CN113149900B - Amide compound and application thereof - Google Patents

Amide compound and application thereof Download PDF

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CN113149900B
CN113149900B CN202011208863.XA CN202011208863A CN113149900B CN 113149900 B CN113149900 B CN 113149900B CN 202011208863 A CN202011208863 A CN 202011208863A CN 113149900 B CN113149900 B CN 113149900B
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compound according
amide compound
amide
compound
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CN113149900A (en
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张立新
张静
裴鸿艳
盛祝波
汪杰
康卓
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Shenyang University of Chemical Technology
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C07D213/81—Amides; Imides
    • C07D213/82—Amides; Imides in position 3
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/34—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom
    • A01N43/40—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom six-membered rings
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01P—BIOCIDAL, PEST REPELLANT, PEST ATTRACTANT OR PLANT GROWTH REGULATORY ACTIVITY OF CHEMICAL COMPOUNDS OR PREPARATIONS
    • A01P7/00—Arthropodicides
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01P—BIOCIDAL, PEST REPELLANT, PEST ATTRACTANT OR PLANT GROWTH REGULATORY ACTIVITY OF CHEMICAL COMPOUNDS OR PREPARATIONS
    • A01P7/00—Arthropodicides
    • A01P7/04—Insecticides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P33/00—Antiparasitic agents
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C237/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups
    • C07C237/28—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atom of at least one of the carboxamide groups bound to a carbon atom of a non-condensed six-membered aromatic ring of the carbon skeleton
    • C07C237/40—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atom of at least one of the carboxamide groups bound to a carbon atom of a non-condensed six-membered aromatic ring of the carbon skeleton having the nitrogen atom of the carboxamide group bound to a carbon atom of a six-membered aromatic ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C255/00—Carboxylic acid nitriles
    • C07C255/01—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms
    • C07C255/32—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms having cyano groups bound to acyclic carbon atoms of a carbon skeleton containing at least one six-membered aromatic ring
    • C07C255/42—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms having cyano groups bound to acyclic carbon atoms of a carbon skeleton containing at least one six-membered aromatic ring the carbon skeleton being further substituted by singly-bound nitrogen atoms, not being further bound to other hetero atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C07D213/84—Nitriles
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2601/00—Systems containing only non-condensed rings
    • C07C2601/02—Systems containing only non-condensed rings with a three-membered ring

Abstract

The application discloses an amide compound and application thereof, wherein the structure of the compound is shown as a general formula I:

Description

Amide compound and application thereof
Technical Field
The application relates to a compound, in particular to a novel amide compound and application thereof.
Background
The problem of pest resistance to pesticides is increasingly serious due to the long-term and large amount of unreasonable use of the existing medicaments. On the other hand, the insecticidal effect of the existing insecticide is still unsatisfactory especially for the activity of rice stem borers, and the use requirement of the insecticide which is continuously improved in reality is difficult to meet. There remains a need in the art to actively develop new pesticides with higher activity to meet the needs of agriculture and other fields.
The compound shown in the general formula I and the insecticidal activity thereof in the prior art are not reported.
Disclosure of Invention
The purpose of the present application is to provide an amide compound having excellent insecticidal activity. It can be used for preparing medicines for controlling pests in agriculture and other fields and medicines for controlling animal parasites in the field of veterinary medicines.
In order to achieve the aim of the application, the application provides the following technical scheme:
an amide compound shown in a general formula I:
in formula I:
R 1 selected from halogen;
R 2 selected from halogen, C 1 -C 4 Haloalkyl or C 1 -C 4 Haloalkoxy groups;
R 3 selected from CF 3 Or CF (CF) 2 CF 3 ；
R 4 Selected from cyano C 1 -C 4 An alkyl group.
In one possible implementation, in formula I,
R 1 selected from halogen;
R 2 selected from halogen, C 1 -C 2 Haloalkyl or C 1 -C 2 Haloalkoxy groups;
R 3 selected from CF 3 Or CF (CF) 2 CF 3 ；
R 4 Selected from cyano C 1 -C 4 An alkyl group.
In one possible implementation, in formula I,
R 1 selected from bromine or iodine;
R 2 selected from bromine and iodineTrifluoromethyl or difluoromethoxy;
R 3 selected from CF 3 Or CF (CF) 2 CF 3 ；
R 4 Selected from CH 2 CN、CH 2 CH 2 CN、CH 2 CH 2 CH 2 CN、CH 2 CH 2 CH 2 CH 2 CN、CH(CH 3 )CN、CH(CH 2 CH 3 )CN、CH(CH 2 CH 2 CH 3 )CN、C(CH 3 )(CH 3 ) CN or C (CH) 3 )(CH 2 CH 3 )CN。
In one possible implementation, in formula I,
R 1 selected from bromine or iodine;
R 2 selected from bromine, iodine or trifluoromethyl;
R 3 selected from CF 3 ；
R 4 Selected from CH 2 CN、CH 2 CH 2 CN、CH 2 CH 2 CH 2 CN or CH 2 CH 2 CH 2 CH 2 CN。
In one possible implementation, the amide is selected from the group consisting of compounds of Table 1, the compounds of Table 1 having a structure according to formula I and R 1 、R 2 、R 3 And R is 4 As shown in table 1:
TABLE 1
The compounds of formula I of the present application can be prepared according to the following method (wherein each group is as defined above unless otherwise indicated, lg=cl, br or I):
compounds of the general formula III and halides R 4 LG is reacted in a suitable solvent at a temperature of from-10℃to the boiling point of the solventThe compound of the general formula II can be prepared in 0.5 to 48 hours, and the reaction is carried out in the presence of alkali and a catalyst; the compounds of formula II are reacted with 6-cyanonicotinoyl chloride in a suitable solvent at a temperature of from-10℃to the boiling point of the solvent for 0.5 to 48 hours to give the compounds of formula I, which can be carried out in the presence of a base and a catalyst. Suitable solvents in the above steps may be the same or different, and include 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 dimethylsulfoxide, and mixed solvents of the above solvents. The base in each of the above steps may be the same or different, and is an organic base such as triethylamine, pyridine, DBU, 4-dimethylaminopyridine, an alkali metal hydride such as sodium hydride and potassium hydride, an alkali metal hydroxide such as sodium hydroxide and potassium hydroxide, an alkaline earth metal hydroxide such as calcium hydroxide, an alkali metal carbonate such as sodium carbonate and potassium carbonate, an alkali metal bicarbonate such as sodium bicarbonate, a metal alkoxide such as sodium methoxide, sodium ethoxide, potassium t-butoxide, sodium t-butoxide, or the like. The catalysts in the above steps may be the same or different potassium iodide, sodium iodide, potassium fluoride, sodium fluoride, potassium bromide or sodium bromide, etc.
The compounds of the general formula III may be prepared according to known methods, for example, as reported in WO20110201687, WO2011093415, WO2005021488, WO2005073165, WO2006137395, JP2007099761, WO2008000438, WO2008074427, WO2008107091, WO2010013567, WO2010018714, WO2010090282, WO2010127926, WO2010127928, JP2011063549, WO2012020483, WO2012020484, WO2012077221, WO2012164698, WO2013050261, WO2014069665, WO2014067838, WO2014161848, WO2014161850, WO2015097091 or WO2015097094, etc.; halogenated material R 4 LG and alkali are generally commercially available and may be self-prepared in accordance with conventional methods.
The embodiment of the application also provides application of the amide compound in preparing pesticides.
In one possible implementation, the insecticide is used to control one or more of the following insects:
beetles (Coleopteran), such as green bean image (Callosobruchus Chinensis), corn image (Sitophilus zeamais), red larch (Tribolium Castaneum), potato ladybug (Epilachna vigintioctomaculata), fine chest beetle (Agriotes ogurae fuscicollis), polychrome tortoise (Anomala rufocuprea), potato leaf beetle (Leptinotarsa decemlineata), diabrotica spp, monochamus alternatus (Monochamus alternatus endai), root image (Lissorhoptrus oryzophilus), brown beetle (Lyctus brunesus);
lepidopteran (lepidopteran) pests, such as, for example, gypsymoth (Lymantria dispar), yellow brown curtain caterpillar (Malacosoma neustria), cabbage caterpillar subspecies (Pieris rapae crucivora), prodenia litura (Spodoptera litura), cabbage loopers (mamestraarassicae), chilo suppressalis (Chilo suppressalis), corn borer (Ostrinia nubilalis), dried fruit moths (Cadra calibrella), chyanokokakumonhamaki (Adoxophyes honmai), apple diamond back moth (Cydia pomonella), yellow tiger (Agrotis setum), large wax moth (Galleria mellonella), plutella xylostella (Plutella xylostella), tobacco bud noctuid (Heliothis virescens), orange moth (Phyllocnistis citrella);
hemiptera (Hemiptera) pests, such as, for example, emblica nigra (Nephotettix cincticeps), brown planthopper (Nilaparvata lugens), mealybugs (Pseudococcus comstocki), paederia scandens (Unaspis yanonensis), myzus persica, aphis mali (Aphis pomi), aphis gossypii (Aphis gossypii), aphis raphis hanensis (Lipaphia erysimi), pimenta pyrica (Stephanitis nashi), celastrus (Nezara spp.), bemisia (Trialeurodes vaporariorum), pshylla spp.;
thysanoptera (Thysanoptera) pests, such as Thrips palmi, frankliniella occidentalis (Franklinella occidentalis);
orthopteran (orthopteran) pests, such as mole cricket africana (Gryllotalpa Africana), mole locusta africana (Locusta migratoria);
blattaria (blattaria) pests, such as german cockroach (Blattella germanica), american cockroach (Periplaneta americana), yellow-chest termite (Reticulitermes speratus), coptotermes formosanus (Coptotermes formosanus);
diptera (diptera) pests such as house fly (Musca domestica), aedes aegypti (aedes aegypti), gray ground fly (dela platura), culex pallidum (Culex pipiens pallens), anopheles sinensis (Anopheles sinensis), culex trichinensis (Culex tritaeniorhynchus), liriomyza sativae (Liriomyza trifolii), and the like.
Agricultural mites such as Tetranychus cinnabarinus (Tetranychus cinnabarinus), tetranychus urticae (Tetrahychus urticae), panonychus citri (Panonechus citri), tetranychus citri Pi Ying mite (Aculops pelekassi), tarsonemus spp, etc.
In one possible implementation, the pesticide is used for preventing and controlling one or more of armyworms, plutella xylostella and striped rice borers.
The embodiment of the application also provides an insecticide preparation, which contains the amide compound as an active component and one or more auxiliary materials.
In one possible implementation, the pesticide formulation is selected from the following dosage forms: solutions, emulsions, wettable powders, particulate wettable powders, suspensions, powders (powders), foams, pastes, tablets, granules, aerosols, natural agents impregnated with active compounds, synthetic agents impregnated with active compounds, microcapsules, seed coating agents, formulations equipped with combustion devices which may be smoke and fog cans, cans and coils, etc., ULV (cold foggers, hot foggers), etc. These pesticide preparations or animal parasite control agents can be prepared in a known manner, for example, by mixing the active ingredient with a filler (e.g., a liquid diluent or carrier, a liquefied gas diluent or carrier, a solid diluent or carrier), and optionally with a surfactant (i.e., an emulsifier and/or a dispersant and/or a foaming agent), etc.
In one possible implementation, the auxiliary materials include 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;
liquid diluents or carriers can include, for example, aromatic hydrocarbons (xylenes, 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, dimethylsulfoxide), water, etc. When water is used as the filler, for example, an organic solvent may be used as the cosolvent;
liquefied gas diluents or carriers may 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.), 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, and the like;
dispersants may include lignin sulfite waste liquor and methylcellulose;
the binder may include carboxymethyl cellulose, natural or synthetic polymers (e.g., gum arabic, polyvinyl alcohol, polyvinyl acetate, etc.).
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 iron, manganese, boron, copper, cobalt, molybdenum or zinc salts.
In addition, the amide compounds of the present application may be present as a mixture with a potentiator, which itself need not be active. More precisely, it is a compound that enhances the activity of an active compound.
In one possible implementation, the above amide-type compound is contained in the pesticide formulation in an amount of 0.1 to 99% by weight, alternatively 0.5 to 90% by weight.
Embodiments of the present application also provide an insecticidal composition comprising a mixture of the above amide compounds and other active compounds (e.g., insecticides, baits, disinfectants, acaricides, nematicides, fungicides, growth regulators, herbicides, etc.). The mixture may be provided in the form of a drug substance, or may be provided in the form of a commercially useful formulation or use made of a formulation thereof.
The embodiment of the application also provides a method for controlling agricultural or forestry pests, which comprises the following steps: applying an effective dose of a material to the pest or growth medium thereof in need of control, the material selected from one or more of the following groups: the amide compound, the insecticide preparation and the insecticide composition.
The embodiment of the application also provides application of the amide compound in preparing an animal parasite control agent. In the veterinary field, i.e. in veterinary science, the amide compounds of the application 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:
the order of the lice (anolurida), such as the genus sanguinea (Haematopinus spp.), the genus pubescent lice (Linognathus spp.), the genus pedicellus (Pediculus spp.), the genus phophonus spp and the genus pedicellus (solenopodites spp.); in particular, representative examples are acanthosis (Linognathus setosus), bovine Guan Shi (Solenopotes capillatus);
the order Mallopharyngodii (Mallopha, niu Eshi (Linognathus vituli), ovine jaw lice (Linognathus ovillus), linognathus oviformis, pediculus humanus (Linognathus pedalis), caprine jaw lice (Linognathus stenopsis), donkey blood lice (Haematopinus asini macrocephalus), bovine blood lice (Haematopinus eurysternus), porcine blood lice (Haematopinus suis), head lice (Pediculus humanus capitis), body lice (Pediculus humanus corporis), vitis vinifera (Phylloera vastatrix), pubic lice (Physalis pubis) gida) and obtuse subgenera (Amblycerina) and fine angular subgenera (Ischnocerin), for example, pubescent genus (trimethon spp.), avian genus (Menopon spp.), megaseries (Triniton spp.), bovine genus (Bovicola spp.), werneckiella spp.), lepikentron spp, animal genus (Damalina spp.), chewing genus (Trichoderma spp.), and cat genus (Felicola spp); in particular, representative examples are cattle lice (bovicobaboovis), wool lice (Bovicola ovis), angora caprae seu ovis (Bovicola limbata), cattle lice (damaliabaovis), canine lice (Trichodectes canis), cat lice (Felicola subrostratus), goat lice (Bovicola caprae), lepikentron ovis, biting lice (Werneckiella equi);
diptera (Diptera) and its long-angle subgenera (nematocida) and short-angle subgenera (Brachycerina), for example, aedes spp, anopheles spp, culex spp, gnat spp, samphium spp, eugnat spp, feusimum spp, sand fly spp, tsetse spp, volcania spp, huang Meng spp, tabanus spp, haemopotus spp, philippica spp, and Juniperus spp stings (stomyxs spp.), black horn flies (haemaggla spp.), moflies (Morellia spp.), toilet flies (Fannia spp.), glossas (Glossina spp.), liriomys (calicop spp.), lucilia spp.), drosophila (Chrysomyia spp.), sedge (wohlfahria spp.), numbing (Sarcophaga spp.), mad flies (Oestrus spp.), dermatophagomphora (Hypoderma spp.), gastric flies (gastophilus spp), louse flies (hippoboscapca), capricosphaera (lipopepena spp.), ticks (melicosphaera spp), rhinomys (melo spp), rhinomys (rhodosporus spp), rhodomys (rhodomys spp.), mosquito-to-the mosquito; in particular the number of the elements to be processed, a representative example of this is the case, aedes aegypti (Aedes aegypti), aedes albopictus (Aedes albopictus), aedes albopictus (Aedes taeniorhynchus), anopheles gambiae (Anopheles gambiae), anopheles pentadactyla (Anopheles maculipennis), red head blowfly (Calliphora erythrocephala), horsefly (Chrysozona pluvialis), culex pentadactyla (Culex quinquefasciatus), culex spinosa (Culex pipiens), culex coral mosquito (Culex tarsystem), tsetse fly (Fannia canicularis), bot (Sarcophaga carnaria), stable fly (Stomoxys calcitrans), big mosquito (tipulpa ludax), cuprina (Lucilia cuprina), lucilia sericata (Lucilia sericata), tseta (Simulium reptans), phlebotius (Phlebotomus papatasi), sand fly (Phlebotomus longipalpis) the formulation may be selected from the group consisting of Tabanus variabilis (Odagmia ornata), ma Wei (Wilhelmia equina), tabanus (Boophthora erythrocephala), tabanus (Tabanus brius), tabanus (Tabanus spodopterus), tabanus (Tabanus atlus), tabanus (Tabanus sudeticus), tabanus (Hybomitra cifea), tabanus (Chrysops caecutiens), huang Yuanban Tabanus (Chrysops relictus), tabanus grandis (Haemaponaria) Haemaponica, sakura aunmalis, musca domestica (Musca domica), hypsida (Haematobia irritans irritans), hypsida (Haematobia irritans exigua), tabanus (Haematobia stimulans), hydrotaea irritans, hypsida (Hydrotaea albipuncta), chrysomya chloropyga, chrysomyia (Chrysomya bezziana), sheep flies (oetrus ovis), cow flies (hypoderm bovis), schlemanides (Hypoderma lineatum), przhevalskiana silenus, human flies (Dermatobia hominis), sheep ticks (Melophagus ovinus), lipoptena capreoli, deer flies (Lipoptena cervi), hippobosca variegata, ma Shiying (Hippobosca equina), enterogastric flies (Gasterophilus intestinalis), red tail gastric flies (Gasterophilus haemorroidalis), naked festival gastric flies (Gasterophilus interrnis), nasogany flies (Gasterophilus nasalis), black horn gastric flies (Gasterophilus nigricornis), black belly gastric flies (Gasterophilus pecorum), bee flies (Braula coeca);
the order of the fleas (siphanapterida), for example, the genus flea (Pulex spp.), the genus Ctenocephalides (Ctenocephalides spp.), the genus daphnia (Tunga spp.), the genus Populus (Xenopsyla spp.), the genus Metridia (Ceratophyllus spp.); in particular, representative examples are, chlamydia canis (Ctenocephalides canis), chlamydia felis (Ctenocephalides felis), human fleas (Pulex iritans), skin penetrating daphnia (Tungarenetrans), and Porphyra yezoensis (Xenopsylla cheopis);
heteroptera (Heteropterida), for example, bugs (Cimex spp.), glabrous (Triatoma spp.), red stinkbug (rhodonius spp.), glabrous (panstrongylous spp.);
blattaria (blattaria), e.g., blattaria orientalis (Blatta orientalis), periplaneta americana, german cockroach, xia Baila cockroach genus (Supella spp.) (e.g., suppella longipalpa);
acarina (Acari) (or Acarina), back valve (Metastigmata) and middle valve (Mesostigmata), for example, sharp-edged ticks (Argas spp.), blunt-edged ticks (Ornithosporus spp.), residual-beak ticks (otobicus spp.), hard ticks (Ixodes spp.), yellow ticks (Amblyomma spp.), bovine ticks (Rhipicephalus (Boophilus) spp.), leather ticks (Dermacentor spp.), haemophilus spp, glazed eye ticks (Hyalomma spp.), dermatophagoides (Dermassus spp.), rhipicephalus spp.) (primordium of heteromain parasitic mites), bird mites (Ornithinosus spp.), pneumocystis (Pneum spp.), pneumocystis spp., pneumocystis spp.), pneumocystis (Pneumocystis spp.), acalymite spp.); in particular, representative examples are, bose sharp-edged ticks (Argas personatus), pigeon sharp-edged ticks (Argas reflexus), african blunt-edged ticks (Ornithodorus moubata), residual ear-mouth ticks (otobium mergnii), microplus (microplus) Rhipicephalus (Boophilus) microplus, achromatopsia (achromatopsia) (Rhipicephalus (Boophilus) decoloratus), loop-bearing ticks (loop-bearing ticks) (Rhipicephalus (Boophilus) annula tus), rectangular-bearing ticks (rectangular-bearing ticks) (Rhipicephalus (Boophilus) calcaratus), hyalomma anatolicum, egyptian glazed ticks (Hyalommaegyptus), hyalomma marginatum, hyalomma transiens, valgus (Rhipicephalus evertsi), rigid castor (Ixodes ricus), hexagonal hard ticks (Ixodes hexagonus) wild hard ticks (Ixodes canisuga), hairy hard ticks (Ixodes pilosus), light red hard ticks (Ixodes rubicundus), shoulder hard ticks (Ixodes scapularis), full-loop hard ticks (Ixodes holocyclus), group-addicted blood ticks (Haemaphysalis concinna), point-carved blood ticks (Haemaphysalis punctata), haemaphysalis cinnabarina, haemaphysalis otophila, canine blood ticks (Haemaphysalis leachi), long angle blood ticks (Haemaphysalis leachi), edge leather ticks (Haemaphysalis leachi), reticulate leather ticks (Haemaphysalis leachi), haemaphysalis leachi ticks (Haemaphysalis leachi), angust ticks (Haemaphysalis leachi), variant leather ticks (Haemaphysalis leachi), red eye ticks (Haemaphysalis leachi), balloon-shaped fan head ticks (Haemaphysalis leachi), african fan head ticks (Haemaphysalis leachi), the method comprises the following steps of (1) a top of a good-angle fan tick (Rhipicephalus capensis), a bottom of a blue fan tick (Rhipicephalus turanicus), a Rhipicephalus zambeziensis, a American chlorpyrifos (Amblyomma americanum), a color-decorated chlorpyrifos (Amblyomma variegatum), a spotted chlorpyrifos (Amblyomma maculatum), a Hibernation chlorpyrifos (Amblyomma hebraeum), a calico chlorpyrifos (Amblyomma cajennense), a panacis gallica (Dermanyssus gallinae), a fowly spider mite (Ornithonyssus bursa), a woody bird spider mite (Ornithonyssus sylviarum) and a bee mite (Varroajacobscon);
the order axopharyngeales (Actinedida) (Prostigmata) and the order anatida (anabroides (anagemata)), for example, the genus acarina (Acarapis spp.), the genus Acarina (Cheylella spp.), the genus Acarina (Ornithohepatica spp.), the genus Myobatus (Myobata spp.), the genus Pneuchus (Psorrgates spp.), the genus Demodex spp), the genus Acarina (Tromphespecially spp), the genus Listeria, the genus Acarina (Acarina spp.), the genus Tyrophagus, the genus Trichoderma (Caloglyphus spp), the genus Pygophus (Hypomyces spp), the genus Pterolicus spp), the genus Psorophymite (Psorophytophus spp), the genus Demodex spp, the genus Sarcops (Otocop spp), the genus Cyclopyra spp (Cytophagus spp), the genus Cyclopentanus spp (Cytophaga spp), the genus Cyclopentanus spp) and the genus Cyclopentanus; in particular the number of the active ingredients, the composition comprises Demodex mitis (C heyletiella yasguri), brucella Ji Aoman (C heyletiellablakei), demodex anis, demodex bovis, demodex ovis, demodex caprae, ma Ruxing mite (Demodex equi), demodex caballi, demodex sui, neotrombicula autumnalis, neotrombiculadesali, neoschonegastia xerothermobia, okara mite (Trombicula akamushi), demodex bovis (Otodectes cynotis), demodex scab mite (Notoedres cati) dog mites (sarcoptics anii), niu Jieman (sarcoptics bovis), sheep mites (sarcoptics ovis), goat mites (Sarcoptes rupicaprae (=s.caprae)), ma Jieman (sarcoptics equi), pig mites (sarcoptics suis), sheep mites (Psoropates ovis), rabbit mites (Psoroptes cuniculi), maman (Psoropates equi), niu Yangman (chord bovis), psoergates ovis, pneumonyssoidic mange, canine nasal scabies (Pneumonyssoides caninum), and bee tarsoneter (Acarapis woodi);
nematodes, such as meloidogyne incognita (Meloidogyne incognita), pine wood nematodes (Bursaphelenchus xylophilus), aphelenchus besseyi (Aphelenchoides besseyi), heterodera sojae (Heterodera glycines), brachycinus spp, and the like;
arthropods, helminths and plasmodium that attack animals. Control of arthropods, helminths and/or plasmodium can reduce mortality in domestic animals and can 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 cat fleas, american dog ticks.
In one possible implementation, the animal comprises one or more of the following: 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, caged birds, ornamental fish; also included are animals used in the experiments, such as hamsters, guinea pigs, rats, mice, and the like.
The embodiment of the application also provides an animal parasite control agent, which comprises the amide compound as an active component 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, etc.), smears, aerosols, pressureless sprays (e.g., pump sprays and nebulized 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 application also provide an animal parasite control composition comprising a mixture of the above amide compounds and other animal parasite control active compounds (e.g., acaricides, insecticides, parasiticides, antimalarial agents, etc.). The mixture may be provided in the form of a drug substance, or may be provided in the form of a commercially useful formulation or use made of a formulation thereof.
The embodiment of the application also provides a method for controlling animal parasites, which comprises the following steps: applying an effective dose of a material selected from one or more of the following groups to an animal parasite or growth medium thereof in need of control: the amide compound; the above animal parasite control agent; the animal parasite control composition. For example: enteral administration is performed by using tablets, capsules, potions, drinkable drugs, granules, pastes, pills and suppositories; parenteral administration based on skin administration, such as injection (intramuscular, subcutaneous, intravenous, intraperitoneal, etc.), implantation, nasal administration, including bathing or soaking, spraying, pouring, drip, washing and dusting, and administration by using a model article containing the active compound, such as a collar, ear tag, label, leg strap (leg strap), mesh, marker, etc. The active compounds of the present application have low toxicity and can be used safely in warm-blooded animals.
Advantageous effects
The amide compounds of the present application have unexpectedly excellent insecticidal effects, which also exhibit suitable control effects on toxic pests, and are not phytotoxic to cultivated crop plants. In addition, the compounds of the present application are useful for controlling a variety of pests, such as harmful piercing-sucking insects, chewing insects, and other plant parasitic pests, storage grain pests, sanitary pests, and the like, and for disinfecting and killing them.
Detailed Description
For the purpose of making the objects, technical solutions and advantages of the embodiments of the present application more apparent, the technical solutions in the embodiments of the present application will be clearly and completely described below, and it is apparent that the described embodiments are some embodiments of the present application, but not all embodiments. All other embodiments, which can be made by those skilled in the art based on the embodiments of the application without making any inventive effort, are intended to be within the scope of the application. .
In addition, numerous specific details are set forth in the following description in order to provide a better illustration of the application. It will be understood by those skilled in the art that the present application may be practiced without some of these specific details. In some embodiments, materials, elements, methods, means, etc. well known to those skilled in the art are not described in detail in order to highlight the gist of the present application.
Throughout the specification and claims, unless explicitly stated otherwise, the term "comprise" or variations thereof such as "comprises" or "comprising" or the like will be understood to include the stated element or component without excluding other elements or components
All materials are commercially available unless otherwise noted.
In the present application, the terms used have the following meanings:
halogen: refers to fluorine, chlorine, bromine or iodine.
Haloalkyl: linear or branched alkyl groups, the hydrogen atoms of these alkyl groups being substituted, in part or in whole, by halogen, e.g. difluoromethyl (CHF) 2 ) Trifluoromethyl (CF) 3 ) Etc.
Haloalkoxy: the hydrogen atoms of the alkoxy groups being partly or wholly substituted by halogen, e.g. difluoromethoxy (OCHF) 2 ) Trifluoromethyl methyl esterOxy (OCF) 3 ) Etc.
Cyanoalkyl: straight-chain or branched alkyl groups, the hydrogen atoms in these alkyl groups being substituted, in part or in whole, by cyano groups, cyano groups C 1 -C 4 C in alkyl 1 -C 4 Representing chain length of alkyl groups, e.g. CH 2 CN、CH 2 CH 2 CN、CH 2 CH 2 CH 2 CN、CH 2 CH 2 CH 2 CH 2 CN、CH(CH 3 )CN、CH(CH 2 CH 3 )CN、CH(CH 2 CH 2 CH 3 )CN、C(CH 3 )(CH 3 ) CN or C (CH) 3 )(CH 2 CH 3 )CN。
And (3) an insecticide: a substance having an insecticidal effect on pests.
Animal parasite control agents: refers to an active compound that is effective in reducing the incidence of various parasites in animals infected with the parasites. By control is meant that the active compound is effective in killing parasites and inhibiting their growth or reproduction.
Synthetic examples
According to the synthetic route, different raw material compounds are adopted to prepare and obtain the compound shown in the general formula I, and the compound is further specifically described as follows:
example 1: preparation of intermediate II.1
To 30 ml of DMF were added 1.00 g (1.80 mmol) of N- (2, 6-dibromo-4-heptafluoroisopropylphenyl) -2-fluoro-3-aminobenzamide (intermediate III-1, produced by the method reported in WO2011093415 or WO 2010018714), 0.37 g (2.68 mmol) of potassium carbonate, 0.27 g (1.80 mmol) of sodium iodide and 0.26 g (2.19 mmol) of bromoacetonitrile, and the mixture was heated to 100 ℃. After the TLC monitoring reaction was completed, water and ethyl acetate were added for extraction, the organic phase was desolventized under reduced pressure, and the residue was purified by column chromatography to obtain 0.50 g of a white solid, intermediate II.1. The nuclear magnetism and mass spectrum data of intermediate ii.1 are as follows:
1 H NMR(600MHz,Chloroform-d)δ8.11(d,1H),7.88(s,2H),7.64–7.58(m,1H),7.29(t,1H),7.05(td,1H),4.52-4.44(br,1H),4.24(d,2H).LC-MS(m/z,ESI):594.01(M+H) + .
example 2: preparation of intermediate II.2
10 g of N- (2-bromo-6-iodo-4-heptafluoroisopropylphenyl) -2-fluoro-3-nitrobenzamide (prepared by 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 were added, and the mixture was heated to 60℃to stir the reaction. After the completion of the TLC monitoring, the organic solvent was distilled off under reduced pressure. 500 ml of ethyl acetate was added, and a proper amount of saturated aqueous sodium hydroxide solution was added to adjust ph=10, after stirring thoroughly, insoluble matters separated out were filtered off with celite, after extraction of the filtrate with ethyl acetate and water, the organic layer was dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure to give a tan solid, and the crude product was purified by column chromatography to give 7.91 g of N- (2-bromo-6-iodo-4-heptafluoroisopropylphenyl) -2-fluoro-3-aminobenzamide (intermediate III-2).
To 30 ml of DMF were added 1.00 g (1.66 mmol) of N- (2-bromo-6-iodo-4-heptafluoroisopropylphenyl) -2-fluoro-3-aminobenzamide (intermediate III-2), 0.34 g (2.46 mmol) of potassium carbonate, 0.25 g (1.67 mmol) of sodium iodide and 0.24 g (2.00 mmol) of bromoacetonitrile, and the mixture was heated to 100 ℃. After the TLC monitoring reaction was completed, water and ethyl acetate were added for extraction, the organic phase was desolventized under reduced pressure, and the residue was purified by column chromatography to obtain 0.43 g of a white solid, intermediate II.2. The nuclear magnetism and mass spectrum data of intermediate ii.2 are as follows:
1 H NMR(600MHz,Chloroform-d)δ8.12(d,1H),8.08(d,1H),7.90(d,1H),7.61(t,1H),7.29(t,1H),7.05(td,1H),4.54-4.47(br,1H),4.24(d,2H).LC-MS(m/z,ESI):642.05(M+H) + .
example 3: preparation of intermediate II.3
To 60 ml of DMF was added 2.00 g (3.67 mmol) of N- (2-bromo-6-trifluoromethyl-4-heptafluoroisopropylphenyl) -2-fluoro-3-aminobenzamide (intermediate III-3, prepared by the method reported in WO2011093415 or WO 2010018714), 0.76 g (5.50 mmol) of potassium carbonate, 0.56 g (3.74 mmol) of sodium iodide and 0.53 g (4.42 mmol) of bromoacetonitrile, and the mixture was heated to 100 ℃. After the TLC monitoring reaction was completed, water and ethyl acetate were added for extraction, the organic phase was desolventized under reduced pressure, and the residue was purified by column chromatography to obtain 0.78 g of a white solid, intermediate II.3. The nuclear magnetism and mass spectrum data of intermediate ii.3 are as follows:
1 H NMR(600MHz,Chloroform-d)δ8.18(d,1H),8.16–8.13(m,1H),7.94–7.90(m,1H),7.63–7.55(m,1H),7.29(t,1H),7.05(td,1H),4.52–4.45(m,1H),4.24(d,2H).LC-MS(m/z,ESI):584.04(M+H) + .
example 4: preparation of intermediate II.4
To 60 ml of DMF were added 2.00 g (3.67 mmol) of N- (2-bromo-6-trifluoromethyl-4-heptafluoroisopropyl phenyl) -2-fluoro-3-aminobenzamide (intermediate III-3), 0.76 g (5.50 mmol) of potassium carbonate, 0.55 g (3.67 mmol) of sodium iodide and 0.59 g (4.40 mmol) of bromopropionitrile, and the mixture was heated to 100 ℃. After the TLC monitoring reaction was completed, water and ethyl acetate were added for extraction, the organic phase was desolventized under reduced pressure, and the residue was purified by column chromatography to obtain 0.22 g of a white solid, intermediate II.4. The nuclear magnetism and mass spectrum data of intermediate ii.4 are as follows:
1 H NMR(600MHz,Chloroform-d)δ8.22(d,1H),8.16–8.13(m,1H),7.93–7.90(m,1H),7.50–7.45(m,1H),7.20(t,1H),6.91(td,1H),4.46–4.38(m,1H),3.63(q,2H),2.72(t,2H).LC-MS(m/z,ESI):598.05(M+H) + .
example 5: preparation of intermediate II.5
To 40ml of DMF were added 1.30 g (2.39 mmol) of N- (2-bromo-6-trifluoromethyl-4-heptafluoroisopropylphenyl) -2-fluoro-3-aminobenzamide (intermediate III-3), 0.49 g (3.55 mmol) of potassium carbonate, 0.36 g (2.40 mmol) of sodium iodide and 0.46 g (3.13 mmol) of bromobutyronitrile, and the mixture was heated to 100 ℃. After the TLC monitoring reaction was completed, water and ethyl acetate were added for extraction, the organic phase was desolventized under reduced pressure, and the residue was purified by column chromatography to obtain 0.19 g of a white solid, intermediate II.5. The nuclear magnetism and mass spectrum data of intermediate ii.5 are as follows:
1 H NMR(600MHz,Chloroform-d)δ8.22(d,1H),8.15–8.13(m,1H),7.92–7.90(m,1H),7.46–7.40(m,1H),7.18(t,1H),6.94(td,1H),4.17–4.09(m,1H),3.43(q,2H),2.54(t,2H),2.08–2.02(m,2H).LC-MS(m/z,ESI):612.06(M+H) + .
example 6: preparation of intermediate II.6
To 50 ml of DMF were added 1.65 g (3.03 mmol) of N- (2-bromo-6-trifluoromethyl-4-heptafluoroisopropylphenyl) -2-fluoro-3-aminobenzamide (intermediate III-3), 0.62 g (4.50 mmol) of potassium carbonate, 0.46 g (3.07 mmol) of sodium iodide and 0.61 g (3.79 mmol) of bromovaleronitrile, and the mixture was heated to 100 ℃. After the TLC monitoring reaction was completed, water and ethyl acetate were added for extraction, the organic phase was desolventized under reduced pressure, and the residue was purified by column chromatography to obtain 0.21 g of a white solid, intermediate II.6. The nuclear magnetism and mass spectrum data of intermediate ii.6 are as follows:
1 H NMR(600MHz,Chloroform-d)δ8.23(d,1H),8.14(d,1H),7.91(d,1H),7.42–7.37(m,1H),7.17(t,1H),6.91(td,1H),4.13–3.98(m,1H),3.28(t,2H),2.45(t,2H),1.93–1.80(m,4H).LC-MS(m/z,ESI):626.05(M+H) + .
example 7: preparation of intermediate II.7
Intermediate ii.7 (white solid) was prepared by reacting intermediate III-4 (prepared as reported in reference to WO2011093415 or WO 2010018714) with bromoacetonitrile according to the procedure described in example 3. The nuclear magnetism and mass spectrum data of intermediate ii.7 are as follows:
1 H NMR(600MHz,Chloroform-d)δ8.37–8.34(m,1H),8.22(d,1H),7.96–7.93(m,1H),7.64–7.57(m,1H),7.29(t,1H),7.05(td,1H),4.52–4.45(m,1H),4.25(d,2H).LC-MS(m/z,ESI):631.99(M+H) + .
example 8: preparation of intermediate II.8
Intermediate II.8 (white solid) was prepared from intermediate III-4 by reaction with bromopropionitrile according to the procedure described in example 4. The nuclear magnetism and mass spectrum data of intermediate ii.8 are as follows:
1 H NMR(600MHz,Chloroform-d)δ8.36(d,1H),8.26(d,1H),7.94(d,1H),7.51–7.46(m,1H),7.21(t,1H),6.92(td,1H),4.47–4.39(m,1H),3.64(q,2H),2.72(t,2H).LC-MS(m/z,ESI):646.02(M+H) + .
example 9: preparation of intermediate II.9
Intermediate II.9 (white solid) was prepared from intermediate III-4 by the reaction of bromobutyronitrile according to the procedure described in example 5. The nuclear magnetism and mass spectrum data of intermediate ii.9 are as follows:
1 H NMR(600MHz,Chloroform-d)δ8.36–8.34(m,1H),8.27(d,1H),7.95–7.92(m,1H),7.45–7.40(m,1H),7.18(td,1H),6.94(td,1H),4.18–4.11(br s,1H),3.43(q,2H),2.54(t,2H),2.08–2.02(m,2H).LC-MS(m/z,ESI):682.24(M+Na) + .
example 10: preparation of intermediate II.10
Intermediate II.10 (white solid) was prepared from intermediate III-4 by reacting with bromovaleronitrile according to the procedure described in example 6. The nuclear magnetism and mass spectrum data of intermediate ii.10 are as follows:
1 H NMR(600MHz,Chloroform-d)δ8.35(d,1H),8.28(d,1H),7.93(d,1H),7.43–7.38(m,1H),7.17(t,1H),6.91(td,1H),4.22–3.90(br s,1H),3.28(t,2H),2.45(t,2H),1.92–1.81(m,4H).LC-MS(m/z,ESI):696.26(M+Na) + .
example 15: preparation of Compound 1
To 20 ml of toluene were added 0.30 g (0.51 mmol) of intermediate II.1 and 0.12 g (0.72 mmol) of 6-cyanonicotinoyl chloride, and the mixture was refluxed. After the TLC monitoring reaction was completed, the solution was removed under reduced pressure, and the residue was purified by column chromatography to obtain 0.23 g of a white solid, namely Compound 1. The nuclear magnetism and mass spectrum data of compound 1 are as follows:
1 H NMR(600MHz,Chloroform-d)δ8.71–8.66(m,1H),8.19(t,1H),7.93–7.86(m,4H),7.64(d,1H),7.58–7.54(m,1H),7.42(t,1H),5.00(d,1H),4.65(d,1H).LC-MS(m/z,ESI):724.15(M+H) + .
example 16: preparation of Compound 5
Compound 5 (white solid) was prepared from intermediate ii.2 and 6-cyanonicotinoyl chloride according to the procedure described in example 15. The nuclear magnetism and mass spectrum data of compound 5 are as follows:
1 H NMR(600MHz,Chloroform-d)δ8.71–8.66(m,1H),8.20(t,1H),8.08(d,1H),7.93–7.85(m,3H),7.63(d,1H),7.58(t,1H),7.43(t,1H),4.99(d,1H),4.66(d,1H).LC-MS(m/z,ESI):772.20(M+H) + .
example 17: preparation of Compound 9
Compound 9 (yellow solid) was prepared from intermediate ii.3 and 6-cyanonicotinoyl chloride according to the procedure described in example 15. The nuclear magnetism and mass spectrum data of compound 9 are as follows:
1 H NMR(600MHz,Chloroform-d)δ8.72–8.57(m,1H),8.23–8.09(m,2H),8.01(d,1H),7.96–7.83(m,2H),7.64(d,1H),7.61–7.55(m,1H),7.43(t,1H),4.98(d,1H),4.66(d,1H).LC-MS(m/z,ESI):736.29(M+Na) + .
example 18: preparation of Compound 10
Compound 10 (yellow solid) was prepared from intermediate ii.4 and 6-cyanonicotinoyl chloride according to the procedure described in example 15. The nuclear magnetism and mass spectrum data of compound 10 are as follows:
1 HNMR(600MHz,Chloroform-d)δ8.64(s,1H),8.13(d,1H),8.05(t,1H),7.96(d,1H),7.91–7.89(m,1H),7.85(dd,1H),7.68(td,1H),7.61(d,1H),7.42(t,1H),4.19(t,2H),3.06–2.96(m,1H),2.95–2.84(m,1H).LC-MS(m/z,ESI):750.32(M+Na) + .
example 19: preparation of Compound 11
Compound 11 (yellow oil) was prepared from intermediate ii.5 and 6-cyanonicotinoyl chloride according to the procedure described in example 15. The nuclear magnetism and mass spectrum data of compound 11 are as follows:
1 H NMR(600MHz,Chloroform-d)δ8.60(s,1H),8.14(d,1H),8.10–8.04(m,1H),7.97(d,1H),7.91(d,1H),7.83(dd,1H),7.62–7.53(m,2H),7.38(t,1H),4.16–4.04(m,2H),2.56(t,2H),2.18–2.02(m,2H).LC-MS(m/z,ESI):764.34(M+Na) + .
example 20: preparation of Compound 12
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Compound 12 (yellow oil) was prepared from intermediate ii.6 and 6-cyanonicotinoyl chloride according to the procedure described in example 15. The nuclear magnetism and mass spectrum data of compound 12 are as follows:
1 HNMR(600MHz,Chloroform-d)δ8.60(s,1H),8.20–8.11(m,2H),8.02(t,1H),7.90(d,1H),7.83–7.76(m,1H),7.58(d,1H),7.55–7.49(m,1H),7.39(t,1H),4.25(br s,1H),3.90–3.79(m,1H),2.57–2.36(m,2H),1.93–1.77(m,4H).LC-MS(m/z,ESI):778.37(M+Na) + .
example 21: preparation of Compound 13
Compound 13 (yellow solid) was prepared from intermediate ii.7 and 6-cyanonicotinoyl chloride according to the procedure described in example 15. The nuclear magnetism and mass spectrum data of compound 13 are as follows:
1 HNMR(600MHz,Chloroform-d)δ8.65(d,1H),8.35(d,1H),8.18–8.12(m,1H),8.07(d,1H),7.94(d,1H),7.89(dd,1H),7.64(d,1H),7.62–7.56(m,1H),7.43(t,1H),4.97(br s,1H),4.67(br s,1H).LC-MS(m/z,ESI):784.32(M+Na) + .
example 22: preparation of Compound 14
Compound 14 (yellow solid) was prepared from intermediate ii.8 and 6-cyanonicotinoyl chloride according to the procedure described in example 15. The nuclear magnetism and mass spectrum data of compound 14 are as follows:
1 H NMR(600MHz,Chloroform-d)δ8.65(s,1H),8.33(d,1H),8.09–7.97(m,2H),7.93(d,1H),7.84(dd,1H),7.69(td,1H),7.60(d,1H),7.43(t,1H),4.19(s,2H),3.08–2.97(m,1H),2.95–2.84(m,1H).LC-MS(m/z,ESI):798.34(M+Na) + .
example 23: preparation of Compound 15
Compound 15 (yellow solid) was prepared from intermediate ii.9 and 6-cyanonicotinoyl chloride according to the procedure described in example 15. The nuclear magnetism and mass spectrum data of compound 15 are as follows:
1 HNMR(600MHz,Chloroform-d)δ8.61(s,1H),8.34(d,1H),8.11–7.97(m,2H),7.93(d,1H),7.86–7.79(m,1H),7.62–7.54(m,2H),7.39(t,1H),4.17–4.04(m,2H),2.56(t,2H),2.18–2.02(m,2H).LC-MS(m/z,ESI):812.36(M+Na) + .
example 24: preparation of Compound 16
Compound 16 (yellow solid) was prepared from intermediate ii.10 and 6-cyanonicotinoyl chloride according to the procedure described in example 15. The nuclear magnetism and mass spectrum data of compound 16 are as follows:
1 HNMR(600MHz,Chloroform-d)δ8.60(s,1H),8.33(d,1H),8.19(s,1H),8.02(t,1H),7.92(d,1H),7.82–7.74(m,1H),7.61–7.50(m,2H),7.39(t,1H),4.26(br s,1H),3.83(br d,1H),2.55–2.36(m,2H),1.90–1.77(m,4H).LC-MS(m/z,ESI):826.41(M+Na) + .
other compounds of formula I of the present application may be prepared with reference to the above examples.
Biological Activity assay
Example 25: biological activity assay of armyworm, plutella xylostella and Chilo suppressalis
The compounds of the present application were used to conduct insecticidal activity assays on several insects. The measurement method is as follows:
after the test compound was dissolved in a mixed solvent of acetone/methanol (1:1), it was diluted to a desired concentration with water containing 0.1% (wt) tween 80.
Taking armyworm, plutella xylostella and Chilo suppressalis as targets, and adopting an airburst spray method to perform activity measurement.
(1) Determination of the insecticidal Activity
The measuring method comprises the following steps: corn leaves were cut into 2cm long leaf segments and the airburst spray treatment was carried out at a pressure of 10psi (approximately 0.7kg/cm 2 ) The front and back sides of each leaf segment are sprayed, and the spraying amount of the compound to be tested is 0.5ml. After shade drying, 10 larvae of 3 ages are inoculated per treatment, and 3 replicates per treatment are obtained. Culturing in an observation room with the temperature of 25 ℃ and the relative humidity of 60-70% after treatment, investigating the number of the survived insects 3 days after the medicine, and calculating the death rate.
The results of the partial test on armyworm are as follows:
at the dosage of 0.05mg/L, the mortality rate of the compounds 1, 5, 9, 10, 11, 12, 13, 14, 15 and 16 to armyworms is more than 90% 3 days after the administration.
(2) Determination of Plutella xylostella killing Activity
The measuring method comprises the following steps: the cabbage leaves are punched with a punch into leaf discs of 2cm diameter and the airburst spray is applied at a pressure of 10psi (approximately 0.7kg/cm 2 ) The front and back sides of each leaf dish are sprayed, and the spraying amount of the compound to be tested is 0.5ml. After shade drying, 10 larvae of 3 ages are inoculated per treatment, and 3 replicates per treatment are obtained. Culturing in an observation room with the temperature of 25 ℃ and the relative humidity of 60-70% after treatment, investigating the number of the survived insects 3 days after the medicine, and calculating the death rate.
The results of the partial test on plutella xylostella are as follows:
at a dose of 1mg/L, the mortality rate of the compounds 1, 5, 9, 10, 11, 12, 13, 14, 15 and 16 to plutella xylostella is above 90%.
At the dosage of 0.05mg/L, the mortality rate of the compounds 9, 10, 11, 12, 13, 14, 15 and 16 to the plutella xylostella is above 90%.
(3) Determination of Chilo suppressalis Activity
The measuring method comprises the following steps: 1) Rice seedling preparation: culturing rice in a plastic small cup with the diameter of 4.5cm and the height of 4cm in a thermostatic chamber (the temperature is 26-28 ℃ and the relative humidity is about 60-80 percent, and the illumination is 16hL:8 hD), and selecting strong rice seedlings with consistent growth vigor to perform medicament treatment when the rice grows to 4-5 leaf stage, wherein the treatment is repeated for 3 times. 2) Preparing for insect test: chilo suppressalis continuously fed indoors and 3-instar larvae. 3) The rice stems are sprayed to collect insects. The rice seedlings are subjected to uniform spraying treatment of the whole plants by adopting a spraying method, and each treatment dose is 15ml. The blank was treated and then the above procedure was repeated in the order of test concentration from low to high. After the rice seedlings are sprayed, the rice seedlings are placed in a shade place to be dried, and the stem is cut off from the base of the stem to be fed with test insects by about 5 cm. Preparing a glass culture dish with the diameter of 90mm, filling filter paper on the bottom of the dish, adding water for moisturizing, putting about 5 rice stems into each dish, inoculating 10 heads of larvae, sealing the culture dish with non-woven fabrics, and culturing in a constant-temperature room. The number of residual live insects was investigated 3 days after the administration.
The results of the partial test on the chilo suppressalis are as follows:
at a dose of 1mg/L, the mortality rate of the compounds 1, 5, 9, 10, 11, 12, 13, 14, 15 and 16 to the chilo suppressalis is above 90%.
At the dosage of 0.125mg/L, the mortality rate of the compounds 9, 10, 11, 12, 13, 14, 15 and 16 to the chilo suppressalis is above 90 percent.
Selecting the compounds 1, 9 and 13 of the application and a control compound to carry out a parallel comparison test (3 days after the drug) of insecticidal activity of chilo suppressalis, wherein the measuring method is the same as that described above; the results are shown in Table 2:
TABLE 2 parallel comparative test of insecticidal Activity of Compounds 1, 9, 13 of the application and control Compounds against Chilo suppressalis
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Note that: in table 2 "-" indicates no measurement. 1-1, 1-2, 2-1, 2-2, 3-1, 3-2 in the tables are all control compounds provided by the application; compounds 1-1, 1-2 are obtainable by the method according to example 15 of the present application; compounds 2-1, 2-2 are obtainable by the method according to example 17 of the present application; compounds 3-1, 3-2 are obtainable by the method according to example 21 of the present application; the raw materials are all prepared according to the method of the embodiment of the application or can be purchased or prepared according to the conventional method.
In the examples of the present application, R is as defined for the compounds of formula I 1 、R 2 、R 3 、R 4 The selection of the groups and their combinations gave compounds with better insecticidal effect, as shown in Table 2, by comparing compound 1 with control compounds 1-1, 1-2, by comparing compound 9 with control compounds 2-1, 2-2, and by comparing compound 13 with control compounds 3-1, 3-2, it can be seen that: the cyano group on the benzene ring and the nitrogen atom adjacent to the cyano group are very important, and the cyano group and the nitrogen atom adjacent to the benzene ring are mutually matched, so that the activity of the compound on the chilo suppressalis is obviously reduced or even lost after the cyano group is reserved and the carbon atom is selected as the nitrogen atom adjacent to the cyano group; when the nitrogen atom is retained and the cyano group adjacent thereto is hydrogen-selected, the compound completely loses activity against chilo suppressalis.
Example 26: insecticidal test against cat fleas
4mg of a test compound was dissolved in 40ml of acetone to obtain an acetone solution having a concentration of 100ppm, 400. Mu.l of the solution was applied to the bottom and side surfaces of a dish having an inner diameter of 5.3cm, and then a film of the compound of the present application was formed on the inner wall of the dish after the evaporation of acetone. The inner wall of the dish used was 40cm 2 The treatment dosage is 1 mug/cm 2 The method comprises the steps of carrying out a first treatment on the surface of the 10 cat flea adults (male-female mixture) were placed therein, covered and stored in a thermostatic chamber at 25 ℃. And checking the dead number after 72 hours, and calculating the dead rate. The test was repeated 3 times. Test results: chemical treatmentThe compounds 1, 5, 9, 10, 11, 12, 13, 14, 15, 16 showed a mortality rate of more than 90%.
Example 27: insecticidal test against American Canine ticks
4mg of the test compound was dissolved in 40ml of acetone to obtain an acetone solution having a concentration of 100ppm, 400. Mu.l of the drug solution was applied to the bottom and side surfaces of 2 petri dishes having an inner diameter of 5.3cm, and then a film of the compound of the present application was formed on the inner wall of the petri dishes after the acetone had evaporated. The inner wall of the dish used was 40cm 2 The treatment dosage is 1 mug/cm 2 .10 American canines were placed therein with 1 st nymph (male-female mix), 2 dishes were pooled, the joints were sealed with tape to prevent escape, and stored in a thermostatic chamber at 25 ℃. And checking the dead insect number after 24 hours, and calculating the dead insect rate. The test was repeated 3 times. Test results: compounds 1, 5, 9, 10, 11, 12, 13, 14, 15, 16 showed mortality of more than 90%.

Claims (16)

1. An amide compound, characterized in that: the structure of the amide compound is shown as a general formula I:
in formula I:
R 1 selected from bromine or iodine;
R 2 selected from C 1 -C 4 Haloalkyl or C 1 -C 4 Haloalkoxy groups;
R 3 selected from CF 3 Or CF (CF) 2 CF 3 ；
R 4 Selected from cyano C 1 -C 4 An alkyl group.
2. A compound according to claim 1, characterized in that: in the general formula I
R 1 Selected from bromine or iodine;
R 2 selected from C 1 -C 2 Haloalkyl or C 1 -C 2 HaloalkanesAn oxy group;
R 3 selected from CF 3 Or CF (CF) 2 CF 3 ；
R 4 Selected from cyano C 1 -C 4 An alkyl group.
3. A compound according to claim 2, characterized in that: in the general formula I
R 1 Selected from bromine or iodine;
R 2 selected from trifluoromethyl or difluoromethoxy;
R 3 selected from CF 3 Or CF (CF) 2 CF 3 ；
R 4 Selected from CH 2 CN、CH 2 CH 2 CN、CH 2 CH 2 CH 2 CN、CH 2 CH 2 CH 2 CH 2 CN、CH(CH 3 )CN、CH(CH 2 CH 3 )CN、CH(CH 2 CH 2 CH 3 )CN、C(CH 3 )(CH 3 ) CN or C (CH) 3 )(CH 2 CH 3 )CN。
4. A compound according to claim 3, characterized in that: in the general formula I
R 1 Selected from bromine or iodine;
R 2 selected from trifluoromethyl;
R 3 selected from CF 3 ；
R 4 Selected from CH 2 CN、CH 2 CH 2 CN、CH 2 CH 2 CH 2 CN or CH 2 CH 2 CH 2 CH 2 CN。
5. The amide compound according to claim 1, wherein the amide compound is selected from the group consisting of compounds of table 1, the compounds of table 1 having a structure of formula I and R 1 、R 2 、R 3 And R is 4 As shown in table 1:
TABLE 1
6. Use of an amide compound according to any one of claims 1 to 5 for the preparation of a pesticide.
7. Use according to claim 6, characterized in that: the pesticide is used for preventing and controlling one or more of armyworms, plutella xylostella and chilo suppressalis.
8. An insecticide formulation, characterized in that: the pesticide preparation contains the amide compound as one of claims 1-5 as an active component and one or more auxiliary materials.
9. The pesticide formulation of claim 8, wherein: the amount of the amide-based compound according to any one of claims 1 to 5 in the insecticide formulation is 0.1 to 99% by weight.
10. The insecticide formulation of claim 9, wherein: the amount of the amide-based compound according to any one of claims 1 to 5 in the insecticide formulation is 0.5 to 90% by weight.
11. A method of controlling agricultural or forestry pests, said method being for non-therapeutic purposes, characterized by: applying an effective dose of a material to the pest or growth medium thereof in need of control, the material selected from one or more of the following groups:
an amide compound according to any one of claims 1 to 5;
an insecticide formulation according to any one of claims 8 to 10.
12. Use of an amide compound according to any one of claims 1 to 5 for the preparation of an animal parasite control agent.
13. Use according to claim 12, characterized in that: the animal parasite control agent is used for controlling one or more of cat fleas and American dog ticks.
14. An animal parasite control agent characterized by: the animal parasite control agent comprises the amide compound of any one of claims 1 to 5 as an active ingredient, and one or more auxiliary materials.
15. The animal parasite control agent according to claim 14, wherein: the amide-based compound according to any one of claims 1 to 5 in an amount of 1 to 80% by weight in an animal parasite control agent.
16. A method of controlling parasites in animals, said method being for non-therapeutic purposes, characterized in that: the method comprises the following steps: applying an effective dose of a material selected from one or more of the following groups to an animal parasite or growth medium thereof in need of control:
an amide compound according to any one of claims 1 to 5;
an animal parasite control agent according to claim 14 or 15.
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