A diamide compound containing isoxazoline and its preparation method and use

Abstract

The present invention discloses a bisamide compound containing isoxazoline, a preparation method and a use thereof, wherein the structural formula is as follows (I), wherein: R 1 , R 2 , R 3 is hydrogen, halogen, cyano, nitro, C1-C6 alkyl, C1-C6 haloalkyl or C1-C6 haloalkoxy; R 4 is hydrogen, halogen, cyano, nitro, C1-C6 alkyl or C1-C6 haloalkyl; R 5 is hydrogen, halogen, nitro, hydroxyl, amino, mercapto, C1-C6 alkoxy, C1-C6 alkenyl, C1-C6 cycloalkyl or C1-C6 aryl; R 6 is a halogen atom, a cyano group, a nitro group, a C1-C6 alkyl group, a C1-C6 cycloalkyl group or a C1-C6 aryl group; M is; wherein R 7 is halogen, ‑CN, ‑NO2, ‑CH3, ‑CH2CH3, ‑CH2CH2CH3, ‑CH2CH2CH2CH3, ‑C(CH3)3, etc.; Z is O, S. The invention has a good insecticidal effect on lepidopteran pests such as fall armyworm.

Description

Technical Field

[0001] The invention relates to the field of chemical industry and pesticides, and in particular to a bisamide compound containing isoxazoline, and also relates to a preparation method of the bisamide compound containing isoxazoline, and application of the bisamide compound containing isoxazoline in preventing and controlling lepidopteran pests. Background Art

[0002] The fall armyworm is a major migratory pest in the world, and has the characteristics of outbreak damage. It has invaded more than 100 countries. It has a wide range of host plants and likes to eat corn, which can cause a 20% to 40% reduction in corn production. In severe cases, it can lead to a total loss of corn. Therefore, the prevention and control of the fall armyworm has become a major problem that needs to be solved in crop production.

[0003] At present, the control of fall armyworm mainly relies on chemical pesticides. The invading fall armyworm carries medium to high resistance to organophosphate, carbamate and nicotine chemical insecticides. However, the current control of fall armyworm mainly relies on joint prevention and control of existing pesticides. Few pesticides are created for fall armyworm. Therefore, it is urgent to develop new high-efficiency and low-risk pesticides with no cross-resistance with existing insecticides to prevent the situation where there is no pesticide available.

[0004] Diamide insecticides have excellent control effects on fall armyworms. In 2020, chlorantraniliprole was designated by my country's Ministry of Agriculture and Rural Affairs as one of the eight pesticides for the control of fall armyworms. However, high levels of resistance to chlorantraniliprole (160 times) and flubendiamide (500 times) have been detected in parts of Puerto Rico, and there is often varying degrees of cross-resistance between diamide insecticides. Therefore, there is an urgent need to find alternatives to diamide insecticides.

[0005] Isoxazoline compounds are five-membered heterocyclic compounds containing nitrogen (N) and oxygen (O) atoms, and exhibit good biological activity against agricultural pests such as Lepidoptera, Thysanoptera, Diptera and Hemiptera, and have the characteristics of broad spectrum, high activity and high selectivity. For example, patents WO2005 / 085216A1, WO2009002809A2, WO2012120399A1 and WO2014090918A1 disclose certain isoxazoline derivatives with insecticidal properties, but most of them are used to control animal parasites. Summary of the invention

[0006] The object of the present invention is to overcome the above disadvantages and provide a bisamide compound containing isoxazoline which has a good insecticidal effect on fall armyworm.

[0007] Another object of the present invention is to provide a method for preparing the isoxazoline-containing bisamide compound.

[0008] Another object of the present invention is to provide an application of the isoxazoline-containing bisamide compound in preventing and controlling lepidopteran pests such as fall armyworm in crops such as corn, rice, and sugarcane.

[0009] To achieve the above object, the present invention adopts the following technical solutions:

[0010] The isoxazoline-containing bisamide compound of the present invention has the following structural formula:

[0011]

[0012] Where: R 1 , R 2 , R 3 is hydrogen, halogen, cyano, nitro, C1-C6 alkyl, C1-C6 haloalkyl or C1-C6 haloalkoxy;

[0013] R 4 is hydrogen, halogen, cyano, nitro, C1-C6 alkyl or C1-C6 haloalkyl;

[0014] R 5 is hydrogen, halogen, nitro, hydroxyl, amino, mercapto, C1-C6 alkoxy, C1-C6 alkenyl, C1-C6 cycloalkyl or C1-C6 aryl;

[0015] R 6 is a halogen atom, a cyano group, a nitro group, a C1-C6 alkyl group, a C1-C6 cycloalkyl group or a C1-C6 aryl group;

[0016] M is

[0017]

[0018] Where R 7 Halogen, -CN, -NO2, -CH3, -CH2CH3, -CH2CH2CH3, -CH2CH2CH2CH3, -C(CH3)3,

[0019] Z is O, S;

[0020] Preferably, R 1 , R 2 , R 3is selected from the group consisting of fluorine, chlorine, bromine, iodine, methyl, ethyl, n-propyl, sec-propyl, n-butyl, sec-butyl, isobutyl, tert-butyl, phenyl, benzyl, pyridyl, pyrazolyl, pyrrolyl, furyl, thienyl, thiazolyl, benzopyrrolyl, pyridazine, pyrimidine, pyrazine, -CF3, -CF2CF3, -CH2CH2CN, -CHCNCH3, -CH2CH2CH2CN, -CH2CHCNCH3, -CHCNCH2CH3, -CH2CH2F, -CHFCH3, -CH2CH2CH2F, -CH2CHFCH3, -CHFCH2CH3, -CH2CH2Cl, -CHClCH3, -CH2CH2CH2Cl, -CH2CHClCH3, -CHClCH2CH3, -CH2CH2Br, -CHBrCH3, -CH2CH2CH2Br, -CH2CHBrCH3, -CHBrCH2CH3,

[0021] R 4 one or more selected from hydrogen, halogen, nitro, hydroxyl, amino, mercapto, methyl, ethyl, n-propyl, sec-propyl, n-butyl, sec-butyl, isobutyl, phenyl, benzyl, pyridyl, -CF3, -CF2Cl, -CHF2, -CF2Br, -CF2CHF2, -CF2CF3, -CF2OCF3, -CH2F, -CH2Cl, -CH2Br, -CH2I, -CHFCl, -CHFBr, -CHCl2, -CF2CF2Cl, -CFClCF3, -CFClCF2Cl, -CF2CF2Br, -CFBrCF3, -CF2CHFCF3, -CF2CF2CF3, -CF(CF3)2, -CF2CFClCF2Cl, -CF2CFBrCF2Cl, -CF2CF2CF2CHF2, -CH2OCH3, -CH2OCH2CH3, -CF2OCF3, -CF2OCH3, -CH2SCH3, -CF2CN, -CN, -C(O)OCH3, -C(O)ONH2, -C(S)NH2;

[0022] R 5is selected from hydrogen, halogen, nitro, cyano, methyl, ethyl, n-propyl, isopropyl, sec-propyl, n-butyl, sec-butyl, isobutyl, phenyl, benzyl, pyridyl, -CF3, -SCH3, -CF2CF3, -CH2OCH3, -CH2OCH2CF3, -CH2SCH3, -CH2S(O)CH3, -CH2SO2CH3, -CH2SCF3, -OCH3, -OCH2CH3, -OCHF2, -OCF3, -OCF2Br, -OCF2CHF2, -SCH3, -SCH2CH3, -SCF3, -N(CH3)2, -C(O)CH3, -C(O)NH2, -C(S)NH2;

[0023] R 6 is selected from hydrogen, halogen, nitro, hydroxyl, amino, mercapto, methyl, ethyl, n-propyl, sec-propyl, n-butyl, sec-butyl, isobutyl, phenyl, benzyl, pyridyl, and may be monosubstituted or disubstituted;

[0024] The present invention discloses a method for preparing a bisamide compound containing isoxazoline, comprising:

[0025]

[0026] in:

[0027] (1) Add the compound of formula II, an aqueous solution of hydroxylamine hydrochloride and an organic solvent into a round-bottom flask, adjust the pH of the reaction solution to neutral with a saturated alkaline solution to obtain the compound of formula III, wherein the molar ratio of the compound of formula II: hydroxylamine hydrochloride: organic solvent is 1:1-3:2-5, and react at -5°C to 40°C to obtain the compound of formula III; the alkali is one of lithium hydroxide, sodium hydroxide, potassium hydroxide, calcium hydroxide, ammonia water, methylamine, ethylamine, propylamine, dimethylamine, diethylamine, dipropylamine, trimethylamine, triethylamine, tripropylamine, N,N-diisopropylethylamine, sodium acetate, potassium acetate or sodium bicarbonate; and the organic solvent is methanol, ethanol, dichloromethane, chloroform, ethyl acetate, acetonitrile, toluene, xylene, tetrahydrofuran, N,N-dimethylformamide, n-propanol or water.

[0028] (2) After the compound of formula III and the chlorination agent are chlorinated, they are reacted with the compound of formula IV in an organic solvent to obtain formula V, wherein the molar ratio of the compound of formula III: the chlorination agent: the compound of formula IV: the organic solvent is 1:1-4:1-3:2-8, and the reaction is carried out at -5°C to 50°C to obtain the compound of formula III; the chlorination agent is N-chlorosuccinimide; the organic solvent is methanol, ethanol, dichloromethane, chloroform, ethyl acetate, acetonitrile, toluene, xylene, tetrahydrofuran, N,N-dimethylformamide, n-propanol or water.

[0029] (3) The compound of formula V is hydrolyzed to obtain the compound of general formula VI, and the hydrolysis is carried out in water, methanol, ethanol, tetrahydrofuran or dioxane.

[0030] Preferably, the hydrolysis in step (3) is carried out in the presence of an alkaline substance, and the alkaline substance is preferably lithium hydroxide, sodium hydroxide or potassium hydroxide, and the molar amount of the alkaline substance is 1 to 5 times that of the compound of formula V.

[0031] (4) reacting the compound of formula VI with a chlorinating agent or a condensing agent for 1 to 8 hours, adding the compound of formula VII and a base, and reacting in an organic solvent to obtain the compound of formula I, wherein the molar ratio of the compound of formula VI: the chlorinating agent or the condensing agent: the compound of formula VII: the base: the organic solvent is 1:1 to 5: 1 to 2: 1 to 2.5: 2 to 8, and reacting at -5°C to 50°C to obtain the compound of formula III; the chlorinating agent used is one or more of thionyl chloride, thionyl chloride, oxalyl chloride, phosgene, phosphorus trichloride or phosphorus pentachloride; the condensing agent used is DCC, DMAP, DIC, HATU, DIEA, EDCI or HOBt;

[0032] The base is triethylamine, N,N-diisopropylethylamine, pyridine, piperidine, 3-methylpyridine, N-methylmorpholine, 3-methylimidazole, alkali metal alcoholate, sodium hydroxide, potassium hydroxide or lithium hydroxide;

[0033] The organic solvent used is dichloromethane, chloroform, carbon tetrachloride, benzene, toluene, xylene, ether, tetrahydrofuran, dioxane, ethyl acetate, acetonitrile or N,N-dimethylformamide.

[0034] The invention discloses an application of an isoxazoline-containing bisamide compound in preventing and controlling lepidopteran pests such as fall armyworm in crops such as corn, rice and sugarcane.

[0035] Compared with the prior art, the present invention has obvious beneficial effects. It can be seen from the above technical scheme that the present invention can effectively control lepidoptera, thysanoptera and other pests by using isoxazoline insecticides, and diamide insecticides show excellent insecticidal activity in controlling lepidoptera insects. The isoxazoline structural unit is introduced into the diamide skeleton. It is experimentally confirmed that some diamide compounds containing isoxazoline, their stereoisomers, their salts, their solvates or their compositions have good insecticidal activity against lepidoptera pests such as fall armyworm, and can be used as agricultural adjuvants or fungicides, insecticides or herbicides. The present invention is easier to disperse when it is dissolved or dispersed in a pesticide acceptable carrier (such as an ionic surfactant or a non-ionic surfactant) as an active component or configured into a preparation for use as an insecticide. DETAILED DESCRIPTION

[0036] The present invention is further described below by way of examples. It should be understood that the methods described in the examples of the present invention are only used to illustrate the present invention, rather than to limit the present invention, and simple improvements to the preparation method of the present invention under the premise of the concept of the present invention are within the scope of protection claimed by the present invention.

[0037] Example 1: N-(3-acetylaminophenyl)-4-(5-phenyl-4,5-dihydroisoxazol-3-yl)benzamide (H1):

[0038] (1) Preparation of methyl (Z)-4-((hydroxyimino)methyl)benzoate:

[0039] Add methyl p-formylbenzoate (10.0 g, 60.92 mmol), hydroxylamine hydrochloride (5.08 g, 73.10 mmol) aqueous solution and 10 mL of anhydrous ethanol into a 100 mL round-bottom flask, adjust the reaction solution to neutrality with saturated sodium carbonate solution, and stir at room temperature for 1 h. After the reaction is completed, extract with ethyl acetate, dry with anhydrous sodium sulfate, concentrate in vacuo, and recrystallize from anhydrous ethanol to obtain 9.8 g of a white solid with a yield of 89.8%; 1 H NMR (500MHz, CDCl3) δ9.23 (s, 1H, OH), 8.16 (s, 1H, CH-N), 8.06–7.98 (m, 2H, Ar-H), 7.62 (d, J = 8.4Hz, 2H, Ar-H), 3.91 (s, 3H, CH3).

[0040] (2) Preparation of methyl 4-(5-phenyl-4,5-dihydroisoxazol-3-yl)benzoate:

[0041] Add (Z)-4-((hydroxyimino)methyl)benzoic acid methyl ester (5.0 g, 27.90 mmol) and NCS (5.59 g, 41.87 mmol) into a 100 mL round-bottom flask, stir and react at 40°C for 40 min, then add styrene (3.49 g, 33.48 mmol) and triethylamine (4.24 g, 41.87 mmol), stir and react at room temperature for 18 hours. After the reaction is completed, wash with water, extract with ethyl acetate, dry with anhydrous sodium sulfate, concentrate in vacuo, and purify by column chromatography to obtain 6.32 g of a white solid with a yield of 80.5%. 1HNMR (500MHz, CDCl3) δ7.91 (d, J=8.2Hz, 1H, Ar-H), 7.55–7.44 (m, 4H, Ar-H), 7.38–7.32 (m, 2H, Ar-H), 7.26 (ddd, J=7.4, 4.0, 1.2Hz, 1H, Ar-H), 3.87 (s, 3H, CH3), 3.49 (q, J = 16.5Hz, 2H, CH2), 2.59 (s, 3H, CH3), 1.80 (s, 3H, CH3).

[0042] (3) Preparation of 4-(5-phenyl-4,5-dihydroisoxazol-3-yl)benzoic acid:

[0043] Add methyl 4-(5-phenyl-4,5-dihydroisoxazol-3-yl)benzoate (5.0 g, 17.77 mmol) and sodium hydroxide (2.13 g, 53.32 mmol) aqueous solution into a 100 mL round-bottom flask, reflux and stir to react for 1 h. After the reaction is completed, pour the reaction solution into 50 mL of ice water, adjust the solution pH to 3-4 with concentrated hydrochloric acid, filter with a Buchner funnel, and dry the filter cake to obtain 4.32 g of a white solid with a yield of 91.0%.

[0044] (4) Preparation of N-(3-acetylaminophenyl)-4-(5-phenyl-4,5-dihydroisoxazol-3-yl)benzamide:

[0045] 4-(5-phenyl-4,5-dihydroisoxazol-3-yl)benzoic acid (0.3 g, 1.12 mmol) and thionyl chloride (2.67 g, 22.45 mmol) were added to a 50 mL round-bottom flask, heated at 45 °C with stirring for 4 h, and then the excess thionyl chloride was removed by rotary evaporation. N,N-diisopropylethylamine (0.22 g, 1.68 mmol) and 15 mL of acetonitrile were added, and N-(3-aminophenyl)acetamide (0.20 g, 1.35 mmol) was added. The mixture was stirred at room temperature for 5 h. After the reaction was completed, the mixture was washed with water, extracted with ethyl acetate, dried over anhydrous sodium sulfate, concentrated in vacuo, and purified by column chromatography to obtain 0.35 g of a white solid with a yield of 78.1%, mp: 230.1–232.0 °C; 1H NMR(500MHz,DMSO-d6)δ10.36(s,1H,NH),10.01(s,1H,NH), 8.08(s,1H,Ar-H),8.02(dd,J=6.6,1.4Hz,2H,Ar-H),7.82(d,J=8.3Hz, 2H,Ar-H),7.45–7.34(m,5H,Ar-H),7.34–7.28(m,2H,Ar-H),7.21(t,J =8.1Hz,1H,Ar-H), 5.75(dd,J=10.8,8.8Hz,1H,CH), 3.90(dd,J=17.2,11.0Hz,1H,isoxazoline-H), 3.43(dd,J=17.2,8.7Hz,1H,isoxazoline-H), 2.01(s,3H,CH3).

[0046] According to the same method as that for preparing compound H1, only the substituents in formula I are replaced with structures as shown in Table 1 to obtain products H4, H8, H12, H14, H19, H22, H24, H27, H28, H29, H30, H32, H34, H35, H38, H40, H42, H43, H45, and H46.

[0047] Example 2: 4-(5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methyl-N-(4-(methylcarbamoyl)phenyl)benzamide (H6):

[0048] (1) Preparation of methyl (Z)-4-(2-hydroxyvinyl)-2-methylbenzoate:

[0049] Add methyl p-formyl-2-methylbenzoate (10.0 g, 56.12 mmol), an aqueous solution of hydroxylamine hydrochloride (4.68 g, 67.34 mmol) and 10 mL of anhydrous ethanol into a 100 mL round-bottom flask, adjust the reaction solution to neutrality with saturated sodium carbonate solution, and stir at room temperature for 1 h. After the reaction is completed, extract with ethyl acetate, dry with anhydrous sodium sulfate, concentrate in vacuo, and recrystallize from anhydrous ethanol to obtain 8.93 g of a yellow solid with a yield of 82.8%; 1 H NMR (500MHz, CDCl3) δ8.11 (s, 1H), 8.07 (s, 1H), 7.92 (d, J = 8.6Hz, 1H), 7.44 (d, J = 6.2Hz, 2H), 3.89 (s, 3H), 2.60 (s, 3H).

[0050] (2) Preparation of methyl 4-(5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methylbenzoate:

[0051] Add (Z)-4-(2-hydroxyvinyl)-2-methylbenzoic acid methyl ester (5.0 g, 25.88 mmol) and NCS (5.18 g, 38.82 mmol) into a 100 mL round-bottom flask, stir and react at 40°C for 40 min, then add 1,3-dichloro-5-(3,3,3-trifluoroprop-1-en-2-yl)benzene (7.49 g, 31.06 mmol) and triethylamine (3.93 g, 38.82 mmol), stir and react at room temperature for 18 hours, after which the reaction is completed, wash with water, extract with ethyl acetate, dry with anhydrous sodium sulfate, concentrate in vacuo, and purify by column chromatography to obtain 7.71 g of a light yellow solid with a yield of 71.2%. 1 H NMR (500MHz, CDCl3) δ7.97– 7.92 (m, 1H, Ar-H), 7.52 (dd, J = 4.0, 2.7Hz, 2H, Ar-H), 7.50 (d, J = 1.5Hz, 2H, Ar-H), 7.41 (t, J = 1.9Hz, 1H, Ar-H), 4.08 (d, J = 17.2Hz, 1H, CH2), 3.90 (s, 3H, CH3), 3.70 (d, J = 17.3Hz, 1H, CH2), 2.61 (s, 3H, CH3).

[0052] (3) Preparation of 4-(5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)benzoic acid:

[0053] Add methyl 4-(5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methylbenzoate (5.0 g, 11.57 mmol) and sodium hydroxide (1.39 g, 34.70 mmol) aqueous solution into a 100 mL round-bottom flask, reflux and stir to react for 1 h. After the reaction is completed, pour the reaction solution into 50 mL of ice water, adjust the solution pH to 3-4 with concentrated hydrochloric acid, filter with a Buchner funnel, and dry the filter cake to obtain 4.43 g of a white solid with a yield of 91.5%; 1 H NMR (500MHz, DMSO-d6) δ7.76 (d, J=1.5Hz, 1H, Ar-H), 7.66 (d, J=8.4Hz, 1H, Ar-H), 7.59 (d, J=1.6Hz, 2H, Ar-H), 7.52–7.47 (m, 2H, Ar-H), 4.28 (dd, J=41.3, 18.3Hz, 2H, CH2), 2.45 (s, 3H, CH3).

[0054] (4) Preparation of 4-(5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methyl-N-(4-(methylcarbamoyl)phenyl)benzamide:

[0055] 4-(5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methylbenzoic acid (0.3 g, 0.72 mmol) and thionyl chloride (2.56 g, 21.52 mmol) were added to a 50 mL round-bottom flask, heated and stirred at 45 °C for 4 h, and then the excess thionyl chloride was removed by rotary evaporation. N,N-diisopropylethylamine (0.14 g, 1.08 mmol) and 15 mL of acetonitrile were added, and 4-amino-N-methylbenzamide (0.13 g, 0.86 mmol) was added. The mixture was stirred at room temperature for 5 h. After the reaction was completed, the mixture was washed with water, extracted with ethyl acetate, dried over anhydrous sodium sulfate, concentrated in vacuo, and purified by column chromatography to obtain 0.22 g of a yellow solid with a yield of 50.0%, mp: 204.8–206.2 °C; 1 H NMR(500MHz,DMSO-d6)δ 10.62(s,1H,NH),8.36(s,1H,NH),7.88–7.78(m,5H,Ar-H),7.66(ddd,J =21.9,16.1,5.7Hz,5H,Ar-H),4.38(dd,J=40.5,18.4Hz,2H,isoxazoline-H),2.78(s,3H,CH3),2.44(s,3H,CH3).

[0056] According to the same method as that for preparing compound H6, only the substituents in formula I are replaced with structures as shown in Table 1 to obtain products H7, H15, H16, H17, H20, H21, H23, H25, H26, H31, H33, H39, H41, and H44.

[0057] Example 3: 4-(5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methyl-N-(2-(methylcarbamoyl)phenyl)benzamide (H9):

[0058] Steps (1) to (3) are the same as steps (1) to (3) in Example 1.

[0059] (4) Preparation of 4-(5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methyl-N-(2-(methylcarbamoyl)phenyl)benzamide:

[0060] 4-(5-phenyl-4,5-dihydroisoxazol-3-yl)benzoic acid (0.3 g, 1.12 mmol) and thionyl chloride (2.67 g, 22.45 mmol) were added to a 50 mL round-bottom flask, heated and stirred at 45 °C for 4 h, and then the excess thionyl chloride was removed by rotary evaporation. N,N-diisopropylethylamine (0.22 g, 1.68 mmol) and 15 mL of acetonitrile were added, and 2-amino-N-methylbenzamide (0.13 g, 0.86 mmol) was added. The mixture was stirred at room temperature for 5 h. After the reaction was completed, the mixture was washed with water, extracted with ethyl acetate, dried over anhydrous sodium sulfate, concentrated in vacuo, and purified by column chromatography to obtain 0.28 g of a white solid with a yield of 70.0%, mp: 134.8–137.0 °C; 1 H NMR (400MHz, DMSO-d6) δ12.11(s,1H,NH),8.83 (s,1H,NH),8.60(d,J=8.3Hz,1H,Ar-H),7.83(t,J=1.9Hz,1H,Ar-H), 7.79(dd,J=8.0,1.3Hz,1H,Ar-H),7.74–7.63(m,5H,Ar-H),7.60–7.54 (m,1H,Ar-H),7.22(td,J=7.9,1.1Hz,1H,Ar-H),4.39(dd,J=38.4,18.4 Hz,2H,isoxazoline-H),2.77(s,3H,CH3),2.49(s,3H,CH3).

[0061] The product H13 can be obtained by following the same method as that for preparing compound H9, except that the substituents in formula I are replaced with the structures shown in Table 1.

[0062] Table 1 Appearance, yield and melting point of compounds of formula I (H1-H46)

[0063]

[0064]

[0065]

[0066]

[0067] The compound has a hydrogen nuclear magnetic resonance spectrum ( 1 H NMR) and carbon spectroscopy ( 13 C NMR) data are shown in Table 2.

[0068] Table 2 Spectral data of compounds of formula I (H1-H46)

[0069]

[0070]

[0071]

[0072]

[0073]

[0074] Experimental Example 1: Determination of the biological activity of the prepared target compound against fall armyworm indoors

[0075] The bioactivity of the test agent against Spodoptera frugiperda was determined by the feed film method. The target compound was dissolved in DMSO to prepare a 5000 mg / L stock solution, and the stock solution was continuously diluted to different concentrations with a buffer solution (0.05% (w / v) Triton X-100). The control group was added with an equal amount of DMSO and 0.05% (w / v) Triton X-100 solution. Artificial feed was added to the multi-well culture plate. After the feed was cooled and formed, 100 μL of the drug solution was added to the surface of the feed. After drying at room temperature, one second-instar larva was inoculated into each well. Each concentration group was repeated three times (12 second-instar larvae were repeated each time). Finally, the 24-well culture plate was stored in an incubator at 26°C, 85% RH (relative humidity) and 16:8h (light: dark photoperiod). The results were checked after 48 hours. The insect body was touched lightly with a needle. If it could not crawl normally, it was considered dead. The corrected mortality rate was evaluated by formula (1), where T represents the mortality rate of the test compound group and C represents the mortality rate of the blank control group (T and C are expressed as percentages). The activity data are shown in Tables 3 and 4:

[0076] Table 3 Insecticidal activity of compounds of formula I (H1-H46) against fall armyworm

[0077]

[0078]

[0079] Table 4 LC of compound H7 against fall armyworm 50 Value (48h)

[0080]

[0081] The insecticidal activity of some target compounds against fall armyworm was determined by the feed film method (Table 3, Table 4). The results showed that most compounds had excellent insecticidal activity against fall armyworm at a concentration of 100 mg / L. In particular, H7 had a 100% lethality against fall armyworm at a concentration of 10 mg / L. Further testing at lower concentrations showed that H7 had excellent insecticidal activity against fall armyworm, better than the control agents fipronil and chlorfenapyr. Preliminary structure-activity relationship studies showed that changes in the amide bond significantly affected the activity of the compound, with the 3- and 4-position amides having significantly better insecticidal activity against fall armyworm than the 2-position amides.

[0082] Experimental Example 2: Field control experiment of compound H7

[0083] Preparation of emulsifiable concentrate of compound H7

[0084] Table 5 Preparation formula of emulsifiable concentrate of compound H7

[0085] name Fold content (W / W,%) Remark Compound H7 5 Active ingredients Calcium dodecylbenzenesulfonate 5 Emulsifier Castor Oil Polyoxyethylene Ether 5 Emulsifier Trimethylbenzene Make up 100 Solvents

[0086] Preparation method: Calculate the amount of each material according to the formula in Table 5, add trimethylbenzene into a 250 mL three-necked flask, add compound H7, calcium dodecylbenzenesulfonate, and castor oil polyoxyethylene ether into the three-necked flask, stir at 40-50°C for 1.5h, filter, and obtain 5% compound H7 emulsifiable concentrate.

[0087] Experimental Example 2-1: Experimental determination of compound H7 for controlling fall armyworm in the field

[0088] Experimental method: Two pesticides were selected to prepare 5% emulsion and sprayed on corn fields seriously damaged by fall armyworm.

[0089] Test agent: A: H7 B: Chlorantraniliprole

[0090] Experimental subjects: Corn at the jointing stage, fall armyworm larvae

[0091] Experimental location: Near Lu Village, Xixiangtang District, Nanning City

[0092] Experimental temperature: 28-35℃

[0093] Experiment time: 2021.08.16

[0094] Experimental design: The test plot was divided into 6 plots, and each pesticide was sprayed at 2g / mu and 3g / mu respectively. Before spraying, the insect population was surveyed and the corn leaf borer rate was counted. Seven damaged corns were randomly selected from each plot and marked with red ropes. The marked corns were surveyed for pest growth status 3d (3 days) and 7d (7 days) after spraying.

[0095] Table 6 Field activity of H7 against fall armyworm

[0096]

[0097] Experimental Example 2-2: Field control experiment with low doses of compound H7

[0098] Experimental method: Spraying pesticides on corn fields seriously damaged by fall armyworm

[0099] Test agent: A: H7 prepared in 5% emulsion B: Chlorantraniliprole (according to the recommended dosage on the package)

[0100] Experimental subjects: Corn at the jointing stage, fall armyworm larvae

[0101] Experimental location: Near Lu Village, Xixiangtang District, Nanning City

[0102] Experimental temperature: 28-35℃

[0103] Experiment time: 2021.09.27

[0104] Experimental design: The experimental plot was divided into two plots, H7 was sprayed at 1g / mu, and chlorantraniliprole was sprayed at the recommended concentration on the package. Before spraying, an insect population survey was conducted to count the rate of corn leaf infestation. Nine infested corn plants were randomly selected from each plot and marked with red ropes. The marked corn plants were surveyed for pest growth status 3d and 7d after spraying.

[0105] Table 7 Field activity of H7 against fall armyworm

[0106]

[0107] The results of the field experiment showed (Table 6) that the control effect of H7 on fall armyworm at 2g / mu and 3g / mu was greater than or equal to chlorantraniliprole, and the rapidity of H7 was better than chlorantraniliprole. The results of further reducing the concentration showed (Table 7) that H7 could still effectively kill fall armyworm at a low dose of 1g / mu, and its control effect on fall armyworm was equivalent to that of chlorantraniliprole (2.4g / mu), which indicated that H7 may be an effective alternative to diamide insecticides for controlling fall armyworm.

Claims

1. A bisamide compound containing isoxazoline, the structural formula of which is as follows: 。 2. A method for preparing a bisamide compound containing isoxazoline as claimed in claim 1, comprising: in: (1) Adding a compound of formula II, an aqueous solution of hydroxylamine hydrochloride and an organic solvent into a round-bottom flask, adjusting the pH of the reaction solution to neutral with a saturated alkaline solution to obtain a compound of formula III, wherein the molar ratio of the compound of formula II: hydroxylamine hydrochloride: organic solvent is 1:1-3:2-5, and reacting at -5°C-40°C to obtain the compound of formula III; the alkali is one of lithium hydroxide, sodium hydroxide, potassium hydroxide, calcium hydroxide, ammonia water, methylamine, ethylamine, propylamine, dimethylamine, diethylamine, dipropylamine, trimethylamine, triethylamine, tripropylamine, N,N-diisopropylethylamine, sodium acetate, potassium acetate or sodium bicarbonate; the organic solvent is selected from methanol, ethanol, dichloromethane, chloroform, ethyl acetate, acetonitrile, toluene, xylene, tetrahydrofuran, N,N-dimethylformamide and n-propanol; (2) After the compound of formula III and the chlorination agent are chlorinated, they are reacted with the compound of formula IV in an organic solvent to obtain formula V, wherein the molar ratio of the compound of formula III: the chlorination agent: the compound of formula IV: the organic solvent is 1:1~4:1~3:2~8, and the reaction is carried out at -5°C~50°C to obtain the formula V; the chlorination agent is N-chlorosuccinimide; and the organic solvent is selected from methanol, ethanol, dichloromethane, chloroform, ethyl acetate, acetonitrile, toluene, xylene, tetrahydrofuran, N,N-dimethylformamide, and n-propanol. (3) hydrolyzing the compound of formula V to obtain the compound of formula VI, and the hydrolysis is carried out in water, methanol, ethanol, tetrahydrofuran or dioxane; (4) reacting the compound of formula VI and a chlorinating agent for 1 to 8 hours, adding formula VII and a base, and reacting in an organic solvent to obtain formula I, wherein the molar ratio of the compound of formula VI: the chlorinating agent: the compound of formula VII: the base: the organic solvent is 1:1 to 5:1 to 2:1 to 2.5:2 to 8, and reacting at -5°C to 50°C to obtain the compound of formula I; the chlorinating agent used is one or more of thionyl chloride, dichlorothionyl, oxalyl chloride, phosgene, phosphorus trichloride or phosphorus pentachloride; The base is triethylamine, N,N-diisopropylethylamine, pyridine, piperidine, 3-methylpyridine, N-methylmorpholine, 3-methylimidazole, alkali metal alcoholate, sodium hydroxide, potassium hydroxide or lithium hydroxide; The organic solvent used is dichloromethane, chloroform, carbon tetrachloride, benzene, toluene, xylene, ether, tetrahydrofuran, dioxane, ethyl acetate, acetonitrile or N,N-dimethylformamide.

3. The method for preparing a bisamide compound containing isoxazoline according to claim 2, wherein the hydrolysis in step (3) is carried out in the presence of an alkaline substance, the alkaline substance is lithium hydroxide, sodium hydroxide or potassium hydroxide, and the amount of the alkaline substance is 1 to 5 times the molar amount of the compound of formula V.

4. Use of the isoxazoline-containing bisamide compound as claimed in claim 1 in controlling fall armyworm in corn, rice and sugarcane crops.

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