CN113264924A - Dioxane pyrimidine derivative and preparation method and application thereof - Google Patents

Dioxane pyrimidine derivative and preparation method and application thereof Download PDF

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CN113264924A
CN113264924A CN202010093096.6A CN202010093096A CN113264924A CN 113264924 A CN113264924 A CN 113264924A CN 202010093096 A CN202010093096 A CN 202010093096A CN 113264924 A CN113264924 A CN 113264924A
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formula
compound represented
compound
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CN113264924B (en
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唐剑峰
迟会伟
赵士胜
吴建挺
徐龙祥
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SHANDONG UNITED PESTICIDE INDUSTRY CO LTD
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/04—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/48—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with two nitrogen atoms as the only ring hetero atoms
    • A01N43/54—1,3-Diazines; Hydrogenated 1,3-diazines

Abstract

The invention provides dioxane pyrimidine derivatives shown as a formula (I) as well as a preparation method and application thereof. The compound shows good activity to various pests and harmful mites in agriculture or other fields, particularly the introduced pentafluorothioether group can obviously improve the activity of the compound and shows excellent control effect to various pests/harmful mites. Moreover, the compounds can obtain good control effect at very low dosage, so the compounds can be used for preparing insecticide and acaricide. In addition, the compound provided by the invention has the advantages of simple preparation steps and high product yield, so that the compound has a good application prospect.

Description

Dioxane pyrimidine derivative and preparation method and application thereof
Technical Field
The invention belongs to the technical field of insecticides and acaricides, and particularly relates to a dioxane pyrimidine derivative and a preparation method and application thereof.
Background
In agricultural and horticultural crop production, damage caused by insect pests and mite pests is still very serious, and development of novel agricultural and horticultural chemicals, particularly insecticides and acaricides, is of great significance because the pests and the mites have resistance to existing chemicals. With the increase of the number of the working personnel of the old-aged farming, the development of a time-saving and labor-saving agricultural and horticultural medicament, in particular an insecticide and an acaricide, is necessary.
Patent document WO2013115391 discloses compounds of general formula of pyrimidines shown below and specific compounds (e.g. CK1 and CK2), and the use of such compounds as pesticides.
Figure BDA0002384373280000011
However, the inventor finds that the control spectrum of the compound is narrow, the effect is slow, and the actual application effect is influenced. At low dosages, the biological activity of these compounds is not satisfactory in all cases. Therefore, it is desired to develop an insecticidal and/or acaricidal agent having more excellent properties.
Disclosure of Invention
In order to improve the problems, the invention provides a compound shown as a formula (I), a stereoisomer, a racemate, a tautomer, a nitrogen oxide or a pharmaceutically acceptable salt thereof,
Figure BDA0002384373280000012
r is the same or different and is independently selected from hydrogen, halogen, cyano, C1-6Alkyl, halo C1-6Alkyl radical, C1-6Alkoxy or halo C1-6An alkoxy group;
n is 0, 1,2, 3 or 4;
x is selected from oxygen or sulfur.
According to an embodiment of the invention, the compound of formula (I) has the following structure,
Figure BDA0002384373280000021
in the formulae (I-1), (I-2) and (I-3),
r is the same or different and is independently selected from hydrogen, fluorine, chlorine, bromine, cyano, methyl, ethyl, trifluoromethyl, methoxy or trifluoromethoxy;
n is 0, 1,2, 3 or 4;
x is selected from oxygen or sulfur.
By way of example, the compounds of formula (I) are selected from the following compounds:
Figure BDA0002384373280000022
Figure BDA0002384373280000023
Figure BDA0002384373280000031
Figure BDA0002384373280000041
Figure BDA0002384373280000051
the invention also provides a preparation method of the compound shown in the formula (I), which comprises the following steps:
Figure BDA0002384373280000052
a) reacting a compound shown in a formula (II-1) with a compound shown in a formula (III) to obtain a compound shown in a formula (I); alternatively, the first and second electrodes may be,
Figure BDA0002384373280000061
b) reacting a compound shown as a formula (VII) with a compound shown as a formula (VI) to obtain a compound shown as a formula (I);
wherein R, X, n has the meaning as described above, L is selected from a leaving group, such as Cl, Br or I.
According to an embodiment of the present invention, the compound of formula (I) is prepared by the following method:
Figure BDA0002384373280000062
wherein R, X, n has the meaning as described above, L is selected from a leaving group, such as Cl, Br or I.
1) Preparing a compound shown in a formula (II) by reacting a compound shown in a formula (V-1) with propylene glycol, or preparing a compound shown in a formula (II-1) by reacting a compound shown in a formula (V) with propylene glycol;
2) the compound shown in the formula (I) is prepared by reacting the compound shown in the formula (II) with the compound shown in the formula (III), or the compound shown in the formula (I-1) is prepared by reacting the compound shown in the formula (II-1) with the compound shown in the formula (III), and then the compound shown in the formula (I) is prepared from the compound shown in the formula (I-1).
According to an embodiment of the invention, the reaction in step 1) may be carried out in the presence of a catalyst, such as p-toluenesulfonic acid.
According to an embodiment of the present invention, the reaction in step 1) may be carried out in a solvent; the solvent may be selected from one, two or more of aromatic hydrocarbon solvents, haloalkane solvents, nitrile solvents, ether solvents, ester solvents, for example, one, two or more selected from ethyl acetate, benzene, toluene, 1, 2-dichloroethane, acetonitrile, tetrahydrofuran or dioxane.
According to an embodiment of the present invention, the temperature of the reaction in step 1) may be 0 ℃ to the reflux temperature of the solvent used.
According to an embodiment of the present invention, the reaction in step 1) can be carried out by a method described in patent document CN104185628A or other similar methods.
According to an embodiment of the present invention, the reaction of the compound represented by the formula (II) with the compound represented by the formula (III) to prepare the compound represented by the formula (I) or the reaction of the compound represented by the formula (II-1) with the compound represented by the formula (III) to prepare the compound represented by the formula (I-1) in step 2) may be carried out in the presence of a base; the base may be selected from organic amines such as triethylamine, N-dimethylaminopyridine, etc., or sodium carbonate, potassium carbonate, cesium carbonate, sodium hydroxide, potassium hydroxide, etc., alkali metal hydrides such as sodium hydride, potassium hydride, etc., alkali metal alkoxides such as potassium tert-butoxide, sodium ethoxide, sodium methoxide, etc., and alkyllithium such as methyllithium, N-butyllithium, etc., inorganic bases.
According to an embodiment of the present invention, in the step 2), the molar amount of the base is 1 to 3 times that of the compound represented by the formula (III).
According to an embodiment of the present invention, the reaction of the compound represented by the formula (II) with the compound represented by the formula (III) to prepare the compound represented by the formula (I) or the reaction of the compound represented by the formula (II-1) with the compound represented by the formula (III) to prepare the compound represented by the formula (I-1) in step 2) may be carried out in a solvent; the solvent may be selected from one, two or more of aromatic hydrocarbon solvents, haloalkane solvents, nitrile solvents, chain or cyclic ether solvents, amides, ketone solvents, and the like, for example, one, two or more selected from toluene, 1, 2-dichloroethane, acetonitrile, propionitrile, N-dimethylacetamide, N-dimethylformamide, diethyl ether, tetrahydrofuran, dioxane, acetone, butanone, dimethyl sulfoxide, sulfolane, N-methylpyrrolidone.
According to an embodiment of the present invention, the temperature of the reaction of the compound represented by formula (II) with the compound represented by formula (III) to prepare the compound represented by formula (I) or the reaction of the compound represented by formula (II-1) with the compound represented by formula (III) to prepare the compound represented by formula (I-1) in step 2) may be 0 ℃ to the reflux temperature of the solvent used.
According to an embodiment of the present invention, in the step 2), the reaction may be performed under an atmosphere of a gas inert to the reaction system, such as nitrogen, argon, or the like.
According to an embodiment of the present invention, in step 2), the compound represented by the formula (I-1) is catalytically hydrogenated in an inert solvent in the presence of an organic base and a catalyst under a hydrogen atmosphere to prepare the compound represented by the formula (I), and formic acid may also be used to generate hydrogen in the reaction system instead of the hydrogen atmosphere.
According to an embodiment of the present invention, the reaction of the compound represented by the formula (I-1) to prepare the compound represented by the formula (I) in the step 2) may be performed in the presence of a catalyst selected from at least one of tetrakis (triphenylphosphine) palladium, palladium on carbon, platinum, raney nickel, and the like.
According to an embodiment of the present invention, in the step 2), the compound represented by the formula (I-1) is reacted to prepare the compound represented by the formula (I) using the catalyst in an amount of about 0.0001 to 0.1 times by mole the compound represented by the formula (I-1).
According to an embodiment of the present invention, the reaction of the compound represented by the formula (I-1) to prepare the compound represented by the formula (I) in step 2) may be carried out in the presence of a phase transfer catalyst such as a quaternary ammonium salt such as tetrabutylammonium bromide, benzyltriethylammonium bromide, or the like.
According to an embodiment of the present invention, in step 2), the reaction of the compound represented by formula (I-1) to prepare the compound represented by formula (I) may be carried out in the presence of a base selected from organic bases such as triethylamine, pyridine, sodium acetate, potassium acetate, etc., or inorganic bases such as sodium carbonate, potassium carbonate, cesium carbonate, sodium hydroxide, potassium hydroxide, etc. The amount of the base to be used is usually about 0.5 to 5 times by mole based on the compound represented by the formula (I-1).
According to an embodiment of the present invention, in step 2), the solvent used in the reaction of the compound represented by formula (I-1) to prepare the compound represented by formula (I) may be selected from one, two or more of alcohols such as methanol, ethanol, etc., ethers such as tetrahydrofuran, dioxane, dimethoxyethane, etc., amides such as N, N-dimethylacetamide, N-dimethylformamide, N-methylpyrrolidone, etc., and water, etc.
According to an embodiment of the present invention, the temperature of the reaction of preparing the compound represented by formula (I) from the compound represented by formula (I-1) in step 2) may be 0 ℃ to the reflux temperature of the solvent used.
According to an embodiment of the present invention, the reaction of preparing the compound represented by formula (I) from the compound represented by formula (I-1) in step 2) is a reaction carried out under a hydrogen atmosphere, and the hydrogen pressure may be selected from a standard pressure to 10 atm. When formic acid is used, the reaction is preferably carried out under an atmosphere inert to the reaction, such as nitrogen and/or argon.
According to an embodiment of the present invention, the reaction of the compound represented by the formula (I-1) to prepare the compound represented by the formula (I) in step 2) may be carried out by a method described in J.org.chem.,1955,20,225 or other similar methods.
According to an embodiment of the present invention, the compound represented by the formula (II) used in the step 2) may be prepared from the compound represented by the formula (II-1) by the same procedure as the reaction conditions for preparing the compound represented by the formula (I) from the compound represented by the formula (I-1).
According to an embodiment of the present invention, the compound represented by formula (V-1) or formula (V) can be carried out by a method described in patent document WO2001017975, or can be obtained commercially.
The preparation of the compounds of the formula (I) and their starting materials here can be carried out, depending on the reaction conditions and the choice of starting materials which are suitable in each case, by replacing, for example, in a one-step reaction only one substituent by another substituent according to the invention or by replacing, in the same reaction step, a plurality of substituents by further substituents according to the invention.
If the individual compounds are not obtainable via the above routes, they can be prepared by derivatizing the other compounds or by routinely varying the synthetic routes described.
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, recrystallization, distillation and, if appropriate, purification of the crude product by chromatography, for example on alumina or silica gel.
The pharmaceutically acceptable salts of the compounds of formula (I) of the present invention may be prepared by known methods. For example by suitable acid treatment to give an acid addition salt of the compound of formula (I). The preparation method comprises the following steps: the pharmaceutically acceptable salts of the compounds of formula (I) can be conveniently obtained by reacting the compounds of formula (I) with an acid such as hydrochloric acid, sulfuric acid, phosphoric acid, acetic acid, trifluoroacetic acid, malic acid or citric acid in a solvent such as water, diethyl ether or toluene.
The above preparation process can obtain isomer mixture of the compound of formula (I), and if desired, pure isomer can be separated by conventional method such as crystallization or chromatography.
All reactions described above may conveniently be carried out at atmospheric pressure or the autogenous pressure of the particular reaction, unless otherwise indicated.
The present invention also provides a pesticidal composition, such as an insecticidal and/or acaricidal composition, comprising, as an active ingredient, one, two or more of a compound represented by formula (I), a stereoisomer, a racemate, a tautomer, a nitrogen oxide, or a pharmaceutically acceptable salt thereof.
According to an embodiment of the invention, the active ingredient is present in the composition in an amount of 0.1 to 99.9% by weight, for example 0.5 to 99% by weight.
According to an embodiment of the invention, one, two or more agriculturally and/or forestry and/or hygienically acceptable carriers are also included in the composition.
According to an embodiment of the invention, the composition may be administered in the form of a formulation.
For example, the compounds of formula (I) as active ingredients are dissolved or dispersed in a carrier or formulated so as to be more easily dispersible for insecticidal and/or acaricidal use.
According to an embodiment of the invention, the formulation includes, but is not limited to, the following forms: granules, dispersible granules, wettable powder, oil suspension, water suspension, emulsion in water, aqueous solution, missible oil or microcapsules and the like.
According to embodiments of the invention, a liquid or solid carrier, and optionally a surfactant, may also be added to the composition.
The invention also provides application of one, two or more of the compounds shown in the formula (I), stereoisomers, racemates, tautomers, nitrogen oxides or pharmaceutically acceptable salts thereof as pesticides, such as insecticides and/or acaricides.
The invention also provides application of one, two or more of the compounds shown in the formula (I), stereoisomers, racemates, tautomers, nitrogen oxides or pharmaceutically acceptable salts thereof in preparation of pesticides, such as insecticides and/or acaricides.
The invention also provides a method for controlling pests and/or mites, which comprises applying an effective amount of at least one of the compounds shown in the formula (I), stereoisomers, racemates, tautomers, nitrogen oxides and pharmaceutically acceptable salts thereof or applying the pesticide composition to a growth medium of the pests and/or the mites.
According to an embodiment of the invention, the effective amount is from 10 to 1000 grams per hectare, preferably from 20 to 500 grams per hectare.
The active substances according to the invention or the active substances to be used according to the invention are suitable, in view of good plant tolerance, favourable warm-blooded animal toxicity and good environmental compatibility, for protecting plants and plant organs, increasing harvest yields, improving the quality of the harvest and for controlling animal pests, especially pests, mites and the like which occur in agriculture, horticulture, animal husbandry, forestry, gardens and leisure facilities, in the protection of pests and materials in warehouses, and in the hygiene sector. They are preferably used as plant protection compositions. They are active against conventional sensitive and resistant species and against all or individual developmental stages.
The pests and mites include but are not limited to:
arthropoda, in particular Arachnida, such as, for example, the genus Amycolatopsis (Acarus spp.), the genus Citrus gall (Aceraschedoni), the genus Dermatophagoides (Aculopsis sp.), the genus Acropyrium (Aculops spp.), the genus Acropyrium spp., the genus Bluella (Amblyomma spp.), the genus Tetranychus (Amphiyranthus flavus), the genus Argase (Arganella spp.), the genus Boophilus spp., the genus Brevurica (Brevipalpus spp.), the genus Bryopbiagrnaemophilus, the genus Bryopyratia (Bryopia spp.), the genus Deuteropyra (Bryopyratia spp.), the genus Detailus spp.), the genus Dermatophus (Dermatophus spp.), the genus Dermatophus spp., the genus Dermatophus spp (Hypoglyphosatus spp.), the genus Dermatophagoides (Hygrophytin), the genus Dermatophagoides (Hygrophytin), the genus Dermatophagoides), the genus Dermatophus spp.), the genus Dermatophagoides (Hygrophytylenchus spp.), the genus Dermatophus spp.), the genus Dermatophagoides (Hygrophytin (Dermatophus spp.), the genus Dermatophagoides (Dermatophus spp.), the genus Dermatophus (Dermatophus spp.), the genus Dermatophus (Hygrophytes) and the genus Dermatophus spp.), the genus Dermatophus (Hygrophytin (the genus Dermatophus spp.), the genus Dermatophus (Hygrophytes (the genus Dermatophus spp.), the genus Dermatophus (Dermatophus spp.), the genus Dermatophus (Hygrophys (Dermatophus (De, Venomous (Latrodectus spp.), Loxosceles spp, Tetranychus (Metatrenchus spp.), Neutratus, Nuphersa spp, Micronychus (Oligonchus spp.), Blastonella (Ornithodorous spp.), Ornithromycotus spp, Ornithronosus spp, Panonychus (Panonychus spp.), Phyllostachys citri (Phytocopterus spp.), Mitragus crenulata (Phytocopterus specvora), Tarsonemus laterosus (Polytarsonemus), Psortus (Psoroptes spp.), Phyllostachys flabellatus (Rhipicephalus spp.), Rhizopus spp., Rhizopus, Tetranychus (Rhynchus spp.), Tetranychus (Tetranychus spp.), Acarus sp., Tetranychus spus (Stepron spp.), Acarus sp., Tetranychus spp.), Tetranychus (Sterculia spyritus spp.), Acarus spp.);
coleoptera (Coleoptera) (beetle): bean species (Acanthoscelides spp.) (elephant), phaseolus vulgaris (Acanthoscelides obtectus) (common pisiform), Ceratoptera alba (Agrilus planipes) and Ceratopteris versicolor (Quadrifolia narrow Germin), Flammulina species (Agriotes spp.) (wireworm), Anoplophora glabripennis (Aphis longipes), Gomphytus species (Anthonoma spp.) (Arthrobacter flavidus), Gomphytus grandis (Anthronus grandis) (Arthrobacter asiaticus), Gomphytus species (Aphidius spp.) (Aprionus spp.) (Arthrospora), Cochlothiaoma sp. (Anacardia), Cochlothiajaponica (Aponia spp.) (grub), Cochlothuroides (Atacys specularis) (Black piss specula (Atanthus spec), Pieris versicolor (Pieris indica) (Pieris indica), Pieris indica (Pieris indica) (Pieris) and Pieris (Pieris indica) (Pieris chinensis (Pieris) of (Pieris) variety (Pieris illustrates (Pieris) and Pieris (Pieris) such as Pieris (Pieris sinensis (Pieris variety (Pieris) and Pieris (Pieris) such as (Pieris) A variety (Pieris) such as Pieris variety (Pieris) and Pieris variety (Pieris) including Pieris variety (Pieris) such, Pieris variety (Pieris) such as Pieris (Pieris variety (Pieris) such, Pieris (Pieris variety (Pieris) including Pieris) such as Pieris (Pieris variety, Pieris) and Pieris variety (Pieris) such), Pieris (Pieris) including Pieris variety (Pieris) and Pieris (Pieris) such), Pieris) such (Pieris) such), Pieris) such as (Pieris variety (Pieris) and Pieris variety (Pieris) such), Pieris variety (Pieris) variety (Pieris variety, Pieris (Pieris) and Pieris) including Pieris (Pieris) variety (Pieris) such) including Pieris variety (Pieris) such (Pieris variety (Pieris) including Pieris (Pieris variety, Pieris (Pieris variety (Pieris) including Pieris variety (Pieris) including Pieris, Cacoesia species (Cacoesia spp.), Callosobruchus maculatus (Callosobruchus maculatus) (southern cowpea weevil), yellow spot dew nail (carpophilus humilis) (xerophys), tortoise shell (Cassida witta), longicorn seed (ccystron spp.), Ceratoma species (Ccrotoma spp.), Ceratoma spp (chrysomella (chromycosis), Ceratoma trifoliate (Ceratoma trifoliate) (Ceratoma), Calycoptera viridis species (Ceratoma spp.), elephant, Chinese cabbage turtle (Ceratonia rubra) (cabbage weevil), turnip elephant (Ceratonia rubra), European cabbage (Ceratoma) nose (cabbage sepedodes (cabbage) weevil), Japanese beetle (Ceratonia), Japanese cabbage (Ceratonia flava), European red cabbage (Ceratonia flavus) (cabbage beetle), European red cabbage (Ceratous flavus (Ceratodes (cabbage), European red cabbage (European red beetle) (European red beetle), European red cabbage (European red beetle) (European red beetle), European red beetle (European red beetle), red cabbage (European red cabbage) (European red cabbage), red cabbage (European red cabbage) and red cabbage (European red cabbage), red cabbage (red cabbage) are (European red cabbage (red cabbage) and red cabbage (red cabbage) are (red cabbage ) are (red cabbage, red cabbage (red cabbage ) and red cabbage, red cabbage) are (red cabbage ) and red cabbage (red cabbage) are red cabbage, red cabbage (red cabbage ) and red cabbage, red cabbage (red cabbage, red cabbage, Examples of such plants include, but are not limited to, Cryptolepis pusillus (Cryptolepis parvum), Cryptolepis pusillus (Cryptolepis granulosus), Cryptolepis species (Ctenora spp.) (nematodes), elephant species (Curculio spp.) (weevil), Rhinocephalus species (Cycleephora spp.) (Holotrichia dioides), Rhinocephalus pseudoptera (Cyclenophora spp.) (Holotrichia dioides), Rhinocephalus pseudoptera (Apolygus grandis), Rhinocephalus pseudoptera) (Rhinocephalus pseudoptera), Rhinocephalus pseudoptera (Deporus marginatus) (Rhinocephalus pseudoptera) (Mesorula-pectinifera), Rhinocephalus (Rhinocephalus pseudoptera), Rhinocephalus pseudoptera (Rhinocephalus) and Rhinocephalus pseudoptera (Membristylis), Rhinocephalus pseudoptera (Rhinocephalus) Pectinopsis), Rhinocephalus pseudoptera (Rhinocephalus) and Rhinocephalus (Pilus) Pilus chinensis (Membriae) or Rhinocephalus) Pilus (Pilus) Pilus chinensis), Rhinocarpus (Pilus) Pilus chinensis (Pilus) and Rhinocarpus) Pilus chinensis (Pilus) or Pilus chinensis (Pilus) Pilus chinensis) and Pilus chinensis (Pilus) or Pilus) Pilus chinensis (Pilus) or Pilus chinensis (Pilus) Pilus chinensis (Pilus) A. sp., Membriatus) A) Pilus) A) Pilus) or Pilus chinensis (Pilus) Pilus chinensis (Pilus) A. sp Alfalfa leaf elephant (Hypera stictica) (alfalfa weevil), Hyperdos species (Hyperdoss spp.) (argentine stem weevil (Hyperdyses weevil)), coffee berry silly (Hypertenemus hamhei) (coffee berry beetle), scolymus species (Ips spp.) (echinacea), tobacco beetle (Lasioderma serricorne) (tobacco beetle), potato beetle (leptotarsa decemlineata) (colorado potato beetle), lipogyns fuscus, lipogynys suturalis, rice water weevil (lissorethrus oryzophilus) (rice water weevil), pink plant species (lycospera spp.) (Mectophysaloides), Mesorus sporus chinensis (Mesorethrus chinensis), Mesorus sporus chinensis (Mesorethephora), Mesorethephora spp (Mesorrel) and Mesorrel beetle (Mesorethephora), Mesorus spp Rhinoceros rhynchophylla (oriycetes rhynchophylla) (date palm beetle), commerical saw beetle (O ryzaephilus beetle) (market saw beetle), cercaria castanea (elephant), cercaria subulata (odontobrama subulata) (saw beetle), rhynchophylla species (oxiphys spp.) (elephant), black horn mud insect (ocellumeyoplus subulata) (orange foot mud insect (cerolate)), rice negative mud insect (ocelluma oryzae), rose short beak elephant species (pandomous spp.) (elephant), phyllopodium parvus (phyllopodium parvum), phyllopomorpha (phyllopomorpha subulata) (ostriatus subulata), phyllopomorpha parva (phyllopomorpha), picrorhiza (ostriatus subulata), picrorhiza kura (ostriatus parvus (ostriatus spp.) (ostriatus parva), picria parva (ostriata), picria subulata (ostriata) species (ostriatus parva (ostriatus sp.) (picea mangle), picea mangle) and picea mangle (picrorhiza) (picea mangle) species (picrorhiza, picea mangle (picror) of picrorhiza, picea mangle (picrorhiza, picea sp. (picea) of picea mangle (picea sp. (picea) of, Root gill species (rhizorgus spp.) (european scarab (european chafer), cryptorhynchophorus species (Rhynchophorus spp.) (elephant), silly species (Scolytus spp.) (wooddull moth), shonophorus species (shonophorus spp.) (cereal elephant), pisum sativum (Sitona linkuntze) (pea leaf weevil)), rice weevil species (Sitophilus spp.) (cereal weevil), rice weevil (Sitophilus grandis) (millworm (gramnevia)), rice weevil (Sitophilus oryzae) (rice weevil)), sitophilum (Stegobium) (drerberry), triphylum purpurum (brown) (larva), and pseudopterocarpus (brown beetle) (red beetle)), or brown beetle (red beetle) (red beetle)), or red beetle (red beetle) (red beetle).
Dermaptera (Dcrmaptcra) (earwigs).
Vein winged order (Dictyoptera) (cockroach): german cockroach (Blattella germanica) (German cockroach), Blatta orientalis (Blatta orientalis), Blatta palustris (cocitria pennymannica), Periplaneta americana (peritland americana) (americana), Blatta australiana (peritland australoache), Blatta australiana (Australia nckroloach), Periplaneta fusca (pcriparia) brown cockroach (brown cockroach), Periplaneta smokaria (perilanta fuliginosa) (black chest cockroach (smoothckn), and Blatta subclinica (brown cockroach)), Blatta green cockroach (brown cockroach), and Periplaneta fuliginosa (brown cockroach) (Periplaneta subclinica cockroach (brown cockroach)).
Diptera (Diptera) (flies): mosquito species (Aedes spp.) (mosquito), lucerne fly larvae (Agromyza frontella) (alfa blotcheminensis), agromyzis species ((Agromyza spp.) (leaf miner), trypetid species (anastrep spp.) (fruit fly), garleria persica (anastrep persica), garleria persica (garleria persica) (garleria persica (calibrella fufly), mosquito species (anophes spp.) (mosquito), fruit fly species (Bactrocera spp.) (fruit fly), melon fly (Bactrocera persica) (melon), citrus fruit fly (Bactrocera persica), mosquito species (deer spp.) (mosquito), midge fly larvae (sartoria midges) (sea fly), sea fly larvae (sea fly larvae) (deer spp.) (moth), sea fly larvae (bilobagrub) (biles persica), sea fly larvae (moth) and sea fly larvae (sea fly larvae) (moth larvae) (sea fly larvae) (moth larvae) (biles sp.) (3652) Leaf of rape mosquito (Dasineura brassicae) (cabbage mosquito), Dimochi species (Delia spp.), Grapholitha californica (Delia platura) (root maggot (seed corn flag)), Drosophila species (Drosophila spp.) (vinegar fly), Musca species (Fannia spp.) (housefly), yellow belly fly (Fannia canthus) (summer fly (litter fly)), Grey belly fly (grey belly fly) (Grey belly fly), Gasterophilus intestinalis (Gasterous intestinalis) (horse bot), Gracillia persea, Haematobia irutans (Haematobia irritans) (Hymenophila), Blastus species (Hymenophila maggot) (root maggot (skin maggot)), Musca (common fly) (Merista typhus (Musca), Musca melanogaster (Musca), Musca species (Merista spongia) and Musca (Musca), Musca fly (leaf fly) (Merista spossius), Musca fly (Musca fly) (Merista) and Musca (leaf), Musca fly (Musca) and Musca (Musca) are included in the genus, Musca variety (Musca) and Musca, and Musca, such as the same, and their preparation, The plant includes, but is not limited to, the species fall houseflies (Muscaa utumnalis) (fall flies (face flies)), houseflies (vusca domestica) (house flies)), sheep houseflies (oesterussovies) (sheep nose flies (skin bot flies)), european stem flies (ostrich flies) (sweden wheat stem flies), beet spring flies (Pegomyia beta) (spinach leaf flies (beet aircraft)), musca spp (P. horbia spp.), carrot stem flies (Psila rosa (carrot flies)), cherry fruit flies (cherry fruit flies), apple fruit flies (rhapontella (apple maggots)), red mud flies (sitophilus mosquitos) (yellow flies (cow yellow flies)), and cattle fly (stable flies) (cattle yellow flies) (horsefly species).
Hemiptera (Hemiptera) (stinkbug): apolygus lucorum (Acrosteronum hieron) (green stink bug), Oryza sativa (Blissus leucopterus) (long stink bug), Oryza sativa (Caloris norvegicus) (potato stink bug), Tropical stink bug (Cimex hemipterus) (tropical stink), stinkbug (Cimex leucopterus) (bed bug), Daghertussis fasciatus, Dichelops furcatus, Oryza sativa (Euonymus sutus), Edessa meditibetus (Euonymus), Oryza sativa (Leyopteris), Oryza sativa (Leiplus), Oryza sativa (Oryza sativa), Oryza sativa (Oryza sativa) and/Oryza sativa (Oryza sativa) for treating, Lygus hesperus (lygushineus) (western tarnished plant bug), hibiscus syriacus (macrocytoericcus hirsutus), neuroolpus longirostris, rice green bugs (Nezara viridula) (southern green stink bug), lygus planticola (phytolocoris spp.) (lygus), california blind bugs (phytoorius californicus), phytoorius relatus, piozodorus guildingii, lygus tetragonorrhoea (Poiococcus lineus) (neurolocked plant bug), Pseusporicola, Pseusaccharous persica, Scaptocasiana and trypanosoma species (nose cone)/trypanosoma (nose cone).
Homoptera (Homoptera) (aphid, scale, whitefly, leafhopper): piper pisum (Acrythosiphopkinsum) (pea aphid)), Coccinum species (Adelges spp.) (adelg ds), Beeuglena brassicae (Aleurodes proteella) (Beeuglena cabbage whitefly), Aleurodicus spiralis (Aleuroderus di spores), Beeurothyrius filiformis (Aleurothrix luteus) (gloomy whitlys), Begonia alba (Aluaspis spp.), Amrasa biguella, Laodermata species (Aphrophophora ra spp.) (leafhopper)), Rhodococcus aurantii (Amadonis nigrella aurantii) (Begonia aphid), Begonia nilaparvata (Begonia), Begonia nilaparvata (Begoniothiaca), Begoniothiaspora (Begoniothiaspora aphid), Begoniothrix gloea (Begoniothrix), Begonia indica (Begoniothiaspora indica), Begonia indica (Begonia), Begoniothiaspora (Begonia), Begonia (Begonia), Begonioth (Begonia), Begonia) and Begonia (Begonia) Aphis viride (Begonia) are (Begonia), Begonia (Begoniothrix) species (Begonia), Begonia (Begonia, Begoniothrix) of Begonia (Begonia), Begonia, Begoniothiaca, Begonia (Begoniothiaca, Begonia, Begoni, Wheat-tail aphid (Brachycolus noxius) (Russian aphid), asparagus tubular aphid (brachycorythrix asparagi) (asparagus aphid), Brevennia rehi, cabbage aphid (brevicornus brassicae) (cabbage aphid), Ceroplastes sp (Ceroplastes spp.), red Ceroplastes (Ceroplastes rubens) (red wax scale), snow shield plant (chilblastes spp.) (scale), round shield plant (chrysomyrod plant sp.) (scale), soft wax plant (cocussp.) (pink leaf fly), red leaf plant (apple leaf plant), green leaf plant (apple leaf plant), apple leaf plant, apple, euphorbia magna (Macrosiphum eupatoria) (potato aphid), Myzus avenae (Ma crosiphugranaria) (English grazing), Long-pipe aphid (Macrosiphum rosa) (rose aphid), Tetranychus tetragonolobus (Macrostemma quadratus) (purple leafhopper (aster leafhopper)), Mahanaranfrimata (Mahanarville frigida), Metaplexis tetragonolobus (Metholophytum dirhodorophytum) (rose aphid), Midis, Myzus persicae (Myzus persicae), Myzus persicae (green leafhopper), Mythifolius (leaf aphid), Mylopathiocarpa melanophora (leaf), Mythiflua nigra (leaf hopper), Mylophathernalis (leaf hopper), Mylophatherphophora nigra (leaf hopper), Mylophatherphophora (leaf hopper), Mylophatta (leaf aphid), Phytophus nigra grandis (leaf), Mylophora grandis (leaf), Mylophathia (leaf aphid), Mylophatherphophora (leaf), Mylophatta) (Piper nigra) and Mylophatta (leaf), Mylophathia grandis (leaf), Mylophathia (leaf), Mylophatherphophora) and Mylophatoda grandis (leaf, Mylophatta), Mylophatoda (leaf), Mylophathia (leaf aphid (leaf, Mylophatta), Mylophathie (leaf aphid) and Mylophathies), Mylophathies (leaf aphid (leaf, Mylophathies), Mylophathies (leaf aphid (leaf, Mylophathies), Mylophathies, The plant diseases include, but are not limited to, desquamation beetle (Physioderma piceae) (sport bud scale), Begonia sp (Planococcus spp.) (mealybug), Begonia sp (pseudo coccocus spp.) (mealybug), Begonia ananas (Psudococcus brcvps) (Pincapulus mcaly), Pirina piricola (Quad raspidiusmus persicus) (San Jose scale)), Begonia sp (Rhapalacia spp.) (Aphis zeae), Rhapathrix maida (Rhapalacia maida) (Phytophus mairei) (Neurospora, Schizophylla (Schizophylla), Piper nigra (Schizophylla), Piper sylvestris (Rhizopus aphid), Piper sylvestris (Rhizopus flavus) (Schizopus), Piper nigra aphid (Schizopus spp.) (Phoma), Piper nigra (Schizopus spp. (Phosphaera), Piper nigra aphid (Schizopus) (Siphonococcus sp. (Schizopus) (Siphonococcus spp.) (Schizopus), Piper nigra (Schizopus) and Triphysa (Schizopus) A. sp. (Schizopus) and Triphysa (Schizopus) including Piper spp. (Schizopus) and Triphys (Schizopus) including Triphys. sp. sp., Whitefly species (Trialeurodes spp.) (whitefly), greenhouse whitefly (Trialeurodes vaporariorum) (greenhouses whitefly), brown wing whitefly (Trialeurodes abutiloneus) (bandtwing whitefly), cupula species (Unaspis spp.) (scale), arrowhead (Unaspis yanonensis) (arrowhead scale), and Zulia entreriana.
Hymenoptera (Hymenoptera) (ants, wasps and bees): incised leaf ant species (Acromyrmex spp.), Sinkiang leaf beehive (Athalia rosae), leaf ant species (Atta spp.) (Ieafcutting ants), black ant species (Camponotus spp.) (carpenter ant)), pine leaf bee species (Diprion spp.) (leaf beehive (saw fly)), ant species (Formica spp.) (Ant), Argentina ant species (Iridogyrmex pollicis) (Argentina), Carcinia subnata (Monorium spp.) (Monocorium little) (littleberlac), Monomerium termite (Monomerium spp.) (Monomerium kummer.) (Monomerinum), termite leaf ant species (Neomerium spp.) (Melissa), and bee species (Solomonus spp.) (Polonella), and bee species (Solomone spp.) (Melilotus spp.) (Legione), and species (Melilotus spp.) (Melilotus spp (Solomon) (Melilotus spp.) (Carya) and Sina) are harvested, Wasp species (vespela spp.) (yellow jack) and trichogramma species (Xylocopa spp.) (carpenter bee).
Isoptera (Isoptera) (termites): coptotermes spp, Coptotermes curcus, Coptotermes curcumine, Coptotermes frutus, Coptotermes formosanus, Formosan subcoternum, Corniteus spp, Coptotermes formosanus, Coptotermes spp, Coptotermes formosanus, Coptotermes formotermes spp, Heterotermes spp, Coptotermes formotermes spp, Coptotermes formosanus spp, Coptotermes formosanus termes spp, Coptotermes formosanus spp, Coptotermes termes formosanus termes spp, Coptotermes termes spp, Coptotermes termes formosanus termes, Coptotermes termes, Coptotermes termes, Coptotermes termes, Coptotermes, Cotermes termes, Cotermes termes, Cotermes termes, Cotermes termes, Cotermes, Reticulitermes banyulensis, Spodoptera grassland (Reticulitermes grassei), Reticulitermes flavipes (Reticulitermes f la vi pes) (eastern soil-dwelling termites), Reticulitermes flavenii (Reticulitermes hagenii), West soil-dwelling termites (Reticulitermes heperus) (West soil-dwelling termites), Moraxella (Reticulitermes santonensis), North-dwelling soil-dwelling termites (Reticulitermes speratus), Reticulitermes nigripes (Reticulitermes tibialis), Reticulitermes virginicus (Reticulitermes virginicus), Reticulitermes formosanus species (Schedorthes spp.) and Zootes spp.
Lepidoptera (Lepidoptera) (moths and butterflies): achoea janata, Trichosporon species (Adoxophyceae spp.), Trichosta gossypii (Adoxophyes orana), Gekko sp (Agrotis spp.), cutworm (Agrotis ipsilon) (Black cutworm), Alabama virescens (Alabama argillaceae) (Cotton leaf worm (cottonleaf worm), Amorbia cuneata, Amylosis tradiatricella (Na orange), Anacamptodia fectaria, Spodoptera punctata (Antarctica Lineata) (peach twig borreria), Heliothis virescens (Anomia sibirica), Pseudocera erecta (Ostrinia), Pseudocera kummer (Ostrinia), Pseudocera punctata (Ostrinia), Pseudocera kummer (Bodinia), Pseudocera armorida (Ostrinia), Spodoptera punctata (Ostrinia), Spodoptera frugiella punctifera (Ostrinia), Spodoptera (Ostrinia) and leaf (Ostrinia) varieties, Spodoptera (Ostrinia) and leaf The species of the genus Spodoptera (Caloptilia spp.) (Spodoptera exigua), Capua reticulana, peach fruit moth (Carposina nipponensis) (peach fruit moth)), Bombycis gramineus (Chilo spp.), mango transverse-thread Philippine moth (Chuumetia transversa) (mango shoot front borner), Rose color cabbage moth (Choristeurosaana) (oblitera) (obliquus)) and Spodoptera species (Chrysodexis p.)), rice leaf roller (Cnaphalous medius) (grass leaf roller)), Bean flour species of the genus Pieris (Colias spp.)), Yao-punctifera (Conmopora reticulata), Spodoptera litura (apple leaf moth) (apple moth), Spodoptera frugiperda (apple moth (Plutella), Spodoptera xylostella), Spodoptera litura (Spodoptera frugiperda (apple moth) (apple moth (Plutella), Spirochaeta (Spirochaeta.) (Chorista), Spodoptera frugiperda (Spodoptera), Spirochaeta) (apple moth (Plutella), Spirocha) (apple moth (Plutella) species (Plutella) and Spirochaeta (moth (Plutella) A) and Spirogra (Plutella) in the family of the family Choristocarpus (Plutella) species (Plutella) and Spiritis sinensis (Plutella) and Spirilis (Spirilis) of the family, Spiritis sinensis (Sporica) and Sporica) species (Sporina) of the family Gracilaria) and Gracilaria (Plutella) of the family Gray moth (Plutella) species (Plutella) and Gracilaria) of the family, Plutella variety (Plutella) of the family, Plutella) and Gracilaria (Plumbum variety (Plutella) of the family, Plumbus (Plumbum variety (Plumbum frugium) and Plumbum variety (Plumbum, Plumbum variety (Plumbum) including the family, Plumbum variety (Plumbum species (Plumbum) including Plumbum variety (Plumbum) including the family, Plumbum species (Plumbum variety (Plumbum) including the family, Plumbum variety (Plumbum species (Plumbum variety (Plumbum) including the family, Plumbum species (Plumbum variety (Plumbum) including the family, Plumbum species (Plumbum) including the family, Plumbum species (Plumbum) such as, Plumbum species (Plumbum) including the family, Plumbum variety (Plumbum ) including the family, Plumbum variety (Plumbum, Plumbum species (Plumbum, Plumbum variety (Plumbum, Plumbum species (Plumbum, the species Darna diducta, Diaphania sp (Diaphania spp.) (stem borer)), borer sp (diaphraea spp.) (stem borer)), borer (diaphraea saccharalis) (sungar borer), southwestern corn stalk (diaphraea grandiosella) (southwester cornborer), diamond-back seed (eared leaf borer), diamond-back seed (eared leaf spot.) (cotton bollworm), diamond-back (earia insulata) (egg yellow diamond-back borm), diamond-back diamond-worm (ear diamond-back) (egg diamond-back diamond), diamond-back (ear diamond-back) of (ear diamond-back) (egg white moth), diamond-back (egg), south phaea larva (stem borer), stem borer (yellow leaf borer), yellow meadow (yellow meadow), yellow meadow (stem borer, yellow borer), yellow meadow (stem borer), yellow borer (yellow borer) (egg borer) (yellow borer) (egg white borer) (egg borer) (yellow borer), yellow borer) (yellow borer), yellow borer (yellow borer) (yellow borer), yellow borer (yellow leaf) (yellow borer), yellow leaf borer (yellow leaf borer), yellow leaf borer) (yellow leaf borer (yellow leaf) (yellow leaf borer), yellow leaf borer (yellow leaf borer), yellow leaf borer (yellow leaf borer), yellow leaf borer (yellow leaf borer), yellow leaf) (yellow leaf borer), yellow leaf borer (yellow leaf borer), brown leaf borer), yellow leaf borer (yellow leaf borer), brown leaf borer (yellow leaf borer), brown leaf borer) (yellow leaf borer), brown leaf borer (yellow leaf borer), brown leaf borer) (yellow leaf borer), examples of the plant diseases include banana cutworm (Erionota thrax) (banana skipper), glossy privet (eupoiiliambiguaella) (grape berry moth)), protorhizoctona auricularis (armychiaris) (armychus), cutworm (armychus species) (armychus), cutworm (ferula spp.) (rhizoctonus), hornworm (Gortyna spp.) (stem borer), oriental moth (Grapholita molesta) (peach (apricot) fruit borer (oriental fruit moth)), trilobia (cabbage moth) (soybean leaf borer) (bean leaf borer), caterpillar (budworm moth) (Helicoverpa sp.) (helicoptera), cotton bollworm (helicoipula terrestris) (corn borer), cotton bollworm (helicopterocarpa armyworm) (corn borer), cotton bollworm (corn borer), cotton bollworm (cabbage moth (corn borer) corn borer (corn borer) and corn borer (corn borer) corn borer (corn borer) corn borer (corn borer) corn borer (corn borer) corn borer (corn borer) corn borer (corn borer) corn borer (corn borer) corn borer (corn borer) corn borer (corn borer) corn borer (corn borer) corn borer (, White-fin eggplant borer (Leucinodes orbornalis) (eggplantfront borre), spiderworm moth (Leuciptera malifoliella), fine moth species (Lithocolletis spp.), grape leaf roller moth (Lobesia borna) (grape fruit moth), Loxagra gruotis species (Loxagrutissp.) (Spodoptera frugiperda), soybean-line root cutting insect (Loxagrus albicans) (western bean fruit moth), gypsy moth (Lymantria dispar) (gypsy moth), peach leaf roller (Lyonetherella), apple leaf roller (apple leaf moth (apple leaf miner)), oil palm moth (Mahasa coreticum) (tomato leaf moth), cabbage (cabbage), cabbage (Mallotus leaf borer), cabbage moth (apple leaf borer) (cabbage caterpillar), cabbage caterpillar (apple leaf borer), cabbage (cabbage caterpillar), cabbage caterpillar (cabbage caterpillar), cabbage caterpillar (cabbage caterpillar) leaf borer (cabbage caterpillar), cabbage caterpillar (cabbage caterpillar, moth (cabbage caterpillar, moth) moth (cabbage caterpillar, rice stem borer, moth (cabbage caterpillar, moth (cabbage caterpillar, moth, cabbage caterpillar, moth, cabbage caterpillar, moth, cabbage caterpillar, moth, cabbage caterpillar, rice stem borer, moth, rice stem borer, moth, rice stem borer, moth, rice, moth, rice stem borer, moth, rice, moth, rice stem borer, moth, rice, moth, rice, moth, rice stem borer, rice stem borer, rice stem, rice, European corn borer (Ostrinia nubilalis) (European corn borer)), Oxydia vesulia, Ostrinia (Pandemiscarana) (common grape leaf moth (common currant torrex)), Spodoptera frugiperda (Pandemia hepes) (brown apple torrex), Pneumoniella africana (Papilio demoduloca), Spodoptera litura (Pectinophora grandiflora) (red bell bollworm (pink bollworm)), Spodoptera species (Peridroma spp.) (root cutting insect), Philobium japonicum (Peridroma saucia) (variegated cutworm), Spodoptera coffea (Perileria lutea), Plutella xylostella (Plumbum xylostella), Plumbum xylostella (Plumbum xylostella) (white moth (Plumbum xylostella), Plumbum xylostella (Plumbum xylostella) (Pimenta) (Plumbum xylostella), Plumbum xylostella (Plumbum xylostella) and Plumbum xylostella (Plumbum xylostella) A), Grape berry moth (polychrosia viroana) (grapple berry moth), orange fruit moth (Prays endooctarps), olive moth (prasys oleae) (olive moth), armyworm species (pseudogleria spp.) (noctuid), pseudoglettia unipunctata (marchantia papulosa), soybean looper (pseudophyllula includens) (soybean looper), inchworm (rachidia nu), tryporyza incertulas (sciophila incertulas), phomopsis nocardia (Sesamia spp.) (stemona), rice stem borer (Sesamia infferi) (pink beet steiners), pink stem borer (Sesamia infringens), copper brown loopers (Sesamia), northern leaf moth (southern looper), Spodopteroma armyworm (Spodoptera spongiosa), Spodoptera frugiperda (Spodoptera spongiosa), Spodopterocarpa punctata (Spodoptera spongiosa), Spodopteroma frugium frugiperda (Spodoptera), Spodoptera frugium frugiperda (Spodoptera) and Spodoptera (Spodoptera) in which are selected from Spodopterocarpus armyworm (Spodoptera) and the genus Spodoptera, Spodoptera (Spodoptera) are also included in which the application of the variety of Spodoptera, the seed of Spodoptera, the species (Spodoptera, Spodoptera (Spodoptera, Spodoptera (Spodoptera) is, Spodoptera (Spodoptera) and the Spodoptera (Spodoptera) can be, Spodoptera (Spodoptera) can, Spodoptera (Spodoptera) can be, Spodoptera (Spodoptera) can, Spodoptera (Spodoptera) can be, Spodoptera (Spodoptera) can, Spodoptera (Spodoptera) can, Spodoptera) can be, Spodoptera) can, Spodoptera (Spodoptera) can be used for example, Spodoptera (Spodoptera) can be, Spodoptera) can, Spodoptera (Spodoptera) can be, the species Heliothis virescens (Synanthon spp.) (root borer), Therla basilides, Thermia gemmatalis, Chlamydia armyworms (Teneola bisseliella) (webbingclotheshes moth), Trichoplusia ni (cab looper), Tomatomyza sativa (Tutsassolutita), Phlebia nidulans (Yonomeuta spp.), Cochlothuria coffea arabica (Zeuzearocoffea) (red branchborer), Zeuzera pyrina (Leopard moth (Leopboard moth)), and Spodoptera litura (Fabricius)).
Mallophaga ((Mallophaga) feather louse (chewing lice)): ovine feather louse (Bovicola ovis) (sheet biting louse), turkey short horn feather louse (chicken feather louse), and chicken feather louse (Menopon gallina) (common henhouse).
Orthoptera (Orthoptera) (grasshopper, locust and cricket): arana nigra (anacrus simplex) (Mormon horns (Mormon cricket)), mole cricket (Gryllotalpidae) (mole cricket)), eastern asia migratory locust (Locusta migratoria), grasshopper species (Melanoplus spp.) (grasshopper), acephala wing spurs (microcentrumretrierve) (angular winged katydia (grasshopper)), pterophora species (pterophora spp.) (pterophora, steleophaga egr, pterygrosaurus (scuddita) (forked tail bush (fork tailed butydia)), and tuberous ridge (vanilloida).
Phthiraptera (Phthiraptera) (sucking lice): the blood sucking lice species (haemattopinus spp.) (cattle and pig lice), sheep jaw lice (sheep lice), head lice (pedigree capitis) (body lice), human body lice (pedigree humanus (body lice) and crab lice (crab lice)).
Siphonaptera (daphnaptera) (fleas): ctenocephalides canis (dog flea), Ctenocephalides felis (cat flea) and human flea (Pulex irutans) (human flea).
Thysanoptera (thrips): frankliniella fusca (Frankliniella fusca) (tobaco third), Frankliniella occidentalis (western flower) Frankliniella hultrias (western flower), Frankliniella shultzii (Frankliniella williamsii) (corn Thrips), Frankliniella glasshouse Thrips (IIelothrips hamoralidis) (greenhous third), Riphisprothrips cruentus, Scirpus sp (Sciroththrips spp), Platycodon grandiflorum (Scirthricirris) (citrus trough), Frankliniella tabacum (Scirthrips spp), Talothriparia (yellow Thrips spp), and Throughthrips (Thripus spp).
Thysanoptera (Thysanura) (bristletail): chlamydomonas species (Lepisma spp.) (silverfish) and locusta species (Thermobia spp.) (locusta spp.).
From the order of Acarina (Acarina) (mites (mite) and cicadas (tick)): woodbee scutellariae (acarapis woodi) (parasitic mites in the trachea of bees), dermatophagoides (Acarus spp.) (food mites), Acarus macrorhynchophylla (Acarus srorona) (grain mite), mango bud mite (Aceria mangifera) (mango bud mite), acanthophyrus sp. (Acarus spp.), acanthophysalis scabrosoides (acanthophyceae), acanthophysalis lycopersici (acanthophysalis septemporosa) (tomato bud mite), acanthophysalis pelekasi, acanthophysalis citri (acanthophysalis peekatsi) (acanthophysalis peeka), acanthophysalis dermalis (acanthophysalis spindalii) (apple gall mite (decapili mite), american tick (acanthophysalis tick (mangifer sporus sp.), Chinese tick (amygdalus persicum), short tick (mangiferous tick (mangifer), or mangiferous tick (mangifer sp.), or mangiferous tick (mangiferous tick) and mangiferous tick (mangiferous tick) species), mangiferous tick (mangiferous tick) and mangiferous tick (mange sp.) including mangiferous tick (mange variety), mange sp.) including mange variety), mange variety (mange variety), mange variety (mange variety), mange variety (mange variety), mange variety (mange variety), mange variety (mange variety), mange variety (mange variety), mange variety (mange variety), mange variety of mange variety (mange variety), mange variety (mange variety), mange variety (mange variety) and mange variety (mange variety), mange variety (mange variety of mange variety (mange variety), mange variety of mange variety (mange variety), mange variety (mange variety), mange variety (mange variety of mange variety (mange variety), mange variety (mange variety), mange variety of mange variety (mange variety of, House dust mite (Dermatophagoides pteronyssinus) (house dust mite), Tetranychus sp (Eotetranus spp.), hornbeam Tetranychus carpesii (Eotetranthus carpini (yellow spider mite), Tetranychus sp.), Gephyrus sp (Epithromyces sp.), Gephylus sp (Eriophenous spp.), hard tick sp (I.D.; es sp.), ticks (tick), Tetranychus sp (Notederus sp.), Microphyrus sp.), Microphycus sp. sp.Ohiophagus (Ochrophycus sp.), Tetranychus sp (Notoednes. cati), Microphycus sp (Oligonychus sp.), Calonychus (Ocynidae) coffee, Tetranychus parvus (Ocigo nuciferus), Tetranychus wintergreen (Oligonychus (Ochrotus) and Tetranychus (Ochrotus sp.), Tetranychus (Tetranychus urticae (Tetranychus), Tetranychus urticae (Tetranychus urticae) (Tetranychus sp.), Tetranychus urticae (Tetranychus), Tetranychus (Tetranychus) and Tetranychus (Tetranychus) or Tetranychus (Tetranychus) or Tetrasticus (Tetrasticus) or (Tetrasticus) or Tetrasticus (Tetrasticus) or Tetrasticus (Tetrasticus) or Tetrasticus (Tetrasticus) or (Tetrasticus) or Tetrasticus (Tetrasticus) or Tetrasticus (Tetrasticus) or Tetrasticus (Tetrasticus) or Tetrasticus (Tetrasticus) or Tetrasticus (Tetrasticus) or Tetrasticus (Tetrasticus) or Tetrasticus, Rhizomorpha species (rhizomorph spp.) (root mite (bulb mite)), Sarcoptes scabies (Sarcoptes scabies) (itch mite), coronaria avocado (tetragonophys perseafarae), Tetranychus species (Tetranychus spp.), Tetranychus urticae (Tetranychus urticae) (twospoked spider mite)) and Varroa destructor (Varroa destructor) (honey bee mite).
Nematoda (nematodes): the species Aphelenchoides (Aphelenchoides spp.) (bud and leaf and pine wood nematodes (bud and leaf & pine wood nematodes)), the species nematodiasis (Belonolaevis spp.) (sting nematodes), the species Cyclotella minor (Criconella spp.) (ring nematodes), the species Dirofilaria immitis (dog heartword), the species Ditylenchus spp. (stem and bulb nematodes), the species Trichophythora (Heterodera spp.) (Cytospora spp.), the species Heterocladia (Heterocladia zeyla) (maize nematodide), the species Melilodinia spp. (Hichlamyella spp.) (Neurospora spp.) (Melilotus spp.)), the species Heterocladospora spp. (Melilotus spp.)), the species Melilotus spp.) (Melilotus spp.)), the species (Melilotus spp.) (Melilotus, Melilotus spp.) (Melilotus spp.)) and Melilotus spp.) (Melilotus spp.)) and Melilotus spp.) (Melilotus, Melilotus spp.) (Melilotus, Melilotus spp.) (Melilotus, Melilotus spp.) (Melilotus spp.)) and Melilotus, Melilotus spp.) (Melilotus spp.)) and Melilotus spp.) (Melilo, The species of the genus Rapholus (Rapholus spp.) (Burrowing nematode) and the species of the Leptochloa (Rotylenchus reniformis) (kidney-shaped nematode).
General class (general classes of insects): white pine worm (Scutigerella immaculata).
Owing to their positive properties, the compounds of the formula (I) can be used advantageously for protecting crops, domestic animals and livestock animals of agricultural and horticultural importance, as well as the environment customary for humans, against pests and/or mites.
The amount of the compound of formula (I) to be used to obtain the desired effect will vary depending on various factors such as the compound used, the crop to be protected, the type of pest, the extent of infection, the climatic conditions, the method of application and the dosage form employed.
The ingredients of the dosage forms or compositions described herein are selected in accordance with the physical properties of the active ingredient, the mode of application and environmental factors such as soil type, moisture and temperature.
Useful dosage forms include solutions such as solutions (including emulsifiable concentrates), suspensions, emulsions (including microemulsions and/or suspensions), and the like, which may optionally be viscous jellies. Useful dosage forms also include solids such as powders, granules, tablets, pills, films, and the like, which may be water dispersible ("wettable") or water soluble. The effective components can be microencapsulated and made into suspension or solid dosage form; in addition, the whole dosage form of the effective components can be encapsulated. The capsule can control or delay the release of the effective components. Sprayable formulations can be diluted in a suitable medium using spray volumes of about one to several hundred liters per hectare. The compositions in high concentrations are mainly used as intermediates for further processing.
Typical solid Diluents are described in Watkins et al, Handbook of Instrument standards and Cariers, 2nd Ed., Dorland Books, Caldwell, N.J.. Typical liquid diluents are described in Marsden, Solventsguide, 2nd Ed., Interscience, New York, 1950. McCutcheon's Detergents and Emulsifiers annular, Allured pub. Corp., Ridgewood, New Jersey, and Sisely and Wood, Encyclopedia of Surface Active Agents, Chemical Publ. Co., Inc., New York, 1964, list surfactants and recommended applications. All formulations may contain small amounts of additives to reduce foaming, coalescence, corrosion, microbial growth, etc., or thickeners to increase viscosity.
Surfactants include, for example, polyethoxylated alcohols, polyethoxylated alkylphenols, polyethoxylated sorbitan fatty acid esters, sulfonated dialkyl succinates, alkyl sulfates, alkyl benzene sulfonates, organosilanes, N-dialkyl taurates, lignosulfonates, aldehyde condensates for naphthalenesulfonates, polycarboxylates, and polyoxyethylene/polyoxypropylene block copolymers.
Solid diluents include, for example, clays such as bentonite, montmorillonite, attapulgite, kaolin, starch, sugar, silica, talc, diatomaceous earth, urea, calcium carbonate, sodium bicarbonate, sodium sulfate, liquid diluents include, for example, water, 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 oil, 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 tetrahydrofurfuryl alcohol.
Solutions, including emulsifiable concentrates, can be prepared by simply mixing the components. Powders and fines can be prepared by mixing and the suspending agents are generally prepared by wet milling, usually by grinding in a hammer mill or liquid energy mill; see, for example, U.S. Pat. No. 3060,084, granules and pellets are prepared by spraying the active substance onto freshly prepared granular carriers or by granulation techniques. See Browning, "Aggloration," Chemical Engineering, Decumber 4, 1967, pp147-48, Perry's Chemical Engineering's Handbook, 4TH Ed., McGraw-Hill, New York, 1963, Pages 8-57and following, and WO 91/13546. The preparation of pellets is described in U.S.4172714, water dispersible and water soluble granules are described in U.S.4144050, U.S.3920442 and DE 3246493 to prepare tablets as described in US 5180587, U.S.5232701 and U.S. 5208030. Films may be prepared by the methods described in GB2095558 and u.s.3299566.
More information on processing can be found in U.S.3,235,361, Col.6, line 16through Chol.7, line 19and EXAMPLES 10-41; U.S. Pat. No. 3,309,192, Col.5, line 43through Col.7, line 62and EXAMPLES 8, 12, 15, 39, 41, 52, 53, 58, 132, 138, 140, 162, 164, 166, 167and 169-182; U.S.2,891,855, col.3, line 66through col.5, line 17and 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.
Herein, for certain applications of the composition, for example in agriculture, one, two or more other bactericides, acaricides, herbicides, plant growth regulators or fertilizers and the like may be added to the insecticidal and/or acaricidal composition of the invention, whereby additional advantages and effects may be produced.
Advantageous effects
The compound of formula (I) shows good activity to various pests and mites in agriculture or other fields. Furthermore, these compounds can be used for the preparation of insecticides and/or acaricides because of their excellent control effect at very low doses.
The inventor of the application finds that the introduction of a pentafluorothioether group into the compound in the formula (I) has a large influence on the activity of the compound, and the biological activity is remarkably improved. Therefore, the compound shows excellent control effect on various pests/pest mites such as aphids, brown planthoppers, frankliniella occidentalis, tetranychus cinnabarinus and the like.
In addition, the compound provided by the invention has the advantages of simple preparation steps and high yield, and therefore, the compound has a good application prospect.
Terms and definitions
Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which the claimed subject matter belongs. All patents, patent applications, and publications cited herein are incorporated by reference in their entirety unless otherwise indicated. If there are multiple definitions of terms herein, the definition in this section controls.
It is understood that reference may be made to (including Carey and Sundberg "ADVANCED ORGANIC CHEMISTRY 4)THED. "Vols.A (2000) and B (2001), Plenum Press, New York). Unless otherwise indicated, conventional methods within the skill of the art are employed, such as mass spectrometry, NMR, IR and UV/Vis spectroscopy, and pharmacological methods. Unless a specific definition is set forth, the terms used herein in the pertinent description of analytical chemistry, organic synthetic chemistry, and pharmaceutical chemistry are known in the art. Can be used in chemical synthesis, chemical analysis, pharmaceutical preparation, preparation and deliveryAnd standard techniques used in the treatment of patients. For example, the reaction and purification can be carried out using the manufacturer's instructions for use of the kit, or in a manner known in the art or as described herein. The techniques and methods described above can generally be practiced according to conventional methods well known in the art, as described in various general and more specific documents referred to and discussed in this specification. In the present specification, groups and substituents thereof may be selected by one skilled in the art to provide stable moieties and compounds. When a substituent is described by a general formula written from left to right, the substituent also includes chemically equivalent substituents obtained when a formula is written from right to left, as long as it complies with the valence rules. For example, CH2O is equivalent to OCH2The substitution position may be bonded with an oxygen atom or a carbon atom of a methylene group.
The term "C1-6Alkyl is understood to mean a straight-chain or branched saturated monovalent hydrocarbon radical having from 1 to 6 carbon atoms. For example methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl, isobutyl, sec-butyl, tert-butyl.
The above for the term "alkyl", e.g. "C1-6The definition of alkyl "applies equally to compounds containing" C1-6Other terms for alkyl ", e.g. the term" halo C1-6Alkyl group "," C1-6Alkoxy group "," halogeno C1-6Alkoxy "and the like.
The term "halogen" is to be understood as fluorine, chlorine, bromine or iodine.
The term "halo C1-6Alkyl is understood to mean straight-chain or branched alkyl radicals in which the hydrogen atoms are partially or completely replaced by halogen atoms, e.g. -CF3。
The term "halo C1-6Alkoxy "is to be understood as meaning that the hydrogen atoms of the alkyl radical of the alkoxy radical may be partially or completely replaced by halogen atoms, such as ClCH2CH2O-。
The term "pharmaceutically acceptable salt" as used herein means that the biological potency of the free acid and free base of the specified compound is retained and is biologically or otherwise non-existentSalts with adverse effects. The compounds of the present application also include pharmaceutically acceptable salts, such as nitrates, hydrochlorides, sulfates, phosphates, or the like. Pharmaceutically acceptable salts refer to the form in which the base group in the parent compound is converted to a salt. Pharmaceutically acceptable salts include, but are not limited to, inorganic or organic acid salts of basic groups such as amine (amino) groups. Pharmaceutically acceptable salts of the present application can be synthesized from the parent compound by reacting a basic group in the parent compound with 1-4 equivalents of an acid in a solvent system. Suitable salts are listed in Remingtong's Pharmaceutical sciences, 17thed., Mack Publishing Company, Easton, Pa.,1985, p.1418 and Journal of Pharmaceutical Science,66,2(1977), for example the hydrochloride salt.
"stereoisomers" as used herein refers to isomers resulting from the 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 and mixtures of formula (I) are as such, including racemic mixtures, as part of the present application. Diastereomeric mixtures can be separated into the individual diastereomers, based on their different physicochemical properties, by well-known means, e.g., resolution of the enantiomers can be converted into the diastereomers by reaction with a suitable optically active substance (e.g., a chiral alcohol or Mosher's moylchloride), which can be separated and converted (e.g., hydrolyzed) into the corresponding individual isomers. Some of the compounds of formula (I) may be atropisomers (e.g., substituted aryl) are also part of this application. Enantiomers can also be separated using a chiral chromatography column. The compounds of formula (I) may exist in different tautomeric forms, which forms are included within the scope of the present application. For example, keto-enol and imine-enamine forms of the compounds.
Detailed Description
The technical solution of the present invention will be further described in detail with reference to specific embodiments. It is to be understood that the following examples are only illustrative and explanatory of the present invention and should not be construed as limiting the scope of the present invention. All the technologies realized based on the above-mentioned contents of the present invention are covered in the protection scope of the present invention.
Unless otherwise indicated, the raw materials and reagents used in the following examples are all commercially available products or can be prepared by known methods.
The following chromatographic conditions were used for the LC-MS detection analysis in the examples below:
a chromatographic column: agilent ZORBAX SB-C18150 mm X4.6 mm, 5 μm (i.d);
detection wavelength: 254 nm; flow rate: 0.8 mL/min; column temperature: 30 ℃;
gradient elution conditions:
time (min) Methanol (%) 0.1 aqueous formic acid solution (% by volume)
0.00 50 50
5.00 50 50
10.00 90 10
20.00 90 10
Synthetic examples
Example 1: preparation of 4- ((5- (1, 3-dioxan-2-yl) pyrimidin-4-yloxy) methyl) phenylpentafluorosulfide (Compound 1)
Figure BDA0002384373280000231
The first step of reaction: preparation of 4, 6-dichloro-5- (1, 3-dioxan-2-yl) pyrimidine: 17.9g (0.1mol) of 4, 6-dichloropyrimidine-5-carbaldehyde were dissolved in 100mL of toluene at room temperature, and the mixture was stirred. To the above mixture were added 1.75g (0.01mol) of p-toluenesulfonic acid and 15.2g (0.2mol) of propylene glycol, respectively. Heated to reflux for 1 hour. After the heating was stopped, the mixture was concentrated under reduced pressure, and 50mL of ethyl acetate was added to the residue, which was washed with a saturated aqueous sodium bicarbonate solution (20mL) and a saturated brine (30mL), respectively. The organic layer was dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to give a crude product. The product is obtained by column chromatography purification, 20.2g and the yield is 86%.
LC-MS[M+H]+＝235.01、[M+Na]+＝256.99、[M+K]+＝272.96。
The second step of reaction: preparation of 4-chloro-5- (1, 3-dioxan-2-yl) pyrimidine: 11.8g (0.05mol) of 4, 6-dichloro-5- (1, 3-dioxan-2-yl) pyrimidine, 8.5g (0.1mol) of sodium ethoxide and 4.6g of palladium on carbon were dissolved in 150mL of ethanol, respectively, at room temperature. And reacting for 6 hours under a hydrogen atmosphere. The mixture was filtered through celite, and the filtrate was concentrated under reduced pressure. To the concentrate was added 10mL of a saturated aqueous sodium bicarbonate solution. Ethyl acetate (3 × 20mL) was extracted. The organic layer was washed with water (20mL) and saturated brine (20mL), and dried over anhydrous magnesium sulfate. The solvent is removed under reduced pressure, and the product is obtained by column chromatography with the yield of 4.1g and 40 percent.
LC-MS[M+H]+＝201.05、[M+Na]+＝223.03、[M+K]+＝239。
The third step of reaction: preparation of 4- ((5- (1, 3-dioxan-2-yl) pyrimidin-4-yloxy) methyl) phenylpentafluorosulfide: 0.44g (0.011mol) of sodium hydride are dissolved in 10mL of N, N-dimethylformamide at 0 ℃. To the mixture was added 2.34g (0.01mol) of 4- (hydroxymethyl) phenylpentafluorosulfide in portions, the temperature being kept below 5 ℃. Then, 1.85g (0.009mol) of 4-chloro-5- (1, 3-dioxan-2-yl) pyrimidine was added to the mixture and reacted at room temperature for 4 hours. The reaction mixture was poured into ice water and extracted with ethyl acetate (3 × 20 mL). The organic layers were combined, washed with water (20mL) and saturated brine (20mL), and dried over anhydrous magnesium sulfate. The solvent is removed under reduced pressure, and the product is obtained by column chromatography with the yield of 75 percent, 2.7 g.
LC-MS[M+H]+＝399.08、[M+Na]+＝421.06、[M+K]+＝437.03。
1HNMR (400MHz, solvent (CD)3)2SO)δ(ppm):2.06(2H,m),3.96(2H,t),4.16(2H,m),
5.61(2H,s),5.80(1H,s),7.68(2H,d),7.94(2H,d),8.62(1H,s),8.80(1H,s)。
Example 2: preparation of 3- ((5- (1, 3-dioxan-2-yl) pyrimidin-4-yloxy) methyl) phenylpentafluorosulfide (Compound 23)
Figure BDA0002384373280000241
0.44g (0.011mol) of sodium hydride are dissolved in 10mL of N, N-dimethylformamide at 0 ℃. To the mixture was added 2.34g (0.01mol) of 3- (hydroxymethyl) phenylpentafluorosulfide in portions, the temperature being kept below 5 ℃. Then, 1.85g (0.009mol) of 4-chloro-5- (1, 3-dioxan-2-yl) pyrimidine was added to the mixture and reacted at room temperature for 4 hours. The reaction mixture was poured into ice water and extracted with ethyl acetate (3 × 20 mL). The organic layers were combined, washed with water (20mL) and saturated brine (20mL), and dried over anhydrous magnesium sulfate. Decompression desolventizing, column chromatography to obtain 2.5g of product with 70% yield.
LC-MS[M+H]+＝399.08、[M+Na]+＝421.06、[M+K]+＝437.03。
1HNMR (400MHz, solvent (CD)3)2SO)δ(ppm):2.07(2H,m),3.96(2H,t),4.16(2H,m),5.62(2H,s),5.80(1H,s),7.72(2H,d),7.78(1H,d),7.84(1H,d),8.61(1H,s),8.80(1H,s)。
Example 3: preparation of 3- ((5- (1, 3-dioxan-2-yl) pyrimidin-4-yloxy) methyl) -5-fluorophenylpentafluorosulfide (Compound 27)
Figure BDA0002384373280000251
0.44g (0.011mol) of sodium hydride are dissolved in 10mL of N, N-dimethylformamide at 0 ℃. To the mixture was added 2.56g (0.01mol) of 3-fluoro-5- (hydroxymethyl) phenylpentafluorosulfide in portions, the temperature being kept below 5 ℃. Then, 1.85g (0.009mol) of 4-chloro-5- (1, 3-dioxan-2-yl) pyrimidine was added to the mixture and reacted at room temperature for 4 hours. The reaction mixture was poured into ice water and extracted with ethyl acetate (3 × 20 mL). The organic layers were combined, washed with water (20mL) and saturated brine (20mL), and dried over anhydrous magnesium sulfate. The solvent is removed under reduced pressure, and the product is obtained by column chromatography, wherein the yield is 2.46g and 65 percent.
LC-MS[M+H]+＝417.07、[M+Na]+＝439.05、[M+K]+＝455.02。
1HNMR (400MHz, solvent (CD)3)2SO)δ(ppm):2.07(2H,m),3.96(2H,t),4.16(2H,m),5.62(2H,s),5.80(1H,s),7.32(1H,d),7.46(1H,d),7.64(1H,d),8.62(1H,s),8.81(1H,s)。
The present invention also synthesizes the compounds in the following tables, with reference to the methods in the above examples, and the results of their characterization are shown in the following tables:
Figure BDA0002384373280000252
Figure BDA0002384373280000261
Figure BDA0002384373280000271
formulation examples
In the following examples, all percentages are by weight and all dosage forms are prepared using conventional methods.
Example 4:
in this example, the compound obtained in the above example is used to prepare a wettable powder, which is specifically prepared by using the following raw material compositions in proportion:
165.0% of compound, 2.0% of dodecylphenol polyethoxy glycol ether, 4.0% of sodium lignosulfonate, 6.0% of sodium aluminosilicate and 23.0% of montmorillonite (calcined).
Example 5:
in this example, granules were prepared using the compounds obtained in the above examples, specifically using the following raw material compositions:
2310.0% of compound, 2% of sodium dodecyl sulfate as other components, 6% of calcium lignosulfonate, 10% of potassium chloride, 1% of polydimethylsiloxane and 100% of soluble starch.
Example 6:
in this example, the compound obtained in the above example is used to prepare an extruded pellet, specifically using the following raw material composition:
2725.0% of compound, 10.0% of anhydrous calcium sulfate, 5.0% of crude calcium lignosulfonate, 1.0% of sodium alkyl naphthalene sulfonate and 59.0% of calcium/magnesium bentonite.
Example 7:
in this example, the compound obtained in the above example is used to prepare emulsifiable concentrate, and specifically, the emulsifiable concentrate is prepared by using the following raw material compositions:
3425.0% of compound, 15060% of solvent, PEG 4005% of Rhodacal 70/B3% of Rhodameen RAM/77%.
Example 8:
in this example, the compound obtained in the above example is used to prepare an aqueous suspension, specifically, the following raw material composition is used to prepare the aqueous suspension:
3930.0%, POE polystyrene phenyl ether sulfate 5.0%, xanthan gum 0.5%, polyethylene glycol 5%, triethanolamine 1%, sorbitol 0.5% and water to 100.0%.
Biological activity assay
Example 9:
1. determination of insecticidal Activity
In this example, several insects were tested for insecticidal activity using the compounds prepared in the above examples.
And (3) testing the insecticidal activity: the test method is that a test compound sample is dissolved by a suitable solvent (the kind of the solvent is acetone, methanol, DMSO, etc., and is selected according to the dissolving capacity of the solvent on the sample) to prepare a test solution with a required concentration. The test cell consisted of a small open container containing 12-15 day old radish plants. The test plants were preimpregnated by placing 30 to 40 pests on a leaf cut from the cultivated plant on one leaf of the test plant (leaf cutting method). As the leaves dehydrate, the pests move on the test plants. After pre-dip dyeing, the soil of the test cell was covered with a layer of sand.
The test method is as follows: the test was repeated three times, and after spraying the prepared test compound solution, each test unit was allowed to dry for 1 hour, and then a black mesh cap was placed on top. The test cells were kept in a growth chamber at 25 ℃ and 70% relative humidity for 6 days. Insect mortality was then visually assessed for each test unit.
(1) Test results for the control of myzus persicae by exemplary example Compounds
At a dose of 600ppm, the compounds with the lethality rate of more than 80% to the green peach aphids comprise: 1. 2, 3, 5, 14, 19, 22, 23, 27, 28, 34, 39, 40, 41;
at a dose of 100ppm, the compounds with the lethality rate of more than 80% to the green peach aphids comprise: 1. 2, 3, 5, 14, 19, 22, 23, 34, 39, 40, 41;
at a dose of 50ppm, the compounds with the lethality rate of more than 80% to the green peach aphids comprise: 1. 2, 3, 5, 19, 22, 23, 34, 39, 40.
(2) Test results for the control of Aphis gossypii by exemplary example Compounds
At a dose of 600ppm, the compounds with the lethality rate of more than 80% to cotton aphid comprise: 1. 2, 3, 5, 14, 19, 22, 23, 27, 28, 34, 39, 40, 41;
at a dose of 100ppm, the compounds with the lethality rate of more than 80% to cotton aphid comprise: 1. 2, 3, 5, 14, 19, 22, 23, 34, 39, 40, 41;
at a dose of 50ppm, the compounds with a lethality rate of more than 80% to Aphis gossypii have the following characteristics: 1. 2, 3, 5, 19, 22, 23, 34, 39, 40.
(3) Test results for controlling frankliniella occidentalis by exemplary example Compounds
At a dose of 600ppm, the compounds with the fatality rate of more than 80 percent to frankliniella occidentalis have the following characteristics: 1. 2, 3, 5, 14, 19, 22, 23, 27, 28, 34, 39, 40, 41;
at a dose of 100ppm, the compounds with the fatality rate of more than 80 percent to frankliniella occidentalis have the following characteristics: 1. 2, 3, 5, 14, 19, 22, 23, 27, 28, 34, 39, 40, 41;
at a dose of 50ppm, the compounds with the fatality rate of more than 80 percent to frankliniella occidentalis have the following characteristics: 1. 2, 3, 5, 14, 19, 22, 23, 34, 39.
(4) Test results for controlling brown planthopper with exemplary example compounds
At a dose of 600ppm, the compounds with a mortality rate of more than 80% to prodenia litura comprise: 1. 2, 3, 5, 14, 19, 22, 23, 27, 28, 34, 39, 40, 41;
at a dose of 100ppm, the compounds with a mortality rate of more than 80% to prodenia litura comprise: 1. 2, 3, 5, 14, 19, 22, 23, 27, 28, 34, 39, 40, 41;
at a dose of 50ppm, the compounds with a mortality rate of more than 80% to prodenia litura comprise: 1. 2, 3, 5, 19, 22, 23, 34, 39, 40, 41.
2. Acaricidal Activity assay
In this example, several mite-killing activity tests were carried out using the compounds prepared in the above examples.
The test method is as follows: a sample of a compound to be tested is dissolved in a suitable solvent (the kind of the solvent is acetone, methanol, DMSO, and the like, and is selected according to the dissolving capacity of the solvent on the sample), and an aqueous solution of tween 80 with a mass fraction of 0.1% is used to prepare a solution to be tested with a required concentration. The double-sided adhesive tape is cut into 2-3 cm long pieces, the double-sided adhesive tape is attached to one end of a microscope slide, paper pieces on the adhesive tape are removed by tweezers, female adult mites which are consistent in size, bright in body color and lively in action are selected by a zero-number brush pen, the backs of the female adult mites are adhered to the double-sided adhesive tape (not to adhere to mite feet, mite whiskers and mouth parts), 2 lines of the double-sided adhesive tape are adhered to each piece, and 15-20 heads of the double-sided adhesive tape are adhered to each line.
The test method is as follows: the test is repeated for 4 times, the test is placed in an incubator with the temperature of 25 +/-1℃, the relative humidity of 85 percent and the light cycle of L: D ═ 16:8) h for 2h, and dead or inactive individuals are removed by binocular observation, and the number of the insects which are repeated each time is ensured to be more than 30. Soaking one end of the glass sheet with the mites into the liquid medicine, slightly shaking for 5s, taking out, and quickly sucking away the mites and the redundant liquid medicine around the mites with absorbent paper. And (4) placing the mites in the incubator, checking the result by using binoculars after 24 hours, lightly touching the mite bodies by using a writing brush, taking the mites with enough immobility as death, and calculating the lethality. The mortality rate was calculated as follows:
Figure BDA0002384373280000291
the following results were obtained for the Tetranychus cinnabarinus part:
at a dose of 600ppm, the compounds with the lethality rate of more than 80 percent to tetranychus cinnabarinus have the following components: 1. 2, 3, 5, 14, 19, 22, 23, 27, 28, 34, 39, 40, 41;
at a dose of 100ppm, the compounds with the lethality rate of more than 80 percent to tetranychus cinnabarinus have the following components: 1. 2, 3, 19, 22, 23, 34, 39.
3. Test results for exemplary example compounds and control agents
This example uses a comparison of the activity of a part of the compounds of the invention with that of a control drug (the structures of control drugs CK1 and CK2, CK1 and CK2 were prepared by themselves according to the method described in patent document WO 2013115391-see background). The test results are shown in the following table.
Figure BDA0002384373280000301
In addition to the compounds listed in the above table, other exemplary compounds of the present invention have better control activity against pests and mites than the control agents. Therefore, the compound shown as the formula (I) shows good activity to various pests and mites in the agricultural field.
The embodiments of the present invention have been described above. However, the present invention is not limited to the above embodiment. Any modification, equivalent replacement, or improvement made within the spirit and principle of the present invention should be included in the protection scope of the present invention.

Claims (10)

1. A compound shown in a formula (I), a stereoisomer, a racemate, a tautomer, a nitrogen oxide or a pharmaceutically acceptable salt thereof,
Figure FDA0002384373270000011
r is the same or different and is independently selected from hydrogen, halogen, cyano, C1-6Alkyl, halo C1-6Alkyl radical, C1-6Alkoxy or halo C1-6An alkoxy group;
n is 0, 1,2, 3 or 4;
x is selected from oxygen or sulfur.
2. The compound of claim 1, wherein the compound of formula (I) has the structure:
Figure FDA0002384373270000012
in the formulae (I-1), (I-2) and (I-3),
r is the same or different and is independently selected from hydrogen, fluorine, chlorine, bromine, cyano, methyl, ethyl, trifluoromethyl, methoxy or trifluoromethoxy;
n is 0, 1,2, 3 or 4;
x is selected from oxygen or sulfur.
3. The compound of claim 1, wherein the compound of formula (I) is selected from the group consisting of:
Figure FDA0002384373270000021
Figure FDA0002384373270000022
Figure FDA0002384373270000031
Figure FDA0002384373270000041
Figure FDA0002384373270000051
4. a process for the preparation of a compound according to any one of claims 1 to 3, comprising the steps of:
Figure FDA0002384373270000052
a) reacting a compound shown in a formula (II-1) with a compound shown in a formula (III) to obtain a compound shown in a formula (I); alternatively, the first and second electrodes may be,
Figure FDA0002384373270000053
b) reacting a compound shown as a formula (VII) with a compound shown as a formula (VI) to obtain a compound shown as a formula (I);
wherein R, X, n has the definition as set forth in any one of claims 1 to 3, L is selected from a leaving group such as Cl, Br or I.
5. The process according to claim 4, wherein the compound of formula (I) is prepared by the following method:
Figure FDA0002384373270000054
wherein R, X, n has the definition as set forth in any one of claims 1-3, L is selected from a leaving group such as Cl, Br or I;
1) preparing a compound shown in a formula (II) by reacting a compound shown in a formula (V-1) with propylene glycol, or preparing a compound shown in a formula (II-1) by reacting a compound shown in a formula (V) with propylene glycol;
2) the compound shown in the formula (I) is prepared by reacting the compound shown in the formula (II) with the compound shown in the formula (III), or the compound shown in the formula (I-1) is prepared by reacting the compound shown in the formula (II-1) with the compound shown in the formula (III), and then the compound shown in the formula (I) is prepared from the compound shown in the formula (I-1).
6. The process according to claim 5, wherein the reaction in step 1) is carried out in the presence of a catalyst, such as p-toluenesulfonic acid;
preferably, the reaction in step 1) may be carried out in a solvent; the solvent may be selected from one, two or more of aromatic hydrocarbon solvents, haloalkane solvents, nitrile solvents, ether solvents, ester solvents, for example, one, two or more selected from ethyl acetate, benzene, toluene, 1, 2-dichloroethane, acetonitrile, tetrahydrofuran or dioxane;
preferably, the temperature of the reaction in step 1) may be 0 ℃ to the reflux temperature of the solvent used.
7. The process according to claim 5, wherein the reaction of the compound represented by the formula (II) with the compound represented by the formula (III) to produce the compound represented by the formula (I) in the step 2), or the reaction of the compound represented by the formula (II-1) with the compound represented by the formula (III) to produce the compound represented by the formula (I-1) is carried out in the presence of a base; the base may be selected from organic amines such as triethylamine, N-dimethylaminopyridine, etc., or sodium carbonate, potassium carbonate, cesium carbonate, sodium hydroxide, potassium hydroxide, etc., alkali metal hydrides such as sodium hydride, potassium hydride, etc., alkali metal alkoxides such as potassium tert-butoxide, sodium ethoxide, sodium methoxide, etc., and alkyllithium such as methyllithium, N-butyllithium, etc., inorganic bases;
preferably, in the step 2), the molar amount of the base is 1-3 times of that of the compound shown in the formula (III);
preferably, in the step 2), the reaction of the compound represented by the formula (II) with the compound represented by the formula (III) to prepare the compound represented by the formula (I), or the reaction of the compound represented by the formula (II-1) with the compound represented by the formula (III) to prepare the compound represented by the formula (I-1) may be carried out in a solvent; the solvent may be selected from one, two or more of aromatic hydrocarbon solvents, haloalkane solvents, nitrile solvents, chain or cyclic ether solvents, amides, ketone solvents, and the like, for example, one, two or more selected from toluene, 1, 2-dichloroethane, acetonitrile, propionitrile, N-dimethylacetamide, N-dimethylformamide, diethyl ether, tetrahydrofuran, dioxane, acetone, butanone, dimethyl sulfoxide, sulfolane, N-methylpyrrolidone;
preferably, in the step 2), the temperature of the reaction of the compound represented by the formula (II) with the compound represented by the formula (III) to prepare the compound represented by the formula (I), or the reaction of the compound represented by the formula (II-1) with the compound represented by the formula (III) to prepare the compound represented by the formula (I-1) may be 0 ℃ to the reflux temperature of the solvent used;
preferably, in step 2), the reaction may be performed under an atmosphere of a gas inert to the reaction system, such as nitrogen, argon, or the like;
preferably, in the step 2), the compound represented by the formula (I-1) is catalytically hydrogenated in an inert solvent in the presence of an organic base and a catalyst under a hydrogen atmosphere to prepare the compound represented by the formula (I), and formic acid can also be used to generate hydrogen in the reaction system instead of the hydrogen atmosphere;
preferably, in the step 2), the reaction of the compound represented by the formula (I-1) to prepare the compound represented by the formula (I) may be carried out in the presence of a catalyst selected from at least one of tetrakis (triphenylphosphine) palladium, palladium carbon, platinum, raney nickel, etc.;
preferably, in the step 2), the catalyst used in the reaction of preparing the compound represented by the formula (I) from the compound represented by the formula (I-1) is about 0.0001-0.1 times by mol of the compound represented by the formula (I-1);
preferably, in step 2), the reaction of the compound represented by the formula (I-1) to prepare the compound represented by the formula (I) may be carried out in the presence of a phase transfer catalyst such as a quaternary ammonium salt such as tetrabutylammonium bromide, benzyltriethylammonium bromide, or the like;
preferably, in the step 2), the reaction of the compound represented by the formula (I-1) to prepare the compound represented by the formula (I) may be carried out in the presence of a base selected from organic bases such as triethylamine, pyridine, sodium acetate, potassium acetate, etc., or inorganic bases such as sodium carbonate, potassium carbonate, cesium carbonate, sodium hydroxide, potassium hydroxide, etc. The amount of the base to be used is usually about 0.5 to 5 times by mole based on the compound represented by the formula (I-1);
preferably, in step 2), the solvent used in the reaction of the compound represented by formula (I-1) to prepare the compound represented by formula (I) may be selected from one, two or more of alcohols such as methanol, ethanol and the like, ethers such as tetrahydrofuran, dioxane, dimethoxyethane and the like, amides such as N, N-dimethylacetamide, N-dimethylformamide, N-methylpyrrolidone and the like, and water and the like;
preferably, in the step 2), the temperature of the reaction of preparing the compound represented by the formula (I) from the compound represented by the formula (I-1) may be 0 ℃ to the reflux temperature of the solvent used;
preferably, the reaction of preparing the compound represented by formula (I) from the compound represented by formula (I-1) in step 2) is carried out under a hydrogen atmosphere, and the hydrogen pressure may be selected from a standard pressure to 10 atm. When formic acid is used, the reaction is preferably carried out under an atmosphere inert to the reaction, such as nitrogen and/or argon;
preferably, in step 2), the reaction of the compound of formula (I-1) to prepare the compound of formula (I) can be carried out according to the method described in J.org.chem.,1955,20,225 or other similar methods;
preferably, in step 2), the compound of formula (II) used may be prepared from the compound of formula (II-1) by the same procedure as the reaction conditions for preparing the compound of formula (I) from the compound of formula (I-1).
8. A pesticidal composition, such as an insecticidal and/or acaricidal composition, comprising as an active ingredient one, two or more of a compound according to any one of claims 1 to 3, a stereoisomer, racemate, tautomer, nitrogen oxide or pharmaceutically acceptable salt thereof;
preferably, the weight percentage of active ingredient in the composition is 0.1-99.9%, for example 0.5-99%;
preferably, the composition also comprises one, two or more of agriculturally and/or forestry and/or hygienically acceptable carriers;
preferably, the composition may be applied in the form of a formulation, which is a granule, a dispersible granule, a wettable powder, an oil suspension, an aqueous emulsion, an aqueous solution, an emulsifiable concentrate or a microcapsule;
preferably, a liquid or solid carrier, and optionally a surfactant, may also be added to the composition.
9. Use of one, two or more of the compounds of any one of claims 1 to 3, stereoisomers, racemates, tautomers, nitrogen oxides or pharmaceutically acceptable salts thereof in the preparation of a pesticide, e.g. an insecticide and/or acaricide.
10. A method for controlling pests and/or mites which comprises applying an effective amount of at least one of the compounds of any one of claims 1 to 3, their stereoisomers, racemates, tautomers, nitrogen oxides, pharmaceutically acceptable salts thereof or the pesticidal composition of claim 8 to a medium in which pests and/or mites grow;
preferably, the effective amount is from 10 grams to 1000 grams per hectare.
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Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2000049001A2 (en) * 1999-02-16 2000-08-24 E.I. Du Pont De Nemours And Company Phenoxy-, phenylthio-, phenylamino-, benzyloxy-, benzylthio- or benzylaminopyrimidine insectidices and acaricides
WO2000071536A1 (en) * 1999-05-20 2000-11-30 E.I. Du Pont De Nemours And Company Heteroaryloxypyrimidine insecticides and acaricides
WO2013115391A1 (en) * 2012-02-01 2013-08-08 日本農薬株式会社 Arylalkyloxy pyrimidine derivative, pesticide for agricultural and horticultural use containing arylalkyloxy pyrimidine derivative as active ingredient, and use of same
CN107043366A (en) * 2017-04-25 2017-08-15 中国药科大学 4 amino-metadiazine compounds, its preparation method and medical usage

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2000049001A2 (en) * 1999-02-16 2000-08-24 E.I. Du Pont De Nemours And Company Phenoxy-, phenylthio-, phenylamino-, benzyloxy-, benzylthio- or benzylaminopyrimidine insectidices and acaricides
WO2000071536A1 (en) * 1999-05-20 2000-11-30 E.I. Du Pont De Nemours And Company Heteroaryloxypyrimidine insecticides and acaricides
WO2013115391A1 (en) * 2012-02-01 2013-08-08 日本農薬株式会社 Arylalkyloxy pyrimidine derivative, pesticide for agricultural and horticultural use containing arylalkyloxy pyrimidine derivative as active ingredient, and use of same
US20150005257A1 (en) * 2012-02-01 2015-01-01 Nihon Nohyaku Co. Oltd. Arylalkyloxy pyrimidine derivative, pesticide for agricultural and horticultural use containing arylalkyloxy pyrimidine derivative as active ingredient, and use of same
CN107043366A (en) * 2017-04-25 2017-08-15 中国药科大学 4 amino-metadiazine compounds, its preparation method and medical usage

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