WO2004010761A2 - Pesticidal cyanine dye derivatives - Google Patents

Pesticidal cyanine dye derivatives Download PDF

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Publication number
WO2004010761A2
WO2004010761A2 PCT/US2003/022986 US0322986W WO2004010761A2 WO 2004010761 A2 WO2004010761 A2 WO 2004010761A2 US 0322986 W US0322986 W US 0322986W WO 2004010761 A2 WO2004010761 A2 WO 2004010761A2
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Prior art keywords
alkyl
hydrogen
taken together
halogen
independently selected
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PCT/US2003/022986
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French (fr)
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WO2004010761A3 (en
Inventor
David S. Rosen
Y. Larry Zhang
Robert N. Ii Henrie
Benjamin J. Dugan
Thomas M. Zydowsky
Shunxiang Zhang
Inna Shulman
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Fmc Corporation
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Priority to AU2003261224A priority Critical patent/AU2003261224A1/en
Publication of WO2004010761A2 publication Critical patent/WO2004010761A2/en
Publication of WO2004010761A3 publication Critical patent/WO2004010761A3/en

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
    • C07D263/52—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings condensed with carbocyclic rings or ring systems
    • C07D263/54—Benzoxazoles; Hydrogenated benzoxazoles
    • C07D263/56—Benzoxazoles; Hydrogenated benzoxazoles with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached in position 2
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/34—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom
    • A01N43/40—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom six-membered rings
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/72—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms
    • A01N43/74—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms five-membered rings with one nitrogen atom and either one oxygen atom or one sulfur atom in positions 1,3
    • A01N43/76—1,3-Oxazoles; Hydrogenated 1,3-oxazoles
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/72—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms
    • A01N43/74—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms five-membered rings with one nitrogen atom and either one oxygen atom or one sulfur atom in positions 1,3
    • A01N43/78—1,3-Thiazoles; Hydrogenated 1,3-thiazoles
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/72—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms
    • A01N43/80—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms five-membered rings with one nitrogen atom and either one oxygen atom or one sulfur atom in positions 1,2
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
    • C07D209/04—Indoles; Hydrogenated indoles
    • C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
    • C07D209/18—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
    • C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
    • C07D215/04—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to the ring carbon atoms
    • C07D215/10—Quaternary compounds
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
    • C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
    • C07D215/12—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
    • C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
    • C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D215/18—Halogen atoms or nitro radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
    • C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
    • C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
    • C07D235/20—Two benzimidazolyl-2 radicals linked together directly or via a hydrocarbon or substituted hydrocarbon radical
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D275/00—Heterocyclic compounds containing 1,2-thiazole or hydrogenated 1,2-thiazole rings
    • C07D275/04—Heterocyclic compounds containing 1,2-thiazole or hydrogenated 1,2-thiazole rings condensed with carbocyclic rings or ring systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
    • C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
    • C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D277/22—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
    • C07D277/30—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
    • C07D277/60—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings condensed with carbocyclic rings or ring systems
    • C07D277/62—Benzothiazoles
    • C07D277/64—Benzothiazoles with only hydrocarbon or substituted hydrocarbon radicals attached in position 2
    • 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
    • C07D413/06—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 carbon chain containing only aliphatic carbon atoms
    • 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
    • C07D417/06—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 carbon chain containing only aliphatic carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
    • C09B—ORGANIC DYES OR CLOSELY-RELATED COMPOUNDS FOR PRODUCING DYES, e.g. PIGMENTS; MORDANTS; LAKES
    • C09B23/00—Methine or polymethine dyes, e.g. cyanine dyes
    • C09B23/02—Methine or polymethine dyes, e.g. cyanine dyes the polymethine chain containing an odd number of >CH- or >C[alkyl]- groups
    • C09B23/04—Methine or polymethine dyes, e.g. cyanine dyes the polymethine chain containing an odd number of >CH- or >C[alkyl]- groups one >CH- group, e.g. cyanines, isocyanines, pseudocyanines
    • C—CHEMISTRY; METALLURGY
    • C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
    • C09B—ORGANIC DYES OR CLOSELY-RELATED COMPOUNDS FOR PRODUCING DYES, e.g. PIGMENTS; MORDANTS; LAKES
    • C09B23/00—Methine or polymethine dyes, e.g. cyanine dyes
    • C09B23/02—Methine or polymethine dyes, e.g. cyanine dyes the polymethine chain containing an odd number of >CH- or >C[alkyl]- groups
    • C09B23/06—Methine or polymethine dyes, e.g. cyanine dyes the polymethine chain containing an odd number of >CH- or >C[alkyl]- groups three >CH- groups, e.g. carbocyanines
    • C—CHEMISTRY; METALLURGY
    • C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
    • C09B—ORGANIC DYES OR CLOSELY-RELATED COMPOUNDS FOR PRODUCING DYES, e.g. PIGMENTS; MORDANTS; LAKES
    • C09B23/00—Methine or polymethine dyes, e.g. cyanine dyes
    • C09B23/02—Methine or polymethine dyes, e.g. cyanine dyes the polymethine chain containing an odd number of >CH- or >C[alkyl]- groups
    • C09B23/08—Methine or polymethine dyes, e.g. cyanine dyes the polymethine chain containing an odd number of >CH- or >C[alkyl]- groups more than three >CH- groups, e.g. polycarbocyanines
    • C—CHEMISTRY; METALLURGY
    • C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
    • C09B—ORGANIC DYES OR CLOSELY-RELATED COMPOUNDS FOR PRODUCING DYES, e.g. PIGMENTS; MORDANTS; LAKES
    • C09B23/00—Methine or polymethine dyes, e.g. cyanine dyes
    • C09B23/10—The polymethine chain containing an even number of >CH- groups
    • C09B23/105—The polymethine chain containing an even number of >CH- groups two >CH- groups

Definitions

  • the present invention generally relates to pesticidal compounds and their use in controlling pests.
  • it pertains to compositions of pesticidal cyanine dye derivatives and pesticidally acceptable salts thereof, and methods for their use in controlling pests, such as insects and acarids.
  • Cyanine dye compounds consisting of two heterocyclic groups, for example quinoline nuclei, connected by a chain of conjugated double bonds containing an odd number of carbon atoms are well known, for example, as set forth in THE CHEMISTRY OF HETEROCYCLIC COMPOUNDS, Volume 18; "The Cyanine Dyes And Related Compounds”; John Wiley & Sons (1964). In recent years, certain cyanine dyes have found utility in areas not related to the dye industry.
  • Z' is a nitrogen-containing heterocyclic radical linked to the substituents Rt and X by the nitrogen atom of the heterocyclic radical
  • Z" is a nitrogen-containing heterocyclic radical linked to the substituents R 3 and X by the nitrogen atom of the heterocyclic radical
  • R] is selected from lower alkyl, benzyl, and phenyl
  • R 2 is selected from hydrogen and lower alkyl
  • R 3 is selected from lower alkyl, benzyl, and phenyl
  • X is an acid anion, in an amount effective against the blight-causing bacteria.
  • Japanese Patent 67014918 discloses the use of compounds (A) and/or (B) as therepeutics for control of flatworms in pearl oysters; wherein the compounds have the following structures:
  • Japanese Patent 6703198 discloses agricultural and horticultural fungicidal compositions containing one or more compounds of the following structure:
  • Zi and Z 2 are a group of atoms, forming with the N, rings of thiazoline, thiazole, benzthiazole, or quinoline optionally substituted;
  • L is methine or N, at least one L being N;
  • n is 0 or 1;
  • Ri. and R 2 are alkyl or aralkyl; and
  • X is an inorganic residue.
  • French Patent 1,448,707 discloses an anthelmintic 2,4,5-trichlorophenol compound of the following structure:
  • Harmful pests include, without limitation, arthropods, such as certain insects and aracnids.
  • Other harmful pests include certain fungi.
  • insecticide market alone was estimated to be about seven billion dollars in the year 2000.
  • insecticides play an important role in public health programs to control diseases, such as malaria and chagas, in the developing world.
  • the largest insecticide markets are fruits, vegetables, cotton, rice, and corn. Control of insects is essential to achieve the yield and quality of crop demanded by growers and consumers. Termites are undisputedly the most destructive of all structural insects.
  • Soil-borne insects such as termites are estimated to cause 1.5 billion dollars of damage to structures annually, and that an additional one billion dollars is spent on treatment. Since termites usually remain hidden within the wood in which they are feeding, in mud tubes, or in the soil, they typically wreak havoc undetected.
  • Fungicides prevent and cure fungal plant diseases, which affect crop yields and crop quality.
  • the fungicide market was estimated at about six billion dollars in the year 2000, mainly for wheat in Europe, rice in Asia Pacific, and for fruits and vegetables in different regions of the world.
  • Ar and Ar 1 are independently selected from
  • compositions of the present invention are comprised of the following compounds of formula I:
  • the present invention is also directed to compositions containing a pesticidally effective amount of at least one of a compound of formula I, and optionally, an effective amount of at least one of a second compound, with at least one pesticidally compatible carrier.
  • the present invention is also directed to methods of controlling pests, where control is desired, which comprise applying a pesticidally effective amount of the above composition to a locus where pests are present or are expected to be present.
  • Ar and Ar 1 are independently selected from
  • p, q and r are independently selected from 0 or 1; where at least one of p, q or r is l;
  • R 5 , R 6 , R 7 , and R 12 are independently selected from hydrogen; alkyl; haloalkyl; hydroxy alkyl; alkoxy alkyl; carboxylalkyl; aryl optionally substituted with at least one halogen or alkyl; arylalkyl; aryloxyalkyl; or sulfonatoalkyl, and may bear a negative charge resulting in an inner salt; and a separate ion is selected from sodium, potassium, lithium, calcium, magnesium, halide, sulfate, bisulfate, alkyl sulfate, alkyl sulfonate, haloalkylsulfonate, arylsulfonate, carbonate, bicarbonate, alkylcarboxylate, phosphate, hydrogen phosphate, dihydrogen phosphate, arylcarboxylate, trialkylammonium, or pyridinium;
  • X and Y; X 1 and Y 1 ; X 2 and Y 2 ; and X 3 and Y 3 are independently selected from hydrogen, halogen, cyano, alkyl, cycloalkyl, haloalkyl, alkoxy, alkylthio, alkylsulfinyl, alkylsulfonyl, aryl, aryl-substituted aryl, arylalkyl, aryloxy, arylalkoxy, arylthio, arylsulfonyl, arylsulfoxide, arylcarbonyl, or heteroaryl; or
  • R 29 through R 44 are independently selected from hydrogen; halogen alkyl; haloalkyl; hydroxy; alkoxy; haloalkoxy; alkylthio; haloalkylthio alkylsulfonyl; haloalkylsulfonyl; alkylsulfinyl; haloalkylsulfinyl; cycloalkyl alkenyl; alkynyl; alkenyloxy; cyano; nitro; amino; alkylamino; dialkylamino alkylcarbonyloxy; alkoxycarbonyl; alkoxycarbonylalkyl; dialkylphosphono; or aryl, arylalkyl, arylalkoxy, aryloxy, arylthio, arylsulfinyl, arylsulfonyl, and heteroaryl wherein the aryl is optionally substituted with at least one halogen, alkyl
  • R 44 together are the same or different
  • Z, Z 1 , Z 2 , and Z 3 are independently selected from -O-, -S-, dialkylmethylene, or NR 48 , where R 48 is selected from hydrogen, alkyl, alkoxyalkyl, haloalkyl, haloalkenyl, aryl, or sulfonatoalkyl, and may bear a negative charge resulting in an inner salt; and, when p, q and r arel ; R through R 4 , inclusively, are independently selected from hydrogen; halogen; alkyl; haloalkyl; cycloalkyl; hydroxyalkyl; alkoxy; alkylthio; cyano; aryl optionally substituted with carboxyl; amino; or arylalkyl; and when q is 0, and p and r are 1; R and R 4 are optionally taken together with 1,2-cyclohexene to form a 3,4,5,6,7- pentahydroindene ring; or taken together
  • R 49 through R 64 are independently selected from hydrogen; halogen; alkyl; haloalkyl; alkoxy; haloalkoxy; or aryl optionally substituted with at least one halogen, alkyl, or alkoxy.
  • compositions of the present invention are comprised of the following compounds of formula I:
  • R 5 is selected from alkyl, haloalkyl, alkoxyalkyl; or sulfonatoalkyl, and may bear a negative charge resulting in an inner salt; and a separate ion is selected from halide, alkyl sulfate, alkyl sulfonate, haloalkylsulfonate, arylsulfonate, alkylcarboxylate, arylcarboxylate, trialkylammonium, pyridinium; sodium, potassium, calcium, or magnesium;
  • R 29 , R 30 , R 31 , and R 32 are independently selected from hydrogen; halogen; alkyl; hydroxy; alkoxy; alkylsulfonyl; nitro; aryl optionally substituted with at least one halogen, alkoxy, haloalkoxy, alkylsulfonyl, or aryl; aryloxy optionally substituted with at least one halogen, alkyl, or alkoxy; or heteroaryl optionally substituted with at least one halogen, alkyl, alkoxy, or aryl; or
  • R 29 and R 30 , or R 30 and R 31 are taken together with -X 4 -(CR 45 R 46 ) S -X 4 - to form a fused azole, where X 4 is -O-, or -S-, R 45 and R 46 are independently selected from hydrogen, halogen, alkyl, or alkoxyalkyl, and s is 1-2; or
  • Z is selected from -O-; or -S-;
  • R 17 and R 22 are independently selected from hydrogen, alkyl, haloalkyl, alkoxyalkyl, or aryl;
  • R 18 through R 21 , and R 23 through R 26 are independently selected from hydrogen, halogen, alkyl, alkoxy, haloalkyl, haloalkoxy, aryl, or aryloxy; or
  • compositions of the present invention are comprised of the following compounds of formula I:
  • R, R 1 , and R 4 are independently selected from hydrogen; alkyl, alkoxy, or aryl;
  • R 5 and R 27 are, independently selected from alkyl, haloalkyl, alkoxyalkyl; or sulfonatoalkyl, and may bear a negative charge resulting in an inner salt; and a separate ion is selected from halide, alkyl sulfate, alkyl sulfonate, haloalkylsulfonate, arylsulfonate, alkylcarboxylate, arylcarboxylate, trialkylammonium, pyridinium; sodium, potassium, calcium, or magnesium;
  • R 29 , R 30 , R 31 , and R 32 , and R 37 , R 38 , R 39 , and R 40 are independently selected from hydrogen; halogen; alkyl; haloalkyl; alkoxy; cyano; nitro; amino; alkylamino; aryl, aryloxy, or arylthio where the aryl is optionally substituted with at least one halogen, alkyl, haloalkyl, alkoxy, or haloalkoxy; or heteroaryl optionally substituted with at least one halogen, alkyl, or alkoxy; or
  • Particularly preferred pesticidal compositions within the scope of a second embodiment of the present invention are comprised of compounds of formula I, wherein R, R , and R are hydrogen; R and R are independently selected from methyl, ethyl, or 2-methoxyethyl; R 29 , R 30 , R 31 , and R 32 , and R 37 , R 38 , R 39 , and R 40 are independently selected from hydrogen; halogen; methyl; ethyl; propyl; butyl; methoxy; ethoxy; propoxy; butoxy; trifluoromethyl; phenyl optionally substituted with halogen; or thien-2-yl or furan-2-yl optionally substituted with halogen or methyl; or R 29 and R 30 , and R 37 and R 38 are taken together with -X 4 -(CR 45 R 46 ) S -X 4 - to form a fused azole, where X 4 is -O-, R 45 and R 46 are hydrogen
  • Certain compounds within the scope of formula I which find utility in the novel pesticidal compositions of the present invention, are new and novel compositions of matter.
  • the compounds within the scope of formula I may possess asymmetric centers, which can give rise to optical enantiomorphs and diastereomers.
  • Compounds within the scope of formula I may exist in two or more forms, i.e., polymorphs, which are significantly different in physical and chemical properties.
  • Compounds within the scope of formula I may also exist as tautomers, which are in equilibrium.
  • Compounds within the scope of formula I may also possess acidic or basic moieties, which may allow for the formation of pesticidally acceptable salts or pesticidally acceptable metal complexes.
  • Pesticidally acceptable salts and metal complexes include, without limitation, for example, ammonium salts, the salts of organic and inorganic acids, such as hydrochloric acid, sulfonic acid, ethanesulfonic acid, trifluoroacetic acid, methylbenzenesulfonic acid, phosphoric acid, gluconic acid, pamoic acid, and other acid salts, and the alkali metal and alkaline earth metal complexes with, for example, sodium, potassium, lithium, magnesium, calcium, and other metals.
  • the methods of the present invention are predicated on causing a pesticidal amount of a compound of formula I to be present within pests in order to kill or control the pest. It is within the scope of the present invention to cause a compound of formula I to be present within pests by contacting the pest with a derivative of that compound, which derivative is converted within the pest to a compound of formula I.
  • This invention includes the use of such compounds, which can be referred to as pro-pesticides, for example, a pro-insecticide.
  • Another aspect of the present invention relates to methods of controlling pests by applying a pesticidally effective amount of a composition set forth above to a locus of, for example, crops such as, without limitation, cereals, cotton, vegetables, and fruits, or other areas where pests are present or are expected to be present.
  • crops such as, without limitation, cereals, cotton, vegetables, and fruits, or other areas where pests are present or are expected to be present.
  • the present invention relates to compositions containing an insecticidally effective amount of at least one compound of formula I and, optionally, an effective amount of at least one pesticidally active second compound, with at least one insecticidally compatible carrier therefore.
  • the compositions of the present invention are satisfactorily effective for the control of various noxious insects and aracnids, examples of which are as follows:
  • Hemiptera Delphacidae; such as Laodelphax stiatellus, Nilaparvata lugens and Sogatella furcifera; Deltocephalidae; such as Nephotettix cincticeps and Nephotettix virescens; Aphididae, Pentatomidae, Aleyrodidae, Coccidae, Tigidae, Psyllidae, as well as other Hemiptera.
  • Lepidoptera Pyralidae, such as Chilo suppressalis, Cnaphalocrocis medinalis, Ostrinia nubilalis, Parapediasia teterrella, Notarcha derogata and Plodia interpunctella; Noctuida, such as Spodoptera litura, Spodoptera exigua, Spotoptera littoralis, Pseudaletia separata, Mamestra brassicae, Agrotis ipsilon, Trichoplusia spp., Heliothis spp., Helicoverpa spp., and Earias spp.; Pieridae, such as Pieris rapae crucivora; Tortricidae, such as Adoxophyes spp.; Carposinidae, such as Grapholita molesta, Cydia pomonella, and Carposina niponensis; Lyonetiidae, such as Lyonet
  • Diptera Culex, such as Culex pipiens pattens, and Culex tritaeniorhynchus; Aedes, such as Aedes aegypti and Aedes albopicyus; Anopheles, such as nophelinae sinensis; Chironomidae; Muscidae, such as Musca domestica and Musca stabulans; Calliphoridae; Sarcophagidae; Fannia canicularis; Anthomyiidae, such as Hylemya platura and Hylemya antiqua; Tryptetidae; Drosophilidae; Psychodidae; Tabanidae; Simuliidae; Stomoxyinae, Agromyzidae, as well as other Diptera.
  • Culex such as Culex pipiens pattens, and Culex tritaeniorhynchus
  • Aedes such as Aedes
  • Diabrotica such as Diabrotica virgifera and Diabrotica undecimpunctata
  • Scarabaeidae such as Anomala cuprea and Anomala rufocuprea
  • Curculionidae such as Sitophilus oryzae, Lissorhoptrus oryzophilus, and Callosobruchus chinensis
  • Tenebrionidae such as Tenebrio molitor and Tribolium castaneum
  • Chrysomelidae such as Phyllotretra striolata and Aulacophora femoralis
  • Anobiidae Epilachna spp., such as Epilachna vigintioctopunctata; Lyctidae; Bostrychidae; Cerambycidae; Paederusfuscipes, as well as other Coleoptera.
  • Dictyoptera Blattella germanica; Periplaneta fuliginosa; Periplaneta American; Periplaneta brunnea; Blatta orientalis, as well as other Dictyoptera.
  • Thysanoptera Thripa palmi; Thrips hawaiiensis, as well as other Thysanoptera.
  • Hymenoptera Formicidae; Vespidae; Bethylidae; Tenthredinidae, such as Athalia rosae japonensis, as well as other Hymenoptera.
  • Orthoptera Gryllotalpidae; Acrididae, as well as other Orthoptera.
  • Siphonoptera Purex irritans, as well as other Siphonoptera.
  • Anoplura Pediculus humanus capitis, Phthirus pubis, as well as other Anoplura.
  • Isoptera (termites): Reticulitermes speratus, Coptotermes formosanus, as well as other Isoptera.
  • Acarina plant parasitic Tetranychidae, such as Tetranychus uriticae; Panonychus citri, Tetranychus cinnabarinus, and Panonychus ulmi; animal parasitic Ixodidae, such as Boophilus microphus, house dust mites, as well as other Acarina.
  • the present invention also includes the use of the compounds and compositions set forth herein for control of i) harmful arthropods other than insects and acarids, ii) non-agricultural insect species, for example, dry wood termites and subterranean termites, and iii) harmful fungi; as well as for use as pharmaceutical agents and compositions thereof.
  • alkyl and alkoxy used alone or as part of a larger moiety, includes straight or branched chains of at least one or two carbon atoms, as appropriate to the substituent, and preferably up to 12 carbon atoms, more preferably up to ten carbon atoms, most preferably up to seven carbon atoms.
  • alkenyl and alkynyl used alone or as part of a larger moiety, includes straight or branched chains of at least two carbon atoms containing at least one carbon-carbon double bond or triple bond, and preferably up to 12 carbon atoms, more preferably up to ten carbon atoms, most preferably up to seven carbon atoms.
  • aryl refers to an aromatic ring structure, including fused rings, having four to ten carbon atoms, for example, without limitation, phenyl or napthyl.
  • heteroaryl refers to an aromatic ring structure, including fused rings, in which at least one of the atoms is other than carbon, for example, without limitation, sulfur, oxygen, or nitrogen.
  • azole refers to a 5-membered ring containing a nitrogen atom where the 5-membered ring is optionally fused with one or more other rings.
  • azine refers to a 6-membered ring containing a nitrogen atom where the 6- membered ring is optionally fused with one or more other rings.
  • DMF N,N-dimethylformamide
  • THF tetrahydrofuran
  • DMSO methyl sulfoxide
  • halogen or halo refers to fluorine, bromine, iodine, or chlorine.
  • ambient temperature or “room temperature” often abbreviated as "RT”, for example, in reference to a chemical reaction mixture temperature, refers to a temperature in the range of 20 °C to 30 °C.
  • RT room temperature
  • the term “pest” refers to any arthropod, such as insects and acarids, and to any fungi capable of causing damage to crops and dwellings utilized by man.
  • pesticide or “pesticidal” therefore refers to a compound or a composition thereof that is an insecticide, an acaricide, or a fungicide that is insecticidally, acaricidally, or fungicidally active to control an insect, acarid, or fungi.
  • Scheme 1 illustrates a general procedure for synthesizing compounds of formula I, where, for example, Ar is structure A (Intermediate 2) and Ar 1 is selected from structure E (Intermediate 3) or structure F (Intermediate 4).
  • Scheme 2 illustrates a general procedure for synthesizing compounds of formula I, where, for example, Ar is structure A (Intermediate 7) and Ar 1 is structure G (derived from Intermediate 7):
  • W is where R 5 is, for -CI or -SH example, CH 3
  • R for example, is hydrogen
  • compounds of formula I designated as compounds of formulae la and lb, were prepared by reacting (reaction a) a 2- halothiazole (Intermediate 1), such as 2,6-dichlorobenzothiazole, with, for example sodium thiomethoxide, to yield the corresponding 2-methylthiobenzothiazole derivative, or by reacting (reaction b) a 2-mercaptothiazole (Intermediate 1), such as 6-ethoxy-2-mercaptobenzothiazole, with an alkyl halide, for example methyl iodide, in an appropriate solvent, to yield the corresponding 2- methylthiobenzothiazole derivative.
  • a 2- halothiazole such as 2,6-dichlorobenzothiazole
  • reaction b a 2-mercaptothiazole
  • an alkyl halide for example methyl iodide
  • the 2-methylthiobenzothiazole derivatives were then N-alkylated (reaction c) with an alkyl halide, for example methyl iodide; to yield the corresponding N-alkyl quaternary ammonium salts (Intermediate 2), for example 6-chloro-3-methyl-2-methylthiobenzothiazolium iodide, or 6-ethoxy- 3-methyl-2-methylthiobenzothiazolium iodide.
  • a substituted azine such as 7-chloro-2-methylquinoline (Intermediate 3) was N- alkylated with an alkyl halide (reaction d), for example ethyl iodide, in a solvent at an elevated temperature, to yield the corresponding N-alkylated quinolinium salt 7- chloro-l-ethyl-2-methylquinolinium iodide (Intermediate 5).
  • compounds of formula I designated as compounds of formula lc, were prepared by N-alkylating (reaction f) an appropriately substituted 2-alkylthiazole (Intermediate 7), such as 2-methyl-6- phenylbenzothiazole, with, for example diethyl sulfate, to yield the corresponding quaternary ammonium salt 3-ethyl-2-methyl-6-phenylbenzothiazolium ethylsulfate (Intermediate 8).
  • 2-alkylthiazole such as 2-methyl-6- phenylbenzothiazole
  • the present pesticidal compounds may be formulated as a granular of relatively large particle size (for example, 8/16 or 4/8 US Mesh), as water-soluble or water-dispersible granules, as powdery dusts, as wettable powders, as emulsifiable concentrates, as aqueous emulsions, as solutions, or as any of other known types of agriculturally-useful formulations, depending on the desired mode of application. It is to be understood that the amounts specified in this specification are intended to be approximate only, as if the word "about” were placed in front of the amounts specified.
  • pesticidal compositions may be applied either as water-diluted sprays, or dusts, or granules to the areas in which suppression of insects is desired.
  • These formulations may contain as little as 0.1%, 0.2% or 0.5% to as much as 95% or more by weight of active ingredient.
  • Dusts are free flowing admixtures of the active ingredient with finely divided solids such as talc, natural clays, kieselguhr, flours such as walnut shell and cottonseed flours, and other organic and inorganic solids which act as dispersants and carriers for the toxicant; these finely divided solids have an average particle size of less than about 50 microns.
  • a typical dust formulation useful herein is one containing 1.0 part or less of the insecticidal compound and 99.0 parts of talc.
  • Wettable powders also useful formulations for pesticides, are in the form of finely divided particles that disperse readily in water or other dispersant.
  • the wettable powder is ultimately applied to the locus where insect control is needed either as a dry dust or as an emulsion in water or other liquid.
  • Typical carriers for wettable powders include Fuller's earth, kaolin clays, silicas, and other highly absorbent, readily wet inorganic diluents. Wettable powders normally are prepared to contain about 5-80% of active ingredient, depending on the absorbency of the carrier, and usually also contain a small amount of a wetting, dispersing or emulsifying agent to facilitate dispersion.
  • a useful wettable powder formulation contains 80.0 parts of the insecticidal compound, 17.9 parts of Palmetto clay, and 1.0 part of sodium lignosulfonate and 0.3 part of sulfonated aliphatic polyester as wetting agents. Additional wetting agent and/or oil will frequently be added to a tank mix for to facilitate dispersion on the foliage of the plant.
  • ECs emulsifiable concentrates
  • ECs emulsifiable concentrates
  • ECs emulsifiable concentrates
  • these concentrates are dispersed in water or other liquid carrier and normally applied as a spray to the area to be treated.
  • the percentage by weight of the essential active ingredient may vary according to the manner in which the composition is to be applied, but in general comprises 0.5 to 95% of active ingredient by weight of the pesticidal composition.
  • Flowable formulations are similar to ECs, except that the active ingredient is suspended in a liquid carrier, generally water.
  • Flowables like ECs, may include a small amount of a surfactant, and will typically contain active ingredients in the range of 0.5 to 95%, frequently from 10 to 50%, by weight of the composition.
  • flowables may be diluted in water or other liquid vehicle, and are normally applied as a spray to the area to be treated.
  • Typical wetting, dispersing or emulsifying agents used in pesticidal formulations include, but are not limited to, the alkyl and alkylaryl sulfonates and sulfates and their sodium salts; alkylaryl polyether alcohols; sulfated higher alcohols; polyethylene oxides; sulfonated animal and vegetable oils; sulfonated petroleum oils; fatty acid esters of polyhydric alcohols and the ethylene oxide addition products of such esters; and the addition product of long-chain mercaptans and ethylene oxide.
  • Many other types of useful surface-active agents are available in commerce. Surface-active agents, when used, normally comprise 1 to 15% by weight of the composition.
  • compositions include suspensions of the active ingredient in a relatively non-volatile solvent such as water, corn oil, kerosene, propylene glycol, or other suitable solvents.
  • Still other useful formulations for pesticidal applications include simple solutions of the active ingredient in a solvent in which it is completely soluble at the desired concentration, such as acetone, alkylated naphthalenes, xylene, or other organic solvents.
  • Granular formulations, wherein the toxicant is carried on relative coarse particles are of particular utility for aerial distribution or for penetration of cover crop canopy.
  • Pressurized sprays typically aerosols wherein the active ingredient is dispersed in finely divided form as a result of vaporization of a low- boiling dispersant solvent carrier may also be used.
  • Water-soluble or water- dispersible granules are free flowing, non-dusty, and readily water-soluble or water-miscible.
  • the granular formulations, emulsifiable concentrates, flowable concentrates, aqueous emulsions, solutions, etc. may be diluted with water to give a concentration of active ingredient in the range of say 0.1% or 0.2% to 1.5% or 2%.
  • the active pesticidal compounds of this invention may be formulated and/or applied with one or more second compounds.
  • Second compounds include, but are not limited to, other pesticides, plant growth regulators, fertilizers, soil conditioners, or other agricultural chemicals.
  • an effective amount and concentration of the active compound is of course employed; the amount may vary in the range of, e.g. about 0.001 to about 3 kg/ha, preferably about 0.03 to about 1 kg/ha.
  • higher application rates e.g., four times the rates mentioned above may be employed.
  • the herbicides include, without limitation, for example: N- (phosphonomethyl)glycine ("glyphosate”); aryloxyalkanoic acids such as (2,4- dichlorophenoxy)acetic acid (“2,4-D"), (4-chloro-2-methylphenoxy)acetic acid (“MCPA”), (+/-)-2-(4chloro-2-methylphenoxy)propanoic acid (“MCPP”); ureas such as N,N-dimethyl-N'-[4-(l-methylethyl)phenyl]urea (“isoproturon”); imidazolinones such as 2-[4,5-dihydro-4-methyl-4-(l-methylethyl)-5-oxo-lH- imidazol-2-yl]-3-pyridinecarboxylic acid (“imazapyr”),
  • the other insecticides include, for example: organophosphate insecticides, such as chlorpyrifos, diazinon, dimethoate, malathion, parathion-methyl, and terbufos; pyrethroid insecticides, such as fenvalerate, deltamethrin, fenpropathrin, cyfluthrin, flucythrinate, alpha- cypermethrin, biphenthrin, resolved cyhalothrin, etofenprox, esfenvalerate, tralomehtrin, tefluthrin, cycloprothrin, betacyfluthrin, and acrinathrin; carbamate insecticides, such as aldecarb, carbaryl, carbofuran, and met
  • the fungicides include, for example: benzimidazole fungicides, such as benomyl, carbendazim, thiabendazole, and thiophanate-methyl; 1,2,4- triazole fungicides, such as epoxyconazole, cyproconazole, flusilazole, flutriafol, propiconazole, tebuconazole, triadimefon, and triadimenol; substituted anilide fungicides, such as metalaxyl, oxadixyl, procymidone, and vinclozolin; organophosphorus fungicides, such as fosetyl, iprobenfos, pyrazophos, edifenphos, and tolclofos-methyl; morpholine fungicides, such as fosetyl, iprobenfos, pyrazophos, edifenphos, and tolclofos-
  • the active pesticidal compounds of the present invention are used in combination with one or more of second compounds, e.g., with other pesticides such as nematicides
  • the nematicides include, for example: carbofuran, carbosulfan, turbufos, aldecarb, ethoprop, fenamphos, oxamyl, isazofos, cadusafos, and other nematicides.
  • the plant growth regulators include, for example: maleic hydrazide, chlormequat, ethephon, gibberellin, mepiquat, thidiazon, inabenfide, triaphenthenol, paclobutrazol, unaconazol, DCPA, prohexadione, trinexapac-ethyl, and other plant growth regulators.
  • Soil conditioners are materials which, when added to the soil, promote a variety of benefits for the efficacious growth of plants. Soil conditioners are used to reduce soil compaction, promote and increase effectiveness of drainage, improve soil permeability, promote optimum plant nutrient content in the soil, and promote better pesticide and fertilizer incorporation.
  • the soil conditioners include organic matter, such as humus, which promotes retention of cation plant nutrients in the soil; mixtures of cation nutrients, such as calcium, magnesium, potash, sodium, and hydrogen complexes; or microorganism compositions which promote conditions in the soil favorable to plant growth.
  • microorganism compositions include, for example, bacillus, pseudomonas, azotobacter, azospirillum, rhizobium, and soil-borne cyanobacteria.
  • Fertilizers are plant food supplements, which commonly contain nitrogen, phosphorus, and potassium.
  • the fertilizers include nitrogen fertilizers, such as ammonium sulfate, ammonium nitrate, and bone meal; phosphate fertilizers, such as superphosphate, triple superphosphate, ammonium sulfate, and diammonium sulfate; and potassium fertilizers, such as muriate of potash, potassium sulfate, and potassium nitrate, and other fertilizers.
  • nitrogen fertilizers such as ammonium sulfate, ammonium nitrate, and bone meal
  • phosphate fertilizers such as superphosphate, triple superphosphate, ammonium sulfate, and diammonium sulfate
  • potassium fertilizers such as muriate of potash, potassium sulfate, and potassium nitrate, and other fertilizers.
  • EXAMPLE 1 This example illustrates one protocol for the preparation of 6-chloro-3- methyl-2-[l-methyl(4-hydroquinolylidene)methyl]benzothiazolium iodide
  • the water and organic layers were separated, and the organic layer was in turn washed with one portion of water, one portion of an aqueous solution saturated with sodium bicarbonate, one portion of water, and one portion of an aqueous solution saturated with sodium chloride.
  • the organic layer was then dried with magnesium sulfate and filtered. The filtrate was concentrated under reduced pressure, yielding 1.2 grams of the subject compound.
  • Step B Synthesis of 6-chloro-3-methyl-2-methylthiobenzothiazolium iodide as an intermediate
  • a mixture of 1.2 grams (0.0056 mole) of 6-chloro-2- methylthiobenzothiazole, 3 mL (excess) of methyl iodide, and 2 mL of acetonitirile in a resealable tube was stirred and heated at 85 °C for about 18 hours, during which time a solid precipitate was formed. After this time, the tube containing the reaction mixture was unsealed and diethyl ether was added to complete precipitation of the solid. The mixture was filtered and the filter cake was washed with three portions of diethyl ether. The filter cake was air-dried, yielding 1.3 grams of the subject compound.
  • Step C Synthesis of 1,4-dimethylquinolinium iodide as an intermediate
  • Step D Synthesis of Compound 13 A mixture of 0.17 gram (0.0005 mole) of 6-chloro-3-methyl-2- methylthiobenzothiazolium iodide, 0.14 gram (0.0005 mole) of 1,4- dimethylquinolinium iodide, and 0.1 gram (0.001 mole) of triethylamine in 5 mL of ethanol was stirred at ambient temperature during which time a red solid precipitate was formed. The solid was collected by filtration, and was washed with two portions of ethanol and four portions of diethyl ether. The solid was then air- dried, yielding 0.13 gram of the subject compound. The NMR spectrum was consistent with the proposed structure.
  • EXAMPLE 2 This example illustrates one protocol for the preparation of 2-[7-chloro-l- ethyl(2-hydroquinolylidene)methyl]-6-ethoxy-3-methylbenzothiazolium iodide (Compound 110 in Table below)
  • Step A Synthesis of 6-ethoxy-2-methylthiobenzothiazole as an intermediate
  • a suspension of 10.0 grams (0.0473 mole) of 6-ethoxy-2- mercaptobenzothiazole in 25 mL of 95% ethanol was stirred and 5.0 grams (0.0500 mole) of triethylamine was added, which produced a dark colored solution.
  • the reaction mixture was heated to reflux where it stirred for 2.5 hours. After this time the reaction mixture was cooled to ambient temperature and filtered to collect a solid.
  • the solid was washed with two portions of diethyl ether and the combined washes and filtrate was concentrated under reduced pressure to an oil.
  • the oil was purified with column chromatography on silica gel using a mixture of 65% methylene chloride and 35% petroleum ether as eluant. The appropriate fractions were combined and concentrated under reduced pressure, yielding 10 grams of the subject compound.
  • the NMR spectrum was consistent with the proposed structure.
  • Step B Synthesis of 6-ethoxy-3-methyl-2-methylthiobenzothiazolium iodide as an intermediate
  • Step C Synthesis of 7-chloro-l-ethyl-2-methylquinolinium iodide as an intermediate
  • a solution of 2.0 grams (0.0115 mole) of 7- chloro-2-methylquinoline in 10 mL of acetonitirile was stirred, and 5 mL (excess) of ethyl iodide was added.
  • the reaction mixture was heated to reflux where it stirred for 2.5 hours; and then it was heated to 75 °C where it stirred for 18 hours. After this time, the reaction mixture was transferred to a resealable tube, and an additional 3 mL of ethyl iodide was added to the reaction mixture.
  • the tube was sealed, and the reaction mixture was heated to 85 °C where it stirred for eight hours, after which time it stood for about 60 hours at ambient temperature. After this time the tube was unsealed and an additional 3 mL of ethyl iodide was added. The tube was again sealed, and the reaction mixture was heated to 85 °C where it stirred for an additional 24 hours. After this time the reaction mixture was cooled to ambient temperature and the tube was unsealed. The reaction mixture was then diluted with diethyl ether and filtered to collect a solid. The filter cake was washed with two portions of diethyl ether and dried under reduced pressure, yielding 1.4 grams of the subject compound. The NMR spectrum was consistent with the proposed structure.
  • Step D Synthesis of Compound 110 This compound was prepared in a manner analogous to that set forth in
  • Step D of Example 1 by the reaction of 0.31 gram (0.0008 mole) of 6-ethoxy-3- methyl-2-methylthiobenzothiazolium iodide, 0.15 mL (excess) of triethylamine, and 0.30 gram (0.0009 mole) of 7-chloro-l-ethyl-2-methylquinolinium iodide in 9 mL of ethanol.
  • the yield of the subject compound was 0.39 gram.
  • the NMR spectrum was consistent with the proposed structure.
  • EXAMPLE 3 This example illustrates one protocol for the preparation of 2-[3-(3-ethyl-6- phenyl(3-hydrobenzothiazol-2-ylidene))prop-l-enyl]-3-ethyl-6- phenylbenzothiazolium ethylsulfate (Compound 201 in Table below)
  • Step A Synthesis of 3-ethyl-2-methyl-6-phenylbenzothiazolium ethylsulfate as an intermediate
  • a stirred mixture of 0.50 gram (0.0022 mole) of 2-methyl-6- phenylbenzothiazole and 0.34 gram (0.0022 mole) of diethyl sulfate was warmed to about 80 °C to 90 °C where it was stirred for 16 hours. After this time the mixture was cooled to ambient temperature and washed with a solution of about 10% to 20% methylene chloride in hexane to remove unreacted starting material. The resultant solid was dried, yielding about 0.45 gram of the subject compound.
  • the NMR spectrum was consistent with the proposed structure.
  • a mixture of 0.25 gram (0.0007 mole) of 3-ethyl-2-methyl-6- phenylbenzothiazolium ethyl sulfate, 0.10 gram (0.0007 mole) of triethyl orthoformate, and 0.25 mL of pyridine was sealed in a microwave reaction tube and reacted at about 150 °C to 175 °C for about 15 seconds, using a CEM Microwave Accelerated Reaction System (sold under the name and trademark of "The Discover System” by CEM Corporation, Matthews, NC 28106-0200), set at 300 Watts.
  • CEM Microwave Accelerated Reaction System sold under the name and trademark of "The Discover System” by CEM Corporation, Matthews, NC 28106-0200
  • reaction mixture was cooled and purified with column chromatography on silica gel using methylene chloride and mixtures of methylene chloride and methanol as eluants. The appropriate fractions were combined and concentrated under reduced pressure, yielding 0.13 gram of the subject compound.
  • the NMR spectrum was consistent with the proposed structure.
  • EXAMPLE 4 This example illustrates one protocol for the preparation of 2-[3-(5-ethoxy- 3-ethyl-6-methylbenzothiazol-2-yl)prop-2-enylidene]-5-ethoxy-3-ethyl-6-methyl- 3-hydrobenzothiazolium ethylsulfate (Compound 184 in Table below)
  • Step A Synthesis of 2,6-dimethyl-5-ethoxy-3-ethylbenzothiazolium ethyl sulfate as an intermediate This compound was prepared in a manner analogous to that set forth in Step A of Example 3, by the reaction of 3.0 grams (0.0145 mole) of 2,6-dimethyl-
  • Step B Synthesis of Compound 184 This compound was prepared in a manner analogous to that set forth in
  • Step B of Example 3 by the reaction of 0.25 gram (0.0007 mole) of 2,6-dimethyl-
  • EXAMPLE 5 This example illustrates one protocol for the preparation of 2-[3-(3-ethyl-6- phenyl(3-hydrobenzothiazol-2-ylidene))prop- 1 -enyl]-3-ethyl-6- phenylbenzothiazolium methyl sulfate (Compound 200 in Table below)
  • Step A of Example 3 by the reaction of 0.25 gram (0.0011 mole) of 2-methyl-6- phenylbenzothiazole and 0.16 mL (0.0106 mole) of dimethyl sulfate.
  • the yield of the subject compound was 0.37 gram.
  • the NMR spectrum was consistent with the proposed structure.
  • Step B Synthesis of Compound 200 This compound was prepared in a manner analogous to that set forth in
  • Step B of Example 3 by the reaction of 0.25 gram (0.0007 mole) of 2,3-dimethyl-
  • EXAMPLE 6 This example illustrates one protocol for the preparation of 2-[3-(3-ethyl-6- (4-fluorophenyl)(3-hydrobenzothiazol-2-ylidene))prop-l-enyl]-3-ethyl-6-(4- fluorophenyl)benzothiazolium ethylsulfate (Compound 210 in Table below)
  • Step B Synthesis of 3-ethyl-2-methyl-6-(4-fluorophenyl)benzothiazolium ethylsulfate as an intermediate
  • This compound was prepared in a manner analogous to that set forth in Step A of Example 3, by the reaction of 0.46 gram (0.0019 mole) of 6-(4- fluorophenyl)benzothiazole and 0.51 gram (0.0033 mole) of diethyl sulfate.
  • the yield of the subject compound was about 0.25 gram.
  • Step C Synthesis of Compound 210 This compound was prepared in a manner analogous to that set forth in
  • Step B of Example 3 by the reaction of 0.25 gram (0.0007 mole) of 3-ethyl-2- methyl-6-(4-fluorophenyl)benzothiazolium ethylsulfate, 0.12 gram (0.0008 mole) of triethyl orthoformate, and 0.38 mL of pyridine.
  • the yield of the subject compound was 0.09 gram.
  • the NMR spectrum was consistent with the proposed structure.
  • EXAMPLE 7 This example illustrates one protocol for the preparation of 2-[3-[6-(5- chloro(2-thienyl))-3-ethyl(3-hydrobenzothiazole-2-ylidene)]propen-l-enyl]-6-(5- chloro(2-thienyl))-3-ethylbenzothiazolium ethylsulfate (Compound 226 in Table below)
  • This compound was prepared in a manner analogous to that set forth in Step A of Example 6, by the reaction of 0.90 gram (0.0033 mole) of 6- iodobenzothiazole, 1.20 grams (0.0074 mole) of 5-chloro-2-thienylboronic acid, 1.56 grams (0.0147 mole) of sodium carbonate, 5.96 mL of water, and 3.6 mL of toluene in the presence of 0.57 gram (catalyst) of tetrakis(triphenylphosphine)palladium(0). The yield of the subject compound was 0.21 gram.
  • Step B Synthesis of 3-ethyl-2-methyl-6-(5-chloro-2- thienyl)benzothiazolium ethylsulfate as an intermediate
  • This compound was prepared in a manner analogous to that set forth in Step A of Example 3, by the reaction of 0.21 gram (0.0008 mole) of 6-(5-chloro-2- thienyl)benzothiazole and 0.15 gram (0.0010 mole) of diethyl sulfate. The yield of the subject compound was about 0.25 gram.
  • Step B of Example 3 by the reaction of 0.23 gram (0.0006 mole) of 3-ethyl-2- methyl-6-(5-chloro-2-thienyl)benzothiazolium ethylsulfate, 0.11 gram (0.0007 mole) of triethyl orthoformate, and 0.38 mL of pyridine.
  • the yield of the subject compound was 0.05 gram.
  • the NMR spectrum was consistent with the proposed structure.
  • EXAMPLE 8 This example illustrates one protocol for the preparation of 2[3-(3-ethyl(3- hydro7H,8H-l,4-dioxino[5,6-g]benzothiazol-2-ylidene))prop-l-enyl]-3-ethyl- 7H,8H-l,4-dioxino[5,6-g]benzothiazolium ethylsulfate (Compound 233 in Table below)
  • Step A Synthesis of l-(2H,3H-benzo[e]l,4-dioxan-6-ylamino)ethane-l- thione as an intermediate
  • Step B Synthesis of 2-methyl-l,4-dioxano[5,6-g]benzothiazole as an intermediate A stirred mixture of 47 grams (0.143 mole) of potassium ferricyanide in
  • Step C Synthesis of 2-methyl-l,4-dioxano[5,6-g]benzothiazolium ethylsulfate as an intermediate This compound was prepared in a manner analogous to that set forth in Step A of
  • Example 3 by the reaction of 0.60 gram (0.0029 mole) of 2-methyl-l,4- dioxano[5,6-g]benzothiazole and 0.54 gram (0.0035 mole) of diethyl sulfate in a minimum (less than 1 mL) of toluene.
  • the yield of subject compound was about
  • This compound was prepared in a manner analogous to that set forth in Step B of Example 3, by the reaction of 0.30 gram (0.0009 mole) of 2-methyl-l,4- dioxano[5,6-g]benzothiazolium ethylsulfate, 0.13 gram (0.0009 mole) of triethyl orthoformate, and 0.38 mL of pyridine. The yield of the subject compound was 0.13 gram. The NMR spectrum was consistent with the proposed structure.
  • Ar is: Ar s:
  • Ar is: Ar s:
  • R 45 and R 46 are hydrogen; and s is 2
  • R 45 and R 46 are hydrogen; and s is 1.
  • R 39 and R 32 is the same as R 40 :
  • R ; R ⁇ is the same as R , and is hydrogen; R is the same as R ; R is the same as R 39 ; and R 32 is the same as R 40 , and is hydrogen:
  • R 27 is the same as or different than R 27 ;
  • R 29 is the same as or different than R 37 ;
  • R 30 is the same as or different than R 38 ;
  • R 31 is the same as or different than R 39 ; and
  • R 32 is the same as or different than R 40 :
  • Ar is: Ar is:
  • R 1 , R 2 , R 4 , R 15 , R 16 , R 25 , R 26 are hydrogen;
  • R 57 is the same as R 61 , and are hydrogen;
  • R 58 is the same as R 62 , and are hydrogen;
  • R 60 is the same as R 64 , and are hydrogen:
  • R [ , R 2 , R 4 , R 10 , R 11 , R 20 _, R 21 are hydrogen;
  • R 49 is the same as R 53 , and are hhyyddrrooggeenn;
  • RR 5500 is the same as R 54 , and are hydrogen;
  • R 52 is the same as R 56 , and are hydrogen:
  • R 1 , R 2 , R 4 , R 10 , R 11 , R 25 , R 26 are hydrogen;
  • R 49 is the same as R 61 , and are hhyyddrrooggeenn;
  • RR 50 is the same as R , and are hydrogen;
  • R is the same as R , and are hydrogen:
  • Triethylamine salt An inner salt
  • Candidate pesticides were evaluated for insecticidal activity against the tobacco budworm (Heliothis virescens [Fabricius]) in a surface-treated diet test.
  • one mL of molten (65-70°C) wheat germ-based artificial diet was pipetted into each well of a four by six (24 well) multi-well plate (ID# 430345-15.5 mm dia. x 17.6 mm deep; Corning Costar Corp., One Alewife Center, Cambridge, MA 02140).
  • the diet was allowed to cool to ambient temperature before treatment with candidate insecticide.
  • solutions of the candidate insecticide were evaluated for insecticidal activity against the tobacco budworm (Heliothis virescens [Fabricius]) in a surface-treated diet test.
  • molten wheat germ-based artificial diet was pipetted into each well of a four by six (24 well) multi-well plate (ID# 430345-15.5 mm dia.
  • Robotic System (Packard Instrument Company, 800 Research Parkway, Meriden, CT 06450), in which the robot first diluted a standard 50 millimolar DMSO solution of candidate insecticide with a 1 : 1 water/acetone solution (V/V) in a ratio of 1:7 stock solution to water/acetone. The robot then pipetted 40 macOliters of the so-prepared solution onto the surface of the diet in each of three wells in the 24 multi-well plate. The process was repeated with solutions of seven other candidate insecticides.
  • V/V water/acetone solution
  • solutions of candidate insecticides may also be prepared for testing using a 96 channel Apricot Personal Pippetter-550 (Apricot Designs, Inc., 825S Primrose Avenue, Suite 1, Monrovia, CA 91016) in the same 1:7 ratio of 50 millimolar stock solution and 1:1 acetone/water. Once treated, the contents of the multi-well plate were allowed to dry, leaving 0.25 millimoles of candidate insecticide on the surface of the diet, or a concentration of 0.25 millimolar. Appropriate untreated controls containing only DMSO on the diet surface are also included in this test.
  • the test was established as described above using sub- multiples of the standard 50 millimolar DMSO solution of candidate insecticide.
  • the standard 50 millimolar solution was diluted by the robot with DMSO to give 5, 0.5, 0.05, 0.005, 0.0005 millimolar, or more dilute solutions of the candidate insecticide.
  • each well of the test plate was placed one second instar tobacco budworm larvea, each weighing approximately five milligrams. After the larvae were placed in each well, the plate was sealed with clear polyfilm adhesive tape. The tape over each well was perforated to ensure an adequate air supply to the insect. The plates were then held in a growth chamber at 25 °C and 60% relative humidity for five days (light 14 hours/day).
  • insecticidal activity for each rate of application of candidate insecticide was assessed as percent inhibition of insect weight when the weight of treated insects was compared to the weight of insects from untreated controls, and percent mortality when the number of dead insects were compared to the total number of insects infested.
  • Insecticidal activity data at selected rates of application are provided in
  • test compounds of formula I are identified by numbers that correspond to those in Table 1.

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Abstract

Cyanine dye derivatives provide unexpected pesticidal activity. These compounds are represented by formula (I): where Ar, Ar1, p, q, r, and R through R4, inclusively, are described. Preferred compounds of formula I include those where Ar is (II); and AR1 is (III); (IV); or (V); where X, Y, Z X2, Y2, Z2, R5, R17 through R27, inclusively, are described. Compositions comprising a pesticidally effective amount of at least one compound of formula I, and optionally, an effective amount of at least one of a second pesticidally active compound, with at least one pesticidally compatible carrier are also disclosed; along with methods of controlling pests comprising applying said compositions to a locus where pests are present or are expected to be present. The compositions of the present invention are of particular interest for their insecticidal and acaricidal activity.

Description

PESTICIDAL CYANINE DYE DERIVATIVES
FIELD OF THE INVENTION
The present invention generally relates to pesticidal compounds and their use in controlling pests. In particular, it pertains to compositions of pesticidal cyanine dye derivatives and pesticidally acceptable salts thereof, and methods for their use in controlling pests, such as insects and acarids.
BACKGROUND OF THE INVENTION
Cyanine dye compounds consisting of two heterocyclic groups, for example quinoline nuclei, connected by a chain of conjugated double bonds containing an odd number of carbon atoms are well known, for example, as set forth in THE CHEMISTRY OF HETEROCYCLIC COMPOUNDS, Volume 18; "The Cyanine Dyes And Related Compounds"; John Wiley & Sons (1964). In recent years, certain cyanine dyes have found utility in areas not related to the dye industry.
United States Patent 3,245,874 claims a method of controlling blight- causing bacteria on vegetation by treatment of the vegetation with a cyanine dye compound of the formula:
Figure imgf000002_0001
wherein Z' is a nitrogen-containing heterocyclic radical linked to the substituents Rt and X by the nitrogen atom of the heterocyclic radical, wherein Z" is a nitrogen-containing heterocyclic radical linked to the substituents R3 and X by the nitrogen atom of the heterocyclic radical, wherein R] is selected from lower alkyl, benzyl, and phenyl, wherein R2 is selected from hydrogen and lower alkyl, wherein R3 is selected from lower alkyl, benzyl, and phenyl, and wherein X is an acid anion, in an amount effective against the blight-causing bacteria.
Japanese Patent 67014918 discloses the use of compounds (A) and/or (B) as therepeutics for control of flatworms in pearl oysters; wherein the compounds have the following structures:
Figure imgf000003_0001
(A) (B)
Japanese Patent 6703198 discloses agricultural and horticultural fungicidal compositions containing one or more compounds of the following structure:
Figure imgf000003_0002
where Zi and Z2 are a group of atoms, forming with the N, rings of thiazoline, thiazole, benzthiazole, or quinoline optionally substituted; L is methine or N, at least one L being N; n is 0 or 1, Ri. and R2 are alkyl or aralkyl; and X is an inorganic residue.
French Patent 1,448,707 discloses an anthelmintic 2,4,5-trichlorophenol compound of the following structure:
Figure imgf000004_0001
There is a continuing demand for new pesticides that are safer, more effective, and less costly for control of certain harmful pests. Harmful pests include, without limitation, arthropods, such as certain insects and aracnids. Other harmful pests include certain fungi.
The insecticide market alone was estimated to be about seven billion dollars in the year 2000. In addition to their use in agriculture, insecticides play an important role in public health programs to control diseases, such as malaria and chagas, in the developing world. The largest insecticide markets are fruits, vegetables, cotton, rice, and corn. Control of insects is essential to achieve the yield and quality of crop demanded by growers and consumers. Termites are undisputedly the most destructive of all structural insects.
Soil-borne insects, such as termites are estimated to cause 1.5 billion dollars of damage to structures annually, and that an additional one billion dollars is spent on treatment. Since termites usually remain hidden within the wood in which they are feeding, in mud tubes, or in the soil, they typically wreak havoc undetected.
Fungicides prevent and cure fungal plant diseases, which affect crop yields and crop quality. The fungicide market was estimated at about six billion dollars in the year 2000, mainly for wheat in Europe, rice in Asia Pacific, and for fruits and vegetables in different regions of the world.
There is no disclosure or suggestion in the art that any of the cyanine dyes have broad pesticidal activity, especially insecticidal, acaricidal, or fungicidal activity. SUMMARY OF THE INVENTION
In accordance with the present invention, it has now been found that certain cyanine dye derivatives (hereinafter termed "compounds of formula I") and pesticidally acceptable salts thereof are useful as active ingredients in the pesticidal compositions and methods of this invention. The compounds of formula I are represented by the following general formula I:
Ar-(CR=CR1) -(CR2=CR3) -(CR4=)rArX
where Ar and Ar1 are independently selected from
Figure imgf000005_0001
B
Figure imgf000005_0002
D E F
Figure imgf000005_0003
G H where p, q, r, X, Xl1, v X2,
Figure imgf000006_0001
and R through R >28 , inclusively, are fully described below.
In a first embodiment, preferred pesticidal compositions of the present invention are comprised of the following compounds of formula I:
Ar-(CR=CR1) -(CR =CR3) -(CR^-Ar1
wherein Ar is and Ar1 is
Figure imgf000006_0002
E
where
X and Y are taken together with -CR 29 =CR ,3J0UCR-, 31 =CR ,32 - * to form a fused azole, where the asterisk denotes attachment at X; R18 and R19, or R19 and R20, or
R ,2/0u and R ,211 are taken together with
Figure imgf000006_0003
to form a fused azine, where the asterisk denotes attachment at R 18 , r R> 19 , or R ,20. ; and R ,23 and R are taken together with -*CR61=CR62CR63=CR64-, to form a fused azine where the asterisk denotes attachment at R ,23 , where p, q, r, R through R , inclusively; R 17 through R ,22 , inclusively; R >25 , R ,26 , R ,29y through R 32 , inclusively; and R ,5M3 through
R ,56 , inclusively, are fully described below.
In a second embodiment, preferred pesticidal compositions of the present invention are comprised of the following compounds of formula I: Ar-(CR=CR1)p-(CR =CR3)q-(CR4=)rAr1 I
wherein Ar is and Ar1 is
Figure imgf000007_0001
G
where
X and Y are taken together with -CR 2Z9 =CR ,3J0UCR >3J1 =CR >32 - to form a fused azole, where the asterisk denotes attachment at X; and X and Y are taken together with -CR37=CR38CR39=CR40-*, to form a fused azole, where the asterisk denotes attachment at X2; where p, q, r, Z, Z2, R through R5, inclusively; R27, R29 through R ~, inclusively; and R through R , inclusively, are fully described below.
The present invention is also directed to compositions containing a pesticidally effective amount of at least one of a compound of formula I, and optionally, an effective amount of at least one of a second compound, with at least one pesticidally compatible carrier.
The present invention is also directed to methods of controlling pests, where control is desired, which comprise applying a pesticidally effective amount of the above composition to a locus where pests are present or are expected to be present.
DETAILED DESCRIPTION OF THE INVENTION
One aspect of the present invention is pesticidal compositions comprising at least one of a pesticidally effective amount of a compound of formula I and at least one pesticidally compatible carrier therefor, wherein the compound of formula I is: Ar-(CR=CR1)p-(CR2=CR3)q-(CR4=)rAr1
where Ar and Ar1 are independently selected from
Figure imgf000008_0001
D E F
Figure imgf000008_0002
G H
p, q and r are independently selected from 0 or 1; where at least one of p, q or r is l;
R5, R6, R7, and R12 are independently selected from hydrogen; alkyl; haloalkyl; hydroxy alkyl; alkoxy alkyl; carboxylalkyl; aryl optionally substituted with at least one halogen or alkyl; arylalkyl; aryloxyalkyl; or sulfonatoalkyl, and may bear a negative charge resulting in an inner salt; and a separate ion is selected from sodium, potassium, lithium, calcium, magnesium, halide, sulfate, bisulfate, alkyl sulfate, alkyl sulfonate, haloalkylsulfonate, arylsulfonate, carbonate, bicarbonate, alkylcarboxylate, phosphate, hydrogen phosphate, dihydrogen phosphate, arylcarboxylate, trialkylammonium, or pyridinium;
X and Y; X1 and Y1; X2 and Y2; and X3 and Y3 are independently selected from hydrogen, halogen, cyano, alkyl, cycloalkyl, haloalkyl, alkoxy, alkylthio, alkylsulfinyl, alkylsulfonyl, aryl, aryl-substituted aryl, arylalkyl, aryloxy, arylalkoxy, arylthio, arylsulfonyl, arylsulfoxide, arylcarbonyl, or heteroaryl; or
-*0=CHCE =C-S- X and Y are taken together with ' ' to form a fused azole, where the asterisk denotes attachment at X; or
X and Y are taken together with -CR29=CR30CR31=CR32-* to form a fused azole, where the asterisk denotes attachment at X;
XI and Y1 are taken together with -CR33=CR34CR35=CR36-* to form a fused azole, where the asterisk denotes attachment at X1;
X2 and Y2 are taken together with -CR37=CR38CR39=CR40-*, to form a fused azole, where the asterisk denotes attachment at X2; and
X3 and Y3 are taken together with -CR41=CR42CR43=CR44-* to form a fused azole, where the astirisk denotes attachment at X3; where
R29 through R44, inclusively, are independently selected from hydrogen; halogen alkyl; haloalkyl; hydroxy; alkoxy; haloalkoxy; alkylthio; haloalkylthio alkylsulfonyl; haloalkylsulfonyl; alkylsulfinyl; haloalkylsulfinyl; cycloalkyl alkenyl; alkynyl; alkenyloxy; cyano; nitro; amino; alkylamino; dialkylamino alkylcarbonyloxy; alkoxycarbonyl; alkoxycarbonylalkyl; dialkylphosphono; or aryl, arylalkyl, arylalkoxy, aryloxy, arylthio, arylsulfinyl, arylsulfonyl, and heteroaryl wherein the aryl is optionally substituted with at least one halogen, alkyl, alkoxy, haloalkoxy, alkylsulfonyl, or aryl; or R29 and R30, or R30 and R31, or R31 and R32, or R33 and R34, or R34 and R35, or R35 and R36; or R37 and R38, or R38 and R39, or R39 and R40, or R41 and R42, or R42 and R43, or R43 and R44 are taken together with i) -C3C6-, or -C4H8- to form a fused azole; or ii) -SCH=CH-, or -CH=CHS- to form a fused azole; or iii) - OCH=CH-, or -CH=CHO- to form a fused azole; or iv) -CH=CHCH=CH- to form a fused azole; or v) -N(phenyl)CH=N(CH3)+-, or -N(CH3)+=CH- N(phenyl)- to form a fused azole; or vi) -N(phenyl)N=N(CH3)+-, or
-C=CHCH=C-CH2 - -N(CH3)+=N-N(phenyl)- to form a fused azole; or vii) ' ' to form a fused azole, or viii) -X4-(CR45R46)S-X4- to form a fused azole, where X4 is -O-, -S-, or -NR47; where R45 and R46 are independently selected from hydrogen, halogen, alkyl, or alkoxyalkyl; R is selected from hydrogen or alkyl; and s is 1-3; and where a ring formed from taking R29 and R30, R30 and R31, and R31 and R32 together; a ring formed from taking R33 and R34, R34 and R35, and R35 and R36 together; and a ring formed from taking R37 and R38, R38 and R39, R39 and R40 together; and a ring formed from taking R41 and R42, R42 and R43, and R43 and
R44 together are the same or different;
Z, Z1, Z2, and Z3 are independently selected from -O-, -S-, dialkylmethylene, or NR48, where R48 is selected from hydrogen, alkyl, alkoxyalkyl, haloalkyl, haloalkenyl, aryl, or sulfonatoalkyl, and may bear a negative charge resulting in an inner salt; and, when p, q and r arel ; R through R4, inclusively, are independently selected from hydrogen; halogen; alkyl; haloalkyl; cycloalkyl; hydroxyalkyl; alkoxy; alkylthio; cyano; aryl optionally substituted with carboxyl; amino; or arylalkyl; and when q is 0, and p and r are 1; R and R4 are optionally taken together with 1,2-cyclohexene to form a 3,4,5,6,7- pentahydroindene ring; or taken together with 3,4,5,6-tetrachloro-l,2-benzene to form a 4,5,6,7-tetrachloroindene ring; R17, R22, R27, and R28 are independently selected from hydrogen; alkyl; haloalkyl; alkoxyalkyl; or aryl optionally substituted with at least one halogen, haloalkoxy, carboxyl, (alkyl-substituted aryl-substituted)benzimidazol-5-yl; or sulfonatoalkyl, and may bear a negative charge resulting in an inner salt; and a separate ion is selected from sodium, potassium, lithium, calcium, magnesium, halide, sulfate, bisulfate, alkyl sulfate, alkyl sulfonate, haloalkylsulfonate, arylsulfonate, carbonate, bicarbonate, alkylcarboxylate, phosphate, hydrogen phosphate, dihydrogen phosphate, arylcarboxylate, trialkylammonium, or pyridinium; and when Ar is moiety A and Ar1 is moiety G, R5 and R27 are optionally taken together with C2-C4 alkylene, or (C1-C2)alkoxy(C1-C2)alkyl to form a fused ring;
R8 through R11, R13 through R16, R18 through R21, and R23 through R26, inclusively, are independently selected from hydrogen, halogen, alkyl, haloalkyl, alkoxy, haloalkoxy, aryl, or aryloxy; or R8 and R9, or R9 and R10, or R10 and R11 are taken together with - *CR49=CR50CR51=CR52- to form a fused azine, where the asterisk denotes attachment at R8, R9, or R10; or
R18 and R19, or R19 and R20, or R20 and R21 are taken together with - *CR53=CR54CR55=CR56- to form a fused azine, where the asterisk denotes attachment at R18, R19, or R20; or
R13 and R14 are taken together with -*CR57=CR58CR59=CR60-, to form a fused azine where the asterisk denotes attachment at R13; or
R23 and R24 ai-e taken together with -*CR61=CR62CR63=CR64-, to form a fused azine where the asterisk denotes attachment at R23; and when R13 and R14, or R23 and R24 are taken together; R15 and R16, and R25 and R26 may be taken together with -CH=CHCH=CH- to form a fused azine; where
R49 through R64, inclusively, are independently selected from hydrogen; halogen; alkyl; haloalkyl; alkoxy; haloalkoxy; or aryl optionally substituted with at least one halogen, alkyl, or alkoxy.
In a first embodiment, preferred pesticidal compositions of the present invention are comprised of the following compounds of formula I:
Ar-(CR=CR -(CR =CR3) -(CR =)_Ar
rein Ar is and Ar is
Figure imgf000012_0001
E
where p and q are 0, and r is 1;
R ,4 i •s selected from hydrogen, halogen, alkyl, alkoxy, or cyano;
R5 is selected from alkyl, haloalkyl, alkoxyalkyl; or sulfonatoalkyl, and may bear a negative charge resulting in an inner salt; and a separate ion is selected from halide, alkyl sulfate, alkyl sulfonate, haloalkylsulfonate, arylsulfonate, alkylcarboxylate, arylcarboxylate, trialkylammonium, pyridinium; sodium, potassium, calcium, or magnesium;
X and Y are taken together with -CR ,2Z9 =CRJUCR ,3J1 =CR ,3J2 -" to form a fused azole where the asterisk denotes attachment at X; where
R29, R30, R31, and R32 are independently selected from hydrogen; halogen; alkyl; hydroxy; alkoxy; alkylsulfonyl; nitro; aryl optionally substituted with at least one halogen, alkoxy, haloalkoxy, alkylsulfonyl, or aryl; aryloxy optionally substituted with at least one halogen, alkyl, or alkoxy; or heteroaryl optionally substituted with at least one halogen, alkyl, alkoxy, or aryl; or
R29 and R30, or R30 and R31 are taken together with -X4-(CR45R46)S-X4- to form a fused azole, where X4 is -O-, or -S-, R45 and R46 are independently selected from hydrogen, halogen, alkyl, or alkoxyalkyl, and s is 1-2; or
R31 and R32 are taken together with -CH=CHCH=CH- to form a fused azole; Z is selected from -O-; or -S-;
R17 and R22 are independently selected from hydrogen, alkyl, haloalkyl, alkoxyalkyl, or aryl;
R18 through R21, and R23 through R26, inclusively, are independently selected from hydrogen, halogen, alkyl, alkoxy, haloalkyl, haloalkoxy, aryl, or aryloxy; or
R18 and R19, or R19 and R20, or R20 and R21 are taken together with - *CR53=CR54CR55=CR56- to form a fused azine, where the asterisk denotes attachment at R18, R19, or R20; or
R23 and R24 are taken together with -*CR61=CR62CR63=CR64-, to form a fused azine where the asterisk denotes attachment at R23; where R53, R54, R55, R56, R61, R62, R63, and R64 are independently selected from hydrogen; halogen; alkyl; alkoxy; or haloalkyl.
Particularly preferred pesticidal compositions within the scope of a first embodiment of the present invention are comprised of compounds of formula I, wherein R4 is hydrogen; R5, R17, and R22 are independently selected from methyl, or ethyl; R29, R30, R31, and R32 are independently selected from hydrogen; halogen, methyl, ethyl, methoxy, ethoxy, or phenyl; X4 is -O-, R45 and R46 are hydrogen, and s is 2; R18 through R21 and R23 through R26, inclusively, are hydrogen, or, R18 and R19 are taken together with -*CR53=CR54CR55=CR56- to form a fused azine, where the asterisk denotes attachment at R18, where R53, R54, R55, R56, R61, R62, R63, and R64 are independently selected from hydrogen, chlorine, methyl, trifluoromethyl, or methoxy.
In a second embodiment, preferred pesticidal compositions of the present invention are comprised of the following compounds of formula I:
Ar-(CR=CR1) -(CR2=CR3) -(CR4=)rAr1
wherein Ar is and Ar1 is
Figure imgf000014_0001
H
where q is 0; and p and r are 1;
R, R1, and R4 are independently selected from hydrogen; alkyl, alkoxy, or aryl;
R5 and R27 are, independently selected from alkyl, haloalkyl, alkoxyalkyl; or sulfonatoalkyl, and may bear a negative charge resulting in an inner salt; and a separate ion is selected from halide, alkyl sulfate, alkyl sulfonate, haloalkylsulfonate, arylsulfonate, alkylcarboxylate, arylcarboxylate, trialkylammonium, pyridinium; sodium, potassium, calcium, or magnesium;
X and Y are taken together with -CR29=CR30CR31=CR32-" to form a fused azole, where the asterisk denotes attachment at X; and
X2 and Y2 are taken together with -CR37=CR38CR39=CR40-*, to form a fused azole, where the asterisk denotes attachment at X2; where R29, R30, R31, and R32, and R37, R38, R39, and R40 are independently selected from hydrogen; halogen; alkyl; haloalkyl; alkoxy; cyano; nitro; amino; alkylamino; aryl, aryloxy, or arylthio where the aryl is optionally substituted with at least one halogen, alkyl, haloalkyl, alkoxy, or haloalkoxy; or heteroaryl optionally substituted with at least one halogen, alkyl, or alkoxy; or
R29 and R30, or R30 and R31, or R37 and R38, or R38 and R39 are taken together with -X4-(CR45R46)S-X4- to form a fused azole, where X4 is -O-, or -S-, and R45 and R46 are independently selected from hydrogen, halogen, alkyl, or alkoxyalkyl, and s is 1-3; or R30 and R31, and R39 and R40 are taken together with -CH=CHCH=CH- to form a fused azole; and Z and Z are independently selected from -O-; or -S-.
Particularly preferred pesticidal compositions within the scope of a second embodiment of the present invention are comprised of compounds of formula I, wherein R, R , and R are hydrogen; R and R are independently selected from methyl, ethyl, or 2-methoxyethyl; R29, R30, R31, and R32, and R37, R38, R39, and R40 are independently selected from hydrogen; halogen; methyl; ethyl; propyl; butyl; methoxy; ethoxy; propoxy; butoxy; trifluoromethyl; phenyl optionally substituted with halogen; or thien-2-yl or furan-2-yl optionally substituted with halogen or methyl; or R29 and R30, and R37 and R38 are taken together with -X4-(CR45R46)S-X4- to form a fused azole, where X4 is -O-, R45 and R46 are hydrogen, and s is 2 or 3. Certain compounds within the scope of formula I, which find utility in the novel pesticidal compositions of the present invention, are new and novel compositions of matter. In addition, in certain cases the compounds within the scope of formula I may possess asymmetric centers, which can give rise to optical enantiomorphs and diastereomers. Compounds within the scope of formula I may exist in two or more forms, i.e., polymorphs, which are significantly different in physical and chemical properties. Compounds within the scope of formula I may also exist as tautomers, which are in equilibrium. Compounds within the scope of formula I may also possess acidic or basic moieties, which may allow for the formation of pesticidally acceptable salts or pesticidally acceptable metal complexes.
This invention includes the use of such enantiomorphs, polymorphs, tautomers, salts and metal complexes. Pesticidally acceptable salts and metal complexes include, without limitation, for example, ammonium salts, the salts of organic and inorganic acids, such as hydrochloric acid, sulfonic acid, ethanesulfonic acid, trifluoroacetic acid, methylbenzenesulfonic acid, phosphoric acid, gluconic acid, pamoic acid, and other acid salts, and the alkali metal and alkaline earth metal complexes with, for example, sodium, potassium, lithium, magnesium, calcium, and other metals.
The methods of the present invention are predicated on causing a pesticidal amount of a compound of formula I to be present within pests in order to kill or control the pest. It is within the scope of the present invention to cause a compound of formula I to be present within pests by contacting the pest with a derivative of that compound, which derivative is converted within the pest to a compound of formula I. This invention includes the use of such compounds, which can be referred to as pro-pesticides, for example, a pro-insecticide.
Another aspect of the present invention relates to compositions containing an pesticidally effective amount of at least one compound of formula I, and an effective amount of at least one second compound, with at least one pesticidally- compatible carrier therefor.
Another aspect of the present invention relates to methods of controlling pests by applying a pesticidally effective amount of a composition set forth above to a locus of, for example, crops such as, without limitation, cereals, cotton, vegetables, and fruits, or other areas where pests are present or are expected to be present.
In particular, the present invention relates to compositions containing an insecticidally effective amount of at least one compound of formula I and, optionally, an effective amount of at least one pesticidally active second compound, with at least one insecticidally compatible carrier therefore. The compositions of the present invention are satisfactorily effective for the control of various noxious insects and aracnids, examples of which are as follows:
Hemiptera: Delphacidae; such as Laodelphax stiatellus, Nilaparvata lugens and Sogatella furcifera; Deltocephalidae; such as Nephotettix cincticeps and Nephotettix virescens; Aphididae, Pentatomidae, Aleyrodidae, Coccidae, Tigidae, Psyllidae, as well as other Hemiptera. Lepidoptera: Pyralidae, such as Chilo suppressalis, Cnaphalocrocis medinalis, Ostrinia nubilalis, Parapediasia teterrella, Notarcha derogata and Plodia interpunctella; Noctuida, such as Spodoptera litura, Spodoptera exigua, Spotoptera littoralis, Pseudaletia separata, Mamestra brassicae, Agrotis ipsilon, Trichoplusia spp., Heliothis spp., Helicoverpa spp., and Earias spp.; Pieridae, such as Pieris rapae crucivora; Tortricidae, such as Adoxophyes spp.; Carposinidae, such as Grapholita molesta, Cydia pomonella, and Carposina niponensis; Lyonetiidae, such as Lyonetia spp.; Gracillariidae, such as Lithocolletis ringoniella; Lymantriidae, such as Lymantria spp., and Euproctis spp.; Yponomeutidae, such as Plutella xylostella; Gelechiidae, such as Pectinophora gossypiella; Arctiidae, such as Hyphantria cunea; Tineidae, such as Tinea translucens and Tineola bisselliella, as well as other Lepidoptera. Diptera: Culex, such as Culex pipiens pattens, and Culex tritaeniorhynchus; Aedes, such as Aedes aegypti and Aedes albopicyus; Anopheles, such as nophelinae sinensis; Chironomidae; Muscidae, such as Musca domestica and Musca stabulans; Calliphoridae; Sarcophagidae; Fannia canicularis; Anthomyiidae, such as Hylemya platura and Hylemya antiqua; Tryptetidae; Drosophilidae; Psychodidae; Tabanidae; Simuliidae; Stomoxyinae, Agromyzidae, as well as other Diptera. Coleoptera: Diabrotica. such as Diabrotica virgifera and Diabrotica undecimpunctata; Scarabaeidae, such as Anomala cuprea and Anomala rufocuprea; Curculionidae, such as Sitophilus oryzae, Lissorhoptrus oryzophilus, and Callosobruchus chinensis; Tenebrionidae, such as Tenebrio molitor and Tribolium castaneum; Chrysomelidae, such as Phyllotretra striolata and Aulacophora femoralis; Anobiidae; Epilachna spp., such as Epilachna vigintioctopunctata; Lyctidae; Bostrychidae; Cerambycidae; Paederusfuscipes, as well as other Coleoptera. Dictyoptera: Blattella germanica; Periplaneta fuliginosa; Periplaneta American; Periplaneta brunnea; Blatta orientalis, as well as other Dictyoptera. Thysanoptera: Thripa palmi; Thrips hawaiiensis, as well as other Thysanoptera. Hymenoptera: Formicidae; Vespidae; Bethylidae; Tenthredinidae, such as Athalia rosae japonensis, as well as other Hymenoptera. Orthoptera: Gryllotalpidae; Acrididae, as well as other Orthoptera. Siphonoptera: Purex irritans, as well as other Siphonoptera. Anoplura: Pediculus humanus capitis, Phthirus pubis, as well as other Anoplura. Isoptera (termites): Reticulitermes speratus, Coptotermes formosanus, as well as other Isoptera. Acarina: plant parasitic Tetranychidae, such as Tetranychus uriticae; Panonychus citri, Tetranychus cinnabarinus, and Panonychus ulmi; animal parasitic Ixodidae, such as Boophilus microphus, house dust mites, as well as other Acarina.
The present invention also includes the use of the compounds and compositions set forth herein for control of i) harmful arthropods other than insects and acarids, ii) non-agricultural insect species, for example, dry wood termites and subterranean termites, and iii) harmful fungi; as well as for use as pharmaceutical agents and compositions thereof.
As used in this specification and unless otherwise indicated the substituent terms "alkyl" and "alkoxy", used alone or as part of a larger moiety, includes straight or branched chains of at least one or two carbon atoms, as appropriate to the substituent, and preferably up to 12 carbon atoms, more preferably up to ten carbon atoms, most preferably up to seven carbon atoms. The term "alkenyl" and "alkynyl" used alone or as part of a larger moiety, includes straight or branched chains of at least two carbon atoms containing at least one carbon-carbon double bond or triple bond, and preferably up to 12 carbon atoms, more preferably up to ten carbon atoms, most preferably up to seven carbon atoms. The term "aryl" refers to an aromatic ring structure, including fused rings, having four to ten carbon atoms, for example, without limitation, phenyl or napthyl. The term "heteroaryl" refers to an aromatic ring structure, including fused rings, in which at least one of the atoms is other than carbon, for example, without limitation, sulfur, oxygen, or nitrogen. The term "azole" refers to a 5-membered ring containing a nitrogen atom where the 5-membered ring is optionally fused with one or more other rings. The term "azine" refers to a 6-membered ring containing a nitrogen atom where the 6- membered ring is optionally fused with one or more other rings. The term "DMF" refers to N,N-dimethylformamide. The term "THF" refers to tetrahydrofuran. The term "DMSO" refers to methyl sulfoxide. The term "halogen" or "halo" refers to fluorine, bromine, iodine, or chlorine. The term "ambient temperature" or "room temperature" often abbreviated as "RT", for example, in reference to a chemical reaction mixture temperature, refers to a temperature in the range of 20 °C to 30 °C. The term "pest" refers to any arthropod, such as insects and acarids, and to any fungi capable of causing damage to crops and dwellings utilized by man. The term "pesticide" or "pesticidal" therefore refers to a compound or a composition thereof that is an insecticide, an acaricide, or a fungicide that is insecticidally, acaricidally, or fungicidally active to control an insect, acarid, or fungi.
The compounds of formula I finding utility in the pesticidal compositions of the present invention can be synthesized by methods that are individually known to one skilled in the art from intermediate compounds readily available in commerce. Scheme 1 below illustrates a general procedure for synthesizing compounds of formula I, where, for example, Ar is structure A (Intermediate 2) and Ar1 is selected from structure E (Intermediate 3) or structure F (Intermediate 4). Scheme 2 below illustrates a general procedure for synthesizing compounds of formula I, where, for example, Ar is structure A (Intermediate 7) and Ar1 is structure G (derived from Intermediate 7):
Scheme 1
Figure imgf000020_0001
where W is where R5 is, for -CI or -SH example, CH3
Figure imgf000020_0002
where R , for example, is hydrogen
Figure imgf000020_0003
Compound of formula lb
a) where W is -CI; NaSCH3 / DMSO /RT; b) where W is -SH; CH3I / (C2H5)3N / 95% C2H5OH, wherein either method converts W to -SCH3; c) R5I /DMF / RT or R5I / CH3CN / 85 °C; yields a quaternary ammonium salt, 2; d) R17I / CH3CN / 75 °C or R2 I / RT; N-alkylates 3 and 4, respectively, affords 5 and 6; e) (C2H5)3N / C2H5OH / RT to reflux, yields Compounds of formulae la and lb. As depicted in Scheme 1, compounds of formula I, designated as compounds of formulae la and lb, were prepared by reacting (reaction a) a 2- halothiazole (Intermediate 1), such as 2,6-dichlorobenzothiazole, with, for example sodium thiomethoxide, to yield the corresponding 2-methylthiobenzothiazole derivative, or by reacting (reaction b) a 2-mercaptothiazole (Intermediate 1), such as 6-ethoxy-2-mercaptobenzothiazole, with an alkyl halide, for example methyl iodide, in an appropriate solvent, to yield the corresponding 2- methylthiobenzothiazole derivative. The 2-methylthiobenzothiazole derivatives were then N-alkylated (reaction c) with an alkyl halide, for example methyl iodide; to yield the corresponding N-alkyl quaternary ammonium salts (Intermediate 2), for example 6-chloro-3-methyl-2-methylthiobenzothiazolium iodide, or 6-ethoxy- 3-methyl-2-methylthiobenzothiazolium iodide. In order to provide reactants with which to react Intermediate 2 to provide compounds of formula la and lb, a substituted azine, such as 7-chloro-2-methylquinoline (Intermediate 3) was N- alkylated with an alkyl halide (reaction d), for example ethyl iodide, in a solvent at an elevated temperature, to yield the corresponding N-alkylated quinolinium salt 7- chloro-l-ethyl-2-methylquinolinium iodide (Intermediate 5). In a like manner a substituted azine, such as 4-methylquinoline (Intermediate 4), was N-alkylated in an alkyl halide solvent, for example methyl iodide, to yield the corresponding N- alkylated quinolinium salt 1,4-dimethylquinolinium iodide (Intermediate 6). Intermediate 2 was in turn reacted (reaction e) with Intermediate 6 in the presence of a base, such as triethylamine, to yield compounds of formula la. In a like manner Intermediate 2 was reacted with Intermediate 5, to afford compounds of formula lb.
Scheme 2
+ an R5-containing anion
Figure imgf000022_0001
Figure imgf000022_0002
+ an R5-containing anion
Compound of formula lc where X = X2; Y = Y2; Z = Z2; R, R1 and R4 are, for example hydrogen; R5 = R27; q is 0, and p and r are 1 f) where R5 is, for example, -C2H5; (C2H50)2S02 / 80 °C to 90 °C; yields a quaternary ammonium salt, 8; g) (C2H50)3CH / pyridine / 150 °C to 175 °C in microwave reactor set at 300 watts; yields Compounds of formula lc
As depicted in Scheme 2, compounds of formula I, designated as compounds of formula lc, were prepared by N-alkylating (reaction f) an appropriately substituted 2-alkylthiazole (Intermediate 7), such as 2-methyl-6- phenylbenzothiazole, with, for example diethyl sulfate, to yield the corresponding quaternary ammonium salt 3-ethyl-2-methyl-6-phenylbenzothiazolium ethylsulfate (Intermediate 8). Intermediate 8 was in turn coupled with itself through, for example a three-carbon chain bridge, by the reaction of Intermediate 8 (reaction g) with triethyl orthofόrmate under basic conditions at elevated temperature using a microwave reactor, to yield compounds of formula lc. One skilled in the art will of course recognize that the formulation and mode of application of a toxicant may affect the activity of the material in a given application. Thus, for agricultural use the present pesticidal compounds may be formulated as a granular of relatively large particle size (for example, 8/16 or 4/8 US Mesh), as water-soluble or water-dispersible granules, as powdery dusts, as wettable powders, as emulsifiable concentrates, as aqueous emulsions, as solutions, or as any of other known types of agriculturally-useful formulations, depending on the desired mode of application. It is to be understood that the amounts specified in this specification are intended to be approximate only, as if the word "about" were placed in front of the amounts specified.
These pesticidal compositions may be applied either as water-diluted sprays, or dusts, or granules to the areas in which suppression of insects is desired. These formulations may contain as little as 0.1%, 0.2% or 0.5% to as much as 95% or more by weight of active ingredient. Dusts are free flowing admixtures of the active ingredient with finely divided solids such as talc, natural clays, kieselguhr, flours such as walnut shell and cottonseed flours, and other organic and inorganic solids which act as dispersants and carriers for the toxicant; these finely divided solids have an average particle size of less than about 50 microns. A typical dust formulation useful herein is one containing 1.0 part or less of the insecticidal compound and 99.0 parts of talc.
Wettable powders, also useful formulations for pesticides, are in the form of finely divided particles that disperse readily in water or other dispersant. The wettable powder is ultimately applied to the locus where insect control is needed either as a dry dust or as an emulsion in water or other liquid. Typical carriers for wettable powders include Fuller's earth, kaolin clays, silicas, and other highly absorbent, readily wet inorganic diluents. Wettable powders normally are prepared to contain about 5-80% of active ingredient, depending on the absorbency of the carrier, and usually also contain a small amount of a wetting, dispersing or emulsifying agent to facilitate dispersion. For example, a useful wettable powder formulation contains 80.0 parts of the insecticidal compound, 17.9 parts of Palmetto clay, and 1.0 part of sodium lignosulfonate and 0.3 part of sulfonated aliphatic polyester as wetting agents. Additional wetting agent and/or oil will frequently be added to a tank mix for to facilitate dispersion on the foliage of the plant.
Other useful formulations for pesticidal applications are emulsifiable concentrates (ECs) which are homogeneous liquid compositions dispersible in water or other dispersant, and may consist entirely of the pesticidal compound and a liquid or solid emulsifying agent, or may also contain a liquid carrier, such as xylene, heavy aromatic naphthas, isphorone, or other non- volatile organic solvents. For pesticidal application these concentrates are dispersed in water or other liquid carrier and normally applied as a spray to the area to be treated. The percentage by weight of the essential active ingredient may vary according to the manner in which the composition is to be applied, but in general comprises 0.5 to 95% of active ingredient by weight of the pesticidal composition.
Flowable formulations are similar to ECs, except that the active ingredient is suspended in a liquid carrier, generally water. Flowables, like ECs, may include a small amount of a surfactant, and will typically contain active ingredients in the range of 0.5 to 95%, frequently from 10 to 50%, by weight of the composition. For application, flowables may be diluted in water or other liquid vehicle, and are normally applied as a spray to the area to be treated. Typical wetting, dispersing or emulsifying agents used in pesticidal formulations include, but are not limited to, the alkyl and alkylaryl sulfonates and sulfates and their sodium salts; alkylaryl polyether alcohols; sulfated higher alcohols; polyethylene oxides; sulfonated animal and vegetable oils; sulfonated petroleum oils; fatty acid esters of polyhydric alcohols and the ethylene oxide addition products of such esters; and the addition product of long-chain mercaptans and ethylene oxide. Many other types of useful surface-active agents are available in commerce. Surface-active agents, when used, normally comprise 1 to 15% by weight of the composition.
Other useful formulations include suspensions of the active ingredient in a relatively non-volatile solvent such as water, corn oil, kerosene, propylene glycol, or other suitable solvents. Still other useful formulations for pesticidal applications include simple solutions of the active ingredient in a solvent in which it is completely soluble at the desired concentration, such as acetone, alkylated naphthalenes, xylene, or other organic solvents. Granular formulations, wherein the toxicant is carried on relative coarse particles, are of particular utility for aerial distribution or for penetration of cover crop canopy. Pressurized sprays, typically aerosols wherein the active ingredient is dispersed in finely divided form as a result of vaporization of a low- boiling dispersant solvent carrier may also be used. Water-soluble or water- dispersible granules are free flowing, non-dusty, and readily water-soluble or water-miscible. In use by the farmer on the field, the granular formulations, emulsifiable concentrates, flowable concentrates, aqueous emulsions, solutions, etc., may be diluted with water to give a concentration of active ingredient in the range of say 0.1% or 0.2% to 1.5% or 2%.
The active pesticidal compounds of this invention may be formulated and/or applied with one or more second compounds. Second compounds include, but are not limited to, other pesticides, plant growth regulators, fertilizers, soil conditioners, or other agricultural chemicals. In applying an active compound of this invention, whether formulated alone or with other agricultural chemicals, an effective amount and concentration of the active compound is of course employed; the amount may vary in the range of, e.g. about 0.001 to about 3 kg/ha, preferably about 0.03 to about 1 kg/ha. For field use, where there are losses of insecticide, higher application rates (e.g., four times the rates mentioned above) may be employed.
When the active pesticidal compounds of the present invention are used in combination with one or more of second compounds, e.g., with other pesticides such as herbicides, the herbicides include, without limitation, for example: N- (phosphonomethyl)glycine ("glyphosate"); aryloxyalkanoic acids such as (2,4- dichlorophenoxy)acetic acid ("2,4-D"), (4-chloro-2-methylphenoxy)acetic acid ("MCPA"), (+/-)-2-(4chloro-2-methylphenoxy)propanoic acid ("MCPP"); ureas such as N,N-dimethyl-N'-[4-(l-methylethyl)phenyl]urea ("isoproturon"); imidazolinones such as 2-[4,5-dihydro-4-methyl-4-(l-methylethyl)-5-oxo-lH- imidazol-2-yl]-3-pyridinecarboxylic acid ("imazapyr"), a reaction product comprising (+/-)-2-[4,5-dihydro-4-methyl-4-(l-methylethyl)-5-oxo-lH-imidazol-2- yl]-4-methylbenzoic acid and (+/-)2-[4,5-dihydro-4-methyl-4-(l-methylethyl)-5- oxo-lH-imidazol-2-yl]-5-methylbenzoic acid ("imazamethabenz"), (+/-)-2-[4,5- dihydro-4-methyl-4-(l-methylethyl)-5-oxo-lH-imidazol-2-yl]-5-ethyl-3- pyridinecarboxylic acid ("imazethapyr"), and (+/-)-2-[4,5-dihydro-4-methyl-4-(l- methylethyl)-5-oxo-lH-imidazol-2-yl]-3-quinolinecarboxylic acid ("imazaquin"); diphenyl ethers such as 5-[2-chloro-4-(trifluoromethyl)phenoxy]-2-nitrobenzoic acid ("acifluorfen"), methyl 5-(2,4-dichlorophenoxy)-2-nitrobenzoate ("bifenox"), and 5-[2-chloro-4-(trifluoromethyl)phenoxy]-N-(methylsulfonyl)-2- nitrobenzamide ("fomasafen"); hydroxybenzonitriles such as 4-hydroxy-3,5- diiodobenzonitrile ("ioxynil") and 3,5-dibromo-4-hydroxybenzonitrile ("bromoxynil"); sulfonylureas such as 2-[[[[(4chloro-6-methoxy-2- pyrimidinyl) amino] earbonyl] amino] sulfonyljbenzoic acid ("chlorimuron"), 2- chloro-N-[ [(4-methoxy-6-methyl- 1 ,3 ,5-triazin-2- yl)amino]carbonyl]benzenesulfonamide (achlorsulfuron"), 2-[[[[[(4,6-dimethoxy- 2-pyrimidinyl)amino]carbonyl]amino]sufonyl]methyl]benzoic acid
("bensulfuron"), 2-[[[[(4,6-dimethoxy-2-pyrimidinyl)amino]carb- onyl] amino] sulf onyl] - 1 -methy- 1 H-pyrazol-4-carboxylic acid ( ' 'pyrazosulf uron " ) , 3-[[[[(4-methoxy-6-methyl-l,3,5-triazin-2-yl)amino]carbonyl]amino]sulfonyl]-2- thiophenecarboxylic acid ("thifensulfuron"), and 2-(2-chloroethoxy)-N[[(4- methoxy-6-methyl-l,3,5-triazin-2-yl)amino]carbonyl]benzenesulfonamide ("triasulfuron"); 2-(4-aryloxyphenoxy)alkanoic acids such as (+/-)-2[4-[(6-chloro- 2-benzoxazolyl)oxy]phenoxy]propanoic acid (fenoxaprop"), (+/-)-2-[4[[5- (trifluoromethyl)-2-pyridinyl]oxy]ρhenoxy]propanoic acid ("fluazifop"), (+/-)-2- [4-(6chloro-2-quinoxalinyl)oxy]phenoxy]propanoic acid ("quizalofop"), and (+ /-) -2-[(2,4-dichlorophenoxy)phenoxy]propanoic acid ("diclofop"); benzothiadiazinones such as 3-(l-methylethyl)-lH-l,2,3-benzothiadiazin-4(3H)- one-2,2-dioxide ("bentazone"); 2-chloroacetanilides such as N-(butoxymethyl)-2- chloro-N-(2,6-diethylphenyl)acetamide ("butachlor"), 2-chloro-N-(2-ethyl-6- methylphenyl)-N-(2-methoxy-l-methylethyl)acetamide ("metolachlor"), 2-chloro- N-(ethoxymethyl)-N-(2-ethyl-6-methylphenyl)acetamide ("acetochlor"), and (RS)- 2-chloro-N-(2,4-dimethyl-3-thienyl)-N-(2-methoxy-l-methylethyl)acetamide ("dimethenamide"); arenecarboxylic acids such as 3,6-dichloro-2-methoxybenzoic acid ("dicamba"); pyridyloxyacetic acids such as [(4-amino-3,5-dichloro-6-fluoiO- 2-pyridinyl)oxy] acetic acid ("fluroxypyr"), and other herbicides.
When the active pesticidal compounds of the present invention are used in combination with one or more of second compounds, e.g., with other pesticides such as other insecticides, the other insecticides include, for example: organophosphate insecticides, such as chlorpyrifos, diazinon, dimethoate, malathion, parathion-methyl, and terbufos; pyrethroid insecticides, such as fenvalerate, deltamethrin, fenpropathrin, cyfluthrin, flucythrinate, alpha- cypermethrin, biphenthrin, resolved cyhalothrin, etofenprox, esfenvalerate, tralomehtrin, tefluthrin, cycloprothrin, betacyfluthrin, and acrinathrin; carbamate insecticides, such as aldecarb, carbaryl, carbofuran, and methomyl; organochlorine insecticides, such as endosulfan, endrin, heptachlor, and lindane; benzoylurea insecticides, such as diflubenuron, triflumuron, teflubenzuron, chlorfluazuron, flucycloxuron, hexaflumuron, flufenoxuron, and lufenuron; and other insecticides, such as amitraz, clofentezine, fenpyroximate, hexythiazox, and imidacloprid.
When the active pesticidal compounds of the present invention are used in combination with one or more of second compounds, e.g., with other pesticides such as fungicides, the fungicides include, for example: benzimidazole fungicides, such as benomyl, carbendazim, thiabendazole, and thiophanate-methyl; 1,2,4- triazole fungicides, such as epoxyconazole, cyproconazole, flusilazole, flutriafol, propiconazole, tebuconazole, triadimefon, and triadimenol; substituted anilide fungicides, such as metalaxyl, oxadixyl, procymidone, and vinclozolin; organophosphorus fungicides, such as fosetyl, iprobenfos, pyrazophos, edifenphos, and tolclofos-methyl; morpholine fungicides, such as fenpropimorph, tridemorph, and dodemorph; other systemic fungicides, such as fenarimol, imazalil, prochloraz, tricyclazole, and triforine; dithiocarbamate fungicides, such as mancozeb, maneb, propineb, zineb, and ziram; non-systemic fungicides, such as chlorothalonil, dichlofluanid, dithianon, and iprodione, captan, dinocap, dodine, fluazinam, gluazatine, PCNB, pencycuron, quintozene, tricylamide, and validamycin; inorganic fungicides, such as copper and sulphur products, and other fungicides. When the active pesticidal compounds of the present invention are used in combination with one or more of second compounds, e.g., with other pesticides such as nematicides, the nematicides include, for example: carbofuran, carbosulfan, turbufos, aldecarb, ethoprop, fenamphos, oxamyl, isazofos, cadusafos, and other nematicides.
When the active pesticidal compounds of the present invention are used in combination with one or more of second compounds, e.g., with other materials such as plant growth regulators, the plant growth regulators include, for example: maleic hydrazide, chlormequat, ethephon, gibberellin, mepiquat, thidiazon, inabenfide, triaphenthenol, paclobutrazol, unaconazol, DCPA, prohexadione, trinexapac-ethyl, and other plant growth regulators.
Soil conditioners are materials which, when added to the soil, promote a variety of benefits for the efficacious growth of plants. Soil conditioners are used to reduce soil compaction, promote and increase effectiveness of drainage, improve soil permeability, promote optimum plant nutrient content in the soil, and promote better pesticide and fertilizer incorporation. When the active pesticidal compounds of the present invention are used in combination with one or more of second compounds, e.g., with other materials such as soil conditioners, the soil conditioners include organic matter, such as humus, which promotes retention of cation plant nutrients in the soil; mixtures of cation nutrients, such as calcium, magnesium, potash, sodium, and hydrogen complexes; or microorganism compositions which promote conditions in the soil favorable to plant growth. Such microorganism compositions include, for example, bacillus, pseudomonas, azotobacter, azospirillum, rhizobium, and soil-borne cyanobacteria. Fertilizers are plant food supplements, which commonly contain nitrogen, phosphorus, and potassium. When the active pesticidal compounds of the present invention are used in combination with one or more of second compounds, e.g., with other materials such as fertilizers, the fertilizers include nitrogen fertilizers, such as ammonium sulfate, ammonium nitrate, and bone meal; phosphate fertilizers, such as superphosphate, triple superphosphate, ammonium sulfate, and diammonium sulfate; and potassium fertilizers, such as muriate of potash, potassium sulfate, and potassium nitrate, and other fertilizers. The following examples further illustrate the present invention, but, of course, should not be construed as in any way limiting its scope. The examples are organized to present protocols for the synthesis of the compounds of formula I of the present invention, set forth a list of such synthesized species, and set forth certain biological data indicating the efficacy of such compounds.
EXAMPLE 1 This example illustrates one protocol for the preparation of 6-chloro-3- methyl-2-[l-methyl(4-hydroquinolylidene)methyl]benzothiazolium iodide
(Compound 13 in table below)
Step A Synthesis of 6-chloro-2-methylthiobenzothiazole as an intermediate
A solution of 1.0 gram (0.0049 mole) of 2,6-dichlorobenzothiazole in 7 mL of methyl sulfoxide was stirred at ambient temperature, and 0.7 gram (0.0100 mole) of sodium thioinethoxide was added in one portion, causing an exothermic reaction. Upon completion of addition, the reaction mixture was stirred for about three hours as it cooled to ambient temperature. The reaction mixture was then partitioned in diethyl ether and water, and the mixture was made acidic to a pH of about 1 with aqueous 10% hydrochloric acid. The water and organic layers were separated, and the organic layer was in turn washed with one portion of water, one portion of an aqueous solution saturated with sodium bicarbonate, one portion of water, and one portion of an aqueous solution saturated with sodium chloride. The organic layer was then dried with magnesium sulfate and filtered. The filtrate was concentrated under reduced pressure, yielding 1.2 grams of the subject compound.
Step B Synthesis of 6-chloro-3-methyl-2-methylthiobenzothiazolium iodide as an intermediate A mixture of 1.2 grams (0.0056 mole) of 6-chloro-2- methylthiobenzothiazole, 3 mL (excess) of methyl iodide, and 2 mL of acetonitirile in a resealable tube was stirred and heated at 85 °C for about 18 hours, during which time a solid precipitate was formed. After this time, the tube containing the reaction mixture was unsealed and diethyl ether was added to complete precipitation of the solid. The mixture was filtered and the filter cake was washed with three portions of diethyl ether. The filter cake was air-dried, yielding 1.3 grams of the subject compound. Step C Synthesis of 1,4-dimethylquinolinium iodide as an intermediate
A mixture of 5.4 grams (0.038 mole) of 4-methylquinoline in 10 mL of methyl iodide was stirred at ambient temperature during which time a solid precipitate was formed. The mixture was slurried in diethyl ether, and the solid was collected by filtration. The filter cake was washed with three portions of diethyl ether and air-dried, yielding 10 grams of the subject compound.
Step D Synthesis of Compound 13 A mixture of 0.17 gram (0.0005 mole) of 6-chloro-3-methyl-2- methylthiobenzothiazolium iodide, 0.14 gram (0.0005 mole) of 1,4- dimethylquinolinium iodide, and 0.1 gram (0.001 mole) of triethylamine in 5 mL of ethanol was stirred at ambient temperature during which time a red solid precipitate was formed. The solid was collected by filtration, and was washed with two portions of ethanol and four portions of diethyl ether. The solid was then air- dried, yielding 0.13 gram of the subject compound. The NMR spectrum was consistent with the proposed structure.
EXAMPLE 2 This example illustrates one protocol for the preparation of 2-[7-chloro-l- ethyl(2-hydroquinolylidene)methyl]-6-ethoxy-3-methylbenzothiazolium iodide (Compound 110 in Table below)
Step A Synthesis of 6-ethoxy-2-methylthiobenzothiazole as an intermediate A suspension of 10.0 grams (0.0473 mole) of 6-ethoxy-2- mercaptobenzothiazole in 25 mL of 95% ethanol was stirred and 5.0 grams (0.0500 mole) of triethylamine was added, which produced a dark colored solution. To this was added 7.4 grams (0.0520 mole) of methyl iodide, which caused an exothermic reaction. Upon completion of addition, the reaction mixture was heated to reflux where it stirred for 2.5 hours. After this time the reaction mixture was cooled to ambient temperature and filtered to collect a solid. The solid was washed with two portions of diethyl ether and the combined washes and filtrate was concentrated under reduced pressure to an oil. The oil was purified with column chromatography on silica gel using a mixture of 65% methylene chloride and 35% petroleum ether as eluant. The appropriate fractions were combined and concentrated under reduced pressure, yielding 10 grams of the subject compound. The NMR spectrum was consistent with the proposed structure.
Step B Synthesis of 6-ethoxy-3-methyl-2-methylthiobenzothiazolium iodide as an intermediate A mixture of 4.5 grams (0.0200 mole) of 6-ethoxy-2- methylthiobenzothiazole, 5 mL (excess) of methyl iodide, and 10 mL of acetonitirile was stirred at ambient temperature during a 68 hour period, during which time a solid precipitate formed. After this time, the reaction mixture was diluted with diethyl ether and filtered to collect the solid. The filter cake was washed with two portions of diethyl ether and dried under reduced pressure, yielding 2.2 grams of the subject compound. The NMR spectrum was consistent with the proposed structure.
Step C ' Synthesis of 7-chloro-l-ethyl-2-methylquinolinium iodide as an intermediate Under a nitrogen atmosphere, a solution of 2.0 grams (0.0115 mole) of 7- chloro-2-methylquinoline in 10 mL of acetonitirile was stirred, and 5 mL (excess) of ethyl iodide was added. The reaction mixture was heated to reflux where it stirred for 2.5 hours; and then it was heated to 75 °C where it stirred for 18 hours. After this time, the reaction mixture was transferred to a resealable tube, and an additional 3 mL of ethyl iodide was added to the reaction mixture. The tube was sealed, and the reaction mixture was heated to 85 °C where it stirred for eight hours, after which time it stood for about 60 hours at ambient temperature. After this time the tube was unsealed and an additional 3 mL of ethyl iodide was added. The tube was again sealed, and the reaction mixture was heated to 85 °C where it stirred for an additional 24 hours. After this time the reaction mixture was cooled to ambient temperature and the tube was unsealed. The reaction mixture was then diluted with diethyl ether and filtered to collect a solid. The filter cake was washed with two portions of diethyl ether and dried under reduced pressure, yielding 1.4 grams of the subject compound. The NMR spectrum was consistent with the proposed structure.
Step D Synthesis of Compound 110 This compound was prepared in a manner analogous to that set forth in
Step D of Example 1, by the reaction of 0.31 gram (0.0008 mole) of 6-ethoxy-3- methyl-2-methylthiobenzothiazolium iodide, 0.15 mL (excess) of triethylamine, and 0.30 gram (0.0009 mole) of 7-chloro-l-ethyl-2-methylquinolinium iodide in 9 mL of ethanol. The yield of the subject compound was 0.39 gram. The NMR spectrum was consistent with the proposed structure.
EXAMPLE 3 This example illustrates one protocol for the preparation of 2-[3-(3-ethyl-6- phenyl(3-hydrobenzothiazol-2-ylidene))prop-l-enyl]-3-ethyl-6- phenylbenzothiazolium ethylsulfate (Compound 201 in Table below)
Step A Synthesis of 3-ethyl-2-methyl-6-phenylbenzothiazolium ethylsulfate as an intermediate A stirred mixture of 0.50 gram (0.0022 mole) of 2-methyl-6- phenylbenzothiazole and 0.34 gram (0.0022 mole) of diethyl sulfate was warmed to about 80 °C to 90 °C where it was stirred for 16 hours. After this time the mixture was cooled to ambient temperature and washed with a solution of about 10% to 20% methylene chloride in hexane to remove unreacted starting material. The resultant solid was dried, yielding about 0.45 gram of the subject compound. The NMR spectrum was consistent with the proposed structure.
Step B Synthesis of Compound 201
A mixture of 0.25 gram (0.0007 mole) of 3-ethyl-2-methyl-6- phenylbenzothiazolium ethyl sulfate, 0.10 gram (0.0007 mole) of triethyl orthoformate, and 0.25 mL of pyridine was sealed in a microwave reaction tube and reacted at about 150 °C to 175 °C for about 15 seconds, using a CEM Microwave Accelerated Reaction System (sold under the name and trademark of "The Discover System" by CEM Corporation, Matthews, NC 28106-0200), set at 300 Watts. After this time, the reaction mixture was cooled and purified with column chromatography on silica gel using methylene chloride and mixtures of methylene chloride and methanol as eluants. The appropriate fractions were combined and concentrated under reduced pressure, yielding 0.13 gram of the subject compound. The NMR spectrum was consistent with the proposed structure.
EXAMPLE 4 This example illustrates one protocol for the preparation of 2-[3-(5-ethoxy- 3-ethyl-6-methylbenzothiazol-2-yl)prop-2-enylidene]-5-ethoxy-3-ethyl-6-methyl- 3-hydrobenzothiazolium ethylsulfate (Compound 184 in Table below)
Step A Synthesis of 2,6-dimethyl-5-ethoxy-3-ethylbenzothiazolium ethyl sulfate as an intermediate This compound was prepared in a manner analogous to that set forth in Step A of Example 3, by the reaction of 3.0 grams (0.0145 mole) of 2,6-dimethyl-
5-ethoxybenzothiazole and 2.7 grams (0.0174 mole) of diethyl sulfate. The yield of the subject compound was 4.3 grams.
Step B Synthesis of Compound 184 This compound was prepared in a manner analogous to that set forth in
Step B of Example 3, by the reaction of 0.25 gram (0.0007 mole) of 2,6-dimethyl-
5-ethoxy-3-ethylbenzothiazolium ethylsulfate, 0.15 gram (0.0011 mole) of triethyl orthoformate, and 0.25 mL of pyridine. The yield of the subject compound was
0.12 gram. The NMR spectrum was consistent with the proposed structure.
EXAMPLE 5 This example illustrates one protocol for the preparation of 2-[3-(3-ethyl-6- phenyl(3-hydrobenzothiazol-2-ylidene))prop- 1 -enyl]-3-ethyl-6- phenylbenzothiazolium methyl sulfate (Compound 200 in Table below)
Step A Synthesis of 2,3-dimethyl-6-phenylbenzothiazolium methylsulfate as an intermediate This compound was prepared in a manner analogous to that set forth in
Step A of Example 3, by the reaction of 0.25 gram (0.0011 mole) of 2-methyl-6- phenylbenzothiazole and 0.16 mL (0.0106 mole) of dimethyl sulfate. The yield of the subject compound was 0.37 gram. The NMR spectrum was consistent with the proposed structure.
Step B Synthesis of Compound 200 This compound was prepared in a manner analogous to that set forth in
Step B of Example 3, by the reaction of 0.25 gram (0.0007 mole) of 2,3-dimethyl-
6-phenylbenzothiazolium methylsulfate, 0.13 gram (0.0009 mole) of triethyl orthoformate, and 0.38 mL of pyridine. The yield of the subject compound was
0.17 gram. The NMR spectrum was consistent with the proposed structure.
EXAMPLE 6 This example illustrates one protocol for the preparation of 2-[3-(3-ethyl-6- (4-fluorophenyl)(3-hydrobenzothiazol-2-ylidene))prop-l-enyl]-3-ethyl-6-(4- fluorophenyl)benzothiazolium ethylsulfate (Compound 210 in Table below)
Step A Synthesis of 6-(4-fluorophenyl)benzothiazole as an intermediate
A solution of 0.90 gram (0.0033 mole) of 6-iodobenzothiazole and 0.69 gram (0.0049 mole) of 4-fluorophenylboronic acid and 3.6 mL of toluene was placed in a 9.5-dram vial, and a solution of 1.04 grams (0.0098 mole) of sodium carbonate in 5.96 mL of water was added. The reaction mixture was vigorously shaken and then purged with dry nitrogen.
Tetrakis(triphenylphosphine)palladium(0), 0.38 gram (catalyst), was then added to the reaction mixture; which was then warmed to about 85 °C where it was shaken for 16 hours. After this time, the reaction mixture was cooled to ambient temperature and treated with five mL of 5% aqueous sodium hydroxide. The mixture was then extracted with methylene chloride and the extract was filtered. The filtrate was concentrated to a residue in a stream of nitrogen gas; which was then purified with column chromatography on silica gel, first using mixtures of methylene chloride and hexane, and then pure methylene chloride as eluants. The appropriate fractions were combined and concentrated under reduced pressure, yielding 0.46 gram of the subject compound. The NMR spectrum was consistent with the proposed structure. Step B Synthesis of 3-ethyl-2-methyl-6-(4-fluorophenyl)benzothiazolium ethylsulfate as an intermediate This compound was prepared in a manner analogous to that set forth in Step A of Example 3, by the reaction of 0.46 gram (0.0019 mole) of 6-(4- fluorophenyl)benzothiazole and 0.51 gram (0.0033 mole) of diethyl sulfate. The yield of the subject compound was about 0.25 gram.
Step C Synthesis of Compound 210 This compound was prepared in a manner analogous to that set forth in
Step B of Example 3, by the reaction of 0.25 gram (0.0007 mole) of 3-ethyl-2- methyl-6-(4-fluorophenyl)benzothiazolium ethylsulfate, 0.12 gram (0.0008 mole) of triethyl orthoformate, and 0.38 mL of pyridine. The yield of the subject compound was 0.09 gram. The NMR spectrum was consistent with the proposed structure.
EXAMPLE 7 This example illustrates one protocol for the preparation of 2-[3-[6-(5- chloro(2-thienyl))-3-ethyl(3-hydrobenzothiazole-2-ylidene)]propen-l-enyl]-6-(5- chloro(2-thienyl))-3-ethylbenzothiazolium ethylsulfate (Compound 226 in Table below)
Step A Synthesis of 6-(5-chloro-2-thienyl)benzothiazole as an intermediate
This compound was prepared in a manner analogous to that set forth in Step A of Example 6, by the reaction of 0.90 gram (0.0033 mole) of 6- iodobenzothiazole, 1.20 grams (0.0074 mole) of 5-chloro-2-thienylboronic acid, 1.56 grams (0.0147 mole) of sodium carbonate, 5.96 mL of water, and 3.6 mL of toluene in the presence of 0.57 gram (catalyst) of tetrakis(triphenylphosphine)palladium(0). The yield of the subject compound was 0.21 gram.
Step B Synthesis of 3-ethyl-2-methyl-6-(5-chloro-2- thienyl)benzothiazolium ethylsulfate as an intermediate This compound was prepared in a manner analogous to that set forth in Step A of Example 3, by the reaction of 0.21 gram (0.0008 mole) of 6-(5-chloro-2- thienyl)benzothiazole and 0.15 gram (0.0010 mole) of diethyl sulfate. The yield of the subject compound was about 0.25 gram.
Step C Synthesis of Compound 226 This compound was prepared in a manner analogous to that set forth in
Step B of Example 3, by the reaction of 0.23 gram (0.0006 mole) of 3-ethyl-2- methyl-6-(5-chloro-2-thienyl)benzothiazolium ethylsulfate, 0.11 gram (0.0007 mole) of triethyl orthoformate, and 0.38 mL of pyridine. The yield of the subject compound was 0.05 gram. The NMR spectrum was consistent with the proposed structure.
EXAMPLE 8 This example illustrates one protocol for the preparation of 2[3-(3-ethyl(3- hydro7H,8H-l,4-dioxino[5,6-g]benzothiazol-2-ylidene))prop-l-enyl]-3-ethyl- 7H,8H-l,4-dioxino[5,6-g]benzothiazolium ethylsulfate (Compound 233 in Table below)
Step A Synthesis of l-(2H,3H-benzo[e]l,4-dioxan-6-ylamino)ethane-l- thione as an intermediate A solution of 11.4 grams (0.059 mole) of N-(2H,3H-benzo[e] l,4-dioxan-6- yl)acetaminde and 17.0 grams (0.042 mole) Lawesson's Reagent in 50 mL of 1,2- dimethoxyethane was warmed to about 60 °C to 70 °C where it stirred for 90 minutes. After this time, the reaction mixture was cooled and concentrated under reduced pressure to a residue. The residue was purified with column chromatography on silica gel, using pure methylene chloride as an eluant. The appropriate fractions were combined and concentrated under reduced pressure, yielding 10.0 grams of the subject compound. The NMR spectrum was consistent with the proposed structure.
Step B Synthesis of 2-methyl-l,4-dioxano[5,6-g]benzothiazole as an intermediate A stirred mixture of 47 grams (0.143 mole) of potassium ferricyanide in
100 mL of aqueous 3M sodium hydroxide was cooled to about 20 °C, and a mixture of 10.0 grams (0.048 mole) of l-(2H,3H-benzo[e]l,4-dioxan-6- ylamino)ethane-l-thione in 100 mL of water was added. Upon completion of addition, the reaction mixture was stirred for about one hour, and then it was extracted with three 50 mL portions of methylene chloride. The combined extracts were dried with sodium sulfate and filtered, then the filtrate was concentrated under reduced pressure to a residue. The residue was purified with column chromatography on alumina, using pure petroleum ether and mixtures of petroleum ether and diethyl ether as eluants. The appropriate fractions were combined and concentrated under reduced pressure, yielding 3.8 grams of the subject compound. The NMR spectrum was consistent with the proposed structure.
Step C Synthesis of 2-methyl-l,4-dioxano[5,6-g]benzothiazolium ethylsulfate as an intermediate This compound was prepared in a manner analogous to that set forth in Step A of
Example 3, by the reaction of 0.60 gram (0.0029 mole) of 2-methyl-l,4- dioxano[5,6-g]benzothiazole and 0.54 gram (0.0035 mole) of diethyl sulfate in a minimum (less than 1 mL) of toluene. The yield of subject compound was about
0.30 gram.
Step D Synthesis of Compound 233
This compound was prepared in a manner analogous to that set forth in Step B of Example 3, by the reaction of 0.30 gram (0.0009 mole) of 2-methyl-l,4- dioxano[5,6-g]benzothiazolium ethylsulfate, 0.13 gram (0.0009 mole) of triethyl orthoformate, and 0.38 mL of pyridine. The yield of the subject compound was 0.13 gram. The NMR spectrum was consistent with the proposed structure.
It is well known to one of ordinary skill in the art that compounds like the compounds of formula I of the present invention can contain optically active and racemic forms. It is also well known in the art that compounds like the compounds of formula I may contain stereoisomeric forms, tautomeric forms and/or exhibit polymorphism. It is to be understood that the present invention encompasses any racemic, optically-active, polymorphic, tautomeric, or stereoisomeric form, or mixtures thereof. It should be noted that it is well known in the art how to prepare optically active forms, for example by resolution of a racemic mixture, or by synthesis from optically-active intermediates. The following table sets forth some additional examples of compounds of the present invention:
Table 1 Pesticidal Derivatives of Formula I
Ar-(CR=CR j -(CR =CR ) -(CR =)_Ar
Ar is: Ar s:
Figure imgf000038_0001
where Z is -S-; p and q are 0; r is 1, R4, R24, R25, and R26 are hydrogen, which provides compounds of formula la below:
Figure imgf000038_0002
Cmpd.
No. X Y R5 R22
1 Ph Ph C2H3 Ph
2 Ph Ph C2H5 4-carboxylPh
Compounds of formula la where X and Y taken together is - D
Figure imgf000038_0003
R2Δ5D, D R26o, R r 29y, τ R,3j0υ, R τj3J11, and RiZ, are hydrogen:
Figure imgf000039_0001
Cmpd. No. R Rz
3 C2H5 4-Cl-Ph 4 C2H5 2-CH3- l-Phbenzimidazol-5-yl
Compounds of formula la where Z is -S-; X and Y taken together is - CR29=CR30CR31=CR32-; and R23 and R24 taken together is -CR61=CR62CR63=CR64- , where R4, R25, R26, R61, R62, and R64 are hydrogen:
Figure imgf000039_0002
la
Pi |_lH H |i| Λ hi| H H H W l^ W IM IM W W I^ I^ H I hlH I^
Pi ffi M a K ffi a ffi BMK K K MNM K K « K ffi S ffi K K K K S ffi MNK ^ Uc UuUUUoUuUijUUUUUUuUUUUUUUuUc
i
Pi UU U U Q O O
Pi ffiWffiffiffiffiffiffiuuffiffiWuWffiffiΛΛ^ffiffigggmmmffi
Pi
Pi ffi K K g a ffi M w ffi ffi ffi K M w a K a M ffi a wnw w w ffiM
Figure imgf000040_0001
Q, o
Figure imgf000040_0002
lO 3 t 00 σs O <-< cNl co * - >-) θ i oo cΛ θ -H c4 cr>
Figure imgf000041_0001
* Compound 57 where R30 and R31 are taken together; and Compound 58 where R29 and R ° are taken together: where X4 is -O-; R45 and R4δ are hydrogen; and s is 2.
Compounds of formula la where Z is -S-; X and Y taken together is - CR29=CR30CR31=CR32-; R22 is CH3; and R23 and R24 taken together is - CR61=CR62CR63=CR64-, where R4, R29, R30, R32 R61, R62, R63, and R64 are hydrogen;
Figure imgf000042_0001
la
No. R5 R31 Rz- Rύ
643 CH3 H H CH3
654* CH3 CI H CH3
661 CH3 H -CH= =CHCH= =CH-
671 C2H5 H -CH= =CHCH= =CH- *One component in a mixture with Compound 90.
Compounds of formula I where: Ar is: Ar1 is:
Figure imgf000042_0002
where p and q are 0; r is 1 ; which provides compounds of formula lb, below:
Figure imgf000043_0001
lb
Cmpd. No. Z X Y R4 R5 R17 R18 R19 R20 R21
68 S Ph Ph H C2H5 CH3 H H H H
Compounds of formula lb where R18 and R19 taken together is - CR53=CR54CR55=CR56-, and R4, R20, R21, R53, R54, R55 and R56 are hydrogen:
Figure imgf000043_0002
lb
Cmpd.
No. X R3 R 17
Figure imgf000043_0003
Compounds of formula lb where X and Y taken together is -
CR29=CR30CR31=CR32_. where R.8j Rl9> RM R21 R ; R30; ^ ^ R32 ^ hydrogen:
Figure imgf000044_0001
lb
Cmpd. No. Z R4 R5 R17
711 s H C2H5 CH3
and Y taken together is
Figure imgf000044_0003
Figure imgf000044_0002
21 53 56
Figure imgf000044_0004
lb
No. Z R5 R4 R29 R30 RJ Rά R1 R 20 R 54 R5
724 s CH3 H H H H H CH3 H H H
731 s CH3 H H H H H C2H5 H H H
741 s C2H5 H H H H H C2H5 H H H
751 s n-C3H7 H H H H H C2H5 H H H
764 s CH3 H H H H H CH3 H CI H
77 ' s CH3 H H H H H C2H5 H CI H
783 s CH3 H H H H H CH3 CH3 H H
794 s CH3 H H H H H CH3 CH3 H H
801 s CH3 H H H H H C2H5 H H CH3
811 s C2H5 H H H H H C2H5 H H CH3
82' s n-C3H7 H H H H H C2H5 H H CH3
835 s CH3 H H H H CI CH3 H H H
844 s CH3 H H H CI H CH3 H CI H
85' s CH3 H H H CI H C2H5 H CI H
864 s CH3 H H H CI H CH3 H H CI Cmpd.
R29 R30 R31 R32
No. Z R5 R4 R17 R20 R54 R55
87 ' s CH3 H H H CI H C2H5 H H CI
884 s CH3 H H H CI H CH3 H CI CI
891 s CH3 H H H CI H C2H5 H H CH3
904' s CH3 H H H CI H CH3 CH3 H H
914 s CH, H H CI H H CH3 CH3 H H
924 s CH3 H H CI H H CH3 H CI H
934 s CH3 H H CI H H CH3 H H CI
941 s CH3 H H CI H CI C2H5 H H H
951 s CH3 H H H Br H C2H5 H H CH3
961 s CH3 H H H F H C2H5 H H H
971 s CH3 H H H F H C2H5 H H CH3
981 s CH3 H H H CH3 H C2H5 H H CH3
99 s C2H5 H H CH3 CH3 H C2H5 H H OCH3
1001 s CH3 H H H OCH3 H C2H5 H H H
1011 s C2H5 H H H OCH3 H C2H5 H H H
1021 s CH3 H H H OCH3 H C2H5 H CI H
1031 s CH3 H H H OCH3 H C2H5 H H CI
1041 s CH3 H H H OCH3 H C2H3 H CI CI
1051 s CH3 H H H OCH3 H C2H5 H CH3 H
1061 s CH3 H H H OCH3 H C2H5 H H CH3
1071 s CH3 H H H OCH3 H C2H5 H H OCH3
108' s C2H5 H H H OCH3 H C2H5 H H OCH3
1091 s CH3 H H OC2H5 H H C2HS H H H
HO1 s CH3 H H OC2H5 H H C2H5 H CI H
1111 s CH3 H H OC2H5 H H C2H5 H H CI
1121 s CH3 H H OC2H5 H H C2H5 H H CH3
1 131 s CH3 H H OC2H5 H H C2H5 H H OCH3
1141 s C2H5 H H CH3 OC2H5 H C2H3 H H CH3
1151 s C2H5 H H Ph H H C2H5 H H H
116 s C2H4OH H H H Ph H CHj H H H
1171 s C2H5 H H H Ph H C2H5 H H CH3
118' s CH3 H H Ph H H C2H5 H H CH3
1191 s C2H5 H -X4-(CR45R 6)S-X4-** H H C2H5 H H CH3
120 s C,H5 H -CH= CHCH=CH- H H C2H5 H H H
1216 s C2H5 H -CH= CHCH=CH- H H C2H5 H H H
1221 0 CH3 H H H H H C2H5 H H H
1231 0 C2H5 H H H H H C2H5 H H H
1241 0 CH3 H H H CI H C2H5 H H H
1251 0 CH3 H H H F H C2H5 H H CH3
1261 0 CH3 H H OCH3 H H 6,RS H H CH3
1271 0 CH3 H H H cyclohexyl H C2H5 H H CH3
1281 0 CH3 H H H Ph H C2H5 H H H
1295 0 C2H5 H H H Ph H C2H5 H H CH3
1301 0 n-C3H7 H H H Ph H C2H5 H H H
1311 0 n-C3H7 H H H Ph H C2H5 H H CH3
*One component in a mixture with Compound 65.
♦♦Compound 119 when R29 and R30 are taken together: X4 is -O-; R45 and R46 are hydrogen; and s is 2. Compounds of formula lb where q is 0; p and r are 1; X and Y taken together is -CR29=CR30CR31=CR32-; and R18 and R19 taken together is - CR53=CR54CR55=CR56-, where R4, R29, R30, R31, R32, R20, R21, R53, R54, R55, and R~ are hydrogen:
Figure imgf000046_0001
lb
Cmpd.
No. Z R5 R R1 Rπ
132 s C2H5 F H C2H5
133 s C2H5 H Ph C2H5
Compounds of formula I where:
Ar is: Ar s:
Figure imgf000046_0002
A G
9 9 9 where q is 0; p and r are l; X = X , Y = Y , and Z = Z ; which provides compounds of formula lc, below:
Figure imgf000046_0003
Cmpd.
No. X = X2 Y = Y2 Z = Z2 R5 = R27 R R1 R4
1345 4-PhPh H s C2H5 H H H
Compounds of formula lc where q and p are 0, and r is 1; X and Y taken together is
-CR29=CR30CR31=CR32-; and X2 and Y2 taken together is -CR37=CR38CR39=CR40- where Z is the same as Z2; R5 is the same as R27; R29 is the same as R37; R30 is the same as R38; R31 is the same as or different than R39; and R32 is the same as R40:
Figure imgf000047_0001
Cmpd.
No. Z = Z^ R5 = R^ RΛJ = RJ Rj 3υ0 = R ,38 r / - 39 R32 = R 40 R4
135 S CH3 H H H H H H
136 S CH3 H H CI H H PhCH20
Compounds of formula lc where p is 1, q and r are 0; R and R1 are hydrogen; X and Y taken together is-CR29=CR30CR31=CR32-; and X2 and Y2 taken together is - CR37=CR38CR39=CR40- where Z is the same as Z2; R5 is different than R27; R29 is the same as R37; R30 is the same as R38; R31 is the same as R39; and R32 is the same as R40:
Figure imgf000047_0002
lc Cmpd.
No. 37
Z = Z R5 / R27 R29 = R R3(, = R 38 R31 = R 39 40
R32 = R
13T C2H5 H Ph H H H
Compounds of formula lc where q is 0; p and r are 1; X and Y taken together is -CR 9=CR30CR31=CR32-; and X2 and Yi taken together is -CR37=CR38CR39=CR40- ; where Z is the same as Z2; R5 is the same as R27; R29 is the same as R37; R30 is the same as R38; R31 is the same as R39; and R32 is the same as R 40.
Figure imgf000048_0001
lc
Figure imgf000049_0001
MM MH MH MM MM MH MM MM HH HM HM HH HH HH HH ^H MM MM MH MM MM MH MM MM
MHHH MHHH HHMH MHHH MHMH MHMH HMM HHM MHHH HMHH MHHH MHHH
Figure imgf000050_0001
Figure imgf000051_0001
Figure imgf000052_0001
Cmpd.
No. z = z2 R5 = R27 R29 = R37 R30 = R38 R31 = R39 R32 = R40 R/R4 R1
2515 0 C2H5 H CH3 H H H/H H
2524 0 CH3 H H CH3 H H/H H
2535 0 C2H5 H H CH3 H H/H H
2545 0 C.H5 H H C(CH3)3 H H/H H
2555 0 C2H5 H H C(CH3)2C2H5 H H/H H
2564 0 CH3 H H cyclohexyl H H/H H
2575 0 C2H5 CH3 H CH3 H H/H H
2584 0 CH3 H CH3 CH3 H H/H H
2595 0 C2H5 H CH3 CH3 H H/H H
2604 0 CH3 H OCH3 H H H/H H
2615 0 C2H5 H H OCH3 H H/H C2H5
2624 0 CH3 H H Ph H H/H H
2635 0 C2H5 H H Ph H H/H H
2645 0 C2H5 H H Ph H H/H C2H5
2652 o C2H4OCH3 H H Ph H H/H H
26612 o n-C3H6S03 " H H Ph H H/H C2H5
26712 0 n-C3H6S03- H H Ph H H/H C2H5
26812 0 n-C3H6S03 " H H Ph H H/H C2H5
26912 0 n-C3H6S03- H H naphth-1-yl H H/H H
2705 0 C2H5 H H 4,5,6,7-tetraydro- H H/H H isoindol-1,3-
Figure imgf000053_0001
♦Compound 233 when R29 and R30, and R37 and R38 are taken together; and Compound 238 when R30 and R31, and R38 and R39 are taken together: X4 is -O-;
R45 and R46 are hydrogen; and s is 2
Compound 237 when R30 and R31, and R38 and R39 are taken together: X4 is -O-
R45 and R46 are hydrogen; and s is 1.
Compounds of formula lc where q is 0; p and r are 1 ; X and Y taken together is -CR =CR30CR31=CR32-; and X2 and Y2 taken together is -CR37=CR38CR39=CR40- ; where Z is the same as Z2; R5 is the same as R27; R1 is hydrogen; R29 is the same as R .37 , and is hydrogen; R ,30 i ■s the same as R 38 , and is hydrogen; R ,31 is the same as R R3399,, aanndd iiss hhyycdrogen; R32 is the same as R40, and is hydrogen; and R and R4 are taken together:
Figure imgf000054_0001
lc
Cmpd. No. Z = Z2 R5 = R27 R / R4
Figure imgf000054_0002
Compounds of formula lc where p and q are 1, and r is 0; R, R1, R2, and R3 are hydrogen; X and Y taken together is -CR29=CR30CR31=CR32-; and X2 and Y2 taken together is -CR37=CR38CR39=CR40- where Z is the same aass ZZ22;; RR55 is different than R27; R29 is the same as R37- R °3ύ0 i ;s" Λ the- s —ame a -s ° R3j8a-; ™ R3i1l is the same as
R39; and R32 is the same as R40:
Figure imgf000055_0001
Cmpd. No. Z = Z R5 / R27 R29 = R 37 R30 = R- 38 R31 = R 39 R32 = R' 40
2805 C2H5 H Ph H H H
I *3
Compounds of formula lc where p, q, and r are 1; and R, R , R , and R are hydrogen; X and Y taken together is -CR29=CR30CR31=CR32-; X2 and Y2 taken together is -CR37=CR38CR39=CR40-; where Z is the same as Z2; R5 is the same as on 0 T7 ^f. ^8 ^ 1
R ; R~ is the same as R , and is hydrogen; R is the same as R ; R is the same as R39; and R32 is the same as R40, and is hydrogen:
Figure imgf000055_0002
lc
Cmpd.No
Z = ZZ R 48 R5 = R 27 Rz RM = R 38 R3I = R39
2811 S C2H5 H H H
282 O — C2H5 H -CH=CHCH=CH-
283 NR48 C2H5 Ph H benzothiazol-2-yl
284 NR48 C2H5 Ph Cl H benzothiazol-2-yl
285 NR48 C2H5 Ph CsN H benzothiazol-2-yl
286 NR48 C2H5 Ph C2H4OH H benzothiazol-2-yl
287 NR48 Ph C2H5 Cl H benzoxazol-2-yl
288 NR48 C2H5 Ph C≡N H benzoxazol-2-yl
Compounds of formula lc where q is 0; p and r are 1; R and R4 are hydrogen;
Figure imgf000055_0003
as or different than R27; R29 is the same as or different than R37; R30 is the same as or different than R38; R31 is the same as or different than R39; and R32 is the same as or different than R40:
Figure imgf000056_0001
lc
Figure imgf000057_0001
Figure imgf000058_0001
Compounds of formula I where: Ar is: Ar is:
Figure imgf000059_0001
G G
where p is 1, q and r are 0; R and R1 are hydrogen; X2 and Y2 taken together is -CR37=CR38CR39=CR40-; which provides compounds of formula Id below:
Figure imgf000059_0002
Id
Cmpd. No. Z2 R27 R37 R38 R39 R40
310 s H H Ph H H
Compounds of formula Id where p and q are 1, and r is 0; R, R 1 , r R.2 , and R are hydrogen; and X2 and Y2 taken together is -CR37=CR38CR39=CR40-:
Figure imgf000059_0003
Id Cmpd.
No. Z2 R27 R37 R38 R39 R40
311 s H H Ph H H
Compounds of formula I where:
Ar is: Ar is:
Figure imgf000060_0001
where q is 0; p and r are 1; R , 113J and R .1144 taken together is -CR57=CR58CR59=CR ,6o0υ-; and Rώ and R24 taken together is -CR61=CR62CR63=CR64-; which provides compounds of formula Ie below:
Figure imgf000060_0002
Ie where R1, R2, R4, R15, R16, R25, R26 are hydrogen; R57 is the same as R61, and are hydrogen; R58 is the same as R62, and are hydrogen; and R60 is the same as R64, and are hydrogen:
Cmpd. No. R12 =R22 R59 =R63
3124 CH3 H 3134 CH3 Cl 3144 CH3 CF3 Compounds of formula I where: Ar is: Ar1 is:
Figure imgf000061_0001
E
where q is 0; p and r are 1; R and R ,9y and Rύ and R19 taken together is
Figure imgf000061_0002
compounds of formula If below:
Figure imgf000061_0003
If where R[, R2, R4, R10, R11, R20_, R21 are hydrogen; R49 is the same as R53, and are hhyyddrrooggeenn;; RR5500 is the same as R54, and are hydrogen; and R52 is the same as R56, and are hydrogen:
Cmpd. No. R7 -=R17 R51 = R5S
3154 CH3 H 3164 CH3 Cl 3174 CH3 CH3 Compounds of formula I where: Ar is: Ar is:
Figure imgf000062_0001
where q is 0; p and r are 1; R° and and R23 and R24 taken together
Figure imgf000062_0002
compounds of formula Ig below:
Figure imgf000062_0003
Ig where R1, R2, R4, R10, R11, R25, R26 are hydrogen; R49 is the same as R61, and are hhyyddrrooggeenn;; RR50 is the same as R , and are hydrogen; and R is the same as R , and are hydrogen:
Cmpd. No. R7 =R22 R51 / R64
3184 CH3 H H
3194 CH3 Cl
Cl
3204 CH3 Cl
CH3 Compounds of formula I where: Ax is: Ar' is:
Figure imgf000063_0001
where q is 0; p and r are 1; X1 and Y1 taken together is -CR33=CR34CR35=CR ,336 and Xi and Y3 taken together is -CR41=CR42CR43=CR44-; which provides compounds of formula Ih below:
Figure imgf000063_0002
Ih where Z1 and Z3 are -S-, R1, R2, and R4 are hydrogen, and R36 is the same as R44, and are hydrogen:
Cmpd No. 6 _ 28 R33 _ R41 R3 4 = R42 R 5 _ R44
Figure imgf000063_0003
''Compound 325, where R33 and R34, and R41 and R42 are taken together where X' is -O-, R ,45 and R ,46 are hydrogen, and s is 2.
Iodide salt "p-Toluenesulfonic acid salt
' 3 Methanesulfonic acid salt 4Methyl sulfate salt
5- Ethyl sulfate salt Chloride salt 7Pyridine salt Propyl sulfate salt 9butyl sulfate salt 10bromide salt
11 Triethylamine salt An inner salt Candidate pesticides were evaluated for insecticidal activity against the tobacco budworm (Heliothis virescens [Fabricius]) in a surface-treated diet test. In this test one mL of molten (65-70°C) wheat germ-based artificial diet was pipetted into each well of a four by six (24 well) multi-well plate (ID# 430345-15.5 mm dia. x 17.6 mm deep; Corning Costar Corp., One Alewife Center, Cambridge, MA 02140). The diet was allowed to cool to ambient temperature before treatment with candidate insecticide. For a determination of insecticidal activity, solutions of the candidate
® insecticides were prepared for testing using a Packard 204DT Multiprobe
Robotic System (Packard Instrument Company, 800 Research Parkway, Meriden, CT 06450), in which the robot first diluted a standard 50 millimolar DMSO solution of candidate insecticide with a 1 : 1 water/acetone solution (V/V) in a ratio of 1:7 stock solution to water/acetone. The robot then pipetted 40 miciOliters of the so-prepared solution onto the surface of the diet in each of three wells in the 24 multi-well plate. The process was repeated with solutions of seven other candidate insecticides. In an alternate method, solutions of candidate insecticides may also be prepared for testing using a 96 channel Apricot Personal Pippetter-550 (Apricot Designs, Inc., 825S Primrose Avenue, Suite 1, Monrovia, CA 91016) in the same 1:7 ratio of 50 millimolar stock solution and 1:1 acetone/water. Once treated, the contents of the multi-well plate were allowed to dry, leaving 0.25 millimoles of candidate insecticide on the surface of the diet, or a concentration of 0.25 millimolar. Appropriate untreated controls containing only DMSO on the diet surface are also included in this test.
For evaluations of the insecticidal activity of a candidate insecticide at varying rates of application, the test was established as described above using sub- multiples of the standard 50 millimolar DMSO solution of candidate insecticide. For example, the standard 50 millimolar solution was diluted by the robot with DMSO to give 5, 0.5, 0.05, 0.005, 0.0005 millimolar, or more dilute solutions of the candidate insecticide. In these evaluations there were six replicates of each rate 64
of application placed on the surface of the diet in the 24 multi-well plate, for a total of four rates of application of candidate insecticide in each plate.
In each well of the test plate was placed one second instar tobacco budworm larvea, each weighing approximately five milligrams. After the larvae were placed in each well, the plate was sealed with clear polyfilm adhesive tape. The tape over each well was perforated to ensure an adequate air supply to the insect. The plates were then held in a growth chamber at 25 °C and 60% relative humidity for five days (light 14 hours/day).
After the five-day exposure period insecticidal activity for each rate of application of candidate insecticide was assessed as percent inhibition of insect weight when the weight of treated insects was compared to the weight of insects from untreated controls, and percent mortality when the number of dead insects were compared to the total number of insects infested.
Insecticidal activity data at selected rates of application are provided in
Table 2. The test compounds of formula I are identified by numbers that correspond to those in Table 1.
Table 2
Insecticidal Activity of Compounds of Formula I When Applied to the Surface of the Diet of Tobacco Budworm (Heliothis virescens [Fabricius])
Percent Percent
Growth Percent Growth Percent
Cmpd. No. Inhibition Mortality Cmpd. No. Inhibition Mortality
3 87 0 4 41 0
5 100 100 6 100 100
7 100 100 8 94 17
9 66 17 10 97 33
11 100 17 12 100 17
13 100 100 14 100 100
15 100 100 16 100 100
17 100 17 18 100 50
19 100 33 20 100 67
21 100 33 22 100 100
23 100 100 24 100 100
25 100 83 26 75 0
28 100 100 29 100 0
30 100 100 31 100 83
32 100 100 33 98 50
34 90 33 35 96 17
36 100 100 37 100 100
38 86 67 39 100 17 Percent Percent
Growth Percent Growth Percent
Cmpd. No. Inhibition Mortality Cmpd. No. Inhibition Mortality
40 100 50 41 100 0
42 100 100 43 100 50
44 73 33 45 100 33
46 100 17 47 100 0
48 100 0 49 100 0
50 12 0 51 99 17
52 100 33 53 93 0
54 60 0 55 79 0
57 100 100 58 100 100
59 100 33 60 91 67
61 100 50 62 86 0
63 100 17 64 70 33
66 82 0 67 94 0
69 86 17 70 82 0
72 68 0 73 93 0
74 74 0 75 99 0
76 100 0 77 98 0
78 100 0 80 61 0
81 63 0 82 63 0
84 100 0 85 97 0
86 98 0 87 100 85
88 74 0 89 86 17
91 99 33 92 99 33
93 100 33 94 100 0
95 98 33 96 58 0
97 94 17 98 58 0
99 98 17 100 , 100 50
101 100 0 102 100 100
103 100 100 104 100 50
105 100 33 106 100 100
107 100 100 108 100 100
109 95 100 110 100 100
111 100 83 112 100 33
113 100 83 114 100 17
115 100 17 116 91 0
117 100 100 118 100 0
119 100 0 120 100 50
121 83 0 122 93 0
123 93 0 124 87 0
125 98 17 126 97 0
127 100 33 128 100 67
130 100 67 131 100 0
132 67 17 133 81 0
138 28 0 140 51 0
142 96 0 143 100 100
144 100 100 145 100 100
146 100 50 147 100 0
148 100 17 149 100 100
150 95 0 151 64 0
152 63 0 153 99 50
154 100 100 155 100 100 Percent Percent
Growth Percent Growth Percent
Cmpd. No. Inhibition Mortality Cmpd. No. Inhibition Mortality
156 100 17 157 100 100
158 67 0 159 100 100
160 100 0 161 100 100
162 100 0 163 100 100
164 100 0 165 100 100
166 100 100 167 100 100
168 95 67 170 100 0
171 100 100 172 70 0
173 43 0 174 100 67
179 100 100 180 100 100
181 100 100 182 95 0
183 100 100 184 100 100
185 100 0 187 100 100
188 100 100 189 100 100
190 100 100 191 100 17
192 100 67 193 100 100
194 100 33 195 100 100
196 100 0 199 85 17
200 100 100 201 100 100
202 100 100 203 90 17
204 100 100 205 93 17
206 100 100 207 100 50
208 100 100 209 100 100
210 100 100 211 100 100
212 100 67 213 100 100
214 100 100 215 100 100
216 100 0 217 100 50
218 100 100 219 96 17
220 100 0 221 100 0
222 100 50 223 100 100
224 100 50 225 100 100
226 100 100 227 100 100
228 100 50 229 82 17
230 57 0 233 100 100
236 58 0 237 72 0
238 99 17 239 56 0
240 100 83 241 100 17
242 100 0 246 100 0
248 100 67 249 100 50
250 100 0 251 100 100
252 100 0 253 100 0
254 100 100 255 97 0
256 100 100 258 100 100
259 100 100 260 100 100
261 100 0 262 100 100
263 100 100 265 100 33
270 99 0 271 100 100
272 100 100 273 100 50
274 100 33 275 100 17
275 100 17 276 100 83
277 100 100 Concentration of the candidate insecticide on the surface of the diet is 0.25 millimolar.
As set forth in the foregoing table, all of the compounds of formula I were insecticidally active at the rate of application tested. Approximately 34% (82 compounds) of those compounds of formula I tested provided 100% inhibition of insect growth. An additional 33% (79 compounds) of those compounds of formula I tested provided 100% inhibition of insect growth and 100% insect mortality. While this invention has been described with an emphasis upon preferred embodiments, it will be understood by those of ordinary skill in the art that variations of the preferred embodiments may be used and that it is intended that the invention may be practiced otherwise than as specifically described herein. Accordingly, this invention includes all modifications encompassed within the spirit and scope of the invention as defined by the following claims.

Claims

WHAT IS CLAIMED IS;
Claim 1. A pesticidal composition comprising a pesticidally effective amount of a compound of formula I and at least one pesticidally compatible carrier therefor, wherein the compound of formula I is:
Ar-(CR=CR1)p-(CR2=CR3) -(CR4=)rAr1
where Ar and Ar1 are independently selected from
Figure imgf000069_0001
B
Figure imgf000069_0002
D E
Figure imgf000069_0003
G H p, q and r are independently selected from 0 or 1 ; where at least one of p, q or r is l;
R5, R6, R7, and R12 are independently selected from hydrogen; alkyl; haloalkyl; hydroxyalkyl; alkoxyalkyl; carboxylalkyl; aryl optionally substituted with at least one halogen or alkyl; arylalkyl; aryloxyalkyl; or sulfonatoalkyl, and may bear a negative charge resulting in an inner salt; and a separate ion is selected from sodium, potassium, lithium, calcium, magnesium, halide, sulfate, bisulfate, alkyl sulfate, alkyl sulfonate, haloalkylsulfonate, arylsulfonate, carbonate, bicarbonate, alkylcarboxylate, phosphate, hydrogen phosphate, dihydrogen phosphate, arylcarboxylate, trialkylammonium, or pyridinium;
X and Y; X1 and Y1; X2 and Y2; and X3 and Y3 are independently selected from hydrogen, halogen, cyano, alkyl, cycloalkyl, haloalkyl, alkoxy, alkylthio, alkylsulfinyl, alkylsulfonyl, aryl, aryl-substituted aryl, arylalkyl, aryloxy, arylalkoxy, arylthio, arylsulfonyl, arylsulfoxide, arylcarbonyl, or heteroaryl; or
-X^CHCH^-S- X and Y are taken together with ' ' to form a fused azole, where the asterisk denotes attachment at X; or
X and Y are taken together with -CR29=CR30CR31=CR32- to form a fused azole, where the asterisk denotes attachment at X;
XI and Y1 are taken together with -CR33=CR34CR35=CR36-* to form a fused azole, where the asterisk denotes attachment at X1;
X2 and Y2 are taken together with -CR37=CR38CR39=CR40-*, to form a fused azole, where the asterisk denotes attachment at X"; and X3 and Y3 are taken together with -CR41=CR42CR43=CR44-* to form a fused azole, where the astirisk denotes attachment at X3; where R29 through R44, inclusively, are independently selected from hydrogen; halogen; alkyl; haloalkyl; hydroxy; alkoxy; haloalkoxy; alkylthio; haloalkylthio; alkylsulfonyl; haloalkylsulfonyl; alkylsulfinyl; haloalkylsulfinyl; cycloalkyl; alkenyl; alkynyl; alkenyloxy; cyano; nitro; amino; alkylamino; dialkylamino; alkylcarbonyloxy; alkoxycarbonyl; alkoxycarbonylalkyl; dialkylphosphono; or aryl, arylalkyl, arylalkoxy, aryloxy, arylthio, arylsulfinyl, arylsulfonyl, and heteroaryl wherein the aryl is optionally substituted with at least one halogen, alkyl, alkoxy, haloalkoxy, alkylsulfonyl, or aryl; or
R29 and R30, or R30 and R31, or R31 and R32, or R33 and R34, or R34 and R35, or R35 and R36; or R37 and R38, or R38 and R39, or R39 and R40, or R41 and R42, or R42 and R43, or R43 and R44 are taken together with i) -C3H6-, or -C4H8- to form a fused azole; or ii) -SCH=CH-, or -CH=CHS- to form a fused azole; or iii) - OCH=CH-, or -CH=CHO- to form a fused azole; or iv) -CH=CHCH=CH- to form a fused azole; or v) -N(phenyl)CH=N(CH3)+-, or -N(CH3)+=CH- N(phenyl)- to form a fused azole; or vi) -N(phenyl)N=N(CH3)+-, or
-C=CHCH=C-CH2 - -N(CH3)+=N-N(phenyl)- to form a fused azole; or vii) ' ' to form a fused azole, or viii) -X4-(CR45R46)S-X4- to form a fused azole, where X4 is -O-, -S-, or -NR47; where R45 and R46 are independently selected from hydrogen, halogen, alkyl, or alkoxyalkyl; R47 is selected from hydrogen or alkyl; and s is 1-3; and where a ring formed from taking R29 and R30, R30 and R31, and R31 and R32 together; a ring formed from taking R33 and R34, R34 and R35, and R35 and R36 together; and a ring formed from taking R37 and R38, R38 and R39, R39 and R40 together; and a ring formed from taking R41 and R42, R42 and R43, and R43 and R44 together are the same or different;
Z, Z , Z , and Z are independently selected from -O-, -S-, dialkylmethylene, or NR48, where R48 is selected from hydrogen, alkyl, alkoxyalkyl, haloalkyl, haloalkenyl, aryl, or sulfonatoalkyl, and may bear a negative charge resulting in an inner salt; and, when p, q and r arel; R through R4, inclusively, are independently selected from hydrogen; halogen; alkyl; haloalkyl; cycloalkyl; hydroxyalkyl; alkoxy; alkylthio; cyano; aryl optionally substituted with carboxyl; amino; or arylalkyl; and when q is 0, and p and r are 1 ; R and R4 are optionally taken together with 1,2-cyclohexene to form a 3,4,5,6,7- pentahydroindene ring; or taken together with 3,4,5,6-tetrachloro-l,2-benzene to form a 4,5,6,7-tetrachloroindene ring;
1 99 On 9R
R , R , R , and R are independently selected from hydrogen; alkyl; haloalkyl; alkoxyalkyl; or aryl optionally substituted with at least one halogen, haloalkoxy, carboxyl, (alkyl-substituted aryl-substituted)benzimidazol-5-yl; or sulfonatoalkyl, and may bear a negative charge resulting in an inner salt; and a separate ion is selected from sodium, potassium, lithium, calcium, magnesium, halide, sulfate, bisulfate, alkyl sulfate, alkyl sulfonate, haloalkylsulfonate, arylsulfonate, carbonate, bicarbonate, alkylcarboxylate, phosphate, hydrogen phosphate, dihydrogen phosphate, arylcarboxylate, trialkylammonium, or pyridinium; and i ^ on when Ar is moiety A and Ar is moiety G, R and R" are optionally taken together with C2-C4 alkylene, or (C1-C2)alkoxy(C1-C )alkyl to form a fused ring; R8 through R11, R13 through R16, R18 through R21, and R23 through R26, inclusively, are independently selected from hydrogen, halogen, alkyl, haloalkyl, alkoxy, haloalkoxy, aryl, or aryloxy; or R8 and R9, or R9 and R10, or R10 and R11 are taken together with -
*CR49=CR50CR51=CR52- to form a fused azine, where the asterisk denotes attachment at R8, R9, or R10; or R18 and R19, or R19 and R20, or R20 and R21 are taken together with -
*CR53=CR54CR55=CR56- to form a fused azine, where the asterisk denotes attachment at R18, R19, or R20; or R13 and R14 are taken together with -*CR57=CR58CR59=CR60-, to form a fused azine where the asterisk denotes attachment at R13; or
R23 and R24 are taken together with -*CR61=CR62CR63=CR64-, to form a fused azine where the asterisk denotes attachment at R 23. ; and when R13 and R14, or R23 and R24 are taken together; R15 and R16, and R25 and R26 may be taken together with -CH=CHCH=CH- to form a fused azine; where R49 through R64, inclusively, are independently selected from hydrogen; halogen; alkyl; haloalkyl; alkoxy; haloalkoxy; or aryl optionally substituted with at least one halogen, alkyl, or alkoxy.
Claim 2. A pesticidal composition of claim 1 , wherein the compound of formula I is:
Ar-(CR=CR1)p-(CR2=CR3)q-(CR4=)rAr1
wherein Ar is and AΛs selected from
Figure imgf000073_0001
E
where , p and q are 0, and r is 1 ;
R4 is selected from hydrogen, halogen, alkyl, alkoxy, or cyano; R5 is selected from alkyl, haloalkyl, alkoxyalkyl; or sulfonatoalkyl, and may bear a negative charge resulting in an inner salt; and a separate ion is selected from halide, alkyl sulfate, alkyl sulfonate, haloalkylsulfonate, arylsulfonate, alkylcarboxylate, arylcarboxylate, trialkylammonium, pyridinium; sodium, potassium, calcium, or magnesium; X and Y are taken together with -CR29=CR30CR31=CR32-* to form a fused azole, where the asterisk denotes attachment at X; where
9Q TO "^ 1 "
R" , R , R , and R are independently selected from hydrogen; halogen; alkyl; hydroxy; alkoxy; alkylsulfonyl; nitro; aryl optionally substituted with at least one halogen, alkoxy, haloalkoxy, alkylsulfonyl, or aryl; aryloxy optionally substituted with at least one halogen, alkyl, or alkoxy; or heteroaryl optionally substituted with at least one halogen, alkyl, alkoxy, or aryl; or
R29 and R30, or R30 and R31 are taken together with -X4-(CR45R46)S-X4- to form a fused azole, where X4 is -O-, or -S-, R45 and R46 are independently selected from hydrogen, halogen, alkyl, or alkoxyalkyl, and s is 1-2; or
R31 and R32 are taken together with -CH=CHCH=CH- to form a fused azole;
Z is selected from -O-; or -S-; and R" are independently selected from hydrogen, alkyl, haloalkyl, alkoxyalkyl, or aryl; R through R , and R through R , inclusively, are independently selected from hydrogen, halogen, alkyl, alkoxy, haloalkyl, haloalkoxy, aryl, or aryloxy; or R18 and R19, or R19 and R20, or R20 and R21 are taken together with -
*CR53=CR54CR55=CR56- to form a fused azine, where the asterisk denotes attachment at R18, R19, or R20; or R23 and R24 are taken together with -*CR61=CR62CR63=CR64-, to form a fused azine where the asterisk denotes attachment at R23; where R53, R54, R55, R56, R61, R62, R63, and R64 are independently selected from hydrogen; halogen; alkyl; alkoxy; or haloalkyl.
Claim 3. A pesticidal composition of claim 2, wherein R is hydrogen; R5,
R17, and R22 are independently selected from methyl, or ethyl; R29, R30, R31, and R32 are independently selected from hydrogen; halogen, methyl, ethyl, methoxy, ethoxy, or phenyl; X4 is -O-, R45 and R46 are hydrogen, and s is 2; R18 through R21 and R through R , inclusively, are hydrogen, or, R and R are taken together with -*CR53=CR54CR55=CR56- to form a fused azine, where the asterisk denotes attachment at R18, where R53, R54, R55, R56, R61, R62, R63, and R64 are independently selected from hydrogen, chlorine, methyl, trifluoromethyl, or methoxy.
Claim 4. A pesticidal composition of claim 1 , wherein the compound of formula I is:
Ar-(CR=CR1) P-(CR2=CR3) 4 -(CR^V *■Ar1
wherein Ar is and Ar is
Figure imgf000075_0001
A H
where q is 0; and p and r are 1 ;
R, R1, and R4 are independently selected from hydrogen; alkyl, alkoxy, or aryl;
R5 and R27 are independently selected from alkyl, haloalkyl, alkoxyalkyl; or sulfonatoalkyl, and may bear a negative charge resulting in an inner salt; and a separate ion is selected from halide, alkyl sulfate, alkyl sulfonate, haloalkylsulfonate, arylsulfonate, alkylcarboxylate, arylcarboxylate, trialkylammonium, pyridinium; sodium, potassium, calcium, or magnesium;
X and Y are taken together with -CR29=CR30CR31=CR32-* to form a fused azole, where the asterisk denotes attachment at X; and
X2 and Y2 are taken together with -CR37=CR38CR39=CR40-*, to form a fused azole, where the asterisk denotes attachment at X2; where R29, R30, R31, and R32, and R37, R38, R39, and R40 are independently selected from hydrogen; halogen; alkyl; haloalkyl; alkoxy; cyano; nitro; amino; alkylamino; aryl, aryloxy, or arylthio where the aryl is optionally substituted with at least one halogen, alkyl, haloalkyl, alkoxy, or haloalkoxy; or heteroaryl optionally substituted with at least one halogen, alkyl, or alkoxy; or R29 and R30, or R30 and R31, or R37 and R38, or R38 and R39 are taken together with
-X4-(CR45R46)S-X4- to form a fused azole, where X4 is -O-, or -S-, and R45 and
R are independently selected from hydrogen, halogen, alkyl, or alkoxyalkyl, and s is 1-3; or
R30 and R31, and R39 and R40 are taken together with -CH=CHCH=CH- to form a fused azole; and Z and Z2 are independently selected from -O-; or -S-.
Claim 5. A pesticidal composition of claim 4, wherein R, R1, and R4 are hydrogen; R and R are independently selected from methyl, ethyl, or 2- methoxyethyl; R29, R30, R31, and R32, and R37, R38, R39, and R40 are independently selected from hydrogen; halogen; methyl; ethyl; propyl; butyl; methoxy; ethoxy; propoxy; butoxy; trifluoromethyl; phenyl optionally substituted with halogen; or thien-2-yl or furan-2-yl optionally substituted with halogen or methyl; or R29 and R30, and R37 and R38 are taken together with -X4-(CR45R46)S-X4- to form a fused azole, where X4 is -O-, R45 and R46 are hydrogen, and s is 2 or 3.
Claim 6. A pesticidal composition of any one of claims 1-5, further comprising one or more second pesticidally active compounds.
Claim 7. A method of controlling pests, comprising applying a pesticidally effective amount of a composition of any one of claims 1-5 to a locus where pests are present or are expected to be present.
Claim 8. A method of controlling pests, comprising applying a pesticidally effective amount of a composition of claim 6 to a locus where pests are present or are expected to be present.
Claim 9. The method of claim 7, wherein said pests are insects.
Claim 10. The method of claim 7, wherein said pests are acarids.
Claim 11. The method of claim 7, wherein said pests are fungi.
Claim 12. The method of claim 8, wherein said pests are insects.
Claim 13. The method of claim 8, wherein said pests are acarids.
Claim 14. The method of claim 8, wherein said pests are fungi.
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Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1643994A2 (en) * 2003-06-19 2006-04-12 Neuronautics, Inc. Methods for inhibiting or reversing tau filament fibrillization
EP1830846A2 (en) * 2004-12-17 2007-09-12 Mycosol, Inc. Thiazolium compounds and uses thereof
JP2007291348A (en) * 2006-03-09 2007-11-08 Fujifilm Corp Compound having polymethine-chain structure, image forming material using the same, planographic printing original plate, image forming method, and mehod of making planographic printing original plate and planographic printing method

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
DATABASE CAPLUS [Online] AVRAM ET AL.: 'Preparation of sterilization marking composition which changes color from pale pink to strong blue at the end of the sterilization', XP002972017 Retrieved from STN Database accession no. 2001:187552 & RO 115 062 B3 29 October 1999 *

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* Cited by examiner, † Cited by third party
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EP1643994A2 (en) * 2003-06-19 2006-04-12 Neuronautics, Inc. Methods for inhibiting or reversing tau filament fibrillization
EP1643994A4 (en) * 2003-06-19 2010-09-08 Neuronautics Inc Methods for inhibiting or reversing tau filament fibrillization
EP1830846A2 (en) * 2004-12-17 2007-09-12 Mycosol, Inc. Thiazolium compounds and uses thereof
EP1830846A4 (en) * 2004-12-17 2008-07-02 Mycosol Inc Thiazolium compounds and uses thereof
JP2007291348A (en) * 2006-03-09 2007-11-08 Fujifilm Corp Compound having polymethine-chain structure, image forming material using the same, planographic printing original plate, image forming method, and mehod of making planographic printing original plate and planographic printing method

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