Mesoion pyrimidinium compound and application thereof

Abstract

The invention belongs to the technical field of pesticides, and particularly relates to a mesoionic pyrimidinium compound, and an N-oxide or salt and application thereof. The compound is shown as a general formula I, wherein Q1 and Q2 respectively and independently represent O or S; x represents a cyano group, a cyano alkyl group, an aryl group or a heterocyclic group; y represents hydrogen, an alkyl group, an alkenyl group, an alkynyl group or the like; and Z1, Z2, R1, R2, R3, R4, R5, R6, R7 and R8 independently represent hydrogen, halogen, cyano, nitro, alkyl and the like. The compound has an excellent prevention and treatment effect on pests such as spodoptera frugiperda, armyworm and prodenia litura.

Description

Technical Field

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

[0002] In recent years, due to the long-term use of pest control agents such as insecticides, pests and diseases have acquired resistance, making them difficult to control with existing insecticides. Furthermore, some known pest control agents are highly toxic, or some damage ecosystems through their long-term residual properties. Despite the numerous known insecticides, such as those disclosed in WO2011017342A2 and WO2009099929A1, there remains a need to develop new pest control agents with low toxicity and low residual properties. Summary of the Invention

[0003] In order to solve the above problems existing in the prior art, the present invention provides a mesoionic pyrimidinium compound, its N-oxide or salt, which has excellent control effects on pests such as fall armyworm, armyworm, and Spodoptera litura.

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

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

[0006]

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

[0008] X represents a cyano group, a cyanoalkyl group, an aryl group or a heterocyclic group;

[0009] Y represents hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, -(CO)R9, -(CO)OR9, heterocyclic or aryl; the "alkyl", "alkenyl" and "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;

[0010] 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;

[0011] n is 0, 1, or 2;

[0012] 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;

[0013] 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;

[0014] 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.

[0015] In one embodiment, X represents a cyano group, a cyano C1-C8 alkyl group, an aryl group or a heterocyclic group;

[0016] 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;

[0017] 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;

[0018] 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;

[0019] 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;

[0020] 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.

[0021] In one embodiment, X represents a cyano group, a cyano C1-C6 alkyl group, an aryl group or a heterocyclic group;

[0022] Y represents hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, -(CO)R9, -(CO)OR9, heterocyclic 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;

[0023] 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;

[0024] 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;

[0025] 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 10or 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;

[0026] R 10 Each independently represents hydrogen, C1-C6 alkyl, halo-substituted C1-C6 alkyl, phenyl or phenyl substituted by at least one group selected from halogen, cyano, nitro, C1-C6 alkyl, halo-substituted C1-C6 alkyl, C1-C6 alkoxycarbonyl, C1-C6 alkylthio, C1-C6 alkylsulfonyl, C1-C6 alkoxy or halo-substituted C1-C6 alkoxy.

[0027] In the definitions of the compounds represented by the above general formula and in all the following structural formulas, the technical terms used, whether used alone or in compound terms, represent the following substituents: Alkyl groups having more than two carbon atoms may be straight-chain or branched. For example, in the compound term "cycloalkylalkyl," the alkyl group may be -CH2-, -CH2CH2-, -CH(CH3)-, -C(CH3)2-, etc. Alkyl groups include, for example, C1 alkyl-methyl; C2 alkyl-ethyl; C3 alkyl-propyl, such as n-propyl or isopropyl; C4 alkyl-butyl, such as n-butyl, isobutyl, tert-butyl, or 2-butyl; C5 alkyl-pentyl, such as n-pentyl; and C6 alkyl-hexyl, such as n-hexyl, isohexyl, and 1,3-dimethylbutyl. Similarly, alkenyl is, for example, vinyl, allyl, 1-methylprop-2-ene-1-yl, 2-methylprop-2-ene-1-yl, but-2-ene-1-yl, but-3-ene-1-yl, 1-methylbut-3-ene-1-yl and 1-methylbut-2-ene-1-yl. Alkynyl is, for example, ethynyl, propargyl, but-2-yn-1-yl, but-3-yn-1-yl, 1-methylbut-3-yn-1-yl. Multiple bonds can be at any position of each unsaturated group. Cycloalkyl is a carbocyclic saturated ring system with, for example, three to six carbon atoms, such as cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl. Similarly, cycloalkenyl is a monocyclic alkenyl with, for example, three to six carbocyclic ring members, such as cyclopropenyl, cyclobutenyl, cyclopentenyl and cyclohexenyl, wherein double bonds can be at any position. Halogen is fluorine, chlorine, bromine or iodine.

[0028] Unless otherwise specified, the "aryl" mentioned in the present invention includes but is not limited to phenyl, naphthyl, The "heterocyclic group" includes but is not limited to saturated or unsaturated non-aromatic cyclic groups etc., and also include but are not limited to heteroaryl, i.e. an aromatic cyclic group containing, for example, 3 to 6 ring atoms and optionally fused to a benzo ring, wherein 1 to 4 (e.g. 1, 2, 3 or 4) heteroatoms in the ring atoms are selected from oxygen, nitrogen and sulfur, for example

[0029] The term "optional" or "optionally" means that the subsequently described event or circumstance may or may not occur, and that the description includes instances where the event or circumstance occurs and instances where the event or circumstance does not occur. For example, the term "optionally substituted with" means that the specified atom or group is unsubstituted or substituted with one or more substituents. If a group is substituted with a group, this should be understood to mean that the group is substituted with one or more identical or different groups selected from those mentioned. In addition, identical or different substitution characters contained in identical or different substituents are independently selected and may be the same or different. The same applies to ring systems formed from different atoms and units. At the same time, the scope of the claims will exclude compounds that are known to those skilled in the art to be chemically unstable under standard conditions.

[0030] In addition, unless otherwise specified, the term "substituted by at least one group" as used herein refers to being substituted by 1, 2, 3, 4 or 5 groups; groups (including heterocyclic groups, aryl groups, etc.) without a specific connection position can be connected at any position, including the position connected to C or N; if it is substituted, the substituent can also be substituted at any position as long as it complies with the chemical bond connection rules. For example, a heteroaryl group substituted by 1 methyl group Can represent wait.

[0031] If various functional groups are present, the present invention also includes any keto and enol tautomeric forms and mixtures and salts thereof.

[0032] Stereoisomers can be obtained from the mixture obtained in the preparation by optical resolution. Stereoisomers can also be selectively prepared by using stereoselective reactions and optically active starting materials and / or auxiliary agents. For optical resolution, conventional methods (see Textbooks of Stereochemistry) can usually be used, such as the following methods for separating the mixture into diastereomers, such as physical methods, such as crystallization, chromatography, especially column chromatography and high pressure liquid chromatography, optionally distillation methods under reduced pressure, extraction methods and other methods, usually using chromatographic separation on a chiral solid phase, which can separate the residual mixture of enantiomeric structures. Suitable for preparation or for industrial scale is such a method, such as crystallization of diastereomeric salts, which can be obtained from compounds using optically active acids, and if an acidic group is present, optically active bases can be used as needed.

[0033] Another embodiment of the present application is a method for preparing the mesoionic pyrimidinium compound, its N-oxide or salt, comprising the following steps:

[0034] 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:

[0035]

[0036] 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 defined as above.

[0037] In one embodiment, the reaction is carried out in the presence of a base and a solvent.

[0038] In a specific embodiment, the base is selected from at least one of an inorganic base (such as NaH, KH, NaOH, KOH, K2CO3, Na2CO3, Cs2CO3, KF, CsF, etc.) or an organic base (such as pyrazole, triethylamine, N,N-diisopropylethylamine, pyridine, DIEA, potassium trimethylsilanolate, AcOK, AcONa, MeONa, EtONa, t-BuONa, t-BuOK, etc.).

[0039] In one embodiment, the solvent is selected from at least one of DCM, diethyl ether, DMF, tetrahydrofuran, methyltetrahydrofuran, diphenyl ether or dioxane.

[0040] The preparation methods of the compounds of the present invention may refer to WO2011017342A2, WO2009099929A1, etc.

[0041] The present invention also relates to an intermediate, as shown in the above formula II.

[0042] The present invention also relates to the use of the compound of formula I (including all stereoisomers), its N-oxide and salt, and compositions containing them in controlling pests.

[0043] The present invention also provides an insecticidal composition comprising at least one of the compound of formula I, its N-oxide or its salt; in one embodiment, further comprising a formulation adjuvant; in one embodiment, further comprising other active ingredients.

[0044] The present invention provides a method for controlling pests, comprising contacting the pests or their environment with a biologically effective amount of a compound of formula I, an N-oxide or a salt thereof, or the above composition.

[0045] The above-mentioned pest environment is plants, animals or seeds.

[0046] The present invention also provides a method for protecting seeds from invertebrate pests, the method comprising contacting the seeds with a biologically effective amount of a compound of formula I, an N-oxide thereof, or a salt thereof. The present invention also relates to the treated seeds.

[0047] The present invention also provides a composition for protecting animals from invertebrate parasitic pests, comprising a parasiticidally effective amount of a compound of formula I, an N-oxide or a salt thereof and at least one carrier.

[0048] The present invention also provides a method for treating, preventing, inhibiting and / or killing external and / or internal parasites, the method comprising administering to an animal and / or on an animal a parasiticidally effective amount of a compound of formula I, its N-oxide or a salt thereof. The present invention also relates to such a method, wherein a parasiticidally effective amount of a compound of formula I, its N-oxide or a salt thereof is administered to the environment in which the animal lives (e.g., a stable or blanket).

[0049] As used herein, the term "invertebrate pests" includes arthropods, gastropods, and nematodes that are economically important pests. The term "arthropod" includes insects, mites, spiders, scorpions, centipedes, millipedes, pill bugs, and symphylans. The term "gastropod" includes snails, slugs, and other animals of the order Stylommatophora. The term "nematode" refers to an organism of the phylum Nematoda. The term "worm" includes roundworms, heartworms, herbivorous nematodes (Nematoda), flukes (Trematoda), acanthocephala, and tapeworms (Cestoda).

[0050] In the context of the present disclosure, "controlling invertebrate pests" refers to inhibiting the growth of invertebrate pests (including mortality, reduced feeding, and / or mating disruption), and related expressions may be defined similarly.

[0051] The term "agronomy" refers to field crop products such as food and fiber, and includes the growth of corn, soybeans and other legumes, rice, cereals (e.g., wheat, oats, barley, rye, rice, corn), leafy vegetables (e.g., lettuce, cabbage and other vegetable crops), fruiting vegetables (e.g., tomatoes, peppers, eggplant, crucifers and cucurbits), potatoes, sweet potatoes, grapes, cotton, tree fruits (e.g., pome, hard seed and citrus), small fruits (berries, cherries), and other specialty crops (e.g., canola, sunflower, olives).

[0052] The term "non-agricultural" refers to applications other than field crops, such as horticultural crops (e.g., greenhouse plants, nursery plants, or ornamental plants that are not grown in fields), residential structures, agronomic structures, commercial structures, and industrial structures, turf (e.g., pastures, rangelands, golf courses, lawns, athletic fields, etc.), wood products, stored products, agroforestry and vegetation management, public health (i.e., human) and animal health (e.g., domesticated animals such as pets, livestock, and poultry, non-domesticated animals such as wildlife) applications.

[0053] Non-agricultural applications include protecting animals from invertebrate parasitic pests by administering to the animals to be protected a parasiticidally effective (i.e., biologically effective) amount of a compound of the invention (generally in the form of a composition formulated for veterinary use). As used in the present disclosure and claims, the terms "parasiticidal" and "parasiticidal" relate to observed effects on invertebrate parasitic pests to provide protection to animals from pests. Parasiticidal effects generally involve reducing the appearance or activity of target invertebrate parasitic pests. Such effects on pests include necrosis, lethality, slowed growth, reduced mobility or reduced ability to remain on or in a host animal, decreased food intake, and inhibition of reproduction. These effects on invertebrate parasitic pests provide control (including prevention, reduction, or elimination) of parasitic infestations or infections of animals.

[0054] The compounds of Formula I are mesoionic inner salts. "Inner salts," also known in the art as "zwitterions," are electrically neutral molecules, but according to valence bond theory, carry formal positive and negative charges in each valence bond structure between different atoms. Furthermore, the molecular structure of the compounds of Formula I can be represented by the following six valence bond structures:

[0055]

[0056] Each carries a formal positive charge and a negative charge on different atoms. Due to this resonance, compounds of Formula I are also described as "mesoions". Although for the sake of brevity, the molecular structure of Formula I is described as a single valence bond structure herein, this specific valence bond structure should be understood as a representative of all six valence bond structures connected within the molecules of compounds of Formula I. Therefore, unless otherwise indicated, reference to Formula I herein relates to all six applicable valence bond structures and other (e.g., molecular orbital theory) structures.

[0057] The compounds of the present invention may exist in the form of one or more stereoisomers. Various stereoisomers include enantiomers, diastereomers, atropisomers, and geometric isomers. Those skilled in the art will appreciate that when one stereoisomer is enriched relative to the other stereoisomers or when it is separated from the other stereoisomers, it may be more active and / or may exhibit beneficial effects. Additionally, those skilled in the art will appreciate how to separate, enrich, and / or selectively prepare the stereoisomers. The compounds of the present invention may exist as mixtures of stereoisomers, as individual stereoisomers, or as optically active forms.

[0058] Due to the limited bond rotation caused by steric hindrance, the compounds of the present invention may exist as one or more conformers. The present invention includes mixtures of conformers. In addition, the present invention includes compounds enriched in one conformer relative to other conformers.

[0059] The compounds selected from Formula I (including all stereoisomers thereof, their N-oxides and salts thereof) generally exist in more than one form, so that Formula I includes all crystalline and amorphous forms of compounds represented by Formula I. Amorphous forms include solid embodiments such as waxes and gums, as well as liquid embodiments such as solutions and melts. Crystalline forms include embodiments representing essentially single crystal forms, and embodiments representing mixtures of polymorphs (i.e., different crystal forms). The term "polymorph" refers to a specific crystalline form of a chemical compound that can crystallize in different crystalline forms, which have different molecular arrangements and / or conformations in the crystal lattice. Although polymorphs may have the same chemical composition, they may also have different compositions, which should be attributed to the presence or absence of co-crystallized water or other molecules that are weakly or strongly bound to the crystal lattice. Polymorphs may have different chemical, physical and biological properties, such as crystal shape, density, hardness, color, chemical stability, melting point, hygroscopicity, suspendability, solubility and bioavailability. Those skilled in the art will appreciate that a polymorph of a compound represented by Formula I may exhibit beneficial effects (e.g., suitability for preparing a useful formulation, improved biological performance) relative to another polymorph or mixture of polymorphs of the same compound represented by Formula I. The preparation and isolation of a specific polymorph of a compound represented by Formula I may be achieved by methods known to those skilled in the art, including, for example, crystallization using a selected solvent and temperature.

[0060] Those skilled in the art will appreciate that not all nitrogen-containing heterocycles can form N-oxides, as nitrogen requires an available lone pair of electrons to oxidize to an oxide; those skilled in the art will recognize those nitrogen-containing heterocycles that can form N-oxides. Those skilled in the art will also appreciate that tertiary amines can form N-oxides. Synthetic methods for preparing N-oxides of heterocycles and tertiary amines are well known to those skilled in the art and include oxidation of heterocycles and tertiary amines using peroxyacids such as peracetic acid and 3-m-chloroperbenzoic acid (MCPBA), hydrogen peroxide, alkyl hydroperoxides such as tert-butyl hydroperoxide, sodium perborate, and dioxiranes such as dimethyldioxirane.

[0061] Those skilled in the art recognize that, because the salt of chemical compound is in balance with their corresponding non-salt form under environment and physiological conditions, therefore salt and non-salt form have common biological use.Therefore, the various salts of formula I compound can be used for preventing and treating invertebrate pests and animal parasites (that is, being applicable to animal health purposes).The salt of formula I compound includes the acid addition salt formed with inorganic acid or organic acid, and the acid is such as hydrobromic acid, hydrochloric acid, nitric acid, phosphoric acid, sulfuric acid, acetic acid, butyric acid, fumaric acid, lactic acid, maleic acid, malonic acid, oxalic acid, propionic acid, salicylic acid, tartaric acid, 4-toluenesulfonic acid or valeric acid.When formula I compound comprises acidic part such as carboxylic acid or phenol, salt also includes those formed with organic base or inorganic base such as pyridine, triethylamine or ammonia or sodium, potassium, lithium, calcium, magnesium or barium amide, hydride, hydroxide or carbonate.Therefore, the present invention includes and is selected from formula I compound, their N-oxide and salt.

[0062] Embodiments of the invention as described in the Summary of the Invention include those described below. In the following embodiments, Formula I includes stereoisomers, N-oxides, and salts thereof, and unless otherwise defined in the embodiments, descriptions referring to "compounds of Formula I" include the definitions of designated substituents in the Summary of the Invention.

[0063] Notably, the compounds of the present invention are characterized by favorable metabolism and / or soil residue patterns and exhibit broad-spectrum control activity against agronomic and non-agronomic invertebrate pests.

[0064] Of particular note, due to the broad spectrum of invertebrate pest control and economic importance, protecting crops from damage or injury by invertebrate pests is an embodiment of the present invention. Due to the advantageous intraplant transfer or systemic properties of the compounds of the present invention, they also protect leaves or other plant parts that have not come into direct contact with the compounds of formula I or compositions comprising said compounds.

[0065] Also noteworthy as embodiments of the present invention are compositions comprising a compound of any of the foregoing embodiments, as well as any other embodiments described herein, and any combination thereof, and at least one additional component and / or formulation adjuvant and / or at least one active ingredient (i.e., a biologically active compound or agent), the additional component being selected from a surfactant, a solid diluent, and a liquid diluent.

[0066] Embodiments of the present invention also include compositions for protecting animals, comprising a compound of any of the preceding embodiments (ie, in a parasiticidally effective amount) and a carrier.

[0067] Embodiments of the present invention also include methods of controlling invertebrate pests, comprising contacting the invertebrate pest or its environment with a biologically effective amount of a compound of any of the preceding embodiments (e.g., a composition as described herein). Of particular note are methods for protecting animals, comprising administering to the animal a parasiticidally effective amount of a compound of any of the preceding embodiments (e.g., a composition as described herein).

[0068] Embodiments of the present invention also include compositions comprising a compound of any of the preceding embodiments in the form of a liquid soil drench formulation. Embodiments of the present invention also include methods of controlling invertebrate pests comprising contacting soil with a liquid composition comprising a biologically effective amount of a compound of any of the preceding embodiments as a soil drench.

[0069] Embodiments of the present invention also include spray compositions for controlling invertebrate pests, comprising a compound of any of the preceding embodiments (i.e., in a biologically effective amount) and a propellant. Embodiments of the present invention also include bait compositions for controlling invertebrate pests, comprising a compound of any of the preceding embodiments (i.e., in a biologically effective amount), one or more food materials, an optional attractant, and an optional wetting agent. Embodiments of the present invention also include devices for controlling invertebrate pests, comprising the bait composition and a housing adapted to contain the bait composition, wherein the housing has at least one opening sized to allow passage of an invertebrate pest so that the invertebrate pest can access the bait composition from a location external to the housing, and wherein the housing is further adapted for placement in or near a location of potential or known invertebrate pest activity.

[0070] Embodiments of the present invention also include methods for controlling invertebrate pests, comprising contacting the invertebrate pest or its environment with a biologically effective amount of a compound of Formula I, an N-oxide thereof, or a salt thereof, such as a composition described herein, with the proviso that the method is not a method of pharmaceutical treatment of the human or animal body by therapy.

[0071] The present invention also relates to such methods, wherein the invertebrate parasitic pest or its environment is contacted with a composition comprising a biologically effective amount of a compound of formula I, an N-oxide thereof or a salt thereof, and further comprising additional components selected from surfactants, solid diluents and liquid diluents, and optionally comprising a biologically effective amount of at least one active ingredient (i.e., a biologically active compound or agent), with the proviso that the method is not a method of pharmaceutical treatment of the human or animal body by therapy.

[0072] 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.

[0073] 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.

[0074] 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.

[0075] 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.

[0076] The formulations will generally contain an effective amount of active ingredient, diluent, and surfactant, in the approximate ranges, totaling 100% by weight.

[0077] 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.

[0078] 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, glyceryl triacetate, 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

[0079] 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.

[0080] Surfactants can be classified as nonionic, anionic or cationic surfactants. Nonionic surfactants that can be used in the present composition include, but are not limited to: alcohol alkoxylates, such as alcohol alkoxylates based on natural and synthetic alcohols (which are branched or linear) and prepared from alcohols and ethylene oxide, propylene oxide, butylene oxide or mixtures thereof; amine ethoxylates, alkanolamides and ethoxylated alkanolamides; alkoxylated triglycerides, such as ethoxylated soybean oil, castor oil and rapeseed oil; alkylphenol alkoxylates, such as octylphenol ethoxylate, nonylphenol ethoxylate, dinonylphenol ethoxylate and dodecylphenol ethoxylate (prepared from phenol and ethylene oxide, propylene oxide, butylene oxide or mixtures thereof); block polymers prepared from ethylene oxide or propylene oxide and reverse block polymers in which the terminal blocks are prepared from propylene oxide; ethoxylated propylene oxide; ethoxylated fatty acids; ethoxylated fatty esters and oils; ethoxylated methyl esters; ethoxylated tristyrylphenols (including those prepared from ethylene oxide, propylene oxide, butylene oxide, or mixtures thereof); fatty acid esters, glycerol esters, lanolin-based derivatives, polyethoxylated esters, such as polyethoxylated sorbitan fatty acid esters, polyethoxylated sorbitan fatty acid esters, and polyethoxylated glycerol fatty acid esters; other sorbitan derivatives, such as sorbitan esters; polymeric surfactants, such as random copolymers, block copolymers, alkyd PEG (polyethylene glycol) resins, graft or comb polymers, and star polymers; polyethylene glycol (PEG); polyethylene glycol fatty acid esters; silicone-based surfactants; and sugar derivatives, such as sucrose esters, alkyl polyglucosides, and alkyl polysaccharides.

[0081] Useful anionic surfactants include, but are not limited to, alkylarylsulfonic acids and their salts; carboxylated alcohol or alkylphenol ethoxylates; diphenylsulfonate derivatives; lignin and lignin derivatives, such as lignin sulfonates; maleic acid or succinic acid or their anhydrides; olefin sulfonates; phosphates, such as the phosphates of alcohol alkoxylates, the phosphates of alkylphenol alkoxylates, and the phosphates of styrylphenol ethoxylates; protein-based surfactants; sarcosine derivatives; styrylphenol ether sulfates; sulfates and sulfonates of oils and fatty acids; sulfates and sulfonates of ethoxylated alkylphenols; sulfates of alcohols; sulfates of ethoxylated alcohols; sulfonates of amines and amides, such as N,N-alkyltaurates; sulfonates of benzene, isopropylbenzene, toluene, xylene, and dodecylbenzene and tridecylbenzene; sulfonates of condensed naphthalene; sulfonates of naphthalene and alkylnaphthalene; sulfonates of petroleum fractions; sulfosuccinamates; and sulfosuccinates and their derivatives, such as dialkylsulfosuccinates.

[0082] Useful cationic surfactants include, but are not limited to, amides and ethoxylated amides; amines such as N-alkylpropylenediamine, tripropylenetriamine, and dipropylenetetramine, as well as ethoxylated amines, ethoxylated diamines, and propoxylated amines (made from amines and ethylene oxide, propylene oxide, butylene oxide, or mixtures thereof); amine salts such as amine acetates and diamine salts; quaternary ammonium salts such as quaternary ammonium salts, ethoxylated quaternary ammonium salts, and diquaternary ammonium salts; and amine oxides such as alkyldimethylamine oxides and di-(2-hydroxyethyl)-alkylamine oxides.

[0083] Also useful in the compositions of the present invention are mixtures of nonionic and anionic surfactants, or mixtures of nonionic and cationic surfactants.

[0084] The compositions of the present invention may also contain formulation aids and additives known to those skilled in the art as formulation aids (some of which may also be considered to function as solid diluents, liquid diluents, or surfactants). Such formulation aids and additives may control: pH (buffers), foaming during processing (defoamers, such as polyorganosiloxanes), settling of the active ingredient (suspending agents), viscosity (thixotropic thickeners), microbial growth in the container (antimicrobials), product freezing (antifreeze agents), color (dye / pigment dispersions), elution (film formers or binders), evaporation (evaporation inhibitors), and other formulation properties. Film formers include, for example, polyvinyl acetate, polyvinyl acetate copolymers, polyvinyl pyrrolidone-vinyl acetate copolymers, polyvinyl alcohol, polyvinyl alcohol copolymers, and waxes.

[0085] The compound of formula I and any other active ingredient are typically incorporated into the composition of the present invention by dissolving the active ingredient in a solvent or by grinding the active ingredient in a liquid or dry diluent. Solutions, including emulsifiable concentrates, can be prepared by simply mixing the ingredients. If the solvent of the liquid composition to be used as an emulsifiable concentrate is immiscible with water, an emulsifier is typically added to emulsify the solvent containing the active ingredient when diluted with water. A media mill can be used to wet-grind an active ingredient slurry with a particle size of up to 2,000 μm to obtain particles with an average diameter of less than 3 μm. The aqueous slurry can be prepared as a finished suspension concentrate (see, for example, US 3,060,084) or further processed into particles dispersible in water by spray drying. Dry formulations typically require a dry grinding step that produces an average particle size in the range of 2 to 10 μm. Dusts and powders can be prepared by mixing, typically by grinding (e.g., with a hammer mill or fluid energy mill). Granules and pellets can be prepared by spraying the active substance onto a preformed granular carrier or by agglomeration techniques.

[0086] The compounds of the present invention exhibit activity against a broad spectrum of invertebrate pests. These pests include invertebrate pests that inhabit a variety of environments such as plant leaves, roots, soil, harvested crops or other foods, buildings or animal fur. These pests include, for example, invertebrate pests that feed on leaves (including leaves, stems, flowers and fruits), seeds, wood, textile fibers or animal blood or tissues, and these pests damage or harm, for example, growing or storing crops, forest crops, greenhouse crops, ornamental plants, nursery crops, stored foods or fiber products, or housing or other structures or their contents, or are harmful to animal health or public health. Those skilled in the art will appreciate that not all compounds have the same effect on all growth stages of all pests.

[0087] Therefore, these compounds of the present invention and composition can be used for protecting field crops from the infringement of phytophagous invertebrate pests in agronomy, and can also be used for protecting other horticultural crops and plants from the infringement of phytophagous invertebrate pests in non-agronomy.This purpose includes protecting crops and other plants (i.e. agronomy and non-agronomy) that include genetic engineering (i.e. transgenic) or mutagenic modification introduction to provide the genetic material of favorable characteristics. The example of such characteristics includes herbicide resistance, tolerance to phytophagous pests (such as insects, mites, aphids, spiders, nematodes, snails, plant pathogenic fungi, bacteria and viruses), plant growth improvement, enhanced tolerance to unfavorable growth environments (such as high or low temperatures, low soil moisture or high soil moisture, and high salinity), flowering or result improvement, harvest increase, faster maturity, the quality and / or nutritional value of the harvested products are higher, or the storage or processability of the harvested products are improved. Transgenic plants can be modified to express a variety of characteristics. Examples of plants containing traits provided by genetic engineering or mutagenesis include varieties of corn, cotton, soybean, and potato expressing insecticide-resistant Bacillus thuringiensis toxins, e.g. and

[0088] and various herbicide-tolerant corn, cotton, soybean, and rapeseed, e.g.

[0089] and As well as crops expressing N-acetyltransferase (GAT) to provide resistance to glyphosate herbicide, or crops containing HRA genes to provide resistance to herbicides, inhibiting acetolactate synthase (ALS). The compounds and compositions of the present invention can interact synergistically with traits introduced by genetic engineering or mutagenesis to enhance the phenotypic expression or effect of the traits, or enhance the invertebrate pest control efficacy of the compounds and compositions of the present invention. Specifically, the compounds and compositions of the present invention can interact synergistically with the phenotypic expression of proteins or other natural products that are toxic to invertebrate pests to provide a greater than additive control effect on these pests.

[0090] Composition of the present invention can also optionally comprise plant nutrients, for example comprise the fertilizer composition of at least one plant nutrient, described plant nutrient is selected from nitrogen, phosphorus, potassium, sulphur, calcium, magnesium, iron, copper, boron, manganese, zinc and molybdenum.It is noteworthy that the composition comprising at least one fertilizer composition, described fertilizer composition comprises at least one plant nutrient selected from nitrogen, phosphorus, potassium, sulphur, calcium and magnesium.The composition of the present invention that also comprises at least one plant nutrient can be liquid or solid form.It is noteworthy that the solid preparation of granule, stick or tablet form.By compound of the present invention or composition and fertilizer composition and formulation ingredients are mixed together, then by the method such as granulating or extruding, prepare preparation, prepare the solid preparation that comprises fertilizer composition.Alternatively, by solution or suspension of compound of the present invention or composition in volatile solvent is sprayed on the fertilizer composition of previously made size-stable mixture form (for example granule, stick or tablet), then evaporate solvent, make solid preparation.

[0091] Examples of agronomic or non-agronomic invertebrate pests include eggs, larvae and adults of Lepidoptera pests, such as Noctuidae armyworms, caterpillars, loopers and cotton bollworms (e.g. Sesamia inferens Walker, Corn borer,

[0092] (Sesamia nonagrioides Lefebvre), southern armyworm (Spodoptera eridaniaCramer), fall armyworm (Spodoptera frugiperda JESmith), beet armyworm (Spodoptera exigua Hübner), cotton leafworm

[0093] (Spodoptera littoralis Boisduval), yellow-banded armyworm (Spodoptera ornithogalli Guenée), black cutworm

[0094] (Agrotis ipsilon Hufnagel), Mucun Bean Moth (Anticarsia gemmatalis Hübner), Green Fruit Moth

[0095] (Lithophane antennata Walker), Cabbage looper (Barathra brassicae Linnaeus), Soybean looper

[0096] (Pseudoplusiaincludens Walker), cabbage looper (Trichoplusia ni Hübner), tobacco aphid (Heliothis virescens Fabricius)); borers, sheath moths, web-spinning caterpillars, pine cone borer, cabbage worm and leaf cutters from the family Pyralidae (e.g. European corn borer (Ostrinia nubilalis Hübner), navel orange borer (Amyelois transitella Walker), corn root borer (Crambus caliginosellus Clemens), meadow borers (Pyralidae: Pyralinae), such as rice leaf cutter (Herpetogramma licarsisalis Walker), sugarcane two-spotted borer (Chiloinfuscatellus Snellen), tomato borer (Neoleucinodes elegantalis Guenée), rice leaf roller (Cnaphalocrocis medinalis) medinalis), grape leaf roller (Desmia funeralis Hübner), melon borer

[0097] (Diaphania nitidalis Stoll), cabbage grub (Hellula hydralis Guenée), yellow stem borer (Scirpophaga incertulas Walker), early seedling borer (Scirpophaga infuscatellus Snellen), white stem borer (Scirpophaga innotata Walker), top seedling borer (Scirpophaganivella Fabricius), rice stem borer (Chilo polychrysus Meyrick), cabbage caterpillar (Crocidolomia binotalis zeller); leaf rollers of the family Cydiaceae, aphids, seed worms, and fruit borers (such as apple moth (Cydia pomonella Linnaeus), grape berry moth (Cydia spp.

[0098] (Endopiza viteana Clemens), pear borer (Grapholita molesta Busck), apple moth (Cryptophlebia leucotreta Meyrick), citrus borer (Ecdytolophaaurantiana Lima), red-banded moth (Argyrotaenia velutinana Walker), rose-banded leaf roller (Choristoneura rosaceana Harris), apple leaf roller (Epiphyas postvittana Walker), privet moth (Eupoecilia ambiguella Hübner), apple bud roller (Pandemis pyrusana Kearfott), omnivorous leaf roller (Platynota stultana Walsingham), striped fruit leaf roller (Pandemiscerasana Hübner), apple brown leaf roller (Pandemis heparana Denis et Schiffermüller); and many other economically important Lepidoptera (e.g., diamondback moth (Plutella xylostella Linnaeus), red boll cotton

[0099] (Pectinophora gossypiella Saunders), Lymantria dispar Linnaeus, Carposina niponensis Walsingham, Anarsialineatella Zeller, Phthorimaea operculella Zeller, Lithocolletis blancardella Fabricius, Lithocolletis ringoniella Matsumura, Lerodea eufala Edwards, Leucoptera scitella Zeller); eggs, pupae and adults of the order Blattodea, including cockroaches from the families Blattariidae and Blattidae (e.g., Blatta orientalis Linnaeus, Blatta asahinai Mizukubo, Blatta germanica Linnaeus), Brown-banded Cockroach (Supella longipalpa Fabricius), American Cockroach (Periplaneta americana Linnaeus), Brown Cockroach (Periplanetabrunnea Burmeister), Madeira Cockroach (Leucophaea maderae Fabricius); Black-breasted Cockroach (Periplaneta fuliginosa Service), Australian Cockroach (Periplaneta australasiae Fabricius)), lobster cockroach (Nauphoeta cinerea Olivier) and smooth cockroach (Symploce pallens Stephens); eggs, leaf-feeding, fruit-feeding, root-feeding, seed-feeding and vesicle-feeding larvae and adults of the order Coleoptera, including weevils from the families of ... Fahraeus; flea beetles, melon beetles, rootworms, leaf beetles, potato beetles, and leaf miners from the Chrysomelidae family (e.g., Colorado potato beetle (Leptinotarsa ​​decemlineata Say), western corn rootworm (Diabrotica virgifera virgifera LeConte)); beetles and other beetles from the Scarabaeidae family (e.g., Japanese beetle (Popillia japonica Newman), Oriental beetle (Anomala orientalis Waterhouse, Exomala orientalis (Waterhouse) Baraud), northern rhinoceros beetle (Cyclocephala borealis Arrow), southern rhinoceros beetle (Cyclocephala immaculata Olivier or C. Lurida Bland), dung beetles and grubs (Aphodius spp.), black beetle (Ataenius spretulus Haldeman), green beetle (Cotinis nitida Linnaeus), and chestnut velvet beetle.

[0100] (Maladera castanea Arrow), May / June scarab beetles (Phyllophaga spp.), and European scarab beetles (Rhizotrogus majalis Razoumowsky); skin beetles of the family Dermestidae; nematodes of the family Coleoptera; bark beetles of the family Ophiopodidae; and weevils of the family Tenebrionidae.

[0101] In addition, agronomic and non-agronomic pests include: eggs, adults and larvae of the order Dermoptera, including earwigs of the family Earwigs (e.g., European earwigs (Forficula auricularia Linnaeus), black earwigs (Chelisoches morio Fabricius)); eggs, immatures, adults and pupae of the orders Hemiptera and Homoptera, such as blind bugs from the family Miridae, cicadas of the family Cicadidae, leafhoppers (e.g., Empoasca spp.), bed bugs of the family Cimex lectularius Linnaeus), wax cicadas of the families Cercopithecidae and Pachyphyllidae, tree cicadas of the family Membracidae, psyllids of the family Psyllidae, whiteflies of the family Aphididae, aphids of the family Aphididae, root nodule aphids of the family Phylloxeracidae, mealybugs of the family Mealycosidae, scale insects of the families Coccinellidae, Coccidae and Coccidae, web bugs of the family Pentatomidae, stink bugs of the family Pentatomidae, sorghum bugs of the family Pentatomidae (e.g., hairy bug (BlissusleucopterushirtusMontandon) and southern wheat bug (BlissusinsularisBarber)) and other bugs of the family Pentatomidae, cicadas of the family Cicadidae, squash bugs of the family Pseudocycodae, and red bugs and cottonworms of the family Red Pentatomidae.

[0102] Agronomic and non-agronomic pests also include: eggs, larvae, pupae and adults of the order Acarina (acarids), such as spider mites and red mites of the family Tetranychus (e.g., apple spider mite (Panonychus ulmi Koch), two-spotted spider mite (Tetranychus urticae Koch), and McDaniel's spider mite (Tetranychus mcdanieli McGregor); grape short-palped mites of the family Tenuipalpidae (e.g., citrus spider mite (Brevipalpus lewisi McGregor)); rust ticks and bud ticks of the family Mylidae, as well as other leaf-feeding mites and mites of importance in human and animal health, namely, dust mites of the family Epidermophoridae, Demodex mites of the family Demodex, and grain mites of the family Glycyrrhizae; ticks commonly known as hard ticks of the family Ixodidae (e.g., deer tick (Ixodes scapularis Say), Australian paralysis tick

[0103] (Ixodes holocyclus Neumann), American dog tick (Dermacentor variabilis Say), lone star tick

[0104] (Amblyomma americanum Linnaeus) and ticks commonly known as soft ticks in the family Cryptorhynchidae (e.g., Ornithodoros turicata, Argas radiatus); itch mites and scabies in the families Itch, Pyreniformes, and Sarcoptes; eggs, adults, and immatures of Orthoptera, including grasshoppers, locusts, and crickets (e.g., migratory grasshoppers (e.g., Locust sanguineus, Thomas the spp.), American grasshoppers (e.g., Schistocerca americana Drury), Desert Locust

[0105] (Schistocerca gregaria Forskal), migratory locust (Locusta migratoria Linnaeus), dwarf grasshopper

[0106] (Zonocerus spp.), house crickets (Acheta domesticus Linnaeus), mole crickets (e.g., Scapteriscus vicinus Scudder and Scapteriscus borellii Giglio-Tos); eggs, adults, and immatures of Diptera, including leafminers (e.g., Liriomyza spp., such as Liriomyza vegetabilis);

[0107] midges, fruit flies (Tephritidae), eye flies (e.g., black rye flies), dung maggots, common house flies (e.g., houseflies), summer toilet flies (e.g., F. femoralis Stein), stable flies (e.g., stable flies), gadflies, horn flies, blowflies (e.g., Chrysomelidae, Melanophora) and other housefly pests, horse flies (e.g., Tabanus), skin flies (e.g., Gastromys, Mylomys), cow flies (e.g., Hippocampus), deer flies (e.g., Tabanus), sheep tick flies (e.g., Lousefly) and other Brachycera, mosquitoes (e.g., Aedes, Anopheles, Culex), black midges (e.g., Protoschisis, Simuli), clippers, sand flies, sharp-eyed fungus gnats and other Longicorns; eggs, adults, and immatures of Thysanoptera, including onion thrips (Thrips tabaci Lindeman), flower thrips (genus Florothrips), and other leaf-feeding thrips; insect pests of the order Hymenoptera, including ants of the family Formicidae, including Camponotus floridanus Buckley, Camponotus ferrugineus Fabricius, Camponotus pennsylvanicus De Geer, Technomyrmex albipes fr. Smith, big-headed ants (genus Pheidole), and Tapinoma melanocephalum Fabricius; Pharaoh ants

[0108] (Monomorium pharaonis Linnaeus), Small Fire Ant (Wasmannia auropunctata Roger), Fire Ant

[0109] (Solenopsis geminata Fabricius), invasive fire ant (Solenopsis invicta Buren), Argentine ant

[0110] (Iridomyrmex humilis Mayr), Crazy Ant (Paratrechina longicornis Latreille), Pavement Ant

[0111] (Tetramorium caespitum Linnaeus), corn ant (Lasius alienus) Other Hymenoptera include bees (including carpenter bees), hornets, wasps, wasps, and sawflies (Neodiprion genera; Cephus genera); Isoptera include termites (e.g., Macrotermes obesus Rambur), Carpentertermes (e.g., Sandertermes), and Rhinortermes (e.g., Reticulitermes, Coptotermes, Dabieshan Reticulitermes), North American Reticulitermes (Kollar), Western Reticulitermes (Banks), Coptotermes formosanus Shiraki, West Indian Drywood Termites, and the like.

[0112] Incisitermes immigrans Snyder, Cryptotermes brevis Walker, Drywood Termites

[0113] (Incisitermes snyderi Light), southeastern subterranean termite (Reticulitermes virginicus Banks), drywood-chopping termite (Incisitermes minor Hagen), arboreal termites such as the genus Incisitermes and other economically important termites; insect pests of the order Thysanura, such as the silverfish (Lepisma saccharina Linnaeus) and the house silverfish

[0114] (Thermobia domestica Packard); insect pests of the order Trichophaga and includes head lice

[0115] (Pediculus humanus capitis De Geer), body lice (Pediculus humanus Linnaeus), chick feather lice

[0116] (Menacanthus stramineus Nitszch), dog feather lice (Trichodectes canis De Geer), hair lice

[0117] (Goniocotes gallinae De Geer), sheep body louse (Bovicola ovis Schrank), cattle blind louse (Haematopinus eurysternus Nitzsch), long-nosed livestock louse (Linognathus vituli Linnaeus), and other sucking and chewing lice that attack humans and animals; insect pests of the order Siphonaptera, including the oriental rat flea

[0118] (Xenopsylla cheopis Rothschild), cat flea (Ctenocephalides felis Bouche), dog flea

[0119] (Ctenocephalides canis Curtis), chicken flea (Ceratophyllus gallinae Schrank), sucking flea (Echidnophaga gallinacea Westwood), human flea (Pulex irritans Linnaeus) and other fleas that cause pain to mammals and birds. Additional arthropod pests include spiders of the order Araneae, such as the brown recluse spider (Loxosceles reclusa Gertsch & Mulaik) and the black widow spider (Latrodectus mactans Fabricius), and centipedes of the order Scolopendra, such as the centipede (Scutigera coleoptrata Linnaeus).

[0120] Examples of invertebrate pests of stored grain include the larger grain borer (Prostephanus truncatus), the smaller grain borer (Rhyzopertha dominica), the rice weevil (Sitophilus oryzae), the maize weevil (Sitophilus zeamais), the cowpea weevil (Callosobruchus maculatus), the red flour beetle (Tribolium castaneum), the corn weevil (Sitophilus granarius), the Indian meal borer (Plodia interpunctella), the Mediterranean flour weevil (Ephestia kuhniella), and the long-horned or rusty flour beetle (Cryptolestes ferrugineus).

[0121] The compounds of the present invention can be used to control the following lepidopteran pests: (e.g., Alabama argillacea Hübner (clothes moth), Archips argyrospila Walker (fruit leaf roller), A.rosana Linnaeus (European leaf roller), and other species of the genus A.rosana, Chilo suppressalis Walker (rice borer), Cnaphalocrocismedinalis Guenée (rice leaf roller), Crambus caliginosellus Clemens (corn root web caterpillar),

[0122] Crambus teterrellus Zincken (Bluegrass borer), Cydia pomonella Linnaeus (Apple moth), Earias insulana Boisduval (Diamond borer), Earias vittella Fabricius (Emerald bollworm), Helicoverpa armigera Hübner (American bollworm), Helicoverpa zea Boddie (Cotton bollworm), Heliothis virescens Fabricius (Tobacco aphid), Herpetogramma licarsisalis Walker (Meadow borer), Lobesia botrana Denis & Schiffermüller (Grape berry moth),

[0123] Pectinophora gossypiella Saunders (pink bollworm), Phyllocnistis citrella Stainton (citrus leafminer), Pieris brassicae Linnaeus (large cabbage butterfly), Pieris rapae Linnaeus (white moth), Plutella xylostella Linnaeus (diamondback moth), Spodoptera exigua Hübner (beet armyworm), Spodoptera litura Fabricius (spodoptera litura, tea silkworm), Spodoptera frugiperda JESmith (fall armyworm), Trichoplusia ni Hübner (cabbage leafminer), and Tutaabsoluta Meyrick (tomato leafminer); Homoptera: Acyrthosiphon pisum Harris (bean aphid), Aphis craccivora Koch (black bean aphid), Aphis fabae Scopoli (broad bean aphid), Aphis gossypii Glover (cotton aphid, melon aphid), Aphis pomi De Geer (apple aphid), Aphis spiraecola Patch (leaf roller aphid), Aulacorthum solani Kaltenbach (eggplant aphid), Chaetosiphon fragaefolii Cockerell (strawberry aphid), Diuraphis noxia Kurdjumov / Mordvilko (Russian wheat aphid), Dysaphis plantaginea Paaserini (red apple aphid), Eriosoma lanigerum Hausmann (woolly apple aphid), Hyalopterus pruni Geoffroy (peach aphid), Lipaphis erysimi Kaltenbach (carrot aphid), Metopolophium dirhodum Walker (wheat aphid), Macrosiphum euphorbiae Thomas (potato aphid), Myzus persicae Sulzer (myzus persicae, peach aphid), Nasonovia ribisnigri Mosley (lettuce aphid), Pemphigus spp. (root and spherical aphids), Rhopalosiphum maidis Fitch (corn leaf aphid),

[0124] Rhopalosiphum padi Linnaeus (wheat aphid), Schizaphis graminum Rondani (greenbug), Sitobion avenae Fabricius (English grain aphid), Therioaphis maculata Buckton (spotted alfalfa aphid), Toxoptera aurantii Boyer de Fonscolombe (black citrus aphid), and Toxoptera citricida Kirkaldy (brown citrus aphid); Adelges spp. (adelgids); Phylloxera devastatrix Pergande (palm phylloxera);

[0125] Bemisia tabaci Gennadius (tobacco whitefly, sweet potato whitefly), Bemisia argentifolii Bellows & Perring (silverleaf whitefly), Dialeurodes citri Ashmead (citrus whitefly), and

[0126] Trialeurodes vaporariorum Westwood (greenhouse whitefly); Empoasca fabae Harris (potato leafhopper), Laodelphax striatellus Fallen (smaller brown planthopper), Macrosteles quadrilineatus Forbes (two-lined spittlebug), Nephotettix cincticeps Uhler (green leafhopper), Nephotettix nigropictus (Muir) (green leafhopper), Nilaparvata lugens (Stal) (brown planthopper), Peregrinus maidis Ashmead (corn planthopper), Sogatella furcifera Horvath (white-backed planthopper), Sogatodes orizicola Muir (rice planthopper), Typhlocyba pomaria McAtee, white apple leafhopper, Erythroneura spp. (grape leafhoppers);

[0127] Magicicada septendecim Linnaeus (periodic cicada); Icerya purchasi Maskell (blooming scale insect), Quadraspidiotus perniciosus Comstock (St. Joseph's bug); Planococcus citriRisso (citrus mealybug); Pseudococcus spp. (other mealybug complex); Cacopsylla pyricola Foerster (pear yellow psyllid), Trioza diospyri Ashmead (persimmon woodlice); and Hemiptera pests: Acrosternumhilare Say (rice green stink bug), Anasa tristis De Geer (squash edge stink bug), Blissus leucopterusleucopterus Say (sorghum long stink bug), Cimex lectularius Linnaeus (stink bug), Corythuchagossypii Fabricius (cotton web stink bug), Cyrtopeltis modesta Distant (tomato stink bug), Dysdercus suturellus Herrich- (cotton bug), Euchistus servus Say (brown stink bug), Euchistusvariolarius Palisot de Beauvois (spotted stink bug), Graptostethus spp. (long-spotted stink bug association), Leptoglossus corculus Say (leaf-root pine seed bug), Lygus lineolaris Palisot de Beauvois (grass blind bug), Nezara viridula Linnaeus (southern green rice bug), Oebalus pugnax Fabricius (rice brown bug), Oncopeltus fasciatus Dallas (large milkweed long-spotted stink bug), Pseudatomoscelis seriatus Reuter (cotton blind bug). Other insect orders controlled by the compounds of the present invention include Thysanoptera (e.g., Frankliniellaoccidentalis Pergande (Western Flower Thrips), Scirthothrips citri Moulton (Citrus Thrips), Sericothrips variabilis Beach (Soybean Thrips), and Thrips tabaci Lindeman (Onion Thrips)); and Coleoptera (e.g., Leptinotarsa ​​decemlineata Say (Colorado Potato Beetle),

[0128] Epilachna varivestis Mulsant (Mexican bean beetle) and Agriotes, Athous or Limonius species (nematodes).

[0129] The compounds of the present invention are also active against members of the classes Nematoda, Cestoda, Trematoda and Acanthocephala, including members of the economically important orders Strongylida, Ascaris, Oxyura, Rhabditis, Spirulina and Orthoptera, such as, but not limited to, economically important agricultural pests (i.e., root-knot nematodes of the genus Meloidogyne, root-rot nematodes of the genus Escherichia, stump nematodes of the genus Trichodesmium, etc.) and pests that endanger animal and human health (i.e., all economically important trematodes, tapeworms and roundworms, such as Strongyloides vulgaris in horses, Toxocara canis in dogs, Haemonchus contortus in sheep, Dirofilaria immitis in dogs, Gymnocephalus foliaceus in horses, Fasciola hepatica in ruminants, etc.).

[0130] It should be noted that some modern classification systems place the Homoptera within the suborder Hemiptera.

[0131] The compounds of the present invention can be mixed with one or more other active ingredients (i.e., biologically active ingredients or agents) including insecticides, fungicides, nematicides, bactericides, acaricides, herbicides, herbicide safeners, growth regulators such as insect molting inhibitors and rooting stimulants, chemosterilants, semiochemicals, repellents, attractants, pheromones, feeding stimulants, other biologically active compounds or entomopathogenic bacteria, viruses or fungi to form multi-component pesticides, conferring an even broader spectrum of agricultural and non-agricultural uses. Therefore, the present invention also relates to a composition comprising a biologically effective amount of a compound of formula I, an N-oxide or a salt thereof, at least one formulation adjuvant selected from a surfactant, a solid diluent and a liquid diluent, and at least one other active ingredient or agent. In the case of mixtures of the present invention, the other active ingredients or agents can be formulated with the compounds of the present invention (including compounds of Formula I) to form a premix, or the other biologically active compounds or agents can be formulated separately from the compounds of the present invention (including compounds of Formula I) and the two formulations mixed together before application (e.g., in a spray tank), or the two formulations can be applied sequentially.

[0132] 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.

[0133] 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.

[0134] Further examples of biologically active compounds or agents that can be formulated with the compounds of the present invention are: fungicides, nematicides, bactericides, acaricides.

[0135] In some cases, the combination of the compounds of the present invention with other biologically active (especially invertebrate pest control) compounds or agents (i.e., active ingredients) can achieve a greater than additive (i.e., synergistic) effect. It is always desirable to reduce the amount of active ingredient released into the environment while ensuring effective pest control. When the invertebrate pest control active ingredients act synergistically at the application rate, imparting an agronomically acceptable degree of invertebrate pest control, such combinations can be advantageously used to reduce crop product costs and reduce environmental loads.

[0136] The compounds of the present invention and their compositions can be applied to plants that have been genetically modified to express proteins toxic to invertebrate pests (such as Bacillus thuringiensis delta-endotoxin). Such applications can provide a broader spectrum of plant protection and can be advantageously used for resistance management. The effects of the compounds of the present invention applied externally to control invertebrate pests can act synergistically with the expressed toxin protein.

[0137] General references to these agronomic protectants (i.e., insecticides, fungicides, nematicides, acaricides, herbicides and biologicals) include "The Pesticide Manual" 13th edition (edited by CDS Tomlin, British Crop Protection Council, Farnham, Surrey, UK, 2003) and "The BioPesticide Manual" 2nd edition (edited by LG Copping, British Crop Protection Council, Farnham, Surrey, UK, 2001).

[0138] For embodiments in which one or more of these various admixture components are used, the weight ratio of these various admixture components (total amount) to the compound of Formula I, its N-oxide, or salt thereof is generally between about 1:3000 and about 3000: 1. Of note are weight ratios between about 1:300 and about 300: 1 (e.g., a ratio between about 1:30 and about 30: 1).

[0139] In agronomic and non-agronomic applications, invertebrate pests are controlled by applying a biologically effective amount of one or more compounds of the invention, usually in the form of a composition, to the pest environment, including infested agronomic and / or non-agronomic loci, to the area to be protected, or directly to the pest to be controlled.

[0140] The present invention thus includes methods for controlling invertebrate pests in agricultural and / or non-agricultural applications, comprising contacting the invertebrate pest or its environment with a biologically effective amount of one or more compounds of the present invention, or with a composition comprising at least one such compound, or with a composition comprising at least one such compound and a biologically effective amount of at least one additional biologically active compound or agent. Examples of suitable compositions comprising a compound of the present invention and a biologically effective amount of at least one additional biologically active compound or agent include granular compositions, wherein the additional active compound is present on the same particles as the particles of the compound of the present invention, or on particles different from those of the particles of the compound of the present invention.

[0141] Embodiments of the methods of the present invention include contacting the environment. Of note are methods wherein the environment is a plant. Also of note are methods wherein the environment is an animal. Also of note are methods wherein the environment is a seed.

[0142] To achieve contact with the compounds or compositions of the present invention to protect field crops from invertebrate pests, the compounds or compositions are typically applied to crop seeds before planting, to the foliage (e.g., leaves, stems, flowers, fruits) of crop plants, or to the soil or other growth media before or after crop planting.

[0143] One embodiment of the contact method is by spraying. Alternatively, a granular composition comprising the compound of the present invention can be applied to plant leaves or soil. The compound of the present invention can also be effectively delivered via plant ingestion by contacting the plant with a composition comprising the compound of the present invention in the form of a soil drench liquid formulation, a granular formulation applied to the soil, a nursery box treatment, or a transplant soak. Of note is the composition of the present invention in the form of a soil drench liquid formulation. Also noteworthy is a method for controlling invertebrate pests, comprising contacting the invertebrate pest or its environment with a biologically effective amount of the compound of the present invention, or contacting a composition comprising a biologically effective amount of the compound of the present invention. Also noteworthy is a method wherein the environment is soil and the composition is applied to the soil as a soil drench formulation. Also noteworthy is the method wherein the environment is soil and the composition is applied to the soil as a soil drench formulation. Also noteworthy is the method wherein the compound of the present invention can be effected by topical application to the infested location. Other contact methods include applying the compound or composition of the present invention by direct spraying and residual spraying, aerial spraying, gels, seed coatings, microencapsulation, systemic absorption, baits, ear tags, boluses, sprayers, fumigants, aerosols, dusts, and many other methods. One embodiment of the contacting method is a dimensionally stable fertilizer granule, stick or tablet comprising a compound or composition of the invention.The compounds of the invention may also be impregnated into materials used to assemble invertebrate control devices (eg, insect screens).

[0144] The compositions of the present invention can also be used in seed treatments that provide protection from invertebrate pests. In the context of this disclosure and the claims, treating seeds refers to contacting the seeds with a biologically effective amount of a compound of the present invention, typically formulated as a composition of the present invention. Such seed treatments protect seeds from invertebrate soil pests and generally also protect the roots and other soil-contacting plant parts of the seedlings developed from the germinated seeds. The seed treatments also provide protection to the leaves by allowing the compounds of the present invention or a second active ingredient to migrate within the developing plant. Seed treatments can be applied to various types of seeds, including those that can germinate to form transgenic plants to express specific characteristics. Representative examples include those that express proteins toxic to invertebrate pests, such as Bacillus thuringiensis toxins, or those that express herbicide resistance, such as the glyphosate acetyltransferase that provides glyphosate resistance.

[0145] One method of seed treatment is to spray or dust the seeds with the compound of the present invention (i.e., as a prepared composition) before sowing the seeds. Compositions prepared for seed treatment generally include film formers or adhesives. Therefore, the seed coating composition of the present invention generally includes a biologically effective amount of a compound of formula I, an N-oxide or its salt and a film former or adhesive. The seeds are coated by spraying a flowable suspension concentrate directly into a seed rolling bed, and then drying the seeds. Alternatively, other formulation types such as wet powders, solutions, suspoemulsions, emulsifiable concentrates and aqueous solutions of emulsions can be sprayed onto the seeds. This method is particularly useful for applying film coating to seeds. Those skilled in the art can adopt various coating equipment and methods.

[0146] Treated seeds typically contain a compound of the invention in an amount of about 0.1 g to 1 kg per 100 kg of seeds (i.e., about 0.0001 to 1% by weight of the seeds before treatment). Flowable suspension formulations for seed treatment typically contain about 0.5 to about 70% active ingredient, about 0.5 to about 30% film-forming binder, about 0.5 to about 20% dispersant, 0 to about 5% thickener, 0 to about 5% pigment and / or dye, 0 to about 2% defoamer, 0 to about 1% preservative, and 0 to about 75% volatile liquid diluent.

[0147] The compounds of the present invention can be incorporated into bait compositions that are ingested by invertebrate pests or used in devices such as traps, bait stations, and the like. Such bait compositions can be in the form of granules comprising (a) an active ingredient, i.e., a biologically effective amount of a compound of Formula I, an N-oxide thereof, or a salt thereof; (b) one or more food materials; optionally (c) an attractant; and optionally (d) one or more wetting agents. Of note, granules or bait compositions comprising about 0.001-5% active ingredient, about 40-99% food material and / or attractant; and optionally about 0.05-10% wetting agent can effectively control soil invertebrate pests at very low application rates, particularly at doses of active ingredient that are lethal upon ingestion rather than direct contact. Certain food materials can be used both as a food source and as an attractant. Food materials include carbohydrates, proteins, and lipids. Examples of food materials are vegetable meal, sugar, starch, animal fat, vegetable oil, yeast extract, and milk solids. Examples of attractants are flavor enhancers and flavorings, such as fruit or plant extracts, spices, or other animal or plant components, pheromones, or other agents known to attract target invertebrate pests. Examples of humectants, i.e., water retaining agents, are ethylene glycol and other polyols, glycerol, and sorbitol. Of note are bait compositions (and methods of using such bait compositions) for controlling at least one invertebrate pest selected from ants, termites, and cockroaches. An apparatus for controlling invertebrate pests comprises a bait composition of the present invention and a housing adapted to contain the bait composition, wherein the housing has at least one opening sized to allow passage of an invertebrate pest so that the invertebrate pest can access the bait composition from a location external to the housing, and wherein the housing is further adapted to be placed in or near a location where potential or known invertebrate pests are active.

[0148] The compounds of the present invention can be administered without other adjuvants, but the most common application is to apply a formulation comprising one or more active ingredients with a suitable carrier, diluent, and surfactant, and possibly in combination with food, depending on the intended end use. One method of application involves spraying an aqueous dispersion or refined oil solution of the compound of the present invention. Combinations with spray oils, spray oil concentrates, spreaders, adjuvants, other solvents, and synergists such as piperonyl butoxide generally enhance the compound's effectiveness. For non-agricultural applications, such sprays can be applied from spray containers such as cans, bottles, or other containers, via a pump, or by releasing the compound from a pressurized container such as a pressurized aerosol spray can. Such spray compositions can take a variety of forms, such as sprays, mists, foams, smoke, or dust clouds. Therefore, such spray compositions may also include propellants, foaming agents, and the like, depending on the desired application. Of note are spray compositions comprising a biologically effective amount of a compound or composition of the present invention, and a carrier. One embodiment of such a spray composition comprises a biologically effective amount of a compound or composition of the present invention, and a propellant. Representative propellants include, but are not limited to, methane, ethane, propane, butane, isobutane, butylene, pentane, isopentane, neopentane, pentene, hydrofluorocarbons, chlorofluorocarbons, dimethyl ether, and mixtures thereof. Of note are spray compositions (and methods of using such spray compositions dispensed from a spray container) for controlling at least one invertebrate pest selected from the group consisting of mosquitoes, black flies, stable flies, deer flies, horse flies, wasps, hornets, hornets, ticks, spiders, ants, gnats, and the like, including any of the foregoing pests or combinations thereof.

[0149] Non-agricultural use refers to the control of invertebrate pests in the area of ​​non-crop fields. The non-agricultural use of the compound of the present invention and composition includes the control of stored grains, beans and other foods and textiles such as clothes and carpets. The non-agricultural use of the compound of the present invention and composition also includes the control of ornamental plants, forest crops, gardens, utility land along roadsides and railways, and turf such as lawns, golf courses and pastures. The non-agricultural use of the compound of the present invention and composition also includes the control of invertebrate pests in homes and other buildings inhabited by humans and / or companion animals, livestock, farm animals, zoo animals or other animals. The non-agricultural use of the compound of the present invention and composition also includes the control of pests such as termites that damage wood or other building materials used in buildings.

[0150] The non-agricultural uses of the compound and composition of the present invention also include protecting the health of humans and animals by controlling invertebrate pests that parasitize or spread infectious diseases. Controlling animal parasites includes controlling external parasites that parasitize on the surface of the host animal body (e.g., shoulders, armpits, abdomen, inner thighs) and internal parasites that parasitize inside the host animal body (e.g., stomach, intestines, lungs, veins, subcutaneous, lymphatic tissue). External parasitic or disease-transmitting pests include, for example, chiggers, ticks, lice, mosquitoes, flies, mites and fleas. Internal parasites include heartworms, hookworms and worms. The compound and composition of the present invention are particularly suitable for resisting external parasitic or disease-transmitting pests. The compound and composition of the present invention are suitable for systemic and / or non-systemic control of infestation or infection caused by parasites to animals.

[0151] Examples of invertebrate parasitic pests controlled by applying a parasiticidally effective amount of the compound of the present invention to the animal to be protected include external parasites (arthropods, mites, etc.) and internal parasites (helminths such as nematodes, trematodes, tapeworms, acanthocephalians, etc.).

[0152] The diseases or class of diseases generally described as helminthiasis are due to infection of an animal host with parasitic worms known as helminths. The term "helminth" is intended to include nematodes, flukes, tapeworms, and acanthocephalians. Helminthiasis is a common and serious economic problem associated with domesticated animals such as pigs, sheep, horses, cattle, goats, dogs, cats, and poultry.

[0153] It is also envisaged that the compounds of the present invention will be effective against a variety of animal ectoparasites, for example arthropod ectoparasites of mammals and birds, although it is also envisaged that certain arthropods may also be endoparasites.

[0154] Thus, the insect and acarid pests include, for example, biting insects such as flies and mosquitoes, mites, ticks, lice, fleas, stink bugs, parasitic maggots and the like.

[0155] Generally speaking, flies, fleas, lice, mosquitoes, gnats, mites, ticks and worms cause huge losses to the livestock and companion animal sectors. Arthropod parasites are also troublesome to humans and can be vectors of disease-causing organisms for both humans and animals.

[0156] Numerous other arthropod pests and ectoparasites are known in the art and are also contemplated for treatment with the compounds of the present invention.

[0157] Biologically active compounds or agents that can be used in the compositions of the present invention include organophosphate insecticides. Such insecticides have a very wide range of activity as insecticides and, in some cases, have anthelmintic activity. Organophosphate insecticides include, for example, dicrotophos, terbufos, dimethoate, dipyraphos, disulfoton, trichlorfon, azinphos-methyl, chlorpyrifos, malathion, acephate, methamidophos, ethyl parathion, methyl parathion, mevinphos, phorate, trithion, and phosalone. Combinations of the methods and compositions of the present invention with carbamate insecticides, including, for example, carbaryl, aldicarb, chlorpyrifos, ethoxysulfuron, and organochlorine insecticides, are also contemplated. Combinations with biopesticides, including repellents, pyrethroids (and synthetic variants thereof, such as allethrin, pyrethrin, permethrin, tralomethrin), and nicotine, which is commonly used as a miticide, are also contemplated. Other contemplated combinations are miscellaneous insecticides including: Bacillus, chlorobenzene, formamidines (such as amitraz), copper compounds (such as copper hydroxide and copper oxychlorosulfate), cyfluthrin, cypermethrin, dicofol, endosulfan, esfenvalerate, fenvalerate, lambda-cyhalothrin, methoxychlor, and sulfur.

[0158] Of note are additional biologically active compounds or agents selected from anthelmintics known in the art, such as avermectins (e.g., ivermectin, moxidectin, milbemycin), benzimidazoles (e.g., albendazole, triclabendazole), salicylanilides (e.g., closantel, hydroxyclozanamide), substituted phenols (e.g., nitroiodobenzonitrile), pyrimidines (e.g., pyrantel), imidazole thiazoles (e.g., levamisole) and praziquantel.

[0159] Other biologically active compounds or agents that can be used in the compositions of the present invention can be selected from insect growth regulators (IGRs) and juvenile hormone analogs (JHAs), such as diflubenzuron, thiocarb, fluazolone, cypermethrin, methoprene, and the like, to provide initial and sustained control of parasites (at all stages of insect growth, including eggs) to the animal subject and the animal subject's environment.

[0160] Of note are biologically active compounds or agents that can be used in the compositions of the present invention that are selected from the antiparasitic avermectin class of compounds. As mentioned above, the avermectin class of compounds is a series of potent antiparasitic agents known to be useful against a wide spectrum of mammalian endoparasites and ectoparasites.

[0161] The compositions of the present invention may also contain a flukeicide. Suitable flukeicides include, for example, triclabendazole, fenbendazole, albendazole, clorsulon and oxbendazole. It will be appreciated that the above combinations may also include combinations of antibiotics, antiparasitic and anti-fluke active compounds.

[0162] In addition to the combinations described above, it is also contemplated to provide the methods and compounds of the present invention as described herein in combination with other animal health drugs, such as trace elements, anti-inflammatory agents, anti-infective agents, hormones, dermatological preparations (including preservatives and disinfectants) and immunological preparations such as vaccines and antisera for the prevention of disease.

[0163] For example, such anti-infective agents include one or more antibiotics that may optionally be administered concurrently during treatment with the compounds or methods of the invention, for example, in the form of a combined composition and / or in separate dosage forms.

[0164] Non-agricultural applications in the veterinary sector are by conventional methods, such as by enteral administration in the form of, for example, tablets, capsules, drinks, drenches, granules, pastes, boluses, feeding procedures or suppositories; or by parenteral administration in the form of, for example, injections (including intramuscular, subcutaneous, intravenous, intraperitoneal) or implants; by nasal administration; by topical administration, for example by dipping or immersing, spraying, washing, coating with powders or applying to small areas of the animal, as well as by articles comprising the composition of the invention in the form of collars, ear tags, tail bands, limb bands or halters.

[0165] Any of the compounds of the present invention or suitable combinations of such compounds can be administered directly to an animal subject and / or indirectly by administering it to the local environment in which the animal resides, such as bedding, pens, etc. Direct administration includes contacting the skin, fur, or feathers of the animal subject with the compound, or feeding the compound to the animal or injecting it into the animal.

[0166] The compounds of the invention can be administered in a controlled release form, for example as a subcutaneous slow release formulation, or in the form of a controlled release device affixed to the animal, such as a flea collar. Collars for the controlled release of insecticides for long-term protection of companion animals from flea infestations are known in the art.

[0167] Typically, the parasiticidal composition according to the present invention comprises a mixture of a compound of formula I, its N-oxide or its salt and one or more pharmaceutically or veterinarily acceptable carriers, wherein the carrier comprises an excipient and an adjuvant, which is selected according to the intended route of administration (e.g., oral administration, topical administration or parenteral administration such as injection) and according to standard procedures. In addition, according to the compatibility with one or more active ingredients in the composition, including the presence of relative stability such as to pH and water content, a suitable carrier is selected. Therefore, it is noteworthy that the composition for protecting animals from the infringement of invertebrate parasitic pests comprises a compound of the present invention comprising at least one carrier and a parasiticidal effective amount.

[0168] For parenteral administration (including intravenous injection, intramuscular injection and subcutaneous injection), the compounds of the present invention can be formulated into suspensions, solutions or emulsions in oily or aqueous carriers and may contain adjuvants such as suspending agents, stabilizers and / or dispersants. The compounds of the present invention can also be formulated for rapid bolus injection or continuous infusion. The pharmaceutical composition for injection includes an aqueous solution of the active ingredient (e.g., a salt of the active compound) in a water-soluble form, preferably in a physiologically compatible buffer solution containing other excipients or adjuvants as known in the field of pharmaceutical formulations. In addition, a suspension of the active compound can be prepared in a lipophilic carrier. Suitable lipophilic carriers include fatty oils such as sesame oil, synthetic fatty acid esters such as ethyl oleate and triglycerides, or substances such as liposomes. The injection suspension aqueous solution may contain substances that increase the viscosity of the suspension, such as sodium carboxymethylcellulose, sorbitol or dextran. The preparation for injection can be present in, for example, an ampoule container or a multidose container in unit dosage form. Alternatively, the active ingredient may be in powder form for constitution with a suitable vehicle, eg, sterile pyrogen-free water, before use.

[0169] In addition to the above-mentioned preparations, the compounds of the present invention can also be formulated into long-acting preparations. Such long-acting preparations can be administered by implantation (e.g., subcutaneous or intramuscular) or by intramuscular injection or subcutaneous injection. With regard to this route of administration, the compounds of the present invention can be formulated with suitable polymeric materials or hydrophobic materials (e.g., in an emulsion containing a pharmaceutically acceptable oil), with an ion exchange resin, or the compound can be formulated into a slightly soluble derivative, such as, but not limited to, a slightly soluble salt.

[0170] For administration by inhalation, the compositions of the present invention can be delivered in the form of an aerosol spray using a pressurized pack or nebulizer and a suitable propellant, such as, but not limited to, dichlorodifluoromethane, trichlorofluoromethane, dichlorotetrafluoroethane, or carbon dioxide. In the case of a pressurized aerosol, the dosage unit can be controlled by providing a valve to deliver a metered amount. Gelatin capsules and cartridges for use in an inhaler or insufflator can be formulated to contain a powder mix of the compound and a suitable powder base such as lactose or starch.

[0171] For oral administration in the form of solutions (the most readily available absorption form), emulsions, suspensions, pastes, gels, capsules, tablets, boluses, powders, granules, rumen retentate, and feed / water / lick bricks, the compounds of the present invention can be formulated with binders / fillers known in the art for oral compositions, such as sugars and sugar derivatives (e.g., lactose, sucrose, mannitol, sorbitol), starches (e.g., corn starch, wheat starch, rice starch, potato starch), cellulose and derivatives (e.g., methylcellulose, carboxymethylcellulose, ethylhydroxycellulose), protein derivatives (e.g., zein, gelatin), and synthetic polymers (e.g., polyvinyl alcohol, polyvinylpyrrolidone). Lubricants (e.g., magnesium stearate), disintegrants (e.g., cross-linked polyvinylpyrrolidone, agar, alginic acid), and dyes or pigments can be added if desired. Pastes and gels also typically contain a binder (e.g., acacia, alginic acid, bentonite, cellulose, xanthan gum, colloidal magnesium aluminum silicate) to help keep the composition in contact with the oral cavity and prevent it from being expelled.

[0172] If the parasiticidal composition is in the form of a feed concentrate, the carrier is typically selected from a high-performance feed, a feed cereal, or a protein concentrate. In addition to the parasiticidal active ingredient, such compositions comprising a feed concentrate may also contain additives that promote animal health or growth, improve the quality of meat from slaughtered animals, or are otherwise useful in animal husbandry. These additives include, for example, vitamins, antibiotics, chemotherapeutic agents, bacteriostats, fungistats, coccidiostats, and hormones.

[0173] The compounds of formula I may also be formulated in rectal compositions such as suppositories or retention enemas, using, for example, conventional suppository bases such as cocoa butter or other glycerides.

[0174] Preparations for topical administration are generally in the form of powders, creams, suspensions, sprays, emulsions, foams, pastes, aerosols, ointments, ointments or gels. Topical preparations are more typically water-soluble solutions, which can be in the form of concentrates diluted before use. Parasiticidal compositions suitable for topical administration generally comprise a compound of the present invention and one or more topical suitable carriers. When the parasiticidal composition is topically applied to the outside of the animal body in the form of lines or dots (i.e., accurate therapy), the active ingredient migrates on the animal body surface to cover most or all of its surface area. Therefore, the treated animal can be protected from the infringement of invertebrate pests such as ticks, fleas and lice that feed on the animal epidermis. Therefore, preparations for local fixed-point administration generally comprise at least one organic solvent to facilitate the active ingredient to be delivered on the animal skin and / or to penetrate into the animal epidermis. Carriers in such formulations include propylene glycol, paraffins, aromatic compounds, esters (such as isopropyl myristate), glycol ethers, alcohols (such as ethanol, n-propanol, 2-octyldodecanol or oleyl alcohol); solutions of monocarboxylic acid esters, such as isopropyl myristate, isopropyl palmitate, lauric acid oxalate, oleyl oleate, decyl oleate, hexyl laurate, chain length C 12 -C 18 solutions of dicarboxylic acid esters, such as dibutyl phthalate, diisopropyl isophthalate, diisopropyl adipate, di-n-butyl adipate, or solutions of aliphatic acid esters (e.g. ethylene glycol). The presence of crystallization inhibitors or dispersants known from the pharmaceutical or cosmetic industry may also be advantageous.

[0175] Pour-on formulations can also be formulated to control parasites in animals of agricultural value. The pour-on formulations of the present invention can be in the form of liquids, powders, emulsions, foams, pastes, aerosols, ointments, creams, or gels. Pour-on formulations are typically liquids. These pour-on formulations can be effectively applied to sheep, cattle, goats, other ruminants, camelids, pigs, and horses. The pour-on formulations are typically applied by pouring the pour-on formulation in one or more thin lines, or precisely pouring it onto the animal's back midline (back) or shoulders. More typically, the pour-on formulation is applied by pouring it along the animal's back, along the spine. The formulation can also be applied via other conventional methods, including wiping the animal with an impregnated substance on at least a small area, or applying it using a commercially available applicator, applying it by syringe, applying it by spraying, or applying it by using a spray barrier. The pour-on formulation includes a carrier and may also include one or more additional ingredients. Examples of suitable additional ingredients are stabilizers such as antioxidants, spreading agents, preservatives, adhesion promoters, active solubilizers such as oleic acid, viscosity modifiers, UV blockers or absorbers, and colorants. Surfactants may also be included in these formulations, including anionic, cationic, nonionic and amphoteric surfactants.

[0176] The formulations of the present invention typically contain an antioxidant such as BHT (butylated hydroxytoluene). The antioxidant is generally present at a level of 0.1% to 5% (weight / volume). Some formulations require a solubilizer such as oleic acid to dissolve the active agent, especially when using spinosad. Common spreading agents used in these pour-on formulations are: IPM, IPP, saturated C 12 -C 18 Caprylic / capric esters of fatty alcohols, oleic acid, oleyl esters, ethyl oleate, triglycerides, silicone oil, and DPM. The pour-on formulations of the present invention can be prepared according to known techniques. When the pour-on is a solution, the repellent / insecticide is mixed with the carrier or vehicle using heating and stirring, if necessary. Auxiliary or additional ingredients can be added to the mixture of active agent and carrier, or mixed with the active agent before adding the carrier. If the pour-on is an emulsion or suspension, these formulations can be prepared similarly using known techniques.

[0177] Other delivery systems for more hydrophobic pharmaceutical compounds can be used. Liposomes and emulsions are examples of well-known delivery vehicles or carriers for hydrophobic drugs. In addition, organic solvents such as dimethyl sulfoxide can be used if desired.

[0178] For agronomic applications, the amount of application required for effective control (i.e., a "biologically effective amount") will depend on factors such as the type of invertebrate pest to be controlled, the pest's life cycle, life stage, size, location, time of year, host crop or animal, feeding behavior, mating behavior, ambient moisture, temperature, and the like. Under normal circumstances, an application rate of about 0.01 to 2 kg of active ingredient per hectare is sufficient to control pests in agronomic ecosystems, but an application rate as low as 0.0001 kg per hectare may also be sufficient, or an application rate as high as 8 kg per hectare may also be required. For non-agronomic applications, an effective amount will be in the range of about 1.0 to 50 mg per square meter, but an application rate as low as 0.1 mg per square meter may also be sufficient, or an application rate as high as 150 mg per square meter may also be required. One skilled in the art can readily determine the biologically effective amount required to achieve the desired level of invertebrate pest control.

[0179] Generally speaking, for veterinary use, a compound of Formula I, its N-oxide, or a salt thereof is applied to an animal in a parasiticidal effective amount to protect it from invertebrate parasitic pests. A parasiticidal effective amount is the amount of active ingredient required to achieve an observed reduction in the incidence or activity of the target invertebrate parasitic pest. Those skilled in the art will appreciate that the parasiticidal effective dose may vary depending on the compounds and compositions of the present invention, the desired parasiticidal effect and duration, the target invertebrate pest species, the animal to be protected, the mode of administration, and the like, and that the amount required to achieve a specific effect can be determined by simple experimentation. DETAILED DESCRIPTION

[0180] 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.

[0181] 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.

[0182] Table 1 Compound structures and their 1 H NMR values

[0183]

[0184]

[0185]

[0186]

[0187]

[0188]

[0189]

[0190]

[0191]

[0192] 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.

[0193] 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.

[0194] Examples of representative compounds are shown below. The synthesis methods of other compounds are similar and will not be described in detail here.

[0195] 1. Synthesis of Compound 6

[0196] (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 a catalytic amount of Pd(dppf)Cl2 were dissolved in dioxane (8 ml) and water (1 ml) and stirred at 100°C for 12 hours under a nitrogen atmosphere. The mixture was extracted with ethyl acetate, and 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%).

[0197]

[0198] (2) Compound 6-3 (140 mg, 0.43 mmol) was dissolved in 5 ml of ethanol and 5 ml of water, and sodium hydroxide (86 mg, 2.16 mmol) was added. The mixture was stirred at room temperature for 3 hours. The reaction mixture was acidified and extracted with ethyl acetate. The organic phase was washed with saturated brine, dried, and concentrated to give crude compound 6-4 (100 mg).

[0199]

[0200] (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 hour. The reaction mixture was placed in a dry ice bath, and compound 6-5 (89 mg, 0.37 mmol) and triethylamine (102 mg, 1.01 mmol) were added and reacted for 1 hour. The reaction solution was concentrated, and the residue was purified by column chromatography to obtain compound 6 (70 mg, 41%).

[0201]

[0202] 2. Synthesis of Compound 18

[0203] (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 thereto. The reaction solution was stirred at 100°C for 4 h under nitrogen atmosphere, and LCMS was used to monitor the completion of the reaction. The reaction solution was poured into water to quench, and then extracted with ethyl acetate three times. The organic phase was combined, washed with saturated brine, dried over anhydrous sodium sulfate, concentrated, and purified by normal phase to obtain compound 18-2 (PE / EA = 2 / 1, 3.3 g, 81%, yellow oil).

[0204]

[0205] (2) Compound 18-2 (3.0 g, 14.45 mmol) was dissolved in 30 mL of 1,4-dioxane, and then cuprous iodide (2.7 g, 14.45 mmol) and isoamyl nitrite (5.0 g, 43.35 mmol) were added thereto. After nitrogen was replaced several times, diiodomethane (11.5 g, 43.35 mmol) was finally added to the reaction solution. The reaction solution was stirred at 100°C for 3 h, and LCMS was used to monitor the completion of the reaction. The reaction solution was poured into water to quench, and then extracted with ethyl acetate. The organic phase was combined, washed with saturated brine, dried over anhydrous sodium sulfate, and then concentrated and purified by normal phase to obtain compound 18-3 (PE / EA = 8 / 1, 2.5 g, 54%, yellow oil).

[0206]

[0207] (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, and 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. The residue was purified by column chromatography to obtain compound 18-4 (PE / EA = 3 / 1, 1.5 g, 74%, light yellow oil).

[0208]

[0209] (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. The mixture was stirred at room temperature for 3 h. The reaction solution was concentrated, the pH was adjusted to acidic with dilute hydrochloric acid, and extracted with ethyl acetate. The organic phase was washed with saturated brine, dried, and concentrated to give crude compound 18-5 (white solid, 400 mg).

[0210]

[0211] (5) Compound 18-5 (400 mg, 1.36 mmol) was dissolved in 15 mL of dichloromethane. 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. The reaction was then placed in a dry ice bath, and compound 18-6 (260 mg, 1.09 mmol) and triethylamine (412 mg, 4.08 mmol) were added. The reaction was allowed to react for 30 min. LCMS monitored the reaction to be complete. The reaction solution was concentrated, and the residue was purified by column chromatography to give compound 18 (EA / MeOH = 8 / 1, 100 mg, 14%, yellow powder).

[0212]

[0213] 3. Synthesis of Compound 21

[0214] (1) Compound 21-1 (3 g, 14.77 mmol) was dissolved in 30 ml of DMF at room temperature, and NIS (3.52 g, 15.66 mmol) was added. The reaction was allowed to proceed at 70°C for 4 h. The reaction was complete after monitoring by LCMS. The reaction solution was diluted with water, the aqueous phase was extracted with ethyl acetate, and the organic phase was washed with saturated brine, dried, and concentrated. The residue was purified by column chromatography (EA / PE = 1 / 5) to afford compound 21-2 (3.5 g, 72.9%) as a white solid.

[0215]

[0216] (2) Under nitrogen atmosphere, compound 21-2 (3.5 g, 10.64 mmol) was dissolved in 30 mL of DMF, and methyl fluorosulfonyldifluoroacetate (6.13 g, 31.91 mmol), HMPA (1.91 g, 10.64 mmol), and cuprous iodide (2.03 g, 10.64 mmol) were added. The mixture was reacted at 70°C for 12 h. LCMS monitoring confirmed the completion of the reaction. The reaction solution was diluted with water, the aqueous phase was extracted with ethyl acetate, and the organic phase was washed with saturated brine, dried, and concentrated. The residue was purified by column chromatography (EA / PE = 1 / 5) to give compound 21-3 (2.2 g, 78.5%) as a white solid.

[0217]

[0218] (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. The reaction was monitored by LCMS. The reaction solution was suction filtered with celite, and the filtrate was rotary evaporated to dryness. 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.

[0219]

[0220] (4) Compound 21-4 (2 g, 8.29 mmol) was dissolved in 30 mL of water, and 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. The reaction was monitored by LCMS to generate a 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. The reaction was monitored by LCMS. 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.

[0221]

[0222] (5) Compound 21-5 (1.5 g, 4.26 mmol) was dissolved in 50 mL of dioxane under a nitrogen atmosphere. 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 reaction was carried out at 90°C for 8 h. 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.

[0223]

[0224] (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. The mixture was allowed to react at room temperature for 4 h. LCMS monitored the reaction to be complete. The reaction solution was diluted with water and extracted with ethyl acetate. The aqueous phase was collected, the pH was adjusted to 2, and then extracted with EA. The organic phase was collected, dried, and concentrated to afford compound 21-7 (1.5 g, 81.44%) as a white solid.

[0225]

[0226] (7) Under nitrogen atmosphere, 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 allowed to proceed for 30 min. The main peak of the product was detected by LCMS. The reaction solution was transferred to -45°C, and the starting material 6-5 was dissolved in 5 mL of DCM and slowly added dropwise to the reaction system. Triethylamine was added to adjust the reaction system to pH 10. After reacting for 1 h, the reaction was complete as monitored by LCMS. 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.

[0227]

[0228] 4. Synthesis of Compound 23

[0229] (1) Compound 23-1 (12.91 g, 40.59 mmol) was dissolved in 90 ml of ethanol. Methylhydrazine aqueous solution (6.41 ml, 121.77 mmol) was added dropwise under an ice-water bath. The mixture was allowed to react at 60°C for 3 h. LCMS indicated the reaction was complete. The reaction solution was concentrated, and the residue was purified by column chromatography (EA / PE = 1 / 1) to afford compound 23-2 (7.30 g, 59.9%) as a yellow solid.

[0230]

[0231] (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 indicated the reaction was complete. The reaction solution was concentrated to remove the phosphorus oxychloride and diluted with water. The aqueous phase was extracted with ethyl acetate, and the organic phase was washed with saturated brine, dried, and concentrated. The residue was purified by column chromatography (EA / PE = 1 / 10) to afford compound 23-3 (1.80 g, 23.2%) as a yellow solid.

[0232]

[0233] (3) Compound 23-3 (1.80 g, 5.66 mmol) was dissolved in 50 ml 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 added successively under nitrogen atmosphere, and the mixture was reacted at 90°C for 8 h. The reaction was monitored by LCMS. The reaction solution was concentrated to remove 1,4-dioxane, and the crude product was diluted with water and ethyl acetate. 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%) as a white solid.

[0234]

[0235] (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 the mixture was reacted at room temperature for 4 h. The reaction was monitored by LCMS. The reaction solution was diluted with water and ethyl acetate, 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%) as a white solid.

[0236]

[0237] (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 the mixture was reacted at room temperature for 30 min. 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 the solution was slowly added dropwise to the above reaction system at -45°C. Triethylamine (2.11 g, 20.96 mmol) was added, and the mixture was reacted at a controlled temperature for 1 h. The reaction was monitored by LCMS. The reaction solution was diluted with water and dichloromethane, 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) as a white solid.

[0238]

[0239] Biological activity evaluation:

[0240] After the original drug is dissolved in acetone, the solution is diluted with distilled water to a gradient dose. Select test insects (spodoptera: fall armyworm, armyworm, armyworm, striped stem borer, beet armyworm) with the same physiological state raised indoors, put them in a disposable transparent box, inoculate 10 test insects with the same growth in each box, and put them into the host plant leaves (corn leaves), and then use a spray tower to spray. After the spraying is completed, close the lid tightly and repeat 3 times. The highest dose of acetone solution is used as a control. The test insects treated with the agent are placed under conventional breeding conditions in the treatment room. Check the number of dead insects after 48 hours, and calculate the death rate according to the formula: mortality rate (%) = (number of dead insects / number of test insects) * 100. Representative experimental results are shown in Table 2.

[0241] Table 2 Insecticidal test results

[0242]

[0243] Note: N stands for no data, reference compound A:

[0244] At the same time, after many tests, it was found that many of the compounds and compositions of the present invention have good control activity against agricultural pests such as Lepidoptera (such as corn borer, striped stem borer, diamondback moth, Spodoptera litura, beet armyworm, cotton bollworm, fall armyworm, armyworm, etc.), Homoptera (such as cotton aphid, radish aphid, pea aphid, peanut aphid, green stink bug, etc.), Acarina (such as two-spotted spider mite, truncate spider mite, Turkestan spider mite, etc.), Diptera (such as leek bradgy fungus gnat, etc.), Coleoptera (such as yellow flea beetle, monkey leaf beetle, etc.) and thrips (such as palm thrips, onion thrips, tobacco thrips, etc.), as well as sanitary pests such as cockroaches (such as termites, cockroaches, etc.) and Muscidae (such as flies, mosquitoes, etc.). They not only have the characteristics of broad spectrum, high efficiency, and strong systemic absorption, but can also effectively control resistant pests and have certain commercial value.

Claims

1. A mesoionic pyrimidinium compound, an N-oxide or a salt thereof as represented by the general formula I: in, 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.

Images