Isoxazoline derivative containing bishydrazide as well as preparation method and application of isoxazoline derivative

Abstract

The invention relates to the field of chemical engineering and pesticides, in particular to an isoxazoline derivative containing dihydrazide as well as a preparation method and application of the isoxazoline derivative. The bishydrazide-containing isoxazoline derivative is a compound as shown in a formula (1). The novel isoxazoline derivative containing dihydrazide is obtained by combining an isoxazoline structure and a dihydrazide structure and carrying out special structural design, and the isoxazoline derivative containing dihydrazide has no cross resistance with existing insecticides, is relatively low in toxic and side effects, and can be applied to the field of pesticides. Meanwhile, the insecticidal composition has broad-spectrum insecticidal activity and an excellent insecticidal effect, and the problem that the pesticide resistance of pests such as spodoptera frugiperda and plutella xylostella is enhanced at present is effectively solved. Formula (1) # imgabs0 #

Description

Technical Field

[0001] The present invention relates to the fields of chemical engineering and pesticides, and particularly relates to an isoxazoline derivative containing bisacylhydrazide, a preparation method thereof, and an application thereof. Background Art

[0002] As highly representative Lepidoptera pests, Plutella xylostella and Spodoptera frugiperda pose a serious threat to the production safety of global crops. Plutella xylostella is tiny in size but has a strong reproductive capacity and adaptability, and is widely distributed around the world. It especially prefers cruciferous vegetables. In recent years, due to long-term chemical pesticide control, Plutella xylostella has developed significant resistance to commonly used pesticides such as abamectin and emamectin benzoate. In some areas, the resistance multiple of field populations is as high as hundreds of times. Spodoptera frugiperda is native to the tropical regions of the Americas. Its adults have the ability to migrate long distances and can fly hundreds of kilometers in one night, quickly spreading to many places around the world. Its larvae have a complex feeding habit, with more than 350 host plants, and cause great harm to food crops such as corn and rice. Spodoptera frugiperda has developed varying degrees of resistance to traditional insecticides such as organophosphates and pyrethroids, as well as some new insecticides, and the control difficulty is increasing day by day.

[0003] Isoxazoline insecticides are a new type of pesticide with a unique mechanism of action and great potential. They can act on the γ-aminobutyric acid (GABA) receptor and glutamate-gated chloride channel of insects, interfere with the normal flow of chloride ions, block the transmission of nerve signals, and thus paralyze and kill insects. Moreover, their mechanism of action has no cross-resistance with existing insecticides. This type of insecticide has a broad insecticidal spectrum and has good control effects on various pests such as Lepidoptera, Coleoptera, and Hemiptera, including Plutella xylostella and Spodoptera frugiperda, and can achieve significant insecticidal effects even at extremely low doses. At the same time, it has a long residual period and can continuously control pests for a long time. In addition, its environmental compatibility is relatively good and it can be degraded quickly in soil and water bodies to reduce the potential harm to the ecological environment, providing strong support for the integrated control of crop pests.

[0004] Bisacylhydrazide insecticides play a key role in the field of pest control. They belong to insect growth regulators and mainly act by mimicking the function of ecdysteroids. Insecticides containing bisacylhydrazide have a relatively broad insecticidal spectrum and have a high selective activity against Lepidoptera pests, and can effectively control pests such as Plutella xylostella, Helicoverpa armigera, and Spodoptera exigua. They have the characteristics of high efficiency, low toxicity, and low residue, are relatively safe for the environment and non-target organisms, meet the current development needs of green agriculture, and are becoming increasingly important in the integrated pest management system.

[0005] In the face of the increasingly intractable pest resistance problem, how to develop a new type of pesticide that has no cross-resistance with existing insecticides, is low-toxic and highly effective based on the above-mentioned insecticides is an urgent problem to be solved in this field. Summary of the Invention

[0006] The object of the present invention is to overcome the problems existing in the above-mentioned prior art, and to provide an isoxazoline derivative containing bisacylhydrazide, a preparation method thereof and an application thereof. The isoxazoline derivative containing bisacylhydrazide has excellent insecticidal effects.

[0007] To achieve the above object, on the one hand, the present invention provides an isoxazoline derivative containing bisacylhydrazide, and the isoxazoline derivative containing bisacylhydrazide is a compound represented by formula (1):

[0008]

[0009] Wherein each R 1 independently selects one or more of H, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 perfluoroalkyl, hydroxyl, cyano, nitro and halogen; R 2 selects one or more of H and C1-C6 perfluoroalkyl; each R 3 independently selects one or more of H and C1-C6 alkyl; R 4 selects one or more of H and C1-C6 alkyl; R 5 selects from one or more of them, wherein R 6 selects from substituted or unsubstituted C1-C 20 alkyl, substituted or unsubstituted C3-C 20 cycloalkyl and substituted or unsubstituted C6-C 20 aryl, wherein the substituents of the substituted C1-C 20 alkyl, substituted C3-C 20 cycloalkyl and substituted C6-C 20 aryl independently select one or more of C1-C 12 alkyl, C1-C 12 alkoxy, C1-C 12 perfluoroalkyl, C1-C 12 perfluoroalkoxy, halogen and nitro.

[0010] On the second aspect, the present invention provides a preparation method of the above-mentioned isoxazoline derivative containing bisacylhydrazide, and the method includes: carrying out a condensation reaction on the compound represented by formula (G) and R 6 COX to obtain the compound represented by formula (1), wherein X selects from halogen;

[0011]

[0012] On the third aspect, the present invention provides an application of the above-mentioned isoxazoline derivative containing bisacylhydrazide in pest control.

[0013] By combining the isoxazoline structure with the bisacylhydrazide structure and conducting a special structural design, the present invention obtains a novel isoxazoline derivative containing bisacylhydrazide. This isoxazoline derivative containing bisacylhydrazide has no cross-resistance with existing insecticides, has low toxicity and side effects, and at the same time has broad-spectrum insecticidal activity and excellent insecticidal effects, effectively solving the problem of enhanced pesticide resistance of pests such as Spodoptera frugiperda and Plutella xylostella at present. Detailed implementation manners

[0014] In the ranges disclosed herein, the endpoints and any values are not limited to the exact ranges or values. These ranges or values should be understood to include values close to these ranges or values. For numerical ranges, the endpoint values of each range, between the endpoint values of each range and individual point values, and between individual point values can be combined with each other to obtain one or more new numerical ranges, and these numerical ranges should be regarded as specifically disclosed herein.

[0015] In the present invention, "substituted or unsubstituted C1-C 12 alkyl" means that the alkyl has 1 to 12 carbon atoms, and the H on these carbon atoms can be substituted by substituents or not; when substituted by substituents, the substituted H can be one or more. When multiple H are substituted, they can be H on the same carbon atom or H on different carbon atoms. The same applies to other similar expressions.

[0016] In the present invention, the alkyl in expressions such as "C1-C 12 alkyl", "C1-C6 alkyl" can be a straight-chain alkyl or a branched-chain alkyl. The same applies to other similar expressions. For example, the alkyl part in "C1-C6 alkoxy" can be straight-chain or contain branches; the alkyl part in "C6-C 20 aryl" can be straight-chain or contain branches; and the same is true for other similar expressions such as "C1-C 12 cycloalkyl".

[0017] On the one hand, the present invention provides an isoxazoline derivative containing bisacylhydrazide, and this isoxazoline derivative containing bisacylhydrazide is a compound shown in formula (1):

[0018]

[0019] Wherein, each R 1 independently selects one or more from H, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 perfluoroalkyl, hydroxy, cyano, nitro, and halogen; R 2 selects one or more from H and C1-C6 perfluoroalkyl; each R 3Each independently selected from one or more of H and C1-C6 alkyl; R 4 Selected from one or more of H and C1-C6 alkyl; R 5 Selected from One or more of them, wherein R 6 Selected from substituted or unsubstituted C1-C 20 Alkyl of, substituted or unsubstituted C3-C 20 Cycloalkyl of and substituted or unsubstituted C6-C 20 One or more of aryl of, wherein the substituents of the substituted C1-C 20 Alkyl of, substituted C3-C 20 Cycloalkyl of and substituted C6-C 20 Aryl of are each independently selected from C1-C 12 Alkyl of, C1-C 12 Alkoxy of, C1-C 12 Perfluoroalkyl of, C1-C 12 Perfluoroalkoxy of, halogen and nitro, one or more of them.

[0020] According to the present invention, in order to further improve the insecticidal performance, the structure of the isoxazoline derivatives containing bisacylhydrazide can be further selected. Preferably, each R 1 Each independently selected from one or more of H, C1-C3 alkyl, C1-C3 alkoxy, C1-C3 perfluoroalkyl, hydroxy, cyano, nitro and halogen; R 2 Selected from one or more of H and C1-C3 perfluoroalkyl; each R 3 Each independently selected from one or more of H and C1-C3 alkyl; R 4 Selected from one or more of H and C1-C3 alkyl; R 5 Selected from One or more of them, wherein R 6 Selected from substituted or unsubstituted C1-C 12 Alkyl of, substituted or unsubstituted C3-C 12 Cycloalkyl of and substituted or unsubstituted C6-C 14 One or more of aryl of, wherein the substituents of the substituted C1-C 12 Alkyl of, substituted C3-C 12 Cycloalkyl of and substituted C6-C 14 Aryl of are each independently selected from C1-C6 alkyl, C1-C6 alkoxy, C1-C6 perfluoroalkyl, C1-C6 perfluoroalkoxy, halogen and nitro, one or more of them.

[0021] More preferably, each R 1Each independently selected from one or more of H, methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, trifluoromethyl, hexafluoroethyl, hydroxy, cyano, nitro, F and Cl; R 2 Selected from one or more of H, trifluoromethyl and hexafluoroethyl; each R 3 Each independently selected from one or more of H, methyl, ethyl, n-propyl and isopropyl; R 4 Selected from one or more of H, methyl, ethyl, n-propyl and isopropyl; R 5 Selected from One or more of them, wherein R 6 Selected from one or more of substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C3-C6 cycloalkyl and substituted or unsubstituted C6-C 10 One or more of aryls, wherein the substituents of the substituted C1-C6 alkyl, substituted C3-C6 cycloalkyl and substituted C6-C 10 Aryl are each independently selected from one or more of methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, n-pentyl, n-hexyl, methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, tert-butoxy, n-pentyloxy, n-hexyloxy, trifluoromethyl, hexafluoroethyl, trifluoromethoxy, hexafluoroethoxy, F, Cl, Br and nitro.

[0022] Even more preferably, at least two Rs 1 Selected from F and / or Cl, more preferably at least two Rs 1 Are Cl, even more preferably, the bisacylhydrazide-containing isoxazoline derivative is a compound represented by formula (1-x):

[0023] Formula (1-x)

[0024] In a preferred embodiment of the present invention, R 5 Selected from the following groups:

[0025]

[0026]

[0027] According to a preferred embodiment of the present invention, the bisacylhydrazide-containing isoxazoline derivative is selected from one or more of the compounds represented by the following formula:

[0028]

[0029]

[0030]

[0031] According to a particularly preferred embodiment of the present invention, the bisacylhydrazide-containing isoxazoline derivatives are selected from one or more of the compounds represented by the following formula:

[0032]

[0033]

[0034] According to a preferred embodiment of the present invention, the bisacylhydrazide-containing isoxazoline derivatives are selected from one or more of the optical isomers represented by the following formula:

[0035]

[0036] According to a particularly preferred embodiment of the present invention, the bisacylhydrazide-containing isoxazoline derivatives are selected from one or more of the optical isomers represented by the following formula:

[0037]

[0038] The second aspect of the present invention provides a method for preparing the above-mentioned bisacylhydrazide-containing isoxazoline derivatives, which method comprises: condensing the compound represented by formula (G) with R 6 COX to obtain the compound represented by formula (1), wherein X is selected from halogen;

[0039]

[0040] According to the present invention, in order to obtain a better reaction effect, preferably, relative to 1 mmol of the compound represented by formula (G), the amount of R 6 COX used is 0.5 - 3 mmol, preferably 0.8 - 1.5 mmol, for example, it can be values such as 0.8 mmol, 1.1 mmol, 1.2 mmol, 1.4 mmol, and 1.5 mmol and the ranges between any of these values.

[0041] According to the present invention, in order for the reaction to proceed smoothly, preferably, the condensation reaction is carried out in the presence of a first basic reagent.

[0042] Preferably, the first basic reagent is selected from one or more of triethylamine, pyridine, sodium hydroxide, potassium hydroxide, 3-methylpyridine, and N,N-diisopropylethylamine, and preferably one or more of triethylamine, pyridine, potassium hydroxide, and sodium hydroxide.

[0043] Preferably, relative to 1 mmol of the compound represented by formula (G), the amount of the first basic reagent used is 0.2 - 2 mmol, preferably 0.5 - 1 mmol, and can be, for example, values such as 0.5 mmol, 0.6 mmol, 0.75 mmol, and 1 mmol and the ranges between any of these values.

[0044] According to the present invention, in order to enable sufficient contact of each material, preferably, the solvent for the condensation reaction is selected from one or more of dichloromethane, chloroform, toluene, xylene, ether, and tetrahydrofuran, and preferably is dichloromethane and / or chloroform.

[0045] Preferably, relative to 1 mmol of the compound represented by formula (G), the amount of the solvent for the condensation reaction used is 2 - 20 mL, preferably 5 - 15 mL, and can be, for example, values such as 5 mL, 8 mL, 10 mL, and 15 mL and the ranges between any of these values.

[0046] According to the present invention, in order to obtain a higher yield, preferably, the conditions for the condensation reaction include: a temperature of 10 - 40 °C and a time of 4 - 24 h; more preferably, the conditions for the condensation reaction include: a temperature of 20 - 30 °C (which can be, for example, values such as 20 °C, 25 °C, 28 °C, and 30 °C and the ranges between any of these values), and a time of 8 - 16 h (which can be, for example, values such as 8 h, 10 h, 12 h, and 16 h and the ranges between any of these values).

[0047] According to the present invention, in order to avoid the generation of impurities, preferably, the condensation reaction is carried out in an inert gas atmosphere. Among them, the inert gas can be, for example, nitrogen and / or argon.

[0048] According to the present invention, after the condensation reaction is completed, the reaction solution can be post-treated. The post-treatment method can be selected within a relatively wide range. Preferably, the post-treatment method for the condensation reaction includes: extracting the reaction solution (for example, extracting with dichloromethane after adding water), washing (for example, washing with saturated brine), drying (for example, drying with desiccants such as anhydrous sodium sulfate and anhydrous magnesium sulfate), and after the organic phase is concentrated to remove the solvent, separating by column chromatography (for example, using a mixed solvent of petroleum ether / ethyl acetate with a volume ratio of 3:1 as the eluent) to obtain the product.

[0049] According to the present invention, in the preparation method of the above-mentioned isoxazoline derivatives containing bis-acylhydrazide, a preparation method of the compound represented by formula (G) can also be included. Among them, the preparation method of the compound represented by formula (G) can be selected within a relatively wide range. Preferably, the preparation method of the compound represented by formula (G) includes: subjecting the compound represented by formula (F) to a first contact reaction with NHR 4 -NH2 to obtain the compound represented by formula (G), wherein R is selected from C1 - C6 alkyl;

[0050]

[0051] According to the present invention, in order to improve the reaction yield, preferably, relative to 1 mmol of the compound represented by formula (F), the amount of NHR 4 -NH2 is 0.05 - 1 mmol, preferably 0.1 - 0.5 mmol, and for example, it can be values such as 0.1 mmol, 0.2 mmol, 0.3 mmol, 0.4 mmol, and 0.5 mmol and the ranges between any of these values.

[0052] Preferably, NHR 4 -NH2 is provided in the form of a solution with a concentration of 50 - 90 wt%, preferably in the form of a solution with a concentration of 60 - 80 wt%, and for example, it can be values such as 60 wt%, 70 wt%, 75 wt%, and 80 wt% and the ranges between any of these values. Among them, the solvent for dissolving NHR 4 -NH2 can be, for example, water.

[0053] According to the present invention, in order to provide a good reaction environment, preferably, the solvent for the first contact reaction is selected from one or more of C1 - C6 alkyl alcohols, preferably methanol and / or ethanol.

[0054] Preferably, relative to 1 mmol of the compound represented by formula (F), the amount of the solvent for the first contact reaction is 0.5 - 5 mL, preferably 1 - 3 mL, and for example, it can be values such as 1 mL, 2 mL, 2.5 mL, and 3 mL and the ranges between any of these values.

[0055] According to the present invention, in order for the reaction to proceed better, preferably, the conditions for the first contact reaction include: the temperature is 40 - 80 °C, and the time is 2 - 10 h; more preferably, the conditions for the first contact reaction include: the temperature is 50 - 70 °C (for example, it can be values such as 50 °C, 55 °C, 60 °C, and 70 °C and the ranges between any of these values), and the time is 5 - 7 h (for example, it can be values such as 5 h, 6 h, 6.5 h, and 7 h and the ranges between any of these values).

[0056] According to the present invention, in order to avoid the generation of impurities, preferably, the first contact reaction is carried out in an inert gas atmosphere. Among them, the inert gas can be, for example, nitrogen and / or argon.

[0057] According to the present invention, after the first contact reaction is completed, the reaction solution can be post-treated. The post-treatment method can be selected within a relatively wide range. Preferably, the post-treatment method of the first contact reaction includes: extracting the reaction solution (for example, extracting with ethyl acetate), washing (for example, washing with saturated brine), drying (for example, drying with desiccants such as anhydrous sodium sulfate and anhydrous magnesium sulfate), and removing the solvent from the organic phase to obtain the product.

[0058] According to the present invention, in the preparation method of the above-mentioned isoxazoline derivatives containing bisacylhydrazide, the preparation method of the compound represented by formula (F) can also be included. Among them, the preparation method of the compound represented by formula (F) can be selected within a relatively wide range. Preferably, the preparation method of the compound represented by formula (F) includes: carrying out an esterification reaction between the compound represented by formula (E) and an alcohol compound to obtain the compound represented by formula (F);

[0059]

[0060] According to the present invention, for better esterification, preferably, the alcohol compound is selected from one or more of C1-C6 alkyl alcohols, preferably methanol and / or ethanol.

[0061] Preferably, relative to 1 mmol of the compound represented by formula (E), the amount of the alcohol compound used is 0.5-5 mL, preferably 1-3 mL, and for example, it can be values such as 1 mL, 2 mL, 2.5 mL, and 3 mL and the ranges between any of these values.

[0062] According to the present invention, for the smooth progress of the esterification reaction, preferably, the esterification reaction is carried out in the presence of a first dehydrating agent.

[0063] Preferably, the first dehydrating agent is selected from SOCl2 and / or H2SO4.

[0064] Preferably, relative to 1 mmol of the compound represented by formula (E), the amount of the first dehydrating agent used is 0.4-2 mmol, preferably 0.6-1.2 mmol, and for example, it can be values such as 0.6 mmol, 0.75 mmol, 0.8 mmol, 1 mmol, and 1.2 mmol and the ranges between any of these values.

[0065] Preferably, the first dehydrating agent is added to the reaction system at -20 to 10 °C, and more preferably, the first dehydrating agent is added to the reaction system at -10 to 0 °C.

[0066] According to the present invention, in order to enhance the rate of the esterification reaction, preferably, the conditions of the esterification reaction include: the temperature is 40 - 80 °C, and the time is 2 - 10 h; more preferably, the conditions of the esterification reaction include: the temperature is 50 - 70 °C (such as values like 50 °C, 55 °C, 60 °C, and 70 °C and the ranges between any of these values), and the time is 5 - 7 h (such as values like 5 h, 6 h, 6.5 h, and 7 h and the ranges between any of these values).

[0067] According to the present invention, in order to avoid the generation of impurities, preferably, the esterification reaction is carried out in an inert gas atmosphere. Among them, the inert gas can be, for example, nitrogen and / or argon.

[0068] According to the present invention, after the esterification reaction is completed, the reaction solution can be post - treated. The post - treatment method can be selected within a relatively wide range. Preferably, the post - treatment method of the esterification reaction includes: extracting the reaction solution (for example, extracting with ethyl acetate), washing (for example, washing with saturated brine), drying (for example, drying with desiccants such as anhydrous sodium sulfate and anhydrous magnesium sulfate), and the product is obtained after the organic phase is rotary - evaporated to remove the solvent.

[0069] According to the present invention, in the preparation method of the above - mentioned isoxazoline derivatives containing biacylhydrazide, the preparation method of the compound shown in formula (E) can also be included. Among them, the preparation method of the compound shown in formula (E) can be selected within a relatively wide range. Preferably, the preparation method of the compound shown in formula (E) includes: subjecting the compound shown in formula (D) to a carboxylation reaction to obtain the compound shown in formula (E);

[0070]

[0071] According to the present invention, in order for the reaction to proceed smoothly, preferably, the carboxylation reaction is carried out in the presence of a second basic reagent.

[0072] Preferably, the second basic reagent is selected from one or more of sodium hydroxide, potassium hydroxide, rubidium hydroxide, and cesium hydroxide, and preferably sodium hydroxide and / or potassium hydroxide.

[0073] Preferably, relative to 1 mmol of the compound shown in formula (D), the dosage of the second basic reagent is 2 - 10 mmol, preferably 4 - 8 mmol, such as values like 5 mmol, 6 mmol, 7 mmol, and 8 mmol and the ranges between any of these values.

[0074] According to the present invention, in order to achieve a better reaction effect, preferably, the solvent for the carboxylation reaction is selected from one or more of water, methanol, and ethanol, preferably a water / ethanol mixed solvent with a volume ratio of 1:2 - 5, and more preferably a water / ethanol mixed solvent with a volume ratio of 1:3 - 4 (such as values like 1:3, 1:3.2, 1:3.5, and 1:4 and the ranges between any of these values).

[0075] Preferably, relative to 1 mmol of the compound shown by formula (D), the amount of the solvent for the carboxylation reaction is 5 - 20 mL, preferably 8 - 15 mL. For example, it can be values such as 8 mL, 10 mL, 12 mL, and 15 mL and the ranges between any of these values.

[0076] According to the present invention, in order to improve the reaction efficiency, preferably, the conditions for the carboxylation reaction include: a temperature of 60 - 150 °C and a time of 4 - 24 h; more preferably, the conditions for the carboxylation reaction include: a temperature of 80 - 130 °C (such as values like 80 °C, 100 °C, 115 °C, and 128 °C and the ranges between any of these values), and a time of 8 - 16 h (such as values like 8 h, 10 h, 12 h, and 16 h and the ranges between any of these values).

[0077] According to the present invention, in order to avoid the generation of impurities, preferably, the carboxylation reaction is carried out in an inert gas atmosphere. Among them, the inert gas can be, for example, nitrogen and / or argon.

[0078] According to the present invention, after the carboxylation reaction is completed, the reaction solution can be post - treated. The post - treatment method can be selected within a relatively wide range. Preferably, the post - treatment method for the carboxylation reaction includes: extracting the reaction solution (for example, extracting with dichloromethane), adjusting the pH of the aqueous phase to acidic (for example, adjusting the pH of the aqueous phase to 3 - 5 with 2M hydrochloric acid aqueous solution), extracting the aqueous phase again (for example, extracting with dichloromethane), washing (for example, washing with saturated brine), drying (for example, drying with anhydrous sodium sulfate), and obtaining the product after removing the solvent from the organic phase by rotary evaporation.

[0079] According to the present invention, in the preparation method of the above - mentioned isoxazoline derivatives containing bis - hydrazide, the preparation method of the compound shown by formula (D) can also be included. Among them, the preparation method of the compound shown by formula (D) can be selected within a relatively wide range. Preferably, the preparation method of the compound shown by formula (D) includes: carrying out a cyanation reaction on the compound shown by formula (C) with a cyanide to obtain the compound shown by formula (D);

[0080]

[0081] According to the present invention, in order to obtain a better yield, preferably, the cyanide is selected from one or more of zinc cyanide, copper cyanide, and potassium ferrocyanide.

[0082] Preferably, relative to 1 mmol of the compound represented by formula (C), the amount of the cyanide used is 0.5 - 3 mmol, preferably 1 - 2 mmol. For example, it can be values such as 1 mmol, 1.2 mmol, 1.5 mmol, 1.8 mmol, and 2 mmol and ranges between any of these values.

[0083] According to the present invention, in order to improve the reaction efficiency, preferably, the cyanation reaction is carried out in the presence of a catalyst, and the catalyst is a palladium catalyst. The palladium catalyst is selected from tetrakis(triphenylphosphine)palladium and / or dichloride [1,1'-bis(diphenylphosphino)ferrocene]palladium.

[0084] Preferably, relative to 1 mmol of the compound represented by formula (C), the amount of the catalyst used is 0.05 - 0.5 mmol, preferably 0.1 - 0.15 mmol. For example, it can be values such as 0.1 mmol, 0.12 mmol, and 0.15 mmol and ranges between any of these values.

[0085] According to the present invention, in order for the reaction to proceed more smoothly, preferably, the solvent for the cyanation reaction is selected from one or more of toluene, N,N-dimethylformamide, N-methylpyrrolidone, xylene, and dimethyl sulfoxide, and preferably toluene and / or N,N-dimethylformamide.

[0086] Preferably, relative to 1 mmol of the compound represented by formula (C), the amount of the solvent for the cyanation reaction used is 2 - 8 mL, preferably 3 - 5 mL. For example, it can be values such as 3 mL, 3.5 mL, 4 mL, and 5 mL and ranges between any of these values.

[0087] According to the present invention, in order to obtain a higher yield and purity, the reaction conditions of the cyanation reaction can be adjusted. Preferably, the conditions of the cyanation reaction include: the temperature is 80 - 180 °C, and the time is 4 - 24 h; more preferably, the conditions of the substitution reaction include: the temperature is 100 - 150 °C (for example, it can be values such as 100 °C, 120 °C, 140 °C, and 150 °C and ranges between any of these values), and the time is 8 - 16 h (for example, it can be values such as 8 h, 10 h, 12 h, and 16 h and ranges between any of these values).

[0088] According to the present invention, in order to avoid the generation of impurities, preferably, the cyanation reaction is carried out in an inert gas atmosphere. Among them, the inert gas can be, for example, nitrogen and / or argon.

[0089] According to the present invention, after the cyanation reaction is completed, the reaction solution can be post-treated, and the post-treatment method can be selected within a wide range. Preferably, the post-treatment method of the cyanation reaction includes: filtering the reaction solution, extracting the filtrate (for example, extracting with ethyl acetate), washing the organic phase (for example, washing with saturated brine), drying (for example, drying with anhydrous sodium sulfate), and removing the solvent from the organic phase and then separating the product by column chromatography (for example, using a petroleum ether / ethyl acetate mixed solvent with a volume ratio of 20:1 to 10:1 as an eluent)

[0090] According to the present invention, the preparation method of the above-mentioned isoxazoline derivative containing bishydrazide may also include a preparation method of the compound shown in formula (C). The preparation method of the compound shown in formula (C) may be selected from a wide range. Preferably, the preparation method of the compound shown in formula (C) comprises: subjecting the compound shown in formula (B) to a ring-closing reaction with hydroxylamine hydrochloride to obtain the compound shown in formula (C);

[0091] Formula (B)

[0092] According to the present invention, in order to obtain a better reaction effect, preferably, relative to 1mmol of the compound represented by formula (B), the amount of hydroxylamine hydrochloride used is 0.5-3mmol, preferably 1-2mmol, for example, it can be 1mmol, 1.2mmol, 1.5mmol and 1.8mmol and the range of any value therebetween.

[0093] According to the present invention, in order to better carry out the reaction, preferably, the ring-closure reaction is carried out in the presence of a third alkaline reagent, and the third alkaline reagent is selected from one or more of sodium hydroxide, potassium hydroxide, sodium bicarbonate and potassium bicarbonate, preferably sodium hydroxide and / or potassium hydroxide.

[0094] Preferably, the third alkaline agent is provided in the form of an aqueous solution with a concentration of 20-40 wt % (eg, 20 wt %, 30 wt %, 35 wt % and 40 wt % and any range therebetween).

[0095] Preferably, relative to 1 mmol of the compound represented by formula (B), the amount of the aqueous solution of the third alkaline agent used is 0.1-0.5 mL, for example, it can be 0.1 mL, 0.13 mL, 0.3 mL and 0.5 mL and any value in between.

[0096] According to the present invention, in order to make the materials fully contact and obtain better reaction effect, the solvent and amount of the ring-closing reaction can be adjusted. Preferably, the solvent of the ring-closing reaction is selected from one or more of methanol, ethanol and dichloromethane.

[0097] Preferably, relative to 1 mmol of the compound represented by formula (B), the amount of the solvent for the ring-closing reaction is 2 - 8 mL, preferably 3 - 5 mL, and can be, for example, numerical values such as 3 mL, 3.5 mL, 4 mL, and 5 mL and ranges between any of these numerical values.

[0098] According to the present invention, in order to obtain a product with better state and higher purity, the reaction conditions of the ring-closing reaction can be adjusted. Preferably, the conditions of the ring-closing reaction include: the temperature is 10 - 40 °C and the time is 2 - 10 h; more preferably, the conditions of the ring-closing reaction include: the temperature is 20 - 30 °C (which can be, for example, numerical values such as 20 °C, 22 °C, 25 °C, and 30 °C and ranges between any of these numerical values), and the time is 4 - 8 h (which can be, for example, numerical values such as 4 h, 5 h, 6 h, and 7 h and ranges between any of these numerical values).

[0099] According to the present invention, in order to avoid the generation of impurities, preferably, the ring-closing reaction is carried out in an inert gas atmosphere. Among them, the inert gas can be, for example, nitrogen and / or argon.

[0100] According to the present invention, after the ring-closing reaction is completed, the reaction solution can be post-treated. The post-treatment method can be selected within a relatively wide range. Preferably, the post-treatment method of the ring-closing reaction includes: subjecting the reaction solution to suction filtration and washing (for example, washing the filter cake with water) to obtain the product.

[0101] According to the present invention, in the preparation method of the above-mentioned isoxazoline derivatives containing biacylhydrazide, the preparation method of the compound represented by formula (B) can also be included. Among them, the preparation method of the compound represented by formula (B) can be selected within a relatively wide range. Preferably, the preparation method of the compound represented by formula (B) includes: subjecting the compound represented by formula (A) to a second contact reaction with a second dehydrating agent to obtain the compound represented by formula (B);

[0102]

[0103] According to the present invention, in order for the second contact reaction to proceed better, the selection and amount of the second dehydrating agent can be adjusted. Preferably, the second dehydrating agent is selected from SOCl2 and / or trifluoroacetic acid.

[0104] Preferably, relative to 1 mmol of the compound represented by formula (A), the amount of the second dehydrating agent is 0.5 - 3 mmol, preferably 0.7 - 2 mmol, and can be, for example, numerical values such as 0.75 mmol, 1 mmol, 1.5 mmol, and 2 mmol and ranges between any of these numerical values.

[0105] According to the present invention, in order for the reaction to proceed smoothly, preferably, the second contact reaction is carried out in the presence of a fourth basic reagent, and the fourth basic reagent is one or more of pyridine, 4-methylpyridine, N,N-diisopropylethylamine, and piperidine, preferably pyridine and / or N,N-diisopropylethylamine.

[0106] Preferably, relative to 1 mmol of the compound represented by formula (A), the amount of the fourth basic reagent used is 5 - 10 mmol, preferably 6 - 8 mmol, and for example, it can be values such as 6 mmol, 6.5 mmol, 7 mmol, and 8 mmol and the ranges between any of these values.

[0107] According to the present invention, in order to increase the reaction rate, the solvent and its amount used in the second contact reaction can be adjusted. Preferably, the solvent for the second contact reaction is selected from one or more of toluene, methyl tert-butyl ether, dichloromethane, chloroform, and acetonitrile, preferably toluene and / or methyl tert-butyl ether.

[0108] Preferably, relative to 1 mmol of the compound represented by formula (A), the amount of the solvent for the second contact reaction used is 1 - 8 mL, preferably 2 - 5 mL, and for example, it can be values such as 2 mL, 3 mL, 4 mL, and 5 mL and the ranges between any of these values.

[0109] According to the present invention, in order to reduce the occurrence of side reactions and obtain a better reaction effect, preferably, the conditions for the second contact reaction include: a temperature of 40 - 90 °C and a time of 3 - 12 h; more preferably, the conditions for the second contact reaction include: a temperature of 50 - 80 °C (for example, it can be values such as 50 °C, 65 °C, 70 °C, and 80 °C and the ranges between any of these values), and a time of 5 - 8 h (for example, it can be values such as 5 h, 6 h, 7 h, and 8 h and the ranges between any of these values).

[0110] According to the present invention, in order to avoid the generation of impurities, preferably, the second contact reaction is carried out in an inert gas atmosphere. Among them, the inert gas can be, for example, nitrogen and / or argon.

[0111] According to the present invention, after the second contact reaction is completed, the reaction solution can be post-treated, and the post-treatment method can be selected within a relatively wide range. Preferably, the post-treatment method for the second contact reaction includes: extracting the reaction solution (for example, extracting with ethyl acetate after adding water), washing (for example, washing with water and saturated brine respectively), drying (for example, drying with anhydrous sodium sulfate), and the organic phase is concentrated to remove the solvent to obtain the product.

[0112] According to the present invention, in the preparation method of the above-mentioned isoxazoline derivatives containing bisacylhydrazide, the preparation method of the compound shown in formula (A) may also be included. Among them, the preparation method of the compound shown in formula (A) can be selected within a relatively wide range. Preferably, the preparation method of the compound shown in formula (A) includes: reacting with in a third contacting reaction to obtain the compound shown in formula (A).

[0113] According to the present invention, in order to obtain a good yield, preferably, relative to 1 mmol of the dosage is 0.5 - 3 mmol, preferably 1 - 2 mmol, for example, it can be values such as 1 mmol, 1.5 mmol, 1.8 mmol, and 2 mmol and the ranges between any of these values.

[0114] According to the present invention, in order for the reaction to proceed better, preferably, the third contacting reaction is carried out in the presence of a fifth basic reagent, and the fifth basic reagent is selected from one or more of triethylamine, DBN, DBU, diethylamine, potassium tert-butoxide, and sodium hydroxide, preferably one or more of triethylamine, DBN, DBU, and diethylamine.

[0115] Preferably, relative to 1 mmol of the dosage of the fifth basic reagent is 0.4 - 2 mmol, preferably 0.6 - 1.5 mmol, for example, it can be values such as 1 mmol, 1.3 mmol, 1.8 mmol, and 2 mmol and the ranges between any of these values.

[0116] According to the present invention, in order to obtain a higher reaction efficiency, the solvent and its dosage for the third contacting reaction can be adjusted. Preferably, the solvent for the third contacting reaction is selected from one or more of toluene, methyl tert-butyl ether, dichloromethane, chloroform, and acetonitrile, preferably toluene and / or methyl tert-butyl ether.

[0117] Preferably, relative to 1 mmol of the dosage of the solvent for the third contacting reaction is 2 - 10 mL, preferably 4 - 8 mL, for example, it can be values such as 4 mL, 5 mL, 6 mL, and 8 mL and the ranges between any of these values.

[0118] According to the present invention, in order to achieve a better reaction effect, preferably, the conditions for the third contacting reaction include: the temperature is 40 - 90 °C, and the time is 3 - 12 h; more preferably, the conditions for the third contacting reaction include: the temperature is 50 - 80 °C (for example, it can be values such as 50 °C, 65 °C, 70 °C, and 80 °C and the ranges between any of these values), and the time is 5 - 8 h (for example, it can be values such as 5 h, 6 h, 7 h, and 8 h and the ranges between any of these values).

[0119] According to the present invention, in order to avoid the generation of impurities, preferably, the third contact reaction is carried out in an inert gas atmosphere. Among them, the inert gas can be, for example, nitrogen and / or argon.

[0120] According to the present invention, after the third contact reaction is completed, the reaction solution can be post-treated. The post-treatment method can be selected within a relatively wide range. Preferably, the post-treatment method of the third contact reaction includes: removing the solvent from the reaction solution by rotary evaporation and then separating the product by column chromatography (for example, using a petroleum ether / ethyl acetate mixed solvent with a volume ratio of 25:1 as the eluent).

[0121] The third aspect of the present invention provides the application of the above-mentioned isoxazoline derivatives containing bisacylhydrazide in pest control. Among them, the isoxazoline derivatives containing bisacylhydrazide have better selectivity and excellent insecticidal effects against Spodoptera frugiperda and Plutella xylostella.

[0122] The present invention combines the isoxazoline structure with the bisacylhydrazide structure and conducts a special structural design to obtain a novel isoxazoline derivative containing bisacylhydrazide. This isoxazoline derivative containing bisacylhydrazide has no cross-resistance with existing insecticides, low toxicity and side effects, and at the same time has broad-spectrum insecticidal activity and excellent insecticidal effects, effectively solving the problem of enhanced pesticide resistance of pests such as Spodoptera frugiperda and Plutella xylostella. The insecticidal activity of the isoxazoline derivative containing bisacylhydrazide of the present invention against Spodoptera frugiperda and Plutella xylostella can be as high as 100%.

[0123] The present invention will be described in detail below through examples.

[0124] In the following examples, the devices used are all conventional experimental devices in the art, the operations adopted are all conventional operations in the art, and the raw materials, reagents, etc. used can all be obtained through commercial purchase. Among them, The tetrakis(triphenylphosphine)palladium catalyst and each compound represented by R 6 COCl were purchased from Shanghai Bide Pharmaceutical Technology Co., Ltd.

[0125] Examples 1-33

[0126] This example is used to illustrate the preparation process of the isoxazoline derivatives containing bisacylhydrazide represented by formulas (1-1) to (1-29), and the preparation process of the optical isomers of the isoxazoline derivatives containing bisacylhydrazide represented by formulas (1-8) and (1-9).

[0127]

[0128] (1) Under a nitrogen atmosphere, 10 mmol It was added to 50 mL of toluene, and 13 mmol of DBN was slowly added. The reaction was carried out at room temperature for 30 min, and then 15 mmol was slowly added. The reaction was carried out at 65 °C for 7 h. After the reaction was completed, it was cooled to room temperature. The reaction solution was rotary evaporated and separated by column chromatography (the eluent was a mixed solvent of petroleum ether / ethyl acetate with a volume ratio of 25:1) to obtain the compound shown by formula (A-a).

[0129] (2) Under a nitrogen atmosphere, 39 mmol of the compound shown by formula (A-a) was added to 123 mL of toluene. 58.5 mmol of SOCl2 and 273 mmol of pyridine were slowly added under an ice bath. The reaction was carried out at 70 °C for 7 h. After the reaction was completed, it was cooled to room temperature. The reaction solution was extracted with ethyl acetate. The organic phase was washed with water and saturated brine respectively, dried over anhydrous sodium sulfate, and rotary evaporated to obtain the compound shown by formula (B-a).

[0130] (3) Under a nitrogen atmosphere, 36.8 mmol of the compound shown by formula (B-a) was added to 168 mL of ethanol. 36.8 mmol of hydroxylamine hydrochloride was added, and 5 mL of 30 wt% aqueous sodium hydroxide solution was slowly added. The reaction was carried out at 25 °C for 5 h. After the reaction was completed, the reaction solution was filtered by suction and the filter cake was washed with water to obtain the compound shown by formula (C-a).

[0131] (4) Under an argon atmosphere, 20 mmol of the compound shown by formula (C-a) was added to 100 mL of N,N-dimethylformamide. 2 mmol of tetrakis(triphenylphosphine)palladium catalyst and 30 mmol of zinc cyanide were added. The reaction was carried out at 150 °C for 16 h. After the reaction was completed, it was cooled to room temperature. The reaction solution was filtered by suction. The filtrate was extracted with ethyl acetate. The organic phase was washed with saturated brine, dried over anhydrous sodium sulfate, and rotary evaporated. It was separated by column chromatography (the eluent was a mixed solvent of petroleum ether / ethyl acetate with a volume ratio of 20:1 to 10:1) to obtain the compound shown by formula (D-a).

[0132] (5) Under a nitrogen atmosphere, 12.4 mmol of the compound shown by formula (D-a) was added to 124 mL of a water / ethanol (volume ratio of 1:3) mixed solvent. 74.4 mmol of sodium hydroxide was slowly added. The reaction was carried out at 128 °C for 12 h. After the reaction was completed, it was cooled to room temperature. The reaction solution was extracted with dichloromethane. The organic phase was washed with saturated brine, dried over anhydrous sodium sulfate, and rotary evaporated to obtain the compound shown by formula (E-a).

[0133] (6) Under a nitrogen atmosphere, 10 mmol of the compound shown by formula (E-a) was added to 15 mL of methanol. 7.5 mmol of SOCl2 was slowly added at -5 °C. The reaction was carried out at 60 °C for 5 h. After the reaction was completed, it was cooled to room temperature. The reaction solution was extracted with ethyl acetate. The organic phase was washed with saturated brine, dried over anhydrous sodium sulfate, and rotary evaporated to obtain the compound shown by formula (F-a).

[0134] (7) Under a nitrogen atmosphere, 10 mmol of the compound represented by formula (F-a) was added to 20 mL of methanol, and 15 mL of an 80 wt% aqueous hydrazine hydrate solution was added at -5°C, and the reaction was carried out at 60°C for 7 h. After the reaction was completed, it was cooled to room temperature, the reaction solution was extracted with ethyl acetate, the organic phase was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated in vacuo to obtain the compound represented by formula (G-a).

[0135] (8) Under a nitrogen atmosphere, 1.1 mmol of the compound represented by formula (G-a) was added to 10 mL of dichloromethane, and 1.1 mmol of R 6 COCl was slowly added, 0.83 mmol of triethylamine was added, and the reaction was carried out at 25°C for 12 h. After the reaction was completed, water was added to the reaction solution and extracted with dichloromethane. The organic phase was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated in vacuo and separated by column chromatography (the eluent was a mixed solvent of petroleum ether / ethyl acetate with a volume ratio of 3:1) to obtain the compound represented by formula (1-a).

[0136] In Examples 1-33, R 6 The structures of COCl and the prepared isoxazoline derivatives containing bisacylhydrazide and the yields of step (8) are shown in Table 1.

[0137] Table 1

[0138]

[0139]

[0140]

[0141]

[0142]

[0143] Test Example

[0144] The isoxazoline derivatives containing bisacylhydrazide prepared in Examples 1-33, as well as lotilaner, S-lotilaner, and R-lotilaner were subjected to bioactivity tests against Spodoptera frugiperda and Plutella xylostella.

[0145] The test agents were accurately weighed with an electronic analytical balance. The original drug was completely dissolved in acetone and added with a 0.1 wt% [Tween-80] aqueous solution to prepare a mother liquor with a certain concentration, and then serially diluted into a series of liquid medicines with a 0.1 wt% [Tween-80] aqueous solution according to the set concentration.

[0146] Spray method: Remove the surface wax layer of the cabbage leaves cultivated in the greenhouse, and use a punch to make circular leaf discs with a diameter of 3 cm. Use a manual sprayer to evenly spray the prepared liquid medicine on both the front and back sides of the leaves, and then place them in a petri dish with a diameter of 6 cm containing filter paper. After natural air drying, inoculate 10 neat and healthy test insects. Take three leaf discs for each liquid medicine for spray treatment, and set another treatment with clear water as the blank control group. Place the petri dishes in an observation room at a temperature of 25 ± 1°C and a relative humidity of 40 - 60%. After 72 hours, check the number of dead and alive insects and calculate the mortality rate. The calculation formula is: Mortality rate (%) = (Number of dead insects after application / Total number of insects after application) × 100; Corrected mortality rate (%) = [(Mortality rate after application - Mortality rate of blank) / (1 - Mortality rate of blank)] × 100.

[0147] The insecticidal activities of the target compounds against Plutella xylostella are shown in Table 2, and the insecticidal activities against Spodoptera frugiperda are shown in Table 3.

[0148] Table 2

[0149]

[0150]

[0151] Table 3

[0152]

[0153] As can be seen from Table 2, at three concentrations of 200 mg / L, 100 mg / L, and 50 mg / L, most of the compounds prepared in Examples 1 - 33 have good insecticidal activities against Plutella xylostella, and the higher the concentration, the better the effect. Among them, the insecticidal activities of some compounds can be as high as 100%. As can be seen from Table 3, at three concentrations of 200 mg / L, 100 mg / L, and 50 mg / L, the compounds prepared in Examples 1 - 33 have good insecticidal activities against Spodoptera frugiperda, and the higher the concentration, the better the effect. Among them, some compounds can reach an insecticidal activity of 100%. In addition, as can be seen from Table 2 and Table 3, the insecticidal activities of S - configuration compounds are better than those of R - configuration compounds.

[0154] In order to intuitively illustrate the performance and characterization process of the isoxazoline derivatives containing bis - hydrazide prepared by the method of the present invention, the present invention exemplarily provides the identification results of the isoxazoline derivatives containing bis - hydrazide prepared in Examples 1 - 33, including proton nuclear magnetic resonance spectrum, carbon nuclear magnetic resonance spectrum, fluorine nuclear magnetic resonance spectrum, high - resolution data, as well as appearance and melting point, as shown in Table 4 specifically.

[0155] Table 4

[0156]

[0157]

[0158]

[0159]

[0160]

[0161]

[0162]

[0163] The preferred embodiments of the present invention are described in detail above. However, the present invention is not limited thereto. Within the scope of the technical concept of the present invention, various simple modifications can be made to the technical solution of the present invention, including any other suitable combination of each technical feature. These simple modifications and combinations should also be regarded as the content disclosed by the present invention and fall within the protection scope of the present invention.

Claims

1. An isoxazoline derivative containing a dihydrazide, characterized in that: The isoxazoline derivative containing dihydrazide is a compound represented by formula (1): Formula (1) Among them, each R 1 Each is independently selected from one or more of H, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 perfluoroalkyl, hydroxyl, cyano, nitro and halogen; R 2 One or more selected from H and C1-C6 perfluoroalkyl; each R 3 Each independently selected from one or more of H and C1-C6 alkyl; R 4 One or more selected from H and C1-C6 alkyl; R 5 Selected from One or more of the following, where R 6 Selected from substituted or unsubstituted C1-C 20 Alkyl, substituted or unsubstituted C3-C 20 Cycloalkyl and substituted or unsubstituted C6-C 20 One or more of the aryl groups, wherein the substituted C1-C 20 Alkyl, substituted C3-C 20 Cycloalkyl and substituted C6-C 20 The substituents of the aryl group are each independently selected from C1-C 12 Alkyl, C1-C 12 Alkoxy, C1-C 12 Perfluoroalkyl, C1-C 12 One or more of a perfluoroalkoxy group, a halogen group and a nitro group.

2. The isoxazoline derivative containing dihydrazide according to claim 1, wherein Each R 1 Each is independently selected from one or more of H, C1-C3 alkyl, C1-C3 alkoxy, C1-C3 perfluoroalkyl, hydroxyl, cyano, nitro and halogen; R 2 One or more selected from H and C1-C3 perfluoroalkyl; each R 3 Each independently selected from one or more of H and C1-C3 alkyl; R 4 One or more selected from H and C1-C3 alkyl; R 5 Selected from One or more of the following, where R 6 Selected from substituted or unsubstituted C1-C 12 Alkyl, substituted or unsubstituted C3-C 12 Cycloalkyl and substituted or unsubstituted C6-C 14 One or more of the aryl groups, wherein the substituted C1-C 12 Alkyl, substituted C3-C 12 Cycloalkyl and substituted C6-C 14 The substituents of the aryl group are each independently selected from one or more of a C1-C6 alkyl group, a C1-C6 alkoxy group, a C1-C6 perfluoroalkyl group, a C1-C6 perfluoroalkoxy group, a halogen group and a nitro group; Preferably, each R 1 Each is independently selected from one or more of H, methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, trifluoromethyl, hexafluoroethyl, hydroxyl, cyano, nitro, F and Cl; R 2 One or more selected from H, trifluoromethyl and hexafluoroethyl; each R 3 Each is independently selected from one or more of H, methyl, ethyl, n-propyl and isopropyl; R 4 is selected from one or more of H, methyl, ethyl, n-propyl and isopropyl; R 5 Selected from One or more of the following, where R 6 is selected from substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C3-C6 cycloalkyl and substituted or unsubstituted C6-C 10 One or more of the aryl groups, wherein the substituted C1-C6 alkyl, the substituted C3-C6 cycloalkyl and the substituted C6-C 10 The substituents of the aryl groups are each independently selected from one or more of methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, n-pentyl, n-hexyl, methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, tert-butoxy, n-pentyloxy, n-hexyl, trifluoromethyl, hexafluoroethyl, trifluoromethoxy, hexafluoroethoxy, F, Cl, Br and nitro; More preferably, R 5 Selected from the following groups:

3. The isoxazoline derivative containing dihydrazide according to claim 1 or 2, wherein: The isoxazoline derivative containing dihydrazide is selected from one or more compounds represented by the following formula: Preferably, the isoxazoline derivative containing a bishydrazide is selected from one or more optical isomers represented by the following formula:

4. The method for preparing the isoxazoline derivative containing dihydrazide according to any one of claims 1 to 3, characterized in that: The method comprises: reacting a compound represented by formula (G) with R 6 COX undergoes a condensation reaction to obtain a compound represented by formula (1), wherein X is selected from halogen; Formula (G) 5. The method according to claim 4, wherein: Relative to 1 mmol of the compound represented by formula (G), R 6 The dosage of COX is 0.5-3 mmol, preferably 0.8-1.5 mmol; Preferably, the condensation reaction is carried out in the presence of a first alkaline agent; more preferably, the first alkaline agent is selected from one or more of triethylamine, pyridine, sodium hydroxide, potassium hydroxide, 3-methylpyridine and N,N-diisopropylethylamine, preferably one or more of triethylamine, pyridine, potassium hydroxide and sodium hydroxide; more preferably, relative to 1 mmol of the compound represented by formula (G), the amount of the first alkaline agent is 0.2-2 mmol, preferably 0.5-1 mmol; Preferably, the solvent for the condensation reaction is selected from one or more of dichloromethane, chloroform, toluene, xylene, ether and tetrahydrofuran, preferably dichloromethane and / or chloroform; Preferably, relative to 1 mmol of the compound represented by formula (G), the amount of the solvent used in the condensation reaction is 2-20 mL, preferably 5-15 mL; Preferably, the conditions for the condensation reaction include: a temperature of 10-40°C and a time of 4-24 hours; more preferably, the conditions for the condensation reaction include: a temperature of 20-30°C and a time of 8-16 hours.

6. The method according to claim 4 or 5, wherein: The preparation method of the compound represented by formula (G) comprises: reacting the compound represented by formula (F) with NHR 4 -NH2 for a first contact reaction to obtain a compound represented by formula (G), wherein R is selected from a C1-C6 alkyl group; Formula (F) 7. The method according to claim 6, wherein: Relative to 1 mmol of the compound represented by formula (F), NHR 4 -NH2 is used in an amount of 0.05-1mmol, preferably 0.1-0.5mmol; Preferably, NHR 4 -NH2 is provided in the form of a solution with a concentration of 50-90 wt%, preferably in the form of a solution with a concentration of 60-80 wt%; Preferably, the solvent for the first contact reaction is selected from C 1- One or more of C6 alkyl alcohols, preferably methanol and / or ethanol; Preferably, the amount of the solvent used in the first contact reaction is 0.5-5 mL, preferably 1-3 mL, relative to 1 mmol of the compound represented by formula (F); Preferably, the conditions of the first contact reaction include: temperature of 40-80°C, and time of 2-10h; more preferably, the conditions of the first contact reaction include: temperature of 50-70°C, and time of 5-7h.

8. The method according to claim 6 or 7, wherein: The preparation method of the compound represented by formula (F) comprises: subjecting the compound represented by formula (E) to an esterification reaction with an alcohol compound to obtain the compound represented by formula (F); Formula (E) 9. The method according to claim 8, wherein: The alcohol compound is selected from one or more C1-C6 alkyl alcohols, preferably methanol and / or ethanol; Preferably, relative to 1 mmol of the compound represented by formula (E), the amount of the alcohol compound used is 0.5-5 mL, preferably 1-3 mL; Preferably, the esterification reaction is carried out in the presence of a first dehydrating agent; more preferably, the first dehydrating agent is selected from SOCl2 and / or H2SO4; more preferably, the amount of the first dehydrating agent is 0.4-2 mmol, preferably 0.6-1.2 mmol, relative to 1 mmol of the compound represented by formula (E); Preferably, the conditions for the esterification reaction include: a temperature of 40-80° C. and a time of 2-10 h; more preferably, the conditions for the esterification reaction include: a temperature of 50-70° C. and a time of 5-7 h.

10. Use of the isoxazoline derivative containing dihydrazide according to any one of claims 1 to 3 in pest control.

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