Pyridazine compound as well as preparation method and application thereof

Abstract

The compound shown in the formula (I) shows good activity on various pests and pest mites in agriculture or other fields. Moreover, the compounds can obtain good prevention and treatment effects at a very low dosage, so that the compounds can be used for preparing insecticides and / or acaricides. # imgabs0 #

Description

Technical Field

[0001] The invention belongs to the technical field of insecticides and miticides, and specifically relates to pyridazine compounds and preparation methods and uses thereof. Background Art

[0002] Pesticides have played an extremely important role in increasing agricultural production and solving the food problem for mankind. With the increasing requirements for the safety of chemical substances and their impact on the environment, it is expected that safer pest control agents will be developed. In addition, due to the long-term use of pest control agents such as insecticides and acaricides, pests have gradually developed resistance to these biological control agents, resulting in unsatisfactory control effects. Therefore, the development of pest control agents with excellent performance such as safety, control effect, and residual effect is a future development trend.

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

[0004]

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

[0006]

[0007] However, the biological activity of the above compounds still needs to be further improved. In order to find insecticides and acaricides with better performance, the inventors conducted in-depth research. Summary of the invention

[0008] To improve the above problems, the present invention provides a compound represented by the following formula (I), its stereoisomers, racemates, tautomers, nitrogen oxides or pharmaceutically acceptable salts thereof:

[0009]

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

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

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

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

[0014] R5 is selected from C3-C6 cycloalkyl, halogenated C3-C6 cycloalkyl, C3-C6 cycloalkylC1-C2 alkyl, halogenated C3-C6 cycloalkylC1-C2 alkyl or C3-C6 epoxyalkylC1-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, halogenated C1-C4 alkyl, C3-C6 cycloalkyl or halogenated C3-C6 cycloalkyl;

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

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

[0021] R4 is selected from methyl or ethyl;

[0022] R5 is selected from C3-C6 cycloalkyl, halogenated C3-C6 cycloalkyl, C3-C6 cycloalkylC1-C2 alkyl, halogenated C3-C6 cycloalkylC1-C2 alkyl or C3-C6 epoxyalkylC1-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, halogenated C1-C3 alkyl, C3-C6 cycloalkyl or halogenated C3-C6 cycloalkyl;

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

[0028] R3 is selected from H or methyl;

[0029] R4 is selected from methyl or ethyl;

[0030] R5 is selected from C3-C6 cycloalkyl, halogenated C3-C6 cycloalkyl, C3-C6 cycloalkylC1-C2 alkyl, halogenated C3-C6 cycloalkylC1-C2 alkyl or C3-C6 epoxyalkylC1-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 the following group substituted by one, two or three F, Cl, Br: cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl.

[0034] According to an embodiment of the present invention, the halogenated C3-C6 cycloalkyl C1-C2 alkyl group is the following group substituted by one, two or three F, Cl or Br: As an example, the halogenated C3-C6 cycloalkyl C1-C2 alkyl 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: 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 the following formula (IA):

[0044]

[0045] wherein A, X, R4 and R5 have the same meanings as 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 ligation site is indicated.

[0061] The present invention also provides a method for preparing the compound represented by the above formula (I), when X is O, comprising the following step A) or step B): step A): the compound of formula (II) and the compound of formula (III) undergo condensation reaction to obtain the compound of formula (I);

[0062]

[0063] Step B):

[0064] B1) reacting the compound of formula (II) with a halogenating agent to obtain a compound of formula (II-1);

[0065] B2) reacting a compound of formula (II-1) with a compound of formula (III) to obtain a compound of formula (I);

[0066]

[0067] wherein R1, R2, R3, R4, R5, A have the definitions as described above; and L is selected from a leaving group, 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′-tetramethyluronium hexafluorophosphate (HATU), and benzotriazol-1-yl-oxytripyrrolidinophosphine 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, and the base can be an inorganic base, for example, 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, and the solvent is, 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, for example, selected 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) may be 0 to 100°C, for example 0 to 50°C, such as 0 to 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, and the base can be selected from an organic base or an inorganic base, such as one, two or more of pyridine, triethylamine, 4-(dimethylamino)pyridine (DMAP), diisopropylethylamine (DIEA), sodium carbonate, potassium carbonate, sodium hydroxide, potassium hydroxide, potassium tert-butoxide or sodium hydride, etc. The preferred solvent can be N,N-dimethylacetamide, N,N-dimethylformamide, dioxane, toluene, dichloromethane, 1,2-dichloroethane;

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

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

[0077]

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

[0079] The reaction can be carried out in the presence of a base, and the base can be an organic base or an inorganic base, for example, 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, and the solvent is, 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, such as 20 to 80°C.

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

[0083]

[0084] wherein R1, R2, R3, R4, R5 and A have the same meanings as above.

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

[0086]

[0087] wherein R1, R2, R3, R4, R5, X, and A have the same meanings as described above.

[0088] According to an embodiment of the present invention, compounds II and III can be purchased as commercial products or can be prepared by methods known in the literature, for example, they can be prepared by methods described in patent documents WO2005040169, WO2008074824 or Journal of Fluorine Chemistry 132 (11), page 995 (2011).

[0089] The preparation of the compounds of formula (I) and their starting materials herein can be carried out according to the reaction conditions and the selection of starting materials that are suitable in each case, for example, by replacing only one substituent with another substituent according to the invention in a single step, or by replacing multiple substituents with other substituents according to the invention in the same reaction step.

[0090] If the individual compounds are not accessible via the routes described above, they can be prepared by derivatization of other compounds or by routine variations of the synthetic routes described.

[0091] After completion of the reaction, the reaction mixture can be worked up in a customary manner, for example by mixing with water, separating the phases and, if appropriate, purifying the crude product by chromatography, for example on aluminum oxide or silica gel.

[0092] The pharmaceutically acceptable salt of the compound of formula (I) of the present invention can be prepared by known methods. For example, the acid addition salt of the compound of formula (I) can be obtained by appropriate acid treatment. The preparation method is as follows: the compound of formula (I) is reacted 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 to conveniently obtain a pharmaceutically acceptable salt of the compound of formula (I).

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

[0094] Unless otherwise stated, all of the above reactions are conveniently carried out at atmospheric pressure or at the native pressure of the particular reaction.

[0095] The present invention also provides a pesticide composition, such as an insecticidal and / or acaricidal composition, which comprises as an active ingredient one, two or more of the compound represented by 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 an embodiment of the present invention, the composition further comprises one, two or more agriculturally and / or forestry- and / or hygienically acceptable carriers.

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

[0099] For example, the compound represented by formula (I) as an active ingredient is dissolved or dispersed in a carrier or formulated into a preparation so that it is easier to disperse when used as an insecticide and / or acaricide.

[0100] According to an embodiment of the present invention, the preparation includes but is not limited to the following forms: wettable powder, oil suspension, water suspension, aqueous emulsion, aqueous solution, emulsifiable concentrate or microcapsule and the like.

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

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

[0103] The present invention also provides the use of one, two or more of the compound represented by formula (I), its 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 compound represented by formula (I), its stereoisomers, racemates, tautomers, nitrogen oxides or pharmaceutically acceptable salts thereof, or the composition to a growth medium of the pests and / or mites.

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

[0106] The active substances according to the invention or the active substances to be used according to the invention are suitable for protecting plants and plant organs, increasing harvest yields, improving the quality of harvested products and controlling harmful animals, especially pests, mites, etc. that occur in agriculture, horticulture, animal husbandry, forestry, gardens and leisure facilities, in warehouse pest protection and material protection, and in the field of hygiene, due to good plant tolerance, favorable homeothermic animal toxicity and good environmental compatibility. They can preferably be used as plant protection compositions. They are active against conventional sensitive and resistant species and against all or individual development stages. The above-mentioned pests and mites include, but are not limited to:

[0107] From the phylum Arthropoda, in particular from the class Arachnida, for example Acarus spp., Aceria sheldoni, Aculops spp., Aculus spp., Amblyomma spp., Amphitetranychus viennensis, Argas spp., Boophilus spp., Brevipalpus spp., Bryobia graminum, Bryobia praetiosa, Centruroides spp., Chorioptes spp.), Dermanyssusgallinae, Dermatophagoidespteronyssinus, Dermatophagoidesfarinae, Dermacentor spp., Eotetranychus spp., Epitrimeruspyri, Eutetranychus spp., Eriophyes spp., Glycyphagusdomesticus, Halotydeusdestructor, Hemitarsonemus spp., Hyalomma spp., Ixodes spp., Latrodectus spp., Loxosceles spp., Metatetranychus spp.), Neutrombiculaautumnalis, Nuphersa spp., Oligonychus spp., Ornithodorus spp., Ornithonyssus spp., Panonychus spp., Phyllocoptrutaoleivora, Polyphagotarsonemuslatus, Psoroptes spp., Rhipicephalus spp., Rhizoglyphus spp., Sarcoptes spp.), Scorpiomaurus, Steneotarsonemus spp., Steneotarsonemus spinki, Tarsonemus spp., Tetranychus spp., Trombicula alfreddugesi, Vaejovis spp., Vasates lycopersici;.

[0108] Coleoptera (Beetles): Acanthoscelides spp. (Weevils), Acanthoscelides obtectus (Common Pea Weevils), Agrilus planipennis (Willow Ash Borer), Agriotes spp. (Wireworms), Anoplophora glabripennis (Asian Longhorn Beetle), Anthonomus spp. (Curculidae), Anthonomus grandis (Cotton Bollworm), Aphidius spp., Apion spp. (Weevils), Apogonia spp. (Grubs), Atacnius sprctulus (Black Velvet Beetle), Atomaria linearis (Pygmy Beetle), mangold beetle, Aulacophore spp., Bothynoderes punctiventris (beetroot weevil), Bruchus spp. (weevil), Bruchus pisorum (pea weevil), Cacoesia spp., Callosobruchus maculatus (southern cowpea weevil), Carpophilus hemipteras (dried fruit beetle), Cassida vittata, Ccrostcrna spp., Ccrotoma spp. (chrysomcides), Cerotoma trifur cata (bean leaf beetle), Ceutorhynchus spp.) (weevils), Ceutorhynchus assimilis (cabbage seedpod weevil), Ceutorhynchus napi (cabbage curculio), Chaetocnema spp. (trichomoniasis), Colaspis spp.) (earth beetle), Conoderus scalaris, Conoderus stigmosus, Conotrachelus nenuphar (Plum cone weevil), Cotinus nitidis (Green June beetle), Crioceris asparagi (Asparagi beetle), Cryptolestes ferrugincus (rusty grain beetle), Cryptolestes pusillus (grain beetle), Cryptolestes turcicus (Turkish grain beetle), Ctenicera spp. (nematodes), Curculio spp. (weevils), Cyclocephala spp. (grubs), Cylindrocpturus adspersus (sunflower stem weevil), Deporaus marginatus (mango leaf-cutting weevil), Dermestes lardarius (ham stem weevil), Dermestes maculates (white-bellied weevil), Diabrotica spp. (leaf beetles), Epilactina varivcstis (Mexican bean beetle), Raustinus cubae, Hylobius pales (pales weevil), Hypera spp. (weevils), Hypera postica (alfalfa weevil), Hyperdoes spp. (Hyperodes weevil), Hypothenemus hampei) (coffee berry beetle), Ips spp.) (engravers), Lasioderma serricorne (tobacco beetle), Leptinotarsa ​​decemlineata (Colorado potato beetle), Liogenys fuscus, Liogenys suturalis, Lissorhoptrus oryzophilus (rice water weevil), Lyctus spp. (powder post beetles), Maecolaspis joliveti, Megascelis spp., Melanotus communis, Meligethes spp., Meligethes aeneus (blossom beetle), Melolontha melolontha (common European beetle), Oberea brevis, Oberea linearis), Oryctes rhinoceros (date palm beetle), Oryzaephilus mercator (merchant grain beetle), Oryzaephilus surinamensis (sawtooth grain beetle), Otiorhynchus spp. (weevils), Oulema melanopus (cerealleaf beetle), Oulema oryzae, Pantomorus spp. (weevils), Phyllophaga spp. (May / June beetles), Phvllophaga cuyabana, Phyllotreta spp.) (Trichomonas), Phynchites spp.), Popillia japonica (Japanese beetle), Prostephanus truncates (larger grain borer), Rhizoperthadominica (lesser grain borer), Rhizotrogus spp. (Eurpoean chafer), Rhynchophorus spp. (weevils), Scolytus spp. (wood moths), Shenophorus spp. (grain weevils), Sitonalincatus (pea leaf weevil), Sitophilus spp. (grain weevils), Sitophilus granaries (granary weevil), Sitophilus oryzae (rice weevil) weevil), Stegobium paniceum (drugstore beetle), Tribolium spp. (face weevil), Tribolium castaneum (red flour beetle), Tribolium confusum (confused flour beetle), Trogoderma variabile (warehouse beetle), and Zabrus tenebioides.

[0109] Dermaptcra (earwigs).

[0110] Dictyoptera (cockroaches): Blattella germanica (German cockroach), Blatta orientalis (Oriental cockroach), Parcoblatta pennylvanica, Periplaneta americana (American cockroach), Periplaneta australoasiae (Australian cockroach), Periplaneta brunnca (brown cockroach), Periplaneta fuliginosa (smoky brown cockroach), Pyncoselus suninamensis (Surinam cockroach), cockroach) and Supella longipalpa (brownbanded cockroach).

[0111] Diptera (flies): Aedes spp. (mosquitoes), Agromyzafrontella (alfalfa blotch leafminer), Agromyza spp. (leafminers), Anastrepha spp. (fruit flies), Anastrepha suspensa (Caribbean fruit fly), Anopheles spp. (mosquitoes), Batrocera spp. (fruit flies), Bactrocera cucurbitae (melon flies), Bactroceradorsalis (orange fruit flies), Ceratitis spp. (fruit flies), Ceratitis capitata (Mediterranean fruit flies), Chrysops spp.) (deer flies), Cochliomyia spp. (bloom fly larvae), Contarinia spp. (mosquitoes), Culex spp. (mosquitoes), Dasineura spp. (mosquitoes), Dasineura brassicae (cabbage midges), Delia spp., Delia pla tura (seed corn maggots), Drosophila spp. (vinegar flies), Fannia spp. (house flies), Fannia canicularis (little house fly), Fannia scalaris (gray-bellied toilet fly), Gasterophilus intestinalis (horse stomach fly), Gracillia perseae, Haematobia irritans (horn fly), Hylemyia spp. (root maggot), Hypoderma lineatum (common cattle grub), Liriomyza spp.) (leaf miner), Liriomyza brassica (serpentine leaf miner), Melophagus ovinus (sheep tick), Musca spp. (muscid fly), Muscaa utumnalis (face fly), Vusca domestica (house fly), Oestrusovis (sheep bot fly), Oscinella frit (Swedish straw fly), Pegomyia betae (beet leaf miner), Phorbia spp., Psila rosae (carrotrust fly), Rhagoletis cerasi (cherry fruit fly), Rhagoletis pomonella (apple maggot), Sitodiplosismosellana (orange wheat blossom midge), stomoxyscalcitruns (stable fly), Tahanus spp. (horse flies), and Tipula spp. (crane flies).

[0112] Hemiptera (Stinkbugs): Acrosternum hilare (green stinkbug), Blissus leucopterus (chinch bug), Calocoris norvegicus (potato mirid), Cimex hemipterus (tropical bed bug), Cimex lectularius (bed hug), Daghertus fasciatus, Dichelops furcatus, Dysdercus suturellus (cotton stainer), Edessa meditabunda, Eurygaster maura (cereal bug), Euschistus heros, Euschistus servus) (brown stink bug), Helopeltis antonii, Helopeltis theivora (tea blightplantbug), Lagynotomus spp. (stink bugs), Leptocorisa oratorius, Leptocorisa varicornis, Lygus spp. (plant bugs), Lygushesperus (western tarnished plant bug), Maconellicoccushirsutus, Neurocolpus longirostris, Nezara viridula (southern greenstink bug), PhyLocoris spp.)(lyssum), Phytocoris californicus, Phytocoris relativus, Piezodorus guildingi, Poecilocapsus lineatus (fourlined plant bug), Psallus vaccinicola, Pseudacystaperseae, Scaptocoris castanea, and Triatoma spp. (bloodsucking conenoses / kissing bugs).

[0113] Homoptera (aphids, scales, whiteflies, leafhoppers): Acrythosiphonpisum (pea aphid), Adelges spp. (adelg ds), Aleurodes proletella (cabbage whitefly), Aleurodicus di sperses, Aleurothrixus flccosus (woolly whitefly), Aluacaspis spp., Amrasca bigutella bigutella, Aphrophora spp. (leafhopper), Aonidiella aurantii (California redscale), Aphis spp. (aphids), Aphis gossypii (cotton aphid), Aphis pomi (apple aphid), Aulacorthitm solani (foxglove aphid), Bemisia spp. (whitefly), Bemisia argentifolii, Bemisia tabaci (sweetpotato whitefly), Bemisia tabaci (Gennadius), Brachycolus noxius (Russian aphid), Brachycorynclia asparagi (asparagus aphid), Brevennia rehi, Brevicoryne brassicae (cabbage aphid), Ceroplastes spp. (scale), Ceroplastes rubens (red wax scale), scale), Chionaspis spp. (scale), Chrysomphalus spp. (scale), Coccus spp. (scale), Dysaphis plantaginea (rosy apple aphid), Empoasca spp.) (leafhopper), Eriosoma lanigerum (woolly apple aphid), Icerya purchasi (cottonycushion scale), Idioscopus nitidulus (mango leafhopper), Laodelphax striatellus (smaller brown planthopper), Lepidosaphes spp., Macrosiphum spp., Macrosiphum euphorbiae (potato aphid), Macrosiphum granarium (English grain aphid), Macrosiphum rosae (rose aphid), Macrosteles quadrilin eatus (aster leafhopper), hopper), 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. (foam bug), Phylloxera vitifoliae (grape phylloxera), Physokermes piceae)(spruce bud scale), Planococcus spp.(mealybugs), Pseudococcus spp.)(mealy bug), Pscudococcus brcvipcs(pincapple mcaly bug), Quad raspidiotus perniciosus(San Jose scale), Rhapalosiphum spp.(aphids), Rhapalosiphum maida(corn leaf aphid), Rhapalosiphumpadi(oatbird-cherry aphid), Saissetia spp.(scale), Saissetiaoleae(black scale), Schizaphis graminum(green bug), Sitobion avenge(British wheat aphid), Sogatella furcifera)(white-backed planthopper), Therioaphis spp.(aphids), Toumeyella spp.(scale), Toxoptera spp.(aphids), Trialeurodes spp.(whitefly), Trialeurodes vaporariorum(greenhouse whitefly), Trialeurodes abutiloneus(bandedwing whitefly), Unaspis spp.(scale), Unaspis yanonensis(arrowhead scale), and Zulia entreriana.

[0114] Hymenoptera (Ants, Wasps and Bees): Acromyrrmex spp., Athalia rosae, Atta spp. (Ieafcutting ants), Camponotus spp. (carpenter ants), Diprion spp. (sawflies), Formica spp. (ants), Iridomyrmex humilis (Argentine ants), Monomorium spp., Monomorium minumum (little black ant), Monomorium pharaonis (Pharaoh ant), Neodiprion spp. (sawflies), Pogonomyrmex humilis (Argentine ants), spp. (harvester ants), Polistes spp. (paper wasps), Solenopsis spp. (fire ants), Tapoinoma sessile (odorous house ant), Tetranomorium spp. (pavement ant), Vespula spp. (yellow jackets), 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), Iletotermes aureus, Kalotermes spp. (drywood termite), Incistitermes spp. (drywood termite), Macrotermes spp. spp.) (fungusgrowing termites), Marginitermes spp. (drywood termites), Microcerotermes spp. (harvester termites), Microtermesobesi, Procornitermes spp., Reticulitermes spp. (soil-dwelling termites), Reticulitermes banyulensis, Reticulitermes grassei, Reticulite rmes flavipes (Eastern soil-dwelling termites), Reticulitermes hageni, Reticulitermes hesperus (Western soil-dwelling termites), Reticulitermes santonensis, Reticulitermes spp. speratus), Reticulitermes tibialis, Reticulitermes virginicus, Schedorhinotermes spp., and Zootermopsis spp. (wood-destroying termites).

[0116] Lepidoptera (moths and butterflies): Achoea janata, Adoxophyes spp., Adoxophyes orana, Agrotis spp. (cutworms), Agrotis ipsilon (black cutworm), Alabama argillacea (cotton leaf worm), Amorbia cuneana, Amyelosi transitella (navel orange worm), Anacamptodes defectaria, Anarsia lineatella (peach twig borer), Anomis sabulijera (jute looper), Anticarsiag emmatalis (velvet bean caterpillar), Archips argyrospila (fruit tree leaf roller), Archips rosana (rose leaf roller), leafroller), Argyrotaenia spp. (tortricid moths), Argyrotaenia citrana (orange tortrix), Autographa gamma, Bonagota cranaodcs, Borbocinnara (rice leaf roller), Buccula trix thurberiella (cotton leaf perforator), Caloptilia spp. (leaf miners), Capua reticulana, Carposina niponensis (peach fruit moth), Chilo spp., Chlumetia transversa (mango shoot borer), Choristoneura rosaceana (obliquebanded leaf roller), Chrysodeixis spp.), Cnaphalocerusmedinalis (grass leafroller), Colias spp., Conpomorpha cramerella, Cossus cossus (wood moth), Crambus 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), Diatraea spp. (stalk borer) borer), Diatraea saccharalis (sugarcane borer), Diatraea graniosella (southwester cornborer), Earias spp. (cotton bollworm), Earias insulata (Egyptian bollworm), Earias vit.ella (rough northern bollworm), Ecdytopophaaurantianum, Elasmopalpus lignosellus (lesser cornstalk borer), Epiphysis postrutta na (light brown apple moth), Ephestia spp. (powdery moth), Ephestia cautella (almond moth), Ephestia elutella) (tobbacomoth), Ephestia kuehniella (Mediterranean flour moth), Epimeces spp.), Epinotiaaporema, Erionota thrax (banana skipper), Eupoeciliaambiguella (grape berry moth), Euxoa auxiliaris (army cutworm), Feltia spp. (cutworms), Gortyna spp. (stem borers), Grapholita molesta (oriental fruit moth), Hedylepta indicata (bean leafwebber), Helicoverpa spp. (snoctuid armyworms), Helicoverpa armigera (cotton bollworm), Helicoverpazea (corn borer / bollworm), Heliothis spp. (noctuid), Heliothis virescens (tobacco budworm), Hellula undalis (cabbage web worm), Indarbela spp. (root borer), Keiferia lycopersicella (tomato pinworm), Leucino desorbonalis (eggplant fruit borer), Leucoptera malifoliella, Lithocollectis spp., Lobesia botrana (grape fruit moth), Loxagrotis spp. (noctuid), Loxagrotis albicosta (western bean cutworm), Lymantria dispar (gypsy moth), Lyonetia clerkella (apple leafminer), Mahasena corbetti (oil palm bagworm), Malacosoma spp.)(tent caterpillars), Mamestra brassicae (cabbage armyworm), Marucatestulalis (bean borer), Metisa plana (grassworm), Mythimna unipuncta (truearmyworm), Neoleucinodes elegantalis (small tomato borer), Nym phulade punctalis (rice leafroller), Operophtherabrumata (winter moth), Ostrinianubilalis (European cornborer), Oxydia vesulia, Pandemiscerasana (common grape leafroller), Pandemis heparana (brown apple tortrix), Papilio demodocus, Pectinophoragossypiella (pink bollworm), Peridroma spp. (cutworm), Peridroma saucia (variegated cutworm), Perileucopte ra coffeella (white coffeeleafminer), Phthorimaea operculella (potato tuber moth), Phyllocnisitis citrella, Phyllonorycter spp.) (leaf miner), Pieris ra pae (imported cabbageworm), Plathypenascabra, Plodia interpunctella (Indian meal moth), Plutellaxylostella (diamondback moth), Polychrosis viteana (grape berry moth), Prays endocarps, Prsys oleae (olive moth), Pseudaletia spp. (spot moth), Pseudaletia unipunctata (army bug), Pseudoplusia includens (soybean looper), Rachiplusia nu, Chilo suppressalis, Scirpophaga incertulas, Sesamia spp.) (stem borers), Sesamia inferens (pink rice stemborer), Sesamianonagrioides, Setora nitens, Sitotroga cerealella (Angoumoisgrain moth), Sparganothis pilleriana, Spodoptera spp. (armyworms), Spodoptera exigua (beet armyworm), Spodoptera crafugipcrda (fall armyworm), Spodoptera oridania (southern armyworm), Synanthedon spp. (root borers), Theclabasilides, Thermisia gemmatalis, Tineola bisselliella) (webbing clothes moth), Trichoplusia ni (cabbage looper), Tutsabsoluta, Yponomeuta spp.), Zeuzeracofee (red branchborer), Zeuzerapyrina (leopard moth), and Spodoptera litura (Fabricius).

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

[0118]

[0043] From the Order of Orthoptera (Grasshoppers, Locusts and Crickets): Anabrus simplex (Mormon cricket), Gryllotalpidae (mole cricket), Locusta migratoria, Melanoplus spp. (grasshoppers), Microcentrum retinerve (angular winged katydid), Pterophylla spp. (katydids), chistocerca gregaria, Scudderia furcata (fork tailed bush katydid) and Valanga nigricorni.

[0119]

[0043] From the order of Phthiraptera (sucking louse): Haematopinus spp. (cattle and pig lice), Linognathus ovillus (sheep louse), Pediculus humanus capitis (body louse), Pediculus humanus humanus (body louse), and Pthirus pubis (crab louse).

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

[0121] Thysanoptera (Thrips): Frankliniella fusca (tobacco thrip), Frankliniella occidentalis (western flower thrips), Frankliniella shultzei, Frankliniella williamsi (corn thrip), Ileiothrips haemorrhaidalis (greenhouse thrip), Riphiphorothrips cruentatus, Scirtothrips spp., Scirtothrips cirri (citrus thrip), Scirtothrips dorsalis (yellow tea thrips), Taeniothrips rhopalantennalis, and Thrips spp.

[0122] From the order of the Thysanura (bristletails): Lepisma spp. (silverfish) and Thermobia spp. (silverfish).

[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 (tomatorus setmite), Aculops pelekasi, Aculus pelekassi, Aculus schlechtendali (apple rust mite), Amblyomma amcricanum (lone star tick), Boophilus spp.) (ticks), Brevipalpus obovatus (privet mite), Brevipalpus phoenicis (red and black flat mite), Demodex spp. (mange mites), Dermacentor spp. (hard ticks), Dermacentor variabilis (American dog tick), Dermatophagoides pteronyssinus (house dust mite), Eotetranycus spp., Eotetranychus carpini (yellow spider mite), Epitimerus spp., Eriophyes spp., Ixodes spp. (ticks), Metatetranycus spp. ( spp.), Notoedres cati, Oligonychus spp., Oligonychus coffee, Oligonychusilicus (southernred mite), Panonychus spp.), Panonychus cirri (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, Tetranychus spp., Tetranychus urticae (twospotted spider mite), mite) and Varroa destructor (honey bee mite).

[0124] Nematodes: Aphelenchoides spp. (bud and leaf & pine wood nematodes), Belonolaimus spp. (sting nematodes), Criconemella spp. (ring nematodes), Dirofilaria immitis (dog heartworm), Ditylenchus spp. (stem and bulb nematodes), Heterodera spp. (cyst nematode), Heterodera zeae (corncystnematode), Hirschmanniella spp. (root nematodes), Hoplolaimus spp. (lance nematodes), Meloidogyne spp.) (root-knot nematode), Meloidogyne incognita (root-knot nematode), Onchocerca volvulus (hook-tail worm), PraLylenchus spp. (lesion nematode), Radopholus spp. (burrowing nematode), and Rotylenchus reniformis (kidney-shaped nematode).

[0125] Synthesize (integrated insect class): White pine borer (Scutigerella immaculata).

[0126] As an example, the pest is selected from green peach aphid, whitefly, scale insect, brown planthopper or tea green leafhopper.

[0127] As an example, the harmful mite is selected from Tetranychus cinnabarinus or Tetranychus urticae.

[0128] Due to their positive properties, the compounds of the formula (I) can be advantageously employed for protecting agriculturally and horticulturally important crops, domestic animals and breeding stock, and the environment frequented by humans from damage by pests and / or acarids.

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

[0130] The selection of ingredients for the dosage forms or compositions described herein should be consistent with the physical properties of the active ingredient, the mode of application, and environmental factors such as soil type, moisture and temperature.

[0131] Useful dosage forms include liquids such as solutions (including emulsifiable concentrates), suspensions, emulsions (including microemulsions and / or suspensions), etc., which may optionally be thickened into jelly-like substances. Useful dosage forms also include solids such as dusts, powders, granules, tablets, pills, films, etc., which may be water-dispersible ("wettable") or water-soluble. The active ingredient can be microencapsulated and then made into a suspension or solid dosage form; in addition, the entire dosage form of the active ingredient can also be encapsulated. Encapsulation can control or delay the release of the active ingredient. Sprayable dosage forms can be diluted in a suitable medium, and the spray volume used is about one hundred to several hundred liters per hectare. High-concentration compositions are mainly 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. Surfactants and recommended applications are listed in 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. All formulations may contain small amounts of additives to reduce foaming, corrosion, microbial growth, etc., or thickeners to increase viscosity.

[0133] The surfactants include, for example, polyethoxylated alcohols, polyethoxylated alkylphenols, polyethoxylated sorbitan fatty acid esters, dialkyl sulfonated succinates, alkyl sulfates, alkylbenzene sulfonates, organosilanes, N,N-dialkyl taurates, lignin sulfonates, condensates of naphthalene sulfonates with aldehydes, polycarboxylates and polyoxyethylene / polyoxypropylene block copolymers.

[0134] Solid diluents include, for example, clays such as bentonite, montmorillonite, attapulgite and kaolin, starch, sugar, silicon dioxide, talc, diatomaceous earth, urea, calcium carbonate, sodium carbonate and sodium bicarbonate, and sodium sulfate, and 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, dodecanol and tetrahydrofuranol.

[0135] Solutions, including emulsifiable concentrates, can be prepared by simply mixing the components. Dusts and fine powders can be prepared by mixing and grinding, usually in a hammer mill or fluid energy mill. Suspensions are generally prepared by wet grinding; see, for example, U.S. Pat. No. 3,060,084, and granules and pellets are prepared by spraying the active substance onto a freshly prepared granular carrier or by granulation techniques. See Browning, "Agglomeration", Chemical Engineering, December 4, 1967, pp147-48, Perry's Chemical Engineer's Handbook, 4TH Ed., McGraw-Hill, New York, 1963, Pages 8-57 and following, and WO 91 / 13546. Pellets are prepared as described in U.S. Pat. No. 4,172,714, and water-dispersible and water-soluble granules are prepared as described in U.S. Pat. No. 4,144,050, U.S. Pat. No. 3,920,442 and DE 3,246,493. Tablets can be prepared as described in US 5180587, US 5232701 and US 5208030. Films can be prepared by the methods described in GB 2095558 and US 3299566.

[0136] For more information on processing, see U.S. Pat. No. 3,235,361, Col. 6, line 16 through Col. 7, line 19 and Examples 10-41; U.S. Pat. No. 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; U.S. Pat. No. 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] Herein, for certain applications of the composition, for example, in agriculture, one, two or more other fungicides, insecticides and acaricides, herbicides, plant growth regulators or fertilizers may be added to the insecticidal and / or acaricidal composition of the present invention, thereby producing additional advantages and effects.

[0138] Beneficial Effects

[0139] The compounds of formula (I) of the present invention show good activity against various pests and mites in agriculture or other fields. Moreover, these compounds can achieve good control effects at very low dosages, and thus can be used to prepare insecticides and / or miticides.

[0140] Definition and explanation of terms

[0141] Unless otherwise defined, all technical terms used herein have the same meaning as commonly understood by those skilled in the art to which the subject matter of the claims pertains. Unless otherwise indicated, all patents, patent applications, and publications cited herein are incorporated herein by reference in their entirety. If there are multiple definitions of a term herein, the definition in this chapter shall prevail.

[0142] It should be understood that references (including Carey and Sundberg "ADVANCED ORGANIC CHEMISTRY 4 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 technical scope of the art, such as mass spectrometry, NMR, IR and UV / Vis spectroscopy and pharmacological methods, are used. Unless specific definitions are provided, the terms used in the relevant descriptions of analytical chemistry, organic synthetic chemistry, and drugs and medicinal chemistry herein are known in the art. Standard techniques can be used in chemical synthesis, chemical analysis, drug preparation, formulation and delivery, and treatment of patients. For example, the manufacturer's instructions for the use of the kit, or in a manner known in the art or the description of this application, the reaction and Purification is performed. The above techniques and methods can be implemented according to conventional methods well known in the art, usually according to the descriptions in the multiple general and more specific documents cited and discussed in this specification. In this specification, groups and substituents thereof can be selected by those skilled in the art to provide stable structural parts and compounds. When substituents are described by conventional chemical formulas written from left to right, the substituents also include chemically equivalent substituents obtained when the structural formula is written from right to left, as long as they comply with the valence bond rules. For example, CH2O is equivalent to OCH2, and the carbon atoms of oxygen atoms or methylene groups can be connected to the substitution position.

[0143] The term "pharmaceutically acceptable salt" as used herein refers to a salt that retains the biological effectiveness of the free acid and free base of the specified compound and has no adverse effects in biology or other aspects. The compounds of the present application also include pharmaceutically acceptable salts, such as nitrates, hydrochlorides, sulfates, phosphates, acetates, trifluoroacetates, malates or citrates, etc., which are generally used in the field of agriculture and horticulture. Pharmaceutically acceptable salts refer to the conversion of the basic group in the parent compound into a salt form. Pharmaceutically acceptable salts include, but are not limited to, inorganic or organic acid salts of basic groups such as amine (amino) groups. The pharmaceutically acceptable salts of the present application can be synthesized from the parent compound, that is, the basic group in the parent compound is reacted with 1-4 equivalents of acid in a solvent system. Suitable salts are listed in Remington's Pharmaceutical Scicences, 17 th ed., Mack Publishing Company, Easton, Pa., 1985, p. 1418 and Journal of Pharmaceutical Science, 66, 2 (1977), e.g., the hydrochloride salt.

[0144] As used herein, "stereoisomer" refers to an isomer resulting from a different arrangement of atoms in a molecule in space. The compounds of formula (I) contain asymmetric or chiral centers and therefore exist in different stereoisomeric forms. All stereostructures of formula (I) are intended to be separated into individual diastereomers based on their different physicochemical properties using well-known methods, for example, enantiomers can be separated by reaction with appropriate optically active substances (e.g., chiral alcohols or Mosher's acid chlorides) to convert them into diastereomers, which are separated and converted (e.g., hydrolyzed) to the corresponding single isomers. Some compounds in formula (I) may be atropisomers (e.g., substituted aromatic groups) and are also part of this application. Enantiomers may also be separated using chiral chromatographic columns. The compounds in formula (I) may exist in different tautomeric forms, all of which are included within the scope of this application. For example, compounds in the form of keto-enol and imine-enamine. DETAILED DESCRIPTION

[0145] The technical scheme of the present invention will be further described in detail below in conjunction with specific embodiments. It should be understood that the following embodiments are only exemplary descriptions 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 included in the scope that the present invention is intended to protect.

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

[0147] The following chromatographic conditions were used for LC-MS analysis in the following examples:

[0148] Chromatographic column: Agilent ZORBAX SB-C18 150 mm × 4.6 mm, 5 μm (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 Example

[0153] Example 1: Preparation of N-(cyclopropylmethyl)-5-methyl-1-(3-methylbutan-2-yl)-N-(pyridazine-4-yl)-1H-pyrazole-4-carboxamide (Compound 1)

[0154]

[0155] Step 1: Preparation of (3-methylbutan-2-ylidene)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 completed, the temperature was raised to 50°C for reaction. After the raw materials reacted completely, the heating was stopped, the reaction solution was filtered, ethyl acetate was added to the filtrate after concentration, the separated liquid was washed with water, and 9.5 g of the product was concentrated.

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

[0157] Second step reaction: Preparation of ethyl 2-((2-(-3-methylbutan-2-ylidene)hydrazine)methylene)-3-oxobutanoate: At room temperature, 9.5 g (0.05 mol) of ethyl 2-(ethoxymethylene)-3-oxobutanoate was added to a flask, and a solution of 6 g (0.06 mol) (3-methylbutan-2-ylidene)hydrazine and 60 ml of methyl tert-butyl ether was added dropwise. After the addition was completed, stirring was continued at room temperature. After the reaction was no longer carried out, the mixture was concentrated under reduced pressure to obtain 11.7 g of the product;

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

[0159] The third step reaction: Preparation of 5-methyl-1-(3-methylbutan-2-yl)-1H-pyrazole-4-carboxylic acid ethyl ester: 11.7g (0.0488mol) of 2-((2-(-3-methylbutan-2-ylidene)hydrazino)methylene)-3-oxobutanoic acid ethyl ester, 6.5g of acetic acid and 50ml of methanol were added to a flask at room temperature, and 3.4g (0.054mol) of sodium cyanoborohydride was added under stirring. After the addition, the mixture was stirred at room temperature for 12h, and the reaction solution was concentrated to remove methanol. 100ml of water was added to the concentrate, and then extracted three times with 50ml of ethyl acetate. The organic phases were combined, washed once with 50ml of water, and the organic phases were concentrated to obtain 10.3g of the 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: 10 g (0.045 mol) of 5-methyl-1-(3-methylbutyl-2-yl)-1H-pyrazole-4-carboxylic acid ethyl ester was added to 40 ml of 5N sodium hydroxide aqueous solution at room temperature, and diluted with 20 ml of ethanol. The reaction mixture was stirred for 12 hours. After the raw material reaction was complete, the reaction solution was concentrated to remove ethanol. The residue was added with 50 ml of water and extracted once with 30 ml of ethyl acetate. The aqueous phase was adjusted to pH 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, and concentrated by suction to obtain 8.6 g of the product.

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

[0163] Step 5: Preparation of 5-methyl-1-(3-methyl-2-butyl)-1H-pyrazole-4-carbonyl chloride: 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 added to 10 ml of 1,2-dichloroethane at room temperature, heated to 80°C, and the mixture was stirred for 2 hours. After the reaction was completed, the solution was concentrated at 40°C under reduced pressure. 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: 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 at room temperature. Heat to 40°C and stir for 3 hours, dilute with ethyl acetate and aqueous solution, and separate the phases. Wash the organic layer with saturated brine and concentrate 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: Dissolve 21g (0.096mol) of a mixture of 3,5-dichloro-N-cyclopropylmethylpyridazine-4-amine and 4,5-dichloro-N-cyclopropylmethylpyridazine-3-amine in 200ml of ethanol, add 1.5g (0.001mol) of 10% Pd / C, and purge the pressure reactor with nitrogen. The pressure reactor is pressurized to 0.02MPa with hydrogen and heated to 35°C. After 5h, the raw materials react completely, the reaction solution is filtered, the filtrate is concentrated to remove ethanol, the residue is adjusted to alkalinity with a saturated potassium carbonate solution, and then extracted three times with 200ml of dichloromethane, the organic phases are combined, dried over anhydrous sodium sulfate, filtered and concentrated to obtain 13.3g 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-methylbutan-2-yl)-N-(pyridazine-4-yl)-1H-pyrazole-4-carboxamide: To a dichloroethane solution of 0.75 g (0.005 mol) of N-cyclopropylmethylpyridazine-4-amine and 0.76 g (0.0075 mol) of triethylamine was added dropwise 1.1 g (0.005 mol) of 5-methyl-1-(3-methyl-2-butyl)-1H-pyrazole-4-carbonyl chloride at 0°C. After stirring at room temperature for 24 h, the mixture was diluted with 100 ml of dichloroethane, washed with 3X 50 ml of saturated saline solution, dried over magnesium sulfate and concentrated. The residue was purified by column chromatography (CH2Cl2 / MeOH) to give 1.12 g of the 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-methylbutan-2-yl)-N-(pyridazin-4-yl)-1H-pyrazole-4-carboxamide (Compound 9)

[0172]

[0173] To a dichloroethane solution of 0.92 g (0.005 mol) of N-((2-chlorocyclopropyl)methyl)pyridazin-4-amine and 0.76 g (0.0075 mol) of triethylamine was added dropwise 1.1 g (0.005 mol) of 5-methyl-1-(3-methyl-2-butyl)-1H-pyrazole-4-carbonyl chloride at 0°C. After stirring at room temperature for 24 h, the mixture was diluted with 100 ml of dichloroethane, washed with 3X 50 ml of saturated saline solution, dried over magnesium sulfate and concentrated. The residue was purified by column chromatography (CH2Cl2 / MeOH) to give 1.18 g of the 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 method 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 are prepared using conventional methods.

[0186] Embodiment 3:

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

[0188] Compound 1 50.0%, dodecylphenol polyethoxyglycol ether 4.0%, sodium lignin sulfonate 6.0%, sodium aluminosilicate 8.0%, montmorillonite (calcined) 32.0%.

[0189] Embodiment 4:

[0190] In this example, the compound obtained in the above example is used to prepare granules, and the raw material composition is specifically used for preparation:

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

[0192] Embodiment 5:

[0193] In this embodiment, the compound obtained in the above embodiment is used to prepare extruded pellets, and the raw material composition is specifically used for preparation:

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

[0195] Embodiment 6:

[0196] This example uses the compound obtained in the above example to prepare emulsifiable concentrate, and specifically adopts the following raw material composition for preparation:

[0197] Compound 12 25.0%, solvent 150 60%, PEG 400 5%, Rhodacal 70 / B 3%, Rhodameen RAM / 77%.

[0198] Embodiment 7:

[0199] In this example, the compound obtained in the above example is used to prepare an aqueous suspension, and the raw material composition is specifically used for preparation:

[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 were added to 100.0%.

[0201] Biological activity assay

[0202] Embodiment 8:

[0203] 1. Determination of insecticidal activity

[0204] In this example, the compounds prepared in the above examples were used to carry out insecticidal activity tests on several insects.

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

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

[0207]

[0208] (1) Test results of exemplary compounds for controlling green peach aphids

[0209] At a dosage of 100 ppm, the compounds with a mortality rate of more than 80% to green peach aphid 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] At a dosage of 20 ppm, the compounds with a mortality rate of more than 80% to green peach aphid 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] At a dosage of 5 ppm, the compounds with a mortality rate of over 80% to peach aphid 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 exemplary compounds for controlling whiteflies

[0213] At a dosage of 100 ppm, the compounds with a mortality rate of more than 80% to Bemisia tabaci 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] At a dosage of 20 ppm, the compounds with a mortality rate of more than 80% to whitefly 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] At a dosage of 5 ppm, the compounds with a mortality rate of over 80% to whitefly 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, 116.

[0216] (3) Test results of the compounds of the examples for controlling tea green leafhoppers

[0217] At a dosage of 100 ppm, the compounds with a mortality rate of more than 80% to tea green leafhoppers 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] At a dosage of 20 ppm, the compounds with a mortality rate of more than 80% to tea green leafhoppers 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] At a dosage of 5 ppm, the compounds with a mortality rate of over 80% to tea green leafhopper 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, 116.

[0220] (4) Exemplary test results of the compounds of the examples for controlling scale insects

[0221] At a dosage of 100 ppm, the compounds with a mortality rate of more than 80% to scale insects 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] At a dosage of 20 ppm, the compounds with a mortality rate of more than 80% to scale insects 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] At a dosage of 5 ppm, the compounds with a mortality rate of over 80% to scale insects 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, 116.

[0224] (5) Illustrative test results of the compounds of the examples for controlling brown planthoppers

[0225] At a dosage of 100 ppm, the compounds with a mortality rate of more than 80% to brown planthoppers 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] At a dosage of 20 ppm, the compounds with a mortality rate of more than 80% to brown planthoppers 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. Determination of acaricidal activity

[0228] In this example, the compounds prepared in the above examples were used to carry out acaricidal activity tests on several types of mite pests.

[0229] The test method is as follows: Dissolve the compound sample to be tested with a suitable solvent (the type of solvent is acetone, methanol, DMSO, etc., and is selected according to its solubility for the sample) to prepare a test solution of the required concentration. Cut the double-sided tape into 2-3 cm long pieces and stick them to one end of the microscope slide. Use tweezers to peel off the paper on the tape, use a No. 0 brush to select female adult mites of uniform size, bright body color, and active movements, and stick their backs to the double-sided tape (note: do not stick the mite legs, whiskers, and mouthparts), stick 4 rows to each piece, and stick 10 heads to each row.

[0230] The test method is as follows: Repeat the test three times, place in a biochemical incubator at a temperature of (25+1)℃ and a relative humidity of about 85% for 4 hours, observe with binoculars, and remove dead or inactive individuals. Dip one end of the glass slide with mites into the liquid medicine, shake gently for 5 seconds, then take it out, and quickly dry the mite body and the excess liquid around it with absorbent paper. Place it in the above biochemical incubator, check the results with binoculars after 24 hours, touch the mite body with a brush, and the mite whose feet do not move is considered dead, and calculate the mortality rate. The mortality rate is calculated as follows:

[0231]

[0232] The results of the test on Tetranychus cinnabarinus are as follows:

[0233] At a dosage of 200 ppm, the compounds with a mortality rate of more than 80% to Tetranychus cinnabarinus 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.

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

[0235] This example conducted an insecticidal activity comparison test of the exemplary example compound and the control agent (prepared according to the method reported in the literature, and the insecticidal test method was 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 above table, the other exemplary compounds of the present invention have significantly better control activities against pests and mites than the control agent. Therefore, the compounds of formula (I) of the present invention show good activity against various pests and mites in the agricultural field.

[0244] The above is an explanation of the embodiments of the present invention. However, the present invention is not limited to the above embodiments. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present invention shall be included in the protection scope of the present invention.

Claims

1. A compound represented by formula (I), its stereoisomer, racemate, tautomer, nitrogen oxide or a pharmaceutically acceptable salt thereof, in, R1 is selected from C1-C6 alkyl, halogenated C1-C4 alkyl, C3-C6 cycloalkyl or halogenated C3-C6 cycloalkyl; R2 is selected from C1-C4 alkyl; R3 is selected from H or C1-C4 alkyl; R4 is selected from C1-C4 alkyl; R5 is selected from C3-C6 cycloalkyl, halogenated C3-C6 cycloalkyl, C3-C6 cycloalkylC1-C2 alkyl, halogenated C3-C6 cycloalkylC1-C2 alkyl or C3-C6 epoxyalkylC1-C2 alkyl; A is selected from CH or N; X is selected from O or S.

2. The compound according to claim 1, characterized in that R1 is selected from C2-C6 alkyl, halogenated C1-C4 alkyl, C3-C6 cycloalkyl or halogenated C3-C6 cycloalkyl; R2 is selected from C1-C4 alkyl; R3 is selected from H or C1-C4 alkyl; R4 is selected from methyl or ethyl; R5 is selected from C3-C6 cycloalkyl, halogenated C3-C6 cycloalkyl, C3-C6 cycloalkylC1-C2 alkyl, halogenated C3-C6 cycloalkylC1-C2 alkyl or C3-C6 epoxyalkylC1-C2 alkyl; A is selected from N or CH; X is selected from O or S.

3. The compound according to claim 1 or 2, characterized in that R1 is selected from C2-C3 alkyl, halogenated C1-C3 alkyl, C3-C6 cycloalkyl or halogenated C3-C6 cycloalkyl; R2 is selected from C1-C3 alkyl; R3 is selected from H or methyl; R4 is selected from methyl or ethyl; R5 is selected from C3-C6 cycloalkyl, halogenated C3-C6 cycloalkyl, C3-C6 cycloalkylC1-C2 alkyl, halogenated C3-C6 cycloalkylC1-C2 alkyl or C3-C6 epoxyalkylC1-C2 alkyl; A is selected from N or CH; X is selected from O or S.

4. The compound according to any one of claims 1 to 3, characterized in that R1 is selected from ethyl, n-propyl, isopropyl, cyclopropyl, cyclobutyl, one, two or more fluorine or chlorine substituted groups: methyl, ethyl, n-propyl, isopropyl, cyclopropyl or cyclobutyl; R2 is selected from methyl, ethyl or propyl; R3 is selected from H or methyl; R4 is selected from methyl or ethyl; R5 is selected from cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, A is selected from N or CH; X is selected from O or S.

5. The compound according to any one of claims 1 to 4, characterized in that Formula (I) is selected from the structure shown in the following formula (IA): Wherein, A, X, R4 and R5 have the definitions as described in any one of claims 1-4.

6. The compound according to claim 5, characterized in that In Formula IA, A is selected from N or CH; X is selected from O or S; R4 is selected from methyl or ethyl; R5 is selected from 7. The compound according to any one of claims 1 to 3, characterized in that The compound of formula (I) is selected from the following compounds, 8. Use of one, two or more of the compound of formula (I) according to any one of claims 1 to 7, its stereoisomers, racemates, tautomers, nitrogen oxides or pharmaceutically acceptable salts thereof as pesticides, such as insecticides and / or miticides.

9. Use of one, two or more of the compound of formula (I) according to any one of claims 1 to 7, its stereoisomers, racemates, tautomers, nitrogen oxides or pharmaceutically acceptable salts thereof in the preparation of pesticides, such as insecticides and / or miticides.

10. A method for controlling pests, comprising applying an effective amount of one, two or more of the compound of formula (I) according to any one of claims 1 to 7, its stereoisomers, racemates, tautomers, nitrogen oxides or pharmaceutically acceptable salts thereof, or the composition to a growth medium of pests and / or mites.

Images