Method for synthesizing 2-benzoyl quinazoline-4 (3H)-ketone by promoting I2 to catalyze amination reaction of C (sp3)-H through visible light

Abstract

The invention discloses a method for synthesizing 2-benzoyl quinazoline-4 (3H)-ketone by promoting I2 to catalyze amination reaction of C (sp3)-H through visible light. The reaction synthesizes the target product in a single quartz tube through a plurality of basic reactions (iodination, Kornblum oxidation, condensation, etc.). The synthesis process of the method comprises the following steps: adding a substrate acetophenone, a 3CZEPAIPN photocatalyst, I2 and a DMSO solvent in a reaction container according to a ratio, carrying out an illumination reaction at 110 DEG C in an air atmosphere for 0.5 h, adding 2-aminobenzamide, continuing to react for 5.5 h, and carrying out column chromatography separation and purification on a crude product to prepare the quinazolinone derivative. The 2-acyl quinazolinone is synthesized by utilizing a visible light catalytic synthesis means to solve the problem of iodine elementary substance catalytic circulation. Meanwhile, the use of chemical oxidants, toxic reagents and expensive raw materials is avoided, and in addition, the reaction is simple and convenient to operate, mild in condition and excellent in separation yield.

Description

Technical Field

[0001] The invention belongs to the field of organic synthetic chemistry, and specifically relates to a method for synthesizing 2-benzoylquinazoline-4(3H)-one. Background Art

[0002] Quinazolinone compounds are an important class of six-membered nitrogen heterocyclic compounds, which are widely found in natural products and synthetic drugs (Tetrahedron, 2006, 62(42): 9787-9826). They have good pharmacological activities, such as anticancer (Bioorganic & Medicinal Chemistry, 2006, 14(14): 5020-5042), antihypertensive (Bioorganic & Medicinal Chemistry, 2007, 15(10): 3457-3462), anti-inflammatory (Bioorganic & Medicinal Chemistry, 2007, 15(1): 235-241) and antimalarial (Journal of Medicinal Chemistry, 2006, 49(15): 4698-4706.). Among them, 2-acylquinazolin-4(3H)-one is the basic skeleton structure of many drug molecules, such as tryptanthrin, which has anticancer activity, and 2-cinnamoylquinazolin-4(3H)-one (CQ), which has cell inhibition. In addition, 2-acylquinazolin-4(3H)-one is also widely present in many natural products (European Journal of Medicinal Chemistry, 2021, 224: 113671). For example, Luotonin F is an alkaloid that can be extracted from nature and has certain anti-tumor effects (Molecules 2011, 16, 4861-4883).

[0003] In organic synthesis, the use of molecular iodine as a catalyst to replace various transition metals is a promising approach. In particular, the amidation of C(sp3)-H bonds with iodine molecules is very attractive and has a wide range of uses in the synthesis of various N-heterocycles. For example, aminobenzamide and acetophenone cyclize to form 2-benzoylquinazolin-4(3H)-one in the presence of iodine (J. Chin. Chem. Soc. 2020, 67(5), 856–863). In addition, styrene can also be used as a raw material to undergo cyclization with o-aminobenzamide to synthesize 2-benzoylquinazolin-4(3H)-one (Eur. J. Org. Chem. 2015,2015(7), 1428–1432). However, these methods have disadvantages, such as the need for additives and inert atmosphere. In 2013, Wu and colleagues reported the I2 / DMSO-catalyzed condensation of 2-aminobenzamide and acetophenone to form 2-benzoyl-substituted quinazolinone. Wu's protocol involves the use of stoichiometric amounts of molecular iodine (110 mol%) to generate 2-benzoyl-substituted quinazolinones via the formation of glyoxal as a key intermediate (Org. Lett. 2013, 15, 378).

[0004] In the one-pot synthesis, there is a problem that the iodine catalyst is difficult to circulate and the operation is complicated. Therefore, it is of theoretical and practical significance to develop a practical, simple and efficient method to realize the catalytic circulation of the iodine catalyst. Based on this, the present invention uses the means of visible light catalytic synthesis to solve the problem of iodine elemental catalytic circulation to synthesize 2-benzoylquinazoline-4(3H)-one. Summary of the invention

[0005] The invention aims to solve the catalytic cycle problem of the iodine catalyst for synthesizing 2-benzoylquinazolinone at present, and utilizes the method for synthesizing 2-benzoylquinazolinone compound by iodine catalysis under visible light conditions, wherein acetophenone undergoes a halogenation reaction with I2, and then is further converted into benzoyl formaldehyde through Kornblum oxidation. Then, it undergoes condensation cyclization with 2-aminobenzamide, and finally is oxidized to obtain the target product 2-benzoylquinazolinone.

[0006] The idea of ​​the present invention is to use 2-aminobenzamide and acetophenone as raw materials, add I2 element, use 3CZEPAIPN as photocatalyst, DMSO as solvent, and efficiently synthesize 2-benzoylquinazolinone compounds under blue light irradiation conditions in an air atmosphere. The 3CZEPAIPN photocatalyst used in the present invention can easily generate excited 3CZEPAIPN under light conditions. * , iodine is generated by halogenation reaction - The ion is excited to the state 3CZEPAIPN *Oxidation generates I2 element, successfully realizing the catalytic cycle of iodine. In addition, the reaction is simple to operate, mild in conditions, and has excellent separation yield, and the substrate has a wide range of applicability.

[0007] The purpose of the present invention is achieved through the following technical solutions.

[0008] The method for synthesizing 2-benzoylquinazolinone compounds by I2 catalysis under visible light conditions is characterized in that it comprises the following steps:

[0009] In a glass reaction container, acetophenone, photocatalyst, and I2 were added in proportion, and an organic solvent was added under air atmosphere. After magnetic stirring at 110 ° C for 0.5 hours under blue light irradiation, 2-aminobenzamide was added. After the reaction was completed, a saturated sodium chloride solution (3 mL) was added, and the reaction mixture was extracted with ethyl acetate (3 × 3 mL). The organic layer was collected, dried over anhydrous sodium sulfate, and vacuum rotary evaporated to obtain a crude product, which was finally separated and purified by column chromatography to obtain the 2-benzoylquinazoline-4(3H)-one derivative.

[0010] Further, the chemical reaction equation for photocatalytic synthesis of 2-benzoylquinazolinone is shown below:

[0011]

[0012] In the formula, R 1 One or more selected from hydrogen, 5-chloro, 4-chloro, 5-bromo, 5-methoxy, 4-methoxyphenyl, 3,4-dimethylphenyl, 1-naphthyl, 2-naphthyl and 2-furyl;

[0013] Furthermore, the molar ratio of the photocatalyst to the 2-aminobenzamide compound is 1:100.

[0014] Furthermore, the molar ratio of I2 to 2-aminobenzamide compounds is 1:10.

[0015] Furthermore, the organic solvent is one or more of DMSO, 1,4-dioxane, and DMF, and DMSO is preferably used as the solvent.

[0016] Further, the visible light promotes I2 to catalyze C(sp 3 The reaction time of the method for synthesizing 2-benzoylquinazoline-4(3H)-one by )-H amination reaction is 4 to 8 hours, and the preferred reaction time is 6 hours.

[0017] Furthermore, the photocatalyst is one or more of 4CZIPN, 3CZEPAIPN, and 3CZMPAIPN, preferably 3CZEPAIPN.

[0018] Furthermore, the target product 2-benzoylquinazolinone derivative is purified by column chromatography, and the eluent can be a mixed solvent of petroleum ether and ethyl acetate, the volume ratio of petroleum ether to ethyl acetate is between 5:1 and 15:1, and the preferred developing solvent is petroleum ether:ethyl acetate = 10:1.

[0019] The principle of the present invention is: acetophenone undergoes a halogenation reaction with I2 to obtain an intermediate product α-iodoacetophenone, which is further converted into benzoyl formaldehyde through Kornblum oxidation. Then, it undergoes a condensation cyclization with 2-aminobenzamide to generate an intermediate 2-benzoyl-2,3-dihydroquinazolin-4(1H)-one. Finally, the intermediate is oxidized to obtain the target product 2-benzoylquinazolin-4(3H)-one. Under light conditions, the photocatalyst 3CZEPAIPN easily generates an excited state of 3CZEPAIPN * , iodine is generated by halogenation reaction - The ion is excited to the state 3CZEPAIPN * Oxidation generates I2 element, successfully realizing the iodine catalytic cycle. * After a series of redox reactions, 3CZEPAIPN is generated. －· After the radical anion is generated, it is oxidized to the ground state 3CZEPAIPN by oxygen for the next catalytic cycle.

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

[0021] (1) The photocatalyst 3CZEPAIPN used in the present invention is easy to generate excited state 3CZEPAIPN * ,3CZEPAIPN * The iodine produced by the halogenation reaction is - The ions are oxidized to produce I2 elemental substance, successfully realizing the catalytic cycle of iodine.

[0022] (2) The present invention realizes the synthesis of 2-benzoylquinazolinone compounds by I2 catalysis under visible light conditions. The reaction does not require the addition of excess oxidant, has mild conditions, is easy to operate, has excellent separation yield, and has a wide range of substrate applications. BRIEF DESCRIPTION OF THE DRAWINGS

[0023] Figure 1 , Figure 2 are the hydrogen spectrum and carbon spectrum of the target product obtained in Example 1;

[0024] Figure 3 , Figure 4 are the hydrogen spectrum and carbon spectrum of the target product obtained in Example 2;

[0025] Figure 5 , Figure 6are the hydrogen spectrum and carbon spectrum of the target product obtained in Example 3;

[0026] Figure 7 , Figure 8 are the hydrogen spectrum and carbon spectrum of the target product obtained in Example 4;

[0027] Fig. 9 , Fig.10 are the hydrogen spectrum and carbon spectrum of the target product obtained in Example 5;

[0028] Fig.11 , Fig.12 are the hydrogen spectrum and carbon spectrum of the target product obtained in Example 6;

[0029] Fig.13 , Fig.14 are the hydrogen spectrum and carbon spectrum of the target product obtained in Example 7;

[0030] Fig.15 , Fig.16 are the hydrogen spectrum and carbon spectrum of the target product obtained in Example 8;

[0031] Fig.17 , Fig.18 are the hydrogen spectrum and carbon spectrum of the target product obtained in Example 9;

[0032] Fig.19 , Fig. 20 are the hydrogen spectrum and carbon spectrum of the target product obtained in Example 10; DETAILED DESCRIPTION

[0034] The present invention is further described below by means of specific examples, but the protection scope and implementation modes of the present invention are not limited thereto.

[0035] Example 1

[0036] Take a quartz reaction tube for use, add weighed acetophenone (0.22 mmol), I2 (10 mol%, 0.02mmol), 3CZEPAIPN (1 mol%, 0.002 mmol) in sequence, add organic solvent DMSO (3 mL), and irradiate with blue light at 110 o C was reacted for 0.5 hours, 2-aminobenzamide (0.2 mmol) was added, and TCL was monitored. After the reaction was completed, saturated sodium chloride solution (3 mL) was added, and the reaction mixture was extracted with ethyl acetate (3 × 3 mL). The organic layer was collected, dried over anhydrous sodium sulfate, and vacuum rotary evaporation was performed to obtain a crude product, which was finally separated and purified by column chromatography to obtain the final product 2-benzoylquinazolinone with a yield of 80%.

[0037] The structural characterization data of the obtained target product are shown below:

[0038] 1 H NMR (500 MHz, DMSO-d6) δ 12.69 (s, 1H), 8.29 – 8.12 (m, 3H), 7.90 (q, J = 7.8 Hz, 1H), 7.77 (dt, J = 20.1, 7.7 Hz, 2H), 7.66 (t, J = 7.7 Hz,1H), 7.60 (q, J = 7.7 Hz, 2H) ppm.

[0039] 13 C{ 1 H} NMR (125 MHz, DMSO-d6) δ 187.7, 161.5, 149.5, 147.6, 135.3,134.8, 134.6, 131.3, 129.1, 128.8, 127.6, 126.5, 123.4 ppm.

[0040] HRMS (ESI-TOF) [M+H] + calcd. for C 15 H 10 N2O2 251.0815; found 251.0815.

[0041] The structure of the target compound is inferred from the above characterization data as follows:

[0042]

[0043] Example 2

[0044] Take a quartz reaction tube for use, add weighed acetophenone (0.22 mmol), I2 (10 mol%, 0.02mmol), 3CZEPAIPN (1 mol%, 0.002 mmol) in sequence, add organic solvent DMSO (3 mL), and irradiate with blue light at 110 o C was reacted for 0.5 hours, 2-amino-5-chlorobenzamide (0.2 mmol) was added, and TCL was monitored. After the reaction was completed, saturated sodium chloride solution (3 mL) was added, and the reaction mixture was extracted with ethyl acetate (3 × 3 mL). The organic layer was collected, dried over anhydrous sodium sulfate, and vacuum rotary evaporation was performed to obtain a crude product, which was finally purified by column chromatography to obtain the final product 2-benzoyl-6-chloroquinazoline-4(3H)-one with a yield of 65%.

[0045] The structural characterization data of the obtained target product are shown below:

[0046] 1H NMR (500 MHz, DMSO-d6) δ 12.88 (s, 1H), 8.15 (d, J = 8.1 Hz, 3H), 7.92 (d, J = 8.8 Hz, 1H), 7.81 (d, J = 8.8 Hz, 1H), 7.75 (t, J = 7.5 Hz, 1H),7.59 (t, J = 7.8 Hz, 2H) ppm.

[0047] 13 C{ 1 H} NMR (125 MHz, DMSO-d6) δ 187.5, 160.7, 150.0, 146.4, 135.3,134.9, 134.5, 133.3, 131.4, 131.0, 129.1, 125.6, 124.7 ppm.

[0048] HRMS (ESI-TOF) [M+H] + calcd. for C 15 H9ClN2O2 285.0452; found 285.0434.

[0049] The structure of the target compound is inferred from the above characterization data as follows:

[0050]

[0051] Example 3

[0052] Take a quartz reaction tube for use, add weighed acetophenone (0.22 mmol), I2 (10 mol%, 0.02mmol), 3CZEPAIPN (1 mol%, 0.002 mmol) in sequence, add DMSO (3 mL), and irradiate with blue light at 110 °C. o C was reacted for 0.5 hours, and 2-amino-5-bromobenzamide (0.2 mmol) was added. TCL monitoring was performed. After the reaction was completed, saturated sodium chloride solution (3 mL) was added, and the reaction mixture was extracted with ethyl acetate (3 × 3 mL). The organic layer was collected, dried over anhydrous sodium sulfate, and evaporated under reduced pressure to obtain a crude product. Finally, the final product 2-benzoyl-6-bromoquinazolin-4(3H)-one was purified by column chromatography with a yield of 68%.

[0053] The structural characterization data of the obtained target product are shown below:

[0054] 1H NMR (500 MHz, DMSO-d6) δ 12.89 (s, 1H), 8.29 (s, 1H), 8.23 ​​– 8.12(m, 2H), 8.03 (d, J = 8.6 Hz, 1H), 7.75 (dt, J = 16.1, 8.6 Hz, 2H), 7.68 –7.55 (m, 2H) ppm.

[0055] 13 C{ 1 H} NMR (125 MHz, DMSO-d6) δ 187.5, 160.5, 150.0, 146.7, 138.1,134.9, 134.4, 131.4, 131.1, 129.1, 128.7, 125.0, 121.7 ppm.

[0056] HRMS (ESI-TOF) [M+H] + calcd. for C 15 H9BrN2O2 328.9920; found 328.9923.

[0057] The structure of the target compound is inferred from the above characterization data as follows:

[0058]

[0059] Example 4

[0060] Take a quartz reaction tube for use, add weighed acetophenone (0.22 mmol), I2 (10 mol%, 0.02mmol), 3CZEPAIPN (1 mol%, 0.002 mmol) in sequence, add DMSO (3 mL), and irradiate with blue light at 110 °C. o C was reacted for 0.5 hours, 2-amino-7-chlorobenzamide (0.2 mmol) was added, and TCL was monitored. After the reaction was completed, saturated sodium chloride solution (3 mL) was added, and the reaction mixture was extracted with ethyl acetate (3 × 3 mL). The organic layer was collected, dried over anhydrous sodium sulfate, and vacuum rotary evaporation was performed to obtain a crude product, which was finally purified by column chromatography to obtain the final product 2-benzoyl-7-chloroquinazoline-4(3H)-one with a yield of 67%.

[0061] The structural characterization data of the obtained target product are shown below:

[0062] 1H NMR (500 MHz, DMSO-d6) δ 12.83 (s, 1H), 8.20 (d, J = 8.4 Hz, 1H), 8.15 (d, J = 7.7 Hz, 2H), 7.85 (s, 1H), 7.75 (t, J = 7.5 Hz, 1H), 7.68 (d, J = 8.3 Hz, 1H), 7.59 (t, J = 7.7 Hz, 2H) ppm; 13 C{ 1 H} NMR (125 MHz, DMSO-d6) δ187.56, 161.21, 151.05, 148.88, 139.85, 135.01, 134.38, 131.41, 129.19,129.14, 128.61, 127.90, 122.23 ppm.

[0063] HRMS (ESI-TOF) m / z: [M+H] + Calculate for C 15 H 10 ClN2O2 285.0425; found285.0434.

[0064] The structure of the target compound is inferred from the above characterization data as follows:

[0065]

[0066] Example 5

[0067] Take a quartz reaction tube for use, add weighed acetophenone (0.22 mmol), I2 (10 mol%, 0.02mmol), 3CZEPAIPN (1 mol%, 0.002 mmol) in sequence, add organic solvent DMSO (3 mL), and irradiate with blue light at 110 o C was reacted for 0.5 hours, 2-amino-5-methoxybenzamide (0.2 mmol) was added, and TCL was monitored. After the reaction was completed, saturated sodium chloride solution (3 mL) was added, and the reaction mixture was extracted with ethyl acetate (3 × 3 mL). The organic layer was collected, dried over anhydrous sodium sulfate, and vacuum rotary evaporation was performed to obtain a crude product, which was finally purified by column chromatography to obtain the final product 2-benzoyl-6-methoxyquinazolin-4(3H)-one with a yield of 75%.

[0068] The structural characterization data of the obtained target product are shown below:

[0069] 1H NMR (500 MHz, DMSO-d6) δ 12.57 (s, 1H), 8.17 (d, J = 7.7 Hz, 2H), 7.74 (dd, J = 12.0, 8.1 Hz, 2H), 7.64 – 7.56 (m, 3H), 7.49 (dd, J = 9.0, 2.9Hz, 1H), 3.92 (s, 3H) ppm.

[0070] 13 C{ 1 H} NMR (125 MHz, DMSO-d6) δ 187.4, 161.3, 159.9, 147.2, 141.8,134.9, 134.5, 131.4, 130.8, 129.0, 124.6, 124.5, 106.9, 56.3 ppm.

[0071] HRMS (ESI-TOF) [M+H] + calcd. for C 16 H 12 N2O3 281.0921; found 281.0921.

[0072] The structure of the target compound is inferred from the above characterization data as follows:

[0073]

[0074] Example 6

[0075] Take a quartz reaction tube for use, add weighed 4-methoxyacetophenone (0.22 mmol), I2 (10 mol%, 0.02 mmol), 3CZEPAIPN (1 mol%, 0.002 mmol) in sequence, add organic solvent DMSO (3 mL), and irradiate with blue light at 110 °C. o C was reacted for 0.5 hours, 2-aminobenzamide (0.2 mmol) was added, and TCL was monitored. After the reaction was completed, saturated sodium chloride solution (3 mL) was added, and the reaction mixture was extracted with ethyl acetate (3 × 3 mL). The organic layer was collected, dried over anhydrous sodium sulfate, and vacuum rotary evaporation was performed to obtain a crude product. Finally, column chromatography was used to obtain the final product 2-(4-methoxybenzoyl)quinazolin-4(3H)-one with a yield of 68%.

[0076] The structural characterization data of the obtained target product are shown below:

[0077] 1H NMR (500 MHz, DMSO-d6) δ 12.62 (s, 1H), 8.28 – 8.12 (m, 3H), 7.89(t, J = 7.7 Hz, 1H), 7.78 (d, J = 8.2 Hz, 1H), 7.65 (t, J = 7.8 Hz, 1H), 7.12(d, J = 7.1 Hz, 2H), 3.89 (s, 3H) ppm.

[0078] 13 C{ 1 H} NMR (125 MHz, DMSO-d6) δ 185.8, 164.8, 161.7, 150.2, 147.9,135.2, 133.9, 132.9, 128.8, 128.7, 127.1, 126.5, 123.3, 114.6, 110.4, 56.3ppm.

[0079] HRMS (ESI-TOF) [M+H] + calcd. for C 16 H 12 N2O3 281.0921; found 281.0926.

[0080] The structure of the target compound is inferred from the above characterization data as follows:

[0081]

[0082] Example 7

[0083] A quartz reaction tube was prepared for use, and weighed 3,4-dimethylacetophenone (0.22 mmol), I2 (10 mol%, 0.02 mmol), 3CZEPAIPN (1 mol%, 0.002 mmol), and DMSO (3 mL) were added in sequence. The reaction mixture was stirred at 110 °C under blue light. o C was reacted for 0.5 hours, and 2-aminobenzamide (0.2 mmol) was added. TCL monitoring was performed. After the reaction was completed, saturated sodium chloride solution (3 mL) was added, and the reaction mixture was extracted with ethyl acetate (3 × 3 mL). The organic layer was collected, dried over anhydrous sodium sulfate, and vacuum rotary evaporation was performed to obtain a crude product. Finally, column chromatography was used to obtain the final product 2-(3,4-dimethylbenzoyl)quinazolin-4(3H)-one with a yield of 70%.

[0084] The structural characterization data of the obtained target product are shown below:

[0085] 1 H NMR (500 MHz, DMSO-d6) δ 12.65 (s, 1H), 8.21 (d, J = 6.4 Hz, 1H), 7.89 (dd, J = 15.4, 8.7 Hz, 3H), 7.77 (d, J = 8.1 Hz, 1H), 7.64 (t, J = 7.6Hz, 1H), 7.35 (d, J = 7.9 Hz, 1H), 2.32 (d, J = 13.3 Hz, 6H) ppm;

[0086] 13 C{ 1 H} NMR (125 MHz, DMSO-d6) δ 187.0, 161.1, 149.6, 147.3, 144.2,136.9, 134.8, 131.9, 131.5, 129.8, 128.8, 128.43, 128.35, 126.1, 122.9, 19.9,19.4 ppm.

[0087] HRMS (ESI-TOF) [M+H] + calcd. for C 17 H 14 N2O2 279.1128; found 279.1131.

[0088] The structure of the target compound is inferred from the above characterization data as follows:

[0089]

[0090] Example 8

[0091] A quartz reaction tube was prepared for use, and weighed 1-naphthylacetophenone (0.22 mmol), I2 (10 mol%, 0.02 mmol), 3CZEPAIPN (1 mol%, 0.002 mmol), and DMSO (3 mL) were added in sequence. The reaction mixture was stirred at 110 °C under blue light. o C was reacted for 0.5 hours, and 2-aminobenzamide (0.2 mmol) was added, and the reaction mixture was monitored by TCL. After the reaction was completed, a saturated sodium chloride solution (3 mL) was added, and the reaction mixture was extracted with ethyl acetate (3 × 3 mL). The organic layer was collected, dried over anhydrous sodium sulfate, and evaporated under reduced pressure to obtain a crude product. Finally, the final product 2-(1-naphthoyl)quinazolin-4(3H)-one was obtained by column chromatography with a yield of 61%.

[0092] The structural characterization data of the obtained target product are shown below:

[0093] 1 H NMR (500 MHz, DMSO-d6) δ 12.83 (s, 1H), 8.47 (d, J = 8.3 Hz, 1H), 8.25 (dd, J = 14.4, 8.0 Hz, 2H), 8.14 (d, J = 7.2 Hz, 1H), 8.10 (d, J = 8.0Hz, 1H), 7.85 (t, J = 7.7 Hz, 1H), 7.66 (q, J = 7.7 Hz, 5H) ppm.

[0094] 13 C{ 1 H} NMR (125 MHz, DMSO) δ 190.1, 161.6, 150.6, 147.7, 135.2,134.3, 133.8, 133.2, 131.7, 131.0, 129.28, 129.25, 129.1, 128.8, 127.2,126.6, 125.4, 125.1, 123.4 ppm.

[0095] HRMS (ESI-TOF) [M+H] + calcd. for C 19 H 12 N2O2 301.0972; found 301.1419.

[0096] The structure of the target compound is inferred from the above characterization data as follows:

[0097]

[0098] Example 9

[0099] A quartz reaction tube was prepared for use, and weighed 2-naphthylacetophenone (0.22 mmol), I2 (10 mol%, 0.02 mmol), 3CZEPAIPN (1 mol%, 0.002 mmol), and DMSO (3 mL) were added in sequence. The reaction mixture was stirred at 110 °C under blue light. oC was reacted for 0.5 hours, and 2-aminobenzamide (0.2 mmol) was added. TCL monitoring was performed. After the reaction was completed, saturated sodium chloride solution (3 mL) was added, and the reaction mixture was extracted with ethyl acetate (3 × 3 mL). The organic layer was collected, dried over anhydrous sodium sulfate, and evaporated under reduced pressure to obtain a crude product. Finally, column chromatography was used to obtain the final product 2-(2-naphthoyl)quinazolin-4(3H)-one with a yield of 63%.

[0100] The structural characterization data of the obtained target product are shown below:

[0101] 1 H NMR (500 MHz, DMSO-d6) δ 12.76 (s, 1H), 8.86 (d, J = 40.5 Hz, 1H), 8.30 – 7.99 (m, 5H), 7.89 (t, J = 7.6 Hz, 1H), 7.81 (d, J = 8.5 Hz, 1H), 7.67(dt, J = 35.2, 7.7 Hz, 3H) ppm.

[0102] 13 C{ 1 H} NMR (125 MHz, DMSO-d6) δ 187.7, 161.7, 150.0, 148.0, 136.0,135.3, 134.5, 133.0, 132.3, 131.9, 130.5, 130.0, 129.0, 128.9, 128.3, 127.7,126.6, 125.5, 123.4 ppm.

[0103] HRMS (ESI-TOF) [M+H] + calcd. for C 19 H 12 N2O2 301.0972; found 301.0972.

[0104] The structure of the target compound is inferred from the above characterization data as follows:

[0105]

[0106] Example 10

[0107] A quartz reaction tube was prepared for use, and weighed 2-acetylfuran (0.22 mmol), I2 (10 mol%, 0.02 mmol), 3CZEPAIPN (1 mol%, 0.002 mmol) and DMSO (3 mL) were added in sequence. After 0.5 hours of reaction under blue light irradiation, 2-aminobenzamide (0.2 mmol) was added and monitored by TCL. After the reaction was completed, a saturated sodium chloride solution (3 mL) was added, and the reaction mixture was extracted with ethyl acetate (3 × 3 mL). The organic layer was collected, dried over anhydrous sodium sulfate, and the crude product was obtained by vacuum rotary evaporation. Finally, the final product 2-furan-2-carbonylquinazolin-4 (3H)-one was obtained by column chromatography with a yield of 75%.

[0108] The structural characterization data of the obtained target product are shown below:

[0109] 1 H NMR (500 MHz, DMSO-d6) δ 12.51 (s, 1H), 8.29 – 8.15 (m, 3H), 7.92 (d, J = 4.1 Hz, 2H), 7.66 (dt, J = 8.2, 4.2 Hz, 1H), 6.87 (s, 1H) ppm.

[0110] 13 C{ 1 H} NMR (125 MHz, DMSO-d6) δ 173.0, 161.3, 150.8, 149.7, 148.1,147.6, 135.3, 129.3, 129.2, 126.6, 123.6, 113.8 ppm.

[0111] HRMS (ESI-TOF) [M+H] + calcd. for C 13 H8N2O3 241.0608; found 241.0611.

[0112] The structure of the target compound is inferred from the above characterization data as follows:

[0113]

[0114] The above-mentioned implementation modes are partial embodiments of the method of the present invention, but they do not limit the specific implementation modes of the present invention. Any other substitutions, basic skeleton changes, and condition simplifications made without departing from the spirit and principle of the present invention should be classified as equivalent replacement methods and are included in the protection scope of the present invention.

Claims

1. A visible light-promoted I2-catalyzed C(sp 3 A method for synthesizing 2-benzoylquinazoline-4(3H)-one by amination reaction of )-H, characterized in that: The following steps are included: In a glass reaction container, acetophenone, I2 and a photocatalyst are added in proportion, and an organic solvent is added under air atmosphere. After irradiation with blue light and magnetic stirring at 110°C for 0.5 hour, 2-aminobenzamide is added and the reaction is continued for 5.5 hours. After the reaction is completed, a saturated sodium chloride solution (3 mL) is added, and the reaction mixture is extracted with ethyl acetate (3 × 3 mL). The organic layer is collected, dried over anhydrous sodium sulfate, and evaporated under reduced pressure to obtain a crude product, which is finally separated and purified by column chromatography to obtain the 2-benzoylquinazoline-4(3H)-one derivative.

2. The synthesis method according to claim 1, characterized in that The chemical reaction equation for synthesizing 2-benzoylquinazoline-4(3H)-one is shown below: ， In the formula, R 1 , R 2 One or more selected from the group consisting of hydrogen, 5-chloro, 4-chloro, 5-bromo, 5-methoxy, 4-methoxyphenyl, 3,4-dimethylphenyl, 1-naphthyl, 2-naphthyl and 2-furyl.

3. The preparation method according to claim 1 or 2, characterized in that: The organic solvent is one or more of DMSO, 1,4-dioxane and DMF.

4. The preparation method according to claim 1 or 2, characterized in that: The photocatalyst is one or more of 4CZIPN, 3CZEPAIPN, and 3CZMPAIPN; the feeding molar ratio of the photocatalyst to the 2-aminobenzamide compound is 1:

100.

5. The preparation method according to claim 1 or 2, characterized in that: The catalyst is I2; the molar ratio of I2 to 2-aminobenzamide compounds is 1:

10.

6. The preparation method according to claim 1 or 2, characterized in that: The method of promoting I2 catalysis C(sp 3 The reaction time of the method for synthesizing 2-benzoylquinazoline-4(3H)-one by )-H amination reaction is 6 hours.

7. The preparation method according to claim 1 or 2, characterized in that: The target product 2-benzoylquinazoline-4(3H)-one 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.

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