5-aryl-cyclopentene pyridine compound, preparation method and application thereof, and plant protective agent

Abstract

The invention provides a 5-aryl-cyclopentene pyridine compound, a preparation method and application thereof and a plant protective agent, and relates to the technical field of plant protection. Aryl Ar is introduced into the 5-aryl-cyclopentene pyridine compound provided by the invention, so that the molecular stability of the compound can be improved, the compound can interact with amino acid in receptor protein, and the biological activity of the compound is further improved. The 5-aryl-cyclopentene pyridine compound provided by the invention has good antiviral, antibacterial and insecticidal effects, and has a good application prospect in plant protection.

Description

Technical Field

[0001] The present invention relates to the technical field of plant protection agents, and in particular to a 5-aryl-cyclopenta-pyridine compound, a preparation method and application thereof, and a plant protection agent. Background Art

[0002] The widespread use of traditional pesticides not only poses a potential threat to the ecosystem and human health, but also causes ecological problems such as drug resistance, residue problems, and high toxicity during the prevention and control of pests and diseases. Therefore, efficient, safe, and environmentally friendly pesticides are gaining more and more attention.

[0003]

[0004] Natural products and their derivatives are important sources of drugs and play an important role in the development of pesticides. For example, Cerbinal (1) was first isolated from the bark of the sea mango and later from Gardenia jasminoides, and has anti-tobacco mosaic virus (TMV) activity, insecticidal activity, and fungicidal activity. However, the structural stability of the above compounds is poor, and their biological activity is low when used as pesticides. Summary of the invention

[0005] In view of this, the object of the present invention is to provide a 5-aryl-cyclopenta-pyridine compound and its preparation method and application, and a plant protection agent. The 5-aryl-cyclopenta-pyridine compound provided by the present invention has a stable structure and high biological activity.

[0006] In order to achieve the above-mentioned object of the invention, the present invention provides the following technical solutions:

[0007] The present invention provides a 5-aryl-cyclopenta-pyridine compound having a structure shown in Formula I:

[0008]

[0009] Preferably, Ar comprises any one of the following structures:

[0010]

[0011] The R 1 Including C1~C6 alkoxy;

[0012] The R 2 ~R 6 Independently include hydrogen, halogen, C1-C6 alkoxy, C1-C6 haloalkyl, cyano, nitro, aldehyde, hydroxyl, C1-C6 haloalkoxy and one or more of the following structures:

[0013]

[0014] The R 7 ~R 12 Independently includes C1~C6 alkyl.

[0015] Preferably, the C1-C6 alkoxy group is methoxy, ethoxy, propoxy, butoxy, pentyloxy or hexyloxy;

[0016] The C1-C6 alkyl group is methyl, ethyl, propyl, butyl, pentyl or hexyl;

[0017] The C1-C6 haloalkyl group is a halomethyl group, a haloethyl group, a halopropyl group, a halobutyl group, a halopentyl group or a halohexyl group;

[0018] The C1-C6 haloalkoxy group is a halomethoxy group, a haloethoxy group, a halopropoxy group, a halobutoxy group, a halopentyloxy group or a halohexyloxy group.

[0019] Preferably, Ar has any one of the following structures:

[0020]

[0021] The present invention also provides a method for preparing the 5-aryl-cyclopenta-pyridine compound described in the above technical solution, comprising the following steps: reacting compound 3 with ArB(OH) 2 Performing a Suzuki coupling reaction to obtain the 5-aryl-cyclopenta-pyridine compound;

[0022]

[0023] Preferably, the compound 3 and ArB(OH) 2 The molar ratio is 1:1-2;

[0024] The Suzuki coupling reaction is carried out under the conditions of a mixed solvent, a catalyst and an inorganic salt;

[0025] The mixed solvent includes an organic solvent and water, and the organic solvent includes one or more of 1,4-dioxane, tetrahydrofuran, acetonitrile, ethanol and methanol;

[0026] The catalyst comprises a palladium-containing catalyst;

[0027] The inorganic salt includes one or more of alkali metal phosphates, alkali metal carbonates and alkali metal halides;

[0028] The temperature of the Suzuki coupling reaction is 60-120° C., and the time is 5-24 hours.

[0029] Preferably, the preparation method of compound 3 comprises the following steps: mixing compound 2 and a bromination reagent, performing a bromination reaction, and obtaining compound 3;

[0030]

[0031] The present invention also provides the use of the 5-aryl-cyclopenta-pyridine compounds described in the above technical solution in plant protection agents.

[0032] Preferably, the plant protection agent comprises one or more of an anti-plant virus agent, an agricultural insecticide and an agricultural fungicide.

[0033] The present invention also provides a plant protection agent, characterized in that it comprises an active component and an auxiliary material; the active component comprises the 5-aryl-cyclopentapyridine compound described in the above technical solution.

[0034] The 5-aryl-cyclopenta-pyridine compounds provided by the present invention introduce an aromatic group Ar, which can not only increase the stability of the compound molecule, but also the conjugated π electrons and different substituents of the aromatic ring can interact with the amino acids in the receptor protein, so that the compound has a stronger interaction with the target, thereby improving the biological activity of the compound. The 5-aryl-cyclopenta-pyridine compounds provided by the present invention have good antiviral, antibacterial and insecticidal effects, and have a good application prospect in plant protection.

[0035] As shown in the test results of the examples, compounds 4d, 4e, 4f, 4g and 4k of the 5-aryl-cyclopentapyridine compounds provided by the present invention show higher anti-TMV activity levels than commercial ribavirin, and in particular, the most active compound 4k shows low toxicity or even slight toxicity to zebrafish. The 5-aryl-cyclopentapyridine compounds provided by the present invention have the activity of killing aphids and diamondback moth larvae, and in particular, compounds 4d, 4e, 4h and 4o show 100% insecticidal activity against diamondback moth larvae at a concentration of 600 μg / mL, and these compounds also show significant insecticidal activity at low concentrations of 200 μg / mL and 100 μg / mL. The 5-aryl-cyclopenta-pyridine compounds provided by the present invention show fungicidal activity against nine pathogens, including rape sclerotia, apple ring spot, wheat sheath blight, rice blast, cucumber gray mold, peanut brown spot, tomato early blight, wheat gibberella and rice sheath blight. In particular, the fungicidal activity of compound 4i against rape sclerotia reached 91.9% at a concentration of 50 μg / mL.

[0036] The preparation method of the 5-aryl-cyclopenta-pyridine compound provided by the invention has the advantages of simple and efficient process, low production cost and suitability for industrial production. BRIEF DESCRIPTION OF THE DRAWINGS

[0037] Figure 1The figure shows the survival rate of zebrafish exposed to compound 4k. DETAILED DESCRIPTION

[0038] The present invention provides a 5-aryl-cyclopenta-pyridine compound having a structure shown in Formula I:

[0039]

[0040] In the present invention, Ar in Formula I preferably includes any one of the following structures:

[0041]

[0042] The R 1 Preferably includes C1-C6 alkoxy; said R 2 ~R 6 Independently preferably include hydrogen, halogen, C1-C6 alkoxy, C1-C6 haloalkyl, cyano, nitro, aldehyde, hydroxyl, C1-C6 haloalkoxy and one or more of the following structures:

[0043]

[0044] The R 7 ~R 12 Independently preferably includes C1-C6 alkyl.

[0045] In the present invention, the halogen preferably includes fluorine, chlorine, bromine or iodine.

[0046] In the present invention, the C1-C6 alkoxy group is preferably a methoxy group, an ethoxy group, a propoxy group, a butoxy group, a pentyloxy group or a hexyloxy group.

[0047] In the present invention, the C1-C6 alkyl group is preferably a methyl group, an ethyl group, a propyl group, a butyl group, a pentyl group or a hexyl group.

[0048] In the present invention, the C1-C6 haloalkyl group is preferably a halomethyl group, a haloethyl group, a halopropyl group, a halobutyl group, a halopentyl group or a halohexyl group; and the halogen in the C1-C6 haloalkyl group preferably includes fluorine, chlorine, bromine or iodine.

[0049] In the present invention, the C1-C6 haloalkoxy group is preferably a halogenated methoxy group, a halogenated ethoxy group, a halogenated propoxy group, a halogenated butoxy group, a halogenated pentyloxy group or a halogenated hexyloxy group; and the halogen in the C1-C6 haloalkoxy group preferably includes fluorine, chlorine, bromine or iodine.

[0050] In the present invention, Ar preferably has any one of the structures:

[0051]

[0052] The 5-aryl-cyclopenta-pyridine compound provided by the present invention introduces an aromatic group Ar in the structural modification of the natural product pesticide molecule Cerbinal (1), which can not only increase the stability of the compound molecule, but also improve the biological activity of the compound by interacting with amino acids in the receptor protein. The 5-aryl-cyclopenta-pyridine compound provided by the present invention has good antiviral, antibacterial and insecticidal effects and has a good application prospect in plant protection.

[0053] The present invention also provides a method for preparing the 5-aryl-cyclopenta-pyridine compound described in the above technical solution, comprising the following steps: reacting compound 3 with ArB(OH) 2 Performing a Suzuki coupling reaction to obtain the 5-aryl-cyclopenta-pyridine compound;

[0054]

[0055] Unless otherwise specified, the materials and equipment used in the present invention are all commercially available products in the art.

[0056] In the present invention, the Suzuki coupling reaction is preferably carried out under the conditions of a mixed solvent, a catalyst and an inorganic salt. Specifically, compound 3, ArB(OH) 2 , an inorganic salt, a catalyst and a mixed solvent are mixed to carry out a Suzuki coupling reaction.

[0057] In the present invention, the compound 3 and ArB(OH) 2 The molar ratio of is preferably 1:1-2, and in specific embodiments can be 1:1.1, 1:1.2, 1:1.3, 1:1.4, 1:1.5, 1:1.6, 1:1.7, 1:1.8, 1:1.9 or 1:2.

[0058] In the present invention, the inorganic salt preferably includes one or more of alkali metal phosphates, alkali metal carbonates and alkali metal halides; the alkali metal phosphates preferably include one or more of potassium phosphate, sodium phosphate and cesium phosphate; the alkali metal carbonates preferably include one or more of potassium carbonate, sodium carbonate and cesium carbonate; the alkali metal halide preferably includes one or more of alkali metal fluoride, alkali metal chloride and alkali metal bromide; the alkali metal fluoride preferably includes one or more of sodium fluoride, potassium fluoride and cesium fluoride; the alkali metal chloride preferably includes one or more of sodium chloride, potassium chloride and cesium chloride; the alkali metal bromide preferably includes one or more of sodium bromide, potassium bromide and cesium bromide. In the present invention, the molar ratio of the compound 3 to the inorganic salt is preferably 1:1-4, and in specific embodiments it can be 1:1, 1:1.5, 1:2, 1:2.5, 1:3, 1:3.5 or 1:4.

[0059] In the present invention, the catalyst preferably comprises a palladium-containing catalyst, and the palladium-containing catalyst preferably comprises Pd(PPh 3 ) 4 , PdCl 2 , PdCl 2 (dppf), Pd(OAc) 2 and Pd(PPh 3 ) 2 Cl 2 In the present invention, the molar ratio of the compound 3 to the catalyst is preferably 1:0.0005-0.05, and in specific embodiments can be 1:0.0005, 1:0.001, 1:0.002, 1:0.005, 1:0.01, 1:0.015, 1:0.02, 1:0.025, 1:0.03, 1:0.035, 1:0.04, 1:0.045 or 1:0.05.

[0060] In the present invention, the mixed solvent preferably includes an organic solvent and water, and the organic solvent preferably includes one or more of 1,4-dioxane, tetrahydrofuran, acetonitrile, ethanol and methanol; the volume ratio of water to organic solvent in the mixed solvent is preferably 1:2-8, and in specific embodiments, it can be 1:2, 1:3, 1:4, 1:5, 1:6, 1:7 or 1:8. In the present invention, the ratio of the amount of the compound 3 to the volume of the mixed solvent is preferably 1mol:8-100L, and in specific embodiments, it can be 1mol:8L, 1mol:10L, 1mol:15L, 1mol:20L, 1mol:30L, 1mol:40L, 1mol:50L, 1mol:60L, 1mol:70L, 1mol:80L, 1mol:90L or 1mol:100L.

[0061] In the present invention, the mixing preferably comprises: mixing compound 3, ArB(OH) 2 and inorganic salt are dissolved in a mixed solvent, and then the catalyst is added and mixed.

[0062] In the present invention, the temperature of the Suzuki coupling reaction is preferably 60-120°C, and in specific embodiments may be 60°C, 65°C, 70°C, 75°C, 80°C, 85°C, 90°C, 95°C, 100°C, 105°C, 110°C, 115°C or 120°C; the time of the Suzuki coupling reaction is preferably 5-24h, and in specific embodiments may be 5h, 6h, 7h, 8h, 9h, 10h, 11h, 12h, 13h, 14h, 15h, 16h, 17h, 18h, 19h, 20h, 21h, 22h, 23h or 24h; the Suzuki coupling reaction is preferably carried out under a protective atmosphere, and the protective atmosphere preferably comprises nitrogen, argon or helium.

[0063] After completing the Suzuki coupling reaction, the present invention preferably further comprises: filtering the reaction solution obtained by the Suzuki coupling reaction with diatomaceous earth, washing the filtrate with water after spin drying, extracting with dichloromethane, drying the obtained organic phase with anhydrous magnesium sulfate, and purifying with a silica gel column to obtain the 5-aryl-cyclopentene pyridine compound. In the present invention, the purpose of the diatomaceous earth filtration is to remove insoluble impurities. In the present invention, the number of dichloromethane extractions is preferably 2 to 5 times, more preferably 3 to 4 times. In the present invention, the eluent used for the silica gel column purification preferably includes a petroleum ether-ethyl acetate mixed solvent or a dichloromethane-methanol mixed solvent; the volume ratio of petroleum ether and ethyl acetate in the petroleum ether-ethyl acetate mixed solvent is preferably 1:1 to 5; the volume ratio of dichloromethane and methanol in the dichloromethane-methanol mixed solvent is preferably 20:1 to 10.

[0064] In the present invention, the preparation method of the compound 3 preferably comprises the following steps: mixing the compound 2 and a bromination reagent, and performing a bromination reaction to obtain the compound 3;

[0065]

[0066] In the present invention, the bromination reagent preferably includes N-bromosuccinimide, 1,3-dibromo-5,5-dimethylhydantoin and pyridinium bromide (PyHBr 3 In the present invention, the molar ratio of the compound 2 to the brominating agent is preferably 1:1 to 1.5, and in specific embodiments can be 1:1, 1:1.1, 1:1.2, 1:1.3, 1:1.4 or 1:1.5.

[0067] In the present invention, the organic solvent used in the bromination reaction preferably includes one or more of toluene, dimethylformamide, chloroform, acetonitrile and dichloromethane, and is more preferably an acetonitrile-dichloromethane mixed solvent. The volume ratio of acetonitrile to dichloromethane in the acetonitrile-dichloromethane mixed solvent is preferably 1:0.2-4, and in specific embodiments it can be 1:0.2, 1:0.5, 1:1, 1:2, 1:3 or 1:4; the organic solvent is preferably an anhydrous organic solvent.

[0068] In the present invention, the ratio of the amount of the compound 2 to the volume of the organic solvent is preferably 1 mol: 5 to 50 L. In specific embodiments, it can be 1 mol: 5 L, 1 mol: 10 L, 1 mol: 15 L, 1 mol: 20 L, 1 mol: 25 L, 1 mol: 30 L, 1 mol: 35 L, 1 mol: 40 L, 1 mol: 45 L or 1 mol: 50 L.

[0069] The present invention preferably dissolves compound 2 in an organic solvent, adds a bromination reagent at a bromination reaction temperature, and performs a bromination reaction. In the present invention, the temperature of the bromination reaction is preferably 0 to 50°C, and in a specific embodiment, it can be 0°C, 5°C, 10°C, 15°C, 20°C, 25°C, 30°C, 35°C, 40°C, 45°C or 50°C, and is more preferably performed under ice-water bath conditions; the time of the bromination reaction is preferably 2 to 3h, and in a specific embodiment, it can be 2h, 2.5h or 3h.

[0070] After the bromination reaction is completed, the present invention preferably further comprises: adding water to the reaction solution obtained by the bromination reaction, extracting with dichloromethane, washing the obtained organic phase with sodium bicarbonate aqueous solution, washing with saturated brine, drying with anhydrous sodium sulfate, and purifying with rapid silica gel column chromatography to obtain compound 3. In the present invention, the number of dichloromethane extractions is preferably 3 to 5 times, more preferably 4 times. In the present invention, the eluent used for the silica gel column purification preferably includes a petroleum ether-dichloromethane mixed solvent or a petroleum ether-ethyl acetate mixed solvent; the volume ratio of petroleum ether to dichloromethane in the petroleum ether-dichloromethane mixed solvent is preferably 10:0.1-10; the volume ratio of petroleum ether to ethyl acetate in the petroleum ether-ethyl acetate mixed solvent is preferably 10:0.1-10.

[0071] The preparation method of the 5-aryl-cyclopenta-pyridine compound provided by the invention has the advantages of simple and efficient process, low production cost and suitability for industrial production.

[0072] The present invention also provides the use of the 5-aryl-cyclopenta-pyridine compounds described in the above technical solution in pesticides.

[0073] In the present invention, the pesticide preferably includes one or more of anti-plant virus agents, agricultural insecticides and agricultural fungicides. In the present invention, the anti-plant virus agents preferably include anti-tobacco mosaic virus agents. In the present invention, the agricultural insecticides preferably include insecticides for aphids and / or diamondback moth larvae. In the present invention, the agricultural fungicide preferably includes any one or more fungicides for rapeseed sclerotia (Ss), apple ring pattern (Pp), wheat sheath blight (Rc), potato late blight (Pi), cucumber gray mold (Bc), peanut brown spot (Ch), tomato early blight (As), wheat fusarium (Fg) and rice sheath blight (Rs).

[0074] The 5-aryl-cyclopenta-pyridine compounds provided by the present invention are active against tobacco mosaic virus, and the activities of many compounds are higher than that of viravirin; they are low-toxic or even slightly toxic to adult zebrafish; they are very active against larvae of diamondback moth, and are active against nine plant pathogens including rape sclerotium, apple ring pattern, wheat sheath blight, rice blast, cucumber gray mold, peanut brown spot, tomato early blight, wheat gibberella and rice sheath blight. The 5-aryl-cyclopenta-pyridine compounds provided by the present invention have good antiviral, antibacterial and insecticidal effects, and have good application prospects in plant protection.

[0075] The present invention also provides a plant protection agent, comprising an active component and an auxiliary material; the active component comprises the 5-aryl-cyclopenta-pyridine compound described in the above technical solution. The present invention has no special limitation on the auxiliary material, and the auxiliary material familiar to those skilled in the art can be used.

[0076] To further illustrate the present invention, the 5-aryl-cyclopenta-pyridine compounds provided by the present invention, their preparation methods and applications, and plant protection agents are described in detail below in conjunction with the examples, but they should not be construed as limiting the scope of protection of the present invention.

[0077] The compounds 4a-4cc prepared in Examples 1-29 used ArB(OH) 2 And Ar in the product is as follows:

[0078]

[0079] Example 1

[0080] Compound 2 (5.82 mmol) was dissolved in anhydrous acetonitrile (165 mL) and dichloromethane (55 mL), and N-bromosuccinimide (NBS, 9.52 mmol) was added under an ice-water bath, and stirred for 2 to 3 hours until the reaction was complete. Water was added, and the mixture was extracted with dichloromethane 4 times, and the organic phases were combined, washed with sodium bicarbonate aqueous solution, washed with saturated brine, dried with anhydrous sodium sulfate, and purified by rapid silica gel column chromatography (volume ratio of petroleum ether / dichloromethane was 5:1 to 1:1) to obtain compound 3 with a yield of 81% and a melting point of 135 to 136°C. 1 H NMR (400 MHz, CDCl 3 )δ9.83(s,1H),9.10(s,1H),7.80-7.75(m,2H),4.31(q,J=7.3Hz,2H),4.03(s,3H),1.63(t,J=7.3Hz,3H); 13 C NMR (100 MHz, CDCl 3 )δ184.17,165.93,144.65,133.76,128.84,128.26,126.01,120.06,119.23,93.08,54.38,52.56,16.87; HRMS(APCI)calculated for C 13 H 14 BrNO 3 [M+H] + 310.0073, found 310.0070.

[0081] Add compound 3 (1.61 mmol), ArB(OH) 2 (2.415mmol), K 3 PO 4 (3.22 mmol), 1,4-dioxane (16 mL) and H 2 O (3.8 mL), and then Pd(PPh 3 ) 4 (0.322mmol), reacted at 95℃ for 8h under argon protection, filtered through diatomaceous earth to remove insoluble impurities, the filtrate was spin-dried and washed with water, extracted with dichloromethane 3 times, the organic phases were combined, dried over anhydrous magnesium sulfate, and purified on a silica gel column (petroleum ether-ethyl acetate mixed solvent or dichloromethane-methanol mixed solvent, the volume ratio of petroleum ether to ethyl acetate in the petroleum ether-ethyl acetate mixed solvent is 1:1-5, and the volume ratio of dichloromethane to methanol in the dichloromethane-methanol mixed solvent is 20:1-10) to obtain compound 4a with a yield of 64% and a melting point of 181-183℃; 1 H NMR (400 MHz, CDCl 3)δ9.94(s,1H),9.17(d,J=1.1Hz,1H),7.89(s,1H),7.83(d,J=1.5Hz,1H),7.41-7.36(m,2H),7 .34-7.31(m,2H),7.29-7.24(m,1H),4.34(q,J=7.3Hz,2H),3.23(s,3H),1.65(t,J=7.3Hz,3H); 13 C NMR (100 MHz, CDCl 3 )δ184.83,167.03,144.07,138.98,133.96,128.70,128.65,128.17,128.04,127. 40,125.81,123.47,120.11,119.40,54.24,51.83,16.95; HRMS(APCI)calculated for C 19 H 18 NO 3 [M+H] + 308.1281, found 308.1270.

[0082] Example 2

[0083] Compound 4b was prepared according to the method of Example 1 with a yield of 72% and a melting point of 191.5-193°C; 1 HNMR (400MHz, CDCl 3 )δ9.97(s,1H),9.25(d,J=1.3Hz,1H),7.96(s,1H),7.91-7.87(m,2H),7.82(d,J=8.2Hz,1H),7.66(d,J=8.4Hz,1H), 7.55-7.50(m,1H),7.48-7.41(m,2H),7.37-7.32(m,1H),4.36(q,J=7.3Hz,2H),2.58(s,3H),1.67(t,J=7.3Hz,3H); 13 C NMR (100 MHz, CDCl 3 )δ184.82,166.71,145.78,137.50,133.97,133.52,132.96,130.33,129.14,128.10,127.52,126.48,126. 43,126.01,125.88,125.59,125.41,121.03,120.06,119.22,54.26,51.24,16.95; HRMS(APCI)calculated for C 22H 20 NO 3 [M+H] + 358.1438, found 358.1424.

[0084] Example 3

[0085] Compound 4c was prepared according to the method of Example 1 with a yield of 61% and a melting point of 168.8-171°C; 1 HNMR (400MHz, CDCl 3 )δ9.96(s,1H),9.23(d,J=1.4Hz,1H),8.45(s,2H),8.02(d,J=1.5Hz,1H),7.83 (s,1H),4.37(q,J=7.3Hz,2H),4.07(s,3H),3.57(s,3H),1.67(t,J=7.3Hz,3H); 13 CNMR (100MHz, CDCl 3 )δ184.99,165.94,164.09,158.17,144.33,134.42,130.14,129.17,127.87,126 .88,20.69,118.35,115.34,54.99,54.54,52.53,17.03; HRMS(APCI)calculated for C 18 H 18 N 3 O 4 [M+H] + 340.1292, found 340.1284.

[0086] Example 4

[0087] Compound 4d was prepared according to the method of Example 1 with a yield of 57% and a melting point of 222-223.6°C; 1 HNMR (400MHz, CDCl 3 )δ9.92(s,1H),9.17(s,1H),7.85(d,J=1.4Hz,1H),7.84(s,1H),7.27(dd,J=7.2,4.4Hz ,2H),7.08(t,J=8.6Hz,2H),4.34(q,J=7.3Hz,2H),3.32(s,3H),1.65(t,J=7.3Hz,3H); 13 C NMR (100 MHz, CDCl 3 )δ184.90,166.97,162.71,160.28,144.13,135.24(d,Jc-f =7.7Hz),134.15,129.76(d,J c-f =7.7Hz),128.83(d,J c-f =18.3Hz),127.46,122.41,120.22,119.31,114.89(d,J=21.2Hz),77.48,77.36,77.16,76.84,54.39,52.05,17.05; 19 FNMR (376MHz, CDCl 3 )δ-117.08; HRMS(APCI)calculated for C 19 H 17 FNO 3 [M+H] + 326.1187, found 326.1174.

[0088] Example 5

[0089] Compound 4e was prepared according to the method of Example 1 with a yield of 83% and a melting point of 167.5-168.7; 1 HNMR (400MHz, CDCl 3 )δ9.93(s,1H),9.18(s,1H),7.87(s,2H),7.33(dd,J=14.1,7.8Hz,1H),7.06(dd,J=12.3,9.2Hz,2H),6. 96(td,J=8.5,2.3Hz,1H),4.35(q,J=7.3Hz,2H),4.02(s,1H),3.34(s,3H),1.65(dd,J=9.4,5.2Hz,4H); 13 C NMR (100 MHz, CDCl 3 )δ185.01,166.89,164.07,161.63,143.99,141.47(d,J c-f =8.3Hz),134.25,129.38(d,J c-f =8.7Hz),129.04,128.71,127.57,124.15(d,J c-f =2.7Hz),122.19,119.85(d,J c-f =98.2Hz),115.15(d,J c-f =21.1Hz),112.62(d,J c-f =21.1Hz),54.44,52.02,17.05. 19F NMR (376 MHz, CDCl 3 )δ-114.22; HRMS(APCI)calculated for C 19 H 17 FNO 3 [M+H] + 326.1187, found 326.1175.

[0090] Example 6

[0091] Compound 4f was prepared according to the method of Example 1 with a yield of 69% and a melting point of 163.5-164.8; 1 HNMR (400MHz, CDCl 3 )δ9.95(s,1H),9.20(s,1H),8.00(d,J=1.1Hz,1H),7.91(s,1H),7.47(t,J=7.6Hz,1H),7.26(m,1H), 7.20(t,J=7.4Hz,1H),7.12-7.04(m,1H),4.35(q,J=7.3Hz,2H),3.41(s,3H),1.66(t,J=7.3Hz,3H); 13 C NMR (100 MHz, CDCl 3 )δ184.95,166.62,159.02,145.25,134.06,130.42(d,J c-f =4.1Hz),129.70,129.64,128.00,127.53(d,J c-f =8.1Hz),123.89(d,J c-f =3.2Hz),120.49,119.50,116.45,114.98,114.76,54.42,51.98,17.06. 19 FNMR (376MHz, CDCl 3 )δ-113.54; HRMS(APCI)calculated for C 19 H 17 FNO 3 [M+H] + 326.1187, found 326.1180.

[0092] Example 7

[0093] 4 g of compound was prepared according to the method of Example 1 with a yield of 73% and a melting point of 189-190.8°C; 1 HNMR (400MHz, CDCl 3)δ9.93(s,1H),9.20(d,J=1.5Hz,1H),8.01(d,J=1.6Hz,1H),7.85(s,1H),7.41(td,J=8.5,6.6Hz,1H),6.95(ddd,J= 8.2, 2.6, 1.3Hz, 1H), 6.85 (ddd, J=10.3, 9.0, 2.6Hz, 1H), 4.35 (q, J=7.3Hz, 2H), 3.50 (s, 3H), 1.66 (t, J=7.4Hz, 3H); 13 C NMR (100 MHz, CDCl 3 )δ184.84,166.36,162.75(d,J c-f =11.9Hz),160.79(dd,J c-f =99.2,11.9Hz),158.83(d,J c-f =11.8Hz),145.06,134.13,130.86(dd,J c-f =9.1,5.7Hz),129.67(d,J c-f =19.0Hz),127.92,123.39(dd,J c-f =16.4,3.7Hz),120.46,119.22,115.43,110.81(dd,J c-f =20.8,3.5Hz),104.08-102.26(m),54.43,52.10,17.02. 19 F NMR (376 MHz, CDCl 3 )δ-109.39(d,J f-f =6.8Hz),-113.40(d,J f-f =6.7Hz); HRMS(APCI)calculated for C 19 H 16 F 2 NO 3 [M+H] + 344.1093, found 344.1083.

[0094] Example 8

[0095] Compound 4h was prepared according to the method of Example 1 with a yield of 70% and a melting point of 195.2-196.5; 1 HNMR (400MHz, CDCl 3)δ9.95(s,1H),9.22(d,J=1.3Hz,1H),8.04(d,J=1.4Hz,1H),7.89(s,1H),7.22(dd,J=7.9 ,5.6Hz,1H),7.14-7.07(m,2H),4.36(q,J=7.3Hz,2H),3.53(s,3H),1.66(t,J=7.3Hz,3H); 13 C NMR (100 MHz, CDCl 3 )δ185.02,166.26,145.07,134.21,129.89,129.69,128.05,125.15,123.51, 120.61,119.34,115.18,114.67,114.50,58.61,54.51,52.11,18.59,17.06.; 19 F NMR (376 MHz, CDCl 3 )δ-138.97(d,J f-f =21.3Hz),-140.13(d,J f-f =21.5Hz); HRMS(APCI)calculated for C 19 H 17 F 2 NO 3 [M+H] + 344.1093, found 344.1081.

[0096] Example 9

[0097] Compound 4i was prepared according to the method of Example 1 with a yield of 64% and a melting point of 224.3-225.8; 1 HNMR (400MHz, CDCl 3 )δ9.94(s,1H),9.21(s,1H),7.92(d,J=1.3Hz,1H),7.81(s,1H),6.91(dd,J =8.5,6.7Hz,2H),4.36(q,J=7.3Hz,2H),3.55(s,3H),1.66(t,J=7.3Hz,3H); 13 C NMR (100 MHz, CDCl 3 )δ185.05,166.32,152.10(d,J c-f =4.4Hz),149.63(d,J c-f =4.4Hz),143.78,139.34(d,J c-f =15.4Hz),136.93,135.44(d,Jc-f =4.7Hz),134.47,129.46,128.41,127.54,120.41,120.23,118.87,112.32(dd,J=15.3,5.5Hz),54.56,52.31,17.06; HRMS(APCI)calculated for C 19 H 17 F 3 NO 3 [M+H] + 362.0999, found 362.0984.

[0098] Example 10

[0099] Compound 4j was prepared according to the method of Example 1 with a yield of 69% and a melting point of 181.5-183.3°C; 1 HNMR (400MHz, CDCl 3 )δ9.91(s,1H),9.15(s,1H),7.82(d,J=17.0Hz,2H),7.28-7.22(m,2H),6.94(d,J= 8.5Hz,2H),4.32(q,J=7.3Hz,2H),3.85(s,3H),3.31(s,3H),1.64(t,J=7.3Hz,3H); 13 C NMR (100 MHz, CDCl 3 )δ184.79,167.18,158.09,144.18,133.93,131.65,129.27,128.74,128.58,127.41, 123.27,120.12,119.52,113.61,55.50,54.27,52.14,17.02; HRMS(APCI)calculated for C 20 H 20 NO 4 [M+H] + 338.1387, found 338.1380.

[0100] Embodiment 11

[0101] Compound 4k was prepared according to the method of Example 1 with a yield of 85% and a melting point of 196.5-197.8; 1 HNMR (400MHz, CDCl 3)δ9.93(s,1H),9.16(s,1H),7.89(s,1H),7.81(s,1H),7.28(dd,J=13.5,5.4Hz,1H),6.91(d,J=7.5Hz,1H), 6.88(s,1H),6.82(d,J=8.2Hz,1H),4.32(q,J=7.2Hz,2H),3.82(s,3H),3.29(s,3H),1.64(t,J=7.2Hz,3H); 13 CNMR (100MHz, CDCl 3 )δ184.84,167.15,159.49,143.82,140.25,134.00,129.02,128.72,128.48,127.33,123.24, 120.71,120.08,119.57,113.10,111.94,55.21,54.26,51.91,16.96; HRMS(APCI)calculated forC 20 H 20 NO 4 [M+H] + 338.1387, found 338.1378.

[0102] Example 12

[0103] Compound 41 was prepared according to the method of Example 1 with a yield of 85% and a melting point of 174.6-175.8; 1 HNMR (400MHz, CDCl 3 )δ9.93(s,1H),9.18(s,1H),7.91(d,J=1.4Hz,1H),7.89(s,1H),7.47(dd,J=7.4,1.4Hz,1H),7.29(d,J=7.8Hz,1H), 7.05(t,J=7.4Hz,1H),6.89(d,J=8.2Hz,1H),4.34(q,J=7.3Hz,2H),3.65(s,3H),3.30(s,3H),1.65(t,J=7.3Hz,3H); 13 C NMR (100 MHz, CDCl 3 )δ184.70,166.93,156.53,145.35,133.87,129.77,128.55,128.30,127.93,127.25,120 .72,120.54,120.23,119.30,109.58,55.03,54.26,51.55,17.03; HRMS(APCI)calculated for C20 H 20 NO 4 [M+H] + 338.1387, found 338.1374.

[0104] Embodiment 13

[0105] Compound 4m was prepared according to the method of Example 1 with a yield of 68% and a melting point of 186.3-188.5°C; 1 HNMR (400MHz, CDCl 3 )δ9.92(s,1H),9.16(s,1H),7.87(s,1H),7.78(d,J=1.5Hz,1H),6.94-6.85(m,3H), 4.33(q,J=7.3Hz,2H),3.93(s,3H),3.89(s,3H),3.32(s,3H),1.65(t,J=7.3Hz,3H); 13 C NMR (100 MHz, CDCl 3 )δ184.88,167.44,148.78,147.51,143.90,134.04,131.98,128.70,128.35,127.35,123.29,120 .27,120.20,119.78,111.68,111.31,56.22,55.91,54.34,52.19,17.05; HRMS(APCI)calculated for C 21 H 21 NO 5 [M+H] + 368.1493, found 368.1480.

[0106] Embodiment 14

[0107] Compound 4n was prepared according to the method of Example 1 with a yield of 69% and a melting point of 214.8-216.5°C; 1 HNMR (400MHz, CDCl 3 )δ9.91(s,1H),9.15(d,J=1.1Hz,1H),7.83(s,1H),7.81(d,J=1.4Hz,1H),6.84(dd,J=4.7,3.0Hz,2H) ,6.76(dd,J=8.0,1.5Hz,1H),5.98(s,2H),4.33(q,J=7.3Hz,2H),3.42(s,3H),1.64(t,J=7.3Hz,3H); 13 C NMR (100 MHz, CDCl3 )δ184.85,167.05,147.48,145.86,144.09,134.01,133.18,128.69,128.64,127.35,123.20, 121.50,120.10,119.47,109.06,108.08,101.01,54.32,52.20,17.03; HRMS(APCI)calculated for C 20 H 18 NO 5 [M+H] + 352.1180, found 352.1171.

[0108] Embodiment 15

[0109] Compound 4o was prepared according to the method of Example 1 with a yield of 66% and a melting point of 202.7-205.6°C; 1 HNMR (400MHz, CDCl 3 )δ9.93(s,1H),9.16(d,J=1.2Hz,1H),7.90(s,1H),7.78(d,J=1.5Hz,1H),6.57(s,2H) ,4.34(q,J=7.3Hz,2H),3.89(s,3H),3.88(s,6H),3.34(s,3H),1.65(t,J=7.3Hz,3H); 13 C NMR (100 MHz, CDCl 3 )δ184.93,167.60,153.20,143.41,136.41,134.72,134.20,128.78,128.27,127.30,123 .31,120.24,119.99,105.19,61.11,56.18,54.42,52.16,17.07; HRMS(APCI)calculated for C 22 H 24 NO 6 [M+H] + 98.1598, found 3398.1584.

[0110] Example 16

[0111] Compound 4p was prepared according to the method of Example 1 with a yield of 51% and a melting point of 223.5-225°C; 1 HNMR (400MHz, CDCl 3)δ9.93(s,1H),9.18(s,1H),7.86(d,J=7.3Hz,2H),7.36(d,J=8.3Hz,2H),7.2 6(t,J=5.7Hz,2H),4.35(q,J=7.3Hz,2H),3.34(s,3H),1.65(t,J=7.3Hz,3H); 13 C NMR (100 MHz, CDCl 3 )δ184.91,166.86,143.99,137.69,134.21,131.63,129.57,129.04,128.71,128. 15,127.56,122.13,120.33,119.28,54.41,52.01,17.04; HRMS(APCI)calculated for C 19 H 17 ClNO 3 [M+H] + 342.0892, found 342.0882.

[0112] Embodiment 17

[0113] Compound 4q was prepared according to the method of Example 1 with a yield of 85% and a melting point of 170-172°C; 1 HNMR (400MHz, CDCl 3 )δ9.93(s,1H),9.18(s,1H),7.88(d,J=0.9Hz,1H),7.87(s,1H),7.33-7.28(m,2H),7.24(d,J =8.1Hz,1H),7.20(d,J=7.5Hz,1H),4.35(q,J=7.3Hz,2H),3.37(s,3H),1.65(t,J=7.3Hz,3H); 13 C NMR (100 MHz, CDCl 3 )δ184.88,166.70,143.86,140.86,134.11,133.74,129.12,128.98,128.56,128.33,127. 47,126.39,125.72,121.78,120.26,119.17,54.32,51.99,16.92; HRMS(APCI)calculated for C 19 H 17 ClNO 3 [M+H] + 342.0892, found 342.0883.

[0114] Embodiment 18

[0115] Compound 4r was prepared according to the method of Example 1 with a yield of 51% and a melting point of 187.5-189.5°C; 1 HNMR (400MHz, CDCl 3 )δ9.94(s,1H),9.20(s,1H),7.90(s,1H),7.85(s,1H),7.43(dd,J=12.0,4.9Hz,2 H),7.18-7.13(m,1H),4.36(q,J=7.3Hz,2H),3.46(s,3H),1.66(t,J=7.3Hz,3H); 13 C NMR (100 MHz, CDCl 3 )δ185.03,166.58,143.90,139.27,134.36,131.87,130.17,129.80,129.56,129.34,128. 59,127.72,127.64,120.73,120.48,119.11,54.51,52.23,17.05; HRMS(APCI)calculated for C 19 H 17 Cl 2 NO 3 [M+H] + 376.0502, found 376.0492.

[0116] Embodiment 19

[0117] Compound 4s was prepared according to the method of Example 1 with a yield of 41% and a melting point of 223-225°C; 1 HNMR (400MHz, CDCl 3 )δ9.95(s,1H),9.21(s,1H),7.90(d,J=1.3Hz,1H),7.89(s,1H),7.64(d,J=7.9Hz,2 H),7.42(d,J=8.1Hz,2H),4.36(q,J=7.3Hz,2H),3.27(s,3H),1.66(t,J=7.3Hz,3H); 13 C NMR (100 MHz, CDCl 3)δ185.04,166.77,143.91,143.02,134.40,129.32,128.84,128.51,128. 03,127.71,125.97,124.96,121.84,120.54,119.26,54.52,51.86,17.06; 19 FNMR (376MHz, CDCl 3 )δ-62.16; HRMS(APCI)calculated for C 20 H 17 F 3 NO 3 [M+H] + 376.1155, found 376.1142.

[0118] Embodiment 20

[0119] Compound 4t was prepared according to the method of Example 1 with a yield of 80% and a melting point of 202.4-203.8°C; 1 HNMR (400MHz, CDCl 3 )δ9.94(s,1H),9.21(s,1H),7.94(d,J=1.1Hz,1H),7.87(s,1H),7.65(d,J=8.2Hz,2 H),7.40(d,J=8.2Hz,2H),4.37(q,J=7.3Hz,2H),3.36(s,3H),1.66(t,J=7.3Hz,3H); 13 C NMR (100 MHz, CDCl 3 )δ185.06,166.47,144.18,143.83,134.53,131.76,129.62,128.82,128.71,127.89, 121.29,120.79,119.45,119.10,108.95,54.58,52.02,17.03; HRMS(APCI)calculated for C 20 H 17 N 2 O 3 [M+H] + 333.1234, found 333.1225.

[0120] Embodiment 21

[0121] Compound 4u was prepared according to the method of Example 1 with a yield of 76% and a melting point of 183.8-186°C; 1 HNMR (400MHz, CDCl3 )δ9.97(s,1H),9.24(s,1H),8.25(d,J=8.6Hz,2H),7.97(s,1H),7.92(s,1H),7 .45(d,J=8.6Hz,2H),4.39(q,J=7.3Hz,2H),3.41(s,3H),1.68(t,J=7.3Hz,3H); 13 CNMR (100MHz, CDCl 3 )δ185.07,166.25,146.15,145.52,143.85,134.51,129.72,128.78,128.50,127. 93,123.26,120.83,120.76,119.01,54.55,52.03,16.96; HRMS(APCI)calculated for C 19 H 17 N 2 O 5 [M+H] + 353.1166, found 353.1120.

[0122] Embodiment 22

[0123] Compound 4v was prepared according to the method of Example 1 with a yield of 68% and a melting point of 193-195°C; 1 HNMR (400MHz, CDCl 3 )δ9.96(s,1H),9.23(s,1H),7.97-7.93(m,3H),7.90(s,1H),7.50(d,J=8.3Hz ,2H),4.38(q,J=7.3Hz,2H),3.33(s,3H),3.10(s,3H),1.67(t,J=7.3Hz,3H); 13 CNMR (100MHz, CDCl 3 )δ184.99,166.37,145.06,143.79,137.27,134.46,129.57,128.80,128.76,127.76, 126.99,120.98,120.64,119.03,54.51,51.90,44.68,16.97; HRMS(APCI)calculated for C 20 H 20 NO 5 S[M+H] + 386.1057, found 386.104.

[0124] Embodiment 23

[0125] Compound 4w was prepared according to the method of Example 1 with a yield of 71% and a melting point of 215-216.2°C; 1 HNMR (400MHz, CDCl 3 )δ10.03(s,1H),9.95(s,1H),9.21(d,J=1.1Hz,1H),7.92(s,2H),7.89(d,J=8.2Hz,2 H),7.47(d,J=8.1Hz,2H),4.37(q,J=7.3Hz,2H),3.31(s,3H),1.66(t,J=7.3Hz,3H); 13 C NMR (100 MHz, CDCl 3 )δ191.94,185.10,166.65,145.80,144.03,134.46,134.01,129.64,129.49,128.92, 128.69,127.97,121.97,120.81,119.38,54.58,52.01,17.05; HRMS(APCI)calculated for C 20 H 18 NO 4 [M+H] + 336.1230, found 336.1220.

[0126] Embodiment 24

[0127] Compound 4x was prepared according to the method of Example 1 with a yield of 77% and a melting point of 253-255°C; 1 H NMR (400MHz, DMSO) δ9.84(s,1H),9.28(s,1H),9.21(d,J=1.1Hz,1H),8.19(d,J=1.4Hz,1H),7.76(s, 1H),7.05-7.02(m,2H),6.78-6.75(m,2H),4.49(d,J=7.2Hz,2H),3.30(s,3H),1.49(t,J=7.2Hz,3H); 13 C NMR (100MHz, DMSO) δ182.73,166.39,155.40,134.21,129.15,128.91,128.62,127 .57,122.00,119.07,118.93,114.75,53.15,51.69,16.80; HRMS(APCI)calculated for C 19 H 18 NO 4[M+H] + 324.1230, found 324.1222.

[0128] Embodiment 25

[0129] Compound 4y was prepared according to the method of Example 1 with a yield of 89% and a melting point of 163.6-165.2°C; 1 HNMR (400MHz, CDCl 3 )δ9.94(s,1H),9.19(d,J=1.4Hz,1H),7.87(d,J=1.4Hz,1H),7.86(s,1H),7.36-7.31 (m,2H),7.27-7.23(m,2H),4.35(q,J=7.4Hz,2H),3.27(s,3H),1.66(t,J=7.4Hz,3H); 13 C NMR (100 MHz, CDCl 3 )δ184.86,166.85,147.32,143.79,138.12,134.16,129.41,129.01,128.70,127.39,121.77,120.69,120.18,119.13,54.33,51.73,16.94; 19 FNMR (376MHz, CDCl 3 )δ-57.89; HRMS(APCI)calculated for C 20 H 17 F 3 NO 4 [M+H] + 392.1104, found 392.1091.

[0130] Embodiment 26

[0131] Compound 4z was prepared according to the method of Example 1 with a yield of 66% and a melting point of 209-212°C; 1 HNMR (400MHz, CDCl 3 )δ9.94(s,1H),9.19(d,J=1.2Hz,1H),7.88(s,1H),7.87(d,J=1.5Hz,1H),7.46(d,J=8.2Hz,2H),7.3 5(d,J=8.2Hz,2H),4.35(q,J=7.3Hz,2H),3.30(s,3H),3.10(d,J=8.2Hz,6H),1.65(t,J=7.3Hz,3H); 13 C NMR (100 MHz, CDCl3 )δ184.97,171.77,166.99,144.06,140.68,134.24,133.66,129.09,128.78,128.04, 127.68,127.20,122.58,120.43,119.45,54.44,51.99,17.05; HRMS(APCI)calculated for C 22 H 23 N 2 O 4 [M+H] + 379.1652, found 379.1642.

[0132] Embodiment 27

[0133] Compound 4aa was prepared according to the method of Example 1 with a yield of 67% and a melting point of 206-208°C; 1 HNMR (400MHz, CDCl 3 )δ9.91(s,1H),9.12(s,1H),7.86(s,1H),7.77(s,1H),7.21(d,J=8.5Hz,2H),6.80(d, J=7.8Hz,2H),4.31(q,J=7.4Hz,2H),3.31(s,3H),2.98(s,6H),1.64(t,J=7.3Hz,3H); 13 C NMR (100 MHz, CDCl 3 )δ184.80,167.45,149.24,144.23,133.75,128.87,128.72,128.31,127.57,127.42, 123.96,120.12,119.73,112.76,54.21,52.30,41.05,17.05; HRMS(APCI)calculated for C 21 H 23 N 2 O 3 [M+H] + 351.1703, found 351.1693.

[0134] Embodiment 28

[0135] Compound 4bb was prepared according to the method of Example 1 with a yield of 59% and a melting point of 175-177.6°C; 1 HNMR (400MHz, CDCl 3)δ9.95(s,1H),9.20(d,J=1.2Hz,1H),8.06(d,J=8.3Hz,2H),7.91(s,1H),7.90(d,J=1.4Hz,1H) ,7.39(d,J=8.3Hz,2H),4.36(q,J=7.3Hz,2H),3.94(s,3H),3.29(s,3H),1.66(t,J=7.3Hz,3H); 13 C NMR (100 MHz, CDCl 3 )δ184.95,167.19,166.68,143.95,134.22,129.33,129.14,128.72,127.98,127.69, 127.22,122.14,120.49,119.28,54.38,52.03,51.87,16.94; HRMS(APCI)calculated for C 21 H 20 NO 5 [M+H] + 366.1336, found 366.1329.

[0136] Embodiment 29

[0137] Compound 4cc was prepared according to the method of Example 1 with a yield of 50% and a melting point of 183-185°C; 1 HNMR (400MHz, CDCl 3 )δ9.93(s,1H),9.16(d,J=1.3Hz,1H),7.88(s,1H),7.82(d,J=1.6Hz,1H),7.34(d,J=8.0Hz,2H),7.28(d,J=8 .2Hz,2H),4.34(q,J=7.4Hz,2H),3.73(t,4H),3.55(s,2H),3.25(s,3H),2.49(s,4H),1.66(t,J=7.3Hz,3H); 13 C NMR (100 MHz, CDCl 3 )δ184.92,167.14,144.23,137.97,135.25,134.08,129.03,128.77,128.73,128.11,127.5 3,123.32,120.24,119.49,67.15,63.37,54.35,53.75,51.86,17.05; HRM(APCI)calculated forC 24 H 27 N 2 O4 [M+H] + 407.1965, found 407.1949.

[0138] Test Example 1

[0139] Testing for anti-tobacco mosaic virus activity

[0140] The compound to be tested was dissolved in DMF to prepare 1×10 5 The mother solution of the compound was prepared by diluting the solution with 1 wt‰ Tween-80 to a concentration of 500 μg / mL and 100 μg / mL. The positive control viraviril was diluted with water to a concentration of 500 μg / mL and 100 μg / mL to obtain a viraviril solution.

[0141] In vivo passivation: Select 3-5 leaf-stage Sansi tobacco with uniform growth, mix the drug solution with an equal volume of virus juice for passivation for 30 minutes, and then inoculate by friction. The virus concentration is 20μg / mL. Rinse with running water immediately after inoculation. Repeat 3 times. Set a 1wt‰ Tween-80 aqueous solution as a control. Count the number of lesions after 3 days and calculate the results.

[0142] In vivo treatment: Select 3-5 leaf-stage Sansi tobacco plants with uniform growth, inoculate the whole leaf with virus using a brush, with the virus concentration of 10μg / mL, and rinse with running water after inoculation. After the leaf surface is dry, spray the whole plant with the drug, and each group is treated 3 times, and a 1‰ Tween-80 aqueous solution is set as a control. Record the number of lesions after 3 days and calculate the prevention effect.

[0143] In vivo protection: Select 3-5 leaf-stage Sansi tobacco plants with uniform growth, spray the whole plant with pesticide, and repeat the treatment 3 times for each group, and set a 1‰ Tween-80 aqueous solution as a control. After 24 hours, sprinkle diamond dust (500 mesh) on the leaves, dip the virus solution with a brush, and gently rub the entire leaf surface along the branch vein direction twice, support the lower part of the leaf with the palm of your hand, the virus concentration is 10μg / mL, and rinse with running water after inoculation. After 3 days, record the number of lesions and calculate the protection effect. The results are shown in Table 1.

[0144] Inhibition rate (%) = [(number of control necrosis spots - number of treated necrosis spots) / number of control necrosis spots] × 100%.

[0145] Table 1 Test results of compounds and ribavirin against tobacco mosaic virus

[0146]

[0147]

[0148] In Table 1, “-” means not measured.

[0149] As shown in Table 1, the inhibitory activity of the target compounds against tobacco mosaic virus (TMV) was evaluated using commercial ribavirin as a positive control. At a concentration of 500 μg / mL, compounds 4d, 4h, 4k, 4m and 4y showed higher activity levels than ribavirin (inactivation effect 39.1±2.6%, therapeutic effect 38.4±1.5%, protective effect 39.6±3.8%). It is worth noting that at a low concentration of 100 μg / mL, compounds 4d, 4e, 4f, 4g and 4k still showed higher anti-TMV activity than ribavirin. In particular, compound 4k containing meta-methoxyphenyl substitution showed the most effective anti-TMV activity (inactivation effect 51.1±1.9%, therapeutic effect 50.7±3.6%, protective effect 53.8±2.8% at 500 μg / mL).

[0150] Test Example 2

[0151] Toxicity of compound 4k to adult zebrafish

[0152] Before the experiment, adult zebrafish (2.5-3.0 cm) were cultured for 7-14 days, fed twice a day, with 14 hours of light and 10 hours of darkness at a temperature of 21-25°C. The toxicity of zebrafish was evaluated by static test method. First, 500 mg of compound 4k was weighed, dissolved in 5 mL of DMSO, and then diluted to 100 mL with deionized water for use as a stock solution. Seven experimental groups were set up: 0 μg / mL, 1 μg / mL, 2 μg / mL, 4 μg / mL, 6 μg / mL, 8 μg / mL, and 10 μg / mL. Three parallel experiments were set up in each concentration gradient experimental group: A, B, and C, and each parallel group had 8 zebrafish. The DMSO content in the blank control group was consistent with the DMSO content in the highest concentration group.

[0153] Within 6 hours after the start of the experiment, observe and record the poisoning symptoms and death of zebrafish at any time, then observe and record every 24 hours, and change the water every 48 hours. During this period, remove the dead fish in time.

[0154] Figure 1 The figure is a survival rate chart of zebrafish exposed to compound 4k. It can be seen that there was no death in the 0μg / mL, 1μg / mL, 2μg / mL, 4μg / mL, and 6μg / mL experimental groups during the eight-day exposure experiment, and the survival rate was 100%. Death occurred in the 8μg / mL experimental group on the seventh day, but no more deaths occurred as time went on, and the survival rate was 96% at the end of the experiment. In the highest concentration group (10μg / mL), deaths did not occur until the sixth day in parallel experiments B and C, and the survival rate dropped to 92%; the death situation did not increase significantly on the seventh day, and the survival rate was 88% at the end of the experiment. The experimental results show that compound 4k has low toxicity to zebrafish, and even has a slight toxic effect.

[0155] Test Example 3

[0156] Insecticidal activity test of compounds 4a to 4cc

[0157] The steps for determining the activity of killing aphids are as follows: the test insects are aphids (Aphis laburni Kaltenbach), which are normal groups raised on laboratory broad bean leaves. Weigh the drug, add 1 mL of DMF to dissolve, add two drops of Tween-20 emulsifier, add a certain amount of distilled water, stir evenly, and prepare the drug solution of the required concentration. Dip the broad bean leaves with aphids (about 60) into the drug for 5 seconds, take them out and gently shake them dry, absorb the excess drug with filter paper, then insert the broad bean branches into the absorbent sponge, cover the branches with a glass cover, and seal them with gauze. Check the results after 96 hours, and repeat 3 times for each compound. For the control, only add emulsifier and solvent to the distilled water and stir evenly.

[0158] Activity test method for diamondback moth larvae: Use the leaf dip method proposed by the International Resistance Action Committee (IRAC). Weigh 2 mg of the agent on an analytical balance in a 10 mL small beaker, add 50 μL of dimethylformamide (analytical grade) to dissolve, and add 10 mL of water to make a 200 mg / kg solution. Use straight-headed ophthalmic tweezers to immerse the cabbage leaves in the solution for 2 to 3 seconds, and shake off the excess solution. One piece at a time, 3 pieces for each sample. Place them on the treatment paper in the order of sample markings. After the solution is dry, place it in a 10 cm long straight tube with a mark, insert a 2nd instar diamondback moth larvae, and cover the tube with gauze. Place the test treatment in a standard treatment room and check the results after 96 hours. Repeat 3 times for each compound. For the control, only add emulsifier and solvent to distilled water and stir evenly.

[0159] The insecticidal activity of the compounds against aphids and diamondback moth larvae was evaluated by leaf dipping method using the botanical insecticide rotenone as a positive control. The results are shown in Table 2. The data in the table are mean ± variance.

[0160] Table 2 Insecticidal effects of compounds and rotenone on aphids and diamondback moth larvae

[0161]

[0162]

[0163] Note: “-” in Table 2 means not tested.

[0164] As shown in Table 2, at the initial screening concentration, some compounds showed lethality to aphids, while all compounds showed insecticidal activity against diamondback moth larvae. Most 5-arylcyclopentapyridine compounds showed higher lethality against diamondback moth larvae than lead compound 2. At a concentration of 600 μg / mL, compounds 4d, 4e, 4h and 4o showed 100% insecticidal activity, and these compounds also showed significant insecticidal activity at low concentrations of 200 μg / mL and 100 μg / mL. Most of these compounds with strong insecticidal activity are fluorine-substituted aromatic compounds.

[0165] Test Example 4

[0166] In vitro bactericidal activity test

[0167] In vitro bactericidal test, bacterial growth rate determination method (plate method):

[0168] Dissolve a certain amount of the drug in an appropriate amount of acetone, then dilute it to the required concentration with an aqueous solution containing 200μg / mL emulsifier, then draw 1mL of the drug solution and inject it into the culture dish, then add 9mL of culture medium respectively, shake well to make a 50μg / mL drug-containing plate, and use a plate with 1mL of sterilized water as a blank control. Use a 4mm diameter puncher to cut the bacterial disc along the outer edge of the hyphae and move it to the drug-containing plate. Repeat each treatment three times. Place the culture dish in a constant temperature incubator at 24±1℃ for culture. After 48h, investigate the expansion diameter of the bacterial disc of each treatment, calculate the average value, and calculate the relative inhibition rate by comparing with the blank control. The results are shown in Table 3, and the data in the table are mean values ​​± variance values.

[0169]

[0170] Table 3 In vitro bactericidal activity test results

[0171]

[0172]

[0173] As shown in Table 3, most compounds showed enhanced fungicidal activity after structural modification at the fifth position, especially against rapeseed sclerotia and apple ring. Compound 4i had a fungicidal activity of 92±3% against rapeseed sclerotia and had strong inhibitory effects on all seven bacteria except peanut brown spot.

[0174] 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 principle of the present invention. These improvements and modifications should also be regarded as the scope of protection of the present invention.

Claims

1. A 5-aryl-cyclopenta-pyridine compound having a structure shown in Formula I:

2. The 5-aryl-cyclopenta-pyridine compound according to claim 1, characterized in that: The Ar includes any one of the following structures: The R1 includes a C1-C6 alkoxy group; The R2-R6 independently include hydrogen, halogen, C1-C6 alkoxy, C1-C6 haloalkyl, cyano, nitro, aldehyde, hydroxyl, C1-C6 haloalkoxy and one or more of the following structures: R7~R 12 Independently includes C1~C6 alkyl.

3. The 5-aryl-cyclopenta-pyridine compound according to claim 2, characterized in that: The C1-C6 alkoxy group is methoxy, ethoxy, propoxy, butoxy, pentyloxy or hexyloxy; The C1-C6 alkyl group is methyl, ethyl, propyl, butyl, pentyl or hexyl; The C1-C6 haloalkyl group is a halomethyl group, a haloethyl group, a halopropyl group, a halobutyl group, a halopentyl group or a halohexyl group; The C1-C6 haloalkoxy group is a halomethoxy group, a haloethoxy group, a halopropoxy group, a halobutoxy group, a halopentyloxy group or a halohexyloxy group.

4. The 5-aryl-cyclopenta-pyridine compound according to any one of claims 1 to 3, characterized in that: The Ar has any one of the following structures:

5. The method for preparing the 5-aryl-cyclopenta-pyridine compound according to any one of claims 1 to 4, comprising the following steps: Compound 3 is subjected to a Suzuki coupling reaction with ArB(OH)2 to obtain the 5-aryl-cyclopenta-pyridine compound; 6. The preparation method according to claim 5, characterized in that: The molar ratio of the compound 3 to ArB(OH)2 is 1:1-2; The Suzuki coupling reaction is carried out under the conditions of a mixed solvent, a catalyst and an inorganic salt; The mixed solvent includes an organic solvent and water, and the organic solvent includes one or more of 1,4-dioxane, tetrahydrofuran, acetonitrile, ethanol and methanol; The catalyst comprises a palladium-containing catalyst; The inorganic salt includes one or more of alkali metal phosphates, alkali metal carbonates and alkali metal halides; The temperature of the Suzuki coupling reaction is 60-120° C., and the time is 5-24 hours.

7. The preparation method according to claim 6, characterized in that: The preparation method of the compound 3 comprises the following steps: Compound 2 and a bromination reagent are mixed to carry out a bromination reaction to obtain compound 3; 8. Use of the 5-aryl-cyclopentapyridine compound according to any one of claims 1 to 4 in a plant protection agent.

9. The use according to claim 8, characterized in that: The plant protection agent includes one or more of an anti-plant virus agent, an agricultural insecticide and an agricultural fungicide.

10. A plant protection agent, characterized in that: It comprises active components and auxiliary materials; the active components comprise the 5-aryl-cyclopenta-pyridine compound according to any one of claims 1 to 4.

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