Mesoionic pyrimidinium compound and use thereof

Abstract

The present invention belongs to the technical field of pesticides, and particularly relates to a mesoionic pyrimidinium compound, an N-oxide or salt thereof and the use thereof. The compound is as shown in general formula (I), wherein X represents cyano, cyanoalkyl, aryl, or heterocycly; Q1 and Q2 each independently represent O or S; M1, M2, M3, M4 and M5 each independently represent CR9 or N, and at least two of them are N; R1, R2, R3, R4, R5, R6, R7, R8 and R9 each independently represent hydrogen, nitro, amino, cyano, halogen, etc. The compound has an excellent control effect on pests such as Chilo suppressalis, Spodoptera frugiperda, Mythimna separata, Spodoptera litura, Aphis craccivora, rice planthopper, etc., and is safe for bees.

Description

Mesoionic pyrimidinium compounds and their applications Technical Field

[0001] The present invention belongs to the technical field of pesticides, and in particular relates to a mesoionic pyrimidinium compound, an N-oxide or salt thereof, and applications thereof. Background Art

[0002] In recent years, due to the long-term use of pest control agents, such as insecticides or fungicides, pests and diseases have acquired drug resistance, making it difficult to control them with existing insecticides or fungicides. In addition, some known pest control agents are highly toxic, or some damage ecosystems through their long-term residual properties. In this situation, although a large number of pesticides are known, such as WO2011017342A1 and WO2020126591A1, which disclose mesoionic pesticides, there is still a need to develop new pest control agents with low toxicity and low residual properties. Summary of the Invention

[0003] In order to solve the above-mentioned problems existing in the prior art, the present invention provides a mesoionic pyrimidinium compound, its N-oxide or salt, which has excellent control effects on pests such as the striped stem borer, fall armyworm, armyworm, Spodoptera litura, peanut aphid, rice planthopper, etc., and is safe for bees.

[0004] The technical solution adopted in the present invention is as follows:

[0005] A mesoionic pyrimidinium compound, an N-oxide or a salt thereof as shown in the general formula I:

[0006] wherein X represents a cyano group, a cyanoalkyl group, an aryl group or a heterocyclic group;

[0007] Q1 and Q2 independently represent O or S;

[0008] M1, M2, M3, M4, and M5 each independently represent CR9 or N, and at least two (e.g., 2, 3, 4, or 5) of them are N;

[0009] R1, R2, R3, R4, R5, R6, R7, R8, and R9 independently represent hydrogen, nitro, amino, cyano, halogen, hydroxy, mercapto, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, haloalkynyl, alkoxy, alkylthio, haloalkoxy, haloalkylthio, formyl, alkylcarbonyl, alkylsulfoxide, alkylsulfonyl, amino substituted with an alkyl group, cycloalkyl, cycloalkenyl, aryl, or heterocyclic group;

[0010] The aforementioned “cycloalkyl” or “cycloalkenyl” is optionally substituted by at least one group selected from halogen, cyano, nitro, alkyl, alkenyl, alkynyl, cycloalkyl, haloalkyl, haloalkenyl, haloalkynyl, halocycloalkyl, cycloalkyl substituted by alkyl, or cycloalkylalkyl;

[0011] The aforementioned “heterocyclyl” or “aryl” is optionally selected from oxo, halogen, cyano, nitro, alkyl, alkenyl, alkynyl, cycloalkyl, haloalkyl, haloalkenyl, haloalkynyl, halocycloalkyl, cycloalkyl substituted by alkyl, cycloalkylalkyl, aryl or heterocyclyl which is unsubstituted or substituted by at least one group selected from halogen, cyano, nitro, alkyl, haloalkyl, alkoxycarbonyl, alkylthio, alkylsulfonyl, alkoxy or haloalkoxy, -OR 10 , -SR 10 ,-(CO)OR 10 ,-(SO)R 10 , -(SO2)R 10 ,-N(R 10 )2,-alkylene-OR 10 ,-alkylene-SR 10 ,-alkylene-(CO)OR 10 ,-alkylene-(SO)R 10 ,-alkylene-(SO2)R 10 ,-alkylene-N(R 10 )2 or -O-alkylene-(CO)OR 10 or two adjacent carbon atoms on the ring form a fused ring with unsubstituted or halogen-substituted -OCH2CH2- or -OCH2O-;

[0012] R 10 Each of the following is independently hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, haloalkyl, haloalkenyl, haloalkynyl, halocycloalkyl, cycloalkyl substituted by alkyl, cycloalkylalkyl, aryl, heterocyclic group, or aryl or heterocyclic group substituted by at least one group selected from halogen, cyano, nitro, alkyl, haloalkyl, alkoxycarbonyl, alkylthio, alkylsulfonyl, alkoxy or haloalkoxy.

[0013] In one embodiment, X represents a cyano group, a cyano C1-C8 alkyl group, an aryl group or a heterocyclic group;

[0014] R1, R2, R3, R4, R5, R6, R7, R8, and R9 independently represent hydrogen, nitro, amino, cyano, halogen, hydroxyl, mercapto, C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, halogenated C1-C8 alkyl, halogenated C2-C8 alkenyl, halogenated C2-C8 alkynyl, C1-C8 alkoxy, C1-C8 alkylthio, halogenated C1-C8 alkoxy, halogenated C1-C8 alkylthio, formyl, C1-C8 alkylcarbonyl, C1-C8 alkylsulfoxide, C1-C8 alkylsulfonyl, amino substituted with C1-C8 alkyl, C3-C8 cycloalkyl, C3-C8 cycloalkenyl, aryl, or heterocyclic group;

[0015] The aforementioned “C3-C8 cycloalkyl” or “C3-C8 cycloalkenyl” is optionally substituted by at least one group selected from halogen, cyano, nitro, C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, C3-C8 cycloalkyl, halogenated C1-C8 alkyl, halogenated C2-C8 alkenyl, halogenated C2-C8 alkynyl, halogenated C3-C8 cycloalkyl, C3-C8 cycloalkyl substituted by C1-C8 alkyl, or C3-C8 cycloalkylC1-C8 alkyl;

[0016] The aforementioned “heterocyclyl” or “aryl” is optionally selected from oxo, halogen, cyano, nitro, C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, C3-C8 cycloalkyl, halogenated C1-C8 alkyl, halogenated C2-C8 alkenyl, halogenated C2-C8 alkynyl, halogenated C3-C8 cycloalkyl, C3-C8 cycloalkyl substituted by C1-C8 alkyl, C3-C8 cycloalkylC1-C8 alkyl, an aryl or heterocyclyl group which is unsubstituted or substituted by at least one group selected from halogen, cyano, nitro, C1-C8 alkyl, halogenated C1-C8 alkyl, C1-C8 alkoxycarbonyl, C1-C8 alkylthio, C1-C8 alkylsulfonyl, C1-C8 alkoxy or halogenated C1-C8 alkoxy, -OR 10 , -SR 10 ,-(CO)OR 10 ,-(SO)R 10 , -(SO2)R 10 ,-N(R 10 )2,-(C1-C8 alkylene)-OR 10 ,-(C1-C8 alkylene)-SR 10 ,-(C1-C8 alkylene)-(CO)OR 10 ,-(C1-C8 alkylene)-(SO)R 10 ,-(C1-C8 alkylene)-(SO2)R 10 ,-(C1-C8 alkylene)-N(R 10 )2 or -O-(C1-C8 alkylene)-(CO)OR10 or two adjacent carbon atoms on the ring form a fused ring with unsubstituted or halogen-substituted -OCH2CH2- or -OCH2O-;

[0017] R 10 Each of the groups is independently hydrogen, C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, C3-C8 cycloalkyl, halogenated C1-C8 alkyl, halogenated C2-C8 alkenyl, halogenated C2-C8 alkynyl, halogenated C3-C8 cycloalkyl, C3-C8 cycloalkyl substituted by C1-C8 alkyl, C3-C8 cycloalkylC1-C8 alkyl, aryl, heterocyclic group, or aryl or heterocyclic group substituted by at least one group selected from halogen, cyano, nitro, C1-C8 alkyl, halogenated C1-C8 alkyl, C1-C8 alkoxycarbonyl, C1-C8 alkylthio, C1-C8 alkylsulfonyl, C1-C8 alkoxy or halogenated C1-C8 alkoxy.

[0018] In another embodiment, X represents cyano, cyano C1-C6 alkyl, aryl or heterocyclic group;

[0019] R1, R2, R3, R4, R5, R6, R7, R8, and R9 independently represent hydrogen, nitro, amino, cyano, halogen, hydroxyl, mercapto, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, halo-C1-C6 alkyl, halo-C2-C6 alkenyl, halo-C2-C6 alkynyl, C1-C6 alkoxy, C1-C6 alkylthio, halo-C1-C6 alkoxy, halo-C1-C6 alkylthio, formyl, C1-C6 alkylcarbonyl, C1-C6 alkylsulfoxide, C1-C6 alkylsulfonyl, amino substituted with C1-C6 alkyl, C3-C6 cycloalkyl, C3-C6 cycloalkenyl, aryl, or heterocyclic group;

[0020] The aforementioned “C3-C6 cycloalkyl” or “C3-C6 cycloalkenyl” is optionally substituted by at least one group selected from halogen, cyano, nitro, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, halo-substituted C1-C6 alkyl, halo-substituted C2-C6 alkenyl, halo-substituted C2-C6 alkynyl, halo-substituted C3-C6 cycloalkyl, C3-C6 cycloalkyl substituted by C1-C6 alkyl, or C3-C6 cycloalkylC1-C6 alkyl;

[0021] The aforementioned “heterocyclyl” or “aryl” is optionally selected from oxo, halogen, cyano, nitro, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, halo-C1-C6 alkyl, halo-C2-C6 alkenyl, halo-C2-C6 alkynyl, halo-C3-C6 cycloalkyl, C3-C6 cycloalkyl substituted by C1-C6 alkyl, C3-C6 cycloalkylC1-C6 alkyl, aryl or heterocyclyl substituted by at least one group selected from halogen, cyano, nitro, C1-C6 alkyl, halo-C1-C6 alkyl, C1-C6 alkoxycarbonyl, C1-C6 alkylthio, C1-C6 alkylsulfonyl, C1-C6 alkoxy or halo-C1-C6 alkoxy, -OR 10 , -SR 10 ,-(CO)OR 10 ,-(SO)R 10 , -(SO2)R 10 ,-N(R 10 )2,-(C1-C6 alkylene)-OR 10 ,-(C1-C6 alkylene)-SR 10 ,-(C1-C6 alkylene)-(CO)OR 10 ,-(C1-C6 alkylene)-(SO)R 10 ,-(C1-C6 alkylene)-(SO2)R 10 ,-(C1-C6 alkylene)-N(R 10 )2 or -O-(C1-C6 alkylene)-(CO)OR 10 or two adjacent carbon atoms on the ring form a fused ring with unsubstituted or halogen-substituted -OCH2CH2- or -OCH2O-;

[0022] R 10 Each of the groups is independently hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, halogenated C1-C6 alkyl, halogenated C2-C6 alkenyl, halogenated C2-C6 alkynyl, halogenated C3-C6 cycloalkyl, C3-C6 cycloalkyl substituted by C1-C6 alkyl, C3-C6 cycloalkylC1-C6 alkyl, aryl, heterocyclic group, or aryl or heterocyclic group substituted by at least one group selected from halogen, cyano, nitro, C1-C6 alkyl, halogenated C1-C6 alkyl, C1-C6 alkoxycarbonyl, C1-C6 alkylthio, C1-C6 alkylsulfonyl, C1-C6 alkoxy or halogenated C1-C6 alkoxy.

[0023] In another specific embodiment, yes

[0024] In the definition of the compounds represented by the above general formula and in all the following structural formulae, the technical terms used, whether used alone or in compound words, represent the following substituents: Alkyl groups with more than two carbon atoms can be straight-chain or branched. For example, the compound word "-alkylene-OR 10 " " in which the alkylene group can be -CH2-, -CH2CH2-, -CH(CH3)-, -C(CH3)2-, etc. The alkyl group is, for example, C1 alkyl-methyl; C2 alkyl-ethyl; C3 alkyl-propyl such as n-propyl or isopropyl; C4 alkyl-butyl such as n-butyl, isobutyl, tert-butyl or 2-butyl; C5 alkyl-pentyl such as n-pentyl; C6 alkyl-hexyl such as n-hexyl, isohexyl and 1,3-dimethylbutyl. Similarly, alkenyl is, for example, vinyl, allyl, 1-methylprop-2-en-1-yl, 2-methylprop-2-en-1-yl, but-2-en-1-yl, but-3-en-1-yl. The term "cycloalkyl" refers to a group consisting of cyclopentyl, cyclohexyl, cyclopentenyl, cyclohex ...

[0025] Unless otherwise specified, the "aryl" mentioned in the present invention includes but is not limited to phenyl, naphthyl, The "heterocyclic group" includes but is not limited to saturated or unsaturated non-aromatic cyclic groups etc., and also include but are not limited to heteroaryl, i.e. an aromatic cyclic group containing, for example, 3 to 6 ring atoms and optionally fused to a benzo ring, wherein 1 to 4 (e.g. 1, 2, 3 or 4) heteroatoms in the ring atoms are selected from oxygen, nitrogen and sulfur, for example

[0026] If a group is substituted by a group, this is understood to mean that the group is substituted by one or more identical or different groups selected from the groups mentioned. Furthermore, identical or different substituent characters contained in identical or different substituents are independently selected and may be identical or different. The same applies to ring systems formed from different atoms and units. At the same time, compounds known to those skilled in the art to be chemically unstable under standard conditions are excluded from the scope of the claims.

[0027] In addition, unless otherwise specified, the term "substituted by at least one group" as used herein refers to being substituted by 1, 2, 3, 4 or 5 groups; groups (including heterocyclic groups, aryl groups, etc.) without a specific connection position can be connected at any position, including the position connected to C or N; if it is substituted, the substituent can also be substituted at any position as long as it complies with the chemical bond connection rules. For example, a heteroaryl group substituted by 1 methyl group Can represent wait.

[0028] Another embodiment of the present application is a method for preparing the mesoionic pyrimidinium compound, its N-oxide or salt, comprising the following steps:

[0029] The compound represented by general formula II is reacted with the compound represented by general formula III to obtain the compound represented by general formula I, and the reaction equation is as follows:

[0030] Wherein, L1 and L2 independently represent halogen or OH, and the substituents X, R1, R2, R3, R4, R5, R6, R7, R8, M1, M2, M3, M4, M5, Q1 and Q2 are defined as above.

[0031] In one embodiment, the reaction is carried out in the presence of a base and a solvent.

[0032] In a specific embodiment, the base is selected from at least one of an inorganic base (such as NaH, KH, NaOH, KOH, K2CO3, Na2CO3, Cs2CO3, KF, CsF, etc.) or an organic base (such as pyrazole, triethylamine, N,N-diisopropylethylamine, pyridine, DIEA, potassium trimethylsilanolate, AcOK, AcONa, MeONa, EtONa, t-BuONa, t-BuOK, etc.).

[0033] In one embodiment, the solvent is selected from at least one of DCM, diethyl ether, DMF, tetrahydrofuran, methyltetrahydrofuran, diphenyl ether or dioxane.

[0034] The preparation methods of the compounds of the present invention can refer to WO2011017342A1, WO2020126591A1, etc.

[0035] The present invention also relates to an intermediate, as shown in the above formula II or III.

[0036] The present invention also relates to the use of the compound of formula I (including all stereoisomers), its N-oxide and salt, and compositions containing them in controlling pests.

[0037] The present invention also provides an insecticide composition comprising at least one of the compound of formula I, its N-oxide or its salt.

[0038] In one embodiment, a formulation aid is also included.

[0039] In one embodiment, other active ingredients are also included.

[0040] In another embodiment, the other active ingredients are selected from at least one of the following compounds:

[0041] (1) Gamma-aminobutyric acid (GABA)-gated chloride channel allosteric modulators:

[0042] (2) Nicotinic acetylcholine receptor (nAChR) allosteric modulators site I: spinosad (CAS No.: 935545-74-7), spinosad (CAS No.: 168316-95-8);

[0043] (3) Allosteric modulators of glutamate-gated chloride channels (GluCl): avermectin benzoate (CAS No.: 155569-91-8), avermectin (CAS No.: 71751-41-2);

[0044] (4) Chitin biosynthesis inhibitors affecting chitin synthase 1 (CHS1): lufenuron (CAS No.: 103055-07-8);

[0045] (5) Uncouplers that interfere with the proton gradient and affect oxidative phosphorylation: chlorfenapyr (CAS No.: 122453-73-0);

[0046] (6) Ecdysone receptor agonist: methoxyfenozide (CAS No.: 161050-58-4);

[0047] (7) Sodium channel modulator: Lambda-cyhalothrin (CAS No. 91465-08-6);

[0048] (8) Voltage-dependent sodium channel blockers:

[0049] (9) Nicotinic acetylcholine receptor (nAChR) competitive modulators: Imidacloprid (CAS No.: 138261-41-3), Thiamethoxam (CAS No.: 153719-23-4);

[0050] (10) Ryanodine receptor modulators: chlorantraniliprole (CAS No.: 500008-45-7), cyantraniliprole (CAS No.: 736994-63-1);

[0051] (11) Voltage-dependent sodium channel blocker: indoxacarb (CAS No.: 144171-61-9);

[0052] (12) Acetylcholinesterase (AChE) inhibitors: chlorpyrifos (CAS No.: 2921-88-2), dichlorvos (CAS No.: 62-73-7), trichlorfon (CAS No.: 52-68-6), phoxim (CAS No.: 14816-18-3), triazophos (CAS No.: 24017-47-8), quinalphos (CAS No.: 13593-03-8), acephate (CAS No.: 30560-19-1), carbosulfan (CAS No.: 55285-14-8), and diazinon (CAS No.: 333-41-5);

[0053] (13) Compounds with unknown mechanism:

[0054] The present invention provides a method for controlling pests, comprising contacting the pests or their environment with a biologically effective amount of a compound of formula I, an N-oxide or a salt thereof, or the above composition.

[0055] The above-mentioned pest environment is plants, animals or seeds.

[0056] The present invention also provides a method for protecting seeds from invertebrate pests, the method comprising contacting the seeds with a biologically effective amount of a compound of formula I, an N-oxide thereof, or a salt thereof. The present invention also relates to the treated seeds.

[0057] The present invention also provides a composition for protecting animals from invertebrate parasitic pests, comprising a parasiticidally effective amount of a compound of formula I, an N-oxide or a salt thereof and at least one carrier.

[0058] The present invention also provides a method for treating, preventing, inhibiting and / or killing external and / or internal parasites, the method comprising administering to an animal and / or on an animal a parasiticidally effective amount of a compound of formula I, its N-oxide or a salt thereof. The present invention also relates to such a method, wherein a parasiticidally effective amount of a compound of formula I, its N-oxide or a salt thereof is administered to the environment in which the animal lives (e.g., a stable or blanket).

[0059] As used herein, the term "invertebrate pests" includes arthropods, gastropods, and nematodes that are economically important pests. The term "arthropod" includes insects, mites, spiders, scorpions, centipedes, millipedes, pill bugs, and symphylans. The term "gastropod" includes snails, slugs, and other animals of the order Stylommatophora. The term "nematode" refers to an organism of the phylum Nematoda. The term "worm" includes roundworms, heartworms, herbivorous nematodes (Nematoda), flukes (Trematoda), acanthocephala, and tapeworms (Cestoda).

[0060] In the context of the present disclosure, "controlling invertebrate pests" refers to inhibiting the growth of invertebrate pests (including mortality, reduced feeding, and / or mating disruption), and related expressions may be defined similarly.

[0061] The term "agronomy" refers to field crop products such as food and fiber, and includes the growth of corn, soybeans and other legumes, rice, cereals (e.g., wheat, oats, barley, rye, rice, corn), leafy vegetables (e.g., lettuce, cabbage and other vegetable crops), fruiting vegetables (e.g., tomatoes, peppers, eggplant, crucifers and cucurbits), potatoes, sweet potatoes, grapes, cotton, tree fruits (e.g., pome, hard seed and citrus), small fruits (berries, cherries), and other specialty crops (e.g., canola, sunflower, olives).

[0062] The term "non-agricultural" refers to applications other than field crops, such as horticultural crops (e.g., greenhouse plants, nursery plants, or ornamental plants that are not grown in fields), residential structures, agronomic structures, commercial structures, and industrial structures, turf (e.g., pastures, rangelands, golf courses, lawns, athletic fields, etc.), wood products, stored products, agroforestry and vegetation management, public health (i.e., human) and animal health (e.g., domesticated animals such as pets, livestock, and poultry, non-domesticated animals such as wildlife) applications.

[0063] Non-agricultural applications include protecting animals from invertebrate parasitic pests by administering to the animals to be protected a parasiticidally effective (i.e., biologically effective) amount of a compound of the invention (generally in the form of a composition formulated for veterinary use). As used in the present disclosure and claims, the terms "parasiticidal" and "parasiticidal" relate to observed effects on invertebrate parasitic pests to provide protection to animals from pests. Parasiticidal effects generally involve reducing the appearance or activity of target invertebrate parasitic pests. Such effects on pests include necrosis, lethality, slowed growth, reduced mobility or reduced ability to remain on or in a host animal, decreased food intake, and inhibition of reproduction. These effects on invertebrate parasitic pests provide control (including prevention, reduction, or elimination) of parasitic infestations or infections of animals.

[0064] The compounds of Formula I are mesoionic inner salts. "Inner salts," also known in the art as "zwitterions," are electrically neutral molecules, but according to valence bond theory, carry formal positive and negative charges in each valence bond structure between different atoms. Furthermore, the molecular structure of the compounds of Formula I can be represented by the following six valence bond structures:

[0065] Each carries a formal positive charge and a negative charge on different atoms. Due to this resonance, compounds of Formula I are also described as "mesoions". Although for the sake of brevity, the molecular structure of Formula I is described as a single valence bond structure herein, this specific valence bond structure should be understood as a representative of all six valence bond structures connected within the molecules of compounds of Formula I. Therefore, unless otherwise indicated, reference to Formula I herein relates to all six applicable valence bond structures and other (e.g., molecular orbital theory) structures.

[0066] The compounds of the present invention may exist in the form of one or more stereoisomers. Various stereoisomers include enantiomers, diastereomers, atropisomers, and geometric isomers. Those skilled in the art will appreciate that when one stereoisomer is enriched relative to the other stereoisomers or when it is separated from the other stereoisomers, it may be more active and / or may exhibit beneficial effects. Additionally, those skilled in the art will appreciate how to separate, enrich, and / or selectively prepare the stereoisomers. The compounds of the present invention may exist as mixtures of stereoisomers, as individual stereoisomers, or as optically active forms.

[0067] Due to the limited bond rotation caused by steric hindrance, the compounds of the present invention may exist as one or more conformers. The present invention includes mixtures of conformers. In addition, the present invention includes compounds enriched in one conformer relative to other conformers.

[0068] The compounds selected from Formula I (including all stereoisomers thereof, their N-oxides and salts thereof) generally exist in more than one form, so that Formula I includes all crystalline and amorphous forms of compounds represented by Formula I. Amorphous forms include solid embodiments such as waxes and gums, as well as liquid embodiments such as solutions and melts. Crystalline forms include embodiments representing essentially single crystal forms, and embodiments representing mixtures of polymorphs (i.e., different crystal forms). The term "polymorph" refers to a specific crystalline form of a chemical compound that can crystallize in different crystalline forms, which have different molecular arrangements and / or conformations in the crystal lattice. Although polymorphs may have the same chemical composition, they may also have different compositions, which should be attributed to the presence or absence of co-crystallized water or other molecules that are weakly or strongly bound to the crystal lattice. Polymorphs may have different chemical, physical and biological properties, such as crystal shape, density, hardness, color, chemical stability, melting point, hygroscopicity, suspendability, solubility and bioavailability. Those skilled in the art will appreciate that a polymorph of a compound represented by Formula I may exhibit beneficial effects (e.g., suitability for preparing a useful formulation, improved biological performance) relative to another polymorph or mixture of polymorphs of the same compound represented by Formula I. The preparation and isolation of a specific polymorph of a compound represented by Formula I may be achieved by methods known to those skilled in the art, including, for example, crystallization using a selected solvent and temperature.

[0069] Those skilled in the art will appreciate that not all nitrogen-containing heterocycles can form N-oxides, as nitrogen requires an available lone pair of electrons to oxidize to an oxide; those skilled in the art will recognize those nitrogen-containing heterocycles that can form N-oxides. Those skilled in the art will also appreciate that tertiary amines can form N-oxides. Synthetic methods for preparing N-oxides of heterocycles and tertiary amines are well known to those skilled in the art and include oxidation of heterocycles and tertiary amines using peroxyacids such as peracetic acid and 3-m-chloroperbenzoic acid (MCPBA), hydrogen peroxide, alkyl hydroperoxides such as tert-butyl hydroperoxide, sodium perborate, and dioxiranes such as dimethyldioxirane.

[0070] Those skilled in the art recognize that, because the salt of chemical compound is in balance with their corresponding non-salt form under environment and physiological conditions, therefore salt and non-salt form have common biological use.Therefore, the various salts of formula I compound can be used for preventing and treating invertebrate pests and animal parasites (that is, being applicable to animal health purposes).The salt of formula I compound includes the acid addition salt formed with inorganic acid or organic acid, and the acid is such as hydrobromic acid, hydrochloric acid, nitric acid, phosphoric acid, sulfuric acid, acetic acid, butyric acid, fumaric acid, lactic acid, maleic acid, malonic acid, oxalic acid, propionic acid, salicylic acid, tartaric acid, 4-toluenesulfonic acid or valeric acid.When formula I compound comprises acidic part such as carboxylic acid or phenol, salt also includes those formed with organic base or inorganic base such as pyridine, triethylamine or ammonia or sodium, potassium, lithium, calcium, magnesium or barium amide, hydride, hydroxide or carbonate.Therefore, the present invention includes and is selected from formula I compound, their N-oxide and salt.

[0071] Embodiments of the invention as described in the Summary of the Invention include those described below. In the following embodiments, Formula I includes stereoisomers, N-oxides, and salts thereof, and unless otherwise defined in the embodiments, descriptions referring to "compounds of Formula I" include the definitions of designated substituents in the Summary of the Invention.

[0072] Notably, the compounds of the present invention are characterized by favorable metabolism and / or soil residue patterns and exhibit broad-spectrum control activity against agronomic and non-agronomic invertebrate pests.

[0073] Of particular note, due to the broad spectrum of invertebrate pest control and economic importance, protecting crops from damage or injury by invertebrate pests is an embodiment of the present invention. Due to the favorable transfer characteristics or systemic properties of the compounds of the present invention within the plant, they also protect leaves or other plant parts that have not come into direct contact with the compounds of formula I or compositions containing said compounds.

[0074] Also noteworthy as embodiments of the present invention are compositions comprising a compound of any of the foregoing embodiments, as well as any other embodiments described herein, and any combination thereof, and at least one additional component and / or formulation adjuvant and / or at least one active ingredient (i.e., a biologically active compound or agent), the additional component being selected from a surfactant, a solid diluent, and a liquid diluent.

[0075] Embodiments of the present invention also include compositions for protecting animals, comprising a compound of any of the preceding embodiments (ie, in a parasiticidally effective amount) and a carrier.

[0076] Embodiments of the present invention also include methods of controlling invertebrate pests, comprising contacting the invertebrate pest or its environment with a biologically effective amount of a compound of any of the preceding embodiments (e.g., a composition as described herein). Of particular note are methods for protecting animals, comprising administering to the animal a parasiticidally effective amount of a compound of any of the preceding embodiments (e.g., a composition as described herein).

[0077] Embodiments of the present invention also include compositions comprising a compound of any of the preceding embodiments in the form of a liquid soil drench formulation. Embodiments of the present invention also include methods of controlling invertebrate pests comprising contacting soil with a liquid composition comprising a biologically effective amount of a compound of any of the preceding embodiments as a soil drench.

[0078] Embodiments of the present invention also include spray compositions for controlling invertebrate pests, comprising a compound of any of the preceding embodiments (i.e., in a biologically effective amount) and a propellant. Embodiments of the present invention also include bait compositions for controlling invertebrate pests, comprising a compound of any of the preceding embodiments (i.e., in a biologically effective amount), one or more food materials, an optional attractant, and an optional wetting agent. Embodiments of the present invention also include devices for controlling invertebrate pests, comprising the bait composition and a housing adapted to contain the bait composition, wherein the housing has at least one opening sized to allow passage of an invertebrate pest so that the invertebrate pest can access the bait composition from a location external to the housing, and wherein the housing is further adapted for placement in or near a location of potential or known invertebrate pest activity.

[0079] Embodiments of the present invention also include methods for controlling invertebrate pests, comprising contacting the invertebrate pest or its environment with a biologically effective amount of a compound of Formula I, an N-oxide thereof, or a salt thereof, such as a composition described herein, with the proviso that the method is not a method of pharmaceutical treatment of the human or animal body by therapy.

[0080] The present invention also relates to such methods, wherein the invertebrate parasitic pest or its environment is contacted with a composition comprising a biologically effective amount of a compound of formula I, an N-oxide thereof or a salt thereof, and further comprising additional components selected from surfactants, solid diluents and liquid diluents, and optionally comprising a biologically effective amount of at least one active ingredient (i.e., a biologically active compound or agent), with the proviso that the method is not a method of pharmaceutical treatment of the human or animal body by therapy.

[0081] The compounds of the present invention will generally be used as invertebrate pest control active ingredients in compositions, i.e., formulations, having at least one additional component serving as a carrier selected from surfactants, solid diluents, and liquid diluents. The formulation or composition ingredients are selected to be consistent with the physical properties of the active ingredient, the mode of application, and environmental factors such as soil type, moisture, and temperature.

[0082] Useful formulations include liquid and solid compositions. Liquid compositions include solutions (including emulsifiable concentrates), suspensions, emulsions (including microemulsions and / or suspoemulsions), etc., which can optionally be thickened into gels. Common types of aqueous liquid compositions are soluble concentrates, suspension concentrates, capsule suspensions, concentrated emulsions, microemulsions, and suspoemulsions. Common types of non-aqueous liquid compositions are emulsifiable concentrates, microemulsifiable concentrates, dispersible concentrates, and oil dispersions.

[0083] The general types of solid compositions are dusts, powders, granules, pellets, pellets, lozenges, tablets, filled films (including seed coatings), etc., which can be water-dispersible ("wettable") or water-soluble. Films and coatings formed from film-forming solutions or flowable suspensions are particularly useful for seed treatment. The active ingredient can be (micro)encapsulated and further formed into a suspension or solid formulation; alternatively, the entire active ingredient formulation can be encapsulated (or "coated"). Encapsulation can control or delay the release of the active ingredient. Emulsifiable particles combine the advantages of both emulsifiable concentrates and dry granular formulations. High-concentration compositions are primarily used as intermediates for other formulations.

[0084] Sprayable preparations are usually dispersed in suitable media before spraying. Such liquid and solid formulations are mixed with the preparations that are easy to dilute in spray medium (normally water). The scope of spray volume can be about one liter to thousands of liters per hectare, but more generally about ten to hundreds of liters per hectare. Sprayable preparations can be mixed with water or another suitable medium in a tank, for processing leaves by air or ground spraying, or are applied to the growth medium of plants. Liquid and dry formulations can directly be quantitatively added to the drip irrigation system, or are quantitatively added to the furrow during planting. Liquid and solid formulations can be applied to the seed of the plant of crops and other expectations when the seed treatment before the plantation, so that the root in the growth and other subsurface plant parts and / or the leaf are protected by systemic absorption.

[0085] The formulation will generally contain effective amounts of active ingredient, diluent and surfactant, within the approximate ranges below, which total 100% by weight.

[0086] Solid diluents include, for example, clays such as bentonite, montmorillonite, attapulgite and kaolin, gypsum, cellulose, titanium dioxide, zinc oxide, starch, dextrin, sugars (e.g., lactose, sucrose), silica, talc, mica, diatomaceous earth, urea, calcium carbonate, sodium carbonate and bicarbonate, and sodium sulfate.

[0087] Liquid diluents include, for example, water, N,N-dimethylalkaneamides (e.g., N,N-dimethylformamide), limonene, dimethyl sulfoxide, N-alkylpyrrolidones (e.g., N-methylpyrrolidone), ethylene glycol, triethylene glycol, propylene glycol, dipropylene glycol, polypropylene glycol, propylene carbonate, butylene carbonate, paraffins (e.g., white mineral oil, n-paraffins, isoparaffins), alkylbenzenes, alkylnaphthalenes, glycerol, sorbitol, glycerol triacetate, aromatic hydrocarbons, dearomatized aliphatic compounds, alkylbenzenes, alkylnaphthalenes, ketones (e.g., cyclohexanone, 2-heptanone, isophorone, and 4-hydroxybenzoic acid), The liquid diluent may also include saturated and unsaturated fatty acids (typically C6-C8). 22 ) glycerides, such as oils from plant seeds and fruits (e.g., olive oil, castor oil, linseed oil, sesame oil, corn oil, peanut oil, sunflower oil, grapeseed oil, safflower oil, cottonseed oil, soybean oil, rapeseed oil, coconut oil, and palm kernel oil), animal fats (e.g., beef tallow, lard, lard, cod liver oil, fish oil), and mixtures thereof. Liquid diluents also include alkylated (e.g., methylated, ethylated, butylated) fatty acids, which can be obtained by hydrolysis of glycerides derived from plants and animals and can be purified by distillation.

[0088] The solid and liquid compositions of the present invention typically contain one or more surfactants. When added to a liquid, surfactants (also known as "surface-active agents") typically alter, and most commonly reduce, the surface tension of the liquid. Depending on the nature of the hydrophilic and lipophilic groups in the surfactant molecule, surfactants can act as wetting agents, dispersants, emulsifiers, or defoaming agents.

[0089] Surfactants can be classified as nonionic, anionic or cationic surfactants. Nonionic surfactants that can be used in the present composition include, but are not limited to: alcohol alkoxylates, such as alcohol alkoxylates based on natural and synthetic alcohols (which are branched or linear) and prepared from alcohols and ethylene oxide, propylene oxide, butylene oxide or mixtures thereof; amine ethoxylates, alkanolamides and ethoxylated alkanolamides; alkoxylated triglycerides, such as ethoxylated soybean oil, castor oil and rapeseed oil; alkylphenol alkoxylates, such as octylphenol ethoxylate, nonylphenol ethoxylate, dinonylphenol ethoxylate and dodecylphenol ethoxylate (prepared from phenol and ethylene oxide, propylene oxide, butylene oxide or mixtures thereof); block polymers prepared from ethylene oxide or propylene oxide and reverse block polymers in which the terminal blocks are prepared from propylene oxide; ethoxylated propylene oxide; ethoxylated fatty acids; ethoxylated fatty esters and oils; ethoxylated methyl esters; ethoxylated tristyrylphenols (including those prepared from ethylene oxide, propylene oxide, butylene oxide, or mixtures thereof); fatty acid esters, glycerol esters, lanolin-based derivatives, polyethoxylated esters, such as polyethoxylated sorbitan fatty acid esters, polyethoxylated sorbitan fatty acid esters, and polyethoxylated glycerol fatty acid esters; other sorbitan derivatives, such as sorbitan esters; polymeric surfactants, such as random copolymers, block copolymers, alkyd PEG (polyethylene glycol) resins, graft or comb polymers, and star polymers; polyethylene glycol (PEG); polyethylene glycol fatty acid esters; silicone-based surfactants; and sugar derivatives, such as sucrose esters, alkyl polyglucosides, and alkyl polysaccharides.

[0090] Useful anionic surfactants include, but are not limited to, alkylarylsulfonic acids and their salts; carboxylated alcohol or alkylphenol ethoxylates; diphenylsulfonate derivatives; lignin and lignin derivatives, such as lignin sulfonates; maleic acid or succinic acid or their anhydrides; olefin sulfonates; phosphates, such as the phosphates of alcohol alkoxylates, the phosphates of alkylphenol alkoxylates, and the phosphates of styrylphenol ethoxylates; protein-based surfactants; sarcosine derivatives; styrylphenol ether sulfates; sulfates and sulfonates of oils and fatty acids; sulfates and sulfonates of ethoxylated alkylphenols; sulfates of alcohols; sulfates of ethoxylated alcohols; sulfonates of amines and amides, such as N,N-alkyltaurates; sulfonates of benzene, isopropylbenzene, toluene, xylene, and dodecylbenzene and tridecylbenzene; sulfonates of condensed naphthalene; sulfonates of naphthalene and alkylnaphthalene; sulfonates of petroleum fractions; sulfosuccinamates; and sulfosuccinates and their derivatives, such as dialkylsulfosuccinates.

[0091] Useful cationic surfactants include, but are not limited to, amides and ethoxylated amides; amines such as N-alkylpropylenediamine, tripropylenetriamine, and dipropylenetetramine, as well as ethoxylated amines, ethoxylated diamines, and propoxylated amines (made from amines and ethylene oxide, propylene oxide, butylene oxide, or mixtures thereof); amine salts such as amine acetates and diamine salts; quaternary ammonium salts such as quaternary ammonium salts, ethoxylated quaternary ammonium salts, and diquaternary ammonium salts; and amine oxides such as alkyldimethylamine oxides and di-(2-hydroxyethyl)-alkylamine oxides.

[0092] Also useful in the compositions of the present invention are mixtures of nonionic and anionic surfactants, or mixtures of nonionic and cationic surfactants.

[0093] The compositions of the present invention may also contain formulation aids and additives known to those skilled in the art as formulation aids (some of which may also be considered to function as solid diluents, liquid diluents, or surfactants). Such formulation aids and additives may control: pH (buffers), foaming during processing (defoamers, such as polyorganosiloxanes), settling of the active ingredient (suspending agents), viscosity (thixotropic thickeners), microbial growth in the container (antimicrobials), product freezing (antifreeze agents), color (dye / pigment dispersions), elution (film formers or binders), evaporation (evaporation inhibitors), and other formulation properties. Film formers include, for example, polyvinyl acetate, polyvinyl acetate copolymers, polyvinyl pyrrolidone-vinyl acetate copolymers, polyvinyl alcohol, polyvinyl alcohol copolymers, and waxes.

[0094] The compound of formula I and any other active ingredient are typically incorporated into the composition of the present invention by dissolving the active ingredient in a solvent or by grinding the active ingredient in a liquid or dry diluent. Solutions, including emulsifiable concentrates, can be prepared by simply mixing the ingredients. If the solvent of the liquid composition to be used as an emulsifiable concentrate is immiscible with water, an emulsifier is typically added to emulsify the solvent containing the active ingredient when diluted with water. A media mill can be used to wet-grind an active ingredient slurry with a particle size of up to 2,000 μm to obtain particles with an average diameter of less than 3 μm. The aqueous slurry can be prepared as a finished suspension concentrate (see, for example, US 3,060,084) or further processed into particles dispersible in water by spray drying. Dry formulations typically require a dry grinding step that produces an average particle size in the range of 2 to 10 μm. Dusts and powders can be prepared by mixing, typically by grinding (e.g., with a hammer mill or fluid energy mill). Granules and pellets can be prepared by spraying the active substance onto a preformed granular carrier or by agglomeration techniques.

[0095] The compounds of the present invention exhibit activity against a broad spectrum of invertebrate pests. These pests include invertebrate pests that inhabit a variety of environments such as plant leaves, roots, soil, harvested crops or other foods, buildings or animal fur. These pests include, for example, invertebrate pests that feed on leaves (including leaves, stems, flowers and fruits), seeds, wood, textile fibers or animal blood or tissues, and these pests damage or harm, for example, growing or storing crops, forest crops, greenhouse crops, ornamental plants, nursery crops, stored foods or fiber products, or housing or other structures or their contents, or are harmful to animal health or public health. Those skilled in the art will appreciate that not all compounds have the same effect on all growth stages of all pests.

[0096] Therefore, these compounds of the present invention and composition can be used for protecting field crops from the infringement of phytophagous invertebrate pests in agronomy, and can also be used for protecting other horticultural crops and plants from the infringement of phytophagous invertebrate pests in non-agronomy.This purpose includes protecting crops and other plants (i.e. agronomy and non-agronomy) that include genetic engineering (i.e. transgenic) or mutagenic modification introduction to provide the genetic material of favorable characteristics. The example of such characteristics includes herbicide resistance, tolerance to phytophagous pests (such as insects, mites, aphids, spiders, nematodes, snails, plant pathogenic fungi, bacteria and viruses), plant growth improvement, enhanced tolerance to unfavorable growth environments (such as high or low temperatures, low soil moisture or high soil moisture, and high salinity), flowering or result improvement, harvest increase, faster maturity, the quality and / or nutritional value of the harvested products are higher, or the storage or processability of the harvested products are improved. Transgenic plants can be modified to express a variety of characteristics. Examples of plants containing traits provided by genetic engineering or mutagenesis include varieties of corn, cotton, soybean, and potato expressing insecticide-resistant Bacillus thuringiensis toxins, such as YIELD and and various herbicide-tolerant corn, cotton, soybean, and rapeseed varieties, such as ROUNDUP LIBERTY and As well as crops expressing N-acetyltransferase (GAT) to provide resistance to glyphosate herbicide, or crops containing HRA genes to provide resistance to herbicides, inhibiting acetolactate synthase (ALS). The compounds and compositions of the present invention can interact synergistically with traits introduced by genetic engineering or mutagenesis to enhance the phenotypic expression or effect of the traits, or enhance the invertebrate pest control efficacy of the compounds and compositions of the present invention. Specifically, the compounds and compositions of the present invention can interact synergistically with the phenotypic expression of proteins or other natural products that are toxic to invertebrate pests to provide a greater than additive control effect on these pests.

[0097] Composition of the present invention can also optionally comprise plant nutrients, for example comprise the fertilizer composition of at least one plant nutrient, described plant nutrient is selected from nitrogen, phosphorus, potassium, sulphur, calcium, magnesium, iron, copper, boron, manganese, zinc and molybdenum.It is noteworthy that the composition comprising at least one fertilizer composition, described fertilizer composition comprises at least one plant nutrient selected from nitrogen, phosphorus, potassium, sulphur, calcium and magnesium.The composition of the present invention that also comprises at least one plant nutrient can be liquid or solid form.It is noteworthy that the solid preparation of granule, stick or tablet form.By compound of the present invention or composition and fertilizer composition and formulation ingredients are mixed together, then by the method such as granulating or extruding, prepare preparation, prepare the solid preparation that comprises fertilizer composition.Alternatively, by solution or suspension of compound of the present invention or composition in volatile solvent is sprayed on the fertilizer composition of previously made size-stable mixture form (for example granule, stick or tablet), then evaporate solvent, make solid preparation.

[0098] Examples of agronomic or non-agronomic invertebrate pests include eggs, larvae and adults of Lepidoptera pests, such as armyworms, caterpillars, loopers and cotton bollworms of the family Noctuidae (e.g., Sesamia inferens Walker, Sesamia nonagrioides Lefebvre, Spodoptera eridania Cramer, Spodoptera frugiperda JESmith, Spodoptera exigua Hübner, Spodoptera littoralis Boisduval, Spodoptera ornithogalli Guenée, Agrotis ipsilon Hufnagel, Anticarsia gemmatalis Hübner, Lithophane antennata Walker, Barathra brassicae Linnaeus), soybean armyworm (Pseudoplusiaincludens Walker), cabbage looper (Trichoplusia ni Hübner), tobacco aphid (Heliothis virescens Fabricius));Borers, sheath moths, web-spinning caterpillars, pine cone borers, cabbage worms and leaf cutters from the family Pyralidae (e.g., European corn borer (Ostrinia nubilalis Hübner), navel orange borer (Amyelois transitella Walker), corn root borer (Crambus caliginosellus Clemens), grass borers (Pyralidae: Pyralinae), such as rice leaf cutter borer (Herpetogramma licarsisalis Walker), sugarcane two-spotted borer (Chilo infuscatellus Snellen), tomato borer (Neoleucinodes elegantalis Guenée), rice leaf roller (Cnaphalocrocis medinalis), grape leaf roller (Desmia funeralis Hübner), melon borer (Diaphania nitidalis Stoll), cabbage grub (Hellula hydralis Guenée), Yellow-stem borer (Scirpophaga incertulas Walker), Early seedling borer (Scirpophaga infuscatellus Snellen), White seed borer (Scirpophaga innotata Walker), Top seedling borer (Scirpophaga nivella Fabricius), Rice dory borer (Chilo polychrysus Meyrick), Cabbage caterpillar (Crocidolomia binotalis English));Leaf rollers, aphids, seed worms, and fruit borers of the family Cydiaceae (e.g., apple moth (Cydia pomonella Linnaeus), grape berry moth (Endopiza viteana Clemens), pear borer (Grapholita molesta Busck), apple shaped moth (Cryptophlebia leucotreta Meyrick), citrus borer (Ecdytolopha aurantiana Lima), red-banded moth (Argyrotaenia velutinana Walker), rose-banded moth (Choristoneura rosaceana Harris), apple pale brown moth (Epiphyas postvittana Walker), privet moth (Eupoecilia ambiguella Hübner), apple bud moth (Pandemis pyrusana Kearfott), omnivorous moth (Platynota stultana Walsingham), striped fruit moth (Pandemis cerasana Hübner), Pandemis heparana Denis & Schiffermüller); and many other economically important Lepidoptera (e.g., Plutella xylostella Linnaeus (diamondback moth), Pectinophora gossypiella Saunders (pink bollworm), Lymantria dispar Linnaeus (gypsy moth), Carposina niponensis Walsingham (peach borer), Anarsia lineatella Zeller (peach moth), Phthorimaea operculella Zeller (potato tuber moth), Lithocolletis blancardella Fabricius (tapeworm-like leafminer), Lithocolletis ringoniella Matsumura (apple golden moth), Lerodea eufala Edwards (rice leaf roller), Leucoptera scitella Zeller (spinwheel leafminer));Eggs, pupae, and adults of the order Blattodea, including cockroaches from the families Blattaria and Blattaria (e.g., Blatta orientalis Linnaeus, Blatta asahinai Mizukubo, Blatta germanica Linnaeus, Supella longipalpa Fabricius, Periplaneta americana Linnaeus, Periplaneta brunnea Burmeister, Leucophaea maderae Fabricius); Periplaneta fuliginosa Service, Periplaneta australasiae Fabr., Nauphoeta cinerea Olivier, and Symplocea pallens Stephens); eggs, leaf-feeding, fruit-feeding, root-feeding, seed-feeding and vesicle-feeding larvae and adults of the order Coleoptera, including weevils from the families of ... decemlineata Say), western corn rootworm (Diabrotica virgifera virgifera LeConte);Scarabs and other beetles from the family Scarabidae (e.g., Japanese scarab (Popillia japonica Newman), Oriental scarab (Anomala orientalis Waterhouse, Exomala orientalis (Waterhouse) Baraud), Northern rhinoceros beetle (Cyclocephala borealis Arrow), Southern rhinoceros beetle (Cyclocephala immaculata Olivier or C. Lurida Bland), dung beetles and grubs (Aphodius spp.), Black scarab (Ataenius spretulus Haldeman), Green scarab (Cotinis nitida Linnaeus), Chestnut scarab (Maladera castanea Arrow), May / June scarab (Phyllophaga spp.), and European scarab (Rhizotrogus majalis Razoumowsky)); skin beetles from the family Dermestidae; nematodes from the family Coleoptera; bark beetles from the family Ophiopodidae, and weevils from the family Tenebrionidae.

[0099] In addition, agronomic and non-agronomic pests include: eggs, adults and larvae of the order Dermoptera, including earwigs of the family Earwigs (e.g., European earwigs (Forficula auricularia Linnaeus), black earwigs (Chelisoches morio Fabricius)); eggs, immatures, adults and pupae of the orders Hemiptera and Homoptera, such as blind bugs from the family Miridae, cicadas of the family Cicadidae, leafhoppers (e.g., Empoasca spp.), bed bugs of the family Cimex lectularius Linnaeus), wax cicadas of the families Cercopithecidae and Pachyphyllidae, tree cicadas of the family Membracidae, psyllids of the family Psyllidae, whiteflies of the family Alyssinidae, aphids of the family Aphididae, root nodule aphids of the family Phylloxeracidae, mealybugs of the family Mealycosidae, scale insects of the family Coccinellidae, Coccidae and Coccidae, web bugs of the family Pentatomidae, stink bugs of the family Pentatomidae, sorghum bugs of the family Pentatomidae (e.g., hairy bug (Blissus leucopterus hirtus Montandon) and southern wheat bug (Blissus insularis Barber)) and other bugs of the family Pentatomidae, cicadas of the family Cicadidae, squash bugs of the family Pseudocycodae, and red bugs and cottonworms of the family Red Pentatomidae.

[0100] Agronomic and non-agronomic pests also include: eggs, larvae, pupae and adults of the order Acarina (acarids), such as spider mites and red mites of the family Tetranychus (e.g., apple spider mite (Panonychus ulmi Koch), two-spotted spider mite (Tetranychus urticae Koch), and McDaniel's spider mite (Tetranychus mcdanieli McGregor); grape short-palped mites of the family Tenuipalpus (e.g., citrus spider mite (Brevipalpus lewisi McGregor)); rust ticks and bud ticks of the family Mylidae, as well as other leaf-feeding mites and mites of importance in human and animal health, namely, dust mites of the family Epidermophoridae, Demodex mites of the family Demodex, and grain mites of the family Glycyrrhizae; ticks of the family Ixodidae, commonly known as hard ticks, such as the deer tick (Ixodes scapularis Say), the Australian paralysis tick (Ixodes holocyclus Neumann), the American dog tick (Dermacentor variabilis Say, lone star tick (Amblyomma americanum Linnaeus)) and ticks commonly known as soft ticks in the family Cryptorhynchidae (e.g., Ornithodoros turicata, common chicken tick (Argas radiatus)); itch mites and scabies mites in the families Itch, Pyreidae, and Sarcoptes; eggs, adults, and immatures of the order Orthoptera, including grasshoppers, locusts, and crickets (e.g., migratory grasshoppers (e.g., black locust, Thomas the spp.), American grasshoppers (e.g., Schistocerca americana Drury), desert locusts (Schistocerca gregaria Forskal), migratory locusts (Locusta migratoria Linnaeus), dwarf grasshoppers (Zonocerus spp.), house crickets (Acheta domesticus Linnaeus), mole crickets (e.g., Scapteriscus vicinus Scudder), and South American mole crickets (Scapteriscus borellii Giglio-Tos); eggs, adults, and immatures of the order Diptera, including leafminers (e.g., Liriomyza spp., such as Liriomyza sativae Blanchard); midges, fruit flies (Tephritidae), eye flies (e.g., ryegrass), dung maggots, common houseflies (e.g., houseflies), summer toilet flies (e.g., F.femoralis Stein), stable flies (e.g., Stable Fly), gadflies, horn flies, blowflies (e.g., Chrysomelidae, Melanophora) and other housefly pests, horseflies (e.g., Tabanus), skin flies (e.g., Gastromys, Mysore), cowhide flies (e.g., Hippophae), deerflies (e.g., Dermatophis), sheep tick flies (e.g., Lousefly) and other Brachycera, mosquitoes (e.g., Aedes, Anopheles, Culex), black midges (e.g., Protocystis, Simulidae), cutting midges, sandflies, sharp-eyed fungus gnats and other Longicorns; eggs, adults, and immatures of the order Thysanoptera, including onion thrips (Thripstabaci Lindeman), flower thrips (Thrips spp.), and other leaf-feeding thrips; insect pests of the order Hymenoptera, including ants of the family Formicidae, including the genus Camponotus floridanus Buckley), Rusty Black Ant (Camponotusferrugineus Fabricius), Black Carpenter Ant (CamponotuspennsylvanicusDeGeer), White-footed Stinky Ant (Technomyrmexalbipesfr.Smith), Big-headed Ant (Pheidole spp.), Black-headed Sour-stinking Ant (Tapinomamelanocephalum Fabricius); Pharaoh Ant (Monomorium pharaonis Linnaeus), Small Fire Ant (Wasmanniaauropunctata Roger), Fire Ant (Solenopsisgeminata Fabricius), Invasive Red Imported Fire Ant (SolenopsisinvictaBuren), Argentine Ant (Iridomyrmex humilisMayr), Crazy Ant (ParatrechinalongicornisLatreille), Pavement Ant (Tetramoriumcaespitum Linnaeus), Corn Hair Ant (Lasiusalienus. ) and smelly house ants (Tapinoma sessile Say). Other Hymenoptera include bees (including carpenter bees), hornets, wasps, wasps, and sawflies (Neodiprion genus; Cephus genus); Isoptera include termites of the family Termitidae (e.g., Macrotermes obesus Rambur), the family Carpentertermes (e.g., Sandertermes genus), and the family Rhinortermes (e.g., Reticulitermes genus, Coptotermes genus, Reticulitermes Dabieshanensis), the North American Reticulitermes Kollar, the Western Reticulitermes Banks, the Coptotermes formosanus Shiraki, the West Indian drywood termite Incisitermes immigrans Snyder, the powder borer termite Cryptotermes brevis Walker, the drywood termite Incisitermes snyderi Light, the southeastern subterranean termite Reticulitermes virginicus Banks, the drywood cutting termite Incisitermes minor Hagen), arboreal termites such as the genus Elephantis and other termites of economic importance; insect pests of the order Thysanura, such as the silverfish (Lepisma saccharina Linnaeus) and the house silverfish (Thermobia domestica Packard); insect pests of the order Trichophagus and including the head louse (Pediculus humanus capitis De Geer), body louse (Pediculus humanus Linnaeus), chick feather louse (Menacanthus stramineus Nitszch), dog feather louse (Trichodectescanis De Geer), velvet louse (Goniocotes gallinae De Geer), sheep body louse (Bovicola ovis Schrank), cattle blind louse (Haematopinus eurysternus Nitzsch), long-nosed livestock louse (Linognathus vituli Linnaeus) and other sucking and chewing lice that attack humans and animals;Insect pests of the order Siphonaptera, including the Oriental rat flea (Xenopsylla cheopis Rothschild), cat flea (Ctenocephalides felis Bouche), dog flea (Ctenocephalides canis Curtis), chicken flea (Ceratophyllus gallinae Schrank), sucking flea (Echidnophaga gallinacea Westwood), human flea (Pulex irritans Linnaeus), and other fleas that cause distress to mammals and birds. Additional arthropod pests include spiders of the order Araneae, such as the brown recluse spider (Loxosceles reclusa Gertsch & Mulaik) and the black widow spider (Latrodectus mactans Fabricius), and centipedes of the order Scolopendra, such as the centipede (Scutigera coleoptrata Linnaeus).

[0101] Examples of invertebrate pests of stored grain include the greater grain borer (Prostephanus truncatus), the smaller grain borer (Rhyzopertha dominica), the rice weevil (Sitophilus oryzae), the maize weevil (Sitophilus zeamais), the cowpea weevil (Callosobruchus maculatus), the red flour beetle (Tribolium castaneum), the corn weevil (Sitophilus granarius), the Indian meal borer (Plodia interpunctella), the Mediterranean flour weevil (Ephestia kuhniella), and the long-horned or rusty flour beetle (Cryptolestes ferrugineus).

[0102] The compounds of the present invention are particularly active against the following lepidopteran pests (e.g. Alabama argillacea Hübner (clothes moth), Archips argyrospila Walker (fruit leaf roller), A. rosana Linnaeus (European leaf roller), and other species of the genus A. rosana, Chilo suppressalis Walker (rice borer), Cnaphalocrocis medinalis Guenée (rice leaf roller), Crambus caliginosellus Clemens (corn root web caterpillar), Crambus teterrellus Zincken (bluegrass borer), Cydia pomonella Linnaeus (apple bollworm), Earias insulana Boisduval (diamond borer), Earias vittella Fabricius (emerald bollworm), Helicoverpa armigera Hübner (American bollworm), Helicoverpa zea Boddie (cotton bollworm), Heliothis virescens Fabricius (tobacco aphid), Herpetogramma licarsisalis Walker (meadow borer), Lobesia botrana Denis & Schiffermüller (grape berry moth), Pectinophora gossypiella Saunders (pink bollworm), Phyllocnistis citrella Stainton (citrus leaf miner), Pieris brassicae Linnaeus (large cabbage butterfly), Pieris rapae Linnaeus (white moth), Plutella xylostella Linnaeus (diamondback moth), Spodoptera exigua Hübner (beet armyworm), Spodoptera litura Fabricius (spodoptera litura, tea silkworm), Spodoptera frugiperda JESmith (fall armyworm), Trichoplusia ni Hübner (cabbage armyworm), and Tuta absoluta Meyrick (tomato leafminer).

[0103] The compounds of the present invention also have significant activity on members of the order Homoptera, including: Acyrthosiphon pisum Harris (bean aphid), Aphis craccivora Koch (black bean aphid), Aphis fabae Scopoli (broad bean aphid), Aphis gossypii Glover (cotton aphid, melon aphid), Aphis pomi De Geer (apple aphid), Aphis spiraecola Patch (leaf roller aphid), Aulacorthum solani Kaltenbach (eggplant aphid), Chaetosiphon fragaefolii Cockerell (strawberry aphid), Diuraphis noxia Kurdjumov / Mordvilko (Russian wheat aphid), Dysaphis plantaginea Paaserini (red apple aphid), Eriosoma lanigerum Hausmann (wool apple aphid), Hyalopterus pruni Geoffroy (peach aphid), Lipaphis erysimi Kaltenbach (carrot aphid), Metopolophium dirhodum Walker (wheat aphid), Macrosiphum euphorbiae Thomas (potato aphid), Myzus persicae Sulzer (myzus persicae, peach aphid), Nasonovia ribisnigri Mosley (lettuce aphid), Pemphigus spp. (root and spherical aphids), Rhopalosiphum maidis Fitch (corn leaf aphid), Rhopalosiphum padi Linnaeus (grain aphid), Schizaphis graminum Rondani (wheat aphid), Sitobion avenae Fabricius (wheat aphid), Therioaphis maculata Buckton (alfalfa aphid), Toxoptera aurantii Boyer de Fonscolombe (citrus aphid), and Toxoptera citricida Kirkaldy (brown citrus aphid); Adelges spp. (aphids);

[0104] Phylloxera devastatrix Pergande (Pecan phylloxera); Bemisia tabaci Gennadius (Bemisia tabaci, sweet potato whitefly), Bemisia argentifolii Bellows & Perring (Silverleaf whitefly), Dialeurodes citri Ashmead (Citrus whitefly), and Trialeurodes vaporariorum Westwood (Greenhouse whitefly); Empoasca fabae Harris (Potato green leafhopper), Laodelphax striatellus Fallen (Gray planthopper), Macrostelesquadrilineatus Forbes (Two-spotted leafhopper), Nephotettix cincticeps Uhler (Green leafhopper), Nephotettix nigropictus (Black-tailed leafhopper), Nilaparvata lugens (brown planthopper), Peregrinus maidis Ashmead (corn waxhopper), Sogatella furcifera Horvath (white-backed planthopper), Sogatodes orizicola Muir (rice planthopper), Typhlocyba pomaria McAtee, white apple leafhopper, Erythroneura spp. (grape leafhopper); Magicicada septendecim Linnaeus (periodic cicada);

[0105] Icerya purchasi Maskell (cotton scale insect), Quadraspidiotus perniciosus Comstock (St. Joseph's worm);

[0106] Planococcus citri Risso (citrus mealybug); Pseudococcus spp. (other mealybug complexes);

[0107] Cacopsylla pyricola Foerster (pear psyllid), Trioza diospyri Ashmead (persimmon psyllid).

[0108] The compounds of the present invention are also active on members of the order Hemiptera, including:

[0109] Acrosternum hilare Say (Rice Green Stink Bug), Anasa tristis De Geer (Pumpkin Margin Stink Bug), Blissus leucopterus leucopterus Say (Sorghum Long-necked Stink Bug), Cimex lectularius Linnaeus (Stink Bug), Corythucha gossypii Fabricius (Cotton Net Stink Bug), Cyrtopeltis modesta Distant (Tomato Bug), Dysdercus suturellus Herrich- (cotton bug), Euchistus servus Say (brown stink bug), Euchistus variolarius Palisot de Beauvois (spotted stink bug), Graptostethus spp. (long-spotted stink bug association), Leptoglossus corculus Say (leaf-root pine seed bug), Lygus lineolaris Palisot de Beauvois (grass blind bug), Nezara viridula Linnaeus (southern green rice bug), Oebalus pugnax Fabricius (rice brown bug), Oncopeltus fasciatus Dallas (large milkweed long-spotted stink bug), Pseudatomoscelis seriatus Reuter (cotton blind bug). Other insect orders controlled by the compounds of the invention include Thysanoptera (e.g., Frankliniella occidentalis Pergande (Western Flower Thrips), Scirthothrips citri Moulton (Citrus Thrips), Sericothrips variabilis Beach (Soybean Thrips), and Thrips tabaci Lindeman (Onion Thrips)); and Coleoptera (e.g., Leptinotarsa ​​decemlineata Say (Colorado Potato Beetle), Epilachna varivestis Mulsant (Mexican Bean Beetle), and Agriotes, Athous, or Limonius species (nematodes)).

[0110] The compounds of the present invention are also active against members of the classes Nematoda, Cestoda, Trematoda and Acanthocephala, including members of the economically important orders Strongylida, Ascaris, Oxyura, Rhabditis, Spirulina and Orthoptera, such as, but not limited to, economically important agricultural pests (i.e., root-knot nematodes of the genus Meloidogyne, root-rot nematodes of the genus Escherichia, stump nematodes of the genus Trichodesmium, etc.) and pests that endanger animal and human health (i.e., all economically important trematodes, tapeworms and roundworms, such as Strongyloides vulgaris in horses, Toxocara canis in dogs, Haemonchus contortus in sheep, Dirofilaria immitis in dogs, Gymnocephalus foliaceus in horses, Fasciola hepatica in ruminants, etc.).

[0111] It should be noted that some modern classification systems place the Homoptera within the suborder Hemiptera.

[0112] Of note, the compounds of the present invention are used to control the potato green leafhopper (Empoasca fabae). Of note, the compounds of the present invention are used to control the corn waxhopper (Peregrinus maidis). Of note, the compounds of the present invention are used to control the cotton aphid (Aphis gossypii). Of note, the compounds of the present invention are used to control the green peach aphid (Myzus persicae). Of note, the compounds of the present invention are used to control the diamondback moth (Plutella xylostella). Of note, the compounds of the present invention are used to control the fall armyworm (Spodoptera frugiperda).

[0113] Of note, the compounds of the invention are useful in controlling southern rice green stink bug (Nezara viridula), bean pod stink bug (Lygus hesperus), rice water weevil (Lissorhoptrus oryzophilus), brown planthopper (Nilaparvata lugens), two-spotted black leafhopper (Nephotettix virescens) and rice stem borer (Chilo suppressalis).

[0114] The compounds of the present invention can be mixed with one or more other active ingredients (i.e., biologically active ingredients or agents) including insecticides, fungicides, nematicides, bactericides, acaricides, herbicides, herbicide safeners, growth regulators such as insect molting inhibitors and rooting stimulants, chemosterilants, semiochemicals, repellents, attractants, pheromones, feeding stimulants, other biologically active compounds or entomopathogenic bacteria, viruses or fungi to form multi-component pesticides, conferring an even broader spectrum of agricultural and non-agricultural uses. Therefore, the present invention also relates to a composition comprising a biologically effective amount of a compound of formula I, an N-oxide or a salt thereof, at least one formulation adjuvant selected from a surfactant, a solid diluent and a liquid diluent, and at least one other active ingredient or agent. In the case of mixtures of the present invention, the other active ingredients or agents can be formulated with the compounds of the present invention (including compounds of Formula I) to form a premix, or the other biologically active compounds or agents can be formulated separately from the compounds of the present invention (including compounds of Formula I) and the two formulations mixed together before application (e.g., in a spray tank), or the two formulations can be applied sequentially.

[0115] Examples of such biologically active compounds or agents with which the compounds of the present invention can be formulated are insecticides such as abamectin, acephate, acetamiprid, acralphos, sulfanilamide, amitraz, avermectin, azadirachtin, methyl azinphos-methyl, sulfanilamide, bifenthrin, bifenazate, bistrifluan, borates, buprofen, cadusafos, carbaryl, carbofuran, cartap, fluazifop, chlorfenapyr, chlorfenapyr, chlorfenapyr, chlorpyrifos, methyl chlorpyrifos, chlorfenapyr, chlorfenapyr, chlorpyrifos, methyl chlorpyrifos, chlorfenapyr, chloranil, cyanamide, fluazifop, cyfluthrin, β-cyfluthrin, triflumuron, chlorfenapyr ... Cypermethrin, gamma-cyhalothrin, lambda-cyhalothrin, cypermethrin, alpha-cypermethrin, zeta-cypermethrin, cypermethrin, deltamethrin, diafenthiuron, diflubenzuron, tetrafluthrin, dimethoate, dimethoate, dinotefuran, diphenyl propyl ether, emamectin, endosulfan, cis-cypermethrin, ethomethrin, ethomethrin, etoxazole, fenbutatin, fenthiocarb, fenoxycarb, cypermethrin, cypermethrin, flubendiamide, flucythrin, flufenoxuron, fluvalinate, τ-fluvalinate, dafusong, fenmethin , thiazophos, chlorfenapyr, hexaflumuron, hexathiazolin, hydrazone, imidacloprid, indoxacarb, insecticidal soap, isofenphos, lufenuron, malathion, chlorfluanid, metaflumizone, snail enemy, methamidophos, methidathion, methiocarb, ethomethoxam, methoprene, methoxychlor, methoxybenfluthrin, monocrotophos, methoxyfenapyr, nitenpyram, nitrothiazole, bisbenzimidazole, polyfluanid, oxamyl, parathion, methyl parathion, permethrin, phorate, phosalone, phosmet, phosphamidon, pirimicarb, profenofos, profluthrin, propargite, pyrethroid ether insecticides, pyrimidine Ketone, pyrazinyl fipronil, pyrethroids, pyridabenzan, pyridalyl, new quinazoline insecticides, pyridinyl fipronil, pyriproxyfen, rotenone, ryanodine, polymyxin, spinosad, tetracycline, spiromesifen, spirotetramat, thioprofen, sulfoxaflor, tebufenozide, tebufenpyrad, diflubenzuron, tefluthrin, terbufos, cypermethrin, pyrethroids, tetrafluthrin, thiacloprid, thiamethoxam, thiodimethoate, dimethomorph, tolfenpyrad, tralomethrin, triazolam, trichlorfon, triflumuron, Bacillus thuringiensis δ-endotoxin, entomopathogenic bacteria, entomopathogenic viruses and entomopathogenic fungi.

[0116] Of note are insecticides such as abamectin, acetamiprid, flumethrin, amitraz, avermectin, azadirachtin, sulfamethoxam, bifenthrin, cypermethrin, cadusafos, carbaryl, cartap, chlorantraniliprole, chlorfenapyr, chlorpyrifos, clothianidin, cyantraniliprole, cyfluthrin, β-cyfluthrin, flucythrin, γ-cyfluthrin, lambda-cyfluthrin, cypermethrin, α-cypermethrin, ζ-cypermethrin, cypermethrin, deltamethrin, dieldrin, dinotefuran, diphenyl ether, methylamino avermectin, endosulfan, cis-cypermethrin, ethiprole, efenamide, etoxazole, fenthiocarb, fenoxycarb, cypermethrin, fipronil, fluazifop, Benomyl, flubendiamide, flufenoxam, fluvalinate, flumethrin, famifostia, hexaflumuron, hydrazone, imidacloprid, indoxacarb, lufenuron, metaflumizone, methoprene, methoprene, methoxyfenozide, nitenpyram, nitrothiazolin, isoflurane, oxamyl, pymetrozine, pyrethroids, pyridabenzone, pyridalyl, pyriproxyfen, ryanodine, polymyxin B, polymyxin B, tebuconazole, tebuconazole, tebuconazole, chlorpyrifos, chlorpyrifos, chlorpyrifos, pyrimidine, chlorpyrifos, chlorpyrifos, pyrimidine, pyrimidine, pyrimidine, pyrimidine, pyrimidine, pyrimidine, pyrimidine, pyrimidine, pyrimidine, pyrimidine, pyrimidine, pyrimidine, pyrimidine, pyrimidine, thiacloprid, thiamethoxam, thiodimethoxam, dimethoate, tralomethrin, triazolam, triflumuron, Bacillus thuringiensis δ-endotoxin, all strains of Bacillus thuringiensis and all strains of nuclear polyhedrosis virus.

[0117] One embodiment of a biological agent for admixture with the compounds of the present invention includes insect pathogenic bacteria such as Bacillus thuringiensis, and encapsulated Bacillus thuringiensis delta-endotoxin such as Prepared by and Biopesticides ( and is a trademark of Mycogen Corporation (Indianapolis, Indiana, USA); entomopathogenic fungi such as Metarhizium anisopliae; and entomopathogenic (naturally occurring and genetically modified) viruses, including baculoviruses, nuclear polyhedrosis viruses (NPVs) such as Spodoptera falciparum nuclear polyhedrosis virus (HzNPV), Spodoptera falciparum nuclear polyhedrosis virus (AfNPV); and granuloviruses (GVs) such as Codling moth granulovirus (CpGV).

[0118] Of particular note are combinations in which the other invertebrate pest control active ingredients belong to a different chemical class than the compound of formula I or have a different site of action therewith. In some cases, combinations with at least one other invertebrate pest control active ingredient having a similar control range but a different site of action will be particularly advantageous for resistance management. Thus, the compositions of the present invention may also comprise a biologically effective amount of at least one additional invertebrate pest control active ingredient having a similar control range but belonging to a different chemical class or having a different site of action. These additional biologically active compounds or agents include, but are not limited to, sodium channel modulators such as bifenthrin, cypermethrin, flucythrin, lambda-flucythrin, flucythrin, beta-flucythrin, deltamethrin, cyfluthrin, cis-cypermethrin, cypermethrin, indoxacarb, cyfluthrin, profluthrin, pyrethrins and tralomethrin; cholinesterase inhibitors such as chlorpyrifos, ethoxycarb, oxamyl, thiophanate-methyl, thiamethoxam; Methomyl and triazolam; neonicotinoids such as acetamiprid, clothianidin, dinotefuran, imidacloprid, nitenpyram, nitrothiazolin, thiacloprid and thiamethoxam; insecticidal macrolides such as cypermethrin, spinosad, abamectin, avermectin and avermectin; GABA (γ-aminobutyric acid)-regulated chloride channel antagonists such as abamectin, or blockers such as ethiprole and fipronil; chitin synthesis inhibitors such as cypermethrin, cypermethrin, and flubendiamide; Urea, hexaflumuron, lufenuron, noflubenzuron, polyflubenzuron and chlorfenapyr; juvenile hormone analogues such as diphenyl ether, fenoxycarb, methoprene and pyriproxyfen; octopamine receptor ligands such as amitraz; molting inhibitors and ecdysone agonists such as azadirachtin, methoxyfenozide and tebufenozide; ryanodine receptor ligands such as ryanodine, anthranilamides such as chlorantraniliprole, cyantraniliprole and flubendiamide; nereistoxin analogues such as cartap; mitochondrial Electron transport inhibitors such as chlorfenapyr, hydrazone, and pyridabenz; lipid biosynthesis inhibitors such as chlorfenapyr and spiromesifen; cycloalkadiene insecticides such as dieldrin or endosulfan; pyrethroids; carbamates; urea fungicides; and biological agents, including nuclear polyhedrosis virus (NPV), members of the Bacillus thuringiensis spore, encapsulated Bacillus thuringiensis delta-endotoxin, and other naturally occurring or genetically modified insecticidal viruses.

[0119] More examples of biologically active compounds or agents that can be formulated with the compounds of the present invention are fungicides such as 1-[4-[4-[5-(2,6-difluorophenyl)-4,5-dihydro-3-isoxazolyl]-2-thiazolyl]-1-piperidinyl]-2-[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]ethanone, benzothiadiazole, cartap, indazolesulfamide, pentoconazole, azoxystrobin, bensulfuron, benomyl, benzylpyridin, isopropylbenzylpyridin, biphenyl, bisbenzimidazole, blasticidin-S, Bordeaux mixture (tribasic copper sulfate), boscalid / nicobifen, fumarole, pyrimidinesulfonate, butanethranil, carboxin, cyproconazole, captan, polyphenols. bacillus aureus, dimethoate, chlorothalonil, thiophanate-methyl, clotrimazole, copper oxychloride, copper salts such as copper sulfate and copper hydroxide, cypermethrin, cyfluanid, cyproconazole, cyproconazole, cyprodinil, dichlorvos, diclofenac, diclofenac, chloranil, ethoprop, dimethomorph, dimethomorph, dimethomorph, dimethomorph, dimethomorph, dimethomorph-M, diclofenac, discostrobin, dithianon, dodecanol, econazole, ethoprofen, dichlorvos, flufenoxam, ethidiumb, thiabendazole, thiabendazole, chlorpyrifos, chlorfenapyr, oxadiazine, fenoxam, chlorfenapyr, fenoxam, chlorfenapyr, fenoxam, chlorfenapyr, triphenyltin acetate, triphenyltin hydroxide, ferbam, ferfurazoate, pyrimidine, Fluazinam, fludioxonil, fluoxazolidinone, fluopyram, fluopyram, fluoxastrobin, fluquinconazole, flusilazole, sulfaquinamide, flutolanil, flutriafol, fluxapyroxad, folpet, fosetyl-aluminum, tetrachlorophthalide, maltol, furalaxyl, forabi, hexaconazole, hymexazol, kerejing, imazalil, amide, biguanide, iodocarb, ipconazole, isoprofen, iprodione, propineb, isoconazole, isothiocyanate, kasugamycin, kesuoxin, mancozeb, mancozeb, maneb, pyraclostrobin, metalaxyl-M, mefenamic acid, metalaxyl, metconazole, sulfaquinoxaline, metiram, metominostrobin / fenaminostrobin, mefenpyrine, mefentrazone, miconazole , myclobutanil, ammonium ferric arsenate (ferric methylarsate), flubendiamide, octhiothione, furamide, orysastrobin, oxadixyl, oxolinic acid, oximidazole, oxycarboxin, paclobutrazol, penconazole, pencuron, penflufenamic acid, penthiopyrad, blastifoglu, phosphonic acid, phthalide, flubosaccharide, picoxystrobin, polyoxin, allylisothiazolin, procymidone, procymidone, propamocarb, propamocarb salt Acid salt, propiconazole, propineb, propoxyquin, prothioconazole, pyraclostrobin, pyraclostrobin, pyraclostrobin, white powder pine, pyrimidine oxime, pyrimidine oxime, pyrimidine oxime, methoxybenzis, nitropyrrolidone, pyroquilone, quinazole, fast nofen, pentachloronitrobenzene, silthiopyrad, silfluazole, spiroxazolam, streptomycin, sulfur, tebuconazole, isobutyl ethoxyquin, tecnazene, keku rot,Tetrachloronitrobenzene, fluconazole, thiabendazole, thiophanate-methyl, thiuram-dithiocarb, thiamethoxam, methyl thiuram, thiazolamide, methyl tolclofos, tolylfluanid, triadimefon, triadimenol, myclobutanil, triazolinone, trimorph, tricyclazole, trifloxystrobin, triamcinol, trichlorfon, triclosan, uniconazole, jinggangmycin, downy mildew, vinylclocloth azole, maneb, ziram and oxamide; nematicides such as aldicarb, oxamyl and fenamiphos; fungicides such as streptomycin; acaricides such as amitraz, chlorpyrifos, chlorfenapyr, tricyclam, dicofol, chlorfenapyr, etoxazole, fenazaquin, fenbutatin, cypermethrin, fenpyrad, hexathiazolin, propargite, pyridabenz and tebufenpyrad.

[0120] Of note are fungicides and compositions comprising fungicides such as 1-[4-[4-[5-(2,6-difluorophenyl)-4,5-dihydro-3-isoxazolyl]-2-thiazolyl]-1-piperidinyl]-2-[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]ethanone, azoxystrobin, copper hydroxide, cymoxanil, cyproconazole, difenoconazole, famoxadone, cyanamide, pyraclostrobin, flusilazole, flutolanil, tetrachlorophthalide, forabiprole, hexaconazole, blastifungin, isotianil, kasugamycin, mancozeb, fenoxystrobin, orysastrobin, pencycuron, penthiopyrad, picoxystrobin, allisothiazole, propiconazole, propoxyquin, pyroquilon, silyfloxacin, thiamidine, tricyclazole, trifloxystrobin, and validamycin.

[0121] In some cases, the combination of the compounds of the present invention with other biologically active (especially invertebrate pest control) compounds or agents (i.e., active ingredients) can achieve a greater than additive (i.e., synergistic) effect. It is always desirable to reduce the amount of active ingredient released into the environment while ensuring effective pest control. When the invertebrate pest control active ingredients act synergistically at the application rate, imparting an agronomically acceptable degree of invertebrate pest control, such combinations can be advantageously used to reduce crop product costs and reduce environmental loads.

[0122] The compounds of the present invention and their compositions can be applied to plants that have been genetically modified to express proteins toxic to invertebrate pests (such as Bacillus thuringiensis delta-endotoxin). Such applications can provide a broader spectrum of plant protection and can be advantageously used for resistance management. The effects of the compounds of the present invention applied externally to control invertebrate pests can act synergistically with the expressed toxin protein.

[0123] General references to these agronomic protectants (i.e., insecticides, fungicides, nematicides, acaricides, herbicides and biologicals) include "The Pesticide Manual" 13th edition (edited by CDS Tomlin, British Crop Protection Council, Farnham, Surrey, UK, 2003) and "The BioPesticide Manual" 2nd edition (edited by LG Copping, British Crop Protection Council, Farnham, Surrey, UK, 2001).

[0124] For embodiments in which one or more of these various admixture components are used, the weight ratio of these various admixture components (total amount) to the compound of Formula I, its N-oxide, or salt thereof is generally between about 1:3000 and about 3000:1. Of note are weight ratios between about 1:300 and about 300:1 (e.g., a ratio between about 1:200 and about 200:1, a ratio between about 1:100 and about 100:1, a ratio between about 1:50 and about 50:1, a ratio between about 1:30 and about 30:1, a ratio between about 1:20 and about 20:1, a ratio between about 1:10 and about 10:1, a ratio between about 1:5 and about 1:1, or a ratio between about 1:1 and about 5:1). One skilled in the art can readily determine by simple experimentation the biologically effective amount of the active ingredient required to achieve the desired range of biological activity. Clearly, the inclusion of these additional components can extend the range of invertebrate pest control beyond that of the compound of Formula I alone.

[0125] In agronomic and non-agronomic applications, invertebrate pests are controlled by applying a biologically effective amount of one or more compounds of the invention, usually in the form of a composition, to the pest environment, including infested agronomic and / or non-agronomic loci, to the area to be protected, or directly to the pest to be controlled.

[0126] The present invention thus includes methods for controlling invertebrate pests in agricultural and / or non-agricultural applications, comprising contacting the invertebrate pest or its environment with a biologically effective amount of one or more compounds of the present invention, or with a composition comprising at least one such compound, or with a composition comprising at least one such compound and a biologically effective amount of at least one additional biologically active compound or agent. Examples of suitable compositions comprising a compound of the present invention and a biologically effective amount of at least one additional biologically active compound or agent include granular compositions, wherein the additional active compound is present on the same particles as the particles of the compound of the present invention, or on particles different from those of the particles of the compound of the present invention.

[0127] Embodiments of the methods of the present invention include contacting the environment. Of note are methods wherein the environment is a plant. Also of note are methods wherein the environment is an animal. Also of note are methods wherein the environment is a seed.

[0128] To achieve contact with the compounds or compositions of the present invention to protect field crops from invertebrate pests, the compounds or compositions are typically applied to crop seeds before planting, to the foliage (e.g., leaves, stems, flowers, fruits) of crop plants, or to the soil or other growth media before or after crop planting.

[0129] One embodiment of the contact method is by spraying. Alternatively, a granular composition comprising the compound of the present invention can be applied to plant leaves or soil. The compound of the present invention can also be effectively delivered via plant ingestion by contacting the plant with a composition comprising the compound of the present invention in the form of a soil drench liquid formulation, a granular formulation applied to the soil, a nursery box treatment, or a transplant soak. Of note is the composition of the present invention in the form of a soil drench liquid formulation. Also noteworthy is a method for controlling invertebrate pests, comprising contacting the invertebrate pest or its environment with a biologically effective amount of the compound of the present invention, or contacting a composition comprising a biologically effective amount of the compound of the present invention. Also noteworthy is a method wherein the environment is soil and the composition is applied to the soil as a soil drench formulation. Also noteworthy is the method wherein the environment is soil and the composition is applied to the soil as a soil drench formulation. Also noteworthy is the method wherein the compound of the present invention can be effected by topical application to the infested location. Other contact methods include applying the compound or composition of the present invention by direct spraying and residual spraying, aerial spraying, gels, seed coatings, microencapsulation, systemic absorption, baits, ear tags, boluses, sprayers, fumigants, aerosols, dusts, and many other methods. One embodiment of the contacting method is a dimensionally stable fertilizer granule, stick or tablet comprising a compound or composition of the invention.The compounds of the invention may also be impregnated into materials used to assemble invertebrate control devices (eg, insect screens).

[0130] The compositions of the present invention can also be used in seed treatments that provide protection from invertebrate pests. In the context of this disclosure and the claims, treating seeds refers to contacting the seeds with a biologically effective amount of a compound of the present invention, typically formulated as a composition of the present invention. Such seed treatments protect seeds from invertebrate soil pests and generally also protect the roots and other soil-contacting plant parts of the seedlings developed from the germinated seeds. The seed treatments also provide protection to the leaves by allowing the compounds of the present invention or a second active ingredient to migrate within the developing plant. Seed treatments can be applied to various types of seeds, including those that can germinate to form transgenic plants to express specific characteristics. Representative examples include those that express proteins toxic to invertebrate pests, such as Bacillus thuringiensis toxins, or those that express herbicide resistance, such as the glyphosate acetyltransferase that provides glyphosate resistance.

[0131] One method of seed treatment is to spray or dust the seeds with the compound of the present invention (i.e., as a prepared composition) before sowing the seeds. Compositions prepared for seed treatment generally include film formers or adhesives. Therefore, the seed coating composition of the present invention generally includes a biologically effective amount of a compound of formula I, an N-oxide or its salt and a film former or adhesive. The seeds are coated by spraying a flowable suspension concentrate directly into a seed rolling bed, and then drying the seeds. Alternatively, other formulation types such as wet powders, solutions, suspoemulsions, emulsifiable concentrates and aqueous solutions of emulsions can be sprayed onto the seeds. This method is particularly useful for applying film coating to seeds. Those skilled in the art can adopt various coating equipment and methods.

[0132] Treated seeds typically contain a compound of the invention in an amount of about 0.1 g to 1 kg per 100 kg of seeds (i.e., about 0.0001 to 1% by weight of the seeds before treatment). Flowable suspension formulations for seed treatment typically contain about 0.5 to about 70% active ingredient, about 0.5 to about 30% film-forming binder, about 0.5 to about 20% dispersant, 0 to about 5% thickener, 0 to about 5% pigment and / or dye, 0 to about 2% defoamer, 0 to about 1% preservative, and 0 to about 75% volatile liquid diluent.

[0133] The compounds of the present invention can be incorporated into bait compositions that are ingested by invertebrate pests or used in devices such as traps, bait stations, and the like. Such bait compositions can be in the form of granules comprising (a) an active ingredient, i.e., a biologically effective amount of a compound of Formula I, an N-oxide thereof, or a salt thereof; (b) one or more food materials; optionally (c) an attractant; and optionally (d) one or more wetting agents. Of note, granules or bait compositions comprising about 0.001-5% active ingredient, about 40-99% food material and / or attractant; and optionally about 0.05-10% wetting agent can effectively control soil invertebrate pests at very low application rates, particularly at doses of active ingredient that are lethal upon ingestion rather than direct contact. Certain food materials can be used both as a food source and as an attractant. Food materials include carbohydrates, proteins, and lipids. Examples of food materials are vegetable meal, sugar, starch, animal fat, vegetable oil, yeast extract, and milk solids. Examples of attractants are flavor enhancers and flavorings, such as fruit or plant extracts, spices, or other animal or plant components, pheromones, or other agents known to attract target invertebrate pests. Examples of humectants, i.e., water retaining agents, are ethylene glycol and other polyols, glycerol, and sorbitol. Of note are bait compositions (and methods of using such bait compositions) for controlling at least one invertebrate pest selected from ants, termites, and cockroaches. An apparatus for controlling invertebrate pests comprises a bait composition of the present invention and a housing adapted to contain the bait composition, wherein the housing has at least one opening sized to allow passage of an invertebrate pest so that the invertebrate pest can access the bait composition from a location external to the housing, and wherein the housing is further adapted to be placed in or near a location where potential or known invertebrate pests are active.

[0134] The compounds of the present invention can be administered without other adjuvants, but the most common application is to apply a formulation comprising one or more active ingredients with a suitable carrier, diluent, and surfactant, and possibly in combination with food, depending on the intended end use. One method of application involves spraying an aqueous dispersion or refined oil solution of the compound of the present invention. Combinations with spray oils, spray oil concentrates, spreaders, adjuvants, other solvents, and synergists such as piperonyl butoxide generally enhance the compound's effectiveness. For non-agricultural applications, such sprays can be applied from spray containers such as cans, bottles, or other containers, via a pump, or by releasing the compound from a pressurized container such as a pressurized aerosol spray can. Such spray compositions can take a variety of forms, such as sprays, mists, foams, smoke, or dust clouds. Therefore, such spray compositions may also include propellants, foaming agents, and the like, depending on the desired application. Of note are spray compositions comprising a biologically effective amount of a compound or composition of the present invention, and a carrier. One embodiment of such a spray composition comprises a biologically effective amount of a compound or composition of the present invention, and a propellant. Representative propellants include, but are not limited to, methane, ethane, propane, butane, isobutane, butylene, pentane, isopentane, neopentane, pentene, hydrofluorocarbons, chlorofluorocarbons, dimethyl ether, and mixtures thereof. Of note are spray compositions (and methods of using such spray compositions dispensed from a spray container) for controlling at least one invertebrate pest selected from the group consisting of mosquitoes, black flies, stable flies, deer flies, horse flies, wasps, hornets, hornets, ticks, spiders, ants, gnats, and the like, including any of the foregoing pests or combinations thereof.

[0135] Non-agricultural use refers to the control of invertebrate pests in the area of ​​non-crop fields. The non-agricultural use of the compound of the present invention and composition includes the control of stored grains, beans and other foods and textiles such as clothes and carpets. The non-agricultural use of the compound of the present invention and composition also includes the control of ornamental plants, forest crops, gardens, utility land along roadsides and railways, and turf such as lawns, golf courses and pastures. The non-agricultural use of the compound of the present invention and composition also includes the control of invertebrate pests in homes and other buildings inhabited by humans and / or companion animals, livestock, farm animals, zoo animals or other animals. The non-agricultural use of the compound of the present invention and composition also includes the control of pests such as termites that damage wood or other building materials used in buildings.

[0136] The non-agricultural uses of the compound and composition of the present invention also include protecting the health of humans and animals by controlling invertebrate pests that parasitize or spread infectious diseases. Controlling animal parasites includes controlling external parasites that parasitize on the surface of the host animal body (e.g., shoulders, armpits, abdomen, inner thighs) and internal parasites that parasitize inside the host animal body (e.g., stomach, intestines, lungs, veins, subcutaneous, lymphatic tissue). External parasitic or disease-transmitting pests include, for example, chiggers, ticks, lice, mosquitoes, flies, mites and fleas. Internal parasites include heartworms, hookworms and worms. The compound and composition of the present invention are particularly suitable for resisting external parasitic or disease-transmitting pests. The compound and composition of the present invention are suitable for systemic and / or non-systemic control of infestation or infection caused by parasites to animals.

[0137] The compounds and compositions of the present invention are suitable for combating parasites that infest animals, including wild animals, livestock, and agricultural working animals such as cattle, sheep, goats, horses, pigs, donkeys, camels, bison, buffaloes, rabbits, hens, turkeys, ducks, and geese (e.g., raised to obtain meat, milk, butter, eggs, fur, leather, feathers, and / or wool). By combating parasites, mortality rates are reduced and reduced profitability (in terms of meat, milk, wool, fur, eggs, honey, etc.) is alleviated, making the use of compositions comprising the compounds of the present invention more economical and making animal husbandry easier.

[0138] The compounds and compositions of the present invention are particularly suitable for combating parasites that infest companion animals and pets (e.g., dogs, cats, pet birds, and ornamental fish), research and laboratory animals (e.g., hamsters, guinea pigs, rats, and mice), and animals kept in zoos, wild habitats, and / or circuses.

[0139] In embodiments of the present invention, the animal is preferably a vertebrate, and more preferably a mammal, bird or fish. In a specific embodiment, the animal object is a mammal (including great apes, such as humans). Other mammal objects include primates (such as monkeys), bovines (such as cattle or cows), swine (such as domestic pigs or wild boars), ovines (such as goats or sheep), equines (such as horses), canines (such as dogs), felines (such as house cats), camels, deer, donkeys, bison, buffaloes, antelopes, rabbits and rodents (such as guinea pigs, squirrels, rats, mice, gerbils and hamsters). Birds include ducks (swans, ducks and geese), columbidae (such as turtledoves and pigeons), pheasants (such as partridges, grouse and turkeys), galliformes (such as chickens), psittacine (such as parakeets, macaws and parrots), game birds and ratites (such as ostriches).

[0140] Birds treated or protected by the compounds of the present invention are associated with commercial or non-commercial bird keeping. These include Anatidae such as swans, geese and ducks, Columbidae such as turtledoves and pigeons, Phasianidae such as partridges, grouse and turkeys, Gallinaceae such as chickens, and Psittacidae such as parakeets, macaws and parrots kept for pet or collector markets, and the like.

[0141] For the purposes of this invention, the term "fish" should be understood to include, without limitation, teleost fish, i.e., bony fish. The orders Salmonidae (which includes the Salmonidae) and Perciformes (which includes the Acanthoides) are both included in the teleosts. Examples of possible fish recipients include the Salmonidae, Flatfishes, Sparidae, Cichlidae, and Acanthoides, among others.

[0142] Other animals that are contemplated to benefit from the methods of the present invention include marsupials (such as kangaroos), reptiles (such as farmed turtles), and other economically important livestock for which the methods of the present invention can safely and effectively treat or prevent parasitic infections or infestations.

[0143] Examples of invertebrate parasitic pests controlled by applying a parasiticidally effective amount of the compound of the present invention to the animal to be protected include external parasites (arthropods, mites, etc.) and internal parasites (helminths such as nematodes, trematodes, tapeworms, acanthocephalians, etc.).

[0144] The diseases or class of diseases generally described as helminthiasis are due to infection of an animal host with parasitic worms known as helminths. The term "helminth" is intended to include nematodes, flukes, tapeworms, and acanthocephalians. Helminthiasis is a common and serious economic problem associated with domesticated animals such as pigs, sheep, horses, cattle, goats, dogs, cats, and poultry.

[0145] Among helminths, a class of worms described as nematodes can cause widespread and sometimes severe infections in many types of animals. Nematode animals contemplated for treatment with the compositions and methods of the present invention include, without limitation, the following genera: Acanthocheilus, Strongyloides, Ancylostoma, Angiostrongylus, Ascaris, Ascaris, Brugia, Bunostomum, Capillaria, Chabertia, Cooperia, Ringworm, Dictyocaulus, Diplocaulus, Acanthocheilus, Diphyllobothrium, Dirofilaria, Dracunculus, Enterobius, Filarialis, Haemonchus genus, Heterakis, Harelip Ascaris, Loa, Manson, Müller, Plate-stomach Nematode, Neck Nematode, Nodular Nematode, Gastrotrichum, Oxycaudatus, Parafilaria, Parascaris, Bubble-winged Nematode, Protostrongylus, Bristle Wireworm, Spirulina, Crown Wireworm, Strongyloides, Strongyloides, Sucking Nematode, Toxocara, Toxocara, Trichinella, Trichostrongylus, Trichostrongylus, Trichostrongylus, Whipworm, Hookworm and Wuchereria.

[0146] In the above, the most common nematode genera that can infect the above-mentioned animals are Haemonchus, Trichostrongylus, Osterleghorn, Gnaphaloma, Cooperia, Ascaris, Bunostomum, Nodularia, Chabelli, Trichuris, Strongyloides, Trichinella, Dictyocaulus, Capillaria, Heterakis, Toxocara, Gallinarum, Oxyura, Ancylostoma, Uncinaria, Toxocara and Parascaris. Some of these, such as Gnaphaloma, Cooperia and Nodularia, mainly attack the intestines, while others, such as Haemonchus and Osterleghorn, are more prevalent in the stomach, and others, such as Dictyocaulus, are present in the lungs. Other parasites are also located in other tissues, such as the heart and blood vessels, subcutaneous tissue and lymphatic tissue.

[0147] Trematodes contemplated for treatment with the compositions and methods of the present invention include, without limitation, the following genera: Brachypterus, Fasciola, Pygmysoma, Opisthorchis, Paragonimus, and Schistosoma.

[0148] It is contemplated that tapeworms treatable with the compositions and methods of the present invention include, without limitation, the following genera: Diphyllobothrium, Dipylidium, Spirometra, and Taenia.

[0149] The most common parasitic genera of the human gastrointestinal tract are Ancylostoma, Desmosthormata, Ascaris, Strongyloides, Trichinella, Capillaria, Trichuris and Enterobius. Other parasitic genera of medical importance that are present in the blood or other tissues and organs outside the gastrointestinal tract are filarial worms such as Wuchereria, Brugia, Onchocerca volvulus and Loa, as well as Dracunculiasis, and other intestinal ascarids such as Strongyloides and Trichinella.

[0150] Numerous other genera and species of helminths are known in the art and are also contemplated for treatment with the compounds of the present invention.

[0151] It is also envisaged that the compounds of the present invention will be effective against a variety of animal ectoparasites, for example arthropod ectoparasites of mammals and birds, although it is also envisaged that certain arthropods may also be endoparasites.

[0152] Thus, the insect and acarid pests include, for example, biting insects such as flies and mosquitoes, mites, ticks, lice, fleas, stink bugs, parasitic maggots and the like.

[0153] Adult flies include, for example, horn flies or blood flies, horse flies or horse flies, stable flies or stable flies, black flies or black flies, deer flies or spotted flies, louse flies or plant lice, tsetse flies or tsetse flies. Parasitic fly maggots include, for example, skin flies (stomach flies and botflies), blow flies or blow flies, spinner maggots or blow fly larvae, cow flies or heel flies, wool fly maggots and horse bot maggots. Mosquitoes include, for example, Culex, Anopheles and Aedes.

[0154] Mites include the genera of the order Mesostigma, such as the Chinese giant mites, such as chicken mites and gallinae; scabies or itch mites, such as the genera of the family Sarcoptes, for example, sarcoptic mange; animal scabies, such as the genera of the family Itchoptidae, including cattle mites and sheep mites; chiggers, such as the genera of the family Troglodytidae, for example, North American chiggers and true chiggers.

[0155] Ticks include, for example, soft-bodied ticks, including Cryptorhynchidae species such as Acanthocephalus and Green Ixodes; hard-bodied ticks include Ixodes species such as Rhipicephalus sanguineus, Dermacentor variabilis, Dermacentor andersoni, Amblyomma americanum, Ixodes scapularis, and Boophilus species.

[0156] Lice include, for example, sucking lice such as the genera Pocillopsis and Trichodesmosis; and hair-feeding lice such as the genera Haematopodi, Longignathi and Bryopsis.

[0157] Fleas include, for example, Ctenocephalides types such as the dog flea (Ctenocephalides canis) and the cat flea (Ctenocephalides felis); Xenopsylla, such as the oriental rat flea (Xenopsylla cheopis); and Pulex, such as the human flea (Pulex irritans).

[0158] Stink bugs include, for example, Cimex lectularius or the common stink bug (Cimex lectularius); the subfamily Cibotinae, including assassin bugs also known as assassin bugs; for example, Echinops rubripes and Triatomine bugs.

[0159] Generally speaking, flies, fleas, lice, mosquitoes, gnats, mites, ticks and worms cause huge losses to the livestock and companion animal sectors. Arthropod parasites are also troublesome to humans and can be vectors of disease-causing organisms for both humans and animals.

[0160] Numerous other arthropod pests and ectoparasites are known in the art and are also contemplated for treatment with the compounds of the present invention.

[0161] In particular, the compounds of the present invention are effective against ectoparasites, including fleas such as Ctenocephalides felis (cat flea) and Ctenocephalides canis (dog flea).

[0162] The compounds of the present invention are also effective against other ectoparasites, including flying insects, such as Haematobia irritans (horn fly), Stomoxys calcitrans (stable fly), Simulium spp. (black fly), Glossina spp. (tsetse fly), Hydrotaea irritans (big-headed fly), Musca autumnalis (fall housefly), Musca domestica (housefly), Morellia simplex (simple housefly), Tabanus spp. (horse fly), Hippocampus spp., Hippocampus spp., Lucilia sericata, Lucilia cuprina, Calliphora spp. (blow flies), Culicoides spp., Oestrus ovis (sheep nose fly), Culicoides spp. (midges), horse flies, horse flies, red horse flies, and horse nose flies; lice, such as cattle lice (Pennis spp.), horse hair lice, donkey blood lice, cat bird lice, dog lice, spiny jaw lice, and dog trichotillomanni; sheep tick flies, such as the sheep tick; mites, such as itch mites, scabies mites, cattle foot mites, horse demodex mites, Cheyletiella spp., cat ear mites, chiggers, and ear mites (ear mites); and ticks, such as Ixodes spp., Boophilus spp., Rhipicephalus spp., Amblyomma spp., Dermacentor spp., Hyalomma spp., and Haemaphysalis spp.

[0163] Biologically active compounds or agents that can be used in the compositions of the present invention include organophosphate insecticides. Such insecticides have a very wide range of activity as insecticides and, in some cases, have anthelmintic activity. Organophosphate insecticides include, for example, dicrotophos, terbufos, dimethoate, dipyraphos, disulfoton, trichlorfon, azinphos-methyl, chlorpyrifos, malathion, acephate, methamidophos, ethyl parathion, methyl parathion, mevinphos, phorate, trithion, and phosalone. Combinations of the methods and compositions of the present invention with carbamate insecticides, including, for example, carbaryl, carbofuran, aldicarb, chlorpyrifos, and ethiophos, are also contemplated, as are combinations with organochlorine insecticides. Combinations with biopesticides are also contemplated, including repellents, pyrethroids (and synthetic variants thereof, such as allethrin, pyrethrin, permethrin, tralomethrin), and nicotine, which is commonly used as a miticide. Other contemplated combinations are miscellaneous insecticides including: Bacillus, chlorobenzene, formamidines (such as amitraz), copper compounds (such as copper hydroxide and copper oxychlorosulfate), cyfluthrin, cypermethrin, dicofol, endosulfan, esfenvalerate, fenvalerate, lambda-cyhalothrin, methoxychlor, and sulfur.

[0164] Of note are additional biologically active compounds or agents selected from anthelmintics known in the art, such as avermectins (e.g., ivermectin, moxidectin, milbemycin), benzimidazoles (e.g., albendazole, triclabendazole), salicylanilides (e.g., closantel, hydroxyclozanamide), substituted phenols (e.g., nitroiodobenzonitrile), pyrimidines (e.g., pyrantel), imidazole thiazoles (e.g., levamisole) and praziquantel.

[0165] Other biologically active compounds or agents that can be used in the compositions of the present invention can be selected from insect growth regulators (IGRs) and juvenile hormone analogs (JHAs), such as diflubenzuron, thiocarb, fluazolone, cypermethrin, methoprene, and the like, to provide initial and sustained control of parasites (at all stages of insect growth, including eggs) to the animal subject and the animal subject's environment.

[0166] Of note are biologically active compounds or agents that can be used in the compositions of the present invention that are selected from the antiparasitic avermectin class of compounds. As mentioned above, the avermectin class of compounds is a series of potent antiparasitic agents known to be useful against a wide spectrum of mammalian endoparasites and ectoparasites.

[0167] The compositions of the present invention may also contain a flukeicide. Suitable flukeicides include, for example, triclabendazole, fenbendazole, albendazole, clorsulon and oxbendazole. It will be appreciated that the above combinations may also include combinations of antibiotics, antiparasitic and anti-fluke active compounds.

[0168] In addition to the combinations described above, it is also contemplated to provide the methods and compounds of the present invention as described herein in combination with other animal health drugs, such as trace elements, anti-inflammatory agents, anti-infective agents, hormones, dermatological preparations (including preservatives and disinfectants) and immunological preparations such as vaccines and antisera for the prevention of disease.

[0169] For example, such anti-infective agents include one or more antibiotics that may optionally be administered concurrently during treatment with the compounds or methods of the invention, for example, in the form of a combined composition and / or in separate dosage forms.

[0170] Non-agricultural applications in the veterinary sector are by conventional methods, such as by enteral administration in the form of, for example, tablets, capsules, drinks, drenches, granules, pastes, boluses, feeding procedures or suppositories; or by parenteral administration in the form of, for example, injections (including intramuscular, subcutaneous, intravenous, intraperitoneal) or implants; by nasal administration; by topical administration, for example by dipping or immersing, spraying, washing, coating with powders or applying to small areas of the animal, as well as by articles comprising the composition of the invention in the form of collars, ear tags, tail bands, limb bands or halters.

[0171] Any of the compounds of the present invention or suitable combinations of such compounds can be administered directly to an animal subject and / or indirectly by administering it to the local environment in which the animal resides, such as bedding, pens, etc. Direct administration includes contacting the skin, fur, or feathers of the animal subject with the compound, or feeding the compound to the animal or injecting it into the animal.

[0172] The compounds of the invention can be administered in a controlled release form, for example as a subcutaneous slow release formulation, or in the form of a controlled release device affixed to the animal, such as a flea collar. Collars for the controlled release of insecticides for long-term protection of companion animals from flea infestations are known in the art.

[0173] Typically, the parasiticidal composition according to the present invention comprises a mixture of a compound of formula I, its N-oxide or its salt and one or more pharmaceutically or veterinarily acceptable carriers, wherein the carrier comprises an excipient and an adjuvant, which is selected according to the intended route of administration (e.g., oral administration, topical administration or parenteral administration such as injection) and according to standard procedures. In addition, according to the compatibility with one or more active ingredients in the composition, including the presence of relative stability such as to pH and water content, a suitable carrier is selected. Therefore, it is noteworthy that the composition for protecting animals from the infringement of invertebrate parasitic pests comprises a compound of the present invention comprising at least one carrier and a parasiticidal effective amount.

[0174] For parenteral administration (including intravenous injection, intramuscular injection and subcutaneous injection), the compounds of the present invention can be formulated into suspensions, solutions or emulsions in oily or aqueous carriers and may contain adjuvants such as suspending agents, stabilizers and / or dispersants. The compounds of the present invention can also be formulated for rapid bolus injection or continuous infusion. The pharmaceutical composition for injection includes an aqueous solution of the active ingredient (e.g., a salt of the active compound) in a water-soluble form, preferably in a physiologically compatible buffer solution containing other excipients or adjuvants as known in the field of pharmaceutical formulations. In addition, a suspension of the active compound can be prepared in a lipophilic carrier. Suitable lipophilic carriers include fatty oils such as sesame oil, synthetic fatty acid esters such as ethyl oleate and triglycerides, or substances such as liposomes. The injection suspension aqueous solution may contain substances that increase the viscosity of the suspension, such as sodium carboxymethylcellulose, sorbitol or dextran. The preparation for injection can be present in, for example, an ampoule container or a multidose container in unit dosage form. Alternatively, the active ingredient may be in powder form for constitution with a suitable vehicle, eg, sterile pyrogen-free water, before use.

[0175] In addition to the above-mentioned preparations, the compounds of the present invention can also be formulated into long-acting preparations. Such long-acting preparations can be administered by implantation (e.g., subcutaneous or intramuscular) or by intramuscular injection or subcutaneous injection. With regard to this route of administration, the compounds of the present invention can be formulated with suitable polymeric materials or hydrophobic materials (e.g., in an emulsion containing a pharmaceutically acceptable oil), with an ion exchange resin, or the compound can be formulated into a slightly soluble derivative, such as, but not limited to, a slightly soluble salt.

[0176] For administration by inhalation, the compositions of the present invention can be delivered in the form of an aerosol spray using a pressurized pack or nebulizer and a suitable propellant, such as, but not limited to, dichlorodifluoromethane, trichlorofluoromethane, dichlorotetrafluoroethane, or carbon dioxide. In the case of a pressurized aerosol, the dosage unit can be controlled by providing a valve to deliver a metered amount. Gelatin capsules and cartridges for use in an inhaler or insufflator can be formulated to contain a powder mix of the compound and a suitable powder base such as lactose or starch.

[0177] The compounds of the present invention have been found to have favorable pharmacokinetic and pharmacodynamic properties, providing systemic availability upon oral administration and ingestion. Thus, upon ingestion by the animal to be protected, parasiticidally effective concentrations of the compounds of the present invention in the blood can protect the treated animal from blood-sucking pests such as fleas, ticks, and lice. Of note are oral compositions (i.e., containing, in addition to a parasiticidally effective amount of the compounds of the present invention, one or more carriers selected from binders and fillers suitable for oral administration and concentrate feed carriers) that protect animals from invertebrate parasitic pests.

[0178] For oral administration in the form of solutions (the most readily available absorption form), emulsions, suspensions, pastes, gels, capsules, tablets, boluses, powders, granules, rumen retentate, and feed / water / lick bricks, the compounds of the present invention can be formulated with binders / fillers known in the art for oral compositions, such as sugars and sugar derivatives (e.g., lactose, sucrose, mannitol, sorbitol), starches (e.g., corn starch, wheat starch, rice starch, potato starch), cellulose and derivatives (e.g., methylcellulose, carboxymethylcellulose, ethylhydroxycellulose), protein derivatives (e.g., zein, gelatin), and synthetic polymers (e.g., polyvinyl alcohol, polyvinylpyrrolidone). Lubricants (e.g., magnesium stearate), disintegrants (e.g., cross-linked polyvinylpyrrolidone, agar, alginic acid), and dyes or pigments can be added if desired. Pastes and gels also typically contain a binder (e.g., acacia, alginic acid, bentonite, cellulose, xanthan gum, colloidal magnesium aluminum silicate) to help keep the composition in contact with the oral cavity and prevent it from being expelled.

[0179] If the parasiticidal composition is in the form of a feed concentrate, the carrier is typically selected from a high-performance feed, a feed cereal, or a protein concentrate. In addition to the parasiticidal active ingredient, such compositions comprising a feed concentrate may also contain additives that promote animal health or growth, improve the quality of meat from slaughtered animals, or are otherwise useful in animal husbandry. These additives include, for example, vitamins, antibiotics, chemotherapeutic agents, bacteriostats, fungistats, coccidiostats, and hormones.

[0180] The compounds of formula I may also be formulated in rectal compositions such as suppositories or retention enemas, using, for example, conventional suppository bases such as cocoa butter or other glycerides.

[0181] Preparations for topical administration are generally in the form of powders, creams, suspensions, sprays, emulsions, foams, pastes, aerosols, ointments, ointments or gels. Topical preparations are more typically water-soluble solutions, which can be in the form of concentrates diluted before use. Parasiticidal compositions suitable for topical administration generally comprise a compound of the present invention and one or more topical suitable carriers. When the parasiticidal composition is topically applied to the outside of the animal body in the form of lines or dots (i.e., accurate therapy), the active ingredient migrates on the animal body surface to cover most or all of its surface area. Therefore, the treated animal can be protected from the infringement of invertebrate pests such as ticks, fleas and lice that feed on the animal epidermis. Therefore, preparations for local fixed-point administration generally comprise at least one organic solvent to facilitate the active ingredient to be delivered on the animal skin and / or to penetrate into the animal epidermis. Carriers in such formulations include propylene glycol, paraffins, aromatic compounds, esters (such as isopropyl myristate), glycol ethers, alcohols (such as ethanol, n-propanol, 2-octyldodecanol or oleyl alcohol); solutions of monocarboxylic acid esters, such as isopropyl myristate, isopropyl palmitate, lauric acid oxalate, oleyl oleate, decyl oleate, hexyl laurate, chain length C 12 -C 18 solutions of dicarboxylic acid esters, such as dibutyl phthalate, diisopropyl isophthalate, diisopropyl adipate, di-n-butyl adipate, or solutions of aliphatic acid esters (e.g. ethylene glycol). The presence of crystallization inhibitors or dispersants known from the pharmaceutical or cosmetic industry may also be advantageous.

[0182] Pour-on formulations can also be formulated to control parasites in animals of agricultural value. The pour-on formulations of the present invention can be in the form of liquids, powders, emulsions, foams, pastes, aerosols, ointments, creams, or gels. Pour-on formulations are typically liquids. These pour-on formulations can be effectively applied to sheep, cattle, goats, other ruminants, camelids, pigs, and horses. The pour-on formulations are typically applied by pouring the pour-on formulation in one or more thin lines, or precisely pouring it onto the animal's back midline (back) or shoulders. More typically, the pour-on formulation is applied by pouring it along the animal's back, along the spine. The formulation can also be applied via other conventional methods, including wiping the animal with an impregnated substance on at least a small area, or applying it using a commercially available applicator, applying it by syringe, applying it by spraying, or applying it by using a spray barrier. The pour-on formulation includes a carrier and may also include one or more additional ingredients. Examples of suitable additional ingredients are stabilizers such as antioxidants, spreading agents, preservatives, adhesion promoters, active solubilizers such as oleic acid, viscosity modifiers, UV blockers or absorbers, and colorants. Surfactants may also be included in these formulations, including anionic, cationic, nonionic and amphoteric surfactants.

[0183] The formulations of the present invention typically contain an antioxidant such as BHT (butylated hydroxytoluene). The antioxidant is generally present at a level of 0.1% to 5% (weight / volume). Some formulations require a solubilizer such as oleic acid to dissolve the active agent, especially when using spinosad. Common spreading agents used in these pour-on formulations are: IPM, IPP, saturated C 12 -C 18 Caprylic / capric esters of fatty alcohols, oleic acid, oleyl esters, ethyl oleate, triglycerides, silicone oil, and DPM. The pour-on formulations of the present invention can be prepared according to known techniques. When the pour-on is a solution, the repellent / insecticide is mixed with the carrier or vehicle using heating and stirring, if necessary. Auxiliary or additional ingredients can be added to the mixture of active agent and carrier, or mixed with the active agent before adding the carrier. If the pour-on is an emulsion or suspension, these formulations can be prepared similarly using known techniques.

[0184] Other delivery systems for more hydrophobic pharmaceutical compounds can be used. Liposomes and emulsions are examples of well-known delivery vehicles or carriers for hydrophobic drugs. In addition, organic solvents such as dimethyl sulfoxide can be used if desired.

[0185] For agronomic applications, the amount of application required for effective control (i.e., a "biologically effective amount") will depend on factors such as the type of invertebrate pest to be controlled, the pest's life cycle, life stage, size, location, time of year, host crop or animal, feeding behavior, mating behavior, ambient moisture, temperature, and the like. Under normal circumstances, an application rate of about 0.01 to 2 kg of active ingredient per hectare is sufficient to control pests in agronomic ecosystems, but an application rate as low as 0.0001 kg per hectare may also be sufficient, or an application rate as high as 8 kg per hectare may also be required. For non-agronomic applications, an effective amount will be in the range of about 1.0 to 50 mg per square meter, but an application rate as low as 0.1 mg per square meter may also be sufficient, or an application rate as high as 150 mg per square meter may also be required. One skilled in the art can readily determine the biologically effective amount required to achieve the desired level of invertebrate pest control.

[0186] Generally speaking, for veterinary use, a compound of Formula I, its N-oxide, or a salt thereof is applied to an animal in a parasiticidal effective amount to protect it from invertebrate parasitic pests. A parasiticidal effective amount is the amount of active ingredient required to achieve an observed reduction in the incidence or activity of the target invertebrate parasitic pest. Those skilled in the art will appreciate that the parasiticidal effective dose may vary depending on the compounds and compositions of the present invention, the desired parasiticidal effect and duration, the target invertebrate pest species, the animal to be protected, the mode of administration, and the like, and that the amount required to achieve a specific effect can be determined by simple experimentation.

[0187] For oral administration to warm-blooded animals, daily dosages of the compounds of the invention are typically in the range of 0.01 mg / kg to about 100 mg / kg, more typically about 0.5 mg / kg to about 100 mg / kg, of the compound of the invention. For topical (e.g., dermal) administration, dips and sprays typically contain about 0.5 ppm to about 5000 ppm, more typically about 1 ppm to about 3000 ppm, of the compound of the invention. DETAILED DESCRIPTION

[0188] The following examples are provided to illustrate the present invention and should not be considered to limit the present invention in any way. The scope of the rights claimed in the present invention is described in the claims.

[0189] Given the economical efficiency and diversity of the compounds, we have selected and synthesized a number of compounds. A selection of these compounds is listed in Table 1 below. The specific compound structures and corresponding compound information are shown in Table 1. The compounds in Table 1 are intended to better illustrate the present invention but are not intended to limit the present invention. Those skilled in the art should not interpret this as limiting the scope of the present invention to the following compounds.

[0190] Table 1 Compound structures and their 1 H NMR values

[0191] Several methods for preparing the compounds of the present invention are described in detail in the following schemes and examples. The starting materials can be purchased commercially or can be prepared by methods known in the literature or as described in detail. It will be understood by those skilled in the art that other synthetic routes can also be used to synthesize the compounds of the present invention. Although the specific starting materials and conditions in the synthetic routes have been described below, they can be easily replaced with other similar starting materials and conditions, and these modifications or variations of the preparation methods of the present invention that result in various isomerizations of the compounds are included within the scope of the present invention. In addition, the preparation methods described below can be further modified according to the present disclosure using conventional chemical methods well known to those skilled in the art. For example, appropriate groups can be protected during the reaction, etc.

[0192] The following process examples are provided to facilitate a further understanding of the preparation methods of the present invention. The specific substances, types, and conditions used are intended to further illustrate the present invention and are not intended to limit its reasonable scope. The reagents used in the synthesis of the compounds shown in the table below are either commercially available or can be readily prepared by one of ordinary skill in the art.

[0193] Examples of representative compounds are shown below. The synthesis methods of other compounds are similar and will not be described in detail here.

[0194] 1. Synthesis of Compound 2

[0195] (1) 2.7 g of 2-1 was dissolved in 30 ml of 10% aqueous HCl. 1.2 equivalents of sodium nitrite were added under ice-cooling. After 30 minutes of reaction, 4 equivalents of solid KI were added. After 1 hour of reaction, the reaction was completed. Aqueous sodium thiosulfate was added to the reaction system to quench the reaction. The reaction was extracted twice with 30 ml of ethyl acetate. The organic phases were combined and silica gel powder was added to the sample. After purification by column chromatography, 2 g of 2-2 was obtained with a yield of 48%.

[0196] (2) 2 g of 2-2 was dissolved in 30 ml of dioxane, and 1.2 equivalents of dimethyl malonate were added. Then, 5% picolinic acid and 5% cuprous iodide were added. After nitrogen displacement three times, the reaction was carried out at 80°C for 16 hours. After the intermediate control reaction was completed, silica gel powder was directly added and the sample was mixed. After purification by column chromatography, 1.3 g of 2-3 was obtained with a yield of 64%.

[0197] (3) 1 g of 2-3 was dissolved in 20 ml of a 1:1 ethanol:water reaction system, and 4 equivalents of sodium hydroxide solution dissolved in water were added. The reaction was carried out at 10°C for 16 hours. After the control was completed, the organic phase was removed by extraction with methyl tert-butyl ether. The aqueous phase was adjusted to pH 2 and then extracted with ethyl acetate. The organic phase was washed with saturated sodium chloride and dried over anhydrous sodium sulfate. The product 2-4 was obtained by spin drying to obtain 500 mg of the product, with a yield of 55%.

[0198] (4) 250 mg of 2-4 was dissolved in 10 ml of DCM, 1 drop of DMF was added, and 2.4 equivalents of oxalyl chloride were added dropwise at 0°C for 30 minutes. After the reaction was complete, 1.1 equivalents of compound 2-5 were added dropwise to the system, followed by 4 equivalents of triethylamine. The reaction was continued at 0°C for 20 minutes. After the reaction was complete, 20 ml of 1 M hydrochloric acid solution was added for extraction. The organic phase was dried and ethyl acetate was added to precipitate the solid, which was directly filtered to obtain a light yellow solid 2 (60 mg, yield 14%).

[0199] 2. Synthesis of compound 3

[0200] (1) 2.5 g of 3-1 was dissolved in 30 ml of 10% HCl aqueous solution. 1.2 equivalents of sodium nitrite aqueous solution was added under ice bath. After 30 minutes of reaction, 4 equivalents of KI solid was added. After 1 hour of reaction, the reaction was completed. Sodium thiosulfate aqueous solution was added to the reaction system to quench the reaction. 30 ml of ethyl acetate was added for extraction twice. The organic phases were combined and silica gel powder was added to the sample. After purification by column chromatography, 2 g of 3-2 was obtained with a yield of 50%.

[0201] (2) 2 g of 3-2 was dissolved in 30 ml of dioxane, and 1.2 equivalents of dimethyl malonate were added. Then, 5% picolinic acid and 5% cuprous iodide were added. After nitrogen displacement three times, the reaction was carried out at 80°C for 16 hours. After the intermediate control reaction was completed, silica gel powder was directly added and the sample was mixed. After purification by column chromatography, 1.5 g of 3-3 was obtained with a yield of 75%.

[0202] (3) 1 g of 3-3 was dissolved in 20 ml of a 1:1 ethanol:water reaction system, and 4 equivalents of sodium hydroxide solution dissolved in water were added. The reaction was carried out at 10°C for 16 hours. After the control was completed, the organic phase was removed by extraction with methyl tert-butyl ether. The aqueous phase was adjusted to pH 2 and then extracted with ethyl acetate. The organic phase was washed with saturated sodium chloride and dried over anhydrous sodium sulfate. The product was dried by spin drying to obtain 600 mg of 3-4, with a yield of 67%.

[0203] (4) 500 mg of 3-4 was dissolved in 10 ml of DCM, 1 drop of DMF was added, and 2.4 equivalents of oxalyl chloride were added dropwise at 0°C for 30 minutes. After the reaction, the intermediate control was completed. 1.1 equivalents of 2-5 were added dropwise to the system, followed by 4 equivalents of triethylamine. The reaction was continued at 0°C for 20 minutes. After the intermediate control was completed, 20 ml of 1 M hydrochloric acid was added for extraction. The organic phase was dried and ethyl acetate was added to precipitate the solid. The product 3 was directly filtered to obtain 150 mg of a light yellow solid with a yield of 17%.

[0204] 3. Synthesis of Compound 51

[0205] (1) Substrate 51-1 (1 eq) was added to a three-necked flask and dissolved in 1,4-dioxane. Dimethyl malonate (2.0 eq), cesium carbonate (2.5 eq), 2-picolinic acid (0.2 eq), and cuprous iodide (0.1 eq) were added. The mixture was stirred at 90°C overnight. The reaction was monitored by liquid chromatography-mass spectrometry to determine completion. Inorganic salts were filtered off with celite pads. The organic phase was mixed with the dry sample and passed through a column to obtain product 51-2 (808 mg, 62% yield).

[0206] (2) 51-2 (1 eq) was added to methanol in a single-necked flask, and a NaOH solution (4.0 eq) was added. The reaction was allowed to react overnight at room temperature. The reaction was complete by liquid chromatography-mass spectrometry. The methanol was dried and extracted with water and dichloromethanol. The product was in the aqueous phase. The aqueous phase was dried to obtain 1.373 g of crude product 51-3.

[0207] (3) Substrate 51-3 (1 eq) was added to a single-necked flask and dissolved in dichloromethane. DMF (2 drops) and oxalyl chloride (4.0 eq) were added and stirred at room temperature for 0.5 h. The reaction was complete as monitored by liquid chromatography-mass spectrometry. The flask was placed on dry ice, 2-5 (1.2 eq) and triethylamine (6.0 eq) were added, and stirred for 0.5 h. The reaction was complete as monitored by liquid chromatography-mass spectrometry. The flask was extracted with dilute hydrochloric acid and dichloromethane. The organic phase was dried and purified by slurrying with THF to obtain product 51 (65 mg, 93% purity).

[0208] 4. Synthesis of Compound 164

[0209] (1) 164-3 (0.3 g, 0.82 mmol, 1 eq), 4-fluorophenylboronic acid (0.17 g, 1.23 mmol, 1.5 eq), and cesium fluoride (0.25 g, 1.64 mmol, 2 eq) were dissolved in dioxane (8 ml) and water (1 ml) and added to a 50 ml single-necked bottle. The mixture was purged with nitrogen once, and a catalytic amount of Pd(dppf)Cl2 was added. The mixture was purged with nitrogen three times and heated under reflux at 100°C for 12 h. After monitoring the reaction completion, the mixture was extracted with water and ethyl acetate. The organic phase was washed twice with saturated brine and dried over anhydrous sodium sulfate. The sample was mixed and the organic phase was purified by column chromatography to obtain 164-4 (0.23 g, purity 91%, yield 74%) as a white solid.

[0210] (2) 164-4 (230 mg, 0.60 mmol, 1 eq) was added to a 50 ml single-necked bottle, and 5 ml of ethanol and 5 ml of water were added. Sodium hydroxide (120 mg, 3.02 mmol, 5 eq) was added with stirring at room temperature. The reaction was allowed to proceed at room temperature for 3 h. The reaction of the raw materials was monitored for complete reaction. The reaction solution was adjusted to acidity and extracted with ethyl acetate. The organic phase was dried to obtain about 120 mg of crude product 164-5, which was used directly in the next step.

[0211] (3) 164-5 (120 mg, 0.34 mmol, 1 eq) was added to a 50 ml single-necked bottle, oxalyl chloride (81 mg, 0.68 mmol, 2 eq) was added, and a drop of DMF was added as a catalyst. The reaction was allowed to react at room temperature for 30 min, and the reaction was monitored for completion using methanol. The reaction bottle was transferred to a dry ice bath and cooled to -20°C. 2-5 (98 mg, 0.41 mmol, 1.2 eq) dissolved in DCM was added dropwise, followed by triethylamine (103 mg, 1.02 mmol, 3 eq). The pH was measured to be 12, and the reaction was kept warm for 1 h. After monitoring the reaction completion, the sample was directly rotary evaporated and separated by normal phase separation to obtain 164 (52 mg, purity 96%, yield 28%) as a light yellow solid.

[0212] 5. Synthesis of Compound 170

[0213] (1) Substrate 170-1 (2.9 g, 10.1 mmol) was dissolved in 30 mL of a mixed solvent (1,4-dioxane:water = 4:1). Compound 170-2 (1.8 g, 10.1 mmol), Cs2CO3 (13.2 g, 40.4 mmol), and Pd(dppf)Cl2 (256 mg, 0.3 mmol) were added. The mixture was reacted at 80°C overnight under nitrogen protection. After the reaction, the mixture was filtered with celite, the dioxane was removed by vortexing, and the mixture was extracted with ethyl acetate (50 mL x 3). The mixture was purified by silica gel column chromatography to obtain intermediate 170-3 as a white solid (2 g, 6.5 mmol, 64.5%).

[0214] (2) Substrate 170-3 (2 g, 6.5 mmol) was dissolved in a 10% aqueous sulfuric acid solution. NaNO2 (539 mg, 7.8 mmol) was added under ice-cooling. KI (5.4 g, 32.5 mmol) was added half an hour later and the mixture was allowed to react at room temperature for 4 h. After completion of the reaction, the mixture was extracted with ethyl acetate (50 mL x 3), and the organic phase was washed with saturated sodium thiosulfate solution and purified by silica gel column chromatography to obtain intermediate 170-4 as a yellow oil (1.6 g, 3.9 mmol, 59.3%).

[0215] (3) Substrate 170-4 (1.6 g, 3.9 mmol) was dissolved in dioxane, and dimethyl malonate (1 g, 7.8 mmol) and cesium carbonate (3.7 g, 11.7 mmol) were added. Picolinic acid (84 mg, 0.78 mmol) and cuprous iodide (146 mg, 0.78 mmol) were then added. The mixture was reacted at 90°C under nitrogen protection overnight. After completion of the reaction, the mixture was filtered through celite, extracted with ethyl acetate (50 mL x 3), and purified by silica gel column chromatography to obtain intermediate 170-5 (520 mg, 3.3 mmol, 85.8%).

[0216] (4) Substrate 170-5 (520 mg, 3.3 mmol) was dissolved in 15 mL of a mixed solvent (ethanol:water = 4:1), and sodium hydroxide (246 mg, 16.5 mmol) was added. The mixture was allowed to react at room temperature for 2 h. After completion of the reaction, the ethanol was removed by vortexing, the pH was adjusted to acidic, and the mixture was extracted with ethyl acetate (40 mL x 3). The solvent was then removed by vortexing to obtain intermediate 170-6 (450 mg, 3.1 mmol, 92.78%).

[0217] (5) Substrate 170-6 (450 mg, 3.1 mmol) was dissolved in dichloromethane, and oxalyl chloride (434 mg, 9.3 mmol) was added. After monitoring the reaction, the reaction solution was placed at -78°C, and compound 2-5 (274 mg, 3.1 mmol) and triethylamine (693 mg, 18.6 mmol) were added and reacted for 1 h. After completion of the reaction, the product was purified by silica gel column chromatography to obtain 170 (201 mg, 0.9 mmol, 29.5%).

[0218] Biological activity evaluation (spray method):

[0219] (1) Test of compound insecticidal activity:

[0220] The compound of the present invention is dissolved in acetone and then diluted with water to form a drug solution with different concentrations (ppm).

[0221] Chilo suppressalis: Select test insects that have been continuously reared indoors and have the same physiological state, place them in disposable culture dishes, and inoculate 10 third-instar larvae into each dish, along with 10 rice buds.

[0222] Fall armyworm, armyworm, and Spodoptera litura: Select test insects that have been continuously reared indoors and have the same physiological state and place them in disposable culture dishes. Inoculate 10 second-instar larvae into each dish and add 4 corn leaves.

[0223] Spraying was then performed using a spray tower, with each dose repeated three times. A control containing the same acetone concentration was used. After application, the insects were transferred to aquaculture conditions. The number of dead insects was examined 48 hours later, and the mortality rate was calculated using the formula: mortality rate (%) = (number of dead insects / number of test insects) * 100. Representative experimental results are shown in Table 2.

[0224] Table 2 Insecticidal test results

[0225] Note: N stands for no data, reference compound A:

[0226] (2) Bee acute toxicity test:

[0227] An acute toxicity test for honey bees was conducted according to the method described in GB / T 31270.10-2014. The toxicity symptoms and mortality rates were observed and recorded 96 hours after treatment. The test results showed that compounds 2 and 3 of the present invention had an acute contact toxicity of >11 μg ai / bee, indicating low toxicity, and an acute oral toxicity of >11 μg ai / bee, indicating low toxicity. In contrast, the control compound B (trifluphenazine) had a mortality rate of 90% at a dose of 1 μg ai / bee, indicating high toxicity. This indicates that the compounds described herein have significantly reduced toxicity to honey bees and are safer.

[0228] (3) Composition insecticide activity determination test:

[0229] 3.1) Test conditions and operating steps

[0230] Test targets: Chilo suppressalis, Fall armyworm, Armyworm, Peanut aphid.

[0231] After the original drug is dissolved in acetone, the solution is diluted with distilled water to a gradient dose. Select test insects (spodoptera frugiperda, armyworm, peanut aphid) with the same physiological state reared indoors, put them in a disposable transparent box, inoculate 10 test insects with the same growth in each box, and put them in the host plant leaves (rice buds for striped stem borer, corn leaves for fall armyworm and armyworm, peanut leaves for peanut aphid), then use a spray tower to spray, cover tightly after spraying, repeat 3 times, and use the highest dose of acetone solution as a control. The test insects treated with the drug are placed in the treatment room under conventional rearing conditions to check the number of dead insects after 48 hours, and the mortality rate is calculated according to the formula: mortality rate (%) = (number of dead insects / number of test insects) * 100.

[0232] 3.2) Qualitative evaluation of efficiency

[0233] Toxicity tests were performed at different ratios within the selected range, and the optimal ratio was selected based on the synergistic effect. A synergistic effect > 0 indicates a synergistic effect; a synergistic effect close to 0 indicates an additive effect; and a synergistic effect < 0 indicates an antagonistic effect.

[0234] Synergistic effect = actual mortality rate - theoretical mortality rate

[0235] Theoretical mortality rate = 1-(1-P1)(1-P2)

[0236] Where, P1, P2 are the mortality rates of each single dose in the mixture.

[0237] Table 3 Qualitative evaluation test results of the composition synergistic effect

[0238] At the same time, after many tests, it was found that many of the compounds and compositions of the present invention have good control activity against agricultural pests such as Lepidoptera (such as corn borer, striped stem borer, diamondback moth, Spodoptera litura, beet armyworm, cotton bollworm, fall armyworm, armyworm, etc.), Homoptera (such as cotton aphid, radish aphid, pea aphid, peanut aphid, green stink bug, etc.), Acarina (such as two-spotted spider mite, truncate spider mite, Turkestan spider mite, etc.), Diptera (such as leek bradgy fungus gnat, etc.), Coleoptera (such as yellow flea beetle, monkey leaf beetle, etc.) and thrips (such as palm thrips, onion thrips, tobacco thrips, etc.), as well as sanitary pests such as cockroaches (such as termites, cockroaches, etc.) and Muscidae (such as flies, mosquitoes, etc.). They not only have the characteristics of broad spectrum, high efficiency, and strong systemic absorption, but can also effectively control resistant pests and have certain commercial value.

Claims

1. A mesoionic pyrimidinium compound, an N-oxide or a salt thereof as represented by the general formula I: in, X represents a cyano group, a cyanoalkyl group, an aryl group or a heterocyclic group; Q1 and Q2 independently represent O or S; M1, M2, M3, M4, and M5 independently represent CR9 or N, and at least two of them are N; R1, R2, R3, R4, R5, R6, R7, R8, and R9 independently represent hydrogen, nitro, amino, cyano, halogen, hydroxy, mercapto, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, haloalkynyl, alkoxy, alkylthio, haloalkoxy, haloalkylthio, formyl, alkylcarbonyl, alkylsulfoxide, alkylsulfonyl, amino substituted with an alkyl group, cycloalkyl, cycloalkenyl, aryl, or heterocyclic group; The aforementioned "cycloalkyl" or "cycloalkenyl" is optionally substituted by at least one group selected from halogen, cyano, nitro, alkyl, alkenyl, alkynyl, cycloalkyl, haloalkyl, haloalkenyl, haloalkynyl, halocycloalkyl, cycloalkyl substituted by alkyl, or cycloalkylalkyl; The aforementioned "heterocyclyl" or "aryl" is optionally selected from oxo, halogen, cyano, nitro, alkyl, alkenyl, alkynyl, cycloalkyl, haloalkyl, haloalkenyl, haloalkynyl, halocycloalkyl, cycloalkyl substituted by alkyl, cycloalkylalkyl, aryl or heterocyclyl which is unsubstituted or substituted by at least one group selected from halogen, cyano, nitro, alkyl, haloalkyl, alkoxycarbonyl, alkylthio, alkylsulfonyl, alkoxy or haloalkoxy, -OR 10 , -SR 10 ,-(CO)OR 10 ,-(SO)R 10 , -(SO2)R 10 ,-N(R 10 )2,-alkylene-OR 10 ,-alkylene-SR 10 ,-alkylene-(CO)OR 10 ,-alkylene-(SO)R 10 ,-alkylene-(SO2)R 10 ,-alkylene-N(R 10 )2 or -O-alkylene-(CO)OR 10 or two adjacent carbon atoms on the ring form a fused ring with unsubstituted or halogen-substituted -OCH2CH2- or -OCH2O-; R 10 Each of the following is independently hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, haloalkyl, haloalkenyl, haloalkynyl, halocycloalkyl, cycloalkyl substituted by alkyl, cycloalkylalkyl, aryl, heterocyclic group, or aryl or heterocyclic group substituted by at least one group selected from halogen, cyano, nitro, alkyl, haloalkyl, alkoxycarbonyl, alkylthio, alkylsulfonyl, alkoxy or haloalkoxy.

2. The mesoionic pyrimidinium compound, its N-oxide or salt according to claim 1, characterized in that: X represents a cyano group, a cyano C1-C8 alkyl group, an aryl group or a heterocyclic group; R1, R2, R3, R4, R5, R6, R7, R8, and R9 independently represent hydrogen, nitro, amino, cyano, halogen, hydroxyl, mercapto, C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, halogenated C1-C8 alkyl, halogenated C2-C8 alkenyl, halogenated C2-C8 alkynyl, C1-C8 alkoxy, C1-C8 alkylthio, halogenated C1-C8 alkoxy, halogenated C1-C8 alkylthio, formyl, C1-C8 alkylcarbonyl, C1-C8 alkylsulfoxide, C1-C8 alkylsulfonyl, amino substituted with C1-C8 alkyl, C3-C8 cycloalkyl, C3-C8 cycloalkenyl, aryl, or heterocyclic group; The aforementioned "C3-C8 cycloalkyl" or "C3-C8 cycloalkenyl" is optionally substituted by at least one group selected from halogen, cyano, nitro, C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, C3-C8 cycloalkyl, halogenated C1-C8 alkyl, halogenated C2-C8 alkenyl, halogenated C2-C8 alkynyl, halogenated C3-C8 cycloalkyl, C3-C8 cycloalkyl substituted by C1-C8 alkyl, or C3-C8 cycloalkylC1-C8 alkyl; The aforementioned "heterocyclyl" or "aryl" is optionally selected from oxo, halogen, cyano, nitro, C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, C3-C8 cycloalkyl, halogenated C1-C8 alkyl, halogenated C2-C8 alkenyl, halogenated C2-C8 alkynyl, halogenated C3-C8 cycloalkyl, C3-C8 cycloalkyl substituted by C1-C8 alkyl, C3-C8 cycloalkylC1-C8 alkyl, an aryl or heterocyclyl group which is unsubstituted or substituted by at least one group selected from halogen, cyano, nitro, C1-C8 alkyl, halogenated C1-C8 alkyl, C1-C8 alkoxycarbonyl, C1-C8 alkylthio, C1-C8 alkylsulfonyl, C1-C8 alkoxy or halogenated C1-C8 alkoxy, -OR 10 , -SR 10 ,-(CO)OR 10 ,-(SO)R 10 , -(SO2)R 10 ,-N(R 10 )2,-(C1-C8 alkylene)-OR 10 ,-(C1-C8 alkylene)-SR 10 ,-(C1-C8 alkylene)-(CO)OR 10 ,-(C1-C8 alkylene)-(SO)R 10 ,-(C1-C8 alkylene)-(SO2)R 10 ,-(C1-C8 alkylene)-N(R 10 )2 or -O-(C1-C8 alkylene)-(CO)OR 10 or two adjacent carbon atoms on the ring form a fused ring with unsubstituted or halogen-substituted -OCH2CH2- or -OCH2O-; R 10 Each of the groups is independently hydrogen, C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, C3-C8 cycloalkyl, halogenated C1-C8 alkyl, halogenated C2-C8 alkenyl, halogenated C2-C8 alkynyl, halogenated C3-C8 cycloalkyl, C3-C8 cycloalkyl substituted by C1-C8 alkyl, C3-C8 cycloalkylC1-C8 alkyl, aryl, heterocyclic group, or aryl or heterocyclic group substituted by at least one group selected from halogen, cyano, nitro, C1-C8 alkyl, halogenated C1-C8 alkyl, C1-C8 alkoxycarbonyl, C1-C8 alkylthio, C1-C8 alkylsulfonyl, C1-C8 alkoxy or halogenated C1-C8 alkoxy.

3. The mesoionic pyrimidinium compound, its N-oxide or salt according to claim 1, characterized in that: X represents a cyano group, a cyano C1-C6 alkyl group, an aryl group or a heterocyclic group; R1, R2, R3, R4, R5, R6, R7, R8, and R9 independently represent hydrogen, nitro, amino, cyano, halogen, hydroxyl, mercapto, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, halo-C1-C6 alkyl, halo-C2-C6 alkenyl, halo-C2-C6 alkynyl, C1-C6 alkoxy, C1-C6 alkylthio, halo-C1-C6 alkoxy, halo-C1-C6 alkylthio, formyl, C1-C6 alkylcarbonyl, C1-C6 alkylsulfoxide, C1-C6 alkylsulfonyl, amino substituted with C1-C6 alkyl, C3-C6 cycloalkyl, C3-C6 cycloalkenyl, aryl, or heterocyclic group; The aforementioned "C3-C6 cycloalkyl" or "C3-C6 cycloalkenyl" is optionally substituted by at least one group selected from halogen, cyano, nitro, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, halo-substituted C1-C6 alkyl, halo-substituted C2-C6 alkenyl, halo-substituted C2-C6 alkynyl, halo-substituted C3-C6 cycloalkyl, C3-C6 cycloalkyl substituted by C1-C6 alkyl, or C3-C6 cycloalkylC1-C6 alkyl; The aforementioned "heterocyclyl" or "aryl" is optionally selected from oxo, halogen, cyano, nitro, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, halo-C1-C6 alkyl, halo-C2-C6 alkenyl, halo-C2-C6 alkynyl, halo-C3-C6 cycloalkyl, C3-C6 cycloalkyl substituted by C1-C6 alkyl, C3-C6 cycloalkylC1-C6 alkyl, aryl or heterocyclyl which is unsubstituted or substituted by at least one group selected from halogen, cyano, nitro, C1-C6 alkyl, halo-C1-C6 alkyl, C1-C6 alkoxycarbonyl, C1-C6 alkylthio, C1-C6 alkylsulfonyl, C1-C6 alkoxy or halo-C1-C6 alkoxy, -OR 10 , -SR 10 ,-(CO)OR 10 ,-(SO)R 10 , -(SO2)R 10 ,-N(R 10 )2,-(C1-C6 alkylene)-OR 10 ,-(C1-C6 alkylene)-SR 10 ,-(C1-C6 alkylene)-(CO)OR 10 ,-(C1-C6 alkylene)-(SO)R 10 ,-(C1-C6 alkylene)-(SO2)R 10 ,-(C1-C6 alkylene)-N(R 10 )2 or -O-(C1-C6 alkylene)-(CO)OR 10 or two adjacent carbon atoms on the ring form a fused ring with unsubstituted or halogen-substituted -OCH2CH2- or -OCH2O-; R 10 are each independently hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, halo-C1-C6 alkyl, halo-C2-C6 alkenyl, halo-C2-C6 alkynyl, halo-C3-C6 cycloalkyl, C3-C6 cycloalkyl substituted by C1-C6 alkyl, C3-C6 cycloalkylC1-C6 alkyl, aryl, heterocyclic group, or aryl or heterocyclic group substituted by at least one group selected from halogen, cyano, nitro, C1-C6 alkyl, halo-C1-C6 alkyl, C1-C6 alkoxycarbonyl, C1-C6 alkylthio, C1-C6 alkylsulfonyl, C1-C6 alkoxy or halo-C1-C6 alkoxy; Preferably, yes More preferably, the compound is selected from any one of Table 1.

4. A method for preparing a mesoionic pyrimidinium compound, an N-oxide or a salt thereof according to any one of claims 1 to 3, comprising the following steps: The compound represented by general formula II is reacted with the compound represented by general formula III to obtain the compound represented by general formula I, and the reaction equation is as follows: wherein L1 and L2 independently represent halogen or OH, and the substituents X, R1, R2, R3, R4, R5, R6, R7, R8, M1, M2, M3, M4, M5, Q1 and Q2 are as defined in any one of claims 1 to 3; Preferably, the reaction is carried out in the presence of a base and a solvent; more preferably, the base is selected from at least one of an inorganic base or an organic base, and the solvent is selected from at least one of DCM, diethyl ether, DMF, tetrahydrofuran, methyltetrahydrofuran, diphenyl ether or dioxane.

5. An insecticidal composition, characterized in that Comprising a biologically effective amount of at least one of the mesoionic pyrimidinium compounds, N-oxides or salts thereof according to any one of claims 1 to 3; preferably, further comprising a formulation adjuvant; more preferably, further comprising other active ingredients.

6. The insecticidal composition according to claim 5, characterized in that The other active ingredients are selected from at least one of the following compounds: (1) Gamma-aminobutyric acid (GABA)-gated chloride channel allosteric modulators: (2) Nicotinic acetylcholine receptor (nAChR) allosteric modulators site I: spinosad, spinosad; (3) Allosteric modulators of glutamate-gated chloride channels (GluCl): avermectin benzoate, avermectin; (4) Chitin biosynthesis inhibitors affecting chitin synthase 1 (CHS1): lufenuron; (5) Uncouplers that interfere with the proton gradient and affect oxidative phosphorylation: chlorfenapyr; (6) Ecdysone receptor agonist: methoxyfenozide; (7) Sodium channel regulator: highly effective chlorfenapyr; (8) Voltage-dependent sodium channel blockers: (9) Nicotinic acetylcholine receptor (nAChR) competitive modulators: Imidacloprid, thiamethoxam; (10) Ryanodine receptor modulators: chlorantraniliprole, cyantraniliprole; (11) Voltage-dependent sodium channel blockers: indoxacarb; (12) Acetylcholinesterase (AChE) inhibitors: chlorpyrifos, dichlorvos, trichlorfon, phoxim, triazophos, quinalphos, acephate, carbosulfan, diazinon; (13) Compounds with unknown mechanism: Preferably, the weight ratio of the mesoionic pyrimidinium compound, its N-oxide or salt to other active ingredients is 1:200-200:1, 1:100-100:1, 1:50-50:1, 1:30-30:1, 1:20-20:1, 1:10-10:1, 1:5-1:1 or 1:1-5:

1.

7. A method for controlling pests, characterized in that: The method comprises contacting the pest or its environment with a biologically effective amount of the mesoionic pyrimidinium compound, its N-oxide or salt according to any one of claims 1 to 3, or the composition according to claim 5 or 6.

8. Use of the mesoionic pyrimidinium compound, its N-oxide or salt according to any one of claims 1 to 3, or the composition according to claim 5 or 6 in controlling pests.

9. An intermediate, as shown in formula II or III of claim 4.

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