WO2021036966A1 - 一种双酰胺类化合物及其应用 - Google Patents

一种双酰胺类化合物及其应用 Download PDF

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WO2021036966A1
WO2021036966A1 PCT/CN2020/110707 CN2020110707W WO2021036966A1 WO 2021036966 A1 WO2021036966 A1 WO 2021036966A1 CN 2020110707 W CN2020110707 W CN 2020110707W WO 2021036966 A1 WO2021036966 A1 WO 2021036966A1
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compound
iii
general formula
bisamide
spp
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PCT/CN2020/110707
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English (en)
French (fr)
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张立新
张静
汪杰
裴鸿艳
盛祝波
康卓
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沈阳化工大学
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Priority to BR112022002171A priority Critical patent/BR112022002171A2/pt
Priority to US17/638,743 priority patent/US20220220073A1/en
Priority to AU2020336740A priority patent/AU2020336740B2/en
Priority to CN202080060723.4A priority patent/CN115038691B/zh
Publication of WO2021036966A1 publication Critical patent/WO2021036966A1/zh

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C07D213/81—Amides; Imides
    • C07D213/82—Amides; Imides in position 3
    • 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
    • A01N37/44—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
    • A01P—BIOCIDAL, PEST REPELLANT, PEST ATTRACTANT OR PLANT GROWTH REGULATORY ACTIVITY OF CHEMICAL COMPOUNDS OR PREPARATIONS
    • A01P7/00—Arthropodicides
    • A01P7/04—Insecticides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P33/00—Antiparasitic agents
    • 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
    • C07C237/40—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 the nitrogen atom of the carboxamide group bound to a carbon atom of a six-membered aromatic ring
    • 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
    • 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
    • C07C255/57—Carboxylic acid nitriles having cyano groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton containing cyano groups and carboxyl groups, other than cyano groups, bound to the carbon skeleton
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/06—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom containing only hydrogen and carbon atoms in addition to the ring nitrogen atom
    • C07D213/16—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom containing only hydrogen and carbon atoms in addition to the ring nitrogen atom containing only one pyridine ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D213/26—Radicals substituted by halogen atoms or nitro radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C07D213/84—Nitriles
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2601/00—Systems containing only non-condensed rings
    • C07C2601/02—Systems containing only non-condensed rings with a three-membered ring
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
    • Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Definitions

  • the invention relates to a compound, in particular to a novel bisamide compound and its application.
  • Bisamide insecticides have been popular products in the market since they came out. Their representative varieties are fluorfenbenzamide and chlorantraniliprole. However, due to the long-term unreasonable use of existing pesticides, the resistance problem has become more and more serious. . On the other hand, the insecticidal effect of existing insecticides, especially the activity of Chilo suppressalis, is still unsatisfactory, and it is difficult to meet the ever-increasing use requirements of insecticides in reality. In this field, there is still a need to actively develop new pesticides with higher activity to meet the needs of agriculture and other fields.
  • the object of the present invention is to provide a bisamide compound with more excellent insecticidal activity. It can be used to prepare drugs for controlling pests in agriculture and other fields, and for preparing drugs for controlling animal parasites in the field of veterinary medicine.
  • the present invention provides the following technical solutions:
  • R 1 is selected from halogen
  • R 2 is selected from halogen, C 1 -C 4 haloalkyl or C 1 -C 4 haloalkoxy;
  • R 3 is selected from CF 3 or CF 2 CF 3 ;
  • R 4 is selected from fluorine, difluoromethyl, trifluoromethyl or cyano.
  • R 1 is selected from halogen
  • R 2 is selected from halogen, C 1 -C 2 haloalkyl or C 1 -C 2 haloalkoxy;
  • R 3 is selected from CF 3 or CF 2 CF 3 ;
  • R 4 is selected from fluorine, difluoromethyl, trifluoromethyl or cyano.
  • R 1 is selected from bromine or iodine
  • R 2 is selected from bromine, iodine, trifluoromethyl or difluoromethoxy
  • R 3 is selected from CF 3 or CF 2 CF 3 ;
  • R 4 is selected from fluorine, difluoromethyl, trifluoromethyl or cyano.
  • R 4 is selected from fluorine, difluoromethyl or trifluoromethyl.
  • the bisamide compound is selected from the compound of Table 1, and the compound of Table 1 has the structure of Formula I and R 1 , R 2 , R 3 and R 4 are as shown in Table 1:
  • the bisamide compound is selected from the compounds in Table 2, and the compounds in Table 2 have the structure of Formula I and R 1 , R 2 , R 3 and R 4 are as shown in Table 2:
  • R 1 is selected from halogen
  • R 2 is selected from halogen, C 1 -C 4 haloalkyl or C 1 -C 4 haloalkoxy;
  • R 3 is selected from CF 3 or CF 2 CF 3 .
  • R 1 is selected from halogen
  • R 2 is selected from halogen, C 1 -C 2 haloalkyl or C 1 -C 2 haloalkoxy;
  • R 3 is selected from CF 3 or CF 2 CF 3 .
  • R 1 is selected from bromine or iodine
  • R 2 is selected from bromine, iodine, trifluoromethyl or difluoromethoxy
  • R 3 is selected from CF 3 or CF 2 CF 3 .
  • the intermediate compound of the general formula II is selected from the compound of Table 3, and the compound of Table 3 has the structure of the general formula II and R 1 , R 2 and R 3 are as shown in Table 3:
  • R 4 is selected from fluorine, difluoromethyl, trifluoromethyl or cyano
  • L is selected from halogen or hydroxyl.
  • the intermediate compound of the general formula III is selected from the compound of Table 4, and the compound of Table 4 has the structure of the general formula III and R 4 and L are as shown in Table 4:
  • the embodiment of the present invention also provides the preparation method of the above-mentioned bisamide compound, and the compounds of general formula I, II, and III can be prepared according to the following method (each group in the formula has the same definition as before unless otherwise specified):
  • the compound of general formula IV and bromomethylcyclopropane are reacted in a suitable solvent at a temperature from -10°C to the boiling point of the solvent for 0.5-48 hours to obtain a compound of general formula II.
  • the reaction can be carried out in the presence of a base;
  • the compound and the compound of the general formula V are reacted in a suitable solvent at a temperature from -10°C to the boiling point of the solvent for 0.5-48 hours to obtain the compound of the general formula I, and the reaction can be carried out in the presence of a base.
  • the solvent includes: aromatic hydrocarbons such as benzene, toluene, and xylene; ketones such as acetone, methyl ethyl ketone and methyl isobutyl ketone; halogenated hydrocarbons such as chloroform and dichloromethane; and methyl acetate , Ethyl acetate and other esters, tetrahydrofuran, dioxane, diethyl ether, 1,2-dimethoxyethane and other ethers, water, acetonitrile, N,N-dimethylformamide, N-methylpyrrolidone , Polar solvents such as dimethyl sulfoxide, or mixed solvents of the above solvents.
  • aromatic hydrocarbons such as benzene, toluene, and xylene
  • ketones such as acetone, methyl ethyl ketone and methyl isobutyl ketone
  • halogenated hydrocarbons such as chloroform
  • Bases include: organic bases such as triethylamine, pyridine, DBU, 4-dimethylaminopyridine, alkali metal hydrides such as sodium hydride and potassium hydride, alkali metal hydroxides such as sodium hydroxide and potassium hydroxide, calcium hydroxide, etc. Alkaline earth metal hydroxides, sodium carbonate, potassium carbonate and other alkali metal carbonates, sodium bicarbonate and other alkali metal bicarbonates, sodium methoxide, sodium ethoxide, potassium ethoxide, potassium tert-butoxide, sodium tert-butoxide and other metal alcohols salt.
  • organic bases such as triethylamine, pyridine, DBU, 4-dimethylaminopyridine
  • alkali metal hydrides such as sodium hydride and potassium hydride
  • alkali metal hydroxides such as sodium hydroxide and potassium hydroxide, calcium hydroxide, etc.
  • Alkaline earth metal hydroxides sodium carbonate, potassium carbonate
  • the compound of general formula IV can be prepared according to known methods, for example, with reference to WO20110201687, WO2011093415, WO2005021488, WO2005073165, WO2006137395, JP2007099761, WO2008000438, WO2008074427, WO2008107091, WO2010013567, WO2010018714, WO2010090282, WO2010127926, WO2010127928, JP20112012549, WO2014842012483, 077, WO201484 WO2013050261, WO2014069665, WO2014067838, WO2014161848, WO2014161850, WO2015097091 or WO2015097094 are prepared by methods reported in WO2013050261, WO2014069665, WO2014067838, WO2014161848, WO2014161850, WO2015097091 or WO2015097094; compounds of general formula V and other reagents are usually commercially
  • 3-Amino-2-fluorobenzoic acid methyl ester and bromomethylcyclopropane are reacted in a suitable solvent at a temperature from -10°C to the boiling point of the solvent for 0.5-48 hours to obtain a compound of general formula VI.
  • the reaction can be carried out in a base
  • the compound of the general formula VI and the compound of the general formula V are reacted in a suitable solvent at a temperature from -10°C to the boiling point of the solvent for 0.5-48 hours to obtain the compound of the general formula VII.
  • the reaction can be carried out in the presence of a base.
  • the solvent includes: aromatic hydrocarbons such as benzene, toluene, and xylene; ketones such as acetone, methyl ethyl ketone and methyl isobutyl ketone; halogenated hydrocarbons such as chloroform and dichloromethane; and methyl acetate , Ethyl acetate and other esters, tetrahydrofuran, dioxane, diethyl ether, 1,2-dimethoxyethane and other ethers, water, acetonitrile, N,N-dimethylformamide, N-methylpyrrolidone , Polar solvents such as dimethyl sulfoxide, or mixed solvents of the above solvents.
  • aromatic hydrocarbons such as benzene, toluene, and xylene
  • ketones such as acetone, methyl ethyl ketone and methyl isobutyl ketone
  • halogenated hydrocarbons such as chloroform
  • Bases include: organic bases such as triethylamine, pyridine, DBU, 4-dimethylaminopyridine, alkali metal hydrides such as sodium hydride and potassium hydride, alkali metal hydroxides such as sodium hydroxide and potassium hydroxide, calcium hydroxide, etc. Alkaline earth metal hydroxides, sodium carbonate, potassium carbonate and other alkali metal carbonates, sodium bicarbonate and other alkali metal bicarbonates, sodium methoxide, sodium ethoxide, potassium ethoxide, potassium tert-butoxide, sodium tert-butoxide and other metal alcohols salt.
  • organic bases such as triethylamine, pyridine, DBU, 4-dimethylaminopyridine
  • alkali metal hydrides such as sodium hydride and potassium hydride
  • alkali metal hydroxides such as sodium hydroxide and potassium hydroxide, calcium hydroxide, etc.
  • Alkaline earth metal hydroxides sodium carbonate, potassium carbonate
  • the compound of the general formula VII can be hydrolyzed to prepare the compound of the general formula III-1 by reacting at a temperature from -10°C to the boiling point of the solvent for 0.5-48 hours in the presence of a basic substance.
  • the base includes: sodium carbonate, potassium carbonate, lithium hydroxide, sodium hydroxide, or potassium hydroxide
  • the solvent includes: any of water, methanol, ethanol, tetrahydrofuran, or dioxane One or at least two mixed solvents.
  • the compound of general formula III-1 can be prepared by reacting compound of general formula III-1 with thionyl chloride, oxalyl chloride, phosgene, phosphorus oxychloride, phosphorus pentachloride, phosphorus trichloride, triphosgene, etc. by using a known method.
  • a compound of general formula III-1 or a compound of general formula III-2 and a compound of general formula VIII can be reacted in a suitable solvent at a temperature from -70°C to the boiling point of the solvent for 0.5-48 hours to obtain a compound of general formula I.
  • the reaction can be carried out in Carry out in the presence of a base.
  • the solvent includes: aromatic hydrocarbons such as benzene, toluene, and xylene; ketones such as acetone, methyl ethyl ketone and methyl isobutyl ketone; halogenated hydrocarbons such as chloroform and dichloromethane; and methyl acetate , Ethyl acetate and other esters, tetrahydrofuran, dioxane, diethyl ether, 1,2-dimethoxyethane and other ethers, water, acetonitrile, N,N-dimethylformamide, N-methylpyrrolidone , Polar solvents such as dimethyl sulfoxide, or mixed solvents of the above solvents.
  • aromatic hydrocarbons such as benzene, toluene, and xylene
  • ketones such as acetone, methyl ethyl ketone and methyl isobutyl ketone
  • halogenated hydrocarbons such as chloroform
  • Bases include: organic bases such as trimethylamine, triethylamine, diisopropylethylamine, tri-n-butylamine, pyridine, DBU, 4-dimethylaminopyridine, and alkali metal hydrogenation such as sodium hydride and potassium hydride
  • organic bases such as trimethylamine, triethylamine, diisopropylethylamine, tri-n-butylamine, pyridine, DBU, 4-dimethylaminopyridine
  • alkali metal hydrogenation such as sodium hydride and potassium hydride
  • Alkali metal hydroxides such as sodium hydroxide and potassium hydroxide
  • alkaline earth metal hydroxides such as calcium hydroxide
  • alkali metal carbonates such as sodium carbonate and potassium carbonate
  • alkali metal bicarbonates such as sodium bicarbonate
  • methanol Metal alkoxides such as sodium, sodium ethoxide, potassium ethoxide, potassium tert-butoxide, and sodium
  • the embodiments of the present invention also provide the use of the above-mentioned bisamide compounds in the preparation of insecticides.
  • the insecticide is used to control one or more of the following insects:
  • Beetles Coldosobruchus Chinensis, Sitophilus zeamais, Tribolium Castaneum, Epilachna vigintioctomaculata, Agfuriots cioglis ), Anomala rufocuprea, Potato leaf beetle (Leptinotarsa decemlineata), Diabrotica spp., Monochamus alternatus endai, Lissorhoptrus oryzophilus, Brown mealy beetle (Lyctus bruneus);
  • Lepidopteran pests for example, Lymantria dispar, Malacosoma neustria, Pieris rapae crucivola, Spodoptera litura, Maestra brassicae), Chilo suppressalis, European corn borer (Ostrinia nubilalis), Cadra cautella, chyanokokakumonhamaki (Adoxophyes honmai), Cydia pomonella, Agrotis segetum, Galleria mellonella, Plutella xylostella, Heliothis virescens, Phyllocnistis citrella;
  • Hemipterous pests such as Nephotettix cincticeps, Nilaparvata lugens, Pseudococcuscomstocki, Unaspis yanonensis, Myzus persicas, Apple aphid (Aphis pomi), cotton aphid (Aphis gossypii), radish aphid (Lipaphis erysimi), pear crown bug (Stephanitis nashi), green stink (Nezara spp.), greenhouse whitefly (Trialeurodes vaporariorum), Pshylla spp. ;
  • Thysanoptera pests, such as palm thrips (Thrips palmi), western flower thrips (Franklinella occidentalis);
  • Orthopteran pests such as Gryllotalpa Africana and Locusta migratoria
  • Blattarian pests such as German cockroach (Blattella germanica), American cockroach (Periplaneta americana), yellow breasted termites (Reticulitermes spermus), house termites (Coptotermes formosanus);
  • Dipterous pests such as Musca domestica, Aedesaegypti, Delia platura, Culex pipiens pallens, Anopheles sinensis, Three Culex tritaeniorhynchus, Liriomyza trifolii, etc.
  • Agricultural pest mites such as Tetranychus cinnabarinus, Tetrahychus urticae, Panonychus citri, Aculops pelekassi, Tarsonemus spp., etc. .
  • the insecticide is used to control one or more of Armyworm, Plutella xylostella, and Chilo suppressalis.
  • the embodiment of the present invention also provides an insecticide formulation, which contains the above-mentioned bisamide compound as an active component, and also contains one or more auxiliary materials.
  • the insecticide preparation is selected from the following dosage forms: solution, emulsion, wettable powder, granular wettable powder, suspension, powder, foam, ointment, tablet, granule Agents, aerosols, natural agents impregnated with active compounds, synthetic agents impregnated with active compounds, microcapsules, seed coatings, preparations equipped with a combustion device (the combustion device may be a chimney, a mist tube, a pot And coils, etc.) and ULV (cold mist, hot mist) and so on.
  • a combustion device may be a chimney, a mist tube, a pot And coils, etc.
  • ULV cold mist, hot mist
  • insecticide preparations or animal parasite control agents can be prepared by known methods, for example, by combining the active ingredients with fillers (such as liquid diluents or carriers, liquefied gas diluents or carriers, solid diluents or carriers) It is prepared by mixing, and optionally with surfactants (ie, emulsifiers and/or dispersants and/or foaming agents) and the like.
  • fillers such as liquid diluents or carriers, liquefied gas diluents or carriers, solid diluents or carriers
  • surfactants ie, emulsifiers and/or dispersants and/or foaming agents
  • the auxiliary material includes one or more of the following: filler (such as: liquid diluent or carrier, liquefied gas diluent or carrier, solid diluent or carrier), surfactant (such as: emulsifier and/or dispersant and/or foaming agent), adhesive, colorant;
  • filler such as: liquid diluent or carrier, liquefied gas diluent or carrier, solid diluent or carrier
  • surfactant such as: emulsifier and/or dispersant and/or foaming agent
  • adhesive such as: emulsifier and/or dispersant and/or foaming agent
  • the liquid diluent or carrier may include, for example, aromatic hydrocarbons (xylene, toluene, alkyl naphthalene, etc.), chlorinated aromatic hydrocarbons or chlorinated aliphatic hydrocarbons (such as chlorobenzene, vinyl chloride, methylene chloride, etc.), aliphatic hydrocarbons (Such as cyclohexane or paraffin wax (such as mineral oil fraction)), alcohol (such as butanol, ethylene glycol, and ether or ester thereof), ketone (such as acetone, methyl ethyl ketone, methyl isobutyl ketone) , Cyclohexanone, etc.), strong polar solvents (such as dimethyl formamide, dimethyl sulfoxide), water, etc.
  • aromatic hydrocarbons xylene, toluene, alkyl naphthalene, etc.
  • chlorinated aromatic hydrocarbons or chlorinated aliphatic hydrocarbons such
  • Liquefied gas diluents or carriers may include those that exist in gaseous form at atmospheric pressure and temperature, for example, propane, nitrogen, carbon dioxide, and aerosol propellants such as halogenated hydrocarbons;
  • the solid diluent may include crushed natural minerals (such as kaolin, clay, talc, chalk, quartz, attapulgite, montmorillonite or diatomaceous earth, etc.) and crushed synthetic minerals (such as finely divided silicic acid, alumina And silicate etc.) etc.;
  • crushed natural minerals such as kaolin, clay, talc, chalk, quartz, attapulgite, montmorillonite or diatomaceous earth, etc.
  • crushed synthetic minerals such as finely divided silicic acid, alumina And silicate etc.
  • Emulsifiers and/or foaming agents may include nonionic and anionic emulsifiers [e.g., polyoxyethylene fatty acid esters, polyoxyethylene fatty acid alcohol ethers (such as alkyl aryl polyethylene glycol ethers), alkyl sulfonates , Alkyl sulfate and aryl sulfonate] and albumin hydrolysate, etc.;
  • nonionic and anionic emulsifiers e.g., polyoxyethylene fatty acid esters, polyoxyethylene fatty acid alcohol ethers (such as alkyl aryl polyethylene glycol ethers), alkyl sulfonates , Alkyl sulfate and aryl sulfonate] and albumin hydrolysate, etc.;
  • the dispersant may include lignin sulfite waste liquid and methyl cellulose;
  • the binder may include carboxymethyl cellulose, natural or synthetic polymers (for example, gum arabic, polyvinyl alcohol, polyvinyl acetate, etc.).
  • the colorant may include inorganic pigments (such as iron oxide, titanium oxide, and Prussian blue, etc.), organic dyes such as alizarin dyes, azo dyes, or metal phthalocyanine dyes; and trace elements such as iron salts, manganese salts, boron salts, copper Salt, cobalt salt, molybdenum salt or zinc salt.
  • inorganic pigments such as iron oxide, titanium oxide, and Prussian blue, etc.
  • organic dyes such as alizarin dyes, azo dyes, or metal phthalocyanine dyes
  • trace elements such as iron salts, manganese salts, boron salts, copper Salt, cobalt salt, molybdenum salt or zinc salt.
  • the bisamide compound of the present invention can exist as a mixture with a synergist, and the synergist itself does not have to be active. More precisely, it is a compound that enhances the activity of the active compound.
  • the amount of the above-mentioned bisamide compound contained in the pesticide formulation is 0.1 to 99% by weight, optionally 0.5 to 90% by weight.
  • the embodiments of the present invention also provide an insecticide composition, which includes the above-mentioned bisamide compound and other active compounds (such as insecticides, baits, disinfectants, acaricides, nematicides, fungicides, Growth regulators, herbicides, etc.).
  • the mixture may be provided in the form of a bulk drug, or may be provided in the form of a commercially available useful preparation or a use form prepared from its preparation.
  • the embodiment of the present invention also provides a method for controlling agricultural or forestry pests, which includes the following steps: applying an effective dose of materials to the pests to be controlled or their growth medium, and the materials are selected from one of the following group Or more: the above-mentioned bisamide compound, the above-mentioned insecticide preparation, and the above-mentioned insecticide composition.
  • the embodiment of the present invention also provides the use of the above-mentioned bisamide compound in the preparation of an animal parasite control agent.
  • the bisamide compound of the present invention can be effectively used to combat a variety of harmful animal parasites, especially endoparasites and ectoparasites.
  • animal parasites include one or more of the following:
  • Anoplurida such as Haematopinus spp., Linognathus spp., Pediculus spp., Phtirus spp, and Solenopotes spp.; in particular, representative examples Yes, Linognathus setosus, Solenopotes capillatus;
  • Trichophagous order (Mallopha, Linognathus vituli), sheep jaw louse (Linognathus ovillus), Linognathus oviformis, foot jaw louse (Linognathus pedalis), goat jaw louse (Linognathus stenopsis), donkey blood louse (Haematopinus asini, macrocephalus) Bovine blood louse (Haematopinus eurysternus), pig blood louse (Haematopinus suis), head louse (Pediculus humanus capitis), body louse (Pediculus humanus corporis), grape phylloxera (Phylloera vastatrix), pubic louse (Phthirus pubis) gida) Amblycerina and Ischnocerin, for example, Trimenopon spp., Menopon spp., Trinoton spp., Bovicola spp.), Werneckiella
  • Bovicola bovis bovine lice
  • wool louse Bovicola ovis
  • Angola goat feather louse Bovicola limbata
  • cattle louse Damalina bovis
  • dog hair louse Trichodectes canis
  • cat feather louse Felicola subrostratus
  • goat feather louse Bovicola caprae
  • Diptera and its Nematocerina and Brachycerina for example, Aedes spp., Anopheles spp., Culex spp .), Simulium spp, Eusimulium spp., Phlebotomus spp., Lutzomyia spp., Culicoides spp., Spotted fly ( Chrysops spp.), Odagmia spp., Wilhelmia spp., Hybomitra spp., Atylotus spp., Tabanus spp., Hemp Haematopota (Haematopota spp.), Philipomyia spp., Braula spp., Musca spp., Hydrotaea spp., Stomoxys spp., Haematobia spp., Morellia spp., Fannia spp., Glossina spp.
  • Lucilia spp. Chrysomyia spp., Wohlfahrtia spp., Sarcophaga spp., Oestrus spp., Hypoderma spp., Stomach Gasterophilus spp., Hippobosca spp., Lipoptena spp., Melophagus spp., Rhinoestrus spp., Crane spp. Tipula spp.);
  • representative examples include Aedes aegypti, Aedes albopictus, Aedes taeniorhynchus, Anopheles gambiae, and Aedes albopictus.
  • Mosquitoes (Anopheles maculipennis), Calliphora erythrocephala, Chrysozona pluvialis, Culex quinquefasciat us), Culex pipiens, Culex tarsalis, Fannia canicularis, Sarcophaga carnaria, Stomoxys calcitrans, Tipula paludosa ), Lucilia cuprina, Lucilia sericata, Simulium reptans, Phlebotomus papatasi, Phlebotomus longipalpis, Odagmia ornata, Wilhelmia equina, Boophthora erythrocephala, Tabanus bromius, Tabanus spodopterus, Tabanus atratus, Tabanus sudeticus Hybomitra ciurea, Chrysops caecutiens, Chrysops relictus, Haematopota pluvialis, Haemato
  • Siphonaptrida for example, Pulex spp., Ctenocephalides spp., Tunga spp., Xenopsylla spp., Ceratophyllus spp.);
  • representative examples include Ctenocephalides canis, Ctenocephalides felis, Pulex irritans, Tunga penetrans, and Ctenocephalides canis (Xenopsylla cheopis);
  • Acari or Acarina
  • Metastigmata and Mesostigmata for example, Argas spp., Ornithodorus spp., Remnant beak tick Otobius spp., Ixodes spp., Amblyomma spp., Rhipicephalus (Boophilus) spp., Dermacentor spp., Haemophysalis spp., Hyalomma (Hyalomma spp.), Dermanyssus spp., Rhipicephalus spp.
  • Acarapis spp. include Argas persicus, Argas reflexus, Ornithodorus moubata, and ear damage Otobius megnini, Rhipicephalus (Boophilus) microplus, Rhipicephalus (Boophilus) decoloratus, Rhipicephalus (Boophilus) decoloratus), Rhipicephalus (Boophilus) decoloratus, Rhipicephalus (Boophilus) decoloratus Rhipicephalus (Boophilus) annulatus), Rhipicephalus (Boophilus) calceratus (Rhipicephalus (Boophilus) calceratus), Hyalomma anatolicum, Hyalomma aegypticum (Hyalomma aegypticum), Hyaloma marginatum, Hyalomma transiens, Rhipicephalus evertsi, Ixodes ricinus,
  • Rhipicephalus capensis Rhipicephalus turanicus
  • Rhipicephalus zambeziensis Amblyomma americanum, Amblyomma variegatum, Amblyomma maculatumh, Emblyomma maculatumh , Amblyomma cajennense, Dermanyssus gallinae, Ornithonyssus bursa, Ornithonyssus sylviarum, Varroa jacobsconi;
  • Actinedida Prostigmata
  • Acaridida Acaridida
  • Acarapis spp. Cheyletiella spp.
  • Ornitrocheyletia spp. Ornitrocheyletia spp.
  • Myobia spp. Psorergates spp.
  • Demodex spp. Trombicula spp.
  • Nematodes such as Meloidogyne incognita, Bursaphelenchus xylophilus, Aphelenchoides besseyi, Heterodera glycines, Pratylenchus spp., etc.;
  • Arthropods, worms and malaria parasites that invade animals. Controlling arthropods, worms and/or malaria parasites can reduce the mortality of domestic animals and improve the productivity (meat, milk, hair, skin, eggs and honey) and health of animals.
  • the animal parasite control agent is used to control one or more of cat fleas and American dog ticks.
  • the animals include one or more of the following: agricultural animals, such as cows, sheep, goats, horses, pigs, donkeys, camels, buffaloes, rabbits, chickens, turkeys, ducks, geese , Farmed fish, bees, etc.; also includes pets called companion animals, such as dogs, cats, caged birds, and ornamental fish; also includes animals used for experiments, such as hamsters, guinea pigs, rats, and mice.
  • agricultural animals such as cows, sheep, goats, horses, pigs, donkeys, camels, buffaloes, rabbits, chickens, turkeys, ducks, geese , Farmed fish, bees, etc.
  • companion animals such as dogs, cats, caged birds, and ornamental fish
  • animals used for experiments such as hamsters, guinea pigs, rats, and mice.
  • the embodiment of the present invention also provides an animal parasite control agent, which contains the above-mentioned bisamide compound as an active component, and also contains one or more auxiliary materials.
  • the animal parasite control agent is selected from the following dosage forms: tablets, capsules, drinks, drinkable drugs, granules, ointments and pills, suppositories, injections (muscle, subcutaneous, intravenous, Intraperitoneal, etc.), smears, aerosols, non-pressure sprays (such as pump sprays and atomized sprays).
  • the amount of the above-mentioned active component contained in the animal parasite control agent is 1 to 80% by weight.
  • the embodiment of the present invention also provides an animal parasite control composition, which includes the above-mentioned bisamide compound and other animal parasite control active compounds (such as acaricides, insecticides, parasiticides, anti-plasmodium Etc.) of the mixture.
  • the mixture may be provided in the form of a bulk drug, or may be provided in the form of a commercially available useful preparation or a use form prepared from its preparation.
  • the embodiment of the present invention also provides a method for controlling animal parasites, which includes the following steps: applying an effective dose of material to the animal parasites or their growth medium to be controlled, and the material is selected from one of the following group: One or more: the above-mentioned bisamide compound; the above-mentioned animal parasite control agent; the above-mentioned animal parasite control composition.
  • suppositories for enteral administration; skin-based non-intestinal administration, such as injection (muscle, subcutaneous, intravenous, Intraperitoneal, etc.), implantation, nasal administration, including bathing or soaking, spraying, pouring, dripping, washing and dusting, and through the use of model products containing active compounds, such as collars, ear tags, labels, legs Use leg brace, net, marker, etc.
  • the active compound of the present invention has low toxicity and can be safely used in warm-blooded animals.
  • the bisamide compound of the present invention has unexpectedly high insecticidal activity and has no phytotoxicity to cultivated crop plants.
  • the compounds of the present invention can be used to control various pests, such as harmful sucking insects, chewing insects, and other plant parasitic pests, stored grain pests, sanitary pests, etc., and can be used to disinfect and kill them.
  • Halogen refers to fluorine, chlorine, bromine or iodine.
  • Halogenated alkyl groups straight or branched chain alkyl groups.
  • the hydrogen atoms on these alkyl groups can be partially or completely replaced by halogens, such as difluoromethyl (CHF 2 ), trifluoromethyl (CF 3 ), and the like.
  • Halogenated alkoxy group The hydrogen atoms on the alkoxy group can be partially or completely replaced by halogen, such as difluoromethoxy (OCHF 2 ), trifluoromethoxy (OCF 3 ), and the like.
  • halogen such as difluoromethoxy (OCHF 2 ), trifluoromethoxy (OCF 3 ), and the like.
  • Insecticides substances that have insecticidal effects on pests.
  • Animal parasite control agent refers to an active compound that can effectively reduce the incidence of various parasites in animals infected by parasites. Control means that the active compound can effectively kill parasites, inhibit their growth or reproduction.
  • the compounds represented by the general formula I, the general formula II and the general formula III of the present invention can be respectively prepared, which are further specifically described as follows:
  • the intermediate compound II.4 was prepared by reacting intermediate compound IV-4 (prepared with reference to the method reported in WO2011093415 or WO2010018714) with bromomethylcyclopropane. (White solid).
  • Example 6 According to the method described in Example 5, Example 6, or Example 7, compound 4 (yellow solid) was prepared by reacting intermediate compound II.4 with intermediate V-1.
  • Example 7 (yellow solid) was prepared by reacting intermediate compound II.3 with intermediate V-2.
  • Example 8 According to the method described in Example 5, Example 6, or Example 7, compound 8 (yellow solid) was prepared by reacting intermediate compound II.4 with intermediate V-2.
  • the NMR data of compound 8 are as follows:
  • Example 6 According to the method described in Example 5, Example 6, or Example 7, compound 9 (white solid) was prepared by reacting intermediate compound II.1 with intermediate V-3.
  • Example 6 According to the method described in Example 5, Example 6, or Example 7, compound 10 (yellow oil) was prepared by reacting intermediate compound II.2 with intermediate V-3.
  • Example 6 According to the method described in Example 5, Example 6, or Example 7, compound 11 (yellow solid) was prepared by reacting intermediate compound II.3 with intermediate V-3.
  • Example 6 According to the method described in Example 5, Example 6, or Example 7, compound 12 (yellow solid) was prepared by reacting intermediate compound II.4 with intermediate V-3.
  • Example 15 Determination of biological activity of Armyworm, Plutella xylostella, Chilo suppressalis
  • the insecticidal activity test of several insects was carried out with the compound of the present invention.
  • the measurement method is as follows:
  • test compound After the test compound is dissolved in a mixed solvent of acetone/methanol (1:1), it is diluted with water containing 0.1% (wt) Tween 80 to the desired concentration.
  • Measurement method cut corn leaves into 2cm leaf sections, the pressure of Airbrush spray treatment is 10psi (approximately 0.7kg/cm 2 ), the front and back sides of each leaf section are sprayed, and the spray volume of the compound to be tested is 0.5ml. After drying in the shade, 10 3rd instar larvae were inserted into each treatment, and repeated 3 times for each treatment. After the treatment, it was placed in an observation room at 25°C and a relative humidity of 60-70%, and the number of surviving insects was investigated 3 days after the treatment, and the mortality rate was calculated.
  • Measurement method Use a punch to punch cabbage leaves into leaf discs with a diameter of 2 cm.
  • the pressure of Airbrush spray treatment is 10 psi (approximately 0.7 kg/cm 2 ), and the front and back sides of each leaf disc are sprayed.
  • the spray volume of the compound to be tested is 0.5ml. After drying in the shade, 10 3rd instar larvae were inserted into each treatment, and repeated 3 times for each treatment. After the treatment, it was placed in an observation room at 25°C and a relative humidity of 60-70%, and the number of surviving insects was investigated 3 days after the treatment, and the mortality rate was calculated.
  • Measurement method 1) Preparation of rice seedlings: cultivate rice in a plastic cup with a diameter of 4.5 cm and a height of 4 cm in a constant temperature room (temperature 26-28°C, relative humidity 60-80%, light 16hL:8hD). At the 4 to 5 leaf stage, select robust and consistent rice seedlings for chemical treatment, and set 3 repetitions for each treatment. 2) Preparation for test insects: Chilo suppressalis, 3rd instar larvae continuously reared indoors. 3) The rice stalk is sprayed with insects. The spray method is adopted to uniformly spray the whole plant of the rice seedlings, and 15 ml of medicine is used for each treatment.
  • the rice seedlings are sprayed, they are placed in a cool place to dry the liquid, and about 5 cm of the stalk at the base of the stem is cut to feed the test insects.
  • the compound 1 is compared with the control compounds 1-1 and 1-2, by comparing the compound 3 with the control compound 2-1, by comparing the compound 7 with the control compound 3-1, and by comparing the compound 11 with the control compound 4-1 Comparing it can be seen that: R 4 and the adjacent nitrogen atom are very important. The two cooperate with each other and are indispensable.
  • R 4 is F, CF 3 , CN
  • the adjacent atom is selected after the carbon atom
  • the activity of the compound against Chilo suppressalis will be significantly reduced, or even lost; by comparing compounds 3, 7, 11 and 5-1, 5-2, it can be seen that when the atom adjacent to R 4 is a nitrogen atom, After selecting hydrogen or chlorine for R 4 , the activity of the compound against Chilo suppressalis will also be significantly reduced or even lost.
  • Example 16 Insecticidal test on cat fleas
  • the present invention provides a bisamide compound with more excellent insecticidal activity. It can be used to prepare drugs for controlling pests in agriculture and other fields, and for preparing drugs for controlling animal parasites in the field of veterinary medicine.

Abstract

本发明公开了一种双酰胺类化合物及其应用，所述化合物结构如通式I所示：(I) 式中各取代基的定义见说明书；说明书还公开了其作为杀虫剂和动物寄生虫防治剂的用途。

Description

一种双酰胺类化合物及其应用
交叉引用
本发明要求在中国专利局提交的、申请号为201910789623.4、发明名称为“一种双酰胺类化合物及其应用”的中国专利申请的优先权，该申请的全部内容通过引用结合在本发明中。
本发明要求在中国专利局提交的、申请号为202010013008.7、发明名称为“一种双酰胺类化合物及其应用”的中国专利申请的优先权，该申请的全部内容通过引用结合在本发明中。
技术领域
本发明涉及一种化合物，具体涉及一种新型的双酰胺类化合物及其应用。
背景技术
双酰胺类杀虫剂自问世以来，就一直是市场的热门产品，其代表品种如氟苯虫酰胺和氯虫苯甲酰胺等；但由于现有药剂长期大量的不合理使用，抗性问题愈演愈烈。另一方面，现有杀虫剂的杀虫效果尤其对水稻二化螟的活性仍不能令人满意，难以满足现实中杀虫剂不断提高的使用要求。在本领域仍需积极开发更高活性的新杀虫剂，以满足农业和其它领域的需求。
现有技术中如本发明通式I所示的化合物及其杀虫活性未见报道。
发明内容
本发明的目的在于提供一种具有更优异杀虫活性的双酰胺类化合物。它可用于制备农业和其它领域中防治害虫的药物以及在兽药领域用于制备控制动物寄生虫的药物。
为实现本发明的发明目的，本发明提供了如下技术方案：
一种双酰胺类化合物，如通式I所示：
Figure PCTCN2020110707-appb-000001
通式I中：
R 1选自卤素；
R 2选自卤素、C 1-C 4卤代烷基或C 1-C 4卤代烷氧基；
R 3选自CF 3或CF 2CF 3；
R 4选自氟、二氟甲基、三氟甲基或氰基。
在一种可能的实现方式中，通式I中，
R 1选自卤素；
R 2选自卤素、C 1-C 2卤代烷基或C 1-C 2卤代烷氧基；
R 3选自CF 3或CF 2CF 3；
R 4选自氟、二氟甲基、三氟甲基或氰基。
在一种可能的实现方式中，通式I中，
R 1选自溴或碘；
R 2选自溴、碘、三氟甲基或二氟甲氧基；
R 3选自CF 3或CF 2CF 3；
R 4选自氟、二氟甲基、三氟甲基或氰基。
在一种可能的实现方式中，通式I中，
R 4选自氟、二氟甲基或三氟甲基。
在一种可能的实现方式中，双酰胺类化合物选自表1化合物，所述表1化合物具有如通式I的结构且R 1、R 2、R 3和R 4如表1中所示：
表1
化合物编号 R 1 R 2 R 3 R 4
1 Br Br CF 3 F
2 Br I CF 3 F
3 Br CF 3 CF 3 F
4 I CF 3 CF 3 F
5 Br Br CF 3 CF 3
6 Br I CF 3 CF 3
7 Br CF 3 CF 3 CF 3
8 I CF 3 CF 3 CF 3
9 Br Br CF 3 CN
10 Br I CF 3 CN
11 Br CF 3 CF 3 CN
12 I CF 3 CF 3 CN
13 Br Br CF 2CF 3 F
14 Br I CF 2CF 3 F
15 Br CF 3 CF 2CF 3 F
16 I CF 3 CF 2CF 3 F
17 Br Br CF 2CF 3 CF 3
18 Br I CF 2CF 3 CF 3
19 Br CF 3 CF 2CF 3 CF 3
20 I CF 3 CF 2CF 3 CF 3
21 Br Br CF 2CF 3 CN
22 Br I CF 2CF 3 CN
23 Br CF 3 CF 2CF 3 CN
24 I CF 3 CF 2CF 3 CN
。
在一种可能的实现方式中，双酰胺类化合物选自表2化合物，所述表2化合物具有如通式I的结构且R 1、R 2、R 3和R 4如表2中所示：
表2
化合物编号 R 1 R 2 R 3 R 4
1 Br Br CF 3 F
2 Br I CF 3 F
3 Br CF 3 CF 3 F
4 I CF 3 CF 3 F
5 Br Br CF 3 CF 3
6 Br I CF 3 CF 3
7 Br CF 3 CF 3 CF 3
8 I CF 3 CF 3 CF 3
13 Br Br CF 2CF 3 F
14 Br I CF 2CF 3 F
15 Br CF 3 CF 2CF 3 F
16 I CF 3 CF 2CF 3 F
17 Br Br CF 2CF 3 CF 3
18 Br I CF 2CF 3 CF 3
19 Br CF 3 CF 2CF 3 CF 3
20 I CF 3 CF 2CF 3 CF 3
。
一种用于制备权利要求1所述的双酰胺类化合物的中间体化合物，其特征在于，中间体化合物如通式II所示：
Figure PCTCN2020110707-appb-000002
通式II中：
R 1选自卤素；
R 2选自卤素、C 1-C 4卤代烷基或C 1-C 4卤代烷氧基；
R 3选自CF 3或CF 2CF 3。
在一种可能的实现方式中，通式II中，
R 1选自卤素；
R 2选自卤素、C 1-C 2卤代烷基或C 1-C 2卤代烷氧基；
R 3选自CF 3或CF 2CF 3。
在一种可能的实现方式中，通式II中，
R 1选自溴或碘；
R 2选自溴、碘、三氟甲基或二氟甲氧基；
R 3选自CF 3或CF 2CF 3。
在一种可能的实现方式中，通式II中间体化合物选自表3化合物，所述表3化合物具有如通式II的结构且R 1、R 2和R 3如表3中所示：
表3
化合物编号 R 1 R 2 R 3
II.1 Br Br CF 3
II.2 Br I CF 3
II.3 Br CF 3 CF 3
II.4 I CF 3 CF 3
II.5 Br Br CF 2CF 3
II.6 Br I CF 2CF 3
II.7 Br CF 3 CF 2CF 3
II.8 I CF 3 CF 2CF 3
。
一种用于制备权利要求1所述的双酰胺类化合物的中间体化合物，其特征在于，化合物如通式III所示：
Figure PCTCN2020110707-appb-000003
通式III中：
R 4选自氟、二氟甲基、三氟甲基或氰基；
L选自卤素或羟基。
在一种可能的实现方式中，通式III中间体化合物选自表4化合物，所述表4化合物 具有如通式III的结构且R 4和L如表4中所示：
表4
化合物编号 R 4 L
III.1 F F
III.2 F Cl
III.3 F Br
III.4 F I
III.5 F OH
III.6 CF 3 F
III.7 CF 3 Cl
III.8 CF 3 Br
III.9 CF 3 I
III.10 CF 3 OH
III.11 CN F
III.12 CN Cl
III.13 CN Br
III.14 CN I
III.15 CN OH
。
本发明实施例还提供了上述双酰胺类化合物的制备方法，通式I、II、III化合物可按照以下方法制备(式中各基团除另有说明外定义同前)：
方法一：
Figure PCTCN2020110707-appb-000004
通式IV化合物与溴甲基环丙烷在适宜的溶剂中，在温度从-10℃到溶剂沸点下反应0.5-48小时可制得通式II化合物，反应可在碱存在下进行；通式II化合物与通式V化合物在适宜的溶剂中，在温度从-10℃到溶剂沸点下反应0.5-48小时可制得通式I化合物，反应可在碱存在下进行。
在一种可能的实现方式中，溶剂包括：苯、甲苯、二甲苯等芳烃类，丙酮、甲乙酮、甲基异丁基酮等酮类，氯仿、二氯甲烷等卤代烃类，乙酸甲酯、乙酸乙酯等酯类，四氢呋喃、二噁烷、二***、1,2-二甲氧基乙烷等醚类，水、乙腈、N,N-二甲基甲酰胺、N-甲基吡咯烷酮、二甲基亚砜等极性溶剂类或上述溶剂的混合溶剂。碱包括：三乙胺、吡 啶、DBU、4-二甲氨基吡啶等有机碱，氢化钠、氢化钾等碱金属氢化物，氢氧化钠、氢氧化钾等碱金属氢氧化物，氢氧化钙等碱土类金属氢氧化物，碳酸钠、碳酸钾等碱金属碳酸盐，碳酸氢钠等碱金属碳酸氢盐，甲醇钠、乙醇钠、乙醇钾、叔丁醇钾、叔丁醇钠等金属醇盐。
通式IV化合物可以按公知方法制备，例如参照WO20110201687、WO2011093415、WO2005021488、WO2005073165、WO2006137395、JP2007099761、WO2008000438、WO2008074427、WO2008107091、WO2010013567、WO2010018714、WO2010090282、WO2010127926、WO2010127928、JP2011063549、WO2012020483、WO2012020484、WO2012077221、WO2012164698、WO2013050261、WO2014069665、WO2014067838、WO2014161848、WO2014161850、WO2015097091或WO2015097094等报道的方法制得；通式V化合物及其它试剂通常有市售，也可按照常规方法自制。
方法二：
Figure PCTCN2020110707-appb-000005
(1)通式VI化合物与通式VII化合物的制备
3-氨基-2-氟苯甲酸甲酯与溴甲基环丙烷在适宜的溶剂中，在温度从-10℃到溶剂沸点下反应0.5-48小时可制得通式VI化合物，反应可在碱存在下进行；通式VI化合物与通式V化合物在适宜的溶剂中，在温度从-10℃到溶剂沸点下反应0.5-48小时可制得通式VII化合物，反应可在碱存在下进行。
在一种可能的实现方式中，溶剂包括：苯、甲苯、二甲苯等芳烃类，丙酮、甲乙酮、甲基异丁基酮等酮类，氯仿、二氯甲烷等卤代烃类，乙酸甲酯、乙酸乙酯等酯类，四氢呋喃、二噁烷、二***、1,2-二甲氧基乙烷等醚类，水、乙腈、N,N-二甲基甲酰胺、N-甲基吡咯烷酮、二甲基亚砜等极性溶剂类或上述溶剂的混合溶剂。碱包括：三乙胺、吡啶、DBU、4-二甲氨基吡啶等有机碱，氢化钠、氢化钾等碱金属氢化物，氢氧化钠、氢氧化钾等碱金属氢氧化物，氢氧化钙等碱土类金属氢氧化物，碳酸钠、碳酸钾等碱金属碳酸盐，碳酸氢钠等碱金属碳酸氢盐，甲醇钠、乙醇钠、乙醇钾、叔丁醇钾、叔丁醇钠等金属醇盐。
(2)通式III-1化合物与通式III-2化合物的制备
通式VII化合物在碱性物质存在下，在温度从-10℃到溶剂沸点下反应0.5-48小时可 水解制得通式III-1化合物。在一种可能的实现方式中，碱包括：碳酸钠、碳酸钾、氢氧化锂、氢氧化钠或氢氧化钾；溶剂包括：水、甲醇、乙醇、四氢呋喃或二氧杂环己烷中的任意一种或至少两种的混合溶剂。
利用公知的方法，通式III-1化合物与亚硫酰氯、草酰氯、碳酰氯、磷酰氯、五氯化磷、三氯化磷、三光气等反应，可制备得到通式III-2化合物。
(3)通式I化合物的制备
通式III-1化合物或通式III-2化合物与通式VIII化合物在适宜的溶剂中，在温度从-70℃到溶剂沸点下反应0.5-48小时可制得通式I化合物，反应可在碱存在下进行。
在一种可能的实现方式中，溶剂包括：苯、甲苯、二甲苯等芳烃类，丙酮、甲乙酮、甲基异丁基酮等酮类，氯仿、二氯甲烷等卤代烃类，乙酸甲酯、乙酸乙酯等酯类，四氢呋喃、二噁烷、二***、1,2-二甲氧基乙烷等醚类，水、乙腈、N,N-二甲基甲酰胺、N-甲基吡咯烷酮、二甲基亚砜等极性溶剂类或上述溶剂的混合溶剂。碱包括：三甲基胺、三乙基胺、二异丙基乙基胺、三正丁基胺、吡啶、DBU、4-二甲氨基吡啶等有机碱，氢化钠、氢化钾等碱金属氢化物，氢氧化钠、氢氧化钾等碱金属氢氧化物，氢氧化钙等碱土类金属氢氧化物，碳酸钠、碳酸钾等碱金属碳酸盐，碳酸氢钠等碱金属碳酸氢盐，甲醇钠、乙醇钠、乙醇钾、叔丁醇钾、叔丁醇钠等金属醇盐。
本发明实施例还提供了上述双酰胺类化合物在制备杀虫剂中的用途。
在一种可能的实现方式中，所述杀虫剂用于防治以下昆虫的一种或多种：
甲虫(鞘翅目昆虫(Coleopteran))，例如绿豆象(Callosobruchus Chinensis)、玉米象(Sitophilus zeamais)、赤拟谷盗(Tribolium Castaneum)、马铃薯瓢虫(Epilachna vigintioctomaculata)、细胸叩甲(Agriotes ogurae fuscicollis)、多色异丽金龟(Anomala rufocuprea)、马铃薯叶甲(Leptinotarsa decemlineata)、叶甲属(Diabrotica spp.)、松墨天牛(Monochamus alternatus endai)、稻根象(Lissorhoptrus oryzophilus)、褐粉蠹(Lyctus bruneus)；
鳞翅目(lepidopteran)害虫，例如，舞毒蛾(Lymantria dispar)、黄褐天幕毛虫(Malacosoma neustria)、菜粉蝶日本亚种(Pieris rapae crucivora)、斜纹夜蛾(Spodoptera litura)、甘蓝夜蛾(Mamestra brassicae)、二化螟(Chilo suppressalis)、欧洲玉米螟(Ostrinia nubilalis)、干果斑螟(Cadra cautella)、chyanokokakumonhamaki(Adoxophyes honmai)、苹果小卷蛾(Cydia pomonella)、黄地老虎(Agrotis segetum)、大蜡螟(Galleria mellonella)、菜蛾(Plutella xylostella)、烟芽夜蛾(Heliothis virescens)、桔潜蛾(Phyllocnistis citrella)；
半翅目(Hemipterous)害虫，例如，黑尾叶蝉(Nephotettix cincticeps)、褐飞虱(Nilaparvata lugens)、康氏粉蚧(Pseudococcus comstocki)、矢尖盾蚧(Unaspis yanonensis)、桃蚜(Myzus persicas)、苹果蚜(Aphis pomi)、棉蚜(Aphis gossypii)、萝卜蚜(Lipaphis erysimi)、梨冠网蝽(Stephanitis nashi)、绿椿属(Nezara spp.)、温室粉虱(Trialeurodes vaporariorum)、Pshylla spp.；
缨翅目(Thysanoptera)害虫，例如棕榈蓟马(Thrips palmi)、西方花蓟马(Franklinella  occidentalis)；
直翅目(orthopteran)害虫，例如非洲蝼蛄(Gryllotalpa Africana)、非洲飞蝗(Locusta migratoria)；
蜚蠊目(blattarian)害虫，例如德国蠊(Blattella germanica)、美洲大蠊(Periplaneta americana)、黄胸散白蚁(Reticulitermes speratus)、家白蚁(Coptotermes formosanus)；
双翅目(Dipterous)害虫，例如家蝇(Musca domestica)、埃及伊蚊(Aedesaegypti)、灰地种蝇(Delia platura)、淡色库蚊(Culex pipiens pallens)、中华按蚊(Anopheles sinensis)、三带喙库蚊(Culex tritaeniorhynchus)、三叶草斑潜蝇(Liriomyza trifolii)等。
农业害螨，如朱砂叶螨(Tetranychus cinnabarinus)、棉叶螨(Tetrahychus urticae)、桔全爪螨(Panonychus citri)、桔刺皮瘿螨(Aculops pelekassi)、跗线螨属(Tarsonemus spp.)等。
在一种可能的实现方式中，所述杀虫剂用于防治粘虫、小菜蛾、二化螟中的一种或几种。
本发明实施例还提供了一种杀虫剂制剂，该杀虫剂制剂中含有上述双酰胺类化合物作为活性组分，还含有一种或多种辅料。
在一种可能的实现方式中，杀虫剂制剂选自以下剂型：溶液剂、乳剂、可湿性粉剂、颗粒状可湿性粉剂、悬浮剂、粉剂(powder)、泡沫剂、膏剂、片剂、颗粒剂、气雾剂、经活性化合物浸渍的天然试剂、经活性化合物浸渍的合成试剂、微胶囊剂、种子包衣剂、装备有燃烧装置的制剂(所述燃烧装置可为烟筒和雾筒、罐和盘管等)以及ULV(冷雾剂、热雾剂)等。这些杀虫剂制剂或动物寄生虫防治剂可用已知的方法制备，例如可通过将活性组分与填充剂(如：液体稀释剂或载体、液化气稀释剂或载体、固体稀释剂或载体)混合，以及可选地与表面活性剂(即乳化剂和/或分散剂和/或发泡剂)等混合而制备。
在一种可能的实现方式中，所述辅料包括以下的一种或多种：填充剂(如：液体稀释剂或载体、液化气稀释剂或载体、固体稀释剂或载体)、表面活性剂(如：乳化剂和/或分散剂和/或发泡剂)、粘合剂、着色剂；
液体稀释剂或载体可包括，例如，芳香烃(二甲苯、甲苯、烷基萘等)、氯代芳烃或氯代脂族烃(例如氯苯、氯乙烯、二氯甲烷等)、脂族烃(例如环己烷或石蜡(例如矿物油馏分))、醇(例如丁醇、乙二醇，及其醚或酯等)、酮(例如丙酮、甲基乙基酮、甲基异丁基酮、环己酮等)、强极性溶剂(例如二甲基甲酰胺、二甲亚砜)、水等。当使用水作为填充剂时，例如，可使用有机溶剂作为助溶剂；
液化气稀释剂或载体可包括在大气压力和温度下以气体形式存在的那些，例如，丙烷、氮气、二氧化碳，以及气溶胶喷射剂例如卤代烃；
固体稀释剂可包括粉碎的天然矿物(例如高岭土、粘土、滑石、白垩、石英、绿坡缕石、蒙脱石或硅藻土等)以及粉碎的合成矿物(例如细分散的硅酸、氧化铝和硅酸盐等)等；
乳化剂和/或发泡剂可包括非离子及阴离子乳化剂[例如，聚氧乙烯脂肪酸酯、聚氧乙 烯脂肪酸醇醚(如烷基芳基聚乙二醇醚)、烷基磺酸盐、烷基硫酸盐和芳基磺酸盐]以及白蛋白水解产物等；
分散剂可包括木质素亚硫酸盐废液和甲基纤维素；
粘合剂可包括羧甲基纤维素、天然或合成的聚合物(例如***树胶、聚乙烯醇和聚乙酸乙烯酯等)。
着色剂可包括无机颜料(例如氧化铁、氧化钛和普鲁士蓝等)、有机染料例如茜素染料、偶氮染料或金属酞菁染料；及微量元素，例如铁盐、锰盐、硼盐、铜盐、钴盐、钼盐或锌盐。
此外，本发明的双酰胺类化合物可作为与一种增效剂的混合物存在，增效剂自身不必具有活性。更确切地，它是增强活性化合物活性的化合物。
在一种可能的实现方式中，杀虫剂制剂中含有的上述双酰胺类化合物的量为0.1至99重量％，可选地为0.5至90重量％。
本发明实施例还提供了一种杀虫剂组合物，其包括上述双酰胺类化合物和其他活性化合物(例如杀虫剂、毒饵剂、消毒剂、杀螨剂、杀线虫剂、杀真菌剂、生长调节剂、除草剂等)的混合物。该混合物可以以原料药的形式提供，也可以以市售有用制剂的形式或者由其制剂制得的使用形式提供。
本发明实施例还提供了一种控制农业或林业害虫的方法，其包括以下步骤：将有效剂量的材料施用于需要控制的害虫或其生长介质上，所述材料选自下组中的一种或多种：上述双酰胺类化合物、上述杀虫剂制剂、上述杀虫剂组合物。
本发明实施例还提供了上述双酰胺类化合物在制备动物寄生虫防治剂中的用途。在兽医领域内，即，兽医科学中，本发明双酰胺类化合物可以有效地用于对抗多种有害的动物类寄生虫，特别是体内寄生虫和体外寄生虫。
在一种可能的实现方式中，动物寄生虫包括以下的一种或多种：
虱目(Anoplurida)，例如血虱属(Haematopinus spp.)、毛虱属(Linognathus spp.)、虱属(Pediculus spp.)、Phtirus spp和管虱属(Solenopotes spp.)；特别地，代表性实例有，棘颚虱(Linognathus setosus)、牛管虱(Solenopotes capillatus)；
食毛目(Mallopha、牛颚虱(Linognathus vituli)、绵羊颚虱(Linognathus ovillus)、Linognathus oviformis、足颚虱(Linognathus pedalis)、山羊颚虱(Linognathus stenopsis)、驴血虱(Haematopinus asini macrocephalus)、牛血虱(Haematopinus eurysternus)、猪血虱(Haematopinus suis)、头虱(Pediculus humanus capitis)、体虱(Pediculus humanus corporis)、葡萄根瘤蚜(Phylloera vastatrix)、阴虱(Phthirus pubis)gida)和钝角亚目(Amblycerina)和细角亚目(Ischnocerin)，例如，毛羽虱属(Trimenopon spp.)、禽虱属(Menopon spp.)、巨羽虱属(Trinoton spp.)、牛羽虱属(Bovicola spp.)、Werneckiella spp.、Lepikentron spp.、畜虱属(Damalina spp.)、嚼虱属(Trichodectes spp.)和猫羽虱属(Felicola spp.)；特别地，代表性实例有，牛毛虱(Bovicola bovis)、羊毛虱(Bovicola ovis)、安哥拉山羊羽虱(Bovicola limbata)、 牛畜虱(Damalina bovis)、犬毛虱(Trichodectes canis)、猫羽虱(Felicola subrostratus)、山羊毛虱(Bovicola caprae)、Lepikentron ovis、咬虱(Werneckiella equi)；
双翅目(Diptera)及其长角亚目(Nematocerina)和短角亚目(Brachycerina)，例如，伊蚊属(Aedes spp.)、按蚊属(Anopheles spp.)、库蚊属(Culex spp.)、蚋属(Simulium spp)、真蚋属(Eusimulium spp.)、白蛉属(Phlebotomus spp.)、罗蛉属(Lutzomyia spp.)、库蠓属(Culicoides spp.)、斑虻属(Chrysops spp.)、短蚋属(Odagmia spp.)、维蚋属(Wilhelmia spp.)、瘤虻属(Hybomitra spp.)、黄虻属(Atylotus spp.)、虻属(Tabanus spp.)、麻虻属(Haematopota spp.)、Philipomyia spp.、蜂虱蝇属(Braula spp.)、家蝇属(Musca spp.)、齿股蝇属(Hydrotaea spp.)、螫蝇属(Stomoxys spp.)、黑角蝇属(Haematobia spp.)、莫蝇属(Morellia spp.)、厕蝇属(Fannia spp.)、舌蝇属(Glossina spp.)、丽蝇属(Calliphora spp.)、绿蝇属(Lucilia spp.)、金蝇属(Chrysomyia spp.)、污蝇属(Wohlfahrtia spp.)、麻蝇属(Sarcophaga spp.)、狂蝇属(Oestrus spp.)、皮蝇属(Hypoderma spp.)、胃蝇属(Gasterophilus spp.)、虱蝇属(Hippobosca spp.)、羊虱蝇属(Lipoptena spp.)、蜱蝇属(Melophagus spp.)、鼻狂蝇属(Rhinoestrus spp.)、大蚊属(Tipula spp.)；特别地，代表性实例有，埃及伊蚊(Aedes aegypti)、白纹伊蚊(Aedes albopictus)、带喙伊蚊(Aedes taeniorhynchus)、冈比亚按蚊(Anopheles gambiae)、五斑按蚊(Anopheles maculipennis)、红头丽蝇(Calliphora erythrocephala)、高额麻虻(Chrysozona pluvialis)、五带淡色库蚊(Culex quinquefasciatus)、尖音库蚊(Culex pipiens)、环喙库蚊(Culex tarsalis)、夏厕蝇(Fannia canicularis)、肉蝇(Sarcophaga carnaria)、厩螯蝇(Stomoxys calcitrans)、欧洲大蚊(Tipula paludosa)、铜绿蝇(Lucilia cuprina)、丝光绿蝇(Lucilia sericata)、爬蚋(Simulium reptans)、静食白蛉(Phlebotomus papatasi)、长须白蛉(Phlebotomus longipalpis)、华丽短蚋(Odagmia ornata)、马维蚋(Wilhelmia equina)、红头厌蚋(Boophthora erythrocephala)、多声虻(Tabanus bromius)、夜蛾虻(Tabanus spodopterus)、北美黑虻(Tabanus atratus)、猪虻(Tabanus sudeticus)、古氏瘤虻(Hybomitra ciurea)、盲斑虻(Chrysops caecutiens)、黄缘斑虻(Chrysops relictus)、高额麻虻(Haematopota pluvialis)、Haematopotaitalica、秋家蝇(Musca autumnalis)、家蝇(Musca domestica)、西方角蝇(Haematobia irritans irritans)、西方角蝇(Haematobia irritans exigua)、刺扰血蝇(Haematobia stimulans)、Hydrotaea irritans、白斑齿股蝇(Hydrotaea albipuncta)、Chrysomya chloropyga、蛆症金蝇(Chrysomya bezziana)、羊狂蝇(Oestrus ovis)、牛皮蝇(Hypoderma bovis)、纹皮蝇(Hypoderma lineatum)、Przhevalskiana silenus、人肤蝇(Dermatobia hominis)、羊蜱蝇(Melophagus ovinus)、Lipoptena capreoli、鹿羊虱蝇(Lipoptena cervi)、Hippobosca variegata、马虱蝇(Hippobosca equina)、肠胃蝇(Gasterophilus intestinalis)、赤尾胃蝇(Gasterophilus haemorroidalis)、裸节胃蝇(Gasterophilus interrnis)、鼻胃蝇(Gasterophilus nasalis)、黑角胃蝇(Gasterophilus nigricornis)、黑腹胃蝇(Gasterophilus pecorum)、蜂虱蝇(Braula coeca)；
蚤目(Siphonapterida)，例如，蚤属(Pulex spp.)、栉首蚤属(Ctenocephalides spp.)、潜蚤属(Tunga spp.)、客蚤属(Xenopsylla spp.)、角叶蚤属(Ceratophyllus spp.)；特别地，代表性 实例有，犬栉首蚤(Ctenocephalides canis)、猫栉首蚤(Ctenocephalides felis)、人蚤(Pulex irritans)、穿皮潜蚤(Tunga penetrans)、印鼠客蚤(Xenopsylla cheopis)；
异翅目(Heteropterida)，例如，臭虫属(Cimex spp.)、锥猎椿属(Triatoma spp.)、红猎蝽属(Rhodnius spp.)、锥蝽属(Panstrongylus spp.)；
蜚蠊目(Blattarida)，例如，东方蜚蠊(Blatta orientalis)、美洲大蠊、德国蠊、夏柏拉蟑螂属(Supella spp.)(例如，Suppella longipalpa)；
蜱螨目(Acari)(或Acarina)，后气门目(Metastigmata)和中气门目(Mesostigmata)，例如，锐缘蜱属(Argas spp.)、钝缘蜱属(Ornithodorus spp.)、残喙蜱属(Otobius spp.)、硬蜱属(Ixodes spp.)、花蜱属(Amblyomma spp.)、牛蜱属(Rhipicephalus(Boophilus)spp.)、革蜱属(Dermacentor spp.)、Haemophysalis spp.、璃眼蜱属(Hyalomma spp.)、皮刺螨属(Dermanyssus spp.)、扇头蜱属(Rhipicephalus spp.)(异主寄生型螨的原属)、禽刺螨属(Ornithonyssus spp.)、肺刺螨属(Pneumonyssus spp.)、Pneumonyssus spp.、刺利螨属(Raillietia spp.)、肺刺螨属(Pneumonyssus spp.)、胸刺螨属(Sternostoma spp.)、蜂螨属(Varroa spp.)、蜂盾螨属(Acarapis spp.)；特别地，代表性实例有，波斯锐缘蜱(Argas persicus)、鸽锐缘蜱(Argas reflexus)、非洲钝缘蜱(Ornithodorus moubata)、耳残喙蜱(Otobius megnini)、微小扇头蜱(微小牛蜱)(Rhipicephalus(Boophilus)microplus)、消色扇头蜱(消色牛蜱)(Rhipicephalus(Boophilus)decoloratus)、具环扇头蜱(具环牛蜱)(Rhipicephalus(Boophilus)annulatus)、有矩扇头蜱(有矩牛蜱)(Rhipicephalus(Boophilus)calceratus)、Hyalomma anatolicum、埃及璃眼蜱(Hyalomma aegypticum)、Hyalomma marginatum、Hyalomma transiens、外翻扇头蜱(Rhipicephalus evertsi)、蓖子硬蜱(Ixodes ricinus)、六角硬蜱(Ixodes hexagonus)、原野硬蜱(Ixodes canisuga)、多毛硬蜱(Ixodes pilosus)、浅红硬蜱(Ixodes rubicundus)、肩突硬蜱(Ixodes scapularis)、全环硬蜱(Ixodes holocyclus)、嗜群血蜱(Haemaphysalis concinna)、刻点血蜱(Haemaphysalis punctata)、Haemaphysalis cinnabarina、Haemaphysalis otophila、犬血蜱(Haemaphysalis leachi)、长角血蜱(Haemaphysalis longicorni)、边缘革蜱(Dermacentor marginatus)、网纹革蜱(Dermacentor reticulatus)、Dermacentor pictus、白纹革蜱(Dermacentor albipictus)、安氏革蜱(Dermacentor andersoni)、变异革蜱(Dermacentor variabilis)、毛里求斯璃眼蜱(Hyalomma mauritanicum)、血红扇头蜱(Rhipicephalus sanguineus)、囊形扇头蜱(Rhipicephalus bursa)、非洲扇头蜱(Rhipicephalus appendiculatus)、好望角扇头蜱(Rhipicephalus capensis)、图兰扇头蜱(Rhipicephalus turanicus)、Rhipicephalus zambeziensis、美洲花蜱(Amblyomma americanum)、彩饰花蜱(Amblyomma variegatum、有斑花蜱(Amblyomma maculatum)、希伯来花蜱(Amblyomma hebraeum)、卡延花蜱(Amblyomma cajennense)、鸡皮刺螨(Dermanyssus gallinae)、囊禽刺螨(Ornithonyssus bursa)、林禽刺螨(Ornithonyssus sylviarum)、大蜂螨(Varroa jacobsconi)；
轴螨目(Actinedida)(前气门亚目(Prostigmata))和粉螨目(Acaridida)(无气门亚目 (Astigmata))，例如，蜂盾螨属(Acarapis spp.)、姬螯螨属(Cheyletiella spp.)、禽螯螨属(Ornithocheyletia spp.)、肉螨属(Myobia spp.)、疮螨属(Psorergates spp.)、蠕形螨属(Demodex spp.)、恙螨属(Trombicula spp.)、Listrophorus spp.、粉螨属(Acarus spp.)、食酪螨属(Tyrophagus spp.)、嗜木螨属(Caloglyphus spp.)、颈下螨属(Hypodectes spp.)、翅螨属(Pterolichus spp.)、痒螨属(Psoroptes spp.)、皮螨属(Chorioptes spp.)、耳疥螨属(Otodectes spp.)、疥螨属(Sarcoptes spp.)、耳螨属(Notoedres spp.)、疙螨属(Knemidocoptes spp.)、气囊螨属(Cytodites spp.)和鸡雏螨属(Laminosioptes spp.)；特别是，雅氏姬螯螨(C heyletiella yasguri)、布氏姬螯螨(C heyletiella blakei)、犬蠕形螨(Demodex canis)、牛蠕形螨(Demodex bovis)、绵羊蠕形螨(Demodex ovis)、山羊蠕形螨(Demodex caprae)、马蠕形螨(Demodex equi)、Demodex caballi、猪蠕形螨(Demodex suis)、Neotrombicula autumnalis、Neotrombicula desaleli、Neoschonegastia xerothermobia、秋收恙螨(Trombicula akamushi)、狗耳螨(Otodectes cynotis)、猫痂螨(Notoedres cati)、狗疥螨(Sarcoptis canis)、牛疥螨(Sarcoptes bovis)、绵羊疥螨(Sarcoptes ovis)、山羊疥螨(Sarcoptes rupicaprae(＝S.caprae))、马疥螨(Sarcoptes equi)、猪疥螨(Sarcoptes suis)、绵羊瘙螨(Psoroptes ovis)、兔瘙螨(Psoroptes cuniculi)、马瘙螨(Psoroptes equi)、牛痒螨(Chorioptes bovis)、Psoergates ovis、Pneumonyssoidic mange、犬鼻疥蟲(Pneumonyssoides caninum)、伍氏蜂跗线螨(Acarapis woodi)；
线虫，例如南方根结线虫(Meloidogyne incognita)、松材线虫(Bursaphelenchus xylophilus)、水稻干尖线虫(Aphelenchoides besseyi)、大豆异皮线虫(Heterodera glycines)、短体线虫属(Pratylenchus spp.)等；
侵袭动物的节肢动物、蠕虫和疟原虫。防治节肢动物、蠕虫和/或疟原虫，可减少家养动物的死亡率，并且可改善动物的生产率(肉、奶、毛、皮、蛋和蜜)和健康。
在一种可能的实现方式中，所述动物寄生虫防治剂用于防治猫蚤、美洲犬蜱中的一种或几种。
在一种可能的实现方式中，动物包括以下的一种或多种：农业动物，例如牛、绵羊、山羊、马、猪、驴、骆驼、水牛、兔、家鸡、火鸡、鸭、鹅、养殖鱼、蜜蜂等；也包括被称为伴侣动物的宠物，例如，狗、猫、笼鸟、观赏鱼；还包括用于实验的动物，例如仓鼠、豚鼠、大鼠和小鼠等。
本发明实施例还提供了一种动物寄生虫防治剂，该动物寄生虫防治剂中含有上述双酰胺类化合物作为活性组分，还含有一种或多种辅料。
在一种可能的实现方式中，动物寄生虫防治剂选自以下剂型：片剂、胶囊剂、饮剂、可饮用药、颗粒剂、膏剂和丸剂、栓剂、注射剂(肌肉、皮下、静脉内、腹膜内等)、涂抹剂、气雾剂、无压喷雾剂(例如泵喷雾剂和雾化喷雾剂)。
在一种可能的实现方式中，动物寄生虫防治剂中含有的上述活性组分的量为1至80重量％的量。
本发明实施例还提供了一种动物寄生虫防治组合物，其包括上述双酰胺类化合物和 其他动物寄生虫防治活性化合物(例如杀螨剂、杀昆虫剂、杀寄生虫剂、抗疟原虫剂等)的混合物。该混合物可以以原料药的形式提供，也可以以市售有用制剂的形式或者由其制剂制得的使用形式提供。
本发明实施例还提供了一种控制动物寄生虫的方法，其包括以下步骤：将有效剂量的材料施于需要控制的动物寄生虫或其生长介质上，所述材料选自下组中的一种或多种：上述双酰胺类化合物；上述动物寄生虫防治剂；上述动物寄生虫防治组合物。例如：采用片剂、胶囊剂、饮剂、可饮用药、颗粒剂、膏剂、丸剂、栓剂进行肠内给药；基于皮肤施用的非肠内给药，例如注射(肌肉、皮下、静脉内、腹膜内等)、植入、鼻部给药，包括洗浴或浸泡、喷雾、泼浇、点滴、清洗和撒粉，和通过使用含有活性化合物的模型制品，例如项圈、耳标、标签、腿部缚带(leg brace)、网、标识器等施用。本发明的活性化合物具有低毒性，可以安全地用于温血动物。
有益效果
本发明的双酰胺类化合物具有意想不到的高杀虫活性，且对栽培的作物植物没有植物毒性。此外，本发明的化合物可用于防治多种害虫，例如有害的刺吸式昆虫、咀嚼式昆虫以及其他植物寄生害虫、储存谷物害虫、卫生害虫等，并且可用于消毒和杀灭它们。
具体实施方式
为使本发明实施例的目的、技术方案和优点更加清楚，下面将对本发明实施例中的技术方案进行清楚、完整地描述，显然，所描述的实施例是本发明一部分实施例，而不是全部的实施例。基于本发明中的实施例，本领域普通技术人员在没有作出创造性劳动前提下所获得的所有其他实施例，都属于本发明保护的范围。。
另外，为了更好的说明本发明，在下文的具体实施方式中给出了众多的具体细节。本领域技术人员应当理解，没有某些具体细节，本发明同样可以实施。在一些实施例中，对于本领域技术人员熟知的原料、元件、方法、手段等未作详细描述，以便于凸显本发明的主旨。
除非另有其它明确表示，否则在整个说明书和权利要求书中，术语“包括”或其变换如“包含”或“包括有”等等将被理解为包括所陈述的元件或组成部分，而并未排除其它元件或其它组成部分
除另有注明外，所用原料均有市售。
本发明中，所用术语具有如下含义：
卤素：指氟、氯、溴或碘。
卤代烷基：直链或支链烷基，在这些烷基上的氢原子可部分或全部被卤素所取代，例如二氟甲基(CHF 2)、三氟甲基(CF 3)等。
卤代烷氧基：烷氧基上的氢原子可部分或全部被卤素所取代，例如二氟甲氧基 (OCHF 2)、三氟甲氧基(OCF 3)等。
氰基：CN。
杀虫剂：对害虫具有杀虫效果的物质。
动物寄生虫防治剂：是指能有效地将被寄生虫感染的动物中的各种寄生虫的发病率减少的活性化合物。防治意味着活性化合物能有效地杀灭寄生虫、抑制其生长或繁殖。
合成实施例
按照上述记载的合成路线，采用不同的原料化合物，即可分别制备获得本发明通式I、通式II及通式III所示化合物，进一步具体描述如下：
实施例1：中间体化合物II.1的制备
Figure PCTCN2020110707-appb-000006
向60毫升DMF中加入2.00克(3.60毫摩尔)N-(2,6-二溴-4-七氟异丙基苯基)-2-氟-3-氨基苯甲酰胺(中间体IV-1，参照WO2011093415或WO2010018714报道的方法制得)、0.74克(5.35毫摩尔)碳酸钾及0.58克(4.30毫摩尔)溴甲基环丙烷，升温至100度反应。TLC监测反应完毕后，加入水和乙酸乙酯萃取，有机相减压脱溶，残余物柱层析纯化，得白色固体0.90克，即中间体II.1。
中间体II.1的核磁及质谱数据如下：
1H NMR(600MHz,Chloroform-d)δ8.21(d,1H),7.87(s,2H),7.42–7.36(m,1H),7.14(t,1H),6.89(td,1H),4.24-4.17(br,1H),3.07-3.02(m,2H),1.19–1.11(m,1H),0.65–0.59(m,2H),0.33-0.27(m,2H).LC-MS(m/z,ESI):609.08[M+H] +.
实施例2：中间体化合物II.2的制备
Figure PCTCN2020110707-appb-000007
加入10克N-(2-溴-6-碘-4-七氟异丙基苯基)-2-氟-3-硝基苯甲酰胺(参照CN109206335A报道的方法制得)、15克无水氯化亚锡、200毫升1,4-二氧六环及8毫升浓盐酸，升温至60度搅拌反应。TLC监测反应结束后，减压蒸馏除去有机溶剂。加入500毫升乙酸乙酯，并加入适量饱和氢氧化钠水溶液调节pH＝10，充分搅拌后使用硅藻土滤除析出的不溶物，滤液用乙酸乙酯和水萃取后，有机层用无水硫酸镁干燥、过滤并减压浓缩，得到灰褐色固体，粗产物柱层析纯化后，得到7.91克N-(2-溴-6-碘-4-七氟异丙基苯基)-2-氟-3-氨基苯甲酰胺，即中间体IV-2。
向60毫升DMF中加入2.00克(3.32毫摩尔)N-(2-溴-6-碘-4-七氟异丙基苯基)-2-氟-3-氨基苯甲酰胺(中间体IV-2)、0.69克(4.99毫摩尔)碳酸钾及0.54克(4.00毫摩尔)溴甲基环丙烷，升温至100度反应。TLC监测反应完毕后，加入水和乙酸乙酯萃取，有机相减压脱溶，残余物柱层析纯化，得白色固体0.83克，即中间体II.2。
中间体II.2的核磁及质谱数据如下：
1H NMR(600MHz,Chloroform-d)δ8.21(d,1H),8.08(d,1H),7.89(d,1H),7.43–7.37(m,1H),7.15(t,1H),6.89(td,1H),4.22(br s,1H),3.07-3.02(m,2H),1.20-1.12(m,1H),0.66–0.59(m,2H),0.33–0.28(m,2H).LC-MS(m/z,ESI):657.07[M+H] +.
实施例3：中间体化合物II.3的制备
Figure PCTCN2020110707-appb-000008
向60毫升DMF中加入2.00克(3.67毫摩尔)N-(2-溴-6-三氟甲基-4-七氟异丙基苯基)-2-氟-3-氨基苯甲酰胺(中间体IV-3，参照WO2011093415、WO20110201687、WO2010013567或WO2010018714等报道的方法制得)、0.76克(5.50毫摩尔)碳酸钾及0.60克(4.44毫摩尔)溴甲基环丙烷，升温至100度反应。TLC监测反应完毕后，加入水和乙酸乙酯萃取，有机相减压脱溶，残余物柱层析纯化，得白色固体0.73克，即中间体II.3。
中间体II.3的核磁及质谱数据如下：
1H NMR(600MHz,Chloroform-d)δ8.27(d,1H),8.14(d,1H),7.91(d,1H),7.41–7.35(m,1H),7.14(t,1H),6.89(td,1H),4.25–4.17(br,1H),3.07-3.02(m,2H),1.20–1.11(m,1H),0.66–0.58(m,2H),0.33–0.27(m,2H).LC-MS(m/z,ESI):599.07[M+H] +.
实施例4：中间体化合物II.4的制备
Figure PCTCN2020110707-appb-000009
按照实施例1、实施例2或实施例3所描述的方法，由中间体化合物IV-4(参照WO2011093415或WO2010018714报道的方法制得)和溴甲基环丙烷反应制备得到中间体化合物II.4(白色固体)。
中间体化合物II.4的核磁及质谱数据如下：
1H NMR(600MHz,Chloroform-d)δ8.38–8.27(m,2H),7.96–7.91(m,1H),7.41–7.35(m,1H),7.15(t,1H),6.92–6.86(m,1H),4.22(br s,1H),3.05(d,2H),1.20–1.11(m, 1H),0.67–0.58(m,2H),0.34-0.27(m,2H).LC-MS(m/z,ESI):669.24[M+Na+H] +.
实施例5：化合物1的制备
Figure PCTCN2020110707-appb-000010
向30毫升甲苯中加入0.50克(0.82毫摩尔)中间体II.1及0.20克(1.25毫摩尔)中间体V-1，加热回流。TLC监测反应完毕后，减压脱溶，残余物柱层析纯化，得黄色固体0.42克，即化合物1。
化合物1的核磁及质谱数据如下：
1H NMR(600MHz,Chloroform-d)δ8.21(s,1H),8.08(t,1H),8.03–7.92(br,1H),7.91-7.76(m,3H),7.54(t,1H),7.33(t,1H),6.81(s,1H),3.90(s,1H),3.74(s,1H),1.17–1.05(br,1H),0.59–0.43(m,2H),0.19(d,2H).LC-MS(m/z,ESI):732.11[M+H] +.
实施例6：化合物2的制备
Figure PCTCN2020110707-appb-000011
向40毫升甲苯中加入0.60克(0.91毫摩尔)中间体II.2及0.22克(1.38毫摩尔)中间体V-1，加热回流。TLC监测反应完毕后，减压脱溶，残余物柱层析纯化，得白色固体0.46克，即化合物2。
化合物2的核磁及质谱数据如下：
1H NMR(600MHz,Chloroform-d)δ8.22(s,1H),8.13–8.04(m,2H),7.96(d,1H),7.88(d,1H),7.85-7.77(br,1H),7.60–7.51(m,1H),7.35(t,1H),6.80(s,1H),3.94(s,1H),3.72(s,1H),1.17–1.05(br,1H),0.58–0.46(m,2H),0.19(d,2H).LC-MS(m/z,ESI):780.11[M+H] +.
实施例7：化合物3的制备
Figure PCTCN2020110707-appb-000012
向30毫升甲苯中加入0.50克(0.83毫摩尔)中间体II.3及0.20克(1.25毫摩尔)中间体V-1，加热回流。TLC监测反应完毕后，减压脱溶，残余物柱层析纯化，得白色固体0.45克，即化合物3。
化合物3的核磁及质谱数据如下：
1H NMR(600MHz,Chloroform-d)δ8.18(s,1H),8.13(d,1H),8.07(t,1H),8.00(d,1H),7.90(d,1H),7.87–7.79(br,1H),7.62–7.53(m,1H),7.35(t,1H),6.82(s,1H),3.96(s,1H),3.70(s,1H),1.17–1.05(br,1H),0.58–0.46(m,2H),0.18(d,2H).LC-MS(m/z,ESI):722.10[M+H] +.
实施例8：化合物4的制备
Figure PCTCN2020110707-appb-000013
按照实施例5、实施例6或实施例7所描述的方法，由中间体化合物II.4与中间体V-1反应制备得到化合物4(黄色固体)。
化合物4的核磁及质谱数据如下：
1H NMR(600MHz,Chloroform-d)δ8.35–8.31(m,1H),8.18(s,1H),8.11–8.00(m,2H),7.95–7.90(m,1H),7.89–7.78(br,1H),7.58(td,1H),7.36(t,1H),6.82(s,1H),4.05–3.89(m,1H),3.75–3.60(m,1H),1.17–1.05(br,1H),0.60–0.44(m,2H),0.18(d,2H).LC-MS(m/z,ESI):770.18[M+H] +.
实施例9：化合物7的制备
Figure PCTCN2020110707-appb-000014
按照实施例5、实施例6或实施例7所描述的方法，由中间体化合物II.3与中间体V-2反应制备得到化合物7(黄色固体)。
化合物7的核磁数据如下：
1H NMR(600MHz,Chloroform-d)δ8.64(s,1H),8.13(d,1H),8.08(t,1H),7.98(d,1H),7.92–7.84(m,1H),7.65–7.53(m,2H),7.37(t,1H),4.08–3.95(m,1H),3.77–3.65(m,1H),1.18–1.07(br,1H),0.61–0.47(m,2H),0.21(d,2H).
实施例10：化合物8的制备
Figure PCTCN2020110707-appb-000015
按照实施例5、实施例6或实施例7所描述的方法，由中间体化合物II.4与中间体V-2反应制备得到化合物8(黄色固体)。化合物8的核磁数据如下：
1H NMR(600MHz,Chloroform-d)δ8.65(s,1H),8.32(d,1H),8.08(t,1H),8.02(d,1H),7.94–7.90(m,1H),7.88(d,1H),7.61(t,1H),7.56(d,1H),7.37(t,1H),4.10–3.96(m,1H),3.75–3.63(m,1H),1.19–1.08(br,1H),0.61–0.46(m,2H),0.21(d,2H).
实施例11：化合物9的制备
Figure PCTCN2020110707-appb-000016
按照实施例5、实施例6或实施例7所描述的方法，由中间体化合物II.1与中间体V-3反应制备得到化合物9(白色固体)。
化合物9的核磁及质谱数据如下：
1H NMR(600MHz,Chloroform-d)δ8.65(s,1H),8.17–8.05(br,1H),7.98–7.74(m,4H),7.63–7.47(m,2H),7.36(t,1H),4.00–3.86(m,1H),3.84–3.70(m,1H),1.17–1.05(br,1H),0.60–0.46(m,2H),0.22(d,2H).LC-MS(m/z,ESI):739.14[M+H] +.
实施例12：化合物10的制备
Figure PCTCN2020110707-appb-000017
按照实施例5、实施例6或实施例7所描述的方法，由中间体化合物II.2与中间体V-3反应制备得到化合物10(黄色油状物)。
化合物10的核磁及质谱数据如下：
1H NMR(600MHz,Chloroform-d)δ8.66(s,1H),8.16–8.08(br,1H),8.07(d,1H),7.94–7.86(m,2H),7.83–7.77(m,1H),7.61–7.51(br,2H),7.37(t,1H),4.02–3.89(m,1H),3.81 –3.68(m,1H),1.17–1.06(br,1H),0.60–0.48(m,2H),0.22(d,2H).LC-MS(m/z,ESI):787.20[M+H] +.
实施例13：化合物11的制备
Figure PCTCN2020110707-appb-000018
按照实施例5、实施例6或实施例7所描述的方法，由中间体化合物II.3与中间体V-3反应制备得到化合物11(黄色固体)。
化合物11的核磁及质谱数据如下：
1H NMR(600MHz,Chloroform-d)δ8.62(s,1H),8.16–8.12(m,1H),8.09(t,1H),8.00–7.89(m,2H),7.82(d,1H),7.63–7.52(m,2H),7.37(t,1H),4.02–3.92(m,1H),3.78–3.67(m,1H),1.17–1.05(br,1H),0.60–0.47(m,2H),0.21(d,2H).LC-MS(m/z,ESI):729.11[M+H] +.
实施例14：化合物12的制备
Figure PCTCN2020110707-appb-000019
按照实施例5、实施例6或实施例7所描述的方法，由中间体化合物II.4与中间体V-3反应制备得到化合物12(黄色固体)。
化合物12的核磁及质谱数据如下：
1H NMR(600MHz,Chloroform-d)δ8.62(s,1H),8.37–8.31(m,1H),8.09(t,1H),8.00(d,1H),7.93(d,1H),7.81(d,1H),7.63–7.53(m,2H),7.37(t,1H),4.05–3.94(m,1H),3.77–3.64(m,1H),1.17–1.05(br,1H),0.61–0.47(m,2H),0.21(d,2H).LC-MS(m/z,ESI):777.21[M+H] +.
参照以上实施例可以制备本发明通式I中其它化合物。
生物活性测定
实施例15：粘虫、小菜蛾、二化螟的生物活性测定
用本发明化合物对几种昆虫进行了杀虫活性测定实验。测定方法如下：
待测化合物用丙酮/甲醇(1:1)的混合溶剂溶解后，用含有0.1％(wt)吐温80的水稀释至所需的浓度。
以粘虫、小菜蛾、二化螟为靶标，采用Airbrush喷雾法进行活性测定。
(1)杀粘虫的活性测定
测定方法：将玉米叶片剪成长2cm的叶段，Airbrush喷雾处理的压力为10psi(约合0.7kg/cm 2)，每叶段正反面喷雾，待测化合物的喷液量为0.5ml。阴干后每处理接入10头3龄幼虫，每处理3次重复。处理后放入25℃、相对湿度60～70％观察室内培养，药后3天调查存活虫数，计算死亡率。
对粘虫的部分测试结果如下：
在0.05mg/L剂量下，药后3天，化合物1、2、3、4、7、8、9、10、11、12对粘虫的致死率均在90％以上。
(2)杀小菜蛾的活性测定
测定方法：将甘蓝叶片用打孔器打成直径2cm的叶碟，Airbrush喷雾处理的压力为10psi(约合0.7kg/cm 2)，每叶碟正反面喷雾，待测化合物的喷液量为0.5ml。阴干后每处理接入10头3龄幼虫，每处理3次重复。处理后放入25℃、相对湿度60～70％观察室内培养，药后3天调查存活虫数，计算死亡率。
对小菜蛾的部分测试结果如下：
在0.5mg/L剂量下，药后3天，化合物1、2、3、4、7、8、9、10、11、12对小菜蛾的致死率均在90％以上。
在0.05mg/L剂量下，药后3天，化合物3、4、7、8、11、12对小菜蛾的致死率均在90％以上。
(3)杀二化螟的活性测定
测定方法：1)稻苗准备：在恒温室(温度26～28℃、相对湿度60～80％左右，光照16hL:8hD)内用直径为4.5cm、高4cm塑料小杯培养水稻，待水稻长至4～5叶期时，选择健壮的、长势一致的水稻幼苗进行药剂处理，每处理设3次重复。2)试虫准备：室内连续饲养的二化螟，3龄幼虫。3)稻茎喷雾接虫。采用喷雾法，对稻苗进行全株均匀喷雾处理，每处理用药15ml。先处理空白对照，然后按试验浓度由低到高的顺序重复上述操作。稻苗喷雾处理后，放置阴凉处将药液晾干，剪取茎基部上5厘米左右茎秆饲喂试虫。准备直径90mm的玻璃培养皿，皿底垫滤纸，加水保湿，每皿放入约5根稻茎，接幼虫10头，用无纺布密闭培养皿，置于恒温房间培养。药后3天调查残留活虫数。
对二化螟的部分测试结果如下：
在1mg/L剂量下，化合物1、2、3、4、7、8、9、10、11、12对二化螟的致死率在90％以上。
在0.5mg/L剂量下，化合物3、4、7、8、11、12对二化螟的致死率在90％以上。
在0.25mg/L剂量下，化合物3、4、11、12对二化螟的致死率在90％以上。
选取本发明化合物1、3、7、11与对照化合物进行二化螟杀虫活性平行比较试验(药后3天)，测定方法同前所述；结果如表5所示：
表5本发明化合物1、3、7、11与对照化合物对二化螟杀虫活性平行比较试验
Figure PCTCN2020110707-appb-000020
Figure PCTCN2020110707-appb-000021
注：表5中“-”表示未测。表中1-1、1-2、2-1、3-1、4-1、5-1、5-2均为本申请提供的对比化合物，这些对比化合物，参照本发明实施例5-14的方法可以获得，原料均为按照本发明实施例方法可以制备得到的或可以购买得到的或按照常规方法可以制得的。
本发明实施例中通过对式I化合物中的R 1、R 2、R 3、R 4基团及其搭配进行选择，获得了杀虫效果更好的化合物，如表5所示，通过将化合物1和对照化合物1-1、1-2进行比较，通过将化合物3和对照化合物2-1进行比较、通过将化合物7和对照化合物3-1进行比较、通过将化合物11和对照化合物4-1进行比较可以看出：R 4和与之相邻的氮原子非常重要，二者相互配合，缺一不可，当R 4为F、CF 3、CN时，与之相邻的原子选择碳原子后，化合物对二化螟的活性会显著降低，甚至丧失；通过将化合物3、7、11和5-1、5-2进行比较可以看出：当与R 4相邻的原子为氮原子时，R 4选择氢或氯后，化合物对二化螟的活性也会显著降低，甚至丧失。
实施例16：对猫蚤的杀虫试验
将4mg待测化合物溶解于40ml丙酮，获得浓度100ppm的丙酮溶液，在内径5.3cm的培养皿的底面和侧面上涂布400μl药液，然后待丙酮挥发，在培养皿的内壁上制作本发明化合物的薄膜。所使用的培养皿的内壁为40cm 2，处理药量为1μg/cm 2；向其中放入10只猫蚤成虫(雌雄混合)，盖好后在25℃的恒温室内保存。检查72h后的死虫数，计算死虫率。试验按3次重复进行。测试结果：化合物1、2、3、4、7、8、9、10、11、12显示出90％以上的死虫率。
实施例17：对美洲犬蜱的杀虫试验
将4mg待测化合物溶解于40ml丙酮，获得浓度100ppm的丙酮溶液，在2个内径5.3cm的培养皿的底面和侧面上，涂布400μl药液，然后待丙酮挥发，在培养皿的内壁上制作本发明化合物的薄膜。所使用的培养皿的内壁为40cm 2，处理药量为1μg/cm 2。向其中放入10只美洲犬蜱的第1若虫(雌雄混合)，合并2个培养皿，使用胶带密封结合部以防止逃亡，在25℃的恒温室中保存。检查24h后的死虫数，计算死虫率。试验按3次重复进行。测试结果：化合物1、2、3、4、7、8、9、10、11、12显示出90％以上的死虫率。
工业实用性
本发明提供了一种具有更优异杀虫活性的双酰胺类化合物。它可用于制备农业和其它领域中防治害虫的药物以及在兽药领域用于制备控制动物寄生虫的药物。

Claims (22)

  1. 一种双酰胺类化合物，其特征在于：所述双酰胺类化合物的结构如通式I所示：
    Figure PCTCN2020110707-appb-100001
    通式I中：
    R 1选自卤素；
    R 2选自卤素、C 1-C 4卤代烷基或C 1-C 4卤代烷氧基；
    R 3选自CF 3或CF 2CF 3；
    R 4选自氟、二氟甲基、三氟甲基或氰基。
  2. 根据权利要求1所述的化合物，其特征在于：通式I中
    R 1选自卤素；
    R 2选自卤素、C 1-C 2卤代烷基或C 1-C 2卤代烷氧基；
    R 3选自CF 3或CF 2CF 3；
    R 4选自氟、二氟甲基、三氟甲基或氰基。
  3. 根据权利要求2所述的化合物，其特征在于：通式I中
    R 1选自溴或碘；
    R 2选自溴、碘、三氟甲基或二氟甲氧基；
    R 3选自CF 3或CF 2CF 3；
    R 4选自氟、二氟甲基、三氟甲基或氰基。
  4. 根据权利要求1-3之一所述的双酰胺类化合物，其特征在于：通式I中
    R 4选自氟、二氟甲基或三氟甲基。
  5. 根据权利要求1所述的双酰胺类化合物，其特征在于，双酰胺类化合物选自：表1化合物，表1化合物具有如通式I的结构且R 1、R 2、R 3和R 4如表1中所示；
    表1
    化合物编号 R 1 R 2 R 3 R 4 1 Br Br CF 3 F 2 Br I CF 3 F
    3 Br CF 3 CF 3 F 4 I CF 3 CF 3 F 5 Br Br CF 3 CF 3 6 Br I CF 3 CF 3 7 Br CF 3 CF 3 CF 3 8 I CF 3 CF 3 CF 3 9 Br Br CF 3 CN 10 Br I CF 3 CN 11 Br CF 3 CF 3 CN 12 I CF 3 CF 3 CN 13 Br Br CF 2CF 3 F 14 Br I CF 2CF 3 F 15 Br CF 3 CF 2CF 3 F 16 I CF 3 CF 2CF 3 F 17 Br Br CF 2CF 3 CF 3 18 Br I CF 2CF 3 CF 3 19 Br CF 3 CF 2CF 3 CF 3 20 I CF 3 CF 2CF 3 CF 3 21 Br Br CF 2CF 3 CN 22 Br I CF 2CF 3 CN 23 Br CF 3 CF 2CF 3 CN 24 I CF 3 CF 2CF 3 CN
    。
  6. 根据权利要求5所述的双酰胺类化合物，其特征在于，双酰胺类化合物选自：表2化合物，表2化合物具有如通式I的结构且R 1、R 2、R 3和R 4如表2中所示；
    表2
    化合物编号 R 1 R 2 R 3 R 4 1 Br Br CF 3 F 2 Br I CF 3 F 3 Br CF 3 CF 3 F 4 I CF 3 CF 3 F 5 Br Br CF 3 CF 3 6 Br I CF 3 CF 3 7 Br CF 3 CF 3 CF 3
    8 I CF 3 CF 3 CF 3 13 Br Br CF 2CF 3 F 14 Br I CF 2CF 3 F 15 Br CF 3 CF 2CF 3 F 16 I CF 3 CF 2CF 3 F 17 Br Br CF 2CF 3 CF 3 18 Br I CF 2CF 3 CF 3 19 Br CF 3 CF 2CF 3 CF 3 20 I CF 3 CF 2CF 3 CF 3
    。
  7. 一种用于制备权利要求1所述的双酰胺类化合物的中间体化合物，其特征在于，中间体化合物如通式II所示：
    Figure PCTCN2020110707-appb-100002
    通式II中：
    R 1选自卤素；
    R 2选自卤素、C 1-C 4卤代烷基或C 1-C 4卤代烷氧基；
    R 3选自CF 3或CF 2CF 3。
  8. 根据权利要求7所述的中间体化合物，其特征在于：通式II中
    R 1选自卤素；
    R 2选自卤素、C 1-C 2卤代烷基或C 1-C 2卤代烷氧基；
    R 3选自CF 3或CF 2CF 3。
  9. 根据权利要求8所述的中间体化合物，其特征在于：通式II中
    R 1选自溴或碘；
    R 2选自溴、碘、三氟甲基或二氟甲氧基；
    R 3选自CF 3或CF 2CF 3。
  10. 根据权利要求9所述的中间体化合物，其特征在于，中间体化合物选自：
    表3化合物，表3化合物具有如通式II的结构且R 1、R 2和R 3如表3中所示；
    表3
    化合物编号 R 1 R 2 R 3 II.1 Br Br CF 3 II.2 Br I CF 3 II.3 Br CF 3 CF 3 II.4 I CF 3 CF 3 II.5 Br Br CF 2CF 3 II.6 Br I CF 2CF 3 II.7 Br CF 3 CF 2CF 3 II.8 I CF 3 CF 2CF 3
    。
  11. 一种用于制备权利要求1所述的双酰胺类化合物的中间体化合物，其特征在于，化合物如通式III所示：
    Figure PCTCN2020110707-appb-100003
    通式III中：
    R 4选自氟、二氟甲基、三氟甲基或氰基；
    L选自卤素或羟基。
  12. 根据权利要求11所述的中间体化合物，其特征在于，中间体化合物选自：
    表4化合物，表4化合物具有如通式III的结构且R 4和L如表4中所示；
    表4
    化合物编号 R 4 L III.1 F F III.2 F Cl III.3 F Br III.4 F I III.5 F OH III.6 CF 3 F III.7 CF 3 Cl III.8 CF 3 Br
    III.9 CF 3 I III.10 CF 3 OH III.11 CN F III.12 CN Cl III.13 CN Br III.14 CN I III.15 CN OH
    。
  13. 一种根据权利要求1-6之一所述的双酰胺类化合物在制备杀虫剂中的用途。
  14. 根据权利要求13所述的用途，其特征在于：所述杀虫剂用于防治粘虫、小菜蛾、二化螟中的一种或几种。
  15. 一种杀虫剂制剂，其特征在于：所述杀虫剂制剂中含有权利要求1-6之一所述的双酰胺类化合物作为活性组分，还含有一种或多种辅料；可选地，杀虫剂制剂中权利要求1-6之一所述的双酰胺类化合物的量为0.1至99重量％，进一步可选地为0.5至90重量％。
  16. 一种杀虫剂组合物，其特征在于：包括权利要求1-6之一所述的双酰胺类化合物和其他活性化合物的混合物，所述其他活性化合物选***虫剂、毒饵剂、消毒剂、杀螨剂、杀线虫剂、杀真菌剂、生长调节剂、除草剂中的一种或多种。
  17. 一种控制农业或林业害虫的方法，其特征在于：将有效剂量的材料施用于需要控制的害虫或其生长介质上，所述材料选自下组中的一种或多种：
    权利要求1-6之一所述的双酰胺类化合物；
    权利要求15所述的杀虫剂制剂；
    权利要求16所述的杀虫剂组合物。
  18. 一种根据权利要求1-6之一所述的双酰胺类化合物在制备动物寄生虫防治剂中的用途。
  19. 根据权利要求18所述的用途，其特征在于：所述动物寄生虫防治剂用于防治猫蚤、美洲犬蜱中的一种或几种。
  20. 一种动物寄生虫防治剂，其特征在于：所述动物寄生虫防治剂中含有权利要求 1-6之一所述的双酰胺类化合物作为活性组分，还含有一种或多种辅料；可选地，动物寄生虫防治剂中权利要求1-6之一所述的双酰胺类化合物的量为1至80重量％。
  21. 一种动物寄生虫防治组合物，其特征在于：包括权利要求1-6之一所述的双酰胺类化合物和其他动物寄生虫防治活性化合物的混合物，所述其他动物寄生虫防治活性化合物选***螨剂、杀昆虫剂、杀寄生虫剂、抗疟原虫剂中的一种或多种。
  22. 一种控制动物寄生虫的方法，其特征在于：包括以下步骤：将有效剂量的材料施于需要控制的动物寄生虫或其生长介质上，所述材料选自下组中的一种或多种：
    权利要求1-6之一所述的双酰胺类化合物；
    权利要求20所述的动物寄生虫防治剂；
    权利要求21所述的动物寄生虫防治组合物。
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