Preparation and application of trifluoroethyl thiophenylpyrimidinamine derivative

Abstract

The invention relates to preparation and application of a trifluoroethyl thiophenylpyrimidinamine derivative. Specifically, the invention relates to a compound as shown in a formula (I), or an isotope labeled compound thereof, or an optical isomer, a geometric isomer, a tautomer or an isomer mixture thereof, or a pharmaceutically acceptable salt thereof, and application of the compound in preparation of insecticides for pest control. The compound can achieve a better pest control effect at a lower dosage, especially for pests such as tetranychidae, microcosaridae, acaridae, tarsonidae, aleuridae and root-knot nematode, and can be used for controlling pests such as tetranychidae, microcosaridae, gall mite, tarsonidae, aleuridae and the like. # imgabs0 #

Description

Technical Field

[0001] The present invention belongs to the field of pesticides, and specifically relates to the preparation and application of trifluoroethylthiophenylpyrimidinamine derivatives. Background Art

[0002] In recent years, due to the long-term and extensive use of acaricides, there have been numerous reports on acaricide-resistant populations. The use of existing acaricides can no longer effectively control harmful mites. Therefore, there is an urgent need to develop new acaricidal active compounds that are effective against existing acaricide-resistant populations. With the continuous development and research by researchers, sulfur-containing compounds substituted with trifluoroethyl groups have gradually come into the view of researchers, and the sulfur-containing compounds substituted with trifluoroethyl groups have been studied in WO1999055668A, CN103664811B, JP5280972B, JP2011219419A, JP2015036377A, WO 2012 / 012086848, WO 2013 / 018928, and WO 2019 / 131575. However, the above research results are still not very satisfactory in terms of efficacy, persistence, toxicity, etc.

[0003] The active compounds described in the above-mentioned documents are still of low killing activity when controlling harmful pests, especially mites. In particular, their acaricidal activity is often unsatisfactory at low application rates, and the control effect on resistant spider mites is even worse. Therefore, there is still an urgent need in agricultural production for new drugs that are highly effective, low-toxic, and have excellent killing effects on resistant mites. Summary of the Invention

[0004] The purpose of the present invention is to provide the preparation and application of a new class of trifluoroethylthiophenylpyrimidinamine derivatives, which can achieve better pest control effects at lower doses, especially against mites such as Tetranychidae, Eriophyidae, Tarsonemidae, and Acaridae.

[0005] In a first aspect, the present invention provides a compound of formula (I) or its isotopically labeled compound, or its optical isomer, geometric isomer, tautomer or isomer mixture, or its agriculturally acceptable salt as a trifluoroethylthiophenylpyrimidinamine derivative,

[0006]

[0007] wherein,

[0008] R1 is selected from H, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkylcarbonyl, C 1-6 haloalkylcarbonyl;

[0009] R2 is selected from C 1-6Alkyl, C 1-6 Halogenated alkyl, C 3-6 Cycloalkyl, C 3-6 Halogenated cycloalkyl;

[0010] R3 is selected from H, C 1-6 Alkyl, C 1-6 Alkylcarbonyl, C 3-6 Cycloalkyl, C 6-12 Aryl, C 3-6 Cycloalkyl C 1-6 Alkyl, C 6-12 Aryl C 1-6 Alkyl, C 6-12 Arylsulfonic acid group, wherein R3 can be optionally substituted by one or more substituents selected from: halogen, C 1-3 Alkyl, C 1-3 Halogenated alkyl, C 1-3 Alkoxycarbonyl;

[0011] n represents the numbers 0, 1.

[0012] In one embodiment of the present invention, wherein,

[0013] R1 is selected from H, C 1-3 Alkyl, C 1-3 Halogenated alkyl, C 1-3 Alkylcarbonyl, C 1-3 Halogenated alkylcarbonyl;

[0014] R2 is selected from C 1-3 Alkyl, C 1-3 Halogenated alkyl, C 3-6 Cycloalkyl, C 3-6 Halogenated cycloalkyl;

[0015] R3 is selected from H, C 1-3 Alkyl, C 1-3 Alkylcarbonyl, C 3-6 Cycloalkyl, C 3-6 Cycloalkyl C 1-3 Alkyl, C 6-12 Aryl C 1-3 Alkyl, C 6-10 Arylsulfonic acid group, wherein R3 can be optionally substituted by one or more substituents selected from: halogen, C 1-3 Alkyl, C 1-3 Halogenated alkyl, C 1-3 Alkoxycarbonyl;

[0016] n represents the numbers 0, 1.

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

[0018] R1 is selected from H, C1-3 alkyl, C 1-3 alkylcarbonyl, C 1-3 haloalkylcarbonyl;

[0019] R2 is selected from C 1-3 alkyl, C 1-3 haloalkyl, C 3-6 cycloalkyl;

[0020] R3 is selected from H, C 1-3 alkyl, C 1-3 alkylcarbonyl, C 3-6 cycloalkyl, C 6-12 arylC 1-3 alkyl, C 6-10 arylsulfonyl, wherein R3 may optionally be substituted by one or more substituents selected from: fluorine, chlorine, bromine, methyl, ethyl, monofluoromethyl, difluoromethyl, trifluoromethyl, methoxycarbonyl;

[0021] n represents the numbers 0, 1.

[0022] In another embodiment of the present invention, wherein,

[0023] R1 is selected from H, methyl, ethyl, methylcarbonyl, ethylcarbonyl, trifluoromethylcarbonyl;

[0024] R2 is selected from methyl, difluoromethyl, trifluoromethyl, isopropyl, cyclopropyl,

[0025] R3 is selected from H, n-propyl, isopropyl, methylcarbonyl, trifluoromethylcarbonyl, cyclopentyl, benzyl, 2,6-difluorobenzyl, 2-trifluoromethylbenzyl, 2-methylcarbomethoxybenzyl, benzenesulfonyl, 4-methylbenzenesulfonyl;

[0026] n represents the numbers 0, 1.

[0027] In another preferred embodiment of the present invention, it may be selected from the following compounds,

[0028]

[0029]

[0030] For the sake of simplicity, the "trifluoroethylthiophenylpyrimidinamine derivative", "compound of formula (I)" or "compound of the present invention" described hereinafter may also cover any isotopically labeled compound of the compound of formula (I), or its optical isomers, geometric isomers, tautomers or mixtures of isomers, or its pesticidally acceptable salts.

[0031] The term "optical isomer" means that when a compound has one or more chiral centers, each chiral center can exist in the R configuration or the S configuration, and the various isomers thus formed are optical isomers. Optical isomers include all diastereoisomers, enantiomers, meso forms, racemates, or mixtures thereof. For example, optical isomers can be separated by a chiral chromatographic column or by chiral synthesis.

[0032] The term "geometric isomer" means that when there is a double bond in a compound, 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.

[0033] The term "tautomer" refers to an isomer produced by the rapid movement of an atom in a molecule between two positions. Those skilled in the art can understand that tautomers can interconvert with each other and may reach an equilibrium state and coexist in a certain state.

[0034] Unless otherwise specified, when referring to "trifluoroethylthiophenylpyrimidinamine derivatives", "compounds of formula (I)", or "compounds of the present invention" herein, it also encompasses isotopically labeled compounds in which any atom in the compound is replaced by 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 but different atomic masses or mass numbers as the atoms normally found in nature.

[0035] 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.

[0036] Isotopically labeled compounds of formula (I) can generally be prepared by conventional techniques known to those skilled in the art or by using a suitable isotopically labeled reagent in place of the previously used unlabeled reagent in a manner similar to the methods described in the examples and preparations appended hereto.

[0037] Compounds of formula (I) can exist in the form of agrochemically acceptable salts, for example, acid addition salts and / or base addition salts of the compounds of formula (I). Unless otherwise specified, the term "agrochemically acceptable salt" as used herein includes acid addition salts or base addition salts that can occur within the compounds of formula (I).

[0038] Agrochemically acceptable salts of the compounds of formula (I) include their acid addition salts and base addition salts. Suitable acid addition salts are formed from 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 the agrochemically acceptable salts of the compounds described herein are known to those skilled in the art.

[0039] To avoid ambiguity, the terms used herein are defined below. Unless otherwise indicated, the meanings of the terms used herein are as follows.

[0040] As used herein, the term "substituted" means that one or more (preferably 1 to 5, more preferably 1 to 3) hydrogen atoms in the group are independently replaced by the corresponding number of substituents.

[0041] As used herein, the term "each independently" means that when the number of substituents exceeds one, these substituents can be the same or different.

[0042] As used herein, the term "alkyl" 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 alkyl" means a straight-chain or branched-chain moiety having 1-8 carbon atoms. The term "C 1-8 alkyl" includes the term "C 1-6"Alkyl", "C1-C3 alkyl", and "C1-C4 alkyl". Examples of alkyl 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, and the like. The alkyl group may optionally be substituted with one or more (e.g., 1 to 5) suitable substituents.

[0043] As used herein, the term "haloalkyl" refers to an alkyl group having one or more halogen substituents (up to a perhaloalkyl group, 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 C 1- C6 alkyl group having one or more halogen substituents (up to a perhaloalkyl group, i.e., each hydrogen atom of the alkyl group is replaced by a halogen atom). As another example, the term "C 1- C3 haloalkyl" refers to a C 1- C3 alkyl group having one or more halogen substituents (up to a perhaloalkyl group, 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, and the like.

[0044] As used herein, the term "n-membered heterocycloalkyl" refers to a heterocycloalkyl having m ring-forming carbon atoms and (n - m) ring-forming heteroatoms selected from O, S, and N. For example, 4- to 6-membered heterocycloalkyls include, but are not limited to, oxetane, thiolane, azetidine, tetrahydrofuran, tetrahydrothiophene, pyrrolidine, tetrahydropyran, tetrahydrothiopyran, piperidine, morpholine, piperazine. In addition, the heterocycloalkyl may optionally be substituted with one or more suitable substituents.

[0045] In this document, the number ranges related to the number of substituents, the number of carbon atoms, and the number of ring atoms represent the individual listing of all integers within that range, and the range is only a simplified notation. 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 number ranges related to the number of substituents, the number of carbon atoms, and the number of ring atoms also cover any of its sub-ranges, and each sub-range is also considered to be disclosed herein.

[0046] The compounds of the present 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 the specific compounds in the specific embodiments of the present invention and make appropriate adjustments to the reaction raw materials and reaction conditions to obtain the synthetic methods of other compounds.

[0047] The following synthetic schemes describe the steps for preparing the compounds disclosed in the present invention. Among them, R1, R2, R3 and n have the meanings described in the present invention.

[0048]

[0049] The compounds of general formula IV and their raw materials can be prepared by referring to the methods reported in WO2006043635, WO2010100189, CN102341376A, WO2013092350, WO2013157229, WO2007131680, WO2013030262, WO2018015852, WO2014202510, WO2014202505, WO2015004028, WO2021056922 or WO2021005081, etc.

[0050] The present invention lists multiple synthesized exemplary compounds, and the specific group selections are shown in the following table, and the compound data are shown in Table 3. It should be understood that the scope of the present invention is not limited to the exemplary compounds listed in the following table, and the group selections of the compounds in Table 1 below can be combined arbitrarily without particular limitation. Some compounds of general formula I of the present invention are shown below, but the present invention is by no means limited to these compounds.

[0051] Table 1 where n = 0, and the specific substituents R1, R2, R3 are shown in the following table

[0052]

[0053]

[0054]

[0055] Table 2 where n = 1, and the specific substituents R1, R2, R3 are the same as in Table 1.

[0056] Table 3 Compound characterization data

[0057]

[0058]

[0059] In a second aspect, the present invention provides an insecticide composition comprising a compound of formula (I) or its isotope-labeled compound, or its optical isomer, geometric isomer, tautomer or mixture of isomers, or its agrochemically acceptable salt, and an agrochemically acceptable carrier.

[0060] The agriculturally 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, petrolatum, mannitol, cellulose, cellulose derivatives, sodium saccharin, magnesium carbonate, brine, glycerol, ethanol, etc. In addition, the insecticide composition may further contain other additives, such as preservatives, stabilizers, emulsifiers, buffers, diluents, binders, wetting agents, lubricants, glidants, etc.

[0061] The dosage form of the insecticide composition of the present invention 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 powders, granules, liquids, suspensions or sprays, preferably wettable powders, wettable liquids, soluble powders, dispersible liquids, aqueous solutions, microemulsions, emulsifiable concentrates, emulsions in water, sprayable solutions, dispersible oil suspensions, microcapsule suspensions, water-dispersible granules, water-soluble granules, macrogranules, granules for broadcasting and soil application, aerosols, ultra-low volume agents and wax products.

[0062] The content of the compound of the present invention in its insecticide composition can be adjusted according to actual needs (such as dosage form, application method, 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.

[0063] The specific application frequency can be determined by those skilled in the relevant art, 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.

[0064] In a third aspect, the present invention provides the use of the compound of formula (I) or its isotope-labeled compound, or its optical isomer, geometric isomer, tautomer or mixture of isomers, or its agriculturally acceptable salt in the preparation of an insecticide for pest control.

[0065] The compounds of the present invention are suitable for controlling pests or mites, that is, controlling pests or mites. The pests or mites refer to harmful or unwanted insects or mites, especially harmful or unwanted insects or mites encountered in the fields of agriculture, forestry, storage protection, material protection and hygiene. When used at low concentrations, the compounds of the present invention also show excellent control effects on various pests or mites, and have insecticidal or acaricidal activity at each stage of the pest or mite life cycle (such as eggs, larvae (nymphs), pupae, adults). The compounds of the present invention also show excellent control activity against pests or mites that have developed resistance to traditional insecticides or acaricides.

[0066] The present invention also relates to a method for controlling pests or acarids, which method comprises applying a controlling effective amount of a compound of formula (I) to the location of the insects, insect habitats, pest habitats, areas to be protected, or directly onto the insects to be controlled. The compounds of the present invention can also be used to control other invertebrate pests or organisms.

[0067] Specifically, the insect habitats, pest habitats or acarid habitats refer to the environments where insects, pests or acarids live or their eggs exist, including the surrounding air, the food they consume or the objects they contact. For example, by applying the active compound to the seeds of plants (before planting), to seedlings, or planted cuttings, leaves, stems, fruits, grains and / or roots, or to the soil or other growth media (before or after crop planting), insects or acarids that eat, damage or contact edible agricultural products, ornamental plants, turf, forage plants or other plants of economic value can be controlled. It is also possible to protect these plants against diseases caused by viruses, fungi or bacteria by controlling sap-sucking pests such as whiteflies, planthoppers, aphids, etc. or acarids such as Tetranychus urticae, Tetranychus cinnabarinus, etc.; the plants include plants obtained by conventional breeding methods, and also plants with insect or acarid resistance, herbicide resistance, high yield / or other beneficial characteristics obtained by genetically modifying through modern biotechnology. It is expected that these compounds can be applied to protect articles and / or places such as fabrics, paper, stored grains, seeds and other foods, houses, buildings, etc., by applying the compounds of the present invention onto or near these objects.

[0068] The inventors of the present invention have found that even when the compounds of the present invention are applied at a relatively low dose, they can still control animal pests encountered in the fields of agriculture, horticulture, livestock breeding, aquaculture, forestry, gardens and leisure facilities, protection of stored products and materials, and hygiene, especially insects, arachnids, worms, nematodes and molluscs. These compounds are preferably used as insecticides. They are effective against both normally sensitive and resistant species, and can resist all or part of the developmental stages. The above pests include:

[0069] Pests from the phylum Arthropoda, especially from the class Arachnida, such as the orders Acari, Metastigmata and Mesostigmata, the families Tetranychidae, Eupodidae, Eriophyidae, Phytoseiidae, Tarsonemidae, Acaridae, and the genera Acarus (e.g., Acarus siro, Aceria kuko, Aceria sheldoni), Aculops spp., Aculus spp. (e.g., Aculus fockeui, Aculus schlechtendali), Amblyomma spp., Amphitetranychus viennensis, Eotetranychus spp., Tetranychus, Panonychus, Oligonychus, Schizotetranychus, Argas spp., Boophilus spp., Brevipalpus spp. (e.g., Brevipalpus phoenicis), Bryobia graminum, Bryobia praetiosa, Centruroides spp., Chorioptes spp., Dermanyssus gallinae, Dermatophagoides pteronyssinus, Dermatophagoides farinae, Dermacentor spp., Ornithodoros spp., Otobius spp., Ixodes spp., Haemophysalis spp., Hyalomma spp., Rhipicephalus spp. (the former genus of heteroxenous mites), Ornithonyssus spp., Pneumonyssus spp.) Raillietia spp., Sternostoma spp., Varroa spp., Acarapis spp., etc.;

[0070] Pests from the order Coleoptera, such as Acalymma vittatum, Acanthoscelides obtectus, Adoretus spp., Agelastica alni, Agriotes spp. (such as Agriotes linneatus, Agriotes mancus), Alphitobius diaperinus, Amphimallon solstitialis, Anobium punctatum, Anoplophora spp., Anthonomus spp. (such as Anthonomus grandis), Anthrenus spp., Apion spp., Apogonia spp., Atomaria spp. (such as Atomaria linearis), Attagenus spp., Baris caerulescens, Bruchidius obtectus, Bruchus spp. (such as Bruchus pisorum, Bruchus rufimanus), Cassida spp., Cerotoma trifurcata, Ceuthorhynchus spp. (such as Ceutorrhynchus assimilis, Ceutorrhynchus quadridens, Ceutorrhynchus rapae), Chaetocnema spp. (such as Chaetocnema confinis, Chaetocnema denticulata, Chaetocnema ectypa), Cleonus mendicus, Conoderus spp., Cosmopolites spp. (such as Cosmopolites sordidus);

[0071] Pests from the order Diptera, such as, Aedes spp. (e.g., Aedes aegypti, Aedes albopictus, Aedes sticticus, Aedes vexans), Agromyza spp. (e.g., Agromyza frontella, Agromyza parvicornis), Anastrepha spp., Anopheles spp. (e.g., Anopheles quadrimaculatus, Anopheles gambiae), Asphondylia spp., 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);

[0072] Pests from the order Heteroptera, for example, Anasa tristis, Antestiopsis spp., Boisea spp., Blissus spp., Calocoris spp., Campylomma livida, Cavelerius spp., Cimex spp. (such as Cimex adjunctus, Cimex hemipterus, Cimex lectularius, Cimex pilosellus), Collaria spp., Creontiades dilutus, Dasynus piperis, Dichelops furcatus, Diconocoris hewetti, Dysdercus spp., Euschistus spp.;

[0073] Pests from the order Homoptera, such as Acizzia acaciaebaileyanae, Acizziadodonaeae, Acizzia uncatoides, Acrida turrita, Acyrthosipon spp. (such as Acyrthosiphon pisum), Acrogonia spp., Aeneolamia spp., Agonoscena spp., Aleyrodes proletella, Aleurolobus barodensis, Aleurothrixus floccosus, Allocaridara malayensis, Amrasca spp. (such as Amrasca bigutulla, Amrasca devastans), Anuraphis cardui, Aonidiella spp. (such as Aonidiella aurantii, Aonidiella citrina, Aonidiella inornata), Aphanostigma piri, Aphis spp (such as Aphis craccivora, Aphis fabae, Aphis forbesi, Aphis glycines, Aphis gossypii, Aphis hederae, Aphis illinoisensis, Aphis middletoni, Aphis nasturtii, Aphis nerii);

[0074] Pests from the order Hymenoptera, such as 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.;

[0075] Pests from the order Isoptera, such as Coptotermes spp. (e.g., Coptotermes formosanus), Cornitermes cumulans, Cryptotermes spp., Incisitermes spp., Microtermes obesi, Odontotermes spp., Reticulitermes spp. (e.g., Reticulitermes flavipes, Reticulitermes hesperus);

[0076] Pests from the order Lepidoptera, such as Achroia grisella, Acronicta major, Adoxophyes spp. (e.g., Adoxophyes orana), Aedia leucomelas, Agrotis spp. (e.g., Agrotis segetum, Agrotis ipsilon), Alabama spp. (e.g., Alabama argillacea), Amyelois transitella, Anarsia spp., Anticarsia spp. (e.g., 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. (e.g., Chiloplejadellus, Chilo suppressalis), Choristoneura spp., Clysia ambiguella, Cnaphalocerus spp., Cnaphalocrocis medinalis, Cnephasia spp., Conopomorpha spp.;

[0077] Pests from the order Orthoptera or Saltatoria, such as Acheta domesticus, Dichroplus spp., Gryllotalpa spp. (such as Gryllotalpa gryllotalpa), Hieroglyphus spp., Locusta spp. (such as Locusta migratoria), Melanoplus spp. (such as Melanoplus devastator), Schistocerca gregaria;

[0078] Pests from the order Thysanoptera, such as Anaphothrips obscurus, Baliothrips biformis, Drepanothris reuteri, Enneothrips flavens, Frankliniella spp. (such as Frankliniella fusca, Frankliniella occidentalis, Frankliniella schultzei, Frankliniella tritici, Frankliniella vaccinii, Frankliniella williamsi), Heliothrips spp., Hercinothrips femoralis, Rhipiphorothrips cruentatus, Scirtothrips spp., Taeniothrips cardamoni, Thrips spp. (such as Thrips palmi, Thrips tabaci);

[0079] Plant pests from the phylum Nematoda, namely plant-parasitic nematodes, especially those of the genera Aglenchus spp. (such as Aglenchus agricola), Anguina spp. (such as Anguina tritici), Aphelenchoides spp. (such as Aphelenchoides arachidis, Aphelenchoides fragariae), Belonolaimus spp. (such as Belonolaimus gracilis, Belonolaimus longicaudatus, Belonolaimus nortoni), Bursaphelenchus spp. (such as Bursaphelenchus cocophilus, Bursaphelenchus eremus, Bursaphelenchus xylophilus); species of the genus Meloidogyne spp.)(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 non-migratory parasitic Meloidogyne spp.); Tylenchulus spp. (e.g., Tylenchulus semipenetrans); Xiphinema spp. (e.g., Xiphinema index).

[0080] Those skilled in the art can understand that the definitions and preferences described in one aspect of the present invention are equally applicable to other aspects. Those skilled in the art can understand that the embodiments of various aspects of the present invention can be combined in various ways without departing from the subject and idea of the present invention, and these combinations are also included within the scope of the present invention.

[0081] The beneficial effects of the present invention are as follows:

[0082] By chemically modifying and molecularly designing aryl sulfides with an aromatic amine structure, heterocyclic substituents were introduced onto the nitrogen atom, resulting in a series of more efficient compounds with excellent activity for use in agricultural or forestry insecticidal or acaricidal applications, particularly showing excellent control effects against Tetranychus urticae, Tetranychus cinnabarinus, Panonychus ulmi, and Panonychus citri. Detailed implementation manners

[0083] The technical solutions in the embodiments of the present invention will be clearly and completely described below in conjunction with the embodiments of the present invention. All other embodiments obtained by those of ordinary skill in the art based on the embodiments of the present invention without creative efforts shall fall within the scope of protection of the present invention.

[0084] The compounds of formula (I) of the present invention can be synthesized by a variety of methods familiar to those skilled in the field of organic synthesis. The following specific examples give some exemplary synthesis methods of the compounds of formula (I), which are well-known in the field of synthetic chemistry. Obviously, referring to the exemplary schemes in this patent, those skilled in the art can easily design other synthetic routes of the compounds of formula (I) by appropriately adjusting the reactants, reaction conditions, and protecting groups.

[0085] Example 1 Synthesis of 2-((2-Fluoro-4-methyl-5-((2,2,2-trifluoroethyl)thio)phenyl)amino)-6-(trifluoromethyl)pyrimidin-4-ol (Compound I-1)

[0086] Comprising the following steps:

[0087]

[0088] Add 50 ml of ethanol to the reaction flask, then add 4-methyl-2-fluoro-5-(2,2,2-trifluoroethylthio)aniline (5 g, 20.90 mmol) and dicyandiamide (3.51 g, 41.80 mmol) respectively, and dropwise add hydrochloric acid. After refluxing at 80 °C until the reaction is complete, stop the reaction, remove the solvent under reduced pressure, and wash the residue multiple times to obtain 4.5 g of Intermediate II with a yield of 76.5%;

[0089]

[0090] Under ice bath conditions, the product of the previous step reaction (3.70 g, 13.15 mmol) was taken in 30 ml of methanol and stirred vigorously. Then, a 30% sodium methoxide solution (1.28 g, 23.68 mmol) was slowly added, and the reaction was carried out at this temperature for 2 h. Then, ethyl trifluoroacetoacetate (2.91 g, 15.79 mmol) was added dropwise. After the addition was complete, the reaction system was slowly heated to 70 °C and stirred until the reaction was complete. Then, the reaction was stopped. After cooling to room temperature, the reaction solution was evaporated to remove methanol. Ethyl acetate was added to the residue to dissolve it, and the insoluble matter was filtered off. The filtrate was collected and concentrated under reduced pressure to obtain 3.4 g of a pale yellow crude product. Column chromatography separation (PE:EA = 4:1) gave 12.5 g of the compound with a yield of 47.2%.

[0091] 1 H NMR (400 MHz, DMSO-d6) δ: 11.72 (s, 1H), 9.09 (s, 1H), 7.96 (d, J = 7.9 Hz, 1H), 7.24 (d, J = 11.6 Hz, 1H), 6.16 (s, 1H), 3.95 (qd, J = 10.4, 3.1 Hz, 3H), 2.37 (s, 3H). LC-MS (m / z, ESI): 402 [M+H] + .

[0092] Example 2. Synthesis of 2-(2-fluoro-4-methyl-5-((2,2,2-trifluoroethyl)thio)phenyl)amino)-6-(trifluoromethyl)pyrimidin-4-ol (Compound I-2)

[0093]

[0094] 4-Methyl-2-fluoro-5-(2,2,2-trifluoroethylthio)aniline (1.0 g, 4.18 mmol) and 2-thiomethyl-4-hydroxy-6-methylpyrimidine (0.65 g, 4.18 mmol) were added to a reaction flask respectively. Then, the reaction system was heated to 160 °C for reaction. The reaction was monitored by TLC until it was complete. Then, the reaction was stopped. After cooling to room temperature, the insoluble matter was filtered off. The organic phase was collected and concentrated under reduced pressure. Column chromatography separation gave 0.3 g of the compound with a yield of 31.2%.

[0095] 1 H NMR (400 MHz, DMSO-d6) δ: 10.85 (s, 1H), 8.61 (s, 1H), 8.50 (d, 1H), 7.26–7.21 (d, 1H), 5.71 (s, 1H), 3.87 (q, J = 10.4 Hz, 2H), 2.35 (s, 3H), 2.10 (d, J = 0.8 Hz, 3H). LC-MS (m / z, ESI): 348 [M+H] + .

[0096] Example 3 Synthesis of 2,2,2-Trifluoro-N-(2-fluoro-4-methyl-5-((2,2,2-trifluoroethyl)thio)phenyl)-N-(4-hydroxy-6-(trifluoromethyl)pyrimidin-2-yl)acetamide (Compound I-10) and 2-((2-Fluoro-4-methyl-5-((2,2,2-trifluoroethyl)thio)phenyl)amino)-6-(trifluoromethyl)pyrimidin-4-yl 2,2,2-trifluoroacetate (Compound I-18)

[0097]

[0098] Under nitrogen protection, add Compound I-1 (0.2 g, 0.49 mmol) to a reaction flask, dissolve it with 20 ml of acetonitrile, then add trifluoroacetic anhydride (0.16 g, 0.75 mmol) to the reaction system. Heat the reaction system to 60 °C for reaction, control the temperature and continue the reaction for 3 - 5 h until the reaction is complete. Cool the reaction solution to room temperature, add water, extract and collect the organic phase. Dry it with anhydrous sodium sulfate and concentrate it under reduced pressure. Separate by column chromatography to obtain 0.098 g of (Compound I-10) with a yield of 39.54%; meanwhile, obtain 0.075 g of (Compound I-18) with a yield of 30.26%.

[0099] Compound I-10: 1 H NMR (400 MHz, CDCl3) δ: 13.54 (s, 1H), 8.40 (d, J = 7.4 Hz, 1H), 7.14 (d, 1H), 6.84 (s, 1H), 3.46 (q, J = 9.5 Hz, 2H), 2.50 (s, 3H). LC-MS (m / z, ESI): 498 [M + H] + .

[0100] Compound I-18: 1 H NMR (400 MHz, CDCl3) δ: 13.12 (s, 1H), 8.02 (d, J = 6.8 Hz, 1H), 7.11 (d, J = 9.3 Hz, 1H), 6.83 (s, 1H), 3.46 (q, J = 9.4 Hz, 2H), 2.40 (s, 3H). LC-MS (m / z, ESI): 498 [M + H] + .

[0101] Example 4 Synthesis of 4-((2,6-Difluorobenzyl)oxy)-N-(2-fluoro-4-methyl-5-((2,2,2-trifluoroethyl)thio)phenyl)-6-(trifluoromethyl)pyrimidin-2-amine (Compound I-40)

[0102]

[0103] Compound I-1 (0.60 g, 1.5 mmol) was added to a reaction flask, dissolved in acetone, and then anhydrous potassium carbonate (0.62 g, 4.5 mmol) and 2,6-difluorobenzyl bromide (340 mg, 1.6 mmol) were added. After the addition, the reaction system was heated to 50 °C and stirred under reflux. The reaction was monitored by TLC until it was complete. The reaction was stopped, and after it was cooled to room temperature, saturated sodium bicarbonate solution was added to the reaction system. It was extracted with EA. The organic phase was washed with saturated NaCl aqueous solution, dried over anhydrous Na2SO4, concentrated under reduced pressure, and separated by column chromatography to obtain 0.5 g of 3, with a yield of 63.41%.

[0104] 1 1H NMR (400 MHz, CDCl3) δ: 8.76 (d, J = 8.1 Hz, 1H), 7.43–7.34 (m, 2H), 7.00 (q, J = 9.7, 8.0 Hz, 3H), 6.61 (s, 1H), 5.55 (s, 2H), 3.47 (q, J = 9.6 Hz, 2H), 2.45 (s, 3H). LC-MS (m / z, ESI): 528 [M+H] + .

[0105] Example 5. Synthesis of 2-((2-fluoro-4-methyl-5-((2,2,2-trifluoroethyl)sulfinyl)phenyl)amino)-6-(trifluoromethyl)pyrimidin-4-ol (Compound II-1)

[0106]

[0107] Compound I-1 (0.5 g, 1.25 mmol) was added to a reaction flask, an appropriate amount of phenol (just enough to dissolve the raw material) was added to the reaction flask, and then 30% H2O2 (4 ml) was added. The reaction was stirred at room temperature. The reaction was monitored by TLC. After the reaction was complete, the reaction was stopped. Subsequently, Na2SO3 and NaOH solution were added to the reaction system in sequence, and then it was extracted with ethyl acetate. The organic phase was collected, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and separated by column chromatography to obtain 0.4 g of Compound 2, with a yield of 77%;

[0108] 1 1H NMR (400 MHz, DMSO-d6) δ: 11.59 (s, 1H), 9.31 (s, 1H), 8.15 (d, J = 7.6 Hz, 1H), 7.40–7.30 (m, 1H), 6.18 (s, 1H), 4.30–4.04 (m, 2H), 2.38 (s, 2H). LC-MS (m / z, ESI): 418 [M+H] + .

[0109] Test Example: Biological Activity Test

[0110] In the following test examples, if the control mortality rate is greater than 10%, the test is repeated. If the control mortality rate is less than 10%, the acaricidal activity is measured by using Abbott's correction formula, the toxicity regression equation is obtained by using the DPS data processing system, and the LC 50 value, 95% confidence limit are calculated, and statistical analysis is carried out.

[0111] Test Example 1: Bioactivity test against adult Tetranychus urticae Koch

[0112] Experimental method: The test was carried out with reference to the agricultural industry standard NY / T 1154.13-2008, and the leaf disc spraying method was used for determination. Kidney bean leaves that were clean, flat, of appropriate size, and of the same leaf age were selected and laid flat in a petri dish with clean filter paper, with the reverse side facing up. The filter paper was moistened with water, and then 30-40 adult Tetranychus urticae mites with basically the same physiological state were introduced onto each leaf with a writing brush. The compound (2 mg) was dissolved in 2 mL of DMSO solvent to form a stock solution with a concentration of 1000 mg / L. The stock solution was diluted 10 times with a 0.1% Tween-80 solution in H2O to obtain a test solution with a concentration of 100 mg / L, and diluted 20 times to obtain a test solution with a concentration of 50 mg / L. More test concentrations were obtained by diluting in the same way. The leaves with adult Tetranychus urticae mites were sprayed with a sprayer until the leaf surface and the mite body surface were just covered with droplets. Each treatment was repeated 3 times, and a blank control was set. The spraying solution used in the control group was an aqueous solution of DMSO and Tween at the same ratio. The experimental target was cultured in an artificial climate chamber (24-26 °C, L:D = 16:8, RH 60%). After 72 h, the death situation of the adult mites was checked and recorded. When the body of the mite was touched with forceps, if the legs did not move or there was no response, it was regarded as a dead mite.

[0113] Calculation method:

[0114] Corrected mortality rate (%) = [(treatment mortality rate - control mortality rate) / (1 - control mortality rate)] × 100%

[0115] Among some of the tested compounds, the following compounds had better control effects against adult Tetranychus urticae Koch at a concentration of 100 mg / L, and the mortality rate was greater than 80%: I-2, I-10, I-12, I-19, I-25, I-28, I-61, I-69, II-3, II-28, II-34, II-48, II-55, II-62.

[0116] The preferred embodiments of the present invention have been described in detail above. However, the present invention is not limited to the specific details in the above embodiments. Within the scope of the technical concept of the present invention, various simple modifications can be made to the technical solutions of the present invention, and these simple modifications all fall within the protection scope of the present invention.

Claims

1. A compound of formula (I) which is a trifluoroethylthiophenylpyrimidinamine derivative, or an isotopically labeled compound thereof, or an optical isomer, geometric isomer, tautomer or mixture of isomers thereof, or a pesticidally acceptable salt thereof, wherein, R1 is selected from H, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkylcarbonyl, C 1-6 haloalkylcarbonyl; R2 is selected from C 1-6 alkyl, C 1-6 haloalkyl, C 3-6 cycloalkyl, C 3-6 halocycloalkyl; R3 is selected from H, C 1-6 alkyl, C 1-6 alkylcarbonyl, C 3-6 cycloalkyl, C 6-12 aryl, C 3-6 cycloalkyl C 1-6 alkyl, C 6-12 aryl C 1-6 alkyl, C 6-12 arylsulfonic acid group, where R3 may optionally be substituted by one or more substituents selected from: halogen, C 1-3 alkyl, C 1-3 haloalkyl, C 1-3 alkoxycarbonyl; n represents the numbers 0, 1.

2. The compound of formula (I) or an isotopically labeled compound thereof, or an optical isomer, geometric isomer, tautomer or mixture of isomers thereof, or a pesticidally acceptable salt thereof according to claim 1, wherein, R1 is selected from H, C 1-3 alkyl, C 1-3 haloalkyl, C 1-3 alkylcarbonyl, C 1-3 haloalkylcarbonyl; R2 is selected from C 1-3 alkyl, C 1-3 haloalkyl, C 3-6 cycloalkyl, C 3-6 halocycloalkyl; R3 is selected from H, C 1-3 alkyl, C 1-3 alkylcarbonyl, C 3-6 cycloalkyl, C 3-6 cycloalkylC 1-3 alkyl, C 6-12 arylC 1-3 alkyl, C 6-10 arylsulfonic acid group, where R3 can optionally be substituted by one or more substituents selected from: halogen, C 1-3 alkyl, C 1-3 haloalkyl, C 1-3 alkoxycarbonyl; n represents the numbers 0, 1.

3. The compound of formula (I) or an isotopically labeled compound thereof, or an optical isomer, geometric isomer, tautomer or mixture of isomers thereof, or a pesticidally acceptable salt thereof according to claim 1, wherein, R1 is selected from H, C 1-3 alkyl, C 1-3 alkylcarbonyl, C 1-3 haloalkylcarbonyl; R2 is selected from C 1-3 alkyl, C 1-3 haloalkyl, C 3-6 cycloalkyl; R3 is selected from H, C 1-3 alkyl, C 1-3 alkylcarbonyl, C 3-6 cycloalkyl, C 6-12 arylC 1-3 alkyl, C 6-10 arylsulfonic acid group, where R3 can optionally be substituted by one or more substituents selected from: fluorine, chlorine, bromine, methyl, ethyl, monofluoromethyl, difluoromethyl, trifluoromethyl, methoxycarbonyl; n represents the numbers 0, 1.

4. The compound of formula (I) or an isotopically labeled compound thereof, or an optical isomer, geometric isomer, tautomer or mixture of isomers thereof, or a pesticidally acceptable salt thereof according to claim 1, wherein, R1 is selected from H, methyl, ethyl, methylcarbonyl, ethylcarbonyl, trifluoromethylcarbonyl; R2 is selected from methyl, difluoromethyl, trifluoromethyl, isopropyl, cyclopropyl, R3 is selected from H, n-propyl, isopropyl, methylcarbonyl, trifluoromethylcarbonyl, cyclopentyl, benzyl, 2,6-difluorobenzyl, 2-trifluoromethylbenzyl, 2-methylcarbomethoxybenzyl, benzenesulfonyl, 4-methylbenzenesulfonyl; n represents the numbers 0, 1.

5. The compound of formula (I) or an isotopically labeled compound thereof, or an optical isomer, geometric isomer, tautomer or mixture of isomers thereof, or a pesticidally acceptable salt thereof according to claim 1, selected from compounds of the following structures:

6. An insecticide composition comprising the compound of formula (I) or an isotopically labeled compound thereof, or an optical isomer, geometric isomer, tautomer or mixture of isomers thereof, or a pesticidally acceptable salt thereof according to any one of claims 1-5, and a pesticidally acceptable carrier.

7. The insecticide composition according to claim 6, wherein the dosage form is selected from powder, granule, liquid, suspension or spray, preferably wettable powder, wettable liquid, soluble powder, dispersible liquid, aqueous solution, microemulsion, emulsifiable concentrate, emulsion in water, sprayable solution, dispersible oil suspension, microcapsule suspension, water dispersible granule, water soluble granule, macrogranule, granule for broadcasting and soil application, aerosol, ultra-low volume agent and wax product.

8. Use of the compound of formula (I) or an isotopically labeled compound thereof, or an optical isomer, geometric isomer, tautomer or mixture of isomers thereof, or a pesticidally acceptable salt thereof according to any one of claims 1-5 in the preparation of an insecticide for pest control.

9. The use according to claim 8, wherein the pests are selected from the families Tetranychidae, Tenuipalpidae, Eriophyidae, Tarsonemidae, Acaridae, Heteroderidae.

10. The use according to claim 9, wherein the pests are selected from Tetranychus urticae, Tetranychus cinnabarinus, Panonychus ulmi, Panonychus citri, Meloidogyne incognita, etc.

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