WO2010005692A2 - Insecticidal cyclic carbonyl amidines - Google Patents

Insecticidal cyclic carbonyl amidines Download PDF

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Publication number
WO2010005692A2
WO2010005692A2 PCT/US2009/047321 US2009047321W WO2010005692A2 WO 2010005692 A2 WO2010005692 A2 WO 2010005692A2 US 2009047321 W US2009047321 W US 2009047321W WO 2010005692 A2 WO2010005692 A2 WO 2010005692A2
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Prior art keywords
methyl
pyridinyl
compound
chme
nme
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PCT/US2009/047321
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French (fr)
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WO2010005692A3 (en
WO2010005692A4 (en
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Wenming Zhang
Stephen Frederick Mccann
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E. I. Du Pont De Nemours And Company
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Publication of WO2010005692A2 publication Critical patent/WO2010005692A2/en
Publication of WO2010005692A3 publication Critical patent/WO2010005692A3/en
Publication of WO2010005692A4 publication Critical patent/WO2010005692A4/en

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • A61P7/04—Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links

Definitions

  • This invention relates to certain cyclic carbonyl amidines, their salts and compositions suitable for agronomic and nonagronomic uses, and methods of their use for controlling invertebrate pests such as arthropods in agronomic and nonagronomic environments.
  • invertebrate pests The control of invertebrate pests is extremely important in achieving high crop efficiency. Damage by invertebrate pests to growing and stored agronomic crops can cause significant reduction in productivity and thereby result in increased costs to the consumer.
  • invertebrate pests in forestry, greenhouse crops, ornamentals, nursery crops, stored food and fiber products, livestock, household, turf, wood products, and public and animal health is also important. Many products are commercially available for these purposes, but the need continues for new compounds that are more effective, less costly, less toxic, and environmentally safer or have different sites of action.
  • PCT Patent Publication WO 07/115643 discloses certain amine derivatives of Formula i as insecticides
  • A is pyrimidinyl, pyrazolyl, thienyl, oxazolyl, isoxazolyl, oxadiazolyl, isothiazolyl, triazolyl or thiadiazolyl
  • B is O, S or methylene
  • R 1 is H, alkyl, alkenyl, alkynyl, cycloalkyl or alkoxy
  • R 2 is H or halogen
  • R 3 is H or alkyl.
  • Y is O, S, NR 5 or CR 3 R 4 , G is a direct bond, and Z is CR 3 R 4 or NR 5 ;
  • Y is CR 3 R 4 , G is a direct bond, and Z is O or S; or Y is O, S, NR 5 or CR 3 R 4 , G is CR 3 R 4 , and Z is O, S, NR 5 or CR 3 R 4 ; or
  • R 1 is H, C 1 -C 3 alkoxy, C(O)R 6 or SO 2 R 7 ; or C 1 -C 4 alkyl, C 3 -C 4 alkenyl, C 3 -C 4 alkynyl, C 3 -C 4 cycloalkyl, C 4 -C 5 cycloalkylalkyl, C 4 -C 5 alkylcycloalkyl or benzyl, each optionally substituted with 1 to 5 halogen;
  • R 2 is H or C 1 -C 2 alkyl
  • each R 3 is independently H or CH 3
  • each R 4 is independently H or CH 3
  • each R 5 is independently H, C 1 -C 2 alkyl or C 1 -C 2 haloalkyl
  • R 6 is C ! -C 2 alk y! or C i-C 2 haloalkyl
  • R 7 is C 1 -C 2 alkyl or C 1 -C 2 haloalkyl
  • Q is a 5- or 6-membered fully unsaturated heterocyclic ring containing as ring members at least one nitrogen atom and other ring members selected from carbon, oxygen and sulfur atoms, said ring optionally substituted with 1 to 3 substituents selected from halogen, cyano, nitro, and C 1 -C 4 alkyl, C 1 -C 4 alkoxy and C 1 -C 3 alkylthio, each optionally substituted with 1 to 5 fluorine or chlorine; or 3-tetrahydrofuranyl.
  • This invention also provides a composition comprising a compound of Formula 1 or a salt thereof (i.e. in a biologically effective amount), and at least one additional component selected from the group consisting of surfactants, solid diluents and liquid diluents.
  • this invention also provides a composition for controlling an invertebrate pest comprising a compound of Formula 1 or a salt thereof, and at least one additional component selected from the group consisting of surfactants, solid diluents and liquid diluents, said composition optionally further comprising at least one additional biologically active compound or agent.
  • This invention provides a method for controlling an invertebrate pest comprising contacting the invertebrate pest or its environment with a biologically effective amount of a compound of Formula 1 or a salt thereof, (e.g., as a composition described herein).
  • This invention also relates to such method wherein the invertebrate pest or its environment is contacted with a composition comprising a biologically effective amount of a compound of Formula 1 or a salt thereof, and at least one additional component selected from the group consisting of surfactants, solid diluents and liquid diluents, said composition optionally further comprising a biologically effective amount of at least one additional biologically active compound or agent.
  • This invention also provides a method for protecting a seed from an invertebrate pest comprising contacting the seed with a biologically effective amount of a compound of Formula 1 or a salt thereof (e.g., as a composition described herein). This invention also relates to the treated seed.
  • the terms “comprises”, “comprising”, “includes”, “including”, “has”, “having”, “contains”, “containing”, “characterized by”, or any other variation thereof, are intended to cover a non-exclusive inclusion, subject to any limitation explicitly indicated.
  • a composition, a mixture, process, method, article, or apparatus that comprises a list of elements is not necessarily limited to only those elements but may include other elements not expressly listed or inherent to such composition, mixture, process, method, article, or apparatus.
  • the term "invertebrate pest” includes arthropods, gastropods and nematodes of economic importance as pests.
  • arthropod includes insects, mites, spiders, scorpions, centipedes, millipedes, pill bugs and symphylans.
  • gastropod includes snails, slugs and other Stylommatophora.
  • nematode refers to a living organism of the Phylum Nematoda. As generally defined, a “parasite” lives or grows inside or feeds on another living organism (such as a plant, animal or human) described as the "host”.
  • parasite pest is particularly a pest that injures or damages tissue or causes other forms of disease in plants, animals (particularly vertebrates) or humans.
  • a parasite "infestation” refers to the presence of parasites in numbers that pose a risk to plants, humans or animals. The presence can be in the environment, e.g., in a human or animal house, or surrounding property or structures, on an agricultural crop or other type of plant, in animal bedding, on the skin or fur of an animal, etc.
  • infestation is also intended to be synonymous with the term, "infection,” as that term is generally understood in the art, unless otherwise stated.
  • invertebrate pest control means inhibition of invertebrate pest development (including mortality, feeding reduction, and/or mating disruption), and related expressions are defined analogously.
  • parasitic and “parasiticidally” refers to observable effects on a parasitic pest to provide protection of a plant, animal or human from the pest. Parasiticidal effects typically relate to diminishing the occurrence or activity of the target parasitic pest. Such effects on the pest include necrosis, death, retarded growth, diminished mobility or lessened ability to remain on or in the host plant, animal or human, reduced feeding and inhibition of reproduction.
  • control of a parasitic pest means achieving a parasiticidal effect on the pest.
  • the expressions "parasiticidally effective amount” and “biologically effective amount” in the context of applying a chemical compound to control a parasitic pest refer to an amount of the compound that is sufficient to control the parasitic pest.
  • agronomic refers to the production of field crops such as for food and fiber and includes the growth of corn, soybeans and other legumes, rice, cereal (e.g., wheat, oats, barley, rye, rice, maize), leafy vegetables (e.g., lettuce, cabbage, and other cole crops), fruiting vegetables (e.g., tomatoes, pepper, eggplant, crucifers and cucurbits), potatoes, sweet potatoes, grapes, cotton, tree fruits (e.g., pome, stone and citrus), small fruit (berries, cherries) and other specialty crops (e.g., canola, sunflower, olives).
  • wheat e.g., wheat, oats, barley, rye, rice, maize
  • leafy vegetables e.g., lettuce, cabbage, and other cole crops
  • fruiting vegetables e.g., tomatoes, pepper, eggplant, crucifers and cucurbits
  • potatoes e.g., sweet potatoes, grapes, cotton, tree fruits (e.g.
  • nonagronomic refers to other than field crops, such as horticultural crops (e.g., greenhouse, nursery or ornamental plants not grown in a field), residential, agricultural, commercial and industrial structures, turf (e.g., sod farm, pasture, golf course, lawn, sports field, etc.), wood products, stored product, agro-forestry and vegetation management, public health (i.e. human) and animal health (e.g., domesticated animals such as pets, livestock and poultry, undomesticated animals such as wildlife) applications.
  • horticultural crops e.g., greenhouse, nursery or ornamental plants not grown in a field
  • turf e.g., sod farm, pasture, golf course, lawn, sports field, etc.
  • wood products e.g., stored product, agro-forestry and vegetation management
  • public health i.e. human
  • animal health e.g., domesticated animals such as pets, livestock and poultry, undomesticated animals such as wildlife
  • alkyl used either alone or in compound words such as “alkylthio” or “haloalkyl” includes straight-chain and branched alkyl, such as, methyl, ethyl, n-propyl, /-propyl, and the different butyl isomers.
  • alkenyl includes straight-chain and branched alkenes such as 1-propenyl, 2-propenyl, and the different butenyl isomers.
  • Alkynyl includes straight-chain and branched alkynes such as 1-propynyl, 2-propynyl and the different butynyl isomers.
  • Alkoxy includes, for example, methoxy, ethoxy, n-propyloxy, isopropyloxy and the different butoxy isomers.
  • Alkylthio includes branched and straight-chain alkylthio moieties such as methylthio, ethylthio, and the different propylthio isomers.
  • Cycloalkyl includes, for example, cyclopropyl and cyclobutyl.
  • the term “cycloalkylalkyl” denotes cycloalkyl substitution on an alkyl moiety. Examples of “cycloalkylalkyl” include cyclopropylmethyl, cyclopropylethyl, and other cycloalkyl moieties bonded to alkyl groups.
  • the term “alkylcycloalkyl” denotes alkyl substitution on a cycloalkyl moiety. Examples of “alkylcycloalkyl” include methylcyclopropyl, ethylcyclopropyl, and other alkyl moieties bonded to cycloalkyl groups.
  • halogen either alone or in compound words such as “haloalkyl”, or when used in descriptions such as “alkyl substituted with halogen” includes fluorine, chlorine, bromine and iodine. Further, when used in compound words such as “haloalkyl”, or when used in descriptions such as “alkyl substituted with halogen” said alkyl may be partially or fully substituted with halogen atoms which may be the same or different. Examples of “haloalkyl” or “alkyl substituted with halogen” include F 3 C, ClCH 2 , CF 3 CH 2 and CF 3 CCl 2 .
  • the chemical abbreviation C(O) as used herein represents a carbonyl moiety.
  • C(O)CH 3 represents an acetyl group.
  • the chemical abbreviations CO 2 and C(O)O as used herein represent an ester moiety.
  • CO 2 Me and C(O)OMe represent a methyl ester.
  • Cj-C The total number of carbon atoms in a substituent group is indicated by the "Cj-C;" prefix where i and j are numbers from 1 to 5.
  • C 1 -C 4 alkyl designates methyl through butyl.
  • a "ring" as a component of Formula 1 is carbocyclic or heterocyclic.
  • heterocyclic ring denotes a ring in which at least one atom forming the ring backbone is not carbon, e.g., nitrogen, oxygen or sulfur. Typically a heterocyclic ring contains no more than 4 nitrogens, no more than 2 oxygens and no more than 2 sulfurs. Unless otherwise indicated, a heterocyclic ring can be a saturated, partially unsaturated, or fully unsaturated ring. When a fully unsaturated heterocyclic ring satisfies H ⁇ ckel's rule, then said ring is also called a "heteroaromatic ring” or "aromatic heterocyclic ring". Unless otherwise indicated, heterocyclic rings and ring systems can be attached through any available carbon or nitrogen by replacement of a hydrogen on said carbon or nitrogen.
  • ring atoms other than carbon and nitrogen are bonded only by single bonds. Accordingly, five- membered fully unsaturated rings contain two alternating double bonds, and six-membered fully unsaturated rings contain three alternating double bonds.
  • Aromaatic indicates that each of the ring atoms is essentially in the same plane and has a/?-orbital perpendicular to the ring plane, and in which (4n + T) ⁇ electrons, where n is a positive integer, are associated with the ring to comply with H ⁇ ckel's rule.
  • the fully unsaturated heterocyclic ring of Q contains at least one nitrogen atom as a ring member, the nitrogen atom can contribute a pair of electrons to supplement the four ⁇ electrons provided by two double bonds. Therefore five-membered as well as six-membered fully unsaturated heterocyclic rings of Q are aromatic according to H ⁇ ckel's rule.
  • Q can be alternatively and equivalently defined as a 5- or 6-membered heteroaromatic ring containing as ring members at least one nitrogen atom and other ring members selected from carbon, oxygen and sulfur atoms, said ring optionally substituted with substituents selected from halogen, cyano and nitro, and C 1 -C 4 alkyl, C 1 -C 4 alkoxy and Q-C 3 alkythio, each optionally substituted with 1 to 5 fluorine or chlorine.
  • substituents selected from halogen, cyano and nitro, and C 1 -C 4 alkyl, C 1 -C 4 alkoxy and Q-C 3 alkythio, each optionally substituted with 1 to 5 fluorine or chlorine.
  • an optionally substituted group may have a substituent at each substitutable position of the group, and each substitution is independent of the other.
  • the 5- or 6-membered nitrogen-containing heterocyclic ring of Q may be attached to the remainder of Formula 1 though any available carbon or nitrogen ring atom, unless otherwise described.
  • Q is a 5- or 6-membered fully unsaturated heterocyclic ring optionally substituted with substituents selected from a group of substituents as defined in the Summary of Invention.
  • substituents selected from a group of substituents as defined in the Summary of Invention.
  • optionally substituted 5- or 6-membered unsaturated aromatic heterocyclic rings include the rings U-6 through U-61 illustrated in Exhibit 1 wherein R v is any substituent as defined in the Summary of the Invention for Q and r is an integer from 0 to 4, limited by the number of available positions on each U group.
  • U-29, U-30, U-36, U-37, U-38, U-39, U-40, U-41, U-42 and U-43 have only one available position, for these U groups r is limited to the integers 0 or 1, and r being 0 means that the U group is unsubstituted and a hydrogen is present at the position indicated by (R v ) r .
  • R v groups are shown in the structures U-6 through U-61, it is noted that they do not need to be present since they are optional substituents. Note that when R v is H when attached to an atom, this is the same as if said atom is unsubstituted. The nitrogen atoms that require substitution to fill their valence are substituted with H or R v . Note that when the attachment point between (R v ) r and the U group is illustrated as floating, (R v ) r can be attached to any available carbon atom or nitrogen atom of the U group.
  • the U group can be attached to the remainder of Formula 1 through any available carbon or nitrogen of the U group by replacement of a hydrogen atom.
  • some U groups can only be substituted with less than 4 R v groups (e.g., U-7 through U-48, and U-52 through U-61).
  • Compounds of this invention can exist as one or more stereoisomers.
  • the various stereoisomers include enantiomers, diastereomers, atropisomers and geometric isomers.
  • one stereoisomer may be more active and/or may exhibit beneficial effects when enriched relative to the other stereoisomer(s) or when separated from the other stereoisomer(s). Additionally, the skilled artisan knows how to separate, enrich, and/or to selectively prepare said stereoisomers.
  • the compounds of the invention may be present as a mixture of stereoisomers, individual stereoisomers or as an optically active form.
  • Non-crystalline forms include embodiments which are solids such as waxes and gums as well as embodiments which are liquids such as solutions and melts.
  • Crystalline forms include embodiments which represent essentially a single crystal type and embodiments which represent a mixture of polymorphs (i.e. different crystalline types).
  • polymorph refers to a particular crystalline form of a chemical compound that can crystallize in different crystalline forms, these forms having different arrangements and/or conformations of the molecules in the crystal lattice.
  • polymorphs can have the same chemical composition, they can also differ in composition due the presence or absence of co-crystallized water or other molecules, which can be weakly or strongly bound in the lattice. Polymorphs can differ in such chemical, physical and biological properties as crystal shape, density, hardness, color, chemical stability, melting point, hygroscopicity, suspensibility, dissolution rate and biological availability.
  • a polymorph of a compound represented by Formula 1 can exhibit beneficial effects (e.g., suitability for preparation of useful formulations, improved biological performance) relative to another polymorph or a mixture of polymorphs of the same compound represented by Formula 1.
  • Preparation and isolation of a particular polymorph of a compound represented by Formula 1 can be achieved by methods known to those skilled in the art including, for example, crystallization using selected solvents and temperatures.
  • salts of chemical compounds are in equilibrium with their corresponding nonsalt forms, salts share the biological utility of the nonsalt forms.
  • the salts of the compounds of Formula 1 include acid-addition salts with inorganic or organic acids such as hydrobromic, hydrochloric, nitric, phosphoric, sulfuric, acetic, butyric, fumaric, lactic, maleic, malonic, oxalic, propionic, salicylic, tartaric, 4-toluenesulfonic or valeric acids.
  • the present invention comprises compounds selected from
  • Embodiments of the present invention as described in the Summary of the Invention include those described below.
  • Formula 1 includes stereoisomers and salts thereof, and reference to "a compound of Formula 1" includes the definitions of substituents specified in the Summary of the Invention unless further defined in the Embodiments.
  • the compound of Formula Ir is a subset of Formula 1.
  • Embodiment 1 A compound of Formula 1 wherein Y is O, G is a direct bond, and Z is CR 3 R 4 or NR 5 .
  • Embodiment Ia A compound of Embodiment 1 wherein Z is CR 3 R 4 .
  • Embodiment Ib A compound of Embodiment 1 wherein Z is NR 5 .
  • Embodiment 2 A compound of Formula 1 or any one of Embodiments 1— Ib wherein R 1 is H; or C 1 -C 3 alkyl or cyclopropyl, each optionally substituted with 1 to 3 halogen.
  • Embodiment 2a A compound of Embodiment 2 wherein R 1 is C ⁇ -C 2 alkyl or cyclopropyl, each optionally substituted with 1 to 3 halogen.
  • Embodiment 2b A compound of Embodiment 2a wherein R 1 is methyl, CH 2 CF 3 ,
  • Embodiment 3 A compound of Formula 1 or any one of Embodiments l-2b wherein
  • R 2 is H or methyl.
  • Embodiment 3a A compound of Embodiment 3 wherein R 2 is H.
  • Embodiment 4 A compound of Formula 1 or any one of Embodiments 1-3 a wherein R 3 is H.
  • Embodiment 5. A compound of Formula 1 or any one of Embodiments 1-4 wherein
  • R 4 is H.
  • Embodiment 6 A compound of Formula 1 or any one of Embodiments 1-5 wherein
  • Embodiment 7 A compound of Formula 1 or any one of Embodiments 1-6 wherein Q is a heterocyclic ring selected from pyridinyl, pyrimidinyl, pyridazinyl, pyrazinyl, pyrazolyl, oxazolyl, isoxazolyl, oxadiazolyl, thiadiazolyl, isothiazolyl, imidazolyl, pyrrolyl, thiazolyl and triazolyl, said ring optionally substituted with 1 to 3 substituents selected from halogen, cyano and nitro, and Q-C 4 alkyl, C ⁇ - C 4 alkoxy and Q-C 3 alkylthio, each optionally substituted with 1 to 5 halogen selected from fluorine and chlorine.
  • Q is a heterocyclic ring selected from pyridinyl, pyrimidinyl, pyridazinyl, pyrazinyl, pyrazolyl, o
  • Embodiment 7a A compound of Embodiment 7 wherein Q is 3 -pyridinyl or 5- thiazolyl optionally substituted with 1 or 2 substituents selected from halogen, cyano and nitro, and Q-C 4 alkyl, Q-C 4 alkoxy and Q-C 3 alkylthio, each optionally substituted with 1 to 3 halogen selected from fluorine and chlorine.
  • Embodiment 7b A compound of Embodiment 7a wherein Q is 3 -pyridinyl or 5- thiazolyl optionally substituted with 1 or 2 substituents selected from halogen, methyl, methoxy and trifluoromethyl.
  • Embodiment 7c A compound of Embodiment 7b wherein the nonhydrogen substituent(s) on the 3 -pyridinyl or 5 -thiazolyl of Q are bonded to ring atom(s) not adjacent to the ring atom connecting Q to the remainder of Formula 1 (i.e. the ring atoms denoted by "*" in the structures below).
  • Embodiment 8 A compound of Formula Ir (Formula 1 wherein G is a direct bond)
  • Y-Z is 0-CR 3 R 4 , S-CR 3 R 4 , NR 5 -CR 3 R 4 or CR 3 R 4 -O (wherein the left end is attached as Y, and the right end is attached as Z);
  • R 1 is H or C 1 -C 3 alkoxy; or C 1 -C 4 alkyl, C 3 -C 4 alkenyl, C 3 -C 4 alkynyl, C 3 -C 4 cycloalkyl, C 4 -C 5 cycloalkylalkyl or C 4 -C 5 alkylcycloalkyl, each optionally substituted with halogen;
  • Embodiment 9 A compound of Formula Ir wherein Y-Z is 0-CR 3 R 4 .
  • Embodiment 9a A compound of Formula Ir or Embodiment 9 wherein R 3 and R 4 are H.
  • Embodiment 10 A compound of Formula Ir wherein R 1 is H; or C 1 -C 3 alkyl or cyclopropyl, each optionally substituted with halogen.
  • Embodiment 10a A compound of Embodiment 10 wherein R 1 is C 1 -C 2 alkyl or cyclopropyl, each optionally substituted with halogen.
  • Embodiment 10b A compound of Embodiment 10a wherein R 1 is methyl, CH 2 CF 3 or cyclopropyl.
  • Embodiment 11 A compound of Formula Ir wherein R 2 is H or methyl.
  • Embodiment 1 Ia A compound of Embodiment 11 wherein R 2 is H.
  • Embodiment 12 A compound of Formula Ir wherein Q is a heterocyclic ring selected from pyridinyl, pyrimidinyl, pyridazinyl, pyrazinyl, pyrazolyl, oxazolyl, isoxazolyl, oxadiazolyl, thiadiazolyl, isothiazolyl, imidazolyl, pyrrolyl, thiazolyl and triazolyl, said ring optionally substituted with substituents selected from halogen, cyano and nitro, and C 1 -C 4 alkyl, C 1 -C 4 alkoxy and C 1 -C 3 alkylthio, each optionally substituted with halogen selected from fluorine and chlorine.
  • Q is a heterocyclic ring selected from pyridinyl, pyrimidinyl, pyridazinyl, pyrazinyl, pyrazolyl, oxazolyl, isoxazoly
  • Embodiment 12a A compound of Embodiment 12 wherein Q is 3 -pyridinyl or 5- thiazolyl optionally substituted with substituents selected from halogen, cyano and nitro, and C 1 -C 4 alkyl, C 1 -C 4 alkoxy and C 1 -C 3 alkylthio, each optionally substituted with halogen selected from fluorine and chlorine.
  • Embodiment 12b A compound of Formula Ir or Embodiment 12 or 12a wherein the optional substituents are selected from halogen, methyl, methoxy and trifluoromethyl.
  • Embodiment 12c A compound of Formula Ir or any one of Embodiments 12 through 12b wherein the nonhydrogen substituent(s) on heterocyclic ring of Q are bonded to ring atom(s) not adjacent to the ring atom connecting Q to the remainder of Formula Ir.
  • Embodiments of this invention can be combined in any manner, and the descriptions of variables in the embodiments pertain not only to the compounds of Formulae 1 and Ir but also to the starting compounds and intermediate compounds useful for preparing the compounds of Formulae 1 and Ir.
  • embodiments of this invention including Embodiments 1-12c above as well as any other embodiments described herein, and any combination thereof, pertain to the compositions and methods of the present invention. Combinations of Embodiments l-7c are illustrated by:
  • Embodiment A A compound of Formula 1 wherein
  • Y is O, G is a direct bond, and Z is CR 3 R 4 or NR 5 ;
  • R 1 is H; or C j -C 3 alkyl or cyclopropyl, each optionally substituted with 1 to 3 halogen;
  • R 2 is H;
  • Q is a heterocyclic ring selected from pyridinyl, pyrimidinyl, pyridazinyl, pyrazinyl, pyrazolyl, oxazolyl, isoxazolyl, oxadiazolyl, thiadiazolyl, isothiazolyl, imidazolyl, pyrrolyl, thiazolyl and triazolyl, said ring optionally substituted with 1 to 3 substituents selected from halogen, cyano and nitro, and C ⁇ -C 4 alkyl, C 1 -C 4 alkoxy and C ⁇ -C 3 alkylthio, each optionally substituted with 1 to 5 halogen selected from fluorine and chlorine.
  • Embodiment B A compound of Embodiment A wherein
  • R 1 is C 1 -C 2 alkyl or cyclopropyl, each optionally substituted with 1 to 3 halogen;
  • R 3 and R 4 are H; R 5 is methyl; and Q is 3 -pyridinyl or 5 -thiazolyl optionally substituted with 1 or 2 substituents selected from halogen, cyano and nitro, and C 1 -C 4 alkyl, C 1 -C 4 alkoxy and C ⁇ -C 3 alkylthio, each optionally substituted with 1 to 3 halogen selected from fluorine and chlorine.
  • Embodiment C A compound of Embodiment B wherein
  • R 1 is methyl, CH 2 CF 3 , CH 2 CF 2 H or cyclopropyl; and Q is 3-pyridinyl or 5-thiazolyl optionally substituted with 1 or 2 substituents selected from halogen, methyl, methoxy and trifluoromethyl.
  • Embodiment D A compound of Embodiment C wherein the nonhydrogen substituent(s) on the 3-pyridinyl or 5-thiazolyl of Q are bonded to ring atom(s) not adjacent to the ring atom connecting Q to the remainder of Formula 1.
  • Specific embodiments include compounds of Formula 1 selected from the group consisting of:
  • Embodiment Al A compound of Formula Ir wherein Y-Z is 0-CR 3 R 4 ;
  • R 1 is ⁇ ; or C 1 -C 3 alkyl or cyclopropyl, each optionally substituted with halogen;
  • R 2 is ⁇ or methyl
  • Q is a heterocyclic ring selected from pyridinyl, pyrimidinyl, pyridazinyl, pyrazinyl, pyrazolyl, oxazolyl, isoxazolyl, oxadiazolyl, thiadiazolyl, isothiazolyl, imidazolyl, pyrrolyl, thiazolyl and triazolyl, said ring optionally substituted with substituents selected from halogen, cyano and nitro, and C 1 -C 4 alkyl, C ⁇ C 4 alkoxy and C 1 -C 3 alkylthio, each optionally substituted with halogen selected from fluorine and chlorine.
  • Embodiment B 1. A compound of Embodiment Al wherein R 3 and R 4 are H;
  • R 1 is C ⁇ -C 2 alkyl or cyclopropyl, each optionally substituted with halogen;
  • R 2 is H; and
  • Q is 3-pyridinyl or 5-thiazolyl optionally substituted with substituents selected from halogen, cyano and nitro, and C 1 -C 4 alkyl, C 1 -C 4 alkoxy and C ⁇ -C 3 alkylthio, each optionally substituted with halogen selected from fluorine and chlorine.
  • Embodiment C 1 A compound of Embodiment B 1 wherein R 1 is methyl, CF 3 CH 2 or cyclopropyl; and
  • Q is 3-pyridinyl or 5-thiazolyl optionally substituted with substituents selected from halogen, methyl, methoxy and trifluoromethyl.
  • Embodiment Dl A compound of Embodiment C 1 wherein the nonhydrogen substituent(s) on the 3-pyridinyl or 5-thiazolyl of Q are bonded to ring atom(s) not adjacent to the ring atom connecting Q to the remainder of Formula Ir.
  • compounds of this invention are characterized by favorable metabolic and/or soil residual patterns and exhibit activity controlling a spectrum of agronomic and nonagronomic invertebrate pests.
  • compositions comprising a compound of any of the preceding Embodiments, as well as any other embodiments described herein, and any combinations thereof, and at least one additional component selected from the group consisting of a surfactant, a solid diluent and a liquid diluent, said compositions optionally further comprising at least one additional biologically active compound or agent.
  • compositions for controlling an invertebrate pest comprising a compound of any of the preceding Embodiments, as well as any other embodiments described herein, and any combinations thereof, and at least one additional component selected from the group consisting of a surfactant, a solid diluent and a liquid diluent, said compositions optionally further comprising at least one additional biologically active compound or agent.
  • Embodiments of the invention further include methods for controlling an invertebrate pest comprising contacting the invertebrate pest or its environment with a biologically effective amount of a compound of any of the preceding Embodiments (e.g., as a composition described herein).
  • Embodiments of the invention also include a composition comprising a compound of any of the preceding Embodiments, in the form of a soil drench liquid formulation.
  • Embodiments of the invention further include methods for controlling an invertebrate pest comprising contacting the soil with a liquid composition as a soil drench comprising a biologically effective amount of a compound of any of the preceding Embodiments.
  • Embodiments of the invention also include a spray composition for controlling an invertebrate pest comprising a biologically effective amount of a compound of any of the preceding Embodiments and a propellant.
  • Embodiments of the invention further include a bait composition for controlling an invertebrate pest comprising a biologically effective amount of a compound of any of the preceding Embodiments, one or more food materials, optionally an attractant, and optionally a humectant.
  • Embodiments of the invention also include a device for controlling an invertebrate pest comprising said bait composition and a housing adapted to receive said bait composition, wherein the housing has at least one opening sized to permit the invertebrate pest to pass through the opening so the invertebrate pest can gain access to said bait composition from a location outside the housing, and wherein the housing is further adapted to be placed in or near a locus of potential or known activity for the invertebrate pest.
  • Embodiments of the invention also include methods for protecting a seed from an invertebrate pest comprising contacting the seed with a biologically effective amount of a compound of any of the preceding Embodiments.
  • Embodiments of the invention also include methods for controlling a parasitic pest comprising contacting the parasitic pest or its environment with a biologically effective amount of a compound of Formula 1 or a salt thereof, (e.g., as a composition described herein), provided that the methods are not methods of medical treatment of a human or animal body by therapy.
  • a compound of Formula Ia (Formula 1 wherein Z is CR 3 R 4 ) can be prepared by reaction of a compound of Formula 2 with an amine of Formula 3.
  • Examples of the leaving group LG in Formula 2 include, but are not limited to, SMe, OMe, OEt and Cl.
  • the reaction is typically performed in an inert solvent such as toluene or xylene.
  • the reaction is typically performed at temperatures from about room temperature to 160 0 C, more typically from about 60 to 160 0 C, and most typically from about 90 to 130 0 C.
  • LG is a Leaving Group
  • compounds of Formula Ia wherein Y is O, S or NR 5 can be prepared by contacting a compound of Formula 4 with an amine of Formula 3 or its salt as illustrated in Scheme 2.
  • Typical salts of amines of Formula 3 include, but are not limited to, those formed with acids such as HCl or HBr.
  • Compounds of Formula 4 can be prepared by a variety of methods described in the literature. For a representative procedure, see: Dow et al. J. Med. Chem.
  • V is H or trimethylsilyl and W is O or S
  • Amines of Formula 3 can be prepared by a variety of methods described in the literature. These methods include reductive amination (i.e. the reaction of aldehydes with amines in the presence of reducing agents) and alkylation of amines with alkyl or heterocycloalkyl alkylating agents. For representitative procedures, see: Tian et al. J. Agri.
  • Compounds of Formula Ia wherein Y is O, S or NR 5 can also be prepared by contacting an amidine of Formula 5 with a carbonylation reagent such as, but not limited to, l,l '-carbonyldiimidazole.
  • a carbonylation reagent such as, but not limited to, l,l '-carbonyldiimidazole.
  • Compounds of Formula 2a can be prepared as shown in Scheme 4.
  • a compound of Formula 4a (Formula 4 wherein V is H and W is O) is treated with a thionating reagent such as P 4 S 10 or Lawesson's Reagent (2,4-bis-(4-methoxyphenyl)- l,3-dithia-2,4-diphosphetane 2,4-disulf ⁇ de) to form a compound of Formula 4b (Formula 4 wherein V is H and W is S).
  • a thionating reagent such as P 4 S 10 or Lawesson's Reagent (2,4-bis-(4-methoxyphenyl)- l,3-dithia-2,4-diphosphetane 2,4-disulf ⁇ de)
  • Compounds of Formula 4b are then treated with alkylating reagents such as, but not limited to, iodomethane, in the presence of a base such as, but not limited to, K 2 CO 3 , Na 2 CO 3 or CH 3 CO 2 Na to obtain the compounds of Formula 2a.
  • alkylating reagents such as, but not limited to, iodomethane
  • a base such as, but not limited to, K 2 CO 3 , Na 2 CO 3 or CH 3 CO 2 Na
  • compounds of Formula 2b can be prepared by contacting a compound of Formula 4a with an alkylating agent such as, but not limited to, iodomethane, iodoethane, or trimethyl- or triethyloxonium tetrafluoroborate as described in Dragovich et al. J. Org. Chem. 2002, 57(3), 741-746.
  • an alkylating agent such as, but not limited to, iodomethane, iodoethane, or trimethyl- or triethyloxonium tetrafluoroborate as described in Dragovich et al. J. Org. Chem. 2002, 57(3), 741-746.
  • Compounds of Formula 2c can be prepared by contacting a compound of Formula 4a with a chlorinating agent such as, but not limited to, phosphorus oxychloride as described in Sercel et al. Syn. Commun. 2007, 57(23), 4199-4208
  • the compound of Formula 2d (Formula 2 wherein Y is CH 2 , G is a bond, Z is CH 2 and LG is OEt) can be prepared according to the procedure of Crockett et al. Org. Syn. 1980, 59, 132-140.
  • compounds of Formula 2b can also be prepared by reacting an imidate of Formula 6 with a carbonylation reagent such as, but not limited to, 1,1 '- carbonyldiimidazole.
  • a carbonylation reagent such as, but not limited to, 1,1 '- carbonyldiimidazole.
  • Compounds of Formula Ia can also be prepared by constructing the heterocyclic ring from the corresponding acyclic components according to methods described in the literature.
  • preparing compounds of Formula Ia by constructing the oxazolone ring (Y is O and G is a bond) from the corresponding acyclic intermediates see: Kurz et al. Synthesis 2006, 11, 1803-1806 and L'abbe et al. Bull. Soc. Chim. BeIg. 1981, 90(1), 99-100.
  • thiazolone ring Y is S and G is a bond
  • G is a direct bond or CR 3 R 4 Z is O or S
  • compounds of Formula Ib wherein G is a direct bond or CR 3 R 4 and Z is
  • O or S can be prepared from compounds of Formula 7a (Formula 7 wherein LG is NH 2 ) as illustrated in Scheme 8.
  • Scheme 8 For a representative procedure of this method, including a method for the preparation of compounds of Formula 7a, see: Moffett et al. J. Het. Chem. 1980, 17(4), 753-758.
  • Z is O or S
  • Compounds of Formula Ib can also be prepared by constructing the oxazolone ring from the corresponding acyclic components according to methods described in the literature; see, for example: Sutin et al. Bioorg. Med. Chem. Lett. 2007, 77(17), 4837-4840. As shown in Scheme 9, compounds of Formula Ib can also be prepared by reaction of compounds of Formula 8 with esters of Formula 9. When Z is O or S, the compounds of Formula 9 are first treated with a base such as, but not limited to, NaH to form the corresponding alkoxide or thiol anion which is then reacted with the compound of Formula 8. For representative procedures, see: Dirlamet al. J. Org. Chem. 1986, 51, 4920-4924.
  • G is a direct bond or CR 3 R 4 Z is O, S or NR 5
  • compounds of Formula Ic can be prepared by reaction of a compound of Formula 10 with appropriately substituted hydrazines, hydroxylamines or sulfenamides of Formula 11.
  • the reaction is typically performed in a solvent such as ethanol or isopropanol, and at a temperature from about room temperature to the reflux temperature of the solvent, more typically at the reflux temperature of the solvent.
  • a solvent such as ethanol or isopropanol
  • compounds of Formula Ie can be prepared by reaction of aminonitriles of Formula 8 with 2,2- dialkyl-l,3-dioxin-4-ones of Formula 12.
  • the reaction is typically performed in a solvent such as toluene, xylenes or dioxane at a temperature typically ranging from 80 0 C to the reflux temperature of the solvent, more typically at the reflux temperature of the solvent.
  • a solvent such as toluene, xylenes or dioxane
  • R a and R are methyl or ethyl
  • Aminonitriles of Formula 8 can be prepared by the reaction of amines of Formula 3 with 1 to 3 molar equivalents of cyanogen bromide in the presence of 1 to 5 molar equivalents of a base such as, but not limited to, triethylamine, ⁇ /,jV-diisopropylethylamine, and potassium carbonate as shown in Scheme 12.
  • the reaction is typically performed in a solvent such as dichloromethane, tetrahydrofuran, or ethyl acetate at a temperature ranging from 0 0 C up to the boiling temperature of the solvent. If a reaction temperature higher than the boiling temperature of the solvent is desired, the reaction can be performed under microwave irradiation in a standard microwave reactor.
  • a base such as, but not limited to, triethylamine, ⁇ /,jV-diisopropylethylamine, and potassium carbonate as shown in Scheme 12.
  • the reaction is typically performed in a solvent such as dichlorome
  • Step A Preparation of ⁇ /-[(6-chloro-3-pyridinyl)methyl]-iV-cyclopropylcyanamide
  • Cyanogen bromide (1.0 mL of a 3.0 M solution in dichloromethane, 3.0 mmol) was added to a solution of 6-chloro- ⁇ /-cyclopropyl-3-pyridinemethanamine (0.51 g, 2.8 mmol) and N, ⁇ /-diisopropylethylamine (0.58 niL, 3.3 mmol) in dichloromethane (3 niL) at 0 °C. The resulting solution was stirred at room temperature for 16 h, diluted with ethyl acetate (10 mL), and concentrated under reduced pressure in the presence of silica gel (2 g). The residue was purified by MPLC on a 24 g silica column eluted with a gradient of 0% to 100% ethyl acetate in hexanes to provide 0.45 g of the title compound as a colorless oil.
  • Step B Preparation of 2,2-dimethyl-4H-l,3-dioxin-4-one 5-Formyl-2,2-dimethyl-l,3-dioxane-4,6-dione (5.0 g, 29 mmol) was added in several portions over 45 min to a boiling solution of 3-pentanone (15.5 mL, 145 mmol) in toluene (58 mL). The resulting solution was heated to boiling for a further 2 h, and then cooled to room temperature and concentrated under reduced pressure in the presence of silica gel (15 g).
  • Step C Preparation of 2-[[(6-chloro-3-pyridinyl)methyl]cyclopropylamino]-4H-l,3- oxazin-4-one
  • n means normal, i means iso, c means cyclo, Me means methyl, Et means ethyl, Pr means propyl, i-Pr means isopropyl, Bu means butyl, OMe means methoxy, and OEt means ethoxy.
  • X-I through X-54 are defined as follows:
  • Q is X-I, R 2 is H, R 3 is H and R 4 is H.
  • Q is X-I, R 2 is Me, R 3 is H and R 4 is H.
  • Q is X-I, R 2 is Me, R 3 is Me and R 4 is H.
  • Q is X-I
  • R 2 is H
  • R 3 is Me
  • R 4 is Me
  • z-Pr z-Bu CH CH 2 CH 2 CH CH 2 Y-I O
  • Q is X-I, R 2 is Me, R 3 is Me and R 4 is Me.
  • Q is X-3, R 2 is H, R 3 is H and R 4 is H.
  • Q is X-3, R 2 is Me, R 3 is H and R 4 is H.
  • Q is X-3, R 2 is H, R 3 is Me and R 4 is H.
  • Q is X-3, R 2 is Me, R 3 is Me and R 4 is H.
  • Q is X-3, R 2 is Me, R 3 is Me and R 4 is Me.
  • Q is X-4, R 2 is H, R 3 is H and R 4 is H.
  • Q is X-4, R 2 is Me, R 3 is H and R 4 is H.
  • Q is X-4, R 2 is H, R 3 is Me and R 4 is H.
  • Q is X-4, R 2 is Me, R 3 is Me and R 4 is H. 2
  • Q is X-4, R 2 is H, R 3 is Me and R 4 is Me.
  • Q is X-5, R 2 is H, R 3 is H and R 4 is H.
  • Q is X-5, R 2 is Me, R 3 is H and R 4 is H.
  • Q is X-5, R 2 is H, R 3 is Me and R 4 is H.
  • Q is X-5, R 2 is Me, R 3 is Me and R 4 is H.
  • Q is X-5, R 2 is H, R 3 is Me and R 4 is Me.
  • Q is X-5, R 2 is Me, R 3 is Me and R 4 is Me.
  • Q is X-6, R 2 is H, R 3 is H and R 4 is H.
  • Q is X-6, R 2 is Me, R 3 is H and R 4 is H.
  • Q is X-6, R 2 is Me, R 3 is Me and R 4 is H.
  • Q is X-6, R 2 is H, R 3 is Me and R 4 is Me.
  • Q is X-6, R 2 is Me, R 3 is Me and R 4 is Me.
  • Q is X-8, R 2 is H, R 3 is H and R 4 is H.
  • Q is X-8, R 2 is Me, R 3 is H and R 4 is H. 2
  • Q is X-8, R 2 is H, R 3 is Me and R 4 is H.
  • Q is X-8, R 2 is Me, R 3 is Me and R 4 is H.
  • Q is X-8, R 2 is H, R 3 is Me and R 4 is Me.
  • Q is X-8, R 2 is Me, R 3 is Me and R 4 is Me.
  • Q is X-I l
  • R 2 is H
  • R 3 is H
  • R 4 is H.
  • Q is X-11, R 2 is Me, R 3 is H and R 4 is H.
  • Q is X-I l
  • R 2 is H
  • R 3 is Me
  • R 4 is H.
  • Q is X-11, R 2 is Me, R 3 is Me and R 4 is H.
  • Q is X-I l
  • R 2 is H
  • R 3 is Me
  • R 4 is Me
  • Q is X-I l
  • R 2 is Me
  • R 3 is Me
  • R 4 is Me.
  • Q is X-13, R 2 is Me, R 3 is H and R 4 is H.
  • Q is X-13, R 2 is H, R 3 is Me and R 4 is H.
  • Q is X-13, R 2 is Me, R 3 is Me and R 4 is H.
  • Q is X-13, R 2 is H, R 3 is Me and R 4 is Me.
  • Q is X-13, R 2 is Me, R 3 is Me and R 4 is Me.
  • Q is X-21, R 2 is H, R 3 is H and R 4 is H.
  • Q is X-21, R 2 is Me, R 3 is H and R 4 is H.
  • Q is X-21, R 2 is H, R 3 is Me and R 4 is H.
  • Q is X-21, R 2 is Me, R 3 is Me and R 4 is H.
  • Q is X-21, R 2 is H, R 3 is Me and R 4 is Me.
  • Q is X-21, R 2 is Me, R 3 is Me and R 4 is Me.
  • Q is X-40, R 2 is H, R 3 is H and R 4 is H.
  • Q is X-40, R 2 is Me, R 3 is H and R 4 is H.
  • Q is X-40, R 2 is H, R 3 is Me and R 4 is H.
  • Q is X-40, R 2 is Me, R 3 is Me and R 4 is H.
  • Q is X-40, R 2 is Me, R 3 is Me and R 4 is Me.
  • Q is X-46, R 2 is H, R 3 is H and R 4 is H.
  • Q is X-46, R 2 is Me, R 3 is H and R 4 is H.
  • Q is X-46, R 2 is H, R 3 is Me and R 4 is H.
  • Q is X-46, R 2 is Me, R 3 is Me and R 4 is H. 2
  • R 3 is Me.
  • R 3 is Me. and R 3 is Me.
  • Q is X-9, R 2 is H and R 3 is H.
  • Q is X-9, R 2 is Me and R 3 is H.
  • Q is X-9, R 2 is H and R J is Me.
  • Q is X-12, R 2 is H and R 3 is H.
  • Q is X-12, R 2 is Me and R 3 is H.
  • Q is X-12, R 2 is H and R J is Me.
  • QisX-15, R 2 is H and R 3 is H.
  • QisX-15, R 2 is Me and R 3 is H.
  • QisX-15, R 2 is H and R 3 is Me.
  • QisX-16, R 2 is H and R 3 is H.
  • QisX-16,R 2 is Me and R 3 is H.
  • QisX-16,R 2 is H and R 3 is Me.
  • QisX-17, R 2 is H and R 3 is H.
  • QisX-17, R 2 is Me and R 3 is H.
  • QisX-17, R 2 is H and R 3 is Me.
  • H and R 3 is Me. H and R 3 is Me.
  • Q is X-19, R 2 is H and R 3 is H.
  • Q is X-19, R 2 is Me and R 3 is H.
  • Q is X-19, R 2 is H and R 3 is Me.
  • Q is X-22, R 2 is H and R 3 is H.
  • Q is X-22, R 2 is Me and R 3 is H.
  • Q is X-22, R 2 is H and R 3 is Me.
  • H and R 3 is Me. H and R 3 is Me.
  • Q is X-24, R 2 is H and R 3 is H.
  • Q is X-24, R 2 is Me and R 3 is H.
  • Q is X-24, R 2 is H and R 3 is Me.
  • Q is X-26, R 2 is H and R 3 is H.
  • Q is X-26, R 2 is Me and R 3 is H.
  • Q is X-26, R 2 is H and R 3 is Me.
  • H and R 3 is Me. H and R 3 is Me.
  • Q is X-28, R 2 is H and R 3 is H.
  • Q is X-28, R 2 is Me and R 3 is H.
  • Q is X-28, R 2 is H and R 3 is Me.
  • Q is X-30, R 2 is H and R 3 is H.
  • Q is X-30, R 2 is Me and R 3 is H.
  • Q is X-30, R 2 is H and R 3 is Me.
  • H and R 3 is Me. H and R 3 is Me.
  • Q is X-32, R 2 is H and R 3 is H.
  • Q is X-32, R 2 is Me and R 3 is H.
  • Q is X-32, R 2 is H and R 3 is Me.
  • Q is X-34, R 2 is H and R 3 is H.
  • Q is X-34, R 2 is Me and R 3 is H.
  • Q is X-34, R 2 is H and R 3 is Me.
  • H and R 3 is Me. H and R 3 is Me.
  • Q is X-36, R 2 is H and R 3 is H.
  • Q is X-36, R 2 is Me and R 3 is H.
  • Q is X-36, R 2 is H and R 3 is Me.
  • Q is X-38, R 2 is H and R 3 is H.
  • Q is X-38, R 2 is Me and R 3 is H.
  • Q is X-38, R 2 is H and R 3 is Me.
  • H and R 3 is Me. H and R 3 is Me.
  • Q is X-41, R 2 is H and R 3 is H.
  • Q is X-41, R 2 is Me and R 3 is H.
  • Q is X-41, R 2 is H and R 3 is Me.
  • Q is X-43, R 2 is H and R 3 is H.
  • Q is X-43, R 2 is Me and R 3 is H.
  • Q is X-43, R 2 is H and R 3 is Me.
  • Q is X-45, R 2 is H and R 3 is H.
  • Q is X-45, R 2 is Me and R 3 is H.
  • Q is X-45, R 2 is H and R 3 is Me.
  • Q is X-48, R 2 is H and R 3 is H.
  • Q is X-48, R 2 is Me and R 3 is H.
  • Q is X-48, R 2 is H and R 3 is Me.
  • H and R 3 is Me. H and R 3 is Me.
  • Q is X-50, R 2 is H and R 3 is H.
  • Q is X-50, R 2 is Me and R 3 is H.
  • Q is X-50, R 2 is H and R 3 is Me.
  • Q is X-52, R 2 is H and R 3 is H.
  • Q is X-52, R 2 is Me and R 3 is H.
  • Q is X-52, R 2 is H and R 3 is Me.
  • H and R 3 is Me. H and R 3 is Me.
  • Q is X-54, R 2 is H and R 3 is H.
  • Q is X-54, R 2 is Me and R 3 is H.
  • Q is X-54, R 2 is H and R 3 is Me.
  • Q is X-56, R 2 is H and R 3 is H.
  • Q is X-56, R 2 is Me and R 3 is H.
  • Q is X-56, R 2 is H and R 3 is Me.
  • R 3 is Me.
  • R 3 is Me.
  • R 3 is Me. and R 3 is Me.
  • R 3 is Me.
  • Q is X-8, R 2 is H and R 3 is H.
  • Q is X-8, R 2 is Me and R 3 is H.
  • Q is X-8, R 2 is H and R J is Me.
  • R 3 is Me.
  • Q is X-40, R 2 is H and R 3 is H.
  • Q is X-40, R 2 is Me and R 3 is H.
  • Q is X-40, R 2 is H and R 3 is Me.
  • Q is X-46, R 2 is H and R 3 is H.
  • Q is X-46, R 2 is Me and R 3 is H.
  • Q is X-46, R 2 is H and R 3 is Me.
  • Q is X-I, R 2 is H and R 3 is H.
  • Q is X-I, R 2 is Me and R 3 is H.
  • Q is X-I, R 2 is H and R 3 is Me.
  • R 3 is Me.
  • R 3 is Me.
  • R 3 is Me. and R 3 is Me.
  • Q is X-6, R 2 is H and R 3 is H.
  • Q is X-6, R 2 is Me and R 3 is H.
  • Q is X-6, R 2 is H and R J is Me.
  • R 3 is Me.
  • Q is X-11, R 2 is H and R 3 is H.
  • Q is X-I l, R 2 is Me and R 3 is H.
  • Q is X-I l, R 2 is H and R J is Me.
  • H and R 3 is Me. H and R 3 is Me.
  • Q is X-21, R 2 is H and R 3 is H.
  • Q is X-21, R 2 is Me and R 3 is H.
  • Q is X-21, R 2 is H and R 3 is Me.
  • Q is X-46, R 2 is H and R 3 is H.
  • Q is X-46, R 2 is Me and R 3 is H.
  • Q is X-46, R 2 is H and R 3 is Me.
  • R 3 is Me.
  • R 3 is Me.
  • R 3 is Me.
  • R 3 is Me. and R 3 is Me.
  • Q is X-6, R 2 is H and R 3 is H.
  • Q is X-6, R 2 is Me and R 3 is H.
  • Q is X-6, R 2 is H and R J is Me.
  • R 3 is Me.
  • Q is X-11, R 2 is H and R 3 is H.
  • Q is X-I l, R 2 is Me and R 3 is H.
  • Q is X-I l, R 2 is H and R J is Me.
  • H and R 3 is Me. H and R 3 is Me.
  • Q is X-21, R 2 is H and R 3 is H.
  • Q is X-21, R 2 is Me and R 3 is H.
  • Q is X-21, R 2 is H and R 3 is Me.
  • Q is X-46, R 2 is H and R 3 is H.
  • Q is X-46, R 2 is Me and R 3 is H.
  • Q is X-46, R 2 is H and R 3 is Me.
  • Q is X-5 and R 2 is H.
  • Q is X-5 and R 2 is Me.
  • QisX-13andR 2 isH.
  • Q is X- 13 and R 2 is Me.
  • R 1 is Me
  • R 1 is Me
  • R 1 is c-Pr
  • R 1 is c-Pr
  • R 1 is Me
  • R 1 is Me
  • a compound of this invention will generally be used as an invertebrate pest control active ingredient in a composition, i.e. formulation, with at least one additional component selected from the group consisting of surfactants, solid diluents and liquid diluents, which serves as a carrier.
  • a composition i.e. formulation
  • additional component selected from the group consisting of surfactants, solid diluents and liquid diluents, which serves as a carrier.
  • the formulation or composition ingredients are selected to be consistent with the physical properties of the active ingredient, mode of application and environmental factors such as soil type, moisture and temperature.
  • Liquid compositions include solutions (including emulsif ⁇ able concentrates), suspensions, emulsions (including microemulsions and/or suspoemulsions) and the like, which optionally can be thickened into gels.
  • aqueous liquid compositions are soluble concentrate, suspension concentrate, capsule suspension, concentrated emulsion, microemulsion and suspo-emulsion.
  • nonaqueous liquid compositions are emulsif ⁇ able concentrate, microemulsifiable concentrate, dispersible concentrate and oil dispersion.
  • compositions are dusts, powders, granules, pellets, prills, pastilles, tablets, filled films (including seed coatings) and the like, 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.
  • Active ingredient can be (micro)encapsulated and further formed into a suspension or solid formulation; alternatively the entire formulation of active ingredient can be encapsulated (or "overcoated”). Encapsulation can control or delay release of the active ingredient.
  • An emulsifiable granule combines the advantages of both an emulsifiable concentrate formulation and a dry granular formulation. High-strength compositions are primarily used as intermediates for further formulation. Sprayable formulations are typically extended in a suitable medium before spraying.
  • Such liquid and solid formulations are formulated to be readily diluted in the spray medium, usually water.
  • Spray volumes can range from about from about one to several thousand liters per hectare, but more typically are in the range from about ten to several hundred liters per hectare.
  • Sprayable formulations can be tank mixed with water or another suitable medium for foliar treatment by aerial or ground application, or for application to the growing medium of the plant.
  • Liquid and dry formulations can be metered directly into drip irrigation systems or metered into the furrow during planting.
  • Liquid and solid formulations can be applied onto seeds of crops and other desirable vegetation as seed treatments before planting to protect developing roots and other subterranean plant parts and/or foliage through systemic uptake.
  • the formulations will typically contain effective amounts of active ingredient, diluent and surfactant within the following approximate ranges which add up to 100 percent by weight.
  • 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.
  • Typical solid diluents are described in Watkins et al., Handbook of Insecticide Dust Diluents and Carriers, 2nd Ed., Dorland Books, Caldwell, New Jersey.
  • Liquid diluents include, for example, water, ⁇ /,iV-dimethylalkanamides (e.g., N, ⁇ /-dimethylformamide), limonene, dimethyl sulfoxide, JV-alkylpyrrolidones (e.g., JV-methylpyrrolidinone), ethylene glycol, Methylene glycol, propylene glycol, dipropylene glycol, polypropylene glycol, propylene carbonate, butylene carbonate, paraffins (e.g., white mineral oils, normal paraffins, isoparaff ⁇ ns), alkylbenzenes, alkylnaphthalenes, glycerine, glycerol triacetate, sorbitol, triacetin, aromatic hydrocarbons, dearomatized aliphatics, alkylbenzenes, alkylnaphthalenes, ketones such as cyclohexanone, 2-heptanone, iso
  • Liquid diluents also include glycerol esters of saturated and unsaturated fatty acids (typically C 6 -C 22 ), such as plant seed and fruit oils (e.g, oils of olive, castor, linseed, sesame, corn (maize), peanut, sunflower, grapeseed, safflower, cottonseed, soybean, rapeseed, coconut and palm kernel), animal-sourced fats (e.g., beef tallow, pork tallow, lard, cod liver oil, fish oil), and mixtures thereof.
  • plant seed and fruit oils e.g, oils of olive, castor, linseed, sesame, corn (maize), peanut, sunflower, grapeseed, safflower, cottonseed, soybean, rapeseed, coconut and palm kernel
  • animal-sourced fats e.g., beef tallow, pork tallow, lard, cod liver oil, fish oil
  • Liquid diluents also include alkylated fatty acids (e.g., methylated, ethylated, butylated) wherein the fatty acids may be obtained by hydrolysis of glycerol esters from plant and animal sources, and can be purified by distillation.
  • alkylated fatty acids e.g., methylated, ethylated, butylated
  • Typical liquid diluents are described in Marsden, Solvents Guide, 2nd Ed., Interscience, New York, 1950.
  • the solid and liquid compositions of the present invention often include one or more surfactants.
  • surfactants also known as “surface-active agents”
  • surface-active agents generally modify, most often reduce, the surface tension of the liquid.
  • surfactants can be useful as wetting agents, dispersants, emulsif ⁇ ers or defoaming agents.
  • Nonionic surfactants useful for the present compositions include, but are not limited to: alcohol alkoxylates such as alcohol alkoxylates based on natural and synthetic alcohols (which may be branched or linear) and prepared from the alcohols and ethylene oxide, propylene oxide, butylene oxide or mixtures thereof; amine ethoxylates, alkanolamides and ethoxylated alkanolamides; alkoxylated triglycerides such as ethoxylated soybean, castor and rapeseed oils; alkylphenol alkoxylates such as octylphenol ethoxylates, nonylphenol ethoxylates, dinonyl phenol ethoxylates and dodecyl phenol ethoxylates (prepared from the phenols and ethylene oxide, propylene oxide, butylene oxide or mixtures thereof); block polymers prepared from ethylene oxide or propylene
  • Useful anionic surfactants include, but are not limited to: alkylaryl sulfonic acids and their salts; carboxylated alcohol or alkylphenol ethoxylates; diphenyl sulfonate derivatives; lignin and lignin derivatives such as lignosulfonates; maleic or succinic acids or their anhydrides; olefin sulfonates; phosphate esters such as phosphate esters of alcohol alkoxylates, phosphate esters of alkylphenol alkoxylates and phosphate esters of styryl phenol ethoxylates; protein-based surfactants; sarcosine derivatives; styryl phenol ether sulfate; sulfates and sulfonates of oils and fatty acids; sulfates and sulfonates of ethoxylated alkylphenols; sulfates of alcohols; sulfates of e
  • Useful cationic surfactants include, but are not limited to: amides and ethoxylated amides; amines such as JV-alkyl propanediamines, tripropylenetriamines and dipropylenetetramines, and ethoxylated amines, ethoxylated diamines and propoxylated amines (prepared from the amines and ethylene oxide, propylene oxide, butylene oxide or mixtures thereof); amine salts such as amine acetates and diamine salts; quaternary ammonium salts such as quaternary salts, ethoxylated quaternary salts and diquaternary salts; and amine oxides such as alkyldimethylamine oxides and bis-(2-hydroxyethyl)-alkylamine oxides.
  • amines such as JV-alkyl propanediamines, tripropylenetriamines and dipropylenetetramines, and ethoxylated
  • Nonionic, anionic and cationic surfactants and their recommended uses are disclosed in a variety of published references including McCutcheon 's Emulsifiers and Detergents, annual American and International Editions published by McCutcheon's Division, The Manufacturing Confectioner Publishing Co.; Sisely and Wood, Encyclopedia of Surface Active Agents, Chemical Publ. Co., Inc., New York, 1964; and A. S. Davidson and B. Milwidsky, Synthetic Detergents, Seventh Edition, John Wiley and Sons, New York, 1987.
  • compositions of this invention may also contain formulation auxiliaries and additives, known to those skilled in the art as formulation aids (some of which may be considered to also function as solid diluents, liquid diluents or surfactants).
  • formulation auxiliaries and additives may control: pH (buffers), foaming during processing (antifoams such polyorganosiloxanes), sedimentation of active ingredients (suspending agents), viscosity (thixotropic thickeners), in-container microbial growth (antimicrobials), product freezing (antifreezes), color (dyes/pigment dispersions), wash-off (film formers or stickers), evaporation (evaporation retardants), and other formulation attributes.
  • Film formers include, for example, polyvinyl acetates, polyvinyl acetate copolymers, polyvinylpyrrolidone-vinyl acetate copolymer, polyvinyl alcohols, polyvinyl alcohol copolymers and waxes.
  • formulation auxiliaries and additives include those listed in McCutcheon 's Volume 2: Functional Materials, annual International and North American editions published by McCutcheon' s Division, The Manufacturing Confectioner Publishing Co.; and PCT Publication WO 03/024222.
  • the compound of Formula 1 and any other active ingredients are typically incorporated into the present compositions by dissolving the active ingredient in a solvent or by grinding in a liquid or dry diluent.
  • Solutions including emulsifiable concentrates, can be prepared by simply mixing the ingredients. If the solvent of a liquid composition intended for use as an emulsifiable concentrate is water-immiscible, an emulsifier is typically added to emulsify the active-containing solvent upon dilution with water. Active ingredient slurries, with particle diameters of up to 2,000 ⁇ m can be wet milled using media mills to obtain particles with average diameters below 3 ⁇ m. Aqueous slurries can be made into finished suspension concentrates (see, for example, U.S. 3,060,084) or further processed by spray drying to form water-dispersible granules.
  • Dusts and powders can be prepared by blending and usually grinding (such as with a hammer mill or fluid-energy mill).
  • Granules and pellets can be prepared by spraying the active material upon preformed granular carriers or by agglomeration techniques. See Browning, "Agglomeration", Chemical Engineering, December 4, 1967, pp 147-48, Perry's Chemical Engineer's Handbook, 4th Ed., McGraw-Hill, New York, 1963, pages 8-57 and following, and WO 91/13546.
  • Pellets can be prepared as described in U.S. 4,172,714.
  • Water-dispersible and water-soluble granules can be prepared as taught in U.S. 4,144,050, U.S. 3,920,442 and DE 3,246,493. Tablets can be prepared as taught in U.S. 5,180,587, U.S. 5,232,701 and U.S. 5,208,030. Films can be prepared as taught in GB 2,095,558 and U.S. 3,299,566.
  • Compound 6 65.0% dodecylphenol polyethylene glycol ether 2.0% sodium ligninsulfonate 4.0% sodium silicoaluminate 6.0% montmorillonite (calcined) 23.0%
  • Compound 26 25.0% anhydrous sodium sulfate 10.0% crude calcium ligninsulfonate 5.0% sodium alkvlnarjhthalenesulfonate 1.0% calcium/magnesium bentonite 59.0%
  • Compound 61 20.00% polyvinylpyrrolidone -vinyl acetate copolymer 5.00% montan acid wax 5.00% calcium ligninsulfonate 1.00% polyoxyethylene/polyoxypropylene block copolymers 1.00% stearyl alcohol (POE 20) 2.00% polyorganosilane 0.20% colorant red dye 0.05% water 65.75%
  • invertebrate pests include invertebrates inhabiting a variety of environments such as, for example, plant foliage, roots, soil, harvested crops or other foodstuffs, building structures or animal integuments.
  • These pests include, for example, invertebrates feeding on foliage (including leaves, stems, flowers and fruits), seeds, wood, textile fibers or animal blood or tissues, and thereby causing injury or damage to, for example, growing or stored agronomic crops, forests, greenhouse crops, ornamentals, nursery crops, stored foodstuffs or fiber products, or houses or other structures or their contents, or being harmful to animal health or public health.
  • foliage including leaves, stems, flowers and fruits
  • seeds wood, textile fibers or animal blood or tissues
  • present compounds and compositions are thus useful agronomically for protecting field crops from phytophagous invertebrate pests, and also nonagronomically for protecting other horticultural crops and plants from phytophagous invertebrate pests.
  • This utility includes protecting crops and other plants (i.e. both agronomic and nonagronomic) that contain genetic material introduced by genetic engineering (i.e. transgenic) or modified by mutagenesis to provide advantageous traits.
  • traits include tolerance to herbicides, resistance to phytophagous pests (e.g., insects, mites, aphids, spiders, nematodes, snails, plant-pathogenic fungi, bacteria and viruses), improved plant growth, increased tolerance of adverse growing conditions such as high or low temperatures, low or high soil moisture, and high salinity, increased flowering or fruiting, greater harvest yields, more rapid maturation, higher quality and/or nutritional value of the harvested product, or improved storage or process properties of the harvested products.
  • Transgenic plants can be modified to express multiple traits.
  • plants containing traits provided by genetic engineering or mutagenesis include varieties of corn, cotton, soybean and potato expressing an insecticidal Bacillus thuringiensis toxin such as YIELD GARD ® , KNOCKOUT R , STARLINK ® , BOLLGARD ® , NuCOTN ® and NEWLEAF ® , and herbicide-tolerant varieties of corn, cotton, soybean and rapeseed such as ROUNDUP READY ® , LIBERTY LINK ® , IMI , STS and CLEARFIELD , as well as crops expressing JV-acetyltransferase (GAT) to provide resistance to glyphosate herbicide, or crops containing the HRA gene providing resistance to herbicides inhibiting acetolactate synthase (ALS).
  • an insecticidal Bacillus thuringiensis toxin such as YIELD GARD ® , KNOCKOUT R , STARLINK ® , BOLLGARD ®
  • compositions of this invention can also optionally comprise plant nutrients, e.g., a fertilizer composition comprising at least one plant nutrient selected from nitrogen, phosphorus, potassium, sulfur, calcium, magnesium, iron, copper, boron, manganese, zinc, and molybdenum.
  • plant nutrients e.g., a fertilizer composition comprising at least one plant nutrient selected from nitrogen, phosphorus, potassium, sulfur, calcium, magnesium, iron, copper, boron, manganese, zinc, and molybdenum.
  • compositions comprising at least one fertilizer composition comprising at least one plant nutrient selected from nitrogen, phosphorus, potassium, sulfur, calcium and magnesium.
  • Compositions of the present invention which further comprise at least one plant nutrient can be in the form of liquids or solids.
  • solid formulations in the form of granules, small sticks or tablets.
  • Solid formulations comprising a fertilizer composition can be prepared by mixing the compound or composition of the present invention with the fertilizer composition together with formulating ingredients and then preparing the formulation by methods such as granulation or extrusion.
  • solid formulations can be prepared by spraying a solution or suspension of a compound or composition of the present invention in a volatile solvent onto a previous prepared fertilizer composition in the form of dimensionally stable mixtures, e.g., granules, small sticks or tablets, and then evaporating the solvent.
  • Nonagronomic uses refer to invertebrate pest control in the areas other than fields of crop plants.
  • Nonagronomic uses of the present compounds and compositions include control of invertebrate pests in stored grains, beans and other foodstuffs, and in textiles such as clothing and carpets.
  • Nonagronomic uses of the present compounds and compositions also include invertebrate pest control in ornamental plants, forests, in yards, along roadsides and railroad rights of way, and on turf such as lawns, golf courses and pastures.
  • Nonagronomic uses of the present compounds and compositions also include invertebrate pest control in houses and other buildings which may be occupied by humans and/or companion, farm, ranch, zoo or other animals.
  • Nonagronomic uses of the present compounds and compositions also include the control of pests such as termites that can damage wood or other structural materials used in buildings.
  • Examples of agronomic or nonagronomic invertebrate pests include eggs, larvae and adults of the order Lepidoptera, such as armyworms, cutworms, loopers, and heliothines in the family Noctuidae (e.g., pink stem borer (Sesamia inferens Walker), corn stalk borer (Sesamia nonagrioides Lefebvre), southern armyworm (Spodoptera eridania Cramer), fall armyworm ⁇ Spodoptera fugiperda J. E.
  • Noctuidae e.g., pink stem borer (Sesamia inferens Walker), corn stalk borer (Sesamia nonagrioides Lefebvre), southern armyworm (Spodoptera eridania Cramer), fall armyworm ⁇ Spodoptera fugiperda J. E.
  • agronomic and nonagronomic pests include: eggs, adults and larvae of the order Dermaptera including earwigs from the family Forf ⁇ culidae (e.g., European earwig (Forficula auricularia Linnaeus), black earwig (Chelisoches mono Fabricius)); eggs, immatures, adults and nymphs of the orders Hemiptera and Homoptera such as, plant bugs from the family Miridae, cicadas from the family Cicadidae, leafhoppers (e.g.
  • eggs, larvae, nymphs and adults of the order Acari such as spider mites and red mites in the family Tetranychidae (e.g., European red mite (Panonychus ulmi Koch), two spotted spider mite (Tetranychus urticae Koch), McDaniel mite (Tetranychus mcdanieli McGregor)); flat mites in the family Tenuipalpidae (e.g., citrus flat mite (Brevipalpus lewisi McGregor)); rust and bud mites in the family Eriophyidae and other foliar feeding mites and mites important in human and animal health, i.e.
  • Tetranychidae e.g., European red mite (Panonychus ulmi Koch), two spotted spider mite (Tetranychus urticae Koch), McDaniel mite (Tetranychus mcdanieli
  • ticks in the family Ixodidae commonly known as hard ticks (e.g., deer tick (Ixodes scapularis Say), Australian paralysis tick (Ixodes holocyclus Neumann), American dog tick (Dermacentor variabilis Say), lone star tick (Amblyomma americanum Linnaeus)) and ticks in the family Argasidae, commonly known as soft ticks (e.g., relapsing fever tick (Ornithodoros turicata), common fowl tick (Argas radiatus)); scab and itch mites in the families Psoroptidae, Pyemotidae, and Sarcoptidae; eggs, adults and immatures of the order Orthoptera including grasshoppers, locus
  • serpentine vegetable leafminer Liriomyza sativae Blanchard
  • midges fruit flies
  • frit flies e.g., Oscinella frit Linnaeus
  • soil maggots e.g., house flies (e.g., Musca domestica Linnaeus), lesser house flies (e.g., Fannia canicularis Linnaeus, F.
  • femoralis Stein stable flies (e.g., Stomoxys calcitrans Linnaeus), face flies, horn flies, blow flies (e.g., Chrysomya spp., Phormia spp.), and other muscoid fly pests, horse flies (e.g., Tabanus spp.), bot flies (e.g., Gastrophilus spp., Oestrus spp.), cattle grubs (e.g., Hypoderma spp.), deer flies (e.g., Chrysops spp.), keds (e.g., Melophagus ovinus Linnaeus) and other Brachycera, mosquitoes (e.g., Aedes spp., Anopheles spp., Culex spp.), black flies (e.g., Prosimulium spp., Simulium s
  • Hymenoptera including bees (including carpenter bees), hornets, yellow jackets, wasps, and sawflies (Neodiprion spp.; Cephus spp.); insect pests of the order Isoptera including termites in the Termitidae (e.g., Macrotermes sp., Odontotermes obesus Rambur), Kalotermitidae (e.g., Cryptotermes sp.), and Rhinotermitidae (e.g., Reticulitermes sp., Coptotermes sp., Heterotermes tenuis Hagen) families, the eastern subterranean termite (Reticulitermes flavipes Kollar), western subterranean termite (Reticulitermes hesperus Banks), Formosan subterranean termite (Coptotermes formosanus Shiraki), West Indian drywood termite (Incisitermes immigrans
  • insect pests of the order Thysanura such as silverfish (Lepisma saccharina Linnaeus) and firebrat (Thermobia domestica Packard); insect pests of the order Mallophaga and including the head louse (Pediculus humanus capitis De Geer), body louse (Pediculus humanus Linnaeus), chicken body louse (Menacanthus stramineus Nitszch), dog biting louse (Trichodectes canis De Geer), fluff louse (Goniocotes gallinae De Geer), sheep body louse (Bovicola ovis Schrank), short-nosed cattle louse (Haematopinus eurysternus Nitzsch), long-nosed cattle louse (Linognathus vituli Linnaeus) and other sucking and chewing parasitic lice that attack man and animals; insect pests of the order Siphonoptera including the oriental rat fle
  • Additional arthropod pests covered include: spiders in the order Araneae such as the brown recluse spider (Loxosceles reclusa Gertsch & Mulaik) and the black widow spider (Latrodectus mactans Fabricius), and centipedes in the order Scutigeromorpha such as the house centipede (Scutigera coleoptrata Linnaeus).
  • spiders in the order Araneae such as the brown recluse spider (Loxosceles reclusa Gertsch & Mulaik) and the black widow spider (Latrodectus mactans Fabricius)
  • centipedes in the order Scutigeromorpha such as the house centipede (Scutigera coleoptrata Linnaeus).
  • Compounds of the present invention also have activity on members of the Classes Nematoda, Cestoda, Trematoda, and Acanthocephala including economically important members of the orders Strongylida, Ascaridida, Oxyurida, Rhabditida, Spirurida, and Enoplida such as but not limited to economically important agricultural pests (i.e. root knot nematodes in the genus Meloidogyne, lesion nematodes in the genus Pratylenchus, stubby root nematodes in the genus Trichodorus, etc.) and animal and human health pests (i.e.
  • Compounds of the invention show particularly high activity against pests in the order Homoptera including: Acyrthosiphon pisum Harris (pea aphid), Aphis craccivora Koch (cowpea aphid), Aphis fabae Scopoli (black bean aphid), Aphis gossypii Glover (cotton aphid, melon aphid), Aphis pomi De Geer (apple aphid), Aphis spiraecola Patch (spirea aphid), Aulacorthum solani Kaltenbach (foxglove aphid), Chaetosiphon fragaefolii Cockerell (strawberry aphid), Diuraphis noxia Kurdjumov/Mordvilko (Russian wheat aphid), Dysaphis plantaginea Paaserini (rosy apple aphid), Eriosoma lanigerum Hausmann (woolly apple aphid), Hyal
  • Compounds of this invention also have activity on members from the order Hemiptera including: Acrosternum hilare Say (green stink bug), Anasa tristis De Geer (squash bug), Blissus leucopterus leucopterus Say (chinch bug), Cimex lectularius Linnaeus (bed bug) Corythuca gossypii Fabricius (cotton lace bug), Cyrtopeltis modesta Distant (tomato bug), Dysdercus suturellus Herrich- S chaffer (cotton stainer), Euchistus servus Say (brown stink bug), Euchistus variolarius Palisot de Beauvois (one-spotted stink bug), Graptosthetus spp.
  • Thysanoptera e.g., Frankliniella occidentalis Pergande (western flower thrips), Scirthothrips citri Moulton (citrus thrips), Sericothrips variabilis Beach (soybean thrips), and Thrips tabaci Lindeman (onion thrips); and the order Coleoptera (e.g., Leptinotarsa decemlineata Say (Colorado potato beetle), Epilachna varivestis Mulsant (Mexican bean beetle) and wireworms of the genera Agriotes, Athous or Limonius).
  • Thysanoptera e.g., Frankliniella occidentalis Pergande (western flower thrips), Scirthothrips citri Moulton (citrus thrips), Sericothrips variabilis Beach (soybean thrips), and Thrips tabaci Lindeman (onion thrips); and
  • compounds of this invention for controlling potato leafhopper (Empoasca fabae). Of note is use of compounds of this invention for controlling corn planthopper (Peregrinus maidis). Of note is use of compounds of this invention for controlling cotton melon aphid ⁇ Aphis gossypi ⁇ ). Of note is use of compounds of this invention for controlling green peach aphid (Myzus persicae).
  • compounds of this invention for controlling imidacloprid-resistant invertebrate pests.
  • compounds of this invention for controlling imidacloprid-resistant rice brown planthopper (Nilaparvata lugens).
  • compounds of this invention for controlling imidacloprid-resistant sweetpotato whitefly (Bemisia tabaci).
  • Compounds of this invention can also be mixed with one or more other biologically active compounds or agents including insecticides, fungicides, nematocides, 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, virus or fungi to form a multi-component pesticide giving an even broader spectrum of agronomic and nonagronomic utility.
  • insecticides fungicides, nematocides, 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 entomopath
  • the present invention also pertains to a composition
  • a composition comprising a biologically effective amount of a compound of Formula 1, at least one additional component selected from the group consisting of surfactants, solid diluents and liquid diluents, and at least one additional biologically active compound or agent.
  • the other biologically active compounds or agents can be formulated together with the present compounds, including the compounds of Formula 1, to form a premix, or the other biologically active compounds or agents can be formulated separately from the present compounds, including the compounds of Formula 1, and the two formulations combined together before application (e.g., in a spray tank) or, alternatively, applied in succession.
  • insecticides such as abamectin, acephate, acequinocyl, acetamiprid, acrinathrin, amidoflumet, amitraz, avermectin, azadirachtin, azinphos-methyl, bifenthrin, bifenazate, bistrifluron, borate, buprofezin, cadusafos, carbaryl, carbofuran, cartap, carzol, chlorantraniliprole, chlorfenapyr, chlorfluazuron, chlorpyrifos, chlorpyrifos- methyl, chromafenozide, clofentezin, clothianidin, cyantraniliprole, cyflumetofen, cyfluthrin, beta-cyfluthrin, cyhalothrin, gamma-cyhaloth
  • insecticides such as abamectin, acetamiprid, acrinathrin, amitraz, avermectin, azadirachtin, bifenthrin, buprofezin, cadusafos, carbaryl, cartap, chlorantraniliprole, chlorfenapyr, chlorpyrifos, clothianidin, cyantraniliprole, cyfluthrin, beta-cyfluthrin, cyhalothrin, gamma-cyhalothrin, lambda-cyhalothrin, cypermethrin, alpha- cypermethrin, zeta-cypermethrin, cyromazine, deltamethrin, dieldrin, dinotefuran, diofenolan, emamectin, endosulfan, esfenvalerate, ethiprole, dinote
  • One embodiment of biological agents for mixing with compounds of this invention include entomopathogenic bacteria such as Bacillus thuringiensis, and the encapsulated delta-endotoxins of Bacillus thuringiensis such as MVP® and MVPII® bioinsecticides prepared by the CellCap® process (CellCap®, MVP® and MVPII® are trademarks of Mycogen Corporation, Indianapolis, Indiana, USA); entomopathogenic fungi such as green muscardine fungus; and entomopathogenic (both naturally occurring and genetically modified) viruses including baculovirus, nucleopolyhedro virus (NPV) such as Helicoverpa zea nucleopolyhedrovirus (HzNPV), Anagrapha falcifera nucleopolyhedrovirus (AfNPV); and granulosis virus (GV) such as Cydia pomonella granulosis virus (CpGV).
  • NPV nucleopolyhedr
  • a combination with at least one other invertebrate pest control active ingredient having a similar spectrum of control but a different site of action will be particularly advantageous for resistance management.
  • a composition of the present invention can further comprise 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.
  • additional biologically active compounds or agents include, but are not limited to, sodium channel modulators such as bifenthrin, cypermethrin, cyhalothrin, lambda-cyhalothrin, cyfluthrin, beta-cyfluthrin, deltamethrin, dimefluthrin, esfenvalerate, fenvalerate, indoxacarb, metofluthrin, profluthrin, pyrethrin and tralomethrin; cholinesterase inhibitors such as chlorpyrifos, methomyl, oxamyl, thiodicarb and triazamate; neonicotinoids such as acetamiprid, clothianidin, dinotefuran, imidacloprid, nitenpyram, nithiazine, thiacloprid and thiamethoxam; insecticidal macrocyclic lactones such as spinetoram, spin
  • biologically active compounds or agents with which compounds of this invention can be formulated are: fungicides such as acibenzolar, aldimorph, amisulbrom, azaconazole, azoxystrobin, benalaxyl, benomyl, benthiavalicarb, benthiavalicarb-isopropyl, binomial, biphenyl, bitertanol, blasticidin-S, Bordeaux mixture (Tribasic copper sulfate), boscalid/nicobifen, bromuconazole, bupirimate, buthiobate, carboxin, carpropamid, captafol, captan, carbendazim, chloroneb, chlorothalonil, chlozolinate, clotrimazole, copper oxychloride, copper salts such as copper sulfate and copper hydroxide, cyazofamid, cyflunamid, cymoxanil,
  • combinations of a compound of this invention with other biologically active (particularly invertebrate pest control) compounds or agents can result in a greater-than-additive (i.e. synergistic) effect. Reducing the quantity of active ingredients released in the environment while ensuring effective pest control is always desirable.
  • synergism of invertebrate pest control active ingredients occurs at application rates giving agronomically satisfactory levels of invertebrate pest control, such combinations can be advantageous for reducing crop production cost and decreasing environmental load.
  • Compounds of this invention and compositions thereof can be applied to plants genetically transformed to express proteins toxic to invertebrate pests (such as Bacillus thuringiensis delta-endotoxins). Such an application may provide a broader spectrum of plant protection and be advantageous for resistance management.
  • the effect of the exogenously applied invertebrate pest control compounds of this invention may be synergistic with the expressed toxin proteins.
  • the weight ratio of these various mixing partners (in total) to the compound of Formula 1 is typically between about 1 :3000 and about 3000:1. Of note are weight ratios between about 1 :300 and about 300:1 (for example ratios between about 1 :30 and about 30:1).
  • weight ratios between about 1 :300 and about 300:1 for example ratios between about 1 :30 and about 30:1).
  • One skilled in the art can easily determine through simple experimentation the biologically effective amounts of active ingredients necessary for the desired spectrum of biological activity. It will be evident that including these additional components can expand the spectrum of invertebrate pests controlled beyond the spectrum controlled by the compound of Formula 1 alone.
  • Table A lists specific combinations of a compound of Formula 1 with other invertebrate pest control agents illustrative of the mixtures, compositions and methods of the present invention and includes additional embodiments of weight ratio ranges for application rates.
  • the first column of Table A lists the specific invertebrate control agents (e.g., "Abamectin" in the first line).
  • the second column of Table A lists the mode of action (if known) or chemical class of the invertebrate pest control agents.
  • the third column of Table A lists embodiment(s) of ranges of weight ratios for rates at which the invertebrate pest control agent can be applied relative to a compound of Formula 1 (e.g., "50:1 to 1 :50" of abamectin relative to a compound of Formula 1 by weight).
  • the first line of Table A specifically discloses the combination of a compound of Formula 1 with abamectin can be applied in a weight ratio between 50:1 to 1 :50.
  • the remaining lines of Table A are to be construed similarly. Table A
  • composition of the present invention wherein the at least one additional biologically active compound or agent is selected from the Invertebrate Pest Control Agents listed in Table A above.
  • the weight ratios of a compound, including a compound of Formula 1 or a salt thereof, to the additional invertebrate pest control agent typically are between 1000:1 and 1 :1000, with one embodiment being between 500:1 and 1 :500, another embodiment being between 250:1 and 1 :200 and another embodiment being between 100:1 and 1 :50.
  • Table B Listed below in Table B are embodiments of specific compositions comprising a compound of Formula 1 (compound numbers refer to compounds in Index Table A) and an additional invertebrate pest control agent.

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Abstract

Disclosed are compounds of Formula (I), including all stereoisomers, and salts thereof, wherein Y is O, S, NR5 or CR3R4, G is a direct bond, and Z is CR3R4 or NR5; or Y is CR3R4, G is a direct bond, and Z is O or S; or Y is O, S, NR5 or CR3R4, G is CR3R4, and Z is O, S, NR5 or CR3R4; or Y is O, and G–Z is CH=CH; or Y–G is CH=CH, and Z is O, S or NR5; and R1, R2, R3, R4, R5 and Q are as defined in the disclosure. Also disclosed are compositions containing the compounds of Formula 1 and methods for controlling an invertebrate pest comprising contacting the invertebrate pest or its environment with a biologically effective amount of a compound or a composition of the invention.

Description

TITLE INSECTICIDAL CYCLIC CARBONYL AMIDINES
FIELD OF THE INVENTION
This invention relates to certain cyclic carbonyl amidines, their salts and compositions suitable for agronomic and nonagronomic uses, and methods of their use for controlling invertebrate pests such as arthropods in agronomic and nonagronomic environments.
BACKGROUND OF THE INVENTION
The control of invertebrate pests is extremely important in achieving high crop efficiency. Damage by invertebrate pests to growing and stored agronomic crops can cause significant reduction in productivity and thereby result in increased costs to the consumer.
The control of invertebrate pests in forestry, greenhouse crops, ornamentals, nursery crops, stored food and fiber products, livestock, household, turf, wood products, and public and animal health is also important. Many products are commercially available for these purposes, but the need continues for new compounds that are more effective, less costly, less toxic, and environmentally safer or have different sites of action.
PCT Patent Publication WO 07/115643 discloses certain amine derivatives of Formula i as insecticides
Figure imgf000002_0001
wherein, inter alia, A is pyrimidinyl, pyrazolyl, thienyl, oxazolyl, isoxazolyl, oxadiazolyl, isothiazolyl, triazolyl or thiadiazolyl, B is O, S or methylene, R1 is H, alkyl, alkenyl, alkynyl, cycloalkyl or alkoxy, R2 is H or halogen, and R3 is H or alkyl.
The cyclic carbonyl amidines of the present invention are not disclosed in this publication.
SUMMARY OF THE INVENTION This invention is directed to compounds of Formula 1 (including all stereoisomers) and salts thereof, and compositions containing them and their use for controlling invertebrate pests:
Figure imgf000003_0001
1 wherein
Y is O, S, NR5 or CR3R4, G is a direct bond, and Z is CR3R4 or NR5; or
Y is CR3R4, G is a direct bond, and Z is O or S; or Y is O, S, NR5 or CR3R4, G is CR3R4, and Z is O, S, NR5 or CR3R4; or
Y is O, and G-Z is CH=CH; or
Y-G is CH=CH, and Z is O, S or NR5;
R1 is H, C1-C3 alkoxy, C(O)R6 or SO2R7; or C1-C4 alkyl, C3-C4 alkenyl, C3-C4 alkynyl, C3-C4 cycloalkyl, C4-C5 cycloalkylalkyl, C4-C5 alkylcycloalkyl or benzyl, each optionally substituted with 1 to 5 halogen;
R2 is H or C1-C2 alkyl; each R3 is independently H or CH3; each R4 is independently H or CH3; each R5 is independently H, C1-C2 alkyl or C1-C2 haloalkyl; R6 is C !-C2 alky! or C i-C2 haloalkyl;
R7 is C1-C2 alkyl or C1-C2 haloalkyl; and
Q is a 5- or 6-membered fully unsaturated heterocyclic ring containing as ring members at least one nitrogen atom and other ring members selected from carbon, oxygen and sulfur atoms, said ring optionally substituted with 1 to 3 substituents selected from halogen, cyano, nitro, and C1-C4 alkyl, C1-C4 alkoxy and C1-C3 alkylthio, each optionally substituted with 1 to 5 fluorine or chlorine; or 3-tetrahydrofuranyl.
This invention also provides a composition comprising a compound of Formula 1 or a salt thereof (i.e. in a biologically effective amount), and at least one additional component selected from the group consisting of surfactants, solid diluents and liquid diluents. In one embodiment, this invention also provides a composition for controlling an invertebrate pest comprising a compound of Formula 1 or a salt thereof, and at least one additional component selected from the group consisting of surfactants, solid diluents and liquid diluents, said composition optionally further comprising at least one additional biologically active compound or agent.
This invention provides a method for controlling an invertebrate pest comprising contacting the invertebrate pest or its environment with a biologically effective amount of a compound of Formula 1 or a salt thereof, (e.g., as a composition described herein). This invention also relates to such method wherein the invertebrate pest or its environment is contacted with a composition comprising a biologically effective amount of a compound of Formula 1 or a salt thereof, and at least one additional component selected from the group consisting of surfactants, solid diluents and liquid diluents, said composition optionally further comprising a biologically effective amount of at least one additional biologically active compound or agent.
This invention also provides a method for protecting a seed from an invertebrate pest comprising contacting the seed with a biologically effective amount of a compound of Formula 1 or a salt thereof (e.g., as a composition described herein). This invention also relates to the treated seed.
DETAILS OF THE INVENTION
As used herein, the terms "comprises", "comprising", "includes", "including", "has", "having", "contains", "containing", "characterized by", or any other variation thereof, are intended to cover a non-exclusive inclusion, subject to any limitation explicitly indicated. For example, a composition, a mixture, process, method, article, or apparatus that comprises a list of elements is not necessarily limited to only those elements but may include other elements not expressly listed or inherent to such composition, mixture, process, method, article, or apparatus. The transitional phrase "consisting of excludes any element, step, or ingredient not specified. If in the claim, such would close the claim to the inclusion of materials other than those recited except for impurities ordinarily associated therewith. When the phrase "consists of appears in a clause of the body of a claim, rather than immediately following the preamble, it limits only the element set forth in that clause; other elements are not excluded from the claim as a whole. The transitional phrase "consisting essentially of is used to define a composition, method or apparatus that includes materials, steps, features, components, or elements, in addition to those literally disclosed, provided that these additional materials, steps, features, components, or elements do materially affect the basic and novel characteristic(s) of the claimed invention. The term "consisting essentially of occupies a middle ground between "comprising" and "consisting of. Where applicants have defined an invention or a portion thereof with an open-ended term such as "comprising," it should be readily understood that (unless otherwise stated) the description should be interpreted to also describe such an invention using the terms "consisting essentially of or "consisting of." Further, unless expressly stated to the contrary, "or" refers to an inclusive or and not to an exclusive or. For example, a condition A or B is satisfied by any one of the following: A is true (or present) and B is false (or not present), A is false (or not present) and B is true (or present), and both A and B are true (or present). Also, the indefinite articles "a" and "an" preceding an element or component of the invention are intended to be nonrestrictive regarding the number of instances (i.e. occurrences) of the element or component. Therefore "a" or "an" should be read to include one or at least one, and the singular word form of the element or component also includes the plural unless the number is obviously meant to be singular.
As referred to in this disclosure, the term "invertebrate pest" includes arthropods, gastropods and nematodes of economic importance as pests. The term "arthropod" includes insects, mites, spiders, scorpions, centipedes, millipedes, pill bugs and symphylans. The term "gastropod" includes snails, slugs and other Stylommatophora. The term "nematode" refers to a living organism of the Phylum Nematoda. As generally defined, a "parasite" lives or grows inside or feeds on another living organism (such as a plant, animal or human) described as the "host". As referred to in the present disclosure and claims a "parasitic pest" is particularly a pest that injures or damages tissue or causes other forms of disease in plants, animals (particularly vertebrates) or humans. A parasite "infestation" refers to the presence of parasites in numbers that pose a risk to plants, humans or animals. The presence can be in the environment, e.g., in a human or animal house, or surrounding property or structures, on an agricultural crop or other type of plant, in animal bedding, on the skin or fur of an animal, etc. When the infestation that is referred to is within an animal, e.g., in the blood or other internal tissues, the term infestation is also intended to be synonymous with the term, "infection," as that term is generally understood in the art, unless otherwise stated.
As referred to in the present disclosure and claims, the term "invertebrate pest control" means inhibition of invertebrate pest development (including mortality, feeding reduction, and/or mating disruption), and related expressions are defined analogously. The terms "parasiticidal" and "parasiticidally" refers to observable effects on a parasitic pest to provide protection of a plant, animal or human from the pest. Parasiticidal effects typically relate to diminishing the occurrence or activity of the target parasitic pest. Such effects on the pest include necrosis, death, retarded growth, diminished mobility or lessened ability to remain on or in the host plant, animal or human, reduced feeding and inhibition of reproduction. These effects on parasitic pests provide control (including prevention, reduction or elimination) of parasitic infestation or infection of the plant, animal or human. Therefore "control" of a parasitic pest means achieving a parasiticidal effect on the pest. The expressions "parasiticidally effective amount" and "biologically effective amount" in the context of applying a chemical compound to control a parasitic pest refer to an amount of the compound that is sufficient to control the parasitic pest.
The term "agronomic" refers to the production of field crops such as for food and fiber and includes the growth of corn, soybeans and other legumes, rice, cereal (e.g., wheat, oats, barley, rye, rice, maize), leafy vegetables (e.g., lettuce, cabbage, and other cole crops), fruiting vegetables (e.g., tomatoes, pepper, eggplant, crucifers and cucurbits), potatoes, sweet potatoes, grapes, cotton, tree fruits (e.g., pome, stone and citrus), small fruit (berries, cherries) and other specialty crops (e.g., canola, sunflower, olives).
The term "nonagronomic" refers to other than field crops, such as horticultural crops (e.g., greenhouse, nursery or ornamental plants not grown in a field), residential, agricultural, commercial and industrial structures, turf (e.g., sod farm, pasture, golf course, lawn, sports field, etc.), wood products, stored product, agro-forestry and vegetation management, public health (i.e. human) and animal health (e.g., domesticated animals such as pets, livestock and poultry, undomesticated animals such as wildlife) applications. In the above recitations, the term "alkyl", used either alone or in compound words such as "alkylthio" or "haloalkyl" includes straight-chain and branched alkyl, such as, methyl, ethyl, n-propyl, /-propyl, and the different butyl isomers. "Alkenyl" includes straight-chain and branched alkenes such as 1-propenyl, 2-propenyl, and the different butenyl isomers. "Alkynyl" includes straight-chain and branched alkynes such as 1-propynyl, 2-propynyl and the different butynyl isomers.
"Alkoxy" includes, for example, methoxy, ethoxy, n-propyloxy, isopropyloxy and the different butoxy isomers. "Alkylthio" includes branched and straight-chain alkylthio moieties such as methylthio, ethylthio, and the different propylthio isomers.
"Cycloalkyl" includes, for example, cyclopropyl and cyclobutyl. The term "cycloalkylalkyl" denotes cycloalkyl substitution on an alkyl moiety. Examples of "cycloalkylalkyl" include cyclopropylmethyl, cyclopropylethyl, and other cycloalkyl moieties bonded to alkyl groups. The term "alkylcycloalkyl" denotes alkyl substitution on a cycloalkyl moiety. Examples of "alkylcycloalkyl" include methylcyclopropyl, ethylcyclopropyl, and other alkyl moieties bonded to cycloalkyl groups. The term "halogen", either alone or in compound words such as "haloalkyl", or when used in descriptions such as "alkyl substituted with halogen" includes fluorine, chlorine, bromine and iodine. Further, when used in compound words such as "haloalkyl", or when used in descriptions such as "alkyl substituted with halogen" said alkyl may be partially or fully substituted with halogen atoms which may be the same or different. Examples of "haloalkyl" or "alkyl substituted with halogen" include F3C, ClCH2, CF3CH2 and CF3CCl2. The chemical abbreviation C(O) as used herein represents a carbonyl moiety. For example, C(O)CH3 represents an acetyl group. The chemical abbreviations CO2 and C(O)O as used herein represent an ester moiety. For example, CO2Me and C(O)OMe represent a methyl ester. When G in Formula 1 is a direct bond, this is the same as if Y were directly bonded to
Z. The total number of carbon atoms in a substituent group is indicated by the "Cj-C;" prefix where i and j are numbers from 1 to 5. For example, C1-C4 alkyl designates methyl through butyl.
Unless otherwise indicated, a "ring" as a component of Formula 1 is carbocyclic or heterocyclic.
The terms "heterocyclic ring" denotes a ring in which at least one atom forming the ring backbone is not carbon, e.g., nitrogen, oxygen or sulfur. Typically a heterocyclic ring contains no more than 4 nitrogens, no more than 2 oxygens and no more than 2 sulfurs. Unless otherwise indicated, a heterocyclic ring can be a saturated, partially unsaturated, or fully unsaturated ring. When a fully unsaturated heterocyclic ring satisfies Hϋckel's rule, then said ring is also called a "heteroaromatic ring" or "aromatic heterocyclic ring". Unless otherwise indicated, heterocyclic rings and ring systems can be attached through any available carbon or nitrogen by replacement of a hydrogen on said carbon or nitrogen.
As used in the present disclosure and claims (e.g., in the definition of Q), the expression "fully unsaturated ring" means a ring of atoms in which the bonds between carbon and/or nitrogen atoms in the ring are single or double bonds according to valence bond theory and furthermore the bonds between carbon and/or nitrogen atoms in the ring include as many double bonds as possible without double bonds being cumulative (i.e. no C=C=C, N=C=C, etc.). In a "fully unsaturated ring" according to the present invention, ring atoms other than carbon and nitrogen are bonded only by single bonds. Accordingly, five- membered fully unsaturated rings contain two alternating double bonds, and six-membered fully unsaturated rings contain three alternating double bonds.
"Aromatic" indicates that each of the ring atoms is essentially in the same plane and has a/?-orbital perpendicular to the ring plane, and in which (4n + T) π electrons, where n is a positive integer, are associated with the ring to comply with Hϋckel's rule. As the fully unsaturated heterocyclic ring of Q contains at least one nitrogen atom as a ring member, the nitrogen atom can contribute a pair of electrons to supplement the four π electrons provided by two double bonds. Therefore five-membered as well as six-membered fully unsaturated heterocyclic rings of Q are aromatic according to Hϋckel's rule. Accordingly, Q can be alternatively and equivalently defined as a 5- or 6-membered heteroaromatic ring containing as ring members at least one nitrogen atom and other ring members selected from carbon, oxygen and sulfur atoms, said ring optionally substituted with substituents selected from halogen, cyano and nitro, and C1-C4 alkyl, C1-C4 alkoxy and Q-C 3 alkythio, each optionally substituted with 1 to 5 fluorine or chlorine. As used herein, the following definitions shall apply unless otherwise indicated. The term "optionally substituted" is used interchangeably with the phrase "substituted or unsubstituted" or with the term "(un)substituted". The expression "optionally substituted with 1 to 4 substituents" means that no substituent is present (i.e. unsubstituted) or that 1, 2, 3 or 4 substituents are present (limited by the number of available bonding positions). Unless otherwise indicated, an optionally substituted group may have a substituent at each substitutable position of the group, and each substitution is independent of the other.
The 5- or 6-membered nitrogen-containing heterocyclic ring of Q may be attached to the remainder of Formula 1 though any available carbon or nitrogen ring atom, unless otherwise described.
As noted above, Q is a 5- or 6-membered fully unsaturated heterocyclic ring optionally substituted with substituents selected from a group of substituents as defined in the Summary of Invention. Examples of optionally substituted 5- or 6-membered unsaturated aromatic heterocyclic rings include the rings U-6 through U-61 illustrated in Exhibit 1 wherein Rv is any substituent as defined in the Summary of the Invention for Q and r is an integer from 0 to 4, limited by the number of available positions on each U group. As U-29, U-30, U-36, U-37, U-38, U-39, U-40, U-41, U-42 and U-43 have only one available position, for these U groups r is limited to the integers 0 or 1, and r being 0 means that the U group is unsubstituted and a hydrogen is present at the position indicated by (Rv)r.
Exhibit 1
Figure imgf000008_0001
U-6 U-7 U-8 U-9 U-IO )r
Figure imgf000008_0002
U-I l U-12 U-13 U-14 U-15
Figure imgf000008_0003
U-16 U-17 U-18 U-19 U-20
Figure imgf000008_0004
U-21 U-22 U-23 U-24 U-25
Figure imgf000009_0001
U-26 U-27 U-28 U-29 U-30
Figure imgf000009_0002
U-31 U-32 U-33 U-34 U-35
Figure imgf000009_0003
U-36 U-37 U-38 U-39 U-40
Figure imgf000009_0004
U-61 Although Rv groups are shown in the structures U-6 through U-61, it is noted that they do not need to be present since they are optional substituents. Note that when Rv is H when attached to an atom, this is the same as if said atom is unsubstituted. The nitrogen atoms that require substitution to fill their valence are substituted with H or Rv. Note that when the attachment point between (Rv)r and the U group is illustrated as floating, (Rv)r can be attached to any available carbon atom or nitrogen atom of the U group. Note that when the attachment point on the U group is illustrated as floating, the U group can be attached to the remainder of Formula 1 through any available carbon or nitrogen of the U group by replacement of a hydrogen atom. Note that some U groups can only be substituted with less than 4 Rv groups (e.g., U-7 through U-48, and U-52 through U-61).
A wide variety of synthetic methods are known in the art to enable preparation of fully unsaturated nitrogen-containing heterocyclic rings; for extensive reviews see the eight volume set of Comprehensive Heterocyclic Chemistry, A. R. Katritzky and C. W. Rees editors-in-chief, Pergamon Press, Oxford, 1984 and the twelve volume set of Comprehensive Heterocyclic Chemistry II, A. R. Katritzky, C. W. Rees and E. F. V. Scriven editors-in-chief, Pergamon Press, Oxford, 1996.
Compounds of this invention can exist as one or more stereoisomers. The various stereoisomers include enantiomers, diastereomers, atropisomers and geometric isomers. One skilled in the art will appreciate that one stereoisomer may be more active and/or may exhibit beneficial effects when enriched relative to the other stereoisomer(s) or when separated from the other stereoisomer(s). Additionally, the skilled artisan knows how to separate, enrich, and/or to selectively prepare said stereoisomers. The compounds of the invention may be present as a mixture of stereoisomers, individual stereoisomers or as an optically active form. Compounds selected from Formula 1 (including all stereoisomers and salts thereof) can exist in more than one form, and Formula 1 thus includes all crystalline and noncrystalline forms of the compounds that Formula 1 represents. Non-crystalline forms include embodiments which are solids such as waxes and gums as well as embodiments which are liquids such as solutions and melts. Crystalline forms include embodiments which represent essentially a single crystal type and embodiments which represent a mixture of polymorphs (i.e. different crystalline types). The term "polymorph" refers to a particular crystalline form of a chemical compound that can crystallize in different crystalline forms, these forms having different arrangements and/or conformations of the molecules in the crystal lattice. Although polymorphs can have the same chemical composition, they can also differ in composition due the presence or absence of co-crystallized water or other molecules, which can be weakly or strongly bound in the lattice. Polymorphs can differ in such chemical, physical and biological properties as crystal shape, density, hardness, color, chemical stability, melting point, hygroscopicity, suspensibility, dissolution rate and biological availability. One skilled in the art will appreciate that a polymorph of a compound represented by Formula 1 can exhibit beneficial effects (e.g., suitability for preparation of useful formulations, improved biological performance) relative to another polymorph or a mixture of polymorphs of the same compound represented by Formula 1. Preparation and isolation of a particular polymorph of a compound represented by Formula 1 can be achieved by methods known to those skilled in the art including, for example, crystallization using selected solvents and temperatures.
One skilled in the art recognizes that because in the environment and under physiological conditions salts of chemical compounds are in equilibrium with their corresponding nonsalt forms, salts share the biological utility of the nonsalt forms. Thus a wide variety of salts of the compounds of Formula 1 are useful for control of invertebrate pests. The salts of the compounds of Formula 1 include acid-addition salts with inorganic or organic acids such as hydrobromic, hydrochloric, nitric, phosphoric, sulfuric, acetic, butyric, fumaric, lactic, maleic, malonic, oxalic, propionic, salicylic, tartaric, 4-toluenesulfonic or valeric acids. Accordingly, the present invention comprises compounds selected from
Formula 1 and salts thereof.
Embodiments of the present invention as described in the Summary of the Invention include those described below. In the following Embodiments, Formula 1 includes stereoisomers and salts thereof, and reference to "a compound of Formula 1" includes the definitions of substituents specified in the Summary of the Invention unless further defined in the Embodiments. The compound of Formula Ir is a subset of Formula 1.
Embodiment 1. A compound of Formula 1 wherein Y is O, G is a direct bond, and Z is CR3R4 or NR5.
Embodiment Ia. A compound of Embodiment 1 wherein Z is CR3R4. Embodiment Ib. A compound of Embodiment 1 wherein Z is NR5.
Embodiment 2. A compound of Formula 1 or any one of Embodiments 1— Ib wherein R1 is H; or C1-C3 alkyl or cyclopropyl, each optionally substituted with 1 to 3 halogen.
Embodiment 2a. A compound of Embodiment 2 wherein R1 is C^-C2 alkyl or cyclopropyl, each optionally substituted with 1 to 3 halogen.
Embodiment 2b. A compound of Embodiment 2a wherein R1 is methyl, CH2CF3,
CH2CF2H or cyclopropyl. Embodiment 3. A compound of Formula 1 or any one of Embodiments l-2b wherein
R2 is H or methyl. Embodiment 3a. A compound of Embodiment 3 wherein R2 is H.
Embodiment 4. A compound of Formula 1 or any one of Embodiments 1-3 a wherein R3 is H. Embodiment 5. A compound of Formula 1 or any one of Embodiments 1-4 wherein
R4 is H. Embodiment 6. A compound of Formula 1 or any one of Embodiments 1-5 wherein
R5 is methyl. Embodiment 7. A compound of Formula 1 or any one of Embodiments 1-6 wherein Q is a heterocyclic ring selected from pyridinyl, pyrimidinyl, pyridazinyl, pyrazinyl, pyrazolyl, oxazolyl, isoxazolyl, oxadiazolyl, thiadiazolyl, isothiazolyl, imidazolyl, pyrrolyl, thiazolyl and triazolyl, said ring optionally substituted with 1 to 3 substituents selected from halogen, cyano and nitro, and Q-C 4 alkyl, Cγ- C4 alkoxy and Q-C 3 alkylthio, each optionally substituted with 1 to 5 halogen selected from fluorine and chlorine. Embodiment 7a. A compound of Embodiment 7 wherein Q is 3 -pyridinyl or 5- thiazolyl optionally substituted with 1 or 2 substituents selected from halogen, cyano and nitro, and Q-C4 alkyl, Q-C4 alkoxy and Q-C 3 alkylthio, each optionally substituted with 1 to 3 halogen selected from fluorine and chlorine.
Embodiment 7b. A compound of Embodiment 7a wherein Q is 3 -pyridinyl or 5- thiazolyl optionally substituted with 1 or 2 substituents selected from halogen, methyl, methoxy and trifluoromethyl.
Embodiment 7c. A compound of Embodiment 7b wherein the nonhydrogen substituent(s) on the 3 -pyridinyl or 5 -thiazolyl of Q are bonded to ring atom(s) not adjacent to the ring atom connecting Q to the remainder of Formula 1 (i.e. the ring atoms denoted by "*" in the structures below).
Figure imgf000012_0001
Embodiment 8. A compound of Formula Ir (Formula 1 wherein G is a direct bond)
Figure imgf000012_0002
Ir wherein Y-Z is 0-CR3R4, S-CR3R4, NR5-CR3R4 or CR3R4-O (wherein the left end is attached as Y, and the right end is attached as Z);
R1 is H or C1-C3 alkoxy; or C1-C4 alkyl, C3-C4 alkenyl, C3-C4 alkynyl, C3-C4 cycloalkyl, C4-C5 cycloalkylalkyl or C4-C5 alkylcycloalkyl, each optionally substituted with halogen;
R2 is H or C1-C2 alkyl; each R3 is independently H or CH3; each R4 is independently H or CH3; each R5 is independently H, C1-C2 alkyl or C1-C2 haloalkyl; and Q is a 5- or 6-membered fully unsaturated heterocyclic ring containing as ring members at least one nitrogen atom and other ring members selected from carbon, oxygen and sulfur atoms, said ring optionally substituted with substituents selected from halogen, cyano, nitro, and C1-C4 alkyl, C1-C4 alkoxy and C1-C3 alkylthio, each optionally substituted with halogen selected from fluorine or chlorine.
Embodiment 9. A compound of Formula Ir wherein Y-Z is 0-CR3R4.
Embodiment 9a. A compound of Formula Ir or Embodiment 9 wherein R3 and R4 are H.
Embodiment 10. A compound of Formula Ir wherein R1 is H; or C1-C3 alkyl or cyclopropyl, each optionally substituted with halogen.
Embodiment 10a. A compound of Embodiment 10 wherein R1 is C1-C2 alkyl or cyclopropyl, each optionally substituted with halogen.
Embodiment 10b. A compound of Embodiment 10a wherein R1 is methyl, CH2CF3 or cyclopropyl. Embodiment 11. A compound of Formula Ir wherein R2 is H or methyl.
Embodiment 1 Ia. A compound of Embodiment 11 wherein R2 is H.
Embodiment 12. A compound of Formula Ir wherein Q is a heterocyclic ring selected from pyridinyl, pyrimidinyl, pyridazinyl, pyrazinyl, pyrazolyl, oxazolyl, isoxazolyl, oxadiazolyl, thiadiazolyl, isothiazolyl, imidazolyl, pyrrolyl, thiazolyl and triazolyl, said ring optionally substituted with substituents selected from halogen, cyano and nitro, and C1-C4 alkyl, C1-C4 alkoxy and C1-C3 alkylthio, each optionally substituted with halogen selected from fluorine and chlorine.
Embodiment 12a. A compound of Embodiment 12 wherein Q is 3 -pyridinyl or 5- thiazolyl optionally substituted with substituents selected from halogen, cyano and nitro, and C1-C4 alkyl, C1-C4 alkoxy and C1-C3 alkylthio, each optionally substituted with halogen selected from fluorine and chlorine. Embodiment 12b. A compound of Formula Ir or Embodiment 12 or 12a wherein the optional substituents are selected from halogen, methyl, methoxy and trifluoromethyl.
Embodiment 12c. A compound of Formula Ir or any one of Embodiments 12 through 12b wherein the nonhydrogen substituent(s) on heterocyclic ring of Q are bonded to ring atom(s) not adjacent to the ring atom connecting Q to the remainder of Formula Ir.
Embodiments of this invention, including Embodiments 1-12c above as well as any other embodiments described herein, can be combined in any manner, and the descriptions of variables in the embodiments pertain not only to the compounds of Formulae 1 and Ir but also to the starting compounds and intermediate compounds useful for preparing the compounds of Formulae 1 and Ir. In addition, embodiments of this invention, including Embodiments 1-12c above as well as any other embodiments described herein, and any combination thereof, pertain to the compositions and methods of the present invention. Combinations of Embodiments l-7c are illustrated by:
Embodiment A. A compound of Formula 1 wherein
Y is O, G is a direct bond, and Z is CR3R4 or NR5;
R1 is H; or Cj-C3 alkyl or cyclopropyl, each optionally substituted with 1 to 3 halogen; R2 is H; and
Q is a heterocyclic ring selected from pyridinyl, pyrimidinyl, pyridazinyl, pyrazinyl, pyrazolyl, oxazolyl, isoxazolyl, oxadiazolyl, thiadiazolyl, isothiazolyl, imidazolyl, pyrrolyl, thiazolyl and triazolyl, said ring optionally substituted with 1 to 3 substituents selected from halogen, cyano and nitro, and C^-C 4 alkyl, C1-C4 alkoxy and C^-C3 alkylthio, each optionally substituted with 1 to 5 halogen selected from fluorine and chlorine. Embodiment B. A compound of Embodiment A wherein
R1 is C1-C2 alkyl or cyclopropyl, each optionally substituted with 1 to 3 halogen;
R3 and R4 are H; R5 is methyl; and Q is 3 -pyridinyl or 5 -thiazolyl optionally substituted with 1 or 2 substituents selected from halogen, cyano and nitro, and C1-C4 alkyl, C1-C4 alkoxy and C^-C3 alkylthio, each optionally substituted with 1 to 3 halogen selected from fluorine and chlorine. Embodiment C. A compound of Embodiment B wherein
R1 is methyl, CH2CF3, CH2CF2H or cyclopropyl; and Q is 3-pyridinyl or 5-thiazolyl optionally substituted with 1 or 2 substituents selected from halogen, methyl, methoxy and trifluoromethyl. Embodiment D. A compound of Embodiment C wherein the nonhydrogen substituent(s) on the 3-pyridinyl or 5-thiazolyl of Q are bonded to ring atom(s) not adjacent to the ring atom connecting Q to the remainder of Formula 1.
Specific embodiments include compounds of Formula 1 selected from the group consisting of:
4-[[(6-chloro-3-pyridinyl)methyl]cyclopropylamino]-2(5H)-oxazolone; 4-[[(6-chloro-3-pyridinyl)methyl]methylamino]-2(5H)-oxazolone; 4-[[(2-chloro-5-thiazoyl)methyl]methylamino]-2(5H)-oxazolone; 4-[[ 1 -(2-chloro-5-thiazoyl)methyl]ethylamino]-2(5H)-oxazolone; 4-[[(2-chloro-5-thiazoyl)methyl]cyclopropylamino]-2(5H)-oxazolone; 4-[[(6-chloro-3-pyridinyl)methyl]ethylamino]-2(5H)-oxazolone; 4-[[(6-fluoro-3-pyridinyl)methyl]methylamino]-2(5H)-oxazolone; 4-[cyclopropyl[(6-fluoro-3-pyridinyl)methyl]amino]-2(5H)-oxazolone; 4-[[(5,6-dichloro-3-pyridinyl)methyl]methylamino]-2(5H)-oxazolone; 4-[cyclopropyl[(5,6-dichloro-3-pyridinyl)methyl]amino]-2(5H)-oxazolone; 4-[[(6-bromo-3-pyridinyl)methyl]methylamino]-2(5H)-oxazolone; 4-[[(6-bromo-3-pyridinyl)methyl]cyclopropylamino]-2(5H)-oxazolone; 4-[[(6-chloro-3-pyridinyl)methyl]cyclopropylamino]-5-methyl-2(5H)-oxazolone; 4-[[(6-chloro-3-pyridinyl)methyl]cyclopropylamino]-2(5H)-thiazolone; 3-[[(6-chloro-3-pyridinyl)methyl]methylamino]-2-methyl-l,2,4-oxadiazol-5(2H)-one; 3-[[(6-chloro-3-pyridinyl)methyl]cyclopropylamino]-2-methyl-l,2,4-oxadiazol-5(2H)-one; and 3-[[(2-chloro-5-thiazolyl)methyl]cyclopropylamino]-2-methyl-l,2,4-oxadiazol-5(2H)-one.
Combinations of Embodiments 8-12c are illustrated by: Embodiment Al . A compound of Formula Ir wherein Y-Z is 0-CR3R4;
R1 is Η; or C1-C3 alkyl or cyclopropyl, each optionally substituted with halogen;
R2 is Η or methyl; and
Q is a heterocyclic ring selected from pyridinyl, pyrimidinyl, pyridazinyl, pyrazinyl, pyrazolyl, oxazolyl, isoxazolyl, oxadiazolyl, thiadiazolyl, isothiazolyl, imidazolyl, pyrrolyl, thiazolyl and triazolyl, said ring optionally substituted with substituents selected from halogen, cyano and nitro, and C1-C 4 alkyl, C ^C 4 alkoxy and C1-C3 alkylthio, each optionally substituted with halogen selected from fluorine and chlorine. Embodiment B 1. A compound of Embodiment Al wherein R3 and R4 are H;
R1 is C^-C2 alkyl or cyclopropyl, each optionally substituted with halogen; R2 is H; and Q is 3-pyridinyl or 5-thiazolyl optionally substituted with substituents selected from halogen, cyano and nitro, and C1-C4 alkyl, C1-C4 alkoxy and C^-C3 alkylthio, each optionally substituted with halogen selected from fluorine and chlorine. Embodiment C 1. A compound of Embodiment B 1 wherein R1 is methyl, CF3CH2 or cyclopropyl; and
Q is 3-pyridinyl or 5-thiazolyl optionally substituted with substituents selected from halogen, methyl, methoxy and trifluoromethyl. Embodiment Dl. A compound of Embodiment C 1 wherein the nonhydrogen substituent(s) on the 3-pyridinyl or 5-thiazolyl of Q are bonded to ring atom(s) not adjacent to the ring atom connecting Q to the remainder of Formula Ir.
Of note is that compounds of this invention are characterized by favorable metabolic and/or soil residual patterns and exhibit activity controlling a spectrum of agronomic and nonagronomic invertebrate pests.
Of particular note, for reasons of invertebrate pest control spectrum and economic importance, protection of agronomic crops from damage or injury caused by invertebrate pests by controlling invertebrate pests are embodiments of the invention. Compounds of this invention because of their favorable translocation properties or systemicity in plants also protect foliar or other plant parts which are not directly contacted with a compound of Formula 1 or a composition comprising the compound. Also noteworthy as embodiments of the present invention are compositions comprising a compound of any of the preceding Embodiments, as well as any other embodiments described herein, and any combinations thereof, and at least one additional component selected from the group consisting of a surfactant, a solid diluent and a liquid diluent, said compositions optionally further comprising at least one additional biologically active compound or agent.
Further noteworthy as embodiments of the present invention are compositions for controlling an invertebrate pest comprising a compound of any of the preceding Embodiments, as well as any other embodiments described herein, and any combinations thereof, and at least one additional component selected from the group consisting of a surfactant, a solid diluent and a liquid diluent, said compositions optionally further comprising at least one additional biologically active compound or agent. Embodiments of the invention further include methods for controlling an invertebrate pest comprising contacting the invertebrate pest or its environment with a biologically effective amount of a compound of any of the preceding Embodiments (e.g., as a composition described herein).
Embodiments of the invention also include a composition comprising a compound of any of the preceding Embodiments, in the form of a soil drench liquid formulation. Embodiments of the invention further include methods for controlling an invertebrate pest comprising contacting the soil with a liquid composition as a soil drench comprising a biologically effective amount of a compound of any of the preceding Embodiments.
Embodiments of the invention also include a spray composition for controlling an invertebrate pest comprising a biologically effective amount of a compound of any of the preceding Embodiments and a propellant. Embodiments of the invention further include a bait composition for controlling an invertebrate pest comprising a biologically effective amount of a compound of any of the preceding Embodiments, one or more food materials, optionally an attractant, and optionally a humectant. Embodiments of the invention also include a device for controlling an invertebrate pest comprising said bait composition and a housing adapted to receive said bait composition, wherein the housing has at least one opening sized to permit the invertebrate pest to pass through the opening so the invertebrate pest can gain access to said bait composition from a location outside the housing, and wherein the housing is further adapted to be placed in or near a locus of potential or known activity for the invertebrate pest. Embodiments of the invention also include methods for protecting a seed from an invertebrate pest comprising contacting the seed with a biologically effective amount of a compound of any of the preceding Embodiments.
Embodiments of the invention also include methods for controlling a parasitic pest comprising contacting the parasitic pest or its environment with a biologically effective amount of a compound of Formula 1 or a salt thereof, (e.g., as a composition described herein), provided that the methods are not methods of medical treatment of a human or animal body by therapy.
One or more of the following methods and variations as described in Schemes 1-14 can be used to prepare the compounds of Formula 1. The definitions of Q, R1, R2, R3, R4, R5, R6, R7, Y, G and Z in the compounds of Formulae 1-14 below are as defined above in the Summary of the Invention unless otherwise noted. Formulae Ia-Ig, 2a-2e, 4a-4b and 7a are various subsets of Formulae 1, 2, 4 and 7 and all substituents for Formulae Ia-Ig, 2a-2e, 4a-4b and 7a are as defined above for Formulae 1, 2, 4 and 7 unless otherwise noted. Room temperature is between about 20 and 25 0C. As shown in Scheme 1, a compound of Formula Ia (Formula 1 wherein Z is CR3R4) can be prepared by reaction of a compound of Formula 2 with an amine of Formula 3. Examples of the leaving group LG in Formula 2 include, but are not limited to, SMe, OMe, OEt and Cl. The reaction is typically performed in an inert solvent such as toluene or xylene. The reaction is typically performed at temperatures from about room temperature to 160 0C, more typically from about 60 to 160 0C, and most typically from about 90 to 130 0C.
Scheme 1
Figure imgf000018_0001
LG is a Leaving Group
Compounds of Formula 1 wherein Y is O, S or NR5, G is CR3R4, and Z is O, S or NR5 can be prepared by methods known in the art; for example, see DE 2807381 19780824 and Chemische Berichte 1985, 118(10), 4196-4202.
Alternatively, compounds of Formula Ia wherein Y is O, S or NR5 can be prepared by contacting a compound of Formula 4 with an amine of Formula 3 or its salt as illustrated in Scheme 2. Typical salts of amines of Formula 3 include, but are not limited to, those formed with acids such as HCl or HBr. For representative procedures, see: Kassab et al. J. Het. Chem. 1979, 16(3), 509-512 and Baranov et al. Khimiya Geterotsiklicheskikh Soedinenii 1968, (6), 987-990. Compounds of Formula 4 can be prepared by a variety of methods described in the literature. For a representative procedure, see: Dow et al. J. Med. Chem.
1991, 34(5), 1538-1544.
Scheme 2
Figure imgf000018_0002
4
V is H or trimethylsilyl and W is O or S
Amines of Formula 3 can be prepared by a variety of methods described in the literature. These methods include reductive amination (i.e. the reaction of aldehydes with amines in the presence of reducing agents) and alkylation of amines with alkyl or heterocycloalkyl alkylating agents. For representitative procedures, see: Tian et al. J. Agri.
Food Chem. 2007, 55(1), 143-147; and Song et al. Yingyong Huaxue 2001, 18(S), 664-666. Compounds of Formula Ia wherein Y is O, S or NR5 can also be prepared by contacting an amidine of Formula 5 with a carbonylation reagent such as, but not limited to, l,l '-carbonyldiimidazole. For a representative procedure, see: Beckert et al. Journal fuer Praktische Chemie (Leipzig) 1990, 552(1), 65-82.
Scheme 3
Figure imgf000019_0001
5
Compounds of Formula 2a (Formula 2 wherein LG is SMe) can be prepared as shown in Scheme 4. A compound of Formula 4a (Formula 4 wherein V is H and W is O) is treated with a thionating reagent such as P4S10 or Lawesson's Reagent (2,4-bis-(4-methoxyphenyl)- l,3-dithia-2,4-diphosphetane 2,4-disulfϊde) to form a compound of Formula 4b (Formula 4 wherein V is H and W is S). For a review of the use of Lawesson's Reagent, see: Cava et al. Tetrahedron 1985, 41(22), 5061-5087. Compounds of Formula 4b are then treated with alkylating reagents such as, but not limited to, iodomethane, in the presence of a base such as, but not limited to, K2CO3, Na2CO3 or CH3CO2Na to obtain the compounds of Formula 2a.
Scheme 4
Figure imgf000019_0002
4a 4b 2a
As illustrated in Scheme 5, compounds of Formula 2b (Formula 2 wherein LG is OMe or OEt) can be prepared by contacting a compound of Formula 4a with an alkylating agent such as, but not limited to, iodomethane, iodoethane, or trimethyl- or triethyloxonium tetrafluoroborate as described in Dragovich et al. J. Org. Chem. 2002, 57(3), 741-746. Compounds of Formula 2c (Formula 2 wherein LG is Cl) can be prepared by contacting a compound of Formula 4a with a chlorinating agent such as, but not limited to, phosphorus oxychloride as described in Sercel et al. Syn. Commun. 2007, 57(23), 4199-4208. Scheme 5
Figure imgf000020_0001
2c
The compound of Formula 2d (Formula 2 wherein Y is CH2, G is a bond, Z is CH2 and LG is OEt) can be prepared according to the procedure of Crockett et al. Org. Syn. 1980, 59, 132-140.
Figure imgf000020_0002
2d
As shown in Scheme 6, compounds of Formula 2b can also be prepared by reacting an imidate of Formula 6 with a carbonylation reagent such as, but not limited to, 1,1 '- carbonyldiimidazole. For a representative procedure, see: Geffken et al. Scientia Pharmaceutica 2001, 69(4), 265-270.
Scheme 6
Figure imgf000020_0003
6 R is Me or Et The method of Scheme 6 is particularly useful for the preparation of intermediates of
Formula 2 wherein Y is O, G is a bond, and Z is CH2 such as the compound of Formula 2e.
Figure imgf000021_0001
2e
Compounds of Formula Ia can also be prepared by constructing the heterocyclic ring from the corresponding acyclic components according to methods described in the literature. For preparing compounds of Formula Ia by constructing the oxazolone ring (Y is O and G is a bond) from the corresponding acyclic intermediates, see: Kurz et al. Synthesis 2006, 11, 1803-1806 and L'abbe et al. Bull. Soc. Chim. BeIg. 1981, 90(1), 99-100. For preparing compounds of Formula Ia by constructing the thiazolone ring (Y is S and G is a bond) from the corresponding acyclic intermediates, see: Hahnemann et al. HeIv. Chim. Acta 2003, 86(6), 1949-1965; and Kamalov et al. Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya 1991, 2, 460-467. For preparing compounds of Formula Ia by constructing the imidazolone ring (Y is NR5 and G is a bond) from the corresponding acyclic intermediates, see: Ramla et al. Bioorg. Med. Chem. 2006, 14(2X), 7324-7332; Constabel et al. Tetrahydron 2001, 57(27), 5785-5789; Schaumann et al. Chem. Ber. 1980, 113(3), 934-940; and Ugi et al. Chem. Ber. 1964, P7(8), 2276-2281.
As shown in Scheme 7, compounds of Formula Ib (Formula 1 wherein Y is CR6R7) wherein G is a direct bond or CR3R4 and Z is O or S can be prepared by reaction of a compound of Formula 7 with an amine of Formula 3. Examples of the leaving group LG in Formula 7 include, but are not limited to, SMe, OMe, OEt and Cl. For a representative procedure of this method, including a method for the preparation of compounds of Formula 7, see: Chen et al. Bioorg. Med. Chem. Lett. 2007, 77(8), 2134-2138.
Scheme 7
Figure imgf000021_0002
7 LG is a Leaving Group
G is a direct bond or CR3R4 Z is O or S Alternatively, compounds of Formula Ib wherein G is a direct bond or CR3R4 and Z is
O or S can be prepared from compounds of Formula 7a (Formula 7 wherein LG is NH2) as illustrated in Scheme 8. For a representative procedure of this method, including a method for the preparation of compounds of Formula 7a, see: Moffett et al. J. Het. Chem. 1980, 17(4), 753-758.
Scheme 8
Figure imgf000022_0001
7a G is a direct bond or CR3R4
Z is O or S
Compounds of Formula Ib can also be prepared by constructing the oxazolone ring from the corresponding acyclic components according to methods described in the literature; see, for example: Sutin et al. Bioorg. Med. Chem. Lett. 2007, 77(17), 4837-4840. As shown in Scheme 9, compounds of Formula Ib can also be prepared by reaction of compounds of Formula 8 with esters of Formula 9. When Z is O or S, the compounds of Formula 9 are first treated with a base such as, but not limited to, NaH to form the corresponding alkoxide or thiol anion which is then reacted with the compound of Formula 8. For representative procedures, see: Dirlamet al. J. Org. Chem. 1986, 51, 4920-4924.
Scheme 9
Q-CHy I 1 CN + H-z-o- Il OEt (w -h^en Z= is- O o*r S) »
R o
G is a direct bond or CR3R4 Z is O, S or NR5
As shown in Scheme 10, compounds of Formula Ic (Formula 1 wherein G is a bond and Z is NR5) can be prepared by reaction of a compound of Formula 10 with appropriately substituted hydrazines, hydroxylamines or sulfenamides of Formula 11. The reaction is typically performed in a solvent such as ethanol or isopropanol, and at a temperature from about room temperature to the reflux temperature of the solvent, more typically at the reflux temperature of the solvent. For representative procedures and preparation of the intermediate of Formula 10, see: Arrowsmith et al. J. Med. Chem. 1989, 32, 562-568. Scheme 10
Figure imgf000023_0001
As shown in Scheme 11, compounds of Formula Ie (Formula 1 wherein Y-G is CH=CH and Z is O) can be prepared by reaction of aminonitriles of Formula 8 with 2,2- dialkyl-l,3-dioxin-4-ones of Formula 12. The reaction is typically performed in a solvent such as toluene, xylenes or dioxane at a temperature typically ranging from 80 0C to the reflux temperature of the solvent, more typically at the reflux temperature of the solvent. For a representative procedure of the method of Scheme 11, see: Chem. Pharm. Bull. 1986, 34, 621-627.
Scheme 11
Figure imgf000023_0002
Ra and R are methyl or ethyl
Aminonitriles of Formula 8 can be prepared by the reaction of amines of Formula 3 with 1 to 3 molar equivalents of cyanogen bromide in the presence of 1 to 5 molar equivalents of a base such as, but not limited to, triethylamine, Λ/,jV-diisopropylethylamine, and potassium carbonate as shown in Scheme 12. The reaction is typically performed in a solvent such as dichloromethane, tetrahydrofuran, or ethyl acetate at a temperature ranging from 0 0C up to the boiling temperature of the solvent. If a reaction temperature higher than the boiling temperature of the solvent is desired, the reaction can be performed under microwave irradiation in a standard microwave reactor. For representative procedures for the method of Scheme 12, see: Bioorg. Med. Chem. 2008, 16, 1613-1631. Scheme 12
base
Br — CN
Compounds of Formula 12 can be prepared as described in Synthesis 1985, 224-226.
As shown in Scheme 13, compounds of Formula If (Formula 1 wherein Y-G is CH=CH and Z is S) can be prepared by reaction of amines of Formula 3 with 2-chloro-l,3- thiazin-4-one (13). The reaction is typically performed in a solvent such as dichloromethane or acetonitrile in the presence of one molar equivalent of a base, typically an amine base such as triethylamine or pyridine, and optionally in the presence of a second molar equivalent of the base. Typical reaction temperatures range from 0 0C up to the reflux temperature of the solvent. For representative procedures for the method of Scheme 13, as well as procedures for the preparation of 2-chloro-l,3-thiazin-4-one (13), see: Justis Liebigs Annalen der Chemie 1977, 1249-1266. Scheme 13
Figure imgf000024_0001
As shown in Scheme 14, compounds of Formula Ig (Formula 1 wherein Y-G is CH=CH and Z is NR5) can be prepared by a method analogous to the one described in Scheme 13 by the reaction of an amine of Formula 3 with an l-alkyl-2-chloro-4- oxopyrimidine of Formula 14. Representative procedures for the method of Scheme 14 are described in Synthetic Communications 1991, 21, 1489. The preparations of l-alkyl-2- chloro-4-oxopyrimidines of Formula 14 are described in J. Chem. Soc. 1955, 855-859. Scheme 14
Figure imgf000025_0001
14 Ig
Compounds of Formula 1 wherein Y is O and G-Z is CH=CH can be prepared by the method described in Monatshefte fuer Chemie 1987, 118(11), 1263-1277.
Examples of intermediates useful in the preparation of compounds of this invention are shown in Table 1-1. In Table 1-1, and in all tables in this disclosure, when "CH=CH" appears between two columns (i.e. two columns are merged into one single column and "CH=CH" appears in the center of this single column), then this means that the entry "CH=CH" represents both variables linked together. For example, the first entry in the last row of Table 1-1, reproduced below,
X Y G Z
Br CH=CH S
represents a structure wherein X is Br, Y-G is CH=CH, and Z is S.
TABLE 1-1
Figure imgf000025_0002
X Y G Z X Y G Z
OMe O bond CH2 OMe O bond CHMe
OEt O bond CH2 OEt O bond CHMe
SMe O bond CH2 SMe O bond CHMe
SEt O bond CH2 SEt O bond CHMe
Cl O bond CH2 Cl O bond CHMe
Br O bond CH2 Br O bond CHMe
Figure imgf000026_0001
Figure imgf000027_0001
Figure imgf000028_0001
X Y G Z X Y G Z
SEt S CH2 NMe SEt S CH2 CH2
Cl S CH2 NMe Cl S CH2 CH2
Br S CH2 NMe Br S CH2 CH2
OMe S CH2 CHMe OMe S CH2 CMe2
OEt S CH2 CHMe OEt S CH2 CMe2
SMe S CH2 CHMe SMe S CH2 CMe2
SEt S CH2 CHMe SEt S CH2 CMe2
Cl S CH2 CHMe Cl S CH2 CMe2
Br S CH2 CHMe Br S CH2 CMe2
OMe NMe CH2 O OMe NMe CH2 S
OEt NMe CH2 O OEt NMe CH2 S
SMe NMe CH2 O SMe NMe CH2 S
SEt NMe CH2 O SEt NMe CH2 S
Cl NMe CH2 O Cl NMe CH2 S
Br NMe CH2 O Br NMe CH2 S
OMe NMe CH2 NMe OMe NMe CH2 CH2
OEt NMe CH2 NMe OEt NMe CH2 CH2
SMe NMe CH2 NMe SMe NMe CH2 CH2
SEt NMe CH2 NMe SEt NMe CH2 CH2
Cl NMe CH2 NMe Cl NMe CH2 CH2
Br NMe CH2 NMe Br NMe CH2 CH2
OMe NMe CH2 CHMe OMe NMe CH2 CMe2
OEt NMe CH2 CHMe OEt NMe CH2 CMe2
SMe NMe CH2 CHMe SMe NMe CH2 CMe2
SEt NMe CH2 CHMe SEt NMe CH2 CMe2
Cl NMe CH2 CHMe Cl NMe CH2 CMe2
Br NMe CH2 CHMe Br NMe CH2 CMe2
OMe CH2 CH2 O OMe CH2 CH2 S
OEt CH2 CH2 O OEt CH2 CH2 S
SMe CH2 CH2 O SMe CH2 CH2 S
SEt CH2 CH2 O SEt CH2 CH2 S
Cl CH2 CH2 O Cl CH2 CH2 S
Br CH2 CH2 O Br CH2 CH2 S
OMe CH2 CH2 NMe OMe CH2 CH2 CH2
OEt CH2 CH2 NMe OEt CH2 CH2 CH2
SMe CH2 CH2 NMe SMe CH2 CH2 CH2
SEt CH2 CH2 NMe SEt CH2 CH2 CH2 X Y G Z X Y G Z
Cl CH2 CH2 NMe Cl CH2 CH2 CH2
Br CH2 CH2 NMe Br CH2 CH2 CH2
OMe CH2 CH2 CHMe OMe CH2 CH2 CMe2
OEt CH2 CH2 CHMe OEt CH2 CH2 CMe2
SMe CH2 CH2 CHMe SMe CH2 CH2 CMe2
SEt CH2 CH2 CHMe SEt CH2 CH2 CMe2
Cl CH2 CH2 CHMe Cl CH2 CH2 CMe2
Br CH2 CH2 CHMe Br CH2 CH2 CMe2
OMe O CHMe O OMe O CHMe S
OEt O CHMe O OEt O CHMe S
SMe O CHMe O SMe O CHMe S
SEt O CHMe O SEt O CHMe S
Cl O CHMe O Cl O CHMe S
Br O CHMe O Br O CHMe S
OMe O CHMe NMe OMe O CHMe CH2
OEt O CHMe NMe OEt O CHMe CH2
SMe O CHMe NMe SMe O CHMe CH2
SEt O CHMe NMe SEt O CHMe CH2
Cl O CHMe NMe Cl O CHMe CH2
Br O CHMe NMe Br O CHMe CH2
OMe O CHMe CHMe OMe O CHMe CMe2
OEt O CHMe CHMe OEt O CHMe CMe2
SMe O CHMe CHMe SMe O CHMe CMe2
SEt O CHMe CHMe SEt O CHMe CMe2
Cl O CHMe CHMe Cl O CHMe CMe2
Br O CHMe CHMe Br O CHMe CMe2
OMe S CHMe O OMe S CHMe S
OEt S CHMe O OEt S CHMe S
SMe S CHMe O SMe S CHMe S
SEt S CHMe O SEt S CHMe S
Cl S CHMe O Cl S CHMe S
Br S CHMe O Br S CHMe S
OMe S CHMe NMe OMe S CHMe CH2
OEt S CHMe NMe OEt S CHMe CH2
SMe S CHMe NMe SMe S CHMe CH2
SEt S CHMe NMe SEt S CHMe CH2
Cl S CHMe NMe Cl S CHMe CH2 X Y G Z X Y G Z
Br S CHMe NMe Br S CHMe CH2
OMe S CHMe CHMe OMe S CHMe CMe2
OEt S CHMe CHMe OEt S CHMe CMe2
SMe S CHMe CHMe SMe S CHMe CMe2
SEt S CHMe CHMe SEt S CHMe CMe2
Cl S CHMe CHMe Cl S CHMe CMe2
Br S CHMe CHMe Br S CHMe CMe2
OMe NMe CHMe O OMe NMe CHMe S
OEt NMe CHMe O OEt NMe CHMe S
SMe NMe CHMe O SMe NMe CHMe S
SEt NMe CHMe O SEt NMe CHMe S
Cl NMe CHMe O Cl NMe CHMe S
Br NMe CHMe O Br NMe CHMe S
OMe NMe CHMe NMe OMe NMe CHMe CH2
OEt NMe CHMe NMe OEt NMe CHMe CH2
SMe NMe CHMe NMe SMe NMe CHMe CH2
SEt NMe CHMe NMe SEt NMe CHMe CH2
Cl NMe CHMe NMe Cl NMe CHMe CH2
Br NMe CHMe NMe Br NMe CHMe CH2
OMe NMe CHMe CHMe OMe NMe CHMe CMe2
OEt NMe CHMe CHMe OEt NMe CHMe CMe2
SMe NMe CHMe CHMe SMe NMe CHMe CMe2
SEt NMe CHMe CHMe SEt NMe CHMe CMe2
Cl NMe CHMe CHMe Cl NMe CHMe CMe2
Br NMe CHMe CHMe Br NMe CHMe CMe2
OMe CH2 CHMe O OMe CH2 CHMe S
OEt CH2 CHMe O OEt CH2 CHMe S
SMe CH2 CHMe O SMe CH2 CHMe S
SEt CH2 CHMe O SEt CH2 CHMe S
Cl CH2 CHMe O Cl CH2 CHMe S
Br CH2 CHMe O Br CH2 CHMe S
OMe CH2 CHMe NMe OMe CH2 CHMe CH2
OEt CH2 CHMe NMe OEt CH2 CHMe CH2
SMe CH2 CHMe NMe SMe CH2 CHMe CH2
SEt CH2 CHMe NMe SEt CH2 CHMe CH2
Cl CH2 CHMe NMe Cl CH2 CHMe CH2
Br CH2 CHMe NMe Br CH2 CHMe CH2
Figure imgf000032_0001
It is recognized that some reagents and reaction conditions described above for preparing compounds of Formula 1 may not be compatible with certain functionalities present in the intermediates. In these instances, the incorporation of protection/deprotection sequences or functional group interconversions into the synthesis will aid in obtaining the desired products. The use and choice of the protecting groups will be apparent to one skilled in chemical synthesis (see, for example, Greene, T. W.; Wuts, P. G. M. Protective Groups in Organic Synthesis, 2nd ed.; Wiley: New York, 1991). One skilled in the art will recognize that, in some cases, after the introduction of a given reagent as it is depicted in any individual scheme, it may be necessary to perform additional routine synthetic steps not described in detail to complete the synthesis of compounds of Formula 1. One skilled in the art will also recognize that it may be necessary to perform a combination of the steps illustrated in the above schemes in an order other than that implied by the particular sequence presented to prepare the compounds of Formula 1. One skilled in the art will also recognize that compounds of Formula 1 and the intermediates described herein can be subjected to various electrophilic, nucleophilic, radical, organometallic, oxidation, and reduction reactions to add substituents or modify existing substituents. Without further elaboration, it is believed that one skilled in the art using the preceding description can utilize the present invention to its fullest extent. The following Synthesis Examples are, therefore, to be construed as merely illustrative, and not limiting of the disclosure in any way whatsoever. Steps in the following Synthesis Examples illustrate a procedure for each step in an overall synthetic transformation, and the starting material for each step may not have necessarily been prepared by a particular preparative run whose procedure is described in other Examples or Steps. Percentages are by weight except for chromatographic solvent mixtures or where otherwise indicated. Parts and percentages for chromatographic solvent mixtures are by volume unless otherwise indicated. 1H NMR spectra are reported in ppm downfϊeld from tetramethylsilane; "s" means singlet, "d" means doublet, "t" means triplet, "q" means quartet, "m" means multiplet, "dd" means doublet of doublets, "br s" means broad singlet, and "br d" means broad doublet. MPLC means medium pressure liquid chromatography.
SYNTHESIS EXAMPLE 1 Preparation of 4-[[(6-chloro-3-pyridinyl)methyl]cyclopropylamino]-2(5H)-oxazolone
Step A: Preparation of 4-thio-oxazolidine-2-one
To a stirred solution of oxazolidine-2,4-dione (0.71 g, 7.03 mmol, prepared according to the method of Liu et al, WO 2006/014262 A2) in toluene (15 mL) in a round bottom flask was added Lawesson's Reagent (1.71 g, 4.2 mmol). The resulting suspension was heated at reflux for 6 h, and then cooled and stirred at room temperature for an additional 16 h. The suspension was filtered through a short pad of silica gel, and the filtered solids were rinsed with 100 mL of 20% ethyl acetate/hexanes followed by 450 mL of ethyl acetate. The combined filtrates were concentrated under reduced pressure to provide the title compound as a pale yellow solid (0.5 g).
1H NMR (CDCl3): δ 9.15 (br s, NH), 5.01 (s, 2H).
Step B: Preparation of 4-methylsulfanyl-5H-oxazol-2-one
To a solution of 4-thio-oxazolidine-2-one (i.e. the product of Step A) (0.25 g, 2.14 mmol) in dichloromethane (10 mL) at 0 0C was added iodomethane (1.33 mL, 10.67 mmol) and sodium acetate (0.27 g, 3.2 mmol). The resulting mixture was stirred for 4 h and allowed to warm to room temperature. Additional iodomethane (1.33 mL, 10.67 mmol) was added, and the reaction mixture was stirred at room temperature for 4 h more. Water was added (20 mL), the phases were separated, and the organic phase was washed with water (2 x 20 mL). The organics were concentrated under reduced pressure, and the resulting residue was purified by flash chromatography to provide the title compound as a clear crystalline solid (0.03 g). 1H NMR (CDCl3): δ 4.90 (s, 2H), 2.73 (s, 3H). Step C: Preparation of 4-[[(6-chloro-3-pyridinyl)methyl]cyclopropylamino]-2(5H)- oxazolone
To a solution of 4-methylsulfanyl-5H-oxazol-2-one (i.e. the product of Step B) (0.03 g, 0.23 mmol) in toluene (3 rnL) in a round bottom flask was added (6-chloropyridin-3- ylmethyl)cyclopropylamine (0.09 g, 0.49 mmol, prepared according to the method of Tian et al. J. Agri. Food Chem. 2007, 55(1), 143-147). The resulting mixture was heated and maintained at 110 0C for 24 h. The suspension was then cooled to room temperature, filtered through a short pad of silica gel, and the isolated solids were rinsed with ethyl acetate. The combined organics were concentrated under reduced pressure to provide the title product, a compound of the present invention, as a pale yellow solid (0.009 g).
1H NMR (CDCl3): δ 8.38 (d, IH), 7.78 (dd, IH), 7.36 (d, IH), 4.90 (s, 2H), 4.80 (s, 2H), 2.62 (m, IH), 0.98 (m, 2H), 0.90 (m, 2H).
SYNTHESIS EXAMPLE 2 Preparation of 4-[[(6-chloro-3-pyridinyl)methyl]methylamino]-2(5H)-oxazolone
To a solution of 4-methylsulfanyl-5H-oxazol-2-one (i.e. the product of Step B of Synthesis Example 1) (0.10 g, 0.76 mmol) in toluene (3 mL) in a round bottom flask was added (6-chloro-pyridin-3-ylmethyl)methylamine (0.096 g, 0.61 mmol, prepared according to the method of Song et al. Yingyong Huaxue 2001, iS(8), 664-666). The reaction mixture was heated and maintained at 113 0C for 24 h. The suspension was cooled to room temperature, filtered through a short pad of silica gel, and the isolated solids were rinsed with ethyl acetate. The combined organics were concentrated under reduced pressure to provide the title compound, a compound of the present invention, as a pale yellow solid (0.13 g).
1H NMR (CDCl3): δ 8.37 (d, IH), 7.77 (dd, IH), 7.36 (d, IH), 4.81 (br s, 4H), 2.97 (s, 3H).
SYNTHESIS EXAMPLE 3
Preparation of 3-[[(6-chloro-3-pyridinyl)methyl]methylamino]-2-methyl- 1 ,2,4-oxadiazol- 5(2H)-one
To a solution of (6-chloropyridin-3-ylmethyl)methylamine (1.07 g, 6.83 mmol, prepared by the method of Tian et al. J. Agri. Food Chem. 2007, 55(1), 143-147) in dry chloroform (30 mL) was added dropwise a solution of ethoxycarbonyl isothiocyanate (0.90 g, 6.86 mmol) in dry chloroform (5 mL). The reaction mixture was stirred for 18 h at room temperature, and then concentrated under reduced pressure, and the resulting residue was purified by flash chromatography to give an intermediate (1.92 g) which was used directly in the next step. To a solution of the above intermediate (0.76 g, 2.64 mmol) in dry tetrahydrofuran (20 rnL) was added sodium hydride (60% in mineral oil, 0.13 g, 3.17 mmol). The resulting suspension was stirred for 1 h at room temperature, a solution of methyl iodide (0.41 g, 2.90 mmol) in dry tetrahydrofuran (1 mL) was added dropwise, and the reaction mixture was stirred overnight. The reaction mixture was concentrated under reduced pressure, and the resulting residue was diluted with methylene chloride and washed with aqueous NaCl. The organic phase was dried over magnesium sulfate, filtered, and concentrated under reduced pressure to give a yellow oil (0.87 g). This oil (0.30 g, 1.0 mmol) was dissolved in 2- propanol (3 mL) containing N-methylhydroxylamine-hydrogen chloride (0.33 g, 4.0 mmol) and sodium acetate (0.41 g, 5.0 mmol), and the reaction mixture was heated at reflux for 4 days. The resulting solution was then evaporated, and the residue was taken up in water and extracted with ethyl acetate. The ethyl acetate was dried over magnesium sulfate, filtered, and concentrated under reduced pressure to yield a residue which was purified by flash chromatography to provide the desired product (0.084 g), a compound of this invention, as a pale yellow solid.
1H NMR (CDCl3): δ 8.35 (d, IH), 7.78 (dd, IH), 7.37 (d, IH), 4.69 (s, 2H), 3.29 (s, 3H), 3.03 (s, 3H).
SYNTHESIS EXAMPLE 4 Alternative preparation of 4-[[(6-chloro-3-pyridinyl)methyl]cyclopropylamino]-2(5H)- oxazolone
To a slurry of 2-hydroxyethanimidic acid ethyl ester hydrochloride (2.0 g, 14 mmol), l,l '-carbonyldiimidazole (3.0 g, 19 mmol), and 4-(dimethylamino)pyridine (0.1 g, 0.8 mmol) in dichloromethane (15 mL) was added triethylamine (3 mL). The clear solution was stirred at room temperature for 24 h. (6-Chloropyridin-3-ylmethyl)cyclopropylamine (1.15 g, 6.3 mmol) was added, and the solution was stirred for 2.5 days. The reaction mixture was concentrated under reduced pressure, and the resulting residue was triturated with diethyl ether (60 mL). The diethyl ether was decanted, and the residue was briefly dried under reduced pressure. The dried residue was then stirred in water (80 mL) to yield a solid. The solid was collected by filtration, washed with water (40 mL), and dried under high vacuum to give 1.2 g of the product, a compound of this invention. 1H NMR data was identical to the 1H NMR data of the compound prepared in Synthesis Example 1.
SYNTHESIS EXAMPLE 5 Preparation of 2- [[(6-chloro-3 -pyridinyl)methyl] cyclopropylamino] -4H- 1 ,3 -oxazin-4-one
Step A: Preparation of Λ/-[(6-chloro-3-pyridinyl)methyl]-iV-cyclopropylcyanamide
Cyanogen bromide (1.0 mL of a 3.0 M solution in dichloromethane, 3.0 mmol) was added to a solution of 6-chloro-Λ/-cyclopropyl-3-pyridinemethanamine (0.51 g, 2.8 mmol) and N,Λ/-diisopropylethylamine (0.58 niL, 3.3 mmol) in dichloromethane (3 niL) at 0 °C. The resulting solution was stirred at room temperature for 16 h, diluted with ethyl acetate (10 mL), and concentrated under reduced pressure in the presence of silica gel (2 g). The residue was purified by MPLC on a 24 g silica column eluted with a gradient of 0% to 100% ethyl acetate in hexanes to provide 0.45 g of the title compound as a colorless oil.
1H NMR (CDCl3): δ 8.37 (s, IH), 7.72 (d, IH), 7.39 (d, IH), 4.20 (s, 2H), 2.58 (quintet, IH), 0.81-0.76 (m, 4H).
Step B: Preparation of 2,2-dimethyl-4H-l,3-dioxin-4-one 5-Formyl-2,2-dimethyl-l,3-dioxane-4,6-dione (5.0 g, 29 mmol) was added in several portions over 45 min to a boiling solution of 3-pentanone (15.5 mL, 145 mmol) in toluene (58 mL). The resulting solution was heated to boiling for a further 2 h, and then cooled to room temperature and concentrated under reduced pressure in the presence of silica gel (15 g). The residue was purified by MPLC on an 80 g silica column eluted with a gradient of 0% to 100% ethyl acetate in hexanes to provide 1.50 g of the title compound as a pale yellow oil. 1H NMR (CDCl3): δ 7.12 (d, IH), 5.35 (d, IH), 2.04-1.96 (m, 4H), 1.00 (t, 6H).
Step C: Preparation of 2-[[(6-chloro-3-pyridinyl)methyl]cyclopropylamino]-4H-l,3- oxazin-4-one
A solution of the product of Step A (0.25 g, 1.2 mmol) and the product of Step B (0.21 g, 1.3 mmol) in toluene (3.7 mL) was heated at 90 0C for 3 h. The reaction mixture was then cooled to room temperature, diluted with acetone (10 mL), and concentrated under reduced pressure in the presence of silica gel (1 g). Purification of the residue by MPLC on a 12 g silica column eluted with a gradient of 0% to 15% ethanol in dichloromethane gave 102 mg of the title compound, a compound of the present invention, as a brown oil. 1H NMR (CDCl3): δ 8.37 (br s, IH), 7.76 (br d, IH), 7.46 (d, IH), 7.31 (d, IH), 6.08 (d, IH), 4.76 (s, 2H), 2.66-2.56 (m, IH), 1.01-0.92 (m, 2H), 0.86-0.78 (m, 2H).
By the procedures described herein together with methods known in the art, the following compounds of Tables 1 to 8 can be prepared. The following abbreviations are used in the Tables which follow: n means normal, i means iso, c means cyclo, Me means methyl, Et means ethyl, Pr means propyl, i-Pr means isopropyl, Bu means butyl, OMe means methoxy, and OEt means ethoxy. X-I through X-54 are defined as follows:
Figure imgf000037_0001
X-I X-2 X-3 X-4
Figure imgf000037_0002
X-5 X-6 X-7 X-8
Figure imgf000037_0003
X-17 X-18 X-19 X-20
Figure imgf000037_0004
X-29 X-30 X-31 X-32
Figure imgf000038_0001
X-42 X-43 X-44
Figure imgf000038_0002
X-46 X-47 X-48
Figure imgf000038_0003
X-50 X-50 X-51
Figure imgf000038_0004
X-51 X-52 X-53 X-54
* denotes attachment point of each X group as Q to the remainder of the molecule in Tables 1-8 below.
Figure imgf000038_0005
Y-I
** denotes attachment point of Y-I as R1 to the remainder of the molecule in Table 1 below.
Figure imgf000039_0001
Q is X-I, R2 is H, R3 is H and R4 is H.
El El El Ei Ei El
H Me Et «-Pr z-Pr z-Bu
OMe OEt CH2CH=CH2 CH2C=CH CH2CH2CH=CH2 Y-I
OCHF2 c-Pr c-Bu CH2-C-Pr 1-CH3-C-Pr
2-CH3-C-Pr CHF2 CH2CH2F CH2CHF2 CH2CF3
Q is X-I, R2 is Me, R3 is H and R4 is H.
Figure imgf000039_0002
z-Pr z-Bu
CH2CH2CH=CH2 Y-I
1-CH3-C-Pr
CH2CF3
Q is
Figure imgf000039_0004
z-Pr z-Bu
CH2CH2CH=CH2 Y-I
1-CH3-C-Pr
CH2CF3
Figure imgf000039_0003
Q is X-I, R2 is Me, R3 is Me and R4 is H.
2
Figure imgf000039_0005
Q is X-I, R2 is H, R3 is Me and R4 is Me.
Figure imgf000039_0006
z-Pr z-Bu CH CH2CH2CH=CH2 Y-I
Figure imgf000039_0007
O
2-C
Figure imgf000040_0001
Q is X-I, R2 is Me, R3 is Me and R4 is Me.
2
Figure imgf000040_0002
Q is X-3, R2 is H, R3 is H and R4 is H.
Figure imgf000040_0003
z-Pr z-Bu
CH2CH2CH=CH2 Y-I
1-CH3-C-Pr
2 CH2CF3
Figure imgf000040_0004
Q is X-3, R2 is Me, R3 is H and R4 is H.
2
Figure imgf000040_0005
Q is X-3, R2 is H, R3 is Me and R4 is H.
Figure imgf000040_0006
z-Pr z-Bu
CH2CH2CH=CH2 Y-I
1-CH3-C-Pr
2 CH2CF3
Figure imgf000040_0007
Q is X-3, R2 is Me, R3 is Me and R4 is H.
2
Figure imgf000040_0008
Q is X-3, R2 is H, R3 is Me and R4 is Me.
2
Figure imgf000041_0001
Q is X-3, R2 is Me, R3 is Me and R4 is Me.
2
Figure imgf000041_0002
Q is X-4, R2 is H, R3 is H and R4 is H.
Figure imgf000041_0003
z-Pr z-Bu
CH2CH2CH=CH2 Y-I
1-CH3-C-Pr
2 CH2CF3
Figure imgf000041_0004
Q is X-4, R2 is Me, R3 is H and R4 is H.
2
Figure imgf000041_0005
Q is X-4, R2 is H, R3 is Me and R4 is H.
Figure imgf000041_0006
z-Pr z-Bu
CH2CH2CH=CH2 Y-I
1-CH3-C-Pr
2 CH2CF3
Figure imgf000041_0007
Q is X-4, R2 is Me, R3 is Me and R4 is H.
Figure imgf000041_0008
2
Figure imgf000042_0001
Q is X-4, R2 is H, R3 is Me and R4 is Me.
Figure imgf000042_0002
z-Pr z-Bu
CH2CH2CH=CH2 Y-I
1-CH3-C-Pr
2 CH2CF3
Figure imgf000042_0003
Q is X-4, R2 is Me, R3 is Me and R4 is Me.
Figure imgf000042_0004
z-Bu 2 Y-I
2
Figure imgf000042_0005
Q is X-5, R2 is H, R3 is H and R4 is H.
Figure imgf000042_0006
z-Pr z-Bu
CH2CH2CH=CH2 Y-I
1-CH3-C-Pr
2 CH2CF3
Figure imgf000042_0007
Q is X-5, R2 is Me, R3 is H and R4 is H.
2
Figure imgf000042_0008
Q is X-5, R2 is H, R3 is Me and R4 is H.
Figure imgf000042_0009
z-Pr z-Bu
CH2CH2CH=CH2 Y-I 1-CH3-C-Pr
Figure imgf000042_0010
2-C
Figure imgf000043_0001
Q is X-5, R2 is Me, R3 is Me and R4 is H.
2
Figure imgf000043_0002
Q is X-5, R2 is H, R3 is Me and R4 is Me.
2
Figure imgf000043_0003
Q is X-5, R2 is Me, R3 is Me and R4 is Me.
Figure imgf000043_0004
z-Pr z-Bu
CH2CH2CH=CH2 Y-I
1-CH3-C-Pr
2 CH2CF3
Figure imgf000043_0005
Q is X-6, R2 is H, R3 is H and R4 is H.
2
Figure imgf000043_0006
Q is X-6, R2 is Me, R3 is H and R4 is H.
Figure imgf000043_0007
z-Pr z-Bu
CH2CH2CH=CH2 Y-I
1-CH3-C-Pr
2 CH2CF3
Figure imgf000043_0008
Q is X-6, R2 is H, R3 is Me and R4 is H.
2
Figure imgf000044_0001
Q is X-6, R2 is Me, R3 is Me and R4 is H.
2
Figure imgf000044_0002
Q is X-6, R2 is H, R3 is Me and R4 is Me.
Figure imgf000044_0003
z-Pr z-Bu
CH2CH2CH=CH2 Y-I
1-CH3-C-Pr
2 CH2CF3
Figure imgf000044_0004
Q is X-6, R2 is Me, R3 is Me and R4 is Me.
2
Figure imgf000044_0005
Q is X-8, R2 is H, R3 is H and R4 is H.
Figure imgf000044_0006
z-Pr z-Bu
CH2CH2CH=CH2 Y-I
1-CH3-C-Pr
2 CH2CF3
Figure imgf000044_0007
Q is X-8, R2 is Me, R3 is H and R4 is H.
Figure imgf000044_0008
2
Figure imgf000045_0001
Q is X-8, R2 is H, R3 is Me and R4 is H.
Figure imgf000045_0002
z-Pr z-Bu
CH2CH2CH=CH2 Y-I
1-CH3-C-Pr
2 CH2CF3
Figure imgf000045_0003
Q is X-8, R2 is Me, R3 is Me and R4 is H.
2
Figure imgf000045_0004
Q is X-8, R2 is H, R3 is Me and R4 is Me.
Figure imgf000045_0005
z-Pr z-Bu
CH2CH2CH=CH2 Y-I
1-CH3-C-Pr
2 CH2CF3
Figure imgf000045_0006
Q is X-8, R2 is Me, R3 is Me and R4 is Me.
Figure imgf000045_0007
z-Bu 2 Y-I
2
Figure imgf000045_0008
Q is X-I l, R2 is H, R3 is H and R4 is H.
Figure imgf000045_0009
z-Pr z-Bu
CH2CH2CH=CH2 Y-I 1-CH3-C-Pr
Figure imgf000045_0010
2-C
Figure imgf000046_0001
Q is X-11, R2 is Me, R3 is H and R4 is H.
2
Figure imgf000046_0002
Q is X-I l, R2 is H, R3 is Me and R4 is H.
2
Figure imgf000046_0003
Q is X-11, R2 is Me, R3 is Me and R4 is H.
Figure imgf000046_0004
z-Pr z-Bu
CH2CH2CH=CH2 Y-I
1-CH3-C-Pr
2 CH2CF3
Figure imgf000046_0005
Q is X-I l, R2 is H, R3 is Me and R4 is Me.
2
Figure imgf000046_0006
Q is X-I l, R2 is Me, R3 is Me and R4 is Me.
Figure imgf000046_0007
z-Pr z-Bu
CH2CH2CH=CH2 Y-I
1-CH3-C-Pr
2 CH2CF3
Figure imgf000046_0008
Q is X-13, R2 is H, R3 is H and R4 is H.
2
Figure imgf000047_0001
Q is X-13, R2 is Me, R3 is H and R4 is H.
2
Figure imgf000047_0002
Q is X-13, R2 is H, R3 is Me and R4 is H.
Figure imgf000047_0003
z-Pr z-Bu
CH2CH2CH=CH2 Y-I
1-CH3-C-Pr
2 CH2CF3
Figure imgf000047_0004
Q is X-13, R2 is Me, R3 is Me and R4 is H.
2
Figure imgf000047_0005
Q is X-13, R2 is H, R3 is Me and R4 is Me.
Figure imgf000047_0006
z-Pr z-Bu
CH2CH2CH=CH2 Y-I
1-CH3-C-Pr
2 CH2CF3
Figure imgf000047_0007
Q is X-13, R2 is Me, R3 is Me and R4 is Me.
z-Bu
Figure imgf000047_0008
2
Figure imgf000048_0001
Q is X-21, R2 is H, R3 is H and R4 is H.
Figure imgf000048_0002
z-Pr z-Bu
CH2CH2CH=CH2 Y-I
1-CH3-C-Pr
2 CH2CF3
Figure imgf000048_0003
Q is X-21, R2 is Me, R3 is H and R4 is H.
2
Figure imgf000048_0004
Q is X-21, R2 is H, R3 is Me and R4 is H.
Figure imgf000048_0005
z-Pr z-Bu
CH2CH2CH=CH2 Y-I
1-CH3-C-Pr
2 CH2CF3
Figure imgf000048_0006
Q is X-21, R2 is Me, R3 is Me and R4 is H.
2
Figure imgf000048_0007
Q is X-21, R2 is H, R3 is Me and R4 is Me.
Figure imgf000048_0008
z-Pr z-Bu
CH2CH2CH=CH2 Y-I 1-CH3-C-Pr
Figure imgf000048_0009
2-C
Figure imgf000049_0001
Q is X-21, R2 is Me, R3 is Me and R4 is Me.
2
Figure imgf000049_0002
Q is X-40, R2 is H, R3 is H and R4 is H.
2
Figure imgf000049_0003
Q is X-40, R2 is Me, R3 is H and R4 is H.
Figure imgf000049_0004
z-Pr z-Bu
CH2CH2CH=CH2 Y-I
1-CH3-C-Pr
2 CH2CF3
Figure imgf000049_0005
Q is X-40, R2 is H, R3 is Me and R4 is H.
2
Figure imgf000049_0006
Q is X-40, R2 is Me, R3 is Me and R4 is H.
Figure imgf000049_0007
z-Pr z-Bu
CH2CH2CH=CH2 Y-I
1-CH3-C-Pr
2 CH2CF3
Figure imgf000049_0008
Q is X-40, R2 is H, R3 is Me and R4 is Me.
2
Figure imgf000050_0001
Q is X-40, R2 is Me, R3 is Me and R4 is Me.
Figure imgf000050_0002
z-Bu 2 Y-I
2
Figure imgf000050_0003
Q is X-46, R2 is H, R3 is H and R4 is H.
Figure imgf000050_0004
z-Pr z-Bu
CH2CH2CH=CH2 Y-I
1-CH3-C-Pr
2 CH2CF3
Figure imgf000050_0005
Q is X-46, R2 is Me, R3 is H and R4 is H.
2
Figure imgf000050_0006
Q is X-46, R2 is H, R3 is Me and R4 is H.
Figure imgf000050_0007
z-Pr z-Bu
CH2CH2CH=CH2 Y-I
1-CH3-C-Pr
2 CH2CF3
Figure imgf000050_0008
Q is X-46, R2 is Me, R3 is Me and R4 is H.
Figure imgf000050_0009
2
Figure imgf000051_0001
X-46, R2 is H, R3 is Me and R4 is Me.
Figure imgf000051_0002
z-Pr z-Bu
CH2CH2CH=CH2 Y-I
1-CH3-C-Pr
2 CH2CF3
Figure imgf000051_0003
X-46, R2 is Me, R3 is Me z ind R4 is Me.
Figure imgf000051_0004
z-Bu 2 Y-I
2
Figure imgf000051_0005
TABLE 2
Figure imgf000051_0006
and R3 is Me.
Figure imgf000051_0007
and R3 is Me.
Figure imgf000051_0008
and R3 is Me.
Figure imgf000052_0001
Q is X-9, R2 is H and R3 is H. Q is X-9, R2 is Me and R3 is H. Q is X-9, R2 is H and RJ is Me.
Figure imgf000052_0002
H CH2CF3 H CH2CF3 H CH2CF3
Me CH2-C-Pr Me CH2-C-Pr Me CH2-C-Pr
Et CH2C=CH Et CH2C=CH Et CH2C≡CH c-Pr CH2CH=CH2 c-Pr CH2CH=CH2 c-Pr CH2CH=CH2 z-Pr CH2CH2F z-Pr CH2CH2F z-Pr CH2CH2F
OCHF2 CH2CHF2 OCHF2 CH2CHF2 OCHF2 CH2CHF2
H and R3 is Me.
Figure imgf000052_0003
Q is X-12, R2 is H and R3 is H. Q is X-12, R2 is Me and R3 is H. Q is X-12, R2 is H and RJ is Me.
Figure imgf000052_0004
H CH2CF3 H CH2CF3 H CH2CF3
Me CH2-C-Pr Me CH2-C-Pr Me CH2-C-Pr
Et CH2C=CH Et CH2C=CH Et CH2C≡CH c-Pr CH2CH=CH2 c-Pr CH2CH=CH2 c-Pr CH2CH=CH2 z-Pr CH2CH2F z-Pr CH2CH2F z-Pr CH2CH2F
OCHF2 CH2CHF2 OCHF2 CH2CHF2 OCHF2 CH2CHF2
is H and R3 is Me.
Figure imgf000052_0005
Q is X- 14, R2 is H and R3 is H. QisX-14,R2 is Me and R3 is H. QisX-14,R2 is H and R3 is Me.
Figure imgf000053_0001
Me CH2-C-Pr Me CH2-C-Pr Me CH2-C-Pr
Et CH2C≡CH Et CH2C=CH Et CH2C≡CH c-Pr CH2CH=CH2 c-Pr CH2CH=CH2 c-Pr CH2CH=CH2 z-Pr CH2CH2F z-Pr CH2CH2F z-Pr CH2CH2F
OCHF2 CH2CHF2 OCHF2 CH2CHF2 OCHF2 CH2CHF2
QisX-15, R2 is H and R3 is H. QisX-15, R2 is Me and R3 is H. QisX-15, R2 is H and R3 is Me.
Figure imgf000053_0002
H CH2CF3 H CH2CF3 H CH2CF3
Me CH2-C-Pr Me CH2-C-Pr Me CH2-C-Pr
Et CH2C=CH Et CH2C=CH Et CH2C≡CH c-Pr CH2CH=CH2 c-Pr CH2CH=CH2 c-Pr CH2CH=CH2 z-Pr CH2CH2F z-Pr CH2CH2F z-Pr CH2CH2F
OCHF2 CH2CHF2 OCHF2 CH2CHF2 OCHF2 CH2CHF2
QisX-16, R2 is H and R3 is H. QisX-16,R2 is Me and R3 is H. QisX-16,R2 is H and R3 is Me.
Figure imgf000053_0003
H CH2CF3 H CH2CF3 H CH2CF3
Me CH2-C-Pr Me CH2-C-Pr Me CH2-C-Pr
Et CH2C=CH Et CH2C=CH Et CH2C≡CH c-Pr CH2CH=CH2 c-Pr CH2CH=CH2 c-Pr CH2CH=CH2 z-Pr CH2CH2F z-Pr CH2CH2F z-Pr CH2CH2F
OCHF2 CH2CHF2 OCHF2 CH2CHF2 OCHF2 CH2CHF2
QisX-17, R2 is H and R3 is H. QisX-17, R2 is Me and R3 is H. QisX-17, R2 is H and R3 is Me.
Figure imgf000053_0004
H CH2CF3 H CH2CF3 H CH2CF3
Me CH2-C-Pr Me CH2-C-Pr Me CH2-C-Pr
Et CH2C=CH Et CH2C=CH Et CH2C≡CH c-Pr CH2CH=CH2 c-Pr CH2CH=CH2 c-Pr CH2CH=CH2 z-Pr CH2CH2F z-Pr CH2CH2F z-Pr CH2CH2F
OCHF2 CH2CHF2 OCHF2 CH2CHF2 OCHF2 CH2CHF2
is H and R3 is Me.
Figure imgf000053_0005
H and R3 is Me.
Figure imgf000054_0001
Q is X-19, R2 is H and R3 is H. Q is X-19, R2 is Me and R3 is H. Q is X-19, R2 is H and R3 is Me.
Figure imgf000054_0002
H CH2CF3 H CH2CF3 H CH2CF3
Me CH2-C-Pr Me CH2-C-Pr Me CH2-C-Pr
Et CH2C=CH Et CH2C=CH Et CH2C≡CH c-Pr CH2CH=CH2 c-Pr CH2CH=CH2 c-Pr CH2CH=CH2 z-Pr CH2CH2F z-Pr CH2CH2F z-Pr CH2CH2F
OCHF2 CH2CHF2 OCHF2 CH2CHF2 OCHF2 CH2CHF2
H and R3 is Me.
Figure imgf000054_0003
Q is X-22, R2 is H and R3 is H. Q is X-22, R2 is Me and R3 is H. Q is X-22, R2 is H and R3 is Me.
Figure imgf000054_0004
H CH2CF3 H CH2CF3 H CH2CF3
Me CH2-C-Pr Me CH2-C-Pr Me CH2-C-Pr
Et CH2C=CH Et CH2C=CH Et CH2C≡CH c-Pr CH2CH=CH2 c-Pr CH2CH=CH2 c-Pr CH2CH=CH2 z-Pr CH2CH2F z-Pr CH2CH2F z-Pr CH2CH2F
OCHF2 CH2CHF2 OCHF2 CH2CHF2 OCHF2 CH2CHF2
H and R3 is Me.
Figure imgf000054_0005
H and R3 is Me.
Figure imgf000055_0001
Q is X-24, R2 is H and R3 is H. Q is X-24, R2 is Me and R3 is H. Q is X-24, R2 is H and R3 is Me.
Figure imgf000055_0002
H CH2CF3 H CH2CF3 H CH2CF3
Me CH2-C-Pr Me CH2-C-Pr Me CH2-C-Pr
Et CH2C=CH Et CH2C=CH Et CH2C≡CH c-Pr CH2CH=CH2 c-Pr CH2CH=CH2 c-Pr CH2CH=CH2 z-Pr CH2CH2F z-Pr CH2CH2F z-Pr CH2CH2F
OCHF2 CH2CHF2 OCHF2 CH2CHF2 OCHF2 CH2CHF2
H and R3 is Me.
Figure imgf000055_0003
Q is X-26, R2 is H and R3 is H. Q is X-26, R2 is Me and R3 is H. Q is X-26, R2 is H and R3 is Me.
Figure imgf000055_0004
H CH2CF3 H CH2CF3 H CH2CF3
Me CH2-C-Pr Me CH2-C-Pr Me CH2-C-Pr
Et CH2C=CH Et CH2C=CH Et CH2C≡CH c-Pr CH2CH=CH2 c-Pr CH2CH=CH2 c-Pr CH2CH=CH2 z-Pr CH2CH2F z-Pr CH2CH2F z-Pr CH2CH2F
OCHF2 CH2CHF2 OCHF2 CH2CHF2 OCHF2 CH2CHF2
H and R3 is Me.
Figure imgf000055_0005
H and R3 is Me.
Figure imgf000056_0001
Q is X-28, R2 is H and R3 is H. Q is X-28, R2 is Me and R3 is H. Q is X-28, R2 is H and R3 is Me.
Figure imgf000056_0002
H CH2CF3 H CH2CF3 H CH2CF3
Me CH2-C-Pr Me CH2-C-Pr Me CH2-C-Pr
Et CH2C=CH Et CH2C=CH Et CH2C≡CH c-Pr CH2CH=CH2 c-Pr CH2CH=CH2 c-Pr CH2CH=CH2 z-Pr CH2CH2F z-Pr CH2CH2F z-Pr CH2CH2F
OCHF2 CH2CHF2 OCHF2 CH2CHF2 OCHF2 CH2CHF2
H and R3 is Me.
Figure imgf000056_0003
Q is X-30, R2 is H and R3 is H. Q is X-30, R2 is Me and R3 is H. Q is X-30, R2 is H and R3 is Me.
Figure imgf000056_0004
H CH2CF3 H CH2CF3 H CH2CF3
Me CH2-C-Pr Me CH2-C-Pr Me CH2-C-Pr
Et CH2C=CH Et CH2C=CH Et CH2C≡CH c-Pr CH2CH=CH2 c-Pr CH2CH=CH2 c-Pr CH2CH=CH2 z-Pr CH2CH2F z-Pr CH2CH2F z-Pr CH2CH2F
OCHF2 CH2CHF2 OCHF2 CH2CHF2 OCHF2 CH2CHF2
H and R3 is Me.
Figure imgf000056_0005
H and R3 is Me.
Figure imgf000057_0001
Q is X-32, R2 is H and R3 is H. Q is X-32, R2 is Me and R3 is H. Q is X-32, R2 is H and R3 is Me.
Figure imgf000057_0002
H CH2CF3 H CH2CF3 H CH2CF3
Me CH2-C-Pr Me CH2-C-Pr Me CH2-C-Pr
Et CH2C=CH Et CH2C=CH Et CH2C≡CH c-Pr CH2CH=CH2 c-Pr CH2CH=CH2 c-Pr CH2CH=CH2 z-Pr CH2CH2F z-Pr CH2CH2F z-Pr CH2CH2F
OCHF2 CH2CHF2 OCHF2 CH2CHF2 OCHF2 CH2CHF2
H and R3 is Me.
Figure imgf000057_0003
Q is X-34, R2 is H and R3 is H. Q is X-34, R2 is Me and R3 is H. Q is X-34, R2 is H and R3 is Me.
Figure imgf000057_0004
H CH2CF3 H CH2CF3 H CH2CF3
Me CH2-C-Pr Me CH2-C-Pr Me CH2-C-Pr
Et CH2C=CH Et CH2C=CH Et CH2C≡CH c-Pr CH2CH=CH2 c-Pr CH2CH=CH2 c-Pr CH2CH=CH2 z-Pr CH2CH2F z-Pr CH2CH2F z-Pr CH2CH2F
OCHF2 CH2CHF2 OCHF2 CH2CHF2 OCHF2 CH2CHF2
H and R3 is Me.
Figure imgf000057_0005
H and R3 is Me.
Figure imgf000058_0001
Q is X-36, R2 is H and R3 is H. Q is X-36, R2 is Me and R3 is H. Q is X-36, R2 is H and R3 is Me.
Figure imgf000058_0002
H CH2CF3 H CH2CF3 H CH2CF3
Me CH2-C-Pr Me CH2-C-Pr Me CH2-C-Pr
Et CH2C=CH Et CH2C=CH Et CH2C≡CH c-Pr CH2CH=CH2 c-Pr CH2CH=CH2 c-Pr CH2CH=CH2 z-Pr CH2CH2F z-Pr CH2CH2F z-Pr CH2CH2F
OCHF2 CH2CHF2 OCHF2 CH2CHF2 OCHF2 CH2CHF2
H and R3 is Me.
Figure imgf000058_0003
Q is X-38, R2 is H and R3 is H. Q is X-38, R2 is Me and R3 is H. Q is X-38, R2 is H and R3 is Me.
Figure imgf000058_0004
H CH2CF3 H CH2CF3 H CH2CF3
Me CH2-C-Pr Me CH2-C-Pr Me CH2-C-Pr
Et CH2C=CH Et CH2C=CH Et CH2C≡CH c-Pr CH2CH=CH2 c-Pr CH2CH=CH2 c-Pr CH2CH=CH2 z-Pr CH2CH2F z-Pr CH2CH2F z-Pr CH2CH2F
OCHF2 CH2CHF2 OCHF2 CH2CHF2 OCHF2 CH2CHF2
H and R3 is Me.
Figure imgf000058_0005
H and R3 is Me.
Figure imgf000059_0001
Q is X-41, R2 is H and R3 is H. Q is X-41, R2 is Me and R3 is H. Q is X-41, R2 is H and R3 is Me.
Figure imgf000059_0002
H CH2CF3 H CH2CF3 H CH2CF3
Me CH2-C-Pr Me CH2-C-Pr Me CH2-C-Pr
Et CH2C=CH Et CH2C=CH Et CH2C≡CH c-Pr CH2CH=CH2 c-Pr CH2CH=CH2 c-Pr CH2CH=CH2 z-Pr CH2CH2F z-Pr CH2CH2F z-Pr CH2CH2F
OCHF2 CH2CHF2 OCHF2 CH2CHF2 OCHF2 CH2CHF2
H and R3 is Me.
Figure imgf000059_0003
Q is X-43, R2 is H and R3 is H. Q is X-43, R2 is Me and R3 is H. Q is X-43, R2 is H and R3 is Me.
Figure imgf000059_0004
H CH2CF3 H CH2CF3 H CH2CF3
Me CH2-C-Pr Me CH2-C-Pr Me CH2-C-Pr
Et CH2C=CH Et CH2C=CH Et CH2C≡CH c-Pr CH2CH=CH2 c-Pr CH2CH=CH2 c-Pr CH2CH=CH2 z-Pr CH2CH2F z-Pr CH2CH2F z-Pr CH2CH2F
OCHF2 CH2CHF2 OCHF2 CH2CHF2 OCHF2 CH2CHF2
H and R3 is Me.
Figure imgf000059_0005
Q is X-44, R2 is H and R3 is H. Q is X-44, R2 is Me and R3 is H. Q is X-44, R2 is H and R3 is Me.
Figure imgf000060_0001
Me CH2-C-Pr Me CH2-C-Pr Me CH2-C-Pr
Et CH2C≡CH Et CH2C=CH Et CH2C≡CH c-Pr CH2CH=CH2 c-Pr CH2CH=CH2 c-Pr CH2CH=CH2 z-Pr CH2CH2F z-Pr CH2CH2F z-Pr CH2CH2F
OCHF2 CH2CHF2 OCHF2 CH2CHF2 OCHF2 CH2CHF2
Q is X-45, R2 is H and R3 is H. Q is X-45, R2 is Me and R3 is H. Q is X-45, R2 is H and R3 is Me.
Figure imgf000060_0002
H CH2CF3 H CH2CF3 H CH2CF3
Me CH2-C-Pr Me CH2-C-Pr Me CH2-C-Pr
Et CH2C=CH Et CH2C=CH Et CH2C≡CH c-Pr CH2CH=CH2 c-Pr CH2CH=CH2 c-Pr CH2CH=CH2 z-Pr CH2CH2F z-Pr CH2CH2F z-Pr CH2CH2F
OCHF2 CH2CHF2 OCHF2 CH2CHF2 OCHF2 CH2CHF2
H and R3 is Me.
Figure imgf000060_0003
Q is X-48, R2 is H and R3 is H. Q is X-48, R2 is Me and R3 is H. Q is X-48, R2 is H and R3 is Me.
Figure imgf000060_0004
H CH2CF3 H CH2CF3 H CH2CF3
Me CH2-C-Pr Me CH2-C-Pr Me CH2-C-Pr
Et CH2C=CH Et CH2C=CH Et CH2C≡CH c-Pr CH2CH=CH2 c-Pr CH2CH=CH2 c-Pr CH2CH=CH2 z-Pr CH2CH2F z-Pr CH2CH2F z-Pr CH2CH2F
OCHF2 CH2CHF2 OCHF2 CH2CHF2 OCHF2 CH2CHF2
H and R3 is Me.
Figure imgf000060_0005
H and R3 is Me.
Figure imgf000061_0001
Q is X-50, R2 is H and R3 is H. Q is X-50, R2 is Me and R3 is H. Q is X-50, R2 is H and R3 is Me.
Figure imgf000061_0002
H CH2CF3 H CH2CF3 H CH2CF3
Me CH2-C-Pr Me CH2-C-Pr Me CH2-C-Pr
Et CH2C=CH Et CH2C=CH Et CH2C≡CH c-Pr CH2CH=CH2 c-Pr CH2CH=CH2 c-Pr CH2CH=CH2 z-Pr CH2CH2F z-Pr CH2CH2F z-Pr CH2CH2F
OCHF2 CH2CHF2 OCHF2 CH2CHF2 OCHF2 CH2CHF2
H and R3 is Me.
Figure imgf000061_0003
Q is X-52, R2 is H and R3 is H. Q is X-52, R2 is Me and R3 is H. Q is X-52, R2 is H and R3 is Me.
Figure imgf000061_0004
H CH2CF3 H CH2CF3 H CH2CF3
Me CH2-C-Pr Me CH2-C-Pr Me CH2-C-Pr
Et CH2C=CH Et CH2C=CH Et CH2C≡CH c-Pr CH2CH=CH2 c-Pr CH2CH=CH2 c-Pr CH2CH=CH2 z-Pr CH2CH2F z-Pr CH2CH2F z-Pr CH2CH2F
OCHF2 CH2CHF2 OCHF2 CH2CHF2 OCHF2 CH2CHF2
H and R3 is Me.
Figure imgf000061_0005
H and R3 is Me.
Figure imgf000062_0001
Q is X-54, R2 is H and R3 is H. Q is X-54, R2 is Me and R3 is H. Q is X-54, R2 is H and R3 is Me.
Figure imgf000062_0002
H CH2CF3 H CH2CF3 H CH2CF3
Me CH2-C-Pr Me CH2-C-Pr Me CH2-C-Pr
Et CH2C=CH Et CH2C=CH Et CH2C≡CH c-Pr CH2CH=CH2 c-Pr CH2CH=CH2 c-Pr CH2CH=CH2 z-Pr CH2CH2F z-Pr CH2CH2F z-Pr CH2CH2F
OCHF2 CH2CHF2 OCHF2 CH2CHF2 OCHF2 CH2CHF2
H and R3 is Me.
Figure imgf000062_0003
Q is X-56, R2 is H and R3 is H. Q is X-56, R2 is Me and R3 is H. Q is X-56, R2 is H and R3 is Me.
Figure imgf000062_0004
H CH2CF3 H CH2CF3 H CH2CF3
Me CH2-C-Pr Me CH2-C-Pr Me CH2-C-Pr
Et CH2C=CH Et CH2C=CH Et CH2C≡CH c-Pr CH2CH=CH2 c-Pr CH2CH=CH2 c-Pr CH2CH=CH2 z-Pr CH2CH2F z-Pr CH2CH2F z-Pr CH2CH2F
OCHF2 CH2CHF2 OCHF2 CH2CHF2 OCHF2 CH2CHF2
Figure imgf000063_0001
R3 is Me.
Figure imgf000063_0002
and R3 is Me.
Figure imgf000063_0003
and R3 is Me.
Figure imgf000063_0004
and R3 is Me.
Figure imgf000063_0005
and R3 is Me.
Figure imgf000064_0001
and R3 is Me.
Figure imgf000064_0002
Q is X-8, R2 is H and R3 is H. Q is X-8, R2 is Me and R3 is H. Q is X-8, R2 is H and RJ is Me.
Figure imgf000064_0003
H CH2CF3 H CH2CF3 H CH2CF3
Me CH2-C-Pr Me CH2-C-Pr Me CH2-C-Pr
Et CH2C=CH Et CH2C=CH Et CH2C≡CH c-Pr CH2CH=CH2 c-Pr CH2CH=CH2 c-Pr CH2CH=CH2 z-Pr CH2CH2F z-Pr CH2CH2F z-Pr CH2CH2F
OCHF2 CH2CHF2 OCHF2 CH2CHF2 OCHF2 CH2CHF2
and R3 is Me.
Figure imgf000064_0004
H and R3 is Me.
Figure imgf000064_0005
H and R3 is Me.
Figure imgf000065_0001
H and R3 is Me.
Figure imgf000065_0002
Q is X-40, R2 is H and R3 is H. Q is X-40, R2 is Me and R3 is H. Q is X-40, R2 is H and R3 is Me.
Figure imgf000065_0003
H CH2CF3 H CH2CF3 H CH2CF3
Me CH2-C-Pr Me CH2-C-Pr Me CH2-C-Pr
Et CH2C=CH Et CH2C=CH Et CH2C≡CH c-Pr CH2CH=CH2 c-Pr CH2CH=CH2 c-Pr CH2CH=CH2 z-Pr CH2CH2F z-Pr CH2CH2F z-Pr CH2CH2F
OCHF2 CH2CHF2 OCHF2 CH2CHF2 OCHF2 CH2CHF2
Q is X-46, R2 is H and R3 is H. Q is X-46, R2 is Me and R3 is H. Q is X-46, R2 is H and R3 is Me.
Figure imgf000065_0004
H CH2CF3 H CH2CF3 H CH2CF3
Me CH2-C-Pr Me CH2-C-Pr Me CH2-C-Pr
Et CH2C=CH Et CH2C=CH Et CH2C≡CH c-Pr CH2CH=CH2 c-Pr CH2CH=CH2 c-Pr CH2CH=CH2 z-Pr CH2CH2F z-Pr CH2CH2F z-Pr CH2CH2F
OCHF2 CH2CHF2 OCHF2 CH2CHF2 OCHF2 CH2CHF2
Figure imgf000066_0001
Q is X-I, R2 is H and R3 is H. Q is X-I, R2 is Me and R3 is H. Q is X-I, R2 is H and R3 is Me.
Figure imgf000066_0002
H CH2CF3 H CH2CF3 H CH2CF3
Me CH2-C-Pr Me CH2-C-Pr Me CH2-C-Pr
Et CH2C≡CH Et CH2C=CH Et CH2C≡CH c-Pr CH2CH=CH2 c-Pr CH2CH=CH2 c-Pr CH2CH=CH2 z-Pr CH2CH2F z-Pr CH2CH2F z-Pr CH2CH2F
OCHF2 CH2CHF2 OCHF2 CH2CHF2 OCHF2 CH2CHF2
and R3 is Me.
Figure imgf000066_0003
and R3 is Me.
Figure imgf000066_0004
and R3 is Me.
Figure imgf000066_0005
and R3 is Me.
Figure imgf000067_0001
Q is X-6, R2 is H and R3 is H. Q is X-6, R2 is Me and R3 is H. Q is X-6, R2 is H and RJ is Me.
Figure imgf000067_0002
H CH2CF3 H CH2CF3 H CH2CF3
Me CH2-C-Pr Me CH2-C-Pr Me CH2-C-Pr
Et CH2C=CH Et CH2C=CH Et CH2C≡CH c-Pr CH2CH=CH2 c-Pr CH2CH=CH2 c-Pr CH2CH=CH2 z-Pr CH2CH2F z-Pr CH2CH2F z-Pr CH2CH2F
OCHF2 CH2CHF2 OCHF2 CH2CHF2 OCHF2 CH2CHF2
and R3 is Me.
Figure imgf000067_0003
Q is X-11, R2 is H and R3 is H. Q is X-I l, R2 is Me and R3 is H. Q is X-I l, R2 is H and RJ is Me.
Figure imgf000067_0004
H CH2CF3 H CH2CF3 H CH2CF3
Me CH2-C-Pr Me CH2-C-Pr Me CH2-C-Pr
Et CH2C=CH Et CH2C=CH Et CH2C≡CH c-Pr CH2CH=CH2 c-Pr CH2CH=CH2 c-Pr CH2CH=CH2 z-Pr CH2CH2F z-Pr CH2CH2F z-Pr CH2CH2F
OCHF2 CH2CHF2 OCHF2 CH2CHF2 OCHF2 CH2CHF2
H and R3 is Me.
Figure imgf000067_0005
H and R3 is Me.
Figure imgf000068_0001
Q is X-21, R2 is H and R3 is H. Q is X-21, R2 is Me and R3 is H. Q is X-21, R2 is H and R3 is Me.
Figure imgf000068_0002
H CH2CF3 H CH2CF3 H CH2CF3
Me CH2-C-Pr Me CH2-C-Pr Me CH2-C-Pr
Et CH2C=CH Et CH2C=CH Et CH2C≡CH c-Pr CH2CH=CH2 c-Pr CH2CH=CH2 c-Pr CH2CH=CH2 z-Pr CH2CH2F z-Pr CH2CH2F z-Pr CH2CH2F
OCHF2 CH2CHF2 OCHF2 CH2CHF2 OCHF2 CH2CHF2
H and R3 is Me.
Figure imgf000068_0003
Q is X-46, R2 is H and R3 is H. Q is X-46, R2 is Me and R3 is H. Q is X-46, R2 is H and R3 is Me.
Figure imgf000068_0004
H CH2CF3 H CH2CF3 H CH2CF3
Me CH2-C-Pr Me CH2-C-Pr Me CH2-C-Pr
Et CH2C=CH Et CH2C=CH Et CH2C≡CH c-Pr CH2CH=CH2 c-Pr CH2CH=CH2 c-Pr CH2CH=CH2 z-Pr CH2CH2F z-Pr CH2CH2F z-Pr CH2CH2F
OCHF2 CH2CHF2 OCHF2 CH2CHF2 OCHF2 CH2CHF2 TABLE 5
Figure imgf000069_0001
R3 is Me.
Figure imgf000069_0002
and R3 is Me.
Figure imgf000069_0003
and R3 is Me.
Figure imgf000069_0004
and R3 is Me.
Figure imgf000069_0005
and R3 is Me.
Figure imgf000070_0001
Q is X-6, R2 is H and R3 is H. Q is X-6, R2 is Me and R3 is H. Q is X-6, R2 is H and RJ is Me.
Figure imgf000070_0002
H CH2CF3 H CH2CF3 H CH2CF3
Me CH2-C-Pr Me CH2-C-Pr Me CH2-C-Pr
Et CH2C=CH Et CH2C=CH Et CH2C≡CH c-Pr CH2CH=CH2 c-Pr CH2CH=CH2 c-Pr CH2CH=CH2 z-Pr CH2CH2F z-Pr CH2CH2F z-Pr CH2CH2F
OCHF2 CH2CHF2 OCHF2 CH2CHF2 OCHF2 CH2CHF2
and R3 is Me.
Figure imgf000070_0003
Q is X-11, R2 is H and R3 is H. Q is X-I l, R2 is Me and R3 is H. Q is X-I l, R2 is H and RJ is Me.
Figure imgf000070_0004
H CH2CF3 H CH2CF3 H CH2CF3
Me CH2-C-Pr Me CH2-C-Pr Me CH2-C-Pr
Et CH2C=CH Et CH2C=CH Et CH2C≡CH c-Pr CH2CH=CH2 c-Pr CH2CH=CH2 c-Pr CH2CH=CH2 z-Pr CH2CH2F z-Pr CH2CH2F z-Pr CH2CH2F
OCHF2 CH2CHF2 OCHF2 CH2CHF2 OCHF2 CH2CHF2
H and R3 is Me.
Figure imgf000070_0005
H and R3 is Me.
Figure imgf000071_0001
Q is X-21, R2 is H and R3 is H. Q is X-21, R2 is Me and R3 is H. Q is X-21, R2 is H and R3 is Me.
Figure imgf000071_0002
H CH2CF3 H CH2CF3 H CH2CF3
Me CH2-C-Pr Me CH2-C-Pr Me CH2-C-Pr
Et CH2C=CH Et CH2C=CH Et CH2C≡CH c-Pr CH2CH=CH2 c-Pr CH2CH=CH2 c-Pr CH2CH=CH2 z-Pr CH2CH2F z-Pr CH2CH2F z-Pr CH2CH2F
OCHF2 CH2CHF2 OCHF2 CH2CHF2 OCHF2 CH2CHF2
H and R3 is Me.
Figure imgf000071_0003
Q is X-46, R2 is H and R3 is H. Q is X-46, R2 is Me and R3 is H. Q is X-46, R2 is H and R3 is Me.
Figure imgf000071_0004
H CH2CF3 H CH2CF3 H CH2CF3
Me CH2-C-Pr Me CH2-C-Pr Me CH2-C-Pr
Et CH2C=CH Et CH2C=CH Et CH2C≡CH c-Pr CH2CH=CH2 c-Pr CH2CH=CH2 c-Pr CH2CH=CH2 z-Pr CH2CH2F z-Pr CH2CH2F z-Pr CH2CH2F
OCHF2 CH2CHF2 OCHF2 CH2CHF2 OCHF2 CH2CHF2 TABLE 6
Figure imgf000072_0001
Q is X-5 and R2 is H. Q is X-5 and R2 is Me.
Ei Ei Ei Ei
H CH2CF3 H CH2CF3
Me CH2-C-Pr Me CH2-C-Pr
Figure imgf000073_0001
Figure imgf000073_0002
Figure imgf000073_0003
Figure imgf000073_0004
QisX-13andR2isH. Q is X- 13 and R2 is Me.
Figure imgf000073_0005
H CH2CF3 H CH2CF3
Me CH2-C-Pr Me CH2-C-Pr
Figure imgf000074_0001
Figure imgf000074_0002
Figure imgf000074_0003
Figure imgf000074_0004
Figure imgf000075_0001
R1 is Me R1 is Me
Y G Z Y G Z
CH2 bond CH2 O CH2 O
CH2 bond CHMe O CH2 S
S bond NMe O CH2 NMe
NMe bond NMe O CH2 CH2
CH2 bond NMe O CH2 CHMe
CH2 bond S S CH2 O
CH2 CH2 O S CH2 S
CH2 CH2 S S CH2 NMe
CH2 CH2 NMe S CH2 CH2
CH2 CH2 CH2 S CH2 CHMe
CH2 CH2 CHMe NMe CH2 NMe
NMe CH2 O NMe CH2 CH2
NMe CH2 S NMe CH2 CHMe
CH=CH O O CH=CH
CH=CH S
CH=CH NMe
R1 is c-Pr R1 is c-Pr
Y G Z Y G Z
CH2 bond CH2 O CH2 O
CH2 bond CHMe O CH2 S
S bond NMe O CH2 NMe
NMe bond NMe O CH2 CH2
CH2 bond NMe O CH2 CHMe
CH2 bond S S CH2 O
CH2 CH2 O S CH2 S
CH2 CH2 S S CH2 NMe Rl is c-Pr R1 is c-Pr
Y G Z Y G Z
CH2 CH2 NMe S CH2 CH2
CH2 CH2 CH2 S CH2 CHMe
CH2 CH2 CHMe NMe CH2 NMe
NMe CH2 O NMe CH2 CH2
NMe CH2 S NMe CH2 CHMe
CH=CH O O CH=CH
CH=CH S
CH=CH NMe
TABLE 8
Figure imgf000076_0001
R1 is Me R1 is Me
Y G Z Y G Z
CH2 bond CH2 O CH2 O
CH2 bond CHMe O CH2 S
S bond NMe O CH2 NMe
NMe bond NMe O CH2 CH2
CH2 bond NMe O CH2 CHMe
CH2 bond S S CH2 O
CH2 CH2 O S CH2 S
CH2 CH2 S S CH2 NMe
CH2 CH2 NMe S CH2 CH2
CH2 CH2 CH2 S CH2 CHMe
CH2 CH2 CHMe NMe CH2 NMe
NMe CH2 O NMe CH2 CH2
NMe CH2 S NMe CH2 CHMe
CH=CH O O CH=CH
CH=CH S
CH=CH NMe R1 is c-Pr R1 is c-Pr
Y G Z Y G Z
CH2 bond CH2 O CH2 O
CH2 bond CHMe O CH2 S
S bond NMe O CH2 NMe
NMe bond NMe O CH2 CH2
CH2 bond NMe O CH2 CHMe
CH2 bond S S CH2 O
CH2 CH2 O S CH2 S
CH2 CH2 S S CH2 NMe
CH2 CH2 NMe S CH2 CH2
CH2 CH2 CH2 S CH2 CHMe
CH2 CH2 CHMe NMe CH2 NMe
NMe CH2 O NMe CH2 CH2
NMe CH2 S NMe CH2 CHMe
CH=CH O O CH=CH
CH=CH S
CH=CH NMe
A compound of this invention will generally be used as an invertebrate pest control active ingredient in a composition, i.e. formulation, with at least one additional component selected from the group consisting of surfactants, solid diluents and liquid diluents, which serves as a carrier. The formulation or composition ingredients are selected to be consistent with the physical properties of the active ingredient, mode of application and environmental factors such as soil type, moisture and temperature.
Useful formulations include both liquid and solid compositions. Liquid compositions include solutions (including emulsifϊable concentrates), suspensions, emulsions (including microemulsions and/or suspoemulsions) and the like, which optionally can be thickened into gels. The general types of aqueous liquid compositions are soluble concentrate, suspension concentrate, capsule suspension, concentrated emulsion, microemulsion and suspo-emulsion. The general types of nonaqueous liquid compositions are emulsifϊable concentrate, microemulsifiable concentrate, dispersible concentrate and oil dispersion. The general types of solid compositions are dusts, powders, granules, pellets, prills, pastilles, tablets, filled films (including seed coatings) and the like, 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. Active ingredient can be (micro)encapsulated and further formed into a suspension or solid formulation; alternatively the entire formulation of active ingredient can be encapsulated (or "overcoated"). Encapsulation can control or delay release of the active ingredient. An emulsifiable granule combines the advantages of both an emulsifiable concentrate formulation and a dry granular formulation. High-strength compositions are primarily used as intermediates for further formulation. Sprayable formulations are typically extended in a suitable medium before spraying.
Such liquid and solid formulations are formulated to be readily diluted in the spray medium, usually water. Spray volumes can range from about from about one to several thousand liters per hectare, but more typically are in the range from about ten to several hundred liters per hectare. Sprayable formulations can be tank mixed with water or another suitable medium for foliar treatment by aerial or ground application, or for application to the growing medium of the plant. Liquid and dry formulations can be metered directly into drip irrigation systems or metered into the furrow during planting. Liquid and solid formulations can be applied onto seeds of crops and other desirable vegetation as seed treatments before planting to protect developing roots and other subterranean plant parts and/or foliage through systemic uptake.
The formulations will typically contain effective amounts of active ingredient, diluent and surfactant within the following approximate ranges which add up to 100 percent by weight.
Weight Percent
Active
Ingredient Diluent Surfactant
Water-Dispersible and Water- 0.001-90 0-99.999 0-15 soluble Granules, Tablets and Powders
Oil Dispersions, Suspensions, 1-50 40-99 0-50 Emulsions, Solutions (including Emulsifiable Concentrates)
Dusts 1-25 70-99 0-5
Granules and Pellets 0.001-99 5-99.999 0-15
High Strength Compositions 90-99 0-10 0-2
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. Typical solid diluents are described in Watkins et al., Handbook of Insecticide Dust Diluents and Carriers, 2nd Ed., Dorland Books, Caldwell, New Jersey. Liquid diluents include, for example, water, Λ/,iV-dimethylalkanamides (e.g., N,Λ/-dimethylformamide), limonene, dimethyl sulfoxide, JV-alkylpyrrolidones (e.g., JV-methylpyrrolidinone), ethylene glycol, Methylene glycol, propylene glycol, dipropylene glycol, polypropylene glycol, propylene carbonate, butylene carbonate, paraffins (e.g., white mineral oils, normal paraffins, isoparaffϊns), alkylbenzenes, alkylnaphthalenes, glycerine, glycerol triacetate, sorbitol, triacetin, aromatic hydrocarbons, dearomatized 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 lactate esters, dibasic esters and γ-butyrolactone, and alcohols, which can be linear, branched, saturated or unsaturated, such as methanol, ethanol, n-propanol, isopropyl alcohol, n-butanol, isobutyl alcohol, n-hexanol, 2-ethylhexanol, n-octanol, decanol, isodecyl alcohol, isooctadecanol, cetyl alcohol, lauryl alcohol, tridecyl alcohol, oleyl alcohol, cyclohexanol, tetrahydrofurfuryl alcohol, diacetone alcohol and benzyl alcohol. Liquid diluents also include glycerol esters of saturated and unsaturated fatty acids (typically C6-C22), such as plant seed and fruit oils (e.g, oils of olive, castor, linseed, sesame, corn (maize), peanut, sunflower, grapeseed, safflower, cottonseed, soybean, rapeseed, coconut and palm kernel), animal-sourced fats (e.g., beef tallow, pork tallow, lard, cod liver oil, fish oil), and mixtures thereof. Liquid diluents also include alkylated fatty acids (e.g., methylated, ethylated, butylated) wherein the fatty acids may be obtained by hydrolysis of glycerol esters from plant and animal sources, and can be purified by distillation. Typical liquid diluents are described in Marsden, Solvents Guide, 2nd Ed., Interscience, New York, 1950.
The solid and liquid compositions of the present invention often include one or more surfactants. When added to a liquid, surfactants (also known as "surface-active agents") generally modify, most often reduce, the surface tension of the liquid. Depending on the nature of the hydrophilic and lipophilic groups in a surfactant molecule, surfactants can be useful as wetting agents, dispersants, emulsifϊers or defoaming agents.
Surfactants can be classified as nonionic, anionic or cationic. Nonionic surfactants useful for the present compositions include, but are not limited to: alcohol alkoxylates such as alcohol alkoxylates based on natural and synthetic alcohols (which may be branched or linear) and prepared from the alcohols and ethylene oxide, propylene oxide, butylene oxide or mixtures thereof; amine ethoxylates, alkanolamides and ethoxylated alkanolamides; alkoxylated triglycerides such as ethoxylated soybean, castor and rapeseed oils; alkylphenol alkoxylates such as octylphenol ethoxylates, nonylphenol ethoxylates, dinonyl phenol ethoxylates and dodecyl phenol ethoxylates (prepared from the phenols and ethylene oxide, propylene oxide, butylene oxide or mixtures thereof); block polymers prepared from ethylene oxide or propylene oxide and reverse block polymers where the terminal blocks are prepared from propylene oxide; ethoxylated fatty acids; ethoxylated fatty esters and oils; ethoxylated methyl esters; ethoxylated tristyrylphenol (including those prepared from ethylene oxide, propylene oxide, butylene oxide or mixtures thereof); fatty acid esters, glycerol esters, lanolin-based derivatives, polyethoxylate esters such as polyethoxylated sorbitan fatty acid esters, polyethoxylated sorbitol fatty acid esters and polyethoxylated glycerol fatty acid esters; other sorbitan derivatives such as sorbitan esters; polymeric surfactants such as random copolymers, block copolymers, alkyd peg (polyethylene glycol) resins, graft or comb polymers and star polymers; polyethylene glycols (pegs); polyethylene glycol fatty acid esters; silicone-based surfactants; and sugar-derivatives such as sucrose esters, alkyl polyglycosides and alkyl polysaccharides.
Useful anionic surfactants include, but are not limited to: alkylaryl sulfonic acids and their salts; carboxylated alcohol or alkylphenol ethoxylates; diphenyl sulfonate derivatives; lignin and lignin derivatives such as lignosulfonates; maleic or succinic acids or their anhydrides; olefin sulfonates; phosphate esters such as phosphate esters of alcohol alkoxylates, phosphate esters of alkylphenol alkoxylates and phosphate esters of styryl phenol ethoxylates; protein-based surfactants; sarcosine derivatives; styryl phenol ether sulfate; 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 7V,iV-alkyltaurates; sulfonates of benzene, cumene, toluene, xylene, and dodecyl and tridecylbenzenes; sulfonates of condensed naphthalenes; sulfonates of naphthalene and alkyl naphthalene; sulfonates of fractionated petroleum; sulfosuccinamates; and sulfosuccinates and their derivatives such as dialkyl sulfosuccinate salts.
Useful cationic surfactants include, but are not limited to: amides and ethoxylated amides; amines such as JV-alkyl propanediamines, tripropylenetriamines and dipropylenetetramines, and ethoxylated amines, ethoxylated diamines and propoxylated amines (prepared from the amines and ethylene oxide, propylene oxide, butylene oxide or mixtures thereof); amine salts such as amine acetates and diamine salts; quaternary ammonium salts such as quaternary salts, ethoxylated quaternary salts and diquaternary salts; and amine oxides such as alkyldimethylamine oxides and bis-(2-hydroxyethyl)-alkylamine oxides.
Also useful for the present compositions are mixtures of nonionic and anionic surfactants or mixtures of nonionic and cationic surfactants. Nonionic, anionic and cationic surfactants and their recommended uses are disclosed in a variety of published references including McCutcheon 's Emulsifiers and Detergents, annual American and International Editions published by McCutcheon's Division, The Manufacturing Confectioner Publishing Co.; Sisely and Wood, Encyclopedia of Surface Active Agents, Chemical Publ. Co., Inc., New York, 1964; and A. S. Davidson and B. Milwidsky, Synthetic Detergents, Seventh Edition, John Wiley and Sons, New York, 1987. Compositions of this invention may also contain formulation auxiliaries and additives, known to those skilled in the art as formulation aids (some of which may be considered to also function as solid diluents, liquid diluents or surfactants). Such formulation auxiliaries and additives may control: pH (buffers), foaming during processing (antifoams such polyorganosiloxanes), sedimentation of active ingredients (suspending agents), viscosity (thixotropic thickeners), in-container microbial growth (antimicrobials), product freezing (antifreezes), color (dyes/pigment dispersions), wash-off (film formers or stickers), evaporation (evaporation retardants), and other formulation attributes. Film formers include, for example, polyvinyl acetates, polyvinyl acetate copolymers, polyvinylpyrrolidone-vinyl acetate copolymer, polyvinyl alcohols, polyvinyl alcohol copolymers and waxes. Examples of formulation auxiliaries and additives include those listed in McCutcheon 's Volume 2: Functional Materials, annual International and North American editions published by McCutcheon' s Division, The Manufacturing Confectioner Publishing Co.; and PCT Publication WO 03/024222. The compound of Formula 1 and any other active ingredients are typically incorporated into the present compositions by dissolving the active ingredient in a solvent or by grinding in a liquid or dry diluent. Solutions, including emulsifiable concentrates, can be prepared by simply mixing the ingredients. If the solvent of a liquid composition intended for use as an emulsifiable concentrate is water-immiscible, an emulsifier is typically added to emulsify the active-containing solvent upon dilution with water. Active ingredient slurries, with particle diameters of up to 2,000 μm can be wet milled using media mills to obtain particles with average diameters below 3 μm. Aqueous slurries can be made into finished suspension concentrates (see, for example, U.S. 3,060,084) or further processed by spray drying to form water-dispersible granules. Dry formulations usually require dry milling processes, which produce average particle diameters in the 2 to 10 μm range. Dusts and powders can be prepared by blending and usually grinding (such as with a hammer mill or fluid-energy mill). Granules and pellets can be prepared by spraying the active material upon preformed granular carriers or by agglomeration techniques. See Browning, "Agglomeration", Chemical Engineering, December 4, 1967, pp 147-48, Perry's Chemical Engineer's Handbook, 4th Ed., McGraw-Hill, New York, 1963, pages 8-57 and following, and WO 91/13546. Pellets can be prepared as described in U.S. 4,172,714. Water-dispersible and water-soluble granules can be prepared as taught in U.S. 4,144,050, U.S. 3,920,442 and DE 3,246,493. Tablets can be prepared as taught in U.S. 5,180,587, U.S. 5,232,701 and U.S. 5,208,030. Films can be prepared as taught in GB 2,095,558 and U.S. 3,299,566.
For further information regarding the art of formulation, see T. S. Woods, "The Formulator's Toolbox - Product Forms for Modern Agriculture" in Pesticide Chemistry and Bioscience, The Food-Environment Challenge, T. Brooks and T. R. Roberts, Eds., Proceedings of the 9th International Congress on Pesticide Chemistry, The Royal Society of Chemistry, Cambridge, 1999, pp. 120-133. See also U.S. 3,235,361, Col. 6, line 16 through Col. 7, line 19 and Examples 10-41; U.S. 3,309,192, Col. 5, line 43 through Col. 7, line 62 and Examples 8, 12, 15, 39, 41, 52, 53, 58, 132, 138-140, 162-164, 166, 167 and 169-182; U.S. 2,891,855, Col. 3, line 66 through Col. 5, line 17 and Examples 1-4; Klingman, Weed Control as a Science, John Wiley and Sons, Inc., New York, 1961, pp 81-96; Hance et al., Weed Control Handbook, 8th Ed., Blackwell Scientific Publications, Oxford, 1989; and Developments in formulation technology, PJB Publications, Richmond, UK, 2000.
In the following Examples, all formulations are prepared in conventional ways. Compound numbers refer to compounds in Index Tables A-B. Without further elaboration, it is believed that one skilled in the art using the preceding description can utilize the present invention to its fullest extent. The following Examples are, therefore, to be constructed as merely illustrative, and not limiting of the disclosure in any way whatsoever. Percentages are by weight except where otherwise indicated. Example A
High Strength Concentrate
Compound 5 98.5% silica aerogel 0.5% synthetic amorphous fine silica 1.0%
Example B
Wettable Powder
Compound 6 65.0% dodecylphenol polyethylene glycol ether 2.0% sodium ligninsulfonate 4.0% sodium silicoaluminate 6.0% montmorillonite (calcined) 23.0%
Example C
Granule
Compound 22 10.0% attapulgite granules (low volatile matter, 0.71/0.30 mm; 90.0%
U.S.S. No. 25-50 sieves)
Example D
Extruded Pellet
Compound 26 25.0% anhydrous sodium sulfate 10.0% crude calcium ligninsulfonate 5.0% sodium alkvlnarjhthalenesulfonate 1.0% calcium/magnesium bentonite 59.0%
Example E Emulsifϊable Concentrate
Compound 31 10.0% polyoxyethylene sorbitol hexoleate 20.0%
Co-CiO fatty acid methyl ester 70.0%
Example F
Microemulsion
Compound 59 5.0% polyvinylpyrrolidone -vinyl acetate copolymer 30.0% alkylpolyglycoside 30.0% glyceryl monooleate 15.0% water 20.0%
Example G
Seed Treatment
Compound 61 20.00% polyvinylpyrrolidone -vinyl acetate copolymer 5.00% montan acid wax 5.00% calcium ligninsulfonate 1.00% polyoxyethylene/polyoxypropylene block copolymers 1.00% stearyl alcohol (POE 20) 2.00% polyorganosilane 0.20% colorant red dye 0.05% water 65.75%
Example H
Fertilizer Stick
Compound 60 2.5% pyrrolidone-styrene copolymer 4.8% tristyrylphenyl 16-ethoxylate 2.3% talc 0.8% corn starch 5.0%
Nitrophoska® Permanent 15-9-15 slow-release fertilizer 36.0%
(BASF) kaolin 38.0% water 10.6%
Compounds of this invention exhibit activity against a wide spectrum of invertebrate pests. These pests include invertebrates inhabiting a variety of environments such as, for example, plant foliage, roots, soil, harvested crops or other foodstuffs, building structures or animal integuments. These pests include, for example, invertebrates feeding on foliage (including leaves, stems, flowers and fruits), seeds, wood, textile fibers or animal blood or tissues, and thereby causing injury or damage to, for example, growing or stored agronomic crops, forests, greenhouse crops, ornamentals, nursery crops, stored foodstuffs or fiber products, or houses or other structures or their contents, or being harmful to animal health or public health. Those skilled in the art will appreciate that not all compounds are equally effective against all growth stages of all pests.
These present compounds and compositions are thus useful agronomically for protecting field crops from phytophagous invertebrate pests, and also nonagronomically for protecting other horticultural crops and plants from phytophagous invertebrate pests. This utility includes protecting crops and other plants (i.e. both agronomic and nonagronomic) that contain genetic material introduced by genetic engineering (i.e. transgenic) or modified by mutagenesis to provide advantageous traits. Examples of such traits include tolerance to herbicides, resistance to phytophagous pests (e.g., insects, mites, aphids, spiders, nematodes, snails, plant-pathogenic fungi, bacteria and viruses), improved plant growth, increased tolerance of adverse growing conditions such as high or low temperatures, low or high soil moisture, and high salinity, increased flowering or fruiting, greater harvest yields, more rapid maturation, higher quality and/or nutritional value of the harvested product, or improved storage or process properties of the harvested products. Transgenic plants can be modified to express multiple traits. Examples of plants containing traits provided by genetic engineering or mutagenesis include varieties of corn, cotton, soybean and potato expressing an insecticidal Bacillus thuringiensis toxin such as YIELD GARD®, KNOCKOUT R, STARLINK®, BOLLGARD®, NuCOTN® and NEWLEAF®, and herbicide-tolerant varieties of corn, cotton, soybean and rapeseed such as ROUNDUP READY®, LIBERTY LINK®, IMI , STS and CLEARFIELD , as well as crops expressing JV-acetyltransferase (GAT) to provide resistance to glyphosate herbicide, or crops containing the HRA gene providing resistance to herbicides inhibiting acetolactate synthase (ALS). The present compounds and compositions may interact synergistically with traits introduced by genetic engineering or modified by mutagenesis, thus enhancing phenotypic expression or effectiveness of the traits or increasing the invertebrate pest control effectiveness of the present compounds and compositions. In particular, the present compounds and compositions may interact synergistically with the phenotypic expression of proteins or other natural products toxic to invertebrate pests to provide greater-than-additive control of these pests. Compositions of this invention can also optionally comprise plant nutrients, e.g., a fertilizer composition comprising at least one plant nutrient selected from nitrogen, phosphorus, potassium, sulfur, calcium, magnesium, iron, copper, boron, manganese, zinc, and molybdenum. Of note are compositions comprising at least one fertilizer composition comprising at least one plant nutrient selected from nitrogen, phosphorus, potassium, sulfur, calcium and magnesium. Compositions of the present invention which further comprise at least one plant nutrient can be in the form of liquids or solids. Of note are solid formulations in the form of granules, small sticks or tablets. Solid formulations comprising a fertilizer composition can be prepared by mixing the compound or composition of the present invention with the fertilizer composition together with formulating ingredients and then preparing the formulation by methods such as granulation or extrusion. Alternatively solid formulations can be prepared by spraying a solution or suspension of a compound or composition of the present invention in a volatile solvent onto a previous prepared fertilizer composition in the form of dimensionally stable mixtures, e.g., granules, small sticks or tablets, and then evaporating the solvent.
Nonagronomic uses refer to invertebrate pest control in the areas other than fields of crop plants. Nonagronomic uses of the present compounds and compositions include control of invertebrate pests in stored grains, beans and other foodstuffs, and in textiles such as clothing and carpets. Nonagronomic uses of the present compounds and compositions also include invertebrate pest control in ornamental plants, forests, in yards, along roadsides and railroad rights of way, and on turf such as lawns, golf courses and pastures. Nonagronomic uses of the present compounds and compositions also include invertebrate pest control in houses and other buildings which may be occupied by humans and/or companion, farm, ranch, zoo or other animals. Nonagronomic uses of the present compounds and compositions also include the control of pests such as termites that can damage wood or other structural materials used in buildings.
Examples of agronomic or nonagronomic invertebrate pests include eggs, larvae and adults of the order Lepidoptera, such as armyworms, cutworms, loopers, and heliothines in the family Noctuidae (e.g., pink stem borer (Sesamia inferens Walker), corn stalk borer (Sesamia nonagrioides Lefebvre), southern armyworm (Spodoptera eridania Cramer), fall armyworm {Spodoptera fugiperda J. E. Smith), beet armyworm {Spodoptera exigua Hϋbner), cotton leafworm {Spodoptera littoralis Boisduval), yellowstriped armyworm {Spodoptera ornithogalli Guenee), black cutworm {Agrotis ipsilon Hufnagel), velvetbean caterpillar {Anticarsia gemmatalis Hϋbner), green fruitworm {Lithophane antennata Walker), cabbage armyworm {Barathra brassicae Linnaeus), soybean looper {Pseudoplusia includens Walker), cabbage looper {Trichoplusia ni Hϋbner), tobacco budworm {Heliothis virescens Fabricius)); borers, casebearers, webworms, coneworms, cabbageworms and skeletonizers from the family Pyralidae (e.g., European corn borer {Ostrinia nubilalis Hϋbner), navel orangeworm {Amyelois transitella Walker), corn root webworm {Crambus caliginosellus Clemens), sod webworms (Pyralidae: Crambinae) such as sod worm {Herpeto gramma licarsisalis Walker), sugarcane stem borer {Chilo infuscatellus Snellen), tomato small borer {Neoleucinodes elegantalis Guenee), green leafroller {Cnaphalocerus medinalis), grape leaffolder {Desmia funeralis Hϋbner), melon worm {Diaphania nitidalis Stoll), cabbage center grub (Helluala hydralis Guenee), yellow stem borer (Scirpophaga incertulas Walker), early shoot borer {Scirpophaga infuscatellus Snellen), white stem borer {Scirpophaga innotata Walker), top shoot borer {Scirpophaga nivella Fabricius), dark- headed rice borer {Chilo polychrysus Meyrick), cabbage cluster caterpillar {Crocidolomia binotalis English)); leafrollers, budworms, seed worms, and fruit worms in the family Tortricidae (e.g., codling moth {Cydia pomonella Linnaeus), grape berry moth {Endopiza viteana Clemens), oriental fruit moth {Grapholita molesta Busck), citrus false codling moth {Cryptophlebia leucotreta Meyrick), citrus borer {Ecdytolopha aurantiana Lima), redbanded leafroller {Argyrotaenia velutinana Walker), obliquebanded leafroller {Choristoneura rosaceana Harris), light brown apple moth {Epiphyas postvittana Walker), European grape berry moth {Eupoecilia ambiguella Hϋbner), apple bud moth {Pandemis pyrusana Kearfott), omnivorous leafroller {Platynota stultana Walsingham), barred fruit-tree tortrix {Pandemis cerasana Hϋbner), apple brown tortrix {Pandemis heparana Denis & Schiffermϋller)); and many other economically important lepidoptera (e.g., diamondback moth {Plutella xylostella Linnaeus), pink bollworm {Pectinophora gossypiella Saunders), gypsy moth {Lymantria dispar Linnaeus), peach fruit borer {Carposina niponensis Walsingham), peach twig borer {Anarsia lineatella Zeller), potato tuberworm {Phthorimaea operculella Zeller), spotted teniform leafminer {Lithocolletis blancardella Fabricius), Asiatic apple leafminer {Lithocolletis ringoniella Matsumura), rice leaffolder {Lerodea eufala Edwards), apple leafminer {Leucoptera scitella Zeller)); eggs, nymphs and adults of the order Blattodea including cockroaches from the families Blattellidae and Blattidae (e.g., oriental cockroach {Blatta orientalis Linnaeus), Asian cockroach {Blatella asahinai Mizukubo), German cockroach {Blattella germanica Linnaeus), brownbanded cockroach {Supella longipalpa Fabricius), American cockroach {Periplaneta americana Linnaeus), brown cockroach {Periplaneta brunnea Burmeister), Madeira cockroach {Leucophaea maderae Fabricius)), smoky brown cockroach {Periplaneta fuliginosa Service), Australian Cockroach {Periplaneta australasiae Fabr.), lobster cockroach {Nauphoeta cinerea Olivier) and smooth cockroach {Symploce pallens Stephens)); eggs, foliar feeding, fruit feeding, root feeding, seed feeding and vesicular tissue feeding larvae and adults of the order Coleoptera including weevils from the families Anthribidae, Bruchidae, and Curculionidae (e.g., boll weevil {Anthonomus grandis Boheman), rice water weevil {Lissorhoptrus oryzophilus Kuschel), granary weevil {Sitophilus granarius Linnaeus), rice weevil {Sitophilus oryzae Linnaeus)), annual bluegrass weevil {Listronotus maculicollis Dietz), bluegrass billbug {Sphenophorus parvulus Gyllenhal), hunting billbug {Sphenophorus venatus vestitus), Denver billbug {Sphenophorus cicatristriatus Fahraeus)); flea beetles, cucumber beetles, rootworms, leaf beetles, potato beetles, and leafminers in the family Chrysomelidae (e.g., Colorado potato beetle {Leptinotarsa decemlineata Say), western corn rootworm {Diabrotica virgifera virgifera LeConte)); chafers and other beetles from the family Scarabaeidae (e.g., Japanese beetle {Popillia japonica Newman), oriental beetle (Anomala orientalis Waterhouse, Exomala orientalis (Waterhouse) Baraud), northern masked chafer (Cyclocephala borealis Arrow), southern masked chafer (Cyclocephala immaculata Olivier or C. lurida Bland), dung beetle and white grub (Aphodius spp.), black turfgrass ataenius (Ataenius spretulus Haldeman), green June beetle (Cotinis nitida Linnaeus), Asiatic garden beetle (Maladera castanea Arrow), May/June beetles (Phyllophaga spp.) and European chafer (Rhizotrogus majalis Razoumowsky)); carpet beetles from the family Dermestidae; wireworms from the family Elateridae; bark beetles from the family Scolytidae and flour beetles from the family Tenebrionidae. In addition, agronomic and nonagronomic pests include: eggs, adults and larvae of the order Dermaptera including earwigs from the family Forfϊculidae (e.g., European earwig (Forficula auricularia Linnaeus), black earwig (Chelisoches mono Fabricius)); eggs, immatures, adults and nymphs of the orders Hemiptera and Homoptera such as, plant bugs from the family Miridae, cicadas from the family Cicadidae, leafhoppers (e.g. Empoasca spp.) from the family Cicadellidae, bed bugs (e.g., Cimex lectularius Linnaeus) from the family Cimicidae, planthoppers from the families Fulgoroidae and Delphacidae, treehoppers from the family Membracidae, psyllids from the family Psyllidae, whiteflies from the family Aleyrodidae, aphids from the family Aphididae, phylloxera from the family Phylloxeridae, mealybugs from the family Pseudococcidae, scales from the families Coccidae, Diaspididae and Margarodidae, lace bugs from the family Tingidae, stink bugs from the family Pentatomidae, chinch bugs (e.g., hairy chinch bug (Blissus leucopterus hirtus Montandon) and southern chinch bug (Blissus insularis Barber)) and other seed bugs from the family Lygaeidae, spittlebugs from the family Cercopidae squash bugs from the family Coreidae, and red bugs and cotton stainers from the family Pyrrhocoridae. Also included are eggs, larvae, nymphs and adults of the order Acari (mites) such as spider mites and red mites in the family Tetranychidae (e.g., European red mite (Panonychus ulmi Koch), two spotted spider mite (Tetranychus urticae Koch), McDaniel mite (Tetranychus mcdanieli McGregor)); flat mites in the family Tenuipalpidae (e.g., citrus flat mite (Brevipalpus lewisi McGregor)); rust and bud mites in the family Eriophyidae and other foliar feeding mites and mites important in human and animal health, i.e. dust mites in the family Epidermoptidae, follicle mites in the family Demodicidae, grain mites in the family Glycyphagidae; ticks in the family Ixodidae, commonly known as hard ticks (e.g., deer tick (Ixodes scapularis Say), Australian paralysis tick (Ixodes holocyclus Neumann), American dog tick (Dermacentor variabilis Say), lone star tick (Amblyomma americanum Linnaeus)) and ticks in the family Argasidae, commonly known as soft ticks (e.g., relapsing fever tick (Ornithodoros turicata), common fowl tick (Argas radiatus)); scab and itch mites in the families Psoroptidae, Pyemotidae, and Sarcoptidae; eggs, adults and immatures of the order Orthoptera including grasshoppers, locusts and crickets (e.g., migratory grasshoppers (e.g., Melanoplus sanguinipes Fabricius, M. differ entialis Thomas), American grasshoppers (e.g., Schistocerca americana Drury), desert locust {Schistocerca gregaria Forskal), migratory locust (Locusta migratoria Linnaeus), bush locust (Zonocerus spp.), house cricket (Acheta domesticus Linnaeus), mole crickets (e.g., tawny mole cricket (Scapteriscus vicinus Scudder) and southern mole cricket (Scapteriscus borellii Giglio-Tos)); eggs, adults and immatures of the order Diptera including leafminers (e.g., Liriomyza spp. such as serpentine vegetable leafminer (Liriomyza sativae Blanchard)), midges, fruit flies (Tephritidae), frit flies (e.g., Oscinella frit Linnaeus), soil maggots, house flies (e.g., Musca domestica Linnaeus), lesser house flies (e.g., Fannia canicularis Linnaeus, F. femoralis Stein), stable flies (e.g., Stomoxys calcitrans Linnaeus), face flies, horn flies, blow flies (e.g., Chrysomya spp., Phormia spp.), and other muscoid fly pests, horse flies (e.g., Tabanus spp.), bot flies (e.g., Gastrophilus spp., Oestrus spp.), cattle grubs (e.g., Hypoderma spp.), deer flies (e.g., Chrysops spp.), keds (e.g., Melophagus ovinus Linnaeus) and other Brachycera, mosquitoes (e.g., Aedes spp., Anopheles spp., Culex spp.), black flies (e.g., Prosimulium spp., Simulium spp.), biting midges, sand flies, sciarids, and other Nematocera; eggs, adults and immatures of the order Thysanoptera including onion thrips (Thrips tabaci Lindeman), flower thrips (Frankliniella spp.), and other foliar feeding thrips; insect pests of the order Hymenoptera including ants of the Family Formicidae including the Florida carpenter ant (Camponotus floridanus Buckley), red carpenter ant (Camponotus ferrugineus Fabricius), black carpenter ant (Camponotus pennsylvanicus De Geer), white-footed ant (Technomyrmex albipes fr. Smith), big headed ants (Pheidole sp.), ghost ant (Tapinoma melanocephalum Fabricius); Pharaoh ant (Monomorium pharaonis Linnaeus), little fire ant (Wasmannia auropunctata Roger), fire ant (Solenopsis geminata Fabricius), red imported fire ant (Solenopsis invicta Buren), Argentine ant (Iridomyrmex humilis Mayr), crazy ant (Paratrechina longicornis Latreille), pavement ant (Tetramorium caespitum Linnaeus), cornfield ant (Lasius alienus Fόrster) and odorous house ant (Tapinoma sessile Say). Other Hymenoptera including bees (including carpenter bees), hornets, yellow jackets, wasps, and sawflies (Neodiprion spp.; Cephus spp.); insect pests of the order Isoptera including termites in the Termitidae (e.g., Macrotermes sp., Odontotermes obesus Rambur), Kalotermitidae (e.g., Cryptotermes sp.), and Rhinotermitidae (e.g., Reticulitermes sp., Coptotermes sp., Heterotermes tenuis Hagen) families, the eastern subterranean termite (Reticulitermes flavipes Kollar), western subterranean termite (Reticulitermes hesperus Banks), Formosan subterranean termite (Coptotermes formosanus Shiraki), West Indian drywood termite (Incisitermes immigrans Snyder), powder post termite (Cryptotermes brevis Walker), drywood termite (Incisitermes snyderi Light), southeastern subterranean termite (Reticulitermes virginicus Banks), western drywood termite (Incisitermes minor Hagen), arboreal termites such as Nasutitermes sp. and other termites of economic importance; insect pests of the order Thysanura such as silverfish (Lepisma saccharina Linnaeus) and firebrat (Thermobia domestica Packard); insect pests of the order Mallophaga and including the head louse (Pediculus humanus capitis De Geer), body louse (Pediculus humanus Linnaeus), chicken body louse (Menacanthus stramineus Nitszch), dog biting louse (Trichodectes canis De Geer), fluff louse (Goniocotes gallinae De Geer), sheep body louse (Bovicola ovis Schrank), short-nosed cattle louse (Haematopinus eurysternus Nitzsch), long-nosed cattle louse (Linognathus vituli Linnaeus) and other sucking and chewing parasitic lice that attack man and animals; insect pests of the order Siphonoptera including the oriental rat flea (Xenopsylla cheopis Rothschild), cat flea (Ctenocephalides felis Bouche), dog flea (Ctenocephalides canis Curtis), hen flea (Ceratophyllus gallinae Schrank), sticktight flea (Echidnophaga gallinacea Westwood), human flea (Pulex irritans Linnaeus) and other fleas afflicting mammals and birds. Additional arthropod pests covered include: spiders in the order Araneae such as the brown recluse spider (Loxosceles reclusa Gertsch & Mulaik) and the black widow spider (Latrodectus mactans Fabricius), and centipedes in the order Scutigeromorpha such as the house centipede (Scutigera coleoptrata Linnaeus). Compounds of the present invention also have activity on members of the Classes Nematoda, Cestoda, Trematoda, and Acanthocephala including economically important members of the orders Strongylida, Ascaridida, Oxyurida, Rhabditida, Spirurida, and Enoplida such as but not limited to economically important agricultural pests (i.e. root knot nematodes in the genus Meloidogyne, lesion nematodes in the genus Pratylenchus, stubby root nematodes in the genus Trichodorus, etc.) and animal and human health pests (i.e. all economically important flukes, tapeworms, and roundworms, such as Strongylus vulgaris in horses, Toxocara canis in dogs, Haemonchus contortus in sheep, Dirofilaria immitis Leidy in dogs, Anoplocephala perfoliata in horses, Fasciola hepatica Linnaeus in ruminants, etc.).
Compounds of the invention show particularly high activity against pests in the order Homoptera including: Acyrthosiphon pisum Harris (pea aphid), Aphis craccivora Koch (cowpea aphid), Aphis fabae Scopoli (black bean aphid), Aphis gossypii Glover (cotton aphid, melon aphid), Aphis pomi De Geer (apple aphid), Aphis spiraecola Patch (spirea aphid), Aulacorthum solani Kaltenbach (foxglove aphid), Chaetosiphon fragaefolii Cockerell (strawberry aphid), Diuraphis noxia Kurdjumov/Mordvilko (Russian wheat aphid), Dysaphis plantaginea Paaserini (rosy apple aphid), Eriosoma lanigerum Hausmann (woolly apple aphid), Hyalopterus pruni Geoffroy (mealy plum aphid), Lipaphis erysimi Kaltenbach (turnip aphid), Metopolophium dirrhodum Walker (cereal aphid), Macrosiphum euphorbiae Thomas (potato aphid), Myzus persicae Sulzer (peach-potato aphid, green peach aphid), Nasonovia ribisnigri Mosley (lettuce aphid), Pemphigus spp. (root aphids and gall aphids), Rhopalosiphum maidis Fitch (corn leaf aphid), Rhopalosiphum padi Linnaeus (bird cherry-oat 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 (pecan phylloxera); Bemisia tabaci Gennadius (tobacco whitefly, sweetpotato whitefly), Bemisia argentifolii Bellows & Perring (silverleaf whitefly), Dialeurodes citri Ashmead (citrus whitefly) and Tήaleurodes vaporariorum Westwood (greenhouse whitefly); Empoasca fabae Harris (potato leafhopper), Laodelphax striatellus Fallen (smaller brown planthopper), Macrolestes quadrilineatus Forbes (aster leafhopper), Nephotettix cinticeps Uhler (green leafhopper), Nephotettix nigropictus Stal (rice leafhopper), Nilaparvata lugens Stal (brown planthopper), Peregrinus maidis Ashmead (corn planthopper), Sogatella furcifera Horvath (white-backed planthopper), Sogatodes orizicola Muir (rice delphacid), Typhlocyba pomaria McAtee white apple leafhopper, Erythroneoura spp. (grape leafhoppers); Magicidada septendecim Linnaeus (periodical cicada); Icerya purchasi Maskell (cottony cushion scale), Quadraspidiotus perniciosus Comstock (San Jose scale); Planococcus citri Risso (citrus mealybug); Pseudococcus spp. (other mealybug complex); Cacopsylla pyricola Foerster (pear psylla), Trioza diospyri Ashmead (persimmon psylla). Compounds of the invention also have activity on members from Lepidoptera (e.g.,
Alabama argillacea Hϋbner (cotton leaf worm), Archips argyrospila Walker (fruit tree leaf roller), A. rosana Linnaeus (European leaf roller) and other Archips species, Chilo suppressalis Walker (rice stem borer), Cnaphalocrosis medinalis Guenee (rice leaf roller), Crambus caliginosellus Clemens (corn root webworm), Crambus teterrellus Zincken (bluegrass webworm), Cydia pomonella Linnaeus (codling moth), Earias insulana Boisduval (spiny bollworm), Earias vittella Fabricius (spotted bollworm), Helicoverpa armigera Hϋbner (American bollworm), Helicoverpa zea Boddie (corn earworm), Heliothis virescens Fabricius (tobacco budworm), Herpetogramma licarsisalis Walker (sod webworm), Lobesia botrana Denis & Schiffermϋller (grape berry moth), Pectinophora gossypiella Saunders (pink bollworm), Phyllocnistis citrella Stainton (citrus leafminer), Pieris brassicae Linnaeus (large white butterfly), Pieris rapae Linnaeus (small white butterfly), Plutella xylostella Linnaeus (diamondback moth), Spodoptera exigua Hϋbner (beet armyworm), Spodoptera litura Fabricius (tobacco cutworm, cluster caterpillar), Spodoptera frugiperda J. E. Smith (fall armyworm), Trichoplusia ni Hϋbner (cabbage looper) and Tuta absoluta Meyrick (tomato leafminer)).
Compounds of this invention also have activity on members from the order Hemiptera including: Acrosternum hilare Say (green stink bug), Anasa tristis De Geer (squash bug), Blissus leucopterus leucopterus Say (chinch bug), Cimex lectularius Linnaeus (bed bug) Corythuca gossypii Fabricius (cotton lace bug), Cyrtopeltis modesta Distant (tomato bug), Dysdercus suturellus Herrich- S chaffer (cotton stainer), Euchistus servus Say (brown stink bug), Euchistus variolarius Palisot de Beauvois (one-spotted stink bug), Graptosthetus spp. (complex of seed bugs), Leptoglossus corculus Say (leaf-footed pine seed bug), Lygus lineolaris Palisot de Beauvois (tarnished plant bug), Nezara viridula Linnaeus (southern green stink bug), Oebalus pugnax Fabricius (rice stink bug), Oncopeltus fasciatus Dallas (large milkweed bug), Pseudatomoscelis seriatus Reuter (cotton fleahopper). Other insect orders controlled by compounds of the invention include Thysanoptera (e.g., Frankliniella occidentalis Pergande (western flower thrips), Scirthothrips citri Moulton (citrus thrips), Sericothrips variabilis Beach (soybean thrips), and Thrips tabaci Lindeman (onion thrips); and the order Coleoptera (e.g., Leptinotarsa decemlineata Say (Colorado potato beetle), Epilachna varivestis Mulsant (Mexican bean beetle) and wireworms of the genera Agriotes, Athous or Limonius).
Note that some contemporary classification systems place Homoptera as a suborder within the order Hemiptera.
Of note is use of compounds of this invention for controlling potato leafhopper (Empoasca fabae). Of note is use of compounds of this invention for controlling corn planthopper (Peregrinus maidis). Of note is use of compounds of this invention for controlling cotton melon aphid {Aphis gossypiϊ). Of note is use of compounds of this invention for controlling green peach aphid (Myzus persicae).
Of note is the use of compounds of this invention for controlling imidacloprid-resistant invertebrate pests. Of particular note is use of compounds of this invention for controlling imidacloprid-resistant rice brown planthopper (Nilaparvata lugens). Of particular note is use of compounds of this invention for controlling imidacloprid-resistant sweetpotato whitefly (Bemisia tabaci).
Compounds of this invention can also be mixed with one or more other biologically active compounds or agents including insecticides, fungicides, nematocides, 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, virus or fungi to form a multi-component pesticide giving an even broader spectrum of agronomic and nonagronomic utility. Thus the present invention also pertains to a composition comprising a biologically effective amount of a compound of Formula 1, at least one additional component selected from the group consisting of surfactants, solid diluents and liquid diluents, and at least one additional biologically active compound or agent. For mixtures of the present invention, the other biologically active compounds or agents can be formulated together with the present compounds, including the compounds of Formula 1, to form a premix, or the other biologically active compounds or agents can be formulated separately from the present compounds, including the compounds of Formula 1, and the two formulations combined together before application (e.g., in a spray tank) or, alternatively, applied in succession.
Examples of such biologically active compounds or agents with which compounds of this invention can be formulated are insecticides such as abamectin, acephate, acequinocyl, acetamiprid, acrinathrin, amidoflumet, amitraz, avermectin, azadirachtin, azinphos-methyl, bifenthrin, bifenazate, bistrifluron, borate, buprofezin, cadusafos, carbaryl, carbofuran, cartap, carzol, chlorantraniliprole, chlorfenapyr, chlorfluazuron, chlorpyrifos, chlorpyrifos- methyl, chromafenozide, clofentezin, clothianidin, cyantraniliprole, cyflumetofen, cyfluthrin, beta-cyfluthrin, cyhalothrin, gamma-cyhalothrin, lambda-cyhalothrin, cypermethrin, alpha- cypermethrin, zeta-cypermethrin, cyromazine, deltamethrin, diafenthiuron, diazinon, dieldrin, diflubenzuron, dimefluthrin, dimehypo, dimethoate, dinotefuran, diofenolan, emamectin, endosulfan, esfenvalerate, ethiprole, etofenprox, etoxazole, fenbutatin oxide, fenothiocarb, fenoxycarb, fenpropathrin, fenvalerate, fϊpronil, flonicamid, flubendiamide, flucythrinate, flufenerim, flufenoxuron, fluvalinate, tau-fluvalinate, fonophos, formetanate, fosthiazate, halofenozide, hexaflumuron, hexythiazox, hydramethylnon, imidacloprid, indoxacarb, insecticidal soaps, isofenphos, lufenuron, malathion, metaflumizone, metaldehyde, methamidophos, methidathion, methiodicarb, methomyl, methoprene, methoxychlor, metofluthrin, monocrotophos, methoxyfenozide, nitenpyram, nithiazine, novaluron, noviflumuron, oxamyl, parathion, parathion-methyl, permethrin, phorate, phosalone, phosmet, phosphamidon, pirimicarb, profenofos, profluthrin, propargite, protrifenbute, pymetrozine, pyrafluprole, pyrethrin, pyridaben, pyridalyl, pyrifluquinazon, pyriprole, pyriproxyfen, rotenone, ryanodine, spinetoram, spinosad, spirodiclofen, spiromesifen, spirotetramat, sulprofos, tebufenozide, tebufenpyrad, teflubenzuron, tefluthrin, terbufos, tetrachlorvinphos, tetramethrin, thiacloprid, thiamethoxam, thiodicarb, thiosultap- sodium, tolfenpyrad, tralomethrin, triazamate, trichlorfon, triflumuron, Bacillus thuringiensis delta-endotoxins, entomopathogenic bacteria, entomopathogenic viruses and entomopathogenic fungi.
Of note are insecticides such as abamectin, acetamiprid, acrinathrin, amitraz, avermectin, azadirachtin, bifenthrin, buprofezin, cadusafos, carbaryl, cartap, chlorantraniliprole, chlorfenapyr, chlorpyrifos, clothianidin, cyantraniliprole, cyfluthrin, beta-cyfluthrin, cyhalothrin, gamma-cyhalothrin, lambda-cyhalothrin, cypermethrin, alpha- cypermethrin, zeta-cypermethrin, cyromazine, deltamethrin, dieldrin, dinotefuran, diofenolan, emamectin, endosulfan, esfenvalerate, ethiprole, etofenprox, etoxazole, fenothiocarb, fenoxycarb, fenvalerate, fϊpronil, flonicamid, flubendiamide, flufenoxuron, fluvalinate, formetanate, fosthiazate, hexaflumuron, hydramethylnon, imidacloprid, indoxacarb, lufenuron, metaflumizone, methiodicarb, methomyl, methoprene, methoxyfenozide, nitenpyram, nithiazine, novaluron, oxamyl, pymetrozine, pyrethrin, pyridaben, pyridalyl, pyriproxyfen, ryanodine, spinetoram, spinosad, spirodiclofen, spiromesifen, spirotetramat, tebufenozide, tetramethrin, thiacloprid, thiamethoxam, thiodicarb, thiosultap-sodium, tralomethrin, triazamate, triflumuron, Bacillus thuringiensis delta-endotoxins, all strains of Bacillus thuringiensis and all strains of Nucleo polyhydrosis viruses. One embodiment of biological agents for mixing with compounds of this invention include entomopathogenic bacteria such as Bacillus thuringiensis, and the encapsulated delta-endotoxins of Bacillus thuringiensis such as MVP® and MVPII® bioinsecticides prepared by the CellCap® process (CellCap®, MVP® and MVPII® are trademarks of Mycogen Corporation, Indianapolis, Indiana, USA); entomopathogenic fungi such as green muscardine fungus; and entomopathogenic (both naturally occurring and genetically modified) viruses including baculovirus, nucleopolyhedro virus (NPV) such as Helicoverpa zea nucleopolyhedrovirus (HzNPV), Anagrapha falcifera nucleopolyhedrovirus (AfNPV); and granulosis virus (GV) such as Cydia pomonella granulosis virus (CpGV). Of particular note is such a combination where the other invertebrate pest control active ingredient belongs to a different chemical class or has a different site of action than the compound of Formula 1. In certain instances, a combination with at least one other invertebrate pest control active ingredient having a similar spectrum of control but a different site of action will be particularly advantageous for resistance management. Thus, a composition of the present invention can further comprise 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. These additional biologically active compounds or agents include, but are not limited to, sodium channel modulators such as bifenthrin, cypermethrin, cyhalothrin, lambda-cyhalothrin, cyfluthrin, beta-cyfluthrin, deltamethrin, dimefluthrin, esfenvalerate, fenvalerate, indoxacarb, metofluthrin, profluthrin, pyrethrin and tralomethrin; cholinesterase inhibitors such as chlorpyrifos, methomyl, oxamyl, thiodicarb and triazamate; neonicotinoids such as acetamiprid, clothianidin, dinotefuran, imidacloprid, nitenpyram, nithiazine, thiacloprid and thiamethoxam; insecticidal macrocyclic lactones such as spinetoram, spinosad, abamectin, avermectin and emamectin; GABA (γ-aminobutyric acid)-gated chloride channel antagonists such as avermectin or blockers such as ethiprole and fipronil; chitin synthesis inhibitors such as buprofezin, cyromazine, flufenoxuron, hexaflumuron, lufenuron, novaluron, noviflumuron and triflumuron; juvenile hormone mimics such as diofenolan, fenoxycarb, methoprene and pyriproxyfen; octopamine receptor ligands such as amitraz; molting inhibitors and ecdysone agonists such as azadirachtin, methoxyfenozide and tebufenozide; ryanodine receptor ligands such as ryanodine, anthranilic diamides such as chlorantraniliprole, cyantraniliprole and flubendiamide; nereistoxin analogs such as cartap; mitochondrial electron transport inhibitors such as chlorfenapyr, hydramethylnon and pyridaben; lipid biosynthesis inhibitors such as spirodiclofen and spiromesifen; cyclodiene insecticides such as dieldrin or endosulfan; pyrethroids; carbamates; insecticidal ureas; and biological agents including nucleopolyhedro viruses (NPV), members of Bacillus thuringiensis, encapsulated delta- endotoxins of Bacillus thuringiensis, and other naturally occurring or genetically modified insecticidal viruses. Further examples of biologically active compounds or agents with which compounds of this invention can be formulated are: fungicides such as acibenzolar, aldimorph, amisulbrom, azaconazole, azoxystrobin, benalaxyl, benomyl, benthiavalicarb, benthiavalicarb-isopropyl, binomial, biphenyl, bitertanol, blasticidin-S, Bordeaux mixture (Tribasic copper sulfate), boscalid/nicobifen, bromuconazole, bupirimate, buthiobate, carboxin, carpropamid, captafol, captan, carbendazim, chloroneb, chlorothalonil, chlozolinate, clotrimazole, copper oxychloride, copper salts such as copper sulfate and copper hydroxide, cyazofamid, cyflunamid, cymoxanil, cyproconazole, cyprodinil, dichlofluanid, diclocymet, diclomezine, dicloran, diethofencarb, difenoconazole, dimethomorph, dimoxystrobin, diniconazole, diniconazole-M, dinocap, discostrobin, dithianon, dodemorph, dodine, econazole, etaconazole, edifenphos, epoxiconazole, ethaboxam, ethirimol, ethridiazole, famoxadone, fenamidone, fenarimol, fenbuconazole, fencaramid, fenfuram, fenhexamide, fenoxanil, fenpiclonil, fenpropidin, fenpropimorph, fentin acetate, fentin hydroxide, ferbam, ferfurazoate, ferimzone, fluazinam, fludioxonil, flumetover, fluopicolide, fluoxastrobin, fluquinconazole, fluquinconazole, flusilazole, flusulfamide, flutolanil, flutriafol, folpet, fosetyl-aluminum, fuberidazole, furalaxyl, furametapyr, hexaconazole, hymexazole, guazatine, imazalil, imibenconazole, iminoctadine, iodicarb, ipconazole, iprobenfos, iprodione, iprovalicarb, isoconazole, isoprothiolane, isopyrazam, kasugamycin, kresoxim-methyl, mancozeb, mandipropamid, maneb, mapanipyrin, mefenoxam, mepronil, metalaxyl, metconazole, methasulfocarb, metiram, metominostrobin/fenominostrobin, mepanipyrim, metrafenone, miconazole, myclobutanil, neo-asozin (ferric methanearsonate), nuarimol, octhilinone, ofurace, orysastrobin, oxadixyl, oxolinic acid, oxpoconazole, oxycarboxin, paclobutrazol, penconazole, pencycuron, penthiopyrad, perfurazoate, phosphonic acid, phthalide, picobenzamid, picoxystrobin, polyoxin, probenazole, prochloraz, procymidone, propamocarb, propamocarb-hydrochloride, propiconazole, propineb, proquinazid, prothioconazole, pyraclostrobin, pryazophos, pyrifenox, pyrimethanil, pyrifenox, pyrolnitrine, pyroquilon, quinconazole, quinoxyfen, quintozene, silthiofam, simeconazole, spiroxamine, streptomycin, sulfur, tebuconazole, techrazene, tecloftalam, tecnazene, tetraconazole, thiabendazole, thifluzamide, thiophanate, thiophanate-methyl, thiram, tiadinil, tolclofos-methyl, tolyfluanid, triadimefon, triadimenol, triarimol, triazoxide, tridemorph, trimoprhamide tricyclazole, trifloxystrobin, triforine, triticonazole, uniconazole, validamycin, vinclozolin, zineb, ziram, and zoxamide; nematocides such as aldicarb, imicyafos, oxamyl and fenamiphos; bactericides such as streptomycin; acaricides such as amitraz, chinomethionat, chlorobenzilate, cyhexatin, dicofol, dienochlor, etoxazole, fenazaquin, fenbutatin oxide, fenpropathrin, fenpyroximate, hexythiazox, propargite, pyridaben and tebufenpyrad.
In certain instances, combinations of a compound of this invention with other biologically active (particularly invertebrate pest control) compounds or agents (i.e. active ingredients) can result in a greater-than-additive (i.e. synergistic) effect. Reducing the quantity of active ingredients released in the environment while ensuring effective pest control is always desirable. When synergism of invertebrate pest control active ingredients occurs at application rates giving agronomically satisfactory levels of invertebrate pest control, such combinations can be advantageous for reducing crop production cost and decreasing environmental load.
Compounds of this invention and compositions thereof can be applied to plants genetically transformed to express proteins toxic to invertebrate pests (such as Bacillus thuringiensis delta-endotoxins). Such an application may provide a broader spectrum of plant protection and be advantageous for resistance management. The effect of the exogenously applied invertebrate pest control compounds of this invention may be synergistic with the expressed toxin proteins.
General references for these agricultural protectants (i.e. insecticides, fungicides, nematocides, acaricides, herbicides and biological agents) include The Pesticide Manual, 13th Edition, C. D. S. Tomlin, Ed., British Crop Protection Council, Farnham, Surrey, U.K., 2003 and The BioPesticide Manual, 2nd Edition, L. G. Copping, Ed., British Crop Protection Council, Farnham, Surrey, U.K., 2001.
For embodiments where one or more of these various mixing partners are used, the weight ratio of these various mixing partners (in total) to the compound of Formula 1 is typically between about 1 :3000 and about 3000:1. Of note are weight ratios between about 1 :300 and about 300:1 (for example ratios between about 1 :30 and about 30:1). One skilled in the art can easily determine through simple experimentation the biologically effective amounts of active ingredients necessary for the desired spectrum of biological activity. It will be evident that including these additional components can expand the spectrum of invertebrate pests controlled beyond the spectrum controlled by the compound of Formula 1 alone.
Table A lists specific combinations of a compound of Formula 1 with other invertebrate pest control agents illustrative of the mixtures, compositions and methods of the present invention and includes additional embodiments of weight ratio ranges for application rates. The first column of Table A lists the specific invertebrate control agents (e.g., "Abamectin" in the first line). The second column of Table A lists the mode of action (if known) or chemical class of the invertebrate pest control agents. The third column of Table A lists embodiment(s) of ranges of weight ratios for rates at which the invertebrate pest control agent can be applied relative to a compound of Formula 1 (e.g., "50:1 to 1 :50" of abamectin relative to a compound of Formula 1 by weight). Thus, for example, the first line of Table A specifically discloses the combination of a compound of Formula 1 with abamectin can be applied in a weight ratio between 50:1 to 1 :50. The remaining lines of Table A are to be construed similarly. Table A
Figure imgf000096_0001
Figure imgf000097_0001
Figure imgf000098_0001
Of note is the composition of the present invention wherein the at least one additional biologically active compound or agent is selected from the Invertebrate Pest Control Agents listed in Table A above.
The weight ratios of a compound, including a compound of Formula 1 or a salt thereof, to the additional invertebrate pest control agent typically are between 1000:1 and 1 :1000, with one embodiment being between 500:1 and 1 :500, another embodiment being between 250:1 and 1 :200 and another embodiment being between 100:1 and 1 :50.
Listed below in Table B are embodiments of specific compositions comprising a compound of Formula 1 (compound numbers refer to compounds in Index Table A) and an additional invertebrate pest control agent.
Table B
Mixture Comp. and Invertebrate Pest Control Mixture Comp. and Invertebrate Pest Control
No. No. Agent No. No. Agent
A-I 22 and Abamectin B-I 26 and Abamectin
A-2 22 and Acetamiprid B-2 26 and Acetamiprid
A-3 22 and Amitraz B-3 26 and Amitraz
A-4 22 and Avermectin B-4 26 and Avermectin
A-5 22 and Azadirachtin B-5 26 and Azadirachtin
A-6 22 and Beta-cyfluthrin B-6 26 and Beta-cyfluthrin
A-7 22 and Bifenthrin B-7 26 and Bifenthrin
A-8 22 and Buprofezin B-8 26 and Buprofezin
A-9 22 and Cartap B-9 26 and Cartap
A-10 22 and Chlorantraniliprole B-10 26 and Chlorantraniliprole
A-I l 22 and Chlorfenapyr B-I l 26 and Chlorfenapyr
A-12 22 and Chlorpyrifos B-12 26 and Chlorpyrifos
A-13 22 and Clothianidin B-13 26 and Clothianidin
A- 14 22 and Cyfluthrin B-14 26 and Cyfluthrin
A-15 22 and Cyhalothrin B-15 26 and Cyhalothrin
A-16 22 and Cypermethrin B-16 26 and Cypermethrin
A-17 22 and Cyromazine B-17 26 and Cyromazine
A-18 22 and Deltamethrin B-18 26 and Deltamethrin
A- 19 22 and Dieldrin B-19 26 and Dieldrin
A-20 22 and Dinotefuran B-20 26 and Dinotefuran
A-21 22 and Diofenolan B-21 26 and Diofenolan Mixture Comp. and Invertebrate Pest Control Mixture Comp. and Invertebrate Pest Control
No. No. Agent No. No. Agent
A-22 22 and Emamectin B-22 26 and Emamectin
A-23 22 and Endosulfan B-23 26 and Endosulfan
A-24 22 and Esfenvalerate B-24 26 and Esfenvalerate
A-25 22 and Ethiprole B-25 26 and Ethiprole
A-26 22 and Fenothiocarb B-26 26 and Fenothiocarb
A-27 22 and Fenoxycarb B-27 26 and Fenoxycarb
A-28 22 and Fenvalerate B-28 26 and Fenvalerate
A-29 22 and Fipronil B-29 26 and Fipronil
A-30 22 and Flonicamid B-30 26 and Flonicamid
A-31 22 and Flubendiamide B-31 26 and Flubendiamide
A-32 22 and Flufenoxuron B-32 26 and Flufenoxuron
A-33 22 and Hexaflumuron B-33 26 and Hexaflumuron
A-34 22 and Hydramethylnon B-34 26 and Hydramethylnon
A-35 22 and Imidacloprid B-35 26 and Imidacloprid
A-36 22 and Indoxacarb B-36 26 and Indoxacarb
A-37 22 and Lambda-cyhalothrin B-37 26 and Lambda-cyhalothrin
A-38 22 and Lufenuron B-38 26 and Lufenuron
A-39 22 and Metaflumizone B-39 26 and Metaflumizone
A-40 22 and Methomyl B-40 26 and Methomyl
A-41 22 and Methoprene B-41 26 and Methoprene
A-42 22 and Methoxyfenozide B-42 26 and Methoxyfenozide
A-43 22 and Nitenpyram B-43 26 and Nitenpyram
A-44 22 and Nithiazine B-44 26 and Nithiazine
A-45 22 and Novaluron B-45 26 and Novaluron
A-46 22 and Oxamyl B-46 26 and Oxamyl
A-47 22 and Pymetrozine B-47 26 and Pymetrozine
A-48 22 and Pyrethrin B-48 26 and Pyrethrin
A-49 22 and Pyridaben B-49 26 and Pyridaben
A-50 22 and Pyridalyl B-50 26 and Pyridalyl
A-51 22 and Pyriproxyfen B-51 26 and Pyriproxyfen
A-52 22 and Ryanodine B-52 26 and Ryanodine
A-53 22 and Spinetoram B-53 26 and Spinetoram
A-54 22 and Spinosad B-54 26 and Spinosad
A-55 22 and Spirodiclofen B-55 26 and Spirodiclofen
A-56 22 and Spiromesifen B-56 26 and Spiromesifen
A-57 22 and Tebufenozide B-57 26 and Tebufenozide Mixture Comp. and Invertebrate Pest Control Mixture Comp. and Invertebrate Pest Control
No. No. Agent No. No. Agent
A-58 22 and Thiacloprid B-58 26 and Thiacloprid
A-59 22 and Thiamethoxam B-59 26 and Thiamethoxam
A-60 22 and Thiodicarb B-60 26 and Thiodicarb
A-61 22 and Thiosultap-sodium B-61 26 and Thiosultap-sodium
A-62 22 and Tralomethrin B-62 26 and Tralomethrin
A-63 22 and Triazamate B-63 26 and Triazamate
A-64 22 and Triflumuron B-64 26 and Triflumuron
A-65 22 and Bacillus thuringiensis B-65 26 and Bacillus thuringiensis
A-66 22 and Bacillus thuringiensis B-66 26 and Bacillus thuringiensis delta-endotoxin delta-endotoxin
A-67 22 and NPV (e.g., Gemstar) B-67 26 and NPV (e.g., Gemstar)
A-68 22 and Cyantraniliprole B-68 26 and Cyantraniliprole
C-I 31 and Abamectin D-I 61 and Abamectin
C-2 31 and Acetamiprid D-2 61 and Acetamiprid
C-3 31 and Amitraz D-3 61 and Amitraz
C-4 31 and Avermectin D-4 61 and Avermectin
C-5 31 and Azadirachtin D-5 61 and Azadirachtin
C-6 31 and Beta-cyfluthrin D-6 61 and Beta-cyfluthrin
C-7 31 and Bifenthrin D-7 61 and Bifenthrin
C-8 31 and Buprofezin D-8 61 and Buprofezin
C-9 31 and Cartap D-9 61 and Cartap
C-IO 31 and Chlorantraniliprole D-IO 61 and Chlorantraniliprole
C-I l 31 and Chlorfenapyr D-I l 61 and Chlorfenapyr
C-12 31 and Chlorpyrifos D-12 61 and Chlorpyrifos
C-13 31 and Clothianidin D-13 61 and Clothianidin
C-14 31 and Cyfluthrin D-14 61 and Cyfluthrin
C-15 31 and Cyhalothrin D-15 61 and Cyhalothrin
C-16 31 and Cypermethrin D-16 61 and Cypermethrin
C-17 31 and Cyromazine D-17 61 and Cyromazine
C-18 31 and Deltamethrin D-18 61 and Deltamethrin
C-19 31 and Dieldrin D-19 61 and Dieldrin
C-20 31 and Dinotefuran D-20 61 and Dinotefuran
C-21 31 and Diofenolan D-21 61 and Diofenolan
C-22 31 and Emamectin D-22 61 and Emamectin
C-23 31 and Endosulfan D-23 61 and Endosulfan
C-24 31 and Esfenvalerate D-24 61 and Esfenvalerate Mixture Comp. and Invertebrate Pest Control Mixture Comp. and Invertebrate Pest Control
No. No. Agent No. No. Agent
C-25 31 and Ethiprole D-25 61 and Ethiprole
C-26 31 and Fenothiocarb D-26 61 and Fenothiocarb
C-27 31 and Fenoxycarb D-27 61 and Fenoxycarb
C-28 31 and Fenvalerate D-28 61 and Fenvalerate
C-29 31 and Fipronil D-29 61 and Fipronil
C-30 31 and Flonicamid D-30 61 and Flonicamid
C-31 31 and Flubendiamide D-31 61 and Flubendiamide
C-32 31 and Flufenoxuron D-32 61 and Flufenoxuron
C-33 31 and Hexaflumuron D-33 61 and Hexaflumuron
C-34 31 and Hydramethylnon D-34 61 and Hydramethylnon
C-35 31 and Imidacloprid D-35 61 and Imidacloprid
C-36 31 and Indoxacarb D-36 61 and Indoxacarb
C-37 31 and Lambda-cyhalothrin D-37 61 and Lambda-cyhalothrin
C-38 31 and Lufenuron D-38 61 and Lufenuron
C-39 31 and Metaflumizone D-39 61 and Metaflumizone
C-40 31 and Methomyl D-40 61 and Methomyl
C-41 31 and Methoprene D-41 61 and Methoprene
C-42 31 and Methoxyfenozide D-42 61 and Methoxyfenozide
C-43 31 and Nitenpyram D-43 61 and Nitenpyram
C-44 31 and Nithiazine D-44 61 and Nithiazine
C-45 31 and Novaluron D-45 61 and Novaluron
C-46 31 and Oxamyl D-46 61 and Oxamyl
C-47 31 and Pymetrozine D-47 61 and Pymetrozine
C-48 31 and Pyrethrin D-48 61 and Pyrethrin
C-49 31 and Pyridaben D-49 61 and Pyridaben
C-50 31 and Pyridalyl D-50 61 and Pyridalyl
C-51 31 and Pyriproxyfen D-51 61 and Pyriproxyfen
C-52 31 and Ryanodine D-52 61 and Ryanodine
C-53 31 and Spinetoram D-53 61 and Spinetoram
C-54 31 and Spinosad D-54 61 and Spinosad
C-55 31 and Spirodiclofen D-55 61 and Spirodiclofen
C-56 31 and Spiromesifen D-56 61 and Spiromesifen
C-57 31 and Tebufenozide D-57 61 and Tebufenozide
C-58 31 and Thiacloprid D-58 61 and Thiacloprid
C-59 31 and Thiamethoxam D-59 61 and Thiamethoxam
C-60 31 and Thiodicarb D-60 61 and Thiodicarb Mixture Comp. and Invertebrate Pest Control Mixture Comp. and Invertebrate Pest Control
No. No. Agent No. No. Agent
C-61 31 and Thiosultap-sodium D-61 61 and Thiosultap-sodium
C-62 31 and Tralomethrin D-62 61 and Tralomethrin
C-63 31 and Triazamate D-63 61 and Triazamate
C-64 31 and Triflumuron D-64 61 and Triflumuron
C-65 31 and Bacillus thuringiensis D-65 61 and Bacillus thuringiensis
C-66 31 and Bacillus thuringiensis D-66 61 and Bacillus thuringiensis delta-endotoxin delta-endotoxin
C-67 31 and NPV (e.g., Gemstar) D-67 61 and NPV (e.g., Gemstar)
C-68 31 and Cyantraniliprole D-68 61 and Cyantraniliprole
The specific mixtures listed in Table B typically combine a compound of Formula 1 with the other invertebrate pest agent in the ratios specified in Table A.
Invertebrate pests are controlled in agronomic and nonagronomic applications by applying one or more compounds of this invention, typically in the form of a composition, in a biologically effective amount, to the environment of the pests, including the agronomic and/or nonagronomic locus of infestation, to the area to be protected, or directly on the pests to be controlled.
Thus the present invention comprises a method for controlling an invertebrate pest in agronomic and/or nonagronomic applications, comprising contacting the invertebrate pest or its environment with a biologically effective amount of one or more of the compounds of the invention, or with a composition comprising at least one such compound or 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 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 granule as the compound of the invention or on granules separate from those of the compound of the invention.
To achieve contact with a compound or composition of the invention to protect a field crop from invertebrate pests, the compound or composition is typically applied to the seed of the crop before planting, to the foliage (e.g., leaves, stems, flowers, fruits) of crop plants, or to the soil or other growth medium before or after the crop is planted.
One embodiment of a method of contact is by spraying. Alternatively, a granular composition comprising a compound of the invention can be applied to the plant foliage or the soil. Compounds of the present invention are noteworthy for their photostability, which makes them more useful than less photostable acyclic neonicotinoid insecticides such as imidacloprid for foliar application. Compounds of the present invention are also noteworthy for excellent systemicity, particularly xylem transport. Accordingly, compounds of this invention can also be effectively delivered through plant uptake by contacting the plant with a composition comprising a compound of this invention applied as a soil drench of a liquid formulation, a granular formulation to the soil, a nursery box treatment or a dip of transplants. Of note is a composition of the present invention in the form of a soil drench liquid formulation. Also of note is a method for controlling an invertebrate pest comprising contacting the invertebrate pest or its environment with a biologically effective amount of a compound of the present invention or with a composition comprising a biologically effective amount of a compound of the present invention. Of further note is this method wherein the environment is soil and the composition is applied to the soil as a soil drench formulation. Of further note is that compounds of this invention are also effective by localized application to the locus of infestation. Other methods of contact include application of a compound or a composition of the invention by direct and residual sprays, aerial sprays, gels, seed coatings, microencapsulations, systemic uptake, baits, ear tags, boluses, foggers, fumigants, aerosols, dusts and many others. One embodiment of a method of contact is a dimensionally stable fertilizer granule, stick or tablet comprising a compound or composition of the invention. The compounds of this invention can also be impregnated into materials for fabricating invertebrate control devices (e.g., insect netting).
Compounds of this invention are also useful in seed treatments for protecting seeds from invertebrate pests. In the context of the present disclosure and claims, treating a seed means contacting the seed with a biologically effective amount of a compound of this invention, which is typically formulated as a composition of the invention. This seed treatment protects the seed from invertebrate soil pests and generally can also protect roots and other plant parts in contact with the soil of the seedling developing from the germinating seed. The seed treatment may also provide protection of foliage by translocation of the compound of this invention or a second active ingredient within the developing plant. Seed treatments can be applied to all types of seeds, including those from which plants genetically transformed to express specialized traits will germinate. Representative examples include those expressing proteins toxic to invertebrate pests, such as Bacillus thuringiensis toxin or those expressing herbicide resistance such as glyphosate acetyltransferase, which provides resistance to glyphosate.
One method of seed treatment is by spraying or dusting the seed with a compound of the invention (i.e. as a formulated composition) before sowing the seeds. Compositions formulated for seed treatment generally comprise a film former or adhesive agent. Therefore typically a seed coating composition of the present invention comprises a biologically effective amount of a compound of Formula 1 or salt thereof, and a film former or adhesive agent. Seed can be coated by spraying a flowable suspension concentrate directly into a tumbling bed of seeds and then drying the seeds. Alternatively, other formulation types such as wetted powders, solutions, suspoemulsions, emulsifiable concentrates and emulsions in water can be sprayed on the seed. This process is particularly useful for applying film coatings on seeds. Various coating machines and processes are available to one skilled in the art. Suitable processes include those listed in P. Kosters et al., Seed Treatment: Progress and Prospects, 1994 BCPC Mongraph No. 57, and references listed therein. The treated seed typically comprises a compound of the present invention in an amount from about 0.1 g to 1 kg per 100 kg of seed (i.e. from about 0.0001 to 1% by weight of the seed before treatment). A flowable suspension formulated for seed treatment typically comprises from about 0.5 to about 70% of the active ingredient, from about 0.5 to about 30% of a film- forming adhesive, from about 0.5 to about 20% of a dispersing agent, from 0 to about 5% of a thickener, from 0 to about 5% of a pigment and/or dye, from 0 to about 2% of an antifoaming agent, from 0 to about 1% of a preservative, and from 0 to about 75% of a volatile liquid diluent.
The compounds of this invention can be incorporated into a bait composition that is consumed by an invertebrate pest or used within a device such as a trap, bait station, and the like. Such a bait composition can be in the form of granules which comprise (a) active ingredients, namely a biologically effective amount of a compound of Formula lor salt thereof; (b) one or more food materials; optionally (c) an attractant, and optionally (d) one or more humectants. Of note are granules or bait compositions which comprise between about 0.001-5% active ingredients, about 40-99% food material and/or attractant; and optionally about 0.05-10% humectants, which are effective in controlling soil invertebrate pests at very low application rates, particularly at doses of active ingredient that are lethal by ingestion rather than by direct contact. Some food materials can function both as a food source and an attractant. Food materials include carbohydrates, proteins and lipids. Examples of food materials are vegetable flour, sugar, starches, animal fat, vegetable oil, yeast extracts and milk solids. Examples of attractants are odorants and flavorants, such as fruit or plant extracts, perfume, or other animal or plant component, pheromones or other agents known to attract a target invertebrate pest. Examples of humectants, i.e. moisture retaining agents, are glycols and other polyols, glycerine and sorbitol. Of note is a bait composition (and a method utilizing such a bait composition) used to control at least one invertebrate pest selected from the group consisting of ants, termites and cockroaches. A device for controlling an invertebrate pest can comprise the present bait composition and a housing adapted to receive the bait composition, wherein the housing has at least one opening sized to permit the invertebrate pest to pass through the opening so the invertebrate pest can gain access to the bait composition from a location outside the housing, and wherein the housing is further adapted to be placed in or near a locus of potential or known activity for the invertebrate pest.
The compounds of this invention can be applied without other adjuvants, but most often application will be of a formulation comprising one or more active ingredients with suitable carriers, diluents, and surfactants and possibly in combination with a food depending on the contemplated end use. One method of application involves spraying a water dispersion or refined oil solution of a compound of the present invention. Combinations with spray oils, spray oil concentrations, spreader stickers, adjuvants, other solvents, and synergists such as piperonyl butoxide often enhance compound efficacy. For nonagronomic uses such sprays can be applied from spray containers such as a can, a bottle or other container, either by means of a pump or by releasing it from a pressurized container, e.g., a pressurized aerosol spray can. Such spray compositions can take various forms, for example, sprays, mists, foams, fumes or fog. Such spray compositions thus can further comprise propellants, foaming agents, etc. as the case may be. Of note is a spray composition comprising a biologically effective amount of a compound or a composition of the present invention and a carrier. One embodiment of such a spray composition comprises a biologically effective amount of a compound or a composition of the present invention and a propellant. Representative propellants include, but are not limited to, methane, ethane, propane, butane, isobutane, butene, pentane, isopentane, neopentane, pentene, hydrofluorocarbons, chlorofluorocarbons, dimethyl ether, and mixtures of the foregoing. Of note is a spray composition (and a method utilizing such a spray composition dispensed from a spray container) used to control at least one invertebrate pest selected from the group consisting of mosquitoes, black flies, stable flies, deer flies, horse flies, wasps, yellow jackets, hornets, ticks, spiders, ants, gnats, and the like, including individually or in combinations.
The rate of application required for effective control (i.e. "biologically effective amount") will depend on such factors as the species of invertebrate to be controlled, the pest's life cycle, life stage, its size, location, time of year, host crop or animal, feeding behavior, mating behavior, ambient moisture, temperature, and the like. Under normal circumstances, application rates of about 0.01 to 2 kg of active ingredients per hectare are sufficient to control pests in agronomic ecosystems, but as little as 0.0001 kg/hectare may be sufficient or as much as 8 kg/hectare may be required. For nonagronomic applications, effective use rates will range from about 1.0 to 50 mg/square meter but as little as 0.1 mg/square meter may be sufficient or as much as 150 mg/square meter may be required. One skilled in the art can easily determine the biologically effective amount necessary for the desired level of invertebrate pest control.
The compounds of this invention prepared by the methods described herein are shown in Index Table A. For mass spectral data, the numerical value reported in the column "AP+ (M+ 1)", is the molecular weight of the observed molecular ion formed by addition of H+ (molecular weight of 1) to the molecule having the greatest isotopic abundance (i.e. M). The presence of molecular ions containing one or more higher atomic weight isotopes of lower abundance (e.g., 37Cl, 81Br) is not reported. The reported M+l peaks were observed by mass spectrometry using atmospheric pressure chemical ionization (AP+).
The following abbreviations are used in the Index Tables which follow: Cmpd means Compound. The abbreviation "Ex." stands for "Example" and is followed by a number indicating in which Synthesis Example the compound is prepared.
INDEX TABLE A
Figure imgf000106_0001
m.p. AP+
Cmpd Q Ei R2 X Y Z (0C) (M+ 1
1 6-chloro-3 -pyridinyl Me H CH2 bond CH2 238
2 6-chloro-3 -pyridinyl c-Pr H CH2 bond CH2 264
3 6-chloro-3 -pyridinyl CH2CF3 H CH2 bond CH2 306
4 2-chloro-5-thiazolyl Me H CH2 bond CH2 * (Ex. 1, 4) 6-chloro-3 -pyridinyl c-Pr H O bond CH2 *
6 (Ex. 2) 6-chloro-3 -pyridinyl Me H O bond CH2 *
7 2-chloro-5-thiazolyl Me H O bond CH2 *
8 2-chloro-5-thiazolyl Me Me O bond CH2 *
9 2-chloro-5-thiazolyl c-Pr H O bond CH2 *
10 6-chloro-3 -pyridinyl Et H O bond CH2 *
11 3 -pyridinyl c-Pr H O bond CH2 232
12 5 -bromo- 3 -pyridinyl Me H O bond CH2 284
13 3 -pyridinyl Me H O bond CH2 206
14 5 -bromo- 3 -pyridinyl c-Pr H O bond CH2 312
15 6-chloro-3 -pyridinyl Pr H O bond CH2 268
16 6-CF3 -3 -pyridinyl Me H O bond CH2 112-113
17 6-CF3 -3 -pyridinyl c-Pr H O bond CH2 *
18 2-chloro-5-thiazolyl CH2(C-Pr) H O bond CH2 286
19 6-chloro-3 -pyridinyl c-Bu H O bond CH2 280
20 2-chloro-5-thiazolyl Et H O bond CH2 260
21 6-chloro-3 -pyridinyl OMe H O bond CH2 256
22 6-fluoro-3 -pyridinyl Me H O bond CH2 115-116
23 6-fluoro-3 -pyridinyl c-Pr H O bond CH2 127-128 24 2,6-dichloro-3 -pyridinyl c-Pr H O bond CH2 300
25 2,6-dichloro-3 -pyridinyl Me H O bond CH2 274
26 5,6-dichloro-3-pyridinyl Me H O bond CH2 274
27 5,6-dichloro-3-pyridinyl c-Pr H O bond CH2 301
28 6-chloro-3 -pyridinyl H H O bond CH2 226
29 6-chloro-3 -pyridinyl z-Pr H O bond CH2 268
30 6-chloro-3 -pyridinyl Me H S bond CH2 256
31 6-chloro-3 -pyridinyl c-Pr H S bond CH2 282
32 6-bromo-3-pyridinyl Me H O bond CH2 284
33 6-bromo-3-pyridinyl c-Pr H O bond CH2 312
34 5-Me-2-pyrazinyl c-Pr H O bond CH2 247
35 6-chloro-3 -pyridinyl Me Me O bond CH2 254
36 6-chloro-3 -pyridinyl c-Pr Me O bond CH2 280
37 6-chloro-3 -pyridinyl H Me O bond CH2 240
38 1 -Me-4-pyrazolyl c-Pr H O bond CH2 235
39 4-pyridinyl c-Pr H O bond CH2 233
40 2 -pyridinyl c-Pr H O bond CH2 233
42 6-methoxy-3 -pyridinyl Me H O bond CH2 236
43 6-methoxy-3 -pyridinyl c-Pr H O bond CH2 262
44 6-chloro-3 -pyridinyl c-Pr H O bond CHMe 280
45 6-chloro-3 -pyridinyl Me H O bond CHMe 254
46 2-chloro-5-thiazolyl c-Pr H O bond CHMe 286
47 6-chloro-3 -pyridinyl c-Pr H CH2 bond S *
48 2-chloro-5-thiazolyl c-Pr H CH2 bond S 288
49 3 -tetrahydrofuranyl H H O bond CH2 185
50 6-CF3 -3 -pyridinyl Me Me O bond CH2 288
51 3 -tetrahydrofuranyl H H O bond CHMe 199
52 2-chloro-5-thiazolyl c-Pr H CHMe bond S 302
53 6-chloro-3 -pyridinyl c-Pr H CH2 bond O *
54 2-chloro-5-thiazolyl c-Pr H CH2 bond O 272
55 6-chloro-3 -pyridinyl Me H CH2 bond O 240
56 2-chloro-5-thiazolyl Me H CH2 bond O 246
57 6-chloro-3 -pyridinyl Me H CH2 bond S 256
58 2-chloro-5-thiazolyl Me H CH2 bond S 262 (Ex. 3) 6-chloro-3 -pyridinyl Me H O bond NMe 255
60 6-chloro-3 -pyridinyl c-Pr H O bond NMe 281
61 2-chloro-5-thiazolyl c-Pr H O bond NMe 287
62 6-chloro-3 -pyridinyl Me H CH2 CH2 S * 63 2-chloro-5-thiazolyl c-Pr H CH2 CH2 S
64 2-chloro-5-thiazolyl Me H CH2 CH2 S
65 2-chloro-5-thiazolyl Me H CH=CH O (Ex. 5) 6-chloro-3 -pyridinyl c-Pr H CH=CH O
67 2-chloro-5-thiazolyl c-Pr H CH=CH O
68 6-chloro-3 -pyridinyl Me H CH=CH O
69 2-chloro-5-thiazolyl CH2CF3 H CH=CH O
* See Index Table B for 1H NMR data.
INDEX TABLE B
Compound ^H NMR Data (CDCI3 solution unless indicated otherwise)a
4 δ 7.51 (s, IH), 4.90 (s, 2H), 3.11 (s, 3H), 2.74 (m, 2H), 2.67 (m, 2H).
5 δ 8.38 (d, IH), 7.78 (dd, IH), 7.36 (d, IH), 4.90 (s, 2H), 4.80 (s, 2H), 2.62 (m, IH), 0.98 (m, 2H), 0.90 (m, 2H).
6 δ 8.37 (d, IH), 7.77 (dd, IH), 7.36 (d, IH), 4.81 (br s, 4H), 2.97 (s, 3H).
7 δ 7.55 (s, IH), 4.88 (s, 2H), 4.76 (s, 2H), 3.01 (s, 3H).
8 δ 7.52 (s, IH), 6.15 (q, IH), 4.77 (s, 2H), 2.82 (s, 3H), 1.70 (d, 3H).
9 δ 7.55 (d, IH), 4.88 (s, 2H), 4.87 (s, 2H), 2.63 (m, IH), 1.02 (m, 2H), 0.92 (m, 2H).
10 δ 8.38 (d, IH), 7.81 (dd, IH), 7.36 (d, IH), 4.82 (s, 2H), 4.81 (s, 2H), 3.22 (q, 2H), 1.27 (t, 3H).
17 δ 8.75 (s, IH), 8.01 (dd, IH), 7.68 (d, IH), 4.93 (s, 2H), 4.90 (s, 2H), 2.67 (m, IH), 1.00 (m,
2H), 0.92 (m, 2H). 47 δ 8.37 (d, IH), 7.75 (dd, IH), 7.32 (d, IH), 4.92 (s, 2H), 3.93 (s, 2H), 2.67 (quintet, IH), 1.01
(d, 4H). 53 δ 8.40 (s, IH), 7.79 (d, IH), 7.35 (d, IH), 4.74 (s, 2H), 4.66 (s, 2H), 2.58 (m, IH), 0.95 (m,
2H), 0.88 (m, 2H).
62 δ 8.4 (m, IH), 7.82 (m, IH), 7.42 (m, IH), 4.93 (s, 2H), 3.28 (m, 2H), 3.19 (s, 3H), 2.49 (m, 2H).
63 δ 7.69 (s, IH), 4.84 (s, 2H), 3.22 (m, 2H), 2.75 (m, IH), 2.44 (m, 4H), 0.94 (m, 4H).
64 (CD3S(O)CD3) δ 7.72 (s, IH), 4.86 (s, 2H), 3.26 (t, 2H), 3.13 (s, 3H), 2.44 (t, 2H).
65 δ 7.50 (br s, IH), 7.40 (d, IH), 6.07 (d, IH), 4.79 (br s, 2H), 3.09 (br s, 3H).
66 δ 8.37 (br s, IH), 7.76 (br d, IH), 7.46 (d, IH), 7.31 (d, IH), 6.08 (d, IH), 4.76 (s, 2H), 2.66- 2.56 (m, IH), 1.01-0.92 (m, 2H), 0.86-0.78 (m, 2H).
67 (CD3S(O)CD3) δ 7.91 (d, IH), 7.72 (s, IH), 6.01 (d, IH), 4.75 (s, 2H), 2.78-2.70 (m, IH), 0.85 (br s, 2H), 0.84 (br s, 2H). 68 δ 8.34 (br s, IH), 7.79 (br s, IH), 7.40 (d, IH), 7.33 (br d, IH), 6.07 (d, IH), 4.77 (br s, 2H), 3.04 (br s, 3H).
69 (CD3C(O)CD3) δ 7.83 (br d, IH), 7.76 (s, IH), 6.04 (d, IH), 4.97 (br s, 2H), 4.42 (q, 2H). a ^H NMR data are in ppm downfield from tetramethylsilane. Couplings are designated by (s)-singlet,
(d)-doublet, (t)-triplet, (q)-quartet, (m)-multiplet, (dd)-doublet of doublets, (br s)-broad singlet, (br d)-broad doublet.
The following Tests demonstrate the control efficacy of compounds of this invention on specific pests. "Control efficacy" represents inhibition of parasitic nematode development (including mortality) that causes significantly reduced feeding. The pest control protection afforded by the compounds is not limited, however, to these species.
BIOLOGICAL EXAMPLES OF THE INVENTION
TEST A
For evaluating control of green peach aphid (Myzus persicae) through contact and/or systemic means, the test unit consisted of a small open container with a 12- 15 -day-old radish plant inside. This was pre-infested by placing on a leaf of the test plant 30-40 aphids on a piece of leaf excised from a culture plant (cut-leaf method). The aphids moved onto the test plant as the leaf piece desiccated. After pre-infestation, the soil of the test unit was covered with a layer of sand.
Test compounds were formulated using a solution containing 10% acetone, 90% water and 300 ppm X-77® Spreader Lo-Foam Formula non-ionic surfactant containing alkylarylpolyoxyethylene, free fatty acids, glycols and isopropanol (Loveland Industries, Inc. Greeley, Colorado, USA). The formulated compounds were applied in 1 mL of liquid through a SUJ2 atomizer nozzle with 1/8 JJ custom body (Spraying Systems Co. Wheaton, Illinois, USA) positioned 1.27 cm (0.5 inches) above the top of each test unit.
Test compounds were formulated and sprayed at 250 and 50 ppm. The applications were replicated three times. After spraying of the formulated test compound, each test unit was allowed to dry for 1 h and then a black, screened cap was placed on top. The test units were held for 6 days in a growth chamber at 19-21 0C and 50-70% relative humidity. Each test unit was then visually assessed for insect mortality.
Of the compounds of Formula 1 tested at 250 ppm, the following resulted in at least 80% mortality: 2, 3, 5, 6, 7, 9, 10, 15, 16, 17, 20, 22, 23, 26, 27, 30, 31, 32, 33, 36, 44, 45, 46, 47, 53, 55, 57, 59, 60 and 61.
Of the compounds of Formula 1 tested at 50 ppm, the following resulted in at least 80% mortality: 5, 6, 7, 9, 10, 20, 26, 27, 30, 31, 32, 33, 44, 45, 46, 59 and 60. TEST B
For evaluating control of cotton melon aphid {Aphis gossypii) through contact and/or systemic means, the test unit consisted of a small open container with a 6-7-day-old cotton plant inside. This was pre-infested with 30-40 insects on a piece of leaf according to the cut- leaf method described for Test A, and the soil of the test unit was covered with a layer of sand.
Test compounds were formulated and sprayed at 250 and 50 ppm as described for Test A. The applications were replicated three times. After spraying, the test units were maintained in a growth chamber and then visually rated as described for Test A. Of the compounds of Formula 1 tested at 250 ppm, the following resulted in at least
80% mortality: 1, 2, 3, 5, 7, 9, 10, 13, 15, 16, 21, 22, 23, 26, 27, 30, 31, 32, 33, 44, 45, 46, 53, 55, 57, 59, 60 and 61.
Of the compounds of Formula 1 tested at 50 ppm, the following resulted in at least 80% mortality: 5, 6, 7, 9, 10, 20, 22, 23, 26, 27, 31, 32, 33, 44, 45, 46, 59, 60 and 61. TEST C
For evaluating control of corn planthopper (Peregrinus maidis) through contact and/or systemic means, the test unit consisted of a small open container with a 3-4-day-old maize plant (spike) inside. White sand was added to the top of the soil prior to application. Test compounds were formulated and sprayed at 250 and 50 ppm and replicated three times as described for Test A. After spraying, the test units were allowed to dry for 1 h before they were post-infested with -15-20 nymphs (18 to 21 day old) by sprinkling them onto the sand with a salt shaker. A black, screened cap was placed on the top of the cylinder. The test units were held for 6 days in a growth chamber at 22-24 0C and 50-70% relative humidity. Each test unit was then visually assessed for insect mortality. Of the compounds of Formula 1 tested at 250 ppm, the following resulted in at least
80% mortality: 2, 5, 6, 7, 8, 9, 10, 11, 13, 15, 20, 22, 23, 27, 32, 33, 44, 45, 59, 60 and 61.
Of the compounds of Formula 1 tested at 50 ppm, the following resulted in at least 80% mortality: 5, 6, 7, 9, 10, 11, 20, 23, 32, 33 and 59.
TEST D For evaluating control of potato leafhopper (Empoasca fabae) through contact and/or systemic means, the test unit consisted of a small open container with a 5-6-day-old Soleil bean plant (primary leaves emerged) inside. White sand was added to the top of the soil and one of the primary leaves was excised prior to application.
Test compounds were formulated and sprayed at 250 and 50 ppm, and the tests were replicated three times as described for Test A. After spraying, the test units were allowed to dry for 1 h before they were post-infested with 5 potato leafhoppers (18-21 -day-old adults). A black, screened cap was placed on the top of the cylinder. The test units were held for 6 days in a growth chamber at 24 0C and 70% relative humidity. Each test unit was then visually assessed for insect mortality.
Of the compounds of Formula 1 tested at 250 ppm the following provided very good to excellent levels of control efficacy (80% or more mortality): 5, 6, 7, 9, 10, 15, 20, 27, 31, 33, 38, 44, 46, 53, 56, 57, 59, 60 and 61.
Of the compounds of Formula 1 tested at 50 ppm the following provided very good to excellent levels of control efficacy (80% or more mortality): 5, 9, 10, 20, 33, 44 and 60.
TEST E
For evaluating control of the silverleaf whitefly (Bemisia argentifolli) through contact and/or systemic means, the test unit consisted of a small open container with a 12-14 day old cotton plant inside. Prior to the spray application, both cotyledons were removed from the plant, leaving one true leaf for the assay. Adult whiteflies were allowed to lay eggs on the plant and then were removed from the test unit. Cotton plants infested with at least 15 eggs were used in the test. Test compounds were formulated and sprayed at 250 and 50 ppm, with three replications as described for Test A. After spraying, the test units were allowed to dry for 1 hour. The units were taken to a growth chamber and held for 13 days at 28 0C and 50-70% relative humidity. Each test unit was then visually assessed for insect mortality.
Of the compounds of Formula 1 tested at 250 ppm the following provided very good to excellent levels of control efficacy (80% or more mortality): 5, 9, 10, 33, 46 and 60.
Of the compounds of Formula 1 tested at 50 ppm the following provided very good to excellent levels of control efficacy (80% or more mortality): 5.
The compounds tested for control of the western flower thrips {Frankliniella occidentalis), fall armyworm (Spodoptera frugiperdά), and diamondback moth (Plutella xylostella) did not provide greater than 80% mortality at the application rates tested.

Claims

CLAIMSWhat is claimed is:
1. A compound selected from Formula 1 or a salt thereof,
Figure imgf000112_0001
1 wherein
Y is O, S, NR5 or CR3R4, G is a direct bond, and Z is CR3R4 or NR5; or
Y is CR3R4, G is a direct bond, and Z is O or S; or
Y is O, S, NR5 or CR3R4, G is CR3R4, and Z is O, S, NR5 or CR3R4; or Y is O, and G-Z is CH=CH; or
Y-G is CH=CH, and Z is O, S or NR5;
R1 is H, C1-C3 alkoxy, C(O)R6 or SO2R7; or C1-C4 alkyl, C3-C4 alkenyl, C3-C4 alkynyl, C3-C4 cycloalkyl, C4-C5 cycloalkylalkyl, C4-C5 alkylcycloalkyl or benzyl, each optionally substituted with 1 to 5 halogen; R2 is H or C1-C2 alkyl; each R3 is independently H or CH3; each R4 is independently H or CH3; each R5 is independently H, C1-C2 alkyl or C1-C2 haloalkyl;
R6 is C1-C2 alkyl or C1-C2 haloalkyl; R7 is C1-C2 alkyl or C1-C2 haloalkyl; and
Q is a 5- or 6-membered fully unsaturated heterocyclic ring containing as ring members at least one nitrogen atom and other ring members selected from carbon, oxygen and sulfur atoms, said ring optionally substituted with 1 to 3 substituents selected from halogen, cyano, nitro, and C1-C4 alkyl, C1-C4 alkoxy and C1-C3 alkylthio, each optionally substituted with 1 to 5 fluorine or chlorine; or 3-tetrahydrofuranyl.
2. A compound of Claim 1 wherein
Y is O, G is a direct bond, and Z is CR3R4 or NR5; R1 is H; or C1-C3 alkyl or cyclopropyl, each optionally substituted with 1 to 3 halogen;
R2 is H; and
Q is a heterocyclic ring selected from pyridinyl, pyrimidinyl, pyridazinyl, pyrazinyl, pyrazolyl, oxazolyl, isoxazolyl, oxadiazolyl, thiadiazolyl, isothiazolyl, imidazolyl, pyrrolyl, thiazolyl and triazolyl, said ring optionally substituted with 1 to 3 substituents selected from halogen, cyano and nitro, and C ^C 4 alkyl, C1- C4 alkoxy and C1-C3 alkylthio, each optionally substituted with 1 to 5 halogen selected from fluorine and chlorine.
3. A compound of Claim 2 wherein
R1 is C1-C2 alkyl or cyclopropyl, each optionally substituted with 1 to 3 halogen; R3 and R4 are H; R5 is methyl; and
Q is 3 -pyridinyl or 5 -thiazolyl optionally substituted with 1 or 2 substituents selected from halogen, cyano and nitro, and Q-C4 alkyl, Q-C4 alkoxy and C1-C3 alkylthio, each optionally substituted with 1 to 3 halogen selected from fluorine and chlorine.
4. A compound of Claim 3 wherein
R1 is methyl, CH2CF3, CH2CF2H or cyclopropyl; and Q is 3 -pyridinyl or 5 -thiazolyl optionally substituted with 1 or 2 substituents selected from halogen, methyl, methoxy and trifluoromethyl.
5. A compound of Claim 4 wherein the nonhydrogen substituent(s) on the 3- pyridinyl or 5 -thiazolyl of Q are bonded to ring atom(s) not adjacent to the ring atom connecting Q to the remainder of Formula 1. 6. A compound of Claim 1 that is selected from the group consisting of
4-[[(6-chloro-3-pyridinyl)methyl]cyclopropylamino]-2(5H)-oxazolone;
4-[[(6-chloro-3-pyridinyl)methyl]methylamino]-2(5H)-oxazolone;
4-[[(2-chloro-5-thiazoyl)methyl]methylamino]-2(5H)-oxazolone;
4-[[ 1 -(2-chloro-5-thiazoyl)methyl]ethylamino]-2(5H)-oxazolone; 4-[[(2-chloro-5-thiazoyl)methyl]cyclopropylamino]-2(5H)-oxazolone;
4-[[(6-chloro-3-pyridinyl)methyl]ethylamino]-2(5H)-oxazolone;
4-[[(6-fluoro-3-pyridinyl)methyl]methylamino]-2(5H)-oxazolone;
4-[cyclopropyl[(6-fluoro-3-pyridinyl)methyl]amino]-2(5H)-oxazolone;
4-[[(5,6-dichloro-3-pyridinyl)methyl]methylamino]-2(5H)-oxazolone; 4-[cyclopropyl[(5,
6-dichloro-3-pyridinyl)methyl]amino]-2(5H)-oxazolone; 4-[[(6-bromo-3-pyridinyl)methyl]methylamino]-2(5H)-oxazolone; 4-[[(6-bromo-3-pyridinyl)methyl]cyclopropylamino]-2(5H)-oxazolone; 4-[ [(6-chloro-3 -pyridinyl)methyl] cyclopropylamino] -5 -methyl-2(5H)-oxazolone; 4-[[(6-chloro-3-pyridinyl)methyl]cyclopropylamino]-2(5H)-thiazolone; 3-[[(6-chloro-3-pyridinyl)methyl]methylamino]-2-methyl- 1 ,2,4-oxadiazol-5(2H)-one;
3-[[(6-chloro-3-pyridinyl)methyl]cyclopropylamino]-2-methyl-l,2,4-oxadiazol-5(2H)-one; and
3-[[(2-chloro-5-thiazolyl)methyl]cyclopropylamino]-2-methyl-l,2,4-oxadiazol-5(2Η)-one.
7. A composition comprising a compound of Claim 1 and at least one additional component selected from the group consisting of surfactants, solid diluents and liquid diluents.
8. The composition of Claim 7 wherein said composition further comprises at least one additional biologically active compound or agent.
9. The composition of Claim 8 wherein the at least one additional biologically active compound or agent is selected from the group consisting of abamectin, acephate, acequinocyl, acetamiprid, acrinathrin, amidoflumet, amitraz, avermectin, azadirachtin, azinphos-methyl, bifenthrin, bifenazate, bistrifluron, borate, 3-bromo-l-(3-chloro-2- pyridinyl)-Λ/-[4-cyano-2-methyl-6-[(methylamino)carbonyl]phenyl]-lH-pyrazole-5- carboxamide, buprofezin, carbaryl, carbofuran, cartap, carzol, chlorantraniliprole, chlorfenapyr, chlorfluazuron, chlorpyrifos, chlorpyrifos-methyl, chromafenozide, clofentezin, clothianidin, cyflumetofen, cyfluthrin, beta-cyfluthrin, cyhalothrin, gamma- cyhalothrin, lambda-cyhalothrin, cypermethrin, alpha-cypermethrin, zeta-cypermethrin, cyromazine, deltamethrin, diafenthiuron, diazinon, dieldrin, diflubenzuron, dimefluthrin, dimehypo, dimethoate, dinotefuran, diofenolan, emamectin, endosulfan, esfenvalerate, ethiprole, etofenprox, etoxazole, fenbutatin oxide, fenothiocarb, fenoxycarb, fenpropathrin, fenvalerate, fipronil, flonicamid, flubendiamide, flucythrinate, flufenerim, flufenoxuron, fluvalinate, tau-fluvalinate, fonophos, formetanate, fosthiazate, halofenozide, hexaflumuron, hexythiazox, hydramethylnon, imidacloprid, indoxacarb, insecticidal soaps, isofenphos, lufenuron, malathion, metaflumizone, metaldehyde, methamidophos, methidathion, methiodicarb, methomyl, methoprene, methoxychlor, metofluthrin, monocrotophos, methoxyfenozide, nitenpyram, nithiazine, novaluron, noviflumuron, oxamyl, parathion, parathion-methyl, permethrin, phorate, phosalone, phosmet, phosphamidon, pirimicarb, profenofos, profluthrin, propargite, protrifenbute, pymetrozine, pyrafluprole, pyrethrin, pyridaben, pyridalyl, pyrifluquinazon, pyriprole, pyriproxyfen, rotenone, ryanodine, spinetoram, spinosad, spirodiclofen, spiromesifen, spirotetramat, sulprofos, tebufenozide, tebufenpyrad, teflubenzuron, tefluthrin, terbufos, tetrachlorvinphos, tetramethrin, thiacloprid, thiamethoxam, thiodicarb, thiosultap-sodium, tolfenpyrad, tralomethrin, triazamate, trichlorfon, triflumuron, all strains of Bacillus thuringiensis, entomopathogenic bacteria, all strains of Nucleo polyhydrosis viruses, entomopathogenic viruses and entomopathogenic fungi.
10. The composition of Claim 9 wherein the at least one additional biologically active compound or agent is selected from the group consisting of abamectin, acetamiprid, amitraz, avermectin, azadirachtin, bifenthrin, 3-bromo-l-(3-chloro-2-pyridinyl)-JV-[4-cyano- 2-methyl-6- [(methylamino)carbonyl]phenyl] - 1 H-pyrazole-5 -carboxamide, buprofezin, cartap, chlorantraniliprole, chlorfenapyr, chlorpyrifos, clothianidin, cyfluthrin, beta- cyfluthrin, cyhalothrin, lambda-cyhalothrin, cypermethrin, cyromazine, deltamethrin, dieldrin, dinotefuran, diofenolan, emamectin, endosulfan, esfenvalerate, ethiprole, fenothiocarb, fenoxycarb, fenvalerate, fipronil, flonicamid, fiubendiamide, flufenoxuron, hexaflumuron, hydramethylnon, imidacloprid, indoxacarb, lufenuron, metaflumizone, methomyl, methoprene, methoxyfenozide, nitenpyram, nithiazine, novaluron, oxamyl, pymetrozine, pyrethrin, pyridaben, pyridalyl, pyriproxyfen, ryanodine, spinetoram, spinosad, spirodiclofen, spiromesifen, tebufenozide, thiacloprid, thiamethoxam, thiodicarb, thiosultap- sodium, tralomethrin, triazamate, trifiumuron, Bacillus thuringiensis subsp. aizawai, Bacillus thuringiensis subsp. kurstaki, nucleopolyhedro viruses and encapsulated delta-endotoxins of Bacillus thuringiensis.
11. A method for controlling an invertebrate pest comprising contacting the invertebrate pest or its environment with a biologically effective amount of a compound of Claim 1.
12. The method of Claim 11 wherein the environment is a plant.
13. The method of Claim 11 wherein the environment is a seed.
14. The method of Claim 13 wherein the seed is coated with the compound of Claim 1 formulated as a composition comprising a film former or adhesive agent.
15. A treated seed comprising a compound of Claim 1 in an amount of from about 0.0001 to 1% by weight of the seed before treatment.
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