Preparation method of 2-phenylquinazoline-4 (3H) ketone compound

Abstract

The invention provides a preparation method of a 2-phenyl quinazoline-4 (3H) ketone compound. According to the method, the benzyl position and the benzyl position are selectively oxidized into the benzo quinazolinone compound with less than one carbon atom, and the 2-position side chain of quinazolinone is directly oxidized and decarbonylated at a relatively low temperature to obtain the 2-benzo quinazoline-4 (3H) ketone compound, so that the method has important significance.

Description

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS

[0002] This application claims priority to Chinese Patent Application No. 2023115519176, filed on November 20, 2023, entitled "Method for preparing 2-acetylquinazoline-4(3H)one compounds", and the disclosed contents of said application are incorporated herein by reference. Technical Field

[0003] The invention relates to medicinal chemistry, to 2-phenylquinazoline-4(3H)one compounds, and in particular to a preparation method of 2-phenylquinazoline-4(3H)one compounds. Background Art

[0004] 4(3H)-quinazolinone is a quinoline alkaloid containing a pyrimidine heterocycle. It is the core structural unit of the commonly used traditional Chinese medicine ingredients, febrifugine, tryptophan, camelinine A, and anomalyshan alkaloids (Guo Rui, Synthesis and Bioactivity Evaluation of Quinazolinone Derivatives, Master's Thesis of Northwest Agriculture and Forestry University, 2018). 2-Substituted 4-(3H)quinazolinone compounds are the most widely bioactive compounds among quinazolinone compounds. A large number of literature reports that they have anticancer, antibacterial, anti-inflammatory, and antimalarial activities, such as Idelalisib, a P13K inhibitor used to treat hematological malignancies, metolazone, a diuretic used to prevent and treat hypertension, and albaconazole, an antifungal agent. Their synthesis and activity evaluation are hot topics in research at home and abroad.

[0005] Direct oxidative decarbonylation is one of the most basic functional group transformation reactions in organic synthesis, and oxidative decarboxylation, in particular, is of great significance not only in organic synthetic chemistry but also in biochemistry and industrial applications. The use of direct oxidative decarbonylation to make carboxylic acid intermediates and finally oxidative decarboxylation to synthesize aromatic compounds with one less carbon atom is an effective transformation route that has not been widely documented. On the one hand, it is not easy to perform late-stage modifications of these structural skeletons with corresponding functional groups in the context of complex molecules. Typically, many simple modifications of the structures of physiologically and pharmacologically active compounds require a lengthy synthetic strategy in which new substituents have to be introduced at an early stage. On the other hand, direct oxidative decarbonylation avoids the production of corresponding impurities of many active pharmaceutical ingredients, especially those containing aromatic or heteroaryl acetic acids, which is beneficial to the beneficial control of cost, safety and environmental factors in industrial production (Gangadurai, C.; Illa, GT; Reddy, DS, FeCl(3)-catalyzed oxidative decarboxylation of aryl / heteroaryl acetic acids: preparation of selected API impurities. Org Biomol Chem 2020, 18(41), 8459-8466.). Summary of the invention

[0006] The present invention provides a method for preparing 2-phenylquinazoline-4(3H)ketone compounds. The present invention utilizes direct oxidative decarbonylation reaction to produce a carboxylic acid compound intermediate, and finally oxidative decarboxylation to synthesize an aromatic compound with one less carbon atom.

[0007] The present invention is achieved by:

[0008] A method for preparing a 2-phenylquinazoline-4(3H)-one compound (Compound III), characterized in that: Compound II is oxidatively decarbonylated to obtain Compound III;

[0009]

[0010] The compound of formula II is prepared from the compound of formula I.

[0011]

[0012] The catalyst for the reaction is a Fe(III) combination catalyst, wherein the Fe(III) combination catalyst comprises FeCl 3 (or FeCl 2 ) and TEMPO.

[0013] A method for preparing 2-phenylquinazoline-4(3H)-one compounds, characterized in that: a compound of formula I and a compound of formula II are reacted with a catalyst under an oxygen atmosphere to obtain a compound of formula II, and then the compound of formula II is oxidatively decarbonylated to obtain a compound of formula III; the Fe(III) combined catalyst comprises FeCl 3 (or FeCl 2 ) and TEMPO. The reaction scheme is as follows:

[0014]

[0015] Among them, R 1 are independently hydrogen, alkoxy, or halogen; R 2 are independently hydrogen, alkyl, alkoxy, nitro or halogen.

[0016] The term "alkoxy" used herein is preferably methoxy or ethoxy. 1 are independently hydrogen, alkoxy, or halogen; R 2 are each independently hydrogen, methyl, methoxy, fluoro, bromo, chloro or nitro.

[0017] The catalyst used to prepare the compound of formula II from the compound of formula I of the present invention is the same catalyst as the catalyst used to prepare the compound of formula III from the compound of formula II.

[0018] In the above Fe(III) combined catalyst, FeCl 3 or FeCl 2 The dosage is 0.01-0.1 equivalent, and the dosage of TEMPO is 0.02-2.0 equivalent. Further, in the above synthesis method, the Fe(III) combined catalyst used in the reaction is FeCl 3 or FeCl 2 The dosage is 0.01-0.06 equivalent, and the dosage of TEMPO is 0.30-1.5 equivalent, calculated as 1 equivalent of the compound of formula I.

[0019] In the synthesis method of the present invention, the solvent used for preparing the compound of formula III by the catalytic reaction of the compound of formula I under an oxygen atmosphere is solvent A, and solvent A is selected from one or a combination of N,N-dimethylformamide, N,N-dimethylacetamide, xylene, and benzene; preferably N,N-dimethylformamide.

[0020] In the synthesis method of the present invention, the reaction temperature for preparing the compound of formula III by the catalytic reaction of the compound of formula I in an oxygen atmosphere is temperature A. In order to improve the yield and purity of the above-mentioned synthesis method, the above-mentioned reaction temperature A is 60-150°C; preferably 80-120°C.

[0021] Specifically, a method for preparing 2-phenylquinazoline-4(3H)-one compounds is characterized in that: a compound of formula I is reacted with a catalyst in an oxygen atmosphere to obtain a compound of formula II intermediate, and then the compound of formula II intermediate is reacted with a catalyst in an oxygen atmosphere to obtain a compound of formula III; the catalyst is an Fe(III) combination catalyst; the Fe(III) combination catalyst includes FeCl 3 and TEMPO, where FeCl 3 The dosage is 0.02-0.05 equivalents, and the dosage of TEMPO is 0.37-1.11 equivalents; in the process of preparing the compound of formula III by catalytic reaction of the compound of formula I under oxygen atmosphere, the solvent A used is N,N-dimethylformamide, and the reaction temperature A is 80-120°C.

[0022] The Fe(III) combined catalyst also includes iodine, and the amount of iodine used is 0.02-2.0 equivalents.

[0023] Further, the III compound is selected from compounds 2a-2m:

[0024] 7-Chloro-2-phenylquinazolin-4(3H)one (2a)

[0025] 2-Phenylquinazolin-4(3H)one (2b)

[0026] 7-Methoxy-2-phenylquinazolin-4(3H)one (2c)

[0027] 2-m-Tolylquinazolin-4(3H)one (2d)

[0028] 2-(3-Fluorophenyl)quinazolin-4(3H)one (2e)

[0029] 2-(3-Methoxyphenyl)quinazolin-4(3H)one (2f)

[0030] 2-(3-Bromophenyl)quinazolin-4(3H)one (2g)

[0031] 2-(4-Chlorophenyl)quinazolin-4(3H)one(2h)

[0032] 2-p-Tolylquinazolin-4(3H)one (2i)

[0033] 2-(4-Methoxyphenyl)quinazolin-4(3H)one (2j)

[0034] 2-(4-Fluorophenyl)quinazolin-4(3H)one (2k)

[0035] Quinazolin-4(3H)one(2l)

[0036] 2-(4-Fluoro-2-methylphenyl)quinazolin-4(3H)one (2m).

[0037] Beneficial Effects

[0038] The present invention provides a method for preparing 2-phenylquinazoline-4(3H)-one compounds. The selective decarbonylation is very difficult for the conversion of quinazoline ketone. The present invention provides a method for preparing 2-phenylquinazoline-4(3H)-one compounds by using FeCl 3 The method of obtaining a decarbonylated product by oxidizing quinazolinone with oxygen using a -TEMPO catalyst can selectively oxidize the benzylic hydrogen at the benzylic position to a benzoquinazolinone compound with one less carbon atom, and directly oxidize and decarbonylate the 2-side chain of quinazolinone at a relatively low temperature to obtain a 2-benzoquinazolin-4 (3H) ketone compound, which is of great significance. The reaction catalyst used in the synthesis method of the present invention is simple and inexpensive, and does not require harsh reaction conditions or an autoclave, and has a short reaction time, which is suitable for industrial production. DETAILED DESCRIPTION

[0039] In order to make the purpose and technical scheme of the present invention clearer, the preferred embodiments of the present invention are described in detail below. It should be noted that the following examples are only used to further illustrate the present invention and should not be construed as limiting the scope of protection of the present invention. Some non-essential improvements and adjustments made by those skilled in the art based on the above content of the present invention all belong to the scope of protection of the present invention. The raw materials and reagents used in the present invention are all commercially available products.

[0040] Example 1

[0041] The inventors used the synthesized quinazolinone compound of formula I to prepare the compound of formula III under the action of a catalyst, and explored the reaction catalyst. The results are listed in Table 1. First, the experiment started with 7-chloro-2-benzylquinazolin-4(3H)-one (compound 1a) and FeCl 3 (2 mol%) in the presence of DMF catalyst. 2 When CF was used as a catalyst, only 43% yield was obtained (entry 2). The performance of different catalysts was then compared. 3 CO 2 Ag replaces FeCl 3 When Zn(OTf) 2 ,AgBr,AlCl 3 The yields were low (entries 3 to 6). 2 O.BF 3 ·C 2 H 5 OC 2 H 5 Replace FeCl 3The desired metallized product could not be obtained (entries 8 and 9). Finally, the best solvent for the reaction was DMF, and the reaction was unsuccessful in DMA or HFIP (entries 10-11). Based on the original conditions, the Tempo-iodine catalytic system was introduced, and an oxygen balloon was added to increase the oxygen concentration. It was found that the reaction time could be shortened to 4 h and the reaction temperature could be shortened to 120 °C for the best yield (entry 12). The yield of oxidation was significantly reduced when Tempo was used (entry 7). In the absence of FeCl 3 In the case of tempo-iodine or tempo-iodine, the reaction did not produce any product (entries 14-17). The next step was to compare the oxidation ability of different transition metal catalysts. 4 ,CuCl,NiCl 2 ,FeCl 2 can be used to obtain the desired products, albeit in relatively low yields (entries 18–21). Among transition metal catalysts, FeCl 2 It can also be used for oxidation reactions, FeCl 3 The yields were the best (entry 1 and entry 12).

[0042] Table 1

[0043]

[0044] Reaction conditions: Unless otherwise stated, all reactions were performed with 2-ethylquinazolinone (0.26 mmol, 1 equivalent)

[0045] FeCl 3 (0.07mmol, 0.04 equivalent), iodine I 2 (1.85-5.55, 0.37-1.11 equiv.), TEMPO (1.85-5.55, 0.37-1.11 equiv.)

[0046] a All solvents are 2 ml;

[0047] b separation yield;

[0048] cNo reaction occurred.

[0049] Embodiment 2:

[0050] Method for obtaining benzoquinazolinone compounds by selective oxidation (2a-2c)

[0051] Add quinazolinone compound (1 equivalent), TEMPO (0.37-1.11 equivalent) and FeCl into a 50 mL three-necked round flask. 3(0.04 equivalent), N,N-dimethylformamide 2mL, prepare oxygen balloon to replace air three times, so that the reaction solution is fully in oxygen atmosphere. The resulting solution is warmed to 120℃ and stirred at this temperature for reaction, and TLC spot plate detection is performed. When the reaction is complete, it is cooled to room temperature, ethyl acetate (30ml) is added, and then activated carbon is added for decolorization, filtered, and the organic layer is washed with saturated brine. The organic layer is dried over anhydrous sodium sulfate, filtered, and the solvent is removed under reduced pressure, and the target product is purified by silica gel column.

[0052] Table 2 examines the range of activity of 2-benzyl-4(3H)-quinazolines in methylene CH oxidation. With the exception of 2-pyridylmethyl-4(3H)-quinazoline (3l), all other quinazolines reacted with oxygen to isolate 2-phenylquinazolin-4(3H)-ones (4a-4m) in yields ranging from 42 to 91%.

[0053] Table 2

[0054]

[0055]

[0056]

[0057] Reaction conditions: 1 equivalent of quinazolinone compound, FeCl 3 The dosage is 0.04 equivalent, the dosage of TEMPO is 0.37-1.11 equivalent, and the dosage of iodine I 2 The dosage is 0.37-1.11 equivalents, the reaction temperature is 120°C, and the reaction time is 4-12h.

[0058] NMR data of the target product

[0059] 7-Chloro-2-phenylquinazolin-4(3H)one (2a, 94.4 mg, 80%), white solid, melting point 156-158°C; 1HNMR (600 MHz, DMSO-d6) δ 12.60 (s, 1H), 8.22–8.19 (m, 2H), 8.18–8.14 (m, 1H), 7.88–7.83 (m, 1H), 7.75 (d, J = 8.0 Hz, 1H), 7.63 (d, J = 8.6 Hz, 2H), 7.56–7.52 (m, 1H); 13C NMR(151MHz,DMSO-d6)δ162.63,151.82,149.06,136.77,135.15,132.04,130.10,129.16,128.01,127.26,126.35,121.49

[0060] 2-Phenylquinazolin-4(3H)one (2b, 84.0 mg, 74%), white solid, melting point 234-236°C; 1H NMR (600 MHz, DMSO-d6) δ12.50 (s, 1H), 8.23–8.15 (m, 3H), 7.86–7.82 (m, 1H), 7.75 (dd, J=8.2, 1.1 Hz, 1H), 7.62–7.51 (m, 4H); 13C NMR (151 MHz, DMSO-d6) δ162.67, 152.78, 149.24, 135.03, 133.23, 131.82, 129.05, 128.23, 127.98, 127.02, 126.32, 121.49.

[0062] 7-Methoxy-2-phenylquinazolin-4(3H)one (2c, 94.4 mg, 91%), white solid, 1H NMR (600 MHz, DMSO-d6) δ12.62 (d, J = 84.8 Hz, 1H), 8.21 (dd, J = 38.3, 7.8 Hz, 1H), 7.96–7.65 (m, 5H), 7.57–7.43 (m, 1H), 7.25 (ddd, J = 106.2, 8.1, 2.0 Hz, 1H), 3.87 (d, J = 17.9 Hz, 3H); 13C NMR(151MHz,DMSO-d6)δ187.23,162.70,159.81,159.55,149.40,147.59,135.20,130.20,130.18,127.06,124.00,120.59,116.85,112.99,55.89

[0063] 2-m-Tolylquinazolin-4(3H)one (2d, 50.4 mg, 68%), white solid, melting point 207-209°C; 1HNMR (600 MHz, DMSO-d6) δ12.47 (s, 1H), 8.17 (d, J = 7.8 Hz, 1H), 8.04 (s, 1H), 7.98 (d, J = 7.5 Hz, 1H), 7.88–7.82 (m, 1H), 7.75 (d, J = 8.1 Hz, 1H), 7.53 (t, J = 7.5 Hz, 1H), 7.43 (dt, J = 15.9, 7.5 Hz, 2H), 2.42 (s, 3H).; 13C NMR(151MHz,DMSO-d6)δ162.67,152.87,149.24,138.38,135.04,133.12,132.47,128.97,128.76,127.95,126.99,126.32,125.36,121.45,21.44

[0064] 2-(3-Fluorophenyl)quinazolin-4(3H)one (2e, 67.7 mg, 58%), white solid, melting point 140-142°C; 1HNMR (600 MHz, DMSO-d6) δ12.55 (s, 1H), 8.17 (dd, J = 7.9, 1.6 Hz, 1H), 8.07 (dt, J = 7.8, 1.2 Hz, 1H), 8.01 (dt, J = 10.4, 2.3 Hz, 1H), 7.87–7.83 (m, 1H), 7.78–

[0065] 7.74(m,1H),7.62–7.59(m,1H),7.56–7.53(m,1H),7.44(d,J=2.7Hz,1H); 13CNMR(151MHz,DMSO-d6)δ163.39 ,148.95,135.11,131.20,131.15,128.08,127.35,126.33,124.39,124.37,121.63,118.75,118.61,115.08.

[0066] 2-(3-Methoxyphenyl)quinazolin-4(3H)one (2f, 46.7 mg, 72%), white solid, melting point 150-152°C; 1H NMR (600 MHz, DMSO-d6) δ 12.62 (d, J = 84.8 Hz, 1H), 8.21 (dd, J = 38.3, 7.8 Hz, 1H), 7.96–7.65 (m, 5H), 7.57–7.43 (m, 1H), 7.25 (ddd, J = 106.2, 8.1, 2.0 Hz, 1H), 3.87 (d, J = 17.9 Hz, 3H); 13C NMR(151MHz,DMSO-d6)δ187.23,161.50,159.81,159.55,149.40,147.59,135.20,130.20,130.18,126.50,124.00,120.81,120.59,115.66,55.89

[0067] 2-(3-Bromophenyl)quinazolin-4(3H)one (2 g, 51.1 mg, 46%), white solid, melting point 140-142°C; 1HNMR (600 MHz, DMSO-d6) δ 12.57 (s, 1H), 8.37 (s, 1H), 8.25 (dd, J = 7.9, 1.5 Hz, 1H), 8.21 (dd, J = 7.8, 1.4 Hz, 1H), 7.96–7.89 (m, 2H), 7.80 (d, J = 8.2 Hz, 1H), 7.68 (t, J = 7.5 Hz, 1H), 7.59–7.55 (m, 1H); 13C NMR (151MHz, DMSO-d6) δ161.40,148.70,147.45,136.95,136.94,136.70,135.16,133.75,131.06,131.04,130.30,126.52,123.51,122.00.

[0069] 2-(4-Chlorophenyl)quinazolin-4(3H)one (2h, 83.4 mg, 72%), white solid, melting point 217-219°C; 1HNMR (600 MHz, DMSO-d6) δ 12.65 (s, 1H), 8.27–8.15 (m, 3H), 7.93–7.82 (m, 1H), 7.81–7.74 (m, 1H), 7.68 (d, J=8.7 Hz, 2H), 7.65–7.51 (m, 1H); 13C NMR (151MHz, DMSO-d6) δ186.42,149.06,139.68,136.77,135.24,135.14,133.34,133.27,132.03,130.10,129.19,129.16,129.14,126.53;

[0070] 2-p-Tolylquinazolin-4(3H)one (2i, 56.4 mg, 78%), white solid, melting point 238-240°C; 1HNMR (600 MHz, DMSO-d6) δ12.41 (s, 1H), 8.17–8.14 (m, 1H), 8.11 (d, J=8.2 Hz, 2H), 7.84–7.80 (m, 1H), 7.73 (d, J=8.1 Hz, 1H), 7.51 (t, J=7.5 Hz, 1H), 7.36 (d, J=8.1 Hz, 2H), 2.40 (s, 3H); 13C NMR(151MHz,DMSO-d6)δ162.69,152.70,149.33,141.89,134.98,130.41,129.63,128.15,127.88,126.81,126.30,121.40,21.44

[0071] 2-(4-Methoxyphenyl)quinazolin-4(3H)one (2j, 56.4 mg, 65%), white solid, melting point 210-212°C; 1HNMR (600 MHz, DMSO-d6) δ12.41 (s, 1H), 8.23–8.17 (m, 2H), 8.14 (dd, J=7.9, 1.2 Hz, 1H), 7.85–7.79 (m, 1H), 7.73–7.68 (m, 1H), 7.52–7.46 (m, 1H), 7.13–7.07 (m, 2H), 3.86 (s, 3H); 13C NMR (151MHz, DMSO-d6) δ162.77,162.34,152.33,149.41,135.01,129.93,127.76,126.59,126.29,125.27,121.16,114.47,55.93.

[0072] 2-(4-Fluorophenyl)quinazolin-4(3H)one (2k, 38.5 mg, 42%), white solid, melting point 147-149°C; 1HNMR (600 MHz, DMSO-d6) δ 13.03 (s, 1H), 8.35–8.22 (m, 1H), 8.02 (dd, J = 8.7, 5.7 Hz, 3H), 7.44 (t, J = 8.9 Hz, 1H), 7.33 (t, J = 8.8 Hz, 3H); 13C NMR(151MHz,DMSO-d6)δ166.82,166.21,164.55,147.55,135.22,134.59,134.52,132.59,132.53,127.84,127.82,126.51,116.14,115.99

[0073] Quinazolin-4(3H)one (2l, 46.4 mg, 65%), white solid, melting point 212-214°C; 1H NMR (600 MHz, DMSO-d6) δ12.27 (s, 1H), 8.19–8.07 (m, 2H), 7.83 (ddd, J=8.5, 7.1, 1.6 Hz, 1H), 7.69 (dd, J=8.2, 1.2 Hz, 1H), 7.54 (ddd, J=8.1, 7.1, 1.2 Hz, 1H); 13C NMR (151 MHz, DMSO-d6) δ161.19, 149.24, 145.85, 134.76, 127.69, 127.19, 126.29, 123.11

[0074] 2-(4-Fluoro-2-methylphenyl)quinazolin-4(3H)one (2m, 40.5mg, 58%), white solid, melting point 194-196°C; 1H NMR (600MHz, DMSO-d6) δ12.59 (s, 1H), 8.23 ​​(d, J=7.6Hz, 1H), 7.95–7.84 (m, 2H), 7.74–7.63 (m, 2H), 7.29–7.15 (m, 2H), 2.08 (s, 3H); 13CNMR (151MHz, DMSO-d6) δ189.27, 165.2 7,163.60,161.46,149.76,147.63,143.37,143.31,135.38,135.32,135.17,131.32,129.14,128.86,126.52,123.38,118.64,118.49,112.91,112.76,51.02,22.56,20.72.

Claims

1. A method for preparing a 2-phenylquinazoline-4(3H)-one compound (III compound), characterized in that: Compound II is oxidatively decarbonylated to produce compound III; Among them, R1 is independently hydrogen, alkoxy, halogen; R2 is independently hydrogen, alkyl, alkoxy, nitro, halogen; the catalyst of the reaction is Fe(III) combined catalyst.

2. The method according to claim 1, characterized in that The compound of formula II is prepared from the compound of formula I; 3. The method according to claim 1 or 2, characterized in that The Fe(III) combined catalyst includes FeCl3 (or FeCl2) and TEMPO.

4. A method for preparing a 2-phenylquinazoline-4 (3H) ketone compound, characterized in that: The compound of formula II is prepared by reacting the compound of formula I with the compound of formula II under an oxygen atmosphere via a catalyst, and the compound of formula III is prepared by oxidative decarbonylation of the compound of formula II; the catalyst comprises FeCl3 (or FeCl2) and TEMPO; The reaction route is as follows: Wherein, R1 is independently hydrogen, alkoxy, or halogen; R2 is independently hydrogen, alkyl, alkoxy, nitro, or halogen.

5. The method according to any one of claims 1 to 4, characterized in that: The term "alkoxy" used herein is preferably methoxy or ethoxy; further, R1 is independently hydrogen, alkoxy or halogen; R2 is independently hydrogen, methyl, methoxy, fluoro, bromo, chloro or nitro.

6. The method according to any one of claims 1 to 5, characterized in that: In the Fe(III) combined catalyst, the amount of FeCl3 or FeCl2 is 0.01-0.1 equivalent, and the amount of TEMPO is 0.02-2.0 equivalent; preferably, in the Fe(III) combined catalyst used in the reaction, the amount of FeCl3 or FeCl2 is 0.01-0.06 equivalent, and the amount of TEMPO is 0.30-1.5 equivalent.

7. The method according to any one of claims 1 to 6, characterized in that: The solvent used in the preparation of the compound of formula III by the catalytic reaction of the compound of formula I under an oxygen atmosphere is solvent A, and solvent A is selected from one or a combination of N,N-dimethylformamide, N,N-dimethylacetamide, xylene, and benzene; the reaction temperature for the preparation of the compound of formula III by the catalytic reaction of the compound of formula I under an oxygen atmosphere is temperature B, and temperature B is 60-150°C.

8. The method according to any one of claims 1 to 7, characterized in that: A compound of formula II is prepared by reacting a compound of formula I with a catalyst in an oxygen atmosphere, and then a compound of formula III is prepared by a one-pot method through a catalytic reaction under an oxygen atmosphere; the catalyst is an Fe(III) combination catalyst; the Fe(III) combination catalyst includes FeCl3 and TEMPO, wherein the amount of FeCl3 is 0.02-0.05 equivalents, and the amount of TEMPO is 0.37-1.11 equivalents; in the process of preparing compound III through a catalytic reaction of the compound of formula I with a catalyst in an oxygen atmosphere, the solvent A used is N,N-dimethylformamide, and the reaction temperature A is 80-120°C.

9. The method according to any one of claims 1 to 8, characterized in that: The Fe(III) combined catalyst also includes iodine, and the amount of iodine used is 0.02-2.0 equivalents.

10. The method according to any one of claims 1 to 9, characterized in that: The IV compound is selected from compounds 2a-2m: 7-Chloro-2-phenylquinazolin-4(3H)one (2a) 2-Phenylquinazolin-4(3H)one (2b) 7-Methoxy-2-phenylquinazolin-4(3H)one (2c) 2-m-Tolylquinazolin-4(3H)one (2d) 2-(3-Fluorophenyl)quinazolin-4(3H)one (2e) 2-(3-Methoxyphenyl)quinazolin-4(3H)one (2f) 2-(3-Bromophenyl)quinazolin-4(3H)one (2g) 2-(4-Chlorophenyl)quinazolin-4(3H)one(2h) 2-p-Tolylquinazolin-4(3H)one (2i) 2-(4-Methoxyphenyl)quinazolin-4(3H)one (2j) 2-(4-Fluorophenyl)quinazolin-4(3H)one (2k) Quinazolin-4(3H)one(2l) 2-(4-Fluoro-2-methylphenyl)quinazolin-4(3H)one (2m).

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