Isoxazoline derivative containing sulfonamide 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 sulfonamide as well as a preparation method and application of the isoxazoline derivative. The sulfonamide-containing isoxazoline derivative is a compound as shown in a formula (1). The novel sulfonamide-containing isoxazoline derivative is obtained by combining an isoxazoline structure and a sulfonamide structure and carrying out special structural design, and the sulfonamide-containing isoxazoline derivative has no cross resistance with the existing insecticide, has low toxic and side effects, and can be applied to the field of agricultural chemicals. 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 sulfonamide, and a preparation method and application thereof. Background Art

[0002] As a "stubborn killer" of cruciferous crops, the diamondback moth is small in size but reproduces rapidly. With its highly flexible ecological adaptability, it spreads widely around the world. The fall armyworm has extremely strong long-distance migration ability and can fly hundreds of kilometers in one night, quickly spreading to many places around the world. Its larvae have a miscellaneous diet and the host plants exceed 350 species, causing great harm to food crops such as rice and corn. Long-term chemical control has made many pests such as the diamondback moth and the fall armyworm highly resistant to conventional insecticides, and the control effect of some pesticides has almost been lost. For example, the diamondback moth has extremely high resistance to abamectin, emamectin benzoate, etc., and the fall armyworm has developed varying degrees of resistance to traditional insecticides such as organophosphates and pyrethroids, as well as some new insecticides. Therefore, both of them have become the key targets to be overcome in the field of pesticide research and development.

[0003] In the field of pesticide science, isoxazoline insecticides have become a research hotspot in recent years due to their unique advantages and action mechanisms. This type of insecticide endows the agent with special biological activities due to its novel chemical structure. When it exerts its effect, it can accurately target the γ-aminobutyric acid (GABA)-gated chloride channel of insects. As a key neurotransmitter inhibitory receptor in insects, after the GABA receptor is allosterically regulated by isoxazoline insecticides, the normal transmembrane flow of chloride ions is blocked, resulting in the interruption of nerve signal transmission, the insect nervous system falls into disorder, showing symptoms such as overexcitation and convulsions, and finally paralysis and death. The insecticidal spectrum of such insecticides is extremely wide, and it has good control effects on many types of pests such as Lepidoptera, Hemiptera, Thysanoptera, Coleoptera, etc., such as diamondback moths, aphids, thrips, beetles, etc. In addition, most isoxazoline insecticides have high efficiency, can exert strong insecticidal activity at low doses, have a long effective period, can reduce the frequency of pesticide application, and reduce the comprehensive control cost.

[0004] Sulfonamide compounds also play an important role in the field of insecticides. The sulfonamide group in its structure can interfere with the normal physiological functions of insects through various mechanisms. When acting on the insect nervous system, it can affect the transmission of neurotransmitters, resulting in abnormal behavior and paralysis and death of insects. Due to its unique mode of action, sulfonamide insecticides have good control effects on a variety of pests, providing new strategies and means for pest control.

[0005] Facing the increasingly intractable problem of pest resistance at present, 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 a sulfonamide-containing isoxazoline derivative, a preparation method and an application thereof. The sulfonamide-containing isoxazoline derivative has excellent insecticidal effects.

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

[0008]

[0009] Wherein each R 1 independently selects one or more of H, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, C 1 -C 6 perfluoroalkyl, hydroxyl, cyano, nitro and halogen; R 2 selects one or more of H and C 1 -C 6 perfluoroalkyl; each R 3 independently selects one or more of H and C 1 -C 6 alkyl; R 4 selects one or more of H and C 1 -C 6 alkyl; R 5 selects one or more of wherein each R 6 independently selects one or more of C 1 -C 6 alkylene; each R 7 independently selects one or more of substituted or unsubstituted C 1 -C 20 alkyl, substituted or unsubstituted C 3 -C 20 cycloalkyl and substituted or unsubstituted C 6 -C 20 aryl, wherein the substituents of the substituted C 1 -C 20 alkyl, the substituted C 3 -C 20 cycloalkyl and the substituted C 6 -C 20 aryl independently select C 1 -C 12 alkyl, C3 -C 12 cycloalkyl group of, C 1 -C 12 one or more of perfluoroalkyl group, halogen, and cyano group.

[0010] The second aspect of the present invention provides a preparation method of the above-mentioned sulfonamide-containing isoxazoline derivatives, and the method includes: contacting the compound shown in formula (G) with to carry out the first contact reaction to obtain the compound shown in formula (1);

[0011] Formula (G)

[0012] The third aspect of the present invention provides an application of the above-mentioned sulfonamide-containing isoxazoline derivatives in pest control.

[0013] By combining the isoxazoline structure with the sulfonamide structure and carrying out special structural design, the present invention obtains a novel sulfonamide-containing isoxazoline derivative. This sulfonamide-containing isoxazoline derivative has no cross-resistance with existing insecticides, has low toxic 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, and these ranges or values should be understood to include values close to these ranges or values. For numerical ranges, between the endpoint values of each range, between the endpoint values of each range and individual point values, and between individual point values, they 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 C 1 -C 12 alkyl group" means that the alkyl group 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, and 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 "C 1 -C 12 alkyl group", "C 1 -C 6 alkyl group" and other expressions of alkyl group can be a straight-chain alkyl group or a branched-chain alkyl group. The same applies to other similar expressions, such as "C 1 -C 6The alkyl part of the "alkoxy" may be straight chain or branched; 6 -C 20 The alkyl part of the "aryl" may be straight chain or branched; 1 -C 12 The same is true for other similar expressions such as "cycloalkyl" and "alkyl"

[0017] In one aspect, the present invention provides an isoxazoline derivative containing sulfonamide, wherein the isoxazoline derivative containing sulfonamide is a compound represented by formula (1):

[0018] Formula (1)

[0019] Among them, each R 1 Each independently selected from H, C 1 -C 6 Alkyl, C 1 -C 6 Alkoxy, C 1 -C 6 One or more of perfluoroalkyl, hydroxyl, cyano, nitro and halogen; R 2 Selected from H and C 1 -C 6 One or more of the perfluoroalkyl groups; each R 3 Each independently selected from H and C 1 -C 6 One or more of the alkyl groups of R 4 Selected from H and C 1 -C 6 One or more of the alkyl groups of R 5 Selected from One or more of, wherein each R 6 Each independently selected from C 1 -C 6 One or more of the alkylene groups, each R 7 are each independently selected from substituted or unsubstituted C 1 -C 20 Alkyl, substituted or unsubstituted C 3 -C 20 Cycloalkyl and substituted or unsubstituted C 6 -C 20 One or more of the aryl groups, wherein the substituted C 1 -C 20 Alkyl, substituted C 3 -C 20 Cycloalkyl and substituted C 6 -C 20 The substituents of the aryl group are each independently selected from C 1 -C12 alkyl, C 3 -C 12 cycloalkyl, C 1 -C 12 one or more of perfluoroalkyl, halogen and cyano.

[0020] According to the present invention, in order to further improve the pest control effect of the compound, the structure of the isoxazoline derivative containing sulfonamide can be further selected. Preferably, each R 1 is independently selected from H, C 1 -C 3 alkyl, C 1 -C 3 alkoxy, C 1 -C 3 one or more of perfluoroalkyl, hydroxyl, cyano, nitro and halogen; R 2 is selected from H and C 1 -C 3 one or more of perfluoroalkyl; each R 3 is independently selected from H and C 1 -C 3 alkyl; R 4 is selected from H and C 1 -C 3 alkyl; R 5 is selected from one or more of them, wherein each R 6 is independently selected from C 1 -C 3 one or more of alkylene; each R 7 is independently selected from substituted or unsubstituted C 1 -C 12 alkyl, substituted or unsubstituted C 3 -C 12 cycloalkyl and substituted or unsubstituted C 6 -C 14 aryl, wherein the substituents of the substituted C 1 -C 12 alkyl, substituted C 3 -C 12 cycloalkyl and substituted C 6 -C 14 aryl are independently selected from C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl, C 1 -C 6One or more of perfluoroalkyl, halogen, and cyano.

[0021] More preferably, each R 1 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 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 each R 6 Independently selected from one or more of methylene, ethylene, n-propylene, and isopropylene; each R 7 Independently selected from substituted or unsubstituted C 1 -C 6 Alkyl of, substituted or unsubstituted C 3 -C 6 Cycloalkyl of, and substituted or unsubstituted C 6 -C 10 Aryl of, one or more of them, wherein the substituents of substituted C 1 -C 6 Alkyl of, substituted C 3 -C 6 Cycloalkyl of, and substituted C 6 -C 10 Aryl of are independently selected from one or more of methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, n-pentyl, n-hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, trifluoromethyl, F, Cl, Br, and cyano.

[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 sulfonamide-containing isoxazoline derivatives are the compounds shown in formula (1-x):

[0023]

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

[0025]

[0026] According to a preferred embodiment of the present invention, the sulfonamide-containing isoxazoline derivatives are selected from one or more of the compounds represented by the following formula:

[0027]

[0028]

[0029] According to a particularly preferred embodiment of the present invention, the sulfonamide-containing isoxazoline derivatives are selected from one or more of the compounds represented by the following formula:

[0030]

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

[0032]

[0033] According to a particularly preferred embodiment of the present invention, the sulfonamide-containing isoxazoline derivatives are selected from one or more of the optical isomers represented by the following formula:

[0034]

[0035] In a second aspect of the present invention, there is provided a method for preparing the above-mentioned sulfonamide-containing isoxazoline derivatives, the method comprising: contacting a compound represented by formula (G) with to carry out a first contact reaction to obtain a compound represented by formula (1);

[0036] Formula (G)

[0037] According to the present invention, in order to improve the yield of the reaction, preferably, relative to 1 mmol of the compound represented by formula (G), the dosage is 0.5 - 3 mmol, preferably 0.8 - 1.5 mmol, and for example, it can be values such as 0.8 mmol, 1 mmol, 1.1 mmol, 1.3 mmol, and 1.5 mmol and the ranges between any of these values.

[0038] According to the present invention, in order for the reaction to proceed smoothly, preferably, the first contact reaction is carried out in the presence of a first basic reagent.

[0039] Preferably, the first basic reagent is selected from one or more of triethylamine, N,N-diisopropylethylamine, pyridine, piperidine, 3-methylpyridine, sodium hydroxide, and potassium hydroxide, and preferably triethylamine and / or N,N-diisopropylethylamine.

[0040] Preferably, relative to 1 mmol of the compound represented by formula (G), the amount of the first basic reagent used is 0.8 - 5 mmol, preferably 1.5 - 3 mmol, and for example, it can be values such as 1.5 mmol, 1.8 mmol, 2 mmol, 2.5 mmol, and 3 mmol, and the ranges between any of these values.

[0041] According to the present invention, in order to improve the reaction efficiency and make the reaction proceed better, preferably, the first contacting reaction is carried out in the presence of a basic catalyst.

[0042] Preferably, the basic catalyst is selected from one or more of DMAP, EDCl, DIC, HATU, and DIEA, and more preferably DMAP and / or EDCl.

[0043] Preferably, relative to 1 mmol of the compound represented by formula (G), the amount of the basic catalyst used is 0.05 - 1 mmol, preferably 0.08 - 0.5 mmol, and for example, it can be values such as 0.08 mmol, 0.1 mmol, 0.3 mmol, and 0.5 mmol, and the ranges between any of these values.

[0044] According to the present invention, in order to make each material contact more fully, preferably, the solvent for the first contacting reaction is selected from one or more of dichloromethane, chloroform, ethyl acetate, and toluene, and preferably one or more of dichloromethane, chloroform, and ethyl acetate.

[0045] Preferably, relative to 1 mmol of the compound represented by formula (G), the amount of the solvent for the first contacting reaction used is 1 - 15 mL, preferably 3 - 10 mL, and for example, it can be values such as 3 mL, 5 mL, 8 mL, and 10 mL, and the ranges between any of these values.

[0046] According to the present invention, in order to obtain a better reaction effect, preferably, the conditions for the first contacting reaction include: the temperature is 10 - 40 °C, and the time is 4 - 24 h; more preferably, the conditions for the first contacting reaction include: the temperature is 20 - 30 °C (for example, it can be values such as 20 °C, 25 °C, 28 °C, and 30 °C, and the 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 the ranges between any of these values).

[0047] According to the present invention, in order to avoid the generation of impurities, preferably, the first contacting 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 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 for the first contact reaction includes: extracting the reaction solution (for example, extracting with dichloromethane), washing (for example, washing with saturated brine), drying (for example, drying with desiccants such as anhydrous sodium sulfate and anhydrous magnesium sulfate), removing the solvent from the organic phase by rotary evaporation, and then separating the product by column chromatography (for example, using a mixed solvent of petroleum ether / ethyl acetate with a volume ratio of 3:1 as the eluent).

[0049] According to the present invention, in the preparation method of the above-mentioned sulfonamide-containing isoxazoline derivatives, the 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: performing a first hydrolysis reaction on the compound represented by formula (F) to obtain the compound represented by formula (G);

[0050] Formula (F)

[0051] According to the present invention, in order for the reaction to proceed better, preferably, the first hydrolysis reaction is carried out in the presence of an acidic reagent.

[0052] Preferably, the acidic reagent is selected from one or more of hydrochloric acid, trifluoroacetic acid, and sulfuric acid, and preferably hydrochloric acid and / or trifluoroacetic acid.

[0053] Preferably, the acidic reagent is provided in the form of a solution, and the concentration of the solution of the acidic reagent is 30-98 wt%, preferably 50-95 wt%, for example, it can be values such as 50 wt%, 70 wt%, 80 wt%, 90 wt%, and 95 wt% and the ranges between any of these values. Among them, the solvent for dissolving the acidic reagent can be selected within a relatively wide range, for example, water is used.

[0054] Preferably, relative to 1 mmol of the compound represented by formula (F), the amount of the solution of the acidic reagent used is 0.1-2 mL, preferably 0.5-1.5 mL, for example, it can be values such as 0.5 mL, 0.8 mL, 1 mL, 1.2 mL, and 1.5 mL and the ranges between any of these values.

[0055] According to the present invention, in order to provide a good reaction environment, preferably, the solvent for the first hydrolysis reaction is selected from one or more of dichloromethane, chloroform, 1,2-dichloroethane, toluene, xylene, and 1,4-dioxane, and preferably dichloromethane and / or chloroform.

[0056] Preferably, relative to 1 mmol of the compound represented by formula (F), the amount of the solvent for the first hydrolysis reaction is 0.5 - 5 mL, preferably 1 - 3 mL, and can be, for example, values such as 1 mL, 1.5 mL, 2 mL, 2.5 mL, and 3 mL and ranges between any of these values.

[0057] According to the present invention, in order to accelerate the reaction rate, preferably, the conditions for the first hydrolysis reaction include: a temperature of 10 - 40 °C and a time of 4 - 24 h; more preferably, the conditions for the first hydrolysis 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 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 ranges between any of these values).

[0058] According to the present invention, in order to avoid the generation of impurities, preferably, the first hydrolysis reaction is carried out in an inert gas atmosphere. Among them, the inert gas can be, for example, nitrogen and / or argon.

[0059] According to the present invention, after the first hydrolysis 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 first hydrolysis reaction includes: extracting the reaction solution (for example, extracting with dichloromethane), 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 concentrated by rotary evaporation to remove the solvent.

[0060] According to the present invention, in the preparation method of the above - mentioned sulfonamide - containing isoxazoline derivatives, it may further include the preparation method of the compound represented by formula (F). 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: condensing the compound represented by formula (E) with NH 2 -R 6 -NH - Boc to obtain the compound represented by formula (F);

[0061] Formula (E)

[0062] According to the present invention, in order to improve the yield, preferably, relative to 1 mmol of the compound represented by formula (E), the amount of NH 2 -R 6 -NH - Boc is 0.5 - 2 mmol, preferably 0.8 - 1.5 mmol, and can be, for example, values such as 0.8 mmol, 1 mmol, 1.2 mmol, and 1.5 mmol and ranges between any of these values.

[0063] According to the present invention, in order to promote the reaction, preferably, the condensation reaction is carried out in the presence of a second basic reagent.

[0064] Preferably, the second 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, sodium hydroxide, and potassium hydroxide.

[0065] Preferably, relative to 1 mmol of the compound represented by formula (E), the amount of the second basic reagent used is 0.5 - 5 mmol, preferably 1 - 3 mmol, and for example, it can be values such as 1 mmol, 1.5 mmol, 2 mmol, and 3 mmol and the ranges between any of these values.

[0066] 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 condensing agent.

[0067] Preferably, the condensing agent is selected from one or more of EDCl, HOBt, DCC, DMAP, DIC, and HATU, preferably EDCl and / or HOBt, and more preferably a mixed condensing agent of EDCl / HOBt with a molar ratio of 1:0.8 - 1.5.

[0068] Preferably, relative to 1 mmol of the compound represented by formula (E), the amount of the condensing agent used is 1 - 5 mmol, preferably 2 - 4 mmol, and for example, it can be values such as 2 mmol, 2.5 mmol, 3 mmol, and 4 mmol and the ranges between any of these values.

[0069] According to the present invention, in order to achieve better reaction effects, preferably, the solvent for the condensation reaction is selected from one or more of dichloromethane, chloroform, toluene, xylene, ether, and tetrahydrofuran, and preferably dichloromethane and / or chloroform.

[0070] Preferably, relative to 1 mmol of the compound represented by formula (E), the amount of the solvent for the condensation reaction used is 1 - 20 mL, preferably 5 - 10 mL, and for example, it can be values such as 5 mL, 6 mL, 8 mL, 9 mL, and 10 mL and the ranges between any of these values.

[0071] According to the present invention, in order to improve the reaction efficiency and yield, preferably, the conditions for the condensation reaction include: the temperature is 10 - 40 °C, and the time is 4 - 24 h; more preferably, the conditions for the condensation reaction include: the temperature is 20 - 30 °C (for example, it can be values such as 20 °C, 25 °C, 28 °C, and 30 °C and the 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 the ranges between any of these values).

[0072] 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.

[0073] 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 of the condensation reaction includes: extracting the reaction solution (for example, extracting with dichloromethane), 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 concentrated by rotary evaporation to remove the solvent.

[0074] According to the present invention, in the preparation method of the above-mentioned isoxazoline derivatives containing sulfonamide, 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);

[0075] Formula (D)

[0076] 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 third basic reagent.

[0077] Preferably, the third 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.

[0078] Preferably, relative to 1 mmol of the compound shown in formula (D), the amount of the third basic reagent used is 2 - 10 mmol, preferably 4 - 8 mmol, and can be, for example, values such as 4 mmol, 6 mmol, 7 mmol, and 8 mmol and the ranges between any of these values.

[0079] 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, and 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 (for example, values such as 1:3, 1:3.5, 1:3.8, and 1:4 and the ranges between any of these values).

[0080] Preferably, relative to 1 mmol of the compound shown in formula (D), the amount of the solvent for the carboxylation reaction used 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.

[0081] 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, 128 °C, 130 °C, etc. and ranges between any of these values), and a time of 8 - 16 h (such as values like 8 h, 10 h, 12 h, 16 h, etc. and ranges between any of these values).

[0082] 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.

[0083] 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 by rotary evaporation of the organic phase.

[0084] According to the present invention, in the preparation method of the above - mentioned sulfonamide - containing isoxazoline derivatives, the preparation method of the compound represented by formula (D) can also be included. Among them, the preparation method of the compound represented by formula (D) can be selected within a relatively wide range. Preferably, the preparation method of the compound represented by formula (D) includes: subjecting the compound represented by formula (C) to a cyanation reaction with a cyanide to obtain the compound represented by formula (D);

[0085] Formula (C)

[0086] 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.

[0087] 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, such as values like 1 mmol, 1.2 mmol, 1.5 mmol, 1.8 mmol, 2 mmol, etc. and ranges between any of these values.

[0088] 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. The catalyst is a palladium catalyst, and the palladium catalyst is selected from tetrakis(triphenylphosphine)palladium and / or dichlorobis(1,1'-bis(diphenylphosphino)ferrocene)palladium.

[0089] 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, and for example, it can be values such as 0.1 mmol, 0.12 mmol, 0.14 mmol, and 0.15 mmol, and the ranges between any of these values.

[0090] 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.

[0091] 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, and for example, it can be values such as 3 mL, 3.5 mL, 4 mL, and 5 mL, and the ranges between any of these values.

[0092] According to the present invention, in order to obtain 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 the 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 the ranges between any of these values).

[0093] According to the present invention, in order to avoid the generation of impurities, preferably, the cyanation reaction is carried out under an inert gas atmosphere. Among them, the inert gas can be, for example, nitrogen and / or argon.

[0094] According to the present invention, after the cyanation 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 cyanation reaction includes: filtering the reaction solution by suction, 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 after the solvent in the organic phase is removed by rotary evaporation, 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 the eluent).

[0095] According to the present invention, in the preparation method of the above-mentioned sulfonamide-containing isoxazoline derivatives, the preparation method of the compound represented by formula (C) may further be included. Among them, the preparation method of the compound represented by formula (C) can be selected within a relatively wide range. Preferably, the preparation method of the compound represented by formula (C) includes: subjecting the compound represented by formula (B) to a ring-closing reaction with hydroxylamine hydrochloride to obtain the compound represented by formula (C);

[0096] Formula (B)

[0097] According to the present invention, in order to obtain a better reaction effect, preferably, relative to 1 mmol of the compound represented by formula (B), the amount of hydroxylamine hydrochloride 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, and 1.8 mmol and the ranges between any of these values.

[0098] According to the present invention, in order for the reaction to proceed better, preferably, the ring-closing reaction is carried out in the presence of a fourth basic reagent.

[0099] Preferably, the fourth basic reagent is selected from one or more of sodium hydroxide, potassium hydroxide, sodium bicarbonate, and potassium bicarbonate, and preferably sodium hydroxide and / or potassium hydroxide.

[0100] Preferably, the fourth basic reagent is provided in the form of an aqueous solution with a concentration of 20 - 40 wt% (for example, it can be values such as 20 wt%, 30 wt%, 35 wt%, and 40 wt% and the ranges between any of these values).

[0101] Preferably, relative to 1 mmol of the compound represented by formula (B), the amount of the aqueous solution of the fourth basic reagent used is 0.1 - 0.5 mL, for example, it can be values such as 0.1 mL, 0.13 mL, 0.3 mL, and 0.5 mL and the ranges between any of these values.

[0102] According to the present invention, in order to make each material fully contact and obtain a better reaction effect, the solvent for the ring-closing reaction and its amount can be adjusted. Preferably, the solvent for the ring-closing reaction is selected from one or more of methanol, ethanol, and dichloromethane.

[0103] Preferably, relative to 1 mmol of the compound represented by formula (B), the amount of the solvent for the ring-closing 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 the ranges between any of these values.

[0104] 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 (such as values like 20°C, 22°C, 25°C, 30°C and the ranges between any of these values), and the time is 4 - 8 h (such as values like 4 h, 5 h, 6 h, 7 h and the ranges between any of these values).

[0105] 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.

[0106] 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: filtering the reaction solution by suction and washing (such as washing the filter cake with water) to obtain the product.

[0107] According to the present invention, in the preparation method of the above - mentioned isoxazoline derivatives containing sulfonamide, the preparation method of the compound shown in formula (B) can also be included. Among them, the preparation method of the compound shown in formula (B) can be selected within a relatively wide range. Preferably, the preparation method of the compound shown in formula (B) includes: carrying out a second contact reaction between the compound shown in formula (A) and a dehydrating agent to obtain the compound shown in formula (B);

[0108] Formula (A)

[0109] According to the present invention, in order for the second contact reaction to proceed better, the selection and dosage of the dehydrating agent can be adjusted. Preferably, the dehydrating agent is selected from SOCl 2 and / or trifluoroacetic acid.

[0110] Preferably, relative to 1 mmol of the compound shown in formula (A), the dosage of the dehydrating agent is 0.5 - 3 mmol, preferably 0.7 - 2 mmol, such as values like 0.75 mmol, 1 mmol, 1.5 mmol, 2 mmol and the ranges between any of these values.

[0111] 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 fifth basic reagent.

[0112] Preferably, the fifth basic reagent is one or more of pyridine, 4 - methylpyridine, N,N - diisopropylethylamine and piperidine, preferably pyridine and / or N,N - diisopropylethylamine.

[0113] Preferably, relative to 1 mmol of the compound represented by formula (A), the amount of the fifth basic reagent is 5 - 10 mmol, preferably 6 - 8 mmol, and can be, for example, numerical values such as 6 mmol, 6.5 mmol, 7 mmol, and 8 mmol, and ranges between any of these numerical values.

[0114] According to the present invention, in order to improve 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, and is preferably toluene and / or methyl tert-butyl ether.

[0115] Preferably, relative to 1 mmol of the compound represented by formula (A), the amount of the solvent for the second contact reaction is 1 - 8 mL, preferably 2 - 5 mL, and can be, for example, numerical values such as 2 mL, 3 mL, 4 mL, and 5 mL, and ranges between any of these numerical values.

[0116] 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 (which can be, for example, numerical values such as 50 °C, 65 °C, 70 °C, and 80 °C, and ranges between any of these numerical values), and a time of 5 - 8 h (which can be, for example, numerical values such as 5 h, 6 h, 7 h, and 8 h, and ranges between any of these numerical values).

[0117] 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.

[0118] According to the present invention, after the second 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 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 product is obtained after removing the solvent from the organic phase by rotary evaporation.

[0119] According to the present invention, in the preparation method of the above-mentioned isoxazoline derivatives containing sulfonamide, the preparation method of the compound represented by formula (A) can also be included. Among them, the preparation method of the compound represented by formula (A) can be selected within a relatively wide range. Preferably, the preparation method of the compound represented by formula (A) includes: Carrying out a third contact reaction to obtain the compound represented by formula (A).

[0120] According to the present invention, in order to obtain a good yield, preferably, relative to 1 mmol the dosage is 0.5 - 3 mmol, preferably 1 - 2 mmol, and 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.

[0121] According to the present invention, in order for the reaction to proceed better, preferably, the third contact reaction is carried out in the presence of a sixth basic reagent.

[0122] Preferably, the sixth basic reagent is selected from one or more of triethylamine, DBN, DBU, diethylamine, potassium tert - butoxide, and sodium hydroxide, and preferably one or more of triethylamine, DBN, DBU, and diethylamine.

[0123] Preferably, relative to 1 mmol the dosage of the sixth basic reagent is 0.4 - 2 mmol, preferably 0.6 - 1.5 mmol, and 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.

[0124] According to the present invention, in order to obtain a higher reaction efficiency, the solvent and its dosage of the third contact reaction can be adjusted. Preferably, the solvent of the third contact reaction is selected from one or more of toluene, methyl tert - butyl ether, dichloromethane, chloroform, and acetonitrile, and preferably toluene and / or methyl tert - butyl ether.

[0125] Preferably, relative to 1 mmol the dosage of the solvent of the third contact reaction is 2 - 10 mL, preferably 4 - 8 mL, and 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.

[0126] According to the present invention, in order to achieve a better reaction effect, preferably, the conditions of the third contact reaction include: the temperature is 40 - 90 °C and the time is 3 - 12 h; more preferably, the conditions of the third contact 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).

[0127] 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.

[0128] 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 performing column chromatography (for example, using a mixed solvent of petroleum ether / ethyl acetate with a volume ratio of 25:1 as the eluent) to separate and obtain the product.

[0129] The third aspect of the present invention provides the application of the above-mentioned sulfonamide-containing isoxazoline derivatives in pest control. Among them, the sulfonamide-containing isoxazoline derivatives have better selectivity and excellent insecticidal effects against Spodoptera frugiperda and Plutella xylostella.

[0130] By combining the isoxazoline structure with the sulfonamide structure and carrying out special structural design, the present invention obtains a novel sulfonamide-containing isoxazoline derivative. This sulfonamide-containing isoxazoline derivative 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 sulfonamide-containing isoxazoline derivative of the present invention against Plutella xylostella can be as high as 100%.

[0131] The present invention will be described in detail below through examples.

[0132] 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, tetrakis(triphenylphosphine)palladium catalyst and each of the compounds shown is purchased from Shanghai Bide Pharmaceutical Technology Co., Ltd.

[0133] Examples 1-33

[0134] This example is used to illustrate the preparation process of the sulfonamide-containing isoxazoline derivatives shown in formulas (1-1) to (1-27), and the preparation process of the optical isomers of the sulfonamide-containing isoxazoline derivatives shown in formulas (1-18), (1-20) and (1-25).

[0135]

[0136]

[0137] (1) Under a nitrogen atmosphere, 10 mmol is added to 50 mL of toluene, 13 mmol of DBN is slowly added, and the reaction is carried out at room temperature for 30 min. Then 15 mmol React at 65 °C for 7 h. After the reaction is completed, cool to room temperature, rotary evaporate the reaction solution and separate by column chromatography (the eluent is a mixed solvent of petroleum ether / ethyl acetate with a volume ratio of 25:1) to obtain the compound shown by formula (A-a).

[0138] (2) Under a nitrogen atmosphere, add 39 mmol of the compound shown by formula (A-a) to 123 mL of toluene, slowly add 58.5 mmol of SOCl 2 and 273 mmol of pyridine, and react at 70 °C for 7 h. After the reaction is completed, cool to room temperature, extract the reaction solution with ethyl acetate, wash the organic phase with water and saturated brine respectively, dry over anhydrous sodium sulfate, and rotary evaporate to obtain the compound shown by formula (B-a).

[0139] (3) Under a nitrogen atmosphere, add 36.8 mmol of the compound shown by formula (B-a) to 168 mL of ethanol, add 36.8 mmol of hydroxylamine hydrochloride, slowly add 5 mL of 30 wt% aqueous sodium hydroxide solution, and react at 25 °C for 5 h. After the reaction is completed, filter the reaction solution and wash the filter cake with water to obtain the compound shown by formula (C-a).

[0140] (4) Under an argon atmosphere, add 20 mmol of the compound shown by formula (C-a) to 100 mL of N,N-dimethylformamide, add 2 mmol of tetrakis(triphenylphosphine)palladium catalyst and 30 mmol of zinc cyanide, and react at 150 °C for 16 h. After the reaction is completed, cool to room temperature, filter the reaction solution, extract the filtrate with ethyl acetate, wash the organic phase with saturated brine, dry over anhydrous sodium sulfate, and rotary evaporate and separate by column chromatography (the eluent is 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).

[0141] (5) Under a nitrogen atmosphere, add 12.4 mmol of the compound shown by formula (D-a) to 124 mL of a water / ethanol (volume ratio of 1:3) mixed solvent, slowly add 74.4 mmol of sodium hydroxide, and react at 128 °C for 12 h. After the reaction is completed, cool to room temperature, extract the reaction solution with dichloromethane, wash the organic phase with saturated brine, dry over anhydrous sodium sulfate, and rotary evaporate to obtain the compound shown by formula (E-a).

[0142] (6) Under a nitrogen atmosphere, add 11.5 mmol of the compound shown by formula (E-a) to 60 mL of dichloromethane, slowly add 23 mmol of triethylamine, 17.25 mmol of EDCl, 17.25 mmol of HOBt, and then slowly add 12.65 mmol React at 25 °C for 12 h. After the reaction is completed, extract the reaction solution with dichloromethane, wash the organic phase with saturated brine, dry over anhydrous sodium sulfate, and rotary evaporate to obtain the compound shown by formula (F-a).

[0143] (7) Under a nitrogen atmosphere, 10 mmol of the compound represented by formula (F-a) was added to 20 mL of dichloromethane, and 8 mL of a 50 wt% hydrochloric acid aqueous solution was slowly added at -5°C, and the reaction was carried out at 25°C for 12 h. After the reaction was completed, the reaction solution was extracted with dichloromethane, 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).

[0144] (8) Under a nitrogen atmosphere, 1.3 mmol of the compound represented by formula (G-a) was added to 7.5 mL of dichloromethane, and 3 mmol of triethylamine, 0.13 mmol of DMAP and 1.2 mmol were slowly added, and the reaction was carried out at 25°C for 12 h. After the reaction was completed, the reaction solution was extracted with dichloromethane, the organic phase was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated in vacuo. The compound represented by formula (1-a) was separated by column chromatography (the eluent was a mixed solvent of petroleum ether / ethyl acetate with a volume ratio of 3:1).

[0145] In Examples 1-33, the structures of the prepared sulfonamide-containing isoxazoline derivatives and the yield of step (8) are shown in Table 1.

[0146] Table 1

[0147]

[0148]

[0149]

[0150]

[0151] Test Example

[0152] The bioactivities of the sulfonamide-containing isoxazoline derivatives prepared in Examples 1-33, as well as lotilaner, S-lotilaner and R-lotilaner against Plutella xylostella were tested.

[0153] The test agents were accurately weighed with an electronic analytical balance. The original drug was completely dissolved in acetone and a mother liquor with a certain concentration was prepared by adding a 0.1 wt% [Tween-80] aqueous solution, and then the series of liquid medicines were diluted to the set concentrations with a 0.1 wt% [Tween-80] aqueous solution respectively.

[0154] Spray method: Remove the surface wax layer from the cabbage leaves cultured 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 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 up a water treatment as a 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%, and check the number of dead and alive insects after 72 hours to calculate the mortality rate. The calculation formula is: Mortality rate (%) = (Number of insects killed by the drug / Total number of insects treated with the drug) × 100; Corrected mortality rate (%) = [(Mortality rate of the drug treatment - Mortality rate of the blank treatment) / (1 - Mortality rate of the blank treatment)] × 100.

[0155] The insecticidal activities of the target compounds against Plutella xylostella are shown in Table 2.

[0156] Table 2

[0157]

[0158] As can be seen from Table 2, at higher concentrations, most of the compounds prepared in Examples 1 - 33 have good insecticidal activities against Plutella xylostella. Among them, the insecticidal activities of some compounds can be as high as 100%. In addition, as can also be seen from Table 2, the insecticidal activities of the S - configuration compounds are better than those of the R - configuration compounds.

[0159] To intuitively illustrate the performance and characterization process of the sulfonamide - containing isoxazoline derivatives prepared by the method of the present invention, the present invention exemplarily provides the identification results of the sulfonamide - containing isoxazoline derivatives prepared in Examples 1 - 33, including 1H NMR, 13C NMR, 19F NMR, high - resolution data, ee value, as well as appearance and melting point, as shown in Table 3 specifically.

[0160] Table 3

[0161]

[0162]

[0163]

[0164]

[0165]

[0166]

[0167]

[0168]

[0169] The preferred embodiments of the present invention have been 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 solutions 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. A sulfonamide-containing isoxazoline derivative, characterized in that: The sulfonamide-containing isoxazoline derivative 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, wherein each R 6 Each R is independently selected from one or more C1-C6 alkylene groups, each R 7 are each independently 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, C3-C 12 Cycloalkyl, C1-C 12 One or more of perfluoroalkyl, halogen and cyano.

2. The sulfonamide-containing isoxazoline derivative 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 is 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, wherein each R 6 Each R is independently selected from one or more C1-C3 alkylene groups, each R 7 are each independently 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 C3-C6 cycloalkyl group, a C1-C6 perfluoroalkyl group, a halogen group and a cyano 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, wherein each R 6 Each R is independently selected from one or more of methylene, ethylene, n-propylene and isopropylene, and each R 7 are each independently 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, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, trifluoromethyl, F, Cl, Br and cyano; More preferably, R 5 Selected from the following groups:

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

4. The method for preparing the sulfonamide-containing isoxazoline derivatives according to any one of claims 1 to 3, characterized in that: The method comprises: reacting a compound represented by formula (G) with Performing a first contact reaction to obtain a compound represented by formula (1); Formula (G) 5. The method according to claim 4, wherein: Relative to 1 mmol of the compound represented by formula (G), or The dosage is 0.5-3mmol, preferably 0.8-1.5mmol; Preferably, the first contact 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, N,N-diisopropylethylamine, pyridine, piperidine, 3-methylpyridine, sodium hydroxide and potassium hydroxide, preferably triethylamine and / or N,N-diisopropylethylamine; more preferably, the amount of the first alkaline agent is 0.8-5 mmol, preferably 1.5-3 mmol, relative to 1 mmol of the compound represented by formula (G); Preferably, the first contact reaction is carried out in the presence of a basic catalyst; more preferably, the basic catalyst is selected from one or more of DMAP, EDCl, DIC, HATU and DIEA, more preferably DMAP and / or EDCl; more preferably, the amount of the basic catalyst is 0.05-1 mmol, preferably 0.08-0.5 mmol, relative to 1 mmol of the compound represented by formula (G); Preferably, the solvent for the first contact reaction is selected from one or more of dichloromethane, chloroform, ethyl acetate and toluene, preferably one or more of dichloromethane, chloroform and ethyl acetate; Preferably, the amount of the solvent used in the first contact reaction is 1-15 mL, preferably 3-10 mL, relative to 1 mmol of the compound represented by formula (G); Preferably, the conditions of the first contact reaction include: temperature of 10-40°C, and time of 4-24h; more preferably, the conditions of the first contact reaction include: temperature of 20-30°C, and time of 8-16h.

6. The method according to claim 4 or 5, wherein: The preparation method of the compound represented by formula (G) comprises: subjecting the compound represented by formula (F) to a first hydrolysis reaction to obtain the compound represented by formula (G); Formula (F) 7. The method according to claim 6, wherein: The first hydrolysis reaction is carried out in the presence of an acidic agent; more preferably, the acidic agent is selected from one or more of hydrochloric acid, trifluoroacetic acid and sulfuric acid, preferably hydrochloric acid and / or trifluoroacetic acid; more preferably, the acidic agent is provided in the form of a solution, and the concentration of the solution of the acidic agent is 30-98wt%, preferably 50-95wt%; more preferably, the amount of the solution of the acidic agent is 0.1-2mL, preferably 0.5-1.5mL, relative to 1mmol of the compound represented by formula (F); Preferably, the solvent of the first hydrolysis reaction is selected from one or more of dichloromethane, chloroform, 1,2-dichloroethane, toluene, xylene and 1,4-dioxane, preferably dichloromethane and / or chloroform; Preferably, the amount of the solvent used in the first hydrolysis 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 hydrolysis reaction include: temperature of 10-40°C, time of 4-24h; more preferably, the conditions of the first hydrolysis reaction include: temperature of 20-30°C, time of 8-16h.

8. The method according to claim 6 or 7, wherein: The preparation method of the compound represented by formula (F) comprises: reacting the compound represented by formula (E) with NH2-R 6 -NH-Boc undergoes condensation reaction to obtain a compound represented by formula (F); Formula (E) 9. The method according to claim 8, wherein: Relative to 1 mmol of the compound represented by formula (E), NH2-R 6 -NH-Boc is used in an amount of 0.5-2 mmol, preferably 0.8-1.5 mmol; Preferably, the condensation reaction is carried out in the presence of a second alkaline agent; more preferably, the second 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, sodium hydroxide and potassium hydroxide; more preferably, the amount of the second alkaline agent is 0.5-5 mmol, preferably 1-3 mmol, relative to 1 mmol of the compound represented by formula (E); Preferably, the condensation reaction is carried out in the presence of a condensation agent; more preferably, the condensation agent is selected from one or more of EDCl, HOBt, DCC, DMAP, DIC and HATU, preferably EDCl and / or HOBt; more preferably, the amount of the condensation agent is 1-5 mmol, preferably 2-4 mmol, relative to 1 mmol of the compound represented by formula (E); 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 (E), the amount of the solvent used in the condensation reaction is 1-20 mL, preferably 5-10 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.

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

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