Preparation and application of novel trifluoroalkyl thiophenyl-containing nitrogen heterocyclic ring derivative

Abstract

The invention relates to preparation and application of a novel trifluoroalkyl thiophenyl-containing nitrogen heterocyclic ring derivative. Specifically, the invention relates to a compound as shown in formula (I), 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 discloses application of the compound in preparation of an acaricide for preventing and treating plant mites. The compound can achieve a better pest control effect at a lower dosage.

Description

Technical Field

[0001] This invention relates to the field of pesticide technology, and more specifically, to the preparation and application of novel nitrogen-containing heterocyclic derivatives containing trifluoroethanethiol phenyl. Background Technology

[0002] 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. These mites can harm more than 1,100 host plants, causing serious damage to various crops such as fruits, vegetables, and flowers, resulting in losses of more than 10 billion yuan in my country every year.

[0003] Currently, chemical control remains the most effective measure for controlling plant mites, with approximately one billion US dollars invested globally annually in chemical acaricides. However, the development and market launch of new acaricides has been slow. Since etoxazole was registered in my country in 2018, no commercially available chemical acaricides with novel mechanisms of action have been introduced to the domestic market in recent years. Due to the long-term overuse of traditional acaricides and the lack of products with novel mechanisms of action, field mites have developed high levels of resistance to most existing acaricides, leading to decreased efficacy and even the inability to effectively control mite populations.

[0004] Trifluoroethyl sulfide (sulfoxide) compounds, a novel class of acaricides currently under development, possess novel structures, unique mechanisms of action, high activity, and long-lasting effects. Several compounds with this skeleton have already obtained ISO generic names and are in the industrialization development stage, promising to become a new generation of mite control tools.

[0005]

[0006] Patent WO1999055668A discloses a class of trifluoroethyl thioether pyrimidine derivatives, but these compounds have significant drawbacks in practical applications: although they exhibit certain acaricidal activity at high concentrations, their control effect is poor at lower application rates and they are costly. Therefore, there is still an urgent need in agricultural production for novel acaricidal compounds with novel mechanisms of action, high efficiency, and low toxicity. Summary of the Invention

[0007] This invention relates to a class of novel trifluoroalkylthiophenyl nitrogen-containing heterocyclic derivatives. Based on an isosteric substitution strategy, and building upon previously discovered highly active trifluoroalkylthiophenyl pyridine derivative structures, a nitrogen atom is further introduced into the pyridine ring, thus non-obviously obtaining the aforementioned compound class. Compared with existing compounds, the compounds provided by this invention exhibit excellent acaricidal activity against agricultural mites at lower concentrations, achieving superior control effects with lower application doses. This helps address the industry challenges of high resistance and poor efficacy commonly found in current acaricides.

[0008] Furthermore, the raw materials for synthesizing the compounds of this invention are readily available and inexpensive, possessing good potential for industrial production. The implementation of this invention not only provides a new technological foundation for the sustainable development of acaricides, but also holds promise for future applications in the control of mites on fruits, vegetables, and other crops, ensuring the quality and safety of agricultural products.

[0009] In a first aspect, the present invention provides a novel compound of formula (I) containing a nitrogen-containing heterocyclic trifluoroalkylthiophenyl derivative, or an isotopically labeled compound thereof, or an optical isomer, geometric isomer, tautomer, or mixture of isomers thereof, or a pesticide-acceptable salt thereof.

[0010]

[0011] in,

[0012] R1 is selected from propyl, C1-C3 haloalkyl, cyanoC1-C3alkyl, C3-C6 cycloalkylC1-C3alkyl;

[0013] R2 and R4 are independently selected from halogen, cyano, C1-C3 alkyl, C1-C3 haloalkyl, and C3-C6 cycloalkyl;

[0014] R3 and R5 are selected from hydrogen;

[0015] Q is selected from It can be mono- or poly-substituted by one or more of the same or different substituents R6, wherein the substituents R6 are selected from halogens, C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkylamino, C1-C3 alkylthio, C1-C3 alkylsulfonyl, hydroxyl, nitro, amino, cyano, aldehyde, carboxyl, amide, and ester.

[0016] n is selected from 0, 1, or 2.

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

[0018] R1 is selected from propyl, tert-butyl, isobutyl, dichloroethyl, trichloroethyl, trichloropropyl, fluoromethyl, difluoromethyl, trifluoromethyl, difluoroethyl (CF2CH3, CH2CHF2, CHFCFH2), trifluoroethyl (CH2CF3, CHFCHF2, CF2CFH2), tetrafluoroethyl (CHFCF3, CF2CHF2), pentafluoroethyl, trifluoropropyl, heptafluoropropyl, 1-cyanomethyl, cyclopropylmethyl, and glycidyloxymethyl.

[0019] R2 and R4 are independently selected from hydrogen, fluorine, chlorine, bromine, iodine, methyl, ethyl, propyl, fluoromethyl, difluoromethyl, trifluoromethyl, trifluoroethyl (CH2CF3, CHFCHF2, CF2CFH2), pentafluoroethyl, trifluoropropyl, heptafluoropropyl, cyano, and cyclopropyl.

[0020] R3 and R5 are selected from hydrogen;

[0021] Q is selected from It can be mono- or poly-substituted by one or more of the same or different substituents R6, wherein the substituents R6 are selected from halogens, C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkylamino, C1-C3 alkylthio, C1-C3 alkylsulfonyl, hydroxyl, nitro, amino, cyano, aldehyde, carboxyl, amide, and ester.

[0022] n is selected from 0, 1, or 2.

[0023] In one embodiment of the present invention, wherein,

[0024] R1 is selected from CF3, CH2CHF2, CH2CF3, CH2CH2CF3, 1-cyanomethyl, cyclopropylmethyl, CH2CHCl2, CH2CCl3, CH2CH2CCl3, and glycidylmethyl.

[0025] R2 and R4 are independently selected from hydrogen, fluorine, chlorine, bromine, methyl, trifluoromethyl, heptafluoropropyl, and cyclopropyl.

[0026] R3 and R5 are selected from hydrogen;

[0027] Q is selected from It can be mono- or poly-substituted by one or more of the same or different substituents, wherein the substituents are selected from fluorine, chlorine, bromine, iodine, methyl, ethyl, propyl, tert-butyl, isopropyl, difluoromethyl, trifluoromethyl, trifluoroethyl, hydroxyl, nitro, amino, cyano, aldehyde, carboxyl, amide, ester, methylamino, dimethylamino, methylthio, methyl sulfoxide, and methyl sulfone.

[0028] n is selected from 0, 1, or 2.

[0029] In another embodiment of the invention, wherein,

[0030] R1 is selected from CF3, CH2CHF2, CH2CF3, CH2CH2CF3, 1-cyanomethyl, and cyclopropylmethyl;

[0031] R2 is selected from fluorine, chlorine, bromine, and methyl; R3 is selected from hydrogen.

[0032] R4 is selected from fluorine, chlorine, bromine, and methyl; R5 is selected from hydrogen.

[0033] Q is selected from It can be mono- or poly-substituted by one or more of the same or different substituents, wherein the substituents are selected from fluorine, chlorine, bromine, trifluoromethyl, nitro, cyano, methylthio, methyl sulfoxide, methyl sulfone, and dimethylamino.

[0034] n is selected from 0.

[0035] In another embodiment of the invention, wherein,

[0036] (I-4)

[0037] R1 is selected from C1-C3 haloalkyl groups, preferably CH2CHF2, CH2CF3, or CH2CH2CF3;

[0038] R2 is selected from C1-C3 alkyl groups and halogens, preferably methyl, fluorine, or chlorine;

[0039] R4 is selected from halogens, preferably fluorine or chlorine;

[0040] X1 and X2 are selected from hydrogen, methyl, fluorine, and chlorine;

[0041] X3 is selected from halogens, C1-C3 haloalkyl groups, C1-C3 alkylthio groups, C1-C3 alkylsulfoxide groups, C1-C3 alkylsulfonyl groups, nitro groups, and cyano groups; preferably fluorine, chlorine, bromine, trifluoromethyl, nitro, cyano, and methylthio groups;

[0042] n is selected from 0.

[0043] In another embodiment of the invention, wherein,

[0044] (I-7)

[0045] R1 is selected from C1-C3 haloalkyl groups, preferably CH2CHF2, CH2CF3, or CH2CH2CF3;

[0046] R2 is selected from C1-C3 alkyl groups and halogens, preferably methyl, fluorine, or chlorine;

[0047] R4 is selected from halogens, preferably fluorine or chlorine;

[0048] X1 and X3 are selected from hydrogen, fluorine, chlorine, and methyl;

[0049] X2 is selected from halogens, C1-C3 haloalkyls, C1-C3 alkylthios, C1-C3 alkylsulfonyls, C1-C3 alkylaminos, nitros, and cyano; preferably fluorine, chlorine, bromine, trifluoromethyl, nitro, cyano, methylthios, methyl sulfoxide, methyl sulfone, and dimethylamino.

[0050] n is selected from 0.

[0051] In another embodiment of the invention, wherein,

[0052] (I-8)

[0053] R1 is selected from C1-C3 haloalkyl groups, preferably CH2CHF2, CH2CF3, or CH2CH2CF3;

[0054] R2 is selected from C1-C3 alkyl groups and halogens, preferably methyl, fluorine, or chlorine;

[0055] R4 is selected from halogens, preferably fluorine or chlorine;

[0056] X1 and X3 are selected from hydrogen, methyl, fluorine, and chlorine;

[0057] X2 is selected from halogens, C1-C3 haloalkyl groups, C1-C3 alkylthio groups, C1-C3 alkylsulfonyl groups, nitro groups, and cyano groups; preferably fluorine, chlorine, bromine, trifluoromethyl, nitro, cyano, methylthio, methyl sulfoxide, and methyl sulfone groups;

[0058] n is selected from 0.

[0059] In another embodiment of the invention, the following compounds may be selected.

[0060] ,

[0061] and the following compounds,

[0062]

[0063] and the following compounds,

[0064] .

[0065] For the sake of brevity, the following terms “novel trifluoroalkylthiophenyl nitrogen-containing heterocyclic derivatives”, “compound of formula (I)” or “compound of the present invention” may also cover any isotopically labeled compound of formula (I), or an optical isomer, geometric isomer, tautomer or mixture of isomers thereof, or a pesticide-acceptable salt thereof.

[0066] 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.

[0067] The term "geometric isomer" refers to the fact that when a compound contains a double bond, it can exist as cis isomers, trans isomers, E-isomers, and Z-isomers. Geometric isomers include cis isomers, trans isomers, E-isomers, Z-isomers, or mixtures thereof.

[0068] 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.

[0069] 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).

[0070] Unless otherwise specified, references herein to “novel trifluoroethanethiphenyl nitrogen-containing heterocyclic derivatives,” “compound of formula (I),” or “compound of the present invention” also encompass isotopically labeled compounds obtained by replacing any atom of that compound with its isotopic atom. The present invention includes all pharmaceutically acceptable isotopically labeled compounds of formula (I), 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.

[0071] 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 and 14 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 18O, and isotopes of sulfur, such as 35 S.

[0072] The isotope-labeled compounds of formula (I) can generally be prepared by conventional techniques known to those skilled in the art or by using a suitable isotope-labeled reagent instead of the previously used unlabeled reagent, in a manner similar to that described in the examples and preparations appended herein.

[0073] Compounds of formula (I) may exist in the form of pesticide-acceptable salts, such as acid addition salts and / or base addition salts of compounds of formula (I). 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).

[0074] Pesticide-acceptable salts of compounds of formula (I) 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.

[0075] 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.

[0076] 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.

[0077] 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.

[0078] 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.

[0079] 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.

[0080] 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.

[0081] 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.

[0082] As used herein, the term "n-membered heterocyclic alkyl" refers to a heterocyclic alkyl group having m carbon atoms forming a ring and (nm) heteroatoms forming a ring, wherein the heteroatoms are selected from O, S, and N. For example, 4-6-membered heterocyclic alkyl groups include, but are not limited to, oxobutane, thiobutane, azabutane, tetrahydrofuran, tetrahydrothiophene, pyrrolidine, tetrahydropyran, tetrahydrothioran, piperidine, morpholine, and piperazine. Furthermore, the heterocyclic alkyl group may optionally be substituted with one or more suitable substituents.

[0083] 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.

[0084] 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.

[0085] The following synthetic scheme describes the steps for preparing the compounds disclosed in this invention. R1, R2, R3, R4, R5, and n have the meanings described in this invention.

[0086]

[0087] Intermediate 1 reacts with different electrophilic reagents under alkaline conditions to yield intermediate 2. Intermediate 2 reacts with sodium nitrite to first generate diazonium benzene, which then undergoes free radical decomposition under the catalysis of cuprous halide to yield the corresponding halobenzene 3. Intermediate 3 is then catalyzed to generate intermediate 4. Intermediate 4 undergoes a Suzuki coupling reaction with a halogenated derivative of Q (a diazonium six-membered heterocycle) 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 a borate ester of Q (a diazonium six-membered heterocycle) to yield the thioether product of formula I.

[0088] In addition, the aforementioned intermediate compounds and their starting 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 55.5 (2010): The method reported in 2048-2054 was used to obtain it.

[0089] This invention lists several exemplary compounds that have been synthesized, with specific group selections shown in the table below, and compound data shown in Table 1. It should be understood that the scope of this invention is not limited to the exemplary compounds listed in the table below, and the group selections of the compounds in Table 1 can be arbitrarily combined without particular limitation. Some compounds of general formula I of this invention are shown below, but this invention is by no means limited to these compounds.

[0090] (I-4)

[0091] Table 1

[0092]

[0093]

[0094] (I-7)

[0095] Table 2

[0096]

[0097]

[0098]

[0099] (I-8)

[0100] Table 3

[0101]

[0102]

[0103] Table 4 Characterization data of some exemplary compounds

[0104] In a second aspect, the present invention provides an insecticide composition comprising a compound of formula (I) 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.

[0105] 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.

[0106] 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.

[0107] The compounds of formula (I) 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, for example, 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, prolong the shelf life of harvested products, and / or improve the processing properties of harvested products.

[0108] 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.

[0109] 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.

[0110] 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.

[0111] In a third aspect, the present invention provides the use of a compound of formula (I) 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.

[0112] 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.

[0113] This invention also relates to a method for controlling pests or mites, comprising applying an effective amount of the compound of formula (I) 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.

[0114] 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.

[0115] In the field of animal health, i.e., veterinary medicine, the compounds of formula (I) 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.

[0116] In the field of veterinary medicine, compounds of formula (I) 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.

[0117] 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.

[0118] 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.

[0119] In the context of animal health, the term "control" or "controlling" as used herein refers to compounds of formula (I) 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) that kill the parasites, inhibit their growth, or suppress their reproduction.

[0120] 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.

[0121] 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.

[0122] 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:

[0123] 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.), the genus *Acarus* (e.g., *Acarus siro*, *Aceria kuko*, *Aceriasheldoni*), the genus *Aculops* spp., and the genus *Aculus* spp. (e.g., *Aculus* freundii). fockeui, apple gall mite (Aculus schlechtendali), flower tick (Amblyomma spp.), sharp-edged tick (Argas spp.), cattle tick (Boophilus spp.), short-haired mite (Brevipalpus spp.) (e.g., purple short-haired mite (Brevipalpus phoenicis)), bryobia graminum (Bryobia graminum), alfalfa bryobia (Bryobia praetiosa)), centruroides spp., foot mite (Chorioptes spp.), dust mite (e.g., house dust mite (Dermatophagoides pteronyssinus), farinae dust mite (Dermatophagoides farinae)), leather tick (Dermacentor spp.), chicken spiny mite (Dermanyssus gallinae);

[0124] 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));

[0125] 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., *Anopheless* 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);

[0126] 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.;

[0127] 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 *Amrascaspp.* (e.g., small green leafhopper *Amrasca bigutulla*, small leafhopper *Amrasca*). The genera *Aeonidiella* include *Aeonidiella devastans*, *Aeonidiella cardui*, *Aeonidiella spp.* (e.g., *Aeonidiella aurantii*, *Aeonidiella citrina*, *Aeonidiella inornata*), *Aphanostigma piri*, and *Aphis spp.* (e.g., *Aphis craccivora*, *Aphis fabae*, *Aphis forbesi*, *Aphis glycines*, *Aphis gossypii*, *Aphis hederae*, *Aphis illinoisensis*, *Aphismiddletoni*, *Aphis nasturtii*, and *Aphis nerii*).

[0128] 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.;

[0129] Pests from the order Isoptera, such as *Coptotermes* spp., *Cornitermes cumulans*, *Cryptotermes* spp., *Incisitermes* spp., *Microtermes obesi*, *Odontotermes* spp., and *Reticulitermes* spp. (e.g., *Reticulitermes flavipes*, *Reticulitermes hesperus*));

[0130] 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 striped wheat moth (Anarsia spp.), the dry-killing cutworm (Anticarsia spp.) (e.g., the soybean cutworm (Anticarsia gemmatalis)), the small striped leafroller (Argyroploce spp.), and the cabbage cutworm (Barathra kirilowii). brassicae, Borbo cinnara, Bucculatrix thurberiella, Bupalus piniarius, Busseola spp., Cacoecia spp., Caloptilia theivora, Capuareticulana, Carpocapsa pomonella, Carposinaniponensis, Cheimatobia brumata, Chilo spp. (e.g., Chiloplejadellus, Chilo suppressalis), Choristoneura spp., Clysia ambiguella, Cnaphalocerus spp., Cnaphalocrocismedinalis, Cnephasia spp.), and the genus *Conopomorpha* spp.;

[0131] 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);

[0132] Pests from the order Thysanoptera, such as the corn thrips (Anaphothrips obscurus), rice thrips (Baliothrips biformis), grape thrips (Drepanothrisreuteri), Enneothrips flavens, thrips genus (Frankliniella spp.) (e.g., smoky brown thrips (Frankliniella fusca), western flower thrips (Frankliniella occidentalis), jasmine thrips (Frankliniella schultzei), wheat thrips (Frankliniella tritici), blueberry thrips (Frankliniella vaccinii), William's 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);

[0133] Plant pests from the phylum Nematoda, i.e., plant-parasitic nematodes, especially those from the genera *Aglenchus* (e.g., *Aglenchus agricola*), *Anguinas* (e.g., wheat nematode *Anguina tritici*), *Aphelenchoides* (e.g., peanut nematode *Aphelenchoides arachidis*, strawberry nematode *Aphelenchoides fragariae*), *Belonolaimus* (e.g., small nematode *Belonolaimus gracilis*, long-tailed nematode *Belonolaimus longicaudatus*, Norton nematode *Belonolaimus nortoni*), and *Bursaphelenchus* (e.g., coconut red ring nematode *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.)

[0134] Arthropods from the order Phthiraptera, such as the genera *Damalinia* spp., *Haematopinus* spp., *Linognathus* spp., *Pediculus* spp., *Phylloxera vastatrix*, *Ptirus pubis*, and *Trichodectes* spp.;

[0135] 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.

[0136] Depending on the circumstances, at certain concentrations or application rates, compounds of formula (I) 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.

[0137] 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.

[0138] The beneficial effects of this invention are:

[0139] Based on long-term research and development, this invention employs an isosteric design strategy to further introduce nitrogen heteroatoms into the pyridine ring, thereby non-obviously obtaining a series of dinitrogen six-membered heterocyclic derivatives (pyrimidine, pyridazine, pyrazine) containing trifluoroalkylthiophenyl groups. Bioactivity assays show that, compared with structurally similar compounds in the prior art, the compounds of this invention exhibit excellent acaricidal activity at significantly lower concentrations, with an activity increase of tens of times or more.

[0140] The compounds of this invention can be used to control agricultural or forestry mites, particularly effective against two-spotted spider mites, carmine spider mites, apple spider mites, citrus spider mites, citrus rust mites, and hawthorn spider mites. These compounds possess novel structures, unique mechanisms of action, and high efficiency. Even at low concentrations, the compounds of this invention exhibit excellent control effects, effectively addressing the common problems of high resistance and poor efficacy in current acaricides. The implementation of this invention provides a new technological foundation for the sustainable development of acaricides and is expected to provide guarantees for the green control of agricultural mites and the safe production of agricultural products in practical applications. Detailed Implementation

[0141] 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.

[0142] The compounds of formula (I) 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 some exemplary methods for synthesizing compounds of formula (I), methods 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) by appropriately adjusting the reactants, reaction conditions, and protecting groups.

[0143] Example 1 Synthesis of 2-chloro-5-(2-fluoro-4-methyl-5-(2,2,2-trifluoroethyl)thio)phenyl)pyrimidine (compound 7-7)

[0144] 1.1 Synthesis of (5-bromo-4-fluoro-2-methylphenyl)(2,2,2-trifluoroethyl) sulfide

[0145]

[0146] Add 15 mL of 48% HBr to 2-fluoro-4-methyl-5-((2,2,2-trifluoroethyl)thio)aniline (5 g, 20.9 mmol), cool to 0 °C, and after 5 min, add 30 mL of NaNO2 (1.6 g, 23.0 mmol) aqueous solution dropwise to the reaction solution. Maintain the temperature at 0–5 °C and stir for 30 min. Then, slowly add a mixed solution of CuBr (4.2 g, 29.3 mmol) and 48% HBr (12.5 mL). After the addition is complete, reflux the reaction at 100 °C for 5 h and monitor the reaction by TLC. After the starting material 2-fluoro-4-methyl-5-((2,2,2-trifluoroethyl)thio)aniline disappeared, saturated brine was added to the reaction solution, and the mixture was extracted with DCM (30 ml * 3). The organic phase was collected, dried over anhydrous sodium sulfate, and the solvent was removed by rotary evaporation. The solution was purified by column chromatography with petroleum ether to obtain (5-bromo-4-fluoro-2-methylphenyl)(2,2,2-trifluoroethyl) thioether in 70.3% yield.

[0147] 1.2 Synthesis of 2-(2-fluoro-4-methyl-5-((2,2,2-trifluoroethyl)thio)phenyl)-4,4,5,5-tetramethyl-1,3,2-dioxorane

[0148]

[0149] 2.0 g (6.80 mmol) of (5-bromo-4-fluoro-2-methylphenyl)(2,2,2-trifluoroethyl) sulfide 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 (50.60% yield). No further purification was required, and the reaction proceeded to the next step.

[0150] 1.3 Synthesis of 2-chloro-5-(2-fluoro-4-methyl-5-(2,2,2-trifluoroethyl)thio)phenyl)pyrimidine (compound 7-7)

[0151]

[0152] Add 0.1 g (0.29 mmol) of the intermediate 2-(2-fluoro-4-methyl-5-((2,2,2-trifluoroethyl)thio)phenyl)-4,4,5,5-tetramethyl-1,3,2-dioxoborane to the reaction flask, dissolve it in a mixed solvent of 1,4-dioxane and water, then add 0.061 g (0.31 mmol) of 5-bromo-2-chloropyrimidine, 0.28 g (0.86 mmol) of cesium carbonate, 0.011 g (0.014 mmol) of DPPF palladium dichloride, and 0.016 g (0.029 mmol) of 1,1'-bis(diphenylphosphine)ferrocene to the reaction system. Then heat the reaction system to 100 °C and reflux for 3 h, monitoring the reaction with 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 the target compound 2-chloro-5-(2-fluoro-4-methyl-5-(2,2,2-trifluoroethyl)thio)phenyl)pyrimidine, with a yield of 66.7%.

[0153] Example 2: Synthesis of 3-chloro-6-(2-fluoro-4-methyl-5-(2,2,2-trifluoroethyl)thio)phenyl)pyridazine (compounds 4-5)

[0154] The synthesis methods in 2.1 and 2.2 are the same as those in 1.1 and 1.2 above;

[0155] 2.3 Synthesis of 3-chloro-6-(2-fluoro-4-methyl-5-(2,2,2-trifluoroethyl)thio)phenyl)pyridazine

[0156]

[0157] Add 0.1 g (0.29 mmol) of the intermediate 2-(2-fluoro-4-methyl-5-((2,2,2-trifluoroethyl)thio)phenyl)-4,4,5,5-tetramethyl-1,3,2-dioxoborane to the reaction flask and dissolve it in a mixed solvent of 1,4-dioxane and water. Then add 0.061 g (0.31 mmol) of 3-bromo-6-chloropyridazine, 0.28 g (0.86 mmol) of cesium carbonate, 0.011 g (0.014 mmol) of DPPF palladium dichloride, and 0.016 g (0.029 mmol) of 1,1'-bis(diphenylphosphine)ferrocene to the reaction system. Then heat the reaction system to 100 °C and reflux for 3 h, and monitor the reaction by TLC. After the raw materials were completely eliminated, 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 the target compound 3-chloro-6-(2-fluoro-4-methyl-5-(2,2,2-trifluoroethyl)thio)phenyl)pyridazine, with a yield of 70.0%.

[0158] Example 3: Synthesis of 2-chloro-5-(2-fluoro-4-methyl-5-(2,2,2-trifluoroethyl)thio)phenyl)pyrazine (compound 8-5)

[0159] The synthesis methods for 3.1 and 3.2 are the same as those for 1.1 and 1.2 above;

[0160] 3.3 Synthesis of 2-chloro-5-(2-fluoro-4-methyl-5-(2,2,2-trifluoroethyl)thio)phenyl)pyrazine

[0161]

[0162] Add 0.1 g (0.29 mmol) of the intermediate 2-(2-fluoro-4-methyl-5-((2,2,2-trifluoroethyl)thio)phenyl)-4,4,5,5-tetramethyl-1,3,2-dioxoborane to the reaction flask and dissolve it in a mixed solvent of 1,4-dioxane and water. Then add 0.061 g (0.31 mmol) of 2-bromo-5-chloropyrazine, 0.28 g (0.86 mmol) of cesium carbonate, 0.011 g (0.014 mmol) of DPPF palladium dichloride, and 0.016 g (0.029 mmol) of 1,1'-bis(diphenylphosphine)ferrocene to the reaction system. Then heat the reaction system to 100 °C and reflux for 3 h, and monitor the reaction by TLC. After the raw material was completely eliminated, 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 the target compound 2-chloro-5-(2-fluoro-4-methyl-5-(2,2,2-trifluoroethyl)thio)phenyl)pyrazine, with a yield of 88.3%.

[0163] Test Example: Bioactivity Test

[0164] Test Example 1: Bioactivity test against adult Tetranychus cinnabarinus

[0165] Experimental Methods: The experiment followed agricultural industry standard NYT 1154.6-2006, employing the immersion method for mite detection. 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 10000 mg / L stock solution. This stock solution was diluted 100 times with a 0.1% Tween 80 aqueous solution to obtain a 100 mg / 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 h, the mortality of adult mites was checked and recorded. The mites were considered dead if their legs did not move or they did not react when touched with tweezers.

[0166] Calculation method:

[0167] Corrected mortality rate (%) = [(treatment mortality rate - control mortality rate) / (1 - control mortality rate)] × 100%

[0168] Among the exemplary compounds of this invention, the following compounds showed good control efficacy against adult Tetranychus carmine at a concentration of 100 mg / L, achieving a mortality rate of 100%: compounds 4-4, 4-5, 4-6, 4-15, 4-20, 4-25, 4-31, 4-32, 4-33, 4-34, 4-35, 4-36, 4-37, 4-38, 4-39, 4-40, 4-41, 4-42, 4-43, 4-46, 4-47, 4-50, 4-51, 4-52, 7-5, 7-7, 7-8, 7-9, 7-15, 7-18, 7-21, 7-22, 7-25, 7-26, 7-27, 7-28, 7 -38, 7-39, 7-40, 7-42, 7-43, 7-44, 7-45, 7-46, 7-47, 7-48, 7-49, 7-50, 7-51, 7-52, 7-53, 7-54, 7-56, 7-59, 7-60, 7-62, 7-68, 7-69, 7-70, 7-71, 7-72, 7-73, 7-74, 7-76, 7-77, 7-80, 8-1, 8-5, 8-6, 8-7, 8-8, 8-9, 8-10, 8-15, 8-29, 8-30, 8-32, 8-34, 8-38.

[0169] 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 4-4, 4-5, 4-6, 4-15, 4-20, 4-25, 4-32, 4-33, 4-34, 4-35, 4-36, 4-37, 4-38, 4-39, 4-40, 4-41, 4-42, 4-43, 4-46, 4-47, 4-50, 4-51, 4-52, 7-5, 7-7, 7-8, 7-9, 7-15, 7-18, 7-21, 7-22, 7-25, 7-26, 7-27, and 7-28. 7-38, 7-39, 7-40, 7-42, 7-43, 7-44, 7-45, 7-46, 7-47, 7-48, 7-49, 7-50, 7-51, 7-52, 7-53, 7-54, 7-56, 7-59, 7-60, 7-62, 7-68, 7-69, 7-70, 7-71, 7-72, 7-73, 7-74, 7-76, 7-77, 7-80, 8-5, 8-6, 8-7, 8-8, 8-9, 8-15, 8-29, 8-30, 8-32, 8-34, 8-38.

[0170] Following the above method, exemplary compounds 3 and 11 in this patent, and compounds II-77 (represented as CK1), II-85 (represented as CK2), and II-93 (represented as CK3) in WO1999055668A1 were selected as positive controls to determine the bioactivity of adult Tetranychus carmine at low concentrations. The results are shown in Table 5.

[0171]

[0172] Table 5. Determination of acaricidal activity against Tetranychus cinnabarinus (72h)

[0173]

[0174] As can be seen from the test results in Table 1 above, the exemplary compounds of the present invention still exhibit excellent acaricidal activity against Tetranychus carmine at low concentrations, while the comparative compounds CK1-CK3 show only moderate activity against Tetranychus carmine at low concentrations. Compared with the prior art, the acaricidal activity of the compounds of the present invention has been greatly improved, with some compounds showing an increase of more than 10 times, achieving significant progress.

[0175] Test Example 2: Bioactivity test against adult two-spotted spider mite (Tetranychus urticae)

[0176] 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 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 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.

[0177] Calculation method:

[0178] Mortality rate (%) = [(Pre-treatment insect population - Post-treatment live insect population) / Pre-treatment insect population] × 100%

[0179] Corrected mortality rate (%) = [(treatment group mortality rate - blank control group mortality rate) / (1 - blank control group mortality rate)] × 100%

[0180] Among the exemplary compounds of this invention, the following compounds exhibit good control efficacy against adult two-spotted spider mites at a concentration of 100 mg / L, achieving a mortality rate of 100%: compounds 4-4, 4-5, 4-6, 4-15, 4-20, 4-25, 4-31, 4-32, 4-33, 4-34, 4-35, 4-36, 4-37, 4-38, 4-39, 4-40, 4-41, 4-42, 4-43, 4-46, 4-47, 4-50, 4-51, 4-52, 7-5, 7-7, 7-18, 7-21, 7-22, 7-25, 7-26, 7-27, 7-28, 7-38, and 7-3. 9, 7-40, 7-42, 7-43, 7-44, 7-45, 7-46, 7-47, 7-48, 7-49, 7-50, 7-51, 7-52, 7-53, 7-54, 7-56, 7-59, 7-60, 7-62, 7-68, 7-69, 7-70, 7-71, 7-72, 7-73, 7-74, 7-76, 7-77, 7-80, 8-1, 8-5, 8-6, 8-7, 8-8, 8-9, 8-10, 8-15, 8-29, 8-30, 8-32, 8-34, 8-38.

[0181] Among the exemplary compounds of this 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%: compounds 4-4, 4-5, 4-6, 4-15, 4-20, 4-25, 4-32, 4-33, 4-34, 4-35, 4-36, 4-37, 4-38, 4-39, 4-40, 4-41, 4-42, 4-43, 4-46, 4-47, 4-50, 4-51, 4-52, 7-5, 7-7, 7-18, 7-21, 7-22, 7-25, 7-26, 7-27, 7-28, and 7-38. 7-39, 7-40, 7-42, 7-43, 7-44, 7-45, 7-46, 7-47, 7-48, 7-49, 7-50, 7-51, 7-52, 7-53, 7-54, 7-56, 7-59, 7-60, 7-62, 7-68, 7-69, 7-70, 7-71, 7-72, 7-73, 7-74, 7-76, 7-77, 7-80, 8-5, 8-6, 8-7, 8-8, 8-9, 8-15, 8-29, 8-30, 8-32, 8-34, 8-38.

Claims

1. A compound of formula (I) as a novel trifluoroalkylthiophenyl containing nitrogen heterocycle derivative 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, wherein, R1 is selected from the group consisting of propyl, C1-C3 haloalkyl, cyano C1-C3 alkyl, C3-C6 cycloalkyl C1-C3 alkyl; R2, R4 are independently from each other selected from the group consisting of halogen, cyano, C1-C3 alkyl, C1-C3 haloalkyl, C3-C6 cycloalkyl; R3, R5 are selected from the group consisting of hydrogen; n is selected from 0, 1 or 2.

2. The compound of formula (I) according to claim 1, wherein, R1 is selected from the group consisting of propyl, tert-butyl, isobutyl, dichloroethyl, trichloroethyl, trichloropropyl, fluoromethyl, difluoromethyl, trifluoromethyl, difluoroethyl, trifluoroethyl, tetrafluoroethyl, pentafluoroethyl, trifluoropropyl, heptafluoropropyl, 1-cyanomethyl, cyclopropylmethyl, epoxypropylmethyl; R2, R4 are independently from each other selected from the group consisting of fluorine, chlorine, bromine, iodine, methyl, ethyl, propyl, fluoromethyl, difluoromethyl, trifluoromethyl, trifluoroethyl, pentafluoroethyl, trifluoropropyl, heptafluoropropyl, cyano, cyclopropyl; R3, R5 are selected from the group consisting of hydrogen; n is selected from 0, 1 or 2.

3. The compound of formula (I) according to claim 1, wherein, R2, R3, R4, R5 are independently from each other selected from the group consisting of fluorine, chlorine, bromine, methyl, trifluoromethyl, heptafluoropropyl, cyclopropyl; R3, R5 are selected from the group consisting of hydrogen; n is selected from 0, 1 or 2.

4. The compound of formula (I) according to claim 1, wherein, R1 is selected from the group consisting of CF3, CH2CHF2, CH2CF3, CH2CH2CF3, 1-cyanomethyl, cyclopropylmethyl; R2 is selected from the group consisting of fluorine, chlorine, bromine, methyl; R3 is selected from the group consisting of hydrogen; R4 is selected from the group consisting of fluorine, chlorine, bromine, methyl; R5 is selected from the group consisting of hydrogen; n is selected from 0.

5. The compound of formula (I) according to claim 1, wherein, R1 is selected from C1-C3 haloalkyl, preferably CH2CHF2, CH2CF3, CH2CH2CF3; R2 is selected from C1-C3 alkyl, halogen, preferably methyl, fluorine, chlorine; R4 is selected from halogen, preferably fluorine, chlorine; X1, X2 are selected from hydrogen, fluorine, chlorine, methyl; X3 is selected from halogen, C1-C3 haloalkyl, C1-C3 alkylthio, C1-C3 alkylsulfone, nitro, cyano; preferably fluorine, chlorine, bromine, trifluoromethyl, nitro, cyano, methylthio, methylsulfoxide, methylsulfone; n is selected from 0. Q is selected from the group consisting of , and can be mono- or poly-substituted with one or more identical or different substituents selected from the group consisting of halogen, C1-C3alkyl, C1-C3haloalkyl, C1-C3alkylamino, C1-C3alkylthio, C1-C3alkylsulfone, nitro, cyano; 6. The compound of formula (I) according to claim 1, wherein, R1 is selected from C1-C3 haloalkyl, preferably CH2CHF2, CH2CF3, CH2CH2CF3; R2 is selected from C1-C3 alkyl, halogen, preferably methyl, fluorine, chlorine; R4 is selected from halogen, preferably fluorine, chlorine; X1, X3 are selected from hydrogen, fluorine, chlorine; X2 is selected from halogen, C1-C3 haloalkyl, C1-C3 alkylthio, C1-C3 alkylsulfone, C1-C3 alkylamino, nitro, cyano; preferably fluorine, chlorine, bromine, trifluoromethyl, nitro, cyano, methylthio, methylsulfoxide, methylsulfone, dimethylamino; n is selected from 0.

2. The compound of formula (I) according to claim 1, characterized in that, 7. The compound of formula (I) according to claim 1, wherein, ​ ​ ​ Q is selected from the group consisting of , and can be mono- or poly-substituted with one or more identical or different substituents selected from the group consisting of halogen, C1-C3alkyl, C1-C3haloalkyl, C1-C3alkylamino, C1-C3alkylthio, C1-C3alkylsulfone, nitro, cyano; ​ 3. The compound of formula (I) according to claim 1, characterized in that ​ R1is selected from CF3, CH2CHF2, CH2CF3, CH2CH2CF3, 1-cyanomethyl, cyclopropylmethyl, CH2CHCl2, CH2CCl3, CH2CH2CCl 3、 epoxypropylmethyl; ​ ​ Q is selected from the group consisting of and can be mono- or poly-substituted with one or more identical or different substituents selected from the group consisting of fluorine, chlorine, bromine, iodine, methyl, ethyl, propyl, tert-butyl, isopropyl, difluoromethyl, trifluoromethyl, trifluoroethyl, nitro, cyano, methylamino, dimethylamino, methylthio, methylsulfoxide, methylsulfone; ​ 4. The compound of formula (I) according to claim 1, characterized in that, ​ ​ ​ ​ Q is selected from the group consisting of and can be mono- or poly-substituted with one or more identical or different substituents selected from the group consisting of fluorine, chlorine, bromine, trifluoromethyl, nitro, cyano, methylsulfanyl, methylsulfinyl, methylsulfone, dimethylamino; ​ ​ (I-4) ​ ​ ​ ​ ​ ​ ​ (I-7) ​ ​ ​ ​ ​ ​ ​ （I-8） R1is selected from the group consisting of C1-C3haloalkyl, preferably CH2CHF2, CH2CF3, CH2CH2CF3; R2is selected from the group consisting of C1-C3alkyl, halogen, preferably methyl, fluorine, chlorine; R4is selected from the group consisting of halogen, preferably fluorine, chlorine; X1, X3are selected from the group consisting of hydrogen, fluorine, chlorine; X2is selected from the group consisting of halogen, C1-C3haloalkyl, C1-C3alkylthio, C1-C3alkylsulfoxy, nitro, cyano; preferably fluorine, chlorine, bromine, trifluoromethyl, nitro, cyano, methylthio, methylsulfoxyl, methylsulfonyl; n is selected from 0.

8. Agrochemical formulation comprising a compound of formula (I) according to claim 1 and an extender and / or a surfactant.

9. A method for controlling animal pests, characterized in that, Bringing a compound of formula (I) according to claim 1 or an agrochemical formulation according to claim 8 into action against animal pests and / or their habitat.

10. Use of a compound of formula (I) according to claim 1 or an agrochemical formulation according to claim 8 for controlling plant pests and acarids.

Images