CN113767908B - Pharmaceutical composition containing m-diamide compound and application thereof - Google Patents

Pharmaceutical composition containing m-diamide compound and application thereof Download PDF

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CN113767908B
CN113767908B CN202111073141.2A CN202111073141A CN113767908B CN 113767908 B CN113767908 B CN 113767908B CN 202111073141 A CN202111073141 A CN 202111073141A CN 113767908 B CN113767908 B CN 113767908B
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pharmaceutical composition
compound
composition containing
active ingredient
weight ratio
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CN113767908A (en
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倪珏萍
相君成
吕亮
洪湖
刘吉永
邵佳礼
周丽琪
刘叙杆
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Cac Nantong Chemical Co ltd
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Cac Nantong Chemical Co ltd
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    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N37/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having three bonds to hetero atoms with at the most two bonds to halogen, e.g. carboxylic acids
    • A01N37/44—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
    • A01N37/46—N-acyl derivatives
    • A—HUMAN NECESSITIES
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    • A01N31/08—Oxygen or sulfur directly attached to an aromatic ring system
    • A01N31/14—Ethers
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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
    • A01N37/18—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
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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
    • A01N37/18—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
    • A01N37/28—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 containing the group; Thio analogues thereof
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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
    • A01N37/34—Nitriles
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    • A01N41/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a sulfur atom bound to a hetero atom
    • A01N41/02—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a sulfur atom bound to a hetero atom containing a sulfur-to-oxygen double bond
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    • A01N41/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a sulfur atom bound to a hetero atom
    • A01N41/02—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a sulfur atom bound to a hetero atom containing a sulfur-to-oxygen double bond
    • A01N41/10—Sulfones; Sulfoxides
    • A—HUMAN NECESSITIES
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    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/02—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms
    • A01N43/24—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 two or more hetero atoms
    • A01N43/32—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 two or more hetero atoms six-membered rings
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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
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    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/64—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with three nitrogen atoms as the only ring hetero atoms
    • A01N43/66—1,3,5-Triazines, not hydrogenated and not substituted at the ring nitrogen atoms
    • A01N43/68—1,3,5-Triazines, not hydrogenated and not substituted at the ring nitrogen atoms with two or three nitrogen atoms directly attached to ring carbon atoms
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
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    • A01N47/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom not being member of a ring and having no bond to a carbon or hydrogen atom, e.g. derivatives of carbonic acid
    • A01N47/08—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom not being member of a ring and having no bond to a carbon or hydrogen atom, e.g. derivatives of carbonic acid the carbon atom having one or more single bonds to nitrogen atoms
    • A01N47/10—Carbamic acid derivatives, i.e. containing the group —O—CO—N<; Thio analogues thereof
    • A01N47/12—Carbamic acid derivatives, i.e. containing the group —O—CO—N<; Thio analogues thereof containing a —O—CO—N< group, or a thio analogue thereof, neither directly attached to a ring nor the nitrogen atom being a member of a heterocyclic ring
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N47/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom not being member of a ring and having no bond to a carbon or hydrogen atom, e.g. derivatives of carbonic acid
    • A01N47/08—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom not being member of a ring and having no bond to a carbon or hydrogen atom, e.g. derivatives of carbonic acid the carbon atom having one or more single bonds to nitrogen atoms
    • A01N47/10—Carbamic acid derivatives, i.e. containing the group —O—CO—N<; Thio analogues thereof
    • A01N47/18—Carbamic acid derivatives, i.e. containing the group —O—CO—N<; Thio analogues thereof containing a —O—CO—N< group, or a thio analogue thereof, directly attached to a heterocyclic or cycloaliphatic ring
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    • A01N47/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom not being member of a ring and having no bond to a carbon or hydrogen atom, e.g. derivatives of carbonic acid
    • A01N47/08—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom not being member of a ring and having no bond to a carbon or hydrogen atom, e.g. derivatives of carbonic acid the carbon atom having one or more single bonds to nitrogen atoms
    • A01N47/10—Carbamic acid derivatives, i.e. containing the group —O—CO—N<; Thio analogues thereof
    • A01N47/22—O-Aryl or S-Aryl esters thereof
    • A—HUMAN NECESSITIES
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    • A01N47/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom not being member of a ring and having no bond to a carbon or hydrogen atom, e.g. derivatives of carbonic acid
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    • A01N47/10—Carbamic acid derivatives, i.e. containing the group —O—CO—N<; Thio analogues thereof
    • A01N47/24—Carbamic acid derivatives, i.e. containing the group —O—CO—N<; Thio analogues thereof containing the groups, or; Thio analogues thereof
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N47/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom not being member of a ring and having no bond to a carbon or hydrogen atom, e.g. derivatives of carbonic acid
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    • A01N47/28—Ureas or thioureas containing the groups >N—CO—N< or >N—CS—N<
    • A01N47/34—Ureas or thioureas containing the groups >N—CO—N< or >N—CS—N< containing the groups, e.g. biuret; Thio analogues thereof; Urea-aldehyde condensation products
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Abstract

The invention provides a pharmaceutical composition containing a m-diamide compound and application thereof, wherein the pharmaceutical composition comprises an active ingredient A and an active ingredient B, the active ingredient A is the m-diamide compound with a structure shown in a formula I, and the active ingredient B comprises any one or a combination of two of other insecticides. The composition containing the effective component A and the effective component B has the unique effects of synergy, controlling resistant pests, expanding an activity spectrum, controlling toxic insects and the like, and can effectively prevent and control various plant diseases and insect pests in crops such as rice, corn, wheat, vegetables, fruit trees, flowers, oil plants, sugar and the like, and in gardening and forestry.

Description

Pharmaceutical composition containing m-diamide compound and application thereof
The application is a divisional application of patent application No. 201910704042.6 (the application date of the original application is 7 months and 31 days in 2019, and the invention name is a pharmaceutical composition containing a m-diamide compound and application thereof). Application to case division
Technical Field
The invention belongs to the technical field of pest control by using a pharmaceutical composition, and relates to a pharmaceutical composition containing a m-diamide compound and application thereof.
Background
In the production of crops such as agriculture and horticulture, the damage caused by diseases and insect pests is still very obvious, and the pests have resistance to the existing pesticides and are not environment-friendly, so that the development of a new pesticide or a pesticide composition with better activity, lower consumption and more environment-friendly is always needed.
For example, CN101208009a discloses that compositions containing m-diamide compounds have insecticidal effects, and in the prior art, various structural types of insecticides and fungicides are widely used for various crops. With the continuous use of pesticides, pests and diseases can generate resistance to some existing pesticide products, and the insecticidal activity of the existing pesticide varieties can not always meet the needs of many agricultural practices.
The pesticide composition has important functions of improving the control effect of the pesticide, expanding the control spectrum and delaying the generation of resistance. Therefore, in the art, it is still desired to develop more efficient pesticide compositions or pesticidal and bactericidal compositions to meet the needs of agriculture as well as forestry.
Disclosure of Invention
Aiming at the problems in the prior art, the invention aims to provide a pharmaceutical composition containing a m-diamide compound and application thereof, wherein the pharmaceutical composition has a synergistic effect and can be used for preventing and treating various agricultural and forestry insect pests and diseases caused by insects, diseases and the like.
In order to achieve the purpose, the invention adopts the following technical scheme:
in one aspect, the invention provides a pharmaceutical composition containing a m-diamide compound, which comprises an active ingredient A and an active ingredient B, wherein the active ingredient A is an amide compound with a structure shown in formula I, and the active ingredient B comprises any one or a combination of two of other insecticides or bactericides;
Figure BDA0003261188380000011
wherein Z is selected from hydrogenFluorine, chlorine, bromine, iodine, cyano, nitro, substituted or unsubstituted 3-to 10-membered heterocyclic group, C 1 -C 6 Alkyl radical, C 1 -C 6 Haloalkyl, C 1 -C 6 Alkoxy radical, C 1 -C 6 Haloalkoxy, C 1 -C 6 Alkylsulfinyl radical, C 1 -C 6 Haloalkylsulfinyl radical, C 1 -C 6 Alkylsulfonyl or C 1 -C 6 A haloalkylsulfonyl group; q is selected from C 3 -C 8 Cycloalkyl or C 3 -C 8 A halocycloalkyl group;
x is selected from hydrogen, fluorine or trifluoromethyl;
Y 1 selected from fluorine, chlorine, bromine, iodine, cyano, nitro, C 1 -C 6 Alkyl radical, C 1 -C 6 Haloalkyl, C 1 -C 6 Haloalkoxy, C 2 -C 4 Alkenyl radical, C 2 -C 4 Halogenated alkenyl group, C 2 -C 4 Alkynyl, C 2 -C 4 Halogenated alkynyl, C 3 -C 8 Cycloalkyl radical, C 3 -C 8 Halogenocycloalkyl, C 1 -C 6 Alkylcarbonyl group, C 1 -C 6 Alkylsulfinyl radical, C 1 -C 6 Haloalkylsulfinyl radical, C 1 -C 6 Alkylsulfonyl or C 1 -C 6 A haloalkylsulfonyl group;
Y 2 selected from bromine, iodine, cyano, nitro, C 1 -C 6 Haloalkyl, C 1 -C 6 Haloalkoxy, C 2 -C 4 Alkenyl radical, C 2 -C 4 Haloalkenyl, C 2 -C 4 Alkynyl, C 2 -C 4 Halogenated alkynyl, C 3 -C 8 Cycloalkyl, C 3 -C 8 Halogenocycloalkyl, C 1 -C 6 Alkylcarbonyl group, C 1 -C 6 Alkylsulfinyl radical, C 1 -C 6 Haloalkylsulfinyl radical, C 1 -C 6 Alkylsulfonyl or C 1 -C 6 A haloalkylsulfonyl group;
R 1 selected from hydrogen, fluoro or methoxy; r 2 Selected from fluoro or trifluoromethyl; r 3 And R 4 Each independently selected from hydrogen, halogen, cyano, nitro, C 1 -C 6 Alkyl radical, C 1 -C 6 Haloalkyl, C 3 -C 8 Cycloalkyl or C 3 -C 8 A halocycloalkyl group;
m represents an integer of 0 to 5 (e.g., 0, 1,2,3, 4 or 5); n represents an integer of 0 to 3 (for example, 0, 1,2 or 3); w is a group of 1 And W 2 Independently an oxygen atom or a sulfur atom.
The m-diamide compound with the structure shown in the formula I is used as an effective component A and is matched with a medicinal composition of an effective component B, due to the synergistic interaction between the effective component A and the effective component B, on one hand, the use amount of a single active component can be reduced, on the other hand, the prevention and treatment effect is remarkably improved, and due to the fact that the effective component A can achieve better insecticidal activity at low dose, the effect is fast to take effect and good quick-acting performance is achieved, the medicinal composition containing the m-diamide compound also has good quick-acting performance, and due to the fact that the effect is good at low dose, damage to plants and human beings caused by overlarge medicament concentration is reduced, and the m-diamide compound generates less medicament residue during application and is more beneficial to environmental protection.
Preferably, the invention provides a pesticide composition containing a compound with m-diamide 3 position substituted by N-cyclopropylmethyl derivative, which comprises an effective component A and an effective component B, wherein the effective component A is a m-diamide compound with a structure shown in formula II, and the effective component B comprises any one or a combination of two of other bactericides, insecticides or acaricides;
Figure BDA0003261188380000021
in the formula II, the reaction solution is shown in the specification,
z is selected from hydrogen, fluorine, chlorine, bromine, iodine, cyano, C 1 -C 6 Haloalkyl, C 1 -C 6 Haloalkoxy, C 1 -C 6 Alkylsulfonyl or C 1 -C 6 Haloalkylsulfonyl radical；
Y is selected from C 1 -C 6 Haloalkyl or C 1 -C 6 A haloalkoxy group;
r is selected from hydrogen or methyl.
In the invention, the m-diamide compound with the structure shown in the formula II is further preferably selected to be matched with the effective component B as the effective component of the pharmaceutical composition, the m-diamide compound and the effective component B have synergistic interaction, the onset of action is fast, the quick-acting property is good, the good effect can be achieved under the condition of low dosage, the drug residue is less, and the environmental protection is facilitated.
In the present invention, as a preferred embodiment, in formula I, Z is selected from hydrogen, fluorine, chlorine, bromine, iodine, cyano, trifluoromethoxy, trifluoromethyl, methylsulfonyl or trifluoromethylsulfonyl; y is selected from trifluoromethyl or trifluoromethoxy; r is selected from hydrogen or methyl.
In a further preferred embodiment of the present invention, the m-diamide compound is any one of compounds represented by the following table 1 having the general formula II.
TABLE 1 active ingredient A
Figure BDA0003261188380000022
Figure BDA0003261188380000031
In Table 1, H is a hydrogen atom, F is a fluorine atom, cl is a chlorine atom, br is a bromine atom, I is an iodine atom, CN is a cyano group, CF 3 Is trifluoromethyl, OCF 3 Is trifluoromethoxy, meS (O) 2 Represents methylsulfonyl, CF 3 S(O) 2 Represents trifluoromethanesulfonyl.
In the present invention, as a particularly preferred embodiment, the m-diamide compound is any one or a combination of at least two selected from the following compounds 1 to 14:
Figure BDA0003261188380000032
Figure BDA0003261188380000041
the term "C" as used in the present invention 1 -C 6 Alkyl "refers to a straight or branched chain alkyl group having 1 to 6 carbon atoms, including without limitation methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, isopentyl, n-hexyl, and the like. The term "C 1 -C 6 Alkoxy "refers to a straight or branched chain alkoxy group having 1 to 6 carbon atoms, including without limitation methoxy, ethoxy, n-propoxy, isopropoxy, tert-butoxy, and the like. The term "C 1 -C 6 Haloalkyl "refers to an alkyl group of 1 to 6 carbon atoms having halogen substitution, including without limitation chloromethyl, 1-chloroethyl, 2-bromo-n-propyl, and the like. The term "C 1 -C 6 Haloalkoxy "refers to alkoxy groups of 1 to 6 carbon atoms having halogen substitution; the same term "C 3 -C 8 Cycloalkyl "refers to cyclic alkyl groups having 3 to 8 carbon atoms in the ring, including without limitation cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, and the like; as used herein, the term "C3-C8 halocycloalkyl" refers to a cyclic alkyl group of 3 to 8 carbon atoms having halogen substitution in the ring, including, without limitation, 1-chlorocyclopropyl, 1-fluorocyclopropyl, perfluorocyclopropyl, 1-chlorocyclobutyl, 1-chlorocyclopentyl, and the like.
In the present invention, C before the specific group 1 -C 6 、C 3 -C 8 Etc. represent the number of carbon atoms contained in the radical, e.g. C 1 -C 6 Represents a group having 1,2,3, 4, 5 or 6 carbon atoms, C 3 -C 8 Represents a group in which the number of carbon atoms may be 3, 4, 5, 6, 7 or 8, and so on.
The effective component B is selected from organophosphorus, pyrethroid, carbamate, nereistoxin or insect growth regulator.
Preferably, the organophosphorus insecticide is selected from chlorpyrifos, acephate, phoxim, dichlorvos, triazophos, profenofos, fosthiazate, malathion, fenitrothion, dimethoate, omethoate, diazinon, isocarbophos or a combination of at least two of the foregoing;
preferably, the synthetic pyrethroid insecticide is selected from the group consisting of lambda-cyhalothrin, deltamethrin, bifenthrin, cypermethrin, ethofenprox, fenpropathrin, fenvalerate, cycloprothrin, cyfluthrin, tefluthrin, tralomethrin, proffluthrin, permethrin, silafluofen, phenothrin, flucythrinate and their various isomers or a combination of at least two of the pyrethroid insecticides.
Preferably, the carbamate pesticide is selected from methomyl, isoprocarb, fenobucarb, carbosulfan, pirimicarb, fenoxycarb or a combination of at least two of the foregoing;
preferably, the nereistoxin insecticide is selected from monosultap, dimehypo, thiocyclam, cartap or a combination of at least two of the foregoing;
preferably, the insect growth regulator is selected from chlorfluazuron, diflubenzuron, hexaflumuron, flufenoxuron, chlorbenzuron, cyromazine, pyriproxyfen, fenoxycarb, tebufenozide, and a hydrazine inhibitor, or a combination of at least two thereof.
In actual production, the traditional organophosphorus, pyrethroid, carbamate and nereistoxin insecticides have no good effect for long-term use or unreasonable use, and the dosage has to be increased when in use.
The insect growth regulator can control pests by preventing the special development processes of molting, metamorphosis and the like of insects, is safe to human and livestock, and is greatly researched and applied; but the problem of poor quick action needs to be compensated by compounding with other medicaments.
As a further preferred embodiment of the present invention, the pharmaceutical composition containing the m-diamide compound is a pharmaceutical composition containing the m-diamide compound (active ingredient a) and the active ingredient B shown in table 2 below, but not limited to the combinations listed in the table.
TABLE 2
Figure BDA0003261188380000042
Figure BDA0003261188380000051
Figure BDA0003261188380000061
Figure BDA0003261188380000071
Figure BDA0003261188380000081
Figure BDA0003261188380000091
The pests such as chilo suppressalis, plutella xylostella, armyworm, alfalfa aphid, brown planthopper, leaf miner, bemisia tabaci and the like are adopted to test the combined action of the pharmaceutical composition, and the composition with the synergistic action is discovered.
The weight ratio of the active ingredient a to the active ingredient B in the present invention is 200.
In the present invention, the preferable weight ratio of the pharmaceutical composition containing the m-diamide compound is different according to the effective component a and the effective component B contained therein, and as a preferable embodiment of the present invention, when the effective component a and the effective component B are selected from the components shown in table 3, the preferable weight ratio and the particularly preferable weight ratio are shown in table 3.
TABLE 3
Figure BDA0003261188380000101
In the present invention, the m-diamide compounds may also be replaced with tautomers, enantiomers, diastereomers, or salts thereof.
In the invention, the pharmaceutical composition containing the tautomer, enantiomer, diastereomer or salt of the m-diamide compound can also exert the same action and effect as the pharmaceutical composition containing the m-diamide compound, and has good insecticidal effect and quick action at low dosage.
In another aspect, the present invention provides a pharmaceutical preparation, which comprises the pharmaceutical composition containing the m-diamide compound as described above, and an agriculturally and pharmaceutically acceptable adjuvant and/or carrier.
Preferably, the pharmaceutical composition containing the m-diamide compound is contained in the pharmaceutical preparation in an amount of 0.01 to 99% by weight, for example, 0.01%, 0.1%, 1%, 3%, 5%, 8%, 10%, 15%, 18%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95% or 99%.
Preferably, the agriculturally pharmaceutically acceptable auxiliary agent includes any one of a dispersant, a wetting agent, an emulsifier, an antifreeze agent, a thickener, an antifoaming agent, a preservative, a stabilizer or a coloring agent or a combination of at least two thereof.
Preferably, the dispersant comprises lignosulfonate, alkylphenol polyoxyethylene ether, sodium salt of naphthalene sulfonic acid formaldehyde condensate, fatty amine polyoxyethylene ether, fatty acid polyoxyethylene ester, glycerol fatty acid ester polyoxyethylene ether, polycarboxylate, formaldehyde condensate, calcium salt of alkylbenzene sulfonic acid, and alkylphenol polyoxyethylene ether. The wetting agent is selected from sodium dodecyl sulfate, alkyl naphthalene sulfonate, nekal BX, polyoxyethylene ether, EO/PO block polyether, fatty alcohol-polyoxyethylene ether sulfate, sodium alkyl phosphate, alkyl naphthalene sulfonate and alkylphenol polyoxyethylene sodium sulfate. The emulsifier is selected from dodecyl benzene sulfonate, alkyl naphthalene sulfonate, alkyl sulfonate, alkylphenol polyoxyethylene, benzyl phenol polyoxyethylene, phenethyl phenol polyoxyethylene and fatty amine polyoxyethylene. The antifreeze is selected from ethylene glycol, propylene glycol and glycerol. The thickener is selected from xanthan gum, hydroxymethyl cellulose, hydroxyethyl cellulose, hydroxypropyl starch, methyl cellulose, sodium starch phosphate, magnesium aluminum silicate and polyvinyl alcohol. The defoaming agent is selected from silicone oil, silicone compounds, tributyl phosphate, C10-C20 saturated fatty acid compounds and polyether defoaming agents. The preservative is selected from formaldehyde, phenyl salicylate, butyl p-hydroxybenzoate and potassium sorbate, the stabilizer is selected from triphenyl phosphite, epoxy chloroalkane, epoxy soybean oil and magnesium aluminum silicate, and the coloring agent is selected from azo pigment, titanium oxide and iron oxide.
Preferably, the carrier comprises a filler and/or a solvent;
preferably, the agriculturally pharmaceutically acceptable carrier includes a solid carrier and/or a liquid carrier.
Preferably, the solid support comprises natural or synthetic clays and silicates, such as natural silica and diatomaceous earth; magnesium silicates such as talc; magnesium aluminum silicates such as kaolinite, montmorillonite and mica; white carbon black, calcium carbonate, light calcium carbonate; calcium sulfate; limestone; sodium sulfate; amine salts such as ammonium sulfate, hexamethylene diamine. Liquid carriers include water and organic solvents including aromatic hydrocarbons such as trimethylbenzene, benzene, xylene, toluene, and the like; chlorinated hydrocarbons such as chlorobenzene, vinyl chloride, chloroform, dichloromethane, etc.; aliphatic hydrocarbons such as petroleum fractions, cyclohexane, light mineral oil; alcohols such as isopropanol, butanol, ethylene glycol, propylene glycol, glycerol and cyclohexanol and ethers and esters thereof; ketones such as acetone, cyclohexanone, and dimethylformamide and N-methyl-pyrrolidone.
The active ingredient may be mixed with a liquid carrier and/or a solid carrier during the formulation of the pesticidal composition (i.e. the pharmaceutical preparation), while adjuvants such as emulsifying agents, dispersing agents, stabilizing agents, wetting agents, binders, antifoaming agents, antioxidants and the like are added.
Preferably, the dosage form of the pharmaceutical preparation is soluble solution, soluble powder, soluble granule, missible oil, wettable powder, aqueous emulsion, suspending agent, dispersible oil suspending agent, water dispersible granule, microcapsule suspending agent, granule, microemulsion, suspoemulsion, microcapsule suspension-suspending agent, ultra-low volume liquid, hot fogging concentrate, film-spreading oil agent, suspended seed coating agent, seed treatment dry powder, seed treatment suspending agent, seed treatment soluble powder, seed treatment dispersible powder, seed treatment emulsion or seed treatment liquid.
Preferably, the dosage form of the pharmaceutical preparation is soluble agent, soluble granule, suspending agent, missible oil, wettable powder, aqueous emulsion, water dispersible granule, dispersible oil suspending agent, microcapsule suspending agent, ultra-low volume liquid, hot fogging concentrate, suspended seed coating agent or seed treatment dispersible powder.
In another aspect, the invention provides the application of the pharmaceutical composition or the pharmaceutical preparation containing the m-diamide compound in the prevention and treatment of plant diseases or insect pests in agriculture, forestry and horticulture.
The pharmaceutical composition or pharmaceutical preparation containing the m-diamide compound is suitable for preventing and treating various agricultural and forestry and horticultural insect pests and sanitary pests and diseases harmful to rice, corn, wheat, potatoes, fruit trees, vegetables, other crops, flowers and the like.
The composition has wide application range, and the applied plants or crops mainly comprise the following types: vegetables, cucumber, luffa, watermelon, melon, pumpkin, snake gourd, spinach, celery, cabbage, gourd, pepper, eggplant, tomato, shallot, ginger, garlic, leek, strawberry, asparagus lettuce, kidney bean, cowpea, broad bean, radish, carrot, potato, yam; cereals, wheat, barley, corn, rice, sorghum; fruit trees, apples, pears, bananas, oranges, grapes, litchis and mangoes; flowers, peony, chinese rose, huohan crane; oil crops, peanuts, soybeans, rape, sunflowers, sesame; sugar crops, sugar beets, sugar cane; other crops, such as potato, sweet potato, tobacco and tea; horticulture, forestry, home health, public health areas, and the like; the above list of plant or crop ranges has no limiting effect on the range of use of the pharmaceutical composition.
In the present invention, the pests include lepidoptera, coleoptera, hemiptera, thysanoptera, diptera, orthoptera, homoptera, isoptera, hymenoptera, spider mite pests, and the diseases include diseases caused by deuteromycetes, ascomycetes, basidiomycetes, and the like.
Preferably, the pests include, but are not limited to: cotton bollworm, plutella xylostella, asparagus caterpillar, prodenia litura, cabbage caterpillar, chilo suppressalis, tryporyza incertulas, sesamia inferens, spodoptera frugiperda, rice leaf roller, rice thrips, western thrips, melon thrips, spring thrips, ginger thrips, mango thrips, green peach aphid, cotton aphid, alfalfa aphid, apple yellow aphid, wheat aphid, flea beetle, stink bug, gray plant hopper, brown plant hopper, sogatella furcifera, termite, mosquito fly, carminespider mite and citrus red spider. The diseases include but are not limited to wheat scab, rice sheath blight, rice blast and the like.
In the present invention, the pharmaceutical composition or pharmaceutical preparation is used in the form of spray, soil treatment, seed treatment, flying prevention, and the like.
In another aspect, the invention provides the use of a pharmaceutical composition comprising a isophthalamide compound, as described above, in the seed treatment of plants, crops or flowers.
In another aspect, the present invention provides a method for controlling plant diseases and insect pests, the method comprising: applying an effective dose of the pharmaceutical composition or the pharmaceutical preparation containing the m-diamide compound to a medium needing to control plant diseases or the growth of the plant diseases.
Preferably, the effective dose is from 10 to 1000g per hectare, for example 10g, 20g, 50g, 80g, 100g, 120g, 150g, 180g, 200g, 250g, 300g, 350g, 400g, 450g, 500g, 600g, 700g, 800g, 900g or 1000g, preferably from 20 to 500g per hectare.
The composition of the present invention may be applied in the form of a formulation on the disease or its growth medium. The compounds of formula I (especially compounds of formula II) are dissolved or dispersed as active ingredients in carriers or formulated so as to be more easily dispersed when used as fungicides. For example: the chemical preparations can be prepared into soluble agents, missible oil, wettable powder, aqueous emulsion, suspending agents, dispersible oil suspending agents, water dispersible granules, seed treatment agents, microcapsule suspending agents, granules, microemulsions, suspension emulsions, suspension-microcapsule suspending agents and the like.
Compared with the prior art, the invention has the following beneficial effects:
compared with the traditional insecticide, the pharmaceutical composition has the following advantages in use:
(1) The composition of the effective component A and the effective component B has a synergistic effect, the usage amount of the composition is greatly reduced compared with that of the composition using a single active component alone, and the prevention and treatment effect is obviously improved; due to the obvious activity of the effective component A to resistant pests, the prevention and control medicine for the important crop diseases and insect pests such as resistant chilo suppressalis, diamond back moth and the like is also solved.
(2) Because of different action mechanisms of the effective component A and the effective component B, the drug resistance of the medicament can be delayed after the composition is compounded, and the composition is an effective resistance risk management tool and prolongs the life cycle of the medicament.
(3) The effective component A and the effective component B are compounded and combined, so that the prevention and control spectrum is expanded, the labor cost of the pesticide is saved, the pesticide composition can be applied to crops such as vegetables, fruit trees, flowers, cereals, oil plants, sugar materials and the like, and various plant diseases and insect pests in gardening, forestry and sanitation, and in addition, the pesticide composition has extremely high activity for emerging Spodoptera frugiperda, can be used for emergency prevention and control, and is favorable for maintaining the ecological safety of the environment and social stability.
Detailed Description
The technical solution of the present invention is further explained by the following embodiments. It should be understood by those skilled in the art that the examples are only for the understanding of the present invention and should not be construed as the specific limitation of the present invention.
Synthetic examples
Synthesis example 1
Preparation of N- [ 2-bromo-4- (1,1,1,2,3,3,3-heptafluoroprop-2-yl) -6- (trifluoromethyl) phenyl ] -3- [ N- (cyclopropylmethyl) -benzamido ] -2-fluorobenzamide (compound No. 1):
(1) Synthesis of methyl 2-fluoro- [3- (cyclopropylmethyl) amino ] benzoate
Figure BDA0003261188380000121
Methyl 2-fluoro-3-aminobenzoate (20g, 118.23mmol), bromomethylcyclopropane (20.75g, 153.70mmol), potassium carbonate (21.24g, 153.70mmol) and N, N-dimethylformamide (200 mL) were added to a reaction flask in this order, stirred under reflux for 1699 h, and heating was turned off when TLC monitoring was stopped until the reaction did not proceed any more, thus ending the reaction. After the reaction solution was cooled to room temperature, water (200 mL) was added to the reaction solution, and the mixture was extracted with ethyl acetate (100 mL), the organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and then concentrated under reduced pressure, and the residue was purified by column chromatography (eluent was petroleum ether: ethyl acetate = 10.
(2) Synthesis of methyl 2-fluoro-3- [ N- (cyclopropylmethyl) benzamido ] benzoate
Figure BDA0003261188380000122
Benzoic acid (6.67g, 53.78mmol), toluene (50 mL) and thionyl chloride (31.99g, 268.9 mmol) were added to the reaction flask in this order, reacted under reflux for 2h, toluene was concentrated under reduced pressure, and the concentrated residue was dissolved in tetrahydrofuran (30 mL) for use. Methyl 2-fluoro-3- (N-cyclopropylmethylamino) benzoate (10.00g, 44.82mmol) was dissolved in tetrahydrofuran (100 mL), pyridine (4.25g, 53.78mmol) was added, the benzoyl chloride tetrahydrofuran solution obtained in the previous step was added dropwise, and the mixture was stirred at room temperature for 4 hours. The reaction was terminated by TLC monitoring until the reaction did not proceed any more. The reaction mixture was dissolved in ethyl acetate (50 mL), and the organic layer was washed with 2M hydrochloric acid and saturated sodium bicarbonate in this order, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and the residue was purified by column chromatography (eluent: petroleum ether: ethyl acetate = 8:1) to give methyl 2-fluoro-3- (N- (cyclopropylmethyl) benzamide) benzoate (13.00 g, yield 88.70%) as a colorless liquid.
(3) Synthesis of 2-fluoro-3- [ N- (cyclopropylmethyl) benzamido ] benzoic acid
Figure BDA0003261188380000123
Methyl 2-fluoro-3- (N- (cyclopropylmethyl) benzamide) benzoate (13.00g, 40.88mmol) was dissolved in methanol (100 mL), 10% aqueous sodium hydroxide (6.54g, 163.52mmol,65.4 mL) was added, and after stirring at room temperature for 2h, the reaction was monitored by TLC for completion. After removing methanol by concentration under reduced pressure, the concentrated residue was dissolved in water (100 mL), extracted with ethyl acetate (50 mL), the organic phase was discarded, the pH of the aqueous phase was adjusted to 7 with 2M aqueous hydrochloric acid solution, extraction was continued with ethyl acetate (100 mL), the organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to give a colorless solution product, 2-fluoro-3- [ N- (cyclopropylmethyl) benzamide ] benzoic acid (12.00 g, yield 93.82%), which was left overnight to stand as a white solid.
(4) Synthesis of N- [ 2-bromo-4- (1,1,1,2,3,3,3-heptafluoroprop-2-yl) -6- (trifluoromethyl) phenyl ] -3- [ N- (cyclopropylmethyl) benzamido ] -2-fluorobenzamide
Figure BDA0003261188380000131
2-fluoro-3- (N- (cyclopropylmethyl) benzamido) benzoic acid (0.40g, 1.28mmol), toluene (6 mL), and thionyl chloride (0.75g, 6.40mmol) were added to a reaction flask in this order, and the reaction was stirred at 140 ℃ for 2 hours, concentrated under reduced pressure, and the concentrated residue was dissolved in tetrahydrofuran (3 mL) for further use.
Dissolving 2-bromo-6-trifluoromethyl-4-heptafluoroisopropylaniline (0.52g, 1.28mmol) in tetrahydrofuran (4 mL), dropwise adding lithium diisopropylamide (0.77mL, 1.54mmol) at-70 ℃, dropwise adding the tetrahydrofuran solution of the 2-fluoro-3- [ N- (cyclopropylmethyl) benzamido ] benzoyl chloride synthesized in the previous step after 5min, stirring at-70 ℃ for 30min, heating to room temperature, and continuing stirring for 30min. The reaction was terminated by TLC monitoring until the reaction did not proceed any more. Water (20 mL) was added to the reaction mixture, and the mixture was extracted with ethyl acetate (20 mL), the organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and the residue was purified by column chromatography (eluent: petroleum ether: ethyl acetate = 3:1) to give N- [ 2-bromo-4- (1,1,1,2,3,3,3-heptafluoroprop-2-yl) -6- (trifluoromethyl) phenyl ] -3- [ N- (cyclopropylmethyl) -benzamido ] -2-fluorobenzamide (0.25 g, yield 27.84%).
Process for preparation of Compound 1 1 H NMR(400MHz,CDCl 3 -d),δ[ppm]：8.15(d,J＝2.1Hz,1H),8.03(br s,2H),7.92(d,J＝2.1Hz,1H),7.55(br s,1H),7.35-7.21(m,5H),3.84(d,J＝93.6Hz,2H),1.14(br s,1H),0.59-0.40(m,2H),0.20(d,J＝42.2Hz,2H)。
Synthesis example 2
Synthesis of N- [ 2-bromo-4- (1,1,1,2,3,3,3-heptafluoroprop-2-yl) -6-trifluoromethoxyphenyl ] -3- [ N- (cyclopropylmethyl) benzamido ] -2-fluorobenzamide (Compound No. 3)
Figure BDA0003261188380000132
2-fluoro-3- (N- (cyclopropylmethyl) benzamide) benzoic acid (0.50g, 1.60mmol), toluene (6 mL), thionyl chloride (1.07g, 9.00mmol) were added to a reaction flask in this order, and the mixture was stirred under reflux for 2 hours, toluene was concentrated under reduced pressure, and the concentrated residue was dissolved in tetrahydrofuran (3 mL) for further use.
Dissolving 2-bromo-4-heptafluoroisopropyl-6-trifluoromethoxyaniline (0.68g, 1.60mmol) in tetrahydrofuran (4 mL), adding 2M lithium diisopropylamide tetrahydrofuran solution (0.96mL, 1.93mmol) dropwise at-70 deg.C, adding the tetrahydrofuran solution for the previous step dropwise after 5min, stirring at-70 deg.C for 30min, heating to room temperature, and stirring for 30min. The reaction was terminated when the reaction was no longer proceeding as monitored by Thin Layer Chromatography (TLC). Water (20 mL) was added to the reaction mixture, and extraction was performed with ethyl acetate (20 mL), the organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and the residue was purified by column chromatography (eluent was petroleum ether: ethyl acetate = 5:1) to obtain the objective product (0.24 g, yield 20.50%) as a white solid.
Process for preparation of Compound 3 1 HNMR(400MHz,CDCl 3 D) data as follows (δ [ ppm)])：8.01-7.81(m,2H),7.58–7.51(m,3H),7.35-7.21(m,6H),3.85(d,J＝64.0Hz,2H),1.20-1.13(m,1H),0.50(d,J＝7.8Hz,2H),0.20(d,J＝32.0Hz,2H).
Synthesis example 3
Preparation of N- [ 2-bromo-4- (1,1,1,2,3,3,3-heptafluoropropan-2-yl) -6- (trifluoromethyl) phenyl ] -3- [ N- (cyclopropylmethyl) -4-cyanobenzamido ] -2-fluorobenzamide (compound No. 4):
(1) Synthesis of methyl 2-fluoro-3- [ N- (cyclopropylmethyl) -4-cyanobenzamido ] benzoate
Figure BDA0003261188380000141
4-Cyanobenzoic acid (0.80g, 5.38mmol), toluene (6 mL), and thionyl chloride (3.2 g,26.9 mmol) were added to a reaction flask in this order, and the mixture was stirred under reflux for 2 hours, toluene was concentrated under reduced pressure, and the concentrated residue was dissolved in tetrahydrofuran (3 mL) for further use. Methyl 2-fluoro- [3- (cyclopropylmethyl) amino ] benzoate (1.0 g, 4.48mmol) was dissolved in tetrahydrofuran (6 mL), triethylamine (0.74g, 5.38mmol) was added thereto, a solution of 4-cyanobenzoyl chloride in tetrahydrofuran was added dropwise, and the mixture was stirred at room temperature for 4 hours. The reaction was terminated by TLC monitoring until the reaction did not proceed any more. Water (20 mL) was added to the reaction mixture, and extraction was performed with ethyl acetate (20 mL), the organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and the residue was purified by column chromatography (eluent was petroleum ether: ethyl acetate = 3:1) to give methyl 2-fluoro-3- [ N- (cyclopropylmethyl) -4-cyanobenzamide ] benzoate (1.40 g, yield 88.83%) as a colorless liquid product.
(2) Synthesis of 2-fluoro-3- [ N- (cyclopropylmethyl) -4-cyanobenzamido ] benzoic acid
Figure BDA0003261188380000142
Methyl 2-fluoro-3- [ N- (cyclopropylmethyl) -4-cyanobenzamido ] benzoate (1.40g, 3.96mmol) was dissolved in methanol (20 mL), 10% aqueous sodium hydroxide (0.63g, 15.86mmol, 6.3mL) was added, the mixture was stirred at room temperature for 2h, and the completion of the reaction was monitored by TLC. After removing methanol by concentration under reduced pressure, the concentrated residue was dissolved in water (20 mL), extracted with ethyl acetate (10 mL), the organic phase was discarded, the pH of the aqueous phase was adjusted to 7 with 2M aqueous hydrochloric acid solution, and further extracted with ethyl acetate (10 mL), and the organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to give 2-fluoro-3- [ N- (cyclopropylmethyl) -4-cyanobenzoylamino ] benzoic acid (1.30 g, yield 96.79%) as a white solid.
(3) Synthesis of N- [ 2-bromo-4- (1,1,1,2,3,3,3-heptafluoropropan-2-yl) -6- (trifluoromethyl) phenyl ] -3- [ N- (cyclopropylmethyl) -4-cyanobenzamido ] -2-fluorobenzamide:
Figure BDA0003261188380000143
2-fluoro-3- [ N- (cyclopropylmethyl) -4-cyanobenzamide ] benzoic acid (0.75g, 2.22mmol), toluene (6 mL) and thionyl chloride (1.31g, 11.10 mmol) were added to a reaction flask in this order, and the reaction was stirred under reflux for 2 hours, concentrated under reduced pressure, and the concentrated residue was dissolved in tetrahydrofuran (3 mL) for further use.
Dissolving 2-bromo-6-trifluoromethyl-4-heptafluoroisopropylaniline (0.90g, 2.22mmol) in tetrahydrofuran (4 mL), dropwise adding lithium diisopropylamide (1.30mL, 2.66mmol) at-70 ℃, dropwise adding the 2-fluoro-3- [ N- (cyclopropylmethyl) -4-cyanobenzamide ] benzoyl chloride tetrahydrofuran solution prepared in the previous step after 5min, stirring at-70 ℃ for 30min, heating to room temperature, and continuing to stir for 30min. The reaction was terminated by TLC monitoring until the reaction did not proceed any more. To the reaction mixture was added a saturated aqueous ammonium chloride solution (20 mL), extracted with ethyl acetate (20 mL), the organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and the residue was purified by column chromatography (eluent was petroleum ether: ethyl acetate = 3:1) to give N- [ 2-bromo-4- (1,1,1,2,3,3,3-heptafluoropropan-2-yl) -6- (trifluoromethyl) phenyl ] -3- [ N- (cyclopropylmethyl) -4-cyanobenzamido ] -2-fluorobenzamide (0.24 g, yield 14.91%).
Process for preparation of Compound 4 1 H NMR(400MHz,CDCl 3 -d),δ[ppm]：8.14(d,J＝2.0Hz,1H),8.12-7.94(m,2H),7.91(t,J＝1.4Hz,1H),7.58-7.39(m,4H),7.32(t,J＝7.9Hz,1H),3.81(dd,J＝76.0,18.8Hz,2H),1.11(br s,1H),0.5(br s,2H),0.20(d,J＝36.7Hz,2H)。
Synthesis example 4
Preparation of N- [ 2-bromo-4- (1,1,1,2,3,3,3-heptafluoropropan-2-yl) -6- (trifluoromethyl) phenyl ] -3- [ N- (cyclopropylmethyl) -4- (trifluoromethyl) benzamido ] -2-fluorobenzamide (compound No. 7):
Figure BDA0003261188380000151
(1) 2-fluoro-3- [ N- (cyclopropylmethyl) -4-trifluoromethylbenzamide ] benzoic acid (0.45g, 1.12mmol), toluene (6 mL), and thionyl chloride (0.67g, 5.60mmol) were added to a reaction flask in this order, and the mixture was stirred under reflux for 2 hours, toluene was concentrated under reduced pressure, and the concentrated residue was dissolved in tetrahydrofuran (3 mL) for further use.
(2) Dissolving 2-bromo-6-trifluoromethyl-4-heptafluoroisopropylaniline (0.46g, 1.12mmol) in tetrahydrofuran (4 mL), dropwise adding lithium diisopropylamide (0.70mL, 1.42mmol) at-70 ℃, dropwise adding the tetrahydrofuran solution for later use in the previous step after 5min, stirring at-70 ℃ for 30min, heating to room temperature, and continuously stirring for 30min. The reaction was terminated by TLC monitoring until the reaction did not proceed any more. Water (20 mL) was added to the reaction solution, and extraction was performed with ethyl acetate (20 mL), the organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and the residue was purified by column chromatography (eluent was petroleum ether: ethyl acetate = 3:1) to obtain the objective product (0.11 g, yield 13.75%).
Process for preparation of Compound 7 1 H NMR(400MHz,CDCl 3 -d)δ[ppm]：8.21-7.79(m,4H),7.66-7.28(m,5H),3.85(d,J＝104.7Hz,2H),1.12(br s,1H),0.51(br s,2H),0.20(d,J＝42.7Hz,1H)。
Synthesis example 5
Preparation of N- [ 2-bromo-4- (1,1,1,2,3,3,3-heptafluoroprop-2-yl) -6- (trifluoromethyl) phenyl ] -3- [ N- (cyclopropylmethyl) -4-fluorobenzamido ] -2-fluorobenzamide (compound No. 8) by the following method:
Figure BDA0003261188380000152
2-fluoro-3- [ N- (cyclopropylmethyl) -4-fluoro-benzamide ] benzoic acid (2.20g, 6.67mmol), toluene (20 mL), thionyl chloride (3.97g, 33.35mmol) were added to a reaction flask in this order, and the mixture was stirred under reflux for 2 hours and concentrated under reduced pressure to give 2-fluoro-3- [ N- (cyclopropylmethyl) -4-fluorobenzamide ] benzoyl chloride. 2-bromo-6-trifluoromethyl-4-heptafluoroisopropylaniline (3.26g, 7.99mmol), N-diisopropylethylamine (1.72g, 13.30mmol) and 4-N, N-dimethylaminopyridine (0.33g, 2.69mmol) were added to 2-fluoro-3- [ N- (cyclopropylmethyl) -4-fluorobenzamide ] benzoyl chloride, respectively, and the mixture was stirred at 120 ℃ for 2 hours, after which time heating was stopped. Water (20 mL) was added to the reaction mixture, and the mixture was extracted with ethyl acetate (20 mL), the organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and the residue was purified by column chromatography (eluent: PE: EA = 3:1) to obtain the objective product (1.80 g, yield 37.5%).
Process for preparation of Compound 8 1 H NMR(400MHz,DMSO-d 6 )δ[ppm]：10.56(s,1H),8.41(s,1H),7.95(s,1H),7.70-7.56(m,2H),7.38-7.32(m,3H),7.09(br s,2H),3.69(br s,2H),1.03-1.01(m,1H),0.41-0.39(m,2H),0.08-0.06(m,2H)。
Synthesis example 6
Preparation of N- [ 2-bromo-4- (1,1,1,2,3,3,3-heptafluoroprop-2-yl) -6- (trifluoromethyl) phenyl ] -3- [ N- (cyclopropylmethyl) -4-chlorobenzamido ] -2-fluorobenzamide (Compound No. 10) by the following method:
Figure BDA0003261188380000161
(1) 2-fluoro-3- [ N- (cyclopropylmethyl) -4-chlorobenzamide ] benzoic acid (0.60g, 1.76mmol), toluene (6 mL), thionyl chloride (1.04g, 8.80mmol) were added to a reaction flask in this order, and the reaction was stirred under reflux for 2 hours, toluene was concentrated under reduced pressure, and the concentrated residue was dissolved in tetrahydrofuran (3 mL) for further use.
(2) Dissolving 2-bromo-6-trifluoromethyl-4-heptafluoroisopropyl aniline (0.72g, 1.76mmol) in tetrahydrofuran (4 mL), dropwise adding lithium diisopropylamide (1.05mL, 2.11mmol) at-70 ℃, dropwise adding the tetrahydrofuran solution for later use in the previous step after 5min, stirring at-70 ℃ for 30min, heating to room temperature, and continuing stirring for 30min. The reaction was terminated by TLC monitoring until the reaction did not proceed any more. Water (20 mL) was added to the reaction mixture, and extraction was performed with ethyl acetate (20 mL), and the organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and the residue was purified by column chromatography (eluent was petroleum ether: ethyl acetate = 3:1) to obtain the objective product (0.15 g, yield 11.63%).
Process for preparation of Compound 10 1 H NMR(400MHz,CDCl 3 -d)δ[ppm]：8.18-7.84(m,4H),7.53(t,J＝7.7Hz,1H),7.37-7.07(m,4H),3.81(d,J＝85.0Hz,2H),1.11(br s,1H),0.49(br s,2H),0.17(d,J＝32.1Hz,2H)。
Synthesis example 7
Preparation of N- [ 2-bromo-4- (1,1,1,2,3,3,3-heptafluoroprop-2-yl) -6- (trifluoromethyl) phenyl ] -3- [ N- (1-cyclopropyl-ethyl) -benzamido ] -2-fluorobenzamide (compound No. 2) as follows:
Figure BDA0003261188380000162
(1) Synthesis of methyl 3- [ N- (1-cyclopropylethyl) amino ] -2-fluorobenzoate
Methyl 2-fluoro-3-aminobenzoate (2.00g, 11.82mmol) was dissolved in 1,2-dichloroethane (65 mL), cyclopropylmethyl ketone (2.98g, 35.47mmol), trifluoroacetic acid (8.08g, 70.92mmol) and sodium triacetoxyborohydride (7.51g, 35.47mmol) were added sequentially at room temperature, and the reaction was heated to 45 ℃ for 1h. TLC monitoring till reaction is not performedWhen the reaction is further carried out, the reaction is terminated. Saturated NaHCO was added to the reaction solution 3 The solution (50 mL) was extracted with dichloromethane (80 mL), the organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure, and the residue was purified by column chromatography (eluent was petroleum ether: ethyl acetate = 10) to obtain the objective product (1.50 g, yield 53.5%) as a colorless oil.
(2) Synthesis of methyl 3- [ N- (1-cyclopropyl) ethyl) benzamido ] -2-fluorobenzoate
Benzoic acid (1.54g, 12.64mmol), toluene (15 mL) and thionyl chloride (6.27g, 52.68mmol) were added to a reaction flask in this order, the reaction was stirred under reflux for 2h, toluene was concentrated under reduced pressure, and the concentrated residue was dissolved in tetrahydrofuran (5 mL) for use.
Methyl 3- [ N- (1-cyclopropyl) ethyl) amino ] -2-fluorobenzoate (2.50g, 10.54mmol) was dissolved in tetrahydrofuran (15 mL), triethylamine (1.60g, 15.80mmol) and a tetrahydrofuran solution of the acid chloride prepared in the previous step were sequentially added, and the reaction was stirred at 80 ℃ for 6h. The reaction was terminated by TLC monitoring until the reaction did not proceed any more. Water (50 mL) was added to the reaction solution, and extraction was performed with ethyl acetate (60 mL), and the organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and the residue was purified by column chromatography (eluent was petroleum ether: ethyl acetate = 10) to obtain the objective product (1.03 g, yield 28.6%) as a yellow solid.
(3) 3- [ N- (1-cyclopropyl) ethyl) benzamido ] -2-fluorobenzoic acid
Methyl 3- [ (1-cyclopropyl-ethyl) benzamido ] -2-fluorobenzoate (1.00g, 2.93mmol) was dissolved in methanol (10 mL), 10% aqueous sodium hydroxide (0.46g, 11.72mmol,4.6 mL) was added, the mixture was stirred at room temperature for 2h, and the completion of the reaction was monitored by TLC. After removing methanol by concentration under reduced pressure, the concentrated residue was dissolved in water (20 mL), extracted with ethyl acetate (10 mL), the organic phase was discarded, the pH of the aqueous phase was adjusted to 3 with 2M aqueous hydrochloric acid solution, extraction was continued with ethyl acetate (10 mL), the organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain the objective product (0.60 g, yield 62.6%).
(4) Synthesis of N- [ 2-bromo-4- (1,1,1,2,3,3,3-heptafluoroprop-2-yl) -6- (trifluoromethyl) phenyl ] -3- [ N- (1-cyclopropyl-ethyl) benzamido ] -2-fluorobenzamide
To a reaction flask were added 3- (N- (1-cyclopropyl) -ethyl) benzamido) -2-fluorobenzoic acid (0.60g, 1.83mmol), toluene (6 mL) and thionyl chloride (1.09g, 9.16mmol) in this order, and the reaction was stirred at 140 ℃ for 2h, the toluene was concentrated under reduced pressure, and the concentrated residue was dissolved in tetrahydrofuran (2 mL) for further use.
Dissolving 2-bromo-6-trifluoromethyl-4-heptafluoroisopropyl aniline (0.75g, 1.83mmol) in tetrahydrofuran (6 mL), dropwise adding lithium diisopropylamide (1.10 mL,2.20 mmol) at-70 ℃, dropwise adding the tetrahydrofuran solution to be used in the previous step after 5min, stirring at-70 ℃ for 30min, heating to room temperature, and continuously stirring for 30min. The reaction was terminated by TLC monitoring until the reaction did not proceed any more. Water (20 mL) was added to the reaction mixture, and extraction was performed with ethyl acetate (20 mL), the organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and the residue was purified by column chromatography (eluent was petroleum ether: ethyl acetate = 5:1) to obtain the objective product (0.23 g, yield 17.5%) as a yellow solid.
Process for preparation of Compound 2 1 H NMR(400MHz,CDCl 3 -d),δ[ppm]：8.19(s,1H),8.05-7.95(m,1H),7.89(s,1H),7.77-7.73(m,1H),7.56-7.52(m,1H),7.28-7.11(m,6H),4.26-4.23(m,1H),1.63(br s,2H),1.51(br s,1H),0.89–0.40(m,5H)。
In addition to the above-described compounds, some of the compounds in Table 1 were prepared by a similar method as in Synthesis examples 1 to 7, and nuclear magnetic data of some of the compounds synthesized by reference to Synthesis examples 1 to 7 are given in Table 4 below.
TABLE 4
Figure BDA0003261188380000171
Other compounds of formula I of the present invention may be synthesized by reference to the methods described above.
Formulation examples
The following examples are provided to illustrate the composition ratios and preparation of the present invention:
formulation example 1:10% compound 8. Hexaflumuron emulsifiable concentrate
The composition of the 10% compound 8. Hexaflumuron emulsion is shown in table 5 below:
TABLE 5
Name (R) Plectranthus (W/W,%) Remarks for note
Compound 8 5 Active ingredient A
Hexaflumuron 5 An active ingredient B
Calcium dodecyl benzene sulfonate 8 Emulsifier
Polyoxyethylene castor oil ether 8 Emulsifier
No. 200 solvent oil Complement 100 Solvent(s)
The preparation method comprises the following steps: calculating the material amount according to the formula, adding 200 # solvent oil into a blending kettle, adding the compound 8 and hexaflumuron into the kettle for complete dissolution, adding the calcium dodecyl benzene sulfonate and the castor oil polyoxyethylene ether, stirring for 1.5 hours at 40-50 ℃, filtering, and recording to obtain 10% of compound 8-hexaflumuron emulsifiable oil.
Formulation example 2:25% compound 4-carbosulfan suspension seed coating agent
The composition of the 25% compound 4 carbosulfan suspension seed coating is shown in table 6 below:
TABLE 6
Figure BDA0003261188380000181
The preparation method comprises the following steps: adding deionized water, the compound 4, carbosulfan, FS3000, TER4894, kasons, SAG1522 and propylene glycol into a batching kettle according to the material proportion, shearing, sanding, controlling the particle size to be about 905 micrometers, transferring into a blending kettle, adding a 2% xanthan gum solution and a pigment F2R, mixing and stirring for 1 hour to obtain the 25% compound 4. Carbosulfan.
Formulation example 3:35% of compound 6 tebufenozide water dispersible granule
The composition of 35% compound 6 tebufenozide water dispersible granules is shown in the following table 7:
TABLE 7
Figure BDA0003261188380000182
Figure BDA0003261188380000191
The preparation method comprises the following steps: calculating the amount of each material according to the formula, uniformly mixing the compound 6, the tebufenozide, the sodium dodecyl sulfate, the sodium lignosulfonate, the sodium naphthalene formaldehyde polymer sulfonate, the ammonium sulfate, the corn starch and the kaolin, crushing the mixture to an average particle size of 10-15 microns by using an airflow crusher, adding water accounting for 17% of the powder amount, kneading the mixture, performing rotary extrusion granulation, drying the mixture for 3 hours at 50 ℃, and screening the mixture to obtain the 35% compound 6 tebufenozide water dispersible granule.
Formulation example 4:15% of compound 8-ethofenprox suspending agent
The composition of the 15% compound 8-ethofenprox suspension is shown in table 8 below:
TABLE 8
Name (R) Pleated (W/W,%) Remarks for note
Compound 8 10 Active ingredient A
Ether chrysanthester 5 An active ingredient B
Fatty alcohol polyoxyethylene ether 1.5 Wetting agent
Tristyrylphenol polyoxyethylene ether phosphate ester 2 Dispersing agent
Lignosulfonic acid sodium salt 3 Dispersing agent
Propylene glycol 4 Antifreezing agent
1% xanthan gum solution 10 Thickening agent
Kathon 0.1 Preservative agent
Polydimethylsiloxane 0.2 Organic silicon defoaming agent
Deionized water Complement 100 Carrier
The preparation method comprises the following steps: calculating the amount of each material according to the formula, uniformly stirring and dissolving deionized water, propylene glycol, tristyrylphenol polyoxyethylene ether phosphate, sodium lignosulphonate, kathon and a defoaming agent, adding ethofenprox and the compound 8, uniformly shearing, grinding by a sand mill until the average particle size is 2 microns, adding 10 parts of 1% xanthan gum solution, and stirring for 30 minutes to obtain the 15% compound 8-ethofenprox suspending agent.
Formulation example 5:5% compound 10-efficient cyhalothrin microcapsule suspending agent
The composition of the 5% compound 10. Lambda-cyhalothrin microcapsule suspension is shown in table 9 below:
TABLE 9
Figure BDA0003261188380000192
Figure BDA0003261188380000201
The preparation method comprises the following steps: calculating the material amount according to the formula, and uniformly dissolving the compound 10, the efficient cyhalothrin, the polyarylpolymethylene polyisocyanate and the trimethylbenzene at 40-50 ℃ to be used as an A phase; dissolving deionized water, D-800 and propylene glycol uniformly to obtain phase B; slowly adding the phase A into the phase B under high shear, shearing to an average particle size of 2-3 microns, then adding the materials into a three-neck flask, adding hexamethylene diamine, stirring and reacting for 10 hours at 50-60 ℃, adding tristyrylphenol polyoxyethylene ether phosphate, carbazone, a defoaming agent and 1% xanthan gum solution, and stirring for 1 hour to obtain a 5% compound 10-efficient cyhalothrin microcapsule suspending agent.
Formulation example 6:25% compound 6-pirimicarb wettable powder
The composition of 25% compound 6-pirimicarb wettable powder is shown in table 10 below:
TABLE 10
Name(s) Pleated (W/W,%) Remarks for note
Compound 6 5 Active ingredient A
Pirimicarb 20 An active ingredient B
Sodium dodecyl sulfate 1.5 Wetting agent
Lignosulfonic acid sodium salt 6 Dispersing agent
Kaolin clay Complement 100 Carrier
The preparation method comprises the following steps: calculating the material amount according to the formula, adding the compound 6, the pirimicarb, the sodium dodecyl sulfate, the sodium lignosulfonate and the kaolin into a material preparation kettle, uniformly mixing, and crushing to obtain 25% compound 6-pirimicarb wettable powder with the average particle size of 10 microns by using a jet mill.
Formulation example 7:50% Compound 7 monosultap dispersible agent
The composition of the 15% compound 7-monosultap dispersible formulation is shown in table 11 below:
TABLE 11
Name (R) Pleated (W/W,%) Remarks to note
Compound 5 5 Active ingredient A
Monosultap 10 An active ingredient B
No. 100 solvent oil 15 Solvent(s)
Cyclohexanone 10 Solvent(s)
Castor oil polyoxyethylene ether (EL 40) 5 Dispersing agent
Fatty alcohol polyoxyethylene ether 10 Wetting agent
Polydimethylsiloxane emulsion (SAG 1522) 0.2 Defoaming agent
Deionized water Complement 100 Carrier
The preparation method comprises the following steps: adding No. 100 solvent oil and cyclohexanone into a batching kettle according to a process proportion, adding the compound 7 and the fluxapyroxamide under stirring, heating to 50 ℃ to completely dissolve the solvent, adding EL40, fatty alcohol-polyoxyethylene ether and SAG1522, continuing stirring for 10 minutes, cooling, and adding deionized water to obtain the 15% compound 7-monosultap dispersible agent.
Formulation embodiment agent 8:18% compound 1-chlorpyrifos aqueous emulsion
The composition of the 18% compound 1 chlorpyrifos emulsion in water is shown in table 12 below:
TABLE 12
Name (R) Plectranthus (W/W,%) Remarks for note
Compound 1 8 Active ingredient A
Chlorpyrifos 10 An active ingredient B
No. 150 solvent oil 15 Cosolvent
TERMUL5030 5.0 Emulsifying agent
Propylene glycol 5.0 Antifreezing agent
SAG1572 0.2 Defoaming agent
Deionized water Complement 100 Continuous phase
The preparation method comprises the following steps: adding No. 150 solvent oil into a batching kettle, starting stirring, adding the compound 1, stirring for dissolving, adding chlorpyrifos and an emulsifier TERMUL5030 after complete dissolution, continuing stirring for 20 minutes, and uniformly mixing to obtain an oil phase for later use; adding deionized water, a defoaming agent and an antifreezing agent into a shearing kettle, starting a shearing device, slowly adding an oil phase material after 5 minutes, and shearing for 10 minutes after the addition to obtain the 18% compound 1-chlorpyrifos aqueous emulsion.
Bioassay examples
The following examples are intended to illustrate some of the practice of the present invention and the present invention is not limited to the following examples.
Bioassay example 1:the active ingredient A is a compound shown as a formula II and has obvious insecticidal activity on various pests
Target: the 3 rd larva of diamondback moth, the 3 rd larva of armyworm and the 3 rd larva of chilo suppressalis are all raised indoors.
The method comprises the following steps: diamondback moth soaking She Siwei method, armyworm soaking leaf feeding method, chilo suppressalis soaking method and rice stem soaking method.
Diamondback moth + immersion She Siwei. With reference to NY/1154.14-2008, the main operations are described as follows: soaking clean bracteatum leaf dishes in the liquid medicine for 10s, airing, placing in culture dishes with 4 dishes in each dish, and placing filter paper in the culture dishes for moisture preservation. Each dish was inoculated with 10 plutella xylostella test insects, and the procedure was repeated 3 times. The cells were placed in a light incubator at 25 ℃ under 10hD light 14hL for cultivation. And (5) investigating the number of dead and live plutella xylostella insects 3 days after the application of the composition, and calculating the mortality.
Feeding method with armyworm and soaked leaves. With reference to NY/1154.14-2008, the main operations are described as follows: putting cleaned corn leaves Duan Jin into the liquid medicine for 10s, airing, placing in culture dishes with 4 pieces per dish, and placing filter paper in the culture dishes for moisture preservation. Each dish was inoculated with 10 test insects of armyworm, and the procedure was repeated 3 times. The cells were placed in a light incubator at 25 ℃ and 10hD under light 14hL. The number of dead and live armyworms of armyworms is investigated 3 days after the drug administration, and the death rate is calculated.
Chilo suppressalis and rice stem soaking method. Referring to NY/T1154.11-2008, the main operations are as follows: soaking clean rice stem in the medicinal liquid for 10s, taking out, air drying in shade, placing into finger tube, inoculating 10 Chilo suppressalis larva of 3 years old, repeating the treatment for 3 times, sealing the tube with cotton black cloth, tightening with rubber band, and culturing in light incubator at 28 deg.C in dark. The number of dead and live chilo suppressalis insects is investigated 3 days after the drug administration, and the mortality rate of each drug treatment is calculated.
The results are shown in Table 13, and it can be seen from the results that the compounds 1-14 have excellent insecticidal activity against diamond back moth, armyworm and chilo suppressalis, and the mortality rate is 100% under the dosage of 1mg/L of diamond back moth, 0.4mg/L of armyworm and 10mg/L of chilo suppressalis.
TABLE 13 indoor insecticidal Activity of Compounds 1-14 against Plutella xylostella, armyworm, chilo suppressalis
Figure BDA0003261188380000211
Figure BDA0003261188380000221
Bioassay example 2:the active ingredient A is a compound of a formula II and the active ingredient B is a composition of chlorpyrifos, acephate, phoxim, dichlorvos, fenitrothion, profenofos, triazophos and the like, and the activity test on armyworms is carried out
Target: armyworm, 3 rd instar larva
The method comprises the following steps: and (4) an insect soaking method. The operation is described as follows: with reference to NY/1154.6-2006, the main operations are described as follows: soaking 10 test insects into the liquid medicine for 10s, airing, placing into culture dishes, placing 4 clean corn leaf segments into each dish, and placing filter paper in each culture dish for moisture preservation. 3 replicates. The cells were placed in a light incubator at 25 ℃ under 10hD light 14hL for cultivation. The number of dead and live armyworms of armyworms is investigated 3 days after the drug administration, and the death rate is calculated.
The evaluation methods and criteria were as follows:
synergistic effect = actual mortality-theoretical mortality%
Theoretical mortality = 1-the mortality of 1-active ingredient a at that dose (1-the mortality of active ingredient B at that dose)
The synergistic effect is more than or equal to 20, and the obvious synergistic effect is shown; the synergistic effect is more than or equal to 10 and less than 20, which represents the synergy; -10. Ltoreq. Synergistic effects < 10, indicating addition; the synergistic effect is less than-10, which represents antagonism, and the larger the negative value is, the greater the antagonism degree is.
The results are shown in table 14, and it can be seen from the results that the compounds 3, 5, 8 and 10 have excellent activity against armyworm, chlorpyrifos, acephate, phoxim, dichlorvos, fenitrothion, profenofos and triazophos have good activity against armyworm, and the combined action shows synergy or significant synergy after the two are combined.
TABLE 14 indoor pesticidal Activity of test Agents against armyworms
Figure BDA0003261188380000222
Figure BDA0003261188380000231
Bioassay example 3:the active ingredient A is a compound shown in the formula II and the active ingredient B is a composition of pesticides such as efficient cyhalothrin, deltamethrin, cypermethrin, bifenthrin, ethofenprox, fenpropathrin and the like, and the composition is used for testing the activity of the alfalfa aphids
Target: and (4) feeding the 3-day-old myzus persicae indoors.
The method comprises the following steps: and (3) an immersion method. The operation is described as follows: culturing the broad bean seedlings indoors for aphids to eat. If aphid preparation: 5 aphids are inoculated to each broad bean leaf, the adult aphids are removed after 24 hours, and if the aphids are larger than 15 leaves before the test, the leaves are selected for the test. The treatment method comprises the following steps: the leaves (with Nepeta aphid) were immersed in the solution for 10s,3 times. Culturing and investigating after treatment: the cells were placed in a light incubator at 25 ℃ under 10hD light 14hL for cultivation. The number of dead and alive aphids is investigated 3 days after the pesticide is applied, and the death rate is calculated.
Evaluation method in the same manner as in production example 2.
The results are shown in table 15, and it can be seen from the results that compounds 6, 8 and 11 have excellent activity on aphis medicaginis, and cyhalothrin, deltamethrin, cypermethrin, bifenthrin, ethofenprox and fenpropathrin have good activity on aphis medicaginis, and after the two are combined, the combined action shows synergy or significant synergy.
TABLE 15 indoor insecticidal Activity of test Agents against Medicago sativa aphid
Test agent or combination name Dosage mg/L 3d mortality% Theoretical mortality% Synergistic effect Mode of combined action
Compound 6 10 57.77 / / /
Compound 8 10 60.87 / / /
Compound 11 10 53.33 / / /
Efficient cyhalothrin 0.4 51.11 / / /
Deltamethrin 0.1 46.67 / / /
Cypermethrin 2.0 55.56 / / /
Biphenthrin 2.0 60.00 / / /
Fenpropathrin 4.0 57.77 / / /
Ether chrysanthester 5.0 62.22 / / /
Compound 8+ lambda-cyhalothrin 10+0.4 100 80.87 19.13 Efficiency enhancement
Compound 6+ deltamethrin 10+0.1 100 77.48 22.52 Significant synergy
Compound 6+ cypermethrin 10+2.0 100 81.23 18.77 Efficiency enhancement
Compound 8+ bifenthrin 10+2.0 100 84.35 15.65 Efficiency enhancement
Compound 11+ fenpropathrin 10+4.0 100 80.29 19.71 Efficiency enhancement
Compound 11+ Ethofenprox 10+5.0 100 82.37 17.63 Efficiency enhancement
Bioassay example 4:the active ingredient A is a compound of a formula II and the active ingredient B is a composition of isoprocarb, methomyl, carbosulfan, pirimicarb and the like, and the composition can be used for testing the activity of brown planthopper
Target: brown planthopper, 3-year-old nymph.
The method comprises the following steps: soaking rice seedling. Refer to NY/T1154.11-2008.
The method operation is described as follows: preparation of the medicament: according to the proportion and dosage of experimental design, a certain amount of original drug is weighed, dissolved by N, N-Dimethylformamide (DMF), and then 0.05% of Tween 80 water is added to prepare mother liquor with a certain concentration. 5-7 doses are set in each proportion, and the mother liquor is sequentially diluted to the test dose according to the test design. Medicament treatment: soaking rice seedlings in the liquid medicine for 10s, then placing the rice seedlings into disposable cups, inoculating 15 insects to each cup, sealing the cups by using a preservative film, and treating 45 test insects each time. During medicine soaking, the same medicines are sequentially soaked from low concentration to high concentration, and a blank control and a solvent control are arranged. After the treatment is finished, the culture medium is placed in a light incubator, the temperature is 28 +/-1 ℃, and the light-dark ratio is 15h. And (4) investigating a result: the number of dead and live insects was investigated 3d after the administration. And (5) counting the mortality.
Evaluation method example 2 was evaluated in the same manner as the standard.
As shown in table 16, it can be seen from the results that compounds 1,2, 4 and 8 have excellent activity against brown planthopper, and isoprocarb, methomyl, carbosulfan and pirimicarb have good activity against brown planthopper, and the combined action of the two shows synergy.
TABLE 16 indoor insecticidal Activity of test Agents against Nilaparvata lugens
Test agent or combination name Dosage mg/L 3d mortality% Theoretical mortality% Synergistic effect Mode of combined action
Compound 1 10 60.00 / / /
Compound 2 10 51.11 / / /
Compound 4 6 55.55 / / /
Compound 8 10 71.11 / / /
Isoprocarb 40 53.33 / / /
Pirimicarb 20 73.33 / / /
Methomyl 10 57.77 / / /
Carbosulfan 5 64.44 / / /
Compound 1+ isoprocarb 10+40 100 81.33 18.67 Efficiency enhancement
Compound 2+ pirimicarb 10+20 100 89.96 13.04 Efficiency enhancement
Compound 4+ methomyl 6+10 100 87.80 18.77 Efficiency enhancement
Chemical combinationSubstance 8+ carbosulfan 10+5 100 89.73 10.27 Efficiency enhancement
Bioassay example 5:the active ingredient A is a compound of a formula II and the active ingredient B is a composition of monosultap, dimehypo, thiocyclam, cartap and the like, and the composition is used for testing the activity of rice stem borers
Target: and (4) feeding chilo suppressalis 3-instar larvae indoors.
The method comprises the following steps: soaking rice stem. The procedure of example 1 was followed, and the evaluation method of example 2 was followed.
The results are shown in table 17, and it can be seen from the results that the compounds 4, 5, 7, 8, 9, 10, 11, 12 and 13 have excellent activity on chilo suppressalis, monosultap, bisultap, thiocyclam and cartap have good activity on chilo suppressalis, and after the two are combined, the combined action shows synergy or significant synergy.
TABLE 17 indoor insecticidal Activity of test Agents against Chilo suppressalis
Figure BDA0003261188380000241
Figure BDA0003261188380000251
Bioassay example 6:testing the activity of armyworm when the effective component A is a compound of a formula II and the effective component B is diflubenzuron, hexaflumuron and tebufenozide
Target: armyworm, 3 rd instar larva
The method comprises the following steps: immersion She Siwei method. The procedure is as described in test example 1. Evaluation method in the same manner as in production example 2.
The results are shown in table 18, and it can be seen from the results that compounds 3 and 5 have excellent activity against armyworm, diflubenzuron, hexaflumuron and tebufenozide have good activity against armyworm, and the combined effect shows synergy or significant synergy after the two are combined.
TABLE 18 indoor insecticidal Activity of test Agents against armyworms
Test agent or combination name Dosage mg/L 3d mortality% Theoretical mortality% Synergistic effect Mode of combined action
Compound 3 0.04 60.00 / / /
Compound 5 0.04 73.33 / / /
Diflubenzuron 2.0 46.67 / / /
Hexaflumuron 0.8 50.00 / / /
Tebufenozide 1.2 60.00 / / /
Compound 3+ diflubenzuron 0.04+2.0 100 78.67 21.33 Significant synergy
Compound 3+ hexaflumuron 0.04+0.8 100 80.00 20.00 Significant synergy
Compound 5+ tebufenozide 0.04+1.0 100 89.33 10.67 Efficiency enhancement
Bioassay example 7:activity test of compound 4 and monosultap composition on chilo suppressalis
An insect source: and (4) feeding chilo suppressalis 3-instar larvae indoors.
The method comprises the following steps: rice stem dipping method, the operation is described in the same manner as in growth example 1. The evaluation method refers to NY/T1154.7-2006, and carries out evaluation by adopting a co-toxicity coefficient.
The co-toxicity coefficient (CTC value) of the mixture is calculated according to the formula (1), the formula (2) and the formula (3):
Figure BDA0003261188380000261
in the formula: ATI-actual virulence index of the mixture;
S-LC of Standard drug 50 In milligrams per liter (mg/L);
M-LC of test Agents 50 In milligrams per liter (mg/L).
TTI＝A×P A +B×P B ························(2)
In the formula: TTI-theoretical virulence index of the mixture;
A-A agent actual virulence index;
P A -the percentage of agent a in the mixture in percent (%);
b-actual virulence index of agent B;
P B the percentage of the agent B in the mixture is given in percentage (%).
Figure BDA0003261188380000262
In the formula: CTC-co-toxicity coefficient; ATI-actual virulence index of the mixture; TTI-theoretical virulence index of the mixture.
The co-toxicity coefficient (CTC) is more than or equal to 120 and shows a synergistic effect; CTC is less than or equal to 80 and shows antagonism; 80 < CTC < 120 showed additive effects.
The results are shown in table 19, and it can be seen from the results that both compound 4 and monosultap have excellent activity against chilo suppressalis; the compound 4 and the monosultap are compounded, the cotoxicity coefficient is 94.75-566.62 when the mixture ratio is 200-1, and the additive or synergistic effect is shown; the ratio is 100.
TABLE 19 Co-toxicity coefficient of combination of Compound 4 and monosultap against Chilo suppressalis
Figure BDA0003261188380000263
Bioassay example 8:activity test of compound 8 and chlorpyrifos composition on chilo suppressalis
Insect sources: and (4) feeding chilo suppressalis 3-instar larvae indoors.
The method comprises the following steps: stem dipping method, description of operation with growth test example 1, evaluation method with growth test example 7.
The results are shown in table 20, and it can be seen from the results that both compound 8 and chlorpyrifos have better activity on chilo suppressalis; the compound 8 and the chlorpyrifos are compounded, the co-toxicity coefficient is 98.44-230.46 when the mixture ratio is 150-1, and the co-toxicity coefficient is shown as addition or synergy; when the mixture ratio is 100.
TABLE 20 Co-toxicity coefficient of combination of Compound 8 and Chlorpyrifos against Chilo suppressalis
Figure BDA0003261188380000271
Bioassay example 9:activity test of combination of compound 7 and isoprocarb against Nilaparvata lugens
Target: brown planthopper, 3-year-old nymph.
The method comprises the following steps: soaking rice seedling. Operation descriptions are given in the same test example 4 and evaluation method in the same test example 7.
The results are shown in table 21, from which it can be seen that compound 7 and isoprocarb have better activity against brown planthopper; the compound 7 is compounded with isoprocarb, the cotoxicity coefficient of 160-1-160 is 103.40-242.04, and shows additive or synergistic effect, and when the mixture ratio is 80.
TABLE 21 Co-toxicity factor against Nilaparvata lugens for the combination of Compound 7 and isoprocarb
Figure BDA0003261188380000272
Figure BDA0003261188380000281
Bioassay example 10:activity test of a combination of Compound 1 and diflubenzuron against Plutella xylostella
Insect sources: and breeding 3-instar larvae of the plutella xylostella indoors.
The method comprises the following steps: immersion She Siwei method. Description of the operation the in-situ test example 1 and the statistical evaluation in-situ test example 7 were carried out.
The results are shown in Table 22, and it can be seen from the results that
The compound 1 and the diflubenzuron have good activity on diamond back moths; the compound 1 and the diflubenzuron are compounded, the cotoxicity coefficient of 160 is 102.51-251.14 according to the proportion of 160-1, and the additive or synergistic effect is shown; the co-toxicity coefficients are all larger than 120 when the mixture ratio is 80.
TABLE 22 Co-toxicity factor against diamondback moth of the combination of Compound 1 and diflubenzuron
Figure BDA0003261188380000282
Bioassay example 11:compound 7 and lambda-cyhalothrinThe composition of (A) is tested for its activity against lucerne aphid
An insect source: and (4) feeding the 3-day-old myzus persicae indoors.
The method comprises the following steps: example 3 was performed in the same manner as in example 7.
The results are shown in table 23, and it can be seen from the results that compound 7 and lambda-cyhalothrin both have good activity on aphis medicaginis; the compound 7 is compounded with the high-efficiency cyhalothrin, the co-toxicity coefficient of each mixture ratio of the mixture ratio is 97.30-416.03, and the mixture ratio is 120; the ratio is 60.
TABLE 23 Co-toxicity coefficient of Compound 7 and lambda-cyhalothrin against Adenophora cerifera
Figure BDA0003261188380000283
Figure BDA0003261188380000291
Bioassay example 12:activity test of a combination of Compound 6 and cyromazine against Liriomyza sativae
Insect sources: and (5) feeding the liriomyza sativae indoors.
The method comprises the following steps: the blade immersion method, referred to NY/1154.14-2008, is described in the following main operations: soaking clean iris japonica leaves in the medicinal liquid for 10s, air-drying, placing in culture dishes with 1 piece per dish, and placing filter paper in the culture dishes for moisture preservation. Each dish received 10 larvae of liriomyza sativae, 3 replicates. The cells were placed in a light incubator at 25 ℃ under 10hD light 14hL for cultivation. The number of dead and live insects is investigated by microscopic examination 3 days after the drug administration, and the mortality is calculated.
Evaluation method in the same manner as in production example 7.
The results are shown in table 24, from which it can be seen that both compound 6 and cyromazine have better activity against liriomyza sativae; the compound 6 is compounded with cyromazine, the cotoxicity coefficient of each proportion of 160 to 160 is 100.99 to 263.29, and the effect is additive or synergistic effect; the ratio of 80.
TABLE 24 Co-toxicity coefficient of combination of Compound 6 and cyromazine against Liriomyza sativae larvae
Figure BDA0003261188380000292
Bioassay example 13:activity test of a combination of Compound 14 and pyriproxyfen against Bemisia tabaci
Insect sources: bemisia tabaci, greenhouse potted plant breeding, crop: eggplant.
The method comprises the following steps: the vial drug film method refers to NY/1154.14-2008, and the main operation is described as follows: the medicament is matched with a glass tube to prepare a medicament film, each tube is connected with 10 heads of the bemisia tabaci adults, and the steps are repeated for 4 times. The cells were placed in a light incubator at 25 ℃ under 10hD light 14hL for cultivation. The number of dead and live insects is checked 8 hours after the drug is taken, and the mortality is calculated.
Evaluation method in the same manner as in production example 7.
The results are shown in table 25, from which it can be seen that both compound 14 and pyriproxyfen have better activity against bemisia tabaci; the compound 14 and the pyriproxyfen are compounded, the cotoxicity coefficient of each proportion of 160 to 160 is 99.49 to 229.94, and the additive or synergistic effect is shown; the ratio of 80.
TABLE 25 Co-toxicity factor of combination of Compound 14 and pyriproxyfen against Bemisia tabaci adults
Figure BDA0003261188380000301
The applicant states that the present invention is illustrated by the above examples to the pharmaceutical composition containing the m-diamide compound and the application thereof, but the present invention is not limited to the above examples, i.e. it does not mean that the present invention must rely on the above examples to be implemented. It should be understood by those skilled in the art that any modification of the present invention, equivalent substitutions of the raw materials of the product of the present invention, addition of auxiliary components, selection of specific modes, etc., are within the scope and disclosure of the present invention.

Claims (37)

1. A pharmaceutical composition containing a m-diamide compound is characterized by comprising an active ingredient A and an active ingredient B, wherein the active ingredient A is an amide compound with a structure shown in a formula II,
the effective component B comprises isoprocarb, diflubenzuron, pirimicarb, fenitrothion, profenofos, hexaflumuron, methomyl, monosultap, dimehypo, phoxim, dichlorvos, tebufenozide, deltamethrin, cypermethrin, cyromazine, lambda-cyhalothrin, chlorpyrifos, acephate, bifenthrin, carbosulfan, cartap, triazophos, fenpropathrin, ethofenprox and pyriproxyfen;
Figure FDA0003784752880000011
in the formula II, the reaction mixture is shown in the specification,
z is selected from hydrogen, fluorine, chlorine, bromine, iodine, cyano, C 1 -C 3 Haloalkyl, C 1 -C 3 Haloalkoxy or C 1 -C 3 An alkylsulfonyl group;
y is selected from trifluoromethyl or trifluoromethoxy;
r is selected from hydrogen or methyl.
2. The pharmaceutical composition containing the m-diamide compound according to claim 1, wherein in formula II,
z is selected from hydrogen, fluorine, chlorine, bromine, iodine, cyano, trifluoromethoxy, trifluoromethyl or methylsulfonyl;
y is selected from trifluoromethyl or trifluoromethoxy;
r is selected from hydrogen or methyl.
3. The pharmaceutical composition containing the m-diamide compound according to claim 1, wherein the m-diamide compound is any one selected from the group consisting of the following compounds 1 to 14:
Figure FDA0003784752880000012
Figure FDA0003784752880000021
4. the pharmaceutical composition containing a isophthalamide compound according to claim 1, wherein the weight ratio of the active ingredient A to the active ingredient B is 200.
5. The pharmaceutical composition containing the m-diamide compound as claimed in claim 1, wherein when the active ingredient B in the pharmaceutical composition containing the m-diamide compound is chlorpyrifos, acephate, phoxim, dichlorvos, fenitrothion, profenofos or triazophos, the weight ratio of the active ingredient A to the active ingredient B is 100.
6. The pharmaceutical composition containing the m-diamide compound as claimed in claim 1, wherein when the active ingredient B in the pharmaceutical composition containing the m-diamide compound is lambda-cyhalothrin, deltamethrin, cypermethrin, bifenthrin, ethofenprox or fenpropathrin, the weight ratio of the active ingredient A to the active ingredient B is 60.
7. The pharmaceutical composition containing the m-diamide compound as claimed in claim 1, wherein when the active ingredient B in the pharmaceutical composition containing the m-diamide compound is isoprocarb, methomyl, carbosulfan or pirimicarb, the weight ratio of the active ingredient A to the active ingredient B is from 80 to 1.
8. The pharmaceutical composition containing the m-diamide compound as claimed in claim 1, wherein when the active ingredient B in the pharmaceutical composition containing the m-diamide compound is monosultap, dimehypo or cartap, the weight ratio of the active ingredient A to the active ingredient B is (100-1).
9. The pharmaceutical composition containing the m-diamide compound as claimed in claim 1, wherein when the active ingredient B in the pharmaceutical composition containing the m-diamide compound is diflubenzuron, hexaflumuron, cyromazine, pyriproxyfen or tebufenozide, the weight ratio of the active ingredient A to the active ingredient B is 80.
10. The pharmaceutical composition containing the isophthalamide compound of claim 3, wherein the pharmaceutical composition comprises the combination of compound 1 and isoprocarb in a weight ratio of 1:4, and the combination of compound 1 and diflubenzuron in a weight ratio of 80.
11. The pharmaceutical composition containing the m-diamide compound as claimed in claim 3, wherein the pharmaceutical composition comprises the combination of the compound 2 and pirimicarb in a weight ratio of 1:2.
12. The pharmaceutical composition containing a isophthalamide compound according to claim 3, wherein the pharmaceutical composition comprises the combination of compound 3 and fenitrothion at a weight ratio of 1.
13. The pharmaceutical composition containing the m-diamide compound as claimed in claim 3, wherein the pharmaceutical composition comprises a combination of compound 4 and methomyl in a weight ratio of 3:5, a combination of compound 4 and monosultap in a weight ratio of 1.
14. The pharmaceutical composition containing a m-diamide compound according to claim 3, which comprises the combination of compound 5 with phoxim in a weight ratio of 1.
15. The pharmaceutical composition containing the m-diamide compound as claimed in claim 3, wherein the pharmaceutical composition comprises a combination of compound 6 and deltamethrin in a weight ratio of 100.
16. The pharmaceutical composition containing the m-diamide compound as claimed in claim 3, wherein the pharmaceutical composition comprises the combination of the compound 7 and the monosultap in a weight ratio of 1.
17. The pharmaceutical composition containing the m-diamide compound as claimed in claim 3, which comprises the combination of the compound 8 and chlorpyrifos in a weight ratio of 100.
18. The pharmaceutical composition containing a isophthalamide compound according to claim 3, wherein the pharmaceutical composition comprises the combination of compound 9 and monosultap in a weight ratio of 1.
19. The pharmaceutical composition containing the m-diamide compound as claimed in claim 3, wherein the pharmaceutical composition comprises the combination of the compound 10 and chlorpyrifos in a weight ratio of 1.
20. The pharmaceutical composition containing the m-diamide compound as claimed in claim 3, wherein the pharmaceutical composition comprises a combination of compound 11 and fenpropathrin in a weight ratio of 2.5, a combination of compound 11 and ethofenprox in a weight ratio of 2:1, a combination of compound 11 and monosultap in a weight ratio of 1.
21. The pharmaceutical composition containing a isophthalamide compound according to claim 3, wherein the pharmaceutical composition comprises the combination of compound 12 and monosultap in a weight ratio of 1.
22. The pharmaceutical composition containing the m-diamide compound according to claim 3, wherein the pharmaceutical composition comprises a combination of compound 13 and monosultap in a weight ratio of 1.
23. The pharmaceutical composition containing the m-diamide compound according to claim 3, wherein the pharmaceutical composition comprises the compound 14 and pyriproxyfen in a weight ratio of 80.
24. A pharmaceutical preparation comprising the pharmaceutical composition containing a m-diamide compound of any one of claims 1 to 23 and an agriculturally pharmaceutically acceptable auxiliary.
25. The pharmaceutical formulation as claimed in claim 24, wherein the agriculturally pharmaceutically acceptable auxiliary agents comprise any one or a combination of at least two of dispersing agents, wetting agents, emulsifying agents, anti-freezing agents, thickening agents, anti-foaming agents, preservatives, stabilizers or coloring agents.
26. The pharmaceutical formulation of claim 24, wherein the adjuvant comprises a filler and/or a solvent.
27. The pharmaceutical formulation of claim 24, wherein the formulation of the pharmaceutical formulation is a soluble solution, a soluble powder, a soluble granule, an emulsifiable concentrate, a wettable powder, an aqueous emulsion, a suspension, an oil-dispersible suspension, a water dispersible granule, a microcapsule suspension, a granule, a microemulsion, a suspoemulsion, a microcapsule suspension-suspension, an ultra-low volume liquid formulation, a hot fogging concentrate, a film-spreading oil formulation, a seed coating suspension, a dry seed treatment powder, a seed treatment suspension, a dispersible seed powder, a seed treatment emulsion, or a seed treatment liquid formulation.
28. The pharmaceutical preparation of claim 27, wherein the pharmaceutical preparation is in the form of a soluble solution, a soluble granule, a suspension, an emulsifiable concentrate, a wettable powder, an aqueous emulsion, a water dispersible granule, a dispersible oil suspension, a microcapsule suspension, an ultra-low volume liquid, a hot fogging concentrate, a seed suspension, or a seed treatment dispersible powder.
29. The pharmaceutical formulation of claim 24, wherein the pharmaceutical composition comprising the isophthalamide is present in the pharmaceutical formulation in an amount within the range of 0.01-99% by weight.
30. The pharmaceutical preparation according to claim 29, wherein the pharmaceutical composition comprising the m-diamide compound is contained in an amount of 0.5 to 95% by weight of the pharmaceutical preparation.
31. Use of a pharmaceutical composition according to any one of claims 1 to 23 or a pharmaceutical formulation according to any one of claims 24 to 30 for the agricultural control of plant diseases or pests.
32. Use of the pharmaceutical composition of any one of claims 1-23 or the pharmaceutical formulation of any one of claims 24-30 for controlling plant diseases or pests in forestry.
33. Use of the pharmaceutical composition of any one of claims 1-23 or the pharmaceutical formulation of any one of claims 24-30 for horticultural control of plant diseases or pests.
34. The use according to any one of claims 31 to 33, wherein application is by spraying, pouring or seed treatment.
35. A method for controlling plant diseases and insect pests, which is characterized by comprising the following steps: applying an effective dose of a pharmaceutical composition comprising a isophthalamide as described in any one of claims 1-23 or a pharmaceutical formulation as described in any one of claims 24-30 to a medium in need of control of a plant pest or growth thereof.
36. A method of controlling plant pests according to claim 35 wherein the effective dose is from 10 to 1000g per hectare.
37. A method of controlling plant pests according to claim 36 wherein the effective dose is from 15 to 900g per hectare.
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