WO2020030093A1 - 一种含有间二酰胺类化合物的药物组合物及其应用 - Google Patents

一种含有间二酰胺类化合物的药物组合物及其应用 Download PDF

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WO2020030093A1
WO2020030093A1 PCT/CN2019/099949 CN2019099949W WO2020030093A1 WO 2020030093 A1 WO2020030093 A1 WO 2020030093A1 CN 2019099949 W CN2019099949 W CN 2019099949W WO 2020030093 A1 WO2020030093 A1 WO 2020030093A1
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active ingredient
compound
pharmaceutical composition
composition containing
suspension
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PCT/CN2019/099949
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English (en)
French (fr)
Inventor
相君成
刘叙杆
吕亮
洪湖
刘吉永
邵佳礼
周丽琪
倪珏萍
Original Assignee
上海泰禾国际贸易有限公司
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Priority claimed from CN201910702255.5A external-priority patent/CN110810410B/zh
Application filed by 上海泰禾国际贸易有限公司 filed Critical 上海泰禾国际贸易有限公司
Publication of WO2020030093A1 publication Critical patent/WO2020030093A1/zh

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    • 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
    • A01N37/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having three bonds to hetero atoms with at the most two bonds to halogen, e.g. carboxylic acids
    • A01N37/18—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having three bonds to hetero atoms with at the most two bonds to halogen, e.g. carboxylic acids containing the group —CO—N<, e.g. carboxylic acid amides or imides; Thio analogues thereof
    • 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
    • A01N37/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having three bonds to hetero atoms with at the most two bonds to halogen, e.g. carboxylic acids
    • A01N37/18—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having three bonds to hetero atoms with at the most two bonds to halogen, e.g. carboxylic acids containing the group —CO—N<, e.g. carboxylic acid amides or imides; Thio analogues thereof
    • A01N37/22—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having three bonds to hetero atoms with at the most two bonds to halogen, e.g. carboxylic acids containing the group —CO—N<, e.g. carboxylic acid amides or imides; Thio analogues thereof the nitrogen atom being directly attached to an aromatic ring system, e.g. anilides
    • 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
    • A01N37/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having three bonds to hetero atoms with at the most two bonds to halogen, e.g. carboxylic acids
    • A01N37/18—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having three bonds to hetero atoms with at the most two bonds to halogen, e.g. carboxylic acids containing the group —CO—N<, e.g. carboxylic acid amides or imides; Thio analogues thereof
    • A01N37/22—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having three bonds to hetero atoms with at the most two bonds to halogen, e.g. carboxylic acids containing the group —CO—N<, e.g. carboxylic acid amides or imides; Thio analogues thereof the nitrogen atom being directly attached to an aromatic ring system, e.g. anilides
    • A01N37/24—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having three bonds to hetero atoms with at the most two bonds to halogen, e.g. carboxylic acids containing the group —CO—N<, e.g. carboxylic acid amides or imides; Thio analogues thereof the nitrogen atom being directly attached to an aromatic ring system, e.g. anilides containing at least one oxygen or sulfur atom being directly attached to the same aromatic ring system
    • 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
    • A01N37/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having three bonds to hetero atoms with at the most two bonds to halogen, e.g. carboxylic acids
    • A01N37/34—Nitriles
    • 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
    • A01N37/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having three bonds to hetero atoms with at the most two bonds to halogen, e.g. carboxylic acids
    • A01N37/44—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having three bonds to hetero atoms with at the most two bonds to halogen, e.g. carboxylic acids containing at least one carboxylic group or a thio analogue, or a derivative thereof, and a nitrogen atom attached to the same carbon skeleton by a single or double bond, this nitrogen atom not being a member of a derivative or of a thio analogue of a carboxylic group, e.g. amino-carboxylic acids
    • 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
    • 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
    • A01N43/64—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with three nitrogen atoms as the only ring hetero atoms
    • A01N43/647—Triazoles; Hydrogenated triazoles
    • A01N43/653—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
    • 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
    • A01N43/64—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with three nitrogen atoms as the only ring hetero atoms
    • A01N43/707—1,2,3- or 1,2,4-triazines; Hydrogenated 1,2,3- or 1,2,4-triazines
    • 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
    • A01N43/90—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having two or more relevant hetero rings, condensed among themselves or with a common carbocyclic ring system
    • 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
    • A01N47/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom not being member of a ring and having no bond to a carbon or hydrogen atom, e.g. derivatives of carbonic acid
    • A01N47/08—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom not being member of a ring and having no bond to a carbon or hydrogen atom, e.g. derivatives of carbonic acid the carbon atom having one or more single bonds to nitrogen atoms
    • A01N47/28—Ureas or thioureas containing the groups >N—CO—N< or >N—CS—N<
    • A01N47/38—Ureas or thioureas containing the groups >N—CO—N< or >N—CS—N< containing the group >N—CO—N< where at least one nitrogen atom is part of a heterocyclic ring; Thio analogues thereof
    • 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
    • A01N47/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom not being member of a ring and having no bond to a carbon or hydrogen atom, e.g. derivatives of carbonic acid
    • A01N47/40—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom not being member of a ring and having no bond to a carbon or hydrogen atom, e.g. derivatives of carbonic acid the carbon atom having a double or triple bond to nitrogen, e.g. cyanates, cyanamides
    • 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
    • A01N51/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds having the sequences of atoms O—N—S, X—O—S, N—N—S, O—N—N or O-halogen, regardless of the number of bonds each atom has and with no atom of these sequences forming part of a heterocyclic ring
    • 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
    • A01N53/00—Biocides, pest repellants or attractants, or plant growth regulators containing cyclopropane carboxylic acids or derivatives thereof
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C237/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups
    • C07C237/28—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atom of at least one of the carboxamide groups bound to a carbon atom of a non-condensed six-membered aromatic ring of the carbon skeleton
    • C07C237/42—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atom of at least one of the carboxamide groups bound to a carbon atom of a non-condensed six-membered aromatic ring of the carbon skeleton having nitrogen atoms of amino groups bound to the carbon skeleton of the acid part, further acylated
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C255/00—Carboxylic acid nitriles
    • C07C255/49—Carboxylic acid nitriles having cyano groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton
    • C07C255/50—Carboxylic acid nitriles having cyano groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton to carbon atoms of non-condensed six-membered aromatic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D271/00—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms
    • C07D271/02—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms not condensed with other rings
    • C07D271/06—1,2,4-Oxadiazoles; Hydrogenated 1,2,4-oxadiazoles

Definitions

  • the present application belongs to the technical field of prevention and control of harmful organisms by pharmaceutical compositions, and relates to a pharmaceutical composition containing metadiamide compounds and its application, and in particular to a pesticide or propyl containing metadiamide compounds and thiamethoxam and the like.
  • Composition of bactericides such as thioconazole and applications thereof.
  • the purpose of the present application is to provide a pharmaceutical composition containing an m-diamide compound and its application.
  • the pharmaceutical composition has a synergistic effect, and can prevent and control diseases caused by pests and diseases.
  • the present application provides a pharmaceutical composition containing an m-diamide compound.
  • the pharmaceutical composition includes an active ingredient A and an active ingredient B.
  • the active ingredient A is an amide compound having a structure represented by Formula I.
  • the active ingredient B includes any one or a combination of two other pesticides or fungicides;
  • Z is selected from hydrogen, fluorine, chlorine, bromine, iodine, cyano, nitro, substituted or unsubstituted 3-10 membered heterocyclic group, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxy, C 1 -C 6 haloalkoxy, C 1 -C 6 alkylsulfinyl, C 1 -C 6 haloalkylsulfinyl, C 1 -C 6 alkylsulfonyl or C 1 -C 6 haloalkylsulfonyl;
  • Q is selected from C 3 -C 8 cycloalkyl or C 3 -C 8 halocycloalkyl;
  • X is selected from hydrogen, fluorine or trifluoromethyl
  • Y 1 is selected from fluorine, chlorine, bromine, iodine, cyano, nitro, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 haloalkoxy, C 2 -C 4 alkenyl , C 2 -C 4 haloalkenyl, C 2 -C 4 alkynyl, C 2 -C 4 haloalkynyl, C 3 -C 8 cycloalkyl, C 3 -C 8 halocycloalkyl, C 1- C 6 alkylcarbonyl, C 1 -C 6 alkylsulfinyl, C 1 -C 6 haloalkylsulfinyl, C 1 -C 6 alkylsulfonyl or C 1 -C 6 haloalkylsulfonyl;
  • Y 2 is selected from bromine, iodine, cyano, nitro, C 1 -C 6 haloalkyl, C 1 -C 6 haloalkoxy, C 2 -C 4 alkenyl, C 2 -C 4 haloalkenyl, C 2 -C 4 alkynyl, C 2 -C 4 haloalkynyl, C 3 -C 8 cycloalkyl, C 3 -C 8 halocycloalkyl, C 1 -C 6 alkylcarbonyl, C 1 -C 6 alkylsulfinyl, C 1 -C 6 haloalkylsulfinyl, C 1 -C 6 alkylsulfonyl or C 1 -C 6 haloalkylsulfonyl;
  • R 1 is selected from hydrogen, fluorine or methoxy
  • R 2 is selected from fluorine or trifluoromethyl
  • R 3 and R 4 are each independently selected from hydrogen, halogen, cyano, nitro, C 1 -C 6 alkyl , C 1 -C 6 haloalkyl, C 3 -C 8 cycloalkyl or C 3 -C 8 halocycloalkyl;
  • n represents an integer of 0 to 3 (for example, 0, 1, 2 or 3); W 1 and W 2 are independently an oxygen atom Or sulfur atom.
  • the pharmaceutical composition using the m-bisamide compound having the structure shown by the formula I as described in the present application as the active ingredient A and blended with the active ingredient B has a synergistic effect between the active ingredient A and the active ingredient B.
  • the control effect is significantly improved, and because the active ingredient A can reach 100% of the insecticidal activity at a low dose, the effect is fast, and the insecticidal activity can be exerted after three days of application.
  • the pharmaceutical composition containing it also has good fast-acting properties, and because of the good effect at low doses, it reduces the damage to plants and humans caused by excessive drug concentrations, and makes the drug residues less during application. , More conducive to environmental protection.
  • the present application provides a pharmaceutical composition containing a compound substituted at the 3-position of m-diamide with an N-cyclopropylmethyl derivative.
  • the pharmaceutical composition includes active ingredient A and active ingredient B.
  • the active ingredient A It is an m-bisamide compound having a structure represented by Formula II, and the active ingredient B includes any one or a combination of other fungicides, insecticides, or acaricides;
  • Z is selected from the group consisting of hydrogen, fluorine, chlorine, bromine, iodine, cyano, C 1 -C 6 haloalkyl, C 1 -C 6 haloalkoxy, C 1 -C 6 alkylsulfonyl, or C 1 -C 6 haloalkyl Sulfonyl
  • Y is selected from C 1 -C 6 haloalkyl or C 1 -C 6 haloalkoxy;
  • R is selected from hydrogen or methyl.
  • Z is selected from hydrogen, fluorine, chlorine, bromine, iodine, cyano, trifluoromethoxy, trifluoromethyl, methanesulfonyl, or trifluoromethanesulfonyl.
  • Y is selected from trifluoromethyl or trifluoromethoxy
  • R is selected from hydrogen or methyl.
  • the m-bisamide compound is any one of the compounds shown in Table 1 below having the general formula II.
  • W 2 is selected from oxygen.
  • H is a hydrogen atom
  • F is a fluorine atom
  • Cl is a chlorine atom
  • Br is a bromine atom
  • I is an iodine atom
  • CN is a cyano group
  • CF 3 is trifluoromethyl Group
  • OCF 3 is trifluoromethoxy
  • MeS (O) 2 represents methanesulfonyl
  • CF 3 S (O) 2 represents trifluoromethanesulfonyl.
  • the m-diamide compound is any one or a combination of at least two selected from the following compounds 1-14:
  • C 1 -C 6 alkyl refers to a straight or branched chain alkyl group having 1 to 6 carbon atoms, and includes, without limitation, methyl, ethyl, n-propyl, isopropyl, N-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, iso-pentyl, n-hexyl and the like.
  • C 1 -C 6 alkoxy refers to a straight or branched chain alkoxy group having 1 to 6 carbon atoms, including without limitation methoxy, ethoxy, n-propoxy, isopropyl Oxy, t-butoxy and the like.
  • C 1 -C 6 haloalkyl refers to an alkyl group having 1 to 6 carbon atoms substituted with a halogen, and includes, without limitation, chloromethyl, 1-chloroethyl, 2-bromo-n-propyl, and the like.
  • C 1 -C 6 haloalkoxy refers to an alkoxy group having 1 to 6 carbon atoms substituted with halogen; similarly the term “C 3 -C 8 cycloalkyl” refers to having 3 to 8 on the ring A cyclic alkyl group of one carbon atom, including but not limited to cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, etc .; the term “C3-C8 halocycloalkane” used in this application "Group” refers to a cyclic alkyl group having 3 to 8 carbon atoms substituted with a halogen on the ring, and includes, without limitation, 1-chlorocyclopropyl, 1-fluorocyclopropyl, perfluorocyclopropyl , 1-chlorocyclobutyl, 1-chlorocyclopentyl and the like.
  • C 1 -C 6 , C 3 -C 8, etc. before the specific group indicate the number of carbon atoms contained in the group, for example, C 1 -C 6 indicates that the number of carbon atoms can be 1, 2 , 3, 4, 5, or 6 groups, C 3 -C 8 represent groups having 3 , 4, 5, 6, 7, or 8 carbon atoms, and so on.
  • the insecticides are mainly used to prevent stabbing / fileting / sucking mouthparts insecticides, and the fungicides are mainly seed treatment agents.
  • the insecticide is selected from neonicotinoid insecticides such as thiamethoxam, imidacloprid, clothianidin, clothianidin, acetamiprid, nitenpyram, furfuran, and epoxifen, Or selected from the group consisting of flupurone, flufenacil, flubendipyram, pymetrozine, buprofezin, triflufenapyr, dichloromethizodiaz, afidopyropen, pyrifluquinazon, benzpyrimoxan and other agents for controlling planthoppers, leafhoppers, aphids, whitefly, thrips, scale insects, etc .; the fungicides are selected from anisole, tebuconazole, prothioconazole, cyclopropazole Alcohol, azoxystrobin, oxystrobin, pyraclostrobin, picoxystrobin, metalaxyl, metalaxyl,
  • the medicinal composition containing the metadiamide compound is a medicinal composition containing the isodiamide compound (active ingredient A) and the active ingredient B described in Table 2 below, but Not limited to the combinations listed in the table:
  • the insecticidal and bactericidal composition containing a metadiamide compound is a composition containing the active ingredient A and the active ingredient B described in Table 1, and the active ingredient B is not limited to the aforementioned pesticide or Fungicide variety.
  • the combined effect of the insecticidal composition was tested and it was found to have synergistic effects; the insecticidal and bactericidal composition was tested for its synergistic and extended spectrum of activity; in addition, when controlling virus-transmitting insects such as planthoppers and whiteflies After waiting for pests, combined with the treatment of viral diseases, the harm of viral diseases can be effectively controlled.
  • the weight ratio of the active ingredient A and the active ingredient B described herein is 200: 1 to 1: 200, for example, 200: 1, 180: 1, 150: 1, 130: 1, 100: 1, 80: 1, and 60: 1, 40: 1, 20: 1, 10: 1, 1: 1, 1:10, 1:30, 1:50, 1:80, 1: 100, 1: 120, 1: 140, 1: 160, 1: 180 or 1: 200.
  • the pharmaceutical composition containing the metadiamide compound has different preferred weight ratios according to the difference between the active ingredient A and the active ingredient B.
  • the active ingredient is When A and active ingredient B are selected from the ingredients described in Table 3, their preferred weight ratios are shown in Table 3.
  • the isodiamide compound represented by Formula I shown in Table 3 as the active ingredient A is replaced with the isodiamide compound represented by Formula II, which also satisfies the preferred weight ratio in Table 3.
  • the m-diamide compound may also be replaced with a tautomer, an enantiomer, a diastereomer or a salt thereof.
  • a pharmaceutical composition containing the tautomer, enantiomer, diastereomer, or a salt of the m-diamide compound can also exert the same properties as the m-diamide-containing compound described in the present application.
  • the pharmaceutical composition has the same action effect, good insecticidal effect and fast-acting effect at a low dose.
  • the present application provides a pharmaceutical formulation comprising a pharmaceutical composition containing an m-diamide compound as described above and an agrochemically acceptable adjuvant and / or carrier.
  • the weight percentage content of the mesodiamide compound-containing pharmaceutical composition is 0.01-99%, such as 0.01%, 0.1%, 1%, 3%, 5%, 8 %, 10%, 15%, 18%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95% or 99%.
  • the agrochemically acceptable adjuvant includes any one or at least one of a dispersant, a wetting agent, an emulsifier, an antifreeze, a thickener, a defoamer, a preservative, a stabilizer, or a colorant. A combination of the two.
  • the dispersant includes lignin sulfonate, alkylphenol polyoxyethylene ether, naphthalenesulfonic acid formaldehyde condensate sodium salt, fatty amine polyoxyethylene ether, fatty acid polyoxyethylene ester, glycerin fatty acid ester polyoxylate Vinyl ether, polycarboxylate, formaldehyde condensate, calcium alkylbenzenesulfonate, alkylphenol polyoxyethylene ether.
  • the wetting agent is selected from the group consisting of sodium lauryl sulfate, alkyl naphthalene sulfonate, pulverized powder BX, polyoxyethylene ether, EO / PO block polyether, fatty alcohol polyoxyethylene ether, and fatty alcohol polyoxylate.
  • the emulsifier is selected from dodecylbenzenesulfonate, alkylnaphthalenesulfonate, alkylsulfonate, alkylphenol polyoxyethylene ether, benzylphenol polyoxyethylene, phenethylphenol polyoxyethylene Ether, fatty amine polyoxyethylene ether.
  • the antifreeze is selected from ethylene glycol, propylene glycol, and glycerol.
  • the thickener is selected from the group consisting of xanthan gum, hydroxymethyl cellulose, hydroxyethyl cellulose, hydroxypropyl starch, methyl cellulose, sodium starch phosphate, magnesium aluminum silicate, and polyvinyl alcohol.
  • the defoaming agent is selected from the group consisting of silicone oil, silicone compounds, tributyl phosphate, C10-C20 saturated fatty acid compounds, and polyether defoamers.
  • the preservative is selected from the group consisting of formaldehyde, phenyl salicylate, butyl parahydroxybenzoate, and potassium sorbate
  • the stabilizer is selected from triphenyl phosphite, epichlorohydrin, epoxy soybean oil, and silicic acid.
  • Magnesium aluminum, the colorant is selected from the group consisting of azo pigments, titanium oxide, and iron oxide.
  • the carrier includes a filler and / or a solvent
  • the agrochemically acceptable carrier includes a solid carrier and / or a liquid carrier.
  • the solid support includes natural or synthetic clays and silicates, such as natural silica and diatomaceous earth; magnesium silicates such as talc; magnesium aluminum silicates such as kaolinite, kaolin, montmorillonite, and mica; White carbon black, calcium carbonate, light calcium carbonate; calcium sulfate; limestone; sodium sulfate; amine salts such as ammonium sulfate and hexamethylene diamine.
  • Liquid carriers include water and organic solvents.
  • Organic solvents include aromatic hydrocarbons such as xylene, benzene, xylene, toluene, etc .; chlorinated hydrocarbons such as chlorobenzene, vinyl chloride, trichloromethane, dichloromethane, etc .; aliphatic hydrocarbons such as petroleum distillates, Cyclohexane, light mineral oil; alcohols such as isopropanol, butanol, ethylene glycol, propylene glycol, glycerol, and cyclohexanol and their ethers and esters; ketones such as acetone, cyclohexanone, and dimethyl Formamide and N-methyl-pyrrolidone.
  • aromatic hydrocarbons such as xylene, benzene, xylene, toluene, etc .
  • chlorinated hydrocarbons such as chlorobenzene, vinyl chloride, trichloromethane, dichloromethane, etc .
  • the active ingredient may be mixed with a liquid carrier and / or a solid carrier, and auxiliary agents such as emulsifiers, dispersants, stabilizers, wetting agents, adhesives Mixtures, defoamers, antioxidants, etc.
  • auxiliary agents such as emulsifiers, dispersants, stabilizers, wetting agents, adhesives Mixtures, defoamers, antioxidants, etc.
  • the dosage form of the pharmaceutical preparation is a solution, a soluble powder, a soluble granule, an emulsifiable concentrate, a wettable powder, an aqueous emulsion, a suspending agent, a dispersible oil suspending agent, a water-dispersible granule, and a microcapsule suspending agent.
  • Granules, microemulsions, suspension emulsions, microcapsule suspension-suspensions ultra-low-volume liquids, hot aerosols, film-spreading oils, suspended seed coatings, dry powders for seeds, suspensions for seeds, and seeds for Powder dissolving agent, seed treatment dispersible powder, seed treatment emulsion or seed treatment liquid.
  • the dosage form of the pharmaceutical preparation is a solution, a soluble granule, a suspension, an emulsifiable concentrate, a wettable powder, an aqueous emulsion, a water-dispersible granule, a dispersible oil suspension, a microcapsule suspension, and an ultra-low capacity.
  • Liquid, hot aerosol, suspension seed coating or seed treatment dispersible powder is a solution, a soluble granule, a suspension, an emulsifiable concentrate, a wettable powder, an aqueous emulsion, a water-dispersible granule, a dispersible oil suspension, a microcapsule suspension, and an ultra-low capacity.
  • the present application provides the application of the pharmaceutical composition or pharmaceutical preparation containing the metadiamide compound as described above in the prevention, control of plant diseases or insect pests in agriculture, forestry, and horticulture.
  • the medicinal composition or medicinal preparation containing the metadiamide compound described in the present application is suitable for controlling various agricultural, forestry, horticultural and health pests that harm rice, corn, wheat, potato, fruit trees, vegetables, other crops and flowers. And disease.
  • the composition of the present application has a wide range of applications, and the scope of plants or crops to be applied mainly includes the following categories: vegetables, cucumbers, loofahs, watermelons, melon, pumpkins, hanging melon, spinach, celery, cabbage, cabbage, gourd, pepper, eggplant , Tomato, shallot, ginger, garlic, leek, strawberry, lettuce, kidney bean, cowpea, broad bean, radish, carrot, potato, yam; cereal, wheat, barley, corn, rice, sorghum; fruit tree, apple, pear, banana , Citrus, grape, lychee, mango; flowers, peony, rose, flamingo; oil crops, peanuts, soybeans, rape, sunflower, sesame; sugar crops, sugar beets, sugar cane; other crops, such as potatoes, sweet potatoes, tobacco and Tea; horticulture, forestry, home health, public health areas, etc .; the above-listed plants or crops have no limiting effect on the scope of use of the pharmaceutical
  • the pests include lepidoptera, coleoptera, hemiptera, tarptera, diptera, orthoptera, homoptera, isoptera, hymenoptera, and spider mite
  • said Diseases include diseases caused by semi-known bacteria, ascomycetes, basidiomycetes, and the like.
  • the pests include but are not limited to: cotton bollworm, diamondback moth, Spodoptera exigua, Spodoptera litura, Pieris rapae, diploid pupae, pupae trichoderma, big pupae, Spodoptera frugipera, rice leaf roller, rice Thrips, western flower thrips, melon thrips, onion thrips, ginger thrips, mango thrips, peach aphid, cotton aphid, alfalfa aphid, apple yellow aphid, wheat aphid, jumping beetle, stink bug, gray planthopper, Brown planthopper, white-backed planthopper, termite, mosquito fly, spider mite, citrus red spider.
  • the diseases include, but are not limited to, wheat scab, rice sheath blight, rice blast and the like.
  • the method of using the pharmaceutical composition or pharmaceutical preparation is spraying, soil treatment, seed treatment, flight prevention, and the like.
  • the present application provides the application of the medicinal compound-containing medicinal composition or medicinal preparation as described above in seed treatment of plants, crops, or flowers.
  • the present application provides a method for controlling plant diseases, which method is: applying an effective dose of a pharmaceutical composition containing an m-diamide compound as described above to a plant disease to be controlled or a growth medium thereof. Or pharmaceutical preparations.
  • the effective dose is 1-1000g per hectare, such as 1g, 5g, 8g, 10g, 20g, 50g, 80g, 100g, 120g, 150g, 180g, 200g, 250g, 300g, 350g, 400g, 450g, 500g , 600g, 700g, 800g, 900g or 1000g, preferably 7.5-500g per hectare.
  • composition of the present application may be applied to the disease or its growth medium in the form of a formulation.
  • the compound of the general formula I (especially the compound of the general formula II) is dissolved or dispersed in a carrier as an active ingredient or formulated into a formulation for easier dispersion when used as a fungicide.
  • these chemical preparations can be formulated as solution, emulsifiable concentrate, wettable powder, water emulsion, suspension, dispersible oil suspension, water-dispersible granule, seed treatment, microcapsule suspension, granule, microemulsion , Suspension emulsion, suspension-microcapsule suspension and so on.
  • the pharmaceutical composition provided by the present application has the following advantages in use:
  • composition of active ingredient A and active ingredient B in this application has a synergistic effect.
  • the amount of the composition used is greatly reduced compared with the single active ingredient alone, and the control effect is significantly improved.
  • composition of the present application can treat both diseases and insects, expand the spectrum of control, reduce the frequency of application, and save labor costs for application.
  • Methyl 2-fluoro-3- (N- (cyclopropylmethyl) benzamide) benzoate (13.00 g, 40.88 mmol) was dissolved in methanol (100 mL), and a 10% aqueous sodium hydroxide solution (6.54 g) was added. , 163.52 mmol, 65.4 mL), after stirring at room temperature for 2 h, the reaction was monitored by TLC for completion. The methanol was concentrated and removed under reduced pressure. The concentrated residue was dissolved in water (100 mL) and extracted with ethyl acetate (50 mL). The organic phase was discarded, and the pH of the aqueous phase was adjusted to 7 with a 2M aqueous hydrochloric acid solution.
  • 2-Bromo-6-trifluoromethyl-4-heptafluoroisopropylaniline (0.52 g, 1.28 mmol) was dissolved in tetrahydrofuran (4 mL), and lithium diisopropylaminoamide (0.77 mL) was added dropwise at -70 ° C. , 1.54 mmol), 5 minutes later, a tetrafluorofuran solution of 2-fluoro-3- [N- (cyclopropylmethyl) benzamido] benzoyl chloride synthesized in one step was added dropwise, stirred at -70 ° C for 30 minutes, and raised to Stirring was continued for 30 min at room temperature.
  • a saturated ammonium chloride aqueous solution (20 mL) was added to the reaction solution, and the mixture was extracted with ethyl acetate (20 mL). The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure.
  • Methyl 2-fluoro-3-aminobenzoate (2.00 g, 11.82 mmol) was dissolved in 1,2-dichloroethane (65 mL), and cyclopropylmethyl ketone (2.98 g, 35.47 mmol) was sequentially added at room temperature. ), Trifluoroacetic acid (8.08 g, 70.92 mmol) and sodium triacetoxyborohydride (7.51 g, 35.47 mmol). The reaction was heated to 45 ° C. for 1 h. When TLC monitored that the reaction was no longer in progress, the reaction was terminated. A saturated NaHCO 3 solution (50 mL) was added to the reaction solution, and extracted with dichloromethane (80 mL).
  • the 1 H NMR (400 MHz, CDCl 3 -d) data of Compound 2 is as follows: ⁇ [ppm]: 8.19 (s, 1H), 8.05-7.95 (m, 1H), 7.89 (s, 1H), 7.77-7.73 (m , 1H), 7.56-7.52 (m, 1H), 7.28-7.11 (m, 6H), 4.26-4.23 (m, 1H), 1.63 (br s, 2H), 1.51 (br s, 1H), 0.89-0.40 (m, 5H).
  • composition of 25% compound 4 ⁇ thiamethoxam water-dispersible granules is shown in Table 5 below:
  • Preparation method Calculate the amount of each material according to the formula, and mix compound 4, thiamethoxam, sodium lauryl sulfate, sodium lignin sulfonate, sodium naphthalene formaldehyde polymer sulfonate, ammonium sulfate, corn starch, and kaolin. Crush with an air jet mill to an average particle size of 10 to 15 microns, add 17% of the amount of water and knead, then granulate by rotary extrusion, dry at 50 ° C for 3 hours, screen, and pass the sampling test. % Compound 4 ⁇ thiamethoxam water-dispersible granules.
  • Preparation method Calculate the amount of each material according to the formula. In a 250ml three-necked flask, add deionized water, add propylene glycol methyl ether, then add compound 8, flupranone, heat to 30-40 ° C, stir for 2 hours, and finally add The fatty alcohol polyoxyethylene ether is uniformly dissolved, filtered, and sampling tests are qualified to obtain a solution of 24% compound 8 ⁇ fluoropyranone.
  • composition of 10% Compound 1 ⁇ acetamiprid EC is shown in Table 7 below:
  • Preparation method Calculate the amount of each material according to the formula, add 200 solvent oil to the batching kettle, and then add compound 1 and acetamiprid after dissolution, then add calcium dodecylbenzenesulfonate and castor oil polyoxyethylene ether Add, stir at 40-50 ° C for 1.5 hours, filter, and pass the sampling test to obtain 10% Compound 1 ⁇ Acetamiprid EC.
  • composition of 30% compound 10 ⁇ pymetrozine wettable powder is shown in Table 8 below:
  • Preparation method Calculate the amount of each material according to the formula. Put compound 10, pymetrozine, sodium lauryl sulfate, sodium lignin sulfonate, and kaolin in the batching kettle. After mixing well, use a jet mill to pulverize to the average size The diameter is 10 micrometers, and the sampling test is qualified to obtain 30% compound 10 ⁇ pymetrozine wettable powder.
  • Active ingredient A Trifluorophenylpyrimidine
  • Active ingredient B Fatty alcohol polyoxyethylene ether 1.5 moisturizer Tristyryl phenol polyoxyethylene ether phosphate 2
  • Dispersant Propylene glycol 4 antifreeze 1% xanthan gum solution 10
  • Thickener Casson 0.1 preservative Polydimethylsiloxane emulsion 0.2 Silicone defoamer Deionized water Make up 100 Carrier
  • Preparation method Calculate the amount of each material according to the formula, deionized water, propylene glycol, polydimethylsiloxane emulsion, tristyryl phenol polyoxyethylene ether phosphate, sodium lignin sulfonate, card pine, and defoaming
  • the agent is stirred and dissolved uniformly.
  • Trifluorophenylpyrimidine and compound 5 are added to shear uniformly, and then ground by a sand mill to an average particle diameter of 2 microns, and 10 parts of a 1% xanthan gum solution are added and stirred for 30 minutes to obtain 20% compound 5 ⁇ Trifluoropyrimidine suspension.
  • composition of the 35% compound 8-cyanenic acid suspension seed coating agent is shown in Table 10 below:
  • Preparation method In a batching kettle, according to the proportion of the materials, deionized water, compound 8, cyanoclostrobin, tristyryl phenol polyoxyethylene ether phosphate triethanolamine salt, block polyoxyethylene ether, and carson The polydimethylsiloxane emulsion and propylene glycol were sanded after shearing to control the particle size of D90 to about 5 microns, and then transferred to a mixing tank. 2% xanthan gum solution and pigment F2R were mixed and stirred for 1 hour. After that, the finished product 35% compound 8 ⁇ cyanenosin suspension seed coating agent was obtained.
  • composition of 15% Compound 1 ⁇ prothioconazole suspension is shown in Table 11 below:
  • Active ingredient A Prothioconazole 5
  • Active ingredient B Fatty alcohol polyoxyethylene ether 1.5 moisturizer Tristyryl phenol polyoxyethylene ether phosphate 2
  • Dispersant Propylene glycol 4 antifreeze 1% xanthan gum solution 10
  • Thickener Casson 0.1 preservative Polydimethylsiloxane emulsion 0.2 Silicone defoamer Deionized water Make up 100 Carrier
  • Preparation method Calculate the amount of each material according to the formula, and stir the deionized water, propylene glycol, fatty alcohol polyoxyethylene ether, tristylenol phenol polyoxyethylene ether phosphate, sodium lignin sulfonate, card pine, and defoamer Dissolve uniformly, add prothioconazole and compound 1 to shear uniformly, and then grind to an average particle size of 2 microns with a sand mill. Add 10 parts of 1% xanthan gum solution and stir for 30 minutes to obtain 15% compound 1 ⁇ propylthiol. Iconazole suspension.
  • composition of the 30% compound 8 dicycloprofen dispersible liquid is shown in Table 12 below:
  • Preparation method In a batching kettle, according to the process ratio, add No. 100 solvent oil and cyclohexanone, add compound 8 and dicycloprofen with stirring, heat to 50 ° C, and add castor oil polyoxyethylene ether. , The fatty alcohol polyoxyethylene ether, polydimethylsiloxane emulsion was continued to stir for 10 minutes, and deionized water was added after the temperature was reduced to obtain 30% of a compound 8 ⁇ biprofen dispersible liquid solution.
  • Formulation agent 9 40% Compound 1 ⁇ Mexamide aqueous emulsion
  • composition of 40% Compound 1 ⁇ Mexamide aqueous emulsion is shown in Table 13 below:
  • Preparation method In a batching kettle, first add solvent oil No. 150, then start stirring, add compound 1 and stir to dissolve. After the dissolution is complete, add prochloraz and emulsifier block polyoxyethylene ether compound, and continue to stir for 20 Minutes, mix evenly into the oil phase and set aside; put deionized water, defoamer and antifreeze in the shear kettle, turn on the shearing device, add the oil phase materials slowly after 5 minutes, and shear for 10 minutes after the addition To obtain 40% Compound 1 ⁇ Mexamide aqueous emulsion.
  • Bioassay Example 1 Active ingredient A has significant activity against various pests
  • Target 3rd instar larvae of Plutella xylostella, 3rd instar larvae of armyworm, 3rd instar larvae of cotton bollworm, all reared indoors.
  • Plutella xylostella + leaf soaking feeding method With reference to NY / 1154.14-2008, the main operation description is as follows: immerse the clean bract leaf dish in the medicinal solution for 10s, dry it and place it in petri dishes, 4 dishes per dish, put filter paper in the petri dish to moisturize. Ten dishes of Plutella xylostella were received in each dish and repeated three times. It was placed in a light incubator at a temperature of 25 ° C under 14hL: 10hD and cultured. The number of dead insects of Plutella xylostella was investigated 3 days after the administration, and the mortality was calculated.
  • Feeding on slime + dipping leaf With reference to NY / 1154.14-2008, the main operation description is as follows: immerse the corn leaf segment in the medicinal solution for 10s, dry it and place it in a petri dish, 4 pieces per dish, put filter paper in the petri dish to moisturize. Ten dishes of slimeworms were received in each dish, and 3 replicates were performed. It was placed in a light incubator at a temperature of 25 ° C under 14hL: 10hD and cultured. The number of dead insects of the armyworm was investigated 3 days after the administration, and the mortality was calculated.
  • Erhuan + rice stalk dipping method With reference to NY / T1154.11-2008, the main operation is as follows: immerse the cleaned rice stalks in the medicinal solution for 10s, remove them, place them in a cool place to dry, put them into finger tubes, and insert 10 third-instar larvae. Each treatment was repeated 3 times. The mouth of the tube was sealed with a black cotton cloth. The rubber band was tied tightly and placed in a light incubator at 28 ° C in the dark. The number of dead worms in P. chinensis was investigated 3 days after the treatment, and the mortality of each treatment was calculated.
  • Bioassay Example 2 Active ingredient A is a compound of formula II and active ingredient B is an insecticide such as acetamiprid, dichlorothiapyrimidine and other insecticides.
  • Target Plutella xylostella 3rd instar larvae, reared indoors.
  • Theoretical Mortality 1-(1-mortality of active ingredient A at this dose) (1- mortality of active ingredient B at this dose)
  • Synergistic effect ⁇ 20 means significant synergy; 10 ⁇ synergistic effect ⁇ 20, synergistic effect; -10 ⁇ synergistic effect ⁇ 10, synergistic effect; synergistic effect ⁇ -10, antagonistic, negative value The greater the degree of antagonism.
  • Test agent or combination name Dose mg / L 3d mortality% Theoretical mortality% Synergy effect Joint mode of action Compound 1 0.01 36.67 / / / Compound 4 0.01 43.33 / / / Compound 8 0.02 53.33 / / Acetamiprid 4.0 60.00 / / / Dichlorothiapyrimidine 4.0 70.00 / / / Compound 1+ Acetamiprid 0.01 + 4.0 100 74.67 25.33
  • Bioassay Example 3 Active ingredient A is a compound of formula II and active ingredient B is a combination of insecticides such as thiamethoxam, trifluorophenylpyrimidin, flufenapron, and other insecticides.
  • Dipping method Dipping method. The operation is described as follows: cabbage dish preparation, moisturizing petioles with cotton balls. If aphids are prepared: 5 aphids are attached to each dish, and then aphids are removed after 24 hours. Leaf discs with more than 15 aphids are selected before the test.
  • the treatment method is the immersion method: immerse the leaf dish (with aphid) in the medicinal solution for 10 s, and repeat it 3 times. Post-treatment culture and investigation: placed in a light incubator at 25 ° C, 14hL: 10hD, and cultured. The number of aphid dead insects was investigated 3 days after the administration, and the mortality was calculated.
  • the evaluation method was the same as that in Example 2.
  • Test agent or combination name Dose mg / L 3d mortality% Theoretical mortality% Synergy effect Joint mode of action
  • Bioassay Example 4 Active ingredient A is a compound of formula II and active ingredient B is a combination of trifluorophenylpyrimidine, epoxifen, and flupyranone insecticides.
  • Target 3rd instar larvae of pupae, indoor breeding.
  • Example 1 of contemporaneous bioassay the evaluation method is the same as that of standard bioassay embodiment 2.
  • Test agent or combination name Dose mg / L 3d mortality% Theoretical mortality% Synergy effect Joint mode of action Compound 5 1.0 63.33 / / / Compound 7 0.5 50.00 / / / Compound 9 1.0 66.67 / / / Compound 10 0.7 50.00 / / / Compound 11 1.0 56.67 / / / Compound 12 1.0 56.67 / / / Compound 13 0.5 33.33 / / / Trifluorophenylpyrimidine 10 56.67 / / / Flupranone 40 76.67 / / / Epoxifen 100 73.33 / / / Compound 5 + trifluorophenylpyrimidine 1.0 + 10 100 84.11 15.89 Synergy Compound 7 + trifluorophenylpyrimidine 0.5 + 10 100 78.33 21.67 Significant synergy Compound 12 + trifluorophenylpyrimidine
  • Bioassay Example 5 Composition of active ingredient A compound of formula II and active ingredient B are fungicides such as prothioconazole and tebuconazole, and its activity against wheat powdery mildew
  • Target powdery mildew of wheat, indoor storage of bacteria.
  • Method Potted spray method. Spray first, then inoculate, then cultivate and investigate.
  • the wheat seedlings were placed on the rotating plate of the biological test spray tower (the frequency was set to F35, which is 14 rpm), and the preparation was sprayed evenly on the prepared wheat seedlings with a throat sprayer, and 3 pots of wheat were processed every time.
  • Spray 12mL of each treatment liquid place in the room to air dry.
  • the same agent is applied sequentially from low concentration to high concentration. Wash the spray tower turntable, throat sprayer reservoir cup and spray head 3 times each before applying and between different medicaments.
  • the powdery mildew spores generated from the diseased wheat leaves about 10 days after the inoculation were shaken down uniformly and inoculated on the potted wheat seedlings, and cultured in a cultivation room at 18-22 ° C.
  • the classification method is as follows: Grade 0: No disease; Grade 1: The diseased area accounts for less than 5% of the entire leaf area; Grade 3: The diseased area accounts for Less than 6% to 15% of the entire leaf area; Level 5: The diseased area accounts for 16% to 25% of the entire leaf area; Level 7: The diseased area accounts for 26% to 50% of the entire leaf area; Grade 9: The area of diseased spots accounts for more than 50% of the entire leaf area.
  • the evaluation method is the same as the standard test example 2.
  • Test agent or combination name Dose mg / L Actual prevention effect% Theoretical prevention effect% Synergy effect Joint mode of action Compound 1 500 0 / / / Compound 1 50 0 / / / Compound 8 5 0 / / / Compound 8 0.05 0 / / / Prothioconazole 5 46 / / / Tebuconazole 5 95 / / / Compound 1 + prothioconazole 500 + 5 50 46 4 Add up Compound 1 + prothioconazole 50 + 5 53 46 7 Add up Compound 8+ Tebuconazole 5 + 5 98 95 3 Add up Compound 8+ Tebuconazole 0.05 + 5 97 95 2 Add up
  • Bioassay Example 6 Active ingredient A is a compound of formula II and active ingredient B is a fungicide composition such as oxystrobin, pyraclostrobin, and other fungicides, and its activity is tested against rice blast
  • Target Rice blast, rice strains kept indoors.
  • Method Potted spray method. Spray first, then inoculate, then cultivate and investigate.
  • Chemical treatment Put every 3 pots of seedlings in the center of the rotary disk of the circular biological spraying tower, set the rotary frequency f of the rotary disk to 35 (14 revolutions / min), and use a laryngeal sprayer (pressure for each processed 10mL) 0.15 MPa) sprayed evenly on the leaf surface of rice, and the medicinal solution was naturally air-dried. For every 3 pots, a blank control was set.
  • spore suspension The rice blast fungus plate was cultured for about 5 days on the rice bran medium, and the spores were washed with a spore eluent (0.1% Tween + 1% glucose + 0.4% yeast extract), 2 to 4 layer gauze filter with a hemocytometer microscopic spores of rice blast fungus were counted and calculated spore concentration was diluted to 106 / mL, and is made of a spore suspension at 10 times magnification standby. Inoculation and cultivation: 24 hours after the treatment with the medicine, evenly inoculate the spore suspension with a throat sprayer (pressure 0.15MP).
  • the inoculation amount of the spore suspension is 30mL / 24 pot seedlings. After inoculation, move to the humidifier, and then use the throat sprayer to the humidifier Spray 40mL of eluent in the middle to increase the humidity of the humidifier (make sure that the relative humidity in the humidifier is 100% and keep the leaf surface dew condensation).
  • the temperature of the artificial climate chamber is set to 28 ° C. Then, the cells were cultured in a humid chamber at 28 ° C. and a relative humidity of 85% to 90% for 12 hours under light / dark conditions for 5 to 7 days. Survey time: 5 to 7 days after treatment, the survey was performed based on the incidence of the blank control (the diseased leaf rate reached above 50%), and the survey was conducted once.
  • Investigation method investigate the total number of plants per treatment, the penultimate leaf of each plant.
  • the grading methods of rice blast are: level 0: whole plant is disease-free; level 1: brown spots are present (1 to 5 lesions); level 3: typical spindle-shaped lesions appear, and the area of lesions accounts for the entire leaf area Less than 5% (5 to 10 lesions); Grade 5: Typical lesions, the area of which is 6 to 25% of the entire leaf area (11 to 16 lesions); Grade 7: Typical lesions, lesions The area accounts for 26% to 50% of the whole leaf area (16 to 25 lesions); level 9: typical lesions, the area of the lesions accounts for more than 50% of the whole leaf area (more than 25 lesions).
  • the evaluation method is the same as the standard test example 2.
  • Test agent or combination name Dose mg / L Actual prevention effect% Theoretical prevention effect% Synergy effect Joint mode of action Compound 8 0.05 0 / / / Compound 8 0.5 0 / / / Compound 10 40 0 / / / Compound 10 400 0 / / / Oxystrobin 4 85 / / / Pyraclostrobin 5 75 / / / Compound 8+ oxystrobin 0.05 + 4 90 85 5 Add up Compound 8+ oxystrobin 0.5 + 4 90 85 5 Add up Compound 10+ pyraclostrobin 40 + 5 80 75 5 Add up Compound 10+ pyraclostrobin 400 + 5 80 75 5 Add up Compound 10+ pyraclostrobin 400 + 5 80 75 5 Add up
  • Bioassay Example 7 Active ingredient A is a compound of formula II and active ingredient B is a composition of fungicides such as prothioconazole and cyanobenil, and is tested for wheat scab
  • Target wheat scab, preserved bacteria indoors.
  • the evaluation method is the same as the standard test example 2.
  • Test agent or combination name Dose (mg / L) Actual prevention effect% Theoretical prevention effect% Synergy effect Joint mode of action Compound 4 0.05 0 Zh Zh Zh Compound 4 0.5 0 Zh Zh Zh Compound 6 40 0 Zh Zh Zh Compound 6 400 0 Zh Zh Zh Prothioconazole 4 80 Zh Zh Zh Cyanurin 5 60 Zh Zh Zh
  • Bioassay Example 8 When the active ingredient A is compound 4 and the active ingredient B is epoxifen, it has a synergistic effect on brown planthoppers
  • Test target Brown planthopper, 3rd instar nymph.
  • the evaluation method refers to NY / T1154.7-2006, and the evaluation is based on the co-toxicity coefficient.
  • the co-toxicity coefficient (CTC value) of the mixture is calculated according to formula (1), formula (2), and formula (3):
  • TTI A ⁇ P A + B ⁇ P B ⁇ ⁇ (2)
  • CTC co-toxicity coefficient
  • ATI mixed actual virulence index
  • TTI mixed theoretical virulence index
  • the co-toxicity coefficient (CTC) ⁇ 120 of the compounding agent is synergistic; CTC ⁇ 80 is antagonistic; 80 ⁇ CTC ⁇ 120 is additive.
  • Bioassay Example 9 A composition in which active ingredient A is compound 7 and active ingredient B is thiamethoxam has a synergistic effect on aphids.
  • Target alfalfa aphids, 3-day-old nymphs.
  • Bioassay Example 3 For method operation, refer to Bioassay Example 3.
  • Medicament treatment immerse the nymph leaves in the medicinal solution for 10s, insert them into a penicillin bottle filled with water, seal them, dry them, and cover them with transparent plastic cups, repeating aphids 15-30 Head, repeated 3 times per treatment. When dipping, the same medicament is performed in order from low concentration to high concentration, and a blank control and a solvent control are set. After the treatment, it was placed in an observation room with an indoor temperature of 19 to 26 ° C., a humidity of 35% to 65%, and a culture rack with 14Lh: 10Dh light.
  • Bioassay Example 10 When the active ingredient A is compound 8 and the active ingredient B is fluprone, it has a synergistic effect on rice brown planthopper.
  • Test target Brown planthopper, 3rd instar nymph.
  • Bioassay Example 11 When active ingredient A is compound 7 and active ingredient B is pymetrozine, it has a synergistic effect on rice brown planthopper.
  • Test target Brown planthopper, 3rd instar nymph.
  • Bioassay Example 12 Activity Test on Plutella xylostella when Active Ingredient A is Compound 1 and Active Ingredient B is Dichlorothiapyrimidine
  • the method of immersed leaf dish feeding method was used to operate the synbiotic test example 1, and the symbiotic test example 8 was evaluated.
  • Target Plutella xylostella 3rd instar larva.
  • Bioassay Example 13 When active ingredient A is compound 7 and active ingredient B is diprofen, it has a synergistic effect on vegetable aphids.
  • the dipping method was used to operate the synbiotic test example 9 and evaluate the syngene test example 8.
  • Target Alfalfa aphids at 3 days old.

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Abstract

一种含有间二酰胺类化合物的药物组合物及其应用，所述药物组合物包括有效成分A和有效成分B，所述有效成分A为具有式I所示结构的间二酰胺类化合物，所述有效成分B为噻虫嗪等杀虫剂、丙硫菌唑等杀菌剂中任意一种或两种的组合。所述含有效成分A和有效成分B的组合物，具有协同增效、扩大防治谱、控制传毒昆虫等独特作用，可有效防治水稻、玉米、小麦、蔬菜、果树、花卉、油料、糖料等作物及园艺、林业上的多种病虫害。

Description

一种含有间二酰胺类化合物的药物组合物及其应用 技术领域
本申请属于药物组合物防治有害生物的技术领域，涉及一种含有间二酰胺类化合物的药物组合物及其应用，尤其涉及一种含有间二酰胺类化合物与噻虫嗪等杀虫剂或丙硫菌唑等杀菌剂的组合物及其应用。
背景技术
在农业及园艺等作物生产中，由病虫害等引起的侵害依然非常显著，由于生物多样性、多种病虫害同时发生，所以，植物保护领域一直需要开发活性更好、用量更低、环境更友好的新杀虫剂或者杀虫剂组合物或者杀虫杀菌组合物。而具有协同或增效的杀虫杀菌组合物对扩大杀虫谱、病虫兼治、控制传毒媒介昆虫来治理病毒病、降低农民施药成本等方面都具有重要的作用。
申请内容
针对现有技术存在的问题，本申请的目的在于提供一种含有间二酰胺类化合物的药物组合物及其应用，所述药物组合物具有协同增效作用，能够防治由害虫和病害等引起的多种农业、林业虫害和病害。
为达此目的，本申请采用以下技术方案：
一方面，本申请提供一种含有间二酰胺类化合物的药物组合物，所述药物组合物包括有效成分A和有效成分B，所述有效成分A为具有式I所示结构的酰胺类化合物，所述有效成分B包括其他杀虫剂或杀菌剂中任意一种或两种的组合；
Figure PCTCN2019099949-appb-000001
其中，Z选自氢、氟、氯、溴、碘、氰基、硝基、取代或未取代的3-10元杂环基、C 1-C 6烷基、C 1-C 6卤代烷基、C 1-C 6烷氧基、C 1-C 6卤代烷氧基、C 1-C 6烷基亚磺酰基、C 1-C 6卤代烷基亚磺酰基、C 1-C 6烷基磺酰基或C 1-C 6卤代烷基磺酰基；Q选自C 3-C 8环烷基或C 3-C 8卤代环烷基；
X选自氢、氟或三氟甲基；
Y 1选自氟、氯、溴、碘、氰基、硝基、C 1-C 6烷基、C 1-C 6卤代烷基、C 1-C 6卤代烷氧基、C 2-C 4烯基、C 2-C 4卤代烯基、C 2-C 4炔基、C 2-C 4卤代炔基、C 3-C 8环烷基、C 3-C 8卤代环烷基、C 1-C 6烷基羰基、C 1-C 6烷基亚磺酰基、C 1-C 6卤代烷基亚磺酰基、C 1-C 6烷基磺酰基或C 1-C 6卤代烷基磺酰基；
Y 2选自溴、碘、氰基、硝基、C 1-C 6卤代烷基、C 1-C 6卤代烷氧基、C 2-C 4烯基、C 2-C 4卤代烯基、C 2-C 4炔基、C 2-C 4卤代炔基、C 3-C 8环烷基、C 3-C 8卤代环烷基、C 1-C 6烷基羰基、C 1-C 6烷基亚磺酰基、C 1-C 6卤代烷基亚磺酰基、C 1-C 6烷基磺酰基或C 1-C 6卤代烷基磺酰基；
R 1选自氢、氟或甲氧基；R 2选自氟或三氟甲基；R 3和R 4分别独立地选自氢、卤素、氰基、硝基、C 1-C 6烷基、C 1-C 6卤代烷基、C 3-C 8环烷基或C 3-C 8卤代环烷基；
m表示0～5的整数(例如0、1、2、3、4或5)；n表示0～3的整数(例如0、1、2或3)；W 1和W 2独立地为氧原子或硫原子。
以本申请所述的式I所示结构的间二酰胺类化合物作为有效成分A，并配合有效成分B的药物组合物，由于有效成分A和有效成分B之间的协同增效作用，一方面可以减少单一活性成分的使用量，另一方面防治效果显著提高，并且由于有效成分A能够在低剂量下达到100％的杀虫活性，起效快，在施用三天后就可以发挥杀虫活性，具有良好的速效性，因此使得含有其的药物组合物同样具有很好的速效性，并且由于低剂量下效果好，减少药物浓度过大对植物以及人类的伤害，并且使得应用时产生药物残留少，更加利于环保。
优选地，本申请提供一种含有间二酰胺3位为N-环丙甲基衍生物取代的化合物的药物组合物，所述药物组合物包括有效成分A和有效成分B，所述有效成分A为具有式II所示结构的间二酰胺类化合物，所 述有效成分B包括其他杀菌剂、杀虫剂或杀螨剂中任意一种或两种的组合；
Figure PCTCN2019099949-appb-000002
式II中，
Z选自氢、氟、氯、溴、碘、氰基、C 1-C 6卤代烷基、C 1-C 6卤代烷氧基、C 1-C 6烷基磺酰基或C 1-C 6卤代烷基磺酰基；
Y选自C 1-C 6卤代烷基或C 1-C 6卤代烷氧基；
R选自氢或甲基。
本申请中，作为优选技术方案，在式II中，Z选自氢、氟、氯、溴、碘、氰基、三氟甲氧基、三氟甲基、甲磺酰基或三氟甲磺酰基；Y选自三氟甲基或三氟甲氧基；R选自氢或甲基。
作为本申请进一步优选的技术方案，所述间二酰胺类化合物为具有通式II的如下表1所示化合物中的任意一种。
表1有效成份A
Figure PCTCN2019099949-appb-000003
表1中W 2选自氧。“H”为氢原子、“F”代表氟原子、“Cl”代表氯原子、“Br”代表溴原子、“I”代表碘原子、“CN”代表氰基、“CF 3”为三氟甲基、“OCF 3”为三氟甲氧基、“MeS(O) 2”代表甲磺酰基、“CF 3S(O) 2”代表三氟甲磺酰基。
本申请中，作为特别优选的技术方案，所述间二酰胺类化合物为选自以下化合物1-14中的任意一种或至少两种的组合：
Figure PCTCN2019099949-appb-000004
Figure PCTCN2019099949-appb-000005
本申请所用术语“C 1-C 6烷基”是指具有1至6个碳原子的直链或支链烷基，非限制性地包括甲基、乙基、正丙基、异丙基、正丁基、异丁基、仲丁基、特丁基、正戊基、异戊基、正己基等。术语“C 1-C 6烷氧基”是指具有1至6个碳原子的直链或支链烷氧基，非限制性地包括甲氧基、乙氧基、正丙氧基、异丙氧基、特丁氧基等。术语“C 1-C 6卤代烷基”是指具有卤素取代的1至6个碳原子的烷基，非限制性地包括氯甲基、1-氯乙基、2-溴正丙基等。术语“C 1-C 6卤代烷氧基”是指具有卤素取代的1至6个碳原子的烷氧基；同理术语“C 3-C 8环烷基”是指在环上具有3至8个碳原子的环状烷基，非限制性地包括环丙基、环丁基、环戊基、环己基、环庚基、环辛基等；本申请所用术语“C3-C8卤代环烷基”是指在环上具有卤素取代的3至8个碳原子的环状烷基，非限制性地包括1-氯代环丙基、1-氟代环丙基、全氟代环丙基、1-氯代环丁基、1-氯代环戊基等。
在本申请中，所述特定基团之前的C 1-C 6、C 3-C 8等表示基团中所含碳原子个数，例如C 1-C 6表示碳原子数可以为1、2、3、4、5或6的基团，C 3-C 8表示碳原子数可以为3、4、5、6、7或8的基团等等，以此类推。
基于扩大活性谱以及作物保护市场的需求，在选择有效成份B时，杀虫剂以防治刺吸/锉吸/吮吸式口器害虫药剂为主，杀菌剂以种子处理药剂为主。
优选地，所述杀虫剂选自噻虫嗪、吡虫啉、噻虫胺、噻虫啉、啶虫脒、烯啶虫胺、呋虫胺、环氧虫啶等新烟碱类杀虫剂，或者选自氟吡呋喃酮、氟啶虫胺腈、氟啶虫酰胺、吡蚜酮、噻嗪酮、三氟苯嘧啶、二氯噻吡嘧(dicloromezotiaz)、双丙环虫酯(afidopyropen)、pyrifluquinazon、benzpyrimoxan等防治飞虱、叶蝉、蚜虫、粉虱、蓟马、蚧壳虫等的药剂；所述杀菌剂选自苯醚甲环唑、戊唑醇、丙硫菌唑、环丙唑醇、嘧菌 酯、肟菌酯、吡唑醚菌酯、啶氧菌酯、精甲霜灵、甲霜灵、咯菌腈、咪鲜胺、氰烯菌酯等用于种子处理防治种传病害或土传病害的药剂。
作为本申请进一步优选的技术方案，所述含有间二酰胺类化合物的药物组合物为含有下表2中所述含有间二酰胺类化合物(有效成分A)和有效成分B的药物组合物，但不限于表中所列组合：
表2
Figure PCTCN2019099949-appb-000006
Figure PCTCN2019099949-appb-000007
Figure PCTCN2019099949-appb-000008
Figure PCTCN2019099949-appb-000009
Figure PCTCN2019099949-appb-000010
Figure PCTCN2019099949-appb-000011
作为本申请的优选技术方案，所述含有间二酰胺类化合物的杀虫杀菌组合物为含有表1中所述有效成分A和有效成分B的组合物，有效成份B不限于上述杀虫剂或杀菌剂品种。
采用水稻二化螟、水稻纵卷叶螟、水稻褐飞虱、水稻恶苗病、蔬菜小菜蛾、蔬菜甜菜夜蛾、蔬菜蚜虫、茄子蓟马、棉花棉铃虫、棉蚜、小麦粘虫、小麦蚜虫等有害生物，测试了杀虫组合物的联合作用，发现了具有增效作用；测试了杀虫杀菌组合物具有协同和扩大活性谱的作用；此外，当控制了传毒昆虫如飞虱、粉虱等害虫后，结合病毒病的药剂处理，可有效控制病毒病的危害。
本申请所述有效成分A和有效成分B的重量比是200:1～1:200，例如200:1、180:1、150:1、130:1、100:1、80:1、60:1、40:1、20:1、10:1、1:1、1:10、1:30、1:50、1:80、1:100、1:120、1:140、1:160、1:180或1:200等。
在本申请中，所述含有间二酰胺类化合物的药物组合物，根据其含有的有效成分A和有效成分B的不同，其优选重量配比不同，作为本申请的优选技术方案，当有效成分A和有效成分B选择表3中所述成分时，其优选的重量配比如表3所示。
表3
Figure PCTCN2019099949-appb-000012
Figure PCTCN2019099949-appb-000013
更优选地，将表3中有效成分A所示式I所述间二酰胺类化合物替换为式II所述间二酰胺类化合物，同样满足表3中的优选重量配比。
在本申请中，所述间二酰胺类化合物还可以替换为其互变异构体、对映体、非对映体或其盐。
在本申请中，包含所述间二酰胺类化合物的互变异构体、对映体、非对映体或其盐的药物组合物同样能够发挥与本申请所述含有间二酰胺类化合物的药物组合物同样的作用效果，在低剂量下杀虫效果好、速效性佳。
另一方面，本申请提供一种药物制剂，所述药物制剂包括如上所述的含有间二酰胺类化合物的药物组合物以及农药学上可接受的助剂和/或载体。
优选地，在所述药物制剂中，所述含有间二酰胺类化合物的药物组合物的重量百分含量为0.01-99％，例如0.01％、0.1％、1％、3％、5％、8％、10％、15％、18％、20％、25％、30％、35％、40％、45％、50％、55％、60％、65％、70％、75％、80％、85％、90％、95％或99％。
优选地，所述农药学上可接受的助剂包括分散剂、润湿剂、乳化剂、防冻剂、增稠剂、消泡剂、防腐剂、稳定剂或染色剂中的任意一种或至少两种的组合。
优选地，所述分散剂包括木质素磺酸盐、烷基酚聚氧乙烯醚、萘磺酸甲醛缩合物钠盐、脂肪胺聚氧乙烯醚、脂肪酸聚氧乙烯酯、甘油脂肪酸酯聚氧乙烯醚、聚羧酸盐、甲醛缩合物、烷基苯磺酸钙盐、烷基酚聚氧乙烯醚。所述润湿剂选自十二烷基硫酸钠、烷基萘磺酸盐、拉开粉BX、聚氧乙烯醚、EO/PO嵌段聚醚、脂肪醇聚氧乙烯醚、脂肪醇聚氧乙烯醚硫酸盐、烷基磷酸钠、烷基萘磺酸盐、烷基酚聚氧乙烯基硫酸钠。所述乳化剂选自十二烷基苯磺酸盐、烷基萘磺酸盐、烷基磺酸盐、烷基酚聚氧乙烯醚、苄基酚聚氧乙烯、苯乙基酚聚氧乙烯醚、脂肪胺聚氧乙烯醚。所述防冻剂选自乙二醇、丙二醇和丙三醇。所述增稠剂选自黄原胶、羟甲基纤维素、羟乙基纤维素、羟丙基淀粉、甲基纤维素、淀粉磷酸酯钠、硅酸镁铝和聚乙烯醇。所述消泡剂选自硅油、硅酮类化合物、磷酸三丁酯、C10～C20饱和脂肪酸类化合物和聚醚类消泡剂。所述防腐剂选自甲醛、水杨酸苯酯、对羟基苯甲酸丁酯和山梨酸钾，所述稳定剂选自亚磷酸三苯酯、环氧氯苯烷、环氧大豆油和硅酸镁铝，所述染色剂选自偶氮颜料、氧化钛和氧化铁。
优选地，所述载体包括填料和/或溶剂；
优选地，所述农药学上可接受的载体包括固体载体和/或液体载体。
优选地，所述固体载体包括天然的或合成的粘土和硅酸盐，例如天然硅石和硅藻土；硅酸镁例如滑石；硅酸铝镁例如高岭石、高岭土、蒙脱土和云母；白碳黑、碳酸钙、轻质碳酸钙；硫酸钙；石灰石；硫酸钠；胺盐如硫酸铵、六甲撑二胺。液体载体包括水和有机溶剂，有机溶剂包括芳烃例如三甲苯、苯、二甲苯、甲苯等；氯代烃例如氯代苯、氯乙烯、三氯甲烷、二氯甲烷等；脂肪烃例如石油馏分、环己烷、轻质矿物油；醇类例如异丙醇、丁醇、乙二醇、丙二醇、丙三醇和环己醇以及它们的醚和酯；酮类例如丙酮、环己酮以及二甲基甲酰胺和N-甲基-吡咯烷酮。
在杀虫剂组合物(即所述药物制剂)的配制过程中可以将活性组分与液体载体和/或固体载体混合，同时加入助剂如乳化剂、分散剂、稳定剂、湿润剂、粘合剂、消泡剂、抗氧化剂等。
优选地，所述药物制剂的剂型为可溶液剂、可溶粉剂、可溶粒剂、乳油、可湿性粉剂、水乳剂、悬浮剂、可分散油悬浮剂、水分散粒剂、微囊悬浮剂、颗粒剂、微乳剂、悬浮乳剂、微囊悬浮-悬浮剂、超低容量液剂、热雾剂、展膜油剂、悬浮种衣剂、种子处理干粉剂、种子处理悬浮剂、种子处理可溶粉剂、种子处理可分散粉剂、种子处理乳剂或种子处理液剂。
优选地，所述药物制剂的剂型为可溶液剂、可溶粒剂、悬浮剂、乳油、可湿性粉剂、水乳剂、水分散粒剂、可分散油悬浮剂、微囊悬浮剂、超低容量液剂、热雾剂、悬浮种衣剂或种子处理可分散粉剂。
另一方面，本申请提供了如上所述的含有间二酰胺类化合物的药物组合物或药物制剂在农业、林业、园艺上防治植物病害或虫害中的应用。
本申请所述的含有间二酰胺类化合物的药物组合物或药物制剂适用于防治危害危害水稻、玉米、小麦、马铃薯、果树、蔬菜、其它作物及花卉等的各种农林、园艺虫害及卫生害虫和病害。
本申请组合物应用范围广泛，所应用的植物或作物范围主要包括以下几类：蔬菜类，黄瓜、丝瓜、西瓜、甜瓜、南瓜、吊瓜、菠菜、芹菜、甘蓝、白菜、葫芦、辣椒、茄子、番茄、葱、姜、蒜、韭菜、草莓、莴笋、菜豆、豇豆、蚕豆、萝卜、胡萝卜、马铃薯、山药；禾谷类，小麦、大麦、玉米、水稻、高粱；果树类，苹果、梨、香蕉、柑橘、葡萄、荔枝、芒果；花卉类，牡丹、月季、火鹤；油料作物，花生、大豆、油菜、向日葵、芝麻；糖料作物，甜菜、甘蔗；其他作物，如马铃薯、甘薯、烟草和茶；园艺、林业、家庭卫生、公共卫生区域等；以上列举植物或作物范围对药物组合物使用范围无限制作用。
在本申请中，所述害虫包括鳞翅目、鞘翅目、半翅目、缨翅目、双翅目、直翅目、同翅目、等翅目、膜翅目、叶螨害虫，所述病害包括由半知菌、子囊菌、担子菌等引起的病害。
优选地，所述害虫包括但不限于：棉铃虫、小菜蛾、甜菜夜蛾、斜纹夜蛾、菜青虫、二化螟、三化螟、大螟、草地夜蛾、稻纵卷叶螟、稻蓟马、西花蓟马、瓜蓟马、葱蓟马、大姜蓟马、芒果蓟马、桃蚜、棉蚜、苜蓿蚜、苹果黄蚜、麦蚜、跳甲、椿象、灰飞虱、褐飞虱、白背飞虱、白蚁、蚊蝇、朱砂叶螨、柑橘红蜘蛛。所述病害包括但不限于小麦赤霉病、水稻纹枯病、水稻稻瘟病等。
在本申请中，所述药物组合物或药物制剂的使用方式为喷雾、土壤处理、种子处理、飞防等。
另一方面，本申请提供了如上所述的含有间二酰胺类化合物的药物组合物或药物制剂在植物、作物或花卉的种子处理中的应用。
另一方面，本申请提供一种防治植物病害的方法，所述方法为：向需要控制的植物病害或其生长的介质上施用有效剂量的如上所述的含有间二酰胺类化合物的药物组合物或药物制剂。
优选地，所述有效剂量为每公顷1-1000g，例如1g、5g、8g、10g、20g、50g、80g、100g、120g、150g、180g、200g、250g、300g、350g、400g、450g、500g、600g、700g、800g、900g或1000g，优选每公顷7.5-500g。
本申请的组合物可以制剂的形式施用在病害或其生长介质上。通式I化合物(特别是通式II化合物)作为活性组分溶解或分散于载体中或配制成制剂以便作为杀菌剂使用时更易于分散。例如：这些化学制剂可被配制成可溶液剂、乳油、可湿性粉剂、水乳剂、悬浮剂、可分散油悬浮剂、水分散粒剂、种子处理剂、微囊悬浮剂、颗粒剂、微乳剂、悬浮乳剂、悬浮-微囊悬浮剂等。
相对于现有技术，本申请具有以下有益效果：
本申请提供的药物组合物与传统杀虫剂相比使用中具有以下优点：
(1)本申请中有效成分A和有效成分B的组合物具有协同增效作用，组合物使用量较单一活性成分单独使用时大大降低，防治效果显著提高。
(2)本申请的药物组合物可以病虫兼治，扩大了防治谱，减少了施药次数，节省了施药人工成本。
(3)由于对传毒昆虫如粉虱、粉虱等害虫具有高效防控作用，也减少了传播病毒的机会，可明显协同控制病毒病的治理。
具体实施方式
下面通过具体实施方式来进一步说明本申请的技术方案。本领域技术人员应该明了，所述实施例仅仅是帮助理解本申请，不应视为对本申请的具体限制。
合成实施例
合成实施例1
N-[2-溴-4-(1,1,1,2,3,3,3-七氟丙-2-基)-6-(三氟甲基)苯基]-3-[N-(环丙甲基)-苯甲酰胺基]-2-氟苯甲酰胺(化合物编号1)的制备：
(1)2-氟-[3-(环丙甲基)胺基]苯甲酸甲酯的合成
Figure PCTCN2019099949-appb-000014
向反应瓶中依次加2-氟-3-胺基苯甲酸甲酯(20g，118.23mmol)、溴甲基环丙烷(20.75g，153.70mmol)，碳酸钾(21.24g，153.70mmol)，N,N-二甲基甲酰胺(200mL)，在回流条件下搅拌16h，TLC监测至反应不再进行时，关闭加热，结束反应。待反应液冷至室温后，向反应液中加入水(200mL)，用乙酸乙酯(100mL)萃取，有机层经饱和食盐水洗涤、无水硫酸钠干燥后，减压下浓缩，残余物经柱色谱提纯(淋洗液为石油醚：乙酸乙酯＝10：1)，得淡黄色液体产物2-氟-[3-(环丙甲基)胺基[苯甲酸甲酯(13g，收率49.39％)。
(2)2-氟-3-[N-(环丙甲基)苯甲酰胺基]苯甲酸甲酯的合成
Figure PCTCN2019099949-appb-000015
向反应瓶中依次加苯甲酸(6.67g，53.78mmol)、甲苯(50mL)和二氯亚砜(31.99g，268.9mmol)，在回流条件下反应2h，减压下浓缩甲苯，将浓缩后的残余物溶解在四氢呋喃(30mL)中待用。将2-氟-3-(N-环丙甲基胺基)苯甲酸甲酯(10.00g，44.82mmol)溶解在四氢呋喃(100mL)，加入吡啶(4.25g，53.78mmol)，滴加上步制得的苯甲酰氯四氢呋喃溶液，常温搅拌4h。TLC监测至反应不再进行时，结束反应。向反应液中加入用乙酸乙酯(50mL)溶解，有机层经依次用2M盐酸和饱和碳酸氢钠洗涤，经无水硫酸钠干燥后，减压下浓缩，残余物经柱色谱提纯(淋洗液为石油醚：乙酸乙酯＝8：1)，得无色液体产物2-氟-3-(N-(环丙甲基)苯甲酰胺)苯甲酸甲酯(13.00g，收率88.70％)。
(3)2-氟-3-[N-(环丙甲基)苯甲酰胺基]苯甲酸的合成
Figure PCTCN2019099949-appb-000016
将2-氟-3-(N-(环丙甲基)苯甲酰胺)苯甲酸甲酯(13.00g，40.88mmol)溶解在甲醇(100mL)中，加入10％的氢氧化钠水溶液(6.54g，163.52mmol，65.4mL)，常温搅拌2h后，TLC监测反应完全。减压下浓缩除去甲醇，将浓缩后的残渣溶解在水(100mL)中，用乙酸乙酯(50mL)萃取，舍弃有机相，用2M盐酸水溶液调节水相的PH为7，继续用乙酸乙酯(100mL)萃取，有机层经饱和食盐水洗涤、无水硫酸钠干燥后，减压下浓缩，得到无色溶液产物，2-氟-3-[N-(环丙甲基)苯甲酰胺]苯甲酸(12.00g，收率93.82％)，放置过夜后成白色固体。
(4)N-[2-溴-4-(1,1,1,2,3,3,3-七氟丙-2-基)-6-(三氟甲基)苯基]-3-[N-(环丙甲基)苯甲酰胺基]-2-氟苯甲酰胺的合成
Figure PCTCN2019099949-appb-000017
向反应瓶中依次加2-氟-3-(N-(环丙甲基)苯甲酰胺基)苯甲酸(0.40g，1.28mmol)、甲苯(6mL)，二氯亚砜(0.75g，6.40mmol)，在140℃下搅拌反应2h，减压下浓缩，将浓缩后的残渣溶解在四氢呋喃(3mL)中待用。
将2-溴-6-三氟甲基-4-七氟异丙基苯胺(0.52g，1.28mmol)溶解在四氢呋喃(4mL)，在-70℃下滴加二异丙基氨基锂(0.77mL，1.54mmol)，5min后滴加上一步合成的2-氟-3-[N-(环丙甲基)苯甲酰胺基]苯甲酰氯的四氢呋喃溶液，在-70℃下搅拌30min，升至室温继续搅拌30min。TLC监测至反应不再进行时，结束反应。向反应液中加入水(20mL)，用乙酸乙酯(20mL)萃取，有机层经饱和食盐水洗涤、无水硫酸钠干燥后，减压下浓缩，残余物经柱色谱提纯(淋洗液为石油醚：乙酸乙酯＝3：1)，得N-[2-溴-4-(1,1,1,2,3,3,3-七氟丙-2-基)-6-(三氟甲基)苯基]-3-[N-(环丙甲基)-苯甲酰胺基]-2-氟苯甲酰胺(0.25g，收率27.84％)。
化合物1的 1H NMR(400MHz,CDCl 3-d)数据如下：δ[ppm]：8.15(d,J＝2.1Hz,1H),8.03(br s,2H),7.92(d,J＝2.1Hz,1H),7.55(br s,1H),7.35-7.21(m,5H),3.84(d,J＝93.6Hz,2H),1.14(br s,1H),0.59-0.40(m,2H),0.20(d,J＝42.2Hz,2H)。
合成实施例2
N-[2-溴-4-(1,1,1,2,3,3,3-七氟丙-2-基)-6-三氟甲氧基苯基]-3-[N-(环丙甲基)苯甲酰胺基]-2-氟苯甲酰胺(化合物编号3)的合成的合成
Figure PCTCN2019099949-appb-000018
向反应瓶中依次加2-氟-3-(N-(环丙甲基)苯甲酰胺)苯甲酸(0.50g，1.60mmol)、甲苯(6mL)，二氯亚砜(1.07g，9.00mmol)，在回流条件下搅拌反应2h，减压下浓缩甲苯，将浓缩后的残渣溶解在四氢呋喃(3mL)中待用。
将2-溴-4-七氟异丙基-6-三氟甲氧基苯胺(0.68g，1.60mmol)溶解在四氢呋喃(4mL)，在-70℃下滴加2M的二异丙基氨基锂四氢呋喃溶液(0.96mL，1.93mmol)，5min后滴加上一步待用的四氢呋喃溶液，在-70℃下搅拌30min，升至室温继续搅拌30min。薄层层析色谱(TLC)监测至反应不再进行时，结束反应。向反应液中加入水(20mL)，用乙酸乙酯(20mL)萃取，有机层经饱和食盐水洗涤、无水硫酸钠干燥后，减压下浓缩，残余物经柱色谱提纯(淋洗液为石油醚：乙酸乙酯＝5：1)，得目标产物(0.24g，收率20.50％)，白色固体。
化合物3的 1H NMR(400MHz,CDCl 3-d)数据如下(δ[ppm])：8.01-7.81(m,2H),7.58–7.51(m,3H),7.35-7.21(m,6H),3.85(d,J＝64.0Hz,2H),1.20-1.13(m,1H),0.50(d,J＝7.8Hz,2H),0.20(d,J＝32.0Hz,2H).
合成实施例3
N-[2-溴-4-(1,1,1,2,3,3,3-七氟丙-2-基)-6-(三氟甲基)苯基]-3-[N-(环丙甲基)-4-氰基苯甲酰胺基]-2-氟苯甲酰胺(化合物编号4)的制备：
(1)2-氟-3-[N-(环丙甲基)-4-氰基苯甲酰胺基]苯甲酸甲酯的合成
Figure PCTCN2019099949-appb-000019
向反应瓶中依次加4-氰基苯甲酸(0.80g，5.38mmol)、甲苯(6mL)，二氯亚砜(3.2g，26.9mmol)，在回流条件下搅拌反应2h，减压下浓缩甲苯，将浓缩后的残渣溶解在四氢呋喃(3mL)中待用。将2-氟-[3-(环丙甲基)胺基]苯甲酸甲酯(1.0g，4.48mmol)溶解在四氢呋喃(6mL)，加入三乙胺(0.74g，5.38mmol)，滴加4-氰基苯甲酰氯的四氢呋喃溶液，常温搅拌4h。TLC监测至反应不再进行时，结束反应。向反应液中加入水(20mL)，用乙酸乙酯(20mL)萃取，有机层经饱和食盐水洗涤、无水硫酸钠干燥后，减压下浓缩，残余物经柱色谱提纯(淋洗液为石油醚：乙酸乙酯＝3:1)，得无色液体产物2-氟-3-[N-(环丙甲基)-4- 氰基苯甲酰胺]苯甲酸甲酯(1.40g，收率88.83％)。
(2)2-氟-3-[N-(环丙甲基)-4-氰基苯甲酰胺基]苯甲酸的合成
Figure PCTCN2019099949-appb-000020
将2-氟-3-[N-(环丙甲基)-4-氰基苯甲酰胺基]苯甲酸甲酯(1.40g,3.96mmol)溶解在甲醇(20mL)中，加入10％的氢氧化钠水溶液(0.63g,15.86mmol,6.3mL)，常温搅拌2h，TLC监测反应完全。减压下浓缩除去甲醇，将浓缩后的残渣溶解在水(20mL)中，用乙酸乙酯(10mL)萃取，舍弃有机相，用2M盐酸水溶液调节水相的PH为7，继续用乙酸乙酯(10mL)萃取，有机层经饱和食盐水洗涤、无水硫酸钠干燥后，减压下浓缩，得到2-氟-3-[N-(环丙甲基)-4-氰基苯甲酰胺基]苯甲酸(1.30g，收率96.79％)，白色固体。
(3)N-[2-溴-4-(1,1,1,2,3,3,3-七氟丙-2-基)-6-(三氟甲基)苯基]-3-[N-(环丙甲基)-4-氰基苯甲酰胺基]-2-氟苯甲酰胺的合成：
Figure PCTCN2019099949-appb-000021
向反应瓶中依次加2-氟-3-[N-(环丙甲基)-4-氰基苯甲酰胺]苯甲酸(0.75g，2.22mmol)、甲苯(6mL)和二氯亚砜(1.31g，11.10mmol)，在回流下搅拌反应2h，减压下浓缩，将浓缩后的残余物溶解在四氢呋喃(3mL)中待用。
将2-溴-6-三氟甲基-4-七氟异丙基苯胺(0.90g，2.22mmol)溶解在四氢呋喃(4mL)，在-70℃下滴加二异丙基氨基锂(1.30mL，2.66mmol)，5min后滴加上一步制得的2-氟-3-[N-(环丙甲基)-4-氰基苯甲酰胺]苯甲酰氯四氢呋喃溶液，在-70℃下搅拌30min，升至室温继续搅拌30min。TLC监测至反应不再进行时，结束反应。向反应液中加入饱和氯化铵水溶液(20mL)，用乙酸乙酯(20mL)萃取，有机层经饱和食盐水洗涤、无水硫酸钠干燥后，减压下浓缩，残余物经柱色谱提纯(淋洗液为石油醚：乙酸乙酯＝3：1)，得N-[2-溴-4-(1,1,1,2,3,3,3-七氟丙-2-基)-6-(三氟甲基)苯基]-3-[N-(环丙甲基)-4-氰基苯甲酰胺基]-2-氟苯甲酰胺(0.24g，收率14.91％)。
化合物4的 1H NMR(400MHz,CDCl 3-d)数据如下：δ[ppm]：8.14(d,J＝2.0Hz,1H),8.12-7.94(m,2H),7.91(t,J＝1.4Hz,1H),7.58-7.39(m,4H),7.32(t,J＝7.9Hz,1H),3.81(dd,J＝76.0,18.8Hz,2H),1.11(br s,1H),0.5(br s,2H),0.20(d,J＝36.7Hz,2H)。
合成实施例4
N-[2-溴-4-(1,1,1,2,3,3,3-七氟丙-2-基)-6-(三氟甲基)苯基]-3-[N-(环丙甲基)-4-(三氟甲基)苯甲酰胺基]-2-氟苯甲酰胺(化合物编号7)的制备：
Figure PCTCN2019099949-appb-000022
(1)向反应瓶中依次加2-氟-3-[N-(环丙甲基)-4-三氟甲基苯甲酰胺]苯甲酸(0.45g，1.12mmol)、甲苯(6mL)，二氯亚砜(0.67g，5.60mmol)，在回流条件下搅拌反应2h，减压下浓缩甲苯，将浓缩后的残 渣溶解在四氢呋喃(3mL)中待用。
(2)将2-溴-6-三氟甲基-4-七氟异丙基苯胺(0.46g，1.12mmol)溶解在四氢呋喃(4mL)，在-70℃下滴加二异丙基氨基锂(0.70mL，1.42mmol)，5min后滴加上一步待用的四氢呋喃溶液，在-70℃下搅拌30min，升至室温继续搅拌30min。TLC监测至反应不再进行时，结束反应。向反应液中加入水(20mL)，用乙酸乙酯(20mL)萃取，有机层经饱和食盐水洗涤、无水硫酸钠干燥后，减压下浓缩，残余物经柱色谱提纯(淋洗液为石油醚：乙酸乙酯＝3：1)，得目标产物(0.11g，收率13.75％)。
化合物7的 1H NMR(400MHz,CDCl 3-d)数据如下：δ[ppm]：8.21-7.79(m,4H),7.66-7.28(m,5H),3.85(d,J＝104.7Hz,2H),1.12(br s,1H),0.51(br s,2H),0.20(d,J＝42.7Hz,1H)。
合成实施例5
N-[2-溴-4-(1,1,1,2,3,3,3-七氟丙-2-基)-6-(三氟甲基)苯基]-3-[N-(环丙甲基)-4-氟苯甲酰胺基]-2-氟苯甲酰胺(化合物编号8)的制备，制备方法如下：
Figure PCTCN2019099949-appb-000023
向反应瓶中依次加2-氟-3-[N-(环丙甲基)-4-氟-苯甲酰胺]苯甲酸(2.20g，6.67mmol)、甲苯(20mL)，二氯亚砜(3.97g，33.35mmol)，在回流条件下搅拌反应2h，减压下浓缩得到2-氟-3-[N-(环丙甲基)-4-氟苯甲酰胺]苯甲酰氯。将2-溴-6-三氟甲基-4-七氟异丙基苯胺(3.26g，7.99mmol)、N,N二异丙基乙胺(1.72g，13.30mmol)、4-N,N-二甲氨基吡啶(0.33g，2.69mmol)分别加入到2-氟-3-[N-(环丙甲基)-4-氟苯甲酰胺]苯甲酰氯中，在120℃下搅拌，反应2h后，停止加热。向反应液中加入水(20mL)，用乙酸乙酯(20mL)萃取，有机层经饱和食盐水洗涤、无水硫酸钠干燥后，减压下浓缩，残余物经柱色谱提纯(淋洗液为PE：EA＝3：1)，得目标产物(1.80g，收率37.5％)。
化合物8的 1H NMR(400MHz,DMSO-d 6)数据如下：δ[ppm]：10.56(s,1H),8.41(s,1H),7.95(s,1H),7.70-7.56(m,2H),7.38-7.32(m,3H),7.09(br s,2H),3.69(br s,2H),1.03-1.01(m,1H),0.41-0.39(m,2H),0.08-0.06(m,2H)。
合成实施例6
N-[2-溴-4-(1,1,1,2,3,3,3-七氟丙-2-基)-6-(三氟甲基)苯基]-3-[N-(环丙甲基)-4-氯苯甲酰胺基]-2-氟苯甲酰胺(化合物编号10)的制备，制备方法如下：
Figure PCTCN2019099949-appb-000024
(1)向反应瓶中依次加2-氟-3-[N-(环丙甲基)-4-氯苯甲酰胺]苯甲酸(0.60g，1.76mmol)、甲苯(6mL)，二氯亚砜(1.04g，8.80mmol)，在回流条件下搅拌反应2h，减压下浓缩甲苯，将浓缩后的残渣溶解在四氢呋喃(3mL)中待用。
(2)将2-溴-6-三氟甲基-4-七氟异丙基苯胺(0.72g，1.76mmol)溶解在四氢呋喃(4mL)，在-70℃下滴加二异丙基氨基锂(1.05mL，2.11mmol)，5min后滴加上一步待用的四氢呋喃溶液，在-70℃下搅拌30min，升至室温继续搅拌30min。TLC监测至反应不再进行时，结束反应。向反应液中加入水(20mL)，用乙酸乙酯(20mL)萃取，有机层经饱和食盐水洗涤、无水硫酸钠干燥后，减压下浓缩，残余物经柱色谱提纯(淋洗液为石油醚：乙酸乙酯＝3：1)，得目标产物(0.15g，收率11.63％)。
化合物10的 1H NMR(400MHz,CDCl 3-d)数据如下：δ[ppm]：8.18-7.84(m,4H),7.53(t,J＝7.7Hz,1H),7.37-7.07(m,4H),3.81(d,J＝85.0Hz,2H),1.11(br s,1H),0.49(br s,2H),0.17(d,J＝32.1Hz,2H)。
合成实施例7
N-[2-溴-4-(1,1,1,2,3,3,3-七氟丙-2-基)-6-(三氟甲基)苯基]-3-[N-(1-环丙基-乙基)-苯甲酰胺基]-2-氟苯甲酰胺(化合物编号2)的制备，制备方法如下：
Figure PCTCN2019099949-appb-000025
(1)3-[N-(1-环丙基乙基)氨基]-2-氟苯甲酸甲酯的合成
将2-氟-3-氨基苯甲酸甲酯(2.00g，11.82mmol)溶解在1,2-二氯乙烷(65mL)中，室温下依次加入环丙基甲基酮(2.98g，35.47mmol)、三氟乙酸(8.08g，70.92mmol)和三乙酰氧基硼氢化钠(7.51g，35.47mmol)，反应加热至45℃反应1h。TLC监测至反应不再进行时，结束反应。向反应液中加入饱和NaHCO 3溶液(50mL)，用二氯甲烷(80mL)萃取，有机层经饱和食盐水洗涤、无水硫酸钠干燥后，减压下浓缩，残余物经柱色谱提纯(淋洗液为石油醚：乙酸乙酯＝10：1)，得目标产物(1.50g，收率53.5％)，无色油状物。
(2)3-[N-(1-环丙基)乙基)苯甲酰胺基]-2-氟苯甲酸甲酯的合成
向反应瓶中依次加苯甲酸(1.54g，12.64mmol)、甲苯(15mL)和二氯亚砜(6.27g，52.68mmol)，在回流条件下搅拌反应2h，减压下浓缩甲苯，将浓缩后的残渣溶解在四氢呋喃(5mL)中待用。
将3-[N-(1-环丙基)乙基)氨基]-2-氟苯甲酸甲酯(2.50g，10.54mmol)溶解在四氢呋喃(15mL)，依次加入三乙胺(1.60g，15.80mmol)和上一步制备的酰氯的四氢呋喃溶液，在80℃下搅拌反应6h。TLC监测至反应不再进行时，结束反应。向反应液中加入水(50mL)，用乙酸乙酯(60mL)萃取，有机层经饱和食盐水洗涤、无水硫酸钠干燥后，减压下浓缩，残余物经柱色谱提纯(淋洗液为石油醚：乙酸乙酯＝10：1)，得目标产物(1.03g，收率28.6％)，黄色固体。
(3)3-[N-(1-环丙基)乙基)苯甲酰胺基]-2-氟苯甲酸
将3-[(1-环丙基-乙基)苯甲酰胺基]-2-氟苯甲酸甲酯(1.00g，2.93mmol)溶解在甲醇(10mL)中，加入10％的氢氧化钠水溶液(0.46g，11.72mmol，4.6mL)，常温搅拌2h，TLC监测反应完全。减压下浓缩除去甲醇，将浓缩后的残渣溶解在水(20mL)中，用乙酸乙酯(10mL)萃取，舍弃有机相，用2M盐酸水溶液调节水相的pH值为3，继续用乙酸乙酯(10mL)萃取，有机层经饱和食盐水洗涤、无水硫酸钠干燥后，减压下浓缩，得目标产物(0.60g，收率62.6％)。
(4)N-[2-溴-4-(1,1,1,2,3,3,3-七氟丙-2-基)-6-(三氟甲基)苯基]-3-[N-(1-环丙基-乙基)苯甲酰胺基]-2-氟苯甲酰胺的合成
向反应瓶中依次加3-(N-(1-环丙)-乙基)苯甲酰胺基)-2-氟苯甲酸(0.60g，1.83mmol)、甲苯(6mL)和二氯亚砜(1.09g，9.16mmol)，在140℃下搅拌反应2h，减压下浓缩甲苯，将浓缩后的残渣溶解在四氢呋喃(2mL)中待用。
将2-溴-6-三氟甲基-4-七氟异丙基苯胺(0.75g，1.83mmol)溶解在四氢呋喃(6mL)，在-70℃下滴加二异丙基氨基锂(1.10mL，2.20mmol)，5min后滴加上一步待用的四氢呋喃溶液，在-70℃下搅拌30min，升至室温继续搅拌30min。TLC监测至反应不再进行时，结束反应。向反应液中加入水(20mL)，用乙酸乙酯(20mL)萃取，有机层经饱和食盐水洗涤、无水硫酸钠干燥后，减压下浓缩，残余物经柱色谱提纯(淋洗液为石油醚：乙酸乙酯＝5：1)，得目标产物(0.23g，收率17.5％)，黄色固体。
化合物2的 1H NMR(400MHz,CDCl 3-d)数据如下：δ[ppm]：8.19(s,1H),8.05-7.95(m,1H),7.89(s,1H),7.77-7.73(m,1H),7.56-7.52(m,1H),7.28-7.11(m,6H),4.26-4.23(m,1H),1.63(br s,2H),1.51(br s,1H),0.89–0.40(m,5H)。
除上面描述的化合物外，表1中部分化合物参照合成实施例1-7中相似的方法制备或可制备，下文表4中给出了参照合成实施例1-7合成的部分化合物的核磁数据。
表4
Figure PCTCN2019099949-appb-000026
本申请的其他通式I或通式II化合物可参照上述方法合成。
制剂实施例
下列实施例用于说明本申请的组成比例及制备方法：
制剂实施例1：25％化合物4·噻虫嗪水分散粒剂
25％化合物4·噻虫嗪水分散粒剂的组成如下表5所示：
表5
名称 折百(W/W，％) 备注
化合物4 10 有效成分A
噻虫嗪 15 有效成分B
十二烷基硫酸钠 1.5 润湿剂
木质素磺酸钠 6 分散剂
萘甲醛聚合物磺酸钠 2 分散剂
硫酸铵 5 崩解剂
玉米淀粉 20 填料
高岭土 补足100 填料
制备方法：按照配方计算出各物料量，将化合物4、噻虫嗪、十二烷基硫酸钠、木质素磺酸钠、萘甲醛聚合物磺酸钠、硫酸铵、玉米淀粉、高岭土混合均匀，通过气流粉碎机粉碎至平均粒径10～15微米， 加入粉体量的17％的水捏合，然后通过旋转挤压造粒，50℃烘干3小时，筛分，取样检验合格，即得25％化合物4·噻虫嗪水分散粒剂。
制剂实施例2：24％化合物8·氟吡呋喃酮可溶液剂
24％化合物8·氟吡呋喃酮可溶液剂的组成如下表6所示：
表6
名称 折百(W/W，％) 备注
化合物8 12 有效成分A
氟吡呋喃酮 12 有效成分B
丙二醇甲醚 10 助溶剂
脂肪醇聚氧乙烯醚 6 润湿剂
去离子水 补足100 溶剂
制备方法：按照配方计算出各物料量，在250ml三口烧瓶里面，加入去离子水，将丙二醇甲醚加入，然后加入化合物8、氟吡呋喃酮，加热到30～40℃搅拌2小时，最后加入脂肪醇聚氧乙烯醚，溶解均匀，过滤，取样检验合格，即得到24％化合物8·氟吡呋喃酮的可溶液剂。
制剂实施例3：10％化合物1·啶虫脒乳油
10％化合物1·啶虫脒乳油的组成如下表7所示：
表7
名称 折百(W/W，％) 备注
化合物1 4 有效成分A
啶虫脒 6 有效成分B
十二烷基苯磺酸钙 5 乳化剂
蓖麻油聚氧乙烯醚 5 乳化剂
200号溶剂油 补足100 溶剂
制备方法：按照配方计算出各物料量，配料釜中，加入200溶剂油，然后将化合物1、啶虫脒加入溶解完全后，再投入十二烷基苯磺酸钙、蓖麻油聚氧乙烯醚加入，在40～50℃搅拌1.5小时，过滤，取样检验合格，即得到10％化合物1·啶虫脒乳油。
制剂实施例4：30％化合物10·吡蚜酮可湿性粉剂
30％化合物10·吡蚜酮可湿性粉剂的组成如下表8所示：
表8
名称 折百(W/W，％) 备注
化合物10 8 有效成分A
吡蚜酮 22 有效成分B
十二烷基硫酸钠 1.5 润湿剂
木质素磺酸钠 6 分散剂
高岭土 补足100 载体
制备方法：按照配方计算出各物料量，在配料釜中投入化合物10、吡蚜酮、十二烷基硫酸钠、木质素磺酸钠、高岭土，混合均匀后，用气流粉碎机粉碎至平均粒径10微米，取样检验合格，即得到30％化合物10·吡蚜酮可湿性粉剂。
制剂实施例5：20％化合物5·三氟苯嘧啶悬浮剂
20％化合物5·三氟苯嘧啶悬浮剂的组成如下表9所示：
表9
名称 折百(W/W，％) 备注
化合物5 10 有效成分A
三氟苯嘧啶 10 有效成分B
脂肪醇聚氧乙烯醚 1.5 润湿剂
三苯乙烯基苯酚聚氧乙烯醚磷酸酯 2 分散剂
木质素磺酸钠 3 分散剂
丙二醇 4 防冻剂
1％黄原胶溶液液 10 增稠剂
卡松 0.1 防腐剂
聚二甲基硅氧烷乳液 0.2 有机硅消泡剂
去离子水 补足100 载体
制备方法：按照配方计算出各物料量，将去离子水、丙二醇、聚二甲基硅氧烷乳液、三苯乙烯基苯酚聚氧乙烯醚磷酸酯、木质素磺酸钠、卡松、消泡剂搅拌溶解均匀，加入三氟苯嘧啶和化合物5剪切均匀，然后通过砂磨机研磨至平均粒径2微米，加入10份1％黄原胶溶液搅拌30分钟，即得到20％化合物5·三氟苯嘧啶悬浮剂。
制剂实施例6：35％化合物8·氰烯菌酯悬浮种衣剂
35％化合物8·氰烯菌酯悬浮种衣剂的组成如下表10所示：
表10
Figure PCTCN2019099949-appb-000027
制备方法：在配料釜中，根据物料配比，投入去离子水、化合物8、氰烯菌酯、三苯乙烯基苯酚聚氧乙烯醚磷酸酯三乙醇胺盐、嵌段聚氧乙烯醚、卡松聚二甲基硅氧烷乳液、丙二醇剪切后砂磨，控制粒径D90 5微米左右，然后转移到调配釜中，加入2％黄原胶溶液、颜料F2R混合搅拌1小时，取样检测，合格后得成品35％化合物8·氰烯菌酯悬浮种衣剂。
制剂实施例7：15％化合物1·丙硫菌唑悬浮剂
15％化合物1·丙硫菌唑悬浮剂的组成如下表11所示：
表11
名称 折百(W/W，％) 备注
化合物1 10 有效成分A
丙硫菌唑 5 有效成分B
脂肪醇聚氧乙烯醚 1.5 润湿剂
三苯乙烯基苯酚聚氧乙烯醚磷酸酯 2 分散剂
木质素磺酸钠 3 分散剂
丙二醇 4 防冻剂
1％黄原胶溶液液 10 增稠剂
卡松 0.1 防腐剂
聚二甲基硅氧烷乳液 0.2 有机硅消泡剂
去离子水 补足100 载体
制备方法：按照配方计算出各物料量，将去离子水、丙二醇、脂肪醇聚氧乙烯醚、三苯乙烯基苯酚聚氧乙烯醚磷酸酯、木质素磺酸钠、卡松、消泡剂搅拌溶解均匀，加入丙硫菌唑和化合物1剪切均匀，然后通过砂磨机研磨至平均粒径2微米，加入10份1％黄原胶溶液搅拌30分钟，即得到15％化合物1·丙硫菌唑悬浮剂。
制剂实施例8：30％化合物8·双丙环虫酯可分散液剂
30％化合物8·双丙环虫酯可分散液剂的组成如下表12所示：
表12
名称 折百(W/W，％) 备注
化合物8 10 活性成分
双丙环虫酯 20 活性成分
100号溶剂油 15 溶剂
环己酮 10 溶剂
蓖麻油聚氧乙烯醚 5 分散剂
脂肪醇聚氧乙烯醚 10 润湿剂
聚二甲基硅氧烷乳液 0.2 消泡剂
去离子水 补齐 载体
制备方法：在配料釜中，根据工艺配比，加入100号溶剂油、环己酮，搅拌下加入化合物8、双丙环虫酯，加热至50℃溶剂完全后，加入蓖麻油聚氧乙烯醚、脂肪醇聚氧乙烯醚、聚二甲基硅氧烷乳液继续搅拌10分钟后，降温后加入去离子水，得30％化合物8·双丙环虫酯可分散液剂。
制剂实施剂9：40％化合物1·咪鲜胺水乳剂
40％化合物1·咪鲜胺水乳剂的组成如下表13所示：
表13
名称 折百(W/W，％) 备注
化合物1 10 活性成分
咪鲜胺 30 活性成分
150号溶剂油 15 助溶剂
嵌段聚氧乙烯醚复合物 5.0 乳化剂
丙二醇 5.0 防冻剂
二甲基硅氧烷乳液 0.2 消泡剂
去离子水 补齐 连续相
制备方法：在配料釜中，先加入150号溶剂油，然后开启搅拌，加入化合物1搅拌溶解，当溶解完全后，再投入咪鲜胺以及乳化剂嵌段聚氧乙烯醚复合物，继续搅拌20分钟，混合均匀为油相，待用；在剪切釜中投入去离子水、消泡剂及防冻剂，开启剪切装置，5分钟后慢慢加入油相物料，加完再剪切10分钟，得40％化合物1·咪鲜胺水乳剂。
生测实施例
下列实施例用于说明本申请技术方案的部分实施，本申请不限于以下实施例。
生测实施例1：有效成份A对多种害虫具有显著活性
靶标：小菜蛾3龄幼虫，粘虫3龄幼虫，棉铃虫3龄幼虫，均为室内饲养。
方法：小菜蛾+浸叶饲喂法，粘虫+浸叶片饲喂法，棉铃虫+点滴法。
小菜蛾+浸叶饲喂法。参照NY/1154.14-2008，主要操作描述如下：将清洁的苞菜叶碟浸入药液中10s，晾干后置于培养皿中，每皿4碟，培养皿内放滤纸保湿。每皿接小菜蛾试虫10头，3次重复。置于光照培养箱内，温度25℃，光照14hL:10hD，培养。药后3天调查小菜蛾死虫数，计算死亡率。
粘虫+浸叶片饲喂法。参照NY/1154.14-2008，主要操作描述如下：将玉米叶段浸入药液中10s，晾干后置于培养皿中，每皿4片，培养皿内放滤纸保湿。每皿接粘虫试虫10头，3次重复。置于光照培养箱内，温度25℃，光照14hL:10hD，培养。药后3天调查粘虫死虫数，计算死亡率。
二化螟+稻茎浸渍法。参照NY/T1154.11-2008，主要操作如下：将清洁的稻茎浸入药液中10s后取出，放置于阴凉处晾干，放入指形管中，接入3龄二化螟幼虫10头，每处理重复3次，用棉黑布封管口，橡皮筋扎紧，置于光照培养箱，温度28℃，黑暗培养。药后3天调查二化螟死活虫数，计算各药剂处理的死亡率。
结果如表14所示，由结果可以看出，化合物1-14均具有极显著杀虫活性。
表14
Figure PCTCN2019099949-appb-000028
Figure PCTCN2019099949-appb-000029
生测实施例2：有效成份A为式II化合物与有效成份B为啶虫脒、二氯噻吡嘧啶等杀虫剂的组合物，对小菜蛾的活性测试
靶标：小菜蛾3龄幼虫，室内饲养。
方法：同生测实施例1。
评价方法与标准如下：
增效效果＝实际死亡率％-理论死亡率％
理论死亡率＝1-(1-有效成份A在该剂量下的死亡率)(1-有效成份B在该剂量下的死亡率)
增效效果≥20，表示显著增效；10≤增效效果＜20，表示增效；-10≤增效效果＜10之间，表示相加；增效效果＜-10，表示拮抗，负值越大，拮抗程度越大。
结果如表15所示，由结果可以看出，有效成份A为化合物1、化合物4、化合物8时，对小菜蛾具有优良活性；有效成份B为啶虫脒、二氯噻吡嘧啶时，对小菜蛾具有较好活性；当A与B组合时，联合作用表现为增效或显著增效。
表15供试药剂室内对小菜蛾的杀虫活性
供试药剂或组合名称 剂量mg/L 3d死亡率％ 理论死亡率％ 增效效果 联合作用方式
化合物1 0.01 36.67 / / /
化合物4 0.01 43.33 / / /
化合物8 0.02 53.33 / / /
啶虫脒 4.0 60.00 / / /
二氯噻吡嘧啶 4.0 70.00 / / /
化合物1+啶虫脒 0.01+4.0 100 74.67 25.33 显著增效
化合物4+啶虫脒 0.01+4.0 100 77.33 22.67 显著增效
化合物8+二氯噻吡嘧啶 0.04+1.0 100 86.00 14.00 增效
生测实施例3：有效成份A为式II化合物与有效成份B为噻虫嗪、三氟苯嘧啶、氟啶虫胺腈等杀虫剂的组合物，对菜缢管蚜的活性测试
靶标：菜缢管蚜若蚜，室内饲养。
方法：浸渍法。操作描述如下：甘蓝叶碟准备，用棉球保湿叶柄。若蚜准备：向每碟接成蚜5头，24h后去成蚜，试验前选取大于15头的叶碟用于试验。处理方法为浸渍法：将叶碟(带若蚜)浸入药液中10s，3次重复。处理后培养与调查：置于光照培养箱内，温度25℃，光照14hL:10hD，培养。药后3天调查蚜虫死虫数，计算死亡率。
评价方法同生测实施例2。
结果如表16所示，由结果可以看出，有效成份A为化合物6、化合物8、化合物10时，对菜缢管蚜具有优良活性；有效成份B为噻虫嗪、三氟苯嘧啶、氟啶虫胺腈时，对菜缢管蚜具有较好活性；当A与B组合时，联合作用表现为增效。
表16供试药剂室内对菜缢管蚜的杀虫活性
供试药剂或组合名称 剂量mg/L 3d死亡率％ 理论死亡率％ 增效效果 联合作用方式
化合物2 10 55.62      
化合物3 10 75.69      
化合物6 10 60.07 / / /
化合物8 10 71.55 / / /
化合物10 10 78.29 / / /
化合物14 10 76.83      
噻虫嗪 0.4 73.22 / / /
三氟苯嘧啶 4 55.86 / / /
氟啶虫胺腈 0.05 45.12 / / /
化合物2+三氟苯嘧啶 10+4 100 80.85 19.15 增效
化合物3+三氟苯嘧啶 10+4 100 89.27 10.73 增效
化合物6+噻虫嗪 10+0.4 100 89.30 10.70 增效
化合物8+三氟苯嘧啶 10+4 100 87.44 12.56 增效
化合物10+氟啶虫胺腈 10+0.05 100 88.09 11.91 增效
化合物14+氟啶虫胺腈 10+0.05 100 87.28 12.72 增效
生测实施例4：有效成份A为式II化合物与有效成份B为三氟苯嘧啶、环氧虫啶、氟吡呋喃酮等杀虫剂的组合物，对水稻二化螟的活性测试
靶标：二化螟3龄幼虫，室内饲养。
方法：二化螟稻茎浸渍法。
方法：同生测实施例1；评价方法与标准同生测实施例2。
结果如表17所示，由结果可以看出，有效成份A为化合物7、化合物10、化合物11时，对二化螟具有优良活性；有效成份B为三氟苯嘧啶、氟吡呋喃酮、环氧虫啶时，对二化螟具有较好活性；当A与B组合时，联合作用表现为增效或显著增效。
表17供试药剂室内对二化螟的杀虫活性
供试药剂或组合名称 剂量mg/L 3d死亡率％ 理论死亡率％ 增效效果 联合作用方式
化合物5 1.0 63.33 / / /
化合物7 0.5 50.00 / / /
化合物9 1.0 66.67 / / /
化合物10 0.7 50.00 / / /
化合物11 1.0 56.67 / / /
化合物12 1.0 56.67 / / /
化合物13 0.5 33.33 / / /
三氟苯嘧啶 10 56.67 / / /
氟吡呋喃酮 40 76.67 / / /
环氧虫啶 100 73.33 / / /
化合物5+三氟苯嘧啶 1.0+10 100 84.11 15.89 增效
化合物7+三氟苯嘧啶 0.5+10 100 78.33 21.67 显著增效
化合物12+三氟苯嘧啶 1.0+10 100 85.56 14.44 增效
化合物13+三氟苯嘧啶 0.5+10 100 71.12 28.89 显著增效
化合物10+氟吡呋喃酮 0.7+100 100 88.33 11.67 增效
化合物11+环氧虫啶 1.0+40 100 88.44 11.56 增效
生测实施例5：有效成份A式II化合物与有效成份B为丙硫菌唑、戊唑醇等杀菌剂的组合物，对小麦白粉病的活性测试
靶标：小麦白粉病，室内活体保存菌种。
方法：盆栽喷雾法。先喷雾，后接种，再培养和调查。将小麦苗放置于生测喷雾塔转盘上(频率设定为F35，即14转/分)，用喉头喷雾器将药剂均匀喷洒于准备好的小麦苗上，每处理3盆钵小麦。喷施各处理药液12mL；放置于室内自然晾干。施药时同种药剂从低浓度到高浓度依次施药。施药前及不同药剂之间清洗喷雾塔转盘、喉头喷雾器贮液杯和喷头各3次。在药剂处理后24小时，将接种后10d左右发病小麦叶片上产生的白粉病菌孢子均匀抖落接种于盆栽小麦苗上，置于18～22℃培养室内培养，光照周期为L/D＝14h/10h。接种后12d，待对照病情稳定后进行调查，共调查1次。调查每盆钵全部植株的茎基部第一片叶片的病情指数，分级方法如下：0级：无病；1级：病斑面积占整片叶面积的5％以下；3级：病斑面积占整片叶面积的6％～15％以下；5级：病斑面积占整片叶面积的16％～25％以下；7级：病斑面积占整片叶面积的26％～50％以下；9级：病斑面积占整片叶面积的50％以上。
评价方法与标准同生测实施例2。
结果如表18所示，由结果可以看出，有效成份A为化合物1、化合物8时，对小麦白粉病无活性；有效成份B为丙硫菌唑、戊唑醇时，对小麦白粉病具有优良活性；当A与B组合时，联合作用表现为相加，可以复配或桶混，扩大防治谱，减少用药次数。
表18供试药剂室内对小麦白粉病的杀菌活性
供试药剂或组合名称 剂量mg/L 实际防效％ 理论防效％ 增效效果 联合作用方式
化合物1 500 0 / / /
化合物1 50 0 / / /
化合物8 5 0 / / /
化合物8 0.05 0 / / /
丙硫菌唑 5 46 / / /
戊唑醇 5 95 / / /
化合物1+丙硫菌唑 500+5 50 46 4 相加
化合物1+丙硫菌唑 50+5 53 46 7 相加
化合物8+戊唑醇 5+5 98 95 3 相加
化合物8+戊唑醇 0.05+5 97 95 2 相加
生测实施例6：有效成份A为式II化合物与有效成份B为肟菌酯、吡唑醚菌酯等杀菌剂的组合物，对水稻稻瘟病的活性测试
靶标：水稻稻瘟病，室内保存菌种。
方法：盆栽喷雾法。先喷雾，后接种，再培养和调查。药剂处理：将每处理3盆苗放到圆形生测喷雾塔转盘中央，设置转盘旋转频率f为35(14转/min)，将配置好的药液(每处理10mL)用喉头喷雾器(压力0.15MPa)均匀喷施于水稻叶面，药液自然风干。每处理3盆，并设空白对照。孢子悬浮液制备：将在米糠培养基上进行产孢培养5d左右的稻瘟菌平板，用孢子洗脱液(0.1％吐温+1％葡萄糖+0.4％酵母膏)洗下孢子，2～4层纱布过滤，用血球计数板在显微镜10倍镜下对稻瘟菌孢子进行计数，计算并稀释孢子浓度至10 6个/mL，制成孢子悬浮液，备用。接种与培养：药剂处理24h后，用喉头喷雾器(压力0.15MP)均 匀接种孢子悬浮液，孢子悬液接种量为30mL/24盆苗，接种后移至保湿箱中，然后用喉头喷雾器向保湿箱中喷40mL洗脱液增加保湿箱的湿度(确保保湿箱中相对湿度100％，保持叶面有结露)，人工气候室温度设为28℃，黑布遮光保湿培养24h。然后在28℃，相对湿度85％～90％的保湿箱中12h光/暗培养5～7d。调查时间：处理后5～7d，视空白对照发病情况(病叶率达到50％以上)进行调查，调查1次。调查方法：每处理调查全部株数，每株调查倒数第1片叶。稻瘟病的分级方法为：0级：整株无病；1级：现褐点病斑(1～5个病斑)；3级：出现典型纺锤形病斑，病斑面积占整叶面积的5％以下(5～10个病斑)；5级：典型病斑，病斑面积占整叶面积的6％～25％(11～16个病斑)；7级：典型病斑，病斑面积占整叶面积的26％～50％(16～25个病斑)；9级：典型病斑，病斑面积占整叶面积的50％以上(25个以上病斑)。
评价方法与标准同生测实施例2。
结果如表19所示，由结果可以看出，有效成份A为化合物8、化合物10时，对水稻稻瘟病无活性；有效成份B为肟菌酯、吡唑醚菌酯时，对水稻稻瘟病具有优良活性；当A与B组合时，联合作用表现为相加，可以复配或桶混，扩大防治谱，减少用药次数。
表19供试药剂室内对水稻稻瘟病的杀菌活性
供试药剂或组合名称 剂量mg/L 实际防效％ 理论防效％ 增效效果 联合作用方式
化合物8 0.05 0 / / /
化合物8 0.5 0 / / /
化合物10 40 0 / / /
化合物10 400 0 / / /
肟菌酯 4 85 / / /
吡唑醚菌酯 5 75 / / /
化合物8+肟菌酯 0.05+4 90 85 5 相加
化合物8+肟菌酯 0.5+4 90 85 5 相加
化合物10+吡唑醚菌酯 40+5 80 75 5 相加
化合物10+吡唑醚菌酯 400+5 80 75 5 相加
生测实施例7：有效成份A为式II化合物与有效成份B为丙硫菌唑、氰烯菌酯等杀菌剂的组合物，对小麦赤霉病的活性测试
靶标：小麦赤霉病，室内保存菌种。
方法：平皿法。操作参照NY/T1156.2-2006。
评价方法与标准同生测实施例2。
结果如表20所示，由结果可以看出，有效成份A为化合物4、化合物6时，对小麦赤霉病无活性；有效成份B为丙硫菌唑、氰烯菌酯时，对小麦赤霉病具有优良活性；当A与B组合时，联合作用表现为相加，可以复配或桶混，扩大防治谱，减少用药次数。
表20供试药剂室内对小麦赤霉病的杀菌活性
供试药剂或组合名称 剂量(mg/L) 实际防效％ 理论防效％ 增效效果 联合作用方式
化合物4 0.05 0      
化合物4 0.5 0      
化合物6 40 0      
化合物6 400 0      
丙硫菌唑 4 80      
氰烯菌酯 5 60      
化合物4+丙硫菌唑 0.05+4 85 80 5 相加
化合物4+丙硫菌唑 0.5+4 85 80 5 相加
化合物6+氰烯菌酯 40+5 65 60 5 相加
化合物6+氰烯菌酯 400+5 65 60 5 相加
化合物6+丙硫菌唑+氰烯菌酯 0.5+4+5 95 92 3 相加
生测实施例8：有效成份A为化合物4与有效成份为B为环氧虫啶时，对褐飞虱具有协同增效作用
方法：稻苗浸渍法。参照NY/T1154.11-2008。
测试靶标：褐飞虱，3龄若虫。
方法操作描述如下：药剂配置：按试验设计的比例和剂量，称取一定量的原药，用N,N-二甲基甲酰胺(DMF)溶解，之后加0.05％吐温80水配制成一定浓度的母液。每个配比设5～7个剂量，按照试验设计，依次用母液稀释至试验剂量。药剂处理：将水稻苗浸入药液中10s，然后装入一次性杯中，每杯接虫15头，用保鲜膜封口，每处理45头试虫。浸药时同种药剂从低浓度到高浓度依次进行，设空白对照和溶剂对照。处理完毕后置于光照培养箱内，温度为28±1℃，光暗比15h:9h。结果调查：药后3d调查死虫数。数据处理：利用DPS(v16.05)统计分析软件，计算各药剂的LC 50值及其的95％置信限。
评价方法参照NY/T1154.7-2006，以共毒系数进行评价。
混剂的共毒系数(CTC值)按式(1)、式(2)、式(3)计算：
Figure PCTCN2019099949-appb-000030
式中：ATI—混剂实际毒力指数；
S—标准药剂的LC 50，单位为毫克每升(mg/L)；
M—测试药剂的LC 50，单位为毫克每升(mg/L)。
TTI＝A×P A+B×P B···································································(2)
式中：TTI—混剂理论毒力指数；
A—A药剂实际毒力指数；
P A—A药剂在混剂中的百分含量，单位为百分率(％)；
B—B药剂实际毒力指数；
P B—B药剂在混剂中的百分含量，单位为百分率(％)。
Figure PCTCN2019099949-appb-000031
式中：CTC—共毒系数；ATI—混剂实际毒力指数；TTI—混剂理论毒力指数。
复配剂的共毒系数(CTC)≥120表现为增效作用；CTC≤80表现为拮抗作用；80＜CTC＜120表现为相加作用。
结果如表21所示，由结果可以看出，化合物4和环氧虫啶对褐飞虱均有较好活性；两者复配，160:1～1:160各个配比的增效系数为91.24～237.55，均表现为相加或增效作用；在配比80:1～1:80表现为增效作用。
表21化合物4和环氧虫啶对褐飞虱的共毒系数
Figure PCTCN2019099949-appb-000032
Figure PCTCN2019099949-appb-000033
生测实施例9：有效成份A为化合物7与有效成份B为与噻虫嗪的组合物对蚜虫具有协同增效作用。
方法：浸虫法
靶标：苜蓿蚜，3日龄若虫。
方法操作参照生测实施例3，药剂处理：将带若虫叶片浸入药液中10s，插入装满清水的青霉素瓶中，封口，晾干后，用透明塑料杯罩住，每重复蚜虫15～30头，每处理3次重复。浸药时同种药剂从低浓度到高浓度依次进行，设空白对照和溶剂对照。处理完毕后置于室内温度19～26℃，湿度35％～65％，培养架光照14Lh:10Dh的观察室中观察。
评价，同生测实施例8。
结果如表22所示，由结果可以看出，化合物7和噻虫嗪对苜蓿蚜均有较好活性；化合物7和噻虫嗪复配，50:1～1:10各个配比的增效系数为83.14～136.22，均表现为相加或增效作用；在配比5:1～25:1时表现为增效作用。
表22化合物7和噻虫嗪对苜蓿蚜的共毒系数
Figure PCTCN2019099949-appb-000034
生测实施例10：有效成份A为化合物8与有效成份B为氟吡呋喃酮时，对水稻褐飞虱具有增效作用。
方法：稻苗浸渍法。同生测实施例8。
测试靶标：褐飞虱，3龄若虫。
结果如表23所示，由结果可以看出，化合物8和氟吡呋喃酮对褐飞虱均有较好活性；两者复配，120:1～1:120各个配比的增效系数为98.37～271.44，均表现为相加或增效作用；在配比60:1～1:60表现为增效作用。
表23化合物8和氟吡呋喃酮对褐飞虱的共毒系数
Figure PCTCN2019099949-appb-000035
生测实施例11：有效成份A为化合物7与有效成份B为吡蚜酮时，对水稻褐飞虱具有协同增效作用。
方法：稻苗浸渍法。同生测实施例8。
测试靶标：褐飞虱，3龄若虫。
结果如表24所示，由结果可以看出，化合物7和吡蚜酮对褐飞虱均有较好活性；两者复配，100:1～1:100各个配比的增效系数为91.24～237.55，均表现为相加或增效作用；在配比50:1～1:50表现为增效作用。
表24化合物7和吡蚜酮对褐飞虱的共毒系数
Figure PCTCN2019099949-appb-000036
Figure PCTCN2019099949-appb-000037
生测实施例12：有效成份A为化合物1与有效成份B为二氯噻吡嘧啶时，对小菜蛾的活性测试
方法：浸叶碟饲喂法，操作同生测实施例1，评价同生测实施例8。
靶标：小菜蛾3龄幼虫。
结果如表25所示，由结果可以看出，化合物1和二氯噻吡嘧啶对蔬菜小菜蛾均有较好活性；两者复配，120:1～1:120各个配比的增效系数为90.30～186.10，均表现为相加或增效作用；在配比80:1～1:80表现为增效作用。
表25化合物1和二氯噻吡嘧啶对小菜蛾的活性测试
Figure PCTCN2019099949-appb-000038
生测实施例13：有效成份A为化合物7与有效成份B为双丙环虫酯时，对蔬菜蚜虫具有协同增效作用。
方法：浸渍法，操作同生测实施例9，评价同生测实施例8。
靶标：苜蓿蚜3日龄若蚜。
结果如表26所示，由结果可以看出，化合物7和双丙环虫酯对苜蓿蚜均有较好活性；两者复配，120:1～1:120各个配比的增效系数为86.17～230.53，均表现为相加或增效作用；在配比80:1～1:80表现为增效作用。
表26化合物7和双丙环虫酯对苜蓿蚜的活性测试
Figure PCTCN2019099949-appb-000039
Figure PCTCN2019099949-appb-000040
申请人声明，本申请通过上述实施例来说明本申请的含有间二酰胺类化合物的药物组合物及其应用，但本申请并不局限于上述实施例，即不意味着本申请必须依赖上述实施例才能实施。所属技术领域的技术人员应该明了，对本申请的任何改进，对本申请产品各原料的等效替换及辅助成分的添加、具体方式的选择等，均落在本申请的保护范围和公开范围之内。

Claims (15)

  1. 一种含有间二酰胺类化合物的药物组合物，其中所述药物组合物包括有效成分A和有效成分B，所述有效成分A为具有式I所示结构的酰胺类化合物，所述有效成分B包括其他杀虫剂或杀菌剂中任意一种或两种的组合；
    Figure PCTCN2019099949-appb-100001
    其中，Z选自氢、氟、氯、溴、碘、氰基、硝基、取代或未取代的3-10元杂环基、C 1-C 6烷基、C 1-C 6卤代烷基、C 1-C 6烷氧基、C 1-C 6卤代烷氧基、C 1-C 6烷基亚磺酰基、C 1-C 6卤代烷基亚磺酰基、C 1-C 6烷基磺酰基或C 1-C 6卤代烷基磺酰基；Q选自C 3-C 8环烷基或C 3-C 8卤代环烷基；X选自氢、氟或三氟甲基；Y 1选自氟、氯、溴、碘、氰基、硝基、C 1-C 6烷基、C 1-C 6卤代烷基、C 1-C 6卤代烷氧基、C 2-C 4烯基、C 2-C 4卤代烯基、C 2-C 4炔基、C 2-C 4卤代炔基、C 3-C 8环烷基、C 3-C 8卤代环烷基、C 1-C 6烷基羰基、C 1-C 6烷基亚磺酰基、C 1-C 6卤代烷基亚磺酰基、C 1-C 6烷基磺酰基或C 1-C 6卤代烷基磺酰基；Y 2选自溴、碘、氰基、硝基、C 1-C 6卤代烷基、C 1-C 6卤代烷氧基、C 2-C 4烯基、C 2-C 4卤代烯基、C 2-C 4炔基、C 2-C 4卤代炔基、C 3-C 8环烷基、C 3-C 8卤代环烷基、C 1-C 6烷基羰基、C 1-C 6烷基亚磺酰基、C 1-C 6卤代烷基亚磺酰基、C 1-C 6烷基磺酰基或C 1-C 6卤代烷基磺酰基；R 1选自氢、氟或甲氧基；R 2选自氟或三氟甲基；R 3和R 4分别独立地选自氢、卤素、氰基、硝基、C 1-C 6烷基、C 1-C 6卤代烷基、C 3-C 8环烷基或C 3-C 8卤代环烷基；m表示0～5的整数；n表示0～3的整数；W 1和W 2独立地为氧原子或硫原子。
  2. 根据权利要求1所述的含有间二酰胺类化合物的药物组合物，其中所述有效成分A为具有如下式II所示结构的间二酰胺类化合物：
    Figure PCTCN2019099949-appb-100002
    式II中，
    Z选自氢、氟、氯、溴、碘、氰基、C 1-C 6卤代烷基、C 1-C 6卤代烷氧基、C 1-C 6烷基磺酰基或C 1-C 6卤代烷基磺酰基；
    Y选自C 1-C 6卤代烷基或C 1-C 6卤代烷氧基；
    R选自氢或甲基。
  3. 根据权利要求2所述的含有间二酰胺类化合物的药物组合物，其中在式II中，
    Z选自氢、氟、氯、溴、碘、氰基、三氟甲氧基、三氟甲基、甲磺酰基或三氟甲磺酰基；
    Y选自三氟甲基或三氟甲氧基；
    R选自氢或甲基。
  4. 根据权利要求1-3中任一项所述的含有间二酰胺类化合物的药物组合物，其中所述间二酰胺类化合物为选自以下化合物1-14中的任意一种或至少两种的组合：
    Figure PCTCN2019099949-appb-100003
  5. 根据权利要求1-4中任一项所述的含有间二酰胺类化合物的药物组合物，其中所述有效成分B选自噻虫嗪、吡虫啉、噻虫胺、噻虫啉、啶虫脒、烯啶虫胺、呋虫胺、环氧虫啶、氟吡呋喃酮、氟啶虫胺腈、氟啶虫酰胺、吡蚜酮、噻嗪酮、三氟苯嘧啶、二氯噻吡嘧啶、双丙环虫酯、pyrifluquinazon、benzpyrimoxan、苯醚甲环唑、戊唑醇、丙硫菌唑、环丙唑醇、嘧菌酯、肟菌酯、吡唑醚菌酯、啶氧菌酯、精甲霜灵、甲霜灵、咯菌腈、咪鲜胺或氰烯菌酯中任意一种或两种。
  6. 根据权利要求1-4中任一项所述的含有间二酰胺类化合物的药物组合物，其中所述有效成分A和有效成分B中杀虫剂的重量比是200:1-1:200。
  7. 根据权利要求6所述的含有间二酰胺类化合物的药物组合物，其中当所述含间二酰胺类化合物的药物组合物中有效成分B为噻虫嗪、吡虫啉、噻虫胺、噻虫啉、啶虫脒、烯啶虫胺、呋虫胺、环氧虫啶时，有效成分A和有效成分B的重量比为80:1-1:80；
    当所述含有间二酰胺类化合物的药物组合物中有效成分B为氟吡呋喃酮、氟啶虫胺腈时，有效成分A和有效成分B的重量比为60:1-1:60；
    当所述含有间二酰胺类化合物的药物组合物中有效成分B为氟啶虫酰胺、吡蚜酮、噻嗪酮时，有效成分A和有效成分B的重量比为100:1～1:100，优选50:1～1:50；
    当所述含有间二酰胺类化合物的药物组合物中有效成分B为三氟苯嘧啶、二氯噻吡嘧啶时，有效成分A和有效成分B的重量比为80:1-1:80；
    当所述含有间二酰胺类化合物的药物组合物中有效成分B为双丙环虫酯、pyrifluquinazon、benzpyrimoxan时，有效成分A和有效成分B的重量比为80:1-1:80；
    当所述含有间二酰胺类化合物的药物组合物中有效成分B为苯醚甲环唑、戊唑醇、丙硫菌唑、环丙唑醇时，有效成分A和有效成分B的重量比为100:1～1:100；
    当所述含有间二酰胺类化合物的药物组合物中有效成分B为嘧菌酯、肟菌酯、吡唑醚菌酯、啶氧菌酯时，有效成分A和有效成分B的重量比为80:1～1:80；或者
    当所述含有间二酰胺类化合物的药物组合物中有效成分B为甲霜灵、精甲霜灵、咯菌腈、咪鲜胺、氰烯菌酯时，有效成分A和有效成分B的重量比为80:1～1:80。
  8. 一种药物制剂，其包括权利要求1-7所述的含有间二酰胺类化合物的药物组合物以及农药学上可接受的助剂和/或载体。
  9. 根据权利要求8所述的药物制剂，其中所述农药学上可接受的助剂包括分散剂、润湿剂、乳化剂、防冻剂、增稠剂、消泡剂、防腐剂、稳定剂或染色剂中的任意一种或至少两种的组合；并且
    所述载体包括填料和/或溶剂。
  10. 根据权利要求8所述的药物制剂，其中所述药物制剂的剂型为可溶液剂、可溶粉剂、可溶粒剂、乳油、可湿性粉剂、水乳剂、悬浮剂、可分散油悬浮剂、水分散粒剂、微囊悬浮剂、颗粒剂、微乳剂、悬浮乳剂、微囊悬浮-悬浮剂、超低容量液剂、热雾剂、展膜油剂、悬浮种衣剂、种子处理干粉剂、种子处理悬浮剂、种子处理可溶粉剂、种子处理可分散粉剂、种子处理乳剂或种子处理液剂；
    优选地，所述药物制剂的剂型为可溶液剂、可溶粒剂、悬浮剂、乳油、可湿性粉剂、水乳剂、水分散粒剂、可分散油悬浮剂、微囊悬浮剂、超低容量液剂、热雾剂、悬浮种衣剂或种子处理可分散粉剂。
  11. 根据权利要求8所述的药物制剂，其中在所述农药制剂中，所述含间二酰胺类化合物的药物组合物的重量百分含量为0.01-99％，优选为0.5～95％。
  12. 根据权利要求1-7中任一项所述的药物组合物或权利要求8-11中任一项所述的药物制剂在农业、林业、园艺上防治植物病害或虫害中的应用。
  13. 根据权利要求12所述的应用，其中在应用时可以采用喷雾、浇灌、种子处理的用药方式。
  14. 一种防治植物病虫害的方法，其为：向需要控制的植物病害或其生长的介质上施用有效剂量的如权利要求1-7中任一项所述的含有间二酰胺类化合物的药物组合物或权利要求8-11中任一项所述的药物制剂。
  15. 根据权利要求14所述的方法，其中所述有效剂量为每公顷1-1000g，优选每公顷7.5-500g。
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