Isoxazoline compound and application thereof

Abstract

The invention discloses an isoxazoline compound as shown in a formula (I) and application thereof. R1, R2 and R3 can be selected from halogen atoms, cyano groups, nitryl groups, C1-C3 halogenated alkyl groups and the like; q can be independently selected from A1 to A6; l1 and L2 may be selected from a carboxyl group, a C1-C6 alkoxycarbonyl group, a hydroxyl-substituted C1-C8 alkyl group, and the like; z1, Z2 may be selected from a hydrogen atom, a C1-C6 alkyl group, a C3-C5 cycloalkyl group, or C (O) M, wherein M is a C1-C6 alkyl group, a C2-C6 alkenyl group, or the like; the isoxazoline compound provided by the invention has no cross resistance with existing insecticides, has the advantages of quick pesticide effect, low dosage and the like, and particularly has an excellent control effect on rice-resistant chilo suppressalis, plutella xylostella, aphid and the like. The invention also provides an isoxazoline compound as a pesticide acceptable salt, a composition and an application of the isoxazoline compound. # imgabs0 #

Description

Technical Field

[0001] The present invention relates to the technical field of pesticides, and in particular to an isoxazoline compound and application thereof. Background Art

[0002] In the process of agricultural and forestry production, insect pests have caused great losses to economic property, and pesticides are widely used in agricultural production and agricultural planting. In recent years, with the large-scale and long-term use of pesticides, pests have developed resistance to a large number of existing pesticides, and the dosage must be increased to achieve the original effect, causing certain problems for agricultural production, environment, and ecology. For example, in the process of rice planting, chlorantraniliprole is an efficient pesticide for preventing and controlling rice stem borers, but after years of continuous use, serious resistance problems have also appeared in most parts of the world, greatly threatening global rice production. In addition, some pesticides are highly toxic, or some destroy the ecosystem through their long-term residual properties. Therefore, there is an urgent need to continue to develop new pesticides with high activity, low toxicity and environmental friendliness. Summary of the invention

[0003] The main purpose of the present invention is to provide an isoxazoline compound and application thereof, aiming to solve the serious resistance problem of current pesticides.

[0004] To achieve the above object, the present invention provides an isoxazoline compound, wherein the isoxazoline compound is a compound having the following structural formula (I) or its tautomer, metabolic isomer, pharmaceutically acceptable salt or prodrug:

[0005]

[0006] Q is selected from any one of the structures of formula A1 to A6;

[0007]

[0008]

[0009] Wherein, Q is A1, L1 is selected from -C(O)OR4, -C(O)SR4 or -C(O)NHR5, wherein R4 is hydrogen, a monovalent metal ion, an ammonium ion, a substituted or unsubstituted C1-C6 alkyl group, a substituted or unsubstituted C2-C6 alkenyl group, a substituted or unsubstituted C2-C6 alkynyl group, a substituted or unsubstituted C3-C5 cycloalkyl group, a substituted or unsubstituted C3-C5 cycloalkyl group, a substituted or unsubstituted C1-C3 alkyl group, a substituted or unsubstituted hydroxyl group, a substituted or unsubstituted C1-C4 alkyl group, a substituted or unsubstituted C1- C2 alkoxy C1-C4 alkyl, R5 is substituted or unsubstituted C1-C2 alkoxy C1-C4 alkyl, C1-C3 alkoxycarbonyl C1-C3 alkyl, wherein the substituent is one or more halogen atoms, nitro, nitroso, cyano, amino, hydroxyl, wherein R1, R2, R3 can be independently selected from halogen atoms, cyano, nitro, C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, C1-C3 alkylthio or C1-C3 haloalkylthio;

[0010] In addition, L1 is selected from one or more hydroxy-substituted C1-C8 alkyl groups, one or more hydroxy-substituted C2-C8 alkenyl groups, one or more hydroxy-substituted C2-C8 alkynyl groups, wherein R1, R2, and R3 can be independently selected from a hydrogen atom, a halogen atom, a cyano group, a nitro group, a C1-C3 alkyl group, a C1-C3 haloalkyl group, a C1-C3 alkoxy group, a C1-C3 haloalkoxy group, a C1-C3 alkylthio group, or a C1-C3 haloalkylthio group;

[0011] Z1 represents a hydrogen atom, an oxygen atom, a halogen atom, a hydroxyl group, a nitro group, a nitroso group, a cyano group, an amino group, a substituted or unsubstituted C1-C6 alkyl group, a substituted or unsubstituted C2-C6 alkenyl group, a substituted or unsubstituted C2-C6 alkynyl group, a substituted or unsubstituted C3-C5 cycloalkyl group, a substituted or unsubstituted C1-C3 alkyl group, a substituted or unsubstituted C1-C5 cycloalkyl group, a substituted or unsubstituted C1-C6 alkoxy group, a substituted or unsubstituted C1-C6 alkylthio group, or -C(O)M , wherein M represents a substituted or unsubstituted C1-C6 alkyl, a substituted or unsubstituted C2-C6 alkenyl, a substituted or unsubstituted C2-C6 alkynyl, a substituted or unsubstituted C3-C5 cycloalkyl, a substituted or unsubstituted C1-C3 alkyl C3-C5 cycloalkyl, a substituted or unsubstituted C1-C6 alkoxy C1-C6 alkyl, a substituted or unsubstituted C1-C6 alkylthio C1-C6 alkyl, wherein the substituent may be one or more halogen atoms, hydroxyl, nitro, nitroso, cyano, amino;

[0012] Q is the structure represented by any one of A2 to A6, R1, R2, and R3 can be independently selected from a hydrogen atom, a halogen atom, a cyano group, a nitro group, a C1-C3 alkyl group, a C1-C3 haloalkyl group, a C1-C3 alkoxy group, a C1-C3 haloalkoxy group, a C1-C3 alkylthio group, or a C1-C3 haloalkylthio group; L2 is selected from -C(O)OR6, -C(O)SR6, or -C(O)NHR7, wherein R6 is hydrogen, a monovalent metal ion, an ammonium ion, a substituted or unsubstituted C1-C6 alkyl group, a substituted or unsubstituted Substituted C2-C6 alkenyl, substituted or unsubstituted C2-C6 alkynyl, substituted or unsubstituted C3-C5 cycloalkyl, substituted or unsubstituted cyclopropyl C1-C3 alkyl, R7 is hydrogen, substituted C1-C6 alkyl, substituted or unsubstituted C2-C6 alkenyl, substituted or unsubstituted C2-C6 alkynyl, substituted or unsubstituted C3-C5 cycloalkyl, substituted or unsubstituted C1-C6 alkoxy, wherein the substituent may be one or more halogen atoms, nitro, nitroso, cyano, amino, C1-C3 alkoxy;

[0013] In addition, L2 can be selected from one or more hydroxy-substituted C1-C8 alkyl groups, one or more hydroxy-substituted C2-C8 alkenyl groups, and one or more hydroxy-substituted C2-C8 alkynyl groups;

[0014] Z2 represents a hydrogen atom, an oxygen atom, a halogen atom, a hydroxyl group, a nitro group, a nitroso group, a cyano group, an amino group, a substituted or unsubstituted C1-C6 alkyl group, a substituted or unsubstituted C2-C6 alkenyl group, a substituted or unsubstituted C2-C6 alkynyl group, a substituted or unsubstituted C3-C5 cycloalkyl group, a substituted or unsubstituted C1-C3 alkyl group, a substituted or unsubstituted C1-C5 cycloalkyl group, a substituted or unsubstituted C1-C6 alkoxy group, a substituted or unsubstituted C1-C6 alkylthio group, or -C(O) M, wherein M represents a substituted or unsubstituted C1-C6 alkyl, a substituted or unsubstituted C2-C6 alkenyl, a substituted or unsubstituted C2-C6 alkynyl, a substituted or unsubstituted C3-C5 cycloalkyl, a substituted or unsubstituted C1-C3 alkyl C3-C5 cycloalkyl, a substituted or unsubstituted C1-C6 alkoxy C1-C6 alkyl, a substituted or unsubstituted C1-C6 alkylthio C1-C6 alkyl, wherein the substituent may be one or more halogen atoms, nitro, nitroso, cyano, amino;

[0015] W means O or S;

[0016] X represents O or CH2.

[0017] In one embodiment, the isoxazoline compound comprises a structure shown in formula A1, wherein L1 in the isoxazoline compound is selected from -C(O)OR4, -C(O)SR4 or -C(O)NHR5, wherein R4 is hydrogen, substituted or unsubstituted C1-C3 alkyl, substituted or unsubstituted C2-C4 alkenyl, substituted or unsubstituted C2-C4 alkynyl, substituted or unsubstituted C3-C4 cycloalkyl, substituted or unsubstituted C3-C4 cycloalkyl C1-C2 alkyl, substituted or unsubstituted hydroxyl C1-C3 alkyl, substituted or unsubstituted C1-C2 alkoxy C1-C3 alkyl; R5 is substituted or unsubstituted C1-C2 alkoxy C1-C2 alkyl, C1-C3 alkoxycarbonyl C1-C2 alkyl, wherein the substituent is one or more halogen atoms, nitro, nitroso, cyano, amino, hydroxyl, wherein R1, R2, R3 can be independently selected from halogen atoms, cyano, nitro, C1-C3 alkyl, C1-C3 haloalkyl; in addition, L1 can be selected from one or more hydroxyl-substituted C1-C5 alkyl , wherein R1, R2, and R3 can be independently selected from halogen atoms, cyano groups, nitro groups, C1-C3 alkyl groups, and C1-C3 haloalkyl groups; Z1 represents a hydrogen atom, a substituted or unsubstituted C1-C3 alkyl group, a substituted or unsubstituted C2-C4 alkenyl group, a substituted or unsubstituted C2-C4 alkynyl group, a substituted or unsubstituted cyclopropyl group, a substituted or unsubstituted C1-C3 alkylcyclopropyl group, a substituted or unsubstituted C1-C3 alkoxy group, a substituted or unsubstituted C1-C3 alkylthio group, a substituted or unsubstituted C1-C3 Alkyl, or C(O)M, wherein M represents substituted or unsubstituted C1-C3 alkyl, substituted or unsubstituted C2-C4 alkenyl, substituted or unsubstituted C2-C4 alkynyl, substituted or unsubstituted cyclopropyl, substituted or unsubstituted C1-C3 alkylcyclopropyl, substituted or unsubstituted C1-C3 alkoxy C1-C3 alkyl, substituted or unsubstituted C1-C3 alkylthio C1-C3 alkyl, wherein the substituent may be one or more halogen atoms, hydroxyl, nitro, nitroso, cyano, amino;

[0018] W represents O or S; and / or,

[0019] The isoxazoline compound comprises a structure shown in formula A1, wherein L1 in the isoxazoline compound is selected from -C(O)OR4, -C(O)SR4 or -C(O)NHR5, wherein R4 is hydrogen, substituted or unsubstituted C1-C3 alkyl, substituted or unsubstituted C2-C4 alkenyl, substituted or unsubstituted C2-C4 alkynyl, substituted or unsubstituted cyclopropyl, substituted or unsubstituted cyclopropylmethyl, substituted or unsubstituted hydroxyl C1-C3 alkyl, substituted or unsubstituted C1-C2 alkoxy C1-C3 alkyl; R5 is substituted or unsubstituted C1-C2 alkoxy C1-C2 alkyl, C1-C2 alkoxycarbonyl C1-C2 alkyl, wherein the substituent is one or more halogen atoms, nitro, nitroso, cyano, amino, hydroxyl, wherein R1, R2, and R3 can be independently selected from halogen atoms, cyano, nitro, C1-C3 alkyl, C1-C2 alkoxycarbonyl C1-C2 alkyl, -C3 haloalkyl; L1 can also be selected from one or more hydroxy-substituted C1-C3 alkyl groups, wherein R1, R2, R3 can be independently selected from hydrogen atoms, halogen atoms, cyano groups, nitro groups, C1-C3 alkyl groups, C1-C3 haloalkyl groups; Z1 represents a hydrogen atom, a substituted or unsubstituted C1-C3 alkyl group, a substituted or unsubstituted C2-C4 alkenyl group, a substituted or unsubstituted C2-C4 alkynyl group, a substituted or unsubstituted cyclopropyl group, a substituted or unsubstituted C1-C2 alkoxy C1-C2 alkyl group, or C(O)M, wherein M represents a substituted or unsubstituted C1-C3 alkyl group, a substituted or unsubstituted C2-C3 alkenyl group, a substituted or unsubstituted C2-C3 alkynyl group, a substituted or unsubstituted cyclopropyl group, a substituted or unsubstituted C1-C2 alkoxy C1-C2 alkyl group, wherein the substituents can be one or more halogen atoms, nitro groups, nitroso groups, cyano groups;

[0020] W represents O or S; and / or,

[0021] The isoxazoline compound comprises a structure shown in formula A1, wherein L1 in the isoxazoline compound is selected from -C(O)OR4, -C(O)SR4 or -C(O)NHR5, wherein R4 is hydrogen, sodium ion, potassium ion, ammonium ion, substituted or unsubstituted methyl, ethyl, n-propyl, isopropyl, vinyl, propenyl, allyl, ethynyl, propynyl, cyclopropyl, cyclopropylmethyl, hydroxyethyl, methoxyethyl, ethoxyethyl; R5 is methoxyethyl, ethoxyethyl, methoxycarbonylmethyl, ethoxycarbonylmethyl, wherein the substituent is one or more halogen atoms, nitro, nitro, cyano, amino, hydroxyl, wherein R1, R2, and R3 can be independently selected from halogen atoms, cyano, nitro, methyl, trifluoromethyl, methoxy, and trifluoromethoxy; L1 can also be selected from -C H2OH, -CH2CH2OH, wherein R1, R2, R3 can be independently selected from hydrogen atom, halogen atom, cyano, nitro, methyl, trifluoromethyl, methoxy, trifluoromethoxy; Z1 represents hydrogen atom, methyl, ethyl, substituted or unsubstituted C2-C3 alkenyl, substituted or unsubstituted C2-C3 alkynyl, substituted or unsubstituted cyclopropyl, substituted or unsubstituted C1-C2 alkoxy C1-C2 alkyl, or C(O)M, wherein M represents substituted or unsubstituted C1-C3 alkyl, substituted or unsubstituted C2-C3 alkenyl, substituted or unsubstituted C2-C3 alkynyl, substituted or unsubstituted cyclopropyl, substituted or unsubstituted C1-C2 alkoxy C1-C2 alkyl, wherein the substituent can be one or more halogen atoms, nitro, nitroso, cyano.

[0022] In one embodiment, the isoxazoline compound comprises a structure represented by any one of formulas A2 to A6, wherein:

[0023] R1, R2, and R3 in the isoxazoline compound can be independently selected from a hydrogen atom, a halogen atom, a cyano group, a nitro group, a C1-C3 alkyl group, a C1-C3 haloalkyl group, a C1-C3 alkoxy group, and a C1-C3 haloalkoxy group;

[0024] L2 is selected from -C(O)OR6, -C(O)SR6 or -C(O)NHR7, wherein R6 is hydrogen, sodium ion, potassium ion, ammonium ion, substituted or unsubstituted C1-C3 alkyl, substituted or unsubstituted C2-C4 alkenyl, substituted or unsubstituted C2-C4 alkynyl, substituted or unsubstituted C3-C4 cycloalkyl, substituted or unsubstituted cyclopropyl C1-C3 alkyl; wherein R7 is hydrogen, substituted C1-C3 alkyl, substituted or unsubstituted C2-C4 alkenyl, substituted or unsubstituted C2-C4 alkynyl, substituted or unsubstituted C3-C4 cycloalkyl, substituted or unsubstituted C1-C3 alkoxy, wherein the substituent is one or more halogen atoms, nitro, nitroso, cyano, amino, C1-C3 alkoxy; L2 can also be selected from one or more hydroxy-substituted C1-C5 alkyl;

[0025] Z2 represents a hydrogen atom, a substituted or unsubstituted C1-C3 alkyl group, a substituted or unsubstituted C2-C4 alkenyl group, a substituted or unsubstituted C2-C4 alkynyl group, a substituted or unsubstituted cyclopropyl group, a substituted or unsubstituted C1-C3 alkylcyclopropyl group, a substituted or unsubstituted C1-C3 alkoxy C1-C3 alkyl group, a substituted or unsubstituted C1-C3 alkylthio C1-C3 alkyl group, or C(O)M, wherein M represents a substituted or unsubstituted C1-C3 alkyl group, a substituted or unsubstituted C2-C4 alkenyl group, a substituted or unsubstituted C2-C4 alkynyl group, a substituted or unsubstituted cyclopropyl group, a substituted or unsubstituted C1-C3 alkylcyclopropyl group, a substituted or unsubstituted C1-C3 alkoxy C1-C3 alkyl group, a substituted or unsubstituted C1-C3 alkylthio C1-C3 alkyl group, wherein the substituent may be one or more halogen atoms, hydroxyl groups, nitro groups, nitroso groups, cyano groups, or amino groups;

[0026] W means O or S;

[0027] X represents O or CH2; and / or,

[0028] R1, R2, and R3 in the isoxazoline compound can be independently selected from a hydrogen atom, a halogen atom, a cyano group, a nitro group, a C1-C3 alkyl group, a C1-C3 haloalkyl group, a C1-C3 alkoxy group, and a C1-C3 haloalkoxy group;

[0029] L2 is selected from -C(O)OR6, -C(O)SR6 or -C(O)NHR7, wherein R6 is hydrogen, substituted or unsubstituted C1-C3 alkyl, substituted or unsubstituted C2-C4 alkenyl, substituted or unsubstituted C2-C4 alkynyl, substituted or unsubstituted cyclopropyl, substituted or unsubstituted cyclopropylmethyl; wherein R7 is hydrogen, substituted C1-C3 alkyl, substituted or unsubstituted C2-C4 alkenyl, substituted or unsubstituted C2-C4 alkynyl, substituted or unsubstituted cyclopropyl, C1-C3 alkoxy, wherein the substituent is one or more halogen atoms, nitro, nitroso, cyano, methoxy, ethoxy; L2 can also be selected from one or more hydroxy-substituted C1-C5 alkyl;

[0030] Z2 represents a hydrogen atom, a substituted or unsubstituted C1-C3 alkyl group, a substituted or unsubstituted C2-C4 alkenyl group, a substituted or unsubstituted C2-C4 alkynyl group, a substituted or unsubstituted cyclopropyl group, a substituted or unsubstituted C1-C2 alkoxy C1-C2 alkyl group, or C(O)M, wherein M represents a substituted or unsubstituted C1-C3 alkyl group, a substituted or unsubstituted C2-C4 alkenyl group, a substituted or unsubstituted C2-C4 alkynyl group, a substituted or unsubstituted cyclopropyl group, a substituted or unsubstituted C1-C3 alkylcyclopropyl group, a substituted or unsubstituted C1-C2 alkoxy C1-C2 alkyl group, wherein the substituent may be one or more halogen atoms, hydroxyl groups, nitro groups, nitroso groups, cyano groups, or amino groups;

[0031] W means O or S;

[0032] X represents O or CH2; and / or,

[0033] The isoxazoline compound comprises a structure represented by any one of formulas A2 to A6, and R1, R2, and R3 in the isoxazoline compound can be independently selected from hydrogen atoms, halogen atoms, cyano groups, nitro groups, methyl groups, trifluoromethyl groups, methoxy groups, and trifluoromethoxy groups;

[0034] L2 is selected from -C(O)OR6, -C(O)SR6 or -C(O)NHR7, wherein R6 is hydrogen, substituted or unsubstituted methyl, ethyl, vinyl, propenyl, allyl, ethynyl, propynyl, cyclopropyl; wherein R7 is hydrogen, halomethyl, haloethyl, halopropyl, vinyl, propenyl, allyl, ethynyl, propynyl, cyclopropyl, methoxy, ethoxy, n-propoxy, isopropoxy, wherein the substituent is one or more halogen atoms, nitro, nitroso, cyano, amino, methoxy, ethoxy; L2 can also be selected from one or more hydroxy-substituted C1-C3 alkyl groups;

[0035] Z2 represents a hydrogen atom, a methyl group, an ethyl group, a substituted or unsubstituted C2-C3 alkenyl group, a substituted or unsubstituted C2-C3 alkynyl group, a substituted or unsubstituted cyclopropyl group, a substituted or unsubstituted C1-C2 alkoxy C1-C2 alkyl group, or C(O)M, wherein M represents a substituted or unsubstituted C1-C3 alkyl group, a substituted or unsubstituted C2-C3 alkenyl group, a substituted or unsubstituted C2-C3 alkynyl group, a substituted or unsubstituted cyclopropyl group, a substituted or unsubstituted C1-C2 alkoxy C1-C2 alkyl group, wherein the substituent may be one or more halogen atoms, a nitro group, a nitroso group, or a cyano group;

[0036] W stands for O;

[0037] X represents CH2.

[0038] In one embodiment, the isoxazoline compound as described above, the isoxazoline compound also includes a structure as shown in Formula I' or its tautomers, and a pharmaceutically acceptable salt thereof, wherein the carbon at position 5 is a chiral carbon, and has an R configuration and an S configuration, and the stereochemical purity of the S configuration is 50% to 100%,

[0039]

[0040] The present invention also provides a use of the isoxazoline compound as described above in the preparation of insecticides.

[0041] The present invention also provides an insecticide for killing insects, the insecticide comprising an active component, the active component comprising the isoxazoline compound as described above and / or the tautomer, enantiomer, diastereomer or pesticide acceptable salt thereof of the isoxazoline compound.

[0042] In one embodiment, the mass of the active ingredient accounts for 0.1% to 99% of the mass of the pesticide.

[0043] In one embodiment, the pests include rice resistant Chilo suppressalis, diamondback moth, aphids or thrips.

[0044] In one embodiment, the pesticide further comprises a pharmaceutically acceptable carrier, excipient, adjuvant or any combination thereof.

[0045] The present invention also provides an insecticide composition, which comprises active components and other active compounds; the active components comprise the isoxazoline compounds as described in any one of the above items or the tautomers, enantiomers, diastereomers or pesticide-acceptable salts thereof of the isoxazoline compounds as described above; the other active compounds comprise one or more of insecticides, baits, disinfectants, miticides, nematicides, fungicides, growth regulators and herbicides; the mass percentage of the active components in the insecticide composition is 1%-99%.

[0046] The present application can improve the lipophilicity and transport properties of the isoxazoline compound by selecting suitable groups for each of Q, R1, R2 and R3, and the mutual coordination of suitable groups between L1, L2, Z1 and Z2, and increase the binding ability of the compound to the target receptor. When it is applied in the field of pesticides, it is easier to be absorbed by pests, thereby having better insecticidal activity. The isoxazoline compound provided by the present application has no cross-resistance with existing insecticides. Compared with existing insecticides on the market, the compound has the advantages of fast efficacy, low dosage, low toxicity and environmental friendliness to plant pests, especially has excellent insecticidal effect on rice-resistant Chilo suppressalis, diamondback moth, aphids, thrips, etc. DETAILED DESCRIPTION

[0047] In order to make the purpose, technical solution and advantages of the embodiments of the present invention clearer, the technical solution in the embodiments of the present invention will be described clearly and completely below. In addition, the meaning of "and / or" appearing in the full text includes three parallel solutions. Taking "A and / or B" as an example, it includes solution A, solution B, or solutions that satisfy both A and B. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without making creative work are within the scope of protection of the present invention.

[0048] Currently, the Chilo suppressalis has also developed serious resistance problems in most parts of the world, posing a great threat to global rice production. In addition, some compounds damage the ecosystem through their long-term persistence.

[0049] In view of this, the present invention provides an isoxazoline compound and its application, wherein the isoxazoline compound is a compound represented by the following structural formula (I) or its tautomer, metabolic isomer, pharmaceutically acceptable salt or prodrug:

[0050]

[0051] Q is selected from any one of the structures of formula A1 to A6;

[0052]

[0053] Wherein, Q is A1, L1 is selected from -C(O)OR4, -C(O)SR4 or -C(O)NHR5, wherein R4 is hydrogen, a monovalent metal ion, an ammonium ion, a substituted or unsubstituted C1-C6 alkyl group, a substituted or unsubstituted C2-C6 alkenyl group, a substituted or unsubstituted C2-C6 alkynyl group, a substituted or unsubstituted C3-C5 cycloalkyl group, a substituted or unsubstituted C3-C5 cycloalkyl group, a substituted or unsubstituted C1-C3 alkyl group, a substituted or unsubstituted hydroxyl group, a substituted or unsubstituted C1-C4 alkyl group, a substituted or unsubstituted C1- C2 alkoxy C1-C4 alkyl, R5 is substituted or unsubstituted C1-C2 alkoxy C1-C4 alkyl, C1-C3 alkoxycarbonyl C1-C3 alkyl, wherein the substituent is one or more halogen atoms, nitro, nitroso, cyano, amino, hydroxyl, wherein R1, R2, R3 can be independently selected from halogen atoms, cyano, nitro, C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, C1-C3 alkylthio or C1-C3 haloalkylthio;

[0054] In addition, L1 is selected from one or more hydroxy-substituted C1-C8 alkyl groups, one or more hydroxy-substituted C2-C8 alkenyl groups, one or more hydroxy-substituted C2-C8 alkynyl groups, wherein R1, R2, and R3 can be independently selected from a hydrogen atom, a halogen atom, a cyano group, a nitro group, a C1-C3 alkyl group, a C1-C3 haloalkyl group, a C1-C3 alkoxy group, a C1-C3 haloalkoxy group, a C1-C3 alkylthio group, or a C1-C3 haloalkylthio group;

[0055] Z1 represents a hydrogen atom, an oxygen atom, a halogen atom, a hydroxyl group, a nitro group, a nitroso group, a cyano group, an amino group, a substituted or unsubstituted C1-C6 alkyl group, a substituted or unsubstituted C2-C6 alkenyl group, a substituted or unsubstituted C2-C6 alkynyl group, a substituted or unsubstituted C3-C5 cycloalkyl group, a substituted or unsubstituted C1-C3 alkyl group, a substituted or unsubstituted C1-C5 cycloalkyl group, a substituted or unsubstituted C1-C6 alkoxy group, a substituted or unsubstituted C1-C6 alkylthio group, or -C(O)M , wherein M represents a substituted or unsubstituted C1-C6 alkyl, a substituted or unsubstituted C2-C6 alkenyl, a substituted or unsubstituted C2-C6 alkynyl, a substituted or unsubstituted C3-C5 cycloalkyl, a substituted or unsubstituted C1-C3 alkyl C3-C5 cycloalkyl, a substituted or unsubstituted C1-C6 alkoxy C1-C6 alkyl, a substituted or unsubstituted C1-C6 alkylthio C1-C6 alkyl, wherein the substituent may be one or more halogen atoms, hydroxyl, nitro, nitroso, cyano, amino;

[0056] Q is the structure represented by any one of A2 to A6, R1, R2, and R3 can be independently selected from a hydrogen atom, a halogen atom, a cyano group, a nitro group, a C1-C3 alkyl group, a C1-C3 haloalkyl group, a C1-C3 alkoxy group, a C1-C3 haloalkoxy group, a C1-C3 alkylthio group, or a C1-C3 haloalkylthio group; L2 is selected from -C(O)OR6, -C(O)SR6, or -C(O)NHR7, wherein R6 is hydrogen, a monovalent metal ion, an ammonium ion, a substituted or unsubstituted C1-C6 alkyl group, a substituted or unsubstituted Substituted C2-C6 alkenyl, substituted or unsubstituted C2-C6 alkynyl, substituted or unsubstituted C3-C5 cycloalkyl, substituted or unsubstituted cyclopropyl C1-C3 alkyl, R7 is hydrogen, substituted C1-C6 alkyl, substituted or unsubstituted C2-C6 alkenyl, substituted or unsubstituted C2-C6 alkynyl, substituted or unsubstituted C3-C5 cycloalkyl, substituted or unsubstituted C1-C6 alkoxy, wherein the substituent may be one or more halogen atoms, nitro, nitroso, cyano, amino, C1-C3 alkoxy;

[0057] In addition, L2 can be selected from one or more hydroxy-substituted C1-C8 alkyl groups, one or more hydroxy-substituted C2-C8 alkenyl groups, and one or more hydroxy-substituted C2-C8 alkynyl groups;

[0058] Z2 represents a hydrogen atom, an oxygen atom, a halogen atom, a hydroxyl group, a nitro group, a nitroso group, a cyano group, an amino group, a substituted or unsubstituted C1-C6 alkyl group, a substituted or unsubstituted C2-C6 alkenyl group, a substituted or unsubstituted C2-C6 alkynyl group, a substituted or unsubstituted C3-C5 cycloalkyl group, a substituted or unsubstituted C1-C3 alkyl group, a substituted or unsubstituted C1-C5 cycloalkyl group, a substituted or unsubstituted C1-C6 alkoxy group, a substituted or unsubstituted C1-C6 alkylthio group, or -C(O) M, wherein M represents a substituted or unsubstituted C1-C6 alkyl, a substituted or unsubstituted C2-C6 alkenyl, a substituted or unsubstituted C2-C6 alkynyl, a substituted or unsubstituted C3-C5 cycloalkyl, a substituted or unsubstituted C1-C3 alkyl C3-C5 cycloalkyl, a substituted or unsubstituted C1-C6 alkoxy C1-C6 alkyl, a substituted or unsubstituted C1-C6 alkylthio C1-C6 alkyl, wherein the substituent may be one or more halogen atoms, nitro, nitroso, cyano, amino;

[0059] W means O or S;

[0060] X represents O or CH2.

[0061] The present application can enhance the lipophilicity of the isoxazoline compound and increase the binding ability of the compound to the receptor by selecting suitable groups for each of Q, R1, R2, and R3, and by the mutual coordination of suitable groups among L1, L2, Z1, and Z2. When the isoxazoline compound is applied in the field of pesticides, it is more easily absorbed by pests, thereby having better insecticidal activity. The isoxazoline compound provided by the present application has no cross-resistance with existing insecticides. Compared with existing insecticides on the market, the compound has the advantages of fast efficacy, low dosage, low toxicity and environmental friendliness to plant pests, and has excellent insecticidal effects on rice-resistant striped stem borer, diamondback moth, aphids, thrips, etc.

[0062] Furthermore, since compounds containing many fluorine atoms are usually highly toxic and generally not easily degraded in the environment, L1 and L2 are preferably selected from ester groups, hydroxyl-substituted alkyl groups and other fluorine-free groups to reduce the number of fluorine atoms in the compound, making the compound less toxic and more environmentally friendly.

[0063] Furthermore, when Q is A1, R1, R2, and R3 are selected from halogen atoms, cyano groups, nitro groups, and C1-C3 haloalkyl groups, especially when R2 is a fluorine atom, and L1 is an ester group or an alkyl group substituted with a hydroxyl group, the interaction sites between the drug and the receptor are increased, thereby increasing the insecticidal effect.

[0064] In some embodiments of the present invention, the isoxazoline compound includes not only the structure of formula (I), but also the structure shown in formula I' or its tautomers, and pharmaceutically acceptable salts, wherein the carbon at position 5 is a chiral carbon having an R configuration and an S configuration, and the chiral 5S configuration has a better effect.

[0065]

[0066] The stereochemical purity of the S configuration is 50% to 100%, preferably 60-100% (S), more preferably 70-100% (S), further preferably 90-100% (S), and further preferably 95-100% (S).

[0067] The present invention also provides an insecticide for killing insects, the insecticide comprising an active component, the active component comprising the isoxazoline compound as described above and / or the tautomer, enantiomer, diastereomer or pesticide acceptable salt thereof of the isoxazoline compound.

[0068] In one embodiment, the mass of the active ingredient accounts for 0.1% to 99% of the mass of the pesticide.

[0069] In the embodiments of the present application, the mass percentage of the active component in the insecticide composition is 1%-99%. In some specific embodiments of the present application, the mass percentage of the active component in the insecticide composition can be, for example, 1%, 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 99%. In some embodiments of the present application, the mass percentage of the active component in the insecticide composition is 20%-70%.

[0070] In the embodiment of the present application, the pests that the pesticide is used to control include Lepidoptera, Coleoptera or mites, but are not actually limited thereto, such as green bean weevils, corn weevils, red flour beetles, potato beetles, slender-breasted beetles, multi-colored scarab beetles, potato leaf beetles, leaf beetles, pine beetles, rice root weevils, brown powder borers; Lepidoptera pests, for example, gypsy moths, yellow-brown tent caterpillars, Pieris rapae Japanese subspecies, Spodoptera litura, cabbage armyworm, Chilo suppressalis, corn borers, dried fruit borers, apple moths, yellow cutworms, greater wax moths, diamondback moths, tobacco budworms , citrus leafminer; Hemiptera pests, for example, black-tailed leafhopper, brown planthopper, mealybug, arrow-pointed shield scale, peach aphid, apple aphid, cotton aphid, radish aphid, pear crown lace bug, green toon, greenhouse whitefly; Thysanoptera pests, for example, palm thrips, western flower thrips; Orthoptera pests, for example, African mole cricket, African migratory locust; Blattodea pests, for example, German cockroach, American cockroach, yellow-breasted termite, house termite; Diptera pests, for example, one or more of housefly, Aedes aegypti, gray ground fly, Culex pipiens pallens, Anopheles sinensis, Culex tritaeniorhynchus, and clover leafminer. In some embodiments of the present application, the pesticide may also refer to acaricide, and the pests used for prevention and control include but are not limited to spiders (Arachnid order), such as mites (Acarina order), for example, soft ticks, hard ticks and sarcoptes, such as the long star tick, tropical flower tick, Persian sharp-edged tick, cattle tick, microscopic cattle tick, ricinus tick, gallinae mite, sheep scabies, human scabies; mites, such as apple rust mite; tenuiphagous mite, such as polyphagous tarsonemus; tenuipalpidate mite, such as purple short-palped mite; spider mite, such as cinnabar leaf mite, etc.

[0071] In one embodiment, the dosage form of the pesticide includes tablets, capsules, granules or aqueous solutions.

[0072] The pesticide preparation includes, but is not limited to, the above-mentioned dosage forms, and may also be solutions, emulsions, wettable powders, granular wettable powders, suspensions, powders, foams, pastes, tablets, granules, aerosols, natural agents impregnated with active compounds, synthetic agents impregnated with active compounds, microcapsules, seed coatings, preparations equipped with combustion devices (the combustion devices may be chimneys and mist cylinders, tanks and coils, etc.), cold fog agents, hot fog agents, etc. These pesticide preparations or animal parasite control agents may be prepared by known methods, for example, by mixing the active ingredient with a filler (such as a liquid diluent or carrier, a liquefied gas diluent or carrier, a solid diluent or carrier), and optionally with a surfactant (i.e., an emulsifier and / or a dispersant and / or a foaming agent) and the like.

[0073] In one embodiment, the insecticide further includes a pharmaceutically acceptable carrier, excipient, adjuvant or any combination thereof, and the insecticide can be replaced according to the usage scenario to achieve the best killing effect.

[0074] The embodiment of the present application also provides an insecticide composition, which includes active components and other active compounds; the active components include the isoxazoline compounds provided in the previous text of the present application and / or the tautomers, enantiomers, diastereomers or their pesticide-acceptable salts of the isoxazoline compounds provided in the previous text of the present application; the other active compounds include one or more of insecticides, baits, disinfectants, miticides, nematicides, fungicides, growth regulators and herbicides.

[0075] In the embodiments of the present application, the mass percentage of the active component in the insecticide composition is 1%-99%. In some specific embodiments of the present application, the mass percentage of the active component in the insecticide composition can be, for example, 1%, 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 99%. In some embodiments of the present application, the mass percentage of the active component in the insecticide composition is 20%-70%.

[0076] The embodiments of the present invention are further described in the following with multiple embodiments. Specifically, some of the isoxazoline compounds described in the present application are as shown in formula (I), Q is A1, A2, A3, and some of the isoxazoline compounds are shown in Table 1, but the isoxazoline compounds described in the present invention are not limited to all the compounds in Table 1:

[0077]

[0078] Where Q represents the following structure:

[0079]

[0080] W is an oxygen atom.

[0081] Table 1: Isoxazoline compounds having the chemical structure shown in formula (I)

[0082]

[0083]

[0084]

[0085]

[0086]

[0087]

[0088]

[0089]

[0090]

[0091]

[0092]

[0093]

[0094]

[0095]

[0096]

[0097]

[0098]

[0099]

[0100]

[0101] In the table: c-pr means cyclopropyl

[0102] Specifically, some of the isoxazoline compounds described in the present application are as shown in formula (I), Q is A4, A5, A6, and some of the isoxazoline compounds are shown in Table 2, but the isoxazoline compounds described in the present invention are not limited to all the compounds in Table 2.

[0103]

[0104] Where Q represents the following structure:

[0105]

[0106]

[0107] W is an oxygen atom.

[0108] Table 2: Isoxazoline compounds having the chemical structure shown in formula (I)

[0109]

[0110]

[0111]

[0112]

[0113]

[0114]

[0115]

[0116]

[0117]

[0118]

[0119]

[0120]

[0121]

[0122]

[0123]

[0124]

[0125]

[0126]

[0127]

[0128] In the table: c-pr means cyclopropyl

[0129] The technical solution of the present invention is further described in detail below in conjunction with specific embodiments. It should be understood that the following embodiments are only used to explain the present invention, and are not used to limit the present invention.

[0130] Example 1

[0131] The synthetic reaction equation of compound No. 1 in Table 1 is as follows:

[0132]

[0133] Preparation method: Add 4-(5-(3,5-dichloro-4-fluorophenyl)-5-trifluoromethyl-4,5-dihydroisoxazol-3-yl)-2-methylbenzoic acid (6.00g, 11.60mmol) and dichlorothionyl (10ml) to the reaction bottle, stir and react for 3-4h under reflux conditions, and concentrate under reduced pressure to obtain 4-(5-(3,5-dichloro-4-fluorophenyl)-5-trifluoromethyl-4,5-dihydroisoxazol-3-yl)-2-methylbenzoyl chloride. Dissolve the obtained acid chloride in ethyl acetate and add it to a saturated sodium carbonate solution of 1-aminocyclopropanecarboxylic acid methyl ester hydrochloride (2.64g, 17.40mmol), react at room temperature, and monitor the reaction progress with a plate. After the reaction is completed, take the organic phase, wash it with a saturated sodium chloride solution, dry it with anhydrous sodium sulfate, and spin dry it to obtain the product as a yellow solid (5.30g, yield 85.67%).

[0134] The H NMR spectrum (500 MHz, DMSO-d6) data of the compound are as follows (δ [ppm]): δ 8.98 (s, 1H), 7.81 (d, J = 6.2 Hz, 2H), 7.60 (d, J = 9.4 Hz, 2H), 7.41 (d, J = 7.8 Hz, 1H), 4.35 (q, J = 18.4 Hz, 2H), 3.65 (s, 3H), 2.40 (s, 3H), 1.45 (q, J = 4.6 Hz, 2H), 1.17 (dd, J = 7.7, 4.6 Hz, 2H).

[0135] ESI-MS (m / z): [MH-] Calculated value: 531.0507, found value: 531.0508.

[0136] Example 2

[0137] The synthetic reaction equation of compound No. 14 in Table 1 is as follows:

[0138] Synthesis of 1-(4-(5-(3,5-dichloro-4-fluorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methylbenzamido)cyclopropane-1-carboxylic acid

[0139]

[0140] Preparation method: 1-(4-(5-(3,5-dichloro-4-fluorophenyl)-5-trifluoromethyl-4,5-dihydroisoxazol-3-yl)-2-methylbenzamido)cyclopropane-1-carboxylic acid methyl ester (3.00 g, 5.63 mmol) was added to a mixture of 5% potassium hydroxide: methanol = 1:1 by volume, and hydrolyzed at 40°C-45°C for 3-4 hours. After the reaction was completed, dilute hydrochloric acid was added to acidify, and solids precipitated. The solids were filtered and washed with distilled water several times and then dried to obtain the product as a yellow solid (2.45 g, yield 83.80%).

[0141] The H NMR spectrum (500 MHz, DMSO-d6) data of the compound are as follows (δ [ppm]): δ 12.45 (s, 1H), 8.87 (s, 1H), 7.81 (d, J = 6.2 Hz, 2H), 7.59 (d, J = 7.1 Hz, 2H), 7.40 (d, J = 8.5 Hz, 1H), 4.41-4.28 (m, 2H), 2.39 (s, 3H), 1.40 (dd, J = 7.6, 4.4 Hz, 2H), 1.10 (q, J = 4.5 Hz, 2H).

[0142] ESI-MS (m / z): [MH-] Calculated value: 517.0350, found value: 517.0351.

[0143] Example 3

[0144] The synthetic reaction equation of compound No. 27 in Table 1 is as follows:

[0145] Synthesis of 1-(4-(5-(3,5-dichloro-4-fluorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methylbenzamido)cyclopropane-1-carboxylic acid ethyl ester

[0146]

[0147] Preparation method: Add 4-(5-(3,5-dichloro-4-fluorophenyl)-5-trifluoromethyl-4,5-dihydroisoxazol-3-yl)-2-methylbenzoic acid (1.00g, 2.29mmol) and dichlorothionyl (5ml) to the reaction bottle, stir and react for 3-4h under reflux conditions, and concentrate under reduced pressure to obtain 4-(5-(3,5-dichloro-4-fluorophenyl)-5-trifluoromethyl-4,5-dihydroisoxazol-3-yl)-2-methylbenzoyl chloride. Dissolve the obtained acid chloride in ethyl acetate and add it to a saturated sodium carbonate solution of 1-aminocyclopropanecarboxylic acid ethyl ester hydrochloride (0.36g, 2.75mmol), react at room temperature, and monitor the reaction progress with a plate. After the reaction is completed, take the organic phase, wash it with a saturated sodium chloride solution, dry it with anhydrous sodium sulfate, and spin dry it to obtain the product as a yellow solid (1.11g, yield 88.79%).

[0148] The H NMR spectrum (500 MHz, DMSO-d6) data of the compound are as follows (δ [ppm]): δ 8.97 (s, 1H), 7.81 (d, J = 6.1 Hz, 2H), 7.68 -7.53 (m, 2H), 7.40 (d, J = 7.8 Hz, 1H), 4.44 -4.26 (m, 2H), 4.10 (q, J = 7.1 Hz, 2H), 2.41 (s, 3H), 1.43 (q, J = 4.6 Hz, 2H), 1.19 (t, J = 7.1 Hz, 3H), 1.15 (q, J = 4.6 Hz, 2H).

[0149] ESI-MS (m / z): [MH-] Calculated value: 545.0658, found value: 545.0662.

[0150] Example 4

[0151] The synthetic reaction equation of compound No. 40 in Table 1 is as follows:

[0152] Synthesis of Cyclopropyl 1-(4-(5-(3,5-dichloro-4-fluorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methylbenzamido)cyclopropane-1-carboxylate

[0153]

[0154] Preparation method: Add 1-(4-(5-(3,5-dichloro-4-fluorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methylbenzamide)cyclopropane-1-carboxylic acid (1.00 g, 1.93 mmol) and dichlorothionyl (5 ml) to a reaction bottle, stir and react for 3-4 hours under reflux conditions, and concentrate under reduced pressure to obtain its acid chloride. Dissolve the acid chloride in dichloromethane and add it to cyclopropanol (0.17 g, 2.90 mmol), then add solid potassium carbonate and react at 40°C for 3-4 hours. After the reaction, filter out potassium carbonate, wash with dilute hydrochloric acid (2 mol / L) and saturated sodium chloride solution in turn, dry with anhydrous sodium sulfate, and spin dry to obtain a yellow solid (0.91 g, yield 84.30%).

[0155] The H NMR spectrum (500 MHz, DMSO-d6) data of the compound are as follows (δ [ppm]): δ 8.95 (s, 1H), 7.81 (d, J = 6.2 Hz, 2H), 7.59 (d, J = 9.0 Hz, 2H), 7.38 (d, J = 7.8 Hz, 1H), 4.40-4.28 (m, 2H), 4.12 (tt, J = 6.3, 3.0 Hz, 1H), 2.38 (s, 3H), 1.42 (q, J = 4.6 Hz, 2H), 1.15 (q, J = 4.6 Hz, 2H), 0.71 (q, J = 6.3 Hz, 2H), 0.63-0.57 (m, 2H).

[0156] ESI-MS (m / z): [MH-] Calculated value: 557.0663, found value: 557.0661.

[0157] Example 5

[0158] The synthetic reaction equation of compound No. 92 in Table 1 is as follows:

[0159] Synthesis of 4-(5-(3,5-dichloro-4-fluorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-N-(1-(hydroxymethyl)cyclopropyl)-2-methylbenzamide

[0160]

[0161] Preparation method: Add 4-(5-(3,5-dichloro-4-fluorophenyl)-5-trifluoromethyl-4,5-dihydroisoxazol-3-yl)-2-methylbenzoic acid (1.00 g, 2.29 mmol) to the reaction bottle, dissolve it with dichloromethane (5 mL), add EDCI (0.65 g, 3.44 mmol), activate it in an ice bath for 30 min, add 1-hydroxybenzotriazole (0.37 g, 3.44 mmol) and triethylamine (0.93 g, 9.17 mmol), and then add 1-aminocyclopropylmethanol (0.30 g, 3.44 mmol), and detect the reaction by spot plate. After the reaction is completed, spin dry and add dichloromethane, wash with dilute hydrochloric acid (2 mol / L), add solid potassium carbonate, stir at room temperature for several hours, filter out potassium carbonate, wash with saturated sodium chloride solution, dry with anhydrous sodium sulfate, and spin dry to obtain a yellow solid (0.81 g, yield 69.83%).

[0162] The H NMR spectrum (500 MHz, DMSO-d6) data of the compound are as follows (δ [ppm]): δ 8.56 (s, 1H), 7.81 (d, J = 6.2 Hz, 2H), 7.56 (d, J = 8.1 Hz, 2H), 7.39 (d, J = 7.8 Hz, 1H), 4.75 (t, J = 5.8 Hz, 1H), 4.41-4.26 (m, 2H), 3.55 (d, J = 5.7 Hz, 2H), 2.32 (d, J = 18.2 Hz, 3H), 0.79-0.72 (m, 2H), 0.72-0.65 (m, 2H).

[0163] ESI-MS (m / z): [MH-] Calculated value: 503.0552, found value: 503.0558.

[0164] Example 6

[0165] The synthetic reaction equation of compound No. 93 in Table 1 is as follows:

[0166] Synthesis of 4-(5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-N-(1-(hydroxymethyl)cyclopropyl)-2-methylbenzamide

[0167]

[0168] Preparation method: Add 4-(5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methylbenzoic acid (1.00 g, 2.39 mmol) to a reaction bottle, dissolve it with dichloromethane (5 mL), add EDCI (0.69 g, 3.59 mmol), activate it in an ice bath for 30 min, then add 1-hydroxybenzotriazole (0.48 g, 3.59 mmol) and triethylamine (0.96 g, 9.56 mmol), then add 1-aminocyclopropylmethanol (0.31 g, 3.59 mmol), and detect the reaction by spot plate until the reaction is completed. Detect the reaction by spot plate until the reaction is completed. After the reaction is completed, the mixture is spin-dried and dichloromethane is added. After washing with dilute hydrochloric acid (2 mol / L), solid potassium carbonate is added and stirred at room temperature for several hours. After filtering out the potassium carbonate, the mixture is washed with a saturated sodium chloride solution, dried over anhydrous sodium sulfate, and spin-dried to obtain a yellow solid (0.85 g, yield 72.96%).

[0169] The compound's hydrogen nuclear magnetic resonance spectrum (400MHz, Chloroform-d) δ7.53 (d, J = 1.8 Hz, 2H), 7.50 (d, J = 7.3 Hz, 2H), 7.45 (t, J = 1.9 Hz, 1H), 7.40 -7.35 (m, 1H), 6.43 (s, 1H), 4.09 (d, J = 17.2 Hz, 1H), 3.73 (d, J = 2.1 Hz, 3H), 2.47 (s, 3H), 1.05-0.99 (m, 2H), 1.00 -0.94 (m, 2H).

[0170] ESI-MS (m / z): [MH-] Calculated value: 485.0647, found value: 485.0652.

[0171] Example 7

[0172] The synthetic reaction equation of compound No. 189 in Table 1 is as follows:

[0173]

[0174] Preparation method: 1-(4-(5-(3,5-dichloro-4-fluorophenyl)-5-trifluoromethyl-4,5-dihydroisoxazol-3-yl)-2-methylbenzamido)cyclopropane-1-carboxylic acid methyl ester (1.00 g, 1.88 mmol) was dissolved in toluene, heated to 80°C-100°C, propionyl chloride (0.52 g, 5.64 mmol) was added, and the reaction was carried out at 100°C for 4-5 hours. After the reaction was completed, dichloromethane was added after drying, and the mixture was washed with dilute hydrochloric acid (2 mol / L), saturated sodium carbonate solution, and saturated sodium chloride solution in turn, dried over anhydrous sodium sulfate, and finally purified by silica gel column chromatography to obtain a white solid (0.54 g, yield 48.74%).

[0175] The H NMR spectrum (500 MHz, DMSO-d6) data of the compound are as follows (δ [ppm]): δ 7.81 (d, J = 6.2 Hz, 2H), 7.63 (s, 1H), 7.56 (d, J = 8.0 Hz, 1H), 7.36 (d, J = 8.0 Hz, 1H), 4.35 (q, J = 18.3 Hz, 2H), 3.69 (s, 3H), 2.72-2.62 (m, 1H), 2.50-2.40 (m, 1H), 2.33 (s, 3H), 1.85-1.70 (m, 3H), 1.24 (d, J = 11.1 Hz, 1H), 0.91 (t, J = 7.2 Hz, 3H).

[0176] ESI-MS (m / z): [MH-] Calculated value: 587.0769, found value: 587.0775.

[0177] Example 8

[0178] The synthetic reaction equation of compound No. 202 in Table 1 is as follows:

[0179]

[0180] Preparation method: 1-(4-(5-(3,5-dichloro-4-fluorophenyl)-5-trifluoromethyl-4,5-dihydroisoxazol-3-yl)-2-methylbenzamido)cyclopropane-1-carboxylic acid methyl ester (1.00 g, 1.88 mmol) was dissolved in toluene, the temperature was raised to 80°C-100°C, acryloyl chloride (0.51 g, 5.64 mmol) was added, and the reaction was carried out at 100°C for 4-5 hours. After the reaction was completed, dichloromethane was added after drying, and the mixture was washed with dilute hydrochloric acid (2 mol / L), saturated sodium carbonate solution, and saturated sodium chloride solution in turn, dried over anhydrous sodium sulfate, and finally purified by silica gel column chromatography to obtain a white solid (0.51 g, yield 46.19%).

[0181] The H NMR spectrum (500 MHz, DMSO-d6) data of the compound are as follows (δ [ppm]): δ 7.81 (d, J = 6.2 Hz, 2H), 7.63 (s, 1H), 7.58 (d, J = 8.0 Hz, 1H), 7.39 (d, J = 8.0 Hz, 1H), 6.52 (dd, J = 16.8, 10.4 Hz, 1H), 6.15 (dd, J = 16.8, 1.4 Hz, 1H), 5.76 (dd, J = 10.4, 1.4 Hz, 1H), 4.35 (q, J = 18.3 Hz, 2H), 3.69 (s, 3H), 2.34 (s, 3H), 1.87-1.74 (m, 2H), 1.58-1.35 (m, 2H).

[0182] ESI-MS (m / z): [MH-] Calculated value: 585.0612, found value: 585.0614.

[0183] Example 9

[0184] The synthetic reaction equation of compound No. 215 in Table 1 is as follows:

[0185]

[0186] Preparation method: 1-(4-(5-(3,5-dichloro-4-fluorophenyl)-5-trifluoromethyl-4,5-dihydroisoxazol-3-yl)-2-methylbenzamido)cyclopropane-1-carboxylic acid methyl ester (1.00 g, 1.88 mmol) was dissolved in toluene, the temperature was raised to 80°C-100°C, methoxyacetyl chloride (0.61 g, 5.64 mmol) was added, and the mixture was reacted at 100°C for 4-5 hours. After the reaction was completed, dichloromethane was added after drying, and the mixture was washed with dilute hydrochloric acid (2 mol / L), saturated sodium carbonate solution, and saturated sodium chloride solution in sequence, dried over anhydrous sodium sulfate, and finally purified by silica gel column chromatography to obtain a white solid (0.75 g, yield 65.90%).

[0187] The H NMR spectrum (400 MHz, DMSO-d6) data of the compound are as follows (δ [ppm]): δ 7.81 (d, J = 6.2 Hz, 2H), 7.67 (s, 1H), 7.58 (d, J = 8.0 Hz, 1H), 7.43 (d, J = 8.1 Hz, 1H), 4.36 (dd, J = 37.5, 18.4 Hz, 3H), 4.15 (t, J = 18.1 Hz, 1H), 3.69 (s, 3H), 3.21 (s, 3H), 2.36 (s, 3H), 1.67 (d, J = 39.6 Hz, 3H), 1.17 (s, 1H).

[0188] ESI-MS (m / z): [MH-] Calculated value: 603.0718, found value: 603.0714.

[0189] Example 10

[0190] The synthetic reaction equation of compound No. 228 in Table 1 is as follows:

[0191]

[0192] Preparation method: 1-(4-(5-(3,5-dichloro-4-fluorophenyl)-5-trifluoromethyl-4,5-dihydroisoxazol-3-yl)-2-methylbenzamido)cyclopropane-1-carboxylic acid methyl ester (1.00 g, 1.88 mmol) was dissolved in toluene, the temperature was raised to 80°C-100°C, cyclopropylcarbonyl chloride (0.59 g, 5.64 mmol) was added, and the reaction was carried out at 100°C for 4-5 hours. After the reaction was completed, dichloromethane was added after drying, and the mixture was washed with dilute hydrochloric acid (2 mol / L), saturated sodium carbonate solution, and saturated sodium chloride solution in sequence, dried over anhydrous sodium sulfate, and finally purified by silica gel column chromatography to obtain a white solid (0.57 g, yield 50.42%).

[0193] The H NMR spectrum (500 MHz, DMSO-d6) data of the compound are as follows (δ [ppm]): δ 7.81 (d, J = 6.2 Hz, 2H), 7.63-7.52 (m, 2H), 7.36 (d, J = 8.0 Hz, 1H), 4.34 (q, J = 18.3 Hz, 2H), 3.71 (s, 3H), 2.32 (s, 3H), 2.03-1.93 (m, 1H), 1.90-1.79 (m, 2H), 1.63 (s, 1H), 1.42 (s, 1H), 0.91-0.72 (m, 4H).

[0194] ESI-MS (m / z): [MH-] Calculated value: 599.0769, found value: 599.0766.

[0195] Embodiment 11

[0196] The synthetic reaction equation of compound No. 258 in Table 1 is as follows:

[0197]

[0198] Preparation method: Add 4-(5-(3-chloro-5-(trifluoromethyl)phenyl)-5-trifluoromethyl-4,5-dihydroisoxazol-3-yl)-1-naphthoic acid (6.00g, 12.30mmol) and dichlorothionyl (10ml) to a reaction bottle, stir and react for 3-4h under reflux conditions, and concentrate under reduced pressure to obtain 4-(5-(3-chloro-5-(trifluoromethyl)phenyl)-5-trifluoromethyl-4,5-dihydroisoxazol-3-yl)-1-naphthoyl chloride. Dissolve the obtained acid chloride in ethyl acetate and add it to a saturated sodium carbonate solution of 1-aminocyclopropanecarboxylic acid methyl ester hydrochloride (2.80g, 18.45mmol), react at room temperature, and monitor the reaction progress with a plate. After the reaction is completed, take the organic phase, wash it with a saturated sodium chloride solution, dry it with anhydrous sodium sulfate, and spin dry it to obtain the product as a yellow solid (6.46g, yield 89.79%).

[0199] The hydrogen nuclear magnetic resonance spectrum (500 MHz, DMSO-d6) data of the compound are as follows (δ [ppm]): δ 9.30 (s, 1H), 8.84-8.77 (m, 1H), 8.37-8.31 (m, 1H), 8.09 (d, J = 23.6 Hz, 2H), 7.98-7.88 (m, 2H), 7.77-7.68 (m, 2H), 7.63 (d, J = 7.5 Hz, 1H), 4.66-4.57 (m, 2H), 3.73 (s, 3H), 1.52 (dd, J = 7.7, 4.6 Hz, 2H), 1.27 (dd, J = 7.8, 4.6 Hz, 2H).

[0200] ESI-MS (m / z): [MH-] Calculated value: 583.0864, ​​found value: 583.0866.

[0201] Example 12

[0202] The synthetic reaction equation of compound No. 473 in Table 1 is as follows:

[0203] Synthesis of 1-(3-methyl-5-(5-(3,4,5-trichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)thiophene-2-carboxamido)cyclopropane-1-carboxylic acid methyl ester

[0204]

[0205] Preparation method: Add 3-methyl-5-(5-(3,4,5-trichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)thiophene-2-benzoic acid (1.00 g, 2.18 mmol) and dichlorothionyl (5 ml) to a reaction bottle, stir and react for 3-4 h under reflux conditions, and concentrate under reduced pressure to obtain 3-methyl-5-(5-(3,4,5-trichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)thiophene-2-benzoyl chloride. Dissolve the obtained acid chloride in ethyl acetate and add it to a saturated sodium carbonate solution of 1-aminocyclopropanecarboxylic acid methyl ester hydrochloride (0.39 g, 2.62 mmol), react at room temperature, and monitor the reaction progress by spot plate. After the reaction, the organic phase was washed with a saturated sodium chloride solution, dried over anhydrous sodium sulfate and then spin-dried to obtain the product as a yellow solid (1.03 g, yield 82.52%).

[0206] The hydrogen nuclear magnetic resonance spectrum (500 MHz, DMSO-d6) data of the compound are as follows (δ [ppm]): 1H NMR (500 MHz, DMSO-d6) 8.84 (s, 1H), 7.82 (s, 2H), 7.34 (s, 1H), 4.43-4.27 (m, 2H), 3.62 (s, 3H), 2.40 (s, 3H), 1.44 (q, J = 4.6 Hz, 2H), 1.18 (q, J = 4.7 Hz, 2H).

[0207] ESI-MS (m / z): [MH-] Calculated value: 552.9770, found value: 552.9782.

[0208] Example 13

[0209] The synthetic reaction equation of compound No. 489 in Table 1 is as follows:

[0210] Synthesis of 1-(3-methyl-5-(5-(3,4,5-trichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)thiophene-2-carboxamido)cyclopropane-1-carboxylic acid ethyl ester

[0211]

[0212] Preparation method: Add 3-methyl-5-(5-(3,4,5-trichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)thiophene-2-benzoic acid (1.00g, 2.18mmol) and dichlorothionyl (5ml) to the reaction bottle, stir and react for 3-4h under reflux conditions, and concentrate under reduced pressure to obtain 3-methyl-5-(5-(3,4,5-trichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)thiophene-2-benzoyl chloride. Dissolve the obtained acid chloride in ethyl acetate and add it to a saturated sodium carbonate solution of 1-aminocyclopropanecarboxylic acid ethyl ester (0.38g, 2.62mmol), react at room temperature, and monitor the reaction progress with a plate. After the reaction is completed, the organic phase is washed with a saturated sodium chloride solution, dried over anhydrous sodium sulfate, and then spin-dried to obtain the product as a yellow solid (1.08g, yield 81.30%).

[0213] The hydrogen nuclear magnetic resonance spectrum (500 MHz, DMSO-d6) data of the compound are as follows (δ [ppm]): 1H NMR (500 MHz, DMSO-d6) 8.85 (s, 1H), 7.82 (s, 2H), 7.34 (s, 1H), 4.42-4.29 (m, 2H), 4.07 (q, J = 7.1 Hz, 2H), 2.40 (s, 3H), 1.43 (q, J = 4.6 Hz, 2H), 1.22-1.08 (m, 5H).

[0214] ESI-MS (m / z): [MH-] Calculated value: 566.9927, found value: 566.9934.

[0215] Embodiment 14

[0216] The synthetic reaction equation of compound No. 516 in Table 1 is as follows:

[0217] Synthesis of N-(1-(Hydroxymethyl)cyclopropyl)-3-methyl-5-(5-(3,4,5-trichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)thiophene-2-carboxamide

[0218]

[0219] Preparation method: Add 3-methyl-5-(5-(3,4,5-trichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)thiophene-2-benzoic acid (1.00 g, 2.18 mmol) to a reaction bottle, dissolve it with dichloromethane (5 mL), add EDCI (0.63 g, 3.28 mmol), activate it in an ice bath for 30 min, then add 1-hydroxybenzotriazole (0.43 g, 3.28 mmol) and triethylamine (0.88 g, 8.73 mmol), then add 1-aminocyclopropylmethanol (0.29 g, 3.28 mmol), and detect by spot plate until the reaction is completed. After the reaction is completed, dichloromethane is added to the mixture, which is then washed with dilute hydrochloric acid (2 mol / L) and then solid potassium carbonate is added and stirred at room temperature for several hours. The potassium carbonate is filtered off and then washed with saturated sodium chloride solution, dried over anhydrous sodium sulfate, and dried to obtain a yellow solid (0.89 g, yield 77.39%).

[0220] The H NMR spectrum (500 MHz, DMSO-d6) data of the compound are as follows (δ [ppm]): δ 8.37 (s, 1H), 7.81 (s, 2H), 7.30 (s, 1H), 5.76 (s, 0H), 4.41-4.28 (m, 2H), 3.51 (s, 2H), 2.37 (s, 3H), 0.81-0.72 (m, 2H), 0.73-0.65 (m, 2H).

[0221] ESI-MS (m / z): [MH-] Calculated value: 524.9821, found value: 524.9828.

[0222] Embodiment 15

[0223] The synthetic reaction equation of compound No. 676 in Table 1 is as follows:

[0224]

[0225] Preparation method: Add 4-(5-(3,5-dichloro-4-fluorophenyl)-5-trifluoromethyl-4,5-dihydroisoxazol-3-yl)-2-methylbenzoic acid (6.00g, 11.60mmol) and dichlorothionyl (10ml) to the reaction bottle, stir and react for 3-4h under reflux conditions, and concentrate under reduced pressure to obtain 4-(5-(3,5-dichloro-4-fluorophenyl)-5-trifluoromethyl-4,5-dihydroisoxazol-3-yl)-2-methylbenzoyl chloride. Dissolve the obtained acid chloride in ethyl acetate and add it to a saturated sodium carbonate solution of 1-aminocyclobutanecarboxylic acid methyl ester (2.25g, 17.40mmol), react at room temperature, and monitor the reaction progress with a plate. After the reaction is completed, take the organic phase, wash it with a saturated sodium chloride solution, dry it with anhydrous sodium sulfate, and spin dry it to obtain the product as a yellow solid (6.12g, yield 96.39%).

[0226] The H NMR spectrum (500 MHz, DMSO-d6) data of the compound are as follows (δ [ppm]): δ 9.15 (s, 1H), 7.82 (d, J = 6.2 Hz, 2H), 7.62 (d, J = 4.6 Hz, 2H), 7.47-7.43 (m, 1H), 4.35 (q, J = 18.4 Hz, 2H), 3.67 (s, 3H), 2.58 (ddd, J = 12.6, 9.0, 6.0 Hz, 2H), 2.38 (s, 3H), 2.33-2.24 (m, 2H), 2.03-1.88 (m, 2H).

[0227] ESI-MS (m / z): [MH-] Calculated value: 545.0663, found value: 545.0658.

[0228] Example 16

[0229] The synthetic reaction equation of compound No. 692 in Table 2 is as follows:

[0230] Synthesis of 1-(4-(5-(3,5-dichloro-4-fluorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methylbenzamido)cyclobutane-1-carboxylic acid

[0231]

[0232] Preparation method: 1-(4-(5-(3,5-dichloro-4-fluorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methylbenzamido)cyclobutane-1-carboxylic acid methyl ester (3.00 g, 5.48 mmol) was added to a mixture of 5% potassium hydroxide: methanol = 1:1 by volume, and hydrolyzed at 40°C-45°C for 3-4 hours. After the reaction was completed, dilute hydrochloric acid was added to acidify, and solids precipitated. The solids were filtered and washed with distilled water several times and then dried to obtain the product as a yellow solid (2.30 g, yield 78.70%).

[0233] The H NMR spectrum (400 MHz, DMSO-d6) data of the compound are as follows (δ [ppm]): δ 12.36 (s, 1H), 9.00 (s, 1H), 7.82 (d, J = 6.2 Hz, 2H), 7.61 (d, J = 6.5 Hz, 2H), 7.44 (d, J = 8.5 Hz, 1H), 4.43-4.28 (m, 2H), 2.60-2.52 (m, 2H), 2.39 (s, 3H), 2.30-2.20 (m, 2H), 2.01-1.90 (m, 2H).

[0234] ESI-MS (m / z): [MH-] Calculated value: 531.0507, found value: 531.0507.

[0235] Embodiment 17

[0236] The synthetic reaction equation of compound No. 708 in Table 2 is as follows:

[0237] Synthesis of Cyclopropyl 1-(4-(5-(3,5-dichloro-4-fluorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methylbenzamido)cyclobutane-1-carboxylate

[0238]

[0239] Preparation method: Add 1-(4-(5-(3,5-dichloro-4-fluorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methylbenzamide)cyclobutane-1-carboxylic acid (1.00 g, 1.88 mmol) and dichlorothionyl (5 ml) to a reaction bottle, stir and react for 3-4 h under reflux conditions, and concentrate under reduced pressure to obtain its acid chloride. Dissolve the acid chloride in dichloromethane and add it to cyclopropanol (0.16 g, 2.82 mmol), then add solid potassium carbonate, and react at 40°C for 3-4 h. After the reaction, filter out the potassium carbonate, wash with dilute hydrochloric acid (2 mol / L) and saturated sodium chloride solution in turn, dry with anhydrous sodium sulfate, and spin dry to obtain a yellow solid (0.85 g, yield 78.86%).

[0240] The H NMR spectrum (500 MHz, DMSO-d6) data of the compound are as follows (δ [ppm]): δ 9.14 (s, 1H), 7.82 (d, J = 6.2 Hz, 2H), 7.61 (d, J = 6.3 Hz, 2H), 7.43-7.39 (m, 1H), 4.41 -4.28 (m, 2H), 4.11 (tt, J = 6.3, 3.0 Hz, 1H), 2.55 (ddd, J = 12.7, 9.0, 5.8 Hz, 2H), 2.37 (s, 3H), 2.26 (dt, J = 12.4, 9.4 Hz, 2H), 2.01-1.86 (m, 2H), 0.71 (q, J = 6.2 Hz, 2H), 0.63-0.56 (m, 2H).

[0241] ESI-MS (m / z): [MH-] Calculated value: 571.0820, found value: 571.0823.

[0242] Embodiment 18

[0243] The synthetic reaction equation of compound No. 740 in Table 1 is as follows:

[0244]

[0245] Preparation method: 1-(4-(5-(3,5-dichloro-4-fluorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methylbenzamide)cyclobutane-1-carboxylic acid (1.00 g, 1.88 mmol) was dissolved in acetonitrile, CDI (0.34 g, 2.07 mmol) was added, and activated at room temperature for 30 min, and then 2,2,2-trifluoroethylamine (0.28 g, 2.82 mmol) and DBU (0.30 g, 1.97 mmol) were added, and the plate was detected until the reaction was completed. After the reaction was completed, dichloromethane was added and washed with dilute hydrochloric acid (2 mol / L), and solid potassium carbonate was added and stirred at room temperature for several hours. After filtering out potassium carbonate, it was washed with saturated sodium chloride solution, dried over anhydrous sodium sulfate, and dried to obtain a yellow solid (0.86 g, yield 74.46%).

[0246] The H NMR spectrum (500 MHz, DMSO-d6) data of the compound are as follows (δ [ppm]): δ 8.91 (s, 1H), 8.13 (t, J = 6.3 Hz, 1H), 7.82 (d, J = 6.2 Hz, 2H), 7.67 (d, J = 8.2 Hz, 1H), 7.61 (d, J = 7.4 Hz, 2H), 4.43-4.29 (m, 2H), 3.95-3.85 (m, 2H), 2.56 (dt, J = 12.2, 9.0 Hz, 2H), 2.38 (s, 3H), 2.24 (dd, J = 19.6, 9.4 Hz, 2H), 2.00-1.81 (m, 2H).

[0247] ESI-MS (m / z): [MH-] Calculated value: 612.0697, found value: 612.0700.

[0248] Embodiment 19

[0249] The synthetic reaction equation of compound No. 1133 in Table 2 is as follows:

[0250] Synthesis of 1-(3-methyl-5-(5-(3,4,5-trichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)thiophene-2-carboxamido)cyclobutane-1-carboxylic acid methyl ester

[0251]

[0252] Preparation method: Add 3-methyl-5-(5-(3,4,5-trichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)thiophene-2-benzoic acid (1.00g, 2.18mmol) and dichlorothionyl (5ml) to a reaction bottle, stir and react for 3-4h under reflux conditions, and concentrate under reduced pressure to obtain 3-methyl-5-(5-(3,4,5-trichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)thiophene-2-benzoyl chloride. Dissolve the obtained acid chloride in ethyl acetate and add it to a saturated sodium carbonate solution of 1-aminocyclobutanecarboxylic acid methyl ester (0.38g, 2.62mmol), react at room temperature, and monitor the reaction progress with a plate. After the reaction is completed, take the organic phase, wash it with a saturated sodium chloride solution, dry it with anhydrous sodium sulfate, and spin dry it to obtain the product as a yellow solid (0.98g, yield 79.67%).

[0253] The H NMR spectrum (500 MHz, DMSO-d6) data of the compound are as follows (δ [ppm]): δ 1H NMR (500 MHz, DMSO-d6) 8.96 (s, 1H), 7.82 (s, 2H), 7.35 (s, 1H), 4.43-4.29 (m, 2H), 3.64 (s, 3H), 2.63-2.52 (m, 2H), 2.40 (s, 3H), 2.35-2.23 (m, 2H), 2.03-1.86 (m, 2H).

[0254] ESI-MS (m / z): [MH-] Calculated value: 566.9927, found value: 566.9929.

[0255] Embodiment 20

[0256] The synthetic reaction equation of compound No. 1149 in Table 2 is as follows:

[0257] Synthesis of N-(1-(Hydroxymethyl)cyclobutyl)-3-methyl-5-(5-(3,4,5-trichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)thiophene-2-carboxamide

[0258]

[0259] Preparation method: 3-methyl-5-(5-(3,4,5-trichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)thiophene-2-benzoic acid (1.00g, 2.18mmol) was dissolved in dichloromethane (5mL), EDCI (0.63g, 3.28mmol) was added, and 1-hydroxybenzotriazole (0.43g, 3.28mmol) and triethylamine (0.88g, 8.73mmol) were added after activation in an ice bath for 30min, and 1-aminocyclobutanemethanol (0.33g, 3.28mmol) was added, and the plate was detected until the reaction was completed. After the reaction was completed, dichloromethane was added and washed with dilute hydrochloric acid (2mol / L), solid potassium carbonate was added, and stirred at room temperature for several hours. After filtering out potassium carbonate, it was washed with saturated sodium chloride solution, dried over anhydrous sodium sulfate, and dried to obtain a yellow solid (0.89g, yield 75.23%).

[0260] The H NMR spectrum (500 MHz, DMSO-d6) data of the compound are as follows (δ [ppm]): δ 7.95 (s, 1H), 7.81 (s, 2H), 7.30 (s, 1H), 4.85 (t, J = 5.8 Hz, 1H), 4.34 (q, J = 18.2 Hz, 2H), 3.61 (d, J = 5.7 Hz, 2H), 2.38 (s, 3H), 2.23 (q, J = 10.0 Hz, 2H), 2.10 (td, J = 9.1, 4.9 Hz, 2H), 1.83 (s, 1H), 1.73 (dt, J = 10.7, 8.5 Hz, 1H).

[0261] ESI-MS (m / z): [MH-] Calculated value: 538.9978, found value: 538.9991.

[0262] Embodiment 21

[0263] The synthetic reaction equation of compound No. 1336 in Table 2 is as follows:

[0264]

[0265] Preparation method: Add 4-(5-(3,5-dichloro-4-fluorophenyl)-5-trifluoromethyl-4,5-dihydroisoxazol-3-yl)-2-methylbenzoic acid (6.00g, 11.60mmol) and dichlorothionyl (10ml) to the reaction bottle, stir and react for 3-4h under reflux conditions, and concentrate under reduced pressure to obtain 4-(5-(3,5-dichloro-4-fluorophenyl)-5-trifluoromethyl-4,5-dihydroisoxazol-3-yl)-2-methylbenzoyl chloride. Dissolve the obtained acid chloride in ethyl acetate and add it to a saturated sodium carbonate solution of 3-aminooxetane-3-carboxylic acid methyl ester (2.28g, 17.40mmol), react at room temperature, and monitor the reaction progress with a plate. After the reaction is completed, take the organic phase, wash it with a saturated sodium chloride solution, dry it with anhydrous sodium sulfate, and spin dry it to obtain the product as a yellow solid (5.46g, yield 88.51%).

[0266] The H NMR spectrum (500 MHz, DMSO-d6) data of the compound are as follows (δ [ppm]): δ 9.62 (s, 1H), 7.81 (t, J = 6.6 Hz, 2H), 7.65 (d, J = 7.2 Hz, 2H), 7.54 (d, J = 8.5 Hz, 1H), 4.93 (d, J = 6.7 Hz, 2H), 4.68 (d, J = 6.7 Hz, 2H), 4.36 (q, J = 18.4 Hz, 2H), 3.76 (s, 3H), 2.40 (s, 3H).

[0267] ESI-MS (m / z): [MH-] Calculated value: 547.0456, found value: 547.0458.

[0268] In the embodiment of the present invention, the isoxazoline compounds shown by other compound numbers in Table 1-2 can be prepared by making corresponding adjustments in the preparation method described in the above embodiment. When the isoxazoline compound is a stereoisomer of the compound of formula I, it can be obtained by conventional methods, such as: starting from optically active reaction raw materials to obtain reaction products with corresponding optical activity, and performing chiral resolution on racemic or meso reaction products. This embodiment will not be discussed in detail, and equivalent changes made in the claims still fall within the scope of the invention.

[0269] Effect Example

[0270] Some of the compounds in this application form were tested for their activity against various pests.

[0271] (1) Determination of Chilo suppressalis activity:

[0272] Preparation of compound solution: Weigh 10 mg of the original drug on a balance, prepare it into 1% stock solution with DMF, and then dilute it with distilled water containing 0.1% Tween-80 to four test concentrations of 10 mg / L, 3.0 mg / L, 1.5 mg / L, and 0.85 mg / L for use.

[0273] Using the immersion method, after soaking the water chestnut slices in the medicine for 30 seconds, put them into a plastic box lined with filter paper to dry naturally in the shade. Inoculate each box with 10 2-3 year old rice stem borers and observe them in a room at 26℃ with 16 hours of light and 8 hours of darkness. After 3 days, observe the number of dead insects and measure the mortality rate.

[0274] The reference compound CK01 is chlorantraniliprole as shown in formula (II), the reference compound CK02 is as shown in formula (III), and the reference compound CK03 is as shown in formula

[0275]

[0276] Among them, the technical drugs are derived from the compounds in Table 1, specifically: 1, 1(5S), 8, 14, 27, 34, 40, 47, 53, 66, 92, 189, 196, 202, 209, 215, 222, 228, 231, 243, 250, 258, 274, 473, 489, 516, 676, 692, 708, 740, 1133, 1149, 1336. The mortality rate of the chilo suppressalis was greater than 80% after 4 days at a concentration of 10 mg / L. Then, some highly active compounds 1, 1(5S), 27, 40, 92, 189, 196, 202, 209, 215, 222, 228, 243 were tested for activity at low concentrations. The results are shown in Table 3.

[0277] Table 3: Activity test results of some compounds in Table 1-2 against Chilo suppressalis

[0278]

[0279]

[0280]

[0281] Note: The compound numbers correspond to those in Table 1-2. The number (5S) after the compound number indicates that the 5th position of the general formula (I) is in S configuration.

[0282] It can be seen from Table 3 that the mortality rates of compounds 1 (5S), 27, 40, 92, 189, 196, 202, 209, 215, 222, 228 and 243 of the present invention to Chilo suppressalis at a low concentration of 0.85 mg / L were all greater than 80%, and at a low concentration of 1.5 mg / L, the mortality rate to Chilo suppressalis was 100%.

[0283] The control compound CK01, namely chlorantraniliprole, had a mortality rate of only 20% against the Chilo suppressalis even at a high concentration of 3.0 mg / L. The mortality rates of CK02 and CK03 against the Chilo suppressalis at 0.85 mg / L were both lower than 50%. Even at a concentration of 1.5 mg / L, the mortality rate against resistant Chilo suppressalis was still difficult to reach 80%.

[0284] (II) Determination of activity of Plutella xylostella:

[0285] Preparation of compound solution: Weigh 10 mg of the original drug on a balance, prepare it into 1% stock solution with DMF, and then dilute it with distilled water containing 0.1% Tween-80 to four test concentrations of 3 mg / L, 1 mg / L, 0.45 mg / L, and 0.225 mg / L for use.

[0286] Using the immersion method, the cabbage leaves were immersed in the medicine for 10 seconds and then placed in a plastic box lined with filter paper to dry naturally in the shade. Ten 3-year-old diamondback moths were inoculated into each box and placed in an observation room at 26°C with 16 hours of light and 8 hours of darkness. After 3 days, the number of dead insects was observed and the mortality rate was measured.

[0287] Among them, the lethality of compounds 1, 1(5S), 8, 14, 27, 34, 40, 47, 53, 66, 92, 189, 196, 202, 209, 215, 222, 228, 231, 243, 250, 258, 274, 473, 489, 516, 676, 692, 708, 740, 1133, 1149, 1336 to Plutella xylostella at a concentration of 3 mg / L after 3 days was greater than 80%. Then, the activity of 1, 1(5S), 27, 40, 92, 189, 196, 202, 209, 215, 222, 228, 243 was tested at low concentrations (1 mg / L, 0.45 mg / L and 0.225 mg / L), and the results are shown in Table 4.

[0288] Table 4: Activity test results of some compounds in Table 1-2 against Plutella xylostella

[0289]

[0290]

[0291] Note: The compound numbers correspond to those in Table 1. (5S) after the compound number indicates that the 5th position of the general formula (I) is in S configuration.

[0292] It can be seen from Table 4 that the mortality rate of compounds 1, 1(5S), 27, 40, 92, 189, 196, 202, 209, 215, 222, 228, and 243 of the present invention to Plutella xylostella at a concentration of 0.225 mg / L is greater than 80%, and at a concentration of 0.45 mg / L, the mortality rate of the compounds of the present invention to Plutella xylostella reaches 100%.

[0293] The control compound CK01, namely chlorantraniliprole, had a mortality rate of only 20% against resistant diamondback moth even at a high concentration of 1 mg / L, while the mortality rates of CK02 and CK03 against diamondback moth at a concentration of 0.225 mg / L were both lower than 50%, and even at a concentration of 0.45 mg / L, the mortality rate against resistant diamondback moth was still difficult to reach 80%.

[0294] It should be noted that the isoxazoline compounds provided by the present invention have high biological activity against both Chilo suppressalis and Plutella xylostella, and the isoxazoline compounds have no cross-resistance with chlorantraniliprole. In small organic molecule pesticide compounds, due to the different types of substituents, group volumes, and electronegativity, the metabolic performance, conduction performance, and binding performance of the entire molecule in the organism will be very different, so the biological activity differences will also be very large, and the metabolic performance, conduction performance, and ability of the molecule to bind to the receptor are unpredictable; generally, compounds containing many fluorine atoms are highly toxic and not easily degraded in the environment. The preferred compounds of the present invention are taken from ester groups, hydroxyl substituted alkyl groups, etc. that do not contain fluorine through L1 and L2, reducing the number of fluorine atoms in such compounds so that the compounds are more environmentally friendly. Compared with existing insecticides on the market, the isoxazoline compounds provided by the present invention have the advantages of fast efficacy, low dosage, and environmental friendliness to plant pests.

[0295] The above are only preferred embodiments of the present invention, and do not limit the patent scope of the present invention. For those skilled in the art, the present invention may have various changes and variations. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present invention shall be included in the patent protection scope of the present invention.

Claims

1. An isoxazoline compound, characterized in that The isoxazoline compound is a compound having the following structural formula (I) or its tautomer, metabolic isomer, pharmaceutically acceptable salt or prodrug: Q is selected from any one of the structures of formula A1 to A6; Wherein, Q is A1, L1 is selected from -C(O)OR4, -C(O)SR4 or -C(O)NHR5, wherein R4 is hydrogen, a monovalent metal ion, an ammonium ion, a substituted or unsubstituted C1-C6 alkyl group, a substituted or unsubstituted C2-C6 alkenyl group, a substituted or unsubstituted C2-C6 alkynyl group, a substituted or unsubstituted C3-C5 cycloalkyl group, a substituted or unsubstituted C3-C5 cycloalkyl group, a substituted or unsubstituted C1-C3 alkyl group, a substituted or unsubstituted hydroxyl group, a substituted or unsubstituted C1-C4 alkyl group, a substituted or unsubstituted C1- C2 alkoxy C1-C4 alkyl, R5 is substituted or unsubstituted C1-C2 alkoxy C1-C4 alkyl, C1-C3 alkoxycarbonyl C1-C3 alkyl, wherein the substituent is one or more halogen atoms, nitro, nitroso, cyano, amino, hydroxyl, wherein R1, R2, R3 can be independently selected from halogen atoms, cyano, nitro, C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, C1-C3 alkylthio or C1-C3 haloalkylthio; In addition, L1 is selected from one or more hydroxy-substituted C1-C8 alkyl groups, one or more hydroxy-substituted C2-C8 alkenyl groups, one or more hydroxy-substituted C2-C8 alkynyl groups, wherein R1, R2, and R3 can be independently selected from a hydrogen atom, a halogen atom, a cyano group, a nitro group, a C1-C3 alkyl group, a C1-C3 haloalkyl group, a C1-C3 alkoxy group, a C1-C3 haloalkoxy group, a C1-C3 alkylthio group, or a C1-C3 haloalkylthio group; Z1 represents a hydrogen atom, an oxygen atom, a halogen atom, a hydroxyl group, a nitro group, a nitroso group, a cyano group, an amino group, a substituted or unsubstituted C1-C6 alkyl group, a substituted or unsubstituted C2-C6 alkenyl group, a substituted or unsubstituted C2-C6 alkynyl group, a substituted or unsubstituted C3-C5 cycloalkyl group, a substituted or unsubstituted C1-C3 alkyl group, a substituted or unsubstituted C1-C5 cycloalkyl group, a substituted or unsubstituted C1-C6 alkoxy group, a substituted or unsubstituted C1-C6 alkylthio group, or -C(O)M , wherein M represents a substituted or unsubstituted C1-C6 alkyl, a substituted or unsubstituted C2-C6 alkenyl, a substituted or unsubstituted C2-C6 alkynyl, a substituted or unsubstituted C3-C5 cycloalkyl, a substituted or unsubstituted C1-C3 alkyl C3-C5 cycloalkyl, a substituted or unsubstituted C1-C6 alkoxy C1-C6 alkyl, a substituted or unsubstituted C1-C6 alkylthio C1-C6 alkyl, wherein the substituent may be one or more halogen atoms, hydroxyl, nitro, nitroso, cyano, amino; Q is the structure represented by any one of A2 to A6, R1, R2, and R3 can be independently selected from a hydrogen atom, a halogen atom, a cyano group, a nitro group, a C1-C3 alkyl group, a C1-C3 haloalkyl group, a C1-C3 alkoxy group, a C1-C3 haloalkoxy group, a C1-C3 alkylthio group, or a C1-C3 haloalkylthio group; L2 is selected from -C(O)OR6, -C(O)SR6, or -C(O)NHR7, wherein R6 is hydrogen, a monovalent metal ion, an ammonium ion, a substituted or unsubstituted C1-C6 alkyl group, a substituted or unsubstituted Substituted C2-C6 alkenyl, substituted or unsubstituted C2-C6 alkynyl, substituted or unsubstituted C3-C5 cycloalkyl, substituted or unsubstituted cyclopropyl C1-C3 alkyl, R7 is hydrogen, substituted C1-C6 alkyl, substituted or unsubstituted C2-C6 alkenyl, substituted or unsubstituted C2-C6 alkynyl, substituted or unsubstituted C3-C5 cycloalkyl, substituted or unsubstituted C1-C6 alkoxy, wherein the substituent may be one or more halogen atoms, nitro, nitroso, cyano, amino, C1-C3 alkoxy; In addition, L2 can be selected from one or more hydroxy-substituted C1-C8 alkyl groups, one or more hydroxy-substituted C2-C8 alkenyl groups, and one or more hydroxy-substituted C2-C8 alkynyl groups; Z2 represents a hydrogen atom, an oxygen atom, a halogen atom, a hydroxyl group, a nitro group, a nitroso group, a cyano group, an amino group, a substituted or unsubstituted C1-C6 alkyl group, a substituted or unsubstituted C2-C6 alkenyl group, a substituted or unsubstituted C2-C6 alkynyl group, a substituted or unsubstituted C3-C5 cycloalkyl group, a substituted or unsubstituted C1-C3 alkyl group, a substituted or unsubstituted C1-C5 cycloalkyl group, a substituted or unsubstituted C1-C6 alkoxy group, a substituted or unsubstituted C1-C6 alkylthio group, or -C(O) M, wherein M represents a substituted or unsubstituted C1-C6 alkyl, a substituted or unsubstituted C2-C6 alkenyl, a substituted or unsubstituted C2-C6 alkynyl, a substituted or unsubstituted C3-C5 cycloalkyl, a substituted or unsubstituted C1-C3 alkyl C3-C5 cycloalkyl, a substituted or unsubstituted C1-C6 alkoxy C1-C6 alkyl, a substituted or unsubstituted C1-C6 alkylthio C1-C6 alkyl, wherein the substituent may be one or more halogen atoms, nitro, nitroso, cyano, amino; W means O or S; X represents O or CH2.

2. The isoxazoline compound according to claim 1, wherein The isoxazoline compound comprises a structure shown in formula A1, wherein L1 in the isoxazoline compound is selected from -C(O)OR4, -C(O)SR4 or -C(O)NHR5, wherein R4 is hydrogen, sodium ion, potassium ion, ammonium ion, substituted or unsubstituted C1-C3 alkyl, substituted or unsubstituted C2-C4 alkenyl, substituted or unsubstituted C2-C4 alkynyl, substituted or unsubstituted C3-C4 cycloalkyl, substituted or unsubstituted C3-C4 cycloalkyl C1-C2 alkyl, substituted or unsubstituted R5 is substituted or unsubstituted C1-C2 alkoxy C1-C2 alkyl, C1-C3 alkoxycarbonyl C1-C2 alkyl, wherein the substituent is one or more halogen atoms, nitro, nitroso, cyano, amino, hydroxyl, wherein R1, R2, R3 can be independently selected from halogen atoms, cyano, nitro, C1-C3 alkyl, C1-C3 haloalkyl; in addition, L1 can be selected from one or more hydroxy substituted C1-C5 alkyl , wherein R1, R2, and R3 can be independently selected from hydrogen atom, halogen atom, cyano, nitro, C1-C3 alkyl, C1-C3 haloalkyl; Z1 represents hydrogen atom, substituted or unsubstituted C1-C3 alkyl, substituted or unsubstituted C2-C4 alkenyl, substituted or unsubstituted C2-C4 alkynyl, substituted or unsubstituted cyclopropyl, substituted or unsubstituted C1-C3 alkylcyclopropyl, substituted or unsubstituted C1-C3 alkoxy C1-C3 alkyl, substituted or unsubstituted C1-C3 alkylthio C1-C3 C3 alkyl, or C(O)M, wherein M represents substituted or unsubstituted C1-C3 alkyl, substituted or unsubstituted C2-C4 alkenyl, substituted or unsubstituted C2-C4 alkynyl, substituted or unsubstituted cyclopropyl, substituted or unsubstituted C1-C3 alkylcyclopropyl, substituted or unsubstituted C1-C3 alkoxy C1-C3 alkyl, substituted or unsubstituted C1-C3 alkylthio C1-C3 alkyl, wherein the substituent may be one or more halogen atoms, hydroxyl, nitro, nitroso, cyano, amino; W represents O or S; and / or, The isoxazoline compound comprises a structure shown in formula A1, wherein L1 in the isoxazoline compound is selected from -C(O)OR4, -C(O)SR4 or -C(O)NHR5, wherein R4 is hydrogen, substituted or unsubstituted C1-C3 alkyl, substituted or unsubstituted C2-C4 alkenyl, substituted or unsubstituted C2-C4 alkynyl, substituted or unsubstituted cyclopropyl, substituted or unsubstituted cyclopropylmethyl, substituted or unsubstituted hydroxyl C1-C3 alkyl, substituted or unsubstituted C1-C2 alkoxy C1-C3 alkyl; R5 is substituted or unsubstituted C1-C2 alkoxy C1-C2 alkyl, C1-C2 alkoxycarbonyl C1-C2 alkyl, wherein the substituent is one or more halogen atoms, nitro, nitroso, cyano, amino, hydroxyl, wherein R1, R2, and R3 can be independently selected from halogen atoms, cyano, nitro, C1-C3 alkyl, C1-C2 alkoxycarbonyl C1-C2 alkyl, -C3 haloalkyl; L1 can also be selected from one or more hydroxy-substituted C1-C3 alkyl groups, wherein R1, R2, R3 can be independently selected from hydrogen atoms, halogen atoms, cyano groups, nitro groups, C1-C3 alkyl groups, C1-C3 haloalkyl groups; Z1 represents a hydrogen atom, a substituted or unsubstituted C1-C3 alkyl group, a substituted or unsubstituted C2-C4 alkenyl group, a substituted or unsubstituted C2-C4 alkynyl group, a substituted or unsubstituted cyclopropyl group, a substituted or unsubstituted C1-C2 alkoxy C1-C2 alkyl group, or C(O)M, wherein M represents a substituted or unsubstituted C1-C3 alkyl group, a substituted or unsubstituted C2-C3 alkenyl group, a substituted or unsubstituted C2-C3 alkynyl group, a substituted or unsubstituted cyclopropyl group, a substituted or unsubstituted C1-C2 alkoxy C1-C2 alkyl group, wherein the substituents can be one or more halogen atoms, nitro groups, nitroso groups, cyano groups; W represents O or S; and / or, The isoxazoline compound comprises a structure shown in formula A1, wherein L1 in the isoxazoline compound is selected from -C(O)OR4, -C(O)SR4 or -C(O)NHR5, wherein R4 is hydrogen, substituted or unsubstituted methyl, ethyl, n-propyl, isopropyl, vinyl, propenyl, allyl, ethynyl, propynyl, cyclopropyl, cyclopropylmethyl, hydroxyethyl, methoxyethyl, ethoxyethyl; R5 is methoxyethyl, ethoxyethyl, methoxycarbonylmethyl, ethoxycarbonylmethyl, wherein the substituent is one or more halogen atoms, nitro, nitro, cyano, amino, hydroxyl, wherein R1, R2, and R3 can be independently selected from halogen atoms, cyano, nitro, methyl, trifluoromethyl, methoxy, and trifluoromethoxy; L1 can also be selected from -CH2OH, - CH2CH2OH, wherein R1, R2, and R3 may be independently selected from a hydrogen atom, a halogen atom, a cyano group, a nitro group, a methyl group, a trifluoromethyl group, a methoxy group, and a trifluoromethoxy group; Z1 represents a hydrogen atom, a methyl group, an ethyl group, a substituted or unsubstituted C2-C3 alkenyl group, a substituted or unsubstituted C2-C3 alkynyl group, a substituted or unsubstituted cyclopropyl group, a substituted or unsubstituted C1-C2 alkoxy C1-C2 alkyl group, or C(O)M, wherein M represents a substituted or unsubstituted C1-C3 alkyl group, a substituted or unsubstituted C2-C3 alkenyl group, a substituted or unsubstituted C2-C3 alkynyl group, a substituted or unsubstituted cyclopropyl group, a substituted or unsubstituted C1-C2 alkoxy C1-C2 alkyl group, wherein the substituent may be one or more halogen atoms, a nitro group, a nitroso group, and a cyano group.

3. The isoxazoline compound according to claim 1, characterized in that The isoxazoline compound comprises a structure shown in any one of formulas A2 to A6, wherein: R1, R2, and R3 in the isoxazoline compound can be independently selected from a hydrogen atom, a halogen atom, a cyano group, a nitro group, a C1-C3 alkyl group, a C1-C3 haloalkyl group, a C1-C3 alkoxy group, and a C1-C3 haloalkoxy group; L2 is selected from -C(O)OR6, -C(O)SR6 or -C(O)NHR7, wherein R6 is hydrogen, sodium ion, potassium ion, ammonium ion, substituted or unsubstituted C1-C3 alkyl, substituted or unsubstituted C2-C4 alkenyl, substituted or unsubstituted C2-C4 alkynyl, substituted or unsubstituted C3-C4 cycloalkyl, substituted or unsubstituted cyclopropyl C1-C3 alkyl; wherein R7 is hydrogen, substituted C1-C3 alkyl, substituted or unsubstituted C2-C4 alkenyl, substituted or unsubstituted C2-C4 alkynyl, substituted or unsubstituted C3-C4 cycloalkyl, substituted or unsubstituted C1-C3 alkoxy, wherein the substituent is one or more halogen atoms, nitro, nitroso, cyano, amino, C1-C3 alkoxy; L2 can also be selected from one or more hydroxy-substituted C1-C5 alkyl; Z2 represents a hydrogen atom, a substituted or unsubstituted C1-C3 alkyl group, a substituted or unsubstituted C2-C4 alkenyl group, a substituted or unsubstituted C2-C4 alkynyl group, a substituted or unsubstituted cyclopropyl group, a substituted or unsubstituted C1-C3 alkylcyclopropyl group, a substituted or unsubstituted C1-C3 alkoxy C1-C3 alkyl group, a substituted or unsubstituted C1-C3 alkylthio C1-C3 alkyl group, or C(O)M, wherein M represents a substituted or unsubstituted C1-C3 alkyl group, a substituted or unsubstituted C2-C4 alkenyl group, a substituted or unsubstituted C2-C4 alkynyl group, a substituted or unsubstituted cyclopropyl group, a substituted or unsubstituted C1-C3 alkylcyclopropyl group, a substituted or unsubstituted C1-C3 alkoxy C1-C3 alkyl group, a substituted or unsubstituted C1-C3 alkylthio C1-C3 alkyl group, wherein the substituent may be one or more halogen atoms, hydroxyl groups, nitro groups, nitroso groups, cyano groups, or amino groups; W means O or S; X represents O or CH2; and / or, R1, R2, and R3 in the isoxazoline compound can be independently selected from a hydrogen atom, a halogen atom, a cyano group, a nitro group, a C1-C3 alkyl group, a C1-C3 haloalkyl group, a C1-C3 alkoxy group, and a C1-C3 haloalkoxy group; L2 is selected from -C(O)OR6, -C(O)SR6 or -C(O)NHR7, wherein R6 is hydrogen, substituted or unsubstituted C1-C3 alkyl, substituted or unsubstituted C2-C4 alkenyl, substituted or unsubstituted C2-C4 alkynyl, substituted or unsubstituted cyclopropyl, substituted or unsubstituted cyclopropylmethyl; wherein R7 is hydrogen, substituted C1-C3 alkyl, substituted or unsubstituted C2-C4 alkenyl, substituted or unsubstituted C2-C4 alkynyl, substituted or unsubstituted cyclopropyl, C1-C3 alkoxy, wherein the substituent is one or more halogen atoms, nitro, nitroso, cyano, methoxy, ethoxy; L2 can also be selected from one or more hydroxy-substituted C1-C5 alkyl; Z2 represents a hydrogen atom, a substituted or unsubstituted C1-C3 alkyl group, a substituted or unsubstituted C2-C4 alkenyl group, a substituted or unsubstituted C2-C4 alkynyl group, a substituted or unsubstituted cyclopropyl group, a substituted or unsubstituted C1-C2 alkoxy C1-C2 alkyl group, or C(O)M, wherein M represents a substituted or unsubstituted C1-C3 alkyl group, a substituted or unsubstituted C2-C4 alkenyl group, a substituted or unsubstituted C2-C4 alkynyl group, a substituted or unsubstituted cyclopropyl group, a substituted or unsubstituted C1-C3 alkylcyclopropyl group, a substituted or unsubstituted C1-C2 alkoxy C1-C2 alkyl group, wherein the substituent may be one or more halogen atoms, hydroxyl groups, nitro groups, nitroso groups, cyano groups, or amino groups; W means O or S; X represents O or CH2; and / or, The isoxazoline compound comprises a structure represented by any one of formulas A2 to A6, and R1, R2, and R3 in the isoxazoline compound can be independently selected from hydrogen atoms, halogen atoms, cyano groups, nitro groups, methyl groups, trifluoromethyl groups, methoxy groups, and trifluoromethoxy groups; L2 is selected from -C(O)OR6, -C(O)SR6 or -C(O)NHR7, wherein R6 is hydrogen, substituted or unsubstituted methyl, ethyl, vinyl, propenyl, allyl, ethynyl, propynyl, cyclopropyl; wherein R7 is hydrogen, halomethyl, haloethyl, halopropyl, vinyl, propenyl, allyl, ethynyl, propynyl, cyclopropyl, methoxy, ethoxy, n-propoxy, isopropoxy, wherein the substituent is one or more halogen atoms, nitro, nitroso, cyano, amino, methoxy, ethoxy; L2 can also be selected from one or more hydroxy-substituted C1-C3 alkyl groups; Z2 represents a hydrogen atom, a methyl group, an ethyl group, a substituted or unsubstituted C2-C3 alkenyl group, a substituted or unsubstituted C2-C3 alkynyl group, a substituted or unsubstituted cyclopropyl group, a substituted or unsubstituted C1-C2 alkoxy C1-C2 alkyl group, or C(O)M, wherein M represents a substituted or unsubstituted C1-C3 alkyl group, a substituted or unsubstituted C2-C3 alkenyl group, a substituted or unsubstituted C2-C3 alkynyl group, a substituted or unsubstituted cyclopropyl group, a substituted or unsubstituted C1-C2 alkoxy C1-C2 alkyl group, wherein the substituent may be one or more halogen atoms, a nitro group, a nitroso group, or a cyano group; W stands for O; X represents CH2.

4. The isoxazoline compound according to claim 1, wherein The isoxazoline compounds also include the structure shown in Formula I' or its tautomers and pharmaceutically acceptable salts, wherein the carbon at position 5 is a chiral carbon having an R configuration and an S configuration, and the stereochemical purity of the S configuration is 50% to 100%.

5. Use of the isoxazoline compound as claimed in claim 4 in the preparation of insecticides.

6. An insecticide for killing insects, characterized in that: The pesticide comprises an active component, and the active component comprises the isoxazoline compound according to any one of claims 1 to 4 and / or the tautomer, enantiomer, diastereomer or pesticide-acceptable salt thereof of the isoxazoline compound.

7. The insecticide according to claim 6, characterized in that The mass of the active component accounts for 0.1% to 99% of the mass of the insecticide.

8. The insecticide according to claim 6, characterized in that The pests include rice resistant Chilo suppressalis, diamondback moth, aphids or thrips.

9. The insecticide according to any one of claims 6 to 8, characterized in that The pesticide further comprises a pharmaceutically acceptable carrier, excipient, adjuvant or any combination thereof.

10. An insecticide composition, characterized in that: The insecticide composition comprises active ingredients and other active compounds; the active ingredients comprise the isoxazoline compound as described in any one of claims 1 to 3 or the tautomers, enantiomers, diastereomers or pesticide-acceptable salts thereof of the isoxazoline compound as described in claim 4; the other active compounds comprise one or more of insecticides, baits, disinfectants, miticides, nematicides, fungicides, growth regulators and herbicides; the mass percentage of the active ingredients in the insecticide composition is 1%-99%.

Images