Pharmaceutical composition containing m-diamide compound and application thereof
阅读说明：本技术 一种含有间二酰胺类化合物的药物组合物及其应用 (Pharmaceutical composition containing m-diamide compound and application thereof ) 是由 相君成 刘叙杆 吕亮 洪湖 刘吉永 邵佳礼 周丽琪 倪珏萍 于 2019-07-31 设计创作，主要内容包括：本发明提供一种含有间二酰胺类化合物的药物组合物及其应用,所述药物组合物包括有效成分A和有效成分B,所述有效成分A为具有式I所示结构的间二酰胺类化合物,所述有效成分B为噻虫嗪等杀虫剂、丙硫菌唑等杀菌剂中任意一种或两种的组合。本发明中含有效成分A和有效成分B的组合物,具有协同增效、扩大防治谱、控制传毒昆虫等独特作用,可有效防治水稻、玉米、小麦、蔬菜、果树、花卉、油料、糖料等作物及园艺、林业上的多种病虫害。(The invention provides a pharmaceutical composition containing a m-diamide compound and application thereof, wherein the pharmaceutical composition comprises an effective component A and an effective component B, the effective component A is the m-diamide compound with a structure shown in a formula I, and the effective component B is any one or combination of two of pesticides such as thiamethoxam and bactericides such as prothioconazole. The composition containing the effective component A and the effective component B has the unique effects of synergy, expansion of prevention and treatment spectrum, control of virus-transmitting insects and the like, and can effectively prevent and treat various plant diseases and insect pests in crops such as rice, corn, wheat, vegetables, fruit trees, flowers, oil plants, sugar materials and the like, and in gardening and forestry.)
1. The pharmaceutical composition containing the m-diamide compound is characterized by comprising an active ingredient A and an active ingredient B, wherein the active ingredient A is the amide compound with the structure shown in the formula I, and the active ingredient B comprises any one or the combination of two of other insecticides or bactericides;
wherein Z is selected from hydrogen, fluorine, chlorine, bromine, iodine, cyano, nitro, substituted or unsubstituted 3-to 10-membered heterocyclic group, C1-C6Alkyl radical, C1-C6Haloalkyl, C1-C6Alkoxy radical, C1-C6Haloalkoxy, C1-C6Alkylsulfinyl radical, C1-C6Haloalkylsulfinyl radical, C1-C6Alkylsulfonyl or C1-C6A haloalkylsulfonyl group; q is selected from C3-C8Cycloalkyl or C3-C8A halocycloalkyl group; x is selected from hydrogen, fluorine or trifluoromethyl; y is1Selected from fluorine, chlorine, bromine, iodine, cyano, nitro, C1-C6Alkyl radical, C1-C6Haloalkyl, C1-C6Haloalkoxy, C2-C4Alkenyl radical, C2-C4Haloalkenyl, C2-C4Alkynyl, C2-C4Halogenated alkynyl, C3-C8Cycloalkyl radical, C3-C8Halogenocycloalkyl, C1-C6Alkylcarbonyl group, C1-C6Alkylsulfinyl radical, C1-C6Haloalkylsulfinyl radical, C1-C6Alkylsulfonyl or C1-C6A haloalkylsulfonyl group; y is2Selected from bromine, iodine, cyano, nitro, C1-C6Haloalkyl, C1-C6Haloalkoxy, C2-C4Alkenyl radical, C2-C4Haloalkenyl, C2-C4Alkynyl, C2-C4Halogenated alkynyl, C3-C8Cycloalkyl radical, C3-C8Halogenocycloalkyl, C1-C6Alkylcarbonyl group, C1-C6Alkylsulfinyl radical, C1-C6Haloalkylsulfinyl radical, C1-C6Alkylsulfonyl or C1-C6A haloalkylsulfonyl group; r1Selected from hydrogen, fluoro or methoxy; r2Selected from fluoro or trifluoromethyl; r3And R4Each independently selected from hydrogen, halogen, cyano, nitro, C1-C6Alkyl radical, C1-C6Haloalkyl, C3-C8Cycloalkyl or C3-C8A halocycloalkyl group; m represents an integer of 0 to 5; n represents an integer of 0 to 3; w1And W2Independently isAn oxygen atom or a sulfur atom.
2. The pharmaceutical composition containing the m-diamide compound as claimed in claim 1, wherein the active ingredient A is the m-diamide compound having the structure shown in the following formula II:
in the formula II, the reaction mixture is shown in the specification,
z is selected from hydrogen, fluorine, chlorine, bromine, iodine, cyano, C1-C6Haloalkyl, C1-C6Haloalkoxy, C1-C6Alkylsulfonyl or C1-C6A haloalkylsulfonyl group;
y is selected from C1-C6Haloalkyl or C1-C6A haloalkoxy group;
r is selected from hydrogen or methyl.
3. The pharmaceutical composition containing the m-diamide compound according to claim 2, wherein in formula II,
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.
4. The pharmaceutical composition containing the m-diamide compound according to any one of claims 1 to 3, wherein the m-diamide compound is any one or a combination of at least two selected from the following compounds 1 to 14:
5. the pharmaceutical composition containing the m-diamide compound as claimed in claims 1 to 4, wherein the active ingredient B is selected from any one or two of thiamethoxam, imidacloprid, clothianidin, thiacloprid, acetamiprid, nitenpyram, dinotefuran, cycloxaprid, flupyridinil, flonicamid, pymetrozine, buprofezin, trifluoropyrimidine, imidazopyridine, dipropionate, pyrifluquinazon, benzpyrimoxan, difenoconazole, tebuconazole, prothioconazole, cyproconazole, azoxystrobin, trifloxystrobin, azoxystrobin, mefenoxam, prochloraz, mefenonil, prochloraz or cyazoxystrobin.
6. The pharmaceutical composition containing the m-diamide compound as claimed in any one of claims 1 to 4, wherein the weight ratio of the pesticide in the effective component A to the pesticide in the effective component B is 200:1-1: 200;
preferably, when the active ingredient B in the pharmaceutical composition containing the isophthalamide compound is thiamethoxam, imidacloprid, clothianidin, thiacloprid, acetamiprid, nitenpyram, dinotefuran and cycloxaprid, the weight ratio of the active ingredient A to the active ingredient B is 80:1-1: 80;
preferably, when the active ingredient B in the pharmaceutical composition containing the m-diamide compound is the fluoropyrafuranone and the sulfoxaflor, the weight ratio of the active ingredient A to the active ingredient B is 60:1-1: 60;
preferably, when the active ingredient B in the pharmaceutical composition containing the m-diamide compound is flonicamid, pymetrozine and buprofezin, the weight ratio of the active ingredient A to the active ingredient B is 100: 1-1: 100, preferably 50: 1-1: 50;
preferably, when the active ingredient B in the pharmaceutical composition containing the m-diamide compound is trifluorobenzene pyrimidine and dithiapyradine, the weight ratio of the active ingredient A to the active ingredient B is 80:1-1: 80;
preferably, when the active ingredient B in the pharmaceutical composition containing the m-diamide compound is the dipropylcyclovir disoproxil, the pyrifluquinazon and the benzpyrimoxan, the weight ratio of the active ingredient A to the active ingredient B is 80:1-1: 80;
preferably, when the active ingredient B in the pharmaceutical composition containing the m-diamide compound is difenoconazole, tebuconazole, prothioconazole and cyproconazole, the weight ratio of the active ingredient A to the active ingredient B is 100: 1-1: 100;
preferably, when the active ingredient B in the pharmaceutical composition containing the m-diamide compound is azoxystrobin, trifloxystrobin, pyraclostrobin and picoxystrobin, the weight ratio of the active ingredient A to the active ingredient B is 80:1-1: 80;
preferably, when the effective component B in the pharmaceutical composition containing the m-diamide compound is metalaxyl, metalaxyl-M, fludioxonil, prochloraz and phenamacril, the weight ratio of the effective component A to the effective component B is 80:1-1: 80.
7. A pharmaceutical preparation, which comprises the pharmaceutical composition containing the m-diamide compound of claims 1-6 and an agriculturally pharmaceutically acceptable adjuvant and/or carrier;
preferably, the agriculturally and pharmaceutically acceptable auxiliary agent comprises any one or a combination of at least two of a dispersing agent, a wetting agent, an emulsifying agent, an antifreezing agent, a thickening agent, an antifoaming agent, a preservative, a stabilizing agent or a coloring agent;
preferably, the carrier comprises a filler and/or a solvent;
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.
8. The pharmaceutical preparation according to claim 7, wherein the weight percentage of the pharmaceutical composition containing the m-diamide compound in the pesticide preparation is 0.01-99%, preferably 0.5-95%.
9. Use of the pharmaceutical composition according to any one of claims 1 to 6 or the pharmaceutical formulation according to claim 7 or 8 for controlling plant diseases or insect pests in agriculture, forestry, horticulture;
preferably, application can be carried out by spraying, pouring, and seed treatment.
10. A method for controlling plant diseases and insect pests, which is characterized by comprising the following steps: applying an effective dose of the pharmaceutical composition containing the m-diamide compound as claimed in any one of claims 1 to 6 or the pharmaceutical preparation as claimed in claim 7 or 8 to a medium in which a plant disease or growth thereof is to be controlled;
preferably, the effective dose is from 1 to 1000g per hectare, preferably from 7.5 to 500g per hectare.
Technical Field
The invention belongs to the technical field of preventing and treating pests by using a pharmaceutical composition, relates to a pharmaceutical composition containing a m-diamide compound and application thereof, and particularly relates to a composition containing a m-diamide compound and insecticides such as thiamethoxam or bactericides such as prothioconazole and application thereof.
Background
In the production of crops such as agriculture and horticulture, damage caused by diseases and insect pests is still very obvious, and due to biodiversity and simultaneous occurrence of various diseases and insect pests, the development of new insecticides or insecticide compositions or insecticidal and bactericidal compositions with better activity, lower dosage and more environment-friendly property is always required in the field of plant protection. The synergistic insecticidal and bactericidal composition has important effects on expanding insecticidal spectrum, controlling diseases and pests, controlling virus-transmitting medium insects to control virus diseases, reducing pesticide application cost of farmers and the like.
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;
wherein Z is selected from hydrogen, fluorine, chlorine, bromine, iodine, cyano, nitro, substituted or unsubstituted 3-to 10-membered heterocyclic group, C1-C6Alkyl radical, C1-C6Haloalkyl, C1-C6Alkoxy radical, C1-C6Haloalkoxy, C1-C6Alkylsulfinyl radical, C1-C6Haloalkylsulfinyl radical, C1-C6Alkylsulfonyl or C1-C6A haloalkylsulfonyl group; q is selected from C3-C8Cycloalkyl or C3-C8A halocycloalkyl group;
x is selected from hydrogen, fluorine or trifluoromethyl;
Y1selected from fluorine, chlorine, bromine, iodine, cyano, nitro, C1-C6Alkyl radical, C1-C6Haloalkyl, C1-C6Haloalkoxy, C2-C4Alkenyl radical, C2-C4Haloalkenyl, C2-C4Alkynyl, C2-C4Halogenated alkynyl, C3-C8Cycloalkyl radical, C3-C8Halogenocycloalkyl, C1-C6Alkylcarbonyl group, C1-C6Alkylsulfinyl radical, C1-C6Haloalkylsulfinyl radical, C1-C6Alkylsulfonyl or C1-C6A haloalkylsulfonyl group;
Y2selected from bromine, iodine, cyano, nitro, C1-C6Haloalkyl, C1-C6Haloalkoxy, C2-C4Alkenyl radical, C2-C4Haloalkenyl, C2-C4Alkynyl, C2-C4Halogenated alkynyl, C3-C8Cycloalkyl radical, C3-C8Halogenocycloalkyl, C1-C6Alkylcarbonyl group, C1-C6Alkylsulfinyl radical, C1-C6Haloalkylsulfinyl radical, C1-C6Alkylsulfonyl or C1-C6A haloalkylsulfonyl group;
R1selected from hydrogen, fluoro or methoxy; r2Selected from fluoro or trifluoromethyl; r3And R4Each independently selected from hydrogen, halogen, cyano, nitro, C1-C6Alkyl radical, C1-C6Haloalkyl, C3-C8Cycloalkyl or C3-C8A 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); w1And W2Independently 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 reach 100% of insecticidal activity under low dose, the effect is quick, the insecticidal activity can be exerted after three days of application, and the quick-acting performance is good, the medicinal composition containing the m-diamide compound also has good quick-acting performance, and due to the fact that the effect is good under low dose, the harm of overlarge medicament concentration to plants and human beings is reduced, and the m-diamide compound generates less medicament residue during application, so that the m-diamide compound is.
Preferably, the invention provides a pharmaceutical composition containing a compound in which the 3-position of the m-diamide is substituted by an N-cyclopropylmethyl derivative, the pharmaceutical composition comprises an effective component A and an effective component B, 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;
in the formula II, the reaction mixture is shown in the specification,
z is selected from hydrogen, fluorine, chlorine, bromine, iodine, cyano, C1-C6Haloalkyl, C1-C6Haloalkoxy, C1-C6Alkylsulfonyl or C1-C6A haloalkylsulfonyl group;
y is selected from C1-C6Haloalkyl or C1-C6A haloalkoxy group;
r is selected from hydrogen or methyl.
In the present invention, as a preferable embodiment, in formula II, 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
W in Table 12Selected from oxygen. "H" is hydrogen atom, "F" represents fluorine atom, "Cl" represents chlorine atom, "Br" represents bromine atom, "I" represents iodine atom, "CN" represents cyano group, "CF3"is trifluoromethyl and" OCF3Is trifluoromethoxy, MeS (O)2"represents a methanesulfonyl group," CF3S(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:
the term "C" as used in the present invention1-C6Alkyl "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 "C1-C6Alkoxy "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 "C1-C6Haloalkyl "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 "C1-C6Haloalkoxy "refers to alkoxy groups of 1 to 6 carbon atoms having halogen substitution; the same term "C3-C8Cycloalkyl "refers to a cyclic alkyl group having 3 to 8 carbon atoms in the ring, including without limitation cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, and the like; book (I)As used herein, the term "C3-C8 halocycloalkyl" refers to a cyclic alkyl group of 3 to 8 carbon atoms having a 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 group1-C6、C3-C8Etc. represent the number of carbon atoms contained in the radical, e.g. C1-C6Represents a group having 1,2,3, 4, 5 or 6 carbon atoms, C3-C8Represents a group in which the number of carbon atoms may be 3, 4, 5, 6, 7 or 8, and so on.
Based on the requirements of expanding the activity spectrum and crop protection markets, when the effective component B is selected, the pesticide is mainly used for preventing pests with piercing sucking/filing sucking/sucking mouthparts, and the bactericide is mainly used for treating seeds.
Preferably, the pesticide is selected from neonicotinoid insecticides such as thiamethoxam, imidacloprid, clothianidin, thiacloprid, acetamiprid, nitenpyram, dinotefuran, cycloxaprid and the like, or agents for controlling plant hoppers, leafhoppers, aphids, whiteflies, thrips, scale insects and the like selected from fluoropyrapone, sulfoxaflor, flonicamid, pymetrozine, buprofezin, trifluoropyrimidine, clopyralid (diclomezotiaz), afidopyropen (afidopyropen), pyrifluquinazon, benzpyrimoxan and the like; the bactericide is selected from difenoconazole, tebuconazole, prothioconazole, cyproconazole, azoxystrobin, trifloxystrobin, pyraclostrobin, picoxystrobin, metalaxyl-M, metalaxyl, fludioxonil, prochloraz, cyhalothrin and other medicaments for preventing and treating seed-borne diseases or soil-borne diseases in seed treatment.
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 described in table 2 below, but not limited to the combinations listed in the table:
TABLE 2
In a preferred embodiment of the present invention, the insecticidal and fungicidal composition containing a m-diamide compound is a composition containing the active ingredient a and the active ingredient B shown in table 1, and the active ingredient B is not limited to the insecticide or fungicide variety described above.
The combined action of the insecticidal composition is tested by using pests such as rice stem borer, rice leaf roller, rice brown planthopper, rice bakanae disease, vegetable diamond back moth, vegetable beet armyworm, vegetable aphid, eggplant thrips, cotton bollworm, cotton aphid, wheat armyworm, wheat aphid and the like, and the synergistic action is found; the insecticidal and bactericidal composition is tested to have the effects of synergy and expansion of an activity spectrum; in addition, after controlling the pests such as planthopper, whitefly and the like, the virus disease can be effectively controlled by combining the treatment of the medicament.
The weight ratio of the active ingredient A to the active ingredient B is 200:1-1:200, such as 200:1, 180:1, 150:1, 130:1, 100:1, 80:1, 60:1, 40:1, 20:1, 10:1, 1:10, 1:30, 1:50, 1:80, 1:100, 1:120, 1:140, 1:160, 1:180 or 1: 200.
In the present invention, the preferable weight ratio of the pharmaceutical composition containing the m-diamide compound is different according to the difference between 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 is shown in table 3.
TABLE 3
More preferably, the m-diamide compound shown in the formula I of the effective component A in the table 3 is replaced by the m-diamide compound shown in the formula II, and the preferable weight ratio in the table 3 is also met.
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 adding adjuvants such as emulsifiers, dispersants, stabilizers, wetting agents, binders, antifoaming agents, antioxidants, and the like.
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 pests, sanitary pests and diseases which harm 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, rose, and 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, fall armyworm, rice leaf roller, rice thrips, western flower thrips, melon thrips, spring onion thrips, ginger thrips, mango thrips, peach aphid, cotton aphid, alfalfa aphid, apple yellow aphid, wheat aphid, flea beetle, stinkbug, gray planthopper, brown planthopper, white back planthopper, termite, mosquito fly, carmine spider 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 present invention provides the use of a pharmaceutical composition or pharmaceutical preparation 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, 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 1 to 1000g per hectare, for example 1g, 5g, 8g, 10g, 20g, 50g, 80g, 100g, 120g, 150g, 180g, 200g, 250g, 300g, 350g, 400g, 450g, 500g, 600g, 700g, 800g, 900g or 1000g, preferably 7.5 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 provided by the invention has the following advantages in use:
(1) the composition of the effective component A and the effective component B has a synergistic effect, the using 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.
(2) The pharmaceutical composition can treat diseases and pests simultaneously, expands the control spectrum, reduces the application times and saves the labor cost of application.
(3) The high-efficiency prevention and control effect on the pests such as whitefly, whitefly and the like of the virus-transmitting insects is realized, the chance of virus transmission is reduced, and the treatment of virus diseases can be obviously and synergistically controlled.
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 limitations of the present invention.
Synthetic examples
Synthesis example 1
Preparation of N- [ 2-bromo-4- (1,1,1,2,3,3, 3-heptafluoropropan-2-yl) -6- (trifluoromethyl) phenyl ] -3- [ N- (cyclopropylmethyl) -benzamido ] -2-fluorobenzamide (compound No. 1):
(1) synthesis of methyl 2-fluoro- [3- (cyclopropylmethyl) amino ] benzoate
Methyl 2-fluoro-3-aminobenzoate (20g, 118.23mmol), bromomethylcyclopropane (20.75g, 153.70mmol), potassium carbonate (21.24g, 153.70mmol) and N, N-dimethylformamide (200mL) were added to the reaction flask in this order, stirred under reflux for 16h, and the heating was turned off to terminate the reaction when TLC monitored that the reaction did not progress. After the reaction solution was cooled to room temperature, water (200mL) was added to the reaction solution, and the mixture was extracted with ethyl acetate (100mL), 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: petroleum ether: ethyl acetate: 10: 1) to give 2-fluoro- [3- (cyclopropylmethyl) amino [ methyl benzoate (13g, yield 49.39%) as a pale yellow liquid product.
(2) Synthesis of methyl 2-fluoro-3- [ N- (cyclopropylmethyl) benzamido ] benzoate
Benzoic acid (6.67g, 53.78mmol), toluene (50mL) and thionyl chloride (31.99g, 268.9mmol) were added sequentially to a reaction flask, reacted under reflux for 2h, toluene was concentrated under reduced pressure, and the concentrated residue was dissolved in tetrahydrofuran (30mL) until use. Methyl 2-fluoro-3- (N-cyclopropylmethylamino) benzoate (10.00g, 44.82mmol) was dissolved in tetrahydrofuran (100mL), pyridine (4.25g, 53.78mmol) was added thereto, the resulting benzoyl chloride tetrahydrofuran solution 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 (50mL), 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 (13.00g, yield 88.70%) as a colorless liquid.
(3) Synthesis of 2-fluoro-3- [ N- (cyclopropylmethyl) benzamido ] benzoic acid
Methyl 2-fluoro-3- (N- (cyclopropylmethyl) benzamide) benzoate (13.00g, 40.88mmol) was dissolved in methanol (100mL), and 10% aqueous sodium hydroxide (6.54g, 163.52mmol, 65.4mL) was added thereto, and after stirring at room temperature for 2 hours, the reaction was monitored by TLC for completion. After removing methanol by concentration under reduced pressure, the concentrated residue was dissolved in water (100mL), extracted with ethyl acetate (50mL), 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 (100mL), 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 (12.00g, 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-heptafluoropropan-2-yl) -6- (trifluoromethyl) phenyl ] -3- [ N- (cyclopropylmethyl) benzamido ] -2-fluorobenzamide
2-fluoro-3- (N- (cyclopropylmethyl) benzamido) benzoic acid (0.40g, 1.28mmol), toluene (6mL), 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 (3mL) for further use.
Dissolving 2-bromo-6-trifluoromethyl-4-heptafluoroisopropylaniline (0.52g, 1.28mmol) in tetrahydrofuran (4mL), 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, raising the temperature to room temperature, and continuing to stir for 30 min. The reaction was terminated by TLC monitoring until the reaction did not proceed any more. Water (20mL) was added to the reaction mixture, and the mixture was extracted with ethyl acetate (20mL), 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 ═ 3:1) to give N- [ 2-bromo-4- (1,1,1,2,3,3, 3-heptafluoropropan-2-yl) -6- (trifluoromethyl) phenyl ] -3- [ N- (cyclopropylmethyl) -benzoylamino ] -2-fluorobenzamide (0.25g, yield 27.84%).
Process for preparation of Compound 11H NMR(400MHz,CDCl3-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-heptafluoropropan-2-yl) -6-trifluoromethoxyphenyl ] -3- [ N- (cyclopropylmethyl) benzamido ] -2-fluorobenzamide (Compound No. 3)
2-fluoro-3- (N- (cyclopropylmethyl) benzamide) benzoic acid (0.50g, 1.60mmol), toluene (6mL), and thionyl chloride (1.07g, 9.00mmol) 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 (3mL) for further use.
Dissolving 2-bromo-4-heptafluoroisopropyl-6-trifluoromethoxyaniline (0.68g, 1.60mmol) in tetrahydrofuran (4mL), dropwise adding 2M lithium diisopropylamide tetrahydrofuran solution (0.96mL, 1.93mmol) at-70 ℃, dropwise adding the tetrahydrofuran solution for later use after 5min, stirring at-70 ℃ for 30min, heating to room temperature, and continuing stirring for 30 min. The reaction was terminated when the reaction was no longer proceeding as monitored by Thin Layer Chromatography (TLC). Water (20mL) was added to the reaction mixture, and extraction was performed with ethyl acetate (20mL), 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 5: 1) to obtain the objective product (0.24g, yield 20.50%) as a white solid.
Process for preparation of Compound 31H NMR(400MHz,CDCl3D) 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
4-Cyanobenzoic acid (0.80g, 5.38mmol), toluene (6mL), and thionyl chloride (3.2g, 26.9mmol) 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 (3mL) for further use. Methyl 2-fluoro- [3- (cyclopropylmethyl) amino ] benzoate (1.0g, 4.48mmol) was dissolved in tetrahydrofuran (6mL), triethylamine (0.74g, 5.38mmol) was added, 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 (20mL) was added to the reaction mixture, and the mixture was extracted with ethyl acetate (20mL), 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 methyl 2-fluoro-3- [ N- (cyclopropylmethyl) -4-cyanobenzamide ] benzoate (1.40g, yield 88.83%) as a colorless liquid product.
(2) Synthesis of 2-fluoro-3- [ N- (cyclopropylmethyl) -4-cyanobenzamido ] benzoic acid
Methyl 2-fluoro-3- [ N- (cyclopropylmethyl) -4-cyanobenzamido ] benzoate (1.40g,3.96mmol) was dissolved in methanol (20mL), 10% aqueous sodium hydroxide (0.63g,15.86mmol,6.3mL) was added, the mixture was stirred at room temperature for 2h, and the reaction was monitored by TLC for completion. After removing methanol by concentration under reduced pressure, the concentrated residue was dissolved in water (20mL), extracted with ethyl acetate (10mL), 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 (10mL), 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 (1.30g, 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:
2-fluoro-3- [ N- (cyclopropylmethyl) -4-cyanobenzamide ] benzoic acid (0.75g, 2.22mmol), toluene (6mL) and thionyl chloride (1.31g, 11.10mmol) were added to a reaction flask in this order, the reaction was stirred under reflux for 2h, concentrated under reduced pressure, and the concentrated residue was dissolved in tetrahydrofuran (3mL) for use.
Dissolving 2-bromo-6-trifluoromethyl-4-heptafluoroisopropylaniline (0.90g, 2.22mmol) in tetrahydrofuran (4mL), 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 30 min. 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 (20mL), extracted with ethyl acetate (20mL), 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 ═ 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-cyanobenzoylamino ] -2-fluorobenzamide (0.24g, yield 14.91%).
Process for preparation of Compound 41H NMR(400MHz,CDCl3-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):
(1) 2-fluoro-3- [ N- (cyclopropylmethyl) -4-trifluoromethylbenzamide ] benzoic acid (0.45g, 1.12mmol), toluene (6mL), and thionyl chloride (0.67g, 5.60mmol) 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 (3mL) for further use.
(2) Dissolving 2-bromo-6-trifluoromethyl-4-heptafluoroisopropylaniline (0.46g, 1.12mmol) in tetrahydrofuran (4mL), 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 continuing stirring for 30 min. The reaction was terminated by TLC monitoring until the reaction did not proceed any more. Water (20mL) was added to the reaction mixture, and extraction was performed with ethyl acetate (20mL), 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 (0.11g, yield 13.75%).
Process for preparation of Compound 71H NMR(400MHz,CDCl3-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-heptafluoropropan-2-yl) -6- (trifluoromethyl) phenyl ] -3- [ N- (cyclopropylmethyl) -4-fluorobenzamido ] -2-fluorobenzamide (Compound No. 8) as follows:
2-fluoro-3- [ N- (cyclopropylmethyl) -4-fluoro-benzamide ] benzoic acid (2.20g, 6.67mmol), toluene (20mL), thionyl chloride (3.97g, 33.35mmol) were added to the reaction flask in this order, stirred under reflux for 2h 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 (20mL) was added to the reaction mixture, and extraction was performed with ethyl acetate (20mL), 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: PE: EA ═ 3:1) to obtain the objective product (1.80g, yield 37.5%).
Process for preparation of Compound 81H NMR(400MHz,DMSO-d6)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-heptafluoropropan-2-yl) -6- (trifluoromethyl) phenyl ] -3- [ N- (cyclopropylmethyl) -4-chlorobenzamido ] -2-fluorobenzamide (Compound No. 10) as follows:
(1) 2-fluoro-3- [ N- (cyclopropylmethyl) -4-chlorobenzamide ] benzoic acid (0.60g, 1.76mmol), toluene (6mL), and 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 (3mL) for further use.
(2) Dissolving 2-bromo-6-trifluoromethyl-4-heptafluoroisopropylaniline (0.72g, 1.76mmol) in tetrahydrofuran (4mL), 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 30 min. The reaction was terminated by TLC monitoring until the reaction did not proceed any more. Water (20mL) was added to the reaction mixture, and extraction was performed with ethyl acetate (20mL), 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 (0.15g, yield 11.63%).
Process for preparation of Compound 101H NMR(400MHz,CDCl3-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-heptafluoropropan-2-yl) -6- (trifluoromethyl) phenyl ] -3- [ N- (1-cyclopropyl-ethyl) -benzamido ] -2-fluorobenzamide (compound No. 2) by the following method:
(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 (65mL), and cyclopropylmethyl ketone (2.98g, 35.47mmol), trifluoroacetic acid (8.08g, 70.92mmol) and sodium triacetoxyborohydride (7.51g, 35.47mmol) were added in this order at room temperature, and the reaction was heated to 45 ℃ for 1 h. The reaction was terminated by TLC monitoring until the reaction did not proceed any more. Adding saturated NaHCO into the reaction solution3The solution (50mL) was extracted with dichloromethane (80mL), 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: dichloromethane)Petroleum ether: ethyl acetate 10: 1) the desired product (1.50g, yield 53.5%) was obtained as a colorless oil.
(2) Synthesis of methyl 3- [ N- (1-cyclopropyl) ethyl) benzamido ] -2-fluorobenzoate
Benzoic acid (1.54g, 12.64mmol), toluene (15mL) 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 (5mL) for use.
Methyl 3- [ N- (1-cyclopropyl) ethyl) amino ] -2-fluorobenzoate (2.50g, 10.54mmol) was dissolved in tetrahydrofuran (15mL), triethylamine (1.60g, 15.80mmol) and a tetrahydrofuran solution of the acid chloride prepared in the previous step were added in this order, and the reaction was stirred at 80 ℃ for 6 h. The reaction was terminated by TLC monitoring until the reaction did not proceed any more. Water (50mL) was added to the reaction mixture, and extraction was performed with ethyl acetate (60mL), 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: 1) to obtain the objective product (1.03g, 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 (10mL), 10% aqueous sodium hydroxide (0.46g, 11.72mmol, 4.6mL) was added, stirring was carried out at room temperature for 2h, and the reaction was monitored by TLC for completion. After removing methanol by concentration under reduced pressure, the concentrated residue was dissolved in water (20mL), extracted with ethyl acetate (10mL), 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 (10mL), the organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain the objective product (0.60g, yield 62.6%).
(4) Synthesis of N- [ 2-bromo-4- (1,1,1,2,3,3, 3-heptafluoropropan-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 (6mL) 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 (2mL) for further use.
Dissolving 2-bromo-6-trifluoromethyl-4-heptafluoroisopropylaniline (0.75g, 1.83mmol) in tetrahydrofuran (6mL), dropwise adding lithium diisopropylamide (1.10mL, 2.20mmol) 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 30 min. The reaction was terminated by TLC monitoring until the reaction did not proceed any more. Water (20mL) was added to the reaction mixture, and extraction was performed with ethyl acetate (20mL), 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 ═ 5: 1) to obtain the objective product (0.23g, yield 17.5%) as a yellow solid.
Process for preparation of Compound 21H NMR(400MHz,CDCl3-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 or preparable by a method similar to that 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
Other compounds of formula I or formula II of the present invention may be synthesized by methods described above.
Formulation examples
The following examples are provided to illustrate the composition ratios and preparation of the present invention:
formulation example 1:25% of compound 4-thiamethoxam water dispersible granule
The composition of the 25% compound 4 thiamethoxam water dispersible granules is shown in the following table 5:
TABLE 5
Name (R)
Pleated (W/W,%)
Remarks for note
Compound 4
10
Active ingredient A
Thiamethoxam
15
An active ingredient B
Sodium dodecyl sulfate
1.5
Wetting agent
Lignosulfonic acid sodium salt
6
Dispersing agent
Naphthalenedicarbaldehyde polymer sodium sulfonate
2
Dispersing agent
Ammonium sulfate
5
Disintegrating agent
Corn starch
20
Filler material
Kaolin clay
Complement 100
Filler material
The preparation method comprises the following steps: calculating the amount of each material according to a formula, uniformly mixing the compound 4, thiamethoxam, sodium dodecyl sulfate, sodium lignosulfonate, sodium naphthalene formaldehyde polymer sulfonate, ammonium sulfate, corn starch and 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 ℃, screening, sampling and inspecting the mixture to be qualified, and obtaining the 25% compound 4-thiamethoxam water dispersible granule.
Formulation example 2:24% of compound 8-fluropyranone soluble solution
The composition of the 24% compound 8-fluoropyranone solubles is shown in table 6 below:
TABLE 6
Name (R)
Pleated (W/W,%)
Remarks for note
Compound 8
12
Active ingredient A
Fluopyrafuranones
12
An active ingredient B
Propylene glycol methyl ether
10
Cosolvent
Fatty alcohol polyoxyethylene ether
6
Wetting agent
Deionized water
Complement 100
Solvent(s)
The preparation method comprises the following steps: calculating the amount of each material according to the formula, adding deionized water into a 250ml three-neck flask, adding propylene glycol methyl ether, then adding the compound 8 and the fluoropyrafuranone, heating to 30-40 ℃, stirring for 2 hours, finally adding the fatty alcohol-polyoxyethylene ether, dissolving uniformly, filtering, sampling, and inspecting to be qualified to obtain the soluble solution of the 24% compound 8. fluoropyrafuranone.
Formulation example 3:10% compound 1. acetamiprid emulsifiable concentrate
The composition of a 10% compound 1 acetamiprid emulsifiable concentrate is shown in table 7 below:
TABLE 7
The preparation method comprises the following steps: calculating the amount of each material according to a formula, adding 200 solvent oil into a material preparation kettle, adding the compound 1 and acetamiprid to be completely dissolved, adding the calcium dodecyl benzene sulfonate and the castor oil polyoxyethylene ether, stirring for 1.5 hours at 40-50 ℃, filtering, sampling, and inspecting to be qualified to obtain the 10% compound 1-acetamiprid missible oil.
Preparation fruitExample 4:30% compound 10. pymetrozine wettable powder
The composition of the 30% compound 10. pymetrozine wettable powder is shown in the following table 8:
TABLE 8
Name (R)
Pleated (W/W,%)
Remarks for note
Compound 10
8
Active ingredient A
Pymetrozine
22
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 10, the pymetrozine, the sodium dodecyl sulfate, the sodium lignin sulfonate and the kaolin into a material preparation kettle, uniformly mixing, crushing to 10 micrometers in average particle size by using an airflow crusher, sampling, and inspecting to be qualified to obtain the 30% compound 10. pymetrozine wettable powder.
Formulation example 5:20% of compound 5-trifluoro-benzene pyrimidine suspending agent
The composition of the 20% compound 5-trifluorobenzene pyrimidine suspension is shown in table 9 below:
TABLE 9
Name (R)
Pleated (W/W,%)
Remarks for note
Compound 5
10
Active ingredient A
Trifluorophenylpyrimidines
10
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
Polydimethylsiloxane emulsion
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, polydimethylsiloxane emulsion, tristyrylphenol polyoxyethylene ether phosphate, sodium lignin sulfonate, karson and a defoaming agent, adding trifluoro-phenylpyrimidine and the compound 5, uniformly shearing, grinding to an average particle size of 2 microns by a sand mill, adding 10 parts of 1% xanthan gum solution, and stirring for 30 minutes to obtain the 20% compound 5-trifluoro-phenylpyrimidine suspension.
Formulation example 6:35% of compound 8-Cyanoxastrobin suspension seed coating agent
The composition of the 35% compound 8-cyhalothrin suspended seed coating is shown in the following table 10:
watch 10
The preparation method comprises the following steps: in a blending kettle, according to the material ratio, adding deionized water, a compound 8, phenamacril, tristyrylphenol polyoxyethylene ether phosphate triethanolamine salt, block polyoxyethylene ether, Kathon polydimethylsiloxane emulsion and propylene glycol, shearing and sanding, controlling the particle size D905 micrometers, transferring to a blending kettle, adding a 2% xanthan gum solution and a pigment F2R, mixing and stirring for 1 hour, sampling and detecting, and obtaining a finished product of 35% of a compound 8-phenamacril suspension seed coating agent after the seed coating agent is qualified.
Formulation example 7: 15% Compound 1. Prothioconazole suspending agent
The composition of the 15% compound 1-propiconazole suspension is shown in table 11 below:
TABLE 11
Name (R)
Pleated (W/W,%)
Remarks for note
Compound 1
10
Active ingredient A
Prothioconazole
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
Polydimethylsiloxane emulsion
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, fatty alcohol-polyoxyethylene ether, tristyrylphenol polyoxyethylene ether phosphate, sodium lignin sulfonate, karson and a defoaming agent, adding prothioconazole and the compound 1, uniformly shearing, grinding the mixture to an average particle size of 2 microns by a sand mill, adding 10 parts of 1% xanthan gum solution, and stirring for 30 minutes to obtain the 15% compound 1-prothioconazole suspending agent.
Formulation example 8:30% compound 8-diproprionate dispersible agent
The composition of the 30% compound 8-diproprionate dispersible agent is shown in table 12 below:
TABLE 12
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 8 and the dipropylcyclobuterol under stirring, heating to 50 ℃ until the solvent is completely dissolved, adding castor oil polyoxyethylene ether, fatty alcohol polyoxyethylene ether and polydimethylsiloxane emulsion, continuing stirring for 10 minutes, cooling, and adding deionized water to obtain the 30% compound 8-dipropylcyclobuterol dispersible agent.
Formulation embodiment 9: 40% compound 1-prochloraz aqueous emulsion
The composition of the 40% compound 1-prochloraz aqueous emulsion is shown in the following table 13:
watch 13
Name (R)
Pleated (W/W,%)
Remarks for note
Compound 1
10
Active ingredient
Prochloraz
30
Active ingredient
No. 150 solvent oil
15
Cosolvent
Block polyoxyethylene ether compound
5.0
Emulsifier
Propylene glycol
5.0
Antifreezing agent
Dimethicone emulsions
0.2
Defoaming agent
Deionized water
Make up well
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 the prochloraz and the emulsifier block polyoxyethylene ether compound after completely dissolving, 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 a 40% compound 1-prochloraz 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 effective component A has obvious activity on various pests
Target: the 3 rd larva of diamondback moth, the 3 rd larva of armyworm and the 3 rd larva of cotton bollworm are all raised indoors.
The method comprises the following steps: diamondback moth feeding method, leaf soaking feeding method, armyworm feeding method, leaf soaking feeding method, cotton bollworm feeding method and dripping method.
Diamondback moth and leaf soaking feeding method. 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. Placing in a light incubator at 25 deg.C under 14hL:10hD for culture. And (5) investigating the dead number of diamondback moth 3 days after the pesticide is applied, and calculating the death rate.
Feeding method with armyworm and soaked leaves. With reference to NY/1154.14-2008, the main operations are described as follows: soaking the corn leaf segments in the medicinal liquid for 10s, air drying, 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. Placing in a light incubator at 25 deg.C under 14hL:10hD for culture. The number of the armyworm dead insects 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 for 3 times, sealing the tube with cotton black cloth, fastening 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 14, and it can be seen from the results that compounds 1 to 14 all had very significant insecticidal activity.
TABLE 14
Bioassay example 2:the active ingredient A is a compound shown in the formula II and the active ingredient B is a composition of pesticides such as acetamiprid, imidazopyridine and the like, and the activity test of the composition on the plutella xylostella is carried out
Target: and breeding 3-instar larvae of the plutella xylostella indoors.
The method comprises the following steps: example 1 was tested in the same manner.
The evaluation methods and criteria were as follows:
the synergistic effect is the percent of actual mortality to theoretical mortality
Theoretical mortality ═ 1- (1-mortality of active a at this dose) (1-mortality of active B at this 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 15, and it can be seen from the results that the effective ingredient a, compound 1, compound 4, compound 8, had excellent activity against plutella xylostella; when the effective component B is acetamiprid and imidazopyridine dichloride, the composition has better activity on diamond back moths; when a is combined with B, the combined effect appears to be synergistic or significant synergistic.
TABLE 15 insecticidal Activity of test Agents against Plutella xylostella indoors
Bioassay example 3: the active ingredient A is a compound shown in the formula II and the active ingredient B is a composition of thiamethoxam, trifluoro-benzene pyrimidine, sulfoxaflor and other insecticides, and the composition is used for testing the activity of the aphid in the salicornia constricta
Target: and (4) feeding the Sinocystis aurantiaca indoors.
The method comprises the following steps: and (3) an immersion method. The operation is described as follows: cabbage leaf disks were prepared and the petioles were moistened with cotton balls. If aphid preparation: 5 aphids are inoculated to each dish, the adult aphids are removed after 24 hours, and leaf dishes with more than 15 aphids are selected for the test before the test. The treatment method comprises the following steps: the leaf discs (with aphids) were immersed in the solution for 10s, 3 times. Culturing and investigating after treatment: placing in a light incubator at 25 deg.C under 14hL:10hD for culture. The number of dead aphids is investigated 3 days after the pesticide application, and the death rate is calculated.
Evaluation method in the same manner as in production example 2.
As shown in table 16, it can be seen from the results that the effective components a, compound 2, compound 3, compound 6, compound 8, compound 10 and compound 14, had excellent activity against the aphid of the leaf-roller aphid; when the effective components B are thiamethoxam, trifluoro-benzene pyrimidine and sulfoxaflor, the pesticide has better activity on the aphid of the sinonovacula constricta; when a is combined with B, the combined effect appears to be synergistic.
TABLE 16 insecticidal Activity of test Agents against Sinonovacula constricta
Test agent or combination name
Dosage mg/L
3d mortality%
Theoretical mortality%
Synergistic effect
Mode of combined action
Compound 2
10
55.62
Compound 3
10
75.69
Compound 6
10
60.07
/
/
/
Compound 8
10
71.55
/
/
/
Compound 10
10
78.29
/
/
/
Compound 14
10
76.83
Thiamethoxam
0.4
73.22
/
/
/
Trifluorophenylpyrimidines
4.0
55.86
/
/
/
Sulfoxaflor
0.05
45.12
/
/
/
Compound 2+ trifluoro-phenylpyrimidine
10+4.0
100
80.85
19.15
Efficiency enhancement
Compound 3+ trifluoro-benzene pyrimidine
10+4.0
100
89.27
10.73
Efficiency enhancement
Compound 6+ thiamethoxam
10+0.4
100
89.30
10.70
Efficiency enhancement
Compound 8+ trifluoro-phenylpyrimidine
10+4.0
100
87.44
12.56
Efficiency enhancement
Compound 10+ sulfoxaflor
10+0.05
100
88.09
11.91
Efficiency enhancement
Compound 14+ sulfoxaflor
10+0.05
100
87.28
12.72
Efficiency enhancement
Bioassay example 4: the active ingredient A is a compound shown in the formula II and the active ingredient B is a composition of pesticides such as trifluoro-benzene pyrimidine, cycloxaprid, flurbiprofuranone and the like, and the activity test of the pesticide on rice stem borer is carried out
Target: and (4) feeding chilo suppressalis 3-instar larvae indoors.
The method comprises the following steps: chilo suppressalis rice stem soaking method.
The method comprises the following steps: example 1 was assayed contemporaneously; evaluation method example 2 was evaluated in the same manner as the standard.
The results are shown in table 17, and it can be seen from the results that when the active ingredient a is compound 5, compound 7, compound 9, compound 10, compound 11, compound 12, compound 13, it has excellent activity against chilo suppressalis; when the effective components B are trifluorobenzene pyrimidine, fluoropyrazine and cycloxaprid, the composition has better activity on chilo suppressalis; when a is combined with B, the combined effect appears to be synergistic or significant synergistic.
TABLE 17 insecticidal Activity of the test Agents against Chilo suppressalis indoors
Test agent or combination name
Dosage mg/L
3d mortality%
Theoretical mortality%
Synergistic effect
Mode of combined action
Compound 5
1.0
63.33
/
/
/
Compound 7
0.5
50.00
/
/
/
Compound 9
1.0
66.67
/
/
/
Compound 10
0.7
50.00
/
/
/
Compound 11
1.0
56.67
/
/
/
Compound 12
1.0
56.67
/
/
/
Compound 13
0.5
33.33
/
/
/
Trifluorophenylpyrimidines
10
56.67
/
/
/
Fluopyrafuranones
40
76.67
/
/
/
Cycloxaprid
100
73.33
/
/
/
Compound 5+ trifluoro-benzene pyrimidine
1.0+10
100
84.11
15.89
Efficiency enhancement
Compound 7+ trifluorobenzene pyrimidinePyridine (I)
0.5+10
100
78.33
21.67
Significant synergy
Compound 9+ trifluoro-phenylpyrimidine
1.0+10
100
85.56
14.44
Efficiency enhancement
Compound 12+ trifluoro-phenylpyrimidine
1.0+10
100
85.56
14.44
Efficiency enhancement
Compound 13+ trifluorobenzene pyrimidine
0.5+10
100
71.12
28.89
Significant synergy
Compound 10+ Fluopyranone
0.7+40
100
88.33
11.67
Efficiency enhancement
Compound 11+ epoxyInsect pyridine
1.0+100
100
88.44
11.56
Efficiency enhancement
Bioassay example 5: composition with active ingredient A, formula II compound and active ingredient B being bactericides such as prothioconazole, tebuconazole and the like, and activity test on wheat powdery mildew
Target: wheat powdery mildew, indoor living body preservation of strains.
The method comprises the following steps: and (4) a potted plant spraying method. Spraying, inoculating, culturing and investigating. Wheat seedlings were placed on a bioassay spray tower turntable (frequency was set to F35, i.e., 14 rpm), and the agent was uniformly sprayed on the prepared wheat seedlings with a throat sprayer, 3 pots of wheat were treated each. Spraying 12mL of each treatment liquid medicine; and (5) placing the mixture indoors for natural drying. The same medicament is applied from low concentration to high concentration in sequence. Before application and between different medicines, the rotary disc of the spray tower, the liquid storage cup of the throat sprayer and the spray head are cleaned for 3 times respectively. And (3) uniformly shaking off powdery mildew spores generated on the infected wheat leaves after about 10 days after the inoculation for 24 hours after the treatment of the medicament, inoculating the powdery mildew spores on potted wheat seedlings, and culturing in a culture room at 18-22 ℃ with the illumination period of 14h/10 h. At 12d after inoculation, investigation was performed after the control disease was stable, for 1 total time. The disease index of the first leaf at the stem base of all plants in each pot is investigated, and the classification method is as follows: level 0: no disease; level 1: the area of the lesion spots accounts for less than 5% of the area of the whole leaf; and 3, level: the area of the lesion spots accounts for less than 6-15% of the area of the whole leaf; and 5, stage: the area of the lesion spots accounts for less than 16-25% of the area of the whole leaf; and 7, stage: the area of the lesion spots accounts for less than 26-50% of the area of the whole leaf; and 9, stage: the area of the lesion spots accounts for more than 50 percent of the area of the whole leaf.
Evaluation method example 2 was evaluated in the same manner as the standard.
The results are shown in table 18, and it can be seen from the results that when the active ingredient a was compound 1 or compound 8, it was inactive against wheat powdery mildew; when the effective component B is prothioconazole and tebuconazole, the compound has excellent activity on wheat powdery mildew; when A and B are combined, the combined action is shown as addition, and the composition can be compounded or mixed in a barrel, so that the prevention and treatment spectrum is expanded, and the medication times are reduced.
TABLE 18 bactericidal Activity of test Agents against wheat powdery mildew indoors
Bioassay example 6: the composition of the compound with the effective component A as the formula II and the bactericide with the effective component B as trifloxystrobin, pyraclostrobin and the like is used for the activity test of the rice blast
Target: rice blast, and indoor preservation of strain.
The method comprises the following steps: and (4) a potted plant spraying method. Spraying, inoculating, culturing and investigating. Medicament treatment: placing 3 pots of seedlings to be treated in the center of a rotary disc of a circular bioassay spraying tower, setting the rotating frequency f of the rotary disc to be 35(14 revolutions per minute), uniformly spraying the prepared liquid medicine (10mL per treatment) on the leaf surfaces of the rice by using a throat sprayer (the pressure is 0.15MPa), and naturally drying the liquid medicine. Each treatment had 3 pots and a blank control was set. Spore suspension preparation: carrying out spore production culture on a rice bran culture medium for about 5 days on a rice blast fungus flat plate, washing spores by using a spore eluent (0.1% Tween + 1% glucose + 0.4% yeast extract), filtering by using 2-4 layers of gauze, counting the rice blast fungus spores by using a blood counting plate under a microscope with a 10-fold microscope, calculating and diluting the concentration of the spores to 106And (4) preparing spore suspension for later use. Inoculation and culture: after the medicament is treated for 24 hours, uniformly inoculating a spore suspension with a throat sprayer (pressure of 0.15MP) with the inoculation amount of 30mL/24 potted seedlings, transferring the inoculated seedlings into a moisturizing box, spraying 40mL of eluent into the moisturizing box by using the throat sprayer to increase the humidity of the moisturizing box (ensuring that the relative humidity in the moisturizing box is 100 percent and the dew condensation on the leaf surface is kept), setting the temperature of an artificial climate chamber to be 28 ℃, shading by using black cloth, moisturizing and culturingAnd (5) cultivating for 24 hours. Then culturing for 5-7 d in a moisture-preserving box with 28 ℃ and 85% -90% of relative humidity for 12h in light/dark. Investigation time: after treatment, the disease incidence condition (the disease leaf rate is more than 50%) is investigated according to blank control 5-7 days, and the investigation is carried out for 1 time. The investigation method comprises the following steps: the total number of plants was investigated for each treatment, and the 1 st leaf from the last was investigated for each plant. The grading method of rice blast comprises the following steps: level 0: the whole plant is disease-free; level 1: brown spot lesions (1-5 lesions); and 3, level: typical fusiform disease spots appear, and the area of the disease spots accounts for less than 5 percent of the area of the whole leaf (5-10 disease spots); and 5, stage: typical scabs, the area of the scab accounts for 6-25% of the whole leaf area (11-16 scabs); and 7, stage: typical scabs, the area of the scab accounts for 26-50% of the whole leaf area (16-25 scabs); and 9, stage: typical lesions, the lesion area accounts for more than 50% of the whole leaf area (more than 25 lesions).
Evaluation method example 2 was evaluated in the same manner as the standard.
As shown in Table 19, it was found from the results that the active ingredients A were Compound 8 and Compound 10, which were inactive against rice blast; when the effective component B is trifloxystrobin and pyraclostrobin, the composition has excellent activity on rice blast; when A and B are combined, the combined action is shown as addition, and the composition can be compounded or mixed in a barrel, so that the prevention and treatment spectrum is expanded, and the medication times are reduced.
TABLE 19 fungicidal Activity of the test Agents against Rice blast in the Room
Bioassay example 7: the composition of the compound with the effective component A as the formula II and the bactericides such as prothioconazole, phenamacril and the like as the effective component B is used for testing the activity of wheat scab
Target: wheat scab, indoor preservation of the strain.
The method comprises the following steps: the plate method. Operation is with reference to NY/T1156.2-2006.
Evaluation method example 2 was evaluated in the same manner as the standard.
As shown in Table 20, it was found that the compounds (4) and (6) as the active ingredient A had no activity against wheat scab; when the effective components B are prothioconazole and phenamacril, the compound has excellent activity on wheat scab; when A and B are combined, the combined action is shown as addition, and the composition can be compounded or mixed in a barrel, so that the prevention and treatment spectrum is expanded, and the medication times are reduced.
TABLE 20 fungicidal Activity of the test Agents against wheat scab in the laboratory
Test agent or combination name
Dosage (mg/L)
Actual control effect%
Theoretical control effect%
Synergistic effect
Mode of combined action
Compound 4
0.05
0
Compound 4
0.5
0
Compound 6
40
0
Compound 6
400
0
Prothioconazole
4
80
Cyanostrobin
5
60
Compound 4+ prothioconazole
0.05+4
85
80
5
Adding
Compound 4+ prothioconazole
0.5+4
85
80
5
Adding
Compound 6+ Cyanoxastrobin
40+5
65
60
5
Adding
Compound 6+ Cyanoxastrobin
400+5
65
60
5
Adding
Compound 6+ prothioconazole + cyhalothrin
0.5+4+5
95
92
3
Adding
Bioassay example 8: when the effective component A is the compound 4 and the effective component B is the cycloxaprid, the composition has synergistic effect on the brown planthopper
The method comprises the following steps: soaking rice seedling. Reference is made to NY/T1154.11-2008.
Testing a target: brown planthopper, 3-year-old nymph.
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, the mixture is placed in an illumination incubator at the temperature of 28 +/-1 ℃ and the light-dark ratio of 15h to 9 h. And (4) investigating a result: the number of dead insects was investigated 3d after the administration. Data processing: using DPS (v16.05) statistical analysis software, LC of each drug was calculated50The values and their 95% confidence limits.
The evaluation method was carried out by the co-toxicity factor with reference to NY/T1154.7-2006.
The co-toxicity coefficient (CTC value) of the mixture is calculated according to the formula (1), the formula (2) and the formula (3):
in the formula: ATI-actual virulence index of the mixture;
S-LC of Standard drug50In milligrams per liter (mg/L);
M-LC of test Agents50In milligrams per liter (mg/L).
TTI＝A×PA+B×PB·····················(2)
In the formula: TTI-theoretical virulence index of the mixture;
A-A agent actual virulence index;
PA-the percentage of agent a in the mixture in percent (%);
b-actual virulence index of agent B;
PBthe percentage of the agent B in the mixture is given in percentage (%).
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) of the compound agent is more than or equal to 120, which 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 21, and it can be seen from the results that both compound 4 and cycloxaprid have better activity against brown planthopper; the two are compounded, the synergistic coefficient of each proportion of 160: 1-1: 160 is 91.24-237.55, and the synergistic coefficient shows additive or synergistic effect; the composition shows a synergistic effect in a ratio of 80:1-1: 80.
TABLE 21 Co-toxicity of Compound 4 and Cycloxaprid against Nilaparvata lugens
Bioassay example 9: the composition of the compound 7 as the effective component A and the thiamethoxam as the effective component B has synergistic effect on aphids.
The method comprises the following steps: method for soaking insects
Target: alfalfa aphid, 3 day old nymph.
Method operation with reference to bioassay example 3, pharmaceutical agent treatment: soaking nymph leaves in the liquid medicine for 10s, inserting the nymph leaves into a penicillin bottle filled with clear water, sealing, airing, covering with a transparent plastic cup, and repeating the steps for 3 times when 15-30 aphids are repeated. 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, the culture rack is placed in an observation room with the indoor temperature of 19-26 ℃, the humidity of 35-65% and the illumination of 14Lh at 10Dh for observation.
Evaluation, example 8 was measured in the same manner.
The results are shown in table 22, and it can be seen from the results that both compound 7 and thiamethoxam have better activity against aphis medicaginis; the compound 7 and the thiamethoxam are compounded, the synergistic coefficient of each mixture ratio is 83.14-136.22 in a ratio of 50: 1-1: 10, and the synergistic coefficient shows additive or synergistic effect; the composition shows a synergistic effect when the ratio is 5: 1-25: 1.
TABLE 22 Co-toxicity coefficients of Compound 7 and thiamethoxam against S.lucerne
Bioassay example 10: when the effective component A is the compound 8 and the effective component B is the fluopyram, the synergistic effect on the brown planthopper can be achieved.
The method comprises the following steps: soaking rice seedling. The same procedure is followed as in example 8.
Testing a target: brown planthopper, 3-year-old nymph.
The results are shown in table 23, and it can be seen from the results that both compound 8 and flupyradifurone have better activity against brown planthopper; the two are compounded, the synergistic coefficient of each mixture ratio of 120: 1-1: 120 is 98.37-271.44, and the synergistic coefficient shows additive or synergistic effect; the composition shows a synergistic effect in a ratio of 60:1-1: 60.
TABLE 23 Co-toxicity of Compound 8 and Fluopyranone against Nilaparvata lugens
Bioassay example 11: when the effective component A is the compound 7 and the effective component B is the pymetrozine, the synergistic effect on the brown planthopper is achieved.
The method comprises the following steps: soaking rice seedling. The same procedure is followed as in example 8.
Testing a target: brown planthopper, 3-year-old nymph.
The results are shown in table 24, and it can be seen from the results that both compound 7 and pymetrozine have better activity against brown planthopper; the two are compounded, the synergistic coefficient of each proportion of 100: 1-1: 100 is 91.24-237.55, and the synergistic coefficient shows additive or synergistic effect; the composition shows a synergistic effect in a ratio of 50: 1-1: 50.
TABLE 24 Co-toxicity of Compound 7 and pymetrozine against Nilaparvata lugens
Bioassay example 12: when the effective component A is the compound 1 and the effective component B is the imidazopyridine dichloride, the activity test on the plutella xylostella is carried out
The method comprises the following steps: leaf-dipping dish feeding method, in the same operation as in example 1, evaluation of example 8.
Target: 3 rd larva of diamondback moth.
The results are shown in table 25, and it can be seen from the results that both compound 1 and pyrantel chloride have better activity against vegetable diamond back moths; the two are compounded, the synergistic coefficient of each mixture ratio of 120: 1-1: 120 is 90.30-186.10, and the synergistic coefficient shows additive or synergistic effect; the composition shows a synergistic effect in a ratio of 80:1-1: 80.
TABLE 25 Activity assay of Compound 1 and Dithiopyrantel against Plutella xylostella
Bioassay example 13: when the effective component A is the compound 7 and the effective component B is the dicyclopropyl tetramisole, the synergistic effect on vegetable aphids is achieved.
The method comprises the following steps: dipping method, in-situ test example 9 was conducted, and in-situ test example 8 was evaluated.
Target: 3-day-old Myzus lucerne.
The results are shown in table 26, and it can be seen from the results that both compound 7 and dicyclopropyl imidacloprid have better activity on aphis medicaginis; the two are compounded, the synergistic coefficient of each mixture ratio of 120: 1-1: 120 is 86.17-230.53, and the synergistic coefficient shows additive or synergistic effect; the composition shows a synergistic effect in a ratio of 80:1-1: 80.
TABLE 26 Activity assay of Compound 7 and Cycloprolide on Adenophora cerifera
The applicant states that the present invention is illustrated by the above examples to the pharmaceutical composition containing the isophthalamide and the application thereof, but the present invention is not limited by the above examples, i.e. it does not mean that the present invention must be implemented by the above examples. 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.
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