phenylquinazolin-4(3H)-one (Im) was subjected to hydrogen and carbon spectrum detection:

[0166] 1 H NMR(600MHz,Chloroform-d)δ8.34(d,J=8.4Hz,1H),7.82(q,J=4.8,3.6Hz,2H),7.54(dq,J=6.6,2.4Hz,1H), 7.34-7.31(m,2H),7.29-7.27(m,1H),7.26-7.23(m,2H),7.13(dd,J=8.4,4.8Hz,2H),7.00(t,J=8.4Hz,2H). 13 C NMR(150MHz,Chloroform-d)δ162.8,162.3,161.2,155.1,147.4,135.2,134.9,133.6,133.5, 130.8,130.8,129.5,128.9,128.2,127.8,127.4,127.,120.8,116.1,116.0.HRMS(ESI)calcd for C 20 H14 FN2O[M+H]+:317.1085,found:317.1091.

[0167] The above is only a preferred embodiment of the present invention. It should be pointed out that for ordinary technicians in this technical field, several improvements and modifications can be made without departing from the principles of the present invention. These improvements and modifications should also be regarded as within the scope of protection of the present invention.

Claims

1. A method for electrochemical synthesis of quinazolinone derivatives, characterized in that: The following steps are involved: mixing an isatoic anhydride compound, a styrene compound, a methylamine hydrochloride compound, an electrolyte and an organic solvent to obtain a reaction solution; applying electricity to the reaction solution to perform an electrochemical reaction to obtain a quinazolinone derivative; The structure of the isatoic anhydride compound is The structure of the styrene compound is The structure of the methylamine hydrochloride compound is The structure of the quinazolinone derivative is Among them, R 1 Contains at least one of hydrogen, an alkyl group having 1 to 3 carbon atoms, a halogen, or an alkoxy group having 1 to 3 carbon atoms; R 2 Contains phenyl, furyl, pyridyl, thienyl or substituted phenyl, wherein the substituent of the substituted phenyl contains alkyl having 1 to 3 carbon atoms, alkoxy having 1 to 3 carbon atoms or halogen; R 3 Contains an alkyl group having 1 to 3 carbon atoms, a benzene ring or a substituted phenyl group; the substituent of the substituted phenyl group contains an alkyl group having 1 to 3 carbon atoms, an alkoxy group having 1 to 3 carbon atoms, a cycloalkyl group having 3 to 5 carbon atoms or a halogen; The organic solvent comprises methanol; The current of the electrochemical reaction is 5-10 mA, the temperature is 60-90° C., and the time is 8-24 hours.

2. The synthesis method according to claim 1, wherein The isatoic anhydride compound of the structure shown in Formula II comprises isatoic anhydride, 6-chloroisatoic anhydride, 6-methylisatoic anhydride or 5-bromoisatoic anhydride; the molar ratio of the isatoic anhydride compound, styrene compound, methylamine hydrochloride compound and electrolyte is 0.5-1:1-5:1-2.5:1-2.

3. The synthesis method according to claim 1 or 2, characterized in that The styrene compound with the structure shown in formula III includes styrene, p-methylstyrene, 2-vinylnaphthalene, 2-vinylthiophene, p-fluorostyrene, p-methoxystyrene or 3,4-dimethoxystyrene.

4. The synthesis method according to claim 1 or 2, characterized in that The methylamine hydrochloride compounds of the structure shown in formula IV include methylamine hydrochloride, ethylamine hydrochloride, cyclopropylamine hydrochloride, aniline hydrochloride, p-methoxyaniline hydrochloride or p-fluoroaniline hydrochloride.

5. The synthesis method according to claim 1 or 2, characterized in that The electrolyte comprises at least one of tetrabutylammonium chloride, tetrabutylammonium perchlorate, potassium hexafluorophosphate, tetrabutylammonium bromide, or tetrabutylammonium tetrafluoroborate.

6. The synthesis method according to claim 1 or 2, characterized in that The organic solvent further comprises at least one of acetonitrile, water, acetone or dimethyl sulfoxide; and the concentration of the isatoic anhydride compound in the reaction solution is 0.0833 to 0.1667 mol / L.

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