Dinanserin derivatives, compositions thereof, uses thereof

Abstract

The application belongs to the technical field of pesticides, and particularly relates to a pyridylalanine derivative, a composition thereof and a use thereof. The compound is shown in the general formula I: wherein X1 represents hydrogen or fluorine, X2 represents hydrogen or fluorine, X3 represents hydrogen or fluorine, X4 represents hydrogen or fluorine, and X1, X2, X3 and X4 are not hydrogen at the same time; R1 and R2 independently represent hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl or -(CO)R3; Y1 represents hydroxyl, alkoxyalkyloxy, trialkylsilyloxy or -O(CO)R3; Y2 represents hydrogen or alkyl; or Y1 and Y2 together form =O. The compound has excellent control effects on pests such as Myzus persicae, Lygus lineolaris, Rhopalosiphum maidis and Bemisia tabaci.

Description

TECHNICAL FIELD

[0001] The present application belongs to the technical field of pesticides, and particularly relates to a pyridalyl derivative and a composition and use thereof. BACKGROUND

[0002] To date, a number of pest control agents having insecticidal activity have been reported. However, insect species having resistance to these pest control agents or which are difficult to control by these pest control agents have been found and further problems of safety to humans and animals exist. Thus, there is still a demand for development of novel pest control agents having potent insecticidal activity. SUMMARY

[0003] To solve the above problems in the prior art, the present application provides a pyridalyl derivative and a composition and use thereof. The compound has excellent control effect on pests such as Myzus persicae, Lygus lineolaris, Sitobion avenae, Bemisia tabaci and the like.

[0004] The technical solution adopted by the present application is as follows:

[0005] A pyridalyl derivative as shown in formula I,

[0006]

[0007] wherein X1 represents hydrogen or fluorine, X2 represents hydrogen or fluorine, X3 represents hydrogen or fluorine, X4 represents hydrogen or fluorine, and X1, X2, X3 and X4 are not hydrogen at the same time;

[0008] R1, R2 independently represent hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl or -(CO)R3;

[0009] Y1 represents hydroxyl, alkoxyalkyloxy, trialkylsilyloxy or -O(CO)R3; Y2 represents hydrogen or alkyl; or Y1, Y2 together form =O;

[0010] R3 independently represents hydrogen, alkyl, alkenyl or alkynyl which is unsubstituted or substituted by at least one group selected from halogen, alkoxy, alkoxycarbonyl or alkylthio, cycloalkyl, cycloalkenyl, aryl or heterocyclyl;

[0011] The aforementioned "cycloalkyl", "cycloalkenyl", "heterocyclyl" or "aryl" is optionally substituted by one or more groups selected from oxo, halogen, cyano, nitro, alkyl, alkenyl, alkynyl, cycloalkyl, halogenated alkyl, halogenated alkenyl, halogenated alkynyl, halogenated cycloalkyl, cycloalkyl substituted by alkyl, -OR 10 , -SR 10 , -(CO)OR 10 , -(SO2)R 10 , -N(R 10 )2 or -O-alkylene-(CO)OR10 substituted or adjacent carbon atoms on the ring form a fused ring with -OCH2CH2- or -OCH2O- which is unsubstituted or substituted with halogen;

[0012] R 10 are each independently hydrogen, alkyl, haloalkyl, phenyl, or phenyl substituted with at least one member selected from the group consisting of halogen, cyano, nitro, alkyl, haloalkyl, alkoxycarbonyl, alkylthio, alkylsulfonyl, alkoxy, or haloalkoxy.

[0013] In one embodiment,

[0014] R1, R2 are each independently hydrogen, C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, C3-C8 cycloalkyl, C3-C8 cycloalkyl C1-C8 alkyl or -(CO)R3;

[0015] Y1 is hydroxy, C1-C8 alkoxy C1-C8 alkyl oxy, tri C1-C8 alkyl silyloxy or -O(CO)R3;

[0016] Y2 is hydrogen or C1-C8 alkyl; or Y1, Y2 together form =O;

[0017] R3 are each independently hydrogen, C1-C8 alkyl, C2-C8 alkenyl or C2-C8 alkynyl, C3-C8 cycloalkyl, C3-C8 cycloalkenyl, aryl or heterocyclyl which are unsubstituted or substituted with at least one member selected from the group consisting of oxo, halogen, cyano, nitro, C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, C3-C8 cycloalkyl, halo C1-C8 alkyl, halo C2-C8 alkenyl, halo C2-C8 alkynyl, halo C3-C8 cycloalkyl, C3-C8 cycloalkyl substituted with C1-C8 alkyl, -OR

[0018] The foregoing "C3-C8 cycloalkyl", "C3-C8 cycloalkenyl", "heterocyclyl" or "aryl" are optionally substituted with at least one member selected from the group consisting of oxo, halogen, cyano, nitro, C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, C3-C8 cycloalkyl, halo C1-C8 alkyl, halo C2-C8 alkenyl, halo C2-C8 alkynyl, halo C3-C8 cycloalkyl, C3-C8 cycloalkyl substituted with C1-C8 alkyl, -OR 10 , -SR 10 , -(CO)OR 10 , -(SO2)R 10 , -N(R 10 )2 or -O-(C1-C8 alkylene)-(CO)OR 10 substituted or adjacent carbon atoms on the ring form a fused ring with -OCH2CH2- or -OCH2O- which is unsubstituted or substituted with halogen;

[0019] R 10are independently hydrogen, C1-C8alkyl, haloC1-C8alkyl, phenyl, or phenyl substituted with at least one group selected from halogen, cyano, nitro, C1-C8alkyl, haloC1-C8alkyl, C1-C8alkyloxycarbonyl, C1-C8alkylthio, C1-C8alkylsulfonyl, C1-C8alkoxy or haloC1-C8alkoxy.

[0020] In a particular embodiment,

[0021] R1, R2are independently hydrogen, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C6cycloalkyl, C3-C6cycloalkylC1-C6alkyl or -(CO)R3;

[0022] Y1represents hydroxy, C1-C6alkyloxyC1-C6alkyloxy, triC1-C6alkylsilyloxy or -O(CO)R3;

[0023] Y2represents hydrogen or C1-C6alkyl; or Y1, Y2together form =O;

[0024] R3is independently hydrogen, C1-C6alkyl, C2-C6alkenyl or C2-C6alkynyl, C3-C6cycloalkyl, C3-C6cycloalkenyl, aryl or heterocyclyl, unsubstituted or substituted with at least one group selected from halogen, C1-C6alkyloxy, C1-C6alkyloxycarbonyl or C1-C6alkylthio;

[0025] the aforementioned "C3-C6cycloalkyl", "C3-C6cycloalkenyl", "heterocyclyl" or "aryl" is optionally substituted with 1 to 3 groups selected from oxo, halogen, cyano, nitro, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C6cycloalkyl, haloC1-C6alkyl, haloC2-C6alkenyl, haloC2-C6alkynyl, haloC3-C6cycloalkyl, C3-C6cycloalkyl substituted with C1-C6alkyl, -OR 10 , -SR 10 , -(CO)OR 10 , -(SO2)R 10 , -N(R 10 )2or -O-(C1-C6alkylene)-(CO)OR 10 , or the adjacent two carbon atoms in the ring form a fused ring with -OCH2CH2- or -OCH2O- unsubstituted or substituted with halogen;

[0026] R 10independently of one another hydrogen, C1-C6-alkyl, halo-C1-C6-alkyl, phenyl, or phenyl substituted by 1 to 3 radicals from the group halogen, cyano, nitro, C1-C6-alkyl, halo-C1-C6-alkyl, C1-C6-alkyloxy-carbonyl, C1-C6-alkylthio, C1-C6-alkylsulfonyl, C1-C6-alkyloxy or halo-C1-C6-alkyloxy.

[0027] In a particular embodiment,

[0028] X1represents hydrogen, X2represents fluorine, X3represents hydrogen, X4represents hydrogen; or X1represents hydrogen, X2represents hydrogen, X3represents fluorine, X4represents hydrogen.

[0029] In a particular embodiment,

[0030] Y1represents hydroxy or -O(CO)R3; Y2represents hydrogen; or Y1, Y2together form =O.

[0031] In the definition of the compounds of the general formulae described above and in all structural formulae below, the professional terms used, whether used alone or in a composite, stand for the following substituents: Alkyl groups having more than two carbon atoms can be straight-chained or branched. As in the composite "O-alkylene-(CO)OR 10 " the alkylene can be -CH2-, -CH2CH2-, -CH(CH3)-, -C(CH3)2-, etc. Alkyl groups are, for example, C1 alkyl - methyl; C2 alkyl - ethyl; C3 alkyl - propyl, such as n-propyl or isopropyl; C4 alkyl - butyl, such as n-butyl, isobutyl, tert-butyl or 2-butyl; C5 alkyl - pentyl, such as n-pentyl; C6 alkyl - hexyl, such as n-hexyl, isohexyl and 1,3-dimethylbutyl. Similarly, alkenyl is, for example, ethenyl, allyl, 1 -methylprop-2-en-1 -yl, 2-methylprop-2-en-1 -yl, but-2-en-1 -yl, but-3-en-1 -yl, 1 -methylbut-3-en-1 -yl and 1 -methylbut-2-en-1 -yl. Alkynyl is, for example, ethynyl, propargyl, but-2-yn-1 -yl, but-3-yn-1 -yl, 1 -methylbut-3-yn-1 -yl. Multiple bonds can be in any position of each unsaturated group. Cycloalkyl is a carbocyclic saturated ring system having, for example, three to six carbon atoms, such as cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl. Similarly, cycloalkenyl is a monocyclic alkenyl group having, for example, three to six carbon ring members, such as cyclopropenyl, cyclobutenyl, cyclopentenyl and cyclohexenyl, wherein the double bond can be in any position. Halogen is fluorine, chlorine, bromine or iodine.

[0032] Unless specifically indicated otherwise, "aryl" as used in the present application includes, but is not limited to, phenyl, naphthyl, The "heterocyclyl" group includes, but is not limited to, saturated or unsaturated non-aromatic cyclic groups and the like, including but not limited to heteroaryl, i.e. an aromatic cyclic group containing, for example, 3 to 6 ring atoms, 1 to 4 (e.g. 1, 2, 3 or 4) of the ring atoms being heteroatoms selected from oxygen, nitrogen and sulfur, for example

[0033] If a group is substituted with a group, this is to be understood as meaning that the group is substituted with one or more identical or different groups selected from those mentioned. In addition, the same or different substituents contained in the same or different substituents are each selected independently of one another, can be identical or different. The same applies to ring systems formed by different atoms and units. At the same time, the scope of the claims is to exclude compounds which are chemically unstable under standard conditions, as is known to the person skilled in the art.

[0034] In addition, unless specifically limited otherwise, "substituted with at least one group" according to the application means substituted with, for example, 1, 2, 3, 4 or 5 groups; groups not marked with a specific position of attachment (including heterocyclyl, aryl and the like) can be attached at any position, including to a C or N; if it is substituted, the substituents can likewise be substituted at any position, provided that the rules for the formation of chemical bonds are observed. For example, a heteroaryl group substituted with 1 methyl group may represent, for example and the like.

[0035] The compound represented by the formula I or a salt thereof has an insecticidal effect on, for example, the following pest species as an active ingredient: lepidopteran pests such as Spodoptera litura, Mamestra brassicae, Pseudaletia separata, green caterpillar, Plutella xylostella, Spodoptera exigua, Chilo suppressalis, Cnaphalocrocis medinalis, Tortricidae, Carposinidae, Lyonetiidae, Lymantriidae, Agrotis spp. pests, Helicoverpa spp. pests, or Heliothis spp. pests, and the like; hemipteran pests such as Aphididae, Adelgidae, or Phylloxeridae, for example, Myzus percicae, Aphis gossypii Glover, Aphis fabae Scop., Adelges laricis Gillette, Adelges laricola

[0036] (Phylloxeridae), for example, Myzus percicae, Aphis gossypii Glover, Aphis fabae Scop., Adelges laricis Gillette, Adelges laricola

[0037] (Aphis fabae), corn leaf aphid (Aphis maidis), pea aphid (Acyrthosiphon pisum), potato aphid (Aulacorthum solani), bean aphid (Aphis craccivora), Macrosiphum euphorbiae, English grain aphid (Macrosiphum avenae), oat aphid (Metopolophium dirhodum), Rhopalosiphum padi, Schizaphis graminum, cabbage aphid (Brevicoryne brassicae), Lipaphis erysimi, Aphis citricola, Rosy apple aphid, apple woolly aphid (Eriosoma lanigerum), Toxoptera aurantii or Toxoptera citricidus, Deltocephalidae, such as Nephotettix cincticeps, leafhopper, such as Tea green leafhopper, Delphacidae, such as Laodelphax striatellus, Nilaparvata lugens or Sogatella furcifera, Pentatomidae, such as Eysarcoris ventralis, Nezara viridula or Trigonotylus caelestialium, Aleyrodidae, such as Bemisia tabaci or Trialeurodes vaporariorum, Coccoidea, such as Pseudococcus comstocki,Planococcus citri Risso or Aonidiella aurantii (e.g. Diaspididae, Margarodidae, Ortheziidae, Aclerdiae, Dactylopiidae, Kerridae, Pseudococcidae, Coccidae, Eriococcidae, Asterolecaniidae, Beesonidae, Lecanodiaspididae or Cerococcidae), and Psyllidae, e.g. Diaphorina citri; Coleopteran pests, e.g. Lissorhoptrus oryzophilus, Callosobruchus chinensis, Tenebrio molitor, Diabrotica virgifera virgifera, Diabrotica undecimpunctata howardi, Anomala cuprea, Anomala rufocuprea, Phyllotreta striolata, Aulacophora femoralis, Leptinotarsa decemlineata, Oulema oryzae, Grapholita molesta or Cerambycidae; Acari, e.g. Tetranychus urticae, Tetranychus kanzawai or Panonychus citri; Hymenopteran pests, e.g. Tenthredinoidea; Orthopteran pests, e.g. Acrididae; Dipteran pests, e.g. Musca domestica Linnaeus or Agromyzidae; Thysanopteran pests,Thrips palmi KARNY or Frankliniella occidentalis; and plant parasitic nematodes, for example Meloidogyne hapla, Pratylenchus, Aphelenchoides besseyi or Bursaphelenchus xylophilus. Examples of animal parasitic worms include Siphonaptera, for example Ctenocephalides felis or Pulex irritans, Anoplura, for example Pediculus spp. or Phtirus spp.; Acari, for example Boophilus spp., Rhipicephalus sanguineus, Haemaphysalis longicornis, Rhipicephalus sanguineus, Haemaphysalis flava, Sarcoptes spp., Dermanyssus spp., Ornithonyssus sylviarum, Ornithonyssus bacoti, and Leptotrombidium; Tabanidae; Diptera, for example Lucilia spp.; mosquitoes, for example Stegomyia albopicta and Culex pipiens pallens; Simuliidae; Ceratopogonidae

[0038] (Haemaphysalis longicornis), Rhipicephalus sanguineus, Haemaphysalis flava, Sarcoptes spp., Dermanyssus spp., Ornithonyssus sylviarum, Ornithonyssus bacoti, and Leptotrombidium; Tabanidae; Diptera, for example Lucilia spp.; mosquitoes, for example Stegomyia albopicta and Culex pipiens pallens; Simuliidae; Ceratopogonidae

[0039] (Haemaphysalis longicornis), Rhipicephalus sanguineus, Haemaphysalis flava, Sarcoptes spp., Dermanyssus spp., Ornithonyssus sylviarum, Ornithonyssus bacoti, and Leptotrombidium; Tabanidae; Diptera, for example Lucilia spp.; mosquitoes, for example Stegomyia albopicta and Culex pipiens pallens; Simuliidae; Ceratopogonidae

[0040] (Ceratopogonidae); Nematoda, for example Strongyloides, for example Strongyloides papillosus or Strongyloides stercoralis, hookworms, for example A. caninum, Ancylostoma tubaeforme or Ancylostoma duodenale; Haemonchus spp; Strongylida, for example mouse Strongyloides; hairworms; Metastrongyloidea, for example Metastrongylus spp., Angiostrongylus cantonensis or Aelurostrongylus

[0041] (Aelurostrongylus); Oxyurida; Heterakidae, for example Heterakis gallinarum

[0042] (Heterakis gallinarum); Anisakis simplex; Ascaroidea, for example Ascaris suum, Parascaris equorum, Toxicara canis or Toxascaris leonine

[0043] (Toxocara cati); Subuluridae; Spiruroidea, for example Gnathostoma spinigerum, Physaloptera, Ascarops strongylina, Draschia megastoma, Acuaria or Ostertagia ostertagi; Filariida, for example Dirofilaria or Onchocerca cervicalis; Order Dioctophymatida; Wipeworms and Trichinosis, for example Trichuris vulpis or Trichinella spiralis; Trematoda, for example Schistosoma toide, for example Schistosoma japonicum or Fasciola hepatica; Acanthocephala

[0044] (Acanthocephala), for example Macracanthorhynchus hirudinaceus or Moniliformis moniliformis; Cestoda, for example Bothriocephaloidea, for example Diphyllobothrium mansoni; Cyclophyllidea, for example Dipylidium caninum, Hymenolepis diminuta, Echinococcus multilocularis or Echinococcus granulosus; and protozoa. Preferred pest species include Hemiptera, Diptera and Thysanoptera pests. Particularly preferred are Hemiptera pests.

[0045] Preferred hemipteran pests include aphids, Aleyrodidae or Pseudococcidae (preferably aphids); leafhoppers, Aleyrodidae, Pentatomidae or Coccoidea (Diaspididae, Pseudococcidae, Lacciferidae, Ortheziidae, Phenacoleidae, Kermesidae, Margarodidae, Pseudococcidae, Coccidae, Eriococcidae, Ortheziidae or Kerrimicidae); and Psylloidae, more preferably Myzus persicae, Aphis gossypii, Empoasca fabae, Bemisia tabaci, Trialeurodes vaporariorum, Trigonotylus caelestialium or Pseudococcus comstocki, Planococcus citri and Diaphorina citri.

[0046] When the compound represented by formula I is used as a pest control agent, the compound represented by formula I can be used directly. Alternatively, the compound represented by formula I can be mixed with a suitable carrier acceptable in agriculture or animal husbandry, such as a solid carrier, a liquid carrier and a gaseous carrier, a surfactant, a dispersant or other adjuvants for formulation, to prepare any suitable formulation, for example, an emulsifiable concentrate, an EW (oil-in-water emulsion), a liquid formulation, a suspension, a wettable powder, a water-dispersible granule, a powder, a DL powder, a fine granule, a granule, a tablet, an oil, an aerosol, a floable, a dry sol or a microcapsule.

[0047] The solid carrier, for example, includes talc, bentonite, clay, kaolin, diatomaceous earth, vermiculite, white carbon or calcium carbonate.

[0048] The liquid carrier, for example, includes alcohols, such as methanol, n-hexanol or ethylene glycol; ketones, such as acetone, methyl ethyl ketone or cyclohexanone; aliphatic hydrocarbons, such as n-hexane, kerosine or kerosene; aromatic hydrocarbons, such as toluene, xylene or methylnaphthalene; ethers, such as diethyl ether, dioxane or tetrahydrofuran; esters, such as ethyl acetate; nitriles, such as acetonitrile or isobutyronitrile; amides, such as dimethylformamide or dimethylacetamide; vegetable oils, such as soybean oil or cottonseed oil; dimethyl sulfoxide; or water.

[0049] The gaseous carrier, for example, includes LPG, air, nitrogen, carbon dioxide and dimethyl ether.

[0050] The surfactant or dispersant that can be used, for example, for emulsification, dispersion or spreading, for example, includes alkyl sulfates, alkyl(aryl)sulfonates, polyoxyalkylene alkyl(aryl)ethers, polyhydric alcohol esters and lignin sulfonates. The adjuvant that can be used to improve the performance of the formulation, for example, includes carboxymethyl cellulose, gum arabic, polyethylene glycol and calcium stearate.

[0051] The above-mentioned carriers, surfactants, dispersants and adjuvants can be used alone or in combination as needed.

[0052] The content of the active ingredient in these formulations is not particularly limited, but is preferably 1 to 75% by weight of an emulsifiable concentrate, 0.3 to 25% by weight of a powder, 1 to 90% by weight of a wettable powder, and 0.5 to 10% by weight of a granule.

[0053] According to another aspect of the present application, there is provided a method for controlling a harmful organism, the method comprising applying an effective amount of a compound represented by Formula I or a salt thereof to a water surface, soil, a nutrient solution in nutrient solution culture, a solid medium in nutrient solution culture, and seeds, roots, tubers, corms, and rhizomes of a plant.

[0054] According to one embodiment of the present application, there is provided a method for controlling a harmful organism, the method comprising applying an effective amount of a compound represented by Formula I or a salt thereof to a harmful organism or its habitat. According to a preferred embodiment of the present application, there is provided a method for controlling a harmful organism, the method comprising applying an effective amount of a compound represented by Formula I or a salt thereof to a plant or soil.

[0055] The compound represented by Formula I or a salt thereof directly exerts a potent control effect on a harmful organism. Furthermore, it is expected that the compound exerts a control effect higher than that achieved when only the compound or another harmful organism control agent is used, as a mixture with the other harmful organism control agent. Accordingly, according to the present application, there is provided a harmful organism control composition comprising at least one compound represented by Formula I or a salt thereof and at least one other harmful organism control agent. Furthermore, according to another embodiment of the present application, there is provided the use of the harmful organism control composition for protecting useful plants (cultivated plants) from harmful organisms. Furthermore, according to another embodiment, there is provided the use of the harmful organism control composition for the production of an agent for protecting useful plants (cultivated plants) from harmful organisms.

[0056] The compositions or compounds useful as the harmful organism control agents of the present application or their admixture with other harmful organism control agents are used for controlling a number of pests on a variety of plants. Target plants include wheat and barley, coarse grains such as corn, millet, foxtail millet, barnyard millet, and food sorghum, fruit trees such as orange, apple, and grape, vegetables such as cucumber, pumpkin, melon, cabbage, eggplant, tomato, and strawberry, tubers such as potato, sweet potato, and taro, leguminous plants such as azuki bean, kidney bean, and soybean, oil crops such as rapeseed, forage crops such as animal feed grasses, sorghum, and corn, ornamental plants, foliage plants, wood, tea, sugar beet, sugarcane, sunflower, hops, cotton, tobacco, arabica coffee, lawn grass, and edible mushroom.

[0057] The compositions or compounds useful as the pest control agents of the present application or their admixture with other pest control agents can be applied to pests, plants and plant propagation materials, in particular, for example, seeds, plant leaves, roots, soil, water surfaces, cultivation materials and spaces in which pests should be prevented from entering. The treatment with the compounds, admixtures and compositions of the present application can be carried out before and after the pests enter.

[0058] The present application includes the killing of animal parasitic pests. The killing of pests can be carried out by applying to habitats, pastures, feed, plants, seeds, soil, materials and growing environments in which the animal parasitic pests grow or will grow, or to materials, plants, seeds, soil and water surfaces in which the animal parasitic pests should be prevented from entering.

[0059] The plant propagation materials to which the present application is applied as the object are plants having the ability to be propagated in the growth of plants, including but not limited to seeds, branches or cuttings (lop), pullout portions of a part of tubers, in particular seeds, roots, fruits, tubers, bulbs, rhizomes, roots, branches and buds. Also included are seedlings or seedlings which are transplanted after germination or rooting. The plant protection agents are applied to these plant propagation materials at the time of settled plating or transplantation for prevention.

[0060] The term "cultivated plants" is to be understood to include plants that have been modified by breeding, mutagenesis and / or genetic engineering. Genetically modified plants (GMO) are plants whose genetic material has been modified by the use of recombinant DNA techniques in a way that does not occur under natural conditions. Generally, one or more genes are integrated into the genetic material of the plants in order to improve certain properties of the plants. Such genetic modifications also include but are not limited to targeted post-translational modification of proteins (oligo- or polypeptides), for example by glycosylation or polymer additions such as prenylation, acetylation or farnesylation moieties or PEG moieties (for example as disclosed in Biotechnol Prog. 2001 Jul-Aug; 17(4):720-8., Protein Eng Des Sel. 2004 Jan; 17(1):57-66, Nat Protoc. 2007; 2(5):1225-35., Curr Opin Chem Biol. 2006 Oct; 10(5):487-91. Epub 2006 Aug 28, Biomaterials. 2001 Mar; 22(5):405-17, Bioconjug Chem. 2005 Jan-Feb; 16(1):113-21).

[0061] The term "cultivated plants" is to be understood to include plants which have been modified by genetic engineering methods, i.e. by the direct manipulation of heritable material, such as genes, and which show characteristics that were not present in the plant species as it grew naturally. The term "cultivated plants" is to be understood to also include plants which have been made tolerant to

[0062] Several cultivated plants have been made tolerant to herbicides by conventional methods of breeding (mutagenesis), for example Clearfield® (registered trademark) winter oilseed rape (Canola) which is tolerant to imidazolinones, such as imazamox. Cultivated plants have also been made tolerant to herbicides by genetic engineering methods, such as soybean, cotton, corn, beets and sunflower which are tolerant to herbicides such as glyphosate or glufosinate-ammonium, some of which are available under the trade names RoundupReady® (registered trademark) (tolerance to glyphosate) and LibertyLink® (registered trademark) (tolerance to glufosinate-ammonium).

[0063] The term "cultivated plants" is to be understood to include plants that are treated with one or more insecticidal or herbicidal proteins by the use of recombinant DNA techniques, such as a delta-endotoxin, for example CryIA(b), CryIA(c), CryIF, CryIF(a2), CryIIA(b), CryIIIA, CryIIIB(b1) or Cry9c; a vegetative insecticidal protein (VIP), for example VIP1, VIP2, VIP3 or VIP3A; an insecticidal protein of the nematode- colonizing bacteria Photorhabdus spp. or Xenorhabdus spp.; an animal- derived toxin, such as a scorpion toxin, a spider toxin, a wasp toxin or other insect-specific neurotoxin; a fungal-derived toxin, such as a Streptomycetes toxin; a plant lectin, such as pea or barley lectin; an agglutinin, a protease inhibitor, such as a trypsin inhibitor, a serine protease inhibitor, patatin, a cystatin or a papain inhibitor, a ribosome-inactivating protein (RIP), such as ricin, corn-RIP, modeccin, a cucurmosin, saporin or bryodin; a steroid metabolism enzyme, such as 3-hydroxy- steroid oxidase, ecdysteroid-IDP-glycosyl-transferase, cholesterol oxidase, ecdysone inhibitor or HMG-CoA reductase; an ion channel blocker, such as a sodium channel or calcium channel blocker; a juvenile hormone esterase; a diuretic hormone receptor (helicokinin receptor); a synthetase, a bibenzyl synthetase, a chitinase or a glucanase.

[0064] In the context of the present application, these insecticidal proteins or toxins are to be specifically understood as also pre-toxins, hybrid proteins, truncated or otherwise modified proteins.

[0065] Hybrid toxins are produced by recombinant techniques using novel combinations of protein domains (see, for example, WO 02 / 015701). Further examples of such toxins or genetically modified plants capable to synthesize such toxins are disclosed, for example, in EP-A 374 753, WO 93 / 007278, WO 95 / 34656, EP-A 427 529, EP-A 451 878, WO 03 / 018810 and WO 03 / 052073. Methods of producing these genetically modified plants are generally known to the person skilled in the art and are described, for example, in the aforementioned publications.

[0066] These insecticidal proteins contained in the genetically modified plants impart to the plants producing these proteins tolerance to certain pests from the taxonomic class of the Arthropoda, especially to beetles (Coleoptera), two-winged insects (Diptera), butterflies and moths (Lepidoptera) and plant parasitic nematodes (Nematoda).

[0067] The term "cultivated plants" is to be understood to include also plants that are by the use of recombinant DNA techniques capable to synthesize one or more new proteins, or to synthesize altered amounts of proteins, thereby allowing increased resistance to bacterial, viral, or fungal pathogens. Examples of such proteins are the so-called "pathogenesis-related proteins" (PR proteins, see e.g. EP-A 0 392 222), plant disease resistance genes (e.g. potato cultivars which express resistance genes against Phytophthora infestans derived from wild potato species S. bulbocastanum), or T4-lysozyme (e.g. potato cultivars which are capable to synthesize these proteins in elevated amounts and which show an increased tolerance to bacteria such as Erwinia amylvora). Methods of producing such genetically modified plants are generally known to the person skilled in the art and are described, e.g., in the publications mentioned above.

[0068] The term "cultivated plants" is to be understood to include also plants that are by the use of recombinant DNA techniques capable to synthesize one or more proteins to increase yield (e.g. biomass, grain yield, sugar content, oil content or protein content), tolerance to drought, salinity or other growth-limiting environmental factors, or tolerance to pests and fungal, bacterial or viral pathogens.

[0069] The term "cultivated plants" is to be understood to include also plants that contain by the use of recombinant DNA techniques a modified amount of substances of content or new substances of content, especially to improve human or animal nutrition, e.g. oilseed crops (e.g. Nexera® rape) that produce health-promoting long-chain omega-3 or unsaturated omega-9 fatty acids.

[0070] The term "cultivated plants" is to be understood to include also plants that contain by the use of recombinant DNA techniques a modified amount of substances of content or new substances of content, especially to improve raw material production, e.g. potatoes that produce increased amounts of amylopectin (e.g. Amflora® potato).

[0071] Preferred methods of applying a compound represented by Formula I or a composition comprising the compound to a plant or soil as a pest control agent include spread treatment, soil treatment, surface treatment, or fumigation treatment. Examples of spread treatment include spreading, spraying, misting, atomizing, granule application, or water surface application. Examples of soil treatment include soil drenching or soil mixing. Examples of surface treatment include coating, dust coating, or covering. In addition, examples of fumigation treatment include covering soil with a polyethylene film after injecting the soil. Thus, the present control method also includes a method in which a compound represented by Formula I or a preparation comprising the compound is applied by fumigation treatment in a closed space.

[0072] Other pest control agents that can be admixed into a compound represented by Formula I or a salt thereof include an insecticide, a fungicide, a miticide or a

[0073] The Pesticide Manual, 13th Edition, published by the British Crop Protection Council; and SHIBUYA INDEX, 14th Edition, published by SHIBUYA INDEX RESEARCH GROUP, 2009. More specific examples thereof are M.1. - M.27. described below:

[0074] M.1. Organophosphate insecticides: acephate, azamethiphos, azinphos-ethyl, azinphos-methyl, chlorethoxyfos, chlorpyrifos (including bifenthrin, chlorpyrifos-methyl, cyhalothrin, cypermethrin, lambda-cyhalothrin, cyromazine, deltamethrin, dichlorvos, dimethoate, dioxabenzofos, esfenvalerate, ethoprophos, etrimfos, fenamiphos, fenitrothion, fenthion, flupyrazophos, fonofos, formothion, furathiocarb, halofenozide, heptachlor, heterophos, imicyafos, isofenphos, isoxathion, malathion, methacrifos, methamidophos, methidathion, naled, oxydeprofos, parathion, phenthoate, phorate, phosalone, phosmet, pirimiphos-ethyl, profenofos, propaphos, prothiofos, prothoate, pyridafenthion, pyridaben, quinalphos, sebufos, sulprofos, tebupirimfos, temephos, terallethrin, tetrachlorvinphos, thiometon, trichlorfon, vamidothion

[0075] (chlorfenvinphos), chlormephos, chlorpyrifos, chlorpyrifos-methyl, coumaphos, cyanophos, demeton-S-methyl, diazinon, dichlorvos / DDVP, dicrotophos, dimethoate, dimethylvinphos, disulfoton, EPN, ethion, ethoprophos, famphur, fenamiphos, fenitrothion, fenthion, flupyrazophos, fosthiazate, heptenophos, isoxathion, malathion, mecarbam, methamidophos, methidathion, mevinphos, monocrotophos, naled, omethoate, oxydemeton-methyl, parathion, parathion-methyl, phenthoate, phorate, phosalone, phosmet, phosphamidon, phoxim, pirimiphos-methyl, profenofos, propetamphos, prothiofos, pyraclofos, pyridaphenthion, quinalphos, sulfotep, tebupirimfos, temephos, terbufos, tetrachlorvinphos, thiometon, triazophos, trichlorfon, vamidothion;

[0076] M.2. Carbamates: aldicarb, alanycarb, bendiocarb, benfuracarb, butocarboxim, butoxycarboxim, carbaryl, carbofuran, carbosulfan, ethiofencarb, fenobucarb, formetanate, furathiocarb, isoprocarb, methiocarb, methomyl, metolcarb, oxamyl, pirimicarb, propoxur, thiodicarb, thiofanox, trimethacarb, XMC, xylylcarb and triazamate;

[0077] M.3. Synthetic pyrethroids: acrinathrin, allethrin, d-cis-trans allethrin, d-trans allethrin, bifenthrin, bioallethrin, bioallethrin S-cylclopentenyl, bioresmethin, cycloprothrin, cyfluthrin, beta-cyfluthrin, (RS) cyhalothrin, lambda-cyhalothrin, gamma- cyhalothrin, cypermethrin, alpha-cypermethrin, beta-cypermethrin, zeta- cypermethrin, cyphenothrin, deltamethrin, dimfral, empenthrin, fenfluthrin, fenpirithrin, fenpropathrin, fenvalerate, ffastethrin, flumethrin, gamma- cypermethrin, imiprothrin, kadethrin, meperfluthrin, metofluthrin, permethrin, phenvalerate, prallethrin, resmethrin, tefluthrin, tetramethrin, tralomethrin, transfluthrin and

[0078] alpha-cypermethrin, beta-cypermethrin, theta-cypermethrin, zeta-cypermethrin, cyphenothrin, deltamethrin, empenthrin, esfenvalerate, etofenprox, fenpropathrin, fenvalerate, flucythrinate, flumethrin, tau-fluvalinate, halfenprox, imiprothrin, metofluthrin, permethrin, phenothrin, prallethrin, profluthrin, pyrethrin (pyrethrum), resmethrin, silafluofen, tefluthrin, tetramethrin, tralomethrin and transfluthrin;

[0079] M.4. Juvenile hormone mimics: hydroprene, kinoprene, methoprene, fenoxycarb and pyriproxyfen;

[0080] M.5. Nicotinic receptor agonist / antagonist compounds: acetamiprid, bensultap, cartap hydrochloride, clothianidin, dinotefuran, imidacloprid, thiamethoxam, nitenpyram, nicotine, spinosad (allosteric agonist), spinetoram (allosteric agonist), thiacloprid, thiocyclam, thiosultap-sodium and AKD 1022;

[0081] M.6. GABA-gated chloride channel antagonist compounds: chlordane, endosulfan, gamma-HCH, ethiprole, fipronil, pyraflprole and pyriprole;

[0082] M.7. Chloride channel activators: abamectin, emamectin benzoate, milbemectin, lepimectin;

[0083] M.8. MET I I compounds: fenazaquin, fenpyroximate, pyrimidifen, pyridaben, tebufenpyrad, tolfenpyrad, flufenerim and rotenone;

[0084] M.9. MET I II compounds: acequinocyl, fluacyprim and hydramethylnon;

[0085] M.10. Oxidative phosphorylation decouplers: chlorfenapyr, DNOC;

[0086] M.11. Other oxidative phosphorylation inhibitors: azocyclotin, cyhexatin, diafenthiuron, fenbutatin oxide, propargite and tetradifon;

[0087] M.12. Moulting disruptors: cryomazine, chromafenozide, halofenozide, methoxyfenozide and tebufenozide;

[0088] M.13. Potentiators: piperonyl butoxide, tribufos;

[0089] M.14. Sodium channel blocker compounds: indoxacarb and metaflumizone;

[0090] M.15. Fumigants: methyl bromide, chloropicrin, sulfuryl fluoride

[0091] M.16. Selective feeding blockers: crylotie, pymetrozine and fionicamid;

[0092] M.17. Mite growth inhibitors: clofentezine, hexythiazox and etoxazole;

[0093] M.18. Chitin synthesis inhibitors: buprofezin, bistrifluron, chlorfluazuron, diflubenzuron, flucycloxuron, flufenoxuron, hexaflumuron, lufenuron, novaluron, noviflumuron, teflubenzuron and triflumuron;

[0094] M.19. Inhibitors of the lipid biosynthesis: spirodiclofen, spiromesifen and spirotetramat;

[0095] M.20. Octapaminergic agonsit: amitraz;

[0096] M.21. Ryanodine receptor modulators: flubendiamide and phtalamid compounds (R)-, (S)-3-chloro-N1-{2-methyl-4-[1,2,2,2-tetrafluoro-1 -(trifluoromethyl)ethyl]phenyl}-N2-(1 -methyl-2-methylsulfonyl- ethyl)phthalamid (M21.1 );

[0097] M.22. Isoxazoline compounds: 4-[5-(3,5-dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro- isoxazol-3-yl]-2-methyl-N-pyridin-2-ylmethyl-benzamide (M22.1 ), 4-[5-(3,5-dichloro- phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-2-methyl-N-(2,2,2-trifluoroethyl)- benzamide (M22.2), 4-[5-(3,5-dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3- yl]-2-methyl-N-[(2,2,2-trifluoroethylcarbamoyl)-methyl]-benzamide (M22.3), 4-[5-(3,5- dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-naphthalene-1 -carboxylic acid [(2,2,2-trifluoroethylcarbamoyl)-methyl]-amide (M22.4), 4-[5-(3,5-dichloro- phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-N-[(methoxyimino)methyl]-2- methylbenzamide (M22.5), 4-[5-(3-chloro-5-trifluoromethyl-phenyl)-5-trifluoromethyl- 4,5-dihydro-isoxazol-3-yl]-2-methyl-N-[(2,2,2-trifluoroethylcarbamoyl)-methyl]-benzamide (M22.6), 4-[5-(3-chloro-5-trifluoromethyl-phenyl)-5-trifluoromethyl-4,5-dihydro- isoxazol-3-yl]-naphthalene-1 -carboxylic acid [(2,2,2-trifluoroethylcarbamoyl)-methyl]- amide (M22.7) and 5-[5-(3,5-dichloro-4-fluorophenyl)-5-trifluoromethyl-4,5-dihydro- isoxazol-3-yl]-2-[1,2,4]triazol-1 -yl-benzonitrile (M22.8);

[0098] M.23. Anthranilamide compounds: chloranthraniliprole, cyantraniliprole; 5-bromo-2-(3-chloro-pyridin-2-yl)-2H-pyrazole-3-carboxylic acid [4-cyano-2-(1- cyclopropyl-ethylcarbamoyl)-6-methyl-phenyl]-amide (M23.1), 5-bromo-2-(3-chloro-pyridin-2-yl)-2H-pyrazole-3-carboxylic acid [2-chloro-4-cyano-6-(1-cyclopropyl- ethylcarbamoyl)-phenyl]-amide (M23.2), 5-bromo-2-(3-chloro-pyridin-2-yl)-2H-pyrazole-3- carboxylic acid [2-bromo-4-cyano-6-(1-cyclopropyl-ethylcarbamoyl)-phenyl]-amide (M23.3), 5-bromo-2-(3-chloro-pyridin-2-yl)-2H-pyrazole-3-carboxylic acid [2-bromo-4-chloro-6-(1- cyclopropyl-ethylcarbamoyl)-phenyl]-amide (M23.4), 5-bromo-2-(3-chloro-pyridin-2-yl)-2H- pyrazole-3-carboxylic acid [2,4-dichloro-6-(1-cyclopropyl-ethylcarbamoyl)-phenyl]-amide (M23.5), 5-bromo-2-(3-chloro-pyridin-2-yl)-2H-pyrazole-3-carboxylic acid [4-chloro-2-(1- cyclopropyl-ethylcarbamoyl)-6-methyl-phenyl]-amide (M23.6), Methyl N'-(2-{[5-bromo-2-(3- chloro-pyridin-2-yl)-2H-pyrazole-3-carbonyl]-amino}-5-chloro-3-methyl-benzoyl)-hydrazinecarboxylate (M23.7), Methyl N'-(2-{[5-bromo-2-(3-chloro-pyridin-2-yl)-2H-pyrazole-3- carbonyl]-amino}-5-chloro-3-methyl-benzoyl)-N'-methyl-hydrazinecarboxylate (M23.8), Methyl N'-(2-{[5-bromo-2-(3-chloro-pyridin-2-yl)-2H-pyrazole-3-carbonyl]-amino}-5-chloro-3- methyl-benzoyl)-N,N'-dimethyl-hydrazinecarboxylate (M23.9), Methyl N'-(3,5-dibromo-2-{[5- bromo-2-(3-chloro-pyridin-2-yl)-2H-pyrazole-3-carbonyl]-amino}-benzoyl)-hydrazinecarboxylate (M23.10), Methyl N'-(3,5-dibromo-2-{[5-bromo-2-(3-chloro-pyridin-2-yl)-2H-pyrazole-3- carbonyl]-amino}-benzoyl)-N'-methyl-hydrazinecarboxylate (M23.11) and Methyl N'-(3,5-dibromo- 2-{[5-bromo-2-(3-chloro-pyridin-2-yl)-2H-pyrazole-3-carbonyl]-amino}-benzoyl)-N,N'- dimethyl-hydrazinecarboxylate (M23.12);

[0099] M.24. Malononitrile compounds: 2-(2,2,3,3,4,4,5,5-octafluoropentyl)-2-(3,3,3- trifluoropropyl)-malononitrile (CF2H-CF2-CF2-CF2-CH2-C(CN)2-CH2-CH2-CF3) (M24.1) and 2-(2,2,3,3,4,4,5,5-octafluoropentyl)-2-(3,3,4,4,4-pentafluorobutyl)- malononitrile (CF2H-CF2-CF2-CF2-CH2-C(CN)2-CH2-CH2-CF2-CF3) (M24.2);

[0100] M.25. Microbial disruptors: Bacillus thuringiensis subsp. israelensi, Bacillus sphaericus, Bacillus thuringiensis subsp. aizawai, Bacillus thuringiensis subsp. kurstaki, Bacillus thuringiensis subsp. tenebrionis;

[0101] M.26. Aminofuranones: 4-{[(6-bromopyridin-3-yl)methyl](2-fluoroethyl)amino}furan- 2(5H)-one (M26.1), 4-{[(6-fluoropyridin-3-yl)methyl](2,2-difluoroethyl)amino}furan- 2(5H)-one (M26.2), 4-{[(2-chloro1,3-thiazol-5-yl)methyl](2-fluoroethyl)amino}furan- 2(5H)-one (M26.3), 4-{[(6-chloropyridin-3-yl)methyl](2-fluoroethyl)amino}furan- 2(5H)-one (M26.4), 4-{[(6-chloropyridin-3-yl)methyl](2,2-difluoroethyl)amino}furan- 2(5H)-one (M26.5), 4-{[(6-chloro-5-fluoropyridin-3-yl)methyl](methyl)amino}furan- 2(5H)-one (M26.6), 4-{[(5,6-dichloropyridin-3-yl)methyl](2-fluoroethyl)amino}furan- 2(5H)-one (M26.7), 4-{[(6-chloro-5-fluoropyridin-3-yl)methyl](cyclopropyl)amino}furan- 2(5H)-one (M26.8), 4-{[(6-chloropyridin-3-yl)methyl](cyclopropyl)amino}furan- 2(5H)-one (M26.9), and 4-{[(6-chloropyridin-3-yl)methyl](methyl)amino}furan- 2(5H)-one (M26.10);

[0102] M.27. Other insecticides: aluminium phosphide, amidoflumet, benclothiaz, benzoximate, bifenazate, borax, bromopropylate, cyanide, cyenopyrafen, cyflumetofen, chinomethionat, dicofol, fluoroacetates, phosphines, pyridalyl, pyrifluquinazon, sulphur, organosulphur compounds, tartar emetic, sulfoxaflor, N-R'-2,2-dihalo-1-R" cyclopropane carboxamide-2-(2,6-dichloro-alpha,alpha,alpha-trifluoro-p-tolyl)hydrazones or N-R'-2,2-di(R"')propionamide-2-(2,6-dichloro-alpha,alpha,alpha-trifluoro-p-tolyl)-hydrazones, wherein R' is a methyl group, an ethyl group or a halogen selected from chlorine or bromine, R" is a hydrogen atom or a methyl group and R'" is a methyl group or an ethyl group, 4-but-2-ynyloxy-6-(3,5-dimethyl-piperidin-1-yl)-2-fluoropyrimidine (M27.1), cyclopropaneacetic acid, 1,1 '-[(3S,4R,4aR,6S,6aS,12R,12aS,12bS)-4-[[(2-cyclopropylacetyl)oxy]methyl]- 1,3,4,4a,5,6,6a,12,12a,12b-decahydro-12-hydroxy-4,6a,12b-trimethyl-11-oxo-9-(3-pyridinyl)- 2H,11H-naphtho[2,1 -b]pyrano[3,4-e]pyran-3,6-diyl] ester (M27.2) and 8-(2-cyclopropylmethoxy-4-trifluoromethylphenoxy)-3-(6-trifluoromethylpyridazin-3-yl)-3- azabicyclo[3.2.1]octane (M27.3).

[0103] Paraoxon and its preparation have been described in Farm Chemicals Handbook, 88th Edition, Meister Publishing Company, 2001. Flupyrazofos has been described in

[0104] Pesticide Science 54, 1988, pages 237-243 and US 4822779. AKD 1022 and its preparation have been described in US 6300348. The anthranilamide compounds M23.1 - M23.6 have been described in WO 2008 / 72743 and WO 200872783. Those M23.7 - M23.12 have been described in WO 2007 / 043677. The phthalic amide M 21.1 is known from WO 2007 / 101540. The acetylenic ether compound M27.1 has been described, for example, in JP 2006131529. The organosulfur compounds have been described in WO 2007060839. The isoxazoline compounds M 22.1 - M 22.8 have been described, for example, in WO 2005 / 085216, WO 2007 / 079162, WO 2007 / 026965, WO 2009 / 126668 and WO 2009 / 051956. The aminofuranone compounds M 26.1 - M 26.10 have been described, for example, in WO 2007 / 115644. The Pyripyropene derivatives M 27.2 have been described in WO 2008 / 66153 and WO 2008 / 108491. The pyridazine compounds M 27.3 have been described in JP 2008 / 115155. The malononitrile compounds such as those (M24.1) and (M24.2) have been described in WO 02 / 089579, WO 02 / 090320, WO 02 / 090321, WO 04 / 006677, WO 05 / 068423, WO 05 / 068432 and WO 05 / 063694.

[0105] In one embodiment, the insecticidal composition comprises a biologically effective amount of at least one of the pyridaben derivatives (component A), and at least one other active ingredient (component B) selected from the following compounds:

[0106] (1) Acetylcholinesterase (AChE) inhibitors: chlorpyrifos (CAS No.: 2921-88-2), acephate (CAS No.: 30560-19-1);

[0107] (2) Y-aminobutyric acid (GABA) gateciion channel antagonists: fipronil (CAS No.: 120068-37-3);

[0108] (3) Sodium channel modulators: lambda-cyhalothrin (CAS No. 91465-08-6), bifenthrin (CAS No. 82657-04-3), deltamethrin (CAS No. 52918-63-5), esfenvalerate (CAS No. 1224510-29-5), cis-cypermethrin (CAS No. 67375-30-8);

[0109] (4) Nicotinic acetylcholine receptor (nAChR) competitive modulators: imidacloprid (CAS No. 138261-41-3), thiamethoxam (CAS No. 153719-23-4), acetamiprid (CAS No. 135410-20-7), dinotefuran (CAS No. 165252-70-0), clothianidin (CAS No. 210880-92-5), sulfoxaflor (CAS No. 946578-00-3), flupyradifurone (CAS No. 951659-40-8), thiacloprid (CAS No. 111988-49-9), pyridalyl (CAS No. 1263133-33-0), flupyradifurone (CAS No. 948994-16-9);

[0110] (5) Glutamate-gated chloride ion channel (GluCl) allosteric modulators: abamectin (CAS No. 71751-41-2), emamectin benzoate (CAS No. 155569-91-8);

[0111] (6) Juvenile hormone mimics: pyriproxyfen (CAS No. 95737-68-1);

[0112] (7) Nicotinic acetylcholine receptor (nAChR) channel blockers: cartap (CAS No. 15263-53-3);

[0113] (8) Chitin biosynthesis inhibitors (type 1): buprofezin (CAS No. 69327-76-0), spiromesifen (CAS No. 283594-90-1);

[0114] (9) Acetyl CoA carboxylase inhibitors: spirotetramat (CAS No. 203313-25-1), metaflumizone (CAS No. 1229023-00-0);

[0115] (10) Ryanodine receptor modulators: cyantraniliprol (CAS No. 736994-63-1);

[0116] (11) Scorpion receptor modulators - unknown target site: flonicamid (CAS No. 158062-67-0), verbutin (CAS No. 1403615-77-9);

[0117] (12) Y-amino butyric acid (GABA) gate chloride channel allosteric modulators: broflanilide (CAS No. 1207727-04-5), flupyrazam (CAS No. 928783-29-3), indoxacarb (CAS No. 2061933-85-3), compound W (CAS No. 2892524-05-7);

[0118] (13) Nicotinic acetylcholine receptor (nAChR) allosteric modulators: spinosad (CAS No. 168316-95-8);

[0119] (14) Others: Metarhizium anisopliae.

[0120] In another embodiment, the weight ratio of the active ingredients A, B in the insecticidal composition is 1:150-150:1, 1:100-100:1, 1:80-80:1, 1:60-60:1, 1:40-40:1, 1:20-20:1, 1:10-10:1, 1:8-8:1, 1:5-5:1 or 1:3-1:1.

[0121] The term "biologically effective amount" means the amount of a biologically active compound (e.g., a compound of Formula I) that, when administered (i.e., contacted) to a pest or its environment, or to a plant, seed from which the plant grows, or locus of the plant (e.g., growth medium) to be protected, is sufficient to produce a desired biological effect, thereby protecting the plant from damage by the pest or achieving other desired effects (e.g., increasing plant vigor). The compounds of the present application can also be administered prophylactically to a locus where a pest or parasite is expected to occur.

[0122] The present application also provides a method for preparing the pyridazinone derivative, which is prepared by using as an intermediate.

[0123] In one embodiment, the method comprises at least one of the following steps (the specific step is selected according to the structure of the target product):

[0124]

[0125] wherein X1, X2, X3, X4, R3 are as defined above.

[0126] wherein, the 1st and 3rd step reactions are carried out in the presence of a solvent and a base; the 2nd, 5th and 9th step reactions are carried out in the presence of a solvent, preferably, a condensing agent is added during the 2nd, 5th and 9th step reactions, with or without the addition of a base; the 4th step reaction is carried out in the presence of an oxidizing agent and a solvent; the 6th step reaction is carried out in the presence of an acidic catalyst and a solvent; the 7th step reaction is carried out in the presence of an organic base and a solvent; the 8th step reaction is carried out in the presence of an acid (such as acetic acid) and a solvent; and the 10th step reaction is carried out in the presence of pyridine hydrofluoride and a solvent.

[0127] In another specific embodiment, the solvent is selected from at least one of water, THF, pyridine, DMF, DMA, methanol, ethanol, acetonitrile, dichloroethane, DMSO, dioxane, dichloromethane (DCM) or ethyl acetate.

[0128] In another specific embodiment, the base is selected from at least one of an inorganic base (such as K2CO3, Na2CO3, Cs2CO3, NaHCO3, KHCO3, KF, CsF, KI, NaI, K3PO4, K2HPO4, NaOH, KOH, NaH, KH, etc.) or an organic base (such as DBU, DMAP, imidazole, pyrazole, triethylamine, DIEA, potassium trimethylsilanolate, AcOK, AcONa, MeONa, EtONa, t-BuONa, etc.).

[0129] In another specific embodiment, the condensing agent is selected from at least one of Py-BOP, Py-AOP, HOBT (1-hydroxybenzotriazole), EDCI (1-(3-dimethylaminopropyl)-3- ethylcarbodiimide hydrochloride), DMAP (4-dimethylaminopyridine), DCC, HBTU or HATU.

[0130] In another specific embodiment, the oxidizing agent is Dess-Martin oxidizing agent or PCC oxidizing agent.

[0131] In another specific embodiment, the acidic catalyst is pyridine p-toluenesulfonate (PPTS) or p-toluenesulfonic acid.

[0132] In another specific embodiment, the compound II is prepared by fermentation culture of Pseudomonas taetrolens with pentafluorobenzoic acid as the substrate.

[0133] In addition, the compound of the present application can also be prepared according to the method shown in WO2011093186, WO2010010955, WO2011148886, etc.

[0134] The present application also provides an intermediate, as shown in formula II.

[0135] The present application also provides a method for preparing the above-mentioned pyridine derivative, which comprises a reduction reaction, wherein X1, X2, X3, X4, Y1, Y2, R1, R2 are defined as above. The reduction reaction is carried out in the presence of sodium borohydride and a solvent, preferably, cerium trichloride can be added.

[0136] In one embodiment, the reduction reaction is carried out in the presence of sodium borohydride and a solvent, preferably, cerium trichloride can be added.

[0137] In another embodiment, the solvent is selected from at least one of THF, DMF, DMA, methanol, ethanol, acetonitrile, dichloroethane, DMSO, Dioxane, dichloromethane or ethyl acetate.

[0138] The present application also provides an intermediate, as shown in formula III.

[0139] According to another aspect of the present application, there is provided a use of a compound represented by formula I or an agriculturally or veterinary acceptable salt thereof as a pest control agent. DETAILED DESCRIPTION

[0140] The following examples are intended to illustrate the present application and should not be construed as limiting the scope thereof. The scope of the right claimed by the present application is defined by the claims.

[0141] In view of the economy and diversity of the compounds, we have preferably synthesized some compounds, among the synthesized compounds, some are selected and listed in Table 1 below. The specific compound structure and the corresponding compound information are shown in Table 1. The compounds in Table 1 are only for better illustrating the present application, but do not limit the present application, and for those skilled in the art, this should not be understood as the scope of the above-mentioned subject matter of the present application is limited to the following compounds.

[0142] Table 1 Compound structure and its 1 H NMR values

[0143]

[0144]

[0145]

[0146]

[0147]

[0148]

[0149]

[0150]

[0151]

[0152]

[0153]

[0154] Several methods for preparing the compounds of the present application are illustrated in the following Schemes and Examples. Starting materials can be purchased from commercial suppliers or made using known procedures or as illustrated. Those skilled in the art will appreciate that other synthetic routes can be used to synthesize the compounds of the present application. Although specific starting materials and conditions are depicted in the following Schemes, other starting materials and conditions can readily be substituted. Modifications of the synthetic routes described below can be made and will be apparent to those skilled in the art, and such modifications are included within the scope of the present application. Further, the synthetic methods described below can be further modified in light of the disclosure provided herein, using conventional chemistry known to those skilled in the art. For example, appropriate groups can be protected during the course of a reaction.

[0155] The following method examples are provided to further illustrate the preparation of the compounds of the present application and the specific materials, types and conditions used therein are not intended to be limiting. The reagents used in the synthesis of the compounds shown in the following table are either commercially available or can be readily prepared by one of ordinary skill in the art.

[0156] Representative compounds are synthesized as follows, and other compounds are synthesized in a similar manner.

[0157] 1. Synthesis of compounds 5 and 38

[0158] (1) Fermentation production of compound 38

[0159] The fermentation broth was filtered to collect the bacteria after fermentation of Pseudofechia multisepata with pentafluorobenzoic acid as substrate, methanol was added and stirred, filtered, and the methanol extract of the bacteria was collected and concentrated under reduced pressure to obtain an oily concentrate. Purification by normal phase silica gel column chromatography gave compound 38.

[0160] (2) Compound 38 (30 mg) was dissolved in methanol (2 ml), after adding 30% sodium methoxide solution (72 mg, 8 eq), it was stirred at room temperature overnight. The reaction was monitored by TLC, then the reaction was quenched by adding aqueous ammonium chloride solution (0.2 ml), the reaction solution was rotary evaporated to dryness, the obtained solid was dissolved in ethyl acetate (4 ml), the solution was filtered, the obtained solid was washed with water, the residual ammonium chloride was removed, and the obtained solid was dried to obtain compound 5-2 (23 mg, yield 97%).

[0161]

[0162] (3) 5-2 (23 mg) was dissolved in dichloromethane (5 ml), 4-dimethylaminopyridine (35 mg, 6 eq), triethylamine (29 mg, 6 eq), cyclopropanoic acid (58 mg, 14 eq) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (110 mg, 12 eq) were added to the solution in turn, the reaction was monitored by TLC after 1 hour, water (2 ml) was added to the solution, the solution was separated, the dichloromethane phase was washed with 0.05 M hydrochloric acid, sodium bicarbonate and sodium chloride in turn, the obtained organic phase was rotary evaporated to dryness, and compound 5-3 (32 mg, yield 97%) was obtained by purification with normal phase silica gel column chromatography.

[0163]

[0164] (4) 5-3 (32 mg) was dissolved in methanol (5 ml), a small amount of water and 1,8-diazabicyclo[5.4.0]undec-7-ene (8 mg, 1.1 eq) were added to the solution in turn, the reaction was stirred at room temperature for 2 hours, the reaction was monitored by TLC, and compound 5 (13 mg, yield 45%) was obtained by purification with normal phase silica gel column chromatography.

[0165]

[0166] 2. Synthesis of compound 9

[0167] (1) TMEDA (0.1 eq) was added to a three-necked flask under ice bath, LHMDS (5 eq) was added dropwise, and the reaction was carried out for 10 minutes, a THF solution of compound 9-1 (1 g) was added, the reaction was carried out for half an hour under ice bath, and then the reaction was carried out for 1 hour at room temperature. After the reaction was completed, the reaction solution was poured into an aqueous ammonium chloride solution, extracted with ethyl acetate, dried and concentrated, and purified by normal phase to obtain 430 mg of compound 9-3, with a yield of 34%.

[0168]

[0169] (2) Compound 9-3 (430 mg) was reacted under 0 mmHg negative pressure in an oil bath at 150 degrees for 15 min to obtain compound 9-4 crude product, which was directly used in the next step.

[0170]

[0171] (3) The compound 9-4 crude product was dissolved in 10 mL THF, 10 mL 80% acetic acid solution was added, and stirring was carried out at room temperature. After the raw material was completely reacted, the reaction solution was poured into saturated sodium bicarbonate solution in an ice bath, and ethyl acetate was extracted. The organic phase was dried and concentrated to obtain 380 mg of compound 9-5 crude product, with a crude product yield of 99%.

[0172]

[0173] (4) Compound 9-5 crude product (380 mg), DMAP (6 eq), EDCI (4 eq), and cyclopropyl carboxylic acid (5 eq) were sequentially added to 10 mL DCM, and reaction was carried out at room temperature. After the reaction was completed, water was added for extraction. The organic phase was washed once with dilute hydrochloric acid, once with saturated sodium bicarbonate solution, and once with sodium chloride solution, dried and concentrated to obtain 460 mg of compound 9-6 crude product, with a crude product yield of 98%.

[0174]

[0175] (5) Compound 9-6 crude product (460 mg) was dissolved in 10 mL THF, 3 mL of pyridine and 2 mL of hydrogen fluoride pyridine solution were added in an ice bath, and after the reaction was completed, the reaction solution was poured into ice water for extraction. The organic phase was washed with saturated sodium bicarbonate solution, dried and concentrated to obtain 240 mg of compound 9-7 crude product, with a crude product yield of 62%.

[0176]

[0177] (6) Compound 9-7 crude product (240 mg) was dissolved in 10 mL THF, and cerium chloride (1.2 eq) and sodium borohydride (2.4 eq) were sequentially added, and reaction was carried out at room temperature. After the reaction was completed, the reaction solution was filtered with diatomite, the filtrate was mixed with silica gel, and normal phase purification was carried out to obtain 60 mg of compound 9 (light yellow solid, yield 25%).

[0178]

[0179] 3. Synthesis of compound 9

[0180] (1) Compound 9-6 (950.0 mg, 1.62 mmol) was dissolved in 5 ml of dichloromethane, and triethylamine (TEA, 1.32 g, 12.96 mmol), cyclopropanecarboxylic acid (696.6 mg, 8.10 mmol), 4-dimethylaminopyridine (DMAP, 395.3 mg, 3.24 mmol) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCI, 1.55 g, 8.10 mmol) were added successively under ice water bath, and stirred at room temperature for 30 min. LCMS showed that the reaction was complete. Water and dichloromethane were added to dilute the reaction solution, and the organic phase was washed successively with saturated ammonium chloride solution and saturated brine, dried and concentrated to obtain compound 9-8 (600.0 mg, yield 51%, light yellow solid).

[0181]

[0182] (2) Compound 9-8 (300.0 mg, 0.41 mmol) was dissolved in a mixed solvent of pyridine / tetrahydrofuran (2 ml / 10 ml), and pyridine hydrofluoride (5 ml) was added dropwise at 0°C, and stirred at room temperature for 12 h. LCMS showed that the reaction was complete. The reaction solution was quenched with saturated aqueous sodium bicarbonate solution, and the aqueous phase was extracted with ethyl acetate, and the organic phase was washed with saturated brine, dried and concentrated. The residue was purified by column chromatography (EA / PE = 30-60%) to obtain compound 9 (150.0 mg, 59.6 mmol, yield 60%, white solid).

[0183]

[0184] 4. Synthesis of compound 43

[0185] Compound 9 (20 mg, 0.03 mmol) was dissolved in 1 ml of dichloromethane, and triethylamine (32 mg, 0.06 mmol), acetic anhydride (6.1 mg, 0.06 mmol) and 4-dimethylaminopyridine (2 mg, 0.03 mmol) were added, and the reaction was carried out at room temperature for 0.5 h. LCMS showed that the reaction was complete. The reaction solution was quenched with aqueous sodium bicarbonate solution, extracted with ethyl acetate, and the organic phase was washed with saturated brine, dried and concentrated. The residue was purified by column chromatography (EA / PE = 1 / 2) to obtain compound 43 (10 mg, yield 47%, light yellow solid).

[0186]

[0187] 5. Synthesis of compound 61

[0188] Compound 5 (100 mg, 0.16 mmol) was dissolved in 1 ml DMF, triethylamine (32 mg, 0.32 mmol), 61-1 (67 mg, 0.32 mmol) and 4-dimethylaminopyridine (2 mg, 0.016 mmol) were added, and the reaction was allowed to react at room temperature for 0.5 h. The reaction was monitored by LCMS to be complete. The reaction was quenched with aqueous sodium bicarbonate solution, extracted with ethyl acetate, and the organic phase was washed with saturated brine, dried and concentrated. The residue was purified by column chromatography (MeOH:DCM = 1:15) to give compound 61 (10 mg, yield 9%, light yellow solid).

[0189]

[0190] 6. Synthesis of compound 95

[0191] Compound 5 (0.50 g, 0.82 mmol) was dissolved in 5 ml dichloromethane in a 100 ml flask, and the reaction was placed in an ice-salt bath. Dess-Martin oxidizing agent (0.52 g, 1.22 mmol) was slowly added, and the temperature was controlled so that it did not exceed 5°C. The reaction was then allowed to react at room temperature for 4 h. After the reaction was monitored by LCMS to be complete, a small amount of saturated sodium thiosulfate solution was added to quench the reaction, and the reaction was extracted with dichloromethane three times. The organic phase was dried over anhydrous sodium sulfate, concentrated, and the residue was purified by column chromatography (PE:EA = 1:1) to give compound 95 (0.11 g, yield 22%, yellow solid).

[0192]

[0193] 7. Synthesis of compound 126

[0194] (1) Compound 126-1 was prepared according to compound 9-7. Compound 126-1 (300 mg, 0.48 mmol) was dissolved in 2 ml 1,2-dichloroethane, and bromomethyl methyl ether (306 mg, 2.46 mmol), TBAI (48 mg, 0.39 mmol) and DIEA (906 mg, 2.46 mmol) were added in turn, and the reaction was allowed to react at room temperature for 12 h. The reaction was monitored by LCMS to be complete. The reaction was diluted with water and dichloromethane, the organic phase was washed with saturated brine, dried and concentrated. The residue was purified by column chromatography (EA:PE = 1:5) to give compound 126-2 (150 mg, yield 47%, light yellow solid).

[0195]

[0196] (2) Compound 126-2 (150 mg, 0.23 mmol) was dissolved in 2 mL of absolute ethanol, and CeCl3-7H2O (85 mg, 0.23 mmol) and NaBH4(16 mg, 0.46 mmol) were added successively under ice water bath. The reaction was stirred at room temperature for 30 min. The reaction was monitored by LCMS. The reaction was quenched by saturated NaHC03 aqueous solution, and extracted by ethyl acetate. The organic phase was washed by water and saturated brine, dried and concentrated. The residue was purified by column chromatography (EA: PE = 1: 1) to give compound 126 (59 mg, yield 38%, light yellow solid).

[0197]

[0198] 8. Synthesis of compound 128

[0199] (1) Compound 5-2 (25.0 g, crude) was dissolved in 200 mL of DMF, and 128-1 (64.3 mL, 526.3 mmol) and 4-methylbenzenesulfonic acid pyridine (6.6 g, 26.3 mmol) were added successively under ice water bath. The reaction was stirred at room temperature for 30 min. The reaction was monitored by LCMS. The reaction was quenched by saturated NaHC03 aqueous solution, and extracted by dichloromethane. The organic phase was washed by water and saturated brine, dried and concentrated to give the crude product. The crude product was slurried by PE: EA = 10: 1, and the filter cake was collected and dried under vacuum to give the crude compound 128-2 (28.0 g, light yellow solid), which was used directly in the next step.

[0200]

[0201] (2) Compound 128-2 (28.0 g, crude) was dissolved in 150 mL of DMF, and tert- butyldimethylsilyl chloride (TBSCl, 16.4 g, 108.8 mmol) and imidazole (7.4 g, 108.8 mmol) were added successively under ice water bath. The reaction was stirred at room temperature for 12 h. The reaction was monitored by LCMS. The reaction was quenched by saturated NH4C1 aqueous solution, and extracted by dichloromethane. The organic phase was washed by water and saturated brine, dried and concentrated to give the crude product. The crude product was slurried by petroleum ether, and the filter cake was collected and dried under vacuum to give the crude compound 128-3 (28 g, light yellow solid), which was used directly in the next step.

[0202]

[0203] (3) Compound 128-3 (28.0 g, crude) was dissolved in 100 mL THF, 1500 mL 80% aqueous AcOH was added under ice water bath, and the mixture was stirred at room temperature for 24 h. The reaction was monitored by LCMS. The pH was adjusted to 7-8 with saturated aqueous sodium bicarbonate solution, and the aqueous phase was extracted with ethyl acetate. The organic phase was washed with saturated brine, dried and concentrated. The residue was purified by column chromatography (EA: PE = 1:5-3:5) to give compound 128-4 (21.0 g, 35.6 mmol, light yellow solid).

[0204]

[0205] (4) Compound 128-4 (500 mg, 0.85 mmol) was dissolved in 2 mL dichloromethane, 4-dimethylaminopyridine (104 mg, 0.85 mmol) and 128-5 (110 mg, 0.85 mmol) were added, and the mixture was stirred at room temperature for 10 h. The reaction was monitored by LCMS. The reaction was quenched with saturated aqueous sodium bicarbonate solution, and the mixture was extracted with dichloromethane. The organic phase was washed with water and saturated brine, dried and concentrated. The residue was purified by column chromatography (THF: PE = 1:4) to give compound 128-6 (500 mg, yield 91%, light yellow solid).

[0206]

[0207] (5) Compound 128-6 (500 mg, 0.77 mmol) was dissolved in 2 mL dichloromethane, triethylamine (623 mg, 6.16 mmol), cyclopropanecarboxylic acid (265 mg, 3.08 mmol), EDCI (590 mg, 3.08 mmol) and 4-dimethylaminopyridine (188 mg, 1.54 mmol) were added at room temperature, and the mixture was stirred for 2 h. The reaction was monitored by LCMS. The reaction was diluted with water and dichloromethane. The organic phase was washed with saturated ammonium chloride and saturated brine, dried and concentrated. The residue was purified by column chromatography (THF: PE = 1:1) to give compound 128-7 (450 mg, yield 82%, light yellow solid).

[0208]

[0209] (6) Compound 128-7 (450 mg, 0.63 mmol) was dissolved in 1 mL of tetrahydrofuran, pyridine (0.5 mL, 6.3 mmol) and hydrofluoric acid / pyridine (0.5 mL, 5.0 mmol) were added under ice water bath, and the reaction was allowed to proceed at room temperature for 12 h. The reaction was monitored by LCMS. The reaction was quenched with aqueous sodium bicarbonate solution, and extracted with ethyl acetate. The organic phase was washed with saturated brine, dried and concentrated. The residue was purified by column chromatography (MeOH:DCM = 1:20) to give compound 128 (49 mg, 13% yield, light yellow solid).

[0210]

[0211] 9. Synthesis of compound 5

[0212] (1) Compound 128-4 (21.0 g, 35.6 mmol) was dissolved in 150 mL of DCM, and triethylamine (TEA, 28.7 g, 284.8 mmol), cyclopropanecarboxylic acid (15.3 g, 178.0 mmol), 4-dimethylaminopyridine (DMAP, 8.7 g, 71.2 mmol) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCI, 27.2 g, 142.4 mmol) were added sequentially under ice water bath, and the reaction was allowed to proceed at room temperature for 12 h. The reaction was monitored by LCMS. The reaction was diluted with water and dichloromethane, and the organic phase was washed with saturated ammonium chloride solution and saturated brine, dried and concentrated. The residue was purified by column chromatography (EA / PE = 10-50%) to give compound 5-4 (17.5 g, 24.1 mmol, white solid).

[0213]

[0214] (2) Compound 5-4 (17.5 g, 24.1 mmol) was dissolved in a mixture of pyridine / tetrahydrofuran (20 mL / 100 mL), and pyridine hydrofluoride (30 mL) was added dropwise at 0°C, and the reaction was allowed to proceed at room temperature for 24 h. The reaction was monitored by LCMS. The reaction was quenched with saturated aqueous sodium bicarbonate solution, and the aqueous phase was extracted with ethyl acetate. The organic phase was washed with water and saturated brine, dried and concentrated. The residue was purified by column chromatography (EA / PE = 30-60%) to give compound 5 (13.4 g, 21.9 mmol, white solid).

[0215]

[0216] 10. Synthesis of compound 131

[0217] (1) Compound 9-7 (120.0 mg, 0.25 mmol) was dissolved in 2 ml 1,2-dichloroethane, and then bromomethyl methyl ether (31.0 mg, 0.25 mmol), TBAI (11.0 mg, 0.03 mmol) and DIEA (32.3 mg, 0.25 mmol) were added successively, and the reaction was allowed to proceed at room temperature for 3 h. The reaction was monitored by LCMS. The reaction solution was diluted with water and dichloromethane, and the organic phase was washed with saturated brine, dried and concentrated, and the residue was purified by column chromatography (EA / PE = 1 / 5) to obtain compound 131-1 (30.0 mg, yield 47%, light yellow solid).

[0218]

[0219] (2) Compound 131-1 (30.0 mg, 0.05 mmol) was dissolved in 1 ml tetrahydrofuran, and then CeCl3·7H2O (18.6 mg, 0.05 mmol) and NaBH4(3.8 mg, 0.10 mmol) were added successively under ice water bath, and the reaction was allowed to proceed at room temperature for 30 min. The reaction was monitored by LCMS. The reaction solution was quenched with saturated NaHCO3 aqueous solution, extracted with ethyl acetate, and the organic phase was washed with water and saturated brine, dried and concentrated, and the residue was purified by column chromatography (EA / PE = 1 / 1) to obtain compound 131 (8.0 mg, yield 27%, light yellow solid).

[0220]

[0221] 11. Synthesis of compound 133

[0222] (1) Compound 9-5 (350 mg, 0.60 mmol) was dissolved in 2 ml dichloromethane, and then 4-dimethylaminopyridine (77.5 mg, 0.60 mmol) and propionic anhydride (72.8 mg, 0.60 mmol) were added, and the reaction was allowed to proceed at room temperature for 30 min. The reaction was monitored by LCMS. The reaction solution was quenched with saturated NaHCO3 aqueous solution, extracted with dichloromethane, and the organic phase was washed with saturated brine, dried and concentrated, and the residue was purified by column chromatography (THF / PE = 1 / 4) to obtain compound 133-1 (140 mg, yield 37%, light yellow solid).

[0223]

[0224] (2) Compound 133-1 (140 mg, 0.22 mmol) was dissolved in 2 ml of dichloromethane, triethylamine (175 mg, 1.74 mmol), cyclopropanecarboxylic acid (73.5 mg, 0.87 mmol), EDCI (164.5 mg, 0.87 mmol) and 4-dimethylaminopyridine (52.5 mg, 0.43 mmol) were added at room temperature, and the reaction was allowed to proceed at room temperature for 2 h. The reaction was monitored by LCMS. The reaction was diluted with water and dichloromethane, and the organic phase was washed with saturated ammonium chloride and saturated brine, dried and concentrated, and the residue was purified by column chromatography (THF / PE = 1 / 3) to obtain compound 133-2 (80 mg, yield 52%, light yellow solid).

[0225]

[0226] (3) Compound 133-2 (80 mg, 0.63 mmol) was dissolved in 1 ml of tetrahydrofuran, and pyridine (0.5 ml, 6.3 mmol) and hydrofluoric acid / pyridine (0.5 ml, 5.0 mmol) were added under ice water bath, and the reaction was allowed to proceed at room temperature for 12 h. The reaction was monitored by LCMS. The reaction was quenched with aqueous sodium bicarbonate solution, extracted with ethyl acetate, and the organic phase was washed with saturated brine, dried and concentrated, and the residue was purified by column chromatography (THF / PE = 1 / 1) to obtain compound 133-3 (50 mg, yield 75%, light yellow solid).

[0227]

[0228] (4) Compound 133-3 (50 mg, 0.08 mmol) was dissolved in 1 ml of tetrahydrofuran, and CeCl3·7H2O (30 mg, 0.08 mmol) and NaBH4(6.5 mg, 0.17 mmol) were added under ice water bath, and the reaction was allowed to proceed at room temperature for 30 min. The reaction was monitored by LCMS. The reaction was quenched with aqueous sodium bicarbonate solution, extracted with ethyl acetate, and the organic phase was washed with saturated brine, dried and concentrated, and the residue was purified by column chromatography (THF / PE = 1 / 1) to obtain compound 133 (30 mg, yield 40%, light yellow solid).

[0229] DETAILED DESCRIPTION

[0231] Biological activity evaluation:

[0232] (1) Insecticidal activity test:

[0233] 1.1) Spray treatment test

[0234] The original drug is dissolved in acetone, and then the drug solution is diluted to a gradient dose with distilled water. Select peach aphid instar and seedling age consistent with potting of aphid-infested radish seedlings, use a handheld spray device to spray, spray evenly and thoroughly on both sides, spray 8-10 times per pot of radish, use water as a control, repeat 3 times, and transfer to the feeding conditions after application. Select 3 instar green plant bugs in a physiological state consistent with indoor feeding, place them in a disposable transparent plastic cup, insert 20 test insects into each cup, and place 4 fruit corn kernels into the cup. Then use a spray tower to spray, cover the cup opening with a cup after spraying is completed, repeat 3 times, use water as a control, and transfer to the feeding conditions after application. Select the wheat aphid instar and seedling age consistent with potting of aphid-infested wheat seedlings, use a handheld spray device to spray, spray evenly and thoroughly on both sides, spray 8-10 times per pot of wheat, use water as a control, repeat 3 times, and transfer to the feeding conditions after application. After n days of investigation, the mortality of each treatment is counted, and the mortality rate is calculated: mortality rate (%) = (number of dead insects / number of test insects) * 100.

[0235] Table 2 Insecticidal test results

[0236]

[0237] Note: N represents no data; Control compound A:

[0238] 1.2) Top-conducting ability test

[0239] Select aphid-infested radish seedling plants planted in disposable transparent plastic cups, 3 radish seedlings per cup, and dry for 24 h before the test; pour 20 mL of prepared liquid into the radish seedling roots, 3 replicates per treatment, set up a water control, and give normal light and culture conditions. Investigate the results 6 days after the drug treatment. Count the mortality of each treatment and calculate the mortality rate. The representative test results are shown in Table 3.

[0240] Mortality rate = (number of dead insects / number of test insects) * 100%

[0241] Table 3 Top-conducting ability test results

[0242]

[0243] Note: Control compound B: bisprotrifenbute.

[0244] (2) Composition insecticide activity determination test:

[0245] 2.1) Test conditions and operation steps

[0246] Test target: peach aphid, whitefly

[0247] Myzus persicae: The original drug is dissolved with acetone, and then diluted with distilled water to a gradient dose. Select the same instar and seedling age of Myzus persicae, and plant the radish seedlings with insects. Use a handheld spray device to spray, evenly spray from both sides, spray 8-10 times per pot of radish, use water as a control, repeat 3 times, and transfer to the feeding conditions after application. After 6 days of investigation, the mortality of each treatment is counted, and the mortality rate is calculated: mortality rate (%) = (dead insects / tested insects) * 100.

[0248] Bemisia tabaci: The original drug is dissolved with acetone, and then diluted with distilled water to a gradient dose. Use a one-liter plastic cup with a lid as a test vessel, cut two true leaves from the baby pumpkin and insert them on the plastic sponge, add an appropriate amount of water to the sponge to keep the pumpkin seedlings moist, and place the treated pumpkin seedlings in the plastic cup to make the test device. About 200 adult Bemisia tabaci are collected and placed in the test device, and the prepared pesticide solution is evenly sprayed from the top hole cover using a handheld electric sprayer, with 3 replicates for each treatment. After the application is completed, place it in a treatment room with a temperature of 25°C and a humidity of 60%. After 3 days of investigation, the mortality of each treatment is counted, and the mortality rate is calculated: mortality rate (%) = (dead insects / tested insects) * 100.

[0249] 2.2) Synergistic qualitative evaluation

[0250] Within the selected ratio range, different ratios are set for toxicity determination, and the best ratio is selected according to the synergistic effect. When the synergistic effect is > 0, it indicates that there is a synergistic effect; when the synergistic effect is close to 0, it indicates that there is an additive effect; when the synergistic effect is < 0, it indicates that there is an antagonistic effect.

[0251] Synergistic effect = actual mortality - theoretical mortality

[0252] Theoretical mortality = 1 - (1-P1)(1-P2)

[0253] In the formula, P1, P2 - the mortality of each single agent in the mixture.

[0254] Table 4 Synergistic qualitative evaluation of composition experimental results

[0255]

[0256]

[0257] Meanwhile, through many tests, it is found that the compound and the composition have good control effect on piercing-sucking mouthpart pests (such as aphids, whiteflies, stink bugs, psyllids, scales, mealybugs and leafhoppers), can reduce the occurrence of virus diseases and bacterial diseases caused by insect vectors, are suitable for economic crops, field crops and ornamental plants, can be used for foliar treatment, seed treatment or soil treatment, have little influence on beneficial arthropods such as natural enemy insects and pollinating insects, can effectively reduce the environmental burden of agricultural sustainable development, are suitable for resistance management and integrated management of pests, and have certain commercial value.

Claims

1. A pirenzepine derivative as shown in formula I, wherein X1 represents hydrogen or fluorine, X2 represents hydrogen or fluorine, X3 represents hydrogen or fluorine, X4 represents hydrogen or fluorine, and X1, X2, X3 and X4 are not hydrogen at the same time; R1, R2 each independently represents -(CO)R3; Y1 represents hydroxyl, C1-C8 alkoxy C1-C8 alkoxyl or -O(CO)R3; Y2 represents hydrogen; or Y1, Y2 together form =O; R3 each independently represents C1-C8 alkyl unsubstituted or substituted by at least one group selected from halogen, or C3-C8 cycloalkyl.

2. The pirenzepine derivative according to claim 1, wherein, R1, R2 each independently represents -(CO)R3; Y1 represents hydroxyl, C1-C6 alkoxy C1-C6 alkoxyl or -O(CO)R3; Y2 represents hydrogen; or Y1, Y2 together form =O; R3 each independently represents C1-C6 alkyl unsubstituted or substituted by at least one group selected from halogen, or C3-C6 cycloalkyl.

3. The pirlindane derivative according to any one of claims 1-2, characterized in that, X1 represents hydrogen, X2 represents fluorine, X3 represents hydrogen, X4 represents hydrogen; or X1 represents hydrogen, X2 represents hydrogen, X3 represents fluorine, X4 represents hydrogen.

4. The pirlindane derivative according to any one of claims 1 to 2, characterized in that The compound is selected from any one of the following compounds:

5. A process for the preparation of a pirlindane derivative according to any one of claims 1 to 4, characterized in that, which are prepared as intermediates; or, which are prepared by reduction of or, which are prepared by reduction of or, which are prepared by reduction of comprising at least one of the following steps: wherein X1, X2, X3, X4, R1, R2, R3, Y1, Y2 are defined as in any one of claims 1-4; wherein the reaction of the first step and the third step is carried out in the presence of a solvent and a base; the reaction of the second step, the fifth step and the ninth step is carried out in the presence of a solvent; the reaction of the fourth step is carried out in the presence of an oxidizing agent and a solvent; the reaction of the sixth step is carried out in the presence of an acidic catalyst and a solvent; the reaction of the seventh step is carried out in the presence of an organic base and a solvent; the reaction of the eighth step is carried out in the presence of an acid and a solvent; the reaction of the tenth step is carried out in the presence of pyridine hydrofluoride and a solvent.

6. The method of claim 5, wherein the preparation of the pirlindane derivative is characterized by, The solvent is selected from at least one of water, THF, pyridine, DMF, DMA, methanol, ethanol, acetonitrile, dichloroethane, DMSO, Dioxane, dichloromethane or ethyl acetate, the base is selected from at least one of an inorganic base or an organic base, the oxidizing agent is Dess-Martin oxidizing agent or PCC oxidizing agent, or the acidic catalyst is pyridine p-toluenesulfonate or p-toluenesulfonic acid.

7. The method for preparing the pyridamole derivative according to claim 5, characterized in that, A condensing agent is added during the reaction of the second step, the fifth step and the ninth step, with or without the addition of a base; or the acid in the eighth step is acetic acid.

8. The method of claim 7, wherein the preparation of the pirlindane derivative is characterized by, The condensing agent is selected from at least one of Py-BOP, Py-AOP, HOBT, EDCI, DMAP, DCC, HBTU or HATU.

9. The method for preparing the pyridamole derivative according to claim 5, characterized in that, The reduction reaction is carried out in the presence of sodium borohydride and a solvent.

10. The method of claim 9, wherein the preparation of the pirlindane derivative is characterized by, Cerium trichloride is added during the reduction reaction; or the solvent in the reduction reaction is selected from at least one of THF, DMF, DMA, methanol, ethanol, acetonitrile, dichloroethane, DMSO, Dioxane, dichloromethane or ethyl acetate.

11. An insecticidal composition, characterized by comprising It comprises a biologically effective amount of at least one of the pirenzepine derivatives according to any one of claims 1-4.

12. The insecticidal composition according to claim 11, wherein Formulation adjuvants are also included.

13. The insecticidal composition according to claim 11 or 12, characterized in that, Other active ingredients are also included.

14. The insecticidal composition according to claim 13, wherein The other active ingredient is selected from at least one of the following compounds: (1) acetylcholinesterase (AChE) inhibitors: chlorpyrifos, acephate; (2) Y-aminobutyric acid (GABA) gate-keeper chloride channel antagonists: fipronil; (3) sodium channel modulators: lambda-cyhalothrin, bifenthrin, deltamethrin, beta-cyfluthrin, cis-cypermethrin; (4) competitive modulators of nicotinic acetylcholine receptors (nAChR): imidacloprid, thiamethoxam, acetamiprid, dinotefuran, clothianidin, flonicamid, flupyradifurone, thiacloprid, triflumuron, flupentioxide; (5) allosteric modulators of glutamate-gated chloride ion channels (GluCl): abamectin, emamectin benzoate; (6) bionic juvenile hormone mimics: pyriproxyfen; (7) blockers of nicotinic acetylcholine receptors (nAChR): cartap; (8) chitin biosynthesis inhibitors: buprofezin, spiromesifen; (9) acetyl CoA carboxylase inhibitors: spirotetramat, etoxazole; (10) ryanodine receptor modulators: cyantraniliprol; (11) string vibration modulators - unknown target site: flonicamid, verbutin; (12) allosteric modulators of Y-aminobutyric acid (GABA) gate-keeper chloride channels: broflanvalerate, flupyrazophos, isoflucypram, compound W with CAS number 2892524-05-7; (13) allosteric modulators of nicotinic acetylcholine receptors (nAChR): spinosad; (14) others: Metarhizium anisopliae.

15. The insecticidal composition according to claim 14, wherein The weight ratio of the pyridalyl derivative to the other active ingredient in the insecticidal composition is 1:150 to 150:

1.

16. The insecticidal composition according to claim 14, wherein The weight ratio of the pyridalyl derivative to the other active ingredient in the insecticidal composition is 1:100 to 100:

1.

17. The insecticidal composition of claim 14, wherein The weight ratio of the pyridalyl derivative to the other active ingredient in the insecticidal composition is 1:80 to 80:

1.

18. The insecticidal composition of claim 14, wherein, The weight ratio of the pyridalyl derivative to the other active ingredient in the insecticidal composition is 1:60 to 60:

1.

19. The insecticidal composition of claim 14, wherein, The weight ratio of the pyridalyl derivative to the other active ingredient in the insecticidal composition is 1:40 to 40:

1.

20. The insecticidal composition of claim 14, wherein The weight ratio of the pyridalyl derivative to the other active ingredient in the insecticidal composition is 1:20 to 20:

1.

21. The insecticidal composition of claim 14, wherein The weight ratio of the pyridalyl derivative to the other active ingredient in the insecticidal composition is 1:10 to 10:

1.

22. The insecticidal composition of claim 14, wherein The weight ratio of the pyridalyl derivative to the other active ingredient in the insecticidal composition is 1:8 to 8:

1.

23. The insecticidal composition of claim 14, wherein The weight ratio of the pyridalyl derivative to the other active ingredient in the insecticidal composition is 1:5 to 5:

1.

24. The insecticidal composition of claim 14, wherein The weight ratio of the pyridalyl derivative to the other active ingredient in the insecticidal composition is 1:3 to 1:

1.

25. A method of controlling a hemipteran pest, comprising contacting the pest with a compound of any one of claims 1-24. The method comprises contacting the pest or its environment with a biologically effective amount of the pyridalyl derivative of any one of claims 1-4 or the composition of any one of claims 11-24.

26. The method of claim 25, wherein, The hemipteran pest is Myzus persicae, Apolygus lucorum, Rhopalosiphum padi and / or Bemisia tabaci.

27. Use of a pyrifenidrol derivative according to any one of claims 1 to 4 or a composition according to any one of claims 11 to 24 for controlling hemipteran pests.

28. Use according to claim 27, characterized in that, The hemipteran pests are Myzus persicae, Lygus lineolaris, Rhopalosiphum maidis and / or Bemisia tabaci.

29. An intermediate of formula II or III according to claim 5.

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