Mesoionic pyrimidinium compound and use thereof

Abstract

The present application relates to the technical field of pesticides, and particularly relates to a mesoionic pyrimidinium compound, an N-oxide or salt thereof, and a use thereof. The compound is represented by general formula I, wherein Q1 and Q2 each independently represent O or S; X represents cyano, cyanoalkyl, aryl, or heterocyclyl; Y represents hydrogen, alkyl, alkenyl, alkynyl, or the like; and Z1, Z2, R1, R2, R3, R4, R5, R6, R7, and R8 each independently represent hydrogen, halogen, cyano, nitro, alkyl, or the like. The compound has an excellent control effect on pests such as spodoptera frugiperda, mythimna separata, spodoptera litura.

Description

Mesogenic pyrimidinium compound and application thereof TECHNICAL FIELD

[0001] The present application belongs to the technical field of pesticides, and particularly relates to a mesogenic pyrimidinium compound, N-oxide or salt thereof and application thereof. BACKGROUND

[0002] In recent years, due to the long-term use of pest control agents such as insecticides, pests have become resistant and are difficult to control by the existing insecticides. In addition, some of the known pest control agents are highly toxic, or some destroy the ecological system through their long-term residual properties. In this case, although a large number of insecticides are known, such as WO2011017342A2, WO2009099929A1 and the like disclose mesogenic insecticides, there is still a need to develop new pest control agents with low toxicity and low residual properties. SUMMARY

[0003] To solve the above problems in the prior art, the present application provides a mesogenic pyrimidinium compound, N-oxide or salt thereof, which has excellent control effect on pests such as Spodoptera exigua, Mythimna separata and Spodoptera litura.

[0004] The technical solution adopted by the present application is as follows:

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

[0006] Q1, Q2 respectively independently represent O or S;

[0007] X represents cyano, cyanoalkyl, aryl or heterocyclyl;

[0008] Y represents hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, -(CO)R9, -(CO)OR9, heterocyclyl or aryl; the "alkyl", "alkenyl" or "alkynyl" is optionally substituted with at least one group selected from halogen, -OR9, -S(O) n R9, -(CO)R9, -(CO)OR9, cycloalkyl, heterocyclyl or aryl;

[0009] Z1, Z2, R1, R2, R3, R4, R5, R6, R7, R8 respectively independently represent hydrogen, halogen, cyano, nitro, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heterocyclyl, -OR9, -(CO)R9, -(CO)OR9, -(CO)N(R9)2, -S(O) n R9 or -N(R9)2, the alkyl, alkenyl or alkynyl is optionally substituted with at least one group selected from halogen, cycloalkyl, aryl, heterocyclyl, -OR9, -(CO)OR9, -S(O)n R9or at least one of the groups in -N(R9)2;

[0010] n is 0, 1 or 2;

[0011] R9independently represents hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heterocyclyl or heterocyclylalkyl, said alkyl, alkenyl or alkynyl being optionally substituted by at least one group selected from halo or alkoxy;

[0012] the aforementioned "cycloalkyl", "heterocyclyl" or "aryl" is optionally substituted by at least one group selected from oxo, halo, cyano, nitro, alkyl, alkenyl, alkynyl, cycloalkyl, haloalkyl, haloalkenyl, haloalkynyl, -OR 10 , -SR 10 , -(CO)R 10 , -(CO)OR 10 , -(CO)N(R 10 )2, -(CS)N(R 10 )2, -(SO)R 10 or -(SO2)R 10 ; or two adjacent carbon atoms in the ring form a fused ring with -OCH2O-, -CH2CH2CH2O- or -CH=CHCH=CH- which is unsubstituted or substituted by halo; or one saturated carbon atom in the ring is linked to both ends of -OCH2CH2O- which is unsubstituted or substituted by halo to form a ring structure;

[0013] R 10 independently represents hydrogen, alkyl, haloalkyl, phenyl or phenyl substituted by at least one group selected from halo, cyano, nitro, alkyl, haloalkyl, alkoxycarbonyl, alkylthio, alkylsulfonyl, alkoxy or haloalkoxy.

[0014] In a particular embodiment, X represents cyano, cyanoC1-C8alkyl, aryl or heterocyclyl;

[0015] Y represents hydrogen, C1-C8alkyl, C2-C8alkenyl, C2-C8alkynyl, C3-C8cycloalkyl, -(CO)R9, -(CO)OR9, heterocyclyl or aryl; said "C1-C8alkyl", "C2-C8alkenyl", "C2-C8alkynyl" being optionally substituted by at least one group selected from halo, -OR9, -S(O) n R9, -(CO)R9, -(CO)OR9, C3-C8cycloalkyl, heterocyclyl or aryl;

[0016] Z1, Z2, R1, R2, R3, R4, R5, R6, R7, and R8 independently represent hydrogen, halogen, cyano, nitro, C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, C3-C8 cycloalkyl, aryl, heterocyclic group, -OR9, -(CO)R9, -(CO)OR9, -(CO)N(R9)2, -S(O) n R9 or -N(R9)2, the C1-C8 alkyl, C2-C8 alkenyl or C2-C8 alkynyl is optionally selected from halogen, C3-C8 cycloalkyl, aryl, heterocyclyl, -OR9, -(CO)OR9, -S(O) n is substituted by at least one group in R9 or -N(R9)2;

[0017] R9 each independently represents hydrogen, C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, C3-C8 cycloalkyl, C3-C8 cycloalkylC1-C8 alkyl, aryl, arylC1-C8 alkyl, heterocyclyl or heterocyclylC1-C8 alkyl, wherein the C1-C8 alkyl, C2-C8 alkenyl or C2-C8 alkynyl is optionally substituted by at least one group selected from halogen or C1-C8 alkoxy;

[0018] The aforementioned "C3-C8 cycloalkyl", "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, -OR 10 、-SR 10 、-(CO)R 10 、-(CO)OR 10 、-(CO)N(R 10 )2、-(CS)N(R 10 )2、-(SO)R 10 or -(SO2)R 10 or two adjacent carbon atoms on the ring form a condensed ring with unsubstituted or halogen-substituted -OCH2O-, -CH2CH2CH2O- or -CH=CHCH=CH-; or a saturated carbon atom on the ring is connected to both ends of unsubstituted or halogen-substituted -OCH2CH2O- to form a ring structure;

[0019] R 10 Each independently represents hydrogen, C1-C8 alkyl, halogenated C1-C8 alkyl, phenyl or phenyl 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.

[0020] In one embodiment, X represents cyano, cyano C1-C6 alkyl, aryl or heterocyclyl;

[0021] Y represents hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, -(CO)R9, -(CO)OR9, heterocyclyl or aryl; said "C1-C6 alkyl", "C2-C6 alkenyl" or "C2-C6 alkynyl" is optionally substituted with at least one group selected from halogen, -OR9, -S(O) n R9, -(CO)R9, -(CO)OR9, C3-C6 cycloalkyl, heterocyclyl or aryl;

[0022] Z1, Z2, R1, R2, R3, R4, R5, R6, R7, R8 each independently represents hydrogen, halogen, cyano, nitro, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, aryl, heterocyclyl, -OR9, -(CO)R9, -(CO)OR9, -(CO)N(R9)2, -S(O) n R9or -N(R9)2, said C1-C6 alkyl, C2-C6 alkenyl or C2-C6 alkynyl is optionally substituted with at least one group selected from halogen, C3-C6 cycloalkyl, aryl, heterocyclyl, -OR9, -(CO)OR9, -S(O) n R9or -N(R9)2;

[0023] R9each independently represents hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C3-C6 cycloalkyl C1-C6 alkyl, aryl, aryl C1-C6 alkyl, heterocyclyl or heterocyclyl C1-C6 alkyl, said C1-C6 alkyl, C2-C6 alkenyl or C2-C6 alkynyl is optionally substituted with at least one group selected from halogen or C1-C6 alkoxy;

[0024] the foregoing "C3-C6 cycloalkyl", "heterocyclyl" or "aryl" is optionally substituted with at least one group 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, -OR 10 , -SR 10 , -(CO)R 10 , -(CO)OR 10 , -(CO)N(R 10 )2, -(CS)N(R 10 )2, -(SO)R 10 or -(SO2)R 10substituted with at least one group selected from the group consisting of halogen, cyano, nitro, C1-C6alkyl, haloC1-C6alkyl, C1-C6alkoxycarbonyl, C1-C6alkylthio, C1-C6alkylsulfonyl, C1-C6alkoxy or haloC1-C6alkoxy; or two adjacent carbon atoms of the ring form a fused ring with -OCH2O-, -CH2CH2CH2O- or -CH=CHCH=CH- which are unsubstituted or substituted with halogen; or one saturated carbon atom of the ring is linked with -OCH2CH2O- which is unsubstituted or substituted with halogen at both ends to form a ring structure;

[0025] R 10 independently represent hydrogen, C1-C6alkyl, haloC1-C6alkyl, phenyl or phenyl substituted with at least one group selected from the group consisting of halogen, cyano, nitro, C1-C6alkyl, haloC1-C6alkyl, C1-C6alkoxycarbonyl, C1-C6alkylthio, C1-C6alkylsulfonyl, C1-C6alkoxy or haloC1-C6alkoxy.

[0026] In the definition of the compounds of the general formulae above and in all the structural formulae below, the professional terms used, whether used alone or in a composite, represent the following substituents: alkyl groups having more than two carbon atoms can be straight-chained or branched. As in the composite "cycloalkylalkyl", the alkyl can be -CH2-, -CH2CH2-, -CH(CH3)-, -C(CH3)2-, etc. Alkyl groups are, for example, C1alkyl - methyl; C2alkyl - ethyl; C3alkyl - propyl, such as n-propyl or isopropyl; C4alkyl - butyl, such as n-butyl, isobutyl, tert-butyl or 2-butyl; C5alkyl - pentyl, such as n-pentyl; C6alkyl - hexyl, such as n-hexyl, isohexyl and 1,3-dimethylbutyl. Similarly, alkenyl is, for example, ethenyl, allyl, 1-methylprop-2-en-1-yl, 2-methylprop-2-en-1-yl, but-2-en-1-yl, but-3-en-1-yl, 1-methylbut-3-en-1-yl and 1-methylbut-2-en-1-yl. Alkynyl is, for example, ethynyl, propargyl, but-2-yn-1-yl, but-3-yn-1-yl, 1-methylbut-3-yn-1-yl. The multiple bonds can be in any position of each unsaturated group. Cycloalkyl is a carbocyclic saturated ring system having, for example, three to six carbon atoms, such as cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl. Similarly, cycloalkenyl is a monocyclic alkenyl group having, for example, three to six carbon ring members, such as cyclopropenyl, cyclobutenyl, cyclopentenyl and cyclohexenyl, wherein the double bonds can be in any position. Halogen is fluorine, chlorine, bromine or iodine.

[0027] Unless otherwise specifically indicated, the term "aryl" as used herein includes, but is not limited to, phenyl, naphthyl, The term "heterocyclyl" as used herein includes, but is not limited to, saturated or unsaturated non-aromatic cyclic groups and also include, but are not limited to, heteroaryl, i.e., aromatic ring-like groups containing, for example, 3 to 6 ring atoms, 1 to 4 (e.g., 1, 2, 3, or 4) of the ring atoms being heteroatoms selected from oxygen, nitrogen, and sulfur, for example, which are optionally fused with a benzene ring, such as

[0028] The term "optionally" or "optional" means that the subsequently described event or circumstance can or can not occur, and that the description includes instances where the event or circumstance occurs and instances where it does not. For example, the term "optionally substituted" means that the designated atom or group is either unsubstituted or substituted with one or more substituents. If a group is substituted with a group, this is to be understood as meaning that the group is substituted with one or more, identical or different, groups selected from those mentioned. In addition, the same or different substituents contained in the same or different groups are each selected independently of one another, which can be the same or different. The same applies to ring systems formed by different atoms and elements. At the same time, the scope of the claims is to exclude those compounds which are chemically unstable under standard conditions, as known to the person skilled in the art.

[0029] In addition, unless specifically limited otherwise, the term "substituted with at least one group" as used herein means substituted with, for example, 1, 2, 3, 4, or 5 groups; groups that are not labeled with a specific position of attachment (including heterocyclyl, aryl, and the like) can be attached at any position, including attachment to a C or N; if it is substituted, the substituents can likewise be substituted at any position, as long as the rules of valency are observed. For example, a heteroaryl group that is substituted with 1 methyl group may represent and the like.

[0030] If various functional groups are present, the application also includes any keto and enol tautomeric forms and mixtures and salts thereof.

[0031] The stereoisomers can be obtained from the mixtures obtained in the preparation by optical resolution. Likewise the stereoisomers can be prepared selectively by using stereoselective reactions and using optically active starting materials and / or auxiliaries. For optical resolution it is generally possible to use customary methods (cf. Textbooks of Stereochemistry), for example the following methods for the resolution of mixtures into diastereomers, for example physical methods such as crystallisation, chromatography, in particular column chromatography and high-pressure liquid chromatography, distillation methods, which are carried out under reduced pressure if appropriate, extraction and other methods, usually with chromatographic separation on chiral stationary phases, it being possible to separate the residual mixtures of enantiomeric structures. Suitable for preparative amounts or for the industrial scale are methods such as crystallisation of diastereomeric salts, which can be obtained from the compounds using optically active acids and, if acidic groups are present, if appropriate using optically active bases.

[0032] Another embodiment of the present application is a method for preparing the mesoionic pyrimidinium compound, N-oxide or salt thereof, comprising the following steps:

[0033] The compound of general formula II is reacted with the compound of general formula III to obtain the compound of general formula I, and the reaction equation is as follows:

[0034] wherein L1, L2 independently represent halogen or OH, and the definitions of substituents X, Y, Z1, Z2, Q1, Q2, R1, R2, R3, R4, R5, R6, R7 and R8 are as described above.

[0035] In one embodiment, the reaction is carried out in the presence of a base and a solvent.

[0036] In one embodiment, the base is at least one selected from inorganic bases (such as NaH, KH, NaOH, KOH, K2CO3, Na2CO3, Cs2CO3, KF, CsF, etc.) or organic bases (such as pyrazole, triethylamine, N,N-diisopropylethylamine, pyridine, DIEA, potassium trimethylsilanolate, AcOK, AcONa, MeONa, EtONa, t-BuONa, t-BuOK, etc.).

[0037] In one embodiment, the solvent is at least one selected from DCM, diethyl ether, DMF, tetrahydrofuran, methyltetrahydrofuran, diphenyl ether or dioxane.

[0038] The preparation method of the compound of the present application can refer to WO2011017342A2, WO2009099929A1, etc.

[0039] The present application also relates to an intermediate, as shown in the above formula II.

[0040] The present application also relates to the use of compounds of formula I (including all stereoisomers), N-oxides, and salts thereof, and compositions comprising them for combating pests.

[0041] The present application also provides a pesticidal composition comprising at least one of the compounds of formula I, N-oxides, or salts thereof; in one embodiment, further comprising a formulation adjuvant; in one embodiment, further comprising another active ingredient.

[0042] The present application provides a method for combating pests, which comprises contacting the pests or their environment with a biologically effective amount of a compound of formula I, N-oxides, or salts thereof, or the above-mentioned compositions.

[0043] The environment of the above-mentioned pests is a plant, an animal, or a seed.

[0044] The present application also provides a method for protecting a seed from invertebrate pests, which comprises contacting the seed with a biologically effective amount of a compound of formula I, N-oxides, or salts thereof. The present application also relates to the treated seed.

[0045] The present application also provides a composition for protecting an animal from invertebrate parasitic pests, which comprises a parasiticidally effective amount of a compound of formula I, N-oxides, or salts thereof and at least one carrier.

[0046] The present application also provides a method of treating, preventing, inhibiting, and / or killing ectoparasites in vitro and / or in vivo, which comprises administering to and / or on an animal a parasiticidally effective amount of a compound of formula I, N-oxides, or salts thereof. The present application also relates to such a method, wherein a parasiticidally effective amount of a compound of formula I, N-oxides, or salts thereof is administered to the environment in which the animal lives (e.g., a stall or a blanket).

[0047] As referred to in the present disclosure, the term "invertebrate pests" includes arthropods, gastropods, and nematodes that are economically important as pests. The term "arthropods" includes insects, mites, spiders, scorpions, centipedes, millipedes, pill bugs, and symphylans. The term "gastropods" includes snails, slugs, and other Stylommatophora. The term "nematodes" refers to organisms of the phylum Nematoda. The term "helminths" includes roundworms, heartworms, plant-parasitic nematodes (Nematoda), flukes (Trematoda), thorny-headed worms (Cestoda), and tapeworms (Cestoda).

[0048] In the context of the present disclosure, "controlling an invertebrate pest" means inhibiting the growth of an invertebrate pest (including death, reduced feeding, and / or mating disruption), and related expressions can be similarly defined.

[0049] The term "agronomic" refers to the growth of field crop products, such as food and fiber, and includes corn, soybeans and other legumes, rice, cereal grains (e.g., wheat, oats, barley, rye, rice, corn), leafy vegetables (e.g., lettuce, cabbage, and other cole crops), fruiting vegetables (e.g., tomato, pepper, eggplant, crucifers, and cucurbits), potatoes, sweet potatoes, grapes, cotton, tree fruits (e.g., pome, stone, and citrus), small fruits (berries, cherries), and other specialty crops (e.g., canola, sunflower, olives).

[0050] The term "non-agronomic" 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 a field), residential structures, agronomic structures, commercial structures and industrial structures, turf (e.g., grasslands, pastures, golf courses, lawns, athletic fields, and the like), 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, and undomesticated animals such as wildlife) applications.

[0051] Non-agronomic applications include protecting animals from invertebrate parasitic pests by administering to the animal a parasiticidally (i.e., biologically) effective amount of a compound of the present disclosure (typically in the form of a veterinary formulation). As used in the disclosure and claims, the terms "parasiticidal" and "parasiticidal properties" relate to the observed effect on invertebrate parasitic pests to provide protection to the animal from the pests. Parasiticidal effects generally involve reducing the occurrence or activity of the target invertebrate parasitic pest. Such effects on pests include necrosis, lethality, retarded growth, reduced mobility or ability to remain on or in the host animal, reduced feeding, and inhibited reproduction. These effects on invertebrate parasitic pests provide control (including prevention, reduction, or elimination) of parasitic infestation or infection of the animal.

[0052] The compounds of Formula I are zwitterionic internal salts. Also known in the art as "inner salts" or "zwitterions" are electrically neutral molecules, but according to valence bond theory, carry a formal positive charge and a formal negative charge in each valence bond structure of different atoms. In addition, the molecular structure of the compounds of Formula I can be represented by the following six valence bond structures:

[0053] Each of the bonds in the various atoms carries a formal positive and negative charge. As a result of this resonance, the compounds of Formula I are also described as "zwitterions." While for simplicity the molecular structure of Formula I is depicted as a single valence bond structure herein, this particular valence bond structure is to be understood as representative of all six valence bond structures involving the intramolecular linkages of the compounds of Formula I. Thus, unless otherwise indicated, a reference herein to Formula I is to all six applicable valence bond structures as well as other (e.g., molecular orbital theory) structures.

[0054] The compounds of the present application can exist in one or more stereoisomers. Stereoisomers include enantiomers, diastereomers, atropisomers, and geometric isomers. Those skilled in the art will appreciate that one stereoisomer can be more active and / or can exhibit a beneficial effect when it is enriched relative to other stereoisomers or when it is separated from other stereoisomers. In addition, those skilled in the art know how to separate, enrich, and / or selectively prepare the stereoisomers. The compounds of the present application can exist as a mixture of stereoisomers, as a single stereoisomer, or as an optically active form.

[0055] The compounds of the present application can exist in one or more conformational isomers due to restricted rotation of bonds caused by steric hindrance. The present application includes mixtures of conformational isomers. In addition, the present application includes compounds enriched in one conformational isomer relative to other conformational isomers.

[0056] The compounds selected from Formula I (including all stereoisomers thereof, N-oxides thereof, and salts thereof) generally exist in more than one form, and thus Formula I includes all crystalline and non-crystalline forms of the compounds represented by Formula I. Non-crystalline forms include embodiments that are solids such as waxes and gums, and embodiments that are liquids such as solutions and melts. Crystalline forms include embodiments that represent a substantially single crystal form, and embodiments that represent a mixture of polymorphs (i.e., different crystal forms). The term "polymorph" refers to a specific crystal form of a chemical compound that can crystallize in different crystal forms having different molecular arrangements and / or conformations in the crystal lattice. While polymorphs can have the same chemical composition, they can also have different compositions due to the presence or absence of co-crystallized water or other molecules weakly or strongly bound within the crystal lattice. Polymorphs can have different chemical, physical, and biological properties, such as crystal shape, density, hardness, color, chemical stability, melting point, hygroscopicity, suspendability, dissolution rate, and bioavailability. Those skilled in the art will appreciate that a polymorph of a compound represented by Formula I can exhibit beneficial effects (e.g., suitability for preparation of useful formulations, 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 particular polymorph of a compound represented by Formula I can be accomplished by methods known to those skilled in the art, including, for example, crystallization using selected solvents and temperatures.

[0057] Those skilled in the art will appreciate that not all nitrogen-containing heterocycles can form N-oxides, as the nitrogen needs to have an available lone pair of electrons that can be oxidized 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, including the use of peroxy acids (such as peracetic acid and 3- chloroperoxybenzoic acid (MCPBA)), hydrogen peroxide, alkyl hydroperoxides (such as t-butyl hydroperoxide), sodium perborate, and dioxiranes (such as dimethyldioxirane) to oxidize the heterocycle or tertiary amine.

[0058] Those skilled in the art recognize that because salts of chemical compounds are in equilibrium with their corresponding non-salt forms under environmental and physiological conditions, salts and non-salt forms have common biological uses. Accordingly, a wide variety of salts of the compounds of Formula I are useful for controlling invertebrate pests and animal parasites (i.e., for animal health uses). Salts of the compounds of Formula I include acid addition salts with inorganic or organic acids such as hydrobromic, hydrochloric, nitric, phosphoric, sulfuric, acetic, butyric, fumaric, lactic, maleic, malonic, oxalic, propionic, salicylic, tartaric, 4-toluenesulfonic, or valeric acids. Salts also include those formed with organic or inorganic bases such as pyridine, triethylamine or ammonia, or amides, hydrides, hydroxides or carbonates of sodium, potassium, lithium, calcium, magnesium or barium when the compounds of Formula I contain acidic moieties such as carboxylic acid or phenol. Accordingly, the present application includes compounds selected from the group consisting of the compounds of Formula I, their N-oxides and salts.

[0059] Embodiments of the present application as described in the SUMMARY include those described below. In the following embodiments, Formula I includes its stereoisomers, its N-oxides and its salts, and unless otherwise defined in the embodiments, the description referring to "compounds of Formula I" includes the definitions of the specified substituents in the SUMMARY.

[0060] Notably, the compounds of the present application are characterized by advantageous metabolic and / or soil residue patterns and exhibit a broad spectrum of control activity against agronomic and non-agronomic invertebrate pests.

[0061] Notably, it is an embodiment of the present application to protect crops from invertebrate pests by controlling invertebrate pests due to the broad spectrum of control and economic importance of the invertebrate pests. Due to the advantageous translocation properties or systemics of the compounds of the present application in the plant, they also protect leaves or other plant parts that are not in direct contact with the compounds of Formula I or compositions comprising the same.

[0062] Also notably, as an embodiment of the present application, are compositions comprising the compounds of any of the foregoing embodiments and any other embodiments described herein and any combinations thereof, and at least one additional component and / or formulation adjuvant and / or at least one active ingredient (i.e., biologically active compound or agent) selected from the group consisting of surfactants, solid diluents and liquid diluents.

[0063] Embodiments of the present application also include compositions for protecting animals comprising the compounds of any of the foregoing embodiments (i.e., in a parasiticidally effective amount) and a carrier.

[0064] Embodiments of the present application also include methods for controlling an invertebrate pest comprising contacting the invertebrate pest or its environment with a biologically effective amount of a compound of any of the preceding embodiments (e.g., as a composition described herein). Of particular note are methods for protecting an animal comprising administering to the animal a parasiticidally effective amount of a compound of any of the preceding embodiments (e.g., as a composition described herein).

[0065] Embodiments of the present application also include compositions comprising a compound of any of the preceding embodiments in the form of a drench liquid formulation. Embodiments of the present application also include methods for controlling an invertebrate pest 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.

[0066] Embodiments of the present application also include spray compositions for controlling an invertebrate pest comprising a compound of any of the preceding embodiments (i.e., in a biologically effective amount) and a propellant. Embodiments of the present application also include bait compositions for controlling an invertebrate pest comprising a compound of any of the preceding embodiments (i.e., in a biologically effective amount), one or more food material, optionally an attractant, and optionally a humectant. Embodiments of the present application also include devices for controlling an invertebrate pest 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, to enable an invertebrate pest to access the bait composition from a location outside the housing, and wherein the housing is further adapted to be placed in or near a locus of potential or known invertebrate pest activity.

[0067] Embodiments of the present application also include methods for controlling an invertebrate pest 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 (e.g., as a composition described herein), with the proviso that the method is not a method of medical treatment of the human or animal body by therapy.

[0068] The present application also relates to such methods wherein the invertebrate 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, which can further comprise additional components selected from the group consisting of surfactants, solid diluents, and liquid diluents, and which composition optionally further comprises 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 medical treatment of the human or animal body by therapy.

[0069] The compounds of the present application will generally be used as an active ingredient for the control of invertebrate pests in a composition, i.e., a formulation, having at least one additional component serving as a carrier, selected from the group consisting of surfactants, solid diluents and liquid diluents. The formulation or composition ingredients are selected to be consistent with the physical characteristics of the active ingredient, the means of application, and the environmental factors such as soil type, moisture and temperature.

[0070] Useful formulations include liquid and solid compositions. Liquid compositions include solutions (including emulsions), suspensions, emulsions (including microemulsions and / or suspoemulsions), etc., which can optionally be thickened into gels. General types of aqueous liquid compositions are soluble concentrates, suspoemulsions, capsule suspensions, emulsions, microemulsions, and suspoemulsions. General types of non-aqueous liquid compositions are emulsifiable concentrates, microemulsifiable concentrates, dispersible concentrates, and oil dispersions.

[0071] General types of solid compositions are dusts, powders, granules, pellets, prills, pastilles, 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 release of the active ingredient. Emulsifiable granules combine the advantages of both emulsifiable concentrate and dry granular formulations. High-concentration compositions are primarily used as intermediates for other formulations.

[0072] Sprayable formulations are generally dispersed in a suitable medium prior to spraying. Such liquid and solid formulations are prepared as formulations which are readily dilutable in the spray medium, usually water. The volume of spray can range from about one liter to several thousand liters per hectare, but more usually from about ten to several hundred liters per hectare. The sprayable formulations can be mixed with water or another suitable medium in a tank for foliar treatment by air or ground spraying, or applied to the growth medium of the plant. Liquid and dry formulations can be metered directly into a drip irrigation system, or metered into furrows during planting. Liquid and solid formulations can be applied to the seeds of crops and other desired plants at the time of seed treatment prior to planting, in order to protect the developing roots and other below-ground plant parts and / or the foliage by systemic uptake.

[0073] The formulations will generally contain an effective amount of active ingredient, diluent, and surfactant, in the approximate ranges, totaling 100% by weight.

[0074] 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.

[0075] Liquid diluents include, for example, water, N,N-dimethylalkanamides (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, triacetin, sorbitol, aromatic hydrocarbons, de-aromatized aliphatics, alkylbenzenes, alkylnaphthalenes, ketones (such as cyclohexanone, 2-heptanone, isophorone, and 4-hydroxy-4-methyl-2-pentanone), acetates (such as isoamyl acetate, hexyl acetate, heptyl acetate, octyl acetate, nonyl acetate, tridecyl acetate, and isobornyl acetate), other esters (such as alkylated lactic acid esters, dibasic esters, and gamma-butyrolactone), and can be linear, branched, saturated, or unsaturated alcohols (such as methanol, ethanol, n-propanol, isopropanol, n-butanol, isobutanol, n-hexanol, 2-ethylhexanol, n-octanol, decanol, isodecanol, isooctadecanol, sperm whale alcohol, lauryl alcohol, tridecyl alcohol, oleyl alcohol, cyclohexanol, tetrahydrofurfuryl alcohol, and benzyl alcohol). Liquid diluents also include glycerol esters of saturated and unsaturated fatty acids (typically C6-C32), such as oils of plant seeds and fruits (e.g., olive oil, castor oil, linseed oil, sesame oil, corn oil, peanut oil, sunflower seed oil, grape seed oil, safflower oil, cottonseed oil, soybean oil, rapeseed oil, coconut oil, and palm kernel oil), fats of animal origin (e.g., beef tallow, lard, hog fat, cod liver oil, fish oil), and mixtures thereof. Liquid diluents also include alkylated (e.g., methylated, ethylated, butylated) fatty acids, where the fatty acids can be obtained by hydrolysis of glycerides derived from plants and animals, and can be purified by distillation. 22 ) of saturated and unsaturated fatty acids (typically C6-C

[0076] The solid and liquid compositions of the present application typically comprise one or more surfactants. When added to a liquid, surfactants (also known as "agents with surface activity") generally change, most often lower, the surface tension of the liquid. Depending on the nature of the hydrophilic and lipophilic groups in the surfactant molecule, the surfactant can act as a wetting agent, dispersant, emulsifier, or defoamer.

[0077] The surfactants can be classified as nonionic, anionic or cationic surfactants. Nonionic surfactants that can be used in the present compositions 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; alkyl phenol alkoxylates, such as octyl phenol ethoxylate, nonyl phenol ethoxylate, dinonyl phenol ethoxylate and dodecyl phenol 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 block is prepared from propylene oxide; ethoxylated fatty acids; ethoxylated fatty esters and oils; ethoxylated methyl esters; ethoxylated tristyryl phenol (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 sorbitol fatty acid esters and polyethoxylated glycerol fatty acid esters; other sorbitan derivatives, such as sorbitan esters; polymeric surfactants, such as random copolymers, block copolymers, alcohol acid PEG (polyethylene glycol) resins, grafted 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.

[0078] Anionic surfactants that can be used include, but are not limited to: alkyl aryl sulfonic acids and their salts; carboxylated alcohols or alkyl phenol ethoxylates; diphenyl sulfonate derivatives; lignin and lignin derivatives, such as lignosulfonates; maleic acid or succinic acid or their anhydrides; olefin sulfonates; phosphate esters, such as phosphate esters of alcohol alkoxylates, alkyl phenol alkoxylates and styryl phenol ethoxylates; protein-based surfactants; sarcosine derivatives; styryl phenol ether sulfates; sulfates and sulfonates of oils and fatty acids; sulfates and sulfonates of ethoxylated alkyl phenols; sulfates of alcohols; sulfates of ethoxylated alcohols; sulfonates of amines and amides, such as N,N-alkyl taurates; sulfonates of benzene, isopropyl benzene, toluene, xylene, and dodecyl and tridecyl benzenes; sulfonates of condensed naphthalenes; sulfonates of naphthalenes and alkyl naphthalenes; sulfonates of petroleum distillates; sulfosuccinamates; and sulfosuccinates and their derivatives, such as dialkyl sulfosuccinates.

[0079] Useful cationic surfactants include, but are not limited to, amides and ethoxylated amides; amines such as N-alkylpropylenediamines, tripropylenetriamine, and dipropylenetetraamine, and 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 salts, ethoxylated quaternary salts, and diquaternary salts; and amine oxides such as alkyl dimethyl amine oxides and di-(2-hydroxyethyl)-alkyl amine oxides.

[0080] Also useful in the compositions of the present application are mixtures of nonionic and anionic surfactants, or mixtures of nonionic and cationic surfactants.

[0081] The compositions of the present application can also contain formulation aids and additives known to those skilled in the art as adjuvants to the formulation (some of which can also be considered to act as solid diluents, liquid diluents, or surfactants). Such formulation aids and additives can control: pH (buffers), foaming during processing (antifoams such as polyorganosiloxanes), settling of active ingredients (suspending agents), viscosity (thixotropic thickening agents), microbial growth in the container (antimicrobials), product freeze (antifreeze agents), color (dye / pigment dispersions), wash-off (film formers or binders), evaporation (antievaporants), and other formulation attributes. Film formers include, for example, polyvinyl acetate, polyvinyl acetate copolymers, polyvinylpyrrolidone-vinyl acetate copolymers, polyvinyl alcohol, polyvinyl alcohol copolymers, and waxes.

[0082] The compounds of Formula I and any other active ingredients are incorporated into the compositions of the present application by dissolving or dispersing them in a solvent or by grinding them in a liquid or dry diluent. Solutions can be prepared by simply mixing the ingredients, including emulsifiable concentrates. If the solvent of a liquid composition to be used as an emulsifiable concentrate is immiscible with water, an emulsifying agent is usually added to cause emulsification of the active ingredient-containing solvent upon dilution with water. A media mill can be used to wet mill slurries of active ingredients having a particle size of up to 2,000 μm to obtain particles having an average diameter of less than 3 μm. Aqueous slurries can be prepared as finished suspension concentrates (see, for example, U.S. 3,060,084) or further processed by spray drying into particles that are dispersible in water. Dry formulations usually require a dry grinding step, which produces an average particle size in the range of 2 to 10 μm. Dusts and powders can be prepared by mixing, usually by grinding (for example, with a hammer mill or fluid energy mill). Granules and pellets can be prepared by spraying active material onto preformed granular carriers or by agglomeration techniques.

[0083] The compounds of the present application exhibit activity against a broad spectrum of invertebrate pests. These pests include invertebrate pests inhabiting a variety of environments such as the foliage, roots, soil, harvested crops or other foodstuffs, buildings, or the fur of animals. These pests include, for example, invertebrate pests that feed on leaves (including foliage, stems, flowers, and fruit), seeds, wood, textile fibers, or the blood or tissues of animals, which cause damage or injury to, for example, growing or stored agricultural crops, forest crops, greenhouse crops, ornamental plants, nursery crops, stored food or fiber products, or dwellings or other structures or their contents, or which are injurious to animal health or public health. Those skilled in the art will recognize that not all compounds will have the same effect on all pests throughout their entire life stage.

[0084] Thus, these compounds and compositions of the present application are useful in agriculture to protect field crops from phytophagous invertebrate pests, and also are useful nonagriculturally to protect other horticultural crops and plants from phytophagous invertebrate pests. This use includes protection of crops and other plants (both agricultural and nonagricultural) that contain genetic material that has been modified by genetic engineering (i.e., transgenic) or mutagenesis to provide a desirable characteristic. Examples of such characteristics include tolerance to herbicides, tolerance to phytophagous pests (e.g., insects, mites, aphids, spiders, nematodes, snails, plant pathogenic fungi, bacteria, and viruses), improved plant growth, increased tolerance to adverse growing conditions (such as high or low temperatures, low or high soil moisture, and high salinity), increased flowering or fruiting, increased harvest yields, faster maturation, higher quality and / or nutritional value of the harvested product, or improved storage or processing characteristics of the harvested product. Transgenic plants can be modified to express a variety of characteristics. Examples of plants that contain characteristics provided by genetic engineering or mutagenesis include various corn, cotton, soybean, and potato plants that express Bacillus thuringiensis insecticidal toxins, such as the YieldGard® and and various herbicide-tolerant corn, cotton, soybean, and canola plants, such as the Roundup Ready® and and crops that express N-acetyltransferase (GAT) to provide tolerance to the herbicide glyphosate or that contain the HRA gene to provide tolerance to herbicides that inhibit acetolactate synthase (ALS). The compounds and compositions of the present application can interact synergistically with characteristics introduced by genetic engineering or mutagenesis to enhance the phenotypic expression or effect of the characteristic or to enhance the invertebrate pest control effect of the compounds and compositions of the present application. In particular, the compounds and compositions of the present application can interact synergistically with the phenotypic expression of proteins or other natural products that are toxic to invertebrate pests to provide greater than additive control of these pests.

[0085] The compositions of the present application can also optionally comprise a plant nutrient, for example a fertilizer composition comprising at least one plant nutrient selected from the group consisting of nitrogen, phosphorus, potassium, sulfur, calcium, magnesium, iron, copper, boron, manganese, zinc, and molybdenum. Of note are compositions comprising at least one fertilizer composition comprising at least one plant nutrient selected from the group consisting of nitrogen, phosphorus, potassium, sulfur, calcium, and magnesium. The compositions of the present application further comprising at least one plant nutrient can be in liquid or solid form. Of note are solid formulations in the form of granules, prills, or tablets. Solid formulations comprising a fertilizer composition are prepared by mixing the compound or composition of the present application with the fertilizer composition and formulating ingredients, followed by a process such as granulation or extrusion to produce the formulation. Alternatively, solid formulations are prepared by spraying a solution or suspension of the compound or composition of the present application in a volatile solvent onto a previously prepared fertilizer composition in the form of a size-stable mixture, such as granules, prills, or tablets, followed by evaporation of the solvent.

[0086] Examples of agricultural or non-agricultural invertebrate pests include eggs, larvae and adults of Lepidoptera pests such as armyworms, caterpillars, geometer moths and bollworms (e.g., Sesamia inferens Walker, Sesamia nonagrioides Lefebvre, Spodoptera eridania Cramer, Spodoptera frugiperda J.E. Smith, Spodoptera exigua Hübner, Spodoptera littoralis Boisduval, Spodoptera ornithogalli Guenée, Agrotis ipsilon Hufnagel, Anticarsia gemmatalis Hübner, Lithophane antennata Walker, Barathra brassicae Linnaeus, Pseudoplusia includens Walker, Trichoplusia ni Hübner, Heliothis virescens Fabricius);borers, casebearers, webworms, pine shoot moths, loopers and leaf rollers from the family Pyralidae (e.g., European corn borer (Ostrinia nubilalis Hübner), navel orangeworm (Amyelois transitella Walker), corn root webworm (Crambus caliginosellus Clemens), grass webworms (Pyralidae: Crambinae), such as rice leaffolder (Herpetogramma licarsisalis Walker), sugarcane borer (Chilo infuscatellus Snellen), tomato leafminer (Neoleucinodes elegantalis Guenée), rice leafroller (Cnaphalocrocis medinalis), grapevine leafroller (Desmia funeralis Hübner), melonworm (Diaphania nitidalis Stoll), cabbage centerworm (Hellula hydralis Guenée), yellow borer (Scirpophaga incertulas Walker), early shoot borer (Scirpophaga infuscatellus Snellen), white borer (Scirpophaga innotata Walker), top shoot borer (Scirpophaga nivella Fabricius), rice borer (Chilo polychrysus Meyrick), cabbage webworm (Crocidolomia binotalis zeller));leafrollers, aphids, seed worms and fruit worms of the family Tortricidae (such as Cydia pomonella Linnaeus, Endopiza viteana Clemens, Grapholita molesta Busck, Cryptophlebia leucotreta Meyrick, Ecdytolopha aurantiana Lima, Argyrotaenia velutinana Walker, Choristoneura rosaceana Harris, Epiphyas postvittana Walker, Eupoecilia ambiguella Hübner, Pandemis pyrusana Kearfott, Platynota stultana Walsingham, Pandemis cerasana Hübner, Pandemis heparana Denis et Schiffermuller); and many other economically important Lepidoptera (such as Plutella xylostella Linnaeus, Pectinophora gossypiella Saunders, Lymantria dispar Linnaeus, Carposina niponensis Walsingham, Anarsia lineatella Zeller, Phthorimaea operculella Zeller, Lithocolletis blancardella Fabricius, Lithocolletis ringoniella Matsumura, Lerodea eufala Edwards, Leucoptera scitella Zeller);Eggs, pupae and adults of the order Blattaria, including cockroaches from the families Blattidae and Blattellidae (such as Blatta orientalis Linnaeus, Blatella asahinai Mizukubo, Blattella germanica Linnaeus, Supella longipalpa Fabricius, Periplaneta americana Linnaeus, Periplaneta brunnea Burmeister, Leucophaea maderae Fabricius); Periplaneta fuliginosa Service, Periplaneta australasiae Fabr., Nauphoeta cinerea Olivier and Symploce pallens Stephens); eggs, leaf-fed, fruit-fed, root-fed, seed-fed and vesicle tissue-fed larvae and adults of the order Coleoptera, including weevils from the families Attelabidae, Curculionidae and Scolytidae (such as Anthonomus grandis Boheman, Lissorhoptrus oryzophilus Kuschel, Sitophilus granarius Linnaeus, Sitophilus oryzae Linnaeus); Listronotus maculicollis Dietz, Sphenophorus parvulus Gyllenhal, Sphenophorus venatus vestitus, Sphenophorus cicatristriatus Fahraeus); flea beetles, squash beetles, rootworms, leaf beetles, potato beetles and leaf miners in the family Chrysomelidae (such as Leptinotarsa decemlineata Say, Diabrotica virgifera virgifera LeConte);Beetles from the family Scarabaeidae and other beetles such as Japanese beetle (Popillia japonica Newman), Oriental beetle (Anomala orientalis Waterhouse, Exomala orientalis (Waterhouse) Baraud), Northern masked chafer (Cyclocephala borealis Arrow), Southern masked chafer (Cyclocephala immaculata Olivier or C. lurida Bland), dung beetle and May / June beetle (Phyllophaga spp.), and European chafer (Rhizotrogus majalis Razoumowsky); buprestid beetles; click beetles; bark beetles; and false wireworms.

[0087] In addition, agricultural and non-agricultural pests include: eggs, adults and larvae of the order Dermaptera, including earwigs (e.g., European earwig (Forficula auricularia Linnaeus), black earwig (Chelisoches morio Fabricius)); eggs, immature stages, adults and pupae of the orders Hemiptera and Homoptera such as plant bugs from the family Miridae, cicadas from the family Cicadidae, leafhoppers (e.g., Empoasca spp.), bed bugs (e.g., Cimex lectularius Linnaeus) from the family Cimicidae, planthoppers from the family Delphacidae and rice delphacid, sharpshooters from the family Cicadellidae, psyllids from the family Chermidae, whiteflies from the family Aleyrodidae, aphids from the family Aphididae, root aphids from the family Pemphigidae, mealybugs from the family Pseudococcidae, scales from the families Kermesidae, Diaspididae and Ortheziidae, stink bugs from the family Pentatomidae, chinch bugs from the family Leptopteridae, southern chinch bug (Blissus insularis Barber) and northern chinch bug (Blissus leucopterus hirtus Montandon) from the family Lygaeidae, spittlebugs from the family Cercopidae, squash bugs from the family Coreidae, and red bugs and boll weevils from the family Dysodidae.

[0088] Agronomy and non-agronomy pests also include: eggs, larvae, pupae and adults of the order Acarina (mites), such as the spider mites of the family Tetranychidae and red mites (e.g., Panonychus ulmi Koch, Tetranychus urticae Koch, Tetranychus mcdanieli McGregor); the grape short mite of the family Cacacidae (e.g., Brevipalpus lewisi McGregor); the rust and bud mites of the family Eriophyidae and other leaf-feeding mites and mites of importance in human and animal health, i.e., the dust mites of the family Epidermoptidae, the Demodex mites of the family Demodexidae, the Tyroglyphid mites of the family Acaridae; the ticks commonly known as hard ticks of the family Ixodidae (e.g., Ixodes scapularis Say, Ixodes holocyclus Neumann, Dermacentor variabilis Say, Amblyomma americanum Linnaeus) and the ticks commonly known as soft ticks of the family Argasidae (e.g., Ornithodoros turicata, Argas radiatus); the itch and scab mites of the families Sarcoptidae, Psoroptidae and Acaridae; the eggs, adults and immature of the order Orthoptera, including grasshoppers, locusts and crickets (e.g., migratory grasshoppers (e.g., Melanoplus sanguinipes, Melanoplus femur-rubrum, Melanoplus bivittatus), Melanoplus differentialis, Melanoplus mexicanus, Melanoplus sordidus, Melanoplus spretus, Melanoplus bivitattus, Melanoplus bivittatus, Melanoplus femur-rubrum, Melanoplus mexicanus, Melanoplus sanguinipes, Melanoplus sordidus, Melanoplus spretus, Melanoplus bivitattus, Melanoplus bivittatus, Melanoplus femur-rubrum, Melanoplus mexicanus, Melanoplus sanguinipes, Melanoplus sordidus, Melanoplus spretus, Melanoplus bivitattus, Melanoplus bivittatus, Melanoplus femur-rubrum, Melanoplus mexicanus, Melanoplus sanguinipes, Melanoplus sordidus, Melanoplus spretus, Melanoplus bivitattus, Melanoplus bivittatus, Melanoplus femur-rubrum, Melanoplusfemoralis Stein), stable flies (e.g. Stomoxys calcitrans), horn flies, biting flies, blow flies (e.g. Chrysomyia spp., Phormia spp.), and other Muscidae, horse flies (e.g. Tabanus spp.), keds (e.g. Lipoptena spp., Haematobia spp.), warble flies (e.g. Hypoderma spp.), deer flies (e.g. Spivacosa spp.), sheep bots (e.g. Oestrus spp.), and other Brachycera; mosquitoes (e.g. Aedes spp., Anopheles spp., Culex spp.), black flies (e.g. Simulium spp., Bittoa spp.), biting midges, sand flies, fungus gnats, and other Nematocera; egg, adult, immature forms of moths in the order Lepidoptera, including onion thrips (Thrips tabaci Lindeman), flower thrips (Frankliniella spp.), and other leaf-feeding thrips; insect pests in the order Hymenoptera, including ants in the family Formicidae, including Camponotus floridanus Buckley, Camponotus ferrugineus Fabricius, Camponotus pennsylvanicus De Geer, Technomyrmex albipes fr. Smith, Pheidole spp., Tapinoma melanocephalum Fabricius; Monomorium pharaonis Linnaeus, Wasmannia auropunctata Roger, Solenopsis geminata Fabricius, Solenopsis invicta Buren, Iridomyrmex humilis Mayr, Paratrechina longicornis Latreille, Tetramorium caespitum Linnaeus, Lasius alienus. ) and the odorous house ant (Tapinoma sessile Say). Other orders of insects pests include bees (including carpenter bees), sawflies, wasps, yellow jackets, and sawflies (Neodiprion spp.; Cephus spp.); insects pests of the order Isoptera, including termites of the family Termitidae (e.g., Macrotermes bellicosus Sjostedt), Kalotermitidae (e.g., Cryptotermes brevis Walker), Rhinotermitidae (e.g., Coptotermes formosanus Shiraki, Reticulitermes flavipes (Kollar), R. virginicus (Banks), R. santonensis (Feytaud), R. griseus (Kirby), R. lucifugus (Roger), R. hesperus (Walker), R. virginicus (Banks), Incisitermes immigrans (Snyder), I. minor (Hagen), I. snyderi (Light), Reticulitermes santonensis (Feytaud), and other termites of economic importance; insects pests of the order Thysanura, such as the silverfish (Lepisma saccharina Linnaeus) and the firebrat (Thermobia domestica Packard); insects pests of the order Mallophaga and include the head louse (Pediculus humanus capitis De Geer), body louse (Pediculus humanus Linnaeus), chicken brood louse (Menacanthus stramineus Nitszch), dog biting louse (Trichodectes canis De Geer), fowl louse (Goniocotes gallinae De Geer), sheep body louse (Bovicola ovis Schrank), cattle louse (Haematopinus eurysternus Nitzsch), long-nosed cattle louse (Linognathus vituli Linnaeus), and other sucking and chewing lice that attack humans and animals;Insect pests of the order Siphonaptera, including Xenopsylla cheopis Rothschild, Ctenocephalides felis Bouche, Ctenocephalides canis Curtis, Ceratophyllus gallinae Schrank, Echidnophaga gallinacea Westwood, Pulex irritans Linnaeus and other fleas that afflict mammals and birds. Additional arthropod pests include spiders of the order Araneae, such as Loxosceles reclusa Gertsch & Mulaik and Latrodectus mactans Fabricius, and centipedes of the order Scutigeromorpha, such as Scutigera coleoptrata Linnaeus.

[0089] Examples of invertebrate pests of stored grain include Prostephanus truncatus, Rhyzopertha dominica, Sitophilus oryzae, Sitophilus zeamais, Callosobruchus maculatus, Tribolium castaneum, Sitophilus granarius, Plodia interpunctella, Ephestia kuhniella and Cryptolestes ferrugineus.

[0090] The compounds of the present application can be active against the following lepidopteran pests: (for example Alabama argillacea Hubner (cotton leafworm), Archips argyrospila Walker (fruittree leafroller), A. rosana Linnaeus (European leafroller), and other Archips species, Chilo suppressalis Walker (rice stem maggot), Cnaphalocrocis medinalis Guenee (rice leaffolder), Crambus caliginosellus Clemens (corn root webworm), Crambus teterrellus Zincken (bluegrass webworm), Cydia pomonella Linnaeus (codling moth), Earias insulana Boisduval (spiny bollworm), Earias vittella Fabricius (tutti fruitti bollworm), Helicoverpa armigera Hubner (American bollworm), Helicoverpa zea Boddie (cotton bollworm), Heliothis virescens Fabricius (tobacco budworm), Herpetogramma licarsisalis Walker (cotton leafroller), Lobesia botrana Denis & Schiffermuller (grapevine moth), Pectinophora gossypiella Saunders (pink bollworm), Phyllocnistis citrella Stainton (citrus leafminer), Pieris brassicae Linnaeus (large white butterfly), Pieris rapae Linnaeus (small white butterfly), Plutella xylostella Linnaeus (diamondback moth), Spodoptera exigua Hubner (beet armyworm), Spodoptera litura Fabricius (tobacco cutworm, tea geometer), Spodoptera frugiperda J.E. Smith (fall armyworm), Trichoplusia ni Hubner (cabbage looper), and Tuta absoluta Meyrick (tomato pinworm)).Homoptera pests: Acyrthosiphon pisum Harris (pea aphid), Aphis craccivora Koch (black bean aphid), Aphis fabae Scopoli (bean aphid), Aphis gossypii Glover (cotton aphid, melon aphid), Aphis pomi De Geer (apple aphid), Aphis spiraecola Patch (spirea aphid), Aulacorthum solani Kaltenbach (foxglove aphid), Chaetosiphon fragaefolii Cockerell (strawberry aphid), Diuraphis noxia Kurdjumov / Mordvilko (Russian wheat aphid), Dysaphis plantaginea Paaserini (red apple aphid), Eriosoma lanigerum Hausmann (woolly aphid), Hyalopterus pruni Geoffroy (peach-pink woolly aphid), Lipaphis erysimi Kaltenbach (turnip aphid), Metopolophium dirhodum Walker (rose grain aphid), Macrosiphum euphorbiae Thomas (potato aphid), Myzus persicae Sulzer (peach-potato aphid), Nasonovia ribisnigri Mosley (lettuce aphid), Pemphigus spp. (root aphids and gall aphids), Rhopalosiphum maidis Fitch (corn leaf aphid), Rhopalosiphum padi Linnaeus (oat bird-cherry aphid), Schizaphis graminum Rondani (English grain aphid), Sitobion avenae Fabricius (black aphid), Therioaphis maculata Buckton (alfalfa spotted aphid), Toxoptera aurantii Boyer de Fonscolombe (orange spirea aphid), and Toxoptera citricida Kirkaldy (brown citrus aphid); Adelges spp. (adelgids); Phylloxera devastatrix Pergande (pecan phylloxera);Bemisia tabaci Gennadius (tobacco whitefly, sweet potato whitefly), Bemisia argentifolii Bellows & Perring (silverleaf whitefly), Dialeurodes citri Ashmead (citrus whitefly), and Trialeurodes vaporariorum Westwood (greenhouse whitefly); Empoasca fabae Harris (potato leafhopper), Laodelphax striatellus Fallen (smaller brown planthopper), Macrosteles quadrilineatus Forbes (two-spotted leafhopper), Nephotettix cincticeps Uhler (green leafhopper), Nephotettix nigropictus; 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); Icerya purchasi Maskell (cotton scale insect), Quadraspidiotus perniciosus Comstock (St. Joseph's insect); Planococcus citri Risso (citrus mealybug); Pseudococcus spp. (other mealybug complex); Cacopsylla pyricola Foerster (pear yellow psyllid), Trioza diospyri Ashmead (persimmon woodlice); and Hemiptera: Acrosternum hilare Say (rice green stink bug), Anasa tristis De Geer (Pumpkin Margin Bug), Blissus leucopterus leucopterus Say (Sorghum Long Bug), Cimex lectularius Linnaeus (Stink Bug), Corythucha gossypii Fabricius (Cotton Net Bug), Cyrtopeltis modesta Distant (Tomato Bug), Dysdercus suturellus Herrich- Euchistus servus Say (brown stink bug), Euchistus variolarius Palisot de Beauvois (one-spotted stink bug), Graptostethus spp. (kissing bugs complex), Leptoglossus corculus Say (leaf-footed pine seed bug), Lygus lineolaris Palisot de Beauvois (tarnished plant bug), Nezara viridula Linnaeus (southern green stink bug), Oebalus pugnax Fabricius (rice stink bug), Oncopeltus fasciatus Dallas (large milkweed bug), Pseudatomoscelis seriatus Reuter (cotton fleahopper). Other insect orders controlled by the compounds of the present application include the 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 the Coleoptera (e.g., Leptinotarsa decemlineata Say (Colorado potato beetle), Epilachna varivestis Mulsant (Mexican bean beetle), and Agriotes, Athous, or Limonius spp. (wireworms)).

[0091] The compounds of the present application are also active against members of the Nematoda, Cestoda, Trematoda, and Acanthocephala classes, including members of the economically important orders Strongylida, Ascaridida, Rhabditida, Diptychia, Spirurida, and Oxyurida, such as, but not limited to, the economically important agricultural pests (i.e., Meloidogyne arenaria root knot nematode, Pratylenchus spp. root lesion nematodes, Heterodera spp. cyst nematodes, etc.) and pests that threaten the health of animals and humans (i.e., all economically important trematodes, cestodes, and ascarids, such as, but not limited to, the common roundworm in horses, the dog heartworm, the barber pole worm in sheep, the dog heartworm, the leaf-shaped bursate fluke in horses, the liver fluke in ruminants, etc.).

[0092] It should be noted that some modern classification systems place the Homoptera in the suborder of the Hemiptera.

[0093] The compounds of the present application can be mixed with one or more other effective ingredients to form a multi-component insecticide, imparting even broader spectrum of agronomic and non-agronomic uses, said effective ingredients (i.e. biologically active ingredients or agents) including insecticides, fungicides, nematicides, bactericides, acaricides, herbicides, herbicide safeners, growth regulators such as insect ecdysis inhibitors and root growth stimulators, chemosterilants, semiochemicals, repellents, attractants, pheromones, feeding stimulants, other biologically active compounds or entomopathogenic bacteria, viruses or fungi. Thus, the present application also relates to a composition consisting of a biologically effective amount of a compound of formula I, an N-oxide or a salt thereof, at least one formulation adjuvant selected from the group consisting of surfactants, solid diluents and liquid diluents, and at least one other effective ingredient or agent. In the case of mixtures of the present application, the other effective ingredients or agents can be formulated together with the compounds of the present application (including compounds of formula I) to form a pre-mix, or the other biologically active compounds or agents can be formulated separately from the compounds of the present application (including compounds of formula I) and the two formulations are mixed together just prior to application (e.g. in a spray tank), or the two formulations are applied sequentially.

[0094] 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.

[0095] 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. In some cases, combinations with at least one other invertebrate pest control active ingredient having a similar spectrum of control but a different site of action can be particularly advantageous for resistance management. Thus, the compositions of the present invention may further comprise a biologically effective amount of at least one additional invertebrate pest control active ingredient having a similar spectrum of control but belonging to a different chemical class or having a different site of action.

[0096] Further examples of biologically active compounds or agents with which the compounds of the present application can be formulated are: fungicides, nematocides, bactericides, acaricides.

[0097] In certain instances, the compounds of the present application in combination with other biologically active (particularly invertebrate pest control) compounds or agents (i.e., active ingredients) can achieve greater than additive (i.e., synergistic) effects. Reducing the amount of active ingredient released into the environment, while ensuring effective pest control, has always been desirable. Such combinations can be advantageously used to reduce crop production costs, and to reduce environmental load, when synergistic effects of invertebrate pest control active ingredients occur at application rates that impart agronomically desirable degrees of invertebrate pest control.

[0098] The compounds of the present application and their compositions can be applied to plants that are transgenic to express proteins toxic to invertebrate pests (such as Bacillus thuringiensis delta-endotoxins). Such applications can provide a broader spectrum of plant protection, and can be advantageously used in resistance management. The effects of topically applied invertebrate pest control compounds of the present application can synergize with the expressed toxin proteins.

[0099] General references for these agricultural protectants (i.e., insecticides, fungicides, nematocides, acaricides, herbicides, and biologicals) include "The Pesticide Manual" 13th Edition (C. D. S. Tomlin, Editor, British Crop Protection Council, Farnham, Surrey, U.K., 2003) and "The BioPesticide Manual" 2nd Edition (L. G. Copping, Editor, British Crop Protection Council, Farnham, Surrey, U.K., 2001).

[0100] For embodiments in which one or more of these different mixing components are used, the weight ratio of the different mixing components (total amount) to the compound of Formula I, N-oxide, or salt thereof is generally between about 1 :3000 and about 3000: 1. Ratios of about 1 :300 and about 300: 1 are of note (e.g., ratios of about 1 :30 and about 30: 1).

[0101] Invertebrate pests are controlled in agricultural and non-agricultural applications by applying to the pest environment, including infested agricultural and / or non-agricultural sites, to the area to be protected, or directly to the pest, a biologically effective amount of one or more compounds of the present application, typically in the form of a composition.

[0102] Accordingly, the present application includes methods for controlling invertebrate pests in agronomic and / or non-agronomic applications, comprising contacting an invertebrate pest, or its environment, with a biologically effective amount of one or more compounds of the present application, or contacting with a composition comprising at least one such compound, or contacting 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 application and a biologically effective amount of at least one additional biologically active compound or agent include granular compositions in which the additional active compound is present on the same granule as the compound of the present application, or on a different granule than those of the compound of the present application.

[0103] Embodiments of the methods of the present application include contacting the environment. Of note are the methods wherein the environment is a plant. Also of note are the methods wherein the environment is an animal. Also of note are the methods wherein the environment is a seed.

[0104] To effect contact with a compound or composition of the present application to protect a field crop from invertebrate pests, the compound or composition is typically applied to the seed of the crop, to the foliage (e.g., leaves, stems, flowers, fruit) of the crop plant, or to the soil or other growth medium before or after planting of the crop.

[0105] One embodiment of the method of contacting is by spraying. Alternatively, a granular composition comprising a compound of the application can be applied to the foliage of a plant or into the soil. Contacting the plant with a composition comprising a compound of the application applied as a drench liquid formulation, as a granular formulation applied to the soil, as a nursery box treatment or as a transplant dip, is also effective to deliver a compound of the application via plant uptake. Of note is a composition of the application in the form of a drench liquid formulation. Also of note is a method of controlling an invertebrate pest comprising contacting the invertebrate pest or its environment with a biologically effective amount of a compound of the application, or contacting a composition comprising a biologically effective amount of a compound of the application. Also of note is a method wherein the environment is soil and the composition is applied to the soil as a drench. Also of note is that a compound of the application can also be made effective by topical application to the site of infestation. Other methods of contacting include application of a compound or composition of the application by direct spray and residual spray, aerial spraying, gels, seed coatings, microencapsulation, systemic uptake, baits, ear tags, boluses, atomizers, fumigants, aerosols, dusts, and many others. One embodiment of the method of contacting is a fertilizer granule, prill or tablet, of a size that is stable, comprising a compound or composition of the application. A compound of the application can also be impregnated into a substance used to assemble an invertebrate control device, such as an insect-proof net.

[0106] A composition of the application can also be used in a seed treatment to provide protection of the seed from invertebrate pests. In the context of the disclosure and claims, treating seed means contacting the seed with a biologically effective amount of a compound of the application, typically formulated as a composition of the application. Such a seed treatment protects the seed from invertebrate soil pests, and can also generally protect the roots and other plant parts of the seedling that develop from the germinated seed that contact the soil. The seed treatment also provides protection to the foliage by allowing a compound of the application or a second active ingredient to move in the developing plant. Seed treatments can be applied to seeds of various types, including those that can germinate to form a transgenic plant to express a particular trait. Representative examples include those that express a protein toxic to invertebrate pests, such as a Bacillus thuringiensis toxin, or those that express a resistance to a herbicide, such as a glyphosate acetyl transferase that provides resistance to glyphosate.

[0107] One method of seed treatment is to spray or dust the seed with the compound of the application (i.e., as a formulated composition) on the seed prior to planting. Compositions formulated for seed treatment generally contain a film-forming agent or binder. Thus, a seed coating composition of the application typically comprises a biologically effective amount of a compound of Formula I, N-oxide, or salt thereof, and a film-forming agent or binder. The seed is coated by spraying a flowable suspension concentrate directly onto a rolling bed of seed, and then drying the seed. Alternatively, other formulation types such as wettable powders, solutions, suspoemulsions, emulsifiable concentrates, and emulsions in water can be sprayed onto the seed. This method is particularly useful for applying a film coating to the seed. Various coating equipment and methods can be employed by those skilled in the art.

[0108] The treated seed typically comprises a compound of the application in an amount of about 0.1 g to 1 kg per 100 kg of seed (i.e., about 0.0001 to 1% by weight of the seed prior to treatment). Flowable suspension formulations for seed treatment typically comprise about 0.5 to about 70% of the active ingredient, about 0.5 to about 30% of a film-forming binder, about 0.5 to about 20% of a dispersing agent, 0 to about 5% of a thickening agent, 0 to about 5% of a pigment and / or dye, 0 to about 2% of an antifoam agent, 0 to about 1% of a preservative, and 0 to about 75% of a volatile liquid diluent.

[0109] The compounds of the present application can be incorporated into bait compositions which can be consumed 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 which comprise (a) an active ingredient, i.e., a biologically effective amount of a compound of Formula I, an N-oxide, or a salt thereof; (b) one or more food materials; optionally (c) an attractant, and optionally (d) one or more humectants. Of note are granular or bait compositions which comprise from about 0.001 to 5% of the active ingredient, from about 40 to 99% of a food material and / or an attractant; and optionally from about 0.05 to 10% of a humectant, which are effective in controlling soil invertebrate pests at very low application rates, especially at doses of active ingredient which are lethal when ingested but not when contacted directly. Certain food materials can serve both as a food source and as an attractant. Food materials include carbohydrates, proteins, and lipids. Examples of food materials are vegetable meals, sugars, starches, animal fats, vegetable oils, yeast extract, and milk solids. Examples of attractants are palatants and flavorants 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 polyhydric alcohols, glycerol, and sorbitol. Of note are bait compositions (and methods of using such bait compositions) for controlling at least one invertebrate pest selected from the group consisting of ants, termites, and cockroaches. Devices for controlling invertebrate pests include a bait composition of the present application and a housing adapted to contain said bait composition, wherein said housing has at least one opening sized to enable passage of an invertebrate pest therethrough to enable the invertebrate pest to access said bait composition from a location external to the housing, and wherein said housing is further adapted to be placed in or near a locus of potential or known invertebrate pest activity.

[0110] The compounds of the present application can be applied without additional adjuvants, but most commonly application is of a formulation which comprises one or more active ingredients with suitable carriers, diluents and surfactants, and possibly in combination with food, depending on the end use envisioned. One method of application involves spraying an aqueous dispersion or a refined oil solution of the compounds of the present application. Combinations with spray oils, spray oil concentrates, stickers, adjuvants, other solvents, and synergists such as piperonyl butoxide often enhance the effectiveness of the compounds. For non-agronomic uses, such sprays can be applied from a spray container such as a tank, bottle or other container, via a pump or by releasing it from a pressurized container, for example, a pressurized aerosol spray can. Such spray compositions can take a variety of forms, for example, a spray, mist, foam, smoke or fog. Thus, such spray compositions can also contain propellants, foaming agents, and the like, as needed for the application. Of note is a spray composition comprising a biologically effective amount of a compound or composition of the present application, and a carrier. One embodiment of such a spray composition comprises a biologically effective amount of a compound or composition of the present application, and a propellant. Representative propellants include, but are not limited to, methane, ethane, propane, butane, isobutane, butene, pentane, isopentane, neopentane, pentene, hydrofluorocarbons, chlorofluorocarbons, dimethyl ether, and mixtures of the foregoing. Of note is a spray composition (and method of using such a spray composition dispensed from a spray container) for controlling at least one invertebrate pest selected from the group consisting of mosquitoes, biting midges, houseflies, horseflies, deerflies, wasps, hornets, yellow jackets, ticks, spiders, ants, gnats, and the like, including various of the foregoing pests or combinations thereof.

[0111] Non-agronomic use refers to the control of invertebrate pests in areas other than crop fields. Non-agronomic uses of the compounds and compositions of the present application include the control of invertebrate pests in stored grain, beans and other foodstuffs, and in textiles such as clothing and carpets. Non-agronomic uses of the compounds and compositions of the present application also include the control of invertebrate pests in ornamental plants, forest crops, gardens, utility areas along roadways and railroads, and turf such as lawns, golf courses and pastures. Non-agronomic uses of the compounds and compositions of the present application also include the control of invertebrate pests in dwellings and other buildings inhabited by humans and / or companion animals, livestock, farm animals, zoo animals or other animals. Non-agronomic uses of the compounds and compositions of the present application also include the control of pests such as termites that damage wood or other building materials used in construction.

[0112] Non-agronomic uses of the compounds and compositions of the present application also include protecting human and animal health by controlling invertebrate pests that are parasitic or that transmit infectious disease. Controlling animal parasites includes controlling ectoparasites that parasitize the external body surfaces (e.g., shoulders, axillae, bellies, inner thighs) of host animals as well as endoparasites that parasitize the internal body (e.g., stomach, intestines, lungs, veins, subcutis, lymphatic tissue) of host animals. Ectoparasitic or disease-transmitting pests include, for example, chiggers, ticks, lice, mosquitoes, flies, mites, and fleas. Endoparasites include Dirofilaria immitis, hookworms, and helminths. The compounds and compositions of the present application are particularly suitable for combating ectoparasitic or disease-transmitting pests. The compounds and compositions of the present application are suitable for systemic and / or non-systemic control of infestation or infection of animals by parasites.

[0113] Examples of invertebrate parasitic pests that are controlled by administering to an animal to be protected a parasiticidally effective amount of a compound of the present application include ectoparasites (arthropods, mites, etc.) and endoparasites (helminths, e.g., nematodes, trematodes, cestodes, acanthocephalans, etc.).

[0114] Diseases or classes of diseases generally described as helminthiases are attributable to infection of an animal host by parasites known as helminths. The term "helminth" is intended to include nematodes, trematodes, cestodes, and acanthocephalans. Helminthiases are a pervasive and serious economic problem associated with domesticated animals such as swine, sheep, horses, cattle, goats, dogs, cats, and poultry.

[0115] It is also contemplated that the compounds of the present application are effective against a variety of ectoparasites of animals, e.g., arthropod ectoparasites of mammals and birds, although it is also contemplated that certain arthropods can also be endoparasites.

[0116] Thus, insect and acarid pests include, for example, biting insects such as flies and mosquitoes, mites, ticks, lice, fleas, stink bugs, botflies, and the like.

[0117] Generally, flies, fleas, lice, mosquitoes, gnats, mites, ticks, and helminths cause great losses in the areas of livestock and companion animals. Arthropod parasites also cause trouble for humans and can be carriers of human and animal pathogenic organisms.

[0118] Numerous other arthropod pests and ectoparasites are known in the art and are also contemplated for treatment with the compounds of the present application.

[0119] Biologically active compounds or agents useful in the compositions of the present application include organophosphate insecticides. Such insecticides have very broad activity as insecticides and, in some cases, as insect repellents. Organophosphate insecticides include, for example, azinphos-methyl, terbufos, dimethoate, diazinon, dibam, trichlorfon, phosmet, malathion, acephate, methamidophos, ethyl-parathion, methyl-parathion, phosalone, phorate, tri- sulfophon and vamidothion. Combinations including the methods and compositions of the present application with carbamate-type insecticides, including, for example, carbofuran, aldicarb, fenamiphos, ethoprophos, carbofuran, and the like, as well as with organochlorine-type insecticides are also contemplated. Combinations including biological insecticides, including repellents, pyrethrins (as well as synthetic variants thereof, such as allethrin, diper-methrin, resmethrin, tetrachlorvinphos) and nicotine, which is commonly used as a miticide, are also contemplated. Other contemplated combinations are miscellaneous insecticides, including: Bacillus sp., chlordene, formamidine (such as amitraz), copper compounds (such as copper hydroxide and copper oxychloride), cyfluthrin, cypermethrin, dicofol, endosulfan, esfenvalerate, fenvalerate, lambda-cyhalothrin, methoxychlor and sulfur.

[0120] Of note are additional biologically active compounds or agents selected from the group consisting of anthelmintics known in the art, such as avermectins (e.g., ivermectin, moxidectin, milbemycin), benzimidazoles (e.g., albendazole, triclabendazole), N- salicylanilides (e.g., closantel, oxyclozanide), substituted phenols (e.g., nitroxynil), pyrimidines (e.g., thiabendazole), imidazothiazoles (e.g., levamisole) and praziquantel.

[0121] Other biologically active compounds or agents useful in the compositions of the present application can be selected from the group consisting of insect growth regulators (IGRs) and juvenile hormone analogs (JHAs), such as diflubenzuron, teflubenzuron, fenoxycarb, hydroprene, 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 environment of the animal subject.

[0122] Of note are biologically active compounds or agents useful in the compositions of the present application selected from the group consisting of anti-parasitic avermectin compounds. As noted above, the avermectin class of compounds are a series of potent anti-parasitic agents known to be useful against a broad spectrum of both endo- and ecto-parasites in mammals.

[0123] The compositions of the present application can also include flukicides. Suitable flukicides include, for example, triclabendazole, fenbendazole, albendazole, clorsulon and oxibendazole. It will be appreciated that the combinations above can also include combinations of antibiotics, anti-parasitic and anti-flukicidal active compounds.

[0124] In addition to the above combinations, it is also envisaged that the methods and compounds of the application as described herein will be provided in combination with other animal health medicaments such as trace elements, anti-inflammatory agents, anti-infective agents, hormones, dermatological agents (including antiseptics and disinfectants) and immunological agents such as vaccines and antisera for the prevention of disease.

[0125] For example, such anti-infective agents include one or more antibiotics which optionally can be administered simultaneously, e.g. in combined composition form and / or separate dosage forms, during treatment with the compounds or methods of the present application.

[0126] Non-agronomic 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, drenches 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, in the form of dips or immersions, sprays, washes, coating or application to a small area of the animal, and by means of articles comprising a composition of the application, such as collars, ear tags, tail tags, limb tags or halters.

[0127] Any of the compounds of the present application or suitable combinations of such compounds can be administered directly to the animal subject, and / or non-directly by administering it to the local environment in which the animal resides (such as bedding, enclosures, etc.). Direct administration includes contacting the skin, fur or feathers of the animal subject with the compound, or feeding or injecting the compound into the animal.

[0128] The compounds of the present application can be administered in controlled release form, for example, as a slow release subcutaneous formulation, or as a controlled release device affixed to the animal such as a flea collar. Collars for controlled release of insecticides for long term protection of companion animals from infestation by fleas are known in the art.

[0129] Generally, the parasiticidal compositions according to the present application comprise a mixture of a compound of formula I, an N-oxide thereof or a salt thereof, with one or more pharmaceutically or veterinarily acceptable carriers, including excipients and auxiliaries, which are selected according to the intended route of administration (e.g. buccal, topical or parenteral, such as injection) and according to standard practices. Furthermore, suitable carriers are selected with respect to their compatibility with the active ingredient or ingredients of the composition, including the presence of relative stability with respect to pH and water content. Thus, of note are compositions for protecting animals from invertebrate parasitic pests, which comprise at least one carrier and a parasiticidally effective amount of a compound of the present application.

[0130] For parenteral administration (including intravenous, intramuscular, and subcutaneous administration), the compounds of the application can be formulated in suspensions, solutions, or emulsions in oily or aqueous vehicles, and can contain adjuvants such as suspending, stabilizing, and / or dispersing agents. The compounds of the application can also be formulated for rapid-onset injection or continuous infusion. Pharmaceutical compositions for injection include aqueous solutions of the active agents in water-soluble form (e.g., salts of the active compounds), preferably in physiologically compatible buffers, with other ingredients included as known in the art of pharmaceutical formulation. Additionally, suspensions of the active compounds can be prepared in a lipophilic vehicle. Suitable lipophilic vehicles include fatty oils, such as sesame oil, synthetic fatty acid esters, such as ethyl oleate, and triglycerides, or substances such as liposomes. Aqueous injection suspensions can contain substances that increase the viscosity of the suspension, such as sodium carboxymethyl cellulose, sorbitol, or dextran. Formulations for injection can be presented in unit dosage form, e.g., in ampoules, or in multi-dose containers. Alternatively, the active ingredient can be in powder form for constitution with a suitable vehicle, e.g., sterile pyrogen-free water, before use.

[0131] In addition to the formulations described above, the compounds of the application can also be formulated in sustained-release preparations. Such sustained-release preparations can be administered by implantation (for example subcutaneously or intramuscularly) or by intramuscular injection or subcutaneous injection. In this case, the compounds of the application can be formulated with suitable polymeric or hydrophobic materials (for example in emulsions that contain a pharmaceutically acceptable oil), with ion exchange resins, or the compounds can be formulated as sparingly soluble derivatives, such as but not limited to sparingly soluble salts.

[0132] For administration by inhalation, the compositions of the application are delivered in the form of an aerosol spray using a pressurized package or a 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 of, for example, gelatin for use in an inhaler or insufflator can be formulated containing a powder mix and a suitable powder base such as lactose or starch.

[0133] For oral administration, the compounds of the present application can be formulated with known compositions suitable for oral administration, such as solutions, emulsions, suspensions, pastes, gels, capsules, tablets, boluses, powders, granules, rumen retentive and feed / water / lick block forms, using binders / fillers known in the art for such 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., methyl cellulose, carboxymethyl cellulose, ethylhydroxy cellulose), protein derivatives (e.g., corn protein, gelatin) and synthetic polymers (e.g., polyvinyl alcohol, polyvinylpyrrolidone). If desired, lubricants (e.g., magnesium stearate), disintegrants (e.g., cross-linked polyvinylpyrrolidone, agar, alginic acid) and dyes or pigments can be added. Pastes and gels will also typically include a binder (e.g., acacia, alginic acid, bentonite, cellulose, xanthan gum, colloidal silicon dioxide, magnesium aluminum silicate) to help keep the composition in contact with the oral cavity and not easily expelled.

[0134] If the parasiticidal composition is in the form of a concentrated feed, the carrier is typically selected from high performance feeds, feed grains or concentrated proteins. In addition to the parasiticidal active ingredient, such compositions comprising concentrated feeds also comprise additives which can promote the health or growth of the animal, improve the quality of meat from slaughtered animals or be useful in animal husbandry. These additives include, for example, vitamins, antibiotics, chemotherapeutic agents, bacteriostatic agents, fungistatic agents, anticoccidials and hormones.

[0135] The compounds of formula I can also be formulated into rectal compositions such as suppositories or retention enemas using, for example, conventional suppository bases such as cocoa butter or other glycerides.

[0136] Formulations for topical administration are typically in the form of a powder, cream, suspension, spray, emulsion, foam, paste, aerosol, ointment, salve, or gel. Topical formulations are more typically aqueous solutions, which can be in the form of a concentrate for dilution prior to use. Parasiticidal compositions suitable for topical administration generally comprise a compound of the present application and one or more suitable carriers for topical use. When the parasiticidal composition is applied topically to the exterior of an animal in the form of a line or spot (i.e., spot-on therapy), the active ingredients migrate over the surface of the animal to cover most or all of the external surface area. Thus, the animal being treated is protected from infestation by invertebrate pests, such as ticks, fleas, and lice, which feed, inter alia, from the skin of the animal. Thus, formulations for topical spot-on administration generally comprise at least one organic solvent to facilitate the transfer and / or penetration of the active ingredients onto and into the skin of the animal. Carriers in such formulations include propylene glycol, paraffin, 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, oxystearate laurate, oleyl oleate, decyl oleate, hexyl laurate, hexanoic acid esters of saturated fatty alcohols of chain length C 12 -C 18 solutions of dicarboxylic acid esters such as dibutyl phthalate, diisopropyl isophthalate, diisopropyl adipate, di-n-butyl adipate or (e.g., glycol) ester solutions of aliphatic acids. The presence of crystallization inhibitors or dispersants known in the pharmaceutical or cosmetic industry can also be advantageous.

[0137] Pour-on formulations can also be formulated to control parasites of animals of agricultural value. Pour-on formulations of the present application can be in the form of a liquid, powder, emulsion, foam, paste, aerosol, ointment, salve, or gel. Pour-on formulations are typically liquids. These pour-on formulations can be effectively applied to sheep, cattle, goats, other ruminants, camelid mammals, swine, and horses. The pour-on formulation is typically applied by pouring the formulation in the form of one or more thin lines, or a spot, on the midline of the back (dorsal) or the shoulders of the animal. More typically, the formulation is applied by pouring the formulation along the back of the animal, following the spine. The formulation can also be applied via other conventional methods, including wiping over at least a small area of the animal with a saturated material, or applying it using a commercially available applicator, by syringe, by spray, or by using a spray raceway. The pour-on formulation includes a carrier and can also contain 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, ultraviolet light blockers or absorbers, and colorants. Surfactants can also be included in these formulations, including anionic, cationic, nonionic, and amphoteric surfactants.

[0138] The formulations of the present application generally contain an antioxidant such as BHT (butylated hydroxytoluene). The antioxidant is generally present in amounts of 0.1% to 5% (weight / volume). Certain formulations require a solubilizing agent, such as oleic acid, to solubilize the active agent, especially when spinosyn is used. Common spreaders used in these pour-on formulations are: IPM, IPP, saturated C 12 -C 18 caprylic / capric esters of fatty alcohols, oleic acid, oleyl alcohol esters, ethyl oleate, triglycerides, silicone oils, and DPM. The pour-on formulations of the present application can be prepared according to known techniques. When the pour-on is a solution, the insect repellent / insecticide is combined with the carrier or vehicle, if necessary, using heat and agitation. Auxiliary or additional ingredients can be added to the mixture of active agent and carrier, or they can be combined with the active agent prior to addition of the carrier. If the pour-on is an emulsion or suspension, these formulations can be prepared similarly using known techniques.

[0139] Other delivery systems for more hydrophobic pharmaceutical compounds can be used. Liposomes and emulsions are known examples of delivery vehicles or carriers for hydrophobic drugs. Also, organic solvents such as dimethyl sulfoxide can be used, if desired.

[0140] For agronomic applications, the amount applied effective to control the desired (i.e., "biologically effective amount") will depend on such factors as the invertebrate pest species to be controlled, the life cycle of the pest, the stage of life, its size, location, time of year, host crop or animal, feeding behavior, mating behavior, environmental moisture, temperature, and the like. Under normal conditions, an application rate of about 0.01 to 2 kg of active ingredient per hectare is sufficient to control pests in an agronomic ecosystem, although application rates as low as 0.0001 kg per hectare can be sufficient or as high as 8 kg per hectare can be needed. For non-agronomic applications, the effective amount will range from about 1.0 to 50 mg per square meter, although application rates as low as 0.1 mg per square meter can be sufficient or as high as 150 mg per square meter can be needed. One skilled in the art will readily be able to determine the biologically effective amount needed to achieve the desired level of invertebrate pest control.

[0141] In general, for veterinary use, the compounds of Formula I, N-oxides, or salts thereof are applied to an animal in a parasiticidally effective amount to protect the animal from invertebrate parasitic pests. A parasiticidally effective amount is that amount of active ingredient needed to achieve the observed reduction in the occurrence or activity of the target invertebrate parasitic pest. Those of skill in the art will appreciate that the parasiticidally effective dose can vary depending on the compound and composition of the present application, the desired parasiticidal effect and duration, the target invertebrate pest species, the animal to be protected, the mode of application, and the like, and that the amount needed to achieve a particular effect can be determined by simple experiment. DETAILED DESCRIPTION

[0142] 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.

[0143] 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.

[0144] Table 1 Compound structures and their 1 H NMR values

[0145] 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.

[0146] 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.

[0147] Examples of representative compounds are shown below. The synthesis methods of other compounds are similar and will not be described in detail here.

[0148] 1. Synthesis of Compound 6

[0149] (1) Compound 6-1 (0.3 g, 1.23 mmol), compound 6-2 (0.62 g, 1.84 mmol), cesium fluoride (0.37 g, 2.46 mmol) and catalytic amount of Pd(dppf)Cl2were dissolved in dioxane (8 ml) and water (1 ml), stirred at 100 °C for 12 h under nitrogen atmosphere. Extraction was performed using ethyl acetate, the organic phase was washed with water and saturated brine, dried and concentrated, the residue was purified by column chromatography (EA / PE = 1 / 3) to give compound 6-3 (140 mg, 35%).

[0150] (2) Compound 6-3 (140 mg, 0.43 mmol) was dissolved in 5 ml of ethanol and 5 ml of water, sodium hydroxide (86 mg, 2.16 mmol) was added, and stirred at room temperature for 3 h. The reaction solution was adjusted to be acidic, extracted with ethyl acetate, and the organic phase was washed with saturated brine, dried and concentrated to give crude compound 6-4 (100 mg).

[0151] (3) Compound 6-4 (100 mg, 0.33 mmol) was dissolved in 5 ml of dichloromethane, oxalyl chloride (86 mg, 0.68 mmol) and 1 drop of DMF were added at 0 °C, and stirred at room temperature for 1 h. The reaction was placed in a dry ice bath, compound 6-5 (89 mg, 0.37 mmol) and triethylamine (102 mg, 1.01 mmol) were added, and the reaction was stirred for 1 h. The reaction solution was concentrated, and the residue was purified by column chromatography to give compound 6 (70 mg, 41%).

[0152] 2. Synthesis of compound 18

[0153] (1) Compound 18-1 (3.8 g, 19.44 mmol) was dissolved in 40 mL of a mixed solvent (1,4-dioxane:water = 10:1), and then 3-aminobenzenboronic acid (3.2 g, 23.33 mmol), potassium carbonate (8.0 g, 58.32 mmol), and Pd(dppf)Cl2(0.3 g, 0.39 mmol) were added. The reaction solution was reacted at 100 °C for 4 h under nitrogen protection, and LCMS was used to monitor the completion of the reaction. The reaction solution was poured into water for quenching, and then extracted with ethyl acetate three times, the organic phase was washed with saturated brine, dried with anhydrous sodium sulfate, concentrated and stirred, and purified by normal phase to give compound 18-2 (PE / EA = 2 / 1, 3.3 g, 81%, yellow oil).

[0154] (2) Compound 18-2 (3.0 g, 14.45 mmol) was dissolved in 30 mL of 1,4-dioxane solution, then cuprous iodide (2.7 g, 14.45 mmol) and isoamyl nitrite (5.0 g, 43.35 mmol) were added, followed by nitrogen replacement for several times, and finally diiodomethane (11.5 g, 43.35 mmol) was added to the reaction solution. The reaction solution was placed at 100 °C for 3 h, and LCMS was used to monitor the completion of the reaction. The reaction solution was poured into water for quenching, then extracted with ethyl acetate, and the organic phase was combined, washed with saturated brine, dried over anhydrous sodium sulfate, concentrated and triturated, and purified by normal phase to obtain compound 18-3 (PE / EA = 8 / 1, 2.5 g, 54%, yellow oil).

[0155] (3) Compound 18-3 (2.0 g, 6.28 mmol), dimethyl malonate (1.65 g, 12.56 mmol), 2-picolinic acid (155 mg, 1.26 mmol), cesium carbonate (6.1 g, 18.84 mmol) and a catalytic amount of cuprous iodide (120 mg, 0.63 mmol) were dissolved in 20 mL of 1,4-dioxane solution, stirred at 90 °C for 12 h under nitrogen atmosphere. The reaction solution was concentrated, diluted with ethyl acetate, and the organic phase was washed with water and saturated brine, dried and concentrated, and the residue was purified by column chromatography to obtain compound 18-4 (PE / EA = 3 / 1, 1.5 g, 74%, light yellow oil).

[0156] (4) Compound 18-4 (0.5 g, 1.55 mmol) was dissolved in 6 mL of ethanol and 3 mL of water, and sodium hydroxide (186 mg, 4.65 mmol) was added, and stirred at room temperature for 3 h. The reaction solution was concentrated, the pH was adjusted to be acidic with dilute hydrochloric acid, extracted with ethyl acetate, and the organic phase was washed with saturated brine, dried and concentrated to obtain crude compound 18-5 (white solid, 400 mg).

[0157] (5) Compound 18-5 (400 mg, 1.36 mmol) was dissolved in 15 mL of dichloromethane solution, and oxalyl chloride (345 mg, 2.72 mmol) and 2 drops of DMF were added at 0 °C, and stirred at room temperature for 1 h. Then the reaction was placed in a dry ice bath, and compound 18-6 (260 mg, 1.09 mmol) and triethylamine (412 mg, 4.08 mmol) were added, and the reaction was carried out for 30 min, and LCMS was used to monitor the completion of the reaction. The reaction solution was concentrated, and the residue was purified by column chromatography to obtain compound 18 (EA / MeOH = 8 / 1, 100 mg, 14%, yellow powder).

[0158] 3. Synthesis of compound 21

[0159] (1) Compound 21-1 (3 g, 14.77 mmol) was dissolved in 30 ml DMF at room temperature, NIS (3.52 g, 15.66 mmol) was added, and the reaction was carried out at 70 °C for 4 h. LCMS was used to monitor the completion of the reaction. The reaction solution was diluted with water, and the aqueous phase was extracted with ethyl acetate. The organic phase was washed with saturated brine, dried and concentrated. The residue was purified by column chromatography (EA / PE = 1 / 5) to obtain compound 21-2 (3.5 g, 72.9%) as a white solid.

[0160] (2) Compound 21-2 (3.5 g, 10.64 mmol) was dissolved in 30 mL DMF under nitrogen atmosphere, methyl fluorosulfonyl difluoroacetate (6.13 g, 31.91 mmol), HMPA (1.91 g, 10.64 mmol) and cuprous iodide (2.03 g, 10.64 mmol) were added, and the reaction was carried out at 70 °C for 12 h. LCMS was used to monitor the completion of the reaction. The reaction solution was diluted with water, and the aqueous phase was extracted with ethyl acetate. The organic phase was washed with saturated brine, dried and concentrated. The residue was purified by column chromatography (EA / PE = 1 / 5) to obtain compound 21-3 (2.2 g, 78.5%) as a white solid.

[0161] (3) Compound 21-3 (2.0 g, 7.37 mmol) was dissolved in 40 mL of methanol, ammonium chloride (0.789 g, 14.75 mmol) (dissolved in 40 mL of water) and iron powder (1.23 g, 22.12 mmol) were added, and the reaction was carried out at 80 °C for 4 h. LCMS was used to monitor the completion of the reaction. The reaction solution was filtered with diatomite, and the filtrate was rotary evaporated. The residue was extracted with H2O / EA, and the organic phase was dried and concentrated. The residue was purified by column chromatography (EA / PE = 1 / 2) to obtain compound 21-4 (1.5 g, 84.35%) as a white solid.

[0162] (4) Compound 21-4 (2 g, 8.29 mmol) was dissolved in 30 mL of water, 1 mL of concentrated sulfuric acid was added dropwise, sodium nitrite (0.86 g, 12.44 mmol) (dissolved in 5 mL of water) was added, and the reaction was carried out for 10 min. LCMS was used to monitor the generation of diazonium salt intermediate; potassium iodide (6.8 g, 41.46 mmol) (dissolved in 30 mL of water) was added, and the reaction was carried out at 0 °C for 2 h. LCMS was used to monitor the completion of the reaction. The reaction solution was poured into ice water to adjust the pH to 10, and then extracted with EA. The organic phase was dried and concentrated. The residue was purified by column chromatography (EA / PE = 1 / 5) to obtain compound 21-5 (1.5 g, 51.38%) as a light yellow solid.

[0163] (5) Compound 21-5 (1.5 g, 4.26 mmol) was dissolved in 50 mL of dioxane, cesium carbonate (4.16 g, 12.78 mmol), dimethyl malonate (1.4 g, 10.65 mmol), cuprous iodide (0.82 g, 4.26 mmol) and picolinic acid (0.79 g, 6.39 mmol) were added, and the mixture was reacted at 90 °C for 8 h under a nitrogen atmosphere. The reaction was monitored by LCMS. The reaction solution was suction filtered with celite, and the filtrate was dried and concentrated. The residue was purified by column chromatography (EA / PE = 1 / 4) to obtain compound 21-6 (1.2 g, 79.06%) as a white solid.

[0164] (6) Compound 21-6 (2 g, 5.61 mmol) was dissolved in 20 mL of methanol, and sodium hydroxide (0.89 g, 22.45 mmol) dissolved in 20 mL of water was added, and the mixture was reacted at room temperature for 4 h. The reaction was monitored by LCMS. After the reaction solution was diluted with water, it was extracted with ethyl acetate, and the aqueous phase was collected. The pH was adjusted to 2, and the reaction solution was extracted with EA. The organic phase was collected, dried and concentrated to obtain compound 21-7 (1.5 g, 81.44%) as a white solid.

[0165] (7) Compound 21-7 (0.4 g, 1.22 mmol) was dissolved in 10 mL of DCM, and 0.5 mL of oxalyl chloride and 2 drops of DMF were added. The reaction was monitored by LCMS, and the main peak of the product was obtained. The reaction solution was transferred to -45 °C, and the raw material 6-5 was dissolved in 5 mL of DCM. The solution was slowly added to the reaction system, and triethylamine was added to adjust the pH to 10. The reaction was monitored by LCMS, and the reaction was complete after 1 h. The reaction solution was concentrated and purified by column chromatography (EA / PE = 1 / 5) to obtain compound 21 (0.2 g, 30.55%) as a yellow solid.

[0166] 4. Synthesis of compound 23

[0167] (1) Compound 23-1 (12.91 g, 40.59 mmol) was dissolved in 90 mL of ethanol, and aqueous methylhydrazine (6.41 mL, 121.77 mmol) was added dropwise under an ice water bath, and the mixture was reacted at 60 °C for 3 h. The reaction was complete as shown by LCMS. The reaction solution was concentrated, and the residue was purified by column chromatography (EA / PE = 1 / 1) to obtain compound 23-2 (7.30 g, 59.9%) as a yellow solid.

[0168] (2) Compound 23-2 (7.30 g, 24.33 mmol) was dissolved in 50 ml of phosphorus oxychloride, and reacted at 90°C for 6 h. LCMS showed that the reaction was complete. The reaction solution was concentrated to remove phosphorus oxychloride, water was added for dilution, and the aqueous phase was extracted with ethyl acetate. The organic phase was washed with saturated brine, dried and concentrated. The residue was purified by column chromatography (EA / PE = 1 / 10) to obtain compound 23-3 (1.80 g, 23.2%) in the form of a yellow solid.

[0169] (3) Compound 23-3 (1.80 g, 5.66 mmol) was dissolved in 50 ml of 1,4-dioxane, and cesium carbonate (3.68 g, 11.32 mmol), dimethyl malonate (1.86 g, 14.15 mmol), cuprous iodide (1.07 g, 5.66 mmol) and picolinic acid (1.04 g, 8.49 mmol) were sequentially added under a nitrogen atmosphere, and reacted at 90°C for 8 h. LCMS showed that the reaction was complete. The reaction solution was concentrated to remove 1,4-dioxane, and the crude product was added to water and ethyl acetate for dilution. The organic phase was washed with saturated brine, dried and concentrated. The residue was purified by column chromatography (EA / PE = 1 / 4) to obtain compound 23-4 (1.79 g, 98.2%) in the form of a white solid.

[0170] (4) Compound 23-4 (1.79 g, 5.56 mmol) was dissolved in 20 mL of methanol, and 20 ml of an aqueous sodium hydroxide solution (0.89 g, 22.24 mmol) was added dropwise, and reacted at room temperature for 4 h. LCMS showed that the reaction was complete. The reaction solution was added to water and ethyl acetate for dilution, and the aqueous phase was collected and adjusted to be acidic. The aqueous phase was extracted with ethyl acetate, and the organic phase was washed with saturated brine, dried and concentrated to obtain compound 23-5 (1.54 g, 95.2%) in the form of a white solid.

[0171] (5) Compound 23-5 (1.54 g, 5.24 mmol) was dissolved in 15 mL of dichloromethane, and oxalyl chloride (1.30 ml, 10.48 mmol) and a catalytic amount of DMF were added, and reacted at room temperature for 30 min. LCMS showed that the main peak of the product was controlled. The reaction solution was transferred to -45°C, and intermediate 6-5 (1.25 g, 5.24 mmol) was dissolved in 5 ml of dichloromethane, and slowly added dropwise to the above reaction system at -45°C. Triethylamine (2.11 g, 20.96 mmol) was added dropwise, and the reaction was controlled at -45°C for 1 h. LCMS showed that the reaction was complete. The reaction solution was added to water and dichloromethane for dilution, and the organic phase was washed with saturated brine, dried and concentrated. The residue was purified by column chromatography (EA / PE = 1 / 5) to obtain compound 23 (884 mg, 1.78 mmol) in the form of a white solid.

[0172] Biological activity evaluation:

[0173] The original drug was dissolved in acetone, and the drug solution was diluted to a gradient dose with distilled water. The test insects (Spodoptera exigua, Mythimna separata, Helicoverpa armigera, Chilo suppressalis, Spodoptera exigua) with consistent physiological conditions were selected and placed in disposable transparent boxes, 10 insects with consistent growth were introduced into each box, and the host plant leaves (corn leaves) were placed in the box. Then a spray tower was used for spraying, and the lid was tightly covered after spraying. The process was repeated 3 times, and the highest dose of acetone solution was used as a control. The test insects treated with the drug were placed in the treatment room under normal feeding conditions. The number of dead insects after 48 h was checked, and the mortality rate was calculated according to the formula: mortality rate (%) = (number of dead insects / number of test insects) * 100. The representative experimental results are shown in Table 2.

[0174] Table 2 Insecticidal test results Note: N represents no data, and control compound A:

[0175] At the same time, through many tests, it is found that the compounds and compositions described in the present application have good control activity on agricultural pests such as Lepidoptera (e.g. corn borer, Chilo suppressalis, Plutella xylostella, Helicoverpa armigera, Spodoptera exigua, cotton bollworm, Spodoptera exigua, Mythimna separata, etc.), Homoptera (e.g. cotton aphid, radish aphid, pea aphid, peanut aphid, green plant bug, etc.), Acarina (e.g. two-spotted spider mite, acarid, Turkey mite, etc.), Diptera (e.g. Allium odonata, etc.), Coleoptera (e.g. yellow curve jumping beetle, small ape leaf beetle, etc.), and Thripidae (e.g. palm thrips, onion thrips, tobacco thrips, etc.), as well as Blattidae (e.g. white ant, cockroach, etc.), Muscidae (e.g. fly, mosquito, etc.) and other health pests. Not only have the characteristics of broad-spectrum, high efficiency, strong systemicity, etc., but also can 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, Q1 and Q2 independently represent O or S; X represents a cyano group, a cyanoalkyl group, an aryl group or a heterocyclic group; Y represents hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, -(CO)R9, -(CO)OR9, heterocyclic or aryl; the "alkyl", "alkenyl", "alkynyl" are optionally selected from halogen, -OR9, -S(O) n is substituted by at least one of R9, -(CO)R9, -(CO)OR9, cycloalkyl, heterocyclic or aryl; Z1, Z2, R1, R2, R3, R4, R5, R6, R7, and R8 independently represent hydrogen, halogen, cyano, nitro, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heterocyclic, -OR9, -(CO)R9, -(CO)OR9, -(CO)N(R9)2, -S(O) n R9 or -N(R9)2, the alkyl, alkenyl or alkynyl group is optionally selected from halogen, cycloalkyl, aryl, heterocyclic group, -OR9, -(CO)OR9, -S(O) n is substituted by at least one group in R9 or -N(R9)2; n is 0, 1, or 2; R9 each independently represents hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heterocyclyl or heterocyclylalkyl, wherein the alkyl, alkenyl or alkynyl group is optionally substituted by at least one group selected from halogen or alkoxy; The aforementioned "cycloalkyl", "heterocyclyl" or "aryl" is optionally selected from oxo, halogen, cyano, nitro, alkyl, alkenyl, alkynyl, cycloalkyl, haloalkyl, haloalkenyl, haloalkynyl, -OR 10 、-SR 10 、-(CO)R 10 、-(CO)OR 10 、-(CO)N(R 10 )2、-(CS)N(R 10 )2、-(SO)R 10 or -(SO2)R 10 or two adjacent carbon atoms on the ring form a condensed ring with unsubstituted or halogen-substituted -OCH2O-, -CH2CH2CH2O- or -CH=CHCH=CH-; or a saturated carbon atom on the ring is connected to both ends of unsubstituted or halogen-substituted -OCH2CH2O- to form a ring structure; R 10 Each independently represents hydrogen, alkyl, haloalkyl, phenyl or phenyl 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; Y represents hydrogen, C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, C3-C8 cycloalkyl, -(CO)R9, -(CO)OR9, heterocyclyl or aryl; the "C1-C8 alkyl", "C2-C8 alkenyl", "C2-C8 alkynyl" are optionally selected from halogen, -OR9, -S(O) n is substituted by at least one of R9, -(CO)R9, -(CO)OR9, C3-C8 cycloalkyl, heterocyclic or aryl; Z1, Z2, R1, R2, R3, R4, R5, R6, R7, and R8 independently represent hydrogen, halogen, cyano, nitro, C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, C3-C8 cycloalkyl, aryl, heterocyclic group, -OR9, -(CO)R9, -(CO)OR9, -(CO)N(R9)2, -S(O) n R9 or -N(R9)2, the C1-C8 alkyl, C2-C8 alkenyl or C2-C8 alkynyl is optionally selected from halogen, C3-C8 cycloalkyl, aryl, heterocyclyl, -OR9, -(CO)OR9, -S(O) n is substituted by at least one group in R9 or -N(R9)2; R9 each independently represents hydrogen, C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, C3-C8 cycloalkyl, C3-C8 cycloalkylC1-C8 alkyl, aryl, arylC1-C8 alkyl, heterocyclyl or heterocyclylC1-C8 alkyl, wherein the C1-C8 alkyl, C2-C8 alkenyl or C2-C8 alkynyl is optionally substituted by at least one group selected from halogen or C1-C8 alkoxy; The aforementioned "C3-C8 cycloalkyl", "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, -OR 10 、-SR 10 、-(CO)R 10 、-(CO)OR 10 、-(CO)N(R 10 )2、-(CS)N(R 10 )2、-(SO)R 10 or -(SO2)R 10 or two adjacent carbon atoms on the ring form a condensed ring with unsubstituted or halogen-substituted -OCH2O-, -CH2CH2CH2O- or -CH=CHCH=CH-; or a saturated carbon atom on the ring is connected to both ends of unsubstituted or halogen-substituted -OCH2CH2O- to form a ring structure; R 10 Each independently represents hydrogen, C1-C8 alkyl, halogenated C1-C8 alkyl, phenyl or phenyl 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; Y represents hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, -(CO)R9, -(CO)OR9, heterocyclyl or aryl; the "C1-C6 alkyl", "C2-C6 alkenyl", "C2-C6 alkynyl" are optionally selected from halogen, -OR9, -S(O) n is substituted by at least one of R9, -(CO)R9, -(CO)OR9, C3-C6 cycloalkyl, heterocyclic or aryl; Z1, Z2, R1, R2, R3, R4, R5, R6, R7, and R8 independently represent hydrogen, halogen, cyano, nitro, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, aryl, heterocyclic group, -OR9, -(CO)R9, -(CO)OR9, -(CO)N(R9)2, -S(O) n R9 or -N(R9)2, the C1-C6 alkyl, C2-C6 alkenyl or C2-C6 alkynyl is optionally selected from halogen, C3-C6 cycloalkyl, aryl, heterocyclic group, -OR9, -(CO)OR9, -S(O) n is substituted by at least one group in R9 or -N(R9)2; R9 each independently represents hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C3-C6 cycloalkylC1-C6 alkyl, aryl, arylC1-C6 alkyl, heterocyclyl or heterocyclylC1-C6 alkyl, wherein the C1-C6 alkyl, C2-C6 alkenyl or C2-C6 alkynyl is optionally substituted by at least one group selected from halogen or C1-C6 alkoxy; The aforementioned "C3-C6 cycloalkyl", "heterocyclyl" or "aryl" is optionally selected from oxo, halogen, cyano, nitro, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, halogenated C1-C6 alkyl, halogenated C2-C6 alkenyl, halogenated C2-C6 alkynyl, -OR 10 、-SR 10 、-(CO)R 10 、-(CO)OR 10 、-(CO)N(R 10 )2、-(CS)N(R 10 )2、-(SO)R 10 or -(SO2)R 10 or two adjacent carbon atoms on the ring form a condensed ring with unsubstituted or halogen-substituted -OCH2O-, -CH2CH2CH2O- or -CH=CHCH=CH-; or a saturated carbon atom on the ring is connected to both ends of unsubstituted or halogen-substituted -OCH2CH2O- to form a ring structure; R 10 Each independently represents hydrogen, C1-C6 alkyl, halo-C1-C6 alkyl, phenyl or phenyl 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, 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, Y, Z1, Z2, Q1, Q2, R1, R2, R3, R4, R5, R6, R7, and R8 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. 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.

7. 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 in controlling pests.

8. An intermediate, as shown in formula II of claim 4.

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