Pyridazine compounds, their preparation methods and uses

Abstract

The compounds represented by formula (I) of this invention exhibit excellent activity against a variety of pests and mites in agriculture or other fields. Furthermore, these compounds achieve good control effects at very low doses, and therefore can be used to prepare insecticides and / or acaricides.

Description

Technical Field

[0001] This invention belongs to the field of insecticide and acaricide technology, specifically relating to pyridazine compounds, their preparation methods, and uses. Background Technology

[0002] Pesticides have played a vital role in increasing agricultural production and solving human food problems. With increasing demands for the safety and environmental impact of chemical substances, there is a growing need to develop safer pest control agents. Furthermore, due to the long-term use of pesticides and acaricides, pests have gradually developed resistance to these biological control agents, leading to unsatisfactory control effects. Therefore, developing pest control agents with excellent safety, control efficacy, and residue effects is a future development trend.

[0003] Patent document WO2010034737 discloses the following general formula compound and pyridazine compound CK1:

[0004]

[0005] Patent document CN 103492378 A discloses the following general formula compound and pyridazine compound CK2:

[0006]

[0007] However, the bioactivity of the aforementioned compounds still needs further improvement. The inventors conducted in-depth research to discover insecticides and acaricides with superior performance. Summary of the Invention

[0008] To address the aforementioned problems, the present invention provides compounds represented by formula (I), their stereoisomers, racemates, tautomers, nitrides, or pharmaceutically acceptable salts thereof.

[0009]

[0010] R1 is selected from C1-C6 alkyl, halo-C1-C4 alkyl, C3-C6 cycloalkyl or halo-C3-C6 cycloalkyl;

[0011] R2 is selected from C1-C4 alkyl groups;

[0012] R3 is selected from H or C1-C4 alkyl groups;

[0013] R4 is selected from C1-C4 alkyl groups;

[0014] R5 is selected from C3-C6 cycloalkyl, halo-C3-C6 cycloalkyl, C3-C6 cycloalkyl C1-C2 alkyl, halo-C3-C6 cycloalkyl C1-C2 alkyl, or C3-C6 epoxy alkyl C1-C2 alkyl;

[0015] A is selected from CH or N;

[0016] X is selected from O or S.

[0017] According to an embodiment of the present invention: in formula (I),

[0018] R1 is selected from C2-C6 alkyl, halo-C1-C4 alkyl, C3-C6 cycloalkyl or halo-C3-C6 cycloalkyl;

[0019] R2 is selected from C1-C4 alkyl groups;

[0020] R3 is selected from H or C1-C4 alkyl groups;

[0021] R4 is selected from methyl or ethyl;

[0022] R5 is selected from C3-C6 cycloalkyl, halo-C3-C6 cycloalkyl, C3-C6 cycloalkyl C1-C2 alkyl, halo-C3-C6 cycloalkyl C1-C2 alkyl, or C3-C6 epoxy alkyl C1-C2 alkyl;

[0023] A is selected from N or CH;

[0024] X is selected from O or S.

[0025] According to an embodiment of the present invention: in formula (I),

[0026] R1 is selected from C2-C3 alkyl, halo-C1-C3 alkyl, C3-C6 cycloalkyl or halo-C3-C6 cycloalkyl;

[0027] R2 is selected from C1-C3 alkyl groups;

[0028] R3 is selected from H or methyl;

[0029] R4 is selected from methyl or ethyl;

[0030] R5 is selected from C3-C6 cycloalkyl, halo-C3-C6 cycloalkyl, C3-C6 cycloalkyl C1-C2 alkyl, halo-C3-C6 cycloalkyl C1-C2 alkyl, or C3-C6 epoxy alkyl C1-C2 alkyl;

[0031] A is selected from N or CH;

[0032] X is selected from O or S.

[0033] According to an embodiment of the present invention, the halogenated C3-C6 cycloalkyl group is a group substituted with one, two, or three F, Cl, or Br groups, namely cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl.

[0034] According to an embodiment of the present invention, the halogenated C3-C6 cycloalkyl C1-C2 alkyl group is a group substituted with one, two, or three F, Cl, or Br groups, such as: As an example, the halogenated C3-C6 cycloalkyl C1-C2 alkyl group is selected from the following:

[0035] According to an embodiment of the present invention: in formula (I),

[0036] R1 is selected from ethyl, n-propyl, isopropyl, cyclopropyl, cyclobutyl, one, two or more fluorine or chlorine-substituted groups of the following: methyl, ethyl, n-propyl, isopropyl, cyclopropyl or cyclobutyl.

[0037] R2 is selected from methyl, ethyl, or propyl;

[0038] R3 is selected from H or methyl;

[0039] R4 is selected from methyl or ethyl;

[0040] R5 is selected from cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl,

[0041] A is selected from N or CH;

[0042] X is selected from O or S.

[0043] According to some embodiments of the present invention, formula (I) is selected from the structure shown in formula (IA):

[0044]

[0045] Among them, A, X, R4, and R5 have the definitions described above.

[0046] According to an embodiment of the present invention, in formula IA, A is selected from N or CH;

[0047] X is selected from O or S;

[0048] R4 is selected from methyl or ethyl;

[0049] R5 is selected from As an example, the compound of formula (I) is selected from the following compounds:

[0050]

[0051]

[0052]

[0053]

[0054]

[0055]

[0056]

[0057]

[0058]

[0059]

[0060] Among the substituents listed above, The location indicates the connection point.

[0061] The present invention also provides a method for preparing the compound shown in formula (I) above, which, when X is O, includes the following steps A) or B): Step A): The compound of formula (II) undergoes a condensation reaction with the compound of formula (III) to obtain the compound of formula (I);

[0062]

[0063] Step B):

[0064] Compound B1) reacts with a halogenating agent to give compound (II-1);

[0065] Compound B2) reacts with compound (III) to give compound (I);

[0066]

[0067] R1, R2, R3, R4, R5, and A have the definitions described above; L is selected from leaving groups, such as Cl, Br, I, or F.

[0068] According to an embodiment of the present invention, the reaction in step A) can be carried out in the presence of a condensing agent, such as at least one selected from N,N′-dicyclohexylcarbodiimide (DCC), N,N′-diisopropylcarbodiimide (DIC), 1-hydroxybenzotriazole (HOBT), 2-(7-azabenzotriazole)-N,N,N′,N′-tetramethylurea hexafluorophosphate (HATU), and benzotriazole-1-yl-oxytripyrrolidinephosphide hexafluorophosphate (PyBOP).

[0069] According to an embodiment of the present invention, the reaction in step A) can be carried out in the presence of a base, which can be an inorganic base, such as at least one selected from pyridine, triethylamine, 4-(dimethylamino)pyridine (DMAP), and diisopropylethylamine (DIEA);

[0070] According to an embodiment of the present invention, the reaction in step A) is carried out in a solvent, the solvent being selected, for example, at least one selected from N,N-dimethylacetamide, N,N-dimethylformamide, tetrahydrofuran, 2-methyltetrahydrofuran, dioxane, acetonitrile, toluene, dichloromethane, and 1,2-dichloroethane;

[0071] According to an embodiment of the present invention, the reaction temperature in step A) can be -5 to 120°C, for example 0 to 50°C, such as 15 to 50°C.

[0072] According to an embodiment of the present invention, the halogenating agent in step B1) is selected, for example, from thionyl chloride, oxalyl chloride, or thionyl chloride;

[0073] According to an embodiment of the present invention, the temperature of the reaction in step B1) can be 0 to 100°C, for example 0-50°C, such as 0-30°C;

[0074] According to an embodiment of the present invention, the reaction in step B2) can be carried out in the presence of a base, which may be selected from organic or inorganic bases, such as pyridine, triethylamine, 4-(dimethylamino)pyridine (DMAP), diisopropylethylamine (DIEA), sodium carbonate, potassium carbonate, sodium hydroxide, potassium hydroxide, potassium tert-butoxide, or sodium hydride, etc., one, two, or more of these. Preferred solvents may be N,N-dimethylacetamide, N,N-dimethylformamide, dioxane, toluene, dichloromethane, or 1,2-dichloroethane.

[0075] According to an embodiment of the present invention, the temperature of the reaction in step B2) can be 0 to 120°C, for example 0-50°C, such as 15-30°C.

[0076] According to the present invention, the compound shown in formula (I) can also be prepared by reacting the compound shown in (I-1) with the compound shown in (IV).

[0077]

[0078] R1, R2, R3, R4, R5, X, and A have the definitions described above; L' is selected from leaving groups, such as Cl, Br, I, or F.

[0079] The reaction can be carried out in the presence of a base, which can be an organic or inorganic base, such as at least one selected from potassium tert-butoxide, sodium tert-butoxide, sodium hydride, cesium carbonate, 4-(dimethylamino)pyridine (DMAP), and diisopropylethylamine (DIEA).

[0080] According to an embodiment of the present invention, the reaction in step A) is carried out in a solvent, the solvent being selected, for example, at least one selected from N,N-dimethylacetamide, N,N-dimethylformamide, 2-methyltetrahydrofuran, dioxane, acetonitrile, and toluene;

[0081] According to an embodiment of the present invention, the reaction temperature in step A) can be -5 to 120°C, for example 20-80°C.

[0082] According to the present invention, when X is S in the compound represented by formula (I), it can be obtained by reacting the carbonyl compound represented by formula (I) with X being O with 2,4-bis(p-methoxyphenyl)-1,3-dithiodiphosphonium heterocyclic butane-2,4-sulfide (Lawson's reagent).

[0083]

[0084] Among them, R1, R2, R3, R4, R5, and A have the definitions described above.

[0085] According to the present invention, the compound of formula (I) can exist in the following three isomers, therefore the isomers described in this application include, but are not limited to, the following three forms:

[0086]

[0087] Among them, R1, R2, R3, R4, R5, X, and A have the definitions described above.

[0088] According to embodiments of the present invention, compounds II and III can be obtained commercially or prepared by methods known in the literature, for example, by methods described in patent documents WO2005040169, WO2008074824 or Journal of Fluorinechemistry 132(11), page 995 (2011).

[0089] The preparation of the compound of formula (I) and its starting materials in this article can be carried out according to the appropriate reaction conditions and the selection of starting materials in each case. For example, in a one-step reaction, only one substituent can be replaced by another substituent according to the invention, or multiple substituents can be replaced by other substituents according to the invention in the same reaction step.

[0090] If the compounds cannot be obtained via the above-described route, they can be prepared by deriving other compounds or by conventionally modifying the synthetic route.

[0091] After the reaction is complete, the reaction mixture can be post-processed in a conventional manner, such as by mixing with water, separating the phase, and, if appropriate, purifying the crude product by chromatography, for example, on alumina or silica gel.

[0092] Pharmaceutically acceptable salts of the compound of formula (I) of this invention can be prepared by known methods. For example, acid addition salts of the compound of formula (I) can be obtained by treatment with a suitable acid. The preparation method is as follows: reacting the compound of formula (I) with an acid such as hydrochloric acid, sulfuric acid, phosphoric acid, acetic acid, trifluoroacetic acid, malic acid, or citric acid in a solvent such as water, ether, or toluene can readily yield pharmaceutically acceptable salts of the compound of formula (I).

[0093] The above preparation method can obtain a mixture of isomers of compound (I). If pure isomers are required, they can be separated by conventional methods such as crystallization or chromatography.

[0094] Unless otherwise specified, all of the above reactions can be conveniently carried out at atmospheric pressure or at the pressure of the specific reaction itself.

[0095] The present invention also provides a pesticide composition, such as an insecticidal and / or acaricidal composition, comprising one, two or more of the following as active ingredients: a compound of formula (I), its stereoisomers, racemates, tautomers, nitrogen oxides or pharmaceutically acceptable salts thereof.

[0096] According to an embodiment of the present invention, the weight percentage of the active ingredient in the composition is 0.1-99.9%, for example, 0.5-99%.

[0097] According to embodiments of the present invention, the composition further includes one, two, or more of agricultural and / or forestry and / or sanitary acceptable carriers.

[0098] According to an embodiment of the present invention, the composition can be administered in the form of a formulation.

[0099] For example, the compound shown in formula (I) is dissolved or dispersed in a carrier or formulated as an active ingredient to facilitate dispersion when used as an insecticide and / or acaricide.

[0100] According to embodiments of the present invention, the formulation includes, but is not limited to, the following forms: wettable powder, oil suspension, water suspension, water emulsion, aqueous solution, emulsifiable concentrate or microcapsule, etc.

[0101] According to embodiments of the invention, a liquid or solid carrier and optionally a surfactant may also be added to the composition.

[0102] The present invention also provides the use of one, two or more of the compounds of formula (I), their stereoisomers, racemates, tautomers, nitrogen oxides or pharmaceutically acceptable salts thereof as pesticides, such as insecticides and / or acaricides.

[0103] The present invention also provides the use of one, two or more of the compounds of formula (I), their stereoisomers, racemates, tautomers, nitrogen oxides or pharmaceutically acceptable salts thereof in the preparation of pesticides, such as insecticides and / or acaricides.

[0104] The present invention also provides a method for controlling pests and / or mites, comprising applying an effective amount of one, two or more of the following: a compound of formula (I), its stereoisomers, racemates, tautomers, nitrogen oxides or pharmaceutically acceptable salts thereof, or applying the composition to a growth medium of pests and / or mites.

[0105] According to an embodiment of the present invention, the effective amount is 10 to 1000 grams per hectare, preferably 20 to 500 grams per hectare.

[0106] The active substances according to the present invention, or the active substances to be used according to the present invention, are suitable for protecting plants and plant organs, increasing yield, improving the quality of harvested products, and controlling pests, particularly in agriculture, horticulture, animal husbandry, forestry, gardens and recreational facilities, in warehouse pest control and material protection, and in the sanitation field, where pests and mites are present. They are preferably used as plant protection compositions. They are active against conventionally susceptible and resistant species and against all or individual developmental stages. The aforementioned pests and mites include, but are not limited to:

[0107] Arthropoda, especially Arachnida, includes species such as *Acarus* spp., *Aceriasheldoni*, *Aculops* spp., *Aculus* spp., *Amblyomma* spp., *Amphitetranychus viennensis*, *Argas* spp., *Boophilus* spp., *Brevipalpus* spp., *Bryobiagraminum*, *Bryobiapraetiosa*, *Centruroides* spp., and *Chorioptes*. spp.), Dermanyssus gallinae, Dermatophagoides pteronyssinus, Dermatophagoides farinae, Dermacentor spp., Eotetranychus spp., Epirimerus pyri, Eutetranychus spp., Eriophyes spp., Glycyphagus domesticus, Halotydeus destructor, Hemitarsonemus spp., Hyalomma spp., Ixodes spp., Latrodectus spp., Loxosceles spp., Metatatetranychus spp.), Neutrombicula autumnnalis, Nuhersa spp., Oligoychus spp., Ornithodorus spp., Ornithonyssus spp., Panonychus spp., Phyllocoptrutaoleivora, Polyphagotarsonemuslatus, Psoroptes spp., Rhipicephalus spp., Rhizoglyphus spp., Sarcoptes spp.), Middle Eastern golden scorpion (Scorpiomaurus), Steneotarsonemus spp., Steneotarsonemus spinki, Tarsonemus spp., Tetranychus spp., Trombicula alfreddugesi, Vaejovis spp., Vasateslycopersici;

[0108] Coleoptera (Beetles): * *Acanthoscelides* spp. (bean weevil), * *Acanthoscelides obtectus* (common pea weevil), * *Agrilus planipennis* (flowering ash beetle), * *Agriotes* spp. (wireworm), * *Anoplophoraglabripennis* (Asian longhorn beetle), * *Anthonomus* spp. (cotton boll weevil), * *Anthonomus grandis* (cotton boll weevil), * *Aphidius* spp. (branch wasp), * *Apion* spp. (weevil), * *Apogonia* spp. (cane beetle grub), * *Atacnius sprctulus* (black velvet beetle), * *Atomaria linearis* (small beetle beetle). The following species are listed: mangold beetle, Aulacophore spp., Bothynoderes punctiventris (beef root weevil), Bruchus spp. (beef weevil), Bruchus pisorum (pea weevil), Cacoesia spp., Callosobrus maculatus (southern cowpea weevil), Carpophilus hempteras (dried fruit beetle), Cassida vittata, Ccrostcrna spp., Ccrotoma spp. (chrysomcids), Cerotoma trifur cata (bean leaf beetle), and Ceutorhynchus (turtle weevil). spp. (weevils), *Ceutorhynchus assimilis* (cabbage seedpod weevil), *Ceutorhynchus napi* (cabbage curculio), *Chaetocnema spp.* (golden trichomoniasis), *Colaspis spp.*(Earth beetle), Conoderus scalaris, Conoderus stigmosus, Conotrachelus nenuphar (Plum beetle), Cotinus nitidis (Green Junebeetle), Crioceris asparagi (Earth beetle), Cryptolestes ferrugincus (Rusty grain beetle), Cryptolestes pusillus (Flat grain beetle), Cryptolestes turcicus (Turkish grain beetle), Ctenicera spp. (Nematode), Curculio spp. (Weevil), Cyclocephala spp. (Grub), Cylindrocpturus (Dense-spotted twig weevil) *Adpersus* (sunflower stem weevil), *Deporaus marginatus* (mango leaf-cutting weevil), *Dermestes lardarius* (ham weevil), *Dermestes maculates* (white-bellied weevil), *Diabrotica spp.* (leaf beetle), *Epilachna varivcstis* (Mexican beetle), *Raustinus cubae* (stem borer), *Hylobius pales* (fighting weevil), *Hypera spp.* (leaf weevil), *Hypera postica* (alfalfa leaf weevil), *Hyperdoes spp.* (Argentine stem weevil), *Hypothenemus* (coffee berry weevil). hampei (coffee fruit beetle), species of the genus Ips spp.(Spiny-legged beetle (engravers)), Tobacco beetle (Lasioderma serricorne), Potato beetle (Leptinotarsa ​​decemlineata), Liogenys fuscus, Liogenys suturalis, Rice water weevil (Lissorhoptrus oryzophilus), Powder beetle (Lyctus spp.), Powder post beetle (Maecolaspis joliveti), Megascelis spp., Corn beetle (Melanotus communis), Blossom beetle (Meligethes spp.), Blossom beetle (Meligethes aeneus), Common European beetle (Melolontha melolontha), Oberea brevis, Longhorn beetle (Oberea brevis) * *linearis*, *Oryctesrhinoceros* (date palm beetle), *Oryzaephilus mercator* (merchant grain beetle), *Oryzaephilus surinamensis* (sawtooth grain beetle), *Otiorhynchus spp.* (weeviler), *Oulemamelanopus* (orange-legged leaf beetle), *Oulema oryzae*, *Pantomorus spp.* (weeviler), *Phyllophaga spp.* (May / June beetle), *Phvllophaga cuyabana*, *Phyllotreta* (yellow-striped flea beetle). spp. (Golden Trichomonas), species of the genus Phynchites spp.), Japanese scarab beetle (Popillia japonica), large grain borer (Prostephanus truncates), lesser grain borer (Rhizoperthadominica), European scarab beetle (Rhizotrogus spp.), weevil (Rhynchophorus spp.), wood moth (Scolytus spp.), grain weevil (Shenophorus spp.), pea leaf weevil (Sitonalincatus), rice weevil (Sitophilus spp.), grain weevil (Sitophilus granaries), rice weevil (Sitophilus oryzae). The following species are listed: *Stegobium paniceum* (drugstore beetle), *Tribolium spp.* (face beetle), *Tribolium castaneum* (red flour beetle), *Tribolium confusum* (confused flour beetle), *Trogoderma variabile* (warehouse beetle), and *Zabrus tenebioides*.

[0109] Dermaptcra (earwigs).

[0110] Neuroptera (cockroaches): German cockroach (Blattella germanica), Oriental cockroach (Blatta orientalis), Pennsylvania wood cockroach (Parcoblatta pennylvanica), American cockroach (Periplaneta americana), Australian cockroach (Periplaneta australoasiae), brown cockroach (Pcriplancta brunnca), smoky brown cockroach (Periplaneta fuliginosa), sugarcane cockroach (Pyncoselus suninamensis). cockroach) and long-bearded cockroach (Supella longipalpa) (brownbanded cockroach).

[0111] Diptera (flies): *Aedes* spp. (mosquito), *Agromyza frontella* (alfalfa leafminer), *Agromyza* spp. (leafminer), *Anastrepha* spp. (fruit fly), *Anastrepha suspensa* (Caribbean fruit fly), *Anopheles* spp. (mosquito), *Batrocera* spp. (fruit fly), *Bactroceracucurbitae* (melon fly), *Bactroceradorsalis* (orange fruit fly), *Ceratitis* spp. (fruit fly), *Ceratitiscapitata* (Mediterranean fruit fly), *Chrysops* (tigerfly). *Cochliomyia spp.* (spp.) (deer fly), *Cochliomyia* spp. (slipper fly larvae), *Contarinia* spp. (slipper fly), *Culex* spp. (mosquito), *Dasineura* spp. (slipper fly), *Dasineura brassicae* (cabbage leaf fly), *Delia* spp., *Delia pla tura* (seed cornmaggot), *Drosophila* spp. (vinegar fly), *Fannia* spp. (housefly), *Fannia canicularis* (little house fly), *Fannia scalaris* (grey-bellied house fly), *Gasterophilus intestinalis* (horse stomach fly), *Gracillia* perseae, Haematobia irritans (hornfly), Hylemyia spp. (root maggot), Hypoderma lineatum (common cattle grub), Liriomyza spp.(Leaf miner), cabbage leafminer (Liriomyza brassica), sheep tick (Melophagus ovinus), housefly (Musca spp.), face fly (Muscaa utumnalis), housefly (Vuscadomestica), sheep bot fly (Oestrusovis), Swedish straw fly (Oscinella frit), beetleafminer (Pegomyia betae), carrot rust fly (Psila rosae), cherry fruit fly (Rhagoletis cerasi), apple fruit fly (Rhagoletis) The following species are listed: *Pomonella* (apple maggot), *Sitodiplosismosellana* (orange wheat blossom midge), *Stomoxyscalcitruns* (stable fly), *Tahanus* spp. (horsefly), and *Tipula* spp. (large mosquito).

[0112] Hemiptera (bugs): * *Acrosternum hilare* (green stinkbug), * *Blissus leucopterus* (chinch bug), * *Calocoris norvegicus* (potato mirid), * *Cimex hemipterus* (tropical bed bug), * *Cimex lectularius* (bed hug bug), * *Daghertus fasciatus*, * *Dichelops furcatus*, * *Dysdercus suturellus* (cottonstainer), * *Edessa meditabunda*, * *Eurygaster maura* (cereal bug), * *Euschistus heros*, * *Euschistus* (brown stink bug). The following species are listed: *Helopeltis antonii* (brown stink bug), *Helopeltis theivora* (tea blightplant bug), *Lagynotomus spp.* (stink bug), *Leptocorisa oratorius* (large rice-margined bug), *Leptocorisa varicornis* (different rice-margined bug), *Lygus spp.* (plant bug), *Lygushesperus* (western tarnished plant bug), *Maconellicoccushirsutus* (hibiscus pink bug), *Neurocolpus longirostris* (southern greenstink bug), and *PhyLocoris spp.* (plant bug).(Mirid bug), California plant mirid bug (Phytocoris californicus), Phytocoris relativus, Piezodorus guildingi, four-lined plant bug (Poecilocapsus lineatus), Psallus vaccinicola, Pseudacystaperseae, Scaptocoris castanea, and Triatoma spp. (bloodsucking conenose bug / kissing bug).

[0113] Homoptera (aphids, scale insects, whiteflies, leafhoppers): Pea aphid (Acrythosiphonpisum), Adelges spp. (adelg ds), cabbage whitefly (Aleurodesproletella), spiral whitefly (Aleurodicus di sperses), woolly whitefly (Aleurothrixus flccosus), white-skinned scale (Aluacaspisspp.), Amrasca bigutella bigutella, leafhopper (Aphropho ra spp.), red scale (Aonidiella aurantii), aphid (Aphis spp.), cotton aphid (Aphis gossypii). Apple aphid (Aphis pomi), foxglove aphid (Aulacorthitm solani), whitefly (Bemisia spp.), silver leaf aphid (Bemisia argentifolii), sweet potato whitefly (Bemisia tabaci), tobacco whitefly (Bemisia tabaci (Gennadius)), Russian aphid (Brachycolus noxius), asparagus aphid (Brachycorynclia asparagi), cabbage aphid (Brevicoryne brassicae), scale insect (Ceroplastes spp.), red wax scale (Ceroplastes rubens). Scale, *Chionaspis* spp. (scale), *Chrysomphalus* spp. (scale), *Coccus* spp. (scale), *Dysaphis plantaginea* (rosy apple aphid), *Empoasca* spp.(Leafhopper), Apple cotton aphid (Eriosoma lanigerum) (woolly apple aphid), Cottony scale (Icerya purchasi) (cottonycushion scale), Mango yellow-lined leafhopper (Idioscopus nitidulus) (mango leafhopper), Smaller brown planthopper (Laodelphax striatellus) (Laodelphax striatellus), Species of Lepidosaphesspp., Species of Macrosiphum spp., Macrosiphum euphorbiae (potato aphid), English grain aphid (Macrosiphum granarium), Rose aphid (Macrosiphum rosae) (rose aphid), Four-lined leafhopper (Macrosteles quadrilin eatus) (aster leafhopper) The following species are listed: Mahanarvafrimbiolata, Metopolophium dirhodum (rose grain aphid), Midis longicornis, Myzus persicae (green peach aphid), Nephotettix spp. (leafhopper), Nephotettix cinctipes (green leafhopper), Nilaparvata lugens (brown planthopper), Parlatoria pergandii (chaff scale), Parlatoriaziziphi (ebony scale), Peregrinus maidis (corn delphacid), Philaenus spp. (blower), Phylloxera vitifoliae (grape phylloxera), Physokermes *Pseudococcus* (spruce bud scale), *Planococcus* spp. (meat scale), *Pseudococcus* spp.(Pincapple mcaly bug), Pineapple mcaly bug (Pscudococcus brcvipcs), Orchard scale (Quad raspidiotus perniciosus) (San Jose scale), Aphid species (Rhapalosiphum spp.) (Aphid), Corn leaf aphid (Rhapalosiphum maida) (corn leafaphid), Oatbird-cherry aphid (Rhapalosiphumpadi), Scale insect (Saissetia spp.) (scale insect), Black scale insect (Saissetiaoleae), Green bug (Schizaphis graminum), British wheat aphid (Sitobion avenge), White-backed planthopper (Sogatella) *Furcifera* (white-backed planthopper), *Therioaphis* spp. (aphid), *Toumeyella* spp. (scale insect), *Toxoptera* spp. (aphid), *Trialeurodes* spp. (whitefly), *Trialeurodes vaporariorum* (greenhouse whitefly), *Trialeurodes abutiloneus* (bandedwing whitefly), *Unaspis* spp. (scale insect), *Unaspis yanonensis* (arrowhead scale), and *Zulia entreriana*.

[0114] Hymenoptera (ants, wasps, and bees): *Acromyrrmex* spp., *Athalia rosae*, *Atta* spp. (leafcutting ants), *Camponotus* spp. (carpenter ant), *Diprion* spp. (sawfly), *Formica* spp. (ant), *Iridomyrmex humilis* (Argentine ant), *Monomorium* spp. (subspecies), *Monomorium minumum* (littleblack ant), *Monomorium pharaonis* (Pharaoh ant), *Neodiprion* spp. (sawfly), *Pogonomyrmex* spp. (harvester ants), Polistes spp. (paperwasp), Solenopsis spp. (fire ants), Tapoinum sessile (odorous house ants), Tetranomorium spp. (pavement ants), Vespula spp. (yellow jacket ants), and Xylocopa spp. (carpenter bees).

[0115] Isoptera (termites): *Coptotermes spp.*, *Coptotermes curvignathus*, *Coptotermes frenchii*, *Coptotermes formosanus* (Formosan subterranean termite), *Cornitermes spp.* (nasute termite), *Cryptotermes spp.* (drywood termite), *Heterotermes spp.* (desert subterranean termite), *Ileterotermes aureus*, *Kalotermes spp.* (drywood termite), *Incistitermes spp.* (drywood termite), *Macrotermes* *Reticulitermes* spp. (fungus growing termite), *Marginitermes* spp. (drywood termite), *Microcerotermes* spp. (harvester termite), *Microtermes obesi*, *Procornitermes* spp., *Reticulitermes* spp. (soil-dwelling termite), *Reticulitermes banyulensis*, *Reticulitermes grassei*, *Reticulitermes f la vi pes* (eastern soil-dwelling termite), *Reticulitermes hageni*, *Reticulitermes hesperus* (western soil-dwelling termite), *Reticulitermes santonensis*, *Reticulitermes santonensis* *Reticulitermes speratus*, *Reticulitermes tibialis*, *Reticulitermes virginicus*, *Schedorhinotermes spp.*, and *Zootermopsis spp.* (wood-rotting termite).

[0116] Lepidoptera (moths and butterflies): *Achoea janata*, *Adoxophyes* spp., *Adoxophyes orana*, *Agrotis* spp. (root cutter), *Agrotis ipsilon* (black root cutter), *Alabama argillacea* (cottonleaf worm), *Amorbia cuneana*, *Amyelosi transitella* (navel orange worm), *Anacamptodes defectaria*, *Anarsia lineatella* (peach twig borer), *Anomis sabulijera* (jute looper), *Anticarsiag emmatalis* (velvetbean caterpillar), *Archips argyrospila* (fruit tree leafroller), *Archips rosana* (rose leafroller). The following moths are listed: leafroller, *Argyrotaenia* spp. (tortricid moths), *Argyrotaenia citrana* (orange tortrix), *Autographa gamma*, *Bonagota cranaodcs*, *Borbocinnara* (rice leafroller), *Buccula trix thurberiella* (cotton leafperforator), *Caloptilia* spp. (leaf miner), *Capua reticulana*, *Carposina niponensis* (peach fruit moth), *Chilo* spp., *Chlumetia transversa* (mango shoot borer), *Choristoneurarosaceana* (obliquebanded leaf roller), and *Chrysodeixis* spp.The following species are listed: *Cnaphalocerus mediumis* (grass leafroller), *Colias spp.*, *Conpomorpha cramerella*, *Cossus cossus* (wood moth), *Crambuss spp.* (Sod webworms), *Cydia funebrana* (plum fruit moth), *Cydia molesta* (oriental fruit moth), *Cydianignicana* (pea moth), *Cydia pomonella* (codling moth), *Darna diducta*, *Diaphania spp.* (stem borer), and *Diatraeas spp.* (stalk borer). (The following are a list of species and their names, not part of the main text): *Diatraea saccharalis* (sugarcane borer), *Diatraea graniosella* (southwester cornborer), *Earias spp.* (cotton bollworm), *Earias insulata* (Egyptianbollworm), *Eariasvit.ella* (rough northern bollworm), *Ecdytopophaaurantianum*, *Elasmopalpus lignosellus* (lesser cornstalk borer), *Epiphysiaspostrutta na* (light brown apple moth), *Ephestia spp.* (almond moth), *Ephestia cautella* (almond moth), *Ephestia* (tobacco white moth). Tobacco moth (Ephestia kuehniella), Mediterranean flour moth (Ephestia kuehniella), and species of the genus Epimeces (Epimeces spp.).), Epinotia aporema, Erionota thrax (bananaskipper), Eupoecilia ambiguella (grape berry moth), Euxoa auxiliaris (armycutworm), Feltia spp. (root cutter), Gortyna spp. (stem borer), Grapholita molesta (peach (apricot) fruit borer), Hedylepta indicata (bean leaf webber), Helicoverpa spp. (noctuid moth), Helicoverpa *Helicoverpazea* (corn borer), *Heliothis* spp. (noctus), *Heliothis virescens* (tobacco budworm), *Hellula undalis* (cabbageweb worm), *Indarbela* spp. (root borer), *Keiferia lycopersicella* (tomato pinworm), *Leucinodesorbonalis* (eggplantfruit borer), *Leucoptera malifoliella*, *Lithocollectis* spp., *Lobesia botrana* (grape fruit moth), *Loxagrotis* spp. (noctus), *Loxagrotis albicosta* (western bean moth) Cutworm, gypsy moth (Lymantria dispar), apple leafminer (Lyonetia clerkella), oil palm bagworm (Mahasenacorbetti), and tent caterpillar (Malacosoma spp.).(tent caterpillars), cabbage armyworm (Mamestra brassicae), bean pod borer (Marucatestulalis), bagworm (Metisa plana), true armyworm (Mythimna unipuncta), small tomato borer (Neoleucinodes elegantalis), rice leaf roller (Nym phulade punctalis), winter moth (Operophtherabrumata), European corn borer (Ostrinianubilalis), Oxydia vesulia, common grape leaf roller (Pandemiscerasana), brown apple leaf roller (Pandemis heparana) The following species are listed: *Pectinophoragos sypiella* (red bollworm), *Peridroma spp.* (root cutter), *Peridroma saucia* (variegated cutworm), *Perileucopte ra coffeella* (white coffeeleafminer), *Phthorimaea operculella* (potato tuber moth), *Phyllocnisitis citrella* (citrus leafminer), and *Phyllonorycter spp.*(Leaf miner), cabbage white butterfly (Pieris ra pae), imported cabbage worm, green armyworm (Plathypenascabra), Indian meal moth (Plodia interpunctella), diamondback moth (Plutellaxylostella), grape berry moth (Polychrosis viteana), citrus endocarps, olive moth (Prsys oleae), armyworm (Pseudaletia spp.), armyworm (Pseudaletia unipunctata), soybean looper (Pseudoplusia includens), inchworm (Rachiplusia nu), rice stem borer (Chilo suppressalis), rice stem borer (Scirpophaga incertulas), stem borer (Sesamia) spp. (stem borer), rice stem borer (Sesamia inferens) (pink rice stemborer), rice stem borer (Sesamianona grioides), copper-spotted brown tussock moth (Setora nitens), wheat moth (Sitotroga cerealella) (Angoumois grain moth), grape long-bearded leafroller (Sparganothis pilleriana), armyworm (Spodoptera spp.), beet armyworm (Spodoptera exigua), fall armyworm (Spodoptcrafugipcrda), southern armyworm (Spodoptera oridania), root borer (Synanthedon spp.), Theclabasilides, Thermisia gemmatalis, clothes moth (Tineola) bisselliella (webbingclothesmoth), Trichoplusia ni (cabbage looper), Tomato leafminer (Tutsabsoluta), and Yponomeuta spp.The species include the coffee leopard moth (Zeuzeracoffeae) (red branchborer), the pear leopard moth (Zeuzerapyrina), and the beet armyworm (Spodoptera litura (Fabricius)).

[0117] Mallophaga (chewing lice): sheep louse (Bovicola ovis), chicken body louse (Menacanthus stramineus), and common hen house louse (Menopon gallinea).

[0118] Orthoptera (grasshoppers, locusts, and crickets): *Anabrus simplex* (Mormon cricket), *Gryllotalpidae* (mole cricket), *Locusta migratoria*, *Melanoplus spp.* (grasshopper), *Microcentrumretinerve* (angular winged katydid), *Pterophylla spp.* (katydid), *chistocerca gregaria*, *Scudderia furcata* (fork-tailed bush katydid), and *Valanga nigricorni*.

[0119] The order Phthiraptera (sucking louse): *Haematopinus spp.* (cattle and pig lice), *Linognathus ovillus* (sheep louse), *Pediculus humanus capitis* (body lice), *Pediculus humanus humanus* (body lice), and *Pthirus pubis* (crab louse).

[0120] Siphonaptera (fleas): Ctenocephalides canis (dog flea), Ctenocephalides felis (cat flea), and Pulex irritans (human flea).

[0121] Thysanoptera (Thrips): Tobacco thrips (Frankliniella fusca), Western flower thrips (Frankliniella occidentalis), Frankliniella shultzei, Corn thrips (Frankliniella williamsi), Greenhouse thrips (Ilioliothrips haemorrhaidalis), Riphiphorothrips cruentatus, Scirtothrips spp., Citrus thrips (Scirtothrips cirri), Yellow tea thrips (Scirtothrips dorsalis), Taeniothrips rhopalantennalis, and Thrips spp.

[0122] Thysanura (bristletails): Lepisma spp. (silverfish) and Thermobia spp. (thermobia).

[0123] Order Acarina (mites and ticks): *Acarapsis woodi* (tracheal mite of honeybee), *Acarus spp.* (food mite), *Acarus siro* (grain mite), *Aceria mangiferae* (mango bud mite), *Aculops spp.*, *Aculops lycopersici* (tomatorussetmite), *Aculops pelekasi*, *Aculus pelekassi*, *Aculus schlechtendali* (apple rust mite), *Amblyommaamcricanum* (lone star tick), *Boophilus* spp. (tick), *Brevipalpus obovatus* (privet mite), *Brevipalpus phoenicis* (red and blackflat mite), *Demodex* spp. (mange mites), *Dermacentors* spp. (hard tick), *Dermacentor variabilis* (American dog tick), *Dermatophagoides pteronyssinus* (house dust mite), *Eotetranycus* spp., *Eotetranychus carpini* (yellow spider mite), *Epitimerus* spp., *Eriophyes* spp., *Metatetranycus* spp. (tick), *Metatetranycus* spp. spp.), cat ear mite (Notoedres cati), small claw mite (Oligonychus spp.), coffee small claw mite (Oligonychus coffee), southern red claw mite (Oligonychus ilicus), panonychus spp.The following are listed as examples of spider mites: * *Panonychuscirri* (citrus-red mite), * *Panonychus ulmi* (European red mite), * *Phyllocoptruta oleivora* (citrus rust mite), * *Polyphagotarsonemun latus* (broad mite), * *Rhipicephalus sanguineus* (brown dog tick), * *Rhizoglyphus spp.* (bulb mite), * *Sarcoptes scabiei* (itch mite), * *Tegolophus perseaflorae* (avocado gall mite), * *Tetranychus spp.* (tetranychus urticae) (two-spotted spider mite). The mite (Varroa destructor) and the bee mite.

[0124] Nematodes (Nematodes): *Aphelenchoides* spp. (bud and leaf nematode and pine wood nematode), *Belonolaimus* spp. (sting nematodes), *Criconemella* spp. (ring nematodes), *Dirofilaria immitis* (dog heartworm), *Ditylenchus* spp. (stem and bulb nematodes), *Heterodera* spp. (cyst nematode), *Heterodera zeae* (corncyst nematode), *Hirschmanniella* spp. (root nematodes), *Hoplolaimus* spp. (lance nematodes), *Meloidogyne* (root-knot nematode). The species *Meloidogyne incognita* (root-knot nematode), *Onchocercavolvulus* (hook-tail worm), *PraLylenchus* (lesion nematode), *Radiopholus* (burrowing nematode), and *Rotylenchus reniformis* (kidney-shaped nematode) are listed.

[0125] Synthetic class (synthetic insects): White pine worm (Scutigerella immaculata).

[0126] As an example, the pests are selected from peach aphids, tobacco whiteflies, scale insects, brown planthoppers, or tea green leafhoppers.

[0127] As an example, the mites are selected from Tetranychus cinnabarinus or Tetranychus two-spotted.

[0128] Due to their positive properties, compounds of formula (I) can be advantageously used to protect important crops, livestock and breeding stock in agriculture and horticulture, as well as environments frequented by humans, from pests and / or mites.

[0129] To achieve the desired effect, the amount of compound (I) used varies depending on various factors, such as the compound used, the crop being protected, the type of pest, the degree of infection, climatic conditions, the application method, and the formulation used.

[0130] The selection of dosage forms or compositional components described herein should be consistent with the physical properties of the active ingredient, the method of application, and environmental factors such as soil type, humidity, and temperature.

[0131] Useful dosage forms include liquids such as solutions (including emulsifiable concentrates), suspensions, emulsions (including microemulsions and / or suspensions), etc., which can optionally be thickened into a gel. Useful dosage forms also include solids such as powders, granules, tablets, pills, films, etc., which can be water-dispersible (“wettable”) or water-soluble. Active ingredients can be microencapsulated and re-formed into suspensions or solid dosage forms; alternatively, the entire dosage form of the active ingredient can be encapsulated. Encapsulation can control or delay the release of the active ingredient. Sprayable formulations can be diluted in a suitable medium, with a spray volume of approximately one hundred to several hundred liters per hectare. High-concentration compositions are primarily used as intermediates for further processing.

[0132] Typical solid diluents are described in Watkins et al., Handbook of Insecticide Dust Diluents and Carriers, 2nd Ed., Dorland Books, Caldwell, New Jersey. Typical liquid diluents are described in Marsden, Solvents Guide, 2nd Ed., Interscience, New York, 1950. McCutcheon's Detergents and Emulsifiers Annual, Allured Publ. Corp., Ridgewood, New Jersey, and Sisely and Wood, Encyclopedia of Surface Active Agents, Chemical Publ. Co., Inc., New York, 1964, list surfactants and recommended applications. All formulations may contain small amounts of additives to reduce foaming, corrosion, microbial growth, etc., or thickeners to increase viscosity.

[0133] Surfactants include, for example, polyethoxylated alcohols, polyethoxylated alkylphenols, polyethoxylated sorbitan fatty acid esters, sulfonated dialkyl succinate, alkyl sulfates, alkylbenzene sulfonates, organosilanes, N,N-dialkyl taurate, lignin sulfonates, naphthalene sulfonates with aldehyde condensates, polycarboxylate esters, and polyoxyethylene / polyoxypropylene block copolymers.

[0134] Solid diluents include, for example, clays such as bentonite, montmorillonite, magnesia and kaolin, starch, sugar, silica, talc, diatomaceous earth, urea, calcium carbonate, sodium carbonate and sodium bicarbonate, and sodium sulfate; liquid diluents include, for example, water, N,N-dimethylformamide, dimethyl sulfone, N-alkylpyrrolidone, ethylene glycol, polypropylene glycol, paraffin, alkylbenzene, alkylnaphthalene, olive oil, castor oil, linseed oil, tung oil, sesame oil, corn oil, peanut oil, cottonseed oil, soybean oil, rapeseed oil and cocoa butter, fatty acid esters, ketones such as cyclohexanone, 2-heptanone, isophorone and 4-hydroxy-4-methyl-2-pentanone, and alcohols such as methanol, cyclohexanol, dodecyl alcohol and tetrahydrofuran alcohol.

[0135] Solutions, including emulsifiable concentrates, can be prepared by simply mixing the components. Powders and fine powders can be prepared by mixing and, typically, by grinding in a hammer mill or hydraulic mill. Suspensions are generally prepared by wet milling; see, for example, US 3060,084. Granules and pellets are prepared by spraying the active ingredient onto freshly made granular carriers or by granulation techniques. See Browning, “Agglomeration,” Chemical Engineering, December 4, 1967, pp. 147-48; Perry’s Chemical Engineer’s Handbook, 4th Ed., McGraw-Hill, New York, 1963, Pages 8-57 and following, and WO 91 / 13546. Pellet preparation is described in US 4172714, and water-dispersible and water-soluble granules are prepared by methods described in US 4144050, US 3920442, and DE 3246493. Tablets may be prepared as described in US 5180587, US5232701, and US5208030. Films may be prepared as described in GB2095558 and US3299566.

[0136] More information on the processing can be found in US 3,235,361, Col. 6, line 16 through Col. 7, line 19 and Examples 10-41; US ​​3,309,192, Col. 5, line 43 through Col. 7, line 62 and Examples 8, 12, 15, 39, 41, 52, 53, 58, 132, 138-140, 162-164, 166, 167 and 169-182; US 2,891,855, Col. 3, line 66 through Col. 5, line 17 and Examples 1-4; Klingman, Weed Control as a Science, John Wiley and Sons, Inc., New York 1961, pp 81-96; and Hance et al., Weed Control Handbook, 8th Ed., Blackwell Scientific Publications, Oxford, 1989.

[0137] In this document, for certain applications of the composition, such as in agriculture, one, two or more other fungicides, insecticides, acaricides, herbicides, plant growth regulators or fertilizers may be added to the insecticidal and / or acaricidal compositions of the present invention, thereby producing additional advantages and effects.

[0138] Beneficial effects

[0139] The compounds of formula (I) described in this invention exhibit excellent activity against a variety of pests and mites in agriculture or other fields. Furthermore, these compounds achieve good control effects at very low doses, and therefore can be used to prepare insecticides and / or acaricides.

[0140] Terminology Definitions and Explanations

[0141] Unless otherwise defined, all technical terms in this document have the same meanings as commonly understood by one of ordinary skill in the art to which the subject matter of the claims pertains. Unless otherwise stated, all patents, patent applications, and publications cited in this document are incorporated herein by reference in their entirety. If multiple definitions exist for terms in this document, the definitions in this chapter shall prevail.

[0142] It should be understood that references (including Carey and Sundberg, "Advanced Organic Chemistry 4") may be included. THDefinitions of standard chemical terms can be found in ED. "Vols. A (2000) and B (2001), Plenum Press, New York". Unless otherwise stated, conventional methods within the scope of the art, such as mass spectrometry, NMR, IR and UV / Vis spectroscopy, and pharmacological methods, are used. Unless specifically defined, the terms used herein in the relevant descriptions of analytical chemistry, organic synthetic chemistry, and pharmaceutical and medicinal chemistry are those known in the art. Standard techniques may be used in chemical synthesis, chemical analysis, drug preparation, formulation and delivery, and in the treatment of patients. For example, reactions and procedures may be carried out using the manufacturer's instructions for use of reagent kits, or in accordance with methods known in the art or the descriptions herein. Purification is then performed. The techniques and methods described above are typically carried out according to conventional methods well known in the art, based on the descriptions in several general and more specific references cited and discussed in this specification. In this specification, groups and their substituents can be selected by those skilled in the art to provide stable structural moieties and compounds. When a substituent is described by a conventional chemical formula written from left to right, the substituent also includes chemically equivalent substituents obtained when the structural formula is written from right to left, provided they conform to the valence bond rules. For example, CH2O is equivalent to OCH2 and can be linked to the substitution position by an oxygen atom or a carbon atom of a methylene group.

[0143] As used herein, the term "pharmaceutically acceptable salt" refers to a salt that retains the bioavailability of the free acid and free base of the specified compound and has no adverse effects in biological or other respects. The compounds in this application also include pharmaceutically acceptable salts, such as nitrates, hydrochlorides, sulfates, phosphates, acetates, trifluoroacetates, malates, or citrates, and other salts generally usable in the agricultural and horticultural fields. A pharmaceutically acceptable salt refers to a salt form obtained by converting a base group in a parent compound into a salt form. Pharmaceutically acceptable salts include, but are not limited to, inorganic or organic acid salts with base groups such as amine (amino) groups. The pharmaceutically acceptable salts of this application can be synthesized from the parent compound by reacting a basic group in the parent compound with 1-4 equivalents of an acid in a solvent system. Suitable salts are listed in Remingtong's Pharmaceutical Sciences, 17. th See, for example, hydrochloride, in Mack Publishing Company, Easton, Pa., 1985, p. 1418 and Journal of Pharmaceutical Science, 66, 2 (1977).

[0144] As used herein, “stereoisomers” refers to isomers resulting from different spatial arrangements of atoms in a molecule. Compounds of Formula (I) contain asymmetric or chiral centers, and therefore, different stereoisomers exist. All stereostructures and mixtures of Formula (I), including racemic mixtures, are included as part of this application. Diastereomeric mixtures can be separated into individual diastereomers based on their different physicochemical properties using well-known methods, such as the resolution of enantiomers by reacting them with a suitable optically active substance (e.g., a chiral alcohol or Mosher's chloride) to convert them to diastereomers, separating and converting them (e.g., hydrolysis) to the corresponding single isomer. Some compounds in Formula (I) may be transisomers (e.g., substituted aryl groups), which are also part of this application. Enantiomers can also be separated using chiral chromatographic columns. Compounds of Formula (I) may exist in different tautomeric forms, all of which are included within the scope of this application. For example, compounds in the keto-enol and imine-enamine forms. Detailed Implementation

[0145] The technical solutions of the present invention will be described in further detail below with reference to specific embodiments. It should be understood that the following embodiments are merely illustrative and explanations of the present invention and should not be construed as limiting the scope of protection of the present invention. All technologies implemented based on the above content of the present invention are encompassed within the scope of protection that the present invention is intended to protect.

[0146] Unless otherwise stated, the raw materials and reagents used in the following examples are commercially available products or can be prepared by known methods.

[0147] The following LC-MS detection and analysis were performed under the following chromatographic conditions:

[0148] Column: Agilent ZORBAX SB-C18 150mm×4.6mm, 5μm (id);

[0149] Detection wavelength: 254 nm; Flow rate: 0.8 mL / min; Column temperature: 30 °C;

[0150] Gradient elution conditions:

[0151] Time (min) Methanol (%) 0.1% formic acid aqueous solution (volume %) 0.00 50 50 5.00 50 50 15.00 90 10 20.00 90 10 25.00 90 10

[0152] Synthesis Examples

[0153] Example 1: Preparation of N-(cyclopropylmethyl)-5-methyl-1-(3-methylbut-2-yl)-N-(pyridazin-4-yl)-1H-pyrazole-4-carboxamide (compound 1)

[0154]

[0155] Step 1: Preparation of (3-methylbut-2-yl)hydrazine: At room temperature, 8.61 g (0.10 mol) of 3-methyl-2-butanone, 50 ml of ethanol and 3.84 g (0.025 mol) of barium oxide were added to a flask, and 7.5 g (0.12 mol) of 80% hydrazine hydrate was added dropwise. After the addition was complete, the temperature was raised to 50 °C and the reaction was stopped after the reactants had reacted completely. The reaction solution was filtered, the filtrate was concentrated, ethyl acetate was added, the mixture was washed with water and separated, and the product was concentrated to obtain 9.5 g.

[0156] GC-MS m / z = 100.10.

[0157] Second step reaction: Preparation of ethyl 2-((2-(-3-methylbut-2-yl)hydrazine)methylene)-3-oxobutyrate: At room temperature, 9.5 g (0.05 mol) of ethyl 2-(ethoxymethylene)-3-oxobutyrate was added to a flask, and 6 g (0.06 mol) of (3-methylbut-2-yl)hydrazine and 60 ml of methyl tert-butyl ether solution were added dropwise. After the addition was complete, the mixture was stirred at room temperature until the reaction stopped. The product was then concentrated under reduced pressure to obtain 11.7 g of product.

[0158] LC-MS[M+H] + =241.16, [M+Na] + =263.14, [M+K] + =279.11.

[0159] Step 3: Preparation of ethyl 5-methyl-1-(3-methylbut-2-yl)-1H-pyrazole-4-carboxylate: At room temperature, 11.7 g (0.0488 mol) ethyl 2-((2-(-3-methylbut-2-yl)hydrazino)methylene)-3-oxobutyrate, 6.5 g acetic acid and 50 ml methanol were added to a flask. 3.4 g (0.054 mol) sodium cyanoborohydride was added with stirring. After the addition was complete, the mixture was stirred at room temperature for 12 h. The reaction solution was concentrated to remove methanol. 100 ml water was added to the concentrate, and then the mixture was extracted three times with 50 ml ethyl acetate. The organic phases were combined and washed once with 50 ml water. The organic phase was concentrated to obtain 10.3 g of product.

[0160] LC-MS[M+H] + =225.16, [M+Na] + =247.14, [M+K] + =263.11.

[0161] Step 4: Preparation of 5-methyl-1-(3-methylbutyl-2-yl)-1H-pyrazole-4-carboxylic acid: At room temperature, 10 g (0.045 mol) of ethyl 5-methyl-1-(3-methylbutyl-2-yl)-1H-pyrazole-4-carboxylic acid was added to 40 ml of 5N sodium hydroxide aqueous solution and diluted with 20 ml of ethanol. The reaction mixture was stirred for 12 hours. After the reactants reacted completely, the reaction solution was concentrated to remove the ethanol. The residue was added to 50 ml of water and extracted once with 30 ml of ethyl acetate. The pH of the aqueous phase was adjusted to 3-4 with 2N hydrochloric acid, and then extracted three times with 100 ml of ethyl acetate. The organic phases were combined, dried over anhydrous sodium sulfate, filtered and concentrated to obtain 8.6 g of product.

[0162] LC-MS[M+H] + =197.13, [M+Na] + =219.11, [M+K] + =235.08.

[0163] Fifth step reaction: Preparation of 5-methyl-1-(3-methyl-2-butyl)-1H-pyrazole-4-carboxylic acid: At room temperature, 1 g (0.005 mol) of 5-methyl-1-(3-methylbutyl-2-yl)-1H-pyrazole-4-carboxylic acid, 0.05 g of N,N-dimethylformamide, and 0.84 g (0.007 mol) of thionyl chloride were sequentially added to 10 mL of 1,2-dichloroethane. The mixture was heated to 80 °C and stirred for 2 hours. After the reaction was completed, the solution was concentrated under reduced pressure at 40 °C. 1.1 g of the product was obtained as a yellow oil.

[0164] Step 6: Preparation of 3,5-dichloro-N-cyclopropylmethylpyridazine-4-amine and 4,5-dichloro-N-cyclopropylmethylpyridazine-3-amine: At room temperature, 18.5 g (0.1 mol) of 3,4,5-trichloropyridazine was dissolved in a mixed solution of 21.4 g (0.3 mol) of cyclopropylmethylamine and 100 ml of ethyl acetate. The mixture was heated to 40 °C and stirred for 3 hours. The solution was diluted with ethyl acetate and aqueous solution, and the phases were separated. The organic layer was washed with saturated brine and concentrated to obtain 21 g of the product.

[0165] LC-MS[M+H] + =218.03, [M+Na] + =240.01, [M+K] + =255.98.

[0166] Step 7: Preparation of N-cyclopropylmethylpyridazine-4-amine: 21 g (0.096 mol) of a mixture of 3,5-dichloro-N-cyclopropylmethylpyridazine-4-amine and 4,5-dichloro-N-cyclopropylmethylpyridazine-3-amine was dissolved in 200 ml of ethanol. 1.5 g (0.001 mol) of 10% Pd / C was added, and the pressurized reactor was purged with nitrogen. The reactor was pressurized to 0.02 MPa with hydrogen and heated to 35 °C. After 5 h, the reaction was complete. The reaction solution was filtered, the filtrate was concentrated to remove ethanol, and the residue was adjusted to alkaline with saturated potassium carbonate solution. Then, it was extracted three times with 200 ml of dichloromethane. The organic phases were combined, dried over anhydrous sodium sulfate, filtered, and concentrated to obtain 13.3 g of the product.

[0167] LC-MS[M+H] + =150.11, [M+Na] + =172.09, [M+K] + =188.06.

[0168] Step 8: Preparation of N-(cyclopropylmethyl)-5-methyl-1-(3-methylbut-2-yl)-N-(pyridazin-4-yl)-1H-pyrazole-4-carboxamide: 1.1 g (0.005 mol) of 5-methyl-1-(3-methyl-2-butyl)-1H-pyrazole-4-carboxyl chloride was added dropwise to a solution of 0.75 g (0.005 mol) N-cyclopropylmethylpyridazin-4-amine and 0.76 g (0.0075 mol) triethylamine in dichloroethane at 0 °C. After stirring at room temperature for 24 h, the solution was diluted with 100 mL of dichloroethane, washed with 3 x 50 mL saturated salt solutions, dried over magnesium sulfate and concentrated. The residue was purified by column chromatography (CH2Cl2 / MeOH) to obtain 1.12 g of product.

[0169] LC-MS[M+H] + =328.22, [M+Na] + =350.20, [M+K] + =366.17.

[0170] 1 H-NMR (400MHz, solvent CDCl3) δ (ppm): 9.06 (1H, s), 8.98 (1H, s), 7.27 (1H, d), 6.94 (1H, s), 3.84 (2H, d), 3.81 (1H, m),2.41(3H,s),1.41(3H,d),1.15(1H,m),0.98(3H,d),0.68(1H,m),0.61(3H,d),0.52(2H,d),0.23(2H,d).

[0171] Example 2: Preparation of N-((2-chlorocyclopropyl)methyl)-5-methyl-1-(3-methylbut-2-yl)-N-(pyridazin-4-yl)-1H-pyrazole-4-carboxamide (compound 9)

[0172]

[0173] 1.1 g (0.005 mol) of 5-methyl-1-(3-methyl-2-butyl)-1H-pyrazole-4-carboxyl chloride was added dropwise to a solution of 0.92 g (0.005 mol) N-((2-chlorocyclopropyl)methyl)pyridazine-4-amine and 0.76 g (0.0075 mol) triethylamine in dichloroethane at 0 °C. After stirring at room temperature for 24 h, the solution was diluted with 100 mL of dichloroethane, washed with 3 x 50 mL saturated salt solutions, dried over magnesium sulfate and concentrated. The residue was purified by column chromatography (CH2Cl2 / MeOH) to give 1.18 g of product.

[0174] LC-MS[M+H] + =362.18, [M+Na] + =384.16, [M+K] + =400.13.

[0175] 1 H-NMR (400MHz, solvent CDCl3) δ (ppm): 9.06 (1H, s), 8.98 (1H, s), 7.27 (1H, d), 6.94 (1H, s), 3.86 (2H, d), 3.81 (1H, m), 2. 58(1H,m),2.41(3H,s),1.79(1H,m),1.41(3H,d),1.15(1H,m),1.12(1H,d),0.98(3H,d),0.84(1H,d),0.61(3H,d).

[0176] The present invention also synthesized the following compounds with reference to the methods in the above embodiments:

[0177] Table 1

[0178]

[0179]

[0180]

[0181]

[0182]

[0183]

[0184] Formulation Examples

[0185] In the following examples, all percentages are by weight, and all dosage forms were prepared using conventional methods.

[0186] Example 3:

[0187] This embodiment uses the compound obtained in the above embodiment to prepare a wettable powder, specifically using the following raw material composition ratio:

[0188] Compound 1 50.0%, dodecylphenol polyethoxyethylene glycol ether 4.0%, sodium lignosulfonate 6.0%, sodium aluminosilicate 8.0%, montmorillonite (calcined) 32.0%.

[0189] Example 4:

[0190] This embodiment uses the compound obtained in the above embodiment to prepare granules, specifically using the following raw material composition ratio:

[0191] Compound 9 20.0%, other components are sodium dodecyl sulfate 2.0%, calcium lignosulfonate 6.0%, potassium chloride 10.0%, polydimethylsiloxane 1.0%, and soluble starch to make up to 100%.

[0192] Example 5:

[0193] This embodiment uses the compound obtained in the above embodiment to prepare extruded pellets, specifically using the following raw material composition ratio:

[0194] Compound 11 30.0%, anhydrous calcium sulfate 9.0%, crude lignin sulfonate calcium 4.0%, sodium alkyl naphthalene sulfonate 1.0%, calcium / magnesium bentonite 56.0%.

[0195] Example 6:

[0196] This embodiment uses the compound obtained in the above embodiment to prepare an emulsifiable concentrate, specifically using the following raw material composition ratio:

[0197] Compound 12 25.0%, solvent 150 60%, PEG400 5%, Rhodacal 70 / B 3%, Rhodameen RAM / 77%.

[0198] Example 7:

[0199] This embodiment uses the compound obtained in the above embodiment to prepare an aqueous suspension, specifically using the following raw material composition ratio:

[0200] Compound 13 30.0%, POE polystyrene phenyl ether sulfate 5.0%, xanthan gum 0.5%, polyethylene glycol 5%, triethanolamine 1%, sorbitol 0.5% and water added to 100.0%.

[0201] Bioactivity assay

[0202] Example 8:

[0203] 1. Insecticidal activity assay

[0204] In this embodiment, the insecticidal activity of the compounds prepared in the above embodiments was tested on several insects.

[0205] Insecticidal activity assay: The test method is as follows: the sample of the compound to be tested is dissolved in a suitable solvent (the type of solvent is such as acetone, methanol, DMSO, etc., and the solvent is selected according to its solubility in the sample) to prepare a test solution of the required concentration. The test unit consists of a small open container containing 12-15 day old radish plants. The plant is pre-infected by placing 30-40 pests located on a leaf cut from a cultivated plant (leaf cutting method) on a leaf of the test plant. As the leaf dehydrates, the pests move on the test plant. After pre-infection, the soil of the test unit is covered with a layer of sand.

[0206] The test method is as follows: The test was repeated three times. After spraying the prepared test compound, each test unit was allowed to dry for 1 hour, and then a black net cover was placed on top. The test units were kept in a growth chamber at 25°C and 70% relative humidity for 6 days. Then, the insect mortality rate (lethality rate) of each test unit was visually evaluated. The lethality rate was calculated as follows:

[0207]

[0208] (1) Exemplary Example: Test Results of Compound Control of Peach Aphids

[0209] The compounds that have a lethality of over 80% against peach aphids at a dose of 100 ppm are: 1, 2, 3, 9, 10, 11, 12, 13, 21, 22, 29, 30, 31, 32, 33, 41, 45, 48, 50, 51, 52, 54, 55, 56, 57, 58, 61, 63, 65, 69, 71, 72, 73, 81, 85, 86, 87, 88, 89, 97, 98, 101, 103, 104, 105, 113, 114, 116;

[0210] The compounds that have a mortality rate of over 80% against peach aphids at a dose of 20 ppm are: 1, 2, 3, 9, 10, 11, 12, 13, 21, 22, 29, 30, 31, 32, 33, 41, 50, 51, 52, 54, 55, 56, 57, 58, 61, 63, 65, 69, 71, 72, 73, 81, 85, 86, 87, 88, 89, 97, 98, 101, 103, 104, 105, 113, 114, 116;

[0211] The compounds that have a mortality rate of over 80% against peach aphids at a dose of 5 ppm are: 1, 9, 10, 11, 12, 13, 21, 29, 30, 31, 32, 33, 50, 51, 54, 55, 56, 57, 58, 61, 69, 71, 72, 73, 81, 85, 86, 87, 88, 89, 113, 114, and 116.

[0212] (2) Test results of the compound in the exemplary embodiment for controlling whiteflies

[0213] The compounds that have a mortality rate of over 80% against whiteflies at a dose of 100 ppm are: 1, 2, 3, 9, 10, 11, 12, 13, 21, 22, 29, 30, 31, 32, 33, 41, 45, 48, 50, 51, 52, 54, 55, 56, 57, 58, 61, 63, 65, 69, 71, 72, 73, 81, 85, 86, 87, 88, 89, 97, 98, 101, 103, 104, 105, 113, 114, 116;

[0214] The compounds that have a mortality rate of over 80% against whiteflies at a dose of 20 ppm are: 1, 2, 3, 9, 10, 11, 12, 13, 21, 22, 29, 30, 31, 32, 33, 41, 50, 51, 52, 54, 55, 56, 57, 58, 61, 63, 65, 69, 71, 72, 73, 81, 85, 86, 87, 88, 89, 97, 98, 101, 103, 104, 105, 113, 114, 116;

[0215] The compounds that have a mortality rate of over 80% against whiteflies at a dose of 5 ppm are: 1, 9, 10, 11, 12, 13, 21, 29, 30, 31, 32, 33, 50, 51, 54, 55, 56, 57, 58, 61, 69, 71, 72, 73, 81, 85, 86, 87, 88, 89, 113, 114, and 116.

[0216] (3) Exemplary Examples: Test Results of Compound Control of Tea Green Leafhopper

[0217] The compounds that have a lethality of over 80% against the tea green leafhopper at a dose of 100 ppm are: 1, 2, 3, 9, 10, 11, 12, 13, 21, 22, 29, 30, 31, 32, 33, 41, 45, 48, 50, 51, 52, 54, 55, 56, 57, 58, 61, 63, 65, 69, 71, 72, 73, 81, 85, 86, 87, 88, 89, 97, 98, 101, 103, 104, 105, 113, 114, 116;

[0218] The compounds that have a lethality of over 80% against the tea green leafhopper at a dose of 20 ppm are: 1, 2, 3, 9, 10, 11, 12, 13, 21, 22, 29, 30, 31, 32, 33, 41, 50, 51, 52, 54, 55, 56, 57, 58, 61, 63, 65, 69, 71, 72, 73, 81, 85, 86, 87, 88, 89, 97, 98, 101, 103, 104, 105, 113, 114, 116;

[0219] The compounds that have a lethality of over 80% against the tea green leafhopper at a dose of 5 ppm are: 1, 9, 10, 11, 12, 13, 21, 29, 30, 31, 32, 33, 50, 51, 54, 55, 56, 57, 58, 61, 69, 71, 72, 73, 81, 85, 86, 87, 88, 89, 113, 114, and 116.

[0220] (4) Exemplary Examples: Test Results of Compound Control on Scale Insects

[0221] The compounds with a lethality of over 80% against scale insects at a dose of 100 ppm are: 1, 2, 3, 9, 10, 11, 12, 13, 21, 22, 29, 30, 31, 32, 33, 41, 45, 48, 50, 51, 52, 54, 55, 56, 57, 58, 61, 63, 65, 69, 71, 72, 73, 81, 85, 86, 87, 88, 89, 97, 98, 101, 103, 104, 105, 113, 114, 116;

[0222] The compounds with a lethality of over 80% against scale insects at a dose of 20 ppm are: 1, 2, 3, 9, 10, 11, 12, 13, 21, 22, 29, 30, 31, 32, 33, 41, 50, 51, 52, 54, 55, 56, 57, 58, 61, 63, 65, 69, 71, 72, 73, 81, 85, 86, 87, 88, 89, 97, 98, 101, 103, 104, 105, 113, 114, 116;

[0223] The compounds that have a lethality of over 80% against scale insects at a dose of 5 ppm are: 1, 9, 10, 11, 12, 13, 21, 29, 30, 31, 32, 33, 50, 51, 54, 55, 56, 57, 58, 61, 69, 71, 72, 73, 81, 85, 86, 87, 88, 89, 113, 114, and 116.

[0224] (5) Exemplary Example: Test Results of Compound Control of Brown Planthopper

[0225] The compounds that have a mortality rate of over 80% against brown planthoppers at a dose of 100 ppm are: 1, 2, 3, 9, 10, 11, 12, 13, 21, 22, 29, 30, 31, 32, 33, 41, 45, 48, 50, 51, 52, 54, 55, 56, 57, 58, 61, 63, 65, 69, 71, 72, 73, 81, 85, 86, 87, 88, 89, 97, 98, 101, 103, 104, 105, 113, 114, 116;

[0226] The compounds that have a mortality rate of over 80% against brown planthoppers at a dose of 20 ppm are: 1, 9, 10, 11, 12, 13, 21, 29, 30, 31, 32, 33, 50, 51, 54, 55, 56, 57, 58, 61, 69, 71, 72, 73, 81, 85, 86, 87, 88, 89, 97, 98, 103, 113, 114, and 116.

[0227] 2. Acaricide activity assay

[0228] In this embodiment, the compounds prepared in the above embodiments were used to conduct acaricidal activity tests on several mite pests.

[0229] The testing method is as follows: Dissolve the sample of the compound to be tested in a suitable solvent (the type of solvent is such as acetone, methanol, DMSO, etc., and the solvent is selected according to its solubility in the sample) to prepare a test solution of the required concentration. Cut double-sided tape into 2-3 cm lengths and attach them to one end of a microscope slide. Use tweezers to peel off the paper off the tape. Use a size 0 brush to select female adult mites that are uniform in size, brightly colored, and active. Stick their backs onto the double-sided tape (Note: Do not stick the mite legs, antennae, and mouthparts). Stick 4 rows per tape, with 10 mites per row.

[0230] The test method is as follows: The test was repeated three times. After 4 hours in a biochemical incubator at approximately (25±1)℃ and 85% relative humidity, the mites were observed using a binocular microscope, and dead or inactive individuals were removed. One end of a slide containing mites was immersed in the drug solution, gently shaken for 5 seconds, and then removed. Excess drug solution was quickly absorbed from the mites and surrounding area using absorbent paper. The slide was placed in the aforementioned biochemical incubator, and after 24 hours, the results were examined using a binocular microscope. The mites were gently touched with a brush; those whose legs did not move were considered dead. The mortality rate was calculated. The mortality rate was calculated as follows:

[0231]

[0232] The results of partial testing of Tetranychus cinnabarinus are as follows:

[0233] The compounds that have a lethality of over 80% against Tetranychus carmine at a dose of 200 ppm are: 1, 2, 3, 9, 10, 11, 12, 13, 21, 22, 29, 30, 31, 32, 33, 41, 45, 48, 50, 51, 52, 54, 55, 56, 57, 58, 61, 63, 65, 69, 71, 72, 73, 81, 85, 86, 87, 88, 89, 97, 98, 101, 103, 104, 105, 113, 114, and 116.

[0234] 3. Test results of exemplary embodiment compounds and control reagents

[0235] This embodiment presents a comparative insecticidal activity test between the exemplary compound and the control agent (prepared according to the methods reported in the literature, and the insecticidal test method is the same as above). The test results are shown in Tables 2 and 3 below.

[0236]

[0237] Table 2

[0238]

[0239]

[0240]

[0241] Table 3

[0242]

[0243] In addition to the compounds listed in the table above, the compounds of other exemplary embodiments of the present invention exhibit significantly better control activity against pests and mites than the control agents. Therefore, the compounds of formula (I) of the present invention show excellent activity against a variety of pests and mites in the agricultural field.

[0244] The embodiments of the present invention have been described above. However, the present invention is not limited to the above embodiments. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the protection scope of the present invention.

Claims

1. The compound represented by formula (I) or a pharmaceutically acceptable salt thereof, in, The compound represented by formula (I) is selected from compounds having the following functional groups defined:

2. Use of one or both of the compounds of formula (I) of claim 1 or pharmaceutically acceptable salts thereof in the preparation of pesticides.

3. The use according to claim 2, wherein, The pesticide is an insecticide and / or an acaricide.

4. A method for controlling pests, comprising applying an effective amount of one or both of the compound of formula (I) of claim 1 or a pharmaceutically acceptable salt thereof to the growth medium of pests and / or mites; The pest control measures are used for purposes other than disease diagnosis and treatment.

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