Quinazolinone derivative containing dihydrocoumarin group as well as preparation method and application of quinazolinone derivative

Abstract

The invention belongs to the technical field of chemical synthesis, and particularly relates to a quinazolinone derivative containing a dihydrocoumarin group and a preparation method and application thereof, the quinazolinone derivative containing the dihydrocoumarin group has a structure shown in the specification, and in the formula, R1 and R2 are respectively and independently hydrogen, C1-C3 alkyl, C1-C3 alkoxy, halogen, nitryl or trifluoromethyl. According to the invention, the quinazolinone derivative and dihydrocoumarin are combined, and the obtained derivative has a relatively good antibacterial effect and has important research value for expanding pesticide types. And # imgabs0 #.

Description

Technical Field

[0001] The present invention belongs to the technical field of chemical synthesis, and specifically relates to a class of quinazolinone derivatives containing a dihydrocoumarin group, and a preparation method and application thereof. Background Art

[0002] Pesticides play an important role in modern agriculture, and their necessity is mainly reflected in the following aspects: In modern agricultural production, pesticides are usually used to inhibit the reproduction of microorganisms, thereby reducing the damage of microorganisms to crops and increasing yields. Extreme weather may exacerbate the outbreak of pests and diseases. For example, warm winters lead to an increase in the overwintering rate of insect eggs, and pesticides can be used as an emergency management tool. In addition, mechanized pesticide spraying is more suitable for large-scale cultivation than manual weeding / catching insects. However, with the extensive use of pesticides, the problem of drug resistance has gradually emerged, reducing the efficacy of pesticides. In order to achieve the desired bacteriostatic effect, it is usually necessary to increase the dosage of pesticides. The increase in the amount of pesticides used will pollute soil resources and water resources, and is likely to bring the risk of increased pesticide residues in food. Summary of the Invention

[0003] In order to solve the above technical problems, the present invention provides a class of quinazolinone derivatives containing a dihydrocoumarin group, and a preparation method and application thereof. The present invention solves the problems of reduced efficacy of traditional pesticides and increased dosage due to drug resistance by developing new compounds with good bacteriostatic effects. The present invention combines quinazolinone derivatives and dihydrocoumarin, and the obtained derivatives have good bacteriostatic effects, which has important research and application value for further studying pesticides with better bacteriostatic effects to replace the use of pesticides that have developed drug resistance and realizing the continuous iteration of pesticides.

[0004] Quinazolinone derivatives have received extensive attention due to their significant biological activities and are applied clinically, such as cardiovascular drugs, lipogenesis inhibitors, anti-infective drugs, anti-cancer drugs, anti-convulsant drugs, etc. As the core skeleton of many natural products, dihydrocoumarin has attracted more and more attention due to its diverse structures and biological activities. Different types of dihydrocoumarin derivatives show diverse biological activities. For example, some of these derivatives have been used as drug candidates, such as anti-leishmanial activity, antibacterial activity, and immunomodulatory candidate drugs, etc.

[0005] 。

[0006] Therefore, the synthesis of such compounds is of great significance. By various synthetic means, expanding the variety of dihydrocoumarin derivatives and their applications can lay a research foundation for the research and application of such derivatives. However, the current synthesis methods have problems such as being environmentally unfriendly or complex, which limit the further large-scale application of these compounds. For this reason, the present invention also proposes a synthesis method of quinazolinone derivatives containing a dihydrocoumarin group. This method is simple, green, and suitable for large-scale production applications, providing method support for subsequent product research.

[0007] The present invention is specifically realized through the following technical solutions.

[0008] The present invention provides a class of quinazolinone derivatives containing a dihydrocoumarin group, and their structures are shown as follows: ; wherein, R 1 , R 2 are each independently hydrogen, a C1-C3 alkyl group (i.e., an alkyl group with 1-3 carbon atoms), a C1-C3 alkoxy group (i.e., an alkoxy group with 1-3 carbon atoms), a halogen, a nitro group or a trifluoromethyl group.

[0009] Preferably, the alkyl group is a methyl group, the alkoxy group is an ethoxy group, and the halogen is one or two of fluorine, chlorine and bromine.

[0010] The present invention also provides a preparation method of the above-mentioned quinazolinone derivatives containing a dihydrocoumarin group, including the following steps: Under a solvent system, using compound 1 and compound 2 as raw materials, through a tandem Michael addition / decarboxylation reaction, compound 3 is prepared; the synthetic route is shown as follows: ; wherein, R 1 , R 2 are each independently hydrogen, a C1-C3 alkyl group, a C1-C3 alkoxy group, a halogen, a nitro group or a trifluoromethyl group.

[0011] Preferably, the molar ratio of compound 1 to compound 2 is 1:1.

[0012] Preferably, the solvent is DMSO.

[0013] Preferably, the reaction temperature is 100°C - 120°C, and the reaction time is 3 hours - 6 hours.

[0014] Preferably, the reaction temperature is 100°C, and the reaction time is 3 hours.

[0015] Preferably, dissolve compound 1 and compound 2 in a solvent, heat up and stir for reaction, and after the reaction is completed, purify by column chromatography.

[0016] The present invention also provides the use of the above-mentioned quinazolinone derivatives containing a dihydrocoumarin group in the preparation of pesticides, and the pesticides are used to inhibit one or more of Gaeumannomyces graminis var. tritici, Rhizoctonia solani, Rhizoctonia cerealis, Fusarium graminearum, Fusarium oxysporum, and Fusarium moniliforme.

[0017] Compared with the prior art, the present invention has the following beneficial effects: The present invention solves the problems of reduced efficacy of traditional pesticides and increased dosage due to drug resistance by developing new compounds with good bacteriostatic effects. For this purpose, a class of quinazolinone derivatives containing a dihydrocoumarin group is provided, and the obtained derivatives have good bacteriostatic effects, which has important research value for expanding the types of pesticides.

[0018] The synthesis method of the present invention is simple, does not require the use of a catalyst, has mild reaction conditions, short reaction time, and simple post-treatment, and is very suitable for large-scale production applications. Description of the Drawings

[0019] Figure 1 is the 1 1H NMR spectrum of compound 3ab.

[0020] Figure 2 is the 1 1H NMR spectrum of compound 3ac.

[0021] Figure 3 is the 1 1H NMR spectrum of compound 3ad.

[0022] Figure 4 is the 1 1H NMR spectrum of compound 3ak.

[0023] Figure 5 is the 1 1H NMR spectrum of compound 3id.

[0024] Figure 6 is the HRMS spectrum of compound 3aa.

[0025] Figure 7 is the HRMS spectrum of compound 3ab.

[0026] Figure 8 is the HRMS spectrum of compound 3ib.

[0027] Figure 9 is the photo of the bacteriostatic effect on Gaeumannomyces graminis var. tritici, where A is the blank control and B is compound 3ib.

[0028] Figure 10 is the photo of the bacteriostatic effect on Rhizoctonia solani, where A is the blank control and B is compound 3ib.

[0029] Figure 11 Photographs of the antibacterial effect against Rhizoctonia cerealis, where A is the blank control and B is compound 3id.

[0030] Figure 12 Photographs of the antibacterial effect against Fusarium graminearum, where A is the blank control and B is compound 3ac.

[0031] Figure 13 Photographs of the antibacterial effect against Fusarium oxysporum, where A is the blank control and B is compound 3ha.

[0032] Figure 14 Photographs of the antibacterial effect against Fusarium moniliforme, where A is the blank control and B is compound 3id. Detailed implementation manners

[0033] In order to enable those skilled in the art to better understand and implement the technical solution of the present invention, the present invention will be further described below in conjunction with specific embodiments and drawings, but the described embodiments shall not be construed as limiting the present invention. In the following embodiments, the experimental methods and detection methods are all conventional methods unless otherwise specified; the reagents and materials are all commercially available unless otherwise specified.

[0034] The present invention first provides a class of quinazolinone derivatives containing a dihydrocoumarin group, and their structures are shown as follows: ; wherein, R 1 , R 2 are each independently hydrogen, C1-C3 alkyl, C1-C3 alkoxy, halogen, nitro or trifluoromethyl.

[0035] Preferably, the alkyl is methyl, the alkoxy is ethoxy, and the halogen is one or two of fluorine, chlorine and bromine.

[0036] The present invention also provides a preparation method of the above-mentioned quinazolinone derivatives containing a dihydrocoumarin group, which includes the following steps: Under a solvent system, using compound 1 and compound 2 as raw materials, compound 3 is prepared through a tandem Michael addition / decarboxylation reaction; the synthetic route is shown as follows: ; wherein, R 1 , R 2 are each independently hydrogen, C1-C3 alkyl, C1-C3 alkoxy, halogen, nitro or trifluoromethyl.

[0037] Preferably, the molar ratio of Compound 1 to Compound 2 is 1:1. The solvent is DMSO. The reaction temperature is 100°C to 120°C, and the reaction time is 3 hours to 6 hours. More preferably, the reaction temperature is 100°C and the reaction time is 3 hours. Dissolve Compound 1 and Compound 2 in the solvent, heat up and stir to react. After the reaction is completed, purify by column chromatography. The eluent for column chromatography is petroleum ether and ethyl acetate, with a specific ratio of 5:1 to 2:1. The synthesis method of the present invention is simple, does not require the use of a catalyst, has mild reaction conditions, a short reaction time, and simple post-treatment, and is very suitable for large-scale production applications. Moreover, the synthesized derivative has a good antibacterial effect and has important research value for expanding the types of pesticides.

[0038] The following specifically describes the content of the present invention.

[0039] Test Examples 1 to 12 The present invention first explores the specific reaction conditions, specifically as in Test Examples 1 to 12, and the synthesis route is as follows: Mix Compound 1a (1 mmol) and Compound 2a (1 mmol), place them in a solvent (10 mL), heat up and stir to react. The obtained compound is purified by silica gel column chromatography, and the eluent is petroleum ether and ethyl acetate, with a specific volume ratio of 5:1, to obtain the target compound 3aa. The reaction solvents, reaction temperatures, reaction times, and corresponding product yields in Test Examples 1 to 12 are shown in Table 1.

[0040] Table 1 Reaction Conditions and Yields It can be seen from Table 1 that when the solvent is DMSO and stirred at 100°C to 120°C for 3 hours to 6 hours, the yield reaches over 90%. More preferably, the temperature is preferably 100°C and the reaction time is 3 hours. The reaction temperature is lower, the reaction time is shorter, and the yield is higher. Therefore, the preferred synthesis conditions are determined as follows: Mix Compound 1a and Compound 2a in a molar ratio of 1:1 in the solvent DMSO, stir and react at 100°C for 3 hours, and the obtained compound can be purified by column chromatography. The following screens different reaction substrates under these preferred reaction conditions, specifically as shown in Examples 1 to 29.

[0041] Examples 1 to 29 According to the above preferred reaction conditions, different substrates are explored, and the synthesis route is as follows: In the above synthetic route, compound 1 (1 mmol) and compound 2 (1 mmol) were mixed with DMSO (10 mL) as the solvent, and the mixture was stirred at 100 °C for 3 hours. The resulting compound was purified by column chromatography. The substituents in the synthetic route and the corresponding yields are shown in Table 2.

[0042] Table 2 Results of different reaction substrates and yields The structural characterization of the above compounds is as follows: Compound 3aa: White solid, mp: 252.8 - 254.2 °C. 1 H NMR (400 MHz, CDCl3) δ 11.80(s, 1H), 8.27 (d, J = 7.8 Hz, 1H), 7.82 (t, J = 7.5 Hz, 1H), 7.74 (d, J = 8.0 Hz,1H), 7.53 (t, J = 7.4 Hz, 1H), 7.25 – 7.19 (m, 2H), 7.05 (t, J = 7.4 Hz, 1H),6.99 (d, J = 8.0 Hz, 1H), 3.92 – 3.85 (m, 1H), 3.10 (dd, J = 14.9, 7.1 Hz, 1H),3.02 (d, J = 7.9 Hz, 1H), 3.00 – 2.96 (m, 2H). 13 C NMR (101 MHz, DMSO- d 6 ) δ167.54, 161.62, 154.47, 151.18, 148.52, 134.41, 128.55, 127.88, 126.85,126.28, 125.72, 125.50, 124.34, 120.92, 116.60, 38.89, 33.50, 32.19. HRMS(ESI) m / z calculated for C 18 H 13 N2O3[M - H] - 305.09262, found 305.09464. Compound 3ab: White solid, mp: 236.9 - 239.5 °C. 1 H NMR (400 MHz, DMSO- d 6 ) δ12.26 (s, 1H), 7.76 (dd, J = 8.2, 2.5 Hz, 1H), 7.43 (d, J = 8.2 Hz, 1H), 7.29 (d, J = 7.5 Hz, 2H), 7.22 (dd, J = 10.7, 8.3 Hz, 1H), 7.09 (dd, J = 7.9, 3.2 Hz, 2H),3.77 – 3.73 (m, 1H), 3.10 – 3.04 (m, 1H), 2.95 (dd, J = 14.9, 6.7 Hz, 1H), 2.85(d, J = 4.1 Hz, 1H), 2.81 (d, J = 2.9 Hz, 1H). 13 C NMR (101 MHz, DMSO- d 6 ) δ 167.51,161.80, 159.07 (d, J = 25 Hz), 155.66, 151.18, 150.70, 135.00 (d, J = 10 Hz),128.59, 127.87, 125.39, 124.37, 122.92, 116.61, 112.74, 112.53, 38.93, 33.46,32.13. HRMS (ESI) m / z calculated for C 18 H 12 FN2O3[M - H] - 323.08320, found323.08533. Compound 3ac: White solid, mp: 267.7 - 270.7 °C. 1 H NMR (400 MHz, DMSO- d 6) δ12.27 (s, 1H), 7.69 (t, J = 8.0 Hz, 1H), 7.55 (d, J = 8.1 Hz, 1H), 7.47 (d, J = 7.7Hz, 1H), 7.29 (t, J = 6.7 Hz, 2H), 7.12 – 7.07 (m, 2H), 3.78 – 3.72 (m, 1H),3.07 (dd, J = 16.3, 6.4 Hz, 1H), 2.94 (dd, J = 14.9, 6.7 Hz, 1H), 2.86 – 2.78 (m,2H). 13 C NMR (101 MHz, DMSO- d 6 ) δ 167.50, 159.79, 155.38, 151.17, 151.05,134.19, 132.36, 128.65, 128.58, 127.87, 126.43, 125.38, 124.36, 117.91,116.60, 38.83, 33.46, 32.11. HRMS (ESI) m / z calculated for C 18 H 12 ClN2O3[M - H] - 339.05364, found 339.05588. Compound 3ad: White solid. mp: 235.4 - 236.5 °C. 1 H NMR (400 MHz, DMSO- d 6 ) δ12.41 (s, 1H), 8.01 (d, J = 2.5 Hz, 1H), 7.82 (dd, J = 8.7, 2.5 Hz, 1H), 7.65 (d, J = 8.7 Hz, 1H), 7.29 (dd, J = 12.3, 4.5 Hz, 2H), 7.09 (t, J = 7.9 Hz, 2H), 3.76(dt, J= 11.2, 5.7 Hz, 1H), 3.07 (dd, J = 16.3, 6.4 Hz, 1H), 2.97 (dd, J = 14.9, 6.7 Hz, 1H), 2.88 – 2.81 (m, 2H). 13 C NMR (101 MHz, DMSO- d 6 ) δ 167.51, 160.66, 155.14, 151.18, 147.24, 134.51, 130.52, 129.11, 128.58, 127.87, 125.37, 124.73, 124.35, 122.21, 116.60, 38.89, 33.47, 32.19. HRMS (ESI) m / z calculated for C 18 H 12 ClN2O3[M - H] - 339.05364, found 339.05582. Compound 3ae: White solid, mp: 271.8 - 273.2 °C. 1 H NMR (400 MHz, DMSO- d 6 ) δ 12.13 (s, 1H), 7.87 (s, 1H), 7.61 (dd, J = 8.3, 2.0 Hz, 1H), 7.53 (d, J = 8.3 Hz, 1H), 7.28 (dd, J = 11.9, 5.7 Hz, 2H), 7.09 (t, J = 6.9 Hz, 2H), 3.77 (td, J = 10.8, 6.7 Hz, 1H), 3.07 (dd, J = 16.3, 6.4 Hz, 1H), 2.94 (dd, J = 14.9, 6.8 Hz, 1H), 2.87 – 2.79 (m, 2H), 2.43 (s, 3H). 13 C NMR (101 MHz, DMSO- d 6) δ 167.54, 161.55,153.53, 151.17, 146.54, 135.90, 135.66, 128.54, 127.88, 126.72, 125.53,125.09, 124.33, 120.66, 116.59, 39.05, 33.52, 32.21, 20.77. HRMS (ESI) m / z calculated for C 19 H 15 N2O3[M - H] - 319.10827, found 319.11035. Compound 3af: White solid, mp: 283.4 - 284.5 °C. 1 H NMR (400 MHz, DMSO- d 6 ) δ12.57 (s, 1H), 8.31 (s, 1H), 8.09 (dd, J = 8.6, 2.0 Hz, 1H), 7.81 (d, J = 8.5 Hz,1H), 7.30 (t, J = 6.6 Hz, 2H), 7.10 (t, J = 7.8 Hz, 2H), 3.86 – 3.72 (m, 1H),3.06 (ddd, J = 21.6, 15.7, 6.5 Hz, 2H), 2.95 – 2.80 (m, 2H). 13 C NMR (101 MHz,DMSO- d 6 ) δ 167.51, 161.03, 157.32, 151.19, 130.43 (d, J = 3 Hz), 128.62,128.33, 127.87, 126.41, 126.09, 125.30, 124.37, 123.18 (q, J = 4 Hz), 122.50,121.01, 116.62, 38.89, 33.47, 32.22. HRMS (ESI) m / z calculated for C 19 H 12 F3N2O3[M - H] -373.08000, found 373.08246. Compound 3ag: White solid, mp: 243.4 - 245.5 °C. 1 H NMR (400 MHz, DMSO- d 6 ) δ12.36 (s, 1H), 8.06 (d, J = 8.5 Hz, 1H), 7.67 (d, J = 1.9 Hz, 1H), 7.51 (dd, J =8.5, 2.1 Hz, 1H), 7.30 (dd, J = 11.4, 4.5 Hz, 2H), 7.10 (t, J = 7.8 Hz, 2H), 3.76(dd, J = 6.7, 4.2 Hz, 1H), 3.08 (dd, J = 16.4, 6.5 Hz, 1H), 2.97 (dd, J = 15.0, 6.7Hz, 1H), 2.91 – 2.79 (m, 2H). 13 C NMR (101 MHz, DMSO- d 6 ) δ 167.53, 161.02,156.23, 151.18, 149.61, 139.00, 128.59, 127.91, 127.86, 126.58, 125.96,125.31, 124.36, 119.77, 116.61, 39.10, 33.51, 32.18.HRMS (ESI) m / z calculatedfor C 18 H 13 ClN2O3[M + H] + 341.0693, found 341.0698. Compound 3ah: White solid, mp: 250.0 - 251.9 °C. 1 H NMR (400 MHz, DMSO- d 6 ) δ12.35 (s, 1H), 7.98 (d, J= 8.5 Hz, 1H), 7.82 (d, J = 1.6 Hz, 1H), 7.64 (dd, J =8.5, 1.8 Hz, 1H), 7.29 (t, J = 7.3 Hz, 2H), 7.10 (t, J = 7.9 Hz, 2H), 3.82 – 3.68(m, 1H), 3.08 (dd, J = 16.4, 6.5 Hz, 1H), 2.97 (dd, J = 15.0, 6.7 Hz, 1H), 2.92 –2.78 (m, 2H). 13 C NMR (101 MHz, DMSO- d 6 ) δ 167.52, 161.15, 156.16, 151.18,149.67, 129.32, 129.04, 128.58, 127.97, 127.91, 127.85, 125.30, 124.35,120.06, 116.60, 39.10, 33.50, 32.17.HRMS (ESI) m / z calculated for C 18 H 13 BrN2O3[M + H] + 385.0188, found 385.0187. Compound 3ai: White solid, mp: 237.9 - 239.2 °C. 1 H NMR (400 MHz, DMSO- d 6 ) δ12.01 (s, 1H), 7.91 (d, J = 7.9 Hz, 1H), 7.64 (d, J = 7.2 Hz, 1H), 7.38 – 7.32(m, 1H), 7.28 (dd, J = 10.9, 4.5 Hz, 2H), 7.09 (t, J = 7.4 Hz, 2H), 3.85 – 3.74(m, 1H), 3.08 (dd, J= 16.2, 6.1 Hz, 1H), 3.02 – 2.90 (m, 2H), 2.89 – 2.81 (m,1H), 2.49 (s, 3H). 13 C NMR (101 MHz, DMSO- d 6 ) δ 167.61, 161.91, 153.22, 151.16,146.98, 134.98, 134.72, 128.53, 127.89, 125.72, 124.34, 123.35, 123.28,120.79, 116.59, 38.90, 33.46, 32.26, 17.17.HRMS (ESI) m / z calculated forC 19 H 16 N2O3[M + H] + 321.1239, found 321.1243. Compound 3aj: White solid, mp: 238.7 - 240.2 °C. 1 H NMR (400 MHz, DMSO- d 6 ) δ12.52 (s, 1H), 7.80 (ddd, J = 10.5, 9.2, 2.9 Hz, 1H), 7.67 – 7.50 (m, 1H), 7.29(d, J = 7.7 Hz, 2H), 7.10 (t, J = 7.0 Hz, 2H), 3.84 – 3.67 (m, 1H), 3.08 (dd, J =16.3, 6.1 Hz, 1H), 2.97 (dd, J = 14.7, 6.9 Hz, 1H), 2.90 – 2.80 (m, 2H). 13 C NMR(101 MHz, DMSO- d 6 ) δ 167.99, 160.64 (t, J = 4 Hz), 158.32 (dd, J = 12 Hz), 156.01(d, J = 12 Hz), 155.27, 151.60, 135.54 (dd,J = 2 Hz), 129.09, 128.31, 125.98, 124.86, 123.88 (dd, J = 2 Hz), 117.11, 110.30 (dd, J = 23 Hz), 106.96 (dd, J = 4Hz), 39.45, 33.89, 32.75. HRMS (ESI) m / z calculated for C 18 H 12 F2N2O3[M + Na] + 365.0714, found 365.0718. Compound 3ak: Yellow solid, mp: 273.4 - 274.5 °C. 1 1H NMR (400 MHz, DMSO - d 6 ) δ12.60 (s, 1H), 8.10 (dd, J = 5.6, 2.4 Hz, 1H), 7.97 – 7.95 (m, 1H), 7.31 (dd, J =14.4, 7.7 Hz, 2H), 7.12 – 7.08 (m, 2H), 3.83 – 3.76 (m, 1H), 3.13 – 3.06 (m,1H), 3.00 – 2.87 (m, 3H). 13 13C NMR (101 MHz, DMSO - d 6 ) δ 167.62, 160.24, 156.12, 151.14, 143.97, 134.05, 131.99, 130.18, 128.64, 127.90, 125.62, 124.40, 124.05, 123.40, 116.66, 38.84, 33.52, 32.10. HRMS (ESI) m / z calculated for C 18 H 11 Cl2N2O3[M - H] - 373.01467, found 373.01712. Compound 3ba: White solid, mp: 256.1 - 258.3 °C. 1 H NMR (400 MHz, DMSO- d 6 ) δ12.21 (s, 1H), 8.08 (d, J = 7.6 Hz, 1H), 7.83 – 7.76 (m, 1H), 7.62 (d, J = 8.1Hz, 1H), 7.52 – 7.43 (m, 2H), 7.34 (dd, J = 8.7, 2.5 Hz, 1H), 7.12 (d, J = 8.6Hz, 1H), 3.84 – 3.72 (m, 1H), 3.05 (ddd, J = 21.2, 15.8, 6.3 Hz, 2H), 2.85 (dt, J = 10.8, 5.8 Hz, 2H). 13 C NMR (101 MHz, DMSO- d 6 ) δ 167.00, 161.59, 154.21,150.10, 148.41, 134.42, 128.31, 127.89, 127.81, 127.57, 126.77, 126.33,125.72, 120.92, 118.42, 40.15, 32.93, 31.98.HRMS (ESI) m / z calculated forC 18 H 13 ClN2O3[M + H] + 341.0693, found 341.0698. Compound 3ca: White solid, mp: 265.8 - 266.7 °C. 1 H NMR (400 MHz, DMSO- d 6 ) δ12.23 (s, 1H), 8.08 (d, J = 7.9 Hz, 1H), 7.80 (t, J = 7.6 Hz, 1H), 7.63 (d, J = 8.1Hz, 1H), 7.48 (t, J= 7.5 Hz, 1H), 7.14 – 7.08 (m, 2H), 6.97 (d, J = 8.2 Hz, 1H),3.74 – 3.68 (m, 1H), 3.05 – 2.96 (m, 2H), 2.83 – 2.76 (m, 2H), 2.21 (s, 3H). 13 C NMR (101 MHz, DMSO- d 6 ) δ 167.65, 161.64, 154.48, 149.11, 148.52, 134.41,133.34, 128.88, 128.21, 126.84, 126.28, 125.71, 125.18, 120.92, 116.31,38.89, 33.42, 32.20, 20.31. HRMS (ESI) m / z calculated for C 19 H 15 N2O3[M - H] - 319.10827, found 319.11032. Compound 3cb: White solid, mp: 279.8 - 281.3 °C. 1 H NMR (400 MHz, DMSO- d 6 ) δ12.27 (s, 1H), 7.77 (dd, J = 8.2, 2.5 Hz, 1H), 7.44 (d, J = 8.2 Hz, 1H), 7.25 –7.20 (m, 1H), 7.14 – 7.08 (m, 2H), 6.97 (d, J = 8.2 Hz, 1H), 3.71 – 3.66 (m,1H), 3.04 – 2.93 (m, 2H), 2.82 – 2.74 (m, 2H), 2.22 (s, 3H). 13 C NMR (101 MHz,DMSO- d 6 ) δ 167.61, 155.65, 150.71, 149.10, 135.06, 134.95, 133.36, 128.91,128.19, 125.07, 122.92 (d,J = 3 Hz), 116.32, 112.73, 112.53, 38.89, 33.38, 32.13, 20.31. HRMS (ESI) m / z calculated for C 19 H 14 FN2O3[M - H] - 337.09885, found 337.10110. Compound 3cd: White solid, mp: 278.8 - 279.6 °C. 1 1H NMR (400 MHz, DMSO- d 6 ) δ12.40 (s, 1H), 8.01 (d, J = 2.5 Hz, 1H), 7.82 (dd, J = 8.7, 2.5 Hz, 1H), 7.65 (d, J = 8.7 Hz, 1H), 7.15 – 7.06 (m, 2H), 6.96 (d, J = 8.2 Hz, 1H), 3.70 (dt, J =12.3, 6.2 Hz, 1H), 3.05 – 2.94 (m, 2H), 2.85 – 2.75 (m, 2H), 2.21 (s, 3H). 13 13C NMR (101 MHz, DMSO- d 6 ) δ 167.62, 160.68, 155.15, 149.10, 147.24, 134.51, 133.36, 130.50, 129.10, 128.91, 128.19, 125.05, 124.72, 122.22, 116.31, 38.90, 33.40, 32.19, 20.31. HRMS (ESI) m / z calculated for C 19 H 14 ClN2O3[M - H] - 353.06930, found 353.07150. Compound 3cf: White solid, mp: 295.1 - 297.0 °C. 11H NMR (400 MHz, DMSO- d 6 ) δ12.57 (s, 1H), 8.32 (s, 1H), 8.12 – 8.08 (m, 1H), 7.81 (dd, J = 11.8, 7.0 Hz,1H), 7.15 – 7.08 (m, 2H), 6.97 (dd, J = 8.1, 5.3 Hz, 1H), 3.75 – 3.69 (m, 1H),3.07 – 3.00 (m, 2H), 2.80 - 2.88 (m, 2H), 2.39 (d, J = 5.3 Hz, 1H), 2.21 (s, 3H). 13 13C NMR (101 MHz, DMSO- d 6 ) δ 167.61, 161.02, 157.30, 151.02, 149.11, 133.39,130.41, 128.94, 128.35, 128.18, 126.08, 124.99, 123.15 (q, J = 4 Hz), 121.04,116.33, 38.89, 33.39, 32.19, 20.30. HRMS (ESI) m / z calculated for C 20 H 14 F3N2O3[M - H] - 387.09565, found 387.09793. Compound 3cl: Yellow solid, mp: 233.7 - 238.1 °C. 1 1H NMR (400 MHz, DMSO- d 6 ) δ12.72 (s, 1H), 8.77 (s, 1H), 8.54 (dd, J = 9.0, 2.7 Hz, 1H), 7.81 (d, J = 9.0 Hz,1H), 7.16 – 7.07 (m, 2H), 6.97 (d, J = 8.2 Hz, 1H), 3.73 (dt, J= 12.3, 6.2 Hz, 1H), 3.08 – 3.01 (m, 2H), 2.90 – 2.80 (m, 2H), 2.22 (s, 3H). 13 C NMR (101 MHz, DMSO- d 6 ) δ 167.59, 160.92, 158.57, 152.70, 149.11, 144.66, 133.40, 128.97, 128.59, 128.42, 128.16, 124.91, 121.87, 121.05, 116.34, 38.89, 33.39, 32.19, 20.31. HRMS (ESI) m / z calculated for C 19 H 14 N3O5[M - H] - 364.09335, found 364.09573. Compound 3da: White solid, mp: 228.6 - 230.7 °C. 1 H NMR (400 MHz, DMSO- d 6 ) δ 12.21 (s, 1H), 8.08 (dd, J = 7.9, 1.1 Hz, 1H), 7.85 – 7.76 (m, 1H), 7.63 (d, J = 8.0 Hz, 1H), 7.52 – 7.45 (m, 1H), 7.03 – 6.95 (m, 2H), 6.78 (dd, J = 6.1, 2.9 Hz, 1H), 4.06 (q, J = 7.1 Hz, 2H), 3.74 (dt, J = 11.3, 5.6 Hz, 1H), 3.05 (dd, J = 16.2, 6.2 Hz, 1H), 2.92 (dd, J = 14.8, 7.1 Hz, 1H), 2.82 (dt, J = 12.4, 5.8 Hz, 2H), 1.35 (t, J = 7.0 Hz, 3H). 13 C NMR (101 MHz, DMSO-d 6 ) δ 167.37, 161.62, 154.50, 148.55, 146.32, 140.21, 134.41, 126.87, 126.51, 126.27, 125.72, 124.27, 120.90, 118.93, 112.48, 64.00, 38.98, 33.43, 32.56, 14.67. HRMS (ESI) m / z calculated for C 20 H 18 N2O4[M + H] + 351.1345, found 351.1347. Compound 3ea: Yellow solid, mp: 251.6 - 252.8 °C. 1 1H NMR (400 MHz, DMSO - d 6 ) δ 12.22 (s, 1H), 8.08 (d, J J = 7.7 Hz, 1H), 7.79 (t, J J = 7.6 Hz, 1H), 7.62 (d, J J = 8.1 Hz, 1H), 7.48 (t, J J = 7.5 Hz, 1H), 7.21 (d, J J = 8.3 Hz, 1H), 7.14 (d, J J = 6.2 Hz, 2H), 3.82 – 3.73 (m, 1H), 3.10 – 2.98 (m, 2H), 2.91 – 2.80 (m, 2H). 13 13C NMR(101 MHz, DMSO - d 6 ) δ 167.24, 161.61, 159.37, 156.98, 154.24, 148.44, 147.49, 134.42, 127.47 (d, J J = 8 Hz), 126.81, 126.33, 125.73, 120.93, 118.18 (d, J J = 9 Hz), 115.12 (d, J J = 23 Hz), 114.46 (d, J= 24 Hz), 38.75, 32.97, 32.07. HRMS(ESI) m / z calculated for C 18 H 12 FN2O3[M - H] - 323.08320, found 323.08533. Compound 3ec: Yellow solid, mp: 244.3 - 246.6 °C. 1 H NMR (400 MHz, DMSO- d 6 ) δ12.26 (s, 1H), 7.70 (t, J = 8.0 Hz, 1H), 7.55 (d, J = 8.2 Hz, 1H), 7.47 (d, J = 7.8Hz, 1H), 7.25 – 7.20 (m, 1H), 7.14 (dd, J = 6.7, 3.1 Hz, 2H), 3.79 – 3.71 (m,1H), 3.02 (ddd, J = 21.3, 15.8, 6.4 Hz, 2H), 2.88 – 2.78 (m, 2H). 13 C NMR (101MHz, DMSO- d 6 ) δ 167.22, 159.78, 157.00, 155.15, 150.97, 147.51, 147.49,134.21, 132.37, 128.70, 127.36 (d, J = 8 Hz), 126.39, 118.17 (d, J = 9 Hz),117.95, 115.15 (d, J = 23 Hz), 114.47 (d, J = 24 Hz), 38.48, 32.93, 31.99. HRMS(ESI) m / z calculated for C 18 H 11 ClFN2O3[M - H] - 357.04422, found 357.04651. Compound 3ef: Yellow solid, mp: 271.7 - 273.4 °C. 1 H NMR (400 MHz, DMSO- d 6 ) δ12.56 (s, 1H), 8.32 (s, 1H), 8.10 (dd, J = 8.6, 2.1 Hz, 1H), 7.81 (d, J = 8.5 Hz,1H), 7.26 – 7.21 (m, 1H), 7.17 – 7.09 (m, 2H), 3.82 – 3.75 (m, 1H), 3.07 (dt, J = 11.9, 6.2 Hz, 2H), 2.93 – 2.83 (m, 2H). 13 C NMR (101 MHz, DMSO- d 6 ) δ 167.21,160.99, 159.39, 157.06, 147.51 (d, J = 2 Hz), 130.45 (t, J = 3 Hz), 128.32,127.28 (d, J = 8 Hz), 126.12, 125.20, 123.18 (d, J = 3 Hz), 121.06, 118.19 (d, J =9 Hz), 115.17 (d, J = 23 Hz), 114.48 (d, J = 25 Hz), 38.90, 32.94, 32.05. HRMS(ESI) m / z calculated for C 19 H 11 F4N2O3[M - H] - 391.07058, found 391.07306. Compound 3fa: White solid, mp: 265.1 - 266.9 °C. 1 H NMR (400 MHz, DMSO- d 6 ) δ12.21 (s, 1H), 8.08 (d, J= 7.2 Hz, 1H), 7.83 – 7.75 (m, 1H), 7.62 (d, J = 8.1Hz, 1H), 7.48 (t, J = 8.0 Hz, 1H), 7.45 (d, J = 2.3 Hz, 1H), 7.35 (dd, J = 8.6, 2.4Hz, 1H), 7.12 (d, J = 8.7 Hz, 1H), 3.83 – 3.73 (m, 1H), 3.05 (ddd, J = 21.2,15.8, 6.3 Hz, 2H), 2.85 (dt, J = 10.6, 5.7 Hz, 2H). 13 C NMR (101 MHz, DMSO- d 6 ) δ167.00, 161.59, 154.21, 150.10, 148.40, 134.42, 128.31, 127.89, 127.81,127.57, 126.77, 126.33, 125.72, 120.92, 118.42, 40.15, 32.93, 31.98.HRMS(ESI) m / z calculated for C 18 H 13 ClN2O3[M + H] + 341.0693, found 341.0697. Compound 3ga: White solid, mp: 272.7 - 273.2 °C. 1 H NMR (400 MHz, DMSO- d 6 ) δ12.22 (s, 1H), 8.08 (d, J = 6.8 Hz, 1H), 7.80 (t, J = 7.0 Hz, 1H), 7.61 (dd, J =12.6, 5.2 Hz, 2H), 7.48 (dd, J = 8.7, 2.5 Hz, 2H), 7.06 (d, J = 8.6 Hz, 1H), 3.77(dd, J= 11.6, 5.9 Hz, 1H), 3.12 – 2.99 (m, 2H), 2.85 (dt, J = 11.8, 6.1 Hz, 2H). 13 C NMR (101 MHz, DMSO- d 6 ) δ 166.96, 161.59, 154.22, 150.57, 148.40, 134.42, 131.20, 130.74, 127.98, 126.77, 126.34, 125.72, 120.92, 118.80, 115.86, 38.89, 32.92, 31.95. HRMS (ESI) m / z calculated for C 18 H 12 BrN2O3[M - H] - 383.00313, found 383.00589. Compound 3ha: White solid, mp: 231.3 - 232.7 °C. 1 H NMR (400 MHz, DMSO- d 6 ) δ8.08 (dd, J = 7.8, 1.4 Hz, 1H), 7.85 – 7.74 (m, 1H), 7.63 (d, J = 8.2 Hz, 1H),7.48 (t, J = 7.5 Hz, 1H), 7.02 – 6.95 (m, 2H), 6.78 (dd, J = 6.3, 2.7 Hz, 1H),4.06 (q, J = 7.0 Hz, 2H), 3.75 (dd, J = 6.9, 4.1 Hz, 1H), 3.05 (dd, J = 16.3, 6.3Hz, 1H), 2.92 (dd, J = 14.7, 7.1 Hz, 1H), 2.82 (dt, J = 12.4, 5.8 Hz, 2H), 1.35(t, J = 6.9 Hz, 3H). 13 C NMR (101 MHz, DMSO-d 6 ) δ 167.39, 161.65, 154.52, 148.56, 146.33, 140.22, 134.41, 126.87, 126.52, 126.28, 125.74, 124.28, 120.91, 118.94, 112.48, 64.01, 40.43, 33.45, 32.58, 14.68. HRMS (ESI) m / z calculated for C 20 H 18 N2O4[M + H] + 351.1345, found 351.1348. Compound 3ia: Yellow solid, mp: 241.2 - 243.3 °C. 1 1H NMR (400 MHz, DMSO - d 6 ) δ 12.20 (s, 1H), 8.07 (d, J J = 6.8 Hz, 1H), 7.80 (t, J J = 6.9 Hz, 1H), 7.62 (dd, J J = 8.0, 5.3 Hz, 2H), 7.46 (dd, J J = 11.5, 4.8 Hz, 2H), 3.81 (dd, J J = 6.5, 3.7 Hz, 1H), 3.16 (dd, J J = 16.5, 6.8 Hz, 1H), 3.02 (dd, J J = 15.4, 6.2 Hz, 1H), 2.90 (dt, J J = 15.4, 4.9 Hz, 2H). 13 13C NMR (101 MHz, DMSO - d 6 ) δ 166.04, 161.55, 154.04, 148.31, 146.25, 134.42, 129.01, 128.23, 127.82, 126.90, 126.67, 126.36, 125.72, 121.27, 120.92, 38.75, 32.71, 32.35. HRMS (ESI) m / z calculated for C18 H 11 Cl2N2O3[M - H] - 373.01467, found 373.01727. Compound 3ib: White solid, mp: 239.7 - 240.2 °C. 1 H NMR (400 MHz, DMSO- d 6 ) δ12.24 (s, 1H), 7.77 (s, 1H), 7.63 (s, 1H), 7.46 – 7.39 (m, 2H), 7.25 – 7.19(m, 1H), 3.78 (m, 1H), 3.16 (dt, J = 15.9, 5.3 Hz, 1H), 2.99 (dd, J = 14.9, 5.3Hz, 1H), 2.94 – 2.84 (m, 2H). 13 C NMR (101 MHz, DMSO- d 6 ) δ 166.02, 161.77,158.84, 155.22, 150.49, 146.24, 135.04 (d, J = 11 Hz), 128.90, 128.26, 127.84,126.90, 122.77, 121.28, 112.73 (d, J = 20 Hz), 110.45 (d, J = 7 Hz), 38.57,32.66, 32.27. HRMS (ESI) m / z calculated for C 18 H 10 Cl2FN2O3[M - H] - 391.00525,found 391.00797. Compound 3id: White solid, mp: 272.1 - 274.0 °C. 1 H NMR (400 MHz, DMSO- d 6 ) δ12.38 (s, 1H), 8.00 (d, J = 2.5 Hz, 1H), 7.83 (dd,J = 8.7, 2.5 Hz, 1H), 7.62(dd, J = 5.6, 3.1 Hz, 2H), 7.44 (d, J = 2.3 Hz, 1H), 3.80 (dt, J = 13.1, 6.7 Hz,1H), 3.16 (dd, J = 16.5, 6.9 Hz, 1H), 3.02 (dd, J = 15.4, 6.1 Hz, 1H), 2.94 –2.87 (m, 2H). 13 C NMR (101 MHz, DMSO- d 6 ) δ 166.03, 160.59, 154.72, 147.03,146.24, 134.55, 130.60, 128.92, 128.89, 128.25, 127.84, 126.90, 124.74,122.23, 121.28, 38.78, 32.67, 32.33. HRMS (ESI) m / z calculated forC 18 H 10 Cl3N2O3[M - H] - 406.97570, found 406.97836. Compound 3ja: White solid, mp: 243.9 - 244.9 °C. 1 H NMR (400 MHz, DMSO- d 6 ) δ12.20 (s, 1H), 8.07 (d, J = 7.2 Hz, 1H), 7.80 (dd, J = 11.2, 4.2 Hz, 1H), 7.61(t, J = 5.7 Hz, 2H), 7.48 (t, J = 7.6 Hz, 1H), 7.44 (d, J = 2.2 Hz, 1H), 3.80 (dt, J = 10.3, 5.2 Hz, 1H), 3.16 (dd, J = 16.5, 6.8 Hz, 1H), 3.02 (dd,J = 15.4, 6.1 Hz, 1H), 2.90 (dt, J = 15.2, 4.1 Hz, 2H). 13 C NMR (101 MHz, DMSO- d 6 ) δ 166.07, 161.58, 154.06, 148.32, 146.27, 134.45, 129.02, 128.25, 127.84, 126.91, 126.69, 126.39, 125.74, 121.30, 120.93, 40.43, 32.74, 32.38. HRMS (ESI) m / z calculated for C 18 H 12 Cl2N2O3 [M + H] + 375.0303, found 375.0301. Compound 3ka: White solid, mp: 238.3 - 239.6 °C. 1 H NMR (400 MHz, DMSO- d 6 ) δ 12.20 (s, 1H), 8.07 (dd, J = 7.9, 1.0 Hz, 1H), 7.82 – 7.77 (m, 1H), 7.73 (d, J = 2.4 Hz, 1H), 7.61 (d, J = 8.0 Hz, 1H), 7.49 – 7.44 (m, 2H), 3.89 – 3.72 (m, 1H), 3.15 (dd, J = 16.4, 6.8 Hz, 1H), 3.01 (dd, J = 15.3, 6.2 Hz, 1H), 2.94 – 2.85 (m, 2H). 13 C NMR (101 MHz, DMSO- d 6) δ 166.21, 161.57, 154.05, 148.32, 147.33, 134.43, 130.99, 128.94, 128.20, 127.48, 126.69, 126.38, 125.73, 120.92, 110.50, 40.43, 32.79, 32.48. HRMS (ESI) m / z calculated for C 18 H 12 BrClN2O3[M + H] + 418.9798, found 418.9801. The spectra of some of the above compounds are as Figures 1 to 8 shown below. Figure 1 This is the 1 1H NMR spectrum of compound 3ab. Figure 2 This is the 1 1H NMR spectrum of compound 3ac. Figure 3 This is the 1 1H NMR spectrum of compound 3ad. Figure 4 This is the 1 1H NMR spectrum of compound 3ak. Figure 5 This is the 1 1H NMR spectrum of compound 3id. Figure 6 This is the HRMS spectrum of compound 3aa. Figure 7 This is the HRMS spectrum of compound 3ab. Figure 8 This is the HRMS spectrum of compound 3ib.

[0043] An antibacterial experiment was carried out on the above synthesized compounds as follows.

[0044] Antibacterial experiment: According to the agricultural industry standard of the People's Republic of China (NY / T1156.2 - 2006), the antibacterial or bacteriostatic activity of the compounds was determined by the mycelial growth rate method. The specific process is as follows: The pathogenic bacteria were activated and cultured a few days before the experiment. The codes and names of the test strains are: A: Gaeumannomyces graminis var. tritici, B: Rhizoctonia solani, C: Rhizoctonia cerealis, D: Fusarium graminearum, E: Fusarium oxysporum, F: Fusarium moniliforme.

[0045] Take 16.6 mg of the test sample and dissolve it in 0.66 mL of DMSO. Then add an aqueous solution containing 0.1% Tween 80 to prepare a stock solution of 500 μg / mL of the original drug. Appropriately pipette the test agent under sterile conditions into a conical flask, shake well, and then pour an equal amount into three Petri dishes with a diameter of 9 cm. The above experiment was set up with a treatment without the agent as a blank control, and each treatment was repeated three times. The antibacterial activity was measured using the common pesticide triadimefon as the control group. By setting a single factor variable of different compounds, the antibacterial effects of different compounds were compared. The cultured pathogenic bacteria were cut into disks with a diameter of 5 mm along the edge of the colony under sterile conditions using a puncher. The disks were inoculated in the center of the drug-containing plate with an inoculator, with the mycelial surface facing up, covered with the Petri dish lid, and the Petri dish was placed in an incubator at a constant temperature of 25 °C. When the diameter of the control colony expanded to more than 6 cm, the diameter of the colony was measured using the cross method, and the average value was taken; at the end of the culture, the inhibition rate was calculated, and the calculation formula was:

[0046] Inhibition rate I = (D0 - D t ) / D0 * 100%; where D0 is the average diameter of the mycelium on the control plate, and D t is the average diameter of the mycelium on the sample plate; the comparison of the antibacterial effects of different compounds against six pathogenic bacteria is shown in Table 3.

[0047] Table 3 Antibacterial result data As can be seen from Table 3 and Figures 9 to 14 it can be seen that the compounds synthesized in the present invention have good antibacterial effects against one or several of the six common pathogenic bacteria in agricultural production, namely Gaeumannomyces graminis var. tritici, Rhizoctonia solani, Rhizoctonia cerealis, Fusarium graminearum, Fusarium oxysporum, and Fusarium moniliforme. It is worth noting that the synthesis method of the present invention is simple, only requiring mixing the raw materials and stirring while heating. The obtained product has a high yield, good antibacterial effect, and has application prospects in pesticides. It provides a research and development idea for further developing pesticides with good antibacterial effects suitable for large-scale production applications, and also expands the application scope of quinazolinone derivatives and coumarin compounds.

[0048] Obviously, those skilled in the art can make various modifications and variations to the present invention without departing from the spirit and scope of the present invention. Thus, if these modifications and variations of the present invention fall within the scope of the claims of the present invention and their equivalent technologies, these modifications and variations are also intended to be included.

Claims

1. A class of quinazolinone derivatives containing a dihydrocoumarin group, characterized in that, Its structure is as follows: ； wherein, R 1 , R 2 are each independently hydrogen, a C1-C3 alkyl group, a C1-C3 alkoxy group, a halogen, a nitro group or a trifluoromethyl group.

2. The quinazolinone derivative containing a dihydrocoumarin group according to claim 1, characterized in that, The alkyl group is methyl, the alkoxy group is ethoxy, and the halogen is one or two of fluorine, chlorine, and bromine.

3. The quinazolinone derivative containing a dihydrocoumarin group according to claim 1, characterized in that, The specific compounds are: Compound 3aa: ; Compound 3ab: ; Compound 3ac: ; Compound 3ad: ; Compound 3ae: ; Compound 3af: ; Compound 3ag: ; Compound 3ah: ; Compound 3ai: ; Compound 3aj: ; Compound 3ak: ; Compound 3ba: ; Compound 3ca: ; Compound 3cb: ; Compound 3cd: ; Compound 3cf: ; Compound 3cl: ; Compound 3da ; Compound 3ea: ; Compound 3ec: ; Compound 3ef: ; Compound 3fa: ; Compound 3ga: ; Compound 3ha: ; Compound 3ia: ; Compound 3ib: ; Compound 3 id: ; Compound 3 ja: ; Compound 3ka: .

4. The preparation method of the quinazolinone derivative containing a dihydrocoumarin group according to any one of claims 1 to 3, characterized in that, It includes the following steps: Under a solvent system, using Compound 1 and Compound 2 as raw materials, Compound 3 is prepared through a tandem Michael addition and decarboxylation reaction. The synthetic route is as follows: ； Among them, R 1 , R 2 are each independently hydrogen, a C1-C3 alkyl group, a C1-C3 alkoxy group, a halogen, a nitro group or a trifluoromethyl group.

5. The preparation method according to claim 4, characterized in that, The molar ratio of Compound 1 to Compound 2 is 1:

1.

6. The preparation method according to claim 4, characterized in that, The solvent is DMSO.

7. The preparation method according to claim 4, characterized in that, The reaction temperature is 100°C to 120°C, and the reaction time is 3 hours to 6 hours.

8. The preparation method according to claim 7, characterized in that, The reaction temperature is 100°C, and the reaction time is 3 hours.

9. The preparation method according to claim 4, characterized in that, Dissolve Compound 1 and Compound 2 in the solvent, raise the temperature and stir for the reaction. After the reaction is completed, purification by column chromatography can be carried out.

10. Use of a quinazolinone derivative containing a dihydrocoumarin group or a pesticidally acceptable salt thereof according to any one of claims 1 to 3 in the preparation of a pesticide, characterized in that, The pesticide is used to inhibit one or several of Gaeumannomyces graminis, Rhizoctonia solani, Rhizoctonia cerealis, Fusarium graminearum, Fusarium oxysporum, and Fusarium moniliforme.

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