Preparation and use of novel trifluoroalkylthiophenylpyridine derivatives

Abstract

The present invention relates to the preparation and use of novel trifluoroalkylthiophenylpyridine derivatives. Specifically, the present invention relates to compounds of formula (I-1) or formula (I-2) as trifluoroalkylthiophenylpyridine derivatives, or isotope labeled compounds thereof, or optical isomers, geometric isomers, tautomers or mixtures of isomers thereof, or agriculturally acceptable salts thereof, as well as the use of said compounds in the preparation of insecticides for pest control. These compounds are capable of achieving better pest control effects at lower dosages, especially against pests and mites such as Tetranychus cinnabarinus, Tetranychus urticae, and Panonychus citri.

Description

Preparation and application of novel trifluoroalkylthiophenylpyridine derivatives

[0001] Cross-references to related applications

[0002] This application claims priority to Chinese Patent Application No. 202411661992.2, filed on November 20, 2024, the entire contents of which are incorporated herein by reference. Technical Field

[0003] This invention relates to the field of pesticide technology, and more specifically, to the preparation and application of novel trifluorothiophenylpyridine derivatives. Background Technology

[0004] Agricultural mites are recognized worldwide as one of the most difficult biological groups to control. They are characterized by rapid reproduction, short generation time, strong adaptability, high mutation rate, easy development of pesticide resistance, and easy outbreaks. They can harm and feed on more than 1,100 host plants, causing serious damage to fruits, vegetables, flowers, etc., and causing losses of more than 10 billion yuan to my country every year.

[0005] Currently, chemical control remains the most effective measure for controlling plant mites, with annual expenditures on chemical acaricides reaching approximately one billion US dollars. Patent WO1999055668A discloses a class of trifluoroethyl thiopyridine derivatives, some of which exhibit a mortality rate of over 90% against the two-spotted spider mite at a concentration of 500 ppm. However, they have significant drawbacks in application, exhibiting insufficient acaricidal activity, especially at lower application rates.

[0006] Trifluoroethyl sulfide (sulfoxide) compounds are a new class of compounds with good acaricidal activity. Flupentiofenox developed by combinatorial chemistry, Sulfiflumin developed by Bayer Crop Science AG, and Bisulflufen developed by Shenyang Sinochem Pesticide & Chemical R&D Co., Ltd. obtained ISO generic names in 2020, 2023, and 2023, respectively. These compounds have shown good acaricidal activity against plant mites and are currently undergoing industrialization development.

[0007] The current acaricide market faces serious problems such as high resistance, poor control effect, severe homogenization, and environmental insecurity. Therefore, there is an urgent need to develop new acaricides to solve these problems. Summary of the Invention

[0008] The purpose of this invention is to provide a new class of novel trifluoroalkylthiophenylpyridine derivatives. These compounds can achieve better pest control effects with lower dosages, and can effectively kill insects, mites, and pests, as well as animal pests (including arthropods, and particularly insects or mites). Furthermore, the compounds provided by this invention have a simple synthetic process, low production cost, and great potential for future development.

[0009] In a first aspect, the present invention provides a compound containing a trifluoroalkylthiophenylpyridine derivative or its isotopically labeled compound, or its optical isomer, geometric isomer, tautomer, or mixture of isomers, or its pesticide-acceptable salt, wherein the trifluoroalkylthiophenylpyridine derivative has the structure of a compound of formula (I-1) or formula (I-2):

[0010] in,

[0011] R1 is selected from C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkoxy, C1-C6 haloalkoxy, cyanoC1-C6 alkyl, C3-C6 cycloalkylC1-C3 alkyl or C3-C6 epoxyalkylC1-C3 alkyl.

[0012] R2 is selected from methyl or chlorine;

[0013] R4 is fluorine;

[0014] X1, X2 and X4 are each independently selected from H, halogen, C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkylamino, C1-C3 alkylthio, C1-C3 alkylsulfonyl, hydroxyl, nitro, amino, cyano, aldehyde, carboxyl, amide or ester.

[0015] X3 is selected from halogen, nitro, cyano, C1-C3 alkylthio or C1-C3 alkylsulfonyl;

[0016] n is 0 or 1.

[0017] In one embodiment of the present invention, wherein,

[0018] R1 is selected from C1-C3 alkyl, C1-C3 haloalkyl, cyanoC1-C3 alkyl or C3-C6 cycloalkylC1-C3 alkyl;

[0019] R2 is selected from methyl or chlorine;

[0020] R4 is fluorine;

[0021] X1, X2 and X4 are each independently selected from H, halogen, C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkylamino, C1-C3 alkylthio, C1-C3 alkylsulfonyl, hydroxyl, nitro, amino, cyano, aldehyde, carboxyl, amide or ester.

[0022] X3 is selected from halogen, nitro, cyano, C1-C3 alkylthio or C1-C3 alkylsulfonyl;

[0023] n is 0 or 1.

[0024] In one embodiment of the present invention, wherein,

[0025] R1 is selected from methyl, ethyl, propyl, tert-butyl, isobutyl, dichloroethyl, trichloroethyl, trichloropropyl, fluoromethyl, difluoromethyl, trifluoromethyl, difluoroethyl, trifluoroethyl, tetrafluoroethyl, pentafluoroethyl, trifluoropropyl, heptafluoropropyl, 1-cyanomethyl, cyclopropylmethyl, or glycidyl methyl.

[0026] R2 is selected from methyl or chlorine;

[0027] R4 is fluorine;

[0028] X1, X2 and X4 are each independently selected from H, halogen, C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkylamino, C1-C3 alkylthio, C1-C3 alkylsulfonyl, hydroxyl, nitro, amino, cyano, aldehyde, carboxyl, amide or ester.

[0029] X3 is selected from halogen, nitro, cyano, C1-C3 alkylthio or C1-C3 alkylsulfonyl;

[0030] n is 0 or 1.

[0031] In one embodiment of the present invention, wherein,

[0032] R1 is selected from CH3, CF3, CH2CH3, CH2CHF2, CH2CF3, CH2CH2CF3, 1-cyanomethyl, cyclopropylmethyl, CH2CHCl2, CH2CCl3, CH2CH2CCl3 or glycidylmethyl;

[0033] R2 is selected from methyl or chlorine;

[0034] R4 is fluorine;

[0035] X1, X2, and X4 are each independently selected from H, fluorine, chlorine, bromine, iodine, methyl, ethyl, propyl, tert-butyl, isopropyl, difluoromethyl, trifluoromethyl, trifluoroethyl, hydroxyl, nitro, amino, cyano, aldehyde, carboxyl, amide, ester, methylamino, methylthio, or methylsulfone.

[0036] X3 is selected from fluorine, chlorine, bromine, iodine, nitro, cyano, methylthio, or methylsulfone.

[0037] n is 0 or 1.

[0038] In another embodiment of the invention, wherein,

[0039] R1 is selected from CH3, CF3, CH2CH3, CH2CHF2, CH2CF3, CH2CH2CF3, 1-cyanomethyl or cyclopropylmethyl;

[0040] R2 is a methyl group;

[0041] R4 is fluorine;

[0042] X1, X2, and X4 are each independently selected from H, fluorine, chlorine, bromine, methyl, cyclopropyl, difluoromethyl, trifluoromethyl, nitro, amino, cyano, carboxyl, or ester groups;

[0043] X3 is selected from fluorine, chlorine, bromine, nitro, cyano or SCH3;

[0044] n is 0.

[0045] In one embodiment of the present invention, the compound of formula (I-1) of the present invention has the structure of formula (I-1-1):

[0046] in,

[0047] R1 is selected from CH2CH3, CH2CHF2, CH2CF3 or CH2CH2CF3;

[0048] R2 is selected from methyl or chlorine;

[0049] R4 is selected from fluorine;

[0050] X1 is selected from H, fluorine, chlorine, or bromine;

[0051] X2 is selected from H, fluorine, chlorine, bromine or methyl;

[0052] X3 is selected from fluorine, chlorine, bromine, cyano, nitro, or methylthio;

[0053] n is 0 or 1.

[0054] In one embodiment of the present invention, the compound of formula (I-1) of the present invention has the structure of formula (I-1-2):

[0055] in,

[0056] X1 is selected from fluorine, chlorine, or bromine;

[0057] X3 is selected from fluorine, chlorine, bromine, nitro, cyano, or methylthio;

[0058] n is 0 or 1.

[0059] In one embodiment of the present invention, the compound of formula (I-1) of the present invention has the structure of formula (I-1-3):

[0060] in,

[0061] X2 is selected from H, fluorine, chlorine, bromine or methyl;

[0062] X3 is selected from fluorine, chlorine, bromine, nitro, cyano, or methylthio;

[0063] n is 0 or 1.

[0064] In one embodiment of the present invention, the compound of formula (I-2) of the present invention has the structure of formula (I-2-1):

[0065] in,

[0066] R1 is selected from CH3, CF3, CH2CH3, CH2CHF2, CH2CF3, CH2CH2CF3, CH2CN, or cyclopropylmethyl;

[0067] R2 is selected from methyl or chlorine;

[0068] R4 is fluorine;

[0069] X2 is selected from H, fluorine, chlorine, bromine, methyl, trifluoromethyl, cyano, or nitro;

[0070] X3 is selected from fluorine, chlorine, bromine, cyano, nitro or SCH3;

[0071] n is 0 or 1.

[0072] In one embodiment of the present invention, the compound of formula (I-2) of the present invention has the structure of formula (I-2-2):

[0073] in,

[0074] R1 is selected from CH2CH3, CH2CHF2, CH2CF3 or CH2CH2CF3;

[0075] X2 is selected from H, fluorine, chlorine, bromine, methyl, trifluoromethyl, cyano, or nitro;

[0076] X3 is selected from fluorine, chlorine, bromine, cyano, nitro or SCH3;

[0077] n is 0 or 1.

[0078] For the sake of brevity, the following terms “novel trifluoroalkylthiophenylpyridine derivatives”, “compound of formula (I-1)”, “compound of formula (I-2)” or “compound of the present invention” may also encompass any isotopically labeled compound of formula (I-1) or formula (I-2), or an optical isomer, geometric isomer, tautomer or mixture of isomers thereof, or a pesticide-acceptable salt thereof.

[0079] The term "optical isomer" refers to the various isomers formed when a compound has one or more chiral centers, each of which can exist in either an R or S configuration. Optical isomers include all diastereomers, enantiomers, meso compounds, racemates, or mixtures thereof. For example, optical isomers can be separated by chiral chromatography or by chiral synthesis.

[0080] The term "geometric isomer" refers to the fact that a compound can exist as cis, trans, E-type, and Z-type isomers when a double bond is present. Geometric isomers include cis, trans, E-type, Z-type isomers, or mixtures thereof.

[0081] The term "tautomer" refers to an isomer that results from the rapid movement of an atom in a molecule to two different positions. Those skilled in the art will understand that tautomers can interconvert and may coexist in an equilibrium state under certain conditions.

[0082] The term "nematode" includes all species of the phylum Nematoda, and in the context, especially species that are parasites on plants (e.g., species of Aphelenchida, root-knot nematodes, Tylenchida, and others).

[0083] Unless otherwise specified, references herein to “novel compounds containing trifluoroalkylthiophenylpyridine derivatives,” “compound of formula (I-1),” “compound of formula (I-2),” or “compounds of the present invention” also encompass isotopically labeled compounds obtained by replacing any atom in the compound with its isotopic atom. The present invention includes all pharmaceutically acceptable isotopically labeled compounds of formula (I-1) or formula (I-2), wherein one or more atoms are replaced by atoms having the same atomic number as atoms commonly found in nature but with different atomic masses or mass numbers.

[0084] Examples of isotopes suitable for inclusion in the compounds of this invention include isotopes of hydrogen, such as... 2 H(D) and 3 H(T), isotopes of carbon, such as 11 C 13 C and14 C, isotopes of chlorine, such as 37 Cl, an isotope of fluorine, such as 18 F, an isotope of iodine, such as 123 I and 125 I, isotopes of nitrogen, such as 13 N and 15 N, an isotope of oxygen, such as 15 O、 17 O and 18 O, and isotopes of sulfur, such as 35 S.

[0085] Isotope-labeled compounds of formula (I-1) or formula (I-2) can generally be prepared by conventional techniques known to those skilled in the art or by using suitable isotope-labeling reagents instead of previously used unlabeled reagents in a manner similar to that described in the examples and preparations appended herein.

[0086] Compounds of formula (I-1) or (I-2) may exist in the form of pesticide-acceptable salts, such as acid addition salts and / or base addition salts of compounds of formula (I-1) or (I-2). Unless otherwise specified, “pesticide-acceptable salts” as used herein includes acid addition salts or base addition salts that may appear in compounds of formula (I-1) or (I-2).

[0087] Pesticide-acceptable salts of compounds of formula (I-1) or (I-2) include their acid addition salts and base addition salts. Suitable acid addition salts are formed by acids that form non-toxic salts. For a review of suitable salts, see Handbook of Pharmaceutical Salts: Properties, Selection and Use by Stahl and Wermuth (Wiley-VCH, 2002). Methods for preparing pesticide-acceptable salts of the compounds described herein are known to those skilled in the art.

[0088] To avoid ambiguity, the terms used in this article are defined below. Unless otherwise stated, the meanings of the terms used in this article are as follows.

[0089] When used herein, the term “substituted” means that one or more (preferably 1 to 5, more preferably 1 to 3) hydrogen atoms in a group are independently replaced by the corresponding number of substituents.

[0090] When used in this document, the term "independently" means that when there are more than one substituent, these substituents can be the same or different.

[0091] As used herein, the term "alkyl" refers to a saturated aliphatic hydrocarbon, including straight-chain and branched chains. In some embodiments, the alkyl group has 1-8, 1-6, or 1-3 carbon atoms. For example, the term "C 1-8 "Alkyl" refers to a straight-chain or branched group of atoms having 1-8 carbon atoms. The term "C"... 1-8 "alkyl" in its definition includes the term "C". 1-6 "alkyl", "C1-C3 alkyl", and "C1-C4 alkyl". Examples of alkyl groups include, but are not limited to, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, pentyl, 2-pentyl, 3-pentyl, isopentyl, neopentyl, (R)-2-methylbutyl, (S)-2-methylbutyl, 3-methylbutyl, 2,3-dimethylpropyl, 2,3-dimethylbutyl, hexyl, etc. The alkyl group may optionally be substituted by one or more (e.g., 1 to 5) suitable substituents.

[0092] As used herein, the term "haloalkyl" refers to an alkyl group having one or more halogen substituents (at most fully haloalkyl, i.e., each hydrogen atom of the alkyl group is replaced by a halogen atom). For example, the term "C 1- "C6 haloalkyl" refers to a C6 alkyl group having one or more halogen substituents. 1- C6 alkyl groups (at most fully haloalkyl, i.e., each hydrogen atom of the alkyl group is replaced by a halogen atom). Another example is the term "C6 alkyl group". 1- "C3 haloalkyl" refers to a C3 haloalkyl group having one or more halogen substituents. 1- C3 alkyl groups (at most fully haloalkyl, i.e., each hydrogen atom of the alkyl group is replaced by a halogen atom). Examples of haloalkyl groups include: CF3, C2F5, CHF2, CH2F, CH2CF3, CH2Cl, etc. In the case of multiple halogenation, the halogen atoms may be the same or different. In the case of this invention, the halogen is fluorine, chlorine, bromine, or iodine, especially fluorine, chlorine, or bromine.

[0093] When used herein, the term "alkoxy" refers to itself or in combination with other terms, such as haloalkoxy, and in this application should be understood to mean O-alkyl, wherein the term "alkyl" is as defined above.

[0094] As used herein, the term "cycloalkyl" refers to C3-C8 cycloalkyl groups, such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, and cyclooctyl. Among these groups, C3-C6 cycloalkyl is preferred. The term "cyclopropyl" is abbreviated as Cyc.

[0095] As used herein, the term "epoxyalkyl" refers to C3-C8-epoxyalkyl, such as epoxypropyl, epoxybutyl, epoxypentyl, epoxyhexyl, epoxyheptyl, and epoxyoctyl. Among these groups, C3-C6-epoxyalkyl is preferred.

[0096] As used herein, the term "C3-C6 cycloalkyl C1-C3 alkyl" refers to a C1-C3 alkyl group having a C3-C6 cycloalkyl substituent, and should be understood in this application as R-(C1-C3)alkyl-(C3-C6)cycloalkyl. The terms "cycloalkyl" and "alkyl" are as defined above.

[0097] As used herein, the term "C3-C6 epoxy alkyl C1-C3 alkyl" refers to a C1-C3 alkyl group having a C3-C6 epoxy alkyl substituent, and should be understood in this application as R-(C1-C3)alkyl-(C3-C6) epoxy alkyl. The terms "epoxy alkyl" and "alkyl" are as defined above.

[0098] In this document, the ranges related to the number of substituents, carbon atoms, and ring atoms represent a list of all integers within that range, and the range is merely a simplified representation. For example, "1-4 substituents" means 1, 2, 3, or 4 substituents; "3-8 ring atoms" means 3, 4, 5, 6, 7, or 8 ring atoms. Therefore, the ranges related to the number of substituents, carbon atoms, and ring atoms also encompass any of their subranges, and each subrange is also considered to be disclosed herein.

[0099] The compounds of this invention can be prepared in a variety of ways known to those skilled in the art of organic synthesis. Those skilled in the art can refer to the synthetic routes of specific compounds in the specific embodiments of this invention, and appropriately adjust the reactants and reaction conditions to obtain synthetic methods for other compounds.

[0100] The following synthetic scheme describes the steps for preparing the compounds disclosed in this invention. R1, R2, R4, and n have the meanings described in this invention.

[0101] Intermediate 1 reacts with different electrophilic reagents under alkaline conditions to yield intermediate 2. Intermediate 2 reacts with sodium nitrite to generate diazonium benzene, which is then decomposed by free radicals under the catalysis of cuprous halide or potassium iodide to yield the corresponding halobenzene 3, where T is bromine or iodine. Intermediate 3 reacts to generate intermediate 4, where X is B(OH)2 or pinecolato boranyl. Intermediate 4 undergoes a Suzuki coupling reaction with the halogenated derivative of Q (pyridyl) to yield the thioether product of formula I. The thioether product of formula I is oxidized to the target oxidized product of formula I in the presence of oxidants such as m-CPBA or hydrogen peroxide. Intermediate 3 can also directly undergo a Suzuki coupling reaction with the boric acid (boronic acid ester) of Q to yield the thioether product of formula I.

[0102] In addition, the aforementioned intermediate compounds and their raw materials can be referenced in WO2006043635, WO2010100189, CN102341376A, WO2013092350, WO2013157229, WO2007131680, WO2013030262, WO2018015852, WO2014202510, WO2014202505, WO2015004028, WO2021056922, WO2021005081 and Fries, Pascal H., and Daniel Imbert. "Parallel NMR based on solution magnetic-susceptibility differences. Application to isotopic effects on self-diffusion." Journal of Chemical & Engineering Data. The method reported in 55.5(2010):2048-2054 was used to prepare it.

[0103] This invention lists several synthesized exemplary compounds, the specific group selections of which are shown in Table 1 or 2 below, and the characterization data of some exemplary compounds are shown in Table 3. It should be understood that the scope of this invention is not limited to the exemplary compounds listed in the tables below, and the group selections of the compounds in Table 1 or 2 below can be arbitrarily combined without particular limitation. Some of the general formula (I-1) or (I-2) compounds of this invention are shown below, but this invention is by no means limited to these compounds.

[0104] Table 1

[0105] Table 2

[0106] Table 3 shows characterization data for some exemplary compounds.

[0107] In a second aspect, the present invention provides an insecticide composition comprising a compound of formula (I-1) or (I-2) or an isotopically labeled compound thereof, or an optical isomer, geometric isomer, tautomer, or mixture of isomers thereof, or a pesticide-acceptable salt thereof, and a pesticide-acceptable carrier. It can be applied to animal pests and / or their habitats to control unwanted animal pests.

[0108] The formulation comprises at least one compound of the present invention and at least one agriculturally useful adjuvant, such as a carrier and / or a surfactant.

[0109] In pesticide science, acceptable carriers can be organic or inorganic inert carrier materials. Suitable carriers include water, gelatin, gum arabic, magnesium stearate, talc, vegetable oils, polyalkylene glycols, petrolatum, mannitol, cellulose, cellulose derivatives, sodium saccharin, magnesium carbonate, brine, glycerin, and ethanol. In addition, insecticide compositions may contain other additives such as preservatives, stabilizers, emulsifiers, buffers, diluents, binders, wetting agents, lubricants, and flow aids.

[0110] The compounds of formula (I-1) or (I-2) of the present invention can also be used in mixtures with one or more suitable substances, such as fungicides, bactericides, acaricides, molluscicides, nematicides, insecticides, microbial agents, beneficial microorganisms, herbicides, fertilizers, bird repellents, phytototonics, sterilants, safeners, chemical pheromones, and / or plant growth regulators, thereby broadening the spectrum of action, prolonging the duration of action, increasing the rate of action, preventing rejection, or preventing the development of resistance. Furthermore, such active ingredient combinations can improve plant growth and / or tolerance to abiotic factors, such as high or low temperatures, drought, or high water content or soil salinity. They can also improve flowering and fruiting performance, optimize germination capacity and root development, promote harvesting and increase yield, influence ripening, improve the quality and / or nutritional value of harvested products, extend the shelf life of harvested products, and / or improve the processing properties of harvested products.

[0111] The insecticide composition of the present invention can be in the form of a liquid, solid, or semi-solid formulation, without particular limitation. In some embodiments, the formulation of the insecticide composition is selected from powders, granules, liquids, suspensions, or sprays, preferably wettable powders, wettable liquids, soluble powders, dispersible liquids, aqueous solutions, microemulsions, emulsifiable concentrates, water-emulsions, sprayable solutions, dispersible oil suspensions, microcapsule suspensions, water-dispersible granules, water-soluble granules, large granules, granules for broadcasting and soil application, aerosols, ultra-low volume formulations, and wax products.

[0112] The content of the compounds of the present invention in their insecticide compositions can be adjusted according to actual needs (e.g., formulation, method of application, target of application, etc.), including but not limited to 0.001 mg / L-10 mg / L, such as 0.001 mg / L, 0.01 mg / L, 0.1 mg / L, 0.5 mg / L, 1 mg / L, 2.5 mg / L, 5 mg / L or 10 mg / L.

[0113] The specific application frequency can be determined by technical personnel in the relevant field, such as once a day, once every two days, once every three days, once every four days, once every five days, once every six days, twice a day, three times a day, etc.

[0114] In a third aspect, the present invention provides the use of a compound of formula (I-1) or formula (I-2) or an isotopically labeled compound thereof, or an optical isomer, geometric isomer, tautomer or mixture of isomers thereof, or a pesticide-acceptable salt thereof, in the preparation of an insecticide for pest control.

[0115] The compounds of this invention are suitable for the prevention and control of pests or mites, i.e., pests or mites refer to harmful or unwanted insects or mites, especially those encountered in agriculture, forestry, storage and material protection, and sanitation. The compounds of this invention show excellent control effects against various pests or mites even at low concentrations. They have insecticidal or acaricidal activity at every stage of the pest or mite life cycle (e.g., egg, larva (nymph), pupa, adult). The compounds of this invention also show excellent control activity against pests or mites that have developed resistance to traditional insecticides or acaricides.

[0116] This invention also relates to a method for controlling pests or mites, comprising applying an effective amount of a compound of formula (I-1) or formula (I-2) to the insect's location, insect habitat, pest habitat, area under protection, or directly to the insect to be controlled. The compounds of this invention can also be used to control other invertebrate pests or organisms.

[0117] Specifically, the insect habitat, pest habitat, or mite habitat refers to the environment in which insects, pests, or mites live or where their eggs are present, including the surrounding air, the food they consume, or the objects they come into contact with. For example, by applying active compounds to the seeds of plants (before planting), to seedlings, or to planted cuttings, leaves, stems, fruits, grains, and / or roots, or to the soil or other growing media (before or after crop planting), it is possible to control insects or mites that consume, damage, or come into contact with edible agricultural products, ornamental plants, turf, forage plants, or other plants of economic value. It is also possible to protect these plants against diseases caused by viruses, fungi, or bacteria by controlling sap-feeding pests such as whiteflies, planthoppers, and aphids, or mites such as two-spotted spider mites and carmine spider mites. The plants include plants propagated through conventional methods, as well as plants genetically modified using modern biotechnology that possess insect or mite resistance, herbicide resistance, high yield, and / or other beneficial characteristics. These compounds are expected to be suitable for protecting textiles, paper, stored grains, seeds and other foods, houses, buildings and / or places by applying the compounds of the present invention to or near these objects, for example by directly using conventional treatment methods or by subjecting the compounds to their environment, habitat or storage space, such as by impregnation, spraying, evaporation, atomization, spreading, smearing, injection, and in the case of propagation materials (especially seeds), by applying one or more layers of coating.

[0118] In the field of animal health, i.e., veterinary medicine, the compounds of formula (I-1) or (I-2) of the present invention are active against animal parasites, particularly ectoparasites or endoparasites. The term "endoparasites" specifically includes worms and protozoa, such as coccidia. Ectoparasites are generally and preferably arthropods, particularly insects or mites.

[0119] In the field of veterinary medicine, compounds of formula (I-1) or formula (I-2) with favorable warm-blooded animal toxicity are suitable for the prevention and control of parasites in animal breeding and animal husbandry of livestock, breeding animals, zoo animals, laboratory animals, experimental animals, and domestic animals. They are active against all or specific developmental stages of the parasites.

[0120] Agricultural livestock include, for example, mammals such as sheep, goats, horses, donkeys, camels, buffalo, rabbits, reindeer, deer, and especially cattle and pigs; or poultry such as turkeys, ducks, geese, and especially chickens; or, for example, fish or crustaceans in aquaculture; or, depending on the circumstances, insects such as bees.

[0121] Domestic animals include, for example, mammals such as hamsters, guinea pigs, rats, mice, chinchillas, ferrets, and especially dogs, cats, caged birds; reptiles, amphibians, or ornamental fish.

[0122] In the context of animal health, the terms "control" or "controlling" as used herein refer to compounds of formula (I-2) that effectively reduce the incidence of specific parasites in animals infected with such parasites to a harmless level. More specifically, "control" as used herein refers to compounds of formula (I-1) or (I-2) that kill the parasites, inhibit their growth, or suppress their reproduction.

[0123] In the context of this patent application, the term "hygienic" should be understood to mean any and all measures, preventive measures, and methods intended to prevent disease—particularly infectious disease—and to protect the health of humans and animals and / or to protect the environment and / or maintain cleanliness. According to the invention, this particularly includes measures for cleaning, disinfecting, and sterilizing, for example, textiles or hard surfaces (particularly surfaces made of glass, wood, cement, porcelain, ceramics, plastic, or metal) to ensure they are free from sanitary pests and / or their secretions. In this respect, the scope of protection of the invention preferably excludes methods of surgical or therapeutic treatment applied to human or animal bodies, as well as diagnostic methods performed on human or animal bodies.

[0124] Therefore, the term "hygiene field" encompasses all areas, technical fields, and industrial applications where these hygiene measures, precautions, and methods are important, such as hygiene in kitchens, bakeries, airports, bathrooms, swimming pools, department stores, hotels, hospitals, livestock pens, animal husbandry, etc.

[0125] The inventors of this invention have discovered that even when applied in low doses, the compounds of this invention are effective in controlling animal pests, particularly insects, arachnids, worms, nematodes, and mollusks, encountered in agriculture, horticulture, livestock farming, aquaculture, forestry, landscaping and recreational facilities, protection of stored products and materials, and sanitation. These compounds are preferably used as insecticides. They are effective against both commonly susceptible and resistant species, and against all or part of the developmental stages. The aforementioned pests include animal pests, and specifically include insects, mites, or nematodes:

[0126] Pests from the phylum Arthropoda, especially from the class Arachnida, such as those from the order Acarina, including the family Tetranychidae (e.g., *Tetranychus* spp., *Eotetranychus* spp., *Panonychus* spp., or *Oligonychus* spp.), such as the genera *Acarus* (e.g., *Acarus siro*, *Aceria kuko*, *Aceriasheldoni*), *Aculops* spp., and *Aculus* spp. (e.g., *Aculus fockeui*, *Aculus*). schlechtendali), Amblyomma spp., Argas spp., Boophilus spp., Brevipalpus spp. (e.g., Brevipalpus phoenicis), Bryobia graminum (e.g., Bryobalpus praetiosa), Centruroides spp., Chorioptes spp., Dermatophagoides pteronyssinus (e.g., Dermatophagoides farinae), Dermacentor spp., Dermanyssus gallinae;

[0127] Pests from the order Coleoptera include, for example, the striped leaf beetle (Acalymma vittatum), the bean weevil (Acanthoscelides obtectus), the beetle (Adoretus spp.), the poplar leaf beetle (Agelasticaalni), the click beetle (Agriotes spp.) (e.g., the straight click beetle (Agriotes linneatus) and the wireworm (Agriotes mancus)), the black fungus beetle (Alphitobius diaperinus), the June beetle (Amphimallon solstitialis), the furniture thieving beetle (Anobium punctatum), the longhorn beetle (Anoplophora spp.), the flower weevil (Anthonomus spp.) (e.g., the cotton boll weevil (Anthonomus grandis)), the leather beetle (Anthrenus spp.), the pear weevil (Apion spp.), and the sugarcane beetle (Apogonia). spp.), genus *Atomaria* (e.g., *Atomaria linearis*), genus *Attagenus*, genus *Baris caerulescens*, genus *Bruchidius obtectus*, genus *Bruchus* (e.g., *Bruchus pisorum*, *Bruchus rufimanus*), genus *Cassida*, genus *Cerotoma trifurcata*, genus *Ceuthorhynchus* (e.g., *Ceutorrhynchus assimilis*, *Ceutorrhynchus quadridens*, *Ceutorrhynchus rapae*), genus *Chaetocnema* (e.g., *Chaetocnema*). Confinis, Chaetocnemadenticulata, Chaetocnema ectypa, Cleonus mendicus, Conoderus spp., Cosmopolites spp. (e.g., Cosmopolites sordidus);

[0128] Pests / arthropods from the order Diptera, such as: *Aedes* spp. (e.g., *Aedes aegypti*, *Aedes albopictus*, *Aedes sticticus*, *Aedes vexans*), *Agromyza* spp. (e.g., *Agromyza frontella*, *Agromyza parvicornis*), *Anastrepha* spp., *Anopheles* spp. (e.g., *Anopheles quadrimaculatus*, *Anopheles gambiae*), *Asphondylia* spp., and *Bactrocera* spp. (e.g., *Bactrocera cucurbitae*, *Bactrocera cucurbitae*). The following are listed: dorsalis, olive fruit fly (Bactrocera oleae), garden hairy fly (Bibio hortulanus), glass fly (Calliphora erythrocephala), red-headed blowfly (Calliphora vicina), Mediterranean fruit fly (Ceratitis capitata), chironomus spp., golden fly (Chrysomyia spp.), tiger fly (Chrysops spp.), high-fronted horsefly (Chrysozona pluvialis), cone fly (Cochliomyia spp.), gall midge (Contarinia spp.) (e.g., grape gall midge (Contarinia johnsoni), cabbage gall midge (Contarinia nasturtii), pear gall midge (Contarinia pyrivora);

[0129] Pests from the order Heteroptera, such as the pumpkin stink bug (Anasa tristis), *Antestiopsis* spp., *Boisea* spp., *Blissus* spp., *Calocoris* spp., *Campylomma livida*, *Cavelerius* spp., *Cimex* spp. (e.g., *Cimex adjunctus*, *Cimex hemipterus*, *Cimexlectularius*, *Cimex pilosellus*), *Collaria* spp., *Creontiades dilutus*, *Dasynus piperis*, *Dichelops furcatus*, and *Diconocoris*. Hewetti, Dysdercus spp., Euschistus spp.;

[0130] Pests from the order Homoptera, such as *Acizzia acaciaebaileyanae*, *Acizzia dodonaeae*, psyllids (*Acizzia uncatoides*), long-headed grasshoppers (*Acrida turrita*), aphids of the genus *Acyrthosipon* (e.g., pea aphid *Acyrthosiphon pisum*), *Acrogonia* spp., *Aeneolamia* spp., *Agonoscena* spp., European cabbage whitefly (*Aleyrodes proletella*), sugarcane whitefly (*Aleurolobus barodensis*), cotton whitefly (*Aleurothrixus floccosus*), malaynsis (*Allocaridara malayensis*), and mango leafhoppers of the genus *Amrasca* (e.g., small green leafhopper *Amrasca bigutulla*, small leafhopper *Amrasca*). The genera *Aphis devastans*, *Aphis cardui*, *Aonidiella* spp. (e.g., *Aonidiella aurantii*, *Aonidiella citrina*, *Aonidiella inornata*), *Aphanostigma piri*, and *Aphis* spp. (e.g., *Aphis craccivora*, *Aphis fabae*, *Aphis forbesi*, *Aphis glycines*, *Aphis gossypii*, *Aphis hederae*, *Aphis illinoisensis*, *Aphis middletoni*, *Aphis nasturtii*, and *Aphis nerii*).

[0131] Pests from the order Hymenoptera, such as the genera *Acromyrmex* spp., *Athalia* spp. (e.g., *Athalia rosae*), *Atta* spp., *Diprion* spp. (e.g., *Diprion similis*), *Hoplocampa* spp. (e.g., *Hoplocampa cookei*, *Hoplocampa testudinea*), and *Lasius* spp.;

[0132] Pests from the order Isoptera, such as the genera *Coptotermes*, *Cornitermes cumulans*, *Cryptotermes*, *Incisitermes*, *Microtermesobesi*, *Odontotermes*, and *Reticulitermes* (e.g., *Reticulitermes flavipes* and *Reticulitermes hesperus*).

[0133] Pests from the order Lepidoptera, such as the small wax moth (Achroia grisella), the mulberry sword-striped cutworm (Acronicta major), the brown-banded leafroller (Adoxophyes spp.) (e.g., the cotton brown-banded leafroller (Adoxophyesorana)), the weeping cutworm (Aedia leucomelas), the cutworm (Agrotis spp.) (e.g., the yellow cutworm (Agrotissegetum) and the small cutworm (Agrotis ipsilon)), the wavy-leaved cutworm (Alabama spp.) (e.g., the cotton leaf wavy-leaved cutworm (Alabama argillacea)), the navel orange borer (Amyelois transitella), the wheat moth (Anarsia spp.), the dry-killing cutworm (Anticarsia spp.) (e.g., the soybean cutworm (Anticarsia gemmatalis)), the striped leafroller (Argyroploce spp.), and the cabbage cutworm (Barathra kirilowii). brassicae, Borbo cinnara, Bucculatrix thurberiella, Bupalus piniarius, Busseolaspp., Cacoecia spp., Caloptilia theivora, Capuareticulana, Carpocapsa pomonella, Carposina niponensis, Cheimatobia brumata, Chilo spp. (e.g., Chilo plejadellus, Chilo suppressalis), Choristoneura spp., Clysia ambiguella, Cnaphalocerus spp., Cnaphalocrocis medinalis, Cnephasia spp.), and the genus *Conopomorpha* spp.;

[0134] Pests from the orders Orthoptera or Saltatoria, such as house crickets (Achetadomesticus), Dichroplus spp., mole crickets (Gryllotalpa spp.) (e.g., European mole cricket (Gryllotalpa gryllotalpa)), cane grasshoppers (Hieroglyphus spp.), migratory grasshoppers (Locusta spp.) (e.g., migratory grasshopper (Locustamigratoria)), black locusts (Melanoplus spp.) (e.g., Melanoplus devastator), and desert locusts (Schistocerca gregaria);

[0135] Pests from the order Thysanoptera, such as the corn thrips (Anaphothrips obscurus), rice thrips (Baliothrips biformis), grape thrips (Drepanothris reuteri), Enneothrips flavens, thrips genus (Frankliniella spp.) (e.g., smoky brown thrips (Frankliniella fusca), western flower thrips (Frankliniella occidentalis), jasmine thrips (Frankliniella schultzei), wheat flower thrips (Frankliniella tritici), blueberry flower thrips (Frankliniella vaccinii), William's flower thrips (Frankliniella williamsi), sun thrips genus (Heliothrips spp.), greenhouse hedge thrips (Hercinothrips femoralis), grape thrips (Rhipiphorothrips cruentatus), and hard thrips genus (Scirtothrips). spp.), Taeniothrips cardamoni, Thrips spp. (e.g., Thrips palmi, Thrips tabaci);

[0136] Plant pests from the phylum Nematoda, i.e., plant-parasitic nematodes, especially those from the genera *Aglenchus* (e.g., *Aglenchus agricola*), *Anguinas* (e.g., *Anguina tritici*), *Aphelenchoides* (e.g., *Aphelenchoides arachidis*, *Aphelenchoides fragariae*), *Belonolaimus* (e.g., *Belonolaimus gracilis*, *Belonolaimus longicaudatus*, *Belonolaimus nortoni*), and *Bursaphelenchus* (e.g., *Bursaphelenchus*). *Cocophilus*, *Bursaphelenchus eremus*, *Bursaphelenchus xylophilus*; and *Meloidogyne* spp., a genus of root-knot nematodes.(For example, *Meloidogyne chitwoodi*, *Meloidogyne fallax*, *Meloidogyne acronea*, *Meloidogyne africana*, *Meloidogyne arenaria*, *Meloidogyne arenaria thamesi*, *Meloidogyneartiella*, *Meloidogyne chitwoodi*, *Meloidogynecoffeicola*, *Meloidogyne ethiopica*, *Meloidogyne exigua*, *Meloidogyne fallax*, *Meloidogyne graminicola*, and other grass root-knot nematodes.) The nematodes include *Meloidogyne graminis*, *Meloidogyne hapla*, *Meloidogyne incognita*, *Meloidogyne incognita acrita*, *Meloidogyne javanica*, *Meloidogyne kikuyensis*, *Meloidogyne minor*, *Meloidogyne naasi*, *Meloidogyne paranaensis*, *Meloidogyne thamesi*, and non-migratory parasitic root-knot nematodes (*Meloidogyne* spp.); *Tylenchulus* spp. (e.g., *Tylenchulus semipenetrans*), and *Xiphinema*. (e.g., labeling xiphinema worms; spp.)

[0137] Arthropods from the order Phthiraptera, such as the genera *Damalinia* spp., *Haematopinus* spp., *Linognathus* spp., *Pediculus* spp., *Phylloxera vastatrix*, *Ptirus pubis*, and *Trichodectes* spp.;

[0138] Arthropods from the order Siphonapterida, such as *Ceratophyllus* spp., *Ctenocephalides* spp., *Pulex* spp., *Tunga* spp., and *Xenopsylla* spp.; as well as unpleasant pests and sanitary pests from the order Blattodea.

[0139] Depending on the circumstances, at certain concentrations or application rates, compounds of formula (I-1) or (I-2) may also be used as herbicides, safeners, growth regulators, or compositions that improve plant characteristics; as microbial agents or gametoxins, such as fungicides, antifungals, bactericides, antivirals (including agents against viroids), or as agents against MLOs (mycoplasma-like organisms) and RLOs (rickettsia-like organisms). Depending on the circumstances, they may also be used as intermediates or precursors for the synthesis of other active ingredients.

[0140] Those skilled in the art will understand that the definitions and preferences described in one aspect of the invention also apply to other aspects. It will be apparent to those skilled in the art that embodiments of various aspects of the invention can be combined in various ways without departing from the subject matter and spirit of the invention, and these combinations are also included within the scope of the invention.

[0141] The beneficial effects of this invention are:

[0142] By chemically modifying and molecularly designing aryl sulfides with aromatic amine structures, and replacing benzene rings with pyridine rings containing heteroatoms, a series of compounds with superior activity were obtained. These compounds exhibit excellent activity for insecticidal or acaricidal purposes in agriculture or forestry, showing particularly outstanding control effects against two-spotted spider mites, carmine spider mites, apple spider mites, and citrus spider mites. Furthermore, their synthesis process is simple, production costs are low, and they have great potential. Detailed Implementation

[0143] The technical solutions of the present invention will be clearly and completely described below with reference to the embodiments of the present invention. All other embodiments obtained by those skilled in the art based on the embodiments of the present invention without creative effort are within the scope of protection of the present invention.

[0144] The compounds of formula (I-1) or (I-2) of this invention can be synthesized using a variety of methods familiar to those skilled in the art of organic synthesis. The following specific examples provide exemplary methods for synthesizing compounds of formula (I-1) or (I-2) that are well-known in the field of synthetic chemistry. Clearly, by referring to the exemplary schemes in this patent, those skilled in the art can readily design synthetic routes for other compounds of formula (I-1) or (I-2) by appropriately adjusting the reactants, reaction conditions, and protecting groups.

[0145] Example 1: Synthesis of 3-chloro-2-(2-fluoro-4-methyl-5-((2,2,2-trifluoroethyl)thio)phenyl)-5-(trifluoromethyl)pyridine (compound 2-94)

[0146] 1.1 Synthesis of 2-(2-fluoro-4-methyl-5-((2,2,2-trifluoroethyl)thio)phenyl)-4,4,5,5-tetramethyl-1,3,2-dioxorane

[0147] 2.0 g (6.80 mmol) of (5-bromo-4-fluoro-2-methylphenyl)(2,2,2-trifluoroethyl)thione was added to a reaction flask and dissolved in 20 mL of 1,4-dioxane. Then, 2.52 g (10.40 mmol) of pinacol diboronate, 1.94 g (20.40 mmol) of potassium acetate, and 0.29 g (0.04 mmol) of DPPF palladium dichloride were added sequentially. The reaction mixture was heated to 110 °C and refluxed for 3 h, monitored by TLC. The reaction was stopped after the starting material had completely disappeared. The reaction mixture was poured into saturated brine, extracted with dichloromethane, and the organic phases were combined, dried, filtered, and the solvent was removed by rotary evaporation to obtain 1.08 g of the intermediate, with a yield of 50.60%. No further purification was required, and the reaction proceeded to the next step.

[0148] 1.2 Synthesis of 3-chloro-2-(2-fluoro-4-methyl-5-((2,2,2-trifluoroethyl)thio)phenyl)-5-(trifluoromethyl)pyridine (compound 2-94)

[0149] 0.1 g (0.3 mmol) of the intermediate from the previous step was added to the reaction flask and dissolved in a mixed solvent of 1,4-dioxane and water. Then, 0.094 g (0.36 mmol) of 2-bromo-3-chloro-5-(trifluoromethyl)pyridine, 0.28 g (0.9 mmol) of cesium carbonate, 0.011 g (0.017 mmol) of DPPF palladium dichloride, and 0.016 g (0.029 mmol) of 1,1'-bis(diphenylphosphine)ferrocene were added to the reaction system. The reaction mixture was then heated to 100 °C and refluxed for 3 h, monitored by TLC. After the starting material had completely disappeared, the reaction was stopped, and the mixture was poured into saturated brine. The solution was extracted with dichloromethane, and the organic phases were combined, dried, and separated by column chromatography to obtain 0.063 g of the target compound 2-94, with a yield of 49.40%.

[0150] Example 2: Synthesis of 2-chloro-5-(2-fluoro-4-methyl-5-((2,2,2-trifluoroethyl)thio)phenyl)pyridine (compound 2-11)

[0151] 0.1 g (0.30 mmol) of 2-(2-fluoro-4-methyl-5-((2,2,2-trifluoroethyl)thio)phenyl)-4,4,5,5-tetramethyl-1,3,2-dioxoborane was added to the reaction flask and dissolved in 1.2 mL of a 5:1 mixture of 1,4-dioxane and water. Then, 0.058 g (0.36 mmol) of 5-bromo-2-chloropyridine, 0.28 g (0.9 mmol) of cesium carbonate, 0.011 g (0.017 mmol) of DPPF palladium dichloride, and 0.016 g (0.029 mmol) of 1,1'-bis(diphenylphosphine)ferrocene were added to the reaction system. The reaction mixture was then heated to 101 °C and refluxed for 3 h, monitored by TLC. After the raw materials had completely disappeared, the reaction was stopped, and the mixture was poured into saturated brine. It was then extracted with dichloromethane, the organic phases were combined, dried, and separated by column chromatography to obtain a total of 0.026 g of the target compound 2-11, with a yield of 26.04%.

[0152] Example 3: Synthesis of 2-chloro-5-(2-fluoro-4-methyl-5-((2,2,2-trifluoroethyl)thio)phenyl)pyridine (compound 2-11)

[0153] 1.0 g (6.35 mmol) of 6-chloropyridine-3-boric acid was added to the reaction flask and dissolved in 16.5 mL of a mixed solvent of 1,4-dioxane:water = 10:1. Then, 2.22 g (6.35 mmol) of (4-fluoro-5-iodo-2-methylphenyl)(2,2,2-trifluoroethyl)thione, 6.21 g (19.06 mmol) of cesium carbonate, and 0.046 g (63.55 μmol) of DPPF dichloride were added to the reaction system. The mixture was heated under reflux in a nitrogen atmosphere for 5 h and then the reaction was stopped. The reaction system was poured into saturated brine and extracted with dichloromethane. The organic phases were combined, dried, and separated by column chromatography to obtain a total of 1.86 g of the target compound 2-11, with a yield of 87.18%.

[0154] Example 4: Synthesis of 5-{2-fluoro-4-methyl-5-[(2,2,2-trifluoroethyl)thio]phenyl}-2-nitropyridine (compound 2-21)

[0155] 0.2 g (0.57 mmol) of 2-(2-fluoro-4-methyl-5-((2,2,2-trifluoroethyl)thio)phenyl)-4,4,5,5-tetramethyl-1,3,2-dioxoborane was added to the reaction flask and dissolved in 1.2 mL of a 5:1 mixture of 1,4-dioxane and water. Then, 0.13 g (0.63 mmol) of 5-bromo-2-nitropyridine, 1.25 g (1.71 mmol) of cesium carbonate, 0.021 g (0.029 mmol) of DPPF palladium dichloride, and 0.032 g (0.057 mmol) of 1,1'-bis(diphenylphosphine)ferrocene were added to the reaction system. The reaction system was then heated to 101 °C and refluxed for 3 h, and monitored by TLC. After the raw materials had completely disappeared, the reaction was stopped, and the mixture was poured into saturated brine. It was then extracted with dichloromethane, the organic phases were combined, dried, and separated by column chromatography to obtain a total of 0.15 g of the target compound 2-21, with a yield of 75.84%.

[0156] Example 5: 5-{2-fluoro-4-methyl-5-[(2,2,2-trifluoroethyl)thio]phenyl}pyridine-2-carboxylonitrile (Compound 2-29)

[0157] 0.2 g (0.57 mmol) of 2-(2-fluoro-4-methyl-5-((2,2,2-trifluoroethyl)thio)phenyl)-4,4,5,5-tetramethyl-1,3,2-dioxoborane was added to the reaction flask and dissolved in 1.2 mL of a 5:1 mixture of 1,4-dioxane and water. Then, 0.11 g (0.63 mmol) of 5-bromo-2-cyanopyridine, 1.25 g (1.71 mmol) of cesium carbonate, 0.016 g (0.029 mmol) of DPPF palladium dichloride, and 0.032 g (0.057 mmol) of 1,1'-bis(diphenylphosphine)ferrocene were added to the reaction system. The reaction system was then heated to 101 °C and refluxed for 3 h, and monitored by TLC. After the raw materials had completely disappeared, the reaction was stopped, and the mixture was poured into saturated brine. The mixture was then extracted with dichloromethane, and the organic phases were combined, dried, and separated by column chromatography to obtain a total of 0.12 g of the target compound 2-29, with a yield of 64.39%.

[0158] Other compounds of the present invention used in the following test examples were also synthesized using similar steps as described in Examples 1-5 above.

[0159] Test Example: Bioactivity Test

[0160] Test Example 1: Bioactivity test against adult Tetranychus cinnabarinus

[0161] Experimental Methods: The experiment followed agricultural industry standard NYT 1154.6-2006, employing the immersion method for testing. Broad bean seedlings with uniform growth were selected, and thick, tender leaves were cut into a two-leaf-one-stem shape. One leaf was then cut to create a one-leaf-one-stem shape, and each leaf was inserted into a 5mL sample bottle filled with water. Thirty adult mites were selected from each leaf. Each test agent was accurately weighed and dissolved in a small amount of DMSO to prepare a 10000mg / L stock solution. This stock solution was diluted 100 times with a 0.1% Tween 80 aqueous solution to obtain a 100mg / L test solution. After the test mites stabilized on the leaves, they were immersed in the prepared solution for 5-10 seconds. Excess solution was absorbed with filter paper, and the leaves were allowed to air dry. Each treatment was repeated three times, with a blank control included. The control group used an immersion solution of equal proportions of DMSO and Tween aqueous solution. The experimental targets were then cultured in an artificial climate chamber (24-26℃, L:D = 16:8, RH 60%). After 72 hours, the mortality of adult mites was checked and recorded. Mites were considered dead if their legs did not move or they did not react when touched with tweezers.

[0162] Calculation method:

[0163] Corrected mortality rate (%) = [(treatment mortality rate - control mortality rate) / (1 - control mortality rate)] × 100%

[0164] Among the exemplary compounds of this invention, the following compounds showed good control efficacy against adult Tetranychus carmineus at a concentration of 100 mg / L, achieving a mortality rate of 100%: compounds 1-2, 1-3, 1-4, 1-7, 1-12, 1-19, 1-27, 1-58, 1-59, 1-60, 1-61, 1-82, 1-89, 1-93, 1-101, 1-110, 2-1, 2-4, 2- 5, 2-7, 2-8, 2-11, 2-12, 2-14, 2-16, 2-18, 2-21, 2-22, 2-23, 2-24, 2-28, 2-29, 2-32, 2-38, 2-41, 2-43, 2-45, 2-46, 2-53, 2-58, 2-63, 2-68, 2-72, 2-74, 2-94, 2-116, 2-117, 2-119 2-120, 2-127, 2-129, 2-130, 2-131, 2-132, 2-134, 2-135, 2-140, 2-146, 2-147, 2-184, 2-185, 2-186, 2-187, 2-188, 2-195, 2-198, 2-199, 2-200, 2-201, 2-202, 2-246, 2-247, 2- 249, 2-250, 2-268, 2-277, 2-294, 2-302, 2-304, 2-307, 2-308, 2-310, 2-312, 2-313, 2-315, 2-316, 2-323, 2-325, 2-326, 2-329, 2-330, 2-335, 2-338, 2-340, 2-341, 2-342, 2-344.

[0165] Among the exemplary compounds of this invention, the following compounds show good control efficacy against adult Tetranychus carmine at a concentration of 10 mg / L, with a mortality rate exceeding 90%: compounds 1-2, 1-4, 1-27, 1-58, 1-59, 1-82, 1-89, 1-93, 1-101, 1-110, 2-4, 2-5, 2-7, 2-11, 2-12, 2-14, 2-18, 2-21, 2-24, 2-29, 2-32, 2-38, 2-41, 2-43, 2-45, 2-46, 2-58, 2-63, 2-68, 2-72, 2-74, 2-79, 2-94, 2-116, 2-117, 2-119, 2-120, 2-127, 2-129. 2-130, 2-131, 2-132, 2-134, 2-135, 2-146, 2-147, 2-184, 2-185, 2-186, 2-187, 2-188, 2-195, 2-198, 2-199, 2-200, 2-201, 2-202, 2-246, 2-247, 2-249, 2-2 50, 2-268, 2-277, 2-302, 2-304, 2-308, 2-310, 2-312, 2-313, 2-315, 2-316, 2-323, 2-325, 2-326, 2-329, 2-330, 2-335, 2-338, 2-340, 2-341, 2-342, 2-344.

[0166] Through further bioactivity studies, we found that the compounds of this invention still exhibit excellent killing activity against mites at extremely low doses (e.g., 1.0 ppm, 0.39 ppm, 0.195 ppm, and even 0.097 ppm). Following the above method, some exemplary compounds in this patent, as well as compound 3 (represented as CK4 in the text) in WO2024007862A1, and compounds II-43 (represented as CK1 in the text), II-61 (represented as CK2 in the text), II-51 (represented as CK5 in the text), and II-69 (represented as CK6 in the text) in WO1999055668A1, were selected as positive controls for bioactivity assays against adult Tetranychus carmineus. The results are shown in Table 4.

[0167] Table 4 shows the acaricidal activity of some exemplary compounds against adult Tetranychus cinnabarinus.

[0168] The inventors have, for the first time, non-obviously designed and synthesized highly active acaricidal compounds containing trifluoroethyl thioether phenyl cyanopyridine, nitropyridine, and difluoropyridine through strategies such as subactive structure splicing, electron isoproliferation, structure-activity relationship analysis, and precise design. Table 3 shows that compounds 2-21, 2-29, and 2-43 exhibit excellent acaricidal activity against mites. At concentrations of 1.0 ppm, 0.39 ppm, and even as low as 0.195 ppm, the mortality rate against adult Tetranychus carmineus is greater than 90%. In contrast, existing compounds (CK1-CK6) at a low concentration of 1 ppm have a mortality rate of less than 50% against Tetranychus carmineus, representing a nearly five-fold difference in activity. This significant improvement in acaricidal activity is difficult to predict.

[0169] Test Example 2: Bioactivity test against adult two-spotted spider mite (Tetranychus urticae)

[0170] The experiment followed the agricultural industry standard NY / T1154.13-2008, employing the leaf-dish spray method. Clean, flat, appropriately sized, and uniformly aged kidney bean leaves were selected and laid flat in a petri dish containing clean filter paper, with the underside facing up. The filter paper was kept moist with water. Then, 30-40 female adult two-spotted spider mites in essentially the same physiological state were inoculated onto each leaf using a brush. The compound (20 mg) was dissolved in 2 mL of DMSO to form a primary stock solution with a concentration of 10000 mg / L. The primary stock solution was diluted 100 times with 0.1% Tween-80 aqueous solution to obtain a secondary stock solution with a concentration of 100 mg / L. The secondary stock solution was diluted 10 times to obtain a test solution with a concentration of 10 mg / L. The 10 mg / L test solution was further diluted 4 times to obtain test solutions with concentrations of 2.5 mg / L and 0.625 mg / L. 2 mL of the pesticide solution was quantitatively sprayed onto the leaves inoculated with female adult two-spotted spider mites using a throat sprayer. Each treatment was repeated three times, with a blank control group included. The blank control group used a spray solution of equal proportions of DMSO and Tween aqueous solution. The sprayed petri dishes were allowed to air dry completely and then sealed with sealing film. The petri dishes were placed in an artificial climate chamber (24-26℃, L:D = 16:8, RH 60%) for 72 hours. The mortality rate of female adult mites was recorded after each 72-hour period.

[0171] Calculation method:

[0172] Mortality rate (%) = [(Pre-treatment insect population - Post-treatment live insect population) / Pre-treatment insect population] × 100%

[0173] Corrected mortality rate (%) = [(treatment group mortality rate - blank control group mortality rate) / (1 - blank control group mortality rate)] × 100%

[0174] Among the exemplary compounds of this invention, the following compounds showed good control efficacy against adult two-spotted spider mites at a concentration of 100 mg / L, achieving a mortality rate of 100%: compounds 1-2, 1-4, 1-58, 1-59, 1-82, 1-89, 1-93, 1-101, 1-110, 2-5, 2-12, 2-14, 2-18, 2-21, 2-28, 2-29, 2-32, 2-38, 2-41, 2-43, 2-45, 2-46, 2-58, 2-63, 2-68, 2-72, 2-74, 2-79, 2-116, 2-117, 2-119, 2-120, 2-127, 2-129, 2-130, and 2-131. 2-132, 2-134, 2-135, 2-146, 2-147, 2-184, 2-185, 2-186, 2-187, 2-188, 2-195, 2-198, 2-199, 2-200, 2-201, 2-202, 2-246, 2-247, 2-249, 2-250, 2-2 68, 2-277, 2-294, 2-302, 2-308, 2-310, 2-312, 2-313, 2-315, 2-316, 2-323, 2-325, 2-326, 2-329, 2-330, 2-335, 2-338, 2-340, 2-341, 2-342, 2-344.

[0175] Among the exemplary compounds in the invention, the following compounds show good control efficacy against adult two-spotted spider mites at a concentration of 10 mg / L, with a mortality rate exceeding 90%: 1-2, 1-4, 1-58, 1-59, 1-82, 1-89, 11-93, 1-101, 1-110, 2-5, 2-12, 2-18, 2-21, 2-29, 2-32, 2-38, 2-41, 2-43, 2-46, 2-58, 2-63, 2-68, 2-79, 2-116, 2-117, 2-119, 2-120, 2-127, 2-129, 2-130, 2-131, 2-132. 2-134, 2-135, 2-146, 2-147, 2-184, 2-185, 2-186, 2-187, 2-188, 2-195, 2-198, 2-199, 2-200, 2-201, 2-202, 2-246, 2-247, 2-249, 2-250, 2-268, 2-277, 2-310, 2-312, 2-313, 2-315, 2-316, 2-323, 2-325, 2-326, 2-329, 2-330, 2-335, 2-338, 2-340, 2-341, 2-342, 2-344.

[0176] Table 4. Acaricidal activity of adult two-spotted spider mites (72 hours after application)

[0177] As shown in Tables 3 and 4, the acaricidal activity assay results indicate that the compounds of this invention (taking compounds 2-21 and 2-29 as examples) not only exhibit excellent acaricidal activity against *Tetranychus carmineus*, but also against *Tetranychus two-spotted*. At a low concentration of 0.625 ppm, the lethality rate against *Tetranychus two-spotted* is greater than 90%, significantly better than the 16.15% of the prior art CK2, and also superior to the latest commercially developed sulfiflumin and the commercial agent etoxazole.

[0178] Test Example 3: Bioactivity test against adult female Panonychus citri.

[0179] The experiment followed the agricultural industry standard NYT 1154.6-2006, employing the immersion method for determination. Clean, flat, appropriately sized, and uniformly aged citrus leaves were selected and laid flat in a petri dish containing clean filter paper, with the underside facing up. The filter paper was kept moist with water. Then, 30-40 female adult citrus paronychia mites of similar physiological state were inoculated onto each leaf using a brush. The compound (20 mg) was dissolved in 2 mL of DMSO to form a primary stock solution with a concentration of 10000 mg / L. The primary stock solution was diluted 10 times with 0.1% Tween-80 aqueous solution to obtain a test solution with a concentration of 100 mg / L, and then diluted 10 times again to obtain a test solution with a concentration of 10 mg / L. After the test insects stabilized on the leaves, they were immersed in the prepared solution for 5-10 seconds. Excess solution was absorbed with filter paper and the leaves were allowed to air dry. Each treatment was repeated three times, and a blank control group was included. The blank control group used an immersion solution of equal proportions of DMSO and Tween aqueous solution. The experimental targets were then cultured in an artificial climate chamber (24-26℃, L:D=16∶8, RH 60%), and the mortality of female adult mites was checked and recorded after 72 hours.

[0180] Mortality rate (%) = [(Pre-treatment insect population - Post-treatment live insect population) / Pre-treatment insect population] × 100%

[0181] Corrected mortality rate (%) = [(treatment group mortality rate - blank control group mortality rate) / (1 - blank control group mortality rate)] × 100%

[0182] Among the exemplary compounds tested in the invention section, the following compounds showed good control efficacy against adult citrus psyllids at a concentration of 10 mg / L, with a mortality rate exceeding 90%: 1-2, 1-4, 1-59, 2-1, 2-5, 2-11, 2-18, 2-21, 2-29, 2-32, 2-38, 2-41, 2-43, 2-45, 2-63, 2-68, 2-146, 2-147, and 2-268.

[0183] Agricultural mites are recognized worldwide as one of the most difficult biological groups to control, and the control of resistant mites is an even greater global challenge. Currently, the control of mites faces challenges and dilemmas such as high resistance, poor efficacy, and large dosage. Developing new and highly effective acaricides has become an urgent task in this field. Derivatives containing trifluoroethyl sulfide phenyl are a hot topic in existing acaricide research and development, with features such as novel structure, unique mechanism, no cross-resistance with existing acaricides, and excellent activity.

[0184] To obtain more active trifluoroethyl thioether phenyl derivatives, this invention, through the non-obvious discovery of pyridine derivatives containing trifluoroethyl thioether phenyl via subactive structural splicing, found that these derivatives exhibit good acaricidal activity against agricultural mites. Based on this, we synthesized a series of compounds of general formula 1 using isosteric design. Subsequently, we conducted in-depth research and analysis on the acaricidal activity and structure-activity relationship of general formula 1. The inventors found that the acaricidal activity was poor when the substituents on the pyridine were electron-donating substituents, while the acaricidal activity was better when the substituents were electron-withdrawing substituents. Guided by this structure-activity relationship, we non-obviously designed and synthesized nitropyridine and cyanopyridine derivatives containing trifluoroethyl thioether phenyl. Through bioactivity assays, we were surprised to find that they still exhibited excellent acaricidal activity against mites at extremely low concentrations, and showed excellent acaricidal activity against a variety of mites such as Tetranychus carmine, Tetranychus two-spotted, and Tetranychus citrus, demonstrating high efficiency and broad spectrum. Compared with compounds disclosed in the prior art, the acaricidal activity of the compounds in this invention is unexpectedly increased by more than 5 times. It is precisely through the flexible application of various strategies such as active substructure splicing, electron isochromatography, and structure-activity relationship analysis in the process of creating novel acaricides that we finally obtained these unexpectedly highly active compounds.

[0185] In summary, the compounds of this invention possess novel structures, unique mechanisms of action, and broad-spectrum efficacy. They exhibit remarkable control effects against various harmful organisms, particularly spider mites such as *Tetranychus carmine*, *Tetranychus two-spotted*, *Tetranychus kanazei*, and *Pterygodon citrinum*, even at low concentrations. Specifically, they demonstrate excellent acaricidal activity against these mites at extremely low concentrations below 1 mg / L (e.g., 0.195 mg / L and 0.625 mg / L), with a mortality rate exceeding 90%. Compared with existing technologies and mainstream commercial pesticides, their acaricidal activity is significantly improved. This effectively addresses the serious problems of high resistance, poor efficacy, and high dosage in agricultural mite control, contributing to the sustainable development of acaricides and ensuring the safety of fruits and vegetables.

[0186] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the scope of protection of the present invention.

Claims

1. A compound containing a trifluoroalkylthiophenylpyridine derivative or its isotopically labeled compound, or an optical isomer, geometric isomer, tautomer, or mixture of isomers, or a pesticide-acceptable salt thereof, having the structure of a compound of formula (I-1) or (I-2): in, R1 is selected from C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkoxy, C1-C6 haloalkoxy, cyanoC1-C6 alkyl, C3-C6 cycloalkylC1-C3 alkyl or C3-C6 epoxyalkylC1-C3 alkyl. R2 is selected from methyl or chlorine; R4 is fluorine; X1, X2 and X4 are each independently selected from H, halogen, C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkylamino, C1-C3 alkylthio, C1-C3 alkylsulfonyl, hydroxyl, nitro, amino, cyano, aldehyde, carboxyl, amide or ester. X3 is selected from halogen, nitro, cyano, C1-C3 alkylthio or C1-C3 alkylsulfonyl; n is 0 or 1.

2. The trifluoroalkylthiophenylpyridine derivative according to claim 1, wherein, R1 is selected from C1-C3 alkyl, C1-C3 haloalkyl, cyanoC1-C3 alkyl or C3-C6 cycloalkylC1-C3 alkyl; R2 is selected from methyl or chlorine; R4 is fluorine; X1, X2 and X4 are each independently selected from H, halogen, C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkylamino, C1-C3 alkylthio, C1-C3 alkylsulfonyl, hydroxyl, nitro, amino, cyano, aldehyde, carboxyl, amide or ester. X3 is selected from halogen, nitro, cyano, C1-C3 alkylthio or C1-C3 alkylsulfonyl; n is 0 or 1.

3. The trifluoroalkylthiophenylpyridine derivative according to claim 1, wherein, R1 is selected from methyl, ethyl, propyl, tert-butyl, isobutyl, dichloroethyl, trichloroethyl, trichloropropyl, fluoromethyl, difluoromethyl, trifluoromethyl, difluoroethyl, trifluoroethyl, tetrafluoroethyl, pentafluoroethyl, trifluoropropyl, heptafluoropropyl, 1-cyanomethyl, cyclopropylmethyl, or glycidyl methyl. R2 is selected from methyl or chlorine; R4 is fluorine; X1, X2 and X4 are each independently selected from H, halogen, C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkylamino, C1-C3 alkylthio, C1-C3 alkylsulfonyl, hydroxyl, nitro, amino, cyano, aldehyde, carboxyl, amide or ester. X3 is selected from halogen, nitro, cyano, C1-C3 alkylthio or C1-C3 alkylsulfonyl; n is 0 or 1.

4. The trifluoroalkylthiophenylpyridine derivative according to claim 1, wherein, R1 is selected from CH3, CF3, CH2CH3, CH2CHF2, CH2CF3, CH2CH2CF3, 1-cyanomethyl, cyclopropylmethyl, CH2CHCl2, CH2CCl3, CH2CH2CCl3 or glycidylmethyl; R2 is selected from methyl or chlorine; R4 is fluorine; X1, X2, and X4 are each independently selected from H, fluorine, chlorine, bromine, iodine, methyl, ethyl, propyl, tert-butyl, isopropyl, difluoromethyl, trifluoromethyl, trifluoroethyl, hydroxyl, nitro, amino, cyano, aldehyde, carboxyl, amide, ester, methylamino, methylthio, or methylsulfone. X3 is selected from fluorine, chlorine, bromine, iodine, nitro, cyano, methylthio, or methylsulfone. n is 0 or 1.

5. The trifluoroalkylthiophenylpyridine derivative according to claim 1, wherein, R1 is selected from CH3, CF3, CH2CH3, CH2CHF2, CH2CF3, CH2CH2CF3, 1-cyanomethyl or cyclopropylmethyl; R2 is a methyl group; R4 is fluorine; X1, X2, and X4 are each independently selected from H, fluorine, chlorine, bromine, methyl, cyclopropyl, difluoromethyl, trifluoromethyl, nitro, amino, cyano, carboxyl, or ester groups; X3 is selected from fluorine, chlorine, bromine, nitro, cyano, or methylthio; n is 0.

6. The trifluoroalkylthiophenylpyridine derivative according to any one of claims 1-5, having the structure of the compound of formula (I-2).

7. An agricultural chemical preparation comprising any one of claims 1-6 containing a trifluorothiophenylpyridine derivative and an extender and / or a surfactant.

8. The agricultural chemical preparation according to claim 7, further comprising other agricultural chemically active ingredients.

9. A method for controlling animal pests, comprising applying a trifluorothiophenylpyridine derivative according to any one of claims 1-6 or an agricultural chemical agent according to claim 7 or 8 to the animal pests and / or their habitat.

10. Use of the trifluorothiophenylpyridine derivative according to any one of claims 1-6 or the agricultural chemical agent according to claim 7 or 8 for the control of animal pests.

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