Isoxazoline compound as well as preparation method and application thereof

Abstract

The invention relates to the technical field of pesticides, and discloses an isoxazoline compound, a preparation method and application thereof, an agricultural composition and a method for preventing and treating invertebrate pests. The invention provides an isoxazoline compound with a structure as shown in a formula (I), or an agriculturally acceptable salt thereof, or a stereoisomer thereof. The isoxazoline compound and the agriculturally acceptable salt thereof provided by the invention show very high prevention and control effects on various pests, especially spider mites represented by tetranychus cinnabarinus, tetranychus urticae, tetranychus shennieri, panonychus citri and the like, and lepidoptera insects represented by plutella xylostella and the like; the acaricidal composition can be used for preventing and treating various pests and harmful mites, has efficient acaricidal and insecticidal activity, and has a good application prospect. # imgabs0 #

Description

Technical Field

[0001] The present invention relates to the technical field of pesticides, and particularly relates to isoxazoline compounds, their preparation methods and applications, agricultural compositions, and methods for controlling invertebrate pests. Background Art

[0002] Pests and mites damage hundreds of plants, especially vegetables, flowers and fruit trees, causing serious economic losses. Aryl isoxazole derivatives containing heterocyclic compounds have unique insecticidal activities in modern crop and animal protection, such as the marketed veterinary drug fluralaner and the insecticide fluxametamide.

[0003] CN114394963B discloses the following isoxazoline compounds, preparation methods and applications, wherein ring A is selected from a quinoline ring or an indole ring.

[0004]

[0005] CN101522672B discloses the following insecticidal isoxazoline compounds, wherein G is selected from a nitrogen-containing five-membered heterocyclic group.

[0006]

[0007] CN114026076B also discloses the following isoxazoline compounds.

[0008]

[0009] Heterocyclic compounds are important intermediates or chemical entities in the synthesis and research and development of pesticides. They have unique chemical structures and biological activities, and many of their derivatives have been developed into agrochemical products.

[0010] Currently, the insecticidal and acaricidal effects of the disclosed compounds are still not satisfactory, and the resistance of pests and mites develops very fast. There is still a need for more efficient new compounds in agricultural production to cope with the increasing development of pest and mite resistance. Summary of the Invention

[0011] The object of the present invention is to overcome the technical problem that existing compounds have low killing activities in the control of invertebrate pests (especially mites and diamondback moths) in the prior art, and to provide a more efficient isoxazoline compound, its preparation method and application, an agricultural composition, and a method for controlling invertebrate pests. The isoxazoline compound provided by the present invention has high acaricidal and insecticidal activities, and particularly shows high control effects against Tetranychus cinnabarinus, diamondback moths, etc.

[0012] To achieve the above object, a first aspect of the present invention provides an isoxazoline compound having the structure shown in formula (I), or an agriculturally acceptable salt thereof, or a stereoisomer thereof.

[0013]

[0014] Wherein,

[0015] X 1 and X 3 are each independently selected from F, Cl, Br, I or CF 3 ;

[0016] X 2 is selected from H, F, Cl, Br, I or CF 3 ;

[0017] R 1 is selected from hydrogen, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, methoxymethyl, methoxyethyl, ethoxymethyl, ethoxyethyl, trifluoromethyl, trichloromethyl, trifluoroethyl or trifluoromethoxymethyl, C 1 -C 6 alkylcarbonyl, halo-C 1 -C 6 alkylcarbonyl, C 3 -C 6 cycloalkylcarbonyl, C 3 -C 6 cycloalkylmethylcarbonyl, C 1 -C 6 alkoxycarbonyl, halo-C 1 -C 6 alkoxycarbonyl, C 1 -C 4 alkoxyC 1 -C 2 alkylcarbonyl, halo-C 1 -C 4 alkoxyC 1 -C 2 alkylcarbonyl, C 1 -C 6 alkyloxalyl, halo-C 1 -C 6 alkyloxalyl, C 1 -C 4 alkoxyoxalyl, halo-C 1 -C 4 alkoxyoxalyl, C 1 -C 4 alkylsulfonyl, halo-C 1 -C 4 alkylsulfonyl, C 1 -C 4Alkylsulfinyl, halo-C 1 -C 4 Alkylsulfinyl, halogen-substituted or unsubstituted benzoyl, halogen-substituted or unsubstituted benzenesulfonyl, a carbonyl group substituted with a five- or six-membered heteroaromatic ring containing 1 to 2 heteroatoms selected from O, S or N;

[0018] R 2 Selected from C 1 -C 3 Alkyl, halo-C 1 -C 3 Alkyl;

[0019] R 3 Selected from C 1 -C 3 Alkoxy, halo-C 1 -C 3 Alkoxy, C 1 -C 3 Alkylamino, halo-C 1 -C 3 Alkylamino.

[0020] In some embodiments, for the compound of formula I, X 1 and X 3 are each independently selected from F, Cl or CF 3 ;

[0021] Wherein the compound of formula I excludes the following substitution cases:

[0022] X 1 and X 3 are simultaneously selected from Cl, X 2 is selected from H;

[0023] X 1 and X 2 are selected from Cl, X 3 is selected from CF 3 ;

[0024] X 1 is selected from CF 3 、X 2 and X 3 are selected from Cl.

[0025] That is, the following compounds are excluded:

[0026]

[0027] In some embodiments, for the compound of formula I, X 1 、X 2 and X 3 are each independently selected from F, Cl or CF 3 ;

[0028] Among them, the general formula I compound excludes the following substitution cases:

[0029] X 1 and X 3 are simultaneously selected from Cl;

[0030] X 1 and X 2 are selected from Cl, X 3 is selected from CF 3 ;

[0031] X 1 is selected from CF 3 、X 2 and X 3 are selected from Cl.

[0032] That is, the following compounds are excluded:

[0033]

[0034] In some embodiments, for the general formula I compound, R 1 is selected from hydrogen, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, methoxymethyl, methoxyethyl, ethoxymethyl, ethoxyethyl, acetyl, propionyl, n-butyryl, cyclopropylcarbonyl, methoxycarbonyl, methoxyacetyl, methoxyacetyl, methoxyoxalyl, ethoxyoxalyl;

[0035] R 2 is selected from methyl, ethyl, chloromethyl;

[0036] R 3 is selected from methoxy, ethoxy, methylamino, ethylamino, propylamino, trifluoroethylamino.

[0037] In a second aspect, the present invention provides the following compounds or their agriculturally acceptable salts, or their stereoisomers:

[0038]

[0039]

[0040]

[0041]

[0042] In a third aspect, the present invention provides a compound having the structure shown in formula (X),

[0043] wherein, X 1 、X 3Each independently selected from F, Cl or CF 3 ;

[0044] X 2 Selected from H, F, Cl or CF 3 ;

[0045] R 2 Selected from methyl, ethyl, chloromethyl;

[0046] R 3 Selected from methoxy, ethoxy, methylamino, ethylamino, propylamino, trifluoroethylamino.

[0047] Fourthly, the present invention provides the use of the compound having the structure shown in formula (X) in the preparation of the isoxazoline compound having the structure shown in formula (IV):

[0048]

[0049] Wherein, X 1 , X 3 Each independently selected from F, Cl or CF 3 ;

[0050] X 2 Selected from H, F, Cl or CF 3 ;

[0051] R 2 Selected from methyl, ethyl, chloromethyl;

[0052] R 3 Selected from methoxy, ethoxy, methylamino, ethylamino, propylamino, trifluoroethylamino.

[0053] Fifthly, the present invention provides a preparation method of the isoxazoline compound shown in formula (I), and the preparation method includes:

[0054] (1) In a first solvent, in the presence of a basic substance A, reacting the compound IV and the compound V to obtain the compound I;

[0055] Wherein, the compound V has the structure shown in formula (V), the compound IV has the structure shown in formula (IV), the compound III has the structure shown in formula (III), and the compound I has the structure shown in formula (I),

[0056]

[0057] In formula (I), formula (IV) and formula (V),

[0058] X 1 and X 3 Each independently selected from F, Cl, Br, I or CF3 ;

[0059] X 2 is selected from H, F, Cl, Br, I or CF 3 ;

[0060] R 1 is selected from hydrogen, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, methoxymethyl, methoxyethyl, ethoxymethyl, ethoxyethyl, trifluoromethyl, trichloromethyl, trifluoroethyl or trifluoromethoxymethyl, C 1 -C 6 alkylcarbonyl, halo C 1 -C 6 alkylcarbonyl, C 3 -C 6 cycloalkylcarbonyl, C 3 -C 6 cycloalkylmethylcarbonyl, C 1 -C 6 alkoxycarbonyl, halo C 1 -C 6 alkoxycarbonyl, C 1 -C 4 alkoxy C 1 -C 2 alkylcarbonyl, halo C 1 -C 4 alkoxy C 1 -C 2 alkylcarbonyl, C 1 -C 6 alkyl oxalyl, halo C 1 -C 6 alkyl oxalyl, C 1 -C 4 alkoxy oxalyl, halo C 1 -C 4 alkoxy oxalyl, C 1 -C 4 alkylsulfonyl, halo C 1 -C 4 alkylsulfonyl, C 1 -C 4 alkylsulfinyl, halo C 1 -C 4 alkylsulfinyl, halogen-substituted or unsubstituted benzoyl, halogen-substituted or unsubstituted benzenesulfonyl, carbonyl substituted by a five- or six-membered heteroaromatic ring containing 1-2 heteroatoms selected from O, S or N;

[0061] R 2 is selected from C 1 -C 3 alkyl, halo C 1 -C3 Alkyl;

[0062] R 3 Selected from C 1 -C 3 Alkoxy, halo C 1 -C 3 Alkoxy, C 1 -C 3 Alkylamino, halo C 1 -C 3 Alkylamino;

[0063] L is selected from chlorine, bromine, iodine, mesyl, trifluoromethanesulfonyl, benzenesulfonyl or p-toluenesulfonyl.

[0064] In some embodiments, the present invention provides a method for preparing a compound represented by formula (IV), the preparation method comprising:

[0065] (1) Reacting compound II and compound III in a second solvent in the presence of a condensing agent A to obtain compound IV;

[0066] Wherein, the compound IV has the structure represented by formula (IV), the compound III has the structure represented by formula (III), and the compound II has the structure represented by formula (II),

[0067]

[0068] In formula (II), formula (III) and formula (IV),

[0069] X 1 and X 3 Each independently is selected from F, Cl, Br, I or CF 3 ;

[0070] X 2 Is selected from H, F, Cl, Br, I or CF 3 ;

[0071] R 2 Selected from C 1 -C 6 Alkyl, halo C 1 -C 6 Alkyl;

[0072] R 3 Selected from amino, C 1 -C 6 Alkoxy, halo C 1 -C 6 Alkoxy, C 1 -C 6 Alkylamino, halo C 1 -C6 Alkylamine group;

[0073] In some embodiments, the present invention provides a method for preparing a compound represented by formula (IV):

[0074] (1) In a third solvent, in the presence of a condensing agent B, reacting compound VI and compound III to obtain compound VII;

[0075] (2) In a fourth solvent, in the presence of a basic substance B, reacting the compound VII and compound VIII to obtain compound IX or a mixture of compound IX and compound X;

[0076] (3) In a fifth solvent, in the presence of a basic substance C or a dehydrating agent, reacting the compound IX to obtain compound X; Step (3) and step (2) can be carried out in the same reaction system or step by step;

[0077] (4) In a sixth solvent, in the presence of a basic substance D, with or without a catalyst, reacting with hydroxylamine or its salt to obtain compound IV;

[0078] Wherein, the compound VI has the structure represented by formula (VI), the compound III has the structure represented by formula (III), the compound VII has the structure represented by formula (VII), the compound VIII has the structure represented by formula (VIII), the compound IX has the structure represented by formula (IX), the compound X has the structure represented by formula (X), and the compound IV has the structure represented by formula (IV);

[0079]

[0080] In formula (VIII), formula (IX), formula (X) and formula (IV),

[0081] X 1 and X 3 each independently selected from F, Cl, Br, I or CF 3 ;

[0082] X 2 is selected from H, F, Cl, Br, I or CF 3 ;

[0083] R 2 is selected from C 1 -C 6 alkyl, halo C 1 -C 6 alkyl;

[0084] R 3 is selected from amino, C1 -C 6 alkoxy, halo-C 1 -C 6 alkoxy, C 1 -C 6 alkylamino, halo-C 1 -C 6 alkylamino.

[0085] In some typical embodiments, the condensing agent A and the condensing agent B are selected from one or more of dicyclohexylcarbodiimide, 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride, 2-(7-azabenzotriazol)-N,N,N',N'-tetramethyluronium hexafluorophosphate, thionyl chloride or oxalyl chloride;

[0086] In some typical embodiments, the first solvent, the second solvent, the third solvent, the fourth solvent, the fifth solvent and the sixth solvent are each independently selected from one or more of toluene, xylene, dichloromethane, dichloroethane, acetonitrile, N,N-dimethylformamide, tetrahydrofuran and acetone;

[0087] In some typical embodiments, the basic substance A, the basic substance A, the basic substance C and the basic substance D are selected from one or more of triethylamine, diisopropylethylamine, pyridine, N-methylmorpholine, sodium carbonate, potassium carbonate, sodium hydroxide, potassium hydroxide, sodium bicarbonate, potassium bicarbonate, sodium hydride and sodium amide;

[0088] In some typical embodiments, the dehydrating agent is selected from acetic anhydride, propionic anhydride, thionyl chloride, acetyl chloride, phosphorus oxychloride.

[0089] In some embodiments, the molar ratio of the compound II to the compound III is 1:0.8 - 1.5.

[0090] In some embodiments, the molar ratio of the compound IV to the compound V is 1:0.7 - 1.5.

[0091] In some embodiments, the molar ratio of the compound II to the condensing agent is 1:0.8 - 1.5.

[0092] In some embodiments, the molar ratio of the compound IV to the basic substance is 1:0.7 - 1.5.

[0093] In some embodiments, the temperature of the first reaction is -10°C to the boiling point of the first solvent, and the reaction time is 10 min - 48 h.

[0094] In some preferred embodiments, the temperature of the first reaction is from -10°C to 210°C, preferably from 0°C to 150°C, more preferably from 10 to 100°C; the time is from 0.5 to 24 h, preferably from 1 to 12 h, more preferably from 2 to 6 h.

[0095] In some embodiments, the temperature of the second reaction is from -10°C to the boiling point of the second solvent, and the reaction time is from 10 min to 48 h.

[0096] In some preferred embodiments, the temperature of the second reaction is from -10°C to 210°C, preferably from 0°C to 150°C, more preferably from 10 to 100°C; the time is from 0.5 to 24 h, preferably from 1 to 12 h, more preferably from 2 to 6 h.

[0097] In a sixth aspect, the present invention provides an application of the aforementioned compound or a compound prepared by the aforementioned preparation method in controlling invertebrate pests, and the invertebrate pests are pests of the family Acaridae, insects, and / or nematodes.

[0098] In some embodiments, the method for controlling invertebrate pests includes: directly or indirectly applying an insecticidally effective amount of at least one of the aforementioned compounds or a compound prepared by the aforementioned preparation method to the invertebrate pests to be controlled and / or the medium on which they grow.

[0099] In some typical embodiments, the method includes: treating a plant on which invertebrate pests grow with an insecticidally effective amount of at least one of the isoxazoline compounds.

[0100] In a seventh aspect, the present invention provides an agricultural composition, which comprises at least one of the aforementioned compounds or a compound prepared by the aforementioned preparation method and at least one liquid carrier or solid carrier.

[0101] The present invention has no particular limitation on the liquid carrier or solid carrier, as long as it can meet the requirements of the present invention. In the composition, the concentration of the isoxazoline compound provided by the present invention is from 0.5 to 35 mg / L. Preferably, the concentration of the isoxazoline compound is from 1 to 30 mg / L, and more preferably, the concentration of the isoxazoline compound is from 10 to 25 mg / L.

[0102] In the present invention, the liquid carrier can be water, various aromatic hydrocarbons, aliphatic hydrocarbons, ketones, ethers, etc., such as one or several of toluene, xylene, acetone, cyclohexanone, xylene, benzene, cyclohexane, isopropanol, ethylene glycol, sorbitol, methanol, ethanol, butanol, dimethylformamide, N-methylpyrrolidone, decalin, machine oil, petroleum ether, cyclohexanone, methyl oleate, methylated soybean oil, etc.; the solid carrier can include natural or synthetic clays and silicates, and the solid carriers suitable for powders can include naturally formed rock powders, chalk, quartz, clay, montmorillonite, silica white, diatomaceous earth, pumice, gypsum, talc, bentonite, kaolin, pottery clay and synthetic ground minerals (such as finely dispersed silicic acid or alumina). Suitable particulate carriers can include crushed and sized natural rocks such as calcite, marble, pumice, sepiolite and dolomite and synthetic particles made from powders of organic and inorganic substances.

[0103] In the present invention, the composition can be applied in the form of a formulation. Among them, the isoxazoline compound provided by the present invention is dissolved or dispersed in a carrier as an active ingredient, or formulated into a formulation to be more easily dispersed when used for insecticidal and acaricidal purposes. For example: the composition can be made into a wettable powder, water dispersible granule, suspension concentrate, emulsion in water, aqueous solution or emulsifiable concentrate, etc. In the composition, at least one liquid or solid carrier is added, and when necessary, a suitable surfactant can also be added. Among them, the surfactant can include dodecylbenzenesulfonate, fatty alcohol sulfate, Tween, agricultural emulsifier, polyoxyethylene sorbitan ether, polyoxyethylene fatty alcohol ether, lignosulfonate, alkylnaphthalenesulfonate, etc.

[0104] In the present invention, for certain applications, such as in agriculture, one or more other insecticides, acaricides, fungicides, herbicides, plant growth regulators or fertilizers, etc. can be added to the agricultural composition of the present invention, whereby additional advantages and effects can be produced.

[0105] In the present invention, the isoxazoline compound also includes its derivatives, but the compounds included in the derivatives of the present invention are by no means limited to these compounds only.

[0106] In the present invention, the so-called agriculturally acceptable salts refer to salts formed by isoxazoline compounds and inorganic acids or organic acids. As inorganic acids, for example, hydrochloric acid, sulfuric acid, hydrobromic acid, etc., and as organic acids, for example, formic acid, acetic acid, methanesulfonic acid, fumaric acid, maleic acid, etc.

[0107] In the present invention, the compound can be used to protect important crops, livestock, etc. in agriculture and horticulture from being damaged by or less damaged by acarids.

[0108] In the present invention, in order to obtain an ideal effect, in some applications, the dosage of the compound varies due to various factors, such as the compound used, the pre-protected crop, the type of pest, the degree of infestation, the application method, the application environment, the dosage form applied, and other factors.

[0109] The present invention has no particular limitation on the direct or indirect manner, as long as the purpose of controlling invertebrate pests can be achieved. For example, the direct manner may include directly contacting a substance containing the isoxazoline compound component with invertebrate pests (including invertebrate pests directly consuming a substance containing the isoxazoline compound component, the body surface of invertebrate pests directly contacting a substance containing the isoxazoline compound component, etc.); the indirect manner may include treating the places where invertebrate pests appear (their habitats or their breeding grounds or the plants, soil where invertebrate pests grow) with a substance containing the isoxazoline compound component or treating their food chain with a substance containing the isoxazoline compound component.

[0110] In the present invention, the invertebrate pests are pests of the family Tetranychidae, insects, and / or nematodes.

[0111] In the present invention, the plants are plants of the Gymnospermae and / or Angiospermae, preferably at least one of plants of the Rutaceae, Solanaceae, Brassicaceae, and Rosaceae.

[0112] The present invention has no particular limitation on the insecticidally effective amount. For example, it may refer to a dosage of 5 grams to 3 kilograms of the isoxazoline compound per hectare, which can provide sufficient control. Preferably, the insecticidally effective amount can be 8 grams to 1000 grams per hectare, and more preferably, the insecticidally effective amount is 10 grams to 300 grams per hectare.

[0113] Through the above technical solutions, the beneficial technical effects obtained by the present invention are as follows:

[0114] (1) The isoxazoline compounds and their agriculturally acceptable salts provided by the present invention show high control effects against a variety of pests, especially against tetranychids represented by Tetranychus cinnabarinus, Tetranychus urticae, Tetranychus kanzawai, Panonychus citri, etc., Lepidoptera insects represented by Plutella xylostella, thrips, flea beetles, etc. They can be used to control a variety of pests and mites, have high acaricidal and insecticidal activities, and have good application prospects.

[0115] (2) The isoxazoline compounds provided by the present invention have high activity against the following invertebrate pests (the objects listed below are only used to illustrate the present invention, but not to limit the present invention): Tetranychidae (such as Tetranychus cinnabarinus, Panonychus citri, Tetranychus urticae, Panonychus ulmi, Tetranychus kanzawai, Tetranychus viennensis), Eriophyidae, Tarsonemidae, Tenuipalpidae, Aphididae (such as Myzus persicae), Lepidoptera insects (such as Plutella xylostella, Spodoptera exigua, Chilo suppressalis, etc.), Thysanoptera insects (such as Frankliniella occidentalis, etc.) and Coleoptera insects (such as Phyllotreta striolata), etc. Therefore, the isoxazoline compounds of the present invention can be used in agriculture or other fields for preparing insecticidal and acaricidal drugs.

[0116] It should be clear that within the scope disclosed in the present invention, various transformations and modifications can be made. Compared with the prior art, the present invention has at least the following advantages:

[0117] The isoxazoline compounds provided by the present invention show excellent insecticidal and acaricidal activities against a variety of pests, especially Tetranychidae represented by Tetranychus urticae, Tetranychus kanzawai, Panonychus citri, etc. and Lepidoptera insects represented by Plutella xylostella.

[0118] The present invention provides a brand-new preparation method for isoxazoline compounds. This method has simple process, mild conditions, high yield and high purity, and is suitable for the industrial production of isoxazoline compounds. Detailed implementation manners

[0119] In the ranges disclosed herein, the endpoints and any values are not limited to the exact ranges or values. These ranges or values should be understood to include values close to these ranges or values. For numerical ranges, between the endpoint values of each range, between the endpoint values of each range and a single point value, and between single 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.

[0120] To further understand the present invention, the technical solutions in the embodiments of the present invention will be clearly and completely described below in conjunction with the embodiments of the present invention. Obviously, the described embodiments are only a part of the embodiments of the present invention, rather than all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without creative efforts shall fall within the scope of protection of the present invention.

[0121] In the following examples, unless otherwise specified, all raw materials used are commercially available and of analytical purity. The present invention relates to the preparation of chiral compounds, which can be synthesized using chiral raw materials or racemic raw materials, and then separated by chiral column chromatography. The chiral column chromatography separation method uses the commonly used separation methods in the art. The following examples are the preparation methods of some compounds of the present invention. The preparation of other compounds can be transformed according to the commonly used raw materials in the art and obtained by known methods.

[0122] Example 1

[0123] Synthesis of methyl 4-(5-(3,5-dichloro-4-fluorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methylbenzoyl)alaninate (Compound I-1):

[0124]

[0125] 4-(5-(3,5-Dichloro-4-fluorophenyl)-5-trifluoromethyl-4,5-dihydroisoxazol-3-yl)-2-methylbenzoic acid (0.872 g, 2 mmol) was added to 1,2-dichloroethane (5 mL). Then, 2-(7-azabenzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate (1.14 g, 3 mmol) and N,N-diisopropylethylamine (0.517 g, 4 mmol) were added successively. After stirring at room temperature for 0.5 h, methyl 2-aminopropionate (0.25 g, 2.4 mmol) was added, and the reaction was carried out at room temperature for 5 h. The system was extracted with water twice, and the organic phase was washed, dried, and rotary evaporated to dryness. It was purified by column chromatography to obtain 0.56 g of white solid.

[0126] 1 H NMR (400 MHz, CDCl3) δ 7.59 (d, J = 6.0 Hz, 2H), 7.52–7.46 (m, 2H), 7.40 (d, J = 8.6 Hz, 1H), 6.12 (t, J = 5.7 Hz, 1H), 4.17–4.04 (m, 1H), 3.68 (s, 3H), 3.49 (q, J = 6.7 Hz, 2H), 2.47 (d, J = 3.2 Hz, 3H), 1.96 (p, J = 7.0 Hz, 3H).

[0127] MS: [M+H] + : 521.43, 523.47.

[0128] Example 2

[0129] Synthesis of ethyl (4-(5-(3,5-dichloro-4-fluorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methylbenzoyl)alaninate (Compound I-2):

[0130]

[0131] 4-(5-(3,5-Dichloro-4-fluorophenyl)-5-trifluoromethyl-4,5-dihydroisoxazol-3-yl)-2-methylbenzoic acid (0.872 g, 2 mmol) was added to 1,2-dichloroethane (5 mL). Subsequently, 2-(7-azabenzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate (1.14 g, 3 mmol) and N,N-diisopropylethylamine (0.517 g, 4 mmol) were added. After stirring at room temperature for 0.5 h, ethyl 2-aminopropionate (0.28 g, 2.4 mmol) was added, and the reaction was carried out at room temperature for 5 h. The system was extracted with water twice, and the organic phase was washed with water, dried, and evaporated to dryness under reduced pressure. Purification by column chromatography gave 0.65 g of a white solid.

[0132] 1 H NMR (400 MHz, CDCl3) δ 7.59 (d, J = 6.0 Hz, 2H), 7.51 (d, J = 7.7 Hz, 2H), 7.47 (d, J = 8.0 Hz, 1H), 6.36 (d, J = 7.4 Hz, 1H), 4.76 (p, J = 7.2 Hz, 1H), 4.25 (q, J = 7.1 Hz, 2H), 4.09 (d, J = 17.3 Hz, 1H), 3.69 (d, J = 17.2 Hz, 1H), 2.48 (s, 3H), 1.53 (d, J = 7.2 Hz, 3H), 1.32 (t, J = 7.1 Hz, 3H)

[0133] MS: [M+H] + : 535.57, 537.55.

[0134] Example 3

[0135] Synthesis of 4-(5-(3,5-dichloro-4-fluorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methyl-N-(1-(methylamino)-1-oxopropan-2-yl)benzamide (Compound I-3):

[0136]

[0137] 4-(5-(3,5-Dichloro-4-fluorophenyl)-5-trifluoromethyl-4,5-dihydroisoxazol-3-yl)-2-methylbenzoic acid (0.872 g, 2 mmol) was added to 1,2-dichloroethane (5 mL). 2-(7-Azabenzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate (1.14 g, 3 mmol) and N,N-diisopropylethylamine (0.517 g, 4 mmol) were added successively. After stirring at room temperature for 0.5 h, 2-amino-N-methylpropanamide (0.245 g, 2.4 mmol) was added, and the reaction was carried out at room temperature for 5 h. The system was extracted with water twice, and the organic phase was washed, dried, and evaporated to dryness by rotary evaporation. It was purified by column chromatography to obtain 0.38 g of a white solid.

[0138] 1 1H NMR (400 MHz, CDCl3) δ 7.59 (d, J = 6.0 Hz, 2H), 7.55–7.41 (m, 3H), 6.53 (d, J = 6.9 Hz, 1H), 6.05 (s, 1H), 4.66–4.58 (m, 1H), 4.08 (d, J = 17.2 Hz, 1H), 3.68 (d, J = 17.2 Hz, 1H), 2.87 (d, J = 4.0 Hz, 3H), 2.46 (s, 3H), 1.49 (d, J = 6.5 Hz, 3H).

[0139] MS: [M+H] + : 521.43, 523.41.

[0140] Example 4

[0141] Synthesis of methyl 4-(5-(3,5-dichloro-4-fluorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methylbenzoyl)-D-alaninate (Compound I-17):

[0142]

[0143] 4-(5-(3,5-Dichloro-4-fluorophenyl)-5-trifluoromethyl-4,5-dihydroisoxazol-3-yl)-2-methylbenzoic acid (0.872 g, 2 mmol) was added to 5 mL of 1,2-dichloroethane. 2-(7-Azabenzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate (1.14 g, 3 mmol) and N,N-diisopropylethylamine (0.65 g, 5 mmol) were added successively. After stirring at room temperature for 0.5 h, D-alanine methyl ester hydrochloride (0.34 g, 2.4 mmol) was added, and the reaction was carried out at room temperature for 5 h. The system was extracted with water twice, and the organic phase was washed, dried, and evaporated to dryness by rotary evaporation. It was purified by column chromatography to obtain 0.29 g of a white solid.

[0144] 1 1H NMR (400 MHz, CDCl3) δ 7.59 (d, J = 6.0 Hz, 2H), 7.54–7.43 (m, 3H), 6.36 (d, J = 7.5 Hz, 1H), 4.78 (p, J = 7.2 Hz, 1H), 4.16–4.08 (m, 1H), 3.80 (s, 3H), 3.69 (d, J = 17.2 Hz, 1H), 2.48 (s, 3H), 1.53 (d, J = 7.1 Hz, 3H).

[0145] MS: [M+H] + : 521.43, 523.41.

[0146] Example 5

[0147] Synthesis of methyl 4-(5-(3,5-dichloro-4-fluorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methylbenzoyl)-L-alaninate (Compound I-18):

[0148]

[0149] 4-(5-(3,5-Dichloro-4-fluorophenyl)-5-trifluoromethyl-4,5-dihydroisoxazol-3-yl)-2-methylbenzoic acid (0.872 g, 2 mmol) was added to 1,2-dichloroethane (5 mL). Subsequently, 2-(7-azabenzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate (1.14 g, 3 mmol) and N,N-diisopropylethylamine (0.517 g, 4 mmol) were added. After stirring at room temperature for 0.5 h, (S)-methyl 2-aminopropanoate (0.25 g, 2.4 mmol) was added, and the reaction was carried out at room temperature for 5 h. The system was extracted with water twice, and the organic phase was washed with water, dried, and evaporated to dryness under reduced pressure. Purification by column chromatography gave 0.62 g of a white solid.

[0150] 1 1H NMR (400 MHz, CDCl3) δ 7.59 (d, J = 6.0 Hz, 2H), 7.51 (dd, J = 7.8, 1.3 Hz, 2H), 7.47 (d, J = 8.6 Hz, 1H), 6.34 (d, J = 7.5 Hz, 1H), 4.79 (p, J = 7.2 Hz, 1H), 4.08 (d, J = 17.2 Hz, 1H), 3.80 (s, 3H), 3.69 (d, J = 17.2 Hz, 1H), 2.48 (s, 3H), 1.53 (d, J = 7.2 Hz, 3H).

[0151] MS: [M+H] + : 521.43, 523.47.

[0152] Example 6

[0153] Synthesis of methyl 4-(5-(3,4-dichloro-5-(trifluoromethyl)phenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methylbenzoyl)-D-alaninate (Compound I-22):

[0154]

[0155] 4-(5-(3,4-Dichloro-5-(trifluoromethyl)phenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methylbenzoic acid (0.97 g, 2 mmol) was added to 1,2-dichloroethane (5 mL). Subsequently, 2-(7-azabenzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate (1.14 g, 3 mmol) and N,N-diisopropylethylamine (0.65 g, 5 mmol) were added successively. After stirring at room temperature for 0.5 h, methyl D-alaninate hydrochloride (0.34 g, 2.4 mmol) was added, and the reaction was carried out at room temperature for 2 h. The system was extracted with water twice, and the organic phase was washed with water, dried, and evaporated to dryness under reduced pressure. The residue was purified by column chromatography to obtain 0.52 g of a white solid.

[0156] 1 H NMR (400 MHz, CDCl 3 ) δ 7.95 (d, J = 1.9 Hz, 1H), 7.84 (s, 1H), 7.59–7.44 (m, 3H), 6.33 (d, J = 7.4 Hz, 1H), 4.86–4.71 (m, 1H), 4.14 (d, J = 17.2 Hz, 1H), 3.80 (s, 3H), 3.70 (d, J = 17.2 Hz, 1H), 2.49 (s, 3H), 1.53 (d, J = 7.2 Hz, 6H).

[0157] MS: [M+H] + : 571.50, 573.59.

[0158] Example 7

[0159] Synthesis of methyl 4-(5-(3,5-dichloro-4-fluorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methylbenzoyl)-D-alaninate (Compound I-17):

[0160] Step 1: Preparation of methyl (4-acetyl-2-methylbenzoyl)-D-alaninate

[0161]

[0162] 4-Acetyl-2-methylbenzoic acid (17.8 g, 100 mmol) was added to 1,2-dichloroethane (200 mL), DMF (0.1 mL) was added, thionyl chloride (16.7 g, 140 mmol) was added, and the mixture was stirred at room temperature for 5 hours. Then the reaction solution was concentrated under reduced pressure at room temperature for 1 hour. Dichloroethane (100 mL) was added to the reaction solution, triethylamine (25.2 g, 250 mmol) was added, and D-alanine methyl ester hydrochloride (18.1 g, 130 mmol) was added under an ice bath. After continuing the reaction for 2 hours, 300 mL of water and 100 mL of dichloroethane were added to the reaction solution. After extraction and separation, the organic phase was concentrated to dryness under reduced pressure, and 20.2 g of a white solid was obtained by column chromatography purification.

[0163] Step 2: Preparation of (Z)-(4-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-2-enyl)-2-methylbenzoyl)-D-alanine methyl ester

[0164]

[0165] (4-Acetyl-2-methylbenzoyl)-D-alanine methyl ester (13.2 g, 100 mmol) was added to 1,2-dichloroethane (100 mL), 1-(3,5-dichloro-4-fluorophenyl)-2,2,2-trifluoroethan-1-one (26.1 g, 100 mmol) was added, potassium carbonate (13.8 g, 100 mmol) and triethylamine (1 g, 10 mmol) were added. After heating and reacting for 5 hours, the reaction solution was concentrated to dryness under reduced pressure, washed with water, and the solid was dried to obtain an off-white powder solid. 16.7 g of an off-white solid was obtained by column chromatography purification.

[0166] Step 3: Preparation of 4-(5-(3,5-dichloro-4-fluorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methylbenzoyl)-D-alanine methyl ester (Compound I-17)

[0167]

[0168] (Z)-(4-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-2-enyl)-2-methylbenzoyl)-D-alanine methyl ester (1.12 g, 2 mmol) was added to 1,2-dichloroethane (10 mL), hydroxylamine hydrochloride (0.21 g, 3 mmol) and TBAB (0.05 g) were added, 40% aqueous sodium hydroxide solution (0.6 g, 6 mmol) was added, and the mixture was stirred at room temperature for 1 hour. Then 30 mL of 1,2-dichloroethane and 30 mL of water were added to the reaction solution. After extraction and separation, the organic phase was concentrated to dryness under reduced pressure, and 0.78 g of a white solid was obtained by column chromatography purification.

[0169] 1 1H NMR (400 MHz, CDCl3) δ 7.59 (d, J = 6.0 Hz, 2H), 7.54–7.43 (m, 3H), 6.36 (d, J = 7.5 Hz, 1H), 4.78 (p, J = 7.2 Hz, 1H), 4.16–4.08 (m, 1H), 3.80 (s, 3H), 3.69 (d, J = 17.2 Hz, 1H), 2.48 (s, 3H), 1.53 (d, J = 7.1 Hz, 3H).

[0170] MS: [M+H] + : 521.43, 523.41.

[0171] Example 8

[0172] Synthesis of methyl 4-(5-(3,4-dichloro-5-(trifluoromethyl)phenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methylbenzoyl)-D-alaninate (Compound I-22):

[0173] Step 1: Preparation of (Z / E)-(4-(3-(3,4-dichloro-5-(trifluoromethyl)phenyl)-4,4,4-trifluorobut-2-en-1-yl)-2-methylbenzoyl)-D-alaninate

[0174]

[0175] Using 1-(3,4-dichloro-5-trifluoromethylphenyl)-2,2,2-trifluoroethan-1-one in place of 1-(3,5-dichloro-4-fluorophenyl)-2,2,2-trifluoroethan-1-one, and referring to the method described in Step 2 of Example 7, Compound X-2, a white solid powder, was prepared.

[0176] Step 2: Preparation of methyl 4-(5-(3,4-dichloro-5-(trifluoromethyl)phenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methylbenzoyl)-D-alaninate (Compound I-22)

[0177]

[0178] Using (Z / E)-(4-(3-(3,4-dichloro-5-(trifluoromethyl)phenyl)-4,4,4-trifluorobut-2-en-1-yl)-2-methylbenzoyl)-D-alaninate in place of (Z / E)-(4-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-2-en-1-yl)-2-methylbenzoyl)-D-alaninate, and referring to the method described in Step 3 of Example 7, Compound I-22, a white solid powder, was prepared.

[0179] 1 H NMR(400MHz,CDCl 3 )δ7.95(d,J = 1.9Hz,1H),7.84(s,1H),7.59–7.44(m,3H),6.33(d,J = 7.4Hz,1H),4.86–4.71(m,1H),4.14(d,J = 17.2Hz,1H),3.80(s,3H),3.70(d,J = 17.2Hz,1H),2.49(s,3H),1.53(d,J = 7.2Hz,6H).

[0180] MS:[M + H] + :571.50,573.59。

[0181] Example 9

[0182] Synthesis of methyl 4 - ((S) - 5 - (3,5 - dichloro - 4 - fluorophenyl) - 5 - (trifluoromethyl) - 4,5 - dihydroisoxazol - 3 - yl) - 2 - methylbenzoyl) - D - alaninate (Compound I - 19):

[0183] Step 1: Preparation of methyl (S) - 4 - (3 - (3,5 - dichloro - 4 - fluorophenyl) - 4,4,4 - trifluoro - 3 - hydroxybutanoyl) - 2 - methylbenzoate

[0184] To a solution of 1 - (3,5 - dichloro - 4 - fluorophenyl) - 2,2,2 - trifluoro - ethanone (10.44 g, 40 mmol) in toluene (42 mL) was added 1 - [3,5 - bis(trifluoromethyl)phenyl] - 3 - [(1R,2R) - (-) - 2 - (dimethylamino)cyclohexyl]thiourea (1.5 g, 3.65 mmol) and methyl 4 - acetyl - 2 - methyl - benzoate (7.0 g, 36.5 mmol), and the mixture was stirred overnight at 20 to 25 °C. After the reaction was complete, the solvent was removed by evaporation under reduced pressure, and the residue was purified by column chromatography to give 4.5 g of a white solid, which is the title compound.

[0185] 1 H NMR(400MHz,Chloroform - d)δ8.00(d,J = 8.6Hz,1H),7.81–7.74(m,2H),7.56(d,J = 6.1Hz,2H),5.66(s,1H),3.94(s,3H),3.84(d,J = 17.6Hz,1H),3.69(d,J = 17.6Hz,1H),2.66(s,3H).

[0186] MS:[M + Na]+ : 475.12, 477.36.

[0187] Step 2: Preparation of Methyl (S)-4-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluoro-3-hydroxy-1-(hydroxyimino)butyl)-2-methylbenzoate

[0188]

[0189] At 20 to 25 °C, solid hydroxylamine hydrochloride (0.31 g, 4.4 mmol) was added to a mixture of methyl (S)-4-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluoro-3-hydroxybutanoyl)-2-methylbenzoate (1 g, 2.2 mmol) and 2,6-lutidine (7 ml). After stirring overnight, 10 ml of ice water was added to quench the reaction, and the mixture was extracted with dichloromethane. The combined organic layers were washed with aqueous hydrochloric acid solution (6 N) and water, dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo. 0.6 g of a light brown oil was obtained, which was the title compound.

[0190] 1 H NMR (400 MHz, Chloroform-d) δ 7.89 (d, J = 8.1 Hz, 1H), 7.41 (d, J = 6.1 Hz, 2H), 7.06 (dd, J = 8.2, 1.8 Hz, 1H), 6.99 (d, J = 1.8 Hz, 1H), 5.23 (s, 1H), 3.91 (s, 3H), 3.32 (d, J = 1.1 Hz, 2H), 2.56 (s, 3H).

[0191] MS: [M+Na] + : 490.49, 492.46.

[0192] Step 3: Preparation of Methyl (S)-4-(5-(3,5-dichloro-4-fluorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methylbenzoate

[0193]

[0194] To a solution of methyl (S)-4-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluoro-3-hydroxy-1-(hydroxyimino)butyl)-2-methylbenzoate (1 g, 2.14 mmol) in anhydrous tetrahydrofuran (10 ml) was added triphenylphosphine (0.84 g, 3.21 mmol). Diethyl azodicarboxylate (0.56 g, 3.21 mmol) was added portionwise below 20 °C, and the mixture was stirred overnight at room temperature. After the reaction was complete, 20 ml of water was added to the system, and the mixture was extracted with dichloromethane and separated. The organic layer was dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo. The concentrate was purified by flash chromatography on silica gel to give 0.5 g of a colorless oil, which was the title compound.

[0195] 1 H NMR(400MHz,CDCl 3 )δ8.08–7.92(m,1H),7.59(d,J=6.0Hz,2H),7.53(d,J=4.5Hz,2H),4.10(d,J=17.2Hz,1H),3.91(s,3H),3.70(d,J=17.2Hz,1H),2.63(s,3H).

[0196] MS:[M+H] + :450.50,452.54。

[0197] Step 4: Preparation of (S)-4-(5-(3,5-dichloro-4-fluorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methylbenzoic acid

[0198]

[0199] To a solution of methyl (S)-4-(5-(3,5-dichloro-4-fluorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methylbenzoate (0.5 g, 1.11 mmol) in tetrahydrofuran (3 ml) was added 10% aqueous lithium hydroxide (0.5 g). The reaction was heated to 70 °C and stirred for 5 h until the reaction was complete. The system was cooled to room temperature, and the pH was adjusted to 2 - 3 with 6M aqueous hydrochloric acid. After extraction with dichloromethane and drying, the solvent was removed to give 0.3 g of a light brown oil.

[0200] MS:[M+H] - :434.57,436.56。

[0201] Step 5: Preparation of methyl 4-((S)-5-(3,5-dichloro-4-fluorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methylbenzoyl)-D-alaninate (Compound I-19)

[0202]

[0203] Replace 4-(5-(3,5-dichloro-4-fluorophenyl)-5-trifluoromethyl-4,5-dihydroisoxazol-3-yl)-2-methylbenzoic acid with (S)4-(5-(3,5-dichloro-4-fluorophenyl)-5-trifluoromethyl-4,5-dihydroisoxazol-3-yl)-2-methylbenzoic acid, and prepare Compound I-19, a white powdery solid, according to the method described in Example 4.

[0204] 1 H NMR(400MHz,CDCl3)δ7.59(d,J=6.0Hz,2H),7.54–7.43(m,3H),6.36(d,J=7.5Hz,1H),4.78(m,1H),4.16–4.08(m,1H),3.80(s,3H),3.69(d,J=17.2Hz,1H),2.48(s,3H),1.53(d,J=7.1Hz,3H).

[0205] MS:[M+H] + :521.43, 523.41.

[0206] Example 10

[0207] Synthesis of methyl 4-((S)-5-(3,4-dichloro-5-(trifluoromethyl)phenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methylbenzoyl)-D-alaninate (Compound I-26):

[0208]

[0209] Replace 4-(5-(3,4-dichloro-5-(trifluoromethyl)phenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methylbenzoic acid with (S)4-(5-(3,4-dichloro-5-(trifluoromethyl)phenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methylbenzoic acid, and prepare the title compound I-26, a white powdery solid, according to the method described in Example 6.

[0210] 1 H NMR(400MHz,CDCl 3)δ 7.95 (d, J = 1.9 Hz, 1H), 7.84 (s, 1H), 7.52 (d, J = 7.1 Hz, 2H), 7.49 (s, 1H), 6.33 (d, J = 7.4 Hz, 1H), 4.86–4.71 (m, 1H), 4.14 (d, J = 17.2 Hz, 1H), 3.80 (s, 3H), 3.70 (d, J = 17.2 Hz, 1H), 2.49 (s, 3H), 1.53 (d, J = 7.2 Hz, 3H).

[0211] MS: [M + H] + : 571.50, 573.59。

[0212] Application Example 1

[0213] Activity test against Tetranychus cinnabarinus:

[0214] Dissolve the compound to be tested in acetone and dilute it with an aqueous solution of 0.1 wt% Tween 80 to the required concentration, with the acetone content not exceeding 5 wt%.

[0215] Remove one true leaf from the kidney bean seedlings that have grown to two true leaves, investigate the base number after inoculating Tetranychus cinnabarinus, and perform whole-plant spraying treatment with a hand-held sprayer. Each treatment is repeated 3 times (the application rate of the preparation is about 0.5 g). After treatment, observe in a constant-temperature observation room, and investigate the number of live mites 72 hours later to calculate the mortality rate. The experiment is repeated 3 times, and the number of Tetranychus cinnabarinus inoculated each time is 35 - 100.

[0216] Mortality rate % = (number of inoculated insects - number of live insects after treatment) ÷ number of inoculated insects × 100%.

[0217] In this test, Compounds I-1, I-3, I-4, I-5, I-15, I-16, I-17, I-18, I-21, I-22, I-23, I-27, and I-31 showed a mortality rate of over 90% against Tetranychus cinnabarinus at 3.125 ppm (3.125 mg / L) respectively.

[0218] As can be seen from the above, the isoxazoline compounds of the present invention still have a high acaricidal effect against Tetranychus cinnabarinus when used at a relatively low concentration.

[0219] According to the above method, select Compounds I-17, I-22, I-27, and I-31 and fluralaner respectively for parallel tests of acaricidal (against Tetranychus cinnabarinus). The test results are shown in Table 1 below.

[0220] Table 1:

[0221]

[0222] As can be seen from Table 1, the mortality rates of Compound I-17, Compound I-22, Compound I-27, and Compound I-31 three days after medication were significantly higher than those of the control agent, fluralaner. Therefore, when used at lower concentrations, I-17, Compound I-22, Compound I-27, and Compound I-31 of the present invention still have a high insecticidal effect on Tetranychus cinnabarinus.

[0223] Application Example 2

[0224] Diamondback moth activity test:

[0225] Test target: Diamondback moth (Plutella xylostella), 3rd instar larvae, sensitive strain reared indoors.

[0226] Test method: First, select fresh cabbage leaves cultivated in a greenhouse. Use a hole punch to make round leaf discs with a diameter of 3 cm from the cabbage leaves. According to the test design, in the order from low dose to high dose, immerse them in the prepared liquid medicine for 10 s. After natural air drying, place them in a 9-cm-diameter petri dish with filter paper, and introduce neat and healthy test insects, 10 insects per treatment, with 3 replicates per treatment. Additionally, set up a blank control.

[0227] In this test, Compound I-1, Compound I-3, Compound I-4, Compound I-5, Compound I-15, Compound I-16, Compound I-17, Compound I-18, Compound I-21, Compound I-22, Compound I-23, Compound I-27, and Compound I-31 showed a lethality rate of over 90% against diamondback moths at 0.78 ppm (0.78 mg / L) respectively.

[0228] According to the above method, parallel tests for killing diamondback moths were respectively conducted on Compound I-22, I-31, and fluralaner. The test results are shown in Table 2 below.

[0229] Table 2:

[0230]

[0231]

[0232] As can be seen from Table 2, at low concentrations (less than or equal to 0.333 ppm), the mortality rates of Compound I-22 and I-31 of the present invention three days after medication were significantly higher than those of the control compound, fluralaner. Therefore, when used at lower concentrations, Compound I-22 and I-31 of the present invention still have a high insecticidal effect on diamondback moths.

[0233] 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 combinations of each technical feature in any other suitable manner. 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 compound of formula (I) or an agriculturally acceptable salt thereof, or a stereoisomer thereof, wherein, X 1 and X 3 each independently selected from F, Cl, Br, I or CF 3 ; X 2 selected from H, F, Cl, Br, I or CF 3 ; R 1 Selected from hydrogen, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, methoxymethyl, methoxyethyl, ethoxymethyl, ethoxyethyl, trifluoromethyl, trichloromethyl, trifluoroethyl or trifluoromethoxymethyl, C 1 -C 6 alkylcarbonyl, halo C 1 -C 6 alkylcarbonyl, C 3 -C 6 cycloalkylcarbonyl, C 3 -C 6 cycloalkylmethylcarbonyl, C 1 -C 6 alkoxycarbonyl, halo C 1 -C 6 alkoxycarbonyl, C 1 -C 4 alkoxy C 1 -C 2 alkylcarbonyl, halo C 1 -C 4 alkoxy C 1 -C 2 alkylcarbonyl, C 1 -C 6 alkyl oxalyl, halo C 1 -C 6 alkyl oxalyl, C 1 -C 4 alkoxy oxalyl, halo C 1 -C 4 alkoxy oxalyl, C 1 -C 4 alkylsulfonyl, halo C 1 -C 4 alkylsulfonyl, C 1 -C 4 alkylsulfinyl, halo C 1 -C 4 alkylsulfinyl, halogen-substituted or unsubstituted benzoyl, halogen-substituted or unsubstituted benzenesulfonyl, carbonyl substituted by a five- or six-membered heteroaromatic ring containing 1-2 heteroatoms selected from O, S or N; R 2 selected from C 1 -C 3 alkyl, halo-C 1 -C 3 alkyl; R 3 selected from C 1 -C 3 alkoxy, halo C 1 -C 3 alkoxy, C 1 -C 3 alkylamino, halo C 1 -C 3 alkylamino.

2. The compound according to claim 1, characterized in that, X 1 and X 3 each independently selected from F, Cl or CF 3 ; X 2 is selected from H, F, Cl or CF 3 , wherein the following substitution cases are excluded for the compound: X 1 and X 3 are simultaneously selected from Cl, X 2 is selected from H; X 1 and X 2 selected from Cl, X 3 selected from CF 3 ; X 1 selected from CF 3 , X 2 and X 3 selected from Cl; Preferably, said X 1 , X 2 and X 3 are each independently selected from F, Cl or CF 3 , wherein the following substitution cases are excluded for the compound: X 1 and X 3 are simultaneously selected from Cl, X 2 is selected from H; X 1 and X 2 selected from Cl, X 3 selected from CF 3 ; X 1 selected from CF 3 、X 2 and X 3 selected from Cl. Preferably, the R 1 is selected from hydrogen, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, methoxymethyl, methoxyethyl, ethoxymethyl, ethoxyethyl, acetyl, propionyl, n-butyryl, cyclopropylcarbonyl, methoxycarbonyl, methoxyacetyl, methoxyacetyl, methoxyoxalyl, ethoxyoxalyl; R 2 selected from methyl, ethyl, chloromethyl; R 3 Selected from methoxy, ethoxy, methylamino, ethylamino, propylamino, trifluoroethylamino.

3. The following compound or an agriculturally acceptable salt thereof, or a stereoisomer thereof:

4. A compound having the structure of formula (X) or an agriculturally acceptable salt thereof, or a stereoisomer thereof, wherein, X 1 、 X 3 each independently selected from F, Cl or CF 3 ; X 2 selected from H, F, Cl or CF 3 ; R 2 selected from methyl, ethyl, chloromethyl; R 3 Selected from methoxy, ethoxy, methylamino, ethylamino, propylamino, trifluoroethylamino.

5. Use of the compound of formula (X) according to claim 4 in the preparation of an isoxazoline compound of formula (IV); wherein, X 1 、X 3 are each independently selected from F, Cl or CF 3 ; X 2 selected from H, F, Cl or CF 3 ; R 2 selected from methyl, ethyl, chloromethyl; R 3 Selected from methoxy, ethoxy, methylamino, ethylamino, propylamino, trifluoroethylamino.

6. A method for preparing a compound of formula (I), the preparation method comprises: (1) Reacting the compound IV and the compound V in a first solvent in the presence of a basic substance A to obtain the compound I; wherein, the basic substance A is selected from one or more of triethylamine, diisopropylethylamine, pyridine, N-methylmorpholine, sodium carbonate, potassium carbonate, sodium hydroxide, potassium hydroxide, sodium bicarbonate, potassium bicarbonate, sodium hydride and sodium amide; the first solvent is selected from one or more of toluene, xylene, dichloromethane, dichloroethane, acetonitrile, N,N-dimethylformamide, tetrahydrofuran and acetone; the compound V has the structure of formula (V), the compound IV has the structure of formula (IV), the compound III has the structure of formula (III), and the compound I has the structure of formula (I), L-R 1 Formula (V); In formula (I), formula (IV) and formula (V), X 1 and X 3 each independently selected from F, Cl, Br, I or CF 3 ; X 2 selected from H, F, Cl, Br, I or CF 3 ; R 1 Selected from hydrogen, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, methoxymethyl, methoxyethyl, ethoxymethyl, ethoxyethyl, trifluoromethyl, trichloromethyl, trifluoroethyl or trifluoromethoxymethyl, C 1 -C 6 alkylcarbonyl, halogenated C 1 -C 6 alkylcarbonyl, C 3 -C 6 cycloalkylcarbonyl, C 3 -C 6 cycloalkylmethylcarbonyl, C 1 -C 6 alkoxycarbonyl, halogenated C 1 -C 6 alkoxycarbonyl, C 1 -C 4 alkoxy C 1 -C 2 alkylcarbonyl, halogenated C 1 -C 4 alkoxy C 1 -C 2 alkylcarbonyl, C 1 -C 6 alkyl oxalyl, halogenated C 1 -C 6 alkyl oxalyl, C 1 -C 4 alkoxy oxalyl, halogenated C 1 -C 4 alkoxy oxalyl, C 1 -C 4 alkylsulfonyl, halogenated C 1 -C 4 alkylsulfonyl, C 1 -C 4 alkylsulfinyl, halogenated C 1 -C 4 alkylsulfinyl, halogen-substituted or unsubstituted benzoyl, halogen-substituted or unsubstituted benzenesulfonyl, carbonyl substituted by a five- or six-membered heteroaromatic ring containing 1-2 heteroatoms selected from O, S or N; R 2 selected from C 1 -C 3 alkyl, halo-C 1 -C 3 alkyl; R 3 selected from C 1 -C 3 alkoxy, halo C 1 -C 3 alkoxy, C 1 -C 3 alkylamino, halo C 1 -C 3 alkylamino; L is selected from chlorine, bromine, iodine, methanesulfonyl, trifluoromethanesulfonyl, benzenesulfonyl or p-toluenesulfonyl.

7. The preparation method according to claim 6, characterized in that, The preparation method of the compound of formula (IV) comprises: (1) Reacting the compound II and the compound III in a second solvent in the presence of a condensing agent A to obtain the compound IV; wherein, the condensing agent A is selected from one or more of dicyclohexylcarbodiimide, 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride, 2-(7-azabenzotriazol)-N,N,N',N'-tetramethyluronium hexafluorophosphate, thionyl chloride or oxalyl chloride; the second solvent is selected from one or more of toluene, xylene, dichloromethane, dichloroethane, acetonitrile, N,N-dimethylformamide, tetrahydrofuran and acetone; the compound IV has the structure of formula (IV), the compound III has the structure of formula (III), and the compound II has the structure of formula (II), In formula (II), formula (III) and formula (IV), X 1 and X 3 each independently selected from F, Cl, Br, I or CF 3 ; X 2 selected from H, F, Cl, Br, I or CF 3 ; R 2 selected from C 1 -C 6 alkyl, halo-C 1 -C 6 alkyl; R 3 selected from amino, C 1 -C 6 -alkoxy, halo-C 1 -C 6 -alkoxy, C 1 -C 6 -alkylamino, halo-C 1 -C 6 -alkylamino.

8. The preparation method according to claim 6, characterized in that, The preparation method of the compound of formula (IV) comprises: (1) Reacting the compound VI and the compound III in a third solvent in the presence of a condensing agent B to obtain the compound VII; (2) Reacting the compound VII and the compound VIII in a fourth solvent in the presence of a basic substance B to obtain the compound IX or a mixture of the compound IX and the compound X; (3) In a fifth solvent, in the presence of basic substance C or a dehydrating agent, the compound IX is subjected to a third reaction to obtain compound X; (4) In a sixth solvent, in the presence of basic substance D, with or without a catalyst added, it undergoes a fourth reaction with hydroxylamine or its salt to obtain compound IV; Wherein, condensing agent B is selected from one or more of dicyclohexylcarbodiimide, 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride, 2-(7-azabenzotriazol)-N,N,N',N'-tetramethylurea hexafluorophosphate, thionyl chloride or oxalyl chloride; the third solvent, the fourth solvent, the fifth solvent and the sixth solvent are each independently selected from one or more of toluene, xylene, dichloromethane, dichloroethane, acetonitrile, N,N-dimethylformamide, tetrahydrofuran and acetone; the basic substances B, C and D are selected from one or more of triethylamine, diisopropylethylamine, pyridine, N-methylmorpholine, sodium carbonate, potassium carbonate, sodium hydroxide, potassium hydroxide, sodium bicarbonate, potassium bicarbonate, sodium hydride and sodium amide; the dehydrating agent is selected from acetic anhydride, propionic anhydride, thionyl chloride, acetyl chloride, phosphorus oxychloride; the compound VI has the structure shown in formula (VI), the compound III has the structure shown in formula (III), the compound VII has the structure shown in formula (VII), the compound VIII has the structure shown in formula (VIII), the compound IX has the structure shown in formula (IX), the compound X has the structure shown in formula (X), and the compound IV has the structure shown in formula (IV); In formula (VIII), formula (IX), formula (X) and formula (IV), X 1 and X 3 each independently selected from F, Cl, Br, I or CF 3 ; X 2 selected from H, F, Cl, Br, I or CF 3 ; R 2 selected from C 1 -C 6 alkyl, halo-C 1 -C 6 alkyl; R 3 Selected from amino, C 1 -C 6 alkoxy, halo C 1 -C 6 alkoxy, C 1 -C 6 alkylamino, halo C 1 -C 6 alkylamino.

9. Use of the compound according to any one of claims 1-3 or the compound prepared by the preparation method according to any one of claims 6-8 in controlling invertebrate pests.

10. An agricultural composition, characterized in that, the composition comprises at least one compound according to any one of claims 1-3 or the compound prepared by the preparation method according to any one of claims 6-8 and at least one liquid carrier or solid carrier.

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