WO2021004541A1 - 氘代烯氨羰基化合物及其制备方法和用途 - Google Patents

氘代烯氨羰基化合物及其制备方法和用途 Download PDF

Info

Publication number
WO2021004541A1
WO2021004541A1 PCT/CN2020/101430 CN2020101430W WO2021004541A1 WO 2021004541 A1 WO2021004541 A1 WO 2021004541A1 CN 2020101430 W CN2020101430 W CN 2020101430W WO 2021004541 A1 WO2021004541 A1 WO 2021004541A1
Authority
WO
WIPO (PCT)
Prior art keywords
spp
compound
deuterated
formula
deuterium
Prior art date
Application number
PCT/CN2020/101430
Other languages
English (en)
French (fr)
Inventor
齐卿卿
王川
Original Assignee
徐州汇川生物科技有限公司
襄阳道农道生物科技有限公司
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority claimed from CN202010065322.XA external-priority patent/CN112279840B/zh
Application filed by 徐州汇川生物科技有限公司, 襄阳道农道生物科技有限公司 filed Critical 徐州汇川生物科技有限公司
Publication of WO2021004541A1 publication Critical patent/WO2021004541A1/zh

Links

Classifications

    • 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
    • A01N43/02—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms
    • A01N43/04—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms with one hetero atom
    • A01N43/06—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms with one hetero atom five-membered rings
    • A01N43/08—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms with one hetero atom five-membered rings with oxygen as the ring hetero atom
    • 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
    • A01N43/34—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom
    • A01N43/40—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom six-membered rings
    • 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
    • C07D405/12—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 linked by a chain containing hetero atoms as chain links

Definitions

  • the present invention relates to the field of pesticide chemistry, in particular to a type of deuterated enaminocarbonyl compound and its preparation method and application.
  • the compound of the present invention can be used to control animal pests.
  • Enaminocarbonyl compounds are compounds with insecticidal activity.
  • Patent EP0539588A1, and CN102336747 describe that such structures can be used to control animal pests, especially arthropods, especially insects.
  • the structure of this type of compound can mimic the natural neurotransmitter acetylcholine, act on the central nervous system of target pests, and act as an agonist of insect nicotinic acetylcholine receptor (nAChR) by bonding with receptor proteins.
  • nAChR insect nicotinic acetylcholine receptor
  • the invention provides a type of deuterated enaminocarbonyl compound with stronger insecticidal effect, longer pharmacological effect and stronger plant protection effect.
  • the first aspect of the present invention provides a compound of formula (I), or its enantiomers or diastereomers or a mixture thereof, or a salt thereof,
  • X is halogen or non-deuterated or one or more deuterated or fully deuterated C 1 -C 6 haloalkyl groups
  • R 1 is non-deuterated or one or more deuterated or fully deuterated C 1 -C 6 haloalkyl, or non-deuterated or one or more deuterated or fully deuterated C 2 -C 6 haloalkenyl;
  • R 2 is hydrogen, deuterium or halogen
  • Y is O, S, NR 10 or CR 11 R 12 ;
  • R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 11 and R 12 are each independently selected from: hydrogen or deuterium;
  • the additional condition is that at least one of R 1 , R 3 or R 4 is deuterated or deuterated.
  • the halogen is fluorine, chlorine or bromine.
  • the deuterium isotope content of deuterium at the deuterium substitution position is at least greater than the natural deuterium isotope content (about 0.015%), preferably greater than 30%, more preferably greater than 50%, more preferably greater than 75%, It is more preferably greater than 95%, and even more preferably greater than 99%.
  • the compound of formula (I) contains at least one deuterium atom, more preferably two deuterium atoms.
  • the compound of formula (I) is substituted with 1, 2, 3 or 4 deuterium atoms.
  • R 1 , R 3 or R 4 have 1, 2, 3 or 4 deuterium atoms in total, preferably 1 or 2.
  • X is halogen or halogenated C 1 -C 6 alkyl.
  • X is fluorine, chlorine, bromine or trifluoromethyl.
  • Y is O.
  • R 1 is non-deuterated or one or more deuterated or fully deuterated C 1 -C 3 haloalkyl or non-deuterated or one or more deuterated or fully deuterated Deuterated C 2 -C 3 haloalkenyl.
  • the R 1 is -CDH-(C 1 -C 5 haloalkyl) or -CD 2 -(C 1 -C 5 haloalkyl), preferably, -CDH-(C 1- C 3 haloalkyl) or -CD 2 -(C 1 -C 3 haloalkyl).
  • the R 1 is difluoromethyl, 2-fluoroethyl, 2,2-difluoroethyl, 2-chloro-2-fluoroethyl, 3-fluoro-n-propyl, 2 -Fluorovinyl, 3,3-difluoroprop-2-enyl, 1,1-dideuterium-2,2-difluoroethyl or 1-deuterium-2,2-difluoroethyl.
  • only one of R 3 and R 4 is deuterium.
  • R 3 and R 4 are both deuterium.
  • R 1 is a non-deuterated C 1 -C 3 haloalkyl group, and only one of R 3 and R 4 is deuterium.
  • R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 11 and R 12 are each independently hydrogen.
  • X, Y, R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 and R 9 are each independently selected from the corresponding compounds described in Table 1. Group.
  • the compound of formula (I) has the structure of formula (Ia):
  • X, Y, R 1 , R 2 , R 3 and R 4 are as defined above.
  • the compound of formula (I) is selected from the following group:
  • the compound of formula I is selected from the following group:
  • the compound of formula I is selected from the following group:
  • the second aspect of the present invention provides a composition comprising the compound described in the first aspect of the present invention, or its enantiomers or diastereomers or a mixture thereof, or a salt thereof.
  • the composition is an insecticide composition.
  • composition further includes an adjuvant.
  • the composition further includes a substance selected from the group consisting of insecticides, attractants, disinfectants, bactericides, acaricides, nematicides, fungicides, growth regulators, Safener, fertilizer, chemical pheromone, or a combination thereof.
  • the third aspect of the present invention provides a compound as described in the first aspect of the present invention, or its enantiomers or diastereomers or a mixture thereof, or a salt thereof, or as described in the second aspect of the present invention
  • the use of the composition is for non-diagnostic and non-therapeutic control of pests.
  • a compound as described in the first aspect of the present invention, or its enantiomers or diastereomers or a mixture thereof, or a salt thereof, or as described in the second aspect of the present invention is provided
  • the purpose of the composition is to control pests.
  • the pests include plant pests, sanitary pests, and/or stored product pests.
  • the pests are arthropods.
  • the pests are insects, arachnids, worms and/or nematodes.
  • the obtained pests are aphids and/or milkfish.
  • the fourth aspect of the present invention provides a compound as described in the first aspect of the present invention, or its enantiomers or diastereomers or a mixture thereof, or a salt thereof, or as described in the second aspect of the present invention
  • the purpose of the composition is to prepare an insecticide for preventing and treating animal parasites.
  • the animal parasites are selected from the group consisting of ticks, scabies mites, spider mites, flies, parasitic fly larvae, lice, lice, feather lice and fleas, or a combination thereof.
  • the animal is selected from the following group: dog, pig, cat, horse or cow.
  • the fifth aspect of the present invention provides a non-therapeutic and non-diagnostic method for controlling pests by combining the compound according to the first aspect of the present invention, or its enantiomers or diastereomers or mixtures thereof, or The salt or the composition according to the second aspect of the present invention is used for pests or their living environment.
  • a method for controlling pests is provided by combining the compound according to the first aspect of the present invention, or its enantiomers or diastereomers or mixtures thereof, or salts or
  • the composition according to the second aspect of the present invention is used for pests or their living environment.
  • the living environment of the pests is selected from the group consisting of plants, soil, product storage areas and/or indoors.
  • Z is OH, halogen, NH 2 or NHR 1 ;
  • R 1 , R 3 , R 4 , R 7 , R 8 and R 9 are as defined in the first aspect of the present invention
  • R 3 and R 4 are both deuterium, and X is chlorine, Z is not hydroxyl and chlorine;
  • R 3 and R 4 When one of R 3 and R 4 is deuterium and the other is hydrogen, and X is fluorine, Z is not a hydroxyl group.
  • R 3 and R 4 are both deuterium.
  • Z is NHR 1
  • R 1 is a deuterated or non-deuterated C 1 -C 6 haloalkyl.
  • Z is NHR 1
  • R 1 is 2-fluoroethyl, 2,2-difluoroethyl or 1,1-dideutero-2,2-difluoroethyl.
  • the compound of formula (Z) is selected from:
  • the seventh aspect of the present invention provides a method for preparing the compound according to the first aspect of the present invention, the method comprising the steps:
  • R 2 is independently H or deuterium
  • X, Y, R 1 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 and R 9 are as defined in the first aspect of the present invention.
  • the acidic catalyst is selected from: sulfuric acid, hydrochloric acid, phosphoric acid, hydrobromic acid, sodium hydrogen sulfate, potassium hydrogen sulfate, acetic acid, p-toluenesulfonic acid, methanesulfonic acid, trifluoroacetic acid, or a combination thereof ,
  • potassium hydrogen sulfate, p-toluenesulfonic acid, acetic acid, sulfuric acid, phosphoric acid or a combination thereof Preferably, potassium hydrogen sulfate, p-toluenesulfonic acid, acetic acid, sulfuric acid, phosphoric acid or a combination thereof.
  • the reaction is carried out in an inert solvent.
  • the inert solvent includes halogenated hydrocarbons, such as dichloromethane, tetrachloroethane, chloroform, carbon tetrachloride, and trichloroethane.
  • amides such as dimethylformamide, N-methylpyrrolidone, N,N-dimethylpropenylurea (DMPU), etc.
  • nitriles such as acetonitrile, butyronitrile Etc.
  • ethers such as methyl tert-butyl ether, tetrahydrofuran, methyltetrahydrofuran, dioxane, anisole, phenylethyl ether, cyclohexyl methyl ether, ethyl ether, diphenyl ether, propyl ether, diisopropyl Ether, di-n-butyl ether, diisobutyl ether, diisoamyl ether, ethylene glycol dimethyl ether; esters, such as ethyl acetate, etc.; aliphatic hydrocarbons, alicyclic hydrocarbons or aromatics, such as Cyclohexyl ether, ethylene glycol dimethyl ether;
  • reaction temperature of the reaction is 10-250°C, preferably, 20-150°C.
  • the molar ratio of the compound of formula (III) to the compound of formula (IV) is 1:10-2:1, preferably, 1:5-1:0.95, more preferably, 1: 2 ⁇ 1:1.
  • the method further includes the steps:
  • step (b) reacting the compound of formula (I) in step (a) with a halogenating reagent to obtain a compound of formula (I) in which R 2 is halogen.
  • the halogenating reagent is selected from the group consisting of NBS, NCS, NIS, or a combination thereof.
  • the time range of the halogenation reaction is 10 minutes to 24 hours, preferably, 30 minutes to 12 hours.
  • the temperature range of the halogenation reaction is -10°C-100°C, preferably, 0°C-35°C.
  • the compound of formula (I) is a compound of formula (Ib), prepared by the following steps (a-1), (a-2) or (a-3):
  • Step (a-1) is to react a compound of formula (IIIa) with a compound of formula (IVa) in an inert solvent in the presence of an acidic catalyst to produce a compound of formula (Ib);
  • Step (a-2) is to react a compound of formula (IIIa) with a compound of formula (IVb) in an inert solvent in the presence of an acid catalyst to produce a compound of formula (Ib), wherein R 13 is a C 1 -C 12 alkyl group, and M 1 is hydrogen or alkali metal;
  • Step (a-3) is to react the compound of formula (IIIa) with the compound of formula (IVc) in an inert solvent in the presence of an acid catalyst to produce a compound of formula (Ib), wherein R 14 is a C 1 -C 12 alkyl group or benzene Group, R 15 is C 1 -C 12 alkyl;
  • X, R 1 , R 3 and R 4 are each independently as defined in the first aspect of the present invention.
  • M 1 is H or K.
  • R 13 , R 14 and R 15 are each independently a C 1 -C 6 alkyl group, preferably, a C 1 -C 3 alkyl group.
  • the acidic catalyst is selected from: sulfuric acid, hydrochloric acid, phosphoric acid, hydrobromic acid, sodium hydrogen sulfate, potassium hydrogen sulfate, acetic acid, p-toluenesulfonic acid, methanesulfonic acid, trifluoroacetic acid, or a combination thereof ,
  • potassium hydrogen sulfate, p-toluenesulfonic acid, acetic acid, sulfuric acid, phosphoric acid or a combination thereof Preferably, potassium hydrogen sulfate, p-toluenesulfonic acid, acetic acid, sulfuric acid, phosphoric acid or a combination thereof.
  • the inert solvent is selected from the group consisting of acetonitrile, butyronitrile, methyl tert-butyl ether, tetrahydrofuran, methyltetrahydrofuran, dioxane, toluene, chlorobenzene, n-butanol, or combination.
  • reaction temperature is 10-250°C, preferably, 20-160°C, more preferably, 20-150°C.
  • reaction time is 3-24h.
  • the molar ratio of the compound of formula (IVa), (IVb), or (IVc) to the compound of formula (IIIa) is 1:10-2:1, preferably, 1:5-1.7:1 , More preferably, 1:2-1.5:1, best, 0.7:1-1.2:1.
  • the compound of formula (IIIa) has the formula (IIIb), and the compound of formula (IIIb) is prepared by the following steps (b-1) or (b-2):
  • Step (b-1) is to react the compound of formula (IIa) in an inert solvent in the absence of deuterium or deuterium-containing reducing agent to produce a compound of formula (IIIb), wherein R 3 , R 4 , R 3 ′ and R 4 'Each independently is hydrogen or deuterium, and at least one of R 3 , R 4 , R 3 'and R 4 ' is deuterium; Ra is C 1 -C 5 haloalkyl;
  • Step (b-1) is to react the compound of formula (IIb) in an inert solvent in the presence of deuterium-free or deuterium-containing reducing agent to produce a compound of formula (IIIb), wherein R 3 , R 4 , R 3 ′ and R 4 'Each independently is hydrogen or deuterium, and at least one of R 3 , R 4 , R 3 ' and R 4 'is deuterium; Ra is a C 1 -C 5 haloalkyl group.
  • the deuterium-containing reducing agent is selected from deuterated borane, deuterated sodium borohydride, deuterated lithium aluminum hydride, or a combination thereof.
  • the deuterium-free reducing agent is borane, sodium borohydride, lithium aluminum hydride, or a combination thereof.
  • the inert solvent is selected from the group consisting of acetonitrile, butyronitrile, methyl tert-butyl ether, tetrahydrofuran, methyltetrahydrofuran, dioxane, toluene, chlorobenzene, n-butanol, methanol, Ethanol, isopropanol, deuterated methanol, deuterated ethanol, deuterated isopropanol, or a combination thereof.
  • reaction temperature is -20°C to 50°C.
  • reaction time is 3-48h.
  • the compound of formula (IIIb) is prepared by the following method:
  • R 3 , R 4 , R 3 ′ and R 4 ′ are each independently hydrogen or deuterium, and at least one of R 3 , R 4 , R 3 ′ and R 4 ′ is deuterium;
  • Ra is a C 1 -C 5 haloalkyl group
  • Rb and Rc are each independently an amino group or a salt thereof or a leaving group, and when one is an amino group or a salt thereof, the other is a leaving group;
  • the leaving group is preferably chlorine, bromine, iodine, -O-p-toluenesulfonyl, -O-methanesulfonyl or -O-trifluoromethanesulfonyl.
  • the compound of formula (A) and formula (B) react in the presence of a base to produce a compound of formula (IIIb).
  • the base is selected from the group consisting of sodium carbonate, sodium bicarbonate, potassium carbonate, Potassium bicarbonate, sodium phosphate, disodium hydrogen phosphate, potassium phosphate, etc., triethylamine, diisopropylethylamine, pyridine, or a combination thereof.
  • the temperature of the reaction is 10-100°C.
  • reaction time is 3-24h.
  • the compound of formula (IIIb) is prepared by the following method:
  • R 3 , R 4 , R 3 ′ and R 4 ′ are each independently hydrogen or deuterium, and at least one of R 3 and R 4 is hydrogen;
  • Ra is C 1 -C 5 haloalkyl
  • the deuterium-free reducing agent is sodium borohydride, sodium triacetoxyborohydride, sodium cyanoborohydride, or a combination thereof.
  • the deuterium-containing reducing agent is deuterated sodium borohydride, deuterated sodium triacetoxyborohydride, deuterated sodium cyanoborohydride, or a combination thereof.
  • the inert solvent is selected from the following group: 1,2-dichloroethane, acetonitrile, butyronitrile, methyl tert-butyl ether, tetrahydrofuran, methyltetrahydrofuran, dioxane, toluene, Chlorobenzene, n-butanol, methanol, ethanol, isopropanol, deuterated methanol, deuterated ethanol, deuterated isopropanol, or a combination thereof.
  • the temperature of the reaction is -10 to 50°C.
  • reaction time is 15min-75h.
  • the deuterated enaminocarbonyl compound of the present invention has better insecticidal effects, longer duration of efficacy, and plant protection activity than non-deuterated similar compounds.
  • the present invention has been completed on this basis.
  • halogen refers to F, Cl, Br, and I. More preferably, the halogen atom is selected from F, Cl and Br.
  • C 1 -C 12 alkyl refers to a straight or branched alkyl group comprising 1-12 carbon atoms (preferably 1-6, more preferably 1-3), such as methyl, ethyl Group, propyl, isopropyl, butyl, isobutyl, tert-butyl, or similar groups.
  • C 1 -C 6 haloalkyl or “halogenated C 1 -C 6 alkyl” are used interchangeably and refer to those containing 1 to 6 carbon atoms substituted by one or more halogen atoms Straight or branched alkyl groups, such as difluoromethyl, 2-fluoroethyl, 2,2-difluoroethyl, 2-chloro-2-fluoroethyl, 3-fluoro-n-propyl, or the like group.
  • C 2 -C 6 haloalkenyl refers to a linear or branched alkenyl group including 1 to 6 carbon atoms substituted by one or more halogen atoms, such as 2-fluorovinyl, 3,3-Difluoroprop-2-enyl or similar group.
  • deuterated refers to the replacement of one or more hydrogens in a compound or group with deuterium. Deuteration can be mono-, di-, poly, or fully-substituted. The terms “one or more deuterated” and “one or more deuterated” are used interchangeably.
  • non-deuterated compound or “non-deuterated” refers to a compound that contains a proportion of deuterium atoms (D, 2 H) not higher than the natural deuterium isotope content (about 0.015%).
  • enantiomers or diastereomers refer to compounds that consist of the same atoms and are bonded by the same bonds, but have different three-dimensional structures.
  • the compound of the present invention contains an olefinic double bond, unless otherwise specified, the compound of the present invention is intended to include E- and Z-geometric isomers.
  • the deuterium isotope content of deuterium at the deuterium substitution position is greater than the natural deuterium isotope content (0.015%), more preferably greater than 50%, more preferably greater than 75%, more preferably greater than 95%, more preferably The content is greater than 97%, more preferably greater than 99%, more preferably greater than 99.5%.
  • N is 14 N and/or O is 16 O.
  • the isotopic content of 14 N at the position of the nitrogen atom in the compound is ⁇ 95%, more preferably ⁇ 99%.
  • the isotopic content of 16 O at the position of the oxygen atom in the compound is ⁇ 95%, more preferably ⁇ 99%.
  • X, Y, R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 and R 9 are as described above.
  • the term also includes the enantiomers or diastereomers of the compound of formula (I) or mixtures thereof, or salts thereof.
  • the salts of the compounds of the present invention include inorganic salts and organic salts.
  • a preferred class of salts are the salts of the compounds of this invention with acids.
  • Acids suitable for salt formation include but are not limited to: hydrochloric acid, hydrobromic acid, hydrofluoric acid, sulfuric acid, nitric acid, phosphoric acid and other inorganic acids; formic acid, acetic acid, trifluoroacetic acid, propionic acid, oxalic acid, malonic acid, succinic acid, Fumaric acid, maleic acid, lactic acid, malic acid, tartaric acid, citric acid, picric acid, benzoic acid, methanesulfonic acid, ethanesulfonic acid, p-toluenesulfonic acid, benzenesulfonic acid, naphthalenesulfonic acid and other organic acids; and Amino acids such as amino acid, phenylalanine, aspartic acid and glutamic acid.
  • R 2 is independently H or deuterium
  • X, Y, R 1 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 and R 9 are as defined in the first aspect of the present invention.
  • the acidic catalyst is selected from: sulfuric acid, hydrochloric acid, phosphoric acid, hydrobromic acid, sodium hydrogen sulfate, potassium hydrogen sulfate, acetic acid, p-toluenesulfonic acid, methanesulfonic acid, trifluoroacetic acid, or a combination thereof ,
  • potassium hydrogen sulfate, p-toluenesulfonic acid, acetic acid, sulfuric acid, phosphoric acid or a combination thereof Preferably, potassium hydrogen sulfate, p-toluenesulfonic acid, acetic acid, sulfuric acid, phosphoric acid or a combination thereof.
  • reaction temperature of the reaction is 10-250°C, preferably, 20-150°C.
  • the molar ratio of the compound of formula (III) to the compound of formula (IV) is 1:10-2:1, preferably, 1:5-1:0.95, more preferably, 1: 2 ⁇ 1:1.
  • the method further includes the steps:
  • step (b) reacting the compound of formula (I) in step (a) with a halogenating reagent to obtain a compound of formula (I) in which R 2 is halogen.
  • the halogenating reagent is selected from the group consisting of NBS, NCS, NIS, or a combination thereof.
  • the time range of the halogenation reaction is 10 minutes to 24 hours, preferably, 30 minutes to 12 hours.
  • the temperature range of the halogenation reaction is -10°C-100°C, preferably, 0°C-35°C.
  • the present invention provides a composition comprising the compound described in the first aspect of the present invention, or its enantiomers or diastereomers or a mixture thereof, or a salt thereof.
  • the compounds of the present invention may exist in a single crystal form, polymorphs or a mixture thereof.
  • the composition of the present invention is an insecticide composition.
  • the composition of the present invention may further include appropriate auxiliary agents.
  • Suitable auxiliary agents include but are not limited to: solvents, liquid carriers, solid carriers or fillers, surfactants, dispersants, emulsifiers, wetting agents, adjuvants, and Solvent, penetration enhancer, protective colloid, adhesive, thickener, humectant, repellent, attractant, eating stimulant, compatibilizer, bactericide, antifreeze, defoamer, colorant, thickener Agents and adhesives.
  • the composition can be conventional preparations, such as solutions, emulsions, suspensions, wettable powders, powders, powders, pastes, ointments, soluble powders, granules, molded products, suspending emulsion concentrates, and those impregnated with active compounds Microcapsules in natural and synthetic materials and polymers.
  • composition can be used in (but not limited to) the following forms: aerosol, spray, foam, gel, vaporizer, shellac paper, poison bait station or bait toss.
  • Suitable liquid solvents are basically: aromatic hydrocarbons such as xylene, toluene, alkylbenzene or alkylnaphthalene, chlorinated aromatic hydrocarbons or chlorinated aliphatic hydrocarbons such as chlorobenzene, vinyl chloride or methylene chloride, and aliphatic hydrocarbons such as cyclohexane Or paraffin (such as mineral oil fractions, mineral oil and vegetable oil), alcohols such as ethanol, propanol, benzyl alcohol, cyclohexanol, butanol or glycol and its ethers and esters, ketones such as acetone, cyclohexanone, Methyl ethyl ketone or methyl isobutyl ketone, esters such as lactate, carbonate, fatty acid ester, strong polar solvents such as amides (N,N-
  • Suitable solid carriers or fillers such as natural mineral powders, such as kaolin, clay, talc, chalk, quartz, attapulgite, montmorillonite or diatomaceous earth, and synthetic mineral powders, such as highly dispersed silica, oxide Aluminum and silicates; suitable solid carriers for granules are: for example, crushed and classified natural rocks such as calcite, marble, pumice, sepiolite and dolomite, as well as synthetic particles of inorganic and organic powders, and organic particles such as Cellulose, starch, such as paper, sawdust, coconut shell powder and other nut shell powder, bark powder, grain flour, corn cob and tobacco stem particles, and their mixtures.
  • natural mineral powders such as kaolin, clay, talc, chalk, quartz, attapulgite, montmorillonite or diatomaceous earth
  • synthetic mineral powders such as highly dispersed silica, oxide Aluminum and silicates
  • suitable solid carriers for granules are: for example, crushed
  • Suitable surfactants are various surface active compounds known in the field of pesticide formulations, including anionic, cationic, nonionic and amphoteric surfactants, block polymers, and polyelectrolytes.
  • the role of this type of surfactant is emulsifier, dispersant, solubilizer, wetting agent, penetration enhancer, protective colloid or auxiliary agent. Mixtures of them can also be used.
  • Suitable anionic surfactants are alkyl sulfonates, alkyl sulfates, aryl sulfonates, phosphates, carboxylates, ammonium salts and mixtures thereof.
  • Suitable nonionic surfactants are alkoxylates, amine oxides, N-substituted fatty acid amides, esters, polymers, sugar-based surfactants, and mixtures of the above components.
  • Suitable cationic surfactants are quaternary ammonium compounds.
  • Suitable amphiphilic surfactants such as alkyl betaines, imidazolines.
  • Suitable polymers such as oligomers and polymers containing ethylene, acrylic acid monomers, alcohols, and amines.
  • Suitable thickeners are polysaccharides (such as carboxymethyl cellulose xanthan gum) and natural or synthetic polymers in powder, granule or latex form (such as gum arabic, polyvinyl alcohol, polyvinyl acetate, and natural phospholipids such as brain Phospholipids and lecithins, and synthetic phospholipids), inorganic clays, silicates.
  • polysaccharides such as carboxymethyl cellulose xanthan gum
  • natural or synthetic polymers in powder, granule or latex form such as gum arabic, polyvinyl alcohol, polyvinyl acetate, and natural phospholipids such as brain Phospholipids and lecithins, and synthetic phospholipids
  • inorganic clays such as silicates.
  • Suitable antifreeze agents are one or more of ethylene glycol, glycerin, urea and glycerin.
  • Stabilizers such as low temperature stabilizers, preservatives, antioxidants, light stabilizers, or other agents that improve chemical and/or physical stability can be added.
  • composition generally contains 0.01-98% by weight of active compound, preferably 0.5-90% by weight of active compound.
  • control includes, but is not limited to, killing or repelling pests, slowing the growth or reproduction rate of pests.
  • insects, arachnids, worms and nematodes encountered in the fields of agriculture, horticulture, animal husbandry, forests, gardens and leisure facilities, storage products and materials protection and sanitation. They are preferably used as plant protection agents. They are active against general sensitive and resistant species and all or part of their developmental stages.
  • the pests include (but are not limited to):
  • Anoplura for example, Damalinia spp., Haematopinus spp., Linognathus spp., Pediculus spp., Trichodectes spp.).
  • Arachnida for example, Acarus siro, Aceriasheldoni, Aculops spp., Aculus spp., Flower ticks Amblyommaspp., Argas spp., Boophilus spp., Brevipalpus spp., Bryobia praet1sa, Chor1ptes spp .), Dermanyssusgallinae, Eotetranychus spp., Epitrimerus pyri, Eutetranychus spp., Er1phyes spp., Half-run Hemitarsonemus spp., Hyalomma spp., Ixodes spp., Black widow spiders (Latrodectus mactans), Metatetranychus spp., Oligonychus spp., Ornithodoros spp., Panonychus spp., such as Panonychus ulmi (Koch), Phylloc
  • Bivalva for example, Dreissena spp.
  • Chilopoda for example, Geophilus spp., Scutigera spp..
  • Diabrotica spp. Epilachna spp., Faustinus cubae, Gibbium psylloides, Heteronychus arator, Hylamorpha elegans, North American Jiatian Cow (Hylotrupes b Camillus), alfalfa leaf weevil (Hypera postica), Hypothenemus spp., sugarcane large brown toothed claw beetle (Lachnosterna consanguinea), bell tomb beetle (Leptinotarsa decemlineata), rice root weevil (Lissorhoptrus) Oryzophilus Lixus spp., Lyctus spp., Melegethes aeneus, Western May branchial beetle (Melolontha melolontha), Migdolus spp., Monochamus spp.
  • Dermaptera Dermaptera (Dermaptera), for example, Forficula auricularia.
  • Diptera From the order of Diptera, for example, Aedes spp., Anopheles spp., Bib1hortulanus, Calliphora erythrocephala, Ceratitis capitata , Chrysomyia spp., Cochl1myia spp., Cordylobia anthropophaga, Culex spp., Cuterebra spp., Dacus oleae, human Dermatobia hominis, Drosophila spp., Fannia spp., Gastrophilus spp., Hylemyia spp., Hyppoboscaspp., Drosophila spp.
  • Liriomyza Lir1myza spp.
  • Lucilia spp. Musca spp.
  • Nezara spp. Oestrus spp. , Oscinella frit, Pegomyia hyoscyami, Phorbia spp., Stomaxys spp., Tabanus spp., Tannia spp., Europe Crane mosquito (Tipula paludosa), spp. (Wohlfahrtia spp.).
  • Gastropoda for example, Arion spp., B1mphalaria spp., Bulinus spp., Deroceras spp., Galba spp., Cone (Lymnaea spp.), Oncomelania spp., Succinea spp.
  • Helminths for example, Ancylostoma duodenale, Ancylostoma ceylanicum, Acylostoma braziliensis, Ancylostoma spp., Ancylostoma spp. Ascaris Iubricoides, Ascarisspp., Brugia malayi, Brugia timori, Bunostomum spp., Chabot spp.
  • Clonorchisspp. (Chabertia spp.), Clonorchisspp., Cooperia spp., Dicrocoelium spp., Dictyocaulus filaria, Schistocephalus latiflorus (Diphyllobothrium latum), Dracunculus medinensis, Echinococcus granulosus, Echinococcus multilocularis, Enterobius vermis Linnaeuspp., Faciolaaeuspp.
  • Haemonchus spp. Heterakis spp., Hymenolepis nana, Hymenolepis spp., Loa Loa, Loa Loa Nematodirus spp., Oesophagos tomum spp., Opisthorchis spp., Onchocerca volvulus, Ostertagia spp.
  • Plant parasitic nematodes include, for example, Anguina spp, Aphelenchoides spp., Belonoaimus spp., Bursaphelenchus spp., Ditylenchus spp.
  • Protozoa such as Eimeria.
  • Heteroptera for example, Anasa tristis, Antest1psis spp., Blissus spp., Calocoris spp., Campylomma livida, Cavelerius spp., Cimex spp., Creontiadesdilutus, Dasynus piperis, Dichelops furcatus, Diconocorishewetti, Dysdercus spp.
  • Amrasca spp. Anuraphis cardui, Aonidiella spp., Aphanostigma piri, Aphis spp, such as Aphis craccivora Koch , Grape leafhopper (Arboridia apicalis), small round shield scale (Aspidiella spp.), round shield scale (Aspidiotus spp.), Atanus spp., Aulacorthum solani, Bemisia spp., Plum short Brachycaudus helichrysii, Brachycolus spp., Brevicoryne brassicae, Calligypona marginata, Carneocephala fulgida, Sugarcane powder horn aphid (Ceratovacuna lanigera), Cercopidae (Cercopidae), Ceroplastes spp.), Strawberry Aphid (Chaetosiphon Fragaefolii), Chionaspis tegalensis
  • Idiocerus spp. Idiocerus spp.
  • Idioscopus spp. Laodelphax striatellus
  • Lecanium spp. Lepidosaphes spp.
  • Lipaphis erysimi Long-tube aphid (Macrosiphum spp.)
  • Mahanarva fimbriolata Melanaphis sacchari, Metcalfiella spp., Metopolophium dirhodum, Monellia costalis, Monelliopsis pecanis, Myzus spp.
  • Nasonovia ribisnigri Nasonovia ribisnigri, Nephotettix spp., Nilaparvata lugens, Oncometopia spp., Orthezia praelonga, Parabemisia myricae (Parabemisia myricae), Paratrioza Parlatoria spp., Pemphigus spp., Peregrinus maidis, Phenacoccus spp., Phloeomyzus passerinii, Pemphigus spp.
  • Aphids Toxoptera spp.
  • Trialeurodes vaporariorum Trialeurodes vaporariorum
  • Trioza spp. Typhlocyba spp.
  • Unaspis spp. Viteus vitifolii
  • Hymenoptera for example, Diprion spp., Hoplocampa spp., Lasius spp., Monomorium pharaonis, Vespa spp. spp.).
  • Isopoda for example, Armadillidium vulgare, Oniscus asellus, and Porcellio scaber.
  • Lepidoptera Lepidoptera
  • Lepidoptera for example, Acronicta major, Aedia leucomelas, Agrotis spp., Alabama argillacea, Alabama argillacea Genus (Anticarsia spp.), Barathra brassicae, cotton moth (Bucculatrix thurberiella), pine looper (Bupaluspiniarius), linseed moth (Cacoecia podana), Capua reticulana, apple moth (Carpocapsa pomonella), winter ruler brumata), Chilo spp., Choristoneura fumiferana, Clysia ambiguella, Cnaphalocerus spp., Egyptian diamond (Earias insulana), Mediterranean pink moth (Ephestia kuehniella) , Euproctis chrysorrhoea (Euproctis chrysorrhoea),
  • Heliothis spp. Hofmannophila pseudospretella, Homona magnanima, Apple brood moth (Hyponomeuta padella), Laphygma spp., Apple fine moth (Lithocolletis blancardella), Green fruit Lithophane antennata, Loxagrotis albicosta, Lymantria spp., Malacosoma neustria, Mamestra brassicae, Maestra brassicae, Lymantria spp.
  • Mocis repanda Mythimna separata, Oria spp., Oulema oryzae, Panolis flammea, Pectinophora gossypiella, Phyllocnistis citrella, Pieris ( Pieris spp., Plutella xylostella, Prodenia spp., Pseudaletia spp., Pseudoplusia includens, Corn borer (Pyrausta nubilalis), Spodoptera spp. ), Thermesia gemmatalis, Tinea pellionella, Tineola bisselliella, Tortrix viridana, Trichoplusia spp..
  • Orthoptera for example, house cricket (Acheta domesticus), oriental cockroach (Blatta orientalis), German cockroach (Blattella germanica), mole cricket (Gryllotalpa spp.), madeira cockroach (Leucophaea), maderae Locusta (Locusta spp.), Melanoplus spp. (Melanoplus spp.), Periplaneta americana (Periplaneta americana), Desert locust (Schistocerca gregaria).
  • Siphonaptera for example, Ceratophyllus spp., Xenopsylla cheopis.
  • Symphyla for example, Scutigerella immaculata.
  • Thysanoptera for example, rice thrips (Baliothrips biformis), Enneothrips flavens, flower thrips (Frankliniella spp.), net thrips (Heliothrips spp.), greenhouse hedge thrips (Hercinothrips femoralis), Card thrips (Kakothrips spp.), grape thrips (Rhipiphorothrips cruentatus), hard thrips (Scirtothrips spp.), Taeniothrips cardamoni, thrips (Thrips spp.).
  • Thysanura for example, Lepisma saccharina.
  • the active compound of the present invention not only acts on plant pests, sanitary pests and stored product pests, but also on animal parasites in the veterinary field (especially skin and hair), such as ticks, animal scabies, spider mites, and flies. , Parasitic fly larvae, lice, hair lice, feather lice and fleas work.
  • composition may also include (but not limited to) substances selected from the group consisting of insecticides, attractants, disinfectants, bactericides, acaricides, nematicides, fungicides, growth regulators, Safener, fertilizer, chemical pheromone, or a combination thereof.
  • substances selected from the group consisting of insecticides, attractants, disinfectants, bactericides, acaricides, nematicides, fungicides, growth regulators, Safener, fertilizer, chemical pheromone, or a combination thereof.
  • Pesticides of biological origin such as abamectin, spinosyn, emamectin benzoate, spinetoram;
  • Nicotinic insecticide flurpyrone
  • Mesoionic insecticides such as trifluorophenyl pyrimidine
  • Carbamate insecticides such as isoprocarb, carbofuran, carbofuran, carbofuran, methomyl, fenoxycarb, sulfacarb, procarb, phenoxycarb, worms Procarb, Carbenecarb, Foroxacarb, Antimucarb, Mealbucarb, Aldicarb, Butacarb, Butacarb, Promethcarb, Thiodicarb, Acrocarb, Ethioncarb, Methiocarb , Mixed carbamicarb, methacarb, methacarb, dimacarb, difluben, isoxocarb, pyrimicarb, pyrazocarb, aldicarb, pendicarb, thiadicarb, methacarb, methacarb Pyrocarb, methoxacarb, fenethacarb, sulfacarb, poxacarb, fenmetacarb
  • plants refer to plants that exist naturally and are obtained through conventional plant breeding and optimization methods, or through biotechnology and genetic engineering methods, such as transgenic plants.
  • the active compounds and their compositions provided by the present invention can be applied to target animal pests and the common environment (such as storage environment) and plant environment related to their lives in a variety of common ways, such as dipping, spraying, misting, evaporation, Broadcasting, smearing, injection, etc.
  • it can also be used for seed protection, such as applying one or more layers of coating for seed treatment.
  • the active compounds provided by the present invention generally have better anti-metabolism properties, which means that compared with similar hydrogen-containing structures, they retain the same excellent systemic activity and at the same time protect plants at the same dosage. Longer duration or greater direct toxicity to target animal pests, so it is more suitable for seed protection.
  • composition of the present invention is suitable for protecting plant seeds used in agriculture, greenhouse, forest or horticulture.
  • plant seeds used in agriculture, greenhouse, forest or horticulture.
  • the present invention provides a new type of deuterated enaminocarbonyl compounds.
  • the deuterated sites of enaminocarbonyl compounds that can be used to control pests have been discovered that can improve the insecticidal effect.
  • the deuterated enaminocarbonyl compound of the present invention has a better insecticidal effect than the non-deuterated compound. Experiments have proved that the deuterated compound of the present invention has a significantly better killing effect on various insect pests than its non-deuterated form.
  • the dosage is smaller, and when the dosage is the same, the effective time is longer.
  • the deuterated enaminocarbonyl compound of the present invention provides a deuterated standard for enaminocarbonyl insecticides, and can be used for the residual mass spectrometry detection of enaminocarbonyl insecticides.
  • the preparation method of the present invention has good deuteration selectivity and high yield.
  • Step 3 Preparation of N-((6-chloropyridin-3-yl)duteuteromethyl)-2,2-difluoroethyl-1-amine:
  • step 2 5-(di-deuterobromomethyl)-2-chloropyridine (0.6g), difluoroethylamine (0.5g) and N,N-diisopropylethylamine (0.7g) are mixed, and the reaction mixture Place it at 45°C and stir overnight, then directly spin dry, and purify by column chromatography, eluting with ethyl acetate/petroleum ether gradient to obtain 0.5 g of the target compound, with a yield of 85%.
  • Step 4 Preparation of 4-(((6-chloropyridin-3-yl)duteuteromethyl)(2,2-difluoroethyl)amino)furan-2(5H)-one:
  • the organic phase was dried (sodium sulfate), filtered with suction, spin-dried, purified by column chromatography, and eluted with a gradient of ethyl acetate/petroleum ether to obtain 0.4 g of the target compound with a yield of 75%.
  • N-((6-chloropyridin-3-yl)dideuteromethyl)-2,2-difluoroethyl-1-amine (0.4g) was dissolved in butyronitrile (15mL), and 4 -Hydroxy-2-oxo-2,5-dihydrofuran-3-carboxylic acid ethyl ester (0.5g) and potassium hydrogen sulfate (0.3g), the resulting mixture was reacted at 92°C for 3h. After cooling the temperature to room temperature, the reaction mixture was washed twice with a saturated aqueous sodium chloride solution.
  • the organic phase was dried (sodium sulfate), filtered with suction, spin-dried, purified by column chromatography, and eluted with a gradient of ethyl acetate/petroleum ether to obtain 0.5 g of the target compound with a yield of 86%.
  • N-((6-chloropyridin-3-yl)dideuteromethyl)-2,2-difluoroethyl-1-amine 0.3g was dissolved in butyronitrile (15mL), and 2 -Ethoxy-4-oxo-4,5-dihydrofuran-3-carboxylic acid ethyl ester (0.4g) and potassium hydrogen sulfate (0.2g), the resulting mixture was reacted at 110°C for 10h. After cooling the temperature to room temperature, the reaction mixture was washed twice with a saturated aqueous sodium chloride solution.
  • the organic phase was dried (sodium sulfate), filtered with suction, spin-dried, purified by column chromatography, and eluted with a gradient of ethyl acetate/petroleum ether to obtain 0.4 g of the target compound with a yield of 92%.
  • N-((6-chloropyridin-3-yl)dideuteromethyl)-2,2-difluoroethyl-1-amine (0.6g) was dissolved in butyronitrile (25mL), and 4 -(Ethoxycarbonyl)-5-oxo-2,5-dihydrofuran-3-potassium oxide (1.3g) and potassium hydrogensulfate (1.0g), the resulting mixture was heated at 100°C for 2h. After cooling the temperature to room temperature, the reaction mixture was washed twice with a saturated aqueous sodium chloride solution.
  • the organic phase was dried (sodium sulfate), filtered with suction, spin-dried, and purified by column chromatography, and eluted with a gradient of ethyl acetate/petroleum ether to obtain 0.6 g of the target compound with a yield of 69%.
  • Step 3 Preparation of N-((6-chloropyridin-3-yl)deuteromethyl)-2,2-difluoroethyl-1-amine:
  • step 2 5-(deuterobromomethyl)-2-chloropyridine (0.6g), difluoroethylamine (0.9g) and N,N-diisopropylethylamine (1.9g) are mixed, and the reaction mixture is placed After stirring overnight at 45°C, it was directly spin-dried, purified by column chromatography, and eluted with a gradient of ethyl acetate/petroleum ether to obtain 0.5 g of the target compound with a yield of 84%.
  • Step 4 Preparation of 4-(((6-chloropyridin-3-yl)deuteromethyl)(2,2-difluoroethyl)amino)furan-2(5H)-one:
  • the organic phase was dried (sodium sulfate), filtered with suction, spin-dried, purified by column chromatography, and eluted with a gradient of ethyl acetate/petroleum ether to obtain 0.3 g of the target compound with a yield of 52%.
  • Step 1 Preparation of 2,2-difluoro-N-((6-(trifluoromethyl)pyridin-3-yl)methyl)acetamide):
  • Step 2 Preparation of N-((6-trifluoromethylpyridin-3-yl)methyl)-1,1-dideuterium-2,2-difluoroethyl-1-amine:
  • step 1 The amide (0.7 g) obtained in step 1 was added to the flask, dissolved in 25 mL of THF, and then NaBD4 (0.5 g) was slowly added. After cooling the system to 0°C, 2.5 mL of BF 3 ether solution was added and stirred overnight. Then quench the reaction with methanol, add 50% sodium hydroxide aqueous solution to adjust the pH>12, extract the reaction liquid with ethyl acetate, wash the organic phase with saturated brine, dry with sodium sulfate, filter with suction, and evaporate under reduced pressure , Eluted with a gradient of ethyl acetate/petroleum ether to obtain 0.4 g of the target compound with a yield of 57%.
  • Step 3 4-(((6-Trifluoromethylpyridin-3-yl)methyl)(1,1-dideuterium-2,2-difluoroethyl)amino)furan-2(5H)-one
  • the organic phase was dried (sodium sulfate), filtered with suction, spin-dried, purified by column chromatography, and eluted with a gradient of ethyl acetate/petroleum ether to obtain 0.3 g of the target compound with a yield of 77%.
  • the deuteration purity of each deuterated site is greater than or equal to 95%, and generally greater than or equal to 98%.
  • deuterium purity in the present invention is as follows: by chemical methods, a stable hydrogen isotope deuterium is used to replace one hydrogen atom or multiple specific hydrogen atoms in a specific position in the chemical structure, and the total content of deuterium in these positions accounts for the positions before the replacement. The percentage of total hydrogen content.
  • Alfalfa aphid experiment (the method of soaking insects and leaves)
  • the mature aphids were attached to cucumber leaves, and 24 hours later, the aphids were removed. 48 hours after the aphid removal, the front and back sides of the cucumber seedling leaves were sprayed with a spray tower and dried. After the required time period, the efficacy in% was determined. 100% means that all aphids have been killed; 0% means that no aphids have been killed.
  • Alfalfa aphid experiment (the method of soaking insects and leaves)
  • Alfalfa aphid experiment (the method of soaking insects and leaves)
  • the mature aphids were attached to the cucumber leaves, 24h later, the aphids were removed. 48h after the aphid removal, the front and back sides of the cucumber seedling leaves were sprayed with a spray tower and dried. After the required time period, the efficacy in% was determined and calculated
  • the LC50 value is used to obtain the relative virulence (relative virulence is used as a control index, expressed by the percentage of the LC 50 value of the control/LC 50 value of the active compound of the present invention. The larger the value, the greater the value indicates that the present invention is relative to the control compound. Active compounds have higher efficacy).
  • Brown planthopper (rice stem dipping method)
  • the rice seedlings were immersed in the liquid medicine for 15 seconds, dried, and placed in a disposable cup. Each cup received 15 third-instar nymphs. After the medicine, the number of dead and alive insects was checked after the required period of time, and the mortality rate was counted.
  • Brown planthopper (rice stem dipping method)
  • the rice seedlings were immersed in the liquid medicine for 15 seconds, dried, and placed in a disposable cup. Each cup received 15 third-instar nymphs. After the medicine, the number of dead and alive insects was checked after the required period of time, and the mortality rate was counted.

Landscapes

  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Pest Control & Pesticides (AREA)
  • Plant Pathology (AREA)
  • Agronomy & Crop Science (AREA)
  • Engineering & Computer Science (AREA)
  • Dentistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Wood Science & Technology (AREA)
  • Zoology (AREA)
  • Environmental Sciences (AREA)
  • Agricultural Chemicals And Associated Chemicals (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

提供了一类氘代烯氨羰基化合物及其制备方法和用途。具体地，一种式(I)化合物，或其对映异构体或非对映异构体或其混合物，或其盐，其中，X为卤素或未氘代的或一次或多次氘代的或全氘代的C 1-C 6卤代烷基；R 1为未氘代的或一次或多次氘代的或全氘代的C 1-C 6卤代烷基，或未氘代的或一次或多次氘代的或全氘代的C 2-C 6卤代烯基；R 2为氢、氘或卤素，Y为O、S、NR 10或CR 11R 12；R 3、R 4、R 5、R 6、R 7、R 8、R 9、R 10、R 11和R 12各自独立地选自：氢或氘；附加条件为R 1、R 3或R 4中至少一个是氘代的或氘。

Description

氘代烯氨羰基化合物及其制备方法和用途 技术领域
本发明涉及农药化学领域，具体地，涉及一类氘代烯氨羰基化合物及其制备方法和用途，本发明的化合物可用于防治动物害虫。
背景技术
烯氨羰基化合物为具有杀昆虫活性的化合物，专利EP0539588A1，以及CN102336747(WO2007115644A1)描述了该类结构可用于防治动物害虫、特别是节肢动物、尤其是昆虫的用途。
该类化合物结构可以模拟天然神经传递素乙酰胆碱，作用于靶标害虫的中枢神经系统，通过与受体蛋白键合，作为昆虫烟碱乙酰胆碱受体(nAChR)的激动剂。然而，与大多数杀虫剂一样，植物和靶标昆虫的代谢作用使得药物实际使用的有效浓度以及剂量都大幅增加，药剂对植物的保护作用相应地被削弱。
因此，需要开发更好的受体蛋白结合剂，抗代谢性质、杀虫效果更强、药效时间更长的化合物，以降低农药用量，还可能减慢害虫对化合物抗性的产生，增强害虫防治效果。
发明内容
本发明提供了一类杀虫效果更强、药效时间更长、植物保护效果更强的氘代烯氨羰基化合物。
本发明第一方面提供了一种式(I)化合物，或其对映异构体或非对映异构体或其混合物，或其盐，
Figure PCTCN2020101430-appb-000001
其中，
X为卤素或未氘代的或一次或多次氘代的或全氘代的C 1-C 6卤代烷基；
R 1为未氘代的或一次或多次氘代的或全氘代的C 1-C 6卤代烷基，或未氘代的或一次或多次氘代的或全氘代的C 2-C 6卤代烯基；
R 2为氢、氘或卤素，
Y为O、S、NR 10或CR 11R 12；
R 3、R 4、R 5、R 6、R 7、R 8、R 9、R 10、R 11和R 12各自独立地选自：氢或氘；
附加条件为R 1、R 3或R 4中至少一个是氘代的或氘。
在另一优选例中，所述卤素为氟、氯或溴。
在另一优选例中，氘在氘取代位置的氘同位素含量至少是大于天然氘同位素含量(约0.015％)，较佳地大于30％，更佳地大于50％，更佳地大于75％，更佳地大于95％，更佳地大于99％。
在另一优选例中，式(I)化合物至少含有1个氘原子,更佳地2个氘原子。
在另一优选例中，所述式(I)化合物为1、2、3或4个氘原子取代的。
在另一优选例中，R 1、R 3或R 4中总共具有1、2、3或4个氘原子，优选地，1或2。
在另一优选例中，X为卤素或卤代的C 1-C 6烷基。
在另一优选例中，X为氟、氯、溴或三氟甲基。
在另一优选例中，Y为O。
在另一优选例中，R 1为未氘代的或一次或多次氘代的或全氘代的C 1-C 3卤代烷基或或未氘代的或一次或多次氘代的或全氘代的C 2-C 3卤代烯基。
在另一优选例中，所述R 1为-CDH-(C 1-C 5卤代烷基)或-CD 2-(C 1-C 5卤代烷基)，较佳地，-CDH-(C 1-C 3卤代烷基)或-CD 2-(C 1-C 3卤代烷基)。
在另一优选例中，所述R 1为二氟甲基、2-氟乙基、2,2-二氟乙基、2-氯-2-氟乙基、3-氟正丙基、2-氟乙烯基、3,3-二氟丙-2-烯基、1，1-二氘-2,2-二氟乙基或1-氘-2,2-二氟乙基。
在另一优选例中，R 3和R 4有且只有一个为氘。
在另一优选例中，R 3和R 4都为氘。
在另一优选例中，R 1为未氘代的C 1-C 3卤代烷基，且R 3和R 4有且只有一个为氘。
在另一优选例中，R 5、R 6、R 7、R 8、R 9、R 10、R 11和R 12各自独立地为氢。
在另一优选例中，X、Y、R 1、R 2、R 3、R 4、R 5、R 6、R 7、R 8和R 9各自独立地选自表1中所述化合物的相应基团。
在另一优选例中，所述式(I)化合物具有式(Ia)结构：
Figure PCTCN2020101430-appb-000002
其中，X、Y、R 1、R 2、R 3和R 4定义如上所述。
在另一优选例中，所述式(I)化合物选自下组：
Figure PCTCN2020101430-appb-000003
Figure PCTCN2020101430-appb-000004
在另一优选例中，所述式I化合物选自下组：
Figure PCTCN2020101430-appb-000005
Figure PCTCN2020101430-appb-000006
在另一优选例中，所述式I化合物选自下组：
Figure PCTCN2020101430-appb-000007
本发明第二方面提供了一种组合物，包含本发明第一方面所述的化合物、或其对映异构体或非对映异构体或其混合物，或其盐。
在另一优选例中，所述组合物为杀虫剂组合物。
在另一优选例中，所述组合物还包括助剂。
在另一优选例中，所述组合物还包括选自下组的物质：杀昆虫剂、引诱剂、消毒剂、杀细菌剂、杀螨虫剂、杀线虫剂、杀真菌剂、生长调节剂、安全剂、肥料、化学信息素，或其组合。
本发明第三方面提供了一种如本发明第一方面所述的化合物、或其对映异构体或非对映异构体或其混合物，或其盐或如本发明第二方面所述组合物的用途，用于非诊断非治疗的防治害虫。
在另一优选例中，提供了如本发明第一方面所述的化合物、或其对映异构体或非对映异构体或其混合物，或其盐或如本发明第二方面所述组合物的用途，用于防治害虫。
在另一优选例中，所述害虫包括植物害虫、卫生害虫、和/或贮存产品害虫。
在另一优选例中，所述害虫为节肢动物。
在另一优选例中，所述害虫为昆虫、蛛形纲动物、蠕虫和/或线虫。
在另一优选例中，得到害虫为蚜虫和/或虱目动物。
本发明第四方面提供了一种如本发明第一方面所述的化合物、或其对映异构体或非对映异构体或其混合物，或其盐或如本发明第二方面所述组合物的用途，用于制备防治动物寄生虫的杀虫剂。
在另一优选例中，所述动物寄生虫选自下组：蜱类、兽疥螨、叶螨、蝇、寄生蝇幼虫、虱、毛虱、羽虱和蚤，或其组合。
在另一优选例中，所述动物选自下组：狗、猪、猫、马或牛。
本发明第五方面提供了一种非治疗非诊断防治害虫的方法，将如本发明第一方面所述的化合物、或其对映异构体或非对映异构体或其混合物，或其盐或如本发明第二方面所述组合物用于害虫或其生活环境。
在另一优选例中，提供了一种防治害虫的方法，将如本发明第一方面所述的化合物、或其对映异构体或非对映异构体或其混合物，或其盐或如本发明第二方面所述组合物用于害虫或其生活环境。
在另一优选例中，所述害虫的生活环境选自：植物、土壤、产品贮藏区域和/或室内。
本发明第六方面，提供一种用于制备如本发明第一方面所述式(I)化合物的中间体，或其对映异构体或非对映异构体或其混合物，或其盐，如式(Z)所示：
Figure PCTCN2020101430-appb-000008
其中，
Z为OH、卤素、NH 2或NHR 1；
X、R 1、R 3、R 4、R 7、R 8和R 9，如本发明第一方面定义，
且当Z不含氘时，R 3、R 4至少有一个为氘；
其中当R 3和R 4均为氘，且X为氯时，Z不为羟基和氯；
当R 3和R 4一个为氘另一个为氢，且X为氟时，Z不为羟基。
在另一优选例中，R 3和R 4都为氘。
在另一优选例中，Z为NHR 1,且R 1为氘代或非氘代的C 1-C 6卤代烷基。
在另一优选例中，Z为NHR 1,且R 1为2-氟乙基、2,2-二氟乙基或1，1-二氘-2,2-二氟乙基。
在另一优选例中，所述式(Z)化合物选自：
Figure PCTCN2020101430-appb-000009
本发明第七方面提供了一种如本发明第一方面所述化合物的制备方法，所述方法包括步骤：
Figure PCTCN2020101430-appb-000010
在酸性催化剂存在下，是(III)与式(IV)进行反应，从而形成式(I)化合物；
其中，各个R 2独立地为为H或氘；和
X、Y、R 1、R 3、R 4、R 5、R 6、R 7、R 8和R 9如本发明第一方面定义。
在另一优选例中，所述酸性催化剂选自：硫酸、盐酸、磷酸、氢溴酸、硫酸氢钠、硫酸氢钾、乙酸、对甲苯磺酸、甲磺酸、三氟乙酸，或其组合，较佳的，硫酸氢钾、对甲苯磺酸、乙酸、硫酸、磷酸或其组合。
在另一优选例中，所述反应在惰性溶剂中进行，优选地，所述惰性溶剂包括卤代烃类，如二氯甲烷、四氯乙烷、氯仿、四氯化碳、三氯乙烷、1，2-二氯乙烷等；酰胺类，如二甲基甲酰胺，N-甲基吡咯烷酮、N,N-二甲基丙烯基脲(DMPU)等；腈类，如乙腈、丁腈等；醚类，如甲基叔丁基醚、四氢呋喃、甲基四氢呋喃、二氧六环、苯甲醚、苯乙醚、环己基甲基醚、乙醚、二苯醚、丙醚、二异丙基醚、二正丁基醚、二异丁基醚、二异戊基醚、乙二醇二甲醚；酯类，如乙酸乙酯等；脂族烃、脂环族烃或芳香族类，如环己烷、苯、甲苯、氯苯等；砜类，如二甲基亚砜等；硝化烃，如硝基甲烷等；醇类溶剂，如乙醇、异丙醇、甲醇、正丁醇等。
在另一优选例中，所述反应的反应温度为10-250℃，较佳地，20-150℃。
在另一优选例中，所述式(III)化合物和式(IV)化合物的摩尔比为1：10-2：1，较佳地，1：5-1：0.95，更佳地，1：2～1：1。
在另一优选例中，所述方法还包括步骤：
(b)将步骤(a)中的式(I)化合物与卤化试剂反应，得到R 2为卤素的式(I)化合物。
在另一优选例中，所述卤化试剂如选自下组：NBS、NCS、NIS，或其组合。
在另一优选例中，所述卤化反应的时间范围为10min至24h，较佳地，30min-12h。
在另一优选例中，卤化反应的温度范围为-10℃-100℃，较佳地，0℃-35℃。
在另一优选例中，所述式(I)化合物为式(Ib)化合物，由下述步骤(a-1)、(a-2)或(a-3)制备：
Figure PCTCN2020101430-appb-000011
其中，
步骤(a-1)为在惰性溶剂中，酸性催化剂存在下，式(IIIa)化合物与式(IVa)化合物反应，生成式(Ib)化合物；
步骤(a-2)为在惰性溶剂中，酸性催化剂存在下，式(IIIa)化合物与式(IVb)化合物反应，生成式(Ib)化合物，其中R 13为C 1-C 12烷基，M 1为氢或碱金属；
步骤(a-3)为在惰性溶剂中，酸性催化剂存在下，式(IIIa)化合物与式(IVc)化合物反应，生成式(Ib)化合物，其中R 14为C 1-C 12烷基或苯基，R 15为C 1-C 12烷基；
和各步骤中X、R 1、R 3和R 4各自独立地如本发明第一方面定义。
在另一优选例中，M 1为H或K。
在另一优选例中，R 13、R 14和R 15各自独立的为C 1-C 6烷基，较佳地，C 1-C 3烷基。
在另一优选例中，所述酸性催化剂选自：硫酸、盐酸、磷酸、氢溴酸、硫酸氢钠、硫酸氢钾、乙酸、对甲苯磺酸、甲磺酸、三氟乙酸，或其组合，较佳的，硫酸氢钾、对甲苯磺酸、乙酸、硫酸、磷酸或其组合。
在另一优选例中，所述惰性溶剂选自下组：乙腈、丁腈、甲基叔丁基醚、四氢呋喃、甲基四氢呋喃、二氧六环、甲苯、氯苯、正丁醇，或其组合。
在另一优选例中，所述反应的温度为10-250℃，较佳地，20-160℃，更佳地，20-150℃。
在另一优选例中，所述反应的时间为3-24h。
在另一优选例中，式(IVa)、(IVb)、或(IVc)化合物和式(IIIa)化合物的摩尔比为1：10-2：1，较佳地，1：5-1.7：1，更佳地，1：2-1.5：1，最佳地，0.7：1-1.2：1。
在另一优选例中，所述式(IIIa)化合物具有式(IIIb)，式(IIIb)化合物是通过下述步骤(b-1)或(b-2)制备的：
Figure PCTCN2020101430-appb-000012
其中，
步骤(b-1)为在惰性溶剂中，式(IIa)化合物在不含氘或含氘还原剂存在下，反应生成式(IIIb)化合物，其中R 3、R 4、R 3’和R 4’各自独立的为氢或氘，且R 3、R 4、R 3’和R 4’至少有一个为氘；Ra为C 1-C 5卤代烷基；
步骤(b-1)为在惰性溶剂中，式(IIb)化合物在不含氘或含氘还原剂存在下，反应生成式(IIIb)化合物，其中R 3、R 4、R 3’和R 4’各自独立的为氢或氘，且R 3、R 4、R 3’和R 4’至少有一个为氘；Ra为C 1-C 5卤代烷基。
在另一优选例中，所述含氘还原剂选自氘代硼烷、氘代硼氢化钠、氘代氢化铝锂，或其组合。
在另一优选例中，所述不含氘还原剂为硼烷、硼氢化钠、氢化铝锂，或其组合。
在另一优选例中，所述惰性溶剂选自下组：乙腈、丁腈、甲基叔丁基醚、四氢呋喃、甲基四氢呋喃、二氧六环、甲苯、氯苯、正丁醇、甲醇、乙醇、异丙醇、氘代甲醇、氘代乙醇、氘代异丙醇，或其组合。
在另一优选例中，所述反应的温度为-20℃到50℃。
在另一优选例中，所述反应的时间为3-48h。
在另一优选例中，式(IIIb)化合物通过下述方法制备：
Figure PCTCN2020101430-appb-000013
其中，R 3、R 4、R 3’和R 4’各自独立的为氢或氘，且R 3、R 4、R 3’和R 4’至少有一个为氘；
Ra为C 1-C 5卤代烷基；和
Rb和Rc各自独立的为氨基或其盐或离去基团，且当一个为氨基或其盐时另一个为离去基团；
在惰性溶剂中，式(A)化合物和式(B)反应生成式(IIIb)化合物；
所述离去基团优选为氯、溴、碘、-O-对甲苯磺酰基、-O-甲磺酰基或-O-三氟甲 磺酰基。
在另一优选例中，式(A)化合物和式(B)在碱存在下反应生成式(IIIb)化合物，优选地，所述碱选自下组：碳酸钠、碳酸氢钠、碳酸钾、碳酸氢钾、磷酸钠、磷酸氢二钠、磷酸钾等、三乙胺、二异丙基乙胺、吡啶，或其组合。
在另一优选例中，所述反应的温度为10-100℃。
在另一优选例中，所述反应的时间为3-24h。
在另一优选例中，式(IIIb)化合物通过下述方法制备：
Figure PCTCN2020101430-appb-000014
其中，R 3、R 4、R 3’和R 4’各自独立的为氢或氘，且R 3和R 4中至少一个为氢；
Ra为C 1-C 5卤代烷基；
在惰性溶剂中，在不含氘或含氘还原剂存在下，式(C)化合物和式(D)反应生成式(IIIb)化合物。
在另一优选例中，所述不含氘还原剂为硼氢化钠、三乙酰氧基硼氢化钠、氰基硼氢化钠，或其组合。
在另一优选例中，所述含氘还原剂为氘代硼氢化钠、氘代三乙酰氧基硼氢化钠、氘代氰基硼氢化钠，或其组合。
在另一优选例中，所述惰性溶剂选自下组：1，2-二氯乙烷、乙腈、丁腈、甲基叔丁基醚、四氢呋喃、甲基四氢呋喃、二氧六环、甲苯、氯苯、正丁醇、甲醇、乙醇、异丙醇、氘代甲醇、氘代乙醇、氘代异丙醇，或其组合。
在另一优选例中，所述反应的温度为-10至50℃。
在另一优选例中，所述反应的时间为15min-75h。
应理解，在本发明范围内中，本发明的上述各技术特征和在下文(如实施例)中具体描述的各技术特征之间都可以互相组合，从而构成新的或优选的技术方案。限于篇幅，在此不再一一累述。
具体实施方式
本发明人经过广泛而深入的研究，通过大量筛选和测试，开发了一类氘代烯氨羰基化合物。令人惊讶的是，本发明的氘代烯氨羰基化合物具有比非氘代的同类化合物更优异的杀虫效果，更长的药效时长，以及植物保护活性。在此基础上完成了本发明。
术语
除非另有定义，否则本文中所用的全部技术术语和科学术语均具有如本发明所属领域普通技术人员通常理解的相同含义。
如本文所用，“卤素”或“卤代”是指F、Cl、Br、和I。更佳地，卤原子选自F、Cl和Br。
如本文所用，“C 1-C 12烷基”是指包括1-12个碳原子(优选1-6个，更优选1-3)的直链或支链的烷基，例如甲基、乙基、丙基、异丙基、丁基、异丁基、叔丁基、或类似基团。
如本文所用，“C 1-C 6卤代烷基”或“卤代的C 1-C 6烷基”可互换使用，是指包括被一个或多个卤素原子取代的1-6个碳原子的直链或支链的烷基，例如二氟甲基、2-氟乙基、2,2-二氟乙基、2-氯-2-氟乙基、3-氟正丙基、或类似基团。
如本文所用，“C 2-C 6卤代烯基”是指包括被一个或多个卤素原子取代的1-6个碳原子的直链或支链的烯基，例如2-氟乙烯基、3,3-二氟丙-2-烯基或类似基团。
如本文所用，“氘代”指化合物或基团中的一个或多个氢被氘所取代。氘代可以是一取代、二取代、多取代或全取代。术语“一个或多个氘代的”与“一次或多次氘代”可互换使用。
如本文所用，“非氘代的化合物”或“未氘代的”是指含氘原子(D， 2H)比例不高于天然氘同位素含量(约0.015％)的化合物。
如本文所用，“对映异构体或非对映异构体”是指由相同原子组成，通过相同的键键合，但具有不同三维结构的化合物。
当本发明的化合物中含有烯双键时，除非另有说明，否则本发明的化合物旨在包含E-和Z-几何异构体。
在另一优选例中，氘在氘取代位置的氘同位素含量是大于天然氘同位素含量(0.015％)，更佳地大于50％，更佳地大于75％，更佳地大于95％，更佳地大于97％，更佳地大于99％，更佳地大于99.5％。
优选地，式(I)化合物中，N为 14N和/或O为 16O。
在另一优选例中，所述化合物中， 14N在氮原子所在位置的同位素含量≥95％，更佳地≥99％。
在另一优选例中，所述化合物中， 16O在氧原子所在位置的同位素含量≥95％，更佳地≥99％。
活性成分
如本文所用，术语“本发明化合物”指式(I)所示的化合物，
Figure PCTCN2020101430-appb-000015
其中，X、Y、R 1、R 2、R 3、R 4、R 5、R 6、R 7、R 8和R 9如上所述。
该术语还包括及式(I)化合物的对映异构体或非对映异构体或其混合物，或其盐。本发明化合物的盐包括无机盐和有机盐。一类优选的盐是本发明化合物与酸形成的盐。适合形成盐的酸包括但并不限于：盐酸、氢溴酸、氢氟酸、硫酸、硝酸、磷酸等无机酸；甲酸、乙酸、三氟乙酸、丙酸、草酸、丙二酸、琥珀酸、富马酸、马来酸、乳酸、苹果酸、酒石酸、柠檬酸、苦味酸、苯甲酸、甲磺酸、乙磺酸、对甲苯磺酸、苯磺酸、萘磺酸等有机酸；以及脯氨酸、苯丙氨酸、天冬氨酸、谷氨酸等氨基酸。
制备方法
下面更具体地描述本发明式(I)结构化合物的制备方法，但这些具体方法不对本发明构成任何限制。本发明化合物还可以任选将在本说明书中描述的或本领域已知的各种合成方法组合起来而方便地制得，这样的组合可由本发明所属领域的技术人员容易地进行。
下面的通用制备路线可以用于合成本发明式(I)结构的化合物：
Figure PCTCN2020101430-appb-000016
在酸性催化剂存在下，是(III)与式(IV)进行反应，从而形成式(I)化合物；
其中，各个R 2独立地为为H或氘；和
X、Y、R 1、R 3、R 4、R 5、R 6、R 7、R 8和R 9如本发明第一方面定义。
在另一优选例中，所述酸性催化剂选自：硫酸、盐酸、磷酸、氢溴酸、硫酸氢钠、硫酸氢钾、乙酸、对甲苯磺酸、甲磺酸、三氟乙酸，或其组合，较佳的，硫酸氢钾、对甲苯磺酸、乙酸、硫酸、磷酸或其组合。
在另一优选例中，所述反应的反应温度为10-250℃，较佳地，20-150℃。
在另一优选例中，所述式(III)化合物和式(IV)化合物的摩尔比为1：10-2：1，较佳地，1：5-1：0.95，更佳地，1：2～1：1。
在另一优选例中，所述方法还包括步骤：
(b)将步骤(a)中的式(I)化合物与卤化试剂反应，得到R 2为卤素的式(I)化合物。
在另一优选例中，所述卤化试剂如选自下组：NBS、NCS、NIS，或其组合。
在另一优选例中，所述卤化反应的时间范围为10min至24h，较佳地，30min-12h。
在另一优选例中，卤化反应的温度范围为-10℃-100℃，较佳地，0℃-35℃。
组合物及用途
本发明提供了一种组合物，包含本发明第一方面所述的化合物、或其对映异构体或非对映异构体或其混合物，或其盐。
如果合适，本发明的化合物可以单一晶型、多晶形或其混合物存在。
通常，本发明的组合物为杀虫剂组合物。本发明的组合物可进一步包括恰当的助剂，合适的助剂包括但不限于：溶剂，液体载体，固体载体或填料，表面活性剂，分散剂，乳化剂，润湿剂，辅助剂，加溶剂，渗透促进剂，保护性胶体，粘附剂，增稠剂，保湿剂，驱除剂，引诱剂，进食刺激剂，相容剂，杀菌剂，防冻剂，消泡剂，着色剂，增粘剂和粘合剂。
所述组合物可为常规制剂，如溶液剂、乳液、悬浮剂、可湿性粉剂、粉剂、粉末剂、糊、膏剂、可溶性粉剂、颗粒剂、模压品、悬乳浓缩剂、经活性化合物浸渍的天然和合成材料以及聚合物中的微胶囊剂。
所述组合物可以(但不限于)以下形式使用：气雾剂、喷雾剂、泡沫剂、凝胶剂、蒸发剂、捕虫胶纸、毒饵站或抛撒饵料。
除了水可以用为填充剂，其他极性或非极性有机溶剂也可被采用作为助溶剂。合适的液体溶剂基本上为：芳烃如二甲苯、甲苯、烷基苯或烷基萘，氯代芳烃或氯代脂族烃如氯苯、氯乙烯或二氯甲烷，脂肪族烃如环己烷或石蜡(如矿物油馏分、矿物油和植物油)，醇类如乙醇、丙醇、苄醇、环己醇、丁醇或乙二醇及其醚和酯，酮类如丙酮、环己酮、甲乙酮、或甲基异丁基酮，酯类如乳酸酯、碳酸酯、脂肪酸酯，强极性溶剂如酰胺类(N,N-二甲基甲酰胺，N-烷基吡咯烷酮)和砜、亚砜类如二甲亚砜。填充剂也可以是上述溶剂的混合物，例如水和丙酮等。
合适的固体载体或填料，如天然矿物粉，如高岭土、粘土、滑石粉、白垩、石英、凹凸棒石、蒙脱石或硅藻土，以及合成矿物粉末，如高度分散的二氧化硅、氧化铝和硅酸盐；用于颗粒剂的合适固体载体为：例如粉碎并分级的天然岩石，如方解石、 大理石、浮石、海泡石和白云石，以及无机和有机粉的合成颗粒，和有机物颗粒如纤维素、淀粉类，如纸张、锯末、椰壳等坚果壳粉、树皮粉、谷粉、玉米穗轴和烟草茎的颗粒，以及他们的混合物。
合适的表面活性剂是农药剂型领域所公知的各种表面活性化合物，包括阴离子、阳离子、非离子和两性表面活性剂，嵌段聚合物，聚电解质。该类表面活性剂的作用为乳化剂、分散剂、加溶剂、润湿剂、渗透促进剂、保护性胶体或辅助剂。它们的混合物也可以被使用。
合适的阴离子表面活性剂是烷基磺酸盐、烷基硫酸盐、芳基磺酸盐、磷酸盐、羧酸盐、铵盐及其混合物。如十二烷基苯磺酸钙、硫酸钠、月桂醇硫酸钠、亚甲基萘磺酸钠、十二烷基苯磺酸钠、十二烷基苯磺酸钙、烷基萘磺酸钠脂肪醇聚氧乙烯基醚、烷基酚聚氧乙烯基醚。
合适的非离子表面活性剂是烷氧基化物，胺氧化物，N-取代的脂肪酸酰胺类，酯类，聚合物、糖基表面活性剂，以及以上组分的混合物。
合适的阳离子表面活性剂如季铵盐类化合物。
合适的两亲性表面活性剂如烷基甜菜碱、咪唑啉类。
合适的聚合物，如含乙烯、丙烯酸单体与醇类、胺类的低聚物、聚合物。
合适的增稠剂是多糖(例如羧甲基纤维素黄原胶)和粉末、颗粒或胶乳形式的天然或合成聚合物(如阿拉伯树胶、聚乙烯醇、聚乙酸乙烯酯，以及天然磷脂如脑磷脂和卵磷脂，以及合成磷脂)，无机粘土、硅酸盐。
合适的防冻剂是乙二醇、甘油、尿素和甘油的一种或多种。
可加入稳定剂如低温稳定剂、防腐剂、抗氧化剂、光稳定剂或其它提高化学和/或物理稳定性的试剂。
所述组合物通常含有0.01-98重量％的活性化合物，优选为0.5-90重量％的活性化合物。
如本文所用，所述“防治”包括但不限于杀死或驱离害虫、减慢害虫生长或繁殖速度。
本发明的化合物、或其对映异构体或非对映异构体或其混合物，或其盐以及本发明的组合物可用于防治害虫。特别是农业、园艺、畜牧业、森林、园林和休闲设施、贮存产品和材料的保护及卫生领域中遇到的昆虫、蛛形纲动物、蠕虫和线虫。它们优选作为植物保护剂。它们对一般的敏感及抗性物种及所有或部分发育阶段均具有活性。所述害虫包括(但并不限于)：
虱目(Anoplura)(Phthiraptera)，例如，畜虱属(Damalinia spp.)、血虱属(Haematopinus spp.)、毛虱属(Linognathus spp.)、虱属(Pediculus spp.)、嚼虱属(Trichodectes spp.)。
蛛形纲(Arachnida)，例如，粗脚粉螨(Acarus siro)、柑橘瘤瘿螨(Aceriasheldoni)、剌皮瘦螨属(Aculops spp.)、针剌瘦螨属(Aculus spp.)、花蜱属(Amblyommaspp.)、锐缘蜱属(Argas spp.)、牛蜱属(Boophilus spp.)、短须螨属(Brevipalpus spp.)、苜猜苔螨(Bryobia praet1sa)、皮螨属(Chor1ptes spp.)、鸡皮剌螨(Dermanyssusgallinae)、始叶螨属(Eotetranychus spp.)、梨上瘦螨(Epitrimerus pyri)、真叶螨属(Eutetranychus spp.)、瘦 螨属(Er1phyes spp.)、半跑线螨属(Hemitarsonemus spp.)、璃眼蜱属(Hyalomma spp.)、硬蜱属(Ixodes spp.)、黑寡妇蜘蛛(Latrodectus mactans)、Metatetranychus spp.、小爪螨属(Oligonychus spp.)、纯缘蜱属(Ornithodoros spp.)、全爪螨属(Panonychus spp.)，如苹果全爪螨((Panonychus ulmi(Koch))、桔芸锈螨(Phyllocoptruta oleivora)、侧多食跑线螨(Polyphagotarsonemus latus)、库螨属(Psoroptes spp.)、扇头蜱属(Rhipicephalusspp.)、根螨属(Rhizoglyphus spp.)、挤螨属(Sarcoptes spp.)、中东金蝎(Scorp1maurus)、狭跗线螨属(Steneotarsonemus spp.)、跑线螨属(Tarsonemus spp.)、叶螨属(Tetranychusspp.)，如朱砂叶螨(Tetranychus cinnabarinus)、番茄刺皮癭蟎(Vasates Iycopersici)、双叶螨属(Amphitetranychus)。
双壳纲(Bivalva)，例如，饰贝属(Dreissena spp.)。
唇足纲(Chilopoda)，例如，地蜈蚣属(Geophilus spp.)、蚰蜒(Scutigera spp.)。
鞘翅目(Coleoptera)，例如，菜豆象(Acanthoscelides obtectus)、喙丽金龟属(Adoretus spp.)、杨树萤叶甲(Agelastica alni)、叩甲属(Agriotes spp.)、马铃墓鳃角金龟(Amphimallon solstitialis)、家具窃蠹(Anobium punctatum)、星天牛属(Anoplophora spp.)、花象属(Anthonomus spp.)、圆皮蠹属(Anthrenus spp.)、阿鳃金龟属(Apogonia spp.)、Atomaria spp.、毛皮蠹属(Attagenus spp.)、恶条豆象(Bruchidius obtectus)、豆象属(Bruchus spp.)、龟象属(Ceuthorhynchus spp.)、Cleonus mendicus、宽胸叩头虫属(Conoderus spp.)、根颈象属(Cosmopolites spp.)、褐新西兰肋翅鳃角金龟(Costelytra zealandica)、象虫属(Curculio spp.)、杨干隐喙象(Cryptorhynchus lapathi)、皮蠹属(Dermestes spp.)、叶甲属(Diabrotica spp.)、食植瓢虫属(Epilachna spp.)、Faustinus cubae、裸蛛甲化(Gibbium psylloides)、黑异爪蔗金龟(Heteronychus arator)、Hylamorpha elegans、北美家天牛(Hylotrupes bajulus)、紫苜蓿叶象(Hypera postica)、Hypothenemus spp.、甘蔗大褐齿爪鳃金龟(Lachnosterna consanguinea)、马铃墓甲虫(Leptinotarsa decemlineata)、稻根象(Lissorhoptrus Oryzophilus)、筒象喙属(Lixus spp.)、粉蠹属(Lyctus spp.)、油莱花露尾甲(Meligethes aeneus)、西方五月鳃角金龟(Melolontha melolontha)、Migdolus spp.、墨天牛属(Monochamus spp.)、Naupactus xanthographus、黄蛛甲(Niptus hololeucus)、椰驻犀金龟(Oryctes rhinoceros)、锯谷盗(Oryzaephilus surinamensis)、黑葡萄耳象(Otiorrhynchus sulcatus)、小青花金龟((kycetonia jucunda)、辣根猿叶虫(Phaedon cochleariae)、食叶鳃金龟属(Phyllophaga spp.)、日本弧丽金龟(Popillia japonica)、Premnotiypes spp.、油菜金头跳甲(Psylliodes chrysocephala)、蛛甲属(Ptinus spp.)、暗色瓢虫(Rhizobius ventralis)、谷蠹(Rhizopertha dominica)、谷象属(Sitophilus spp.)、尖隐喙象属(Sphenophorus spp.)、茎干象属(Sternechus spp.)、Symphyletes spp.、黄粉虫(Tenebrio molitor)、拟谷盗属(Tribolium spp.)、斑皮蠹属(Trogoderma spp.)、籽象属(Tychius spp.)、脊虎天牛属(Xylotrechus spp.)、距步甲属(Zabrus spp.)。
弹尾目(Collembola)，例如，武装棘跳虫(Onychiurus armatus)。
革翅目(Dermaptera)，例如，欧洲球螋(Forficula auricularia)。
倍足目(Diplopoda)，例如，Blaniulus guttulatus。
双翅目(Diptera)，例如，伊蚊属(Aedes spp.)、按蚊属(Anopheles spp.)、花园毛蚊 (Bib1hortulanus)、红头丽蝇(Calliphora erythrocephala)、地中海蜡实蝇(Ceratitis capitata)、金蝇属(Chrysomyia spp.)、锥蝇属(Cochl1myia spp.)、Cordylobia anthropophaga、库蚊属(Culex spp.)、黄蝇属(Cuterebra spp.)、橄榄大实蝇(Dacus oleae)、人肤蝇(Dermatobia hominis)、果蝇属(Drosophila spp.)、厕蝇属(Fannia spp.)、胃蝇属(Gastrophilus spp.)、黑蝇属(Hylemyia spp.)、Hyppoboscaspp.、皮蝇属(Hypoderma spp.)、斑潜蝇属(Lir1myza spp.)、绿蝇属(Lucilia spp.)、家蝇属(Musca spp.)、绿蝽属(Nezara spp.)、狂蝇属(Oestrus spp.)、瑞典麦杆蝇(Oscinella frit)、藜泉蝇(Pegomyia hyoscyami)、草种蝇属(Phorbia spp.)、螫蝇属(Stomoxys spp.)、虻属(Tabanus spp.)、Tannia spp.、欧洲大蚊(Tipula paludosa)、污蝇属(Wohlfahrtia spp.)。
腹足纲(Gastropoda)，例如，Arion spp.、双脐螺属(B1mphalaria spp.)、小泡螺属(Bulinus spp.)、Deroceras spp.、土蜗属(Galba spp.)、椎实螺属(Lymnaea spp.)、钉螺属(Oncomelania spp.)、琥珀螺属(Succinea spp.)。
螺虫纲(Helminths)，例如，十二指肠钩口线虫(Ancylostoma duodenale)、斯里兰卡钩口线虫(Ancylostoma ceylanicum)、巴西钩口线虫(Acylostoma braziliensis)、钩口线虫属(Ancylostoma spp.)、似引蛔线虫(Ascaris Iubricoides)、蛔虫属(Ascarisspp.)、马来布鲁线虫(Brugia malayi)、帝汉布鲁线虫(Brugia timori)、仰口线虫属(Bunostomum spp.)、夏柏特线虫属(Chabertia spp.)、枝睾吸虫属(Clonorchisspp.)、古柏线虫属(Cooperia spp.)、双腔吸虫属(Dicrocoelium spp.)、丝状网尾线虫(Dictyocaulus filaria)、阔节裂头绦虫(Diphyllobothrium latum)、麦地那龙线虫(Dracunculus medinensis)、细粒棘球绦虫(Echinococcus granulosus)、多房棘球绦虫(Echinococcus multilocularis)、蠕形住肠线虫(Enterobius vermicularis Linnaeus)、Faciola spp.、血毛线虫属(Haemonchus spp.)、异刺线虫属(Heterakis spp.)、矮小啮壳绦虫(Hymenolepis nana)、猪圆线虫属(Hyostrongulus spp.)、罗阿罗阿线虫(Loa Loa)、细颈线虫属(Nematodirus spp.)、结节线虫属(Oesophagos tomum spp.)、后睾吸虫属(Opisthorchis spp.)、旋盘尾丝虫(Onchocerca volvulus)、奥斯脱线虫属(Ostertagia spp.)、并殖吸虫属(Paragonimus spp.)、Schistosomen spp.、富氏类圆线虫(Strongyloides fuelleborni)、粪类圆线虫(Strongyloides stercoralis)、粪圆线虫属(Stronyloides spp.)、牛带绦虫(Taenia saginata)、猪带绦虫(Taenia solium)、旋毛形线虫(Trichinella spiralis)、本地毛形线虫(Trichinella nativa)、株布氏旋毛虫(Trichinella britovi)、南方旋毛虫(Trichinella nelsoni)、Trichinella pseudopsiralis、毛圆线虫属(Trichostrongulus spp.)、Trichuris trichuria、班氏吴策线虫(Wuchereria bancrofti)。
植物寄生线虫包括，例如，粒线虫属(Anguina spp)、滑刃线虫属(Aphelenchoides spp.)、刺线虫属(Belonoaimus spp.)、伞滑刃线虫属(Bursaphelenchus spp.)、起绒草茎线虫(Ditylenchus dipsaci)、球异皮线虫属(Globodera spp.)、螺旋线虫属(Heliocotylenchus spp.)、异皮线虫属(Heterodera spp.)、长针线虫属(Longidorus spp.)、根结线虫属(Meloidogyne spp.)、短体线虫属(Pratylenchus spp.)、相似穿孔线虫(Radopholus similis)、盘旋属(Rotylenchus spp.)、毛刺线虫属(Trichodorus spp.)、矮化线虫属(Tylenchorhynchus spp.)、小垫刃线虫属(Tylenchulus spp.)、半穿刺线虫(Tylenchulus semipenetrans)、剑线虫属(Xiphinema spp.)。
原生动物，例如艾美虫(Eimeria)。
异翅目(Heteroptera)，例如，南瓜缘蝽(Anasa tristis)、拟丽蝽属(Antest1psis spp.)、土长鋳属(Blissus spp.)、俊盲蝽属(Calocoris spp.)、Campylomma livida、异背长蝽属(Cavelerius spp.)、臭虫属(Cimex spp.)、Creontiadesdilutus、胡椒缘蝽(Dasynus piperis)、Dichelops furcatus、厚氏长棒网蝽(Diconocorishewetti)、棉红蝽属(Dysdercus spp.)、美洲蝽属(Euschistus spp.)、扁盾蝽属(Eurygaster spp.)、Heliopeltis spp.、Horcias nobilellus、稻缘蝽属(Leptocorisaspp.)、叶喙蝽(Leptoglossus phyllopus)、草盲蝽属(Lygus spp.)、蔗黑长蝽(Macropesexcavatus)、盲蝽科(Miridae)、绿蝽属、Oebalus spp.、Pentomidae、方背皮蝽(Piesmaquadrata)、壁蝽属(Piezodorus spp.)、棉伪斑腿盲蝽(Psallus seriatus)、Pseudacystapersea、红猎蝽属(Rhodnius spp.)、可可褐盲蝽(Sahlbergella singularis)、黑蝽属(Scotinophora spp.)、梨冠网蝽(Stephanitis nashi)、Tibraca spp.、锥猎蝽属(Triatoma spp.)。
同翅目(Homoptera)，例如，无网长管蚜属(Acyrthosipon spp.)、Aeneolamia spp.、隆脉木虱属(Agonoscena spp.)、Aleurodes spp.、蔗粉虱属(Aleurolobus barodensis)、Aleurothrixus spp.杧果叶蝉属(Amrasca spp.)、Anuraphis cardui、肾圆盾蚧属(Aonidiella spp.)、苏联黄粉蚜(Aphanostigma piri)、蚜属(Aphis spp)，如苜蓿蚜(Aphis craccivora Koch)、葡萄叶蝉(Arboridia apicalis)、小圆盾蚧属(Aspidiella spp.)、圆盾蚧属(Aspidiotus spp.)、Atanus spp.、茄沟无网蚜(Aulacorthum solani)、Bemisia spp.、李短尾蚜(Brachycaudus helichrysii)、Brachycolus spp.、甘蓝蚜(Brevicoryne brassicae)、小褐稻虱(Calligypona marginata)、Carneocephala fulgida、甘蔗粉角蚜(Ceratovacuna lanigera)、沫蝉科(Cercopidae)、蜡蚧属(Ceroplastes spp.)、草莓钉蚜(Chaetosiphon fragaefolii)、蔗黄雪盾阶(Chionaspis tegalensis)、荼绿叶蝉(Chlorita onukii)、核桃黑斑蚜(Chromaphis juglandicola)、黑褐圆盾蚧(Chrysomphalus ficus)、玉米叶蝉(Cicadulina mbila)、Coccomytilus halli、软蚧属(Coccus spp.)、茶藨隐瘤蚜(Cryptomyzus ribis)、Dalbulus spp.、Dialeurodes spp.、Diaphorina spp.、白背盾蚧属(Diaspis spp.)、Doralis spp.、履绵蚧属(Drosicha spp.)、西圆尾蚜属(Dysaphis spp.)、灰粉蚧属(Dysmicoccus spp.)、小绿叶蝉属(Empoasca spp.)、绵蚜属(Eriosoma spp.)、Erythroneura spp.、Euscelis bilobatus、咖啡地粉蚧(Geococcus coffeae)、假桃病毒叶蝉(Homalodisca coagulata)、梅大尾蚜(Hyalopterus arundinis)、吹绵蚧属(Icerya spp.)、片角叶蝉属(Idiocerus spp.)、扁喙叶蝉属(Idioscopus spp.)、灰飞虱(Laodelphax striatellus)、Lecanium spp.、蛎盾蚧属(Lepidosaphes spp.)、萝卜蚜(Lipaphis erysimi)、长管蚜属(Macrosiphum spp.)、Mahanarva fimbriolata、高粱蚜(Melanaphis sacchari)、Metcalfiella spp.、麦无网蚜(Metopolophium dirhodum)、黑缘平翅斑蚜(Monellia costalis)、Monelliopsis pecanis、瘤蚜属(Myzus spp.)、莴苣衲长管蚜(Nasonovia ribisnigri)、黑尾叶蝉属(Nephotettix spp.)、褐飞虱(Nilaparvata lugens)、Oncometopia spp.、Orthezia praelonga、杨梅缘粉虱(Parabemisia myricae)、Paratrioza spp.、片盾蚧属(Parlatoria spp.)、瘿绵蚜属(Pemphigus spp.)、玉米蜡蝉(Peregrinus maidis)、绵粉蚧属(Phenacoccus spp.)、杨平翅绵蚜(Phloeomyzus passerinii)、忽布疣蚜(Phorodon humuli)、葡萄根瘤蚜属(Phylloxera spp.)、苏铁褐点并盾蚧(Pinnaspis aspidistrae)、臀纹粉蚧属(Planococcus spp.)、梨形原 绵蚧(Protopulvinaria pyriformis)、桑白盾蚧(Pseudaulacaspis pentagona)、粉蚧属(Pseudococcus spp.)、木虱属(Psylla spp.)、金小蜂属(Pteromalus spp.)、Pyrilla spp.、笠圆盾蚧属(Quadraspidiotus spp.)、Quesada gigas、平刺粉蚧属(Rastrococcus spp.)、缢管蚜属(Rhopalosiphum spp.)、黑盔蚧属(Saissetia spp.)、Scaphoides titanus、麦二叉蚜(Schizaphis graminum)、苏铁刺圆盾蚧(Selenaspidus articulatus)、长唇基飞虱属(Sogata spp.)、白背飞虱(Sogatella furcifera)、Sogatodes spp.、Stictocephala festina、Tenalaphara malayensis、Tinocalliscaryaefoliae、广胸沫蝉属(Tomaspis spp.)、声蚜属(Toxoptera spp.)、温室粉虱(Trialeurodes vaporariorum)、个木虱属(Trioza spp.)、小叶蝉属(Typhlocyba spp.)、尖盾蚧属(Unaspis spp.)、葡萄根瘤虱(Viteus vitifolii)。
膜翅目(Hymenoptera)，例如，松叶蜂属(Diprion spp.)、实叶蜂属(Hoplocampa spp.)、毛蚁属(Lasius spp.)、小家蚁(Monomorium pharaonis)、胡蜂属(Vespa spp.)。
等足目(Isopoda)，例如，鼠妇(Armadillidium vulgare)、栉水虱(Oniscus asellus)、球鼠妇(Porcellio scaber)。
等翅目(Isoptera)，例如，散白蚁属(Reticulitermes spp.)、土白蚁(Odontotermes spp.)。
鳞翅目(Lepidoptera)，例如，桑剑纹夜蛾(Acronicta major)、烦夜蛾(Aedia leucomelas)、地老虎属(Agrotis spp.)、棉叶波纹夜蛾(Alabama argillacea)、干煞夜蛾属(Anticarsia spp.)、Barathra brassicae、棉潜蛾(Bucculatrix thurberiella)、松尺蠖(Bupaluspiniarius)、亚麻黄卷蛾(Cacoecia podana)、Capua reticulana、苹果小卷蛾(Carpocapsa pomonella)、冬尺蛾(Cheimatobia brumata)、禾草螟属(Chilo spp.)、枞色卷蛾(Choristoneura fumiferana)、葡萄果蠹蛾(Clysia ambiguella)、Cnaphalocerus spp.、埃及金刚钻(Earias insulana)、地中海粉斑螟(Ephestia kuehniella)、黄毒蛾(Euproctis chrysorrhoea)、切根虫属(Euxoa spp.)、脏切夜蛾属(Feltia spp.)、大蜡螟(Galleria mellonella)、棉铃虫属(Helicoverpa spp.)、实夜蛾属(Heliothis spp.)、褐织蛾(Hofmannophila pseudospretella)、茶长卷蛾(Homona magnanima)、苹果巢蛾(Hyponomeuta padella)、贪夜蛾属(Laphygma spp.)、苹细蛾(Lithocolletis blancardella)、绿果冬夜蛾(Lithophane antennata)、豆白隆切根虫(Loxagrotis albicosta)、毒蛾属(Lymantria spp.)、黄褐天幕毛虫(Malacosoma neustria)、甘蓝夜蛾(Mamestra brassicae)、稻毛胫夜蛾(Mocis repanda)、粘虫(Mythimna separata)、Oria spp.、水稻负泥虫(Oulema oryzae)、小眼夜蛾(Panolis flammea)、红铃麦蛾(Pectinophora gossypiella)、桔潜蛾(Phyllocnistis citrella)、菜粉蝶属(Pieris spp.)、菜蛾(Plutella xylostella)、斜纹夜蛾属(Prodenia spp.)、Pseudaletia spp.、大豆夜蛾(Pseudoplusia includens)、玉米螟(Pyrausta nubilalis)、灰翅夜蛾属(Spodoptera spp.)、Thermesia gemmatalis、袋谷蛾(Tinea pellionella)、幕谷蛾(Tineola bisselliella)、栎绿卷蛾(Tortrix viridana)、粉夜蛾属(Trichoplusia spp.)。
直翅目(Orthoptera)，例如，家蟋(Acheta domesticus)、东方蜚蠊(Blatta orientalis)、德国蠊(Blattella germanica)、蝼蛄属(Gryllotalpa spp.)、马德拉蜚蠊(Leucophaea maderae)、飞蝗属(Locusta spp.)、黑蝗属(Melanoplus spp.)、美洲大蠊(Periplaneta americana)、沙漠蝗(Schistocerca gregaria)。
蚤目(Siphonaptera)，例如，角叶蚤属(Ceratophyllus spp.)、印鼠客蚤(Xenopsylla cheopis)。
综合目(Symphyla)，例如，白松虫(Scutigerella immaculata)。
缨翅目(Thysanoptera)，例如，稻蓟马(Baliothrips biformis)、Enneothrips flavens、花蓟马属(Frankliniella spp.)、网蓟马属(Heliothrips spp.)、温室条篱蓟马(Hercinothrips femoralis)、卡蓟马属(Kakothrips spp.)、葡萄蓟马(Rhipiphorothrips cruentatus)、硬蓟马属(Scirtothrips spp.)、Taeniothrips cardamoni、蓟马属(Thrips spp.)。
缨尾目(Thysanura)，例如，衣鱼(Lepisma saccharina)。
本发明活性化合物不仅对植物害虫、卫生害虫和贮存产品害虫起作用，而且也对对兽医领域中的动物(尤其是皮肤、毛发中)寄生虫，如蜱类、兽疥螨、叶螨、蝇、寄生蝇幼虫、虱、毛虱、羽虱和蚤起作用。
所述组合物还可包括(但并不限于)选自下组的物质：杀昆虫剂、引诱剂、消毒剂、杀细菌剂、杀螨虫剂、杀线虫剂、杀真菌剂、生长调节剂、安全剂、肥料、化学信息素，或其组合。下面列举部分实例：
生物源类的农药，如阿维菌素、多杀菌素、甲氨基阿维菌素苯甲酸盐、乙基多杀菌素；
烟碱类杀虫剂：氟吡呋喃酮；
拟除虫菊酯类的杀虫剂，氯氟氰菊酯、醚菊酯、联苯菊酯、甲氰菊酯、七氟菊酯；
介离子类杀虫剂，如三氟苯嘧啶；
氨基甲酸酯类杀虫剂，如异丙威、丁硫克百威、丙硫克百威、克百威、灭多威、仲丁威、速灭威、残杀威、苯氧威、恶虫威、甲萘威、呋线威、抗姆威、棉铃威、涕灭威、丁酮威、丁酮砜威、杀线威、硫双威、久效威、乙硫苯威、甲硫威、混杀威、灭除威、灭杀威、地麦威、敌蝇威、异索威、嘧啶威、吡唑威、涕灭砜威、戊氰威、噻螨威、除害威、灭害威、合杀威、畜虫威、除线威、害扑威、混灭威、二氧威、多杀威、兹克威、蜱虱威、猛杀威、乙苯威(fenethacarb)或氯灭杀威(carbanolate)。
本发明中植物是指天然存在及经由常规植物育种和优选法获得的植物，或者通过生物技术和遗传工程方法，如转基因植物。
本发明所提供的活性化合物及其组合物，可通过多种常见方式施用于靶标动物害虫和其生活所相关的普通环境(如仓储环境)、植物环境，如浸渍、喷雾、弥雾、蒸发、撒播、涂抹、注射等。此外，还可用于种子保护，如可施用一层或多层包衣进行种子处理。
根据生物学实验结果，本发明所提供的活性化合物或普遍具有更好的抗代谢特性，意味着与相似含氢结构相比，保留了同样优异的内吸活性同时，同等剂量下对植物的保护期更长，或对靶标动物害虫的直接毒性更大，因此更适用于种子保护。
本发明组合物适于保护在农业、温室、森林或园艺中使用的植物种子。如玉米、花生、油菜、油籽油菜、大豆、棉花、甜菜、苜蓿、水稻、蜀黍和粟、小麦、大麦、燕麦、黑麦、向日葵、烟草、马铃薯或蔬菜(例如西红柿、卷心菜植物)，以及水果植物(如柑橘等)的种子。
本发明的主要优点包括：
1.本发明提供了一类新型的氘代烯氨羰基化合物，首次发现了可用于防治害虫的烯氨羰基化合物的能够提高杀虫效果的氘代位点。
2.本发明的氘代烯氨羰基化合物杀虫效果比非氘代的化合物更好，实验证明，本发明的氘代化合物对多种虫害的杀灭效果显著优于其非氘代形式。
3.本发明的氘代烯氨羰基化合物杀虫取得同等效果时用量更小，同等用量时，药效时间更长。
4.本发明的氘代代烯氨羰基化合物为烯氨羰基类杀虫剂提供了氘代标准品，可用于烯氨羰基类杀虫剂的残留质谱检测。
5.本发明的制备方法氘代选择性好、收率高。
下面结合具体实施例，进一步阐述本发明。应理解，这些实施例仅用于说明本发明而不用于限制本发明的范围。下列实施例中未注明具体条件的实验方法，通常按照常规条件，或按照制造厂商所建议的条件。除非另外说明，否则百分比和份数是重量百分比和重量份数。本发明实施例中所用原料或仪器，若非特别说明，均市售可得。
实施例1
4-(((6-氯吡啶-3-基)二氘甲基)(2,2-二氟乙基)氨基)呋喃-2(5H)-酮的制备：
Figure PCTCN2020101430-appb-000017
化合物1
步骤1：(6-氯吡啶-3-基)-二氘甲基-醇的制备：
将6-氯烟酸乙酯(1.9g)溶于THF(30mL)中，向溶液中加入NaBD 4(2.7g)，搅拌0.5h
后，滴入甲醇(8mL)，反应室温搅拌过夜。加水淬灭后，水相用乙酸乙酯萃取，有机相用饱和食盐水洗涤，干燥(硫酸钠)，抽滤，旋干，柱层析纯化，以乙酸乙酯/石油醚梯度洗脱得到目标化合物0.9g，收率64％。
步骤2：5-(二氘代溴甲基)-2-氯吡啶的制备：
将步骤1中(6-氯吡啶-3-基)-二氘甲基-醇(0.7g)溶于二氯甲烷(30mL)中，在0℃下滴入PBr 3(2.5g),搅拌4h后，用3N NaOH水溶液淬灭反应，乙酸乙酯萃取水相，有机相用饱和食盐水洗涤，干燥(硫酸钠)，抽滤，旋干，柱层析纯化，以乙酸乙酯/石油醚梯度洗脱得到目标化合物0.8g，收率80％。
步骤3：N-((6-氯吡啶-3-基)二氘甲基)-2,2-二氟乙基-1-胺的制备：
步骤2中5-(二氘代溴甲基)-2-氯吡啶(0.6g)、二氟乙胺(0.5g)和N,N-二异丙基乙胺(0.7g)混合，反应混合物置于45℃搅拌过夜，之后直接旋干，柱层析纯化，以乙酸乙酯/石油醚梯度洗脱得到目标化合物0.5g，收率85％。
步骤4：4-(((6-氯吡啶-3-基)二氘甲基)(2,2-二氟乙基)氨基)呋喃-2(5H)-酮的制备：
将步骤3中N-((6-氯吡啶-3-基)二氘甲基)-2,2-二氟乙基-1-胺(0.4g)溶解在甲苯(15mL)中，并向其中先后加入特窗酸(0.5g)和对甲苯磺酸(0.6g)，得到的混合物在分水器上加热回流过夜。将温度冷却到室温后，反应混合物用饱和氯化钠水溶液洗两次。将有机相干燥(硫酸钠)，抽滤，旋干，柱层析纯化，以乙酸乙酯/石油醚梯度洗脱得到目标化合物0.4g，收率75％。
实施例2
4-(((6-氯吡啶-3-基)二氘甲基)(2,2-二氟乙基)氨基)呋喃-2(5H)-酮的制备：
Figure PCTCN2020101430-appb-000018
化合物1
N-((6-氯吡啶-3-基)二氘甲基)-2,2-二氟乙基-1-胺(0.4g)溶解在丁腈(15mL)中，并向其中先后加入4-羟基-2-氧代-2,5-二氢呋喃-3-羧酸乙酯(0.5g)和硫酸氢钾(0.3g)，得到的混合物在92℃反应3h。将温度冷却到室温后，反应混合物用饱和氯化钠水溶液洗两次。将有机相干燥(硫酸钠)，抽滤，旋干，柱层析纯化，以乙酸乙酯/石油醚梯度洗脱得到目标化合物0.5g，收率86％。
实施例3
4-(((6-氯吡啶-3-基)二氘甲基)(2,2-二氟乙基)氨基)呋喃-2(5H)-酮的制备：
Figure PCTCN2020101430-appb-000019
化合物1
N-((6-氯吡啶-3-基)二氘甲基)-2,2-二氟乙基-1-胺(0.3g)溶解在丁腈(15mL)中，并向其中先后加入2-乙氧基-4-氧代-4,5-二氢呋喃-3-羧酸乙酯(0.4g)和硫酸氢钾(0.2g)，得到的混合物在110℃反应10h。将温度冷却到室温后，反应混合物用饱和氯化钠水溶液洗两次。将有机相干燥(硫酸钠)，抽滤，旋干，柱层析纯化，以乙酸乙酯/石油醚梯度洗脱得到目标化合物0.4g，收率92％。
实施例4
4-(((6-氯吡啶-3-基)二氘甲基)(2,2-二氟乙基)氨基)呋喃-2(5H)-酮的制备：
Figure PCTCN2020101430-appb-000020
化合物1
N-((6-氯吡啶-3-基)二氘甲基)-2,2-二氟乙基-1-胺(0.6g)溶解在丁腈(25mL)中，并向其中先后加入4-(乙氧基羰基)-5-氧代-2，5-二氢呋喃-3-氧化钾(1.3g)和硫酸氢钾(1.0g)，得到的混合物100℃加热2h。将温度冷却到室温后，反应混合物用饱和氯化钠水溶液洗两次。将有机相干燥(硫酸钠)，抽滤，旋干，柱层析纯化，以乙酸乙酯/石油醚梯度洗脱得到目标化合物0.6g，收率69％。
实施例5
4-(((6-氯吡啶-3-基)氘甲基)(2,2-二氟乙基)氨基)呋喃-2(5H)-酮的制备：
Figure PCTCN2020101430-appb-000021
化合物2
步骤1：(6-氯吡啶基-3-基)氘甲基-醇的制备：
将6-氯烟醛(1.4g)溶于甲醇(45mL)中，缓慢加入NaBD 4(2.5g)，室温并拌过夜。在加水淬灭后，水相用乙酸乙酯萃取，有机相用饱和食盐水洗涤，干燥(硫酸钠)，抽滤，旋干，柱层析纯化，以乙酸乙酯/石油醚梯度洗脱得到目标化合物1.3g，收率90％。
步骤2：5-(氘溴甲基)-2-氯吡啶的制备：
将步骤1中(6-氯吡啶基-3-基)氘甲基-醇(0.7g)溶于二氯甲烷(35mL)中，在0℃下滴入PBr 3(2.5g)，搅拌4h后，用3N NaOH水溶液淬灭反应，乙酸乙酯萃取水相，有机相用饱和食盐水洗涤，干燥(硫酸钠)，抽滤，旋干，柱层析纯化，以乙酸乙酯/石油醚梯度洗脱得到目标化合物0.8g，收率79％。
步骤3：N-((6-氯吡啶-3-基)氘甲基)-2,2-二氟乙基-1-胺的制备：
步骤2中5-(氘溴甲基)-2-氯吡啶(0.6g)、二氟乙胺(0.9g)和N,N-二异丙基乙胺(1.9g)混合，反应混合物置于45℃搅拌过夜，之后直接旋干，柱层析纯化，以乙酸乙酯/石油醚梯度洗脱得到目标化合物0.5g，收率84％。
步骤4：4-(((6-氯吡啶-3-基)氘甲基)(2,2-二氟乙基)氨基)呋喃-2(5H)-酮的制备：
将步骤3中N-((6-氯吡啶-3-基)氘甲基)-2,2-二氟乙基-1-胺(0.4g)溶解在甲苯(35mL)中，并向其中先后加入4-羟基-2-氧代-2,5-二氢呋喃-3-羧酸乙酯(0.7g)和硫酸氢钾(0.3g)，得到的混合物在90℃反应5.5h。将温度冷却到室温后，反应混合物用饱和氯化钠水溶液洗两次。有机相干燥(硫酸钠)，抽滤，旋干，柱层析纯化，以乙酸乙酯/石油醚梯度洗脱得到目标化合物0.3g，收率52％。
实施例6
3-氯-4-(((6-氯吡啶-3-基)二氘甲基)(2，2-二氟乙基)氨基)呋喃-2(5H)-酮的制备：
Figure PCTCN2020101430-appb-000022
化合物4
将4-(((6-氯吡啶-3-基)二氘甲基)(2,2-二氟乙基)氨基)呋喃-2(5H)-酮(0.3g)溶于乙腈(40mL)中，加入三乙胺(0.5g)和NCS(0.5g)。室温搅拌20h后，直接旋干，柱层析纯化，以乙酸乙酯/石油醚梯度洗脱得到目标化合物0.1g，收率36％。
实施例7
4-(((6-三氟甲基吡啶-3-基)甲基)(1,1-二氘-2,2-二氟乙基)氨基)呋喃-2(5H)-酮的制备：
Figure PCTCN2020101430-appb-000023
化合物5
步骤1：2,2-二氟-N-((6-(三氟甲基)吡啶-3-基)甲基)乙酰胺)的制备：
将((6-三氟甲基)吡啶-3-基)甲胺(1.0g)溶于65mL DCM中，向其中滴加二氟乙酸酐(0.9mL)，室温搅拌4h后，减压旋干溶剂，以乙酸乙酯/石油醚梯度洗脱得到目标化合物1.1g，收率77％。
步骤2：N-((6-三氟甲基吡啶-3-基)甲基)-1,1-二氘-2,2-二氟乙基-1-胺的制备：
向烧瓶中加入的步骤1中所得酰胺(0.7g)，用25mL THF溶解，之后慢慢加入NaBD4(0.5g)。将体系冷却至0℃后，加入2.5mL的BF 3乙醚溶液，并搅拌过夜。之后 用甲醇淬灭反应，再加入50％的氢氧化钠水溶液，调节pH>12，用乙酸乙酯萃取反应液，有机相用饱和食盐水洗涤后，用硫酸钠干燥，抽滤，减压蒸发，以乙酸乙酯/石油醚梯度洗脱得到目标化合物0.4g，收率57％。
步骤3：4-(((6-三氟甲基吡啶-3-基)甲基)(1,1-二氘-2,2-二氟乙基)氨基)呋喃-2(5H)-酮的制备：
将步骤2中N-((6-三氟甲基吡啶-3-基)甲基)-1,1-二氘-2,2-二氟乙基-1-胺(0.3g)溶解在丁腈(25mL)中，并向其中先后加入2-乙氧基-4-氧代-4,5-二氢呋喃-3-羧酸乙酯(0.5g)和硫酸氢钾(0.4g)，得到的混合物在125℃回流5h。将温度冷却到室温后，反应混合物用饱和氯化钠水溶液洗两次。将有机相干燥(硫酸钠)，抽滤，旋干，柱层析纯化，以乙酸乙酯/石油醚梯度洗脱得到目标化合物0.3g，收率77％。
实施例8
(6-三氟甲基吡啶-3-基)-二氘甲基-胺的制备：
Figure PCTCN2020101430-appb-000024
ZJT-12
步骤1：(6-三氟甲基吡啶基-3-基)二氘甲基-醇的制备
将6-三氟甲基烟酸乙酯(1.0g)溶于THF(20mL)中，向溶液中加入NaBD 4(1.9g)，搅拌0.5h后，滴入甲醇(5mL)，反应室温搅拌过夜。加水淬灭后，水相用乙酸乙酯萃取，有机相用饱和食盐水洗涤，干燥(硫酸钠)，抽滤，旋干，柱层析纯化，以乙酸乙酯/石油醚梯度洗脱得到目标化合物0.6g，收率74％。
步骤2：5-(二氘溴甲基)-2-三氟甲基吡啶的制备
将步骤1中(6-三氟甲基吡啶基-3-基)二氘甲基-醇(0.6g)溶于二氯甲烷(20mL)中，在0℃下滴入PBr 3(1.8g),搅拌4h后，用3N NaOH水溶液淬灭反应，乙酸乙酯萃取水相，有机相用饱和食盐水洗涤，干燥(硫酸钠)，抽滤，旋干，柱层析纯化，以乙酸乙酯/石油醚梯度洗脱得到目标化合物0.7g，收率86％。
步骤3：(6-三氟甲基吡啶-3-基)-二氘甲基-胺的制备：
将5-(二氘溴甲基)-2-三氟甲基吡啶(241mg)加入10mL的THF与甲醇1:1的混合溶剂中，加入3mL 25％的氨水,室温搅拌24h。旋干有机溶剂，用乙酸乙酯萃取，用无水硫酸钠干燥，抽滤，减压蒸发，以乙酸乙酯/石油醚梯度洗脱得到目标化合物94mg，收率53％。
通过与上述合成实施例中相似的方法获得本发明的其他化合物，化合物列表如表1所示：
表1
Figure PCTCN2020101430-appb-000025
Figure PCTCN2020101430-appb-000026
Figure PCTCN2020101430-appb-000027
根据与实施例类似的制备方法，合成并可用于制备式(I)化合物的一些中间体，中间体列表如表2所示：
表2
Figure PCTCN2020101430-appb-000028
Figure PCTCN2020101430-appb-000029
Figure PCTCN2020101430-appb-000030
生物实验
下列生物学测试实验所使用的本发明活性化合物，其每个氘代位点的氘代纯度均大于等于95％，一般为大于等于98％。
本发明中氘代纯度的定义如下：通过化学方法，用氢的稳定同位素氘替代化学结构中特定位置的一个氢原子或多个特定氢原子，这些位置中氘的总含量占替换前这 些位置中氢的总含量的百分比。
实施例9：
苜蓿蚜实验(浸虫浸叶法)
溶剂：丙酮
将带有3日龄苜蓿蚜若蚜的蚕豆苗在药液中浸10s，装入预先装有清水的小三角瓶中进行保湿、培养，经所需时间段后，确定以％计的药效。100％意指所有蚜虫被杀死；0％意指没有蚜虫被杀死。
以下制备实施例的化合物在本试验中显示出了良好活性：
实例 活性化合物浓度(mg/L) 3天后的杀灭率(％)
化合物1 40 100％
化合物2 40 100％
化合物6 40 100％
化合物7 10 98％
化合物8 10 93％
化合物9 10 94％
化合物4 4 85％
实施例10：
黄瓜蚜虫实验(叶碟喷雾法)
溶剂：丙酮
将成蚜接在黄瓜叶片上，24h后去成蚜，去成蚜后48h后用喷雾塔将黄瓜幼苗叶片正反面喷雾，晾干，经所需时间段后，确定以％计的药效。100％意指所有蚜虫被杀死；0％意指没有蚜虫被杀死。
以下制备实施例的化合物在本试验中显示出了良好活性：
实例 活性化合物浓度(mg/L) 3天后的杀灭率％
化合物1 4 100 a
化合物2 2 >90％
化合物4 10 >90％
化合物6 2 >90％
化合物7 10 >90％
化合物8 2 >90％
a2天后的杀灭率％
生物学对照实验
实施例11
苜蓿蚜实验(浸虫浸叶法)
溶剂：丙酮
将带有3日龄苜蓿蚜若蚜的蚕豆苗在药液中浸10s，装入预先装有清水的小三角瓶中进行保湿、培养，经所需时间段后，确定以％计的药效。100％意指所有蚜虫被杀死；0％意指没有蚜虫被杀死。通过药效比较氘代化合物与未氘代化合物的活性差别。
以下为部分制备实施例的化合物及其未氘代化合物活性对比：
Figure PCTCN2020101430-appb-000031
实施例12
烟粉虱(浸叶法)
溶剂：丙酮
将叶碟在药液中浸10s，装入预先装有培养基的离心管中进行保湿，接入烟粉虱培养，3天后，确定以％计的药效，计算其LC50值，以得到相对毒力大小(相对毒力作为对照指标，由对照的LC 50值/本发明活性化合物实例的LC 50值的百分数表示，该数值越大，表明相对于对照化合物，本发明活性化合物具有更高的药效)。
Figure PCTCN2020101430-appb-000032
实施例13
苜蓿蚜实验(浸虫浸叶法)
溶剂：丙酮
将带有3日龄苜蓿蚜若蚜的蚕豆苗在药液中浸10s，装入预先装有清水的小三角瓶中进行保湿、培养，经所需时间段后，确定以％计的药效，计算其LC50值，以得到相对毒力大小(相对毒力作为对照指标，由对照的LC 50值/本发明活性化合物实例LC 50值的百分数表示，该数值越大，表明相对于对照化合物，本发明活性化合物具有更高的药效)。
Figure PCTCN2020101430-appb-000033
Figure PCTCN2020101430-appb-000034
实施例14
黄瓜蚜虫(叶碟喷雾法)
溶剂：丙酮
将成蚜接在黄瓜叶片上，24h后去成蚜，去成蚜后48h后用喷雾塔将黄瓜幼苗叶片正反面喷雾，晾干，经所需时间段后，确定以％计的药效，计算其LC50值，以得到相对毒力大小(相对毒力作为对照指标，由对照的LC 50值/本发明活性化合物实例LC 50值的百分数表示，该数值越大，表明相对于对照化合物，本发明活性化合物具有更高的药效)。
Figure PCTCN2020101430-appb-000035
实施例15
烟粉虱(浸叶法)
溶剂：丙酮
接粉虱前将黄瓜叶片打成叶碟，装入预先装有培养基的离心管中进行保湿，接入烟粉虱培养，经所需时间段后，调查死活虫数，确定以％计的药效。100％意指所有粉虱被杀死；0％意指没有粉虱被杀死。
以下制备实施例的化合物在本试验中均显示出了相比对照化合物更优异的防除效果：
Figure PCTCN2020101430-appb-000036
实施例16
褐飞虱(稻茎浸渍法)
溶剂：丙酮
将稻苗在药液中浸15s，晾干后置于一次性杯中，每杯接入3龄若虫15头，药后经所需时间段后检查死活虫数，统计死亡率。
Figure PCTCN2020101430-appb-000037
实施例17
褐飞虱(稻茎浸渍法)
溶剂：丙酮
将稻苗在药液中浸15s，晾干后置于一次性杯中，每杯接入3龄若虫15头，药后经所需时间段后检查死活虫数，统计死亡率。
Figure PCTCN2020101430-appb-000038
实施例18
番茄根结线虫
溶剂：丙酮
24孔板每孔加0.5mL虫悬液，按系列浓度每孔加0.5mL药液，每个处理3次重复，空白对照加0.5mL无菌水。经所需时间段后检查死活虫数，虫体僵直不动视为死虫，统计死亡率。
Figure PCTCN2020101430-appb-000039
在本发明提及的所有文献都在本申请中引用作为参考，就如同每一篇文献被单独引用作为参考那样。此外应理解，在阅读了本发明的上述讲授内容之后，本领域技术人员可以对本发明作各种改动或修改，这些等价形式同样落于本申请所附权利要求书所限定的范围。

Claims (14)

  1. 一种式(I)化合物，或其对映异构体或非对映异构体或其混合物，或其盐，
    Figure PCTCN2020101430-appb-100001
    其中，
    X为卤素或未氘代的或一次或多次氘代的或全氘代的C 1-C 6卤代烷基；
    R 1为未氘代的或一次或多次氘代的或全氘代的C 1-C 6卤代烷基，或未氘代的或一次或多次氘代的或全氘代的C 2-C 6卤代烯基；
    R 2为氢、氘或卤素，
    Y为O、S、NR 10或CR 11R 12；
    R 3、R 4、R 5、R 6、R 7、R 8、R 9、R 10、R 11和R 12各自独立地选自：氢或氘；
    附加条件为R 1、R 3或R 4中至少一个是氘代的或氘。
  2. 如权利要求1所述的化合物，其特征在于，所述R 1为-CDH-(C 1-C 5卤代烷基)或-CD 2-(C 1-C 5卤代烷基)，较佳地，-CDH-(C 1-C 3卤代烷基)或-CD 2-(C 1-C 3卤代烷基)。
  3. 如权利要求1所述的化合物，其特征在于，所述R 1为二氟甲基、2-氟乙基、2,2-二氟乙基、2-氯-2-氟乙基、3-氟正丙基、2-氟乙烯基、3,3-二氟丙-2-烯基、1，1-二氘-2,2-二氟乙基或1-氘-2,2-二氟乙基。
  4. 如权利要求1所述的化合物，其特征在于，R 1为未氘代的C 1-C 3卤代烷基，且R 3和R 4有且只有一个为氘。
  5. 如权利要求1所述的化合物，其特征在于，所述式(I)化合物具有式(Ia)结构：
    Figure PCTCN2020101430-appb-100002
    其中，X、Y、R 1、R 2、R 3和R 4的定义如权利要求1。
  6. 如权利要求1所述的化合物，其特征在于，所述式(I)化合物选自下组：
    Figure PCTCN2020101430-appb-100003
    Figure PCTCN2020101430-appb-100004
  7. 如权利要求1所述的化合物，其特征在于，所述式I化合物选自下组：
    Figure PCTCN2020101430-appb-100005
  8. 一种组合物，包含如权利要求1所述的化合物、或其对映异构体或非对映异构体或其混合物，或其盐。
  9. 一种如权利要求1所述的化合物、或其对映异构体或非对映异构体或其混合物，或其盐或包含它们的组合物的用途，用于防治害虫。
  10. 如权利要求9所述的用途，其特征在于，所述害虫包括植物害虫、卫生害虫、和/或贮存产品害虫。
  11. 一种如权利要求1所述的化合物、或其对映异构体或非对映异构体或其混合物，或其盐或包含它们的组合物的用途，用于制备防治动物寄生虫的杀虫剂。12.一种防治害虫的方法，将如权利要求1所述的化合物、或其对映异构体或非对映异构体或其混合物，或其盐或包含它们的组合物用于害虫或其生活环境。
  12. 一种用于制备如权利要求1所述式(I)化合物的中间体，或其对映异构体或非对映异构体或其混合物，或其盐，如式(Z)所示：
    Figure PCTCN2020101430-appb-100006
    其中，
    Z为OH、卤素、NH 2或NHR 1；
    X、R 1、R 3、R 4、R 7、R 8和R 9，如权利要求1定义，
    且当Z不含氘时，R 3、R 4至少有一个为氘；
    其中当R 3和R 4均为氘，且X为氯时，Z不为羟基和氯；
    当R 3和R 4一个为氘另一个为氢，且X为氟时，Z不为羟基。
  13. 如权利要求13所述的中间体，其特征在于，所述式(Z)化合物选自下组：
    Figure PCTCN2020101430-appb-100007
    Figure PCTCN2020101430-appb-100008
  14. 一种如权利要求1所述化合物的制备方法，所述方法包括步骤：
    Figure PCTCN2020101430-appb-100009
    在酸性催化剂存在下，是(III)与式(IV)进行反应，从而形成式(I)化合物；
    其中，各个R 2独立地为为H或氘；和
    X、Y、R 1、R 3、R 4、R 5、R 6、R 7、R 8和R 9如权利要求1定义。
PCT/CN2020/101430 2019-07-11 2020-07-10 氘代烯氨羰基化合物及其制备方法和用途 WO2021004541A1 (zh)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
CN201910626698.0 2019-07-11
CN201910626698 2019-07-11
CN202010065322.X 2020-01-20
CN202010065322.XA CN112279840B (zh) 2019-07-11 2020-01-20 氘代烯氨羰基化合物及其制备方法和用途

Publications (1)

Publication Number Publication Date
WO2021004541A1 true WO2021004541A1 (zh) 2021-01-14

Family

ID=74114378

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/CN2020/101430 WO2021004541A1 (zh) 2019-07-11 2020-07-10 氘代烯氨羰基化合物及其制备方法和用途

Country Status (1)

Country Link
WO (1) WO2021004541A1 (zh)

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101065015A (zh) * 2004-10-01 2007-10-31 拜尔农作物科学股份公司 用于处理种子的药剂
CN101466705A (zh) * 2006-03-31 2009-06-24 拜尔农作物科学股份公司 被取代的烯氨羰基化合物
US20110150957A1 (en) * 2008-08-27 2011-06-23 Bayer Cropscience Ag Method Of Controlling Soil Insects

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101065015A (zh) * 2004-10-01 2007-10-31 拜尔农作物科学股份公司 用于处理种子的药剂
CN101466705A (zh) * 2006-03-31 2009-06-24 拜尔农作物科学股份公司 被取代的烯氨羰基化合物
US20110150957A1 (en) * 2008-08-27 2011-06-23 Bayer Cropscience Ag Method Of Controlling Soil Insects

Similar Documents

Publication Publication Date Title
US9339032B2 (en) Heterocyclic compounds as pesticides
US9688681B2 (en) Heterocyclic compounds as pest control agents
KR101732924B1 (ko) 헤테로방향족 및 헤테로사이클릭 치환체를 갖는 안트라닐산 디아미드 유도체
TWI475956B (zh) 作為殺蟲劑之經四唑取代之鄰胺基苯甲醯胺類
KR101423077B1 (ko) 치환된 엔아미노카보닐 화합물
CN103119036B (zh) 作为杀虫剂的杂环化合物
KR101410281B1 (ko) 디옥사진- 및 옥사디아진-치환된 아릴아미드
KR20090030343A (ko) Ｎ'-시아노-ｎ-알킬 할라이드 이미드 아미드 유도체
KR20080110869A (ko) 살충제로 사용되는 치환된 엔아미노카보닐 화합물
KR20080108309A (ko) 치환된 엔아미노카보닐 화합물
BRPI0817298B1 (pt) Combinações de substâncias ativas com propriedades inseticidas e acaricidas
BRPI0922042B1 (pt) derivados de 1-arilpirazol diméricos
TWI457347B (zh) 二聚合的阿佛菌素（ａｖｅｒｍｅｃｔｉｎ）及密倍脈心（ｍｉｌｂｅｍｙｃｉｎ）衍生物
US20110118319A1 (en) Insecticidal Arylpyrroline Compounds
US8536202B2 (en) Triazole-substituted anthranilamides as pesticides
KR20130103320A (ko) 감마-니트로케톤으로부터 피롤린을 제조하는 방법 및 살해충제로서 감마-니트로케톤의 용도
JP2012062267A (ja) 殺虫性ピロリンｎ−オキサイド誘導体
CN102469787A (zh) 苯基三唑通过浇水、弥雾或浸渍或者通过处理种子而用于防治昆虫和叶螨的用途
EP2227951A1 (de) Verwendung von Enaminocarbonylverbindungen zur Bekämpfung von durch Insekten übertragenen Viren
KR20070085530A (ko) 살충제로서의 ｎ-헤테로사이클릴 프탈산 디아미드
KR20100051089A (ko) 살충 및 살비성을 지니는 활성 성분 배합물
KR20080015443A (ko) 치환된 아릴 옥심
WO2021004541A1 (zh) 氘代烯氨羰基化合物及其制备方法和用途
US8173641B2 (en) 4-amino-1,2,3-benzoxathiazine-derivatives as pesticides
CN112279840B (zh) 氘代烯氨羰基化合物及其制备方法和用途

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 20836702

Country of ref document: EP

Kind code of ref document: A1

122 Ep: pct application non-entry in european phase

Ref document number: 20836702

Country of ref document: EP

Kind code of ref document: A1