An isoxazoline oxime ester derivative, a preparation method and application thereof

Abstract

The application provides an isoxazoline oxime ester derivative, a preparation method and application thereof, and the isoxazoline oxime ester derivative is a compound represented by formula I, or a stereoisomer, a tautomer, an isotopic derivative and a pesticide-acceptable salt thereof. The isoxazoline oxime ester derivative has high insecticidal activity, still has good insecticidal effect at a low dose, is more conducive to environmental protection, and has very excellent killing effect on lepidopteran pests, such as diamondback moth.

Description

Technical Field

[0001] This application belongs to the field of insecticides, specifically relating to an isoxazoline oxime ester derivative, its preparation method, and its application. Background Technology

[0002] In recent years, isoxazoline insecticides have been found to exhibit high insecticidal activity while maintaining low toxicity, and are particularly safe for mammals. Isoxazoline compounds are an important class of five-membered heterocyclic compounds. Representative isoxazoline insecticides include fluralaner, afoxolaner, sarolaner, lotilaner, and isocycloseram. Fluralaner was one of the earlier developed isoxazoline compounds, initially used for agricultural pest control. Now, most fluralaner compounds are formulated as veterinary drugs for pet deworming. Its mechanism of action is to inhibit the activity of γ-aminobutyric acid receptors, interfering with nerve impulse transmission, causing excessive excitation and paralysis in insects, leading to their death. Afoxolaner, as an isoxazoline insecticide, has been experimentally reported in the literature to kill *Hemanoptera hemangiosum*, showing good insecticidal activity and persistence against *Hemanoptera hemangiosum*.

[0003] However, with the widespread use of pesticides, insect resistance and the harm to the environment and human health are becoming increasingly prominent. Therefore, research and application of isoxazoline insecticides should be further strengthened. Summary of the Invention

[0004] The purpose of this application is to provide an isoxazoline oxime ester derivative with high insecticidal activity, which still has a good insecticidal effect at low doses and is more conducive to environmental protection.

[0005] To achieve the above objectives, in a first aspect, this application provides an isoxazoline oxime ester derivative, which is a compound represented by Formula I, or a stereoisomer, tautomer, isotopic derivative thereof, or a pesticide-acceptable salt thereof:

[0006] ,

[0007] Wherein, R is an optionally substituted aryl or optionally substituted heteroaryl; wherein the substituent on the aryl or heteroaryl is selected from one or more of halogen, amino, hydroxyl, nitro, cyano, mercapto, optionally substituted alkyl, optionally substituted alkyloxy, optionally substituted alkylthio, or optionally substituted alkylamino.

[0008] R1 and R3 are each independently selected from halogen, amino, hydroxyl, nitro, cyano, mercapto, optionally substituted alkyl, optionally substituted alkyloxy, optionally substituted alkylthio, or optionally substituted alkylamine.

[0009] R2 is a haloalkyl group;

[0010] The substituents on the optionally substituted alkyl, optionally substituted alkyloxy, optionally substituted alkylthio, or optionally substituted alkylamine groups are selected from one or more of halogen, amino, hydroxy, nitro, cyano, and mercapto groups;

[0011] n is 0, 1, 2, 3, 4 or 5;

[0012] m can be 0, 1, 2, 3, or 4.

[0013] In one set of embodiments, R is an optionally substituted C6-14 aryl or an optionally substituted 5-14 heteroaryl; the alkyl group is a C1-8 alkyl group.

[0014] In one set of embodiments, R is an optionally substituted C6-10 aryl or an optionally substituted 5-10 heteroaryl; more preferably, R is an optionally substituted phenyl or an optionally substituted 5-6 heteroaryl, wherein the heteroaryl contains 1-3 heteroatoms selected from N, O, and S.

[0015] In one set of embodiments, R is a phenyl group substituted with one or more (e.g., 1, 2, 3, 4 or 5) substituents selected from halogen, cyano, C1-8 alkyl, C1-8 alkyloxy, C1-8 haloalkyl; or R is furanyl or thiophene.

[0016] In one set of embodiments, R is Ph-, (4-Me)Ph-, (4-MeO)Ph-, (2-Me)Ph-, (3-Me)Ph-, (3-MeO)Ph-, (2-MeO)Ph-, (3-Br)Ph-, (4-Br)Ph-, (2-Br)Ph-, (4-Cl)Ph-, (4-CN)Ph-, (4-I)Ph-, (2-Cl)Ph-, (3-Cl)Ph-, (2-F)Ph-, (3-CF3)Ph-, 3-chloro-4-fluoro-Ph-; or R is 2-furanyl or 2-thienyl.

[0017] In one set of embodiments, R1 and R3 are each independently selected from halogens and C1-8 alkyl groups; preferably, R1 is selected from halogens and R3 is selected from C1-8 alkyl groups; more preferably, -(R1) n It is 3,5-dichloro-4-fluoro, -(R3) m It is a methyl group located at the meta position of the isoxazoline group.

[0018] In one set of embodiments, R2 is a C1-8 haloalkyl group, preferably a halomethyl group, and more preferably a trifluoromethyl group.

[0019] In one set of embodiments, the compound represented by formula I is the same as the compound represented by formula IA:

[0020] .

[0021] Specifically, the compound represented by formula IA is one of the following compounds 1-20:

[0022]

[0023] Secondly, this application provides a method for preparing the isoxazoline oxime ester derivative, comprising the following steps:

[0024] .

[0025] In one embodiment, the oxime compound of Formula II is condensed with acyl chloride RCOCl in the presence of a base to prepare the isoxazoline oxime ester derivative of Formula I. The base used in the condensation reaction can be any acid-binding agent known in the art, such as an inorganic or organic base, for example, one or more of sodium hydroxide, potassium carbonate, triethylamine, diethylamine, pyridine, and cesium carbonate, preferably triethylamine. The amount of the acid-binding agent used, relative to the amount of the compound of Formula II, is preferably 0.5-1.5 equivalents, more preferably 0.8-1.2 equivalents, and even more preferably 0.9-1.0 equivalents.

[0026] In one set of embodiments, the method for preparing the compound of formula II includes the following steps:

[0027] ;

[0028] R4 is an alkyl group, preferably a C1-8 alkyl group.

[0029] In one embodiment, the carboxylic acid compound of formula VI is condensed with R4OH or R4I in the presence of a base to prepare an ester compound of formula V. The base used in the condensation reaction can be any acid-binding agent known in the art, such as an inorganic or organic base, for example, one or more of sodium hydroxide, potassium carbonate, triethylamine, diethylamine, pyridine, and cesium carbonate, preferably potassium carbonate. The amount of the acid-binding agent used, relative to the amount of the compound of formula VI, is preferably 0.5-1.5 equivalents, more preferably 0.8-1.2 equivalents, and even more preferably 0.9-1.0 equivalents.

[0030] In one embodiment, the ester compound of formula V is reduced by a reducing agent to prepare a primary alcohol compound of formula VI. The reducing agent used in the reduction reaction can be any reducing agent known in the art for ester reduction, such as DIBAL-H, lithium aluminum hydride, sodium borohydride, etc., preferably DIBAL-H. The amount of the reducing agent used, relative to the amount of compound of formula V, is preferably 1.5-3 equivalents, more preferably 1.8-2.5 equivalents, and even more preferably 2.0-2.2 equivalents.

[0031] In one embodiment, the primary alcohol compound of formula VI is oxidized by an oxidizing agent to prepare an aldehyde compound of formula III. The oxidizing agent used in the above oxidation reaction can be a reducing agent known in the art for alcohol oxidation, such as Dysmartin oxidant, PCC, Swern oxidant, TEMPO, etc., preferably Dysmartin oxidant. The amount of the oxidizing agent used, relative to the amount of compound of formula VI, is preferably 1-3 equivalents, more preferably 1.2-2.5 equivalents, and even more preferably 1.5-2.0 equivalents.

[0032] In one embodiment, the aldehyde compound of formula III is reacted with hydroxylamine hydrochloride to prepare the oxime compound of formula II. The reaction can be carried out in the presence of sodium acetate. The amount of hydroxylamine hydrochloride used, relative to the amount of the compound of formula III, is preferably 1-3 equivalents, more preferably 1.2-2.5 equivalents, and even more preferably 1.5-2.0 equivalents. The amount of sodium acetate used, relative to the amount of the compound of formula III, is preferably 1-3 equivalents, more preferably 1.5-2.5 equivalents, and even more preferably 1.8-2.0 equivalents.

[0033] In a third aspect, this application provides an insecticidal composition having at least one of the isoxazoline oxime derivatives described in the first aspect of this application as an active ingredient; the insecticidal composition optionally includes a pesticide-acceptable carrier and / or adjuvant.

[0034] The insecticidal composition of this application can be applied in the form of a formulation, wherein the isoxazoline oxime derivative is dissolved or dispersed in a carrier as an active ingredient or formulated into a formulation for easier dispersion when used as an insecticide. The insecticidal composition can be formulated into various dosage forms such as liquids, emulsifiable concentrates, suspensions, aqueous suspensions, microemulsions, emulsions, water-in-oil emulsions, powders, wettable powders, soluble powders, granules, water-dispersible granules, or capsules.

[0035] The insecticidal composition of this application may contain one or more other insecticides, fungicides, herbicides, plant growth regulators, or fertilizers.

[0036] In a fourth aspect, this application also provides the use of the isoxazoline oxime ester derivative described in the first aspect or the insecticidal composition described in the third aspect in the control of pests, particularly in the control of plant pests; preferably for use in agriculture, forestry, horticulture, and sanitation. Preferably, an insecticidally effective amount of the isoxazoline oxime ester derivative described above or the insecticidal composition described above is applied to plants, pests, and / or habitats.

[0037] In a fifth aspect, this application also provides a method for controlling pests, comprising applying an insecticidal effective amount of the isoxazoline oxime derivative described in the first aspect or the insecticidal composition described in the third aspect to plants and / or pests and / or habitats.

[0038] The pests described in this application include Lepidoptera, Coleoptera, Hemiptera, Thysanoptera, Diptera, Orthoptera, Homoptera, Isoptera, Hymenoptera, Blattodea, mites, nematodes, etc., especially Lepidoptera, Coleoptera, and Diptera pests. Preferably, the pests include, but are not limited to, diamondback moth, rice stem borer, cotton bollworm, and corn stink bug.

[0039] The isoxazoline oxime derivatives described in the first aspect of this application are suitable for controlling various agricultural, forestry, and horticultural pests, sanitary pests, and nematodes that harm plants. The isoxazoline oxime derivatives described in the first aspect and the insecticidal composition described in the third aspect of this application can be used in conjunction with one or more other insecticides, fungicides, herbicides, plant growth regulators, or fertilizers.

[0040] The beneficial effects of this invention are as follows:

[0041] This application provides an isoxazoline oxime derivative that exhibits particularly excellent insecticidal activity against pests, especially lepidopteran pests such as the diamondback moth.

[0042] Compared with isoxazoline oxime alkyl ester derivatives, the isoxazoline oxime derivatives described in this application have better insecticidal effects at both high and low doses, and are more environmentally friendly. Attached Figure Description

[0043] Figure 1 Symptoms of diamondback moth toxicity after 48 h of use of compounds 10 and 14 (concentration of 50 µg / mL) in Examples (CK: blank control). Detailed Implementation

[0044] The following provides a detailed description of specific embodiments of the present invention. It should be understood that the specific embodiments described herein are for illustrative and explanatory purposes only and are not intended to limit the scope of the invention.

[0045] The endpoints and any values ​​of the ranges 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 endpoint values ​​of the various ranges, the endpoint values ​​of the various ranges and individual point values, and individual point values ​​can be combined with each other to obtain one or more new numerical ranges, which should be considered as specifically disclosed herein.

[0046] Before describing the invention in detail, it should be understood that the terminology used herein is for describing particular embodiments only and is not intended to limit the scope of the invention, which is defined only by the appended claims. For a more complete understanding of the invention described herein, the following terms are used, and their definitions are as follows. Unless otherwise defined, all technical and scientific terms used herein have the same meaning as understood by one of ordinary skill in the art to which this invention pertains.

[0047] definition

[0048] Unless otherwise specified, the following terms used in this invention have the following definitions.

[0049] Features described or illustrated as part of one implementation or set of implementations may be used in another implementation or set of implementations to produce further implementations.

[0050] The "isoxazoline oxime ester derivatives" described in this application include compounds represented by Formula I, or their stereoisomers, tautomers, isotopic compounds, and pesticide-acceptable salts; and the preferred embodiments described in detail.

[0051] In this application, the ring group on , indicating that there can be n R1s attached to any possible position on the cyclic group.

[0052] In this application, some substituents contain " The "" indicates the connection point.

[0053] Unless otherwise stated, “optional substitution” means that the hydrogen on the substituted group is not substituted or that one or more substituted sites of the substituted group are independently substituted by a substituent, which is independently selected from one or more of deuterium, halogen, amino, hydroxyl, nitro, cyano, mercapto, oxo, optionally substituted alkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, optionally substituted alkyloxy, optionally substituted alkylthio, optionally substituted alkylamine; the substituent on the aryl, heteroaryl, cycloalkyl, and heterocycloalkyl groups may be one or more of deuterium, halogen, amino, hydroxyl, nitro, cyano, mercapto, oxo, optionally substituted alkyl, optionally substituted alkyloxy, optionally substituted alkylthio, optionally substituted alkylamine; the substituent on the alkyl group is selected from one or more of deuterium, halogen, amino, hydroxyl, nitro, cyano, and mercapto; when the substituent is selected as “oxo”, it means that two hydrogen atoms at the same substitution position are replaced by an oxygen atom.

[0054] The term "aryl" refers to an aromatic carbocyclic system containing 6-18 carbon atoms, preferably 6-14 or 6-10 carbon atoms, including monocyclic, bicyclic, and tricyclic systems. Examples of aryl groups include phenyl and naphthyl groups, such as 1-naphthyl, 2-naphthyl, 3-naphthyl, and 4-naphthyl.

[0055] The term "heteroaryl" refers to a 5-18 member structure, or preferably a 5-14 member, 5-10 member, 5-8 member, 5-6 member, or 6-18 member, 6-14 member, 6-10 member, or 6-8 member structure, with a preference for 5-6 member aromatic monocyclic or polycyclic (e.g., bicyclic, tricyclic) cyclic system, wherein one, two, three, four, or more ring atoms are heteroatoms and the remaining atoms are carbon atoms, the heteroatoms being independently selected from O, N, or S, and the number of heteroatoms is preferably one, two, three, or four. The heteroaryl group may be an aromatic monocyclic ring containing 1-3, preferably 1-2, 5-6 member structures selected from N, S, or O, and more preferably an aromatic monocyclic ring containing 1-2 O or S member structures. Examples of heteroaryl groups include, but are not limited to, furanyl, thiophene, oxazolyl, thiazolyl, isoxazolyl, oxadiazolyl, thiadiazolyl, pyrrole, pyrazolyl, imidazole, triazolyl, tetrazolyl, pyridyl, pyrimidinyl, pyrazinyl, thiodiazolyl, triazinyl, phthalazinyl, quinolinyl, isoquinolinyl, pteridinyl, purine, indole, isoindole, indazole, benzofuranyl, benzothiophene, and benzopyridyl. Benzopyrimidinyl, benzopyrazinyl, benzimidazolyl, benzophthalazinyl, pyrrolo[2,3-b]pyridinyl, imidazo[1,2-a]pyridinyl, pyrazolo[1,5-a]pyridinyl, pyrazolo[1,5-a]pyrimidinyl, imidazo[1,2-b]pyridazinyl, [1,2,4]triazolo[4,3-b]pyridazinyl, [1,2,4]triazolo[1,5-a]pyrimidinyl, [1,2,4]triazolo[1,5-a]pyridinyl, pyridin-1-yl, pyridin-2-yl, pyridin-3-yl, pyridin-4-yl, quinoline-2-yl, quinoline-3-yl, quinoline-4-yl, quinoline-5-yl, quinoline-6-yl, quinoline-7-yl, quinoline-8-yl, etc.

[0056] The term "alkyl" refers to a monovalent saturated aliphatic hydrocarbon group, preferably containing 1-20 or 1-18 carbon atoms, more preferably 1-8 carbon atoms (C1-8 alkyl) straight-chain or branched group (the number of carbon atoms is between 1 and 8, specifically 1, 2, 3, 4, 5, 6, 7 or 8), more preferably containing 1-6 carbon atoms (i.e., C1-6 alkyl, the number of carbon atoms is between 1 and 6, specifically 1, 2, 3, 4, 5 or 6). Examples include, but are not limited to, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, sec-butyl, n-pentyl, neopentyl, 1,1-dimethylpropyl, 1,2-dimethylpropyl, 2,2-dimethylpropyl, 1-ethylpropyl, 2-methylbutyl, 3-methylbutyl, n-hexyl, n-heptyl, n-octyl, etc.

[0057] The terms "alkyloxy," "alkylthio," and "alkylamino" refer to -O-alkyl, -S-alkyl, -NH-alkyl, or dialkylamino groups, respectively, with the alkyl group defined as above. Examples include, but are not limited to, methoxy, ethoxy, propoxy, isopropoxy, butoxy, 1-methylpropoxy, 2-methylpropoxy, tert-butoxy, etc.; methylthio, ethylthio, propylthio, isopropylthio, butylthio, 1-methylpropylthio, 2-methylpropylthio, tert-butylthio, etc.; methylamino, ethylamino, propylamino, dimethylamino, diethylamino, dipropylamino, methylethylamino, etc.

[0058] The term "halogen" refers to F, Cl, Br, and I.

[0059] The isoxazoline oxime ester derivatives described in this application are interpreted as including the compound of Formula I and its stereoisomers, tautomers, isotopic compounds, or pesticide-acceptable salts thereof. The stereoisomers, tautomers, isotopic compounds, or pesticide-acceptable salts thereof are obtained by conventional techniques in the art and exert the same or similar effects in vitro and in vivo through substantially the same mechanism of action as the compound.

[0060] The term "stereoisomer" refers to isomers resulting from different spatial arrangements of atoms in a molecule, including configurational isomers and conformational isomers. Configurational isomers include geometric isomers (or cis-trans isomers) and optical isomers (including enantiomers and diastereomers). Geometric isomers may be present in this compound. Optical isomers refer to substances with identical molecular structures and similar physicochemical properties, but different optical rotations. The compounds of this invention may contain asymmetrically substituted carbon atoms in the R or S configuration, wherein the terms "R" and "S" are as defined in IUPAC 1974 Recommendations for Section E, Fundamental Stereochemistry, Pure Appl. Chem. (1976) 45, 13-10. Compounds with asymmetrically substituted carbon atoms (having equal numbers of R and S configurations) are racemic at those carbon atoms. Having an excess of atoms in one configuration (relative to another) results in a higher quantity of that configuration, preferably an excess of about 85%-90%, more preferably an excess of about 95%-99%, and even more preferably an excess greater than about 99%. Accordingly, the present invention includes racemic mixtures, relative and absolute optical isomers, and mixtures of relative and absolute optical isomers.

[0061] The term "tautomer" refers to structural isomers with different energies that can interconvert through a low energy barrier. If tautomerism is possible (e.g., in solution), chemical equilibrium can be achieved for the tautomers. For example, proton tautomers (also called proton transfer tautomers) involve interconversions via proton migration, such as keto-enol isomerization and imine-enamine isomerization. Valence tautomers involve interconversions via the rearrangement of some bonding electrons.

[0062] The term "isotope derivative" refers to compounds of the present invention that can exist in an isotopically traced or enriched form, containing one or more atoms whose atomic weights or mass numbers differ from the atomic weights or mass numbers of the most abundant atoms found in nature. Isotopes can be radioactive or non-radioactive. Isotopes of atoms such as hydrogen, carbon, phosphorus, sulfur, fluorine, chlorine, bromine, and iodine include, but are not limited to: 2 H, 3 H, 13 C, 14 C, 15 N, 18 O, 32 P, 35 S, 18 F, 36 Cl, 80 Br and 125 I. Compounds containing these and / or other isotopes are within the scope of this invention. The isotopically labeled compounds of this invention can be prepared using general methods well known to those skilled in the art.

[0063] The term "pesticide-acceptable salt" refers to a salt obtained by reacting the isoxazoline oxime ester derivative of this application with a chemically acceptable acid, wherein the chemically acceptable acid can be an inorganic acid (such as hydrochloric acid, sulfuric acid, phosphoric acid, or hydrobromic acid) or an organic acid (such as oxalic acid, maleic acid, fumaric acid, malic acid, tartaric acid, citric acid, or benzoic acid); the pesticide-acceptable salt can also be a salt obtained by reacting the isoxazoline oxime ester derivative of this application with a chemically acceptable base, wherein the chemically acceptable base can be an inorganic base (such as sodium hydroxide, potassium hydroxide, calcium hydroxide, sodium carbonate, potassium carbonate, sodium bicarbonate, or potassium bicarbonate) or an organic base (such as trimethylamine, triethylamine, etc.). Further, the pesticide-acceptable salt can be a potassium salt, sodium salt, ammonium salt, calcium salt, pyridine salt, choline salt, hydrochloride salt, phosphate salt, acetate salt, benzenesulfonate salt, or oxalate salt.

[0064] The term "pesticide-acceptable carriers and / or adjuvants" includes, but is not limited to, surfactants, including ionic and nonionic surfactants. The surfactants include emulsifiers, dispersants, or wetting agents. Specifically, the emulsifiers may be polyoxyethylene fatty acid esters, polyoxyethylene fatty alcohol ethers, polyoxyethylene fatty amines, and commercially available emulsifiers; the dispersants include sodium lignosulfonate, dispersing agents, calcium lignosulfonate, or methylnaphthalenesulfonate formaldehyde condensate, etc.; the wetting agents include sodium lauryl sulfate, sodium dodecylbenzenesulfonate, or alkylnaphthalenesulfonate, etc. The pesticide-acceptable carriers include solid carriers and / or liquid carriers. Preferably, the solid carriers include natural or synthetic clays and silicates, such as natural silica and diatomaceous earth; magnesium silicate, such as talc; magnesium aluminum silicate, such as kaolinite, montmorillonite, and mica; white carbon black, calcium carbonate, light calcium carbonate; calcium sulfate; limestone; sodium sulfate; and amine salts such as ammonium sulfate and hexamethylenediamine. Preferably, the liquid carrier comprises water and an organic solvent; when water is used as a solvent or diluent, the organic solvent can be used as an adjuvant or antifreeze additive. Preferably, the organic solvent includes aromatic hydrocarbons (e.g., benzene, xylene, or toluene), chlorinated hydrocarbons (e.g., chlorobenzene, vinyl chloride, chloroform, or dichloromethane), aliphatic hydrocarbons (e.g., petroleum fractions, cyclohexane, or light mineral oil), alcohol solvents (e.g., isopropanol, butanol, ethylene glycol, glycerol, or cyclohexanol), ether solvents, ester solvents, ketone solvents (e.g., acetone, cyclohexanone, or N-methylpyrrolidone), or dimethylformamide. During the formulation of the insecticide composition, the active ingredient can be mixed with the liquid carrier and / or solid carrier, and surfactants (e.g., emulsifiers, dispersants, stabilizers, wetting agents) can be added, as well as other adjuvants (e.g., binders, defoamers, oxidants, etc.).

[0065] According to this application, the isoxazoline oxime derivative can be used in conjunction with one or more other insecticides, fungicides, herbicides, plant growth regulators or fertilizers, and the components can be applied simultaneously, sequentially or separately.

[0066] The effects of specific compounds of this application will be described in detail below through examples.

[0067] Preparation Example 1

[0068] Synthetic routes of methyl ester compounds

[0069]

[0070] A certain amount of the starting material carboxylic acid compound was dissolved in dry DMF, and then appropriate amounts of potassium carbonate and iodomethane were added. The reaction was stirred at room temperature, and the reaction progress was monitored by TLC. After the reaction was completed, water was added to quench the reaction. The reaction solution was diluted with water, extracted with ethyl acetate, washed with saturated brine, and dried over anhydrous Na2SO4. After filtration and concentration, the product was purified by column chromatography to obtain pure product.

[0071] The physicochemical properties of methyl ester compounds are as follows:

[0072] (1) White solid, yield 98%;

[0073] (2) Hydrogen nuclear magnetic resonance spectrum ( 1 H-NMR (400 MHz) characteristics:

[0074] Using deuterated chloroform as solvent and TMS as internal standard, the peaks were assigned as follows: d 7.95 (d, J = 8.6 Hz, 1H), 7.59 (d, J = 6.0 Hz, 2H), 7.56–7.50 (m, 2H), 4.10 (d, J = 17.2 Hz, 1H), 3.91 (s,3H), 3.70 (d, J = 17.2 Hz, 1H), 2.62 (s, 3H).

[0075] Synthetic routes of primary alcohols

[0076]

[0077] One equivalent of the methyl ester compound was dissolved in DCM. The reaction system was placed in an ice-water bath, and two equivalents of DIBAL-H were added dropwise using a syringe. After the addition was complete, the reaction continued. The reaction progress was monitored by TLC. After the reaction was completed, methanol was added to quench the reaction. The reaction solution was diluted with methyl tert-butyl ether, and then saturated potassium sodium tartrate solution was added and stirred thoroughly until both phases were clear. The solution was then extracted twice with ethyl acetate. The combined organic phases were washed with saturated brine and dried over anhydrous Na2SO4. After filtration and concentration, the product was purified by column chromatography.

[0078] The physicochemical properties of primary alcohols are as follows:

[0079] (1) White solid, yield 76%;

[0080] (2) Hydrogen nuclear magnetic resonance spectrum ( 1 H-NMR (400MHz) characteristics:

[0081] Using deuterated chloroform as solvent and TMS as internal standard, the peaks were assigned as follows: d7.59 (d, J = 6.0 Hz, 2H),7.49 (s, 1H), 7.46 (s, 2H), 4.73 (s, 2H), 4.09 (d, J = 17.2 Hz, 1H), 3.69 (d, J =17.2 Hz, 1H), 2.34 (s, 3H).

[0082] Synthetic routes of aldehyde compounds

[0083]

[0084] One equivalent of the primary alcohol compound was dissolved in DCM. The reaction system was placed in an ice-water bath, and then 1.5 equivalents of Des Martin oxidant were added. After the addition was complete, the reaction continued, and the reaction progress was monitored by TLC. After the reaction was completed, water was added to quench the reaction. The reaction solution was diluted with water and extracted twice with ethyl acetate. The combined organic phases were washed with NaOH aqueous solution (1.0 M) and saturated brine, respectively, and dried over anhydrous Na2SO4. After filtration and concentration, the product was purified by column chromatography.

[0085] The physicochemical properties of aldehyde compounds are as follows:

[0086] (1) Colorless oily liquid, yield 80%;

[0087] (2) Hydrogen nuclear magnetic resonance spectrum ( 1 H-NMR (400 MHz) characteristics:

[0088] Using deuterated chloroform as solvent and TMS as internal standard, the peaks were assigned as follows: d : 10.28 (s, 1H), 7.84 (d, J = 8.0 Hz, 1H), 7.63 (d, J = 8.0 Hz, 1H), 7.58 (d, J = 6.2 Hz, 3H), 4.12 (d, J =17.2 Hz, 1H), 3.74 (d, J = 17.2 Hz, 1H), 2.69 (s, 3H).

[0089] Synthetic routes of oxime compounds

[0090]

[0091] One equivalent of the aldehyde compound was dissolved in a mixed solvent of ethanol and water. Then, 1.5 equivalents of hydroxylamine hydrochloride and 2 equivalents of sodium acetate were added. After the addition was complete, the reaction continued. The reaction progress was monitored by TLC. After the reaction was completed, the ethanol was removed by rotary evaporation under reduced pressure. The reaction solution was diluted with water and extracted twice with ethyl acetate. The combined organic phases were washed with saturated brine and dried over anhydrous Na2SO4. After filtration and concentration, the product was purified by column chromatography.

[0092] The physicochemical properties of oxime compounds are as follows:

[0093] (1) White solid, yield 82%;

[0094] (2) Hydrogen nuclear magnetic resonance spectrum ( 1 H-NMR (400 MHz) characteristics:

[0095] Using deuterated chloroform as solvent and TMS as internal standard, the peaks were assigned as follows: d : 8.39 (s, 1H), 7.74 (d, J =4.0 Hz, 1H), 7.59 (d, J = 6.0 Hz, 2H), 7.49 (d, J = 9.2 Hz, 2H), 4.09 (d, J = 17.4Hz, 1H), 3.69 (d, J = 17.2 Hz, 1H), 2.45 (s, 3H).

[0096] Example 1: Synthesis of isoxazoline oxime derivatives 1-20

[0097] One equivalent of the oxime compound was dissolved in dichloromethane, followed by the sequential addition of 0.9 equivalents of triethylamine and 1.2 equivalents of acyl chloride. After the addition was complete, the reaction was continued, and the reaction progress was monitored by TLC. After the reaction was completed, the reaction solution was diluted with water and extracted twice with ethyl acetate. The combined organic phases were washed with saturated brine and dried over anhydrous Na₂SO₄. After filtration and concentration, the solution was purified by column chromatography to obtain a white solid.

[0098] The general reaction formula is as follows:

[0099] .

[0100] The physicochemical properties of compound 1 are as follows:

[0101] (1) White solid, yield 71%;

[0102] (2) The proton nuclear magnetic resonance spectrum of this compound ( 1 H-NMR (300 MHz) characteristics:

[0103] Using deuterated chloroform as solvent and TMS as internal standard, the peaks were assigned as follows: d : 8.82 (s, 1H), 8.17–8.15 (m, 1H), 8.13 (d, J = 1.5 Hz, 1H), 8.05 (d, J = 8.2 Hz, 1H), 7.67–7.57 (m, 4H), 7.55–7.52 (m, 1H), 7.52–7.47 (m, 2H), 4.16–4.07 (m, 1H), 3.72 (d, J = 17.2 Hz, 1H), 2.56 (s, 3H).

[0104] (3) HRMS(ESI): calcd for C 25 H 16 Cl2F4N2O3Na [M+Na] + , 561.0372, found561.0363.

[0105] The physicochemical properties of compound 2 are as follows:

[0106] (1) White solid, yield 85%;

[0107] (2) The proton nuclear magnetic resonance spectrum of this compound ( 1 H-NMR (400 MHz) characteristics:

[0108] Using deuterated chloroform as solvent and TMS as internal standard, the peaks were assigned as follows: d : 8.81 (s, 1H), 8.03 (dd, J =8.5, 3.9 Hz, 3H), 7.60 (d, J = 5.2 Hz, 3H), 7.52 (d, J = 8.2 Hz, 1H), 7.30 (d, J =8.0 Hz, 2H), 4.11 (d, J = 17.1 Hz, 1H), 3.72 (d, J = 17.2 Hz, 1H), 2.55 (s, 3H), 2.45 (s, 3H).

[0109] (3) HRMS(ESI): calcd for C 26 H 18 Cl2F4N2O3Na [M+Na] +, 575.0528, found575.0533.

[0110] The physicochemical properties of compound 3 are as follows:

[0111] (1) White solid, yield 72%;

[0112] (2) The proton nuclear magnetic resonance spectrum of this compound ( 1 H-NMR (400 MHz) characteristics:

[0113] Using deuterated chloroform as solvent and TMS as internal standard, the peaks were assigned as follows: d : 8.79 (s, 1H), 8.10 (d, J =8.4 Hz, 2H), 8.03 (d, J = 8.1 Hz, 1H), 7.59 (d, J = 3.8 Hz, 3H), 7.51 (d, J = 8.3Hz, 1H), 6.97 (d, J = 8.4 Hz, 2H), 4.11 (d, J = 17.1 Hz, 1H), 3.89 (s, 3H), 3.72(d, J = 17.1 Hz, 1H), 2.55 (s, 3H).

[0114] (3) HRMS(ESI): calcd for C 26 H 18 Cl2F4N2O4Na [M+Na] + , 591.0477, found591.0476.

[0115] The physicochemical properties of compound 4 are as follows:

[0116] (1) White solid, yield 81%;

[0117] (2) The proton nuclear magnetic resonance spectrum of this compound ( 1 H-NMR (400 MHz) characteristics:

[0118] Using deuterated chloroform as solvent and TMS as internal standard, the peaks were assigned as follows: d : 8.78 (s, 1H), 8.04 (d, J =8.2 Hz, 1H), 7.96 (d, J = 7.8 Hz, 1H), 7.60 (d, J= 4.2 Hz, 3H), 7.52 (d, J = 8.3Hz, 1H), 7.47 (t, J = 7.5 Hz, 1H), 7.30 (t, J = 9.0 Hz, 2H), 4.11 (d, J = 17.2 Hz, 1H), 3.72 (d, J = 17.1 Hz, 1H), 2.67 (s, 3H), 2.55 (s, 3H).

[0119] (3) HRMS(ESI): calcd for C 26 H 18 Cl2F4N2O3Na [M+Na] + , 575.0528, found575.0526.

[0120] The physicochemical properties of compound 5 are as follows:

[0121] (1) White solid, yield 74%;

[0122] (2) The proton nuclear magnetic resonance spectrum of this compound ( 1 H-NMR (400 MHz) characteristics:

[0123] Using deuterated chloroform as solvent and TMS as internal standard, the peaks were assigned as follows: d : 8.82 (s, 1H), 8.04 (d, J =8.1 Hz, 1H), 7.94 (d, J = 10.2 Hz, 2H), 7.60 (d, J = 5.5 Hz, 3H), 7.52 (d, J = 8.2Hz, 1H), 7.44 (d, J = 7.6 Hz, 1H), 7.39 (t, J = 7.6 Hz, 1H), 4.11 (d, J = 17.0 Hz, 1H), 3.72 (d, J = 17.2 Hz, 1H), 2.56 (s, 3H), 2.44 (s, 3H).

[0124] (3) HRMS(ESI): calcd for C 26 H 18 Cl2F4N2O3Na [M+Na]+ , 575.0528, found575.0531.

[0125] The physicochemical properties of compound 6 are as follows:

[0126] (1) White solid, yield 74%;

[0127] (2) The proton nuclear magnetic resonance spectrum of this compound ( 1 H-NMR (400 MHz) characteristics:

[0128] Using deuterated chloroform as solvent and TMS as internal standard, the peaks were assigned as follows: d : 8.81 (s, 1H), 8.03 (d, J =8.1 Hz, 1H), 7.73 (d, J = 7.6 Hz, 1H), 7.64 (s, 1H), 7.60 (d, J = 5.2 Hz, 3H), 7.52 (d, J = 8.2 Hz, 1H), 7.41 (t, J = 8.0 Hz, 1H), 7.17 (d, J = 8.0 Hz, 1H), 4.11(d, J = 17.1 Hz, 1H), 3.89 (s, 3H), 3.72 (d, J = 17.1 Hz, 1H), 2.56 (s, 3H).

[0129] (3) HRMS(ESI): calcd for C 26 H 18 Cl2F4N2O4Na [M+Na] + , 591.0477, found591.0480.

[0130] The physicochemical properties of compound 7 are as follows:

[0131] (1) White solid, yield 76%;

[0132] (2) The proton nuclear magnetic resonance spectrum of this compound ( 1 H-NMR (400 MHz) characteristics:

[0133] Using deuterated chloroform as solvent and TMS as internal standard, the peaks were assigned as follows: d : 8.74 (s, 1H), 8.02 (d, J =8.1 Hz, 1H), 7.83 (d,J = 7.6 Hz, 1H), 7.59 (d, J = 5.8 Hz, 3H), 7.52 (d, J = 8.2Hz, 2H), 7.03 (t, J = 8.0 Hz, 2H), 4.11 (d, J = 17.2 Hz, 1H), 3.93 (s, 3H), 3.71(d, J = 17.2 Hz, 1H), 2.53 (s, 3H).

[0134] (3) HRMS(ESI): calcd for C 26 H 18 Cl2F4N2O4Na [M+Na] + , 591.0477, found591.0477.

[0135] The physicochemical properties of compound 8 are as follows:

[0136] (1) White solid, yield 57%;

[0137] (2) The proton nuclear magnetic resonance spectrum of this compound ( 1 H-NMR (400 MHz) characteristics:

[0138] Using deuterated chloroform as solvent and TMS as internal standard, the peaks were assigned as follows: d :8.82 (s, 1H), 8.27 (s,1H), 8.08 (d, J = 7.8 Hz, 1H), 8.03 (d, J = 8.2 Hz, 1H), 7.76 (d, J = 8.2 Hz, 1H), 7.60 (d, J = 6.0 Hz, 3H), 7.53 (d, J = 8.0 Hz, 1H), 7.39 (t, J = 7.9 Hz, 1H), 4.11(d, J = 17.1 Hz, 1H), 3.71 (d, J = 17.2 Hz, 1H), 2.56 (s, 3H).

[0139] (3) HRMS(ESI): calcd for C 25 H 15BrCl2F4N2O3Na [M+Na] + , 638.9477, found638.9480.

[0140] The physicochemical properties of compound 9 are as follows:

[0141] (1) White solid, yield 86%;

[0142] (2) The proton nuclear magnetic resonance spectrum of this compound ( 1 H-NMR (400 MHz) characteristics:

[0143] Using deuterated chloroform as solvent and TMS as internal standard, the peaks were assigned as follows: d : 8.77 (s, 1H), 8.01 (d, J =8.2 Hz, 1H), 7.97 (d, J = 3.1 Hz, 1H), 7.66 (d, J = 5.0 Hz, 1H), 7.59 (d, J = 4.9Hz, 3H), 7.52 (d, J = 8.2 Hz, 1H), 7.18 (t, J = 4.4 Hz, 1H), 4.11 (d, J = 17.2 Hz, 1H), 3.71 (d, J = 17.2 Hz, 1H), 2.55 (s, 3H).

[0144] (3) HRMS(ESI): calcd for C 23 H 14 Cl2F4N2O3SNa [M+Na] + , 566.9936, found566.9931.

[0145] The physicochemical properties of compound 10 are as follows:

[0146] (1) White solid, yield 71%;

[0147] (2) The proton nuclear magnetic resonance spectrum of this compound ( 1 H-NMR (400 MHz) characteristics:

[0148] Using deuterated chloroform as solvent and TMS as internal standard, the peaks were assigned as follows: d : 8.80 (s, 1H), 8.01 (t, J =8.20 Hz, 3H), 7.65 (d,J = 8:2 Hz, 2H), 7.59 (d, J = 5.9 Hz, 3H), 7.53 (d, J = 8.2Hz, 1H), 4.11 (d, J = 17.2 Hz, 1H), 3.71 (d, J = 17.2 Hz, 1H), 2.56 (s, 3H).

[0149] (3) HRMS(ESI): calcd for C 25 H 15 BrCl2F4N2O3Na [M+Na] + , 638.9477, found638.9478.

[0150] The physicochemical properties of compound 11 are as follows:

[0151] (1) White solid, yield 81%;

[0152] (2) The proton nuclear magnetic resonance spectrum of this compound ( 1 H-NMR (400 MHz) characteristics:

[0153] Using deuterated chloroform as solvent and TMS as internal standard, the peaks were assigned as follows: d : 8.77 (s, 1H), 8.01 (d, J =8.2 Hz, 1H), 7.82 (dd, J = 7.2, 2.2 Hz, 1H), 7.71 (d, J = 7.4 Hz, 1H), 7.59 (d, J =5.0 Hz, 3H), 7.53 (d, J = 8.2 Hz, 1H), 7.47 – 7.34 (m, 2H), 4.11 (d, J = 17.1 Hz, 1H), 3.71 (d, J = 17.2 Hz, 1H), 2.54 (s, 3H).

[0154] (3) HRMS(ESI): calcd for C 25 H 15 BrCl2F4N2O3Na [M+Na] + , 638.9477, found638.9479.

[0155] The physicochemical properties of compound 12 are as follows:

[0156] (1) White solid, yield 81%;

[0157] (2) The proton nuclear magnetic resonance spectrum of this compound ( 1 H-NMR (400 MHz) characteristics:

[0158] Using deuterated chloroform as solvent and TMS as internal standard, the peaks were assigned as follows: d : 8.78 (s, 1H), 8.01 (d, J =8.2 Hz, 1H), 7.67 (s, 1H), 7.59 (d, J = 5.1 Hz, 3H), 7.52 (d, J = 8.1 Hz, 1H), 7.35 (d, J = 3.6 Hz, 1H), 6.59 (t, J = 1.7 Hz, 1H), 4.10 (d, J = 17.4 Hz, 1H), 3.71(d, J = 17.2 Hz, 1H), 2.54 (s, 3H).

[0159] (3) HRMS(ESI): calcd for C 23 H 14 Cl2F4N2O4Na [M+Na] + , 551.0164, found551.0167.

[0160] The physicochemical properties of compound 13 are as follows:

[0161] (1) White solid, yield 88%;

[0162] (2) The proton nuclear magnetic resonance spectrum of this compound ( 1 H-NMR (400 MHz) characteristics:

[0163] Using deuterated chloroform as solvent and TMS as internal standard, the peaks were assigned as follows: d : 8.80 (s, 1H), 8.07 (d, J =8.3 Hz, 2H), 8.01 (d, J = 8.1 Hz, 1H), 7.59 (d, J = 5.7 Hz, 3H), 7.53 (d, J= 8.1Hz, 1H), 7.48 (d, J = 8.3 Hz, 2H), 4.11 (d, J = 17.1 Hz, 1H), 3.71 (d, J = 17.1 Hz, 1H), 2.55 (s, 3H).

[0164] (3) HRMS(ESI): calcd for C 25 H 15 Cl3F4N2O3Na [M+Na] + , 594.9982, found594.9979.

[0165] The physicochemical properties of compound 14 are as follows:

[0166] (1) White solid, yield 84%;

[0167] (2) The proton nuclear magnetic resonance spectrum of this compound ( 1 H-NMR (400 MHz) characteristics:

[0168] Using deuterated chloroform as solvent and TMS as internal standard, the peaks were assigned as follows: d : 8.82 (s, 1H), 8.24 (d, J =8.2 Hz, 2H), 8.02 (d, J = 8.1 Hz, 1H), 7.81 (d, J = 8.2 Hz, 2H), 7.63 – 7.58 (m,3H), 7.54 (d, J = 8.2 Hz, 1H), 4.11 (d, J = 17.2 Hz, 1H), 3.71 (d, J = 17.2 Hz, 1H), 2.56 (s, 3H).

[0169] (3) HRMS(ESI): calcd for C 26 H 15 Cl2F4N3O3Na [M+Na] + , 586.0324, found586.0315.

[0170] The physicochemical properties of compound 15 are as follows:

[0171] (1) White solid, yield 83%;

[0172] (2) The proton nuclear magnetic resonance spectrum of this compound ( 1 H-NMR (400 MHz) characteristics:

[0173] Using deuterated chloroform as solvent and TMS as internal standard, the peaks were assigned as follows: d : 8.80 (s, 1H), 8.02 (d, J =8.1 Hz, 1H), 7.85 (q, J = 8.3 Hz, 4H), 7.59 (d, J = 5.5 Hz, 3H), 7.52 (d, J = 8.1Hz, 1H), 4.11 (d, J = 17.2 Hz, 1H), 3.73 (s, 1H), 2.55 (s, 3H).

[0174] (3) HRMS(ESI): calcd for C 25 H 15 Cl2F4IN2O3Na [M+Na] + , 686.9338, found686.9329.

[0175] The physicochemical properties of compound 16 are as follows:

[0176] (1) White solid, yield 86%;

[0177] (2) The proton nuclear magnetic resonance spectrum of this compound ( 1 H-NMR (400 MHz) characteristics:

[0178] Using deuterated chloroform as solvent and TMS as internal standard, the peaks were assigned as follows: d : 8.77 (s, 1H), 8.01 (d, J =8.1 Hz, 1H), 7.87 (d, J = 7.6 Hz, 1H), 7.59 (d, J = 5.4 Hz, 3H), 7.56 – 7.44 (m,3H), 7.38 (t, J = 7.3 Hz, 1H), 4.11 (d, J = 17.2 Hz, 1H), 3.71 (d, J = 17.2 Hz, 1H), 2.54 (s, 3H).

[0179] (3) HRMS(ESI): calcd for C25 H 15 Cl3F4N2O3Na [M+Na] + , 594.9982, found594.9974.

[0180] The physicochemical properties of compound 17 are as follows:

[0181] (1) White solid, yield 94%;

[0182] (2) The proton nuclear magnetic resonance spectrum of this compound ( 1 H-NMR (400 MHz) characteristics:

[0183] Using deuterated chloroform as solvent and TMS as internal standard, the peaks were assigned as follows: d :8.82 (s, 1H), 8.11 (s,1H), 8.02 (d, J = 8.0 Hz, 2H), 7.59 (d, J = 5.5 Hz, 4H), 7.53 (d, J = 8.1 Hz, 1H), 7.45 (t, J = 7.9 Hz, 1H), 4.11 (d, J = 17.2 Hz, 1H), 3.72 (d, J = 17.1 Hz (1H), 2.56 (s, 3H).

[0184] (3) HRMS(ESI): calcd for C 25 H 15 Cl3F4N2O3Na [M+Na] + , 594.9982, found594.9986.

[0185] The physicochemical properties of compound 18 are as follows:

[0186] (1) White solid, yield 67%;

[0187] (2) The proton nuclear magnetic resonance spectrum of this compound ( 1 H-NMR (400 MHz) characteristics:

[0188] Using deuterated chloroform as solvent and TMS as internal standard, the peaks were assigned as follows: d : 8.79 (s, 1H), 8.03 (dd, J =11.9, 7.6 Hz, 2H), 7.59 (d, J= 5.4 Hz, 4H), 7.53 (d, J = 8.0 Hz, 1H), 7.29 (d, J =7.6 Hz, 1H), 7.24 – 7.15 (m, 1H), 4.11 (d, J = 17.2 Hz, 1H), 3.71 (d, J = 17.2Hz, 1H), 2.55 (s, 3H).

[0189] (3) HRMS(ESI): calcd for C 25 H 15 Cl2F5N2O3Na [M+Na] + , 579.0278, found579.0279.

[0190] The physicochemical properties of compound 19 are as follows:

[0191] (1) White solid, yield 65%;

[0192] (2) The proton nuclear magnetic resonance spectrum of this compound ( 1 H-NMR (400 MHz) characteristics:

[0193] Using deuterated chloroform as solvent and TMS as internal standard, the peaks were assigned as follows: d :8.85 (s, 1H), 8.39 (s,1H), 8.34 (d, J = 8.0 Hz, 1H), 8.03 (d, J = 8.1 Hz, 1H), 7.89 (d, J = 8.0 Hz, 1H), 7.67 (t, J = 7.8 Hz, 1H), 7.60 (d, J = 6.6 Hz, 3H), 7.54 (d, J = 8.2 Hz, 1H), 4.11(d, J = 17.1 Hz, 1H), 3.72 (d, J = 17.2 Hz, 1H), 2.57 (s, 3H).

[0194] (3) HRMS(ESI): calcd for C 26 H 15 Cl2F7N2O3Na [M+Na] +, 629.0246, found629.0244.

[0195] The physicochemical properties of compound 20 are as follows:

[0196] (1) White solid, yield 63%;

[0197] (2) The proton nuclear magnetic resonance spectrum of this compound ( 1 H-NMR (400 MHz) characteristics:

[0198] Using deuterated chloroform as solvent and TMS as internal standard, the peaks were assigned as follows: d : 8.81 (s, 1H), 8.21 (d, J =7.0 Hz, 1H), 8.03 (dd, J = 12.6, 7.2 Hz, 2H), 7.59 (d, J = 6.3 Hz, 3H), 7.53 (d, J = 8.1 Hz, 1H), 7.28 (d, J = 8.6 Hz, 1H), 4.11 (d, J = 17.1 Hz, 1H), 3.71 (d, J =17.2 Hz, 1H), 2.56 (s, 3H).

[0199] Test Example 1: Insecticidal Activity Determination of Isoxazoline Oxime Derivatives 1-20

[0200] Life test experiment of diamondback moth:

[0201] 1. Test insects:

[0202] Diamondback moth ( Plutella xylostella Linnaeus, a sensitive population of this species, was raised indoors by the College of Horticulture and Plant Protection, Henan University of Science and Technology. The temperature range was 24℃-26℃, humidity range was 60%-80%, and light intensity (L:D) was 16h:8h. Second-instar larvae of the diamondback moth were used in the experiment.

[0203] 2. Samples and reagents

[0204] Compounds 1-20 prepared in the examples, and comparative compounds 1-2; acetone (solvent, brand: Greatent, AR).

[0205] 3. Bioassay Methods

[0206] Preparation of test solutions: Weigh 4.0 mg of the test compound and the control compound, and add 8 mL of acetone to prepare a test solution of 500 µg / mL; take another 2 mL of the 500 µg / mL test solution and dilute it 10 times to obtain a test solution of 50 µg / mL.

[0207] Small leaf disc addition method: Using acetone as a blank control, the insecticidal activity of the compound was determined at two concentrations: 500 µg / mL and 50 µg / mL.

[0208] A layer of filter paper was placed at the bottom of a 9 cm diameter petri dish, and sterile water was added to maintain humidity. Ten healthy second-instar diamondback moth larvae of uniform size were selected from each dish, with each dish constituting one replicate, and three replicates for each treatment. Fresh cabbage leaves were cut into 1 × 1 cm pieces. 2 The small leaf butterflies were immersed in pre-prepared test and control solutions for 3 seconds and then air-dried naturally (acetone was used as a blank control). After starving the test insects for 3-4 hours, 10 poisoned leaf discs were added to the petri dish. After 12 hours, the number of leaves consumed by the test insects was recorded, and the number of dead insects and symptoms of poisoning were observed and recorded. New poisoned leaf discs were then added. The dish was placed at (25 ± 2) o C. The insects were reared under conditions of 60%–80% relative humidity and a photoperiod of 16 h / 8 h. The poisoned leaf discs were replaced every 12 hours for a total of 4 treatments, and the number of leaves consumed was recorded. Afterward, a sufficient amount of non-toxic fresh leaf discs were added daily, and the number of insect deaths was recorded.

[0209] Calculate the mortality rate (%) and adjusted mortality rate (%) for different periods using the following formulas.

[0210]

[0211]

[0212] Table 1. Insecticidal activity of isoxazoline oxime derivatives against diamondback moth at concentrations of 500 µg / mL and 50 µg / mL.

[0213]

[0214] Figure 1 The graph shows the toxicity symptoms of diamondback moths after 48 h of treatment with representative compounds 10 and 14 (concentration of 50 µg / mL) (CK: blank control). It is evident that diamondback moths exhibited significant poisoning symptoms after treatment with the isoxazoline oxime derivatives of this application.

[0215] The poisoned test insects initially become excited, then paralyzed. In the early stages of poisoning, their movements slow down, but their heads sway upwards. As time progresses, the test insects gradually become limp and die, their bodies shrinking after death.

[0216] in conclusion:

[0217] The above insecticidal data show that the insecticidal activity of the isoxazoline oxime derivatives described in this application is superior to that of isoxazoline oxime derivatives with R being methyl or ethyl at concentrations of 500 µg / mL and 50 µg / mL. At 48 h, at a concentration of 500 µg / mL, isoxazoline oxime derivatives 1, 3-6, 8-10, 12-14, and 17-19 exhibited significant insecticidal activity against the diamondback moth, with a corrected mortality rate of 100%. When the isoxazoline oxime derivatives were diluted to 50 µg / mL, at 48 h, derivatives 1, 3, 8-10, 12, 14, and 18 also showed significant insecticidal activity against the diamondback moth, with a corrected mortality rate >95%; additionally, derivatives 1, 9, and 12 showed excellent insecticidal activity against the diamondback moth, with a corrected mortality rate of 100%. This indicates that isoxazoline oxime derivatives 1, 3, 8-10, 12, 14, and 18 of this application are preferred compounds for such isoxazoline oxime derivative insecticides.

[0218] The above description is merely a preferred embodiment of the present invention and is not intended to limit the present invention in any way. Although the present invention has been disclosed above with reference to preferred embodiments, it is not intended to limit the present invention. Any person skilled in the art can make some modifications or alterations to the above-described technical content to create equivalent embodiments without departing from the scope of the present invention. Any simple modifications, equivalent changes, and alterations made to the above embodiments based on the technical essence of the present invention without departing from the scope of the present invention shall still fall within the scope of the present invention.

Claims

1. An isoxazoline oxime ester derivative, characterized in that, For compounds represented by formula IA and pesticide-acceptable salts: Wherein, R is Ph-, (4-Me)Ph-, (4-MeO)Ph-, (2-Me)Ph-, (3-Me)Ph-, (3-MeO)Ph-, (2-MeO)Ph-, (3-Br)Ph-, (4-Br)Ph-, (4-Cl)Ph-, (4-CN)Ph-, (4-I)Ph-, (2-Cl)Ph-, (3-Cl)Ph-, (2-F)Ph-, (3-CF3)Ph-; or R is 2-furanyl or 2-thienyl.

2. An insecticidal composition, characterized in that, The insecticidal composition may contain at least one of the isoxazoline oxime derivatives of claim 1 as an active ingredient; the insecticidal composition may optionally contain a pesticide-acceptable carrier and / or adjuvant.

3. Use of the isoxazoline oxime ester derivative of claim 1 or the insecticidal composition of claim 2 for controlling pests, wherein the pest is the diamondback moth.

4. A method for controlling plant pests, characterized in that, This includes applying an insecticidal effective amount of the isoxazoline oxime derivative of claim 1 or the insecticidal composition of claim 2 to plants, and / or pests, and / or habitats, wherein the pest is the diamondback moth.

Images