Isoxazoline compound, and preparation method therefor and use thereof

Abstract

The present invention relates to an isoxazoline compound or an isomer thereof, and a preparation method therefor and the use thereof, and the use thereof for preventing and controlling invertebrate pests. The isoxazoline compound has a structure as shown in formula (I), and the definition of each group in the formula is as shown in the description. The isoxazoline compound provided in the present invention shows a very high prevention and control effect on invertebrate pests in agriculture, horticulture, animal husbandry and sanitation, can be used for preventing and controlling various pests and mites, and has good application prospects.

Description

Isoxazoline compounds and their preparation methods and applications

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS

[0002] This application claims the benefit of Chinese patent application 202311580050.7 filed on November 24, 2023, the contents of which are incorporated herein by reference. Technical Field

[0003] The present invention relates to isoxazoline compounds, a preparation method and application thereof, and an application thereof in preventing and controlling invertebrate pests. Background Art

[0004] In agriculture, horticulture, animal husbandry, and health, losses caused by pests continue to be substantial. Pests resistant to existing drugs are emerging. From the perspectives of impact on environmental organisms and labor conservation, there is a desire to develop insecticides and acaricides for controlling invertebrate pests that have novel properties, minimal impact on natural enemies and beneficial insects, and possess osmotic and translocation activity.

[0005] CN1930136B discloses an isoxazole compound with excellent insecticide and acaricide effects, and the general structural formula is as follows:

[0006] The following compounds are listed on page 188 of the specification:

[0007] CN115785017B discloses an isoxazole compound with excellent insecticidal effect, and the general structural formula is as follows:

[0008] It is specifically disclosed that the following compound I-9 has high insecticidal activity against Plutella xylostella at 0.5 ppm:

[0009] The insecticide and acaricide effects of currently disclosed compounds are still unsatisfactory, and there is still a need for more efficient new compounds to prevent and control the occurrence of insect pests and acarid pests. Summary of the Invention

[0010] The present invention aims to overcome the technical problem of low insecticide activity of existing compounds in the prior art for controlling invertebrate pests, and to provide a more efficient isoxazoline compound, a preparation method, and an application thereof, as well as a method for controlling invertebrate pests. The isoxazoline compound provided by the present invention has highly efficient insecticidal activity, particularly showing a high control effect against Plutella xylostella and the like.

[0011] In order to achieve the above-mentioned object, the present invention provides a compound represented by formula I, or a stereoisomer thereof,

[0012] in,

[0013] R1 is selected from hydrogen, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, methoxymethyl, methoxyethyl, ethoxymethyl, ethoxyethyl, acetyl, propionyl, n-butyryl, cyclopropylformyl, methoxyformyl, methoxyacetyl, methoxyoxalyl, ethoxyoxalyl;

[0014] R2 is selected from C1-C3 alkyl, halogenated C1-C3 alkyl;

[0015] R3 is selected from C1-C3 alkylamino and halogenated C1-C3 alkylamino.

[0016] In some embodiments, the R1 is selected from hydrogen, methyl, methoxymethyl, acetyl, methoxyformyl, methoxyoxalyl;

[0017] R2 is selected from methyl, ethyl, propyl, isopropyl, optionally, any one or more hydrogen atoms on the methyl, ethyl, propyl and isopropyl groups are optionally substituted by halogen atoms;

[0018] R3 is selected from methylamino, ethylamino, propylamino and isopropylamino, and optionally, any one or more hydrogen atoms of the alkyl moiety of methylamino, ethylamino, propylamino and isopropylamino are optionally substituted by halogen atoms.

[0019] In some typical embodiments, said R1 is selected from hydrogen, methyl, acetyl;

[0020] R2 is selected from methyl, ethyl, isopropyl;

[0021] R3 is selected from methylamino, ethylamino, propylamino, 2,2,2-trifluoroethylamino, 2,2-difluoroethylamino, and 2-fluoroethylamino.

[0022] The present invention provides a compound represented by formula Ia, or a stereoisomer thereof,

[0023] wherein R1, R2 and R3 are as defined in formula (I);

[0024] For the carbon connected to the trifluoromethyl group on the isoxazoline ring with R or S configuration (position 5), the S configuration content is 60-100%, preferably 70-100%, more preferably 80-100%, further preferably 90-100%, and even more preferably 95-100%.

[0025] The present invention provides a compound represented by formula Ib, or a stereoisomer thereof,

[0026] wherein R1, R2 and R3 are as defined in formula (I);

[0027] For the carbon connected to the R2 group (position shown in 2) having R or S configuration, the content of the R configuration is 60-100%, preferably 70-100%, more preferably 80-100%, further preferably 90-100%, and further preferably 95-100%.

[0028] The present invention provides a compound represented by formula Ic, or a stereoisomer thereof,

[0029] wherein R1, R2 and R3 are as defined above;

[0030] For the carbon connected to the trifluoromethyl group on the isoxazoline ring with R or S configuration (position shown in 5), the content of the S configuration is 60-100%, preferably 70-100%, more preferably 80-100%, further preferably 90-100%, and further preferably 95-100%; and for the carbon connected to the R2 group (position shown in 2) with R or S configuration, the content of the R configuration is 60-100%, preferably 70-100%, more preferably 80-100%, further preferably 90-100%, and further preferably 95-100%.

[0031] In some embodiments, the compound of formula I is selected from at least one of the compounds shown in Table 1.

[0032] Table 1

[0033] In a second aspect, the present invention provides the following compound or an agriculturally acceptable salt thereof, or a stereoisomer thereof:

[0034] The compounds encompassed by the present invention may exist as E-isomers and Z-isomers depending on the type of substituents. The present invention encompasses these E-isomers, Z-isomers, or mixtures thereof in any ratio. Furthermore, the compounds encompassed by the present invention include optically active forms arising from the presence of one or more asymmetric carbon atoms. The present invention encompasses all optically active forms, racemates, and mixtures thereof in any ratio.

[0035] In a third aspect, the present invention provides a compound having a structure shown in formula (X), or a stereoisomer thereof

[0036] R2 is selected from C1-C3 alkyl, halogenated C1-C3 alkyl;

[0037] R3 is selected from C1-C3 alkylamino and halogenated C1-C3 alkylamino.

[0038] In a fourth aspect, the present invention provides the use of a compound having a structure represented by formula (X) or a stereoisomer thereof in the preparation of an isoxazoline compound having a structure represented by formula (IV) or a stereoisomer thereof:

[0039] R2 is selected from C1-C3 alkyl, halogenated C1-C3 alkyl;

[0040] R3 is selected from C1-C3 alkylamino and halogenated C1-C3 alkylamino.

[0041] In a fifth aspect, the present invention provides a method for preparing an isoxazoline compound represented by formula (I) or a stereoisomer thereof, the preparation method comprising:

[0042] (1) reacting the compound IV with the compound V in a first solvent in the presence of a basic substance A to obtain a compound I;

[0043] Wherein, the compound V has a structure shown in formula (V), the compound IV has a structure shown in formula (IV), the compound III has a structure shown in formula (III), and the compound I has a structure shown in formula (I).

[0044] In formula (I), formula (IV) and formula (V),

[0045] R1 is selected from hydrogen, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, methoxymethyl, methoxyethyl, ethoxymethyl, ethoxyethyl, acetyl, propionyl, n-butyryl, cyclopropylformyl, methoxyformyl, methoxyacetyl, methoxyoxalyl, ethoxyoxalyl;

[0046] R2 is selected from C1-C3 alkyl, halogenated C1-C3 alkyl;

[0047] R3 is selected from C1-C3 alkylamino, halogenated C1-C3 alkylamino;

[0048] L is selected from chlorine, bromine, and iodine.

[0049] In some embodiments, the present invention provides a method for preparing a compound represented by formula (IV), comprising:

[0050] (1) reacting compound II and compound III in a second solvent in the presence of a condensing agent A to obtain compound IV;

[0051] Wherein, the compound IV has a structure shown by formula (IV), the compound III has a structure shown by formula (III), and the compound II has a structure shown by formula (II).

[0052] In formula (II), formula (III) and formula (IV),

[0053] R2 is selected from C1-C3 alkyl, halogenated C1-C3 alkyl;

[0054] R3 is selected from C1-C3 alkylamino and halogenated C1-C3 alkylamino.

[0055] In some embodiments, the method for preparing the compound represented by formula (IV) comprises:

[0056] (1) In a third solvent, in the presence of a condensing agent B, compound VI and compound III undergo a first reaction to obtain compound VII;

[0057] (2) in a fourth solvent, in the presence of a basic substance B, subjecting the compound VII and the compound VIII to a second reaction to obtain a compound IX or a mixture of the compound IX and the compound X;

[0058] (3) in a fifth solvent, in the presence of a basic substance C or a dehydrating agent, subjecting the compound IX to a third reaction to obtain a compound X;

[0059] (4) in the sixth solvent, in the presence of a basic substance D, with or without a catalyst, carrying out a fourth reaction with hydroxylamine or a salt thereof to obtain compound IV;

[0060] Wherein, the condensing agent B is selected from one or more of dicyclohexylcarbodiimide, 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride, 2-(7-azabenzotriazole)-N,N,N',N'-tetramethyluronium 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 alkaline substance B, the alkaline substance C and the alkaline substance D are selected from triethylamine, diisopropylethylamine, pyridine, N-methylmorpholine, sodium carbonate, carbonyl chloride, methyl benzoate ... One or more of potassium hydroxide, 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 a structure shown in formula (VI), the compound III has a structure shown in formula (III), the compound VII has a structure shown in formula (VII), the compound VIII has a structure shown in formula (VIII), the compound IX has a structure shown in formula (IX), the compound X has a structure shown in formula (X), and the compound IV has a structure shown in formula (IV);

[0061] In formula (III), formula (VII), formula (IX), formula (X) and formula (IV),

[0062] R2 is selected from C1-C3 alkyl, halogenated C1-C3 alkyl;

[0063] R3 is selected from C1-C3 alkylamino and halogenated C1-C3 alkylamino.

[0064] 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-azabenzotriazole)-N,N,N',N'-tetramethyluronium hexafluorophosphate, thionyl chloride or oxalyl chloride;

[0065] 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;

[0066] In some typical embodiments, the alkaline substance A, alkaline substance A, alkaline substance C and alkaline 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;

[0067] In some typical embodiments, the dehydrating agent is selected from acetic anhydride, propionic anhydride, thionyl chloride, acetyl chloride, and phosphorus oxychloride.

[0068] In a sixth aspect, the present invention provides a use of the aforementioned compound or its isomers in controlling invertebrate pests in agriculture, forestry, animal husbandry or health fields, wherein the invertebrate pests are acarid pests, insects and / or nematodes.

[0069] In some embodiments, the method for controlling invertebrate pests comprises applying an insecticidally effective amount of at least one of the aforementioned compounds or compounds prepared by the aforementioned preparation methods directly or indirectly to the invertebrate pests to be controlled and / or the medium in which they grow.

[0070] In some typical embodiments, the method comprises treating a plant on which an invertebrate pest grows with an insecticidally effective amount of at least one isoxazoline compound.

[0071] In a seventh aspect, the present invention provides an agricultural composition comprising at least one of the aforementioned compounds or the compound obtained by the aforementioned preparation method and at least one liquid carrier or solid carrier.

[0072] The present invention has no particular limitation on the liquid carrier or solid carrier, as long as it can meet the needs of the present invention. In the composition, the concentration of the isoxazoline compound provided by the present invention is 0.5-35 mg / L. Preferably, the concentration of the isoxazoline compound is 1-30 mg / L, more preferably, the concentration of the isoxazoline compound is 10-25 mg / L.

[0073] In the present invention, liquid carrier can be water, various aromatic hydrocarbons, aliphatic hydrocarbons, ketones, ethers etc., such as toluene, xylene, acetone, cyclohexanone, xylene, benzene, cyclohexane, isopropyl alcohol, ethylene glycol, sorbitol, methanol, ethanol, butanol, dimethylformamide, N-methylpyrrolidone, decalin, motor oil, petroleum ether, cyclohexanone, methyl oleate, methylated soybean oil etc. one or more; Solid carrier can include natural or synthetic clay and silicate, solid carrier suitable for powder can include naturally formed rock powder, chalk, quartz, clay, montmorillonite, white carbon black, diatomaceous earth, pumice, gypsum, talc, bentonite, kaolin, clay and synthetic ground mineral matter (such as micro-dispersed silicic acid or aluminum oxide). Suitable particle carrier can include crushed and graded natural rock such as calcite, marble, pumice, sepiolite and dolomite and synthetic particles made of organic and inorganic powder.

[0074] In the present invention, the composition can be applied in the form of a preparation. The isoxazoline compound provided by the present invention is dissolved or dispersed in a carrier as an active ingredient, or is configured into a preparation so that it is easier to disperse when used for insecticides and acaricides. For example, the composition can be prepared into a wettable powder, a water-dispersible granule, a suspension, an aqueous emulsion, an aqueous solution or an emulsifiable concentrate. At least one liquid or solid carrier is added to the composition, and when necessary, an appropriate surfactant can also be added. The surfactant can include dodecylbenzene sulfonate, fatty alcohol sulfate, Tween, agricultural milk, sorbitol polyoxyethylene ether, fatty alcohol polyoxyethylene ether, lignin sulfonate, alkylnaphthalene sulfonate, etc.

[0075] In the present invention, for certain applications, such as in agriculture, one or more other insecticides, acaricides, fungicides, herbicides, plant growth regulators or fertilizers may be added to the agricultural composition of the present invention, thereby producing additional advantages and effects.

[0076] In the present invention, the isoxazoline compounds also include derivatives thereof, but the compounds included in the derivatives of the present invention are by no means limited to these compounds.

[0077] In the present invention, the compound can be used to protect important crops, livestock and the like in agriculture and horticulture from or from being harmed by harmful mites.

[0078] In the present invention, in order to obtain the desired effect, in some applications, the dosage of the compound varies depending on various factors, such as the compound used, the crop to be protected, the type of pest, the degree of infection, the application method, the application environment, the application formulation, and the like.

[0079] The present invention has no particular limitation on direct or indirect methods, as long as the purpose of controlling invertebrate pests can be achieved. For example, a direct method may include directly contacting a substance containing the components of the isoxazoline compound with an invertebrate pest (including invertebrate pests directly consuming a substance containing the components of the isoxazoline compound, direct contact between the surface of the invertebrate pest and a substance containing the components of the isoxazoline compound, etc.); an indirect method may include treating a place where invertebrate pests are present (their habitat or their breeding ground or plants or soil where invertebrate pests grow) with a substance containing the components of the isoxazoline compound, or treating their food chain with a substance containing the components of the isoxazoline compound.

[0080] In the present invention, the invertebrate pests are acarid pests, insects and / or nematodes.

[0081] In the present invention, the plant is a plant of the phylum Gymnosperms and / or Angiosperms, preferably at least one of the family Rutaceae, Solanaceae, Cruciferae and Rosaceae.

[0082] The present invention does not particularly limit the insecticidal effective amount. For example, a dosage of 5 grams to 3 kilograms of the isoxazoline compound applied per hectare can provide sufficient control. Preferably, the insecticidal effective amount can be 8 grams to 1000 grams per hectare, and more preferably, the insecticidal effective amount is 10 grams to 300 grams per hectare.

[0083] Through the above technical solution, the beneficial technical effects achieved by the present invention are as follows:

[0084] (1) The isoxazoline compounds or isomers thereof provided by the present invention have shown high control effects on various pests, especially on spider mites represented by Tetranychus cinnabarinus, Tetranychus urticae, Tetranychus kanzawa, and Tetranychus citri, lepidopteran insects represented by Plutella xylostella, thrips, and flea beetles. They can be used to control various pests and mites, have high acaricidal and insecticidal activities, and have good application prospects.

[0085] (2) The isoxazoline compounds or isomers 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): Tetranychus cinnabarinus (such as Tetranychus cinnabarinus, Panonychus citri, Tetranychus urticae, Panonychus porcis, Tetranychus kanzawa, Tetranychus villosa), Tetranychus cercis, Tetranychus chinensis, Tetranychus sempervirens), Tetranychus cercis, Tetranychus sempervirens, Tetranychus sempervirens), Tetranychus cercis, Tetranychus sempervirens, Aphididae (such as Myzus persicae), Lepidoptera (such as Plutella xylostella, Spodoptera exigua, Chilo suppressalis, etc.), Thysanoptera (such as Western Flower Thrips, etc.), and Coleoptera (such as Yellow Striped Flea Beetle). Therefore, the isoxazoline compounds of the present invention can be used in agriculture or other fields to prepare insecticides and acaricides.

[0086] It should be clear that various changes and modifications can be made within the scope of the present invention. Compared with the prior art, the present invention has at least the following advantages:

[0087] The isoxazoline compounds or isomers thereof provided by the present invention exhibit excellent insecticidal and acaricidal activities against various harmful organisms, in particular, against spider mites represented by Tetranychus cinnabarinus and lepidopteran insects represented by Plutella xylostella.

[0088] The present invention provides a novel method for preparing isoxazoline compounds or isomers thereof. The method has simple process, mild conditions, high yield and high purity, and is suitable for the industrial production of isoxazoline compounds. BRIEF DESCRIPTION OF THE DRAWINGS

[0089] FIG1 is a chromatogram of chiral liquid chromatography detection of the compound prepared in Example 2.

[0090] FIG2 is a chromatogram of chiral liquid chromatography detection of the compound prepared in Example 3.

[0091] FIG3 is a chromatogram of chiral liquid chromatography detection of the compound prepared in Example 4.

[0092] FIG4 is a chromatogram of chiral liquid chromatography detection of the compound prepared in Example 5. DETAILED DESCRIPTION

[0093] The endpoints of the ranges and any values ​​disclosed herein are not limited to the precise ranges or values, and these ranges or values ​​should be understood to include values ​​close to these ranges or values. For numerical ranges, the endpoints of each range, the endpoints of each range and individual point values, and the individual point values ​​can be combined with each other to obtain one or more new numerical ranges, which should be considered to be specifically disclosed herein.

[0094] To further understand the present invention, the following will clearly and completely describe the technical solutions in the embodiments of the present invention in conjunction with the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without making creative efforts shall fall within the scope of protection of the present invention.

[0095] In the following examples, unless otherwise specified, all raw materials used are commercially available and of analytical grade. The present invention relates to the preparation of chiral compounds, which can be synthesized using chiral raw materials or racemic raw materials, followed by chiral column chromatography for separation. The chiral column chromatography separation method uses separation methods commonly used in the art. The following examples are methods for preparing some of the compounds of the present invention. The preparation of other compounds can be obtained by converting raw materials commonly used in the art and preparing them according to known methods.

[0096] Chiral liquid chromatography test conditions are as follows:

[0097] Chromatographic column and model: CHIRALPAK IB N-3, 4.6mmI.D*250mmL, filler 3 micron.

[0098] Mobile phase composition: n-hexane (70%), ethanol (30%).

[0099] Detection wavelength: 238nm

[0100] Preparation Example 1: Synthesis of 4-(5-(3,5-dichloro-4-fluorophenyl)-5-trifluoromethyl-4,5-dihydroisoxazol-3-yl)-2-methylbenzoic acid

[0101] Step 1: Synthesis of 4-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluoro-3-hydroxybutyryl)-2-methylbenzoic acid

[0102] 4-Acetyl-2-methylbenzoic acid (40 g, 224 mmol, content 92%) was added to the reactor, followed by 1-(3,5-dichloro-4-fluorophenyl)-2,2,2-trifluoroethane-1-one (91.87 g, 246.4 mmol, content 70%), toluene (80 mL), and triethylamine (34 g, 336 mmol) was slowly added. The system was heated to 80°C and kept warm for 3-4 hours. The temperature was slowly lowered to -5°C and kept warm for two hours. The mixture was filtered, and the filter cake was washed with toluene and dried to obtain 111.88 g of an off-white solid, which was the triethylamine salt of the target product with an HPLC purity of 96.5%.

[0103] 1 H NMR(400MHz,DMSO-d6)δ7.87(d,J=6.4Hz,2H),7.79-7.65(m,2H),7.60(d,J=7.9Hz,1H),4.4 3(d,J=18.1Hz,1H),3.94(s,1H),2.93(q,J=7.2Hz,6H),2.49(s,3H),1.15(t,J=7.2Hz,9H).

[0104] Step 2: Synthesis of 4-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-2-enoyl)-2-methylbenzoic acid

[0105] 4-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluoro-3-hydroxybutyryl)-2-methylbenzoic acid (106.8 g, 243.3 mmol) was added to 200 ml of tetrahydrofuran, and propionic anhydride (57 g, 437.9 mmol) and DMAP (0.53 g, 4.4 mmol) were added in sequence. The system was heated to 60°C and kept warm for 4 h. The solvent in the system was evaporated, methanol (300 mL) was added with stirring, and the mixture was filtered with suction. The filter cake was dried to obtain 87.88 g of a yellow-green solid with an HPLC purity of 92%.

[0106] 1 H NMR (400MHz, DMSO-d6) δ13.30 (s, 1H) 8.01-7.84 (m, 2H), 7.85-7.68 (m, 2H), 7.60 (d, J = 6.3Hz, 2H), 2.56 (s, 3H).

[0107] Step 3

[0108] Prepared by referring to the method described in step 5 of Example 1 of patent CN117886806A. Toluene (25 mL) and tetrabutylammonium bromide (0.65 g) were added to a round-bottom flask, and 4-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluoro-2-butenoyl)-2-methylbenzoic acid (8.5 g, 20 mol) was added. The reaction solution was stirred at 0°C; then sodium hydroxide (3.36 g, 84 mmol), purified water (25 ml) and hydroxylamine hydrochloride (2.78 g, 40 mmol) were added in sequence, and the reaction flask was stirred in an ice bath for 5 hours.

[0109] The reaction solution was added with 20 mL of concentrated hydrochloric acid, 100 mL of water, and 100 mL of ethyl acetate; the mixture was extracted and separated, and 100 mL of ethyl acetate was added to the aqueous phase again. After extraction and separation, the organic phases were combined, 10 g of anhydrous sodium sulfate was added to the organic phase, and dried, and then rotary evaporated to dryness to obtain 7.2 g of an off-white solid. 1 H NMR (500MHz, DMSO-d6) δ13.11 (s, 1H) 7.94-7.86 (m, 1H), 7.81 (d, J = 6.1Hz, 2H), 7.64 (d, J = 7.3Hz, 2H), 4.44-4.26 (m, 2H), 2.56 (s, 3H).

[0110] Preparation Example 2: Synthesis of (S)-4-(5-(3,5-dichloro-4-fluorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methylbenzoic acid:

[0111] Step 1: Preparation of (S)-methyl 4-(3-(3,5-dichloro-4-fluorophenyl)-4,4-(4-trifluoro-3-hydroxybutyryl)-2-methylbenzoate

[0112] To a solution of 1-(3,5-dichloro-4-fluorophenyl)-2,2,2-trifluoro-ethanone (10.44 g, 40 mmol) in toluene (42 mL) were 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 at 20 to 25°C overnight. After completion of the reaction, the solvent was removed by concentration under reduced pressure, and the residue was purified by column chromatography to give 4.5 g of a white solid, the title compound.

[0113] 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,2 H),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).

[0114] MS: [M+Na] + :475.12,477.36.

[0115] Step 2: Preparation of methyl (S)-4-(3-(3,5-dichloro-4-fluorophenyl)-4,4-(4-trifluoro-3-hydroxy-1-(hydroxyimino)butyl)-2-methylbenzoate

[0116] To a mixture of methyl (S)-4-(3-(3,5-dichloro-4-fluorophenyl)-4,4-4-trifluoro-3-hydroxybutyryl)-2-methylbenzoate (1 g, 2.2 mmol) and 2,6-lutidine (7 ml) at 20 to 25°C was added solid hydroxylamine hydrochloride (0.31 g, 4.4 mmol). After stirring overnight, the mixture was quenched with 10 ml of ice water and extracted with dichloromethane. The combined organic layers were washed with aqueous hydrochloric acid (6N) 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.

[0117] 1 H NMR(400MHz,Chloroform-d)δ7.89(d,J=8.1Hz,1H),7.41(d,J=6.1Hz,2H),7.06(dd,J=8.2,1. 8Hz,1H),6.99(d,J=1.8Hz,1H),5.23(s,1H),3.91(s,3H),3.32(d,J=1.1Hz,2H),2.56(s,3H).

[0118] MS: [M+Na] + :490.49,492.46.

[0119] Step 3: Preparation of (S)-methyl 4-(5-(3,5-dichloro-4-fluorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methylbenzoate

[0120] To a solution of methyl (S)-4-(3-(3,5-dichloro-4-fluorophenyl)-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 at room temperature overnight. After the reaction was complete, 20 ml of water was added to the system, and the mixture was extracted with dichloromethane, 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, the title compound.

[0121] 1 H NMR (400MHz, CDCl3) 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).

[0122] MS: [M+H] + :450.50,452.54.

[0123] Step 4: Preparation of (S)-4-(5-(3,5-dichloro-4-fluorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methylbenzoic acid

[0124] To a solution (3 ml) of (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 was added 10% aqueous lithium hydroxide solution (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 6 M aqueous hydrochloric acid. The mixture was extracted with dichloromethane and dried to obtain 0.3 g of a light brown oil, which was then cooled to an off-white solid.

[0125] MS: [M+H] - :434.57,436.56.

[0126] Example 1

[0127] 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 117):

[0128] 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), and 2-(7-azabenzotriazole)-N,N,N',N'-tetramethyluronium hexafluorophosphate (1.14 g, 3 mmol) and N,N-diisopropylethylamine (0.517 g, 4 mmol) were added in sequence. After stirring at room temperature for 0.5 h, 2-amino-N-methylpropionamide (0.245 g, 2.4 mmol) was added and reacted at room temperature for 5 h. The system was extracted with water twice, and the dried organic phase was washed with water and evaporated to dryness. It was purified by column chromatography to obtain 0.38 g of a white solid.

[0129] 1 H NMR (400MHz, CDCl3) δ7.59(d,J=6.0Hz,2H),7.55-7.41(m,3H),6.53(d,J=6.9Hz,1H),6.05(s,1H),4.66-4.58(m ,1H),4.08(d,J=17.2Hz,1H),3.68(d,J=17.2Hz,1H),2.87(d,J=4.0Hz,3H),2.46(s,3H),1.49(d,J=6.5Hz,3H).

[0130] MS:[M+H] + :521.43,523.41.

[0131] Example 2

[0132] Synthesis of 4-((S)-5-(3,5-dichloro-4-fluorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methyl-N-((R)-1-oxo-1-(2,2,2-trifluoroethyl)amino)propan-2-yl)benzamide (Compound 7)

[0133] Step 1: Synthesis of (R)-4-acetyl-2-methyl-N-(1-oxo-1-(2,2,2-trifluoroethyl)amino)propan-2-yl)benzamide

[0134] 2-Methyl-4-acetylbenzoic acid (17.8 g, 100 mmol) was added to 100 ml of dichloroethane and thionyl chloride (14.3 g, 120 mmol). The temperature was raised to 60°C and kept warm for 3 h. After the solvent was evaporated under reduced pressure, 150 ml of dichloroethane was added to fully dissolve the mixture. After the temperature dropped to room temperature, (R)-2-amino-N-(2,2,2-trifluoroethyl)propionamide hydrochloride was added and stirred evenly. Triethylamine (26.2 g, 260 mmol) was added dropwise under ice bath. After the addition was complete, the ice bath was removed and the mixture was reacted at room temperature for 2 h. The reaction solution was directly filtered, washed with water and dried to obtain 22.4 g of a light yellow solid with HPLC purity of 95.3%.

[0135] 1 H NMR (400MHz, DMSO-d6) δ8.62(dt,J=6.5,2.7Hz,2H),7.81(d,J=7.8Hz,2H),7.48(d,J=7.8Hz,1 H),4.49(p,J=7.2Hz,1H),4.07-3.81(m,2H),2.59(s,3H),2.39(s,3H),1.31(d,J=7.2Hz,3H).

[0136] Step 2: Synthesis of 4-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-2-enoyl)-2-methyl-N-(1-oxo-1-(2,2,2-trifluoroethyl)amino)propan-2-yl)benzamide

[0137] (R)-4-Acetyl-2-methyl-N-(1-oxo-1-(2,2,2-trifluoroethyl)amino)propan-2-yl)benzamide (16.5 g, 50 mmol) was added to toluene (100 mL), followed by 1-(3,5-dichloro-4-fluorophenyl)-2,2,2-trifluoroethane-1-one (13.0 g, 50 mmol), sodium carbonate (5.3 g, 50 mmol), and triethylamine (5.0 g, 5 mmol). The reaction mixture was heated under reflux for 10 hours, cooled to room temperature, and filtered under reduced pressure. The filter cake was washed with water (300 mL) and then filtered under reduced pressure again. Methanol (100 mL) was added, stirred, and filtered under reduced pressure again. The filter cake was dried to yield 18.2 g of an off-white solid. HPLC purity was 91.25%.

[0138] Step 3: Synthesis of 4-((S)-5-(3,5-dichloro-4-fluorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methyl-N-((R)-1-oxo-1-(2,2,2-trifluoroethyl)amino)propan-2-yl)benzamide

[0139] 2,3,4,5,6-Pentafluorophenyl-methylquinine bromide (Example 3 of WO2011104089A1, 4.96 mmol) was added to 250 ml of dichloromethane, followed by aqueous hydroxylamine hydrochloride solution (4.54 g, 65.4 mmol) and aqueous sodium hydroxide solution (4.36 g + 7 g water, 109 mmol). The temperature was lowered to 0°C, and 4-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-2-enoyl)-2-methyl-N-(1-oxo-1-(2,2,2-trifluoroethyl)amino)prop-2-yl)benzamide (25 g, 43.6 mmol) was added. The mixture was allowed to react for 1 hour, and HPLC analysis was performed to determine if the remaining starting material was less than 2%. The reaction solution was filtered to remove insoluble solids, including the phase transfer catalyst. The filtrate was added with water (200 mL) and dichloromethane (200 mL), extracted and separated, and the filtrate was evaporated to dryness to obtain 22.3 g of a light brown-gray solid. The solid was added with 100 mL of petroleum ether and 10 mL of ethyl acetate, stirred for 30 minutes, and then filtered. The filter cake was dried to obtain 14.5 g of an off-white solid with an HPLC purity of 99.75% (wavelength: 254 nm). The melting point was 210.52-212.87°C. The optical rotation was [α]D 18.8 =49.879°(c 0.4g / 100ml, acetone)

[0140] The chromatogram of each isomer detected by chiral liquid chromatography is shown in Figure 1, and the retention time and peak area ratio data of each isomer are shown in the following table:

[0141] The content of the target compound (Compound 7) was 95.023%.

[0142] Example 3

[0143] Synthesis of 4-(5-(3,5-dichloro-4-fluorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methyl-N-((R)-1-oxo-1-(2,2,2-trifluoroethyl)amino)propan-2-yl)benzamide (Compound 4)

[0144] 4-(5-(3,5-dichloro-4-fluorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methylbenzoic acid (4.36 g, 10 mmol) was added to toluene (50 mL), and thionyl chloride (1.43 g, 12 mmol) was added. The reaction solution was heated to 90°C for 2 hours. The solvent and acidic gas were partially removed by distillation under reduced pressure at 50°C. 50 mL of toluene was added, and (R)-2-amino-N-(2,2,2-trifluoroethyl)propionamide hydrochloride (3.09 g, 15 mmol) and triethylamine (3.03 g, 30 mmol) were added. The reaction was continued at room temperature for 1 hour. Water (100 mL) and ethyl acetate (100 mL) were added to the reaction solution, and the liquids were extracted. The organic phase was evaporated to dryness under reduced pressure and purified by column chromatography to obtain 2.59 g of an off-white solid with an HPLC purity of 97.65% (wavelength: 254 nm).

[0145] The chromatograms of each isomer detected by chiral liquid chromatography are shown in Figure 2, and the retention time and peak area ratio data of each isomer are shown in the following table:

[0146] The content of the target compound (Compound 4) was 97.163%.

[0147] Example 4

[0148] Synthesis of 4-(5-(3,5-dichloro-4-fluorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methyl-N-((S)-1-oxo-1-(2,2,2-trifluoroethyl)amino)propan-2-yl)benzamide (Compound 3)

[0149] The target compound, 4-(5-(3,5-dichloro-4-fluorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methyl-N-((S)-1-oxo-1-(2,2,2-trifluoroethyl)amino)propan-2-yl)benzamide, was prepared by referring to the method described in Example 3, using (S)-2-amino-N-(2,2,2-trifluoroethyl)propanamide hydrochloride instead of (R)-2-amino-N-(2,2,2-trifluoroethyl)propanamide hydrochloride. The product had an HPLC purity of 98.27% (wavelength: 254 nm).

[0150] The chromatogram of each isomer detected by chiral liquid chromatography is shown in Figure 3, and the retention time and peak area ratio data of each isomer are shown in the following table:

[0151] The content of the target compound (Compound 3) was 98.75%.

[0152] Example 5

[0153] Synthesis of 4-(5-(3,5-dichloro-4-fluorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methyl-N-(1-oxo-1-(2,2,2-trifluoroethyl)amino)propan-2-yl)benzamide (Compound 9)

[0154] The target compound, 4-(5-(3,5-dichloro-4-fluorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methyl-N-(1-oxo-1-(2,2,2-trifluoroethyl)amino)propan-2-yl)benzamide, was prepared by referring to the method described in Example 4, using 2-amino-N-(2,2,2-trifluoroethyl)propanamide hydrochloride instead of (R)-2-amino-N-(2,2,2-trifluoroethyl)propanamide hydrochloride. The product had an HPLC purity of 96.40% (wavelength: 254 nm).

[0155] The chromatograms of each isomer detected by chiral liquid chromatography are shown in Figure 4, and the retention time and peak area ratio data of each isomer are shown in the following table:

[0156] The content of the target compound (Compound 9) was 96.73%.

[0157] The above lists only the preparation methods of representative compounds of the present invention. The preparation methods of other compounds can be prepared by referring to the methods of Examples 1-7, simply by replacing simple commercially available raw materials. The mass spectrum and hydrogen spectrum data of some compounds of the present invention are shown in Table 2 below.

[0158] Application Example 1

[0159] Activity test of Tetranychus cinnabarinus:

[0160] The test compound was dissolved in acetone and diluted to the desired concentration with a 0.1 wt % Tween 80 aqueous solution, with the acetone content not exceeding 5 wt %.

[0161] Bean seedlings grown to two true leaves were inoculated with Tetranychus cinnabarinus, and one true leaf removed. The plant population was then assessed and sprayed with a handheld sprayer. Each treatment was repeated three times (applying approximately 0.5 g of the formulation). The plants were observed in a constant-temperature observation room after treatment. After 72 hours, the number of live mites was counted, and the mortality rate was calculated. The experiment was repeated three times, with 35-100 Tetranychus cinnabarinus mites inoculated each time.

[0162] Mortality rate (%) = (number of inoculated insects - number of live insects after drug administration) ÷ number of inoculated insects × 100%.

[0163] In this test, some of the tested compounds such as 4, 7, 9, 13, 45, 117, 220, 328, 436, 439, 1081 showed more than 90% mortality against Tetranychus cinnabarinus at 3.125 ppm (3.125 mg / L), respectively.

[0164] Application Example 2

[0165] Western flower thrips activity test:

[0166] Test target: Thrips nymphs.

[0167] Experimental Method: First, fresh greenhouse-grown cabbage leaves were punched into 1cm diameter circular discs. These discs were then immersed in the prepared solution for 5 seconds, starting with the lowest dose and progressing to the highest dose. After air-drying in the shade, the discs were placed in finger tubes. Approximately 15-20 thrips nymphs were aspirated using a sucker and added to the tubes. The tubes were covered with 200-mesh gauze and secured with a rubber band. The tubes were inserted into a test tube rack and tilted in an incubation room. The tubes were incubated for 72 hours at 27°C and 30-40% relative humidity. The number of live and dead thrips was recorded. Three replicates were used for each treatment, with a blank control provided.

[0168] In this test, some of the tested compounds, such as 4, 7, 9, 13, 220, 328, 436, 439, and 1081, showed a mortality rate of more than 90% against thrips nymphs at 1.56 mg / L.

[0169] Application Example 3

[0170] Activity test of yellow striped flea beetle:

[0171] Test target: Adult yellow striped flea beetle.

[0172] Experimental Method: First, fresh greenhouse-grown cabbage leaves were punched into circular discs with a diameter of 3 cm. The leaves were then immersed in the prepared solution for 10 seconds, starting with the lowest dose and progressing to the highest. After air-drying, the leaves were placed in flat-bottomed test tubes and neatly seeded with healthy adult yellow flea beetles (10 per treatment). The tubes were sealed with perforated plastic wrap and rubber bands. After treatment, all test organisms were transferred to an observation room at 27°C and a relative humidity of 50-70% and incubated for 6 days. The number of live and dead insects was recorded. Each treatment was replicated three times, with a blank control.

[0173] In this test, some of the tested compounds such as 4, 7, 436, and 439 showed more than 90% mortality against adults of the yellow striped flea beetle at 1.56 ppm (1.56 mg / L).

[0174] Application Example 4

[0175] Diamondback moth activity test:

[0176] Test target: Diamondback moth (Plutella xylostella), third instar larvae, susceptible strain reared indoors.

[0177] Test Method: First, fresh cabbage leaves grown in a greenhouse were punched into circular leaflets with a diameter of 3 cm. These leaves were then immersed in the prepared solution for 10 seconds, starting from the lowest dose and progressing to the highest dose. After air-drying, the leaves were placed in a 9 cm diameter Petri dish lined with filter paper and neatly seeded with healthy test insects. Ten insects were treated per group, with three replicates per group. A blank control was also included. After 72 hours, the number of live insects was counted, and the mortality rate (% mortality) was calculated. (% mortality = (number of inoculated insects - number of live insects after treatment) ÷ number of inoculated insects × 100%).

[0178] In this test, some of the tested compounds such as 4, 7, 9, 13, 45, 117, 220, 328, 436, 439, and 1081 showed a mortality rate of more than 90% against Plutella xylostella at 0.39 mg / L.

[0179] According to the above method, compounds 4, 7, 436, and 439 were selected and tested against Plutella xylostella in parallel with CK1 and CK2. The test results are shown in Table 3 below.

[0180] Table 3

[0181] CK1 is the compound in CN1930136B and was prepared according to the method of Example 5 of the present invention, except that 2-amino-N-(2,2,2-trifluoroethyl)acetamide hydrochloride was used instead of 2-amino-N-(2,2,2-trifluoroethyl)propionamide hydrochloride. 1H NMR (400MHz, DMSO-d6) δ8.63(t,J=6.1Hz,2H),7.81(d,J=6.2Hz,2H),7.61(dd,J=6.1,1.9Hz ,2H),7.52(d,J=8.5Hz,1H),4.35(d,J=9.1Hz,2H),4.03-3.88(m,4H),2.41(s,3H).MS:[M+H] + :574.14. HPLC purity: 97.03%.

[0182] CK2 is the compound in CN115785017B and was prepared according to the method of Example 8 of CN115785017B. 1 H NMR (400MHz, DMSO-d6) δ8.85(s,1H),8.31(t,J=6.4Hz,1H),7.81(d,J=6.2Hz,2H),7.66(d,J=8.5Hz,1H),7.60(dd,J=5.8,2.0Hz,2 H),4.42-4.25(m,2H),3.90(qd,J=9.8,5.1Hz,2H),2.38(s,3H),1.38(q,J=4.4Hz,2H),1.08(dq,J=10.8,4.6,4.2Hz,2H).MS:[M+H] + :600.33. HPLC purity: 96.39%.

[0183] The preferred embodiments of the present invention are described in detail above, but the present invention is not limited thereto. Within the technical concept of the present invention, various simple variations of the technical solution of the present invention may be made, including combining the various technical features in any other appropriate manner. These simple variations and combinations should also be regarded as the contents disclosed by the present invention and fall within the scope of protection of the present invention.

Claims

1. A compound represented by formula (I), or a stereoisomer thereof, in, R1 is selected from hydrogen, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, methoxymethyl, methoxyethyl, ethoxymethyl, ethoxyethyl, acetyl, propionyl, n-butyryl, cyclopropylformyl, methoxyformyl, methoxyacetyl, methoxyoxalyl, ethoxyoxalyl; R2 is selected from C1-C3 alkyl, halogenated C1-C3 alkyl; R3 is selected from C1-C3 alkylamino and halogenated C1-C3 alkylamino.

2. The compound or stereoisomer thereof according to claim 1, characterized in that The R1 is selected from hydrogen, methyl, methoxymethyl, acetyl, methoxyformyl, methoxyoxalyl; R2 is selected from methyl, ethyl, propyl, isopropyl, optionally, any one or more hydrogen atoms on the methyl, ethyl, propyl and isopropyl groups are optionally substituted by halogen atoms; R3 is selected from methylamino, ethylamino, propylamino and isopropylamino, and optionally, any one or more hydrogen atoms of the alkyl moiety of methylamino, ethylamino, propylamino and isopropylamino are optionally substituted by halogen atoms.

3. The compound or stereoisomer thereof according to claim 2, characterized in that: The R1 is selected from hydrogen, methyl, and acetyl; R2 is selected from methyl, ethyl, isopropyl; R3 is selected from methylamino, ethylamino, propylamino, 2,2,2-trifluoroethylamino, 2,2-difluoroethylamino, and 2-fluoroethylamino.

4. A compound according to claim 1, characterized in that For the carbon connected to the trifluoromethyl group on the isoxazoline ring with R or S configuration, the content of S configuration is 60-100%, preferably 70-100%, more preferably 80-100%, further preferably 90-100%, and further preferably 95-100%.

5. A compound according to claim 1, characterized in that The carbon connected to the R2 group has an R or S configuration, and the content of the R configuration is 60-100%, preferably 70-100%, more preferably 80-100%, further preferably 90-100%, and further preferably 95-100%.

6. A compound according to claim 4 or 5, characterized in that For the carbon connected to the trifluoromethyl group on the isoxazoline ring with R or S configuration, the content of S configuration is 60-100%, preferably 70-100%, more preferably 80-100%, further preferably 90-100%, and further preferably 95-100%; for the carbon connected to the R2 group with R or S configuration, the content of R configuration is 60-100%, preferably 70-100%, more preferably 80-100%, further preferably 90-100%, and further preferably 95-100%.

7. A compound having a structure represented by formula (X), or a stereoisomer thereof, R2 is selected from C1-C3 alkyl, halogenated C1-C3 alkyl; R3 is selected from C1-C3 alkylamino and halogenated C1-C3 alkylamino.

8. Use of the compound of formula (X) or its stereoisomer according to claim 7 in the preparation of isoxazoline compounds of formula (IV) or their stereoisomers; R2 is selected from C1-C3 alkyl, halogenated C1-C3 alkyl; R3 is selected from C1-C3 alkylamino and halogenated C1-C3 alkylamino.

9. A method for preparing a compound represented by formula (I) or a stereoisomer thereof, the method comprising: (1) reacting the compound IV with the compound V in a first solvent in the presence of a basic substance A to obtain a compound I; Wherein, the alkaline 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 a structure shown in formula (V), the compound IV has a structure shown in formula (IV), and the compound I has a structure shown in formula (I), In formula (I), formula (IV) and formula (V), R1 is selected from hydrogen, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, methoxymethyl, methoxyethyl, ethoxymethyl, ethoxyethyl, acetyl, propionyl, n-butyryl, cyclopropylformyl, methoxyformyl, methoxyacetyl, methoxyoxalyl, ethoxyoxalyl; R2 is selected from C1-C3 alkyl, halogenated C1-C3 alkyl; R3 is selected from C1-C3 alkylamino, halogenated C1-C3 alkylamino; L is selected from chlorine, bromine and iodine.

10. The preparation method according to claim 9, characterized in that: The preparation method of the compound represented by formula (IV) comprises: (1) reacting compound II and compound III in a second solvent in the presence of a condensing agent A to obtain compound IV; wherein the condensing agent A is selected from one or more of dicyclohexylcarbodiimide, 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride, 2-(7-azabenzotriazole)-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 a structure shown in formula (IV), the compound III has a structure shown in formula (III), and the compound II has a structure shown in formula (II), In formula (II), formula (III) and formula (IV), R2 is selected from C1-C3 alkyl, halogenated C1-C3 alkyl; R3 is selected from C1-C3 alkylamino and halogenated C1-C3 alkylamino.

11. The preparation method according to claim 9, characterized in that: The preparation method of the compound represented by formula (IV) comprises: (1) in a third solvent, in the presence of a condensing agent B, subjecting compound VI and compound III to a first reaction to obtain compound VII; (2) in a fourth solvent, in the presence of a basic substance B, subjecting the compound VII and the compound VIII to a second reaction to obtain a compound IX or a mixture of the compound IX and the compound X; (3) in a fifth solvent, in the presence of a basic substance C or a dehydrating agent, subjecting the compound IX to a third reaction to obtain a compound X; (4) in the sixth solvent, in the presence of a basic substance D, with or without a catalyst, carrying out a fourth reaction with hydroxylamine or a salt thereof to obtain compound IV; Wherein, the condensing agent B is selected from one or more of dicyclohexylcarbodiimide, 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride, 2-(7-azabenzotriazole)-N,N,N',N'-tetramethyluronium 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 alkaline substance B, the alkaline substance C and the alkaline substance D are selected from triethylamine, diisopropylethylamine, pyridine, N-methylmorpholine, sodium carbonate, carbon The compound VI has a structure as shown in formula (VI), the compound III has a structure as shown in formula (III), the compound VII has a structure as shown in formula (VII), the compound VIII has a structure as shown in formula (VIII), the compound IX has a structure as shown in formula (IX), the compound X has a structure as shown in formula (X), and the compound IV has a structure as shown in formula (IV); In formula (III), formula (VII), formula (IX), formula (X) and formula (IV), R2 is selected from C1-C3 alkyl, halogenated C1-C3 alkyl; R3 is selected from C1-C3 alkylamino and halogenated C1-C3 alkylamino.

12. Use of a compound according to any one of claims 1 to 6 or a stereoisomer thereof in controlling invertebrate pests.

13. The use according to claim 12, characterized in that: Use of the compound according to any one of claims 1 to 6 or its stereoisomers in controlling invertebrate pests in agriculture.

14. The use according to claim 12, characterized in that: Use of the compound according to any one of claims 1 to 6 or its stereoisomers in controlling invertebrate pests in forestry.

15. The use according to claim 12, characterized in that: Use of the compound according to any one of claims 1 to 6 or its stereoisomers in controlling invertebrate pests in animal husbandry.

16. The use according to claim 12, characterized in that: Use of a compound according to any one of claims 1 to 6 or a stereoisomer thereof for controlling invertebrate pests for non-therapeutic purposes in hygiene.

17. An agricultural composition, characterized in that The composition comprises at least one compound according to any one of claims 1 to 6 or a stereoisomer thereof and at least one liquid carrier or solid carrier.

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