Preparation and application of novel trifluoroalkyl-containing thiophenyl pyridine derivative

Abstract

The invention relates to preparation and application of a novel trifluoroalkyl-containing thiophenyl pyridine derivative. Specifically, the invention relates to a compound as shown in a formula (I-1) or (I-2) or an isotope labeled compound of the compound, or an optical isomer, a geometric isomer, a tautomer or an isomer mixture of the compound, or a pharmaceutically acceptable salt of the compound, the invention also relates to application of the compound in preparation of insecticide for pest control. The compound can achieve a better pest control effect at a lower dosage, especially for pests and pest mites such as tetranychus cinnabarinus, tetranychus urticae and panonychus citri.

Description

Cross Reference to Related Applications

[0001] This application claims priority to Chinese Patent Application No. 202411661992.2, filed November 20, 2024, the entire contents of which are incorporated herein by reference. TECHNICAL FIELD

[0002] The present application relates to the technical field of pesticides, in particular, to the preparation and application of novel trifluoroalkylthio phenyl pyridine derivatives. BACKGROUND

[0003] Agricultural mites are one of the most difficult-to-control biological groups in the world, with characteristics of fast reproduction, short generation period, strong adaptability, high mutation rate, easy resistance to drugs, and easy outbreak. They can harm more than 1,100 host plants, causing serious damage to fruits, vegetables, flowers, and other plants, resulting in annual losses of more than 10 billion yuan in China.

[0004] Currently, chemical control is still the most effective measure to prevent and control plant mites, with an annual investment of about $1 billion in chemical acaricides to control plant mites. Patent WO1999055668A discloses a class of trifluoroethyl sulfide pyridine derivatives, some of which have a mortality rate of more than 90% for Tetranychus urticae at a concentration of 500 ppm. However, they have obvious shortcomings in use, with insufficient acaricidal activity, especially at lower application rates.

[0005] Trifluoroethyl sulfide (sulfoxide) compounds are a new class of compounds with good acaricidal activity. Flupentiofenox developed by combinatorial chemistry, Sulfiflumin developed by Bayer CropScience AG, and Bisulflufen developed by Shenyang Sinochem Pesticide Chemical Research & Development Co., Ltd. have obtained ISO generic names in 2020, 2023, and 2023, respectively. These compounds have shown good acaricidal activity against plant mites and are now being developed for industrialization.

[0006] The current acaricide market is facing serious problems such as high resistance, poor control effect, severe homogeneity, and environmental unsafety, so there is an urgent need to develop new acaricides to solve these problems. SUMMARY

[0007] The present application aims to provide a new type of novel trifluoroalkylthiophenyl pyridine derivatives, which can achieve better pest control effect at a lower dose, can kill insects and mites efficiently, and can be used for controlling animal pests (including arthropods and particularly representatives of the order of insects or acarids). Moreover, the synthesis process of the compound provided by the present application is simple, the production cost is low, and the future development potential is huge.

[0008] In a first aspect, the present application provides a trifluoroalkylthiophenyl pyridine derivative or an isotopically labeled compound thereof, or an optical isomer, a geometric isomer, a tautomer or an isomer mixture thereof, or a pesticidally acceptable salt thereof, the trifluoroalkylthiophenyl pyridine derivative having the structure of a compound of formula (I-1) or formula (I-2): (I-1)

[0009] wherein, R1 is selected from C1-C6 alkyl, C1 C6 haloalkyl, C2 C6 alkenyl, C2 C6 alkynyl, C1 C6 alkoxy, C1 C6 haloalkoxy, cyano C1 C6 alkyl, C3 C6 cycloalkyl C1 C3 alkyl or C3 C6 cycloalkyl C1 C3 alkyl; R2 is selected from methyl or chloro; R4 is fluoro; 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 alkylsulfone, hydroxyl, nitro, amino, cyano, aldehyde, carboxyl, amide or ester; X3 is selected from halogen, nitro, cyano, C1-C3 alkylthio or C1-C3 alkylsulfone; n is 0 or 1.

[0010] In an embodiment of the present application, wherein, R1 is selected from C1-C3 alkyl, C1-C3 haloalkyl, cyano C1-C3 alkyl or C3-C6 cycloalkyl C1-C3 alkyl; R2 is selected from methyl or chloro; R4 is fluoro; X1, X2and X4are each independently selected from H, halogen, C1-C3alkyl, C1-C3haloalkyl, C1-C3alkylamino, C1-C3alkylthio, C1-C3alkylsulfone, hydroxyl, nitro, amino, cyano, aldehyde, carboxyl, amido, or ester; X3is selected from halogen, nitro, cyano, C1-C3alkylthio, or C1-C3alkylsulfone; n is 0 or 1.

[0011] In one embodiment of the present application, wherein, R1is selected from methyl, ethyl, propyl, t-butyl, isobutyl, dichloroethyl, trichloroethyl, trichloropropyl, fluoromethyl, difluoromethyl, trifluoromethyl, difluoroethyl, trifluoroethyl, tetrafluoroethyl, pentafluoroethyl, trifluoropropyl, heptafluoropropyl, 1-cyanomethyl, cyclopropylmethyl, or epoxypropylmethyl; R2is selected from methyl or chloro; R4is fluoro; X1, X2and X4are each independently selected from H, halogen, C1-C3alkyl, C1-C3haloalkyl, C1-C3alkylamino, C1-C3alkylthio, C1-C3alkylsulfone, hydroxyl, nitro, amino, cyano, aldehyde, carboxyl, amido, or ester; X3is selected from halogen, nitro, cyano, C1-C3alkylthio, or C1-C3alkylsulfone; n is 0 or 1.

[0012] In one embodiment of the present application, wherein, R1is selected from CH3, CF3, CH2CH3, CH2CHF2, CH2CF3, CH2CH2CF3, 1-cyanomethyl, cyclopropylmethyl, CH2CHCl2, CH2CCl3, CH2CH2CCl3, or epoxypropylmethyl; R2is selected from methyl or chloro; R4is fluoro; X1, X2and X4are each independently selected from H, halogen, C1-C3alkyl, C1-C3haloalkyl, C1-C3alkylamino, C1-C3alkylthio, C1-C3alkylsulfone, hydroxyl, nitro, amino, cyano, aldehyde, carboxyl, amido, or ester; X3is selected from halogen, nitro, cyano, C1-C3alkylthio, or C1-C3alkylsulfone; n is 0 or 1.

[0013] In one embodiment of the present application, wherein, R1is selected from CH3, CF3, CH2CH3, CH2CHF2, CH2CF3, CH2CH2CF3, 1-cyanomethyl, or cyclopropylmethyl; R2is methyl; R4is fluorine; X1, X2and X4are each independently selected from H, fluorine, chlorine, bromine, methyl, cyclopropyl, difluoromethyl, trifluoromethyl, nitro, amino, cyano, carboxyl or ester group; X3is selected from fluorine, chlorine, bromine, nitro, cyano or SCH3; n is 0.

[0014] In one embodiment of the present application, the compound of formula (I-1) of the present application has the structure of formula (I-1-1):

[0015] wherein, R1is selected from CH2CH3, CH2CHF2, CH2CF3or CH2CH2CF3; R2is selected from methyl or chlorine; R4is selected from fluorine; X1is selected from H, fluorine, chlorine or bromine; X2is selected from H, fluorine, chlorine, bromine or methyl; X3is selected from fluorine, chlorine, bromine, cyano, nitro or methylthio; n is 0 or 1.

[0016] In one embodiment of the present application, the compound of formula (I-1) of the present application has the structure of formula (I-1-2):

[0017] wherein, X1is selected from fluorine, chlorine or bromine; X3is selected from fluorine, chlorine, bromine, nitro, cyano or methylthio; n is 0 or 1.

[0018] In one embodiment of the present application, the compound of formula (I-1) of the present application has the structure of formula (I-1-3):

[0019] wherein, X2is selected from H, fluorine, chlorine, bromine or methyl; X3is selected from fluorine, chlorine, bromine, nitro, cyano or methylthio; n is 0 or 1.

[0020] In one embodiment of the present application, the compound of formula (I-2) of the present application has the structure of formula (I-2-1):

[0021] wherein, R1is selected from CH3, CF3, CH2CH3, CH2CHF2, CH2CF3, CH2CH2CF3, CH2CN or cyclopropylmethyl; R2is selected from methyl or chloro; R4is fluoro; X2is selected from H, fluoro, chloro, bromo, methyl, trifluoromethyl, cyano or nitro; X3is selected from fluoro, chloro, bromo, cyano, nitro or SCH3; n is 0 or 1.

[0022] In one embodiment of the present application, the compound of formula (I-2) of the present application has the structure of formula (I-2-2):

[0023] wherein, R1is selected from CH2CH3, CH2CHF2, CH2CF3or CH2CH2CF3; X2is selected from H, fluoro, chloro, bromo, methyl, trifluoromethyl, cyano or nitro; X3is selected from fluoro, chloro, bromo, cyano, nitro or SCH3; n is 0 or 1.

[0024] For the sake of brevity, hereinafter the "novel trifluoroalkylthiophenylpyridine derivative", "compound of formula (I-1)", "compound of formula (I-2)" or "compound of the present application" can also encompass any isotopically-labeled compound of formula (I-1) or formula (I-2), or an optical isomer, a geometric isomer, a tautomer or an isomer mixture thereof, or a pesticidally acceptable salt thereof.

[0025] The term "optical isomer" means that, when a compound has one or more chiral centers, each chiral center can exist in the R or S configuration, and the various isomers thus constituted are optical isomers. Optical isomers include all diastereomers, enantiomers, meso forms, racemates or mixtures thereof. Optical isomers can be separated, for example, by a chiral chromatographic column or by chiral synthesis.

[0026] The term "geometric isomer" means that, when a compound has a double bond, the compound can exist as a cis isomer, a trans isomer, an E isomer and a Z isomer. Geometric isomers include cis isomers, trans isomers, E isomers, Z isomers or mixtures thereof.

[0027] The term "tautomer" refers to isomers that differ in the position of a proton. It is understood by those skilled in the art that tautomers can be converted into each other and can coexist in a certain state in equilibrium.

[0028] The term "nematodes" includes all species of the phylum Nematoda and, in context, particularly species that are parasitic on plants (e.g., species of Aphelenchida, root knot nematodes, Tylenchida, and others).

[0029] Unless otherwise specified, a reference to a "novel trifluoroalkylthiophenylpyridine derivative", a "compound of formula (I-1)", a "compound of formula (I-2)", or a "compound of the invention" herein is also a reference to isotopically-labeled compounds and hydrates of such compounds. 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 an atom having the atomic mass or mass number different from the atomic mass or mass number usually found in nature.

[0030] Examples of isotopes suitable for inclusion in the compounds of the present invention include isotopes of hydrogen, such as 2 H (D), and 3 H (T), isotopes of carbon, such as 11 C, 13 C, and 14 C, isotopes of chlorine, such as 37 Cl, isotopes of fluorine, such as 18 F, isotopes of iodine, such as 123 I, and 125 I, isotopes of nitrogen, such as 13 N, and 15 N, isotopes of oxygen, such as 15 O, 17 O, and 18 O, and isotopes of sulfur, such as 35 S.

[0031] Isotopically-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 the

[0032] The compounds of formula (I-1) or formula (I-2) can exist in the form of a salt which is acceptable in the art of agrochemicals, such as, for example, an acid addition salt and / or a base addition salt of a compound of formula (I-1) or formula (I-2). As used herein, "salt acceptable in the art of agrochemicals" includes an acid addition salt or a base addition salt which can occur within a compound of formula (I-1) or formula (I-2), unless otherwise indicated.

[0033] Pesticidally acceptable salts of the compound of formula (I-1) or the compound of formula (I-2) include acid and base addition salts thereof. Suitable acid addition salts are formed from acids which form nontoxic salts. For a review on suitable salts see Handbook of Pharmaceutical Salts: Properties, Selection and Use by Stahl and Wermuth (Wiley-VCH, 2002). Methods for preparing the pesticidally acceptable salts of the compounds described herein are known to those skilled in the art.

[0034] To avoid ambiguity, the following definitions are provided for terms used herein. Unless otherwise indicated, the terms used herein have the following meanings.

[0035] The term "substituted", when used herein, means that one or more (preferably 1 to 5, more preferably 1 to 3) hydrogen atoms of a group are independently replaced with a corresponding number of substituents.

[0036] The term "independently", when used herein, means that when the number of substituents is more than one, these substituents can be the same or different.

[0037] The term "alkyl", when used herein, means a saturated aliphatic hydrocarbon, including straight-chain and branched-chain. In some embodiments, the alkyl group has 1-8, or 1-6, or 1-3 carbon atoms. For example, the term "C 1-8 The term "alkyl" means a straight-chain or branched-chain radical having 1-8 carbon atoms. The terms "C 1-8 The term "alkyl" means a straight-chain or branched-chain radical having 1-8 carbon atoms. The terms "C 1-6 The term "alkyl" means a straight-chain or branched-chain radical having 1-8 carbon atoms. The terms "C Examples of alkyl groups include, but are not limited to, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, t-butyl, pentyl, 2-pentyl, 3-pentyl, isopentyl, neopentyl, (R)-2-methylbutyl, (S)-2-methylbutyl, 3-methylbutyl, 2,3-dimethylpropyl, 2,3-dimethylbutyl, hexyl, and the like. The alkyl group can be optionally substituted with one or more (e.g., 1 to 5) suitable substituents.

[0038] The term "haloalkyl", when used herein, means an alkyl group having one or more halogen substituents (up to perhaloalkyl, i.e., each hydrogen atom of the alkyl group is replaced with a halogen atom). For example, the term "C 1- The term "haloalkyl", when used herein, means an alkyl group having one or more halogen substituents (up to perhaloalkyl, i.e., each hydrogen atom of the alkyl group is replaced with a halogen atom). For example, the term "C 1- The term "haloalkyl", when used herein, means an alkyl group having one or more halogen substituents (up to perhaloalkyl, i.e., each hydrogen atom of the alkyl group is replaced with a halogen atom). For example, the term "C1- C3haloalkyl" means a C3alkyl group having one or more halogen substituents 1- C3alkyl group (up to perhaloalkyl, 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 polyhalo, the halogen atoms can be the same or different. In the context of the present application, the halogen is fluorine, chlorine, bromine or iodine, in particular fluorine, chlorine or bromine.

[0039] The term "alkoxy", as used herein, denotes O-alkyl, wherein the term "alkyl" is defined above, either by itself or in combination with other terms, e.g. haloalkoxy.

[0040] The term "cycloalkyl", as used herein, denotes C3-C8-cycloalkyl, such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl and cyclooctyl. Of these, C3-C6-cycloalkyl is preferred. The term "cyclopropyl" is abbreviated as Cyc.

[0041] The term "cycloalkyl", as used herein, denotes C3-C8-cycloalkyl, such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl and cyclooctyl. Of these, C3-C6-cycloalkyl is preferred. The term "cyclopropyl" is abbreviated as Cyc.

[0042] The term "C3-C6-cycloalkyl C1-C3-alkyl", as used herein, denotes a C1-C3-alkyl group having a C3-C6-cycloalkyl substituent, which is to be understood as R-(C1-C3)alkyl-(C3-C6)cycloalkyl in the present application. The terms "cycloalkyl", "alkyl" are defined above.

[0043] The term "C3-C6-cycloalkyl C1-C3-alkyl", as used herein, denotes a C1-C3-alkyl group having a C3-C6-cycloalkyl substituent, which is to be understood as R-(C1-C3)alkyl-(C3-C6)cycloalkyl in the present application. The terms "cycloalkyl", "alkyl" are defined above.

[0044] Herein, numerical ranges are used to indicate that an amount, size, or other quantity that can be exactly recited in the disclosure can be approximated by a range of amounts, sizes, or other quantities. For example, a range of "1 to 4" indicates that an amount, size, or other quantity can be 1, 2, 3, or 4. Thus, a numerical range is a convenient approximation of a specific number that can be recited in the disclosure. Numerical ranges are also inclusive of their endpoints. For example, a range of "1 to 4" includes 1 and 4. Any numerical range recited herein is intended to include all sub-ranges of the same numbers. For example, a range of "1 to 4" is intended to include a range of "2 to 6," "3 to 5," etc.

[0045] The compounds of the present application can be prepared in a variety of ways known to one skilled in the art of organic synthesis. One skilled in the art, with reference to the synthetic routes to specific compounds of particular embodiments of the present application, can adapt the starting materials and reaction conditions to prepare other compounds.

[0046] The following synthetic schemes describe the preparation of the compounds disclosed in the present application. In the schemes, R1, R2, R4and n have the meanings described in the present application.

[0047]

[0048] Intermediate 1 is reacted with different electrophiles in the presence of a base to give intermediate 2, which is first converted to diazonium salt with sodium nitrite, and then halogenated with cuprous halide or potassium iodide to give the corresponding halobenzene 3, where T is Br or I. Intermediate 3 is formed by reaction to give intermediate 4, where X is B(OH)2or Pinacolato boranyl. Intermediate 4 is subjected to Suzuki coupling with halide of Q (pyridyl) to give the sulfide product of Formula I. The sulfide product of Formula I is oxidized with an oxidant such as m-CPBA or hydrogen peroxide to give the oxidized target product of Formula I. Intermediate 3 can also be directly subjected to Suzuki coupling with boronic acid (boronate) of Q to give the sulfide product of Formula I.

[0049] In addition, the above-mentioned intermediate compounds and their starting materials can be prepared according to the methods reported 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 55.5 (2010): 2048-2054.

[0050] The present application lists a plurality of synthesized exemplary compounds, the selection of the specific groups of which are shown in Table 1 or 2 below, and part of the exemplary compound characterization data is shown in Table 3. It should be understood that the scope of the present application is not limited to the exemplary compounds listed in the following tables, and the selection of each group of the compounds in Table 1 or 2 below can be combined in any combination without particular limitation. Part of the compounds of general formula (I-1) or (I-2) of the present application are shown below, but the present application is by no means limited to these compounds.

[0051]

[0052] Table 1

[0053]

[0054] Table 2

[0055] Table 3 Part of Exemplary Compound Characterization Data

[0056] In a second aspect, the present application provides an insecticide composition comprising a compound of formula (I-1) or formula (I-2) or an isotopically-labeled compound thereof, or an optical isomer, a geometric isomer, a tautomer, or an isomer mixture thereof, or a pesticidally acceptable salt thereof, and a pesticidally acceptable carrier. It can be applied to animal pests and / or their habitats to control unwanted animal pests.

[0057] The formulations comprise at least one compound of the present application and at least one agriculturally useful adjuvant, such as carriers and / or surfactants.

[0058] The agrochemically acceptable carrier can be an organic or inorganic inert carrier material. For example, suitable carriers include water, gelatin, gum arabic, magnesium stearate, talc, vegetable oils, polyalkylene glycols, vaseline, mannitol, cellulose, cellulose derivatives, sodium saccharin, magnesium carbonate, saline, glycerol, ethanol, and the like. In addition, the insecticide composition can also contain other additives, such as preservatives, stabilizers, emulsifiers, buffers, diluents, binders, wetting agents, lubricants, flow agents, and the like.

[0059] The compound of formula (I-1) or formula (I-2) of the present application can also be used in the form of a mixture with one or more suitable fungicides, bactericides, acaricides, molluscicides, nematicides, insecticides, microbials, beneficial microorganisms, herbicides, fertilizers, bird repellents, phytotonics, sterilants, safeners, semiochemicals and / or plant growth regulators, for example, to broaden the spectrum of action, to prolong the duration of action, to increase the rate of action, to prevent repellence or to prevent the development of resistance. In addition, such active ingredient combinations can improve plant growth and / or tolerance to abiotic factors, such as high or low temperatures, drought, high water content or soil salinity. Flowering and fruiting performance, germination capacity and root development can also be optimized, harvest can be facilitated and yield increased, ripening can be influenced, the quality and / or nutritional value of the harvested products can be increased, the shelf life of the harvested products can be extended and / or the processing properties of the harvested products can be improved.

[0060] The dosage form of the insecticide composition of the present application can be a liquid dosage form, a solid dosage form or a semi-solid dosage form, without particular limitation. In some embodiments, the dosage form of the insecticide composition is selected from a powder, a granule, a liquid, a suspension or a spray, preferably a wettable powder, a wettable liquid, a soluble powder, a dispersible liquid, an aqueous agent, a microemulsion, an emulsion oil, an aqueous emulsion, a sprayable solution, a dispersible oil suspension, a microcapsule suspension, a water dispersible granule, a water soluble granule, a large granule, a granule for sowing and soil application, an aerosol, an ultra-low volume agent and a wax product.

[0061] The content of the compound of the present application in its insecticide composition can be adjusted according to the actual needs (e.g. dosage form, mode of application, application object, etc.), including but not limited to 0.001 mg / L-10 mg / L, for example 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.

[0062] The specific frequency of application can be determined by a person skilled in the relevant art, for example 1 time per day, 1 time per 2 days, 1 time per 3 days, 1 time per 4 days, 1 time per 5 days, 1 time per 6 days, 2 times per day, 3 times per day, etc.

[0063] In a third aspect, the present application provides the use of a compound of formula (I-1) or formula (I-2), or an isotopically-labeled compound thereof, or an optical isomer, a geometric isomer, a tautomer, or a mixture of isomers thereof, or a pesticidally acceptable salt thereof, for the preparation of a pesticide for the control of pests.

[0064] The compounds of the present application are suitable for controlling pests or insect pests, i.e. for controlling harmful or unwanted insects or mites, especially in agricultural, in forestry, in the protection of stored products and materials and in the hygiene sector, and show excellent activity against a broad spectrum of pests or insect pests at low rates of application and are active against various pests or insect pests at all stages of development, i.e. eggs, larvae (nymphs), pupae, and adults, and also show excellent activity against pests or insect pests that are resistant, have become resistant or are developing resistance to conventional insecticides or acaricides.

[0065] The present application also relates to a method for controlling pests or insect pests, which comprises applying to the site, locus, habitat of insects, pests, area to be protected, or directly on the insects to be controlled a controlling effective amount of a compound of formula (I-1) or formula (I-2). The compounds of the present application can also be used for controlling other invertebrate pests or organisms.

[0066] In particular, the insect habitat, pest habitat or pest mite habitat refers to the environment in which the insects, pests or pest mites live or in which their eggs exist, including the surrounding air, the food consumed or the objects touched. For example, by applying the active compounds to the seeds of the plants (before planting), to the seedlings, or to the planted cuttings, leaves, stems, fruits, grains and / or roots, or to the soil or other growth medium (before or after planting of the crop), insects or pest mites which feed on, destroy or touch the edible agricultural crops, ornamental plants, turf, forage plants or other plants of economic value can be controlled, and also by controlling sap-feeding pests such as whiteflies, plant hoppers, aphids and the like or pest mites such as two-spotted spider mites, carmine spider mites and the like, these plants can be protected against diseases caused by viruses, fungi or bacteria; the plants include those which are propagated by conventional methods and also those which have been modified by modern biotechnology to have insect or pest mite resistance, herbicide resistance, high yield and / or other advantageous properties. It is to be expected that the compounds are suitable for protecting fabrics, paper, stored grain, seeds and other foodstuffs, houses, buildings and the like from infestation by insects or mites, by applying the compounds of the present application to such materials and / or the localities where they occur, for example directly to the materials or in the vicinity of the materials to be protected, for example by the customary methods of application, such as by immersion, spraying, vaporizing, atomizing, scattering, spreading, injecting and, in the case of propagation material, especially in the case of seeds, also by applying one or more coats.

[0067] In the field of animal health, i.e. veterinary medicine, the compounds of formula (I-1) or formula (I-2) of the present application have activity against animal parasites, in particular ectoparasites or endoparasites. The term "endoparasites" includes in particular helminths and protozoa, such as coccidia. Ectoparasites are typically and preferably arthropods, in particular insects or mites.

[0068] In the field of veterinary medicine, the compounds of formula (I-1) or formula (I-2) having a favorable toxicity to warm-blooded animals are suitable for controlling parasites which occur in the animal breeding and animal keeping of domestic animals, breeding animals, zoo animals, laboratory animals, experimental animals and pet animals. They have activity against all or specific developmental stages of the parasites.

[0069] Agricultural domestic animals include, for example, mammals such as sheep, goats, horses, donkeys, camels, water buffalo, rabbits, reindeer, fallow deer, and in particular cattle and swine; or poultry such as turkeys, ducks, geese, and in particular chickens; or, for example, fish or crustaceans in aquaculture; or, as appropriate, insects such as bees.

[0070] Pet animals include, for example, mammals such as hamsters, guinea pigs, rats, mice, chinchillas, ferrets, and in particular dogs, cats, caged birds; reptiles, amphibians or ornamental fish.

[0071] With regard to the field of animal health, the term "control" or "controlling" herein means that the compounds of formula (I-2) are effective in reducing the incidence of a particular parasite to a non-damaging level in animals infected with such parasites. More specifically, "control" herein means that the compounds of formula (I-1) or formula (I-2) kill, inhibit the growth of, or inhibit the reproduction of, the respective parasite.

[0072] In the context of the present patent application, the term "hygiene" is to be understood as meaning any and all measures, precautions and methods which are aimed at preventing illnesses, in particular infectious diseases, and which serve to protect the health of humans and animals and / or to protect the environment and / or to maintain cleanliness. In accordance with the present application, this includes in particular measures for cleaning, disinfecting and sterilizing, for example, textiles or hard surfaces, in particular surfaces made of glass, wood, cement, porcelain, ceramic, plastic or metal, in order to ensure that they are protected from hygiene pests and / or their secretions. In this respect, the scope of protection of the present application preferably excludes methods which are applied in surgical or therapeutic treatment of the human or animal body and diagnostic methods which are carried out on the human or animal body.

[0073] The term "hygiene" thus encompasses all areas, technical fields and industrial applications in which these hygiene measures, precautions and methods are important, for example hygiene in kitchens, bakeries, airports, bathrooms, swimming pools, department stores, hotels, hospitals, stables, animal husbandry, etc.

[0074] The inventors of the present application have found that the compounds of the present application are capable of controlling animal pests, especially insects, arachnids, helminths, nematodes and molluscs, encountered in the fields of agriculture, horticulture, livestock breeding, aquaculture, forestry, landscaping and leisure facilities, protection of stored products and materials, and hygiene, even when applied at lower doses. These compounds are preferably used as insecticides. They are effective against both usually susceptible and resistant species and against all or part of the developmental stages. The pests mentioned above include animal pests and include insects, mites or nematodes, in particular: pests from the phylum Arthropoda, especially from the class Arachnida, for example Acarina, such as Tetranychidae (for example Tetranychus spp. such as Amphi tetranychus viennensis, Eotetranychus spp., Panonychus spp. or Oligonychus spp.), Aculops spp., Aculus spp. (for example Aculus fockeui, Aculus schlechtendali), Amblyomma spp., Argas spp., Boophilus spp., Brevipalpus spp. (for example Brevipalpus phoenicis), Bryobia spp. (for example Bryobia graminum, Bryobia praetiosa), Centruroides spp., Chorioptes spp., Dermatophagoides spp. (for example Dermatophagoides pteronyssinus, Dermatophagoides farinae), Dermacentor spp., Dermanyssus gallinae; 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 (Anoplophoras spp.), the flower weevil (Anthonomus spp.) (e.g., the cotton boll weevil (Anthonomus grandis)), the round 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., sweet potato flea beetle (Chaetocnema confinis), Chaetocne madenticulata, corn flea beetle (Chaetocnema ectypa)), Cleonus mendicus, broad-breasted click beetle (Conoderus spp.), root weevil (e.g., banana black weevil (Cosmopolites sordidus)); a pest / invertebrate from the order Diptera (Diptera), for example, 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., Bactrocera spp. (e.g., Bactrocera cucurbitae, Bactrocera dorsalis, Bactrocera oleae), Bibio hortulanus, Calliphora erythrocephala, Calliphora vicina, Ceratitis capitata, Chironomus spp., Chrysomyia spp., Chrysops spp., Chrysozona pluvialis, Cochliomyia spp., Contarinia spp. (e.g., Contarinia johnsoni, Contarinia nasturtii, Contarinia pyrivora); pests from the order of the Heteroptera, for example, Anasa tristis, Antestiopsis spp., Boisea spp., Blissus spp., Calocoris spp., Campylomma livida, Cavelerius spp., Cimex spp. (for example Cimex adjunctus, Cimex hemipterus, Cimex lectularius, Cimex pilosellus), Collaria spp., Creontiades dilutus, Dasynus piperis, Dichelops furcatus, Diconocoris hewetti, Dysdercus spp., Euschistus spp.; pests from the order Homoptera, for example Acizzia acaciaebaileyanae, Acizzia dodonaeae, Acizzia uncatoides, Acrida turrita, Acyrthosipon spp. (e.g. Acyrthosiphon pisum), Acrogonia spp., Aeneolamia spp., Agonoscena spp., Aleyrodes proletella, Aleurolobus barodensis, Aleurothrixus floccosus, Allocaridara malayensis, Amrasca spp. (e.g. Amrasca bigutulla, Amrasca devastans), Anuraphis cardui, Aonidiella spp. (e.g. Aonidiella aurantii, Aonidiella citrina, Aonidiella inornata), Aphanostigma piri, Aphis spp (e.g. Aphis craccivora, Aphis fabae, Aphis forbesi, Aphis glycines, Aphis gossypii, Aphis hederae, Aphis illinoisensis, Aphis middletoni, Aphis nasturtii, Aphis nerii; pests from the order of the hymenoptera (hymenoptera), for example, acromyrmex spp., athalia spp. (e.g. athalia rosae), atta spp., diprion spp. (e.g. diprion similis), hoplocampa spp. (e.g. hoplocampa cookei, hoplocampa testudinea), lasius spp., leptinotarsa spp. (e.g. leptinotarsa decemlineata), monomorium spp., myrmica spp., pheidole spp., solenopsis spp. (e.g. solenopsis invicta, solenopsis richteri, solenopsis geminata), cephoides spp., campylomma livida, cryptotympana atrata, dacus spp., grapholita molesta, hyphantria cunea, leucoptera scitella, lithocolletis spp., loxostege sticticalis, orysago spp., plathycoma ni, spodoptera spp. (e.g. spodoptera exigua, spodoptera littoralis, spodoptera littura), yponomeuta padella; pests from the order of the isoptera (isoptera), for example, coptotermes spp., cornitermes cumulans, cryptotermes spp., incisitermes spp., microtermes obesi, odontotermes spp., reticulitermes spp. (e.g. reticulitermes flavipes, reticulitermes hesperus); pests from the order Lepidoptera, for example, Achroia grisella, Acronicta major, Adoxophyes spp. (for example, Adoxophyes orana), Aedia leucomelas, Agrotis spp. (for example, Agrotis segetum, Agrotis ipsilon), Alabama spp. (for example, Alabama argillacea), Amyelois transitella, Anarsia spp., Anticarsia spp. (for example, Anticarsia gemmatalis), Argyroploce spp., Barathra brassicae, Borbo cinnara, Bucculatrix thurberiella, Bupalus piniarius, Busseola spp., Cacoecia spp., Caloptilia theivora, Capua reticulana, Carpocapsa pomonella, Carposina niponensis, Cheimatobia brumata, Chilo spp. (for example, Chilo plejadellus, Chilo suppressalis), Choristoneura spp., Clysia ambiguella, Cnaphalocerus spp., Cnaphalocrocis medinalis, Cnephasia spp., Conopomorpha spp.; pests from the order Orthoptera or Saltatoria, for example, Acheta domesticus, Dichroplus spp., Gryllotalpa spp. (for example Gryllotalpa gryllotalpa), Hieroglyphus spp., Locusta spp. (for example Locusta migratoria), Melanoplus spp. (for example Melanoplus devastator), Schistocerca gregaria; pests from the order Thysanoptera, for example, Anaphothrips obscurus, Baliothrips biformis, Drepanothris reuteri, Enneothrips flavens, Frankliniella spp. (for example Frankliniella fusca, Frankliniella occidentalis, Frankliniella schultzei, Frankliniella tritici, Frankliniella vaccinii, Frankliniella williamsi), Heliothrips spp., Hercinothrips femoralis, Rhipiphorothrips cruentatus, Scirtothrips spp., Taeniothrips cardamoni, Thrips spp. (for example Thrips palmi, Thrips tabaci); Plant pests from the phylum Nematoda, i.e. plant parasitic nematodes, in particular Aglenchus spp. (e.g. Aglenchus agricola), Anguina spp. (e.g. Anguina tritici), Aphelenchoides spp. (e.g. Aphelenchoides arachidis, Aphelenchoides fragariae), Belonolaimus spp. (e.g. Belonolaimus gracilis, Belonolaimus longicaudatus, Belonolaimus nortoni), Bursaphelenchus spp. (e.g. Bursaphelenchus cocophilus, Bursaphelenchus eremus, Bursaphelenchus xylophilus), Meloidogyne spp. (e.g. Meloidogyne arenaria, Meloidogyne chitwoodi, Meloidogyne hapla, Meloidogyne incognita), Pratylenchus spp. (e.g. Pratylenchus alleni, Pratylenchus curvitatus, Pratylenchus goodeyi, Pratylenchus neglectus, Pratylenchus penetrans, Pratylenchus scriputeri, Pratylenchus vulnus), Radopholus spp. (e.g. Radopholus similis), Tylenchulus spp. (e.g. Tylenchulus semipenetrans), and Xiphinema spp. (e.g. Xiphinema index).) (e.g., Meloidogyne chitwoodi, Meloidogyne fallax, Meloidogyne acronea, Meloidogyne africana, Meloidogyne arenaria, Meloidogyne arenaria thamesi, Meloidogyne artiella, Meloidogyne chitwoodi, Meloidogyne coffeicola, Meloidogyne ethiopica, Meloidogyne exigua, Meloidogyne fallax, Meloidogyne graminicola, Meloidogyne graminis, Meloidogyne hapla, Meloidogyne incognita, Meloidogyne incognita acrita, Meloidogyne javanica, Meloidogyne kikuyensis, Meloidogyne minor, Meloidogyne naasi, Meloidogyne paranaensis, Meloidogyne thamesi, and Meloidogyne spp. that are non-migratory parasites; Tylenchulus spp. (e.g., Tylenchulus semipenetrans), Xiphinema spp. (e.g., Xiphinema index); Arthropods from the order Phthiraptera, such as the genera *Damalinia* spp., *Haematopinus* spp., *Linognathus* spp., *Pediculus* spp., *Phylloxera vastatrix*, *Ptirus pubis*, and *Trichodectes* spp.; Arthropods from the order Siphonapterida, such as *Ceratophyllus* spp., *Ctenocephalides* spp., *Pulex* spp., *Tungas* spp., and *Xenopsyllas* spp.; as well as unpleasant pests and sanitary pests from the order Blattodea.

[0075] 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.

[0076] 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.

[0077] The beneficial effects of this invention are: 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

[0078] 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.

[0079] The compounds of formula (I-1) or formula (I-2) can be synthesized by various methods familiar to those skilled in the art of organic synthesis. Some exemplary methods for synthesizing the compounds of formula (I-1) or formula (I-2) are given in the following specific examples, which are well known in the art of synthetic chemistry. It will be apparent to one skilled in the art, with the benefit of this disclosure, that referring to the exemplary schemes in this patent, one can readily design other synthetic routes to the compounds of formula (I-1) or formula (I-2) by making appropriate adjustments to the reactants, reaction conditions, and protecting groups.

[0080] Example 1: Synthesis of 3-chloro-2-(2-fluoro-4-methyl-5-((2,2,2- trifluoroethyl)thio)phenyl)-5-(trifluoromethyl)pyridine (Compound 2-94) 1.1 Synthesis of 2-(2-fluoro-4-methyl-5-((2,2,2-trifluoroethyl)thio)phenyl)-4,4,5,5- tetramethyl-1,3,2-dioxaborolane

[0081] To the reaction flask was added (5-bromo-4-fluoro-2-methylphenyl)(2,2,2- trifluoroethyl)sulfane 2.0 g (6.80 mmol) dissolved in 20 mL of 1,4-dioxane, followed by the addition of pinacol diboronic acid 2.52 g (10.40 mmol), potassium acetate 1.94 g (20.40 mmol), DPPF palladium dichloride 0.29 g (0.04 mmol), and the reaction system was warmed to 110 °C and refluxed for 3 h, and monitored by TLC. After the starting material was completely consumed, the reaction was stopped, the reaction system was poured into saturated brine, extracted with dichloromethane, the organic phases were combined, dried, filtered, and the solvent was removed by rotary evaporation to give intermediate 1.08 g in a yield of 50.60%, which was used without purification for the next step.

[0082] 1.2 Synthesis of 3-chloro-2-(2-fluoro-4-methyl-5-((2,2,2-trifluoroethyl)thio)phenyl)-5- (trifluoromethyl)pyridine (Compound 2-94)

[0083] To the reaction flask was added 2-(2-fluoro-4-methyl-5-((2,2,2- trifluoroethyl)thio)phenyl)-4,4,5,5-tetramethyl-l,3,2-dioxaborolane 0.1 g (0.30 mmol) dissolved in 1.2 mL of 1,4-dioxane: water = 5: 1 mixed solvent, then 5-bromo-2- chloropyridine 0.058 g (0.36 mmol), cesium carbonate 0.28 g (0.9 mmol), DPPF palladium dichloride 0.011 g (0.017 mmol), 1,1'-bis(diphenylphosphino) ferrocene 0.016 g (0.029 mmol) were added to the reaction system, and then the reaction system was heated to 101 °C, refluxed for 3 h, and TLC was used for monitoring. After the raw material completely disappeared, the reaction was stopped, poured into saturated brine, extracted with dichloromethane, the organic phases were combined, dried, and column chromatography was used for separation to obtain the target compound 2-11, a total of 0.026 g, with a yield of 26.04%.

[0084] Example 2: Synthesis of 2-chloro-5-(2-fluoro-4-methyl-5-((2,2,2- trifluoroethyl)thio)phenyl)pyridine (compound 2-11)

[0085] To the reaction flask was added 2-(2-fluoro-4-methyl-5-((2,2,2- trifluoroethyl)thio)phenyl)-4,4,5,5-tetramethyl-l,3,2-dioxaborolane 0.1 g (0.30 mmol) dissolved in 1.2 mL of 1,4-dioxane: water = 5: 1 mixed solvent, then 5-bromo-2- chloropyridine 0.058 g (0.36 mmol), cesium carbonate 0.28 g (0.9 mmol), DPPF palladium dichloride 0.011 g (0.017 mmol), 1,1'-bis(diphenylphosphino) ferrocene 0.016 g (0.029 mmol) were added to the reaction system, and then the reaction system was heated to 101 °C, refluxed for 3 h, and TLC was used for monitoring. After the raw material completely disappeared, the reaction was stopped, poured into saturated brine, extracted with dichloromethane, the organic phases were combined, dried, and column chromatography was used for separation to obtain the target compound 2-11, a total of 0.026 g, with a yield of 26.04%.

[0086] Example 3: Synthesis of 2-chloro-5-(2-fluoro-4-methyl-5-((2,2,2- trifluoroethyl)thio)phenyl)pyridine (compound 2-11)

[0087] Into a reaction flask was placed 6-chloropyridine-3-boronic acid 1.0 g (6.35 mmol) dissolved in 16.5 mL of a 1,4-dioxane:water = 10:1 mixture, followed by the addition of (4-fluoro-5-iodo-2-methylphenyl)(2,2,2-trifluoroethyl)sulfane 2.22 g (6.35 mmol), cesium carbonate 6.21 g (19.06 mmol), DPPF dichloride 0.046 g (63.55 μmol) to the reaction system, and the reaction was heated to reflux under a nitrogen atmosphere. After 5 h, the reaction was stopped, the reaction system was poured into saturated brine, extracted with dichloromethane, the organic phases were combined, dried, and column chromatography was used to isolate the target compound 2-11, which was obtained in a total of 1.86 g at a yield of 87.18%.

[0088] Example 4: Synthesis of 5-{2-fluoro-4-methyl-5-[(2,2,2-trifluoroethyl)thio]phenyl}-2- nitropyridine (compound 2-21)

[0089] Into a reaction flask was placed 6-chloropyridine-3-boronic acid 1.0 g (6.35 mmol) dissolved in 16.5 mL of a 1,4-dioxane:water = 10:1 mixture, followed by the addition of (4-fluoro-5-iodo-2-methylphenyl)(2,2,2-trifluoroethyl)sulfane 2.22 g (6.35 mmol), cesium carbonate 6.21 g (19.06 mmol), DPPF dichloride 0.046 g (63.55 μmol) to the reaction system, and the reaction was heated to reflux under a nitrogen atmosphere. After 5 h, the reaction was stopped, the reaction system was poured into saturated brine, extracted with dichloromethane, the organic phases were combined, dried, and column chromatography was used to isolate the target compound 2-11, which was obtained in a total of 1.86 g at a yield of 87.18%.

[0090] Example 5: 5-{2-fluoro-4-methyl-5-[(2,2,2-trifluoroethyl)thio]phenyl}pyridine-2- carbonitrile (compound 2-29)

[0091] Into a reaction flask was added 2-(2-fluoro-4-methyl-5-((2,2,2- trifluoroethyl)thio)phenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane 0.2 g (0.57 mmol) dissolved in 1.2 mL of a 1,4-dioxane:water = 5:1 mixture, followed by 5-bromo-2- cyanopyridine 0.11 g (0.63 mmol), cesium carbonate 1.25 g (1.71 mmol), DPPF palladium dichloride 0.016 g (0.029 mmol), 1,1'-bis(diphenylphosphino) ferrocene 0.032 g (0.057 mmol), and the reaction system was then warmed to 101 °C and refluxed for 3 h, with TLC monitoring. After the raw material completely disappeared, the reaction was stopped, poured into saturated brine, extracted with dichloromethane, the organic phases were combined, dried, and column chromatography was used to isolate the target compound 2-29, which was obtained in a total of 0.12 g, with a yield of 64.39%.

[0092] Other compounds of the application used in the following test examples were also synthesized according to similar procedures as described above in Examples 1-5.

[0093] Test Example: Biological activity test Test Example 1: Biological activity test against Tetranychus cinnabarinus adult Experimental method: The test was performed according to the agricultural industry standard NYT 1154.6-2006, using the immersion method. Vicia faba seedlings with consistent growth vigor were selected, and thick and tender leaves were grown, which were cut into two leaves and one stem shape, and one leaf was cut from the middle, which was inserted into a 5 mL sample bottle filled with water, and 30 adult mites were selected for each leaf. Each test agent was accurately weighed, dissolved in a small amount of DMSO, and prepared into a 10000 mg / L stock solution. The stock solution was diluted 100 times with 0.1% Tween 80 aqueous solution to obtain a test solution with a concentration of 100 mg / L. After the test insects were stable on the leaves, they were immersed in the prepared solution for 5-10 s, the excess solution was absorbed with filter paper and naturally dried, each treatment was repeated 3 times, and a blank control was set, and the immersion solution used for the control group was the same proportion of DMSO and Tween aqueous solution. Then the experimental target was placed in an artificial climate chamber (24-26 °C, L:D = 16:8, RH 60%) for culture, and the mortality of adult mites was checked and recorded after 72 h. The mites were considered dead if they did not move or react when touched with tweezers.

[0094] Calculation method: Corrected mortality (%) = [(treatment mortality - control mortality) / (1 - control mortality)] x 100% Among the exemplary compounds of the present application, the following compounds have better control effect on T. c. adults at a concentration of 100 mg / L, and the mortality rate reaches 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.

[0095] Among the part of the exemplary compounds of the present application, the following compounds have better control effect on T. c. adults at a concentration of 10 mg / L, and the mortality rate is more than 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, 2-250, 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.

[0096] Through further biological activity research, we found that the compounds of the present application still exhibit excellent killing activity to the pest mites at very low doses (for example, 1.0 ppm, 0.39 ppm, 0.195 ppm, or even 0.097 ppm). According to the above method, part of the exemplary compounds in the present patent and compound 3 (denoted as CK4 herein) in WO2024007862A1, compound II-43 (denoted as CK1 herein), II-61 (denoted as CK2 herein), II-51 (denoted as CK5 herein), and II-69 (denoted as CK6 herein) in WO1999055668A1 were selected as positive controls to conduct biological activity determination of T. c. adults, and the results are shown in Table 4.

[0097]

[0098] Table 4 Acaricidal activity of part of the exemplary compounds on T. c. adults

[0099] The inventors first non-obviously designed and synthesized high-activity acaricidal compounds containing cyano pyridine, nitro pyridine, difluoro pyridine and the like with trifluoroethyl sulfide phenyl through strategies such as sub-active structure splicing, electronic isostere, structure-activity relationship analysis and precise design. It can be concluded from the acaricidal activity determination results in Table 3 that the compounds 2-21, 2-29 and 2-43 and the like of the present application exhibit excellent acaricidal activity against mites, and the mortality of Tetranychus cinnabarinus adults is greater than 90% at a concentration of 1.0 ppm, 0.39 ppm or even as low as 0.195 ppm. The mortality of Tetranychus cinnabarinus adults of the prior art compounds CK1-CK6 is less than 50% at a low concentration of 1 ppm, and the activity difference is nearly 5 times or more. The substantial improvement in acaricidal activity is unpredictable.

[0100] Test Example 2: Biological activity test on Tetranychus urticae Koch (Tetranychus urticae) adults Tetranychus urticae ) adults The test refers to the agricultural industry standard NY / T 1154.13-2008, and the leaf disc spray method is used for determination. Clean and flat kidney bean leaves with appropriate size and uniform leaf age are selected, laid flat in a culture dish with clean filter paper, the reverse side is upward, the filter paper is moisturized by adding water, and then 30-40 female adult Tetranychus urticae mites in a physiological state are introduced into each leaf disc with a brush. The compound (20 mg) is dissolved in 2 mL of DMSO solvent to form a primary stock solution with a concentration of 10,000 mg / L. The primary stock solution is diluted 100 times with 0.1% Tween-80 aqueous solution to obtain a secondary stock solution with a concentration of 100 mg / L, and the secondary stock solution is diluted 10 times to obtain a test solution with a concentration of 10 mg / L. The test solution with a concentration of 10 mg / L is further diluted 4 times to obtain test solutions with concentrations of 2.5 mg / L and 0.625 mg / L. The leaf discs with female adult Tetranychus urticae mites are quantitatively sprayed with 2 ml of the test solution using a throat sprayer. Each treatment is repeated 3 times, and a blank control group is set. The spraying solution used in the blank control group is the same proportion of DMSO and Tween water solution. The sprayed culture dish leaves are thoroughly dried and sealed with sealing film. The culture dishes are placed in an artificial climate chamber (24-26℃, L:D=16:8, RH 60%) for incubation, and the mortality of female adult mites is checked and recorded after 72 h. Calculation method: Mortality (%) = [(pre-treatment insect population base - post-treatment live insect number) / pre-treatment insect population base] x 100% Corrected mortality (%) = [(treatment group mortality - blank control group mortality) / (1 - blank control group mortality)] x 100% Among the exemplary compounds of the present application, the following compounds have better control effect on T. urticae adult at a concentration of 100 mg / L, with 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, 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, 2-294, 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.

[0101] Among the exemplary compounds of the present application, the following compounds have better control effect on T. urticae adult at a concentration of 10 mg / L, with a mortality rate of more than 90%: 1-2, 1-4, 1-58, 1-59, 1-82, 1-89, 1-93, 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.

[0102] Table 4, Acaricidal activity of adult two-spotted spider mites (after 72h)

[0103] From the results of the acaricidal activity determination in Table 3 and Table 4, it can be seen that the compounds of the present application (for example, compounds 2-21 and 2-29) not only have excellent acaricidal activity against T. cinnabarinus, but also have excellent acaricidal activity against T. urticae. At a low concentration of 0.625 ppm, the mortality rate of T. urticae is greater than 90%, which is significantly better than 16.15% of the prior art CK2, and is also better than sulfiflumin and the commercial acaricide ethoxyquin.

[0104] Test Example 3: Biological activity test against female adult mites of Panonychus citri Panonychus citri The test was performed according to the agricultural industry standard NYT 1154.6-2006 using the immersion method. Clean and flat citrus leaves of appropriate size and uniform leaf age were placed in a culture dish with clean filter paper, with the reverse side facing up. The filter paper was moistened with water, and then 30-40 female adult mites of Panonychus citri in a physiological state were introduced onto each leaf using a brush. The compound (20 mg) was dissolved in 2 mL of DMSO solvent to form a primary stock solution with a concentration of 10,000 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 to obtain a test solution with a concentration of 10 mg / L. After the test insects were stable on the leaves, they were immersed in the prepared solution for 5-10 seconds, the excess solution was absorbed with filter paper, and then naturally dried. Each treatment was repeated 3 times, and a blank control group was set up. The immersion solution used in the blank control group was the same proportion of DMSO and Tween aqueous solution. Then the experimental target was placed in an artificial climate chamber (24-26 ℃, L:D=16:8, RH 60%) for cultivation. After 72 hours, the mortality of female adult mites was checked and recorded.

[0105] Mortality rate (%) = [(pre-treatment insect population base - post-treatment live insect number) / pre-treatment insect population base] x 100% Corrected mortality rate (%) = [(treatment group mortality rate - blank control group mortality rate) / (1 - blank control group mortality rate)] x 100% Among the exemplary compounds of the present application determined, the following compounds had better control effect on adult Panonychus citri at a concentration of 10 mg / L, with a mortality rate of more than 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. ​

[0106] Agricultural mites are one of the most recognized biological groups that are difficult to control in the world, and the control of resistant mites is a worldwide problem. In the control of mites, there are challenges and difficulties such as high resistance, poor control effect, and large dosage. Developing new high-efficiency miticides has become a top priority in this field. Derivatives containing trifluoroethyl sulfide phenyl are a hot spot in the development of existing miticides, and have the characteristics of novel structure, unique mechanism, no cross-resistance with existing miticides, and excellent activity.

[0107] In order to obtain trifluoroethyl sulfide phenyl derivatives with higher activity, the inventors found that pyridine derivatives containing trifluoroethyl sulfide phenyl have good miticidal activity against agricultural mites through non-obvious sub-activity structure splicing. On this basis, the inventors designed and synthesized a series of compounds of general formula 1 through electronic isosteric design, and subsequently conducted in-depth research and analysis on the miticidal activity and structure-activity relationship of the compounds of general formula 1. The inventors found that when the substituents on the pyridine are electron-donating substituents, the miticidal activity is poor, and when the substituents are electron-withdrawing substituents, the miticidal activity is good. Under the guidance of this structure-activity relationship, the inventors non-obviously designed and synthesized nitro pyridine and cyano pyridine derivatives containing trifluoroethyl sulfide phenyl. Through biological activity determination, the inventors surprisingly found that they still exhibit excellent miticidal activity against mites at very low concentrations, and have excellent miticidal activity against Tetranychus cinnabarinus, Tetranychus urticae, and Panonychus citri and other mites, with high efficiency and broad spectrum. Compared with the compounds disclosed in the prior art, the miticidal activity of the compounds of the present application is unexpectedly increased by more than 5 times. In the process of creating new miticides, the flexible application of various strategies such as sub-activity structure splicing, electronic isosteric, and structure-activity relationship analysis ultimately leads to these unexpected high-activity compounds.

[0108] In summary, the compounds of the present application have the characteristics of novel structure, unique mechanism, broad-spectrum high efficiency, and the like. At low concentrations, they exhibit excellent control effect against various harmful organisms, especially against leaf mites represented by Tetranychus cinnabarinus, Tetranychus urticae, and Panonychus citri. Specifically, at very low concentrations such as 0.195 mg / L and 0.625 mg / L, they exhibit excellent miticidal activity against Tetranychus cinnabarinus, Tetranychus urticae, and Panonychus citri and other mites, with a mortality rate of more than 90%. Whether compared with the prior art or compared with existing mainstream commercial pesticides, the miticidal activity is greatly improved, which can effectively solve the serious problems of high resistance, poor control effect, and large dosage in the process of controlling agricultural mites, and make contributions to the sustainable development of miticides and the safety protection of fruits and vegetables.

[0109] The above merely describes preferred embodiments of the present application and is not intended to limit the present application. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present application shall be included in the scope of protection of the present application.

Claims

1. 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, having the structure of a compound of formula (I-1) or (I-2): (I-1) in, R1 is selected from C1-C6 alkyl groups, C1 C6 haloalkyl, C2 C6 alkenyl, C2 C6 ynyl group, C1 C6 alkoxy, C1 C6 haloalkoxy, cyanoC1 C6 alkyl, C3 C6 cycloalkyl C1 C3 alkyl or C3 C6 epoxy alkyl C1 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 glycidyloxymethyl; 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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