阅读说明：本技术 一种双酰胺类化合物及其应用 (Bisamide compound and application thereof ) 是由 张立新 张静 汪杰 裴鸿艳 盛祝波 康卓 于 2020-08-24 设计创作，主要内容包括：本发明公开了一种双酰胺类化合物及其应用,所述化合物结构如通式I所示：式中各取代基的定义见说明书；说明书还公开了其作为杀虫剂和动物寄生虫防治剂的用途。(The invention discloses a bisamide compound and application thereof, wherein the structure of the compound is shown as a general formula I:)

1. A bisamide compound is shown as a general formula I:

in formula I:

R₁selected from halogens;

R₂selected from halogen, C₁-C₄Haloalkyl or C₁-C₄A haloalkoxy group;

R₃selected from CF₃Or CF₂CF₃；

R₄Selected from fluoro, difluoromethyl, trifluoromethyl or cyano.

2. The compound of claim 1, wherein: in the general formula I

R₁Selected from halogens;

R₂selected from halogen, C₁-C₂Haloalkyl or C₁-C₂A haloalkoxy group;

R₃selected from CF₃Or CF₂CF₃；

R₄Selected from fluoro, difluoromethyl, trifluoromethyl or cyano.

3. The compound of claim 2, wherein: in the general formula I

R₁Selected from bromine or iodine;

R₂selected from bromo, iodo, trifluoromethyl or difluoromethoxy;

R₃selected from CF₃Or CF₂CF₃；

R₄Selected from fluoro, difluoromethyl, trifluoromethyl or cyano.

4. The bisamide-based compound according to any one of claims 1 to 3, wherein: in the general formula I

R₄Selected from fluorine, difluoromethyl or trifluoromethyl.

5. The bisamide-based compound according to claim 1, wherein the bisamide-based compound is selected from the group consisting of:

the compounds of Table 1, the compounds of Table 1 have the structure as shown in formula I and R₁、R₂、R₃And R₄As shown in table 1;

TABLE 1

。

6. The bisamide-based compound according to claim 5, wherein the bisamide-based compound is selected from the group consisting of:

the compounds of Table 2, the compounds of Table 2 having the structure of formula I and R₁、R₂、R₃And R₄As shown in table 2;

TABLE 2

。

7. An intermediate compound for preparing the bisamide compound of claim 1, wherein the intermediate compound is represented by the general formula II:

in formula II:

R₁selected from halogens;

R₂selected from halogen, C₁-C₄Haloalkyl or C₁-C₄A haloalkoxy group;

R₃selected from CF₃Or CF₂CF₃。

8. The intermediate compound of claim 7, wherein: in the general formula II

R₁Selected from halogens;

R₂selected from halogen, C₁-C₂Haloalkyl or C₁-C₂A haloalkoxy group;

R₃selected from CF₃Or CF₂CF₃。

9. The intermediate compound of claim 8, wherein: in the general formula II

R₁Selected from bromine or iodine;

R₂selected from bromo, iodo, trifluoromethyl or difluoromethoxy;

R₃selected from CF₃Or CF₂CF₃。

10. Intermediate compound according to claim 9, characterized in that the intermediate compound is selected from:

the compounds of Table 3, the compounds of Table 3 having the structure of formula II and R₁、R₂And R₃As shown in table 3;

TABLE 3

。

11. An intermediate compound for preparing the bisamide compound of claim 1, wherein the compound is represented by the general formula III:

in formula III:

R₄selected from fluoro, difluoromethyl, trifluoromethyl or cyano;

l is selected from halogen or hydroxyl.

12. Intermediate compound according to claim 11, characterized in that the intermediate compound is selected from:

the compounds of Table 4, the compounds of Table 4 having the structure of formula III and R₄And L is as shown in table 4;

TABLE 4

。

13. Use of bisamide compounds according to any one of claims 1 to 6 for the preparation of insecticides.

14. Use according to claim 13, characterized in that: the pesticide is used for preventing and controlling one or more of armyworm, diamondback moth and chilo suppressalis.

15. An insecticide formulation characterized by: the pesticide preparation contains the bisamide compound as an active component according to any one of claims 1 to 6, and also contains one or more auxiliary materials; alternatively, the bisamide compound according to any one of claims 1 to 6 is present in the pesticide preparation in an amount of 0.1 to 99% by weight, further alternatively 0.5 to 90% by weight.

16. An insecticide composition characterized by: a mixture comprising the bisamide compounds according to any one of claims 1 to 6 and further active compounds selected from one or more of insecticides, baits, disinfectants, acaricides, nematicides, fungicides, growth regulators, herbicides.

17. A method of controlling agricultural or forestry pests, comprising: applying an effective amount of a material to a pest or its growth medium in need of control, the material being selected from one or more of the following:

the bisamide-based compound according to any one of claims 1 to 6;

the pesticide formulation of claim 15;

the insecticide composition of claim 16.

18. Use of bisamide-based compounds according to any one of claims 1 to 6 for the preparation of an animal parasite control agent.

19. Use according to claim 18, characterized in that: the animal parasite control agent is used to control one or more of cat fleas, American dog ticks.

20. An animal parasite control agent characterized by: the animal parasite control agent contains the bisamide-based compound according to any one of claims 1 to 6 as an active ingredient, and further contains one or more auxiliary materials; alternatively, the bisamide-based compound as described in any one of claims 1 to 6 in the animal parasite control agent is in an amount of 1 to 80% by weight.

21. An animal parasite control composition, characterized by: a mixture comprising the bisamide compounds according to any one of claims 1 to 6 and a further animal parasite control active compound selected from one or more of an acaricide, an insecticide, a parasiticide, an plasmodium repellent.

22. A method of controlling parasites on animals comprising: the method comprises the following steps: administering to an animal parasite or its growth medium in need of control an effective amount of a material selected from one or more of the group consisting of:

the bisamide-based compound according to any one of claims 1 to 6;

the animal parasite control agent of claim 20;

the animal parasite control composition of claim 21.

Technical Field

The invention relates to a compound, in particular to a novel bisamide compound and application thereof.

Background

Bisamide insecticides have been popular products in the market since the advent of the market, and represent varieties such as flubendiamide and chlorantraniliprole; however, the problem of resistance is becoming more acute due to the long term use of large amounts of currently available agents. On the other hand, the insecticidal effect of the existing insecticide is still unsatisfactory especially on the activity of rice stem borer, and the continuously improved use requirement of the insecticide in reality is difficult to meet. There is still a need in the art to actively develop new insecticides with higher activity to meet the needs of agriculture and other fields.

The compounds shown in the general formula I and the insecticidal activity thereof in the prior art are not reported.

Disclosure of Invention

The invention aims to provide a bisamide compound with more excellent insecticidal activity. It can be used for preparing medicaments for controlling pests in agriculture and other fields and for preparing medicaments for controlling animal parasites in the field of veterinary medicaments.

In order to realize the purpose of the invention, the invention provides the following technical scheme:

a bisamide compound is shown as a general formula I:

in formula I:

R₁selected from halogens;

R₂selected from halogen, C₁-C₄Haloalkyl or C₁-C₄A haloalkoxy group;

R₃selected from CF₃Or CF₂CF₃；

R₄Selected from fluoro, difluoromethyl, trifluoromethyl or cyano.

In one possible implementation, in formula I,

R₁selected from halogens;

R₂selected from halogen, C₁-C₂Haloalkyl or C₁-C₂A haloalkoxy group;

R₃selected from CF₃Or CF₂CF₃；

R₄Selected from fluoro, difluoromethyl, trifluoromethyl or cyano.

In one possible implementation, in formula I,

R₁selected from bromine or iodine;

R₂selected from bromo, iodo, trifluoromethyl or difluoromethoxy;

R₃selected from CF₃Or CF₂CF₃；

R₄Selected from fluoro, difluoromethyl, trifluoromethyl or cyano.

In one possible implementation, in formula I,

R₄selected from fluorine, difluoromethyl or trifluoromethyl.

In one possible implementation mode, the bisamide compound is selected from the compounds in table 1, the compounds in table 1 have the structure shown as the general formula I, and R₁、R₂、R₃And R₄As shown in table 1:

TABLE 1

。

In one possible implementation, the bisamide compounds are selected from the compounds in table 2, the compounds in table 2 have the structure shown as the general formula I, and R is₁、R₂、R₃And R₄As shown in table 2:

TABLE 2

。

An intermediate compound for preparing the bisamide compound of claim 1, wherein the intermediate compound is represented by the general formula II:

in formula II:

R₁selected from halogens;

R₂selected from halogen, C₁-C₄Haloalkyl or C₁-C₄A haloalkoxy group;

R₃selected from CF₃Or CF₂CF₃。

In one possible implementation, in formula II,

R₁selected from halogens;

R₂selected from halogen, C₁-C₂Haloalkyl or C₁-C₂A haloalkoxy group;

R₃selected from CF₃Or CF₂CF₃。

In one possible implementation, in formula II,

R₁selected from bromine or iodine;

R₂selected from bromo, iodo, trifluoromethyl or difluoromethoxy;

R₃selected from CF₃Or CF₂CF₃。

In one possible implementation, the intermediate compound of formula II is selected from the compounds of table 3, said compound of table 3 having a structure as in formula II and R₁、R₂And R₃As shown in table 3:

TABLE 3

。

An intermediate compound for preparing the bisamide compound of claim 1, wherein the compound is represented by the general formula III:

in formula III:

R₄selected from fluoro, difluoromethyl, trifluoromethyl or cyano;

l is selected from halogen or hydroxyl.

In one possible implementation, the intermediate compound of formula III is selected from the compounds of table 4, said compounds of table 4 having a structure as in formula III and R₄And L is as shown in table 4:

TABLE 4

。

The embodiment of the invention also provides a preparation method of the bisamide compounds, and the compounds in the general formulas I, II and III can be prepared according to the following method (all groups in the formula are defined as the same as the previous groups except for other indications):

the method comprises the following steps:

reacting the compound of the general formula IV with bromomethyl cyclopropane in a proper solvent at the temperature of between 10 ℃ below zero and the boiling point of the solvent for 0.5 to 48 hours to obtain a compound of a general formula II, wherein the reaction can be carried out in the presence of alkali; the compound of the general formula I can be prepared by reacting the compound of the general formula II with the compound of the general formula V in a suitable solvent at the temperature of between 10 ℃ below zero and the boiling point of the solvent for 0.5 to 48 hours, and the reaction can be carried out in the presence of alkali.

In one possible implementation, the solvent includes: aromatic hydrocarbons such as benzene, toluene, and xylene, ketones such as acetone, methyl ethyl ketone, and methyl isobutyl ketone, halogenated hydrocarbons such as chloroform and methylene chloride, esters such as methyl acetate and ethyl acetate, ethers such as tetrahydrofuran, dioxane, diethyl ether, and 1, 2-dimethoxyethane, polar solvents such as water, acetonitrile, N-dimethylformamide, N-methylpyrrolidone, and dimethyl sulfoxide, or a mixed solvent of the above solvents. The base comprises: organic bases such as triethylamine, pyridine, DBU, and 4-dimethylaminopyridine, alkali metal hydrides such as sodium hydride and potassium hydride, alkali metal hydroxides such as sodium hydroxide and potassium hydroxide, alkali earth metal hydroxides such as calcium hydroxide, alkali metal carbonates such as sodium carbonate and potassium carbonate, alkali metal bicarbonates such as sodium bicarbonate, and metal alkoxides such as sodium methoxide, sodium ethoxide, potassium tert-butoxide, and sodium tert-butoxide.

The compounds of formula IV can be prepared according to known methods, for example, by methods reported in WO20110201687, WO2011093415, WO2005021488, WO2005073165, WO2006137395, JP2007099761, WO2008000438, WO2008074427, WO2008107091, WO2010013567, WO2010018714, WO2010090282, WO2010127926, WO2010127928, JP2011063549, WO2012020483, WO2012020484, WO2012077221, WO2012164698, WO 2013050260260261, WO2014069665, WO2014067838, WO2014161848, WO2014161850, WO2015097091 or WO 2015097094; the compounds of formula V and other reagents are generally commercially available or may be prepared by conventional methods.

(1) Preparation of Compounds of formula VI and VII

Reacting methyl 3-amino-2-fluorobenzoate with bromomethylcyclopropane in a suitable solvent at a temperature of from-10 ℃ to the boiling point of the solvent for 0.5 to 48 hours to obtain a compound of the general formula VI, wherein the reaction can be carried out in the presence of a base; the compound of formula VI is reacted with the compound of formula V in a suitable solvent at a temperature of from-10 ℃ to the boiling point of the solvent for 0.5 to 48 hours to produce the compound of formula VII, which can be carried out in the presence of a base.

In one possible implementation, the solvent includes: aromatic hydrocarbons such as benzene, toluene, and xylene, ketones such as acetone, methyl ethyl ketone, and methyl isobutyl ketone, halogenated hydrocarbons such as chloroform and methylene chloride, esters such as methyl acetate and ethyl acetate, ethers such as tetrahydrofuran, dioxane, diethyl ether, and 1, 2-dimethoxyethane, polar solvents such as water, acetonitrile, N-dimethylformamide, N-methylpyrrolidone, and dimethyl sulfoxide, or a mixed solvent of the above solvents. The base comprises: organic bases such as triethylamine, pyridine, DBU, and 4-dimethylaminopyridine, alkali metal hydrides such as sodium hydride and potassium hydride, alkali metal hydroxides such as sodium hydroxide and potassium hydroxide, alkali earth metal hydroxides such as calcium hydroxide, alkali metal carbonates such as sodium carbonate and potassium carbonate, alkali metal bicarbonates such as sodium bicarbonate, and metal alkoxides such as sodium methoxide, sodium ethoxide, potassium tert-butoxide, and sodium tert-butoxide.

(2) Preparation of Compounds of formula III-1 and Compounds of formula III-2

The compound of formula VII can be hydrolyzed to obtain the compound of formula III-1 in the presence of alkaline substance at the temperature of-10 ℃ to the boiling point of the solvent for 0.5-48 hours. In one possible implementation, the base comprises: sodium carbonate, potassium carbonate, lithium hydroxide, sodium hydroxide, or potassium hydroxide; the solvent comprises: any one or a mixed solvent of at least two of water, methanol, ethanol, tetrahydrofuran and dioxane.

The compound of the general formula III-2 can be prepared by reacting the compound of the general formula III-1 with thionyl chloride, oxalyl chloride, carbonyl chloride, phosphorus oxychloride, phosphorus pentachloride, phosphorus trichloride, triphosgene and the like by a known method.

(3) Preparation of the Compounds of the formula I

The compound of the general formula I can be prepared by reacting the compound of the general formula III-1 or the compound of the general formula III-2 with the compound of the general formula VIII in a suitable solvent at a temperature of between-70 ℃ and the boiling point of the solvent for 0.5 to 48 hours, and the reaction can be carried out in the presence of alkali.

In one possible implementation, the solvent includes: aromatic hydrocarbons such as benzene, toluene, and xylene, ketones such as acetone, methyl ethyl ketone, and methyl isobutyl ketone, halogenated hydrocarbons such as chloroform and methylene chloride, esters such as methyl acetate and ethyl acetate, ethers such as tetrahydrofuran, dioxane, diethyl ether, and 1, 2-dimethoxyethane, polar solvents such as water, acetonitrile, N-dimethylformamide, N-methylpyrrolidone, and dimethyl sulfoxide, or a mixed solvent of the above solvents. The base comprises: organic bases such as trimethylamine, triethylamine, diisopropylethylamine, tri-n-butylamine, pyridine, DBU, and 4-dimethylaminopyridine, alkali metal hydrides such as sodium hydride and potassium hydride, alkali metal hydroxides such as sodium hydroxide and potassium hydroxide, alkaline earth metal hydroxides such as calcium hydroxide, alkali metal carbonates such as sodium carbonate and potassium carbonate, alkali metal hydrogencarbonates such as sodium hydrogencarbonate, and metal alkoxides such as sodium methoxide, sodium ethoxide, potassium tert-butoxide, and sodium tert-butoxide.

The embodiment of the invention also provides application of the bisamide compound in preparation of an insecticide.

In one possible implementation, the insecticide is used to control one or more of the following insects:

beetles (Coleopteran), such as the green bean (Callosobruchus Chinensis), corn (Sitophilus zeamais), Tribolium Castaneum (Tribolium Castaneum), calabash (epilaeachothamella), kowter (agriotica grossedentata), polychrome beetle (Anomala rubra), potato beetle (leptotamus decemlineata), Diabrotica spp (Diabrotica spp), Monochamus alternatus (Monochamus alternatus), rice root (lissorophus oryzae), brown powder (lycotus brunneus);

lepidopteran (lepidopteran) pests, for example, gypsy moth (Lymantria dispar), Trichoplusia lutea (Malacomonas neustria), Pieris rapae subspecies Japan (Pieris rapae cruvora), Spodoptera litura (Spodoptera litura), cabbage looper (Mamestra brassicae), Chilo supressalis (Chilo supressalis), European corn borer (Ostrinia nubilalis), Kalophaga medinalis (Cadra caudaella), Chyanokakkumura (Adoxophyceae honmai), apple leaf roller (Cydia pomonella), yellow cutworm (Agrotis segetum), Heliotis incertus (Galleria mellonella), cabbage moth (Plutella xylostella), tobacco bud (Heliothis virescens), and Crypthecodinia punctata (Phlebia punctifera);

hemiptera (Hemipterous) pests, for example, leafhopper melanogaster (Nephotettix cincticeps), brown planthopper (Nilaparvata lugens), mealybugs conoidea (Pseudococcus comstocki), arrowhead (Unaspis yanonensis), green peach aphid (Myzus persicas), apple aphid (Aphis pomi), cotton aphid (Aphis gossypii), radish aphid (liparis physmii), cercospora pyricularis (stephanis nashi), green Chinese toona (Nezara spp.), green house whitefly (greenhouse whitefly), and pseudolla spp.;

pests of the order Thysanoptera (Thysanoptera), such as Thrips palmi (Thrips palmi), Thrips occidentalis (Franklinella occidentalis);

orthopteran pests such as mole cricket in africa (Gryllotalpa Africana), Locusta migratoria (Locusta);

pests of the order blattaria (blattaria), such as the german cockroach (blattaria germanica), the american cockroach (Periplaneta americana), the yellow mealworm (rotigotermes speratus), the domesticated termite (coptottermes formosanus);

diptera (Dipterous) pests, for example, houseflies (Musca domestica), Aedes aegypti (Aedesaegypti), Musca grisea (Delia platura), Culex pipiens pallens (Culex pipiens pallens), Anopheles sinensis (Anopheles sinensis), Culex tritaeniorhynchus (Culex tritaeniorhynchus), Liriomyza trifolii (Liriomyza trifolii), etc.

Agricultural harmful mites, such as Tetranychus cinnabarinus (Tetranychus cinnabarinus), Tetranychus urticae (Tetrahychus urticae), Panonychus citri (Panychus citri), Denychus citri (Aculops pelekassi), Tarsonemus spp.

In one possible implementation mode, the pesticide is used for controlling one or more of armyworm, plutella xylostella and chilo suppressalis.

The embodiment of the invention also provides an insecticide preparation, which contains the bisamide compound as an active component and one or more auxiliary materials.

In one possible implementation, the insecticide formulation is selected from the following dosage forms: solutions, emulsions, wettable powders, granulated wettable powders, suspensions, powders (powder), foams, pastes, tablets, granules, aerosols, natural agents impregnated with active compounds, synthetic agents impregnated with active compounds, microcapsules, seed coatings, formulations equipped with combustion devices which can be smokers and fogs, pots and coils, etc., and ULVs (cold fogging, hot fogging), etc. These insecticide preparations or animal parasite control agents can be prepared by known methods, for example by mixing the active ingredient with extenders, such as liquid diluents or carriers, liquefied gas diluents or carriers, solid diluents or carriers, and optionally with surfactants, i.e. emulsifiers and/or dispersants and/or foaming agents, and the like.

In one possible implementation, the auxiliary material includes one or more of the following: fillers (e.g., liquid diluents or carriers, liquefied gas diluents or carriers, solid diluents or carriers), surfactants (e.g., emulsifiers and/or dispersants and/or foaming agents), binders, colorants;

the liquid diluent or carrier may include, for example, aromatic hydrocarbons (xylene, toluene, alkylnaphthalenes, etc.), chlorinated aromatic or chlorinated aliphatic hydrocarbons (e.g., chlorobenzene, vinyl chloride, methylene chloride, etc.), aliphatic hydrocarbons (e.g., cyclohexane or paraffin (e.g., mineral oil fractions)), alcohols (e.g., butanol, ethylene glycol, and ethers or esters thereof, etc.), ketones (e.g., acetone, methyl ethyl ketone, methyl isobutyl ketone, cyclohexanone, etc.), strongly polar solvents (e.g., dimethylformamide, dimethyl sulfoxide), water, and the like. When water is used as the filler, for example, an organic solvent may be used as a co-solvent;

liquefied gas diluents or carriers can include those that exist in gaseous form at atmospheric pressure and temperature, e.g., propane, nitrogen, carbon dioxide, and aerosol propellants such as halogenated hydrocarbons;

solid diluents may include crushed natural minerals (e.g., kaolin, clay, talc, chalk, quartz, attapulgite, montmorillonite or diatomaceous earth, etc.) as well as crushed synthetic minerals (e.g., finely divided silicic acid, alumina, silicates, etc.), and the like;

emulsifiers and/or foaming agents may include nonionic and anionic emulsifiers [ e.g., polyoxyethylene fatty acid esters, polyoxyethylene fatty acid alcohol ethers (such as alkylaryl polyglycol ethers), alkyl sulfonates, alkyl sulfates and aryl sulfonates ], and albumin hydrolysates, among others;

dispersants may include lignosulfite waste liquors and methylcellulose;

the binder may include carboxymethyl cellulose, natural or synthetic polymers (e.g., gum arabic, polyvinyl alcohol, polyvinyl acetate, and the like).

The colorant may include inorganic pigments (e.g., iron oxide, titanium oxide, prussian blue, etc.), organic dyes such as alizarin dyes, azo dyes, or metal phthalocyanine dyes; and trace elements such as salts of iron, manganese, boron, copper, cobalt, molybdenum or zinc.

Furthermore, the bisamide compounds of the invention may be present as a mixture with a synergist, which does not have to be active per se. More precisely, it is a compound which enhances the activity of the active compound.

In one possible implementation, the amount of the bisamide compound contained in the pesticide preparation is 0.1 to 99% by weight, alternatively 0.5 to 90% by weight.

Embodiments of the present invention also provide an insecticide composition comprising a mixture of the above bisamide compounds and other active compounds (e.g., insecticides, baits, disinfectants, acaricides, nematicides, fungicides, growth regulators, herbicides, etc.). The mixture can be provided in the form of raw material medicine, or can be provided in the form of a commercially available preparation or a use form prepared from the preparation.

The embodiment of the invention also provides a method for controlling agricultural or forestry pests, which comprises the following steps: applying an effective amount of a material to a pest or its growth medium in need of control, the material being selected from one or more of the following: the bisamide compound, the insecticide preparation, and the insecticide composition.

The embodiment of the invention also provides application of the bisamide compounds in preparing an animal parasite control agent. In the veterinary field, i.e. veterinary science, the bisamide compounds of the invention can be effectively used against a variety of harmful animal parasites, in particular endoparasites and ectoparasites.

In one possible implementation, the animal parasite comprises one or more of the following:

from the order of the Anoplura (Anopluria), for example the genera Haematopinus spp, pediculosus spp (Linogaphus spp.), pediculosis spp (Pediculus spp.), Phtirus spp and pediculosis spp (Solenoptes spp.); in particular, representative examples are acanthamoeba (Linogathus setosus), bovines californica (Solenopotes capsulatus);

mallophaga (Mallopha, bamboos visuli (linogluchus), ovine palaemons (linogluchus), linogluchus oviformis, podophyllus pepulis (linogluchus pedalis), caprine palaemons (linogluchus stenopsis), donkey blood lice (Haematopinus asini macrocarpulus), bovine blood lice (Haematopinus eurytenus), porcine blood lice (Haematopinus suis), head lice (pee humanus capitis), body lice (pee humanus coproporus), grape root aphid (phyllera vasta), crab lice (phyllus purpura) and blunt sub-orders (ambyceria) and sub-orders of microcentrences (ischioptera), such as trichoderma, louse, and louse, such as trichoderma, louse, and leptopodium sp; in particular, representative examples are cow hair lice (Bovicola bovis), wool lice (Bovicola ovis), angora goat feather lice (Bovicola limcata), cow animal lice (Damalina bovis), dog hair lice (trichodices canis), cat feather lice (Felicola subclautus), goat hair lice (Bovicola caprae), lepentron ovis, bite lice (wereckiella equi);

diptera (Diptera) and its subclasses Petera (Nematococcus) and Brachydicta (Brachydictana), e.g. the genera Aedes (Aedes spp.), Anopheles (Anopheles spp.), Culex (Culex spp.), Kupffer (Culex spp.), Schistogna (Simulium spp.), Eumulus (Eulimulus spp.), phlebotomis (Phlebomes spp.), Lutzenliana (Lutzomyia spp.), Culicoides spp.), Tabanus (Chrysophthalmus spp.), Brevus (Leguminosae spp.), Brevus (Odagmia spp.), genus Wilhelmia spp., Strict spp., Strictus (Leguminosae spp.), femora spp., Tamarianus spp., Spanis., Sphagus, Sphagous spp., Pilus (Leguminosae spp.), Strauss spp.), gras spp., Leguminosae spp., Tabyssus spp., Musca, Sphagus (Mucoralis, Sphagus spp.), Sphagus spp., Tabyssus (Legiones spp.), Sphaga (Mus spp.), Sphagus), Strictus spp., Tabyssus (Legiones), Spiricus (Musca), Sphagus spp.), Spiricus (Musca) and Sphaga Sphagus spp. (Legiones (Musca), Sphagus spp.), Musca) of Strictus spp., Tabyssus (Musca), Spirisfiella (Musca) genus, Spirisfiella (Musca) and Spirisfiella) genus, Callyphora (callyphora spp.), Lucilia (Lucilia spp.), chrysomyl (Chrysomyia spp.), dirty muscoid (Wohlfahritia spp.), sarcophagemid (Sarcophaga spp.), lyssodomyl (Oestrus spp.), dermomyl (Hypoderma spp.), gastromyl (Gasterophilus spp.), pedicomyl (Hippoboca spp.), ovis (Lipopepta spp.), tick (Melophas spp.), nasus (Rhinoestus spp.), and rhynchus (Rhinoestus spp.), and mosquito (Tipula spp.); in particular, representative examples are Aedes aegypti (Aedes aegypti), Aedes albopictus (Aedes albopictus), Aedes coracois (Aedes taeniorhihynchus), Anopheles gambiensis (Anopheles gambiae), Anopheles pentamaculans (Anopheles macuripennis), Orthostis erythropolis (Calliphora erythrephala), Takavas magna (Chrysozona pluvialis), Culex quinans (Culex quinquefasciatus), Culex pipiens (Culex pipiens), Culex tarentus (Culex tarsalis), Corydus aestivus (Fannis), Sarcoporia (Sarcina), Sarcoporia (Sarcoporia), Sarcoporia gallica (Stomopsis), Sarcoporia great variety (Tiillus), Lucifera indica (Tacifolia), Lucifera leucopterica (Tacifolia), Lucifera leucopteria (Lucifolia), Lucifera indica), Lucifolia (Lucifera leucotrichia indica), Lucifolia (Lucifolia), Lucifera leucotrichia melanogaster indica), Lucifolia (Lucifolia), Lucifera leucotrichia terreus strain (Lucifolia), Lucifolia (Lucifolia), Luciferries pacifica (Lucifolia), Luciferries terreus strain (Luciferries terreus, hermetia cubeba (Hybomita), hermetia illucens (Chrysosporium humans), hermetia lutea (Chrysosporium lucidus), Hermatopsis pleius (Haematopota pluvialis), Haematopotalalis, Okayata melanogaster (Musca autumnalis), Musca domestica (Musca domestica), Sarcophaga capitata (Haematobia irdans), Sarcophaga glabra (Haematobia irdans), Sarcophaga ciliata (Haematobia stimulans), Hydrotaea irtans, Sarcophaga leucoderma (Hydrotala alprepucata), Chrysomya Chrysomya, Chrysomya japonica (Chrysomya bezoar), Oyama pallidum (Ovoviridae), Sarcophaga pallidus, and Sarcophaga nivea, skin flies (Hypoderma linearis), Przhevaldiana silenus, human skin flies (Dermatobia hominis), kefir flies (Melophagus ovinus), Lipopetia capreoli, deer sheep lice flies (Lipopetia cervi), Hippoboca variegata, horse lice flies (Hippoboca equina), stomach flies (Gasterophilus intestinalis), stomach flies (Gasterophilus nigroceris), stomach flies (Gasterophilus petatus), and bees (Braziula coeca);

the order Siphonapterida, for example, the genera Siphonapterida (Pulex spp.), Ctenocephalides (Ctenocephalides spp.), Dinophyides (Tunga spp.), Dinophyides (Xenopsylla spp.), and Ceratophyllus spp.); in particular, representative examples are Ctenocephalides canis (Ctenocephacides canis), Ctenocephalides felis (Ctenocephacides felis), human fleas (Pulex irritans), Tetranychus penetrans (Tunga pierrans), Xenopsylla cheopis (Xenopsylla cheopis);

heteroptera (Heteropterida), for example, the genera Clerodera (Cimex spp.), Tolyptera (Triatoma spp.), Triptera triandra (Rhodnius spp.), Triptera (Prussonetia spp.), and Prussonetia (Panstrongylus spp.);

the order of the Blattarida (Blattarida), for example, Blatta orientalis (Blatta orientalis), Periplaneta americana, Blattella germanica, the genus Charcot roach (Supella spp.) (e.g., Supella longipapa);

acarina (Acari) (or Acarina), Metavalvales (Metastigmata) and Mesotimata, for example, Irelaphus (Argas spp.), Iridaceae (Ornithodoros spp.), Ornithodoros (Ornithodoros spp.), Otobius spp, Elyrifos (Ixodes spp.), Ordinium (Amblyomma spp.), Orixomelas (Rhipicephalus Boophilus) spp, Dermacentor spp, Haemophysalis spp, Hymenoptera (Hyomorpha spp.), Dermansussubusspp, Rhipicephalus (Rhipicephalus spp.), Isochrysis (Isochrysophyces spp.), Orthophys (Orthophys spp.), Orthophys spp

Pneumonyssimus spp, Pneumonyssis spp, Ceramix spp, Sternstoma spp, Beauveria spp, and Apis spp; in particular, representative examples are Oryza sativa (Argas persicus), Oryza sativa (Argas reflexus), Oryza sativa (Ornithodoros moubata), Otobius (Otobius megnini), Rhipicephalus microplus (Rhipicephalus) microplus, Rhipicephalus achlus (Rhipicephalus) sarcolus, Rhipicephalus achypus (Rhipicephalus) decolonis, Rhipicephalus annulatus (Rhipicephalus) sarcophilus, Rhipicephalus annulatus (Rhipicephalus) annuatus), Rhipicephalus fasciatus (Rhipicephalus) annuatus, Rhipicephalus pallens (Rhipicephalus) calcineurus, Hyaloma anatorum, Egyptis hyalomylus (Hyalomyxomyxos) and Hyalomyxomyxomyxos glaucosus (Hyalomyxomyxoma)

aegypticum), Hyalomma marginatum, Hyalomma transitions, Rhipicephalus everlasting (Rhipicephalus)

evertsi, Rhizopus communis (Ixodes ricinus), Rhizopus hexangularis (Ixodes hexagonus), Rhizopus rudis (Ixodes canisuga), Rhizopus hirsutus (Ixodes pellus), Rhizopus sanguineus (Ixodes rubicundus), Rhizopus scaphii (Ixodes scapularis), Rhizopus annulatus (Ixodes holomycus), Haemaphys sanguineus (Haemaphys concina), Rhizopus incisus (Haemaphysalis punctata), Haemaphysalis cirrhosa, Haemaphysalis oculus, Rhizopus appendiculatus, Rhizopus sanguineus, Rhizopus sanguis, Rhizopus sanguineus, Rhizopus (Rhizopus sanguineus, Rhizopus sanguisus sanguineus, Rhizopus sanguis, Rhizopus sanguisus, Rhizopus sanguis, Rhizopus sanguisus, Rhizopus sanguisus, Rhizopus sanguisus, Rhizopus sanguisus, Rhizopus, Ornithodoros florida (Amblyomma variegatum, Amblyomma maculatum (Amblyomma maculatum), Amblyomma hebracteatum (Amblyomma hebraeum), Amblyomma cajennense (Amblyomma cajennnense), Dermanyssus gallinae (Dermanyssus gallinae), Onychidae (Ornithonysus bursa), Onychidae (Ornithonysus sylvestris), and Melissus macropterus (Varroa jacobsoni);

from the orders of the axyriales (actinodida) (prospectate) and the order of the acarida (acarida) (aspergillia), for example, the genera fagaceae (Acarapis spp.), acanthomonas (cheletella spp.), acanthomonas (avian streptococci spp.), sarcophaga (Myobia spp.), psorales (Psorergates spp.), Demodex spp.), tsutsutsuga (Trombicula spp.), listerorutorus spp.), Acarus (Acarus spp.), tyrosomus (tyroglobus spp.), trichophagous (trichophagous spp.), psorales (trichophys spp.), Psoroptes (trichophys spp.), psorales (trichophys spyptes), psorales (trichophys spp.), psorales (trichophys), psorales (psorales, acarina, psorales (psorales), psorales (trichophytes), psorales (psorales), psorales (trichophytes), psorales (trichophytes sp.); in particular, Geranium elegans (C heylectiella yasguri), Geranium brucei (C heylectiella blakei), Demodex canis (Demodex canis), Demodex bovis (Demodex bovis), Demodex ovis (Demodex ovis), Demodex capris (Demodex caprae), Demodex equi (Demodex equi), Demodex calalli, Demodex suis (Demodex suis), Neotromella autumnalis, Neotrompilus, Demodex giganteus, and Demodex giganteus

desaleli, neosporangentia xenobiota, harvest dust mite (Trombicula akamushi), dog ear mite (otonectes cynomolgus), cat scab mite (Notoederes cati), dog scab mite (Sarcoptis caris), cow scab mite (Sarcoptes bovis), sheep scab mite (Sarcoptes ovis), goat scab mite (Sarcoptes rucapae ═ S.caprae), horse scab mite (Sarcoptes equi), pig scab (Sarcoptes suis), sheep scrapie (Psopotes ovis), rabbit scrapie (Oroptes cunicululi), horse scab (Psopoptes eq), cow scab (Choroptes bovis), horse scab (Psopoptes ovis), sheep scab (Psorospermum), Pneumonidae (Pneumonidae), bee larva of bee (Psorospermum trichomonas), and bee);

nematodes such as Meloidogyne incognita (Meloidogyne incognita), Bursaphelenchus xylophilus (Bursaphelenchus xylophilus), Aphelenchoides besseyi (Aphelenchus besseyi), Heterodera glycines (Heterodera glycines), Heterodera pratyloides spp, and the like;

arthropods, worms and plasmodia that attack animals. Control arthropods, helminths and/or plasmodia, reduce mortality in domestic animals, and improve animal productivity (meat, milk, wool, skin, eggs and honey) and health.

In one possible implementation, the animal parasite control agent is used to control one or more of fleas and American dog ticks.

In one possible implementation, the animal includes one or more of: agricultural animals such as cattle, sheep, goats, horses, pigs, donkeys, camels, buffalo, rabbits, chickens, turkeys, ducks, geese, farmed fish, bees, etc.; also included are pets known as companion animals, e.g., dogs, cats, cage birds, aquarium fish; animals used for experiments such as hamsters, guinea pigs, rats, mice and the like are also included.

The embodiment of the invention also provides an animal parasite control agent, which contains the bisamide compounds as active components and one or more auxiliary materials.

In one possible implementation, the animal parasite control agent is selected from the following dosage forms: tablets, capsules, drinks, drinkable drugs, granules, ointments and pills, suppositories, injections (intramuscular, subcutaneous, intravenous, intraperitoneal and the like), smears, aerosols, non-pressurized sprays (e.g., pump sprays and aerosol sprays).

In one possible implementation, the above-mentioned active ingredient is contained in the animal parasite control agent in an amount of 1 to 80% by weight.

Embodiments of the present invention also provide an animal parasite control composition comprising a mixture of the above bisamide compounds and other animal parasite control active compounds (e.g., acaricides, insecticides, parasiticides, malaria parasites, etc.). The mixture can be provided in the form of raw material medicine, or can be provided in the form of a commercially available preparation or a use form prepared from the preparation.

Embodiments of the present invention also provide a method of controlling parasites on animals, comprising the steps of: administering to an animal parasite or its growth medium in need of control an effective amount of a material selected from one or more of the group consisting of: the bisamide-based compounds described above; the above-mentioned animal parasite control agent; the animal parasite control composition described above. For example: enterally administering tablets, capsules, potables, drinkable drugs, granules, ointments, pills, and suppositories; parenteral administration based on dermal administration, such as injection (intramuscular, subcutaneous, intravenous, intraperitoneal and the like), implantation, nasal administration, including bathing or soaking, spraying, pouring, dripping, washing and dusting, and by using model articles containing the active compound, such as collars, ear tags, labels, leg bands (leg bands), nets, markers and the like. The active compounds of the invention have low toxicity and can be safely used in warm-blooded animals.

Advantageous effects

The bisamide compounds have unexpectedly high insecticidal activity and have no phytotoxicity to cultivated crop plants. In addition, the compounds of the present invention are useful for controlling a wide variety of pests, such as harmful piercing-sucking insects, chewing insects and other plant parasitic pests, stored grain pests, sanitary pests and the like, and for disinfecting and killing them.

Detailed Description

In order to make the objects, technical solutions and advantages of the embodiments of the present invention clearer, the technical solutions in the embodiments of the present invention will be clearly and completely described below, and it is obvious that the described embodiments are a part of the embodiments of the present invention, but not all of the embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention. .

Furthermore, in the following detailed description, numerous specific details are set forth in order to provide a better understanding of the present invention. It will be understood by those skilled in the art that the present invention may be practiced without some of these specific details. In some embodiments, materials, elements, methods, means, and the like that are well known to those skilled in the art are not described in detail in order to not unnecessarily obscure the present invention.

Throughout the specification and claims, unless explicitly stated otherwise, the word "comprise", or variations such as "comprises" or "comprising", will be understood to imply the inclusion of a stated element or component but not the exclusion of any other element or component

The starting materials are commercially available unless otherwise indicated.

In the present invention, the terms used have the following meanings:

halogen: refers to fluorine, chlorine, bromine or iodine.

Halogenated alkyl groups: straight-chain or branched alkyl radicals in which the hydrogen atoms may be partially or wholly replaced by halogen, e.g. difluoromethyl (CHF)₂) Trifluoromethyl (CF)₃) And the like.

Halogenated alkoxy: the hydrogen atoms of the alkoxy radicals being substituted partly or wholly by halogen, e.g. difluoromethoxy (OCHF)₂) Trifluoromethoxy group (OCF)₃) And the like.

Cyano group: and (C) CN.

Insecticide: a substance having an insecticidal effect on pests.

Animal parasite control agents: refers to active compounds that are effective in reducing the incidence of various parasites in animals infected with the parasite. Control means that the active compounds are effective against parasites, inhibiting their growth or reproduction.

Synthetic examples

The compounds of formula I, formula II and formula III of the present invention can be prepared according to the above-mentioned synthetic routes using different starting compounds, and are further described in detail as follows:

example 1: preparation of intermediate Compound II.1

To 60 ml of DMF were added 2.00 g (3.60 mmol) of N- (2, 6-dibromo-4-heptafluoroisopropylphenyl) -2-fluoro-3-aminobenzamide (intermediate IV-1, obtained by the method reported in WO2011093415 or WO 2010018714), 0.74 g (5.35 mmol) of potassium carbonate and 0.58 g (4.30 mmol) of bromomethylcyclopropane, and the mixture was heated to 100 ℃. After TLC monitoring reaction, adding water and ethyl acetate for extraction, decompressing and desolventizing the organic phase, and purifying the residue by column chromatography to obtain 0.90 g of white solid, namely the intermediate II.1.

Nuclear magnetic and mass spectral data for intermediate ii.1 are as follows:

¹H NMR (600 MHz, Chloroform-d) δ 8.21 (d, 1H), 7.87 (s, 2H), 7.42 – 7.36 (m, 1H), 7.14 (t, 1H), 6.89 (td, 1H), 4.24 - 4.17 (br, 1H),3.07 - 3.02 (m, 2H), 1.19 – 1.11 (m, 1H), 0.65 – 0.59 (m, 2H), 0.33 - 0.27 (m, 2H). LC-MS(m/z, ESI): 609.08[M+H]⁺.

example 2: preparation of intermediate Compound II.2

10 g of N- (2-bromo-6-iodo-4-heptafluoroisopropylphenyl) -2-fluoro-3-nitrobenzamide (prepared according to the method reported in CN 109206335A), 15 g of anhydrous stannous chloride, 200 ml of 1, 4-dioxane and 8 ml of concentrated hydrochloric acid are added, and the mixture is heated to 60 ℃ and stirred for reaction. After the completion of the TLC monitoring reaction, the organic solvent was distilled off under reduced pressure. Adding 500 ml of ethyl acetate, adding a proper amount of saturated aqueous sodium hydroxide solution to adjust the pH to be =10, fully stirring, filtering out a precipitated insoluble substance by using kieselguhr, extracting a filtrate by using ethyl acetate and water, drying an organic layer by using anhydrous magnesium sulfate, filtering, and concentrating under reduced pressure to obtain a grey brown solid, and purifying a crude product by column chromatography to obtain 7.91 g of N- (2-bromo-6-iodo-4-heptafluoroisopropylphenyl) -2-fluoro-3-aminobenzamide, namely an intermediate IV-2.

To 60 ml of DMF were added 2.00 g (3.32 mmol) of N- (2-bromo-6-iodo-4-heptafluoroisopropylphenyl) -2-fluoro-3-aminobenzamide (intermediate IV-2), 0.69 g (4.99 mmol) of potassium carbonate and 0.54 g (4.00 mmol) of bromomethylcyclopropane, and the mixture was heated to 100 ℃. After TLC monitoring reaction, adding water and ethyl acetate for extraction, decompressing and desolventizing the organic phase, and purifying the residue by column chromatography to obtain 0.83 g of white solid, namely the intermediate II.2.

Nuclear magnetic and mass spectral data for intermediate ii.2 are as follows:

¹H NMR (600 MHz, Chloroform-d) δ 8.21 (d, 1H), 8.08 (d, 1H), 7.89 (d, 1H), 7.43 – 7.37 (m, 1H), 7.15 (t, 1H), 6.89 (td, 1H), 4.22 (br s, 1H), 3.07 - 3.02 (m, 2H), 1.20 - 1.12(m, 1H), 0.66 – 0.59 (m, 2H), 0.33 – 0.28 (m, 2H). LC-MS(m/z, ESI): 657.07[M+H]⁺.

example 3: preparation of intermediate Compound II.3

To 60 ml of DMF were added 2.00 g (3.67 mmol) of N- (2-bromo-6-trifluoromethyl-4-heptafluoroisopropylphenyl) -2-fluoro-3-aminobenzamide (intermediate IV-3, obtained by the method reported in WO2011093415, WO20110201687, WO2010013567, or WO2010018714, etc.), 0.76 g (5.50 mmol) of potassium carbonate, and 0.60 g (4.44 mmol) of bromomethylcyclopropane, and the mixture was heated to 100 ℃. After TLC monitoring reaction, adding water and ethyl acetate for extraction, decompressing and desolventizing the organic phase, and purifying the residue by column chromatography to obtain 0.73 g of white solid, namely the intermediate II.3.

Nuclear magnetic and mass spectral data for intermediate ii.3 are as follows:

¹H NMR (600 MHz, Chloroform-d) δ 8.27 (d, 1H), 8.14 (d, 1H), 7.91 (d, 1H), 7.41 – 7.35 (m, 1H), 7.14 (t, 1H), 6.89 (td, 1H), 4.25 – 4.17 (br, 1H), 3.07 - 3.02 (m, 2H),1.20 – 1.11 (m, 1H), 0.66 – 0.58 (m, 2H), 0.33 – 0.27 (m, 2H). LC-MS(m/z, ESI): 599.07[M+H]⁺.

example 4: preparation of intermediate Compound II.4

Intermediate compound ii.4 (white solid) was prepared by reacting intermediate compound IV-4 (prepared according to the methods reported in WO2011093415 or WO 2010018714) with bromomethylcyclopropane as described in example 1, example 2 or example 3.

Nuclear magnetic and mass spectral data for intermediate compound ii.4 are as follows:

¹H NMR (600 MHz, Chloroform-d) δ 8.38 – 8.27 (m, 2H),7.96 – 7.91 (m, 1H),7.41 – 7.35 (m, 1H),7.15 (t, 1H), 6.92 – 6.86 (m, 1H), 4.22 (br s, 1H), 3.05 (d, 2H), 1.20 – 1.11 (m,

1H),0.67 – 0.58 (m, 2H), 0.34 - 0.27 (m, 2H).LC-MS(m/z, ESI): 669.24[M+Na+H]⁺.

example 5: preparation of Compound 1

To 30 ml of toluene were added 0.50 g (0.82 mmol) of intermediate II.1 and 0.20 g (1.25 mmol) of intermediate V-1, and the mixture was refluxed. After the completion of the TLC monitoring reaction, the reaction mixture was desolventized under reduced pressure and the residue was purified by column chromatography to obtain 0.42 g of a yellow solid, i.e., Compound 1.

Nuclear magnetic and mass spectral data for compound 1 are as follows:

¹H NMR (600 MHz, Chloroform-d) δ 8.21 (s, 1H),8.08 (t, 1H), 8.03 – 7.92 (br, 1H),7.91 - 7.76(m, 3H), 7.54 (t, 1H), 7.33 (t, 1H), 6.81 (s, 1H), 3.90 (s, 1H), 3.74 (s, 1H),1.17 – 1.05 (br, 1H),0.59 – 0.43 (m, 2H), 0.19 (d, 2H). LC-MS(m/z, ESI): 732.11[M+H]⁺.

example 6: preparation of Compound 2

To 40ml of toluene were added 0.60 g (0.91 mmol) of intermediate II.2 and 0.22 g (1.38 mmol) of intermediate V-1, and the mixture was refluxed. After the completion of the TLC monitoring reaction, the reaction mixture was desolventized under reduced pressure and the residue was purified by column chromatography to obtain 0.46 g of a white solid, i.e., Compound 2.

Nuclear magnetic and mass spectral data for compound 2 are as follows:

¹H NMR (600 MHz, Chloroform-d) δ 8.22 (s, 1H),8.13 – 8.04 (m, 2H), 7.96 (d, 1H), 7.88 (d, 1H),7.85 - 7.77 (br, 1H), 7.60 – 7.51 (m, 1H), 7.35 (t, 1H), 6.80 (s, 1H), 3.94 (s, 1H), 3.72 (s, 1H), 1.17 – 1.05 (br, 1H), 0.58 – 0.46 (m, 2H), 0.19 (d, 2H). LC-MS(m/z, ESI): 780.11[M+H]⁺.

example 7: preparation of Compound 3

To 30 ml of toluene were added 0.50 g (0.83 mmol) of intermediate II.3 and 0.20 g (1.25 mmol) of intermediate V-1, and the mixture was refluxed. After the completion of the TLC monitoring reaction, the reaction mixture was desolventized under reduced pressure and the residue was purified by column chromatography to obtain 0.45 g of a white solid, i.e., Compound 3.

Nuclear magnetic and mass spectral data for compound 3 are as follows:

¹H NMR (600 MHz, Chloroform-d) δ 8.18 (s, 1H), 8.13 (d, 1H), 8.07 (t, 1H), 8.00 (d, 1H), 7.90 (d, 1H), 7.87 – 7.79 (br, 1H),7.62 – 7.53 (m, 1H), 7.35 (t, 1H), 6.82 (s, 1H), 3.96 (s, 1H), 3.70 (s, 1H),1.17 – 1.05 (br, 1H), 0.58 – 0.46 (m, 2H),0.18 (d, 2H). LC-MS(m/z, ESI): 722.10[M+H]⁺.

example 8: preparation of Compound 4

Compound 4 (yellow solid) was prepared from intermediate compound ii.4 by the method described in example 5, example 6 or example 7 by reaction with intermediate V-1.

Nuclear magnetic and mass spectral data for compound 4 are as follows:

¹H NMR (600 MHz, Chloroform-d) δ 8.35 – 8.31 (m, 1H), 8.18 (s, 1H),8.11 – 8.00 (m, 2H), 7.95 – 7.90 (m, 1H), 7.89 – 7.78 (br, 1H),7.58 (td, 1H), 7.36 (t, 1H), 6.82 (s, 1H), 4.05 – 3.89 (m, 1H), 3.75 – 3.60 (m, 1H),1.17 – 1.05 (br, 1H), 0.60 – 0.44 (m, 2H), 0.18 (d, 2H).LC-MS(m/z, ESI): 770.18[M+H]⁺.

example 9: preparation of Compound 7

Compound 7 (yellow solid) was prepared from intermediate compound ii.3 by the method described in example 5, example 6 or example 7, and by reaction with intermediate V-2.

The nuclear magnetic data for compound 7 is as follows:

¹H NMR (600 MHz, Chloroform-d) δ 8.64 (s, 1H), 8.13 (d, 1H), 8.08 (t, 1H), 7.98 (d, 1H), 7.92 – 7.84 (m, 1H),7.65 – 7.53 (m, 2H),7.37 (t, 1H), 4.08 – 3.95 (m, 1H), 3.77 – 3.65 (m, 1H), 1.18 – 1.07 (br, 1H), 0.61 – 0.47 (m, 2H), 0.21 (d, 2H).

example 10: preparation of Compound 8

Compound 8 (yellow solid) was prepared from intermediate compound ii.4 by the method described in example 5, example 6 or example 7, and intermediate V-2. The nuclear magnetic data for compound 8 is as follows:

¹H NMR (600 MHz, Chloroform-d) δ 8.65 (s, 1H), 8.32 (d, 1H), 8.08 (t, 1H), 8.02 (d, 1H), 7.94 – 7.90 (m, 1H), 7.88 (d, 1H), 7.61 (t, 1H), 7.56 (d, 1H), 7.37 (t, 1H), 4.10 – 3.96 (m, 1H), 3.75 – 3.63 (m, 1H), 1.19 – 1.08 (br, 1H), 0.61 – 0.46 (m, 2H), 0.21 (d, 2H).

example 11: preparation of Compound 9

Compound 9 (white solid) was prepared from intermediate compound ii.1 by the method described in example 5, example 6 or example 7, and intermediate V-3.

Nuclear magnetic and mass spectral data for compound 9 are as follows:

¹H NMR (600 MHz, Chloroform-d) δ 8.65 (s, 1H), 8.17 – 8.05 (br, 1H),7.98 – 7.74 (m, 4H),7.63 – 7.47 (m, 2H), 7.36 (t, 1H),4.00 – 3.86 (m, 1H), 3.84 – 3.70 (m, 1H),1.17 – 1.05 (br, 1H), 0.60 – 0.46 (m, 2H), 0.22 (d, 2H).LC-MS(m/z, ESI): 739.14[M+H]⁺.

example 12: preparation of Compound 10

Compound 10 (yellow oil) was prepared from intermediate compound ii.2 by the method described in example 5, example 6 or example 7, and intermediate V-3.

Nuclear magnetic and mass spectral data for compound 10 are as follows:

¹H NMR (600 MHz, Chloroform-d) δ 8.66 (s, 1H),8.16 – 8.08 (br, 1H), 8.07 (d, 1H),7.94 – 7.86 (m, 2H),7.83 – 7.77 (m, 1H),7.61 – 7.51 (br, 2H), 7.37 (t, 1H), 4.02 – 3.89 (m, 1H), 3.81 – 3.68 (m, 1H),1.17 – 1.06 (br, 1H), 0.60 – 0.48 (m, 2H), 0.22 (d, 2H).LC-MS(m/z, ESI): 787.20[M+H]⁺.

example 13: preparation of Compound 11

Compound 11 (yellow solid) was prepared from intermediate compound ii.3 by the method described in example 5, example 6 or example 7, and by reaction with intermediate V-3.

Nuclear magnetic and mass spectral data for compound 11 are as follows:

¹H NMR (600 MHz, Chloroform-d) δ 8.62 (s, 1H), 8.16 – 8.12 (m, 1H), 8.09 (t, 1H),

8.00 – 7.89 (m, 2H), 7.82 (d, 1H), 7.63 – 7.52 (m, 2H), 7.37 (t, 1H), 4.02 – 3.92 (m, 1H), 3.78 – 3.67 (m, 1H), 1.17 – 1.05 (br, 1H), 0.60 – 0.47 (m, 2H), 0.21 (d, 2H).LC-MS(m/z, ESI): 729.11[M+H]⁺.

example 14: preparation of Compound 12

Compound 12 (yellow solid) was prepared from intermediate compound ii.4 by the method described in example 5, example 6 or example 7, and by reaction with intermediate V-3.

Nuclear magnetic and mass spectral data for compound 12 are as follows:

¹H NMR (600 MHz, Chloroform-d) δ 8.62 (s, 1H), 8.37 – 8.31 (m, 1H), 8.09 (t, 1H), 8.00 (d, 1H), 7.93 (d, 1H), 7.81 (d, 1H), 7.63 – 7.53 (m, 2H), 7.37 (t, 1H),4.05 – 3.94 (m, 1H), 3.77 – 3.64 (m, 1H),1.17 – 1.05 (br, 1H), 0.61 – 0.47 (m, 2H), 0.21 (d, 2H).LC-MS(m/z, ESI): 777.21[M+H]⁺.

other compounds of formula I of the present invention may be prepared by reference to the above examples.

Biological activity assay

Example 15: biological activity assay of armyworm, diamondback moth and chilo suppressalis

Several insects were tested for insecticidal activity using the compounds of the present invention. The measurement method is as follows:

after dissolving a test compound in a mixed solvent of acetone/methanol (1: 1), the test compound was diluted with water containing 0.1% (wt) Tween 80 to a desired concentration.

Takes armyworm, diamondback moth and chilo suppressalis as targets, and adopts an Airbrush spray method to carry out activity determination.

(1) Activity assay for armyworm killing

The determination method comprises the following steps: the corn leaves were cut into 2cm long sections and the pressure of the Airbrush spray treatment was 10psi (approximately 0.7 kg/cm)²) Spraying on the front and back sides of each leaf segment, wherein the liquid spraying amount of the compound to be detected is 0.5 ml. After drying in the shade, 10 larvae of 3 instar larvae were inoculated per treatment, and the treatment was repeated 3 times. Culturing in an observation room with 25 deg.C and 60-70% relative humidity, and examining the number of surviving insects 3 days after the treatmentAnd calculating the mortality.

The results of the partial test on armyworm are as follows:

at the dose of 0.05mg/L, the lethality of the compounds 1, 2, 3, 4, 7, 8, 9, 10, 11 and 12 to armyworms is more than 90 percent 3 days after the administration.

(2) Activity assay for killing diamondback moth

The determination method comprises the following steps: the cabbage leaves were punched into a 2 cm-diameter dish by means of a punch, and the pressure of the Airbrush spray treatment was 10psi (approximately 0.7 kg/cm)²) Spraying on the front and back sides of each leaf disc, wherein the spraying amount of the compound to be detected is 0.5 ml. After drying in the shade, 10 larvae of 3 instar larvae were inoculated per treatment, and the treatment was repeated 3 times. After treatment, the treated insects are placed into an observation room with the temperature of 25 ℃ and the relative humidity of 60-70% for culture, the number of the survival insects is investigated 3 days after the treatment, and the death rate is calculated.

Partial test results for plutella xylostella are as follows:

the lethality of the compounds 1, 2, 3, 4, 7, 8, 9, 10, 11 and 12 to plutella xylostella is more than 90% in the dose of 0.5 mg/L and 3 days after the administration.

At the dose of 0.05mg/L, the lethality of the compounds 3, 4, 7, 8, 11 and 12 to plutella xylostella is more than 90 percent 3 days after the administration.

(3) Activity assay for Chilo suppressalis killing

The determination method comprises the following steps: 1) preparing rice seedlings: culturing rice in a constant temperature chamber (temperature is 26-28 ℃, relative humidity is about 60-80%, illumination is 16hL:8 hD) by using a plastic cup with the diameter of 4.5cm and the height of 4cm, and selecting robust rice seedlings with consistent growth vigor for medicament treatment when the rice grows to 4-5 leaf stages, wherein the treatment is repeated for 3 times. 2) Preparing a test insect: chilo suppressalis bred continuously indoors and larvae of 3 years old. 3) Spraying rice stems to inoculate insects. The spraying method is adopted to evenly spray the whole rice seedlings, and 15ml of the pesticide is used for each treatment. The blank control was treated first and the above procedure was repeated in order of the test concentrations from low to high. After the rice seedlings are sprayed, the rice seedlings are placed in a shade place to be dried in the air, and stems about 5cm from the stem base parts are cut to feed the test insects. Preparing glass culture dishes with the diameter of 90mm, filling filter paper at the bottom of the culture dishes, adding water for moisturizing, putting about 5 rice stems into each culture dish, connecting 10 larvae, sealing the culture dishes by using non-woven fabrics, and placing the culture dishes in a constant temperature room for culture. The number of remaining live insects was investigated 3 days after the administration.

The results of the partial test on chilo suppressalis are as follows:

the lethality of the compounds 1, 2, 3, 4, 7, 8, 9, 10, 11 and 12 to Chilo suppressalis is more than 90% at the dose of 1 mg/L.

The lethality of the compounds 3, 4, 7, 8, 11 and 12 to Chilo suppressalis is more than 90% at the dose of 0.5 mg/L.

The lethality of the compounds 3, 4, 11 and 12 to Chilo suppressalis is more than 90% at the dose of 0.25 mg/L.

Selecting the compounds 1, 3, 7 and 11 of the invention and a control compound to carry out a chilo suppressalis insecticidal activity parallel comparison test (3 days after drug administration), wherein the determination method is the same as that described above; the results are shown in Table 5:

TABLE 5 parallel comparison of insecticidal Activity of Compounds 1, 3, 7, 11 of the invention with control Compounds on Chilo suppressalis

Note: in Table 5, "-" indicates no measurement. In the tables, 1-1, 1-2, 2-1, 3-1, 4-1, 5-1 and 5-2 are all comparative compounds provided herein, which are obtainable by the methods of examples 5-14 of the present invention, and the starting materials are all either commercially available or prepared by conventional methods.

Examples of the inventionBy reacting R in the compound of formula I₁、R₂、R₃、R₄The groups and their combinations were selected to obtain compounds with better insecticidal effect, as shown in table 5, by comparing compound 1 with control compounds 1-1, 1-2, by comparing compound 3 with control compound 2-1, by comparing compound 7 with control compound 3-1, by comparing compound 11 with control compound 4-1: r₄And the adjacent nitrogen atom are very important, and the two are mutually matched, but the one is not, when R is₄Is F, CF₃When CN and adjacent atoms are carbon atoms, the activity of the compound to chilo suppressalis is obviously reduced and even lost; as can be seen by comparing compounds 3, 7, 11 and 5-1, 5-2: when with R₄When the adjacent atom is a nitrogen atom, R₄After selecting hydrogen or chlorine, the activity of the compound on chilo suppressalis is also remarkably reduced or even lost.

Example 16: insecticidal test against cat fleas

After dissolving 4mg of a test compound in 40ml of acetone to obtain an acetone solution having a concentration of 100ppm, 400. mu.l of a drug solution was applied to the bottom and side surfaces of a petri dish having an inner diameter of 5.3cm, and acetone was evaporated, a thin film of the compound of the present invention was formed on the inner wall of the petri dish. The inner wall of the culture dish used was 40cm²The treatment dose is 1 mu g/cm²(ii) a 10 adult fleas (male and female mixed) were put into the container, covered and stored in a thermostatic chamber at 25 ℃. And (5) checking the number of dead insects after 72h, and calculating the dead insect rate. The test was repeated 3 times. And (3) testing results: compounds 1, 2, 3, 4, 7, 8, 9, 10, 11, 12 showed a mortality rate of 90% or more.

Example 17: insecticidal test on American Canine ticks

After dissolving 4mg of a test compound in 40ml of acetone to obtain an acetone solution with a concentration of 100ppm, 400. mu.l of a drug solution was applied to the bottom and side surfaces of 2 petri dishes with an inner diameter of 5.3cm, and acetone was evaporated, a thin film of the compound of the present invention was formed on the inner wall of the petri dish. The inner wall of the culture dish used was 40cm²The treatment dose is 1 mu g/cm². Into which 10 American dog ticks are placed1 st nymph (male-female mix), 2 dishes were pooled, the junction was sealed with tape to prevent escape, and stored in a thermostatic chamber at 25 ℃. And (5) checking the number of dead insects after 24h, and calculating the dead insect rate. The test was repeated 3 times. And (3) testing results: compounds 1, 2, 3, 4, 7, 8, 9, 10, 11, 12 showed a mortality rate of 90% or more.