WO2022160466A1 - 2-氰基丙烯酸酯类化合物及其制备方法和应用 - Google Patents

2-氰基丙烯酸酯类化合物及其制备方法和应用 Download PDF

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WO2022160466A1
WO2022160466A1 PCT/CN2021/086372 CN2021086372W WO2022160466A1 WO 2022160466 A1 WO2022160466 A1 WO 2022160466A1 CN 2021086372 W CN2021086372 W CN 2021086372W WO 2022160466 A1 WO2022160466 A1 WO 2022160466A1
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alkyl
halogenated
cycloalkyl
alkoxy
alkylamino
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PCT/CN2021/086372
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English (en)
French (fr)
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马忠华
吴宁捷
王洪雷
陈云
许天明
曹杨
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浙江大学
浙江省化工研究院有限公司
江苏省农药研究所股份有限公司
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Priority to EP21922065.4A priority Critical patent/EP4238958A4/en
Publication of WO2022160466A1 publication Critical patent/WO2022160466A1/zh

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C255/00—Carboxylic acid nitriles
    • C07C255/01—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms
    • C07C255/32—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms having cyano groups bound to acyclic carbon atoms of a carbon skeleton containing at least one six-membered aromatic ring
    • C07C255/42—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms having cyano groups bound to acyclic carbon atoms of a carbon skeleton containing at least one six-membered aromatic ring the carbon skeleton being further substituted by singly-bound nitrogen atoms, not being further bound to other hetero atoms
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    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
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    • C07C255/32—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms having cyano groups bound to acyclic carbon atoms of a carbon skeleton containing at least one six-membered aromatic ring
    • C07C255/41—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms having cyano groups bound to acyclic carbon atoms of a carbon skeleton containing at least one six-membered aromatic ring the carbon skeleton being further substituted by carboxyl groups, other than cyano groups
    • 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
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    • 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
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    • 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
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    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
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    • 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
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    • 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
    • A01N43/44—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom three- or four-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
    • A01N43/34—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom
    • A01N43/46—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom rings with more than six members
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/48—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with two nitrogen atoms as the only ring hetero atoms
    • A01N43/60—1,4-Diazines; Hydrogenated 1,4-diazines
    • 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
    • A01N43/72—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms
    • A01N43/84—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms six-membered rings with one nitrogen atom and either one oxygen atom or one sulfur atom in positions 1,4
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01P—BIOCIDAL, PEST REPELLANT, PEST ATTRACTANT OR PLANT GROWTH REGULATORY ACTIVITY OF CHEMICAL COMPOUNDS OR PREPARATIONS
    • A01P3/00—Fungicides
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C255/00—Carboxylic acid nitriles
    • C07C255/01—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms
    • C07C255/32—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms having cyano groups bound to acyclic carbon atoms of a carbon skeleton containing at least one six-membered aromatic ring
    • C07C255/42—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms having cyano groups bound to acyclic carbon atoms of a carbon skeleton containing at least one six-membered aromatic ring the carbon skeleton being further substituted by singly-bound nitrogen atoms, not being further bound to other hetero atoms
    • C07C255/44—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms having cyano groups bound to acyclic carbon atoms of a carbon skeleton containing at least one six-membered aromatic ring the carbon skeleton being further substituted by singly-bound nitrogen atoms, not being further bound to other hetero atoms at least one of the singly-bound nitrogen atoms being acylated
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D203/00—Heterocyclic compounds containing three-membered rings with one nitrogen atom as the only ring hetero atom
    • C07D203/04—Heterocyclic compounds containing three-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings
    • C07D203/06—Heterocyclic compounds containing three-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
    • C07D203/08—Heterocyclic compounds containing three-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to the ring nitrogen atom
    • C07D203/14—Heterocyclic compounds containing three-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to the ring nitrogen atom with carbocyclic rings directly attached to the ring nitrogen atom
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    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D205/00—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom
    • C07D205/02—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings
    • C07D205/04—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
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    • C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
    • C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
    • C07D295/14—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C07D295/155—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals with the ring nitrogen atoms and the carbon atoms with three bonds to hetero atoms separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings

Definitions

  • the invention belongs to the field of fungicides, and in particular relates to a 2-cyanoacrylate compound and its application for preventing and controlling fungal diseases of crops.
  • 2-cyanoacrylate compounds not only have antitumor and other medicinal activities, but also have herbicidal, antifungal, anti-plant virus and other pesticide activities, so they have been paid much attention in the field of pesticide creation.
  • the fungicide variety cyanobacteryl can effectively control diseases such as wheat scab, rice bakanae disease and so on.
  • Patent document CN1160318C discloses a class of 2-cyano-3-substituted phenyl acrylate compounds represented by the following general formula (a), which have control effects on various diseases caused by Fusarium such as wheat scab ;
  • Patent document CN109879834A discloses a class of 2-cyano-3-amino acrylate compounds represented by the following general formula (b), and this type of Mannich base fungicide is effective against plant diseases caused by Fusarium spp. have preventive effect;
  • Patent document CN109867623A discloses a class of 3-pyridyl 3-amino-2-cyanoacrylate compounds represented by the following general formula (c), which are effective against wheat scab, rice bakanae disease, watermelon wilt Disease, banana fusarium wilt and other crop diseases have control effect;
  • the purpose of the present invention is to provide a novel 2-cyanoacrylate compound with high bactericidal activity, which is used for preventing and treating diseases of crops.
  • the present invention proposes a 2-cyanoacrylate compound whose structural formula is shown in formula (I):
  • L is an integer of 1-5.
  • the L is an integer of 1-4.
  • the said L is an integer of 1-3.
  • the said L is an integer of 1-2.
  • the X is selected from -NR 1 R 2 .
  • R 1 and R 2 are independently selected from hydrogen, hydroxyl, amino, C 1 -C 10 alkyl, halogenated C 1 -C 10 alkyl, C 3 -C 10 cycloalkyl , halogenated C 3 -C 10 cycloalkyl, C 3 -C 10 cycloalkyl C 1 -C 6 alkyl, cyano C 1 -C 10 alkyl, C 1 -C 10 alkoxy, halogenated C 1 -C 10 alkoxy, hydroxy C 1 -C 10 alkyl, C 1 -C 10 alkoxy C 1 -C 6 alkyl, halogenated C 1 -C 10 alkoxy C 1 -C 6 alkyl , C 2 -C 10 alkenyl, C 2 -C 10 alkenyl C 1 -C 6 alkyl, C 2 -C 10 alkynyl, C 2 -C 10 alkynyl C 1 -
  • the substituents R 1 and R 2 are independently selected from hydrogen, hydroxyl, amino, C 1 -C 6 alkyl, halogenated C 1 -C 6 alkyl, C 3 -C 6 ring Alkyl, halogenated C 3 -C 6 cycloalkyl, C 3 -C 6 cycloalkyl C 1 -C 6 alkyl, cyano C 1 -C 6 alkyl, C 1 -C 6 alkoxy, halogen Substituted C 1 -C 6 alkoxy, hydroxy C 1 -C 6 alkyl, C 1 -C 6 alkoxy C 1 -C 6 alkyl, halogenated C 1 -C 6 alkoxy C 1 -C 6 Alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkenyl, C 1 -C 6 alkyl, C 2 -C 6 alkynyl, C 2 -C 6 alkynyl, C 1 -C 6 al
  • the substituents R 1 and R 2 are independently selected from hydrogen, hydroxyl, amino, C 1 -C 3 alkyl, halogenated C 1 -C 3 alkyl, C 3 -C 6 cycloalkane group, halogenated C 3 -C 6 cycloalkyl, C 3 -C 6 cycloalkyl C 1 -C 3 alkyl, cyano C 1 -C 3 alkyl, C 1 -C 3 alkoxy, halogenated C 1 -C 3 alkoxy, hydroxy C 1 -C 3 alkyl, C 1 -C 3 alkoxy C 1 -C 3 alkyl, halogenated C 1 -C 3 alkoxy C 1 -C 3 alkane base, C 2 -C 3 alkenyl, C 2 -C 3 alkenyl, C 1 -C 3 alkyl, C 2 -C 3 alkynyl, C 2 -C 3 alkynyl, C 1 -C 3 alky
  • the substituents R 1 and R 2 are independently selected from hydrogen, C 1 -C 3 alkyl, halogenated C 1 -C 3 alkyl, C 3 -C 6 cycloalkyl, halogen Substituted C 3 -C 6 cycloalkyl, C 3 -C 6 cycloalkyl C 1 -C 3 alkyl, cyano C 1 -C 3 alkyl, hydroxy C 1 -C 3 alkyl, C 1 -C 3 Alkoxy C 1 -C 3 alkyl, halogenated C 1 -C 3 alkoxy C 1 -C 3 alkyl, amino C 1 -C 3 alkyl, C 1 -C 3 alkylamino C 1 -C 3 alkyl, C 1 -C 3 dialkylamino C 1 -C 3 alkyl, C 1 -C 3 alkylcarbonyl, C 1 -C 3 alkoxycarbonyl, C 1 -C 3 alky
  • R 3 , R 4 , and R 5 are independently selected from hydrogen, hydroxyl, amino, C 1 -C 10 alkyl, halogenated C 1 -C 10 Alkyl, C 3 -C 10 cycloalkyl, halogenated C 3 -C 10 cycloalkyl, C 1 -C 10 alkoxy, halogenated C 1 -C 10 alkoxy, C 1 -C 10 alkyl Amino, C 1 -C 10 dialkylamino, halogenated C 1 -C 10 alkylamino, halogenated C 1 -C 10 dialkylamino.
  • the substituents R 3 , R 4 and R 5 are independently selected from hydrogen, hydroxyl, amino, C 1 -C 6 alkyl, halogenated C 1 -C 6 alkyl, C 3 -C C 6 cycloalkyl, halogenated C 3 -C 6 cycloalkyl, C 1 -C 6 alkoxy, halogenated C 1 -C 6 alkoxy, C 1 -C 6 alkylamino, C 1 -C 6 dialkylamino, halogenated C 1 -C 6 alkylamino, halogenated C 1 -C 6 dialkylamino.
  • the substituents R 3 , R 4 and R 5 are independently selected from hydrogen, hydroxyl, amino, C 1 -C 3 alkyl, halogenated C 1 -C 3 alkyl, C 3 -C 6 -cycloalkyl, halogenated C 3 -C 6 cycloalkyl, C 1 -C 3 alkoxy, halogenated C 1 -C 3 alkoxy, C 1 -C 3 alkylamino, C 1 -C 3 Dialkylamino, halogenated C 1 -C 3 alkylamino, halogenated C 1 -C 3 dialkylamino.
  • the above -NR 1 R 2 structure can also exist in the following cyclized form:
  • the -NR 1 R 2 structure exists in the following cyclized form:
  • R 6 and R 7 are independently selected from hydrogen, hydroxyl, amino, C 1 -C 10 alkyl, halogenated C 1 -C 10 alkyl, C 3 -C 10 cycloalkyl, halogenated C 3 -C 10 cycloalkyl, C 1 -C 10 alkoxy, halogenated C 1 -C 10 alkoxy, C 1 -C 10 alkylamino, C 1 -C 10 dialkylamino, halogenated C 1 -C 10 alkylamino, halogenated C 1 -C 10 dialkylamino.
  • the substituents R 6 and R 7 are independently selected from hydrogen, hydroxyl, amino, C 1 -C 6 alkyl, halogenated C 1 -C 6 alkyl, C 3 -C 6 ring Alkyl, halogenated C 3 -C 6 cycloalkyl, C 1 -C 6 alkoxy, halogenated C 1 -C 6 alkoxy, C 1 -C 6 alkylamino, C 1 -C 6 dioxane amino, halogenated C 1 -C 6 alkylamino, halogenated C 1 -C 6 dialkylamino.
  • the substituents R 6 and R 7 are independently selected from hydrogen, hydroxyl, amino, C 1 -C 3 alkyl, halogenated C 1 -C 3 alkyl, C 3 -C 6 cycloalkane base, halogenated C 3 -C 6 cycloalkyl, C 1 -C 3 alkoxy, halogenated C 1 -C 3 alkoxy, C 1 -C 3 alkylamino, C 1 -C 3 dialkyl Amino, halogenated C 1 -C 3 alkylamino, halogenated C 1 -C 3 dialkylamino.
  • the substituent R 6 is independently selected from hydrogen, C 1 -C 3 alkyl, halogenated C 1 -C 3 alkyl, C 3 -C 6 cycloalkyl, halogenated C 3 -C 6 cycloalkyl.
  • m is an integer of 1-4.
  • the m is an integer of 1-3.
  • the said m is an integer of 1-2.
  • Y is independently selected from hydrogen, C 1 -C 10 alkyl, halogenated C 1 -C 10 alkyl, C 3 - C 10 cycloalkyl or one of the following structures represented by Y 1 to Y 3 :
  • the substituent Y is independently selected from hydrogen, C 1 -C 6 alkyl, halogenated C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl or the following Y 1 to Y 3 one of the structures shown.
  • the substituent Y is independently selected from hydrogen, C 1 -C 3 alkyl, halogenated C 1 -C 3 alkyl, C 3 -C 6 cycloalkyl or the following Y 1 to Y 3 one of the structures shown.
  • the substituent Y is independently selected from hydrogen, C 1 -C 3 alkyl, halogenated C 1 -C 3 alkyl, or one of the structures represented by Y 1 to Y 2 below.
  • n is an integer of 1 to 10.
  • the n is an integer of 1-6.
  • n is an integer of 1-3.
  • n is an integer of 1-2.
  • alkyl refers to straight or branched chain forms, such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl , n-pentyl, isopentyl, n-hexyl and other groups;
  • cycloalkyl refers to groups including cyclic chain forms, such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and other groups;
  • alkenyl refers to straight Chain or branched forms, such as vinyl, 1-propenyl, allyl, isopropenyl, 1-butenyl, 1,3-butadienyl, 1-hexenyl, etc.;
  • alkynyl is Refers to straight or branched chain forms, such as ethynyl, 1-propynyl, propargyl, 2-
  • Index Table 1 lists typical compounds represented by structural formula (I-1), but the typical compounds described in Index Table 1 do not limit the scope of the present invention.
  • the 2-cyanoacrylate compound represented by the general formula (I) is selected from at least one of the compounds represented by the following structural formula,
  • Index Table 2 lists typical compounds represented by structural formula (I-2), but the typical compounds described in Index Table 2 do not limit the scope of the present invention.
  • Index Table 3 lists typical compounds represented by the structural formula (I-3), but the typical compounds described in Index Table 3 do not limit the scope of the present invention.
  • Table 4 below is the NMR data of some compounds in Index Tables 1-3.
  • the compound numbers described in Table 4 correspond to the compound numbers described in Index Tables 1-3, that is, the compound of Compound No. 1 described in Table 4 is consistent with the compound of Compound No. 1 described in Index Table 1.
  • s is a singlet
  • d is a doublet
  • dd is a doublet
  • t is a triplet
  • td is a triplet
  • q is a quartet
  • m is a multiplet.
  • the present invention also provides a preparation method of the 2-cyanoacrylate compound represented by the above-mentioned structural formula (I-1), the method comprising:
  • the preparation method comprises the following steps:
  • the intermediate (A) reacts with the protecting group reagent to form the intermediate (B), and the organic solvent is selected from methanol, ethanol, toluene, dichloromethane, acetonitrile , at least one of acetone, tetrahydrofuran, dioxane, N,N-dimethylformamide and dimethyl sulfoxide; the protecting group reagent is selected from at least one of amino protecting group reagents;
  • the intermediate (B) reacts with the reducing reagent to generate the intermediate (C)
  • the organic solvent is selected from methanol, ethanol, toluene, dichloromethane, acetonitrile, At least one of acetone, tetrahydrofuran, dioxane, N,N-dimethylformamide and dimethyl sulfoxide
  • the reducing agent is selected from iron powder, zinc powder, stannous chloride, hydrogen/palladium carbon , at least one of the commonly used reducing reagents such as hydrogen/Raney nickel, sodium dithionite, hydrazine hydrate;
  • intermediate (C) In an organic solvent, in the presence of a base, at a temperature of 0 to 100° C., intermediate (C), R 1 X and R 2 X undergo a two-step reaction to generate intermediate (D), and the organic solvent is selected from At least one selected from methanol, ethanol, toluene, dichloromethane, acetonitrile, acetone, tetrahydrofuran, dioxane, N,N-dimethylformamide and dimethylsulfoxide; the base is selected from organic bases and inorganic bases At least one of bases; said R 1 X and R 2 X are selected from at least one of alkylating reagents, acylating reagents, and sulfonylating reagents;
  • the intermediate (D) and the deprotection reagent are reacted to generate a 2-cyanoacrylate compound represented by the general formula (I-1);
  • the organic solvent At least one selected from methanol, ethanol, toluene, dichloromethane, acetonitrile, acetone, tetrahydrofuran, dioxane, N,N-dimethylformamide and dimethyl sulfoxide;
  • the deprotection reagent is for At least one of the deprotection reagents for amino protecting groups.
  • the present invention also provides an application of the 2-cyanoacrylate compound represented by the general formula (I), and the 2-cyanoacrylate compound represented by the general formula (I) is suitable for controlling fungal diseases.
  • the 2-cyanoacrylate compound represented by the general formula (I) is used for preventing and controlling fungal diseases
  • the 2-cyanoacrylate compound represented by the general formula (I) is used for preventing and treating diseases caused by Fusarium Caused by at least one of the genus, Aeruginosa, Phytophthora, Alternaria, Acrocystis, Black powder, Aspergillus, Ascoidis, Botrytis and Rhizoctonia disease.
  • the 2-cyanoacrylate compound represented by the general formula (I) is used for controlling fungal diseases
  • the 2-cyanoacrylate compound represented by the general formula (I) is used for preventing and treating Gibberella in crops at least one of disease, bakanae, fusarium wilt, rice blast, botrytis, and anthracnose.
  • the present invention also provides a pesticide formulation, which contains 0.001%-99.99% by weight of the 2-cyanoacrylate compound represented by the general formula (I).
  • the pesticide preparation can be formulated into emulsifiable concentrate, suspension, water suspension, microemulsion, (water) emulsion, powder, wettable powder, soluble powder, (water dispersible) granule or capsule and the like.
  • the pesticide formulation provided by the present invention may further contain an agriculturally acceptable carrier in addition to 0.001%-99.99% by weight of the 2-cyanoacrylate compound represented by the general formula (I).
  • the carrier can be solid or liquid.
  • Suitable solid carriers include 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, hexamethylenediamine.
  • Liquid carriers include water and organic solvents. When water is used as a solvent or diluent, organic solvents can also be used as adjuvants or antifreeze additives.
  • Suitable organic solvents include aromatic hydrocarbons such as benzene, xylene, toluene, etc.; chlorinated hydrocarbons, such as chlorobenzene, vinyl chloride, chloroform, methylene chloride, etc.; aliphatic hydrocarbons, such as petroleum fractions, cyclohexane, light minerals oils; alcohols, such as isopropanol, butanol, ethylene glycol, glycerol, and cyclohexanol; and their ethers and esters; and ketones, such as acetone, cyclohexanone, and dimethylformamide and N-methyl-pyrrolidone.
  • aromatic hydrocarbons such as benzene, xylene, toluene, etc.
  • chlorinated hydrocarbons such as chlorobenzene, vinyl chloride, chloroform, methylene chloride, etc.
  • aliphatic hydrocarbons such as petroleum fractions, cyclohexane, light minerals oils
  • the carrier can also be a surfactant.
  • Suitable surfactants may be emulsifying agents, dispersing agents or wetting agents; may be ionic or nonionic.
  • Nonionic emulsifiers such as polyoxyethylene fatty acid esters, polyoxyethylene fatty alcohol ethers, polyoxyethylene fatty ammonia, and commercially available emulsifiers: agricultural milk 2201B, agricultural milk 0203B, agricultural milk 100 # , agricultural milk 500 # , Agriculture Milk 600 # , Agriculture Milk 600-2 # , Agriculture Milk 1601, Agriculture Milk 2201, Agriculture Milk NP-10, Agriculture Milk NP-15, Agriculture Milk 507 # , Agriculture Milk OX-635, Agriculture Milk OX-622, Agriculture Milk Milk Milk OX-653, Agricultural Milk OX-667, Ningru 36 # .
  • the dispersing agent includes sodium lignosulfonate, pulling powder, calcium lignosulfonate, methylnaphthalenesulfonate formaldehyde condensate and the like.
  • Wetting agents are: sodium lauryl sulfate, sodium dodecylbenzenesulfonate, sodium alkylnaphthalenesulfonate, etc.
  • the present invention also provides a sterilization method, the method comprising: applying the 2-cyanoacrylate compound represented by the general formula (I) to the pathogen to be controlled or a medium on which it grows.
  • the application amount is 10-1000 grams per hectare.
  • the present invention provides a novel 2-cyanoacrylate compound, which has good bactericidal activity, especially good bactericidal activity against Fusarium fungi. Therefore, the compound can be used for preparing fungicides in the fields of agriculture and horticulture, and has the advantages of high efficiency, low toxicity and environmental friendliness.
  • Embodiment 3 wettable powder formulation
  • Embodiment 4 emulsifiable concentrate formula
  • Embodiment 5 granule formulation
  • Embodiment 6 water dispersible granule formulation
  • Embodiment 7 water suspending agent formula
  • Embodiment 8 antibacterial activity determination test
  • the inhibitory activity of the compounds to be tested against the test pathogens was determined by the mycelial growth rate method.
  • the test pathogens were placed on the PDA plate, and when the growth rate reached the logarithmic phase, the bacteria blocks with a diameter of 0.5 cm were punched at the edge of the fresh colony and inoculated onto the PDA plate containing a certain concentration of the drug to be tested, and the bacteria blocks were inoculated at the same time. to PDA medium without the drug to be tested as a control. Cultivate in a 25°C incubator for 2-3 days. When the test pathogens overgrown the plate, take pictures and measure the growth diameter of the colonies by the cross method.
  • the experiment was repeated 2 times with 2 dishes each time.
  • the test pathogens were Fusarium oxysporum (Fusarium graminearum and Fusarium asiatica), cucurbit Fusarium wilt (Fusarium oxysporum), Fusarium oxysporum on banana (Fusarium oxysporum), rice baica (Fusarium moniliformes), ash Mold pathogens and rice blast pathogens.
  • the present invention evaluates the in vitro bactericidal activity of the numbered compounds described in Index Tables 1-3, and the results show that the compounds of the present invention have good bactericidal activity, especially against Fusarium spp. fungi, "mg/L "All refer to per mg of active substance/liter, cyanobacteryl as the control agent, as follows:
  • compounds 2, 3, 7, and 11 also showed good bacteriostatic activity against partial cyanobacterial-resistant gibberellin.
  • the mycelial growth inhibition rates of compounds 2, 3, 7, and 11 to the mutant strains of type I myosin S217A, M375A, F419A, and I581A were all greater than 60%.
  • Mycelial growth inhibition rates were 1.2%, 25%, 19%, and 33%, respectively.
  • Compounds 2, 3, 7 and 11 showed good bacteriostatic activities against Fusarium oxysporum, Fusarium wilt of banana and Bacillus oryzae. At a concentration of 1 mg/L, compounds 2, 3, 7, and 11 had a growth inhibition rate of more than 90% on the mycelial growth of these pathogens.

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Abstract

一种2-氰基丙烯酸酯类化合物及其对农作物真菌病害的防治应用，属于杀菌剂领域。所述2-氰基丙烯酸酯类化合物具有良好的杀菌活性，特别是对镰刀菌属真菌具有很好的杀菌活性，适合用于防治农作物真菌病害。因此，该化合物可用于制备农业、园艺等领域的杀菌剂，具有高效、低毒、环境友好的优点。

Description

2-氰基丙烯酸酯类化合物及其制备方法和应用 技术领域
本发明属于杀菌剂领域，具体涉及一种2-氰基丙烯酸酯类化合物及其对农作物真菌病害的防治应用。
背景技术
2-氰基丙烯酸酯类化合物不仅具有抗肿瘤等医药活性，而且具有除草、抗真菌、抗植物病毒等农药活性，因此在农药创制领域一直备受重视。例如杀菌剂品种氰烯菌酯，可以有效防治小麦赤霉病、水稻恶苗病等病害。
专利文献CN1160318C公开了一类如下通式(a)所示的2-氰基-3-取代苯基丙烯酸酯类化合物，该类化合物对小麦赤霉病等镰刀菌引起的多种病害具有防效；
Figure PCTCN2021086372-appb-000001
专利文献CN109879834A公开了一类如下通式(b)所示的2-氰基-3-氨基丙烯酸酯类化合物，该类曼尼希碱类杀菌剂对小麦赤霉病等镰刀菌引起的植物病害具有防治效果；
Figure PCTCN2021086372-appb-000002
专利文献CN109867623A公开了一类如以下通式(c)所示的3-吡啶基3-氨基-2-氰基丙烯酸酯类化合物，该化合物对麦类赤霉病、水稻恶苗病、西瓜枯萎病、香蕉枯萎病等多种作物病害具有防治效果；
Figure PCTCN2021086372-appb-000003
发明内容
本发明的目的在于提供一种具有高杀菌活性的新型2-氰基丙烯酸酯类化合物，用于防治农作物的病害。
为实现上述目的，本发明提出了结构式如式(I)所示的2-氰基丙烯酸酯类化合物：
Figure PCTCN2021086372-appb-000004
本发明提供的通式(I)所示的2-氰基丙烯酸酯类化合物中，L为1～5的整数。
作为一种优选的方式，所述L为1～4的整数。
作为进一步优选的方式，所述L为1～3的整数。
作为更进一步优选的方式，所述L为1～2的整数。
本发明提供的通式(I)所示的2-氰基丙烯酸酯类化合物中，X独立地选自-NR 1R 2、-N＝CR 3R 4、-N＝NR 5。
作为一种优选的方式，所述X选自-NR 1R 2。
上述-NR 1R 2结构中，R 1、R 2独立地选自氢、羟基、氨基、C 1-C 10烷基、卤代C 1-C 10烷基、C 3-C 10环烷基、卤代C 3-C 10环烷基、C 3-C 10环烷基C 1-C 6烷基、氰基C 1-C 10烷基、C 1-C 10烷氧基、卤代C 1-C 10烷氧基、羟基C 1-C 10烷基、C 1-C 10烷氧基C 1-C 6烷基、卤代C 1-C 10烷氧基C 1-C 6烷基、C 2-C 10烯基、C 2-C 10烯基C 1-C 6烷基、C 2-C 10炔基、C 2-C 10炔基C 1-C 6烷基、C 1-C 10烷基氨基、C 1-C 10二烷基氨基、卤代C 1-C 10烷基氨基、卤代C 1-C 10二烷基氨基、氨基C 1-C 10烷基、C 1-C 10烷基氨基C 1-C 6烷基、C 1-C 10二烷基氨基C 1-C 6烷基、C 1-C 10烷基羰基、C 1-C 10烷氧基羰基、C 1-C 10烷基氨基羰基、C 1-C 10二烷基氨基羰基、C 1-C 10烷基磺酰基、C 1-C 10烷氧基磺酰基、C 1-C 10烷基氨基磺酰基。
作为一种优选的方式，所述取代基R 1、R 2独立地选自氢、羟基、氨基、C 1-C 6烷基、卤代C 1-C 6烷基、C 3-C 6环烷基、卤代C 3-C 6环烷基、C 3-C 6环烷基C 1-C 6烷基、氰基C 1-C 6烷基、C 1-C 6烷氧基、卤代C 1-C 6烷氧基、羟基C 1-C 6烷基、C 1-C 6烷氧基C 1-C 6烷基、卤代C 1-C 6烷氧基C 1-C 6烷基、C 2-C 6烯基、C 2-C 6烯基C 1-C 6烷基、C 2-C 6炔基、C 2-C 6炔基C 1-C 6烷基、C 1-C 6烷基氨基、C 1-C 6二烷基氨基、卤代C 1-C 6烷基氨基、卤代C 1-C 6二烷基氨基、氨基C 1-C 6烷基、C 1-C 6烷基氨基C 1-C 6烷基、C 1-C 6二烷基氨基C 1-C 6烷基、C 1-C 6烷基羰基、C 1-C 6烷氧基羰基、C 1-C 6烷基氨基羰基、C 1-C 6二烷基氨基羰基、C 1-C 6烷基磺酰基、C 1-C 6烷氧基磺酰基、C 1-C 6烷基氨基磺酰基。
作为进一步优选的方式，所述取代基R 1、R 2独立地选自氢、羟基、氨基、C 1-C 3烷基、卤代C 1-C 3烷基、C 3-C 6环烷基、卤代C 3-C 6环烷基、C 3-C 6环烷基C 1-C 3烷基、氰基C 1-C 3烷基、C 1-C 3烷氧基、卤代C 1-C 3烷氧基、羟基C 1-C 3烷基、C 1-C 3烷氧基C 1-C 3烷基、卤代C 1-C 3烷氧基C 1-C 3烷基、C 2-C 3烯基、C 2-C 3烯基C 1-C 3烷基、C 2-C 3炔基、C 2-C 3炔基C 1-C 3烷基、C 1-C 3烷基氨基、C 1-C 3二烷基氨基、卤代C 1-C 3烷基氨基、卤代C 1-C 3二烷基氨基、氨基C 1-C 3烷基、C 1-C 3烷基氨基C 1-C 3烷基、C 1-C 3二烷基氨基C 1-C 3烷基、C 1-C 3烷基羰基、C 1-C 3烷氧基羰基、C 1-C 3烷基氨基羰基、C 1-C 3二烷基氨基羰基、C 1-C 3烷基磺酰基、C 1-C 3烷氧基磺酰基、C 1-C 3烷基氨基磺酰基。
作为更进一步优选的方式，所述取代基R 1、R 2独立地选自氢、C 1-C 3烷基、卤代C 1-C 3烷基、C 3-C 6环烷基、卤代C 3-C 6环烷基、C 3-C 6环烷基C 1-C 3烷基、氰基C 1-C 3烷基、羟基C 1-C 3烷基、C 1-C 3烷氧基C 1-C 3烷基、卤代C 1-C 3烷氧基C 1-C 3烷基、氨基C 1-C 3烷基、C 1-C 3烷基氨基C 1-C 3烷基、C 1-C 3二烷基氨基C 1-C 3烷基、C 1-C 3烷基羰基、C 1-C 3烷氧基羰基、C 1-C 3烷基氨基羰基、C 1-C 3二烷基氨基羰基。
上述-N＝CR 3R 4、-N＝NR 5结构中，R 3、R 4、R 5独立地选自氢、羟基、氨基、C 1-C 10烷基、卤代C 1-C 10烷基、C 3-C 10环烷基、卤代C 3-C 10环烷基、C 1-C 10烷氧基、卤代C 1-C 10烷氧基、C 1-C 10烷基氨基、C 1-C 10二烷基氨基、卤代C 1-C 10烷基氨基、卤代C 1-C 10二烷基氨基。
作为一种优选的方式，所述取代基R 3、R 4、R 5独立地选自氢、羟基、氨基、C 1-C 6烷基、卤代C 1-C 6烷基、C 3-C 6环烷基、卤代C 3-C 6环烷基、C 1-C 6烷氧基、卤代C 1-C 6烷氧基、C 1-C 6烷基氨基、C 1-C 6二烷基氨基、卤代C 1-C 6烷基氨基、卤代C 1-C 6二烷基氨基。
作为进一步优选的方式，所述取代基R 3、R 4、R 5独立地选自氢、羟基、氨基、C 1-C 3烷基、卤代C 1-C 3烷基、C 3-C 6环烷基、卤代C 3-C 6环烷基、C 1-C 3烷氧基、卤代C 1-C 3烷氧基、C 1-C 3烷基氨基、C 1-C 3二烷基氨基、卤代C 1-C 3烷基氨基、卤代C 1-C 3二烷基氨基。
上述-NR 1R 2结构，也能以下述环合的形式存在：
Figure PCTCN2021086372-appb-000005
作为一种优选的方式，所述-NR 1R 2结构，以下述环合的形式存在：
Figure PCTCN2021086372-appb-000006
上述环合结构中，R 6、R 7独立地选自氢、羟基、氨基、C 1-C 10烷基、卤代C 1-C 10烷基、C 3-C 10环烷基、卤代C 3-C 10环烷基、C 1-C 10烷氧基、卤代C 1-C 10烷氧基、C 1-C 10烷基氨基、C 1-C 10二烷基氨基、卤代C 1-C 10烷基氨基、卤代C 1-C 10二烷基氨基。
作为一种优选的方式，所述取代基R 6、R 7独立地选自氢、羟基、氨基、C 1-C 6烷基、卤代C 1-C 6烷基、C 3-C 6环烷基、卤代C 3-C 6环烷基、C 1-C 6烷氧基、卤代C 1-C 6烷氧基、C 1-C 6烷基氨基、C 1-C 6二烷基氨基、卤代C 1-C 6烷基氨基、卤代C 1-C 6二烷基氨基。
作为进一步优选的方式，所述取代基R 6、R 7独立地选自氢、羟基、氨基、C 1-C 3烷基、卤代C 1-C 3烷基、C 3-C 6环烷基、卤代C 3-C 6环烷基、C 1-C 3烷氧基、卤代C 1-C 3烷氧基、C 1-C 3烷基氨基、C 1-C 3二烷基氨基、卤代C 1-C 3烷基氨基、卤代C 1-C 3二烷基氨基。
作为更进一步优选的方式，所述取代基R 6独立地选自氢、C 1-C 3烷基、卤代C 1-C 3烷基、C 3-C 6环烷基、卤代C 3-C 6环烷基。
上述环合结构中，m为1～4的整数。
作为一种优选的方式，所述m为1～3的整数。
作为进一步优选的方式，所述m为1～2的整数。
本发明提供的通式(I)所示的2-氰基丙烯酸酯类化合物中，Y独立地选自氢、C 1-C 10烷基、卤代C 1-C 10烷基、C 3-C 10环烷基或如下Y 1至Y 3所示结构中的一种：
Figure PCTCN2021086372-appb-000007
作为一种优选的方式，所述取代基Y独立地选氢、C 1-C 6烷基、卤代C 1-C 6烷基、C 3-C 6环烷基或如下Y 1至Y 3所示结构中的一种。
作为进一步优选的方式，所述取代基Y独立地选自氢、C 1-C 3烷基、卤代C 1-C 3烷基、C 3-C 6环烷基或如下Y 1至Y 3所示结构中的一种。
作为更进一步优选的方式，所述取代基Y独立地选自氢、C 1-C 3烷基、卤代C 1-C 3烷基或如下Y 1至Y 2所示结构中的一种。
上述Y 1至Y 3所示的结构中，n为1～10的整数。
作为一种优选的方式，所述n为1～6的整数。
作为进一步优选的方式，所述n为1～3的整数。
作为更进一步优选的方式，所述n为1～2的整数。
本发明所述的取代基中：烷基是指直链或支链形式，例如甲基、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、正己基等基团；环烷基是指包括环状链形式，例如环丙基、环丁基、环戊基、环己基等基团；烯基是指直链或支链形式，例如乙烯基、1-丙烯基、烯丙基、异丙烯基、1-丁烯基、1，3-丁二烯基、1-己烯基等基团；炔基是指直链或支链形式，例如乙炔基、1-丙炔基、炔丙基、2-丁炔基、2-戊炔基、3-己炔基等基团；卤代烷基是指烷基被一个或多个卤原子取代的基团；烷氧基是指烷基末端连有氧原子的基团；卤代烷氧基是指烷基被一个或多个卤原子取代，末端连有氧原子的基团；卤素是指氟、氯、溴、碘；烷基氨基是指烷基末端连有氮原子的基团；卤代烷基氨基是指烷基被一个或多个卤原子取代，末端连有氮原子的基团；烷基羰基是指烷基末端连有羰基的基团；烷氧基羰基是指烷基末端连有氧原子，氧原子再与羰基相连的基团；烷基氨基羰基是指烷基末端连有氮原子，氮原子再与羰基相连的基团；烷基磺酰基是指烷基末端连有磺酰基的基团；烷氧基磺酰基是指烷基末端连有氮原子，氮原子再与磺酰基相连的基团；烷基氨基磺酰基是指烷基末端连有氮原子，氮原子再与羰基相连的基团。
本发明所述的通式(I)所示的2-氰基丙烯酸酯类化合物，X为-NR 1R 2、L为1时，其具有以下结构式(I-1)，
Figure PCTCN2021086372-appb-000008
索引表1列举了结构式(I-1)表示的典型化合物，但索引表1所述典型化合物并不限制本发明的范围。
索引表1
Figure PCTCN2021086372-appb-000009
Figure PCTCN2021086372-appb-000010
Figure PCTCN2021086372-appb-000011
Figure PCTCN2021086372-appb-000012
Figure PCTCN2021086372-appb-000013
作为最为优选的实施方式，上述通式(I)所示的2-氰基丙烯酸酯类化合物选自以下结构式所示化合物中的至少一种，
Figure PCTCN2021086372-appb-000014
Figure PCTCN2021086372-appb-000015
本发明所述的通式(I)表所示的2-氰基丙烯酸酯类化合物，X为-N＝CR 3R 4、L为1时，其具有以下结构式(I-2)，
Figure PCTCN2021086372-appb-000016
索引表2列举了结构式(I-2)表示的典型化合物，但索引表2所述典型化合物并不限制本发明的范围。
索引表2
Figure PCTCN2021086372-appb-000017
Figure PCTCN2021086372-appb-000018
Figure PCTCN2021086372-appb-000019
本发明所述的通式(I)表所示的2-氰基丙烯酸酯类化合物，X为-N＝NR 5、L为1时，其具有以下结构式(I-3)，
Figure PCTCN2021086372-appb-000020
索引表3列举了结构式(I-3)表示的典型化合物，但索引表3所述典型化合物并不限制本发明的范围。
索引表3
Figure PCTCN2021086372-appb-000021
Figure PCTCN2021086372-appb-000022
以下表4为索引表1-3中部分化合物的核磁数据。表4中所述化合物编号与索引表1-3中所述化合物编号相对应，即：表4所述化合物编号1的化合物与索引表1所述化合物编号1的化合物一致。表4中，s为单峰，d为双峰，dd为双二重峰，t为三重峰，td为三重二重峰，q为四重峰，m为多重峰。
表4化合物核磁数据
Figure PCTCN2021086372-appb-000023
Figure PCTCN2021086372-appb-000024
本发明还提供了一种上述结构式(I-1)所示的2-氰基丙烯酸酯类化合物的制备方法，所述方法包括：
Figure PCTCN2021086372-appb-000025
所述取代基R 1、R 2、Y的定义如前所述。
所述制备方法包括以下步骤：
(1)在有机溶剂中，在0～100℃温度下，中间体(A)和保护基试剂反应生成中间体(B)，所述有机溶剂选自甲醇、乙醇、甲苯、二氯甲烷、乙腈、丙酮、四氢呋喃、二氧六环、N,N-二甲基甲酰胺和二甲亚砜中的至少一种；所述保护基试剂选自氨基保护基试剂中的至少一种；
(2)在有机溶剂中，在0～100℃温度下，中间体(B)和还原试剂反应生成中间体(C)，所述有机溶剂选自甲醇、乙醇、甲苯、二氯甲烷、乙腈、丙酮、四氢呋喃、二氧六环、N,N-二甲基甲酰胺和二甲亚砜中的至少一种；所述还原试剂选自铁粉、锌粉、氯化亚锡、氢气/钯碳、氢气/兰尼镍、连二亚硫酸钠、水合肼等常用还原试剂中的至少一种；
(3)在有机溶剂中，在碱存在下，在0～100℃温度下，中间体(C)和R 1X、R 2X经两步反应生成中间体(D)，所述有机溶剂选自甲醇、乙醇、甲苯、二氯甲烷、乙腈、丙酮、四氢呋喃、二氧六环、N,N-二甲基甲酰胺和二甲亚砜的至少一种；所述碱选自有机碱和无机碱 中的至少一种；所述R 1X、R 2X选自烷基化试剂、酰基化试剂、磺酰基化试剂中的至少一种；
(4)在有机溶剂中，在0～100℃温度下，中间体(D)和脱保护试剂反应生成通式(I-1)所示的2-氰基丙烯酸酯类化合物；所述有机溶剂选自甲醇、乙醇、甲苯、二氯甲烷、乙腈、丙酮、四氢呋喃、二氧六环、N,N-二甲基甲酰胺和二甲亚砜中的至少一种；所述脱保护试剂为针对氨基保护基的脱保护试剂中的至少一种。
本发明还提供一种通式(I)所示的2-氰基丙烯酸酯类化合物的应用，所述通式(I)所示的2-氰基丙烯酸酯类化合物适合用于防治真菌病害。
当所述通式(I)所示的2-氰基丙烯酸酯类化合物用于防治真菌病害时，所述通式(I)所示的2-氰基丙烯酸酯类化合物用于防治由镰刀菌属、盘梗霉属、疫霉属、链格孢属、顶囊壳属、黑粉菌属、曲霉菌属、壳二孢属、葡萄孢属和丝核菌属中的至少一种引起的病害。
当所述通式(I)所示的2-氰基丙烯酸酯类化合物用于防治真菌病害时，所述通式(I)所示的2-氰基丙烯酸酯类化合物用于防治农作物赤霉病、恶苗病、枯萎病、稻瘟病、灰霉病、和炭疽病中的至少一种病害。
本发明还提供一种农药制剂，所述农药制剂含有0.001％-99.99％重量百分比的通式(I)所示的2-氰基丙烯酸酯类化合物。所述农药制剂，可以被配制成乳油、悬浮剂、水悬剂、微乳剂、(水)乳剂、粉剂、可湿性粉剂、可溶性粉剂、(水分散性)颗粒剂或胶囊剂等。
本发明提供的农药制剂，除含有0.001％-99.99％重量百分比的通式(I)所示的2-氰基丙烯酸酯类化合物外，还可以进一步地含有农业上可接受的载体。
载体可以是固体或液体。合适的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，当用水做溶剂或稀释剂时，有机溶剂也能用做辅助剂或防冻添加剂。合适的有机溶剂包括芳烃例如苯、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、丙三醇和环己醇等；以及它们的醚和酯；还有酮类，例如丙酮、环己酮以及二甲基甲酰胺和N-甲基-吡咯烷酮。
载体也可以是表面活性剂。合适的表面活性剂可以是乳化剂、分散剂或湿润剂；可以是离子型的或非离子型的。非离子型乳化剂例如聚氧乙烯脂肪酸脂、聚氧乙烯脂肪醇醚、聚氧乙烯脂肪氨，以及市售的乳化剂：农乳2201B、农乳0203B、农乳100 #、农乳500 #、农乳600 #、农乳600-2 #、农乳1601、农乳2201、农乳NP-10、农乳NP-15、农乳507 #、农乳OX-635、农乳OX-622、农乳OX-653、农乳OX-667、宁乳36 #。分散剂包括木质素磺酸钠、拉开粉、木质素磺酸钙、甲基萘磺酸甲醛缩合物等。湿润剂为：月桂醇硫酸钠、十二烷基苯磺酸钠、烷基萘磺酸钠等。
本发明还提供一种杀菌方法，所述方法包括：将通式(I)所示的2-氰基丙烯酸酯类化合物施用于需要控制的病菌或其生长的介质上。当将通式(I)所示的2-氰基丙烯酸酯类化合物施用于需要控制的病菌或其生长的介质上时，其施用量为每公顷10～1000克。
本发明具备的有益效果：
本发明提供了一种新型的2-氰基丙烯酸酯类化合物，该化合物具有良好的杀菌活性，特别是对镰刀菌属真菌具有很好的杀菌活性。因此，该化合物可用于制备农业、园艺等领域的杀菌剂，具有高效、低毒、环境友好的优点。
具体实施方式
下面结合具体实施例来对本发明进行进一步说明，但并不将本发明局限于这些具体实施方式。本领域技术人员应该认识到，本发明涵盖了权利要求书范围内所可能包括的所有备选方案、改进方案和等效方案。
在本发明中，若非特指，所有的份、百分比均为重量单位，所采用的设备和原料等均可从市场购得或是本领域常用的。下述实施例中的方法，如无特别说明，均为本领域的常规方法。
一、化合物制备
实施例1：化合物3的合成
步骤1：中间体3b的合成
Figure PCTCN2021086372-appb-000026
将7.0g原料3a、150mL二氯甲烷加入反应瓶中，冰浴下加入11.7g Boc酸酐，再缓慢加入6.0g三乙胺和3.3g DMAP，冰浴下继续搅拌0.5小时后升至室温，再搅拌5小时。反应结束后，向反应液中加入1M盐酸，分出有机相，有机相再用纯水和饱和食盐水各洗涤一次。有机相经无水Na 2SO 4干燥后浓缩，得到9.6g中间体3b，该粗品未经进一步纯化直接投入下一步反应。
步骤2：中间体3c的合成
Figure PCTCN2021086372-appb-000027
将9.6g中间体3b、120mL乙醇、24mL水加入反应瓶中，升温至90℃，加入3.7g铁粉和12mL饱和氯化铵溶液，继续反应4小时。反应结束后，加硅藻土过滤，滤液浓缩后加入水，乙酸乙酯萃取三次。合并有机相，浓缩后用柱层析分离(洗脱剂为乙酸乙酯与石油醚，体积比为1：2)，得到4.5g中间体3c，收率51.1％。
步骤3：中间体3d的合成
Figure PCTCN2021086372-appb-000028
冰浴下将0.19g氢化钠加入20mL四氢呋喃中，再加入1.0g中间体3c，升至室温后搅拌30分钟。再加入0.38g碘乙烷，室温搅拌过夜。反应结束后，加入水淬灭反应，再用乙酸乙酯萃取三次。合并有机相，浓缩后用柱层析分离(洗脱剂为乙酸乙酯与石油醚，体积比为1：5)，得到0.52g中间体3d，收率48.1％。
步骤4：化合物3的合成
Figure PCTCN2021086372-appb-000029
将0.52g中间体3d、20mL四氢呋喃加入反应瓶中，通过浓硫酸滴加氯化钠制取氯化氢气体，缓慢通入反应液，1小时后停止通气，室温搅拌过夜。反应结束后，加入饱和碳酸氢钠水溶液，并用乙酸乙酯萃取两次。合并有机相，浓缩后用柱层析分离(洗脱剂为乙酸乙酯与石油醚，体积比为1：2)，得到0.35g化合物3，收率93.3％。
实施例2：化合物11的合成
步骤1：中间体11d的合成
Figure PCTCN2021086372-appb-000030
冰浴下将0.19g氢化钠加入20mL四氢呋喃中，再加入1.0g中间体3c，升至室温后搅拌30分钟。再加入2.07g碘乙烷，升温至60℃反应24小时。反应结束后，加入水淬灭反应，再用乙酸乙酯萃取三次。合并有机相，浓缩后用柱层析分离(洗脱剂为乙酸乙酯与石油醚，体积比为1：2)，得到0.66g中间体11d，收率56.4％。
步骤2：化合物11的合成
Figure PCTCN2021086372-appb-000031
将0.66g中间体11d、20mL二氯甲烷加入反应瓶中，冰浴下滴加1.5mL三氟乙酸，室温搅拌过夜。反应结束后，加入饱和碳酸氢钠水溶液，并用乙酸乙酯萃取两次。合并有机相，浓缩后用柱层析分离(洗脱剂为乙酸乙酯与石油醚，体积比为1：1)，得到0.45g化合物11，收率91.8％。
二、制剂制备
以下实施例3至实施例7给出以本发明的化合物(I)作为活性物质组份，加工配制几种杀菌剂剂型的实际例子，需要指出的是本发明并不仅仅局限在下述实例的范围内。在这些配方例子中，所有的“％”均指重量百分比。
实施例3、可湿性粉剂配方
将15％的化合物(I)(索引表1和索引表2)、5％的木质素磺酸盐(M q)、1％的月桂醇聚氧乙烯醚(JFC)、40％的硅藻土和44％的轻质碳酸钙均匀地混合，粉碎，即得可湿性粉剂。
实施例4、乳油配方
将10％的化合物(I)(索引表1和索引表2)、5％的农乳500号(钙盐)、5％的农乳602号、5％的N-甲基-2-吡咯烷酮和75％的二甲苯加热搅拌均匀，即得乳油。
实施例5、粒剂配方
将5％的化合物(I)(索引表1和索引表2)、1％的聚乙烯醇(PVA)、4％的萘磺酸钠甲醛缩合物(NMO)和90％粘土均匀地混合，粉碎，然后向此100份混合物加入20份水，捏合，用挤压成粒机，制成14－32目的颗粒，干燥，即得颗粒剂。
实施例6、水分散性颗粒剂配方
将20％的化合物(I)(索引表1和索引表2)、萘磺酸盐甲醛缩合物4％、萘磺酸盐1％、白炭黑2％和73％高岭土进行混合粉碎，再加水捏合后，加入装有一定规格筛网的造粒机中进行造粒。然后再经干燥、筛分(按筛网范围)即得颗粒状产品。
实施例7、水悬浮剂配方
将20％的化合物(I)(索引表1和索引表2)、脂肪醇聚氧乙烯醚1％、松香嵌段聚氧乙烯醚聚氧丙烯醚磺酸盐3％、硅酸镁铝1％、有机硅消泡剂0.4％、丙二醇5％和去离子水(69.5％)进行预先混合均匀，再加入砂磨机中砂磨，过滤后得到悬浮母液，加入配置好的黄原胶(0.1％)水溶液剪切混合均匀即可。
三、活性测试
下面给出使用本发明的化合物进行生物活性测定的实例，需要指出的是本发明并不仅仅局限在下述实例的范围内。
实施例8、抑菌活性测定试验
采用菌丝生长速率法测定待测化合物对试验病原菌的抑制活性。将试验病原菌置于PDA平板上，待生长速率达到对数期，在新鲜菌落边缘用打孔器打直径0.5cm的菌块接种到含有一定浓度待测药物的PDA平板上，同时将菌块接种到不含待测药物的PDA培养基作为对照。25℃培养箱内培养2-3天，当试验病原菌长满平板后，进行拍照，并用十字交叉法测量菌落生长直径。其中菌丝生长抑制率(MGIR)用以下公式计算，MGIR％＝[(C-N)/C]×100％，其中C为对照组菌落直径，N为有处理组的菌落直径。实验重复2次，每次重复2皿。试验病原菌为小麦赤霉病菌(禾谷镰刀菌和亚洲镰刀菌)、瓜类枯萎病(尖孢镰刀菌)、香蕉枯萎病菌(尖孢镰刀菌)、水稻恶苗病菌(串珠镰刀菌)、灰霉病原菌和稻瘟病原病。
本发明对索引表1-3中所述编号化合物进行离体杀菌活性评价，结果表明：本发明化合物具有良好的杀菌活性，特别是对镰刀菌属真菌具有很好的杀菌活性，“mg/L”均指每毫克活性物/升，氰烯菌酯作为对照药剂，具体如下：
在0.5mg/L浓度下，化合物1、2、3、4、7、8、11、14、15、16、17、20、25、26、27、28、34、35、36、37对赤霉病原菌的菌丝生长抑制率均大于90％，对照药剂氰烯菌酯对赤霉病原菌的菌丝生长抑制率约为70％；在0.25mg/L浓度下，化合物2、3、4、7、8、11、14、15、16、17对赤霉病原菌的菌丝生长抑制率均大于90％，显著高于对照药剂氰烯菌酯；在0.125mg/L浓度下，化合物2、3、7、11对赤霉病原菌的菌丝生长抑制率均大于90％，显著高于对照药剂氰烯菌酯。各个化合物对赤霉病菌菌丝生长抑制率见下表。
表5
Figure PCTCN2021086372-appb-000032
Figure PCTCN2021086372-appb-000033
此外，化合物2、3、7、11对部分氰烯菌酯抗性的赤霉病菌也显示良好抑菌的活性。在2mg/L浓度下，化合物2、3、7、11对I型肌球蛋白S217A、M375A、F419A、I581A突变菌株的菌丝生长抑制率均大于60％，对照药剂氰烯菌酯对上述菌株菌丝生长抑制率分别为1.2％、25％、19％、33％。
化合物2、3、7、11对瓜类枯萎病菌、香蕉枯萎病菌和水稻恶苗病菌表现良好抑菌的活性。在1mg/L浓度下，化合物2、3、7、11对这些病菌的菌丝生长抑制率均大于90％，对照药剂氰烯菌酯对上述病菌菌丝生长抑制率为25％。

Claims (10)

  1. 一种结构式如式(I)所示的2-氰基丙烯酸酯类化合物，
    Figure PCTCN2021086372-appb-100001
    其中：X独立地选自-NR 1R 2、-N＝CR 3R 4、-N＝NR 5；
    所述-NR 1R 2中，R 1、R 2独立地选自氢、羟基、氨基、C 1-C 10烷基、卤代C 1-C 10烷基、C 3-C 10环烷基、卤代C 3-C 10环烷基、C 3-C 10环烷基C 1-C 6烷基、氰基C 1-C 10烷基、C 1-C 10烷氧基、卤代C 1-C 10烷氧基、羟基C 1-C 10烷基、C 1-C 10烷氧基C 1-C 6烷基、卤代C 1-C 10烷氧基C 1-C 6烷基、C 2-C 10烯基、C 2-C 10烯基C 1-C 6烷基、C 2-C 10炔基、C 2-C 10炔基C 1-C 6烷基、C 1-C 10烷基氨基、C 1-C 10二烷基氨基、卤代C 1-C 10烷基氨基、卤代C 1-C 10二烷基氨基、氨基C 1-C 10烷基、C 1-C 10烷基氨基C 1-C 6烷基、C 1-C 10二烷基氨基C 1-C 6烷基、C 1-C 10烷基羰基、C 1-C 10烷氧基羰基、C 1-C 10烷基氨基羰基、C 1-C 10二烷基氨基羰基、C 1-C 10烷基磺酰基、C 1-C 10烷氧基磺酰基、C 1-C 10烷基氨基磺酰基；
    或者-NR 1R 2结构为环合的形式：
    Figure PCTCN2021086372-appb-100002
    Figure PCTCN2021086372-appb-100003
    其中R 6、R 7独立地选自氢、羟基、氨基、C 1-C 10烷基、卤代C 1-C 10烷基、C 3-C 10环烷基、卤代C 3-C 10环烷基、C 1-C 10烷氧基、卤代C 1-C 10烷氧基、C 1-C 10烷基氨基、C 1-C 10二烷基氨基、卤代C 1-C 10烷基氨基、卤代C 1-C 10二烷基氨基；
    m为1～4的整数；
    R 3、R 4、R 5独立地选自氢、羟基、氨基、C 1-C 10烷基、卤代C 1-C 10烷基、C 3-C 10环烷基、卤代C 3-C 10环烷基、C 1-C 10烷氧基、卤代C 1-C 10烷氧基、C 1-C 10烷基氨基、C 1-C 10二烷基氨基、卤代C 1-C 10烷基氨基、卤代C 1-C 10二烷基氨基；
    L为1～5的整数；
    Y独立地选自氢、C 1-C 10烷基、卤代C 1-C 10烷基、C 3-C 10环烷基或如下Y 1至Y 3所示结构中的一种：
    Figure PCTCN2021086372-appb-100004
    n为1～10的整数。
  2. 如权利要求1所述的2-氰基丙烯酸酯类化合物，其特征在于，
    所述-NR 1R 2中，R 1、R 2独立地选自氢、羟基、氨基、C 1-C 6烷基、卤代C 1-C 6烷基、C 3-C 6环烷基、卤代C 3-C 6环烷基、C 3-C 6环烷基C 1-C 6烷基、氰基C 1-C 6烷基、C 1-C 6烷氧基、卤代C 1-C 6烷氧基、羟基C 1-C 6烷基、C 1-C 6烷氧基C 1-C 6烷基、卤代C 1-C 6烷氧基C 1-C 6烷基、C 2-C 6烯基、C 2-C 6烯基C 1-C 6烷基、C 2-C 6炔基、C 2-C 6炔基C 1-C 6烷基、C 1-C 6烷基氨基、C 1-C 6二烷基氨基、卤代C 1-C 6烷基氨基、卤代C 1-C 6二烷基氨基、氨基C 1-C 6烷基、C 1-C 6烷基氨基 C 1-C 6烷基、C 1-C 6二烷基氨基C 1-C 6烷基、C 1-C 6烷基羰基、C 1-C 6烷氧基羰基、C 1-C 6烷基氨基羰基、C 1-C 6二烷基氨基羰基、C 1-C 6烷基磺酰基、C 1-C 6烷氧基磺酰基、C 1-C 6烷基氨基磺酰基；
    或者-NR 1R 2结构为环合的形式时，R 6、R 7独立地选自氢、羟基、氨基、C 1-C 6烷基、卤代C 1-C 6烷基、C 3-C 6环烷基、卤代C 3-C 6环烷基、C 1-C 6烷氧基、卤代C 1-C 6烷氧基、C 1-C 6烷基氨基、C 1-C 6二烷基氨基、卤代C 1-C 6烷基氨基、卤代C 1-C 6二烷基氨基；m为1～3的整数；
    R 3、R 4、R 5独立地选自氢、羟基、氨基、C 1-C 6烷基、卤代C 1-C 6烷基、C 3-C 6环烷基、卤代C 3-C 6环烷基、C 1-C 6烷氧基、卤代C 1-C 6烷氧基、C 1-C 6烷基氨基、C 1-C 6二烷基氨基、卤代C 1-C 6烷基氨基、卤代C 1-C 6二烷基氨基；
    L为1～4的整数；
    Y独立地选自氢、C 1-C 6烷基、卤代C 1-C 6烷基、C 3-C 6环烷基或如Y 1至Y 3所示结构中的一种，其中n为1～6的整数。
  3. 如权利要求2所述的2-氰基丙烯酸酯类化合物，其特征在于，
    所述-NR 1R 2中，R 1、R 2独立地选自氢、羟基、氨基、C 1-C 3烷基、卤代C 1-C 3烷基、C 3-C 6环烷基、卤代C 3-C 6环烷基、C 3-C 6环烷基C 1-C 3烷基、氰基C 1-C 3烷基、C 1-C 3烷氧基、卤代C 1-C 3烷氧基、羟基C 1-C 3烷基、C 1-C 3烷氧基C 1-C 3烷基、卤代C 1-C 3烷氧基C 1-C 3烷基、C 2-C 3烯基、C 2-C 3烯基C 1-C 3烷基、C 2-C 3炔基、C 2-C 3炔基C 1-C 3烷基、C 1-C 3烷基氨基、C 1-C 3二烷基氨基、卤代C 1-C 3烷基氨基、卤代C 1-C 3二烷基氨基、氨基C 1-C 3烷基、C 1-C 3烷基氨基C 1-C 3烷基、C 1-C 3二烷基氨基C 1-C 3烷基、C 1-C 3烷基羰基、C 1-C 3烷氧基羰基、C 1-C 3烷基氨基羰基、C 1-C 3二烷基氨基羰基、C 1-C 3烷基磺酰基、C 1-C 3烷氧基磺酰基、C 1-C 3烷基氨基磺酰基；
    或者-NR 1R 2结构为环合的形式时，R 6、R 7独立地选自氢、羟基、氨基、C 1-C 3烷基、卤代C 1-C 3烷基、C 3-C 6环烷基、卤代C 3-C 6环烷基、C 1-C 3烷氧基、卤代C 1-C 3烷氧基、C 1-C 3烷基氨基、C 1-C 3二烷基氨基、卤代C 1-C 3烷基氨基、卤代C 1-C 3二烷基氨基；m为1～2的整数；
    R 3、R 4、R 5独立地选自氢、羟基、氨基、C 1-C 3烷基、卤代C 1-C 3烷基、C 3-C 6环烷基、卤代C 3-C 6环烷基、C 1-C 3烷氧基、卤代C 1-C 3烷氧基、C 1-C 3烷基氨基、C 1-C 3二烷基氨基、卤代C 1-C 3烷基氨基、卤代C 1-C 3二烷基氨基；
    L为1～3的整数；
    Y独立地选自氢、C 1-C 3烷基、卤代C 1-C 3烷基、C 3-C 6环烷基或如Y 1至Y 3所示结构中的一种，其中n为1～3的整数。
  4. 如权利要求3所述的2-氰基丙烯酸酯类化合物，其特征在于，
    X独立地选自-NR 1R 2；
    R 1、R 2独立地选自氢、C 1-C 3烷基、卤代C 1-C 3烷基、C 3-C 6环烷基、卤代C 3-C 6环烷基、C 3-C 6环烷基C 1-C 3烷基、氰基C 1-C 3烷基、羟基C 1-C 3烷基、C 1-C 3烷氧基C 1-C 3烷基、卤代C 1-C 3烷氧基C 1-C 3烷基、氨基C 1-C 3烷基、C 1-C 3烷基氨基C 1-C 3烷基、C 1-C 3二烷基氨基C 1-C 3烷基、C 1-C 3烷基羰基、C 1-C 3烷氧基羰基、C 1-C 3烷基氨基羰基、C 1-C 3二烷基氨基羰基；
    或者-NR 1R 2结构为环合的形式：
    Figure PCTCN2021086372-appb-100005
    Figure PCTCN2021086372-appb-100006
    R 6独立地选自氢、C 1-C 3烷基、卤代C 1-C 3烷基、C 3-C 6环烷基、卤代C 3-C 6环烷基；m为1～2的整数；
    L为1～2的整数；
    Y独立地选自氢、C 1-C 3烷基、卤代C 1-C 3烷基或如Y 1、Y 2所示结构中的一种，n为1～2的整数。
  5. 如权利要求4所述的2-氰基丙烯酸酯类化合物，其特征在于，所述化合物选自以下结构式所示化合物中的至少一种，
    Figure PCTCN2021086372-appb-100007
  6. 如权利要求1所述的2-氰基丙烯酸酯类化合物的制备方法，其特征在于，所述化合物结构中X为-NR 1R 2、L为1，所述制备方法包括以下步骤：
    (1)在有机溶剂中，在0～100℃温度下，结构式如(A)所示的化合物和氨基保护基试剂反应生成中间体B；
    Figure PCTCN2021086372-appb-100008
    (2)在有机溶剂中，在0～100℃温度下，中间体B和还原试剂反应生成中间体C，所述还原试剂选自铁粉、锌粉、氯化亚锡、氢气/钯碳、氢气/兰尼镍、连二亚硫酸钠、水合肼中的至少一种；
    (3)在有机溶剂中，在碱存在下，在0～100℃温度下，中间体C和R 1X、R 2X经两步反应生成中间体D，所述碱选自有机碱和无机碱中的至少一种；所述R 1X、R 2X选自烷基化试剂、酰基化试剂、磺酰基化试剂中的至少一种；
    (4)在有机溶剂中，在0～100℃温度下，中间体D和脱保护试剂反应生成所述的2-氰基丙烯酸酯类化合物；；所述脱保护试剂为针对氨基保护基的脱保护试剂中的至少一种；
    步骤(1)-(4)中有机溶剂选自甲醇、乙醇、甲苯、二氯甲烷、乙腈、丙酮、四氢呋喃、二氧六环、N,N-二甲基甲酰胺和二甲亚砜中的至少一种。
  7. 如权利要求1-5任一项所述的2-氰基丙烯酸酯类化合物在防治农作物真菌病害的应用。
  8. 如权利要求7所述的应用，其特征在于，所述农作物真菌病害为镰刀菌属、盘梗霉属、链格孢属、顶囊壳属、黑粉菌属、曲霉菌属、壳二孢属、葡萄孢属中丝核菌属中的至少一种引起的病害。
  9. 如权利要求7所述的应用，所述2-氰基丙烯酸酯类化合物的施用量为每公顷10～1000克。
  10. 一种农药制剂，其特征在于：所述农药制剂含有0.001％-99.99％重量百分比的权利要求1-5任一项所述的2-氰基丙烯酸酯类化合物。
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