WO2006138147A1 - Pesticidal 5-di-(substituted)aminopyrazole derivatives - Google Patents

Pesticidal 5-di-(substituted)aminopyrazole derivatives Download PDF

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WO2006138147A1
WO2006138147A1 PCT/US2006/022356 US2006022356W WO2006138147A1 WO 2006138147 A1 WO2006138147 A1 WO 2006138147A1 US 2006022356 W US2006022356 W US 2006022356W WO 2006138147 A1 WO2006138147 A1 WO 2006138147A1
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alkyl
haloalkyl
och
compound
halogen
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PCT/US2006/022356
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French (fr)
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Thomas Zydowsky
Syed F. Ali
Walter H. Yeager
John W. Lyga
John A. Dixson
Stephen F. Donovan
George Theodoridis
Elizabeth G. Rowley
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Bayer Cropscience Ag
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Publication of WO2006138147A1 publication Critical patent/WO2006138147A1/en

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
    • C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
    • C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D231/14—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members 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
    • C07D231/38—Nitrogen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
    • C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
    • C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D231/14—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members 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
    • C07D231/44—Oxygen and nitrogen or sulfur and nitrogen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • 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
    • C07D413/04—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 directly linked by a ring-member-to-ring-member bond
    • 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
    • C07D417/04—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 directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D419/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen, oxygen, and sulfur atoms as the only ring hetero atoms
    • C07D419/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen, oxygen, and sulfur atoms as the only ring hetero atoms containing two hetero rings
    • C07D419/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen, oxygen, and sulfur atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond

Definitions

  • the present invention relates to novel compounds and their use in controlling pests such as insects, acarids, general household pests and animal pests.
  • pests such as insects, acarids, general household pests and animal pests.
  • it pertains to 5-di-(substituted)aminopyrazole derivatives, insecticidally acceptable salts thereof, compositions containing them and methods for their use in controlling agricultural pests.
  • the invention also relates to 5-di- (substituted)aminopyrazole derivatives, pesticidally acceptable salts thereof, compositions containing them and methods for their use in controlling general household pests.
  • the invention also relates to 5-di-(substituted)aminopyrazole derivatives, veterinarily acceptable salts thereof, compositions containing them and methods for their use in controlling parasites in or on domestic and non-domestic animals.
  • insects in general can cause significant damage, not only to crops grown in agriculture, but also, for example, to structures and turf where the damage is caused by soil-borne insects, such as termites and white grubs. Such damage may result in the loss of millions of dollars of value associated with a given crop, turf or structures.
  • Insecticides and acaricides are useful for controlling insects and acarids which may otherwise cause significant damage to crops such as wheat, corn, soybeans, potatoes, and cotton to name a few.
  • insecticides and acaricides are desired which can control the insects and acarids without damaging the crops, and which have no deleterious effects to mammals and other living organisms.
  • novel 5- di-(substituted)aminopyrazole derivatives are surprisingly active in the control of insects, acarids, general household pests and domestic and non-domestic animal parasites when used in the pesticidal compositions and methods of this invention.
  • the novel derivatives are represented by the following general formula I:
  • W is C-halogen, C-CH 3 , C-CH 2 F, C-CHF 2 , C-CF 3 , C-NO 2 or N;
  • R 1 is selected from halogen, cyano, (Ci-C 4 )alkyl, (CrC 4 )haloalkyl, (C 3 -
  • R 1 is -CR ⁇ N-O-Y 1 , wherein R 7 is hydrogen, alkyl or R 7 and Y 1 are taken together to form a 5 or 6 member ring or R 7 is -NR 8 R 9 , wherein R 8 and R 9 are independently hydrogen or alkyl and Y 1 is hydrogen, alkenyl, alkynyl, formyl, alkylcarbonyl, cycloalkylcarbonyl, haloalkylcarbonyl, aroyl, arylalkylcarbonyl, alkylsulfonyl, arylsulfonyl, haloalkylcarbonyl, aminoalkylcarbonyl, alkylaminoalkylcarbonyl, dialkylaminocarbonyl, al
  • R 2 is selected from hydrogen, halogen, -S(O) n R 10 , (Q-C ⁇ alkyl, (CrC ⁇ haloalkyl, (C 3 -C 5 )alkenyl, (C 3 -C 5 )haloalkenyl, (C 3 -C 6 )cycloalkyl, (C 3 -C 6 )halocycloalkyl, (C 3 -C 5 )alkynyl, aryl, heteroaryl, -NR 8 R 9 , -CO 2 R 15 , nitro or cyano; n is an integer selected from 0,1 and 2;
  • R is hydrogen, halogen, cyano, formyl, acetyl, alkyl, haloalkyl or nitro;
  • R 4 is halogen, (C r C 4 )alkyl, (C r C 4 )haloalkyl, (C 3 -C 5 )alkenyl, (C 3 -C 5 )alkynyl, (C 1 -
  • a and B are independently selected from alkylene and haloalkylene;
  • X and Y are independently selected from O, N-R 11 , N(O)-R 13 , SiR 10 R 10 , and S(O) n ;
  • R 5 and R 6 are independently selected from hydrogen, (C 3 -C 5 )alkenyl, (C 3 - C 5 )haloalkenyl, (C 3 -C 5 )alkynyl, (C 3 -C 5 )haloalkynyl, (C 3 -C 6 )cycloalkyl, - (CH 2 ) q R 12 , -(CH 2 ) q R 13 and -NR 15 R 16 ; or is (Q-C ⁇ alkyl unsubstituted or substituted by one or more radicals selected from the group consisting of halogen
  • p is an integer selected from O or 1 ;
  • q is an integer selected from O, 1 , 2 and 3;
  • t is an integer selected from 0,1 and 2;
  • R 10 is alkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, cycloalkyl or halocycloalkyl ;
  • R 11 hydrogen, alkyl and haloalkyl
  • R 12 is phenyl unsubstituted or substituted by one or more radicals selected from the group consisting of halogen, alkyl, haloalkyl, alkoxy, haloalkoxy, -CN, -NO 2 , -
  • R 13 is haloalkyl, alkylcarbonyl or alkoxycarbonyl
  • R is heterocyclyl unsubstituted or substituted by one or more radicals selected from the group consisting of halogen, alkyl, haloalkyl, alkoxy, haloalkoxy, -CN,
  • R 15 and R 17 are each independently hydrogen, alkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, cycloalkyl, cycloalkylalkyl, -(CH 2 ) q R 18 or -(CH 2 ) q R 14 ;
  • R 16 and R 19 are each independently hydrogen, alkyl, haloalkyl, cycloalkyl or cycloalkylalkyl;
  • R 18 is phenyl unsubstituted or substituted by one or more radicals selected from the group consisting of halogen, alkyl, haloalkyl, alkoxy, haloalkoxy,-CN, -NO 2 , -
  • R 20 and R 21 are independently selected from hydrogen, alkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, cycloalkyl, cycloalkylalkyl, -(CH 2 ) q R 18 , - (CH 2 ) q R 14 , -COalkyl, -S(O) n alkyl or
  • R 22 is hydrogen, alkyl, alkoxy, alkoxyalkyl, alkylthioalkyl or alkylsulfmylalkyl; and each heterocyclyl in the above-mentioned radicals is independently a heterocyclic radical having 3 to 7 ring atoms and 1 , 2 or 3 hetero atoms in the ring selected from the group consisting of N, O and S; and pesticidally acceptable salts thereof; provided that when R 1 is cyano and R 2 is -S(O) n R 10 , then A and B are other than methylene, X and Y are other than O and R 5 and R 6 are other than methyl.
  • the present invention also includes compositions containing a pesticidally effective amount of at least one compound of formula I, and optionally, an effective amount of at least one additional compound, with at least one pesticidally compatible carrier.
  • the present invention also includes methods of controlling insects, general household pests and animal parasites in an area where control is desired, which comprise applying a pesticidally effective amount of the above composition to the locus of crops, buildings, soil, animals or other areas where insects, general house hold pests or animal parasites are present or are expected to be present.
  • the present invention generally relates to pesticidal compositions of 5-di-
  • the pesticidal compositions of the present invention are comprised of 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:
  • W is C-halogen, C-CH 3 , C-CH 2 F, C-CHF 2 , C-CF 3 , C-NO 2 or N;
  • R 1 is -CR ⁇ N-O-Y 1 , wherein R 7 is hydrogen, alkyl or R 7 and Y 1 are taken together to form a 5 or 6 member ring or R 7 is -NR 8 R 9 , wherein R 8 and R 9 are independently hydrogen or alkyl and Y 1 is hydrogen, alkenyl, alkynyl, formyl, alkylcarbonyl, cycloalkylcarbonyl, haloalkylcarbonyl, aroyl, arylalkylcarbonyl, alkylsulfonyl, arylsulfonyl, haloalkylcarbonyl, aminoalkylcarbonyl, alkylaminoalkylcarbonyl, dialkylaminocarbonyl, alkoxyalkylcarbonyl, arylalkoxycarbonyl, alkylthioalkylcarbonyl, alkylsulfonylalkylcarbonyl, arylthioalkoxycarbonyl,
  • R 2 is selected from hydrogen, halogen, -S(O) n R 10 , (Q-GOalkyl, (Ci-C 4 )haloalkyl, (C 3 -C 5 )alkenyl, (C 3 -C 5 )haloalkenyl, (C 3 -C 6 )cycloalkyl, (C 3 -C 6 )halocycloalkyl, (C 3 -C 5 )alkynyl, aryl, heteroaryl, -NR 8 R 9 , -CO 2 R 15 , -CR ⁇ N-O-Y 1 , nitro or cyano; n is an integer selected from 0,1 and 2;
  • R 3 is hydrogen, halogen, cyano, formyl, acetyl, alkyl, haloalkyl or nitro;
  • R 4 is halogen, (C 3 -C 5 )alkenyl, (C 3 -C 5 )alkynyl, (C 1 -
  • a and B are independently selected from (C 2 -C 7 )alkylene and haloalkylene;
  • X and Y are independently selected from O, N-R 11 , N(O)-R 13 , SiR 10 R 10 , and S(O) n ;
  • R 5 and R 6 are independently selected from hydrogen, (C 3 -C 5 )alkenyl, (C 3 - C 5 )haloalkenyl, (C 3 -C 5 )alkynyl, (C 3 -C 5 )haloalkynyl, (C 3 -C 6 )cycloalkyl, - (CH 2 ) q R 12 , -(CH 2 ) q R 13 and -NR 15 R 16 ; or is (Q-C ⁇ alkyl unsubstituted or substituted by one or more radicals selected from the group consisting of halogen, alkoxy, haloalkoxy, alkenyloxy, haloalkenyloxy, alkynyloxy, haloalkynyloxy, trialkylsilyl, cycloalkyl, -S(O) n R 13 , -CN, -NO 2 , -OH, -OR 12 , -OR 14 , -
  • R 10 is alkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, cycloalkyl or halocycloalkyl;
  • R 11 hydrogen, alkyl and haloalkyl
  • R 12 is phenyl unsubstiruted or substituted by one or more radicals selected from the group consisting of halogen, alkyl, haloalkyl, alkoxy, haloalkoxy, -CN, -NO 2 , -
  • R 13 is haloalkyl, alkylcarbonyl or alkoxycarbonyl
  • R 14 is heterocyclyl unsubstituted or substituted by one or more radicals selected from the group consisting of halogen, alkyl, haloalkyl, alkoxy, haloalkoxy, -CN,
  • R 15 and R 17 are each independently hydrogen, alkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, cycloalkyl, cycloalkylalkyl, -(CH 2 ) q R 1 i 8 ⁇ or -(CH 2 ) q R , 1 1 4 4 .;
  • R 16 and R 19 are each independently hydrogen, alkyl, haloalkyl, cycloalkyl or cycloalkylalkyl;
  • R is phenyl unsubstituted or substituted by one or more radicals selected from the group consisting of halogen, alkyl, haloalkyl, alkoxy, haloalkoxy,-CN, -NO 2 , -
  • R and R are independently selected from hydrogen, alkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, cycloalkyl, cycloalkylalkyl, -(CH 2 ) q R 18 , -
  • R 22 is hydrogen, alkyl, alkoxy, alkoxyalkyl, alkylthioalkyl or alkylsulfmylalkyl; and each heterocyclyl in the above-mentioned radicals is independently a heterocyclic radical having 3 to 7 ring atoms and 1, 2 or 3 hetero atoms in the ring selected from the group consisting of N, O and S; and pesticidally acceptable salts thereof; provided that when R 1 is cyano and R 2 is -S(O) n R 10 , then A and B are other than methylene, X and Y are other than O and R 5 and R 6 are other than methyl.
  • Preferred 5-di-(substituted)aminopyrazole derivatives from the group set forth above are those where: W is C-halogen; R 1 is cyano;
  • R 2 is, -S(O) n R 10 or haloalkyl;
  • R 3 is halogen;
  • R 4 is haloalkyl;
  • a and B are each -CH 2 -;
  • X and Y are each O or S(O) n ; and R 5 and R 6 are each (Q-C ⁇ alkyl or are taken together to form a ring of formula (9), formula (11) or formula (12).
  • 5-di-(substituted)aminopyrazole derivatives of the group set forth above are those where: W is C-Cl;
  • R 2 is, -S(O)CF 3 or CF 3 ;
  • R 3 is chlorine;
  • R 4 is CF 3 ;
  • X and Y are each O or S(O) n where n is 0; and R 5 and R 6 are each methyl or ethyl.
  • the compounds of the present invention may exist as tautomers, in which migration of a hydrogen atom within the molecule results in two or more structures, which are in equilibrium.
  • compounds of formula I wherein R 1 is - CR ⁇ N-O-Y 1 , in which R 7 represents -NR 8 R 9 , in which R 8 represents hydrogen and R represents hydrogen or alkyl may exist in tautomeric forms as shown in formulae Ia and Ib.
  • Such tautomerism is well known as is described in S. Patai (The Chemistry of Functional Groups: Amidines and Imidates, VoI 2, 1991, pages 276- 277). It will be understood that all such tautomeric forms are embraced by the present invention.
  • the compounds of the present invention may possess asymmetric centers, which can give rise to optical enantiomorphs and diastereomers.
  • the compounds may exist in two or more forms, i.e., polymorphs, which are significantly different in physical and chemical properties.
  • the compounds of the present invention may also possess acidic or basic moieties, which may allow for the formation of agriculturally acceptable salts or agriculturally acceptable metal complexes. This invention includes the use of such enantiomorphs, polymorphs, tautomers, salts and metal complexes.
  • Insecticidally 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.
  • 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
  • alkali metal and alkaline earth metal complexes with, for example, sodium, potassium, lithium, magnesium, calcium, and
  • the methods of the present invention comprise causing an insecticidally effective amount of a compound of formula I to be administered to insects in order to kill or control the insects.
  • Preferred insecticidally effective amounts are those that are sufficient to kill the insect. It is within the scope of the present invention to cause a compound of formula I to be present within insects by contacting the insects with a derivative of that compound, which derivative is converted within the insect to a compound of formula I. This invention includes the use of such compounds, which are referred to as pro-insecticides.
  • compositions containing an insecticidally effective amount of at least one compound of formula I relates to compositions containing an insecticidally effective amount of at least one compound of formula I.
  • compositions containing an insecticidally effective amount of at least one compound of formula I, and an effective amount of at least one additional compound are also useful.
  • Another aspect of the present invention relates to methods of controlling insects by applying an insecticidally effective amount of a composition as set forth above to a locus of crops such as, without limitation, cereals, cotton, vegetables, and fruits, or other areas where insects are present or are expected to be present.
  • the present invention also includes the use of the compounds and compositions set forth herein for control of non-agricultural insect species, for example, dry wood termites and subterranean termites; as well as for use as pharmaceutical agents.
  • the compounds of the present invention are expected to be effective, orally, parenterally and topically, against certain endo- and ecfo-parasites, such as insects and worms, which prey on animals. Examples of such animal parasites include, without limitation, Gastrophilus spp., Stomoxys spp., Trichodectes spp., Rhodnius spp., Ctenocephalides cards, and other species.
  • the compounds of the present invention are generally more efficacious or have a reduced insect resistance factor or have a broader spectrum of activity or are safer (e.g. less toxic to mammals) or have other more advantageous properties than the compounds of the prior art.
  • 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.
  • alkylene is to be understood as meaning a straight or branched saturated carbon chain having from 1 to 12 atoms.
  • haloalkylene is to be understood as meaning a straight or branched saturated carbon chain having from 1 to 12 atoms, in which one or more hydrogen atoms are replaced by the same number of halogen atoms.
  • haloalkyl and haloalkoxy 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, wherein one or more hydrogen atoms have been replaced with halogen atoms, for example, trifluoromethyl or 2,2,2- trifiuoroethoxy.
  • 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.
  • aroyl designates a carbonyl aromatic radical, that is, aryl- C(O)-, which is preferably a benzoyl optionally substituted by one or more alkyl, alkoxy or halogen groups.
  • aryl refers to an aromatic ring structure, including fused rings, having six to ten carbon atoms, for example, phenyl, indanyl, indenyl, naphthyl or 5,6,7,8-tetrahydronaphthyl.
  • 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. Heteroaryl rings include, without limitation, for example, oxazolyl, thiazolyl, imidazolyl, pyrazolyl, triazolyl or thiadiazolyl.
  • DMF refers to N 5 N- dimethylformamide.
  • THF tetrahydrofuran
  • halogen or halo refers to fluorine, bromine, iodine, or chlorine.
  • ambient temperature for example, in reference to a chemical reaction mixture temperature, refers to a temperature in the range of 20 0 C to 30 °C.
  • insecticidal or “acaricidal”
  • insecticide or “acaricide” refers to a compound of the present invention, either alone or in admixture with at least one additional compound, or with at least one compatible carrier, which causes the destruction or the inhibition of action of insects or acarids.
  • the term "independently selected from” as set forth above and in the claims section of the present specification refers to the possibility that moieties, for example the R 5 and R 6 , may be the same or they may be different within the group that the selection is made.
  • the term "general household pest” refers to any insect or pest, such as German cockroach, American cockroach, Smokey-Brown cockroach, Oriental cockroach, house fly, biting fly, filth fly, red imported fire ant (RIFA), odorous house ant, carpenter ant, pharaoh ant, termite, Argentine ant, mosquito, tick, flea, sowbug, pillbug, centipede, spider, silverfish, scorpion and bed bug, that cause harm or nuisance to person or property.
  • the 5-di-(substituted)aminopyrazole derivatives of formula I can be synthesized by methods that are individually known to one skilled in the art from available intermediate compounds. A number of the compounds of the present invention were prepared
  • the formulation and mode of application of a toxicant may affect the activity of the material in a given application.
  • the present insecticidal 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 useful formulations, depending on the desired mode of application.
  • 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.
  • insecticidal 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 insecticides, 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 insecticidal 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 agricultural 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 insecticidal 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 insecticidal compounds of this invention may be formulated and/or applied with one or more additional compound.
  • Such combinations may provide certain advantages, such as, without limitation, exhibiting synergistic effects for greater control of insect pests, reducing rates of application of insecticide thereby minimizing any impact to the environment and to worker safety, controlling a broader spectrum of insect pests, safening of crop plants to phytotoxicity, and improving tolerance by non-pest species, such as mammals and fish.
  • Additional compounds include, without limitation, 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)glycines such as glyphosate; aryloxyalkanoic acids such as 2,4- D, MCPA, and MCPP; ureas such as isoproturon; imidazolinones such as imazapyr, imazamethabenz, imazethapyr, and imazaquin; diphenyl ethers such as acifluorfen, bifenox, and fomasafen; hydroxybenzonitriles such as ioxynil and bromoxynil; sulfonylureas such as chlorimuron, achlorsulfuron, bensulfuron, pyrazosulfuron, thifensulfuron, and triasulfuron; 2-(4-aryloxymethyl)glycines such as glyphosate; aryloxyalkanoic acids such as 2,4- D, MCPA, and MCPP;
  • 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, ⁇ f ⁇ /z ⁇ -cypermethrin, ⁇ et ⁇ -cypermethrin, zet ⁇ -cypermethrin, bifenthrin, cypermethrin, permethrin, resolved cyhalothrin, etofenprox, esfenvalerate, tralomehtrin, tefluthrin, cyclopro
  • organophosphate insecticides such as chlorpyrifos, diazinon, dimethoate, malathion, parathion- methyl,
  • 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, simeconazole, 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
  • the active insecticidal compounds of the present invention are used in combination with at least one additional compound, e.g., with other pesticides such as nematicides
  • the nematicides include, for example: carbofuran, carbosulfan, terbufos, 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.
  • 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.
  • 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 compounds may be administered alone or in a formulation appropriate to the specific use envisaged and to the particular species of host animal being treated and the parasite involved.
  • the methods by which the compounds may be administered include oral administration by capsule, bolus, tablet or drench, or as a pour-on or spot-on formulation, or alternatively, they can be administered by injection (e.g. subcutaneously, intramuscularly or intravenously), dip, spray, mousse, shampoo, powder, or as an implant.
  • Such formulations are prepared in a conventional manner in accordance with standard veterinary practice.
  • capsules, boluses or tablets may be prepared by mixing the active ingredient with a suitable finely divided diluent or carrier additionally containing a disintegrating agent and/or binder such as starch, lactose, talc, magnesium stearate etc.
  • Oral drenches are prepared by dissolving or suspending the active ingredient in a suitable medium.
  • injectable formulations may be prepared in the form of a sterile solution which may contain other substances, for example, enough salts or glucose to make the solution isotonic with blood.
  • Acceptable liquid carriers include the vegetable oils such as sesame oil and the like, glycerides such as triacetin and the like, esters such as benzyl benzoate, isopropyl myristate and fatty acid derivatives of propylene glycol and the like, as well as organic solvents such as pyrrolidone, glycerol formal and the like.
  • the formulations are prepared by dissolving or suspending the active ingredient in the liquid carrier such that the final formulation contains from 0.01 to 10% by weight of the active ingredient.
  • compositions will vary with regard to the weight of active compound contained therein depending on the species of host animal to be treated, the severity and type of infection and the body weight of the host.
  • topical e.g. using pour-on or spot-on, dip, spray, mousse, shampoo or powder to deliver the compound
  • typical dose ranges of the active ingredient are 0.01-100 mg per kg of body weight of the animal.
  • the range is 0.1 to 10 mg per kg.
  • the compounds may be administered with the animal feedstuff and for this purpose a concentrated feed additive or premix may be prepared for mixing with the normal animal feed.
  • the compounds of the invention may, in particular, be used in the field of veterinary medicine and livestock husbandry against arthropods, helminths or protozoa which are parasitic internally or externally upon vertebrates, particularly warm-blooded vertebrates, for example domestic and non-domestic animals, e.g. cattle, sheep, goats, equines, swine, poultry, dogs, and cats.
  • the compounds of the invention are particularly useful in controlling arthropods, helminths or protozoa which are present inside the host animals or which feed in or on the skin or suck the blood of the animal, for which purpose they may be administered orally, parenterally, percutaneously or topically.
  • a pesticidal formulation comprising a compound of the invention, in admixture with a compatible adjuvant, diluent or carrier.
  • the formulation is adapted for topical administration.
  • the invention further provides a compound of the invention for use as a pesticide; and a method of treating a pest infestation at a locus, which comprises treatment of the locus with an effective amount of a compound of the invention.
  • the locus is the skin or fur of an animal.
  • EXAMPLE 1 This example illustrates one protocol for the preparation of l-(2,6-dichloro-4- trifluoromethylphenyl)-5-(l,5,3-dioxazaperhydroepin-3-yl)-4- (ttfluoromethylsulfinyl)-pyrazole-3-carbonitrile
  • Patent 5,232,940 in 10 mL of THF was added to a stirred, cold (0°C) mixture of 0.2 gram (0.005 mole) of a 60% sodium hydride suspension in mineral oil in 10 mL of THF.
  • the cold reaction mixture was stirred for 10 minutes and 0.61 gram (0.005 mole) of bromomethyl methyl ether was added.
  • the cold reaction mixture was stirred for 3 hours.
  • the reaction mixture was diluted with ethyl acetate, washed in succession with an aqueous saturated ammonium chloride solution, an aqueous saturated sodium bicarbonate solution and an aqueous saturated sodium chloride solution, and then dried with magnesium sulfate. The solution was filtered and the filtrate was concentrated under reduced pressure leaving an oil.
  • Step B 1 (2,6-dichloro-4-trifluoromethyl ⁇ henyl)-5-(l ,5,3- dioxaza ⁇ erhydroepin-3-yl)-4-(trifluoromethylsulfinyl)-pyrazole-3- carbonitrile (Compound 3-10)
  • the reaction mixture was concentrated under reduced pressure leaving a residue.
  • the residue was purified by column chromatography on silica gel, eluting with mixtures of ethyl acetate in hexanes. The appropriate fractions were combined and concentrated under reduced pressure, yielding 0.09 gram of the title compound as a solid.
  • the NMR spectrum was consistent with the proposed structure.
  • This example illustrates one protocol for the preparation of l-(2,6-dichloro-4- trifluoromethylphenyl)-5- ⁇ [(2-cyanoethoxy)methyl](methoxymethyl)amino ⁇ -4- (trifluoromethylsulfinyl)pyrazole-3-carbonitrile (Compound 1-58) and l-(2,6- dichloro-4-trifluoromethylphenyl)-5- ⁇ bis[(2-cyanoethoxy)methyl]amino ⁇ -4-
  • This example illustrates one protocol for the preparation of 3- (amino(hydroxyimino)methyl)-l-(2,6-dichloro-4-trifluoromethylphenyl)-5- [bis(methoxymethyl) amino] -4-(trifluoromethylsulf ⁇ nyl)pyrazole (Compound 1 -5)
  • the reaction mixture was concentrated under reduced pressure leaving a residue.
  • the residue was partitioned between ethyl acetate and water.
  • the organic phase was washed with an aqueous saturated sodium chloride solution, dried with magnesium sulfate and filtered.
  • the filtrate was concentrated under reduced pressure to a residue.
  • the residue was purified by column chromatography on silica gel, eluting with mixtures of ethyl acetate and hexanes. The appropriate fractions were combined and concentrated under reduced pressure to yield 0.1 gram of the title compound as a solid.
  • the NMR spectrum was consistent with the proposed structure.
  • 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.
  • test compounds of formula I are identified by numbers that correspond to those in Table 1 :
  • Candidate insecticides were evaluated for activity against the tobacco budworm (Heliothis virescens [Fabricius]) in a surface-treated diet test.
  • one mL of molten (65-7O 0 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 diameter 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 the candidate insecticide.
  • solutions of the candidate insecticide were evaluated for activity against the tobacco budworm (Heliothis virescens [Fabricius]) in a surface-treated diet test.
  • molten 65-7O 0 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 diameter x 17.6 mm deep; Corning Costar Corp., One Alewife Center
  • Appropriate untreated controls containing only DMSO on the diet surface were 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 a second instar tobacco budworm larvae, 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. 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 relative to the weight of insects from untreated controls, and percent mortality when compared to the total number of insects infested.
  • Insecticidal activity data at selected rates of application from this test are provided in Table 3.
  • the test compounds of formula I are identified by numbers that correspond to those in Table 1.
  • Concentration of the candidate insecticide on the surface of the diet is 0.25 millimolar
  • Candidate insecticides were evaluated for insecticidal activity by observing mortality in a population of treated cotton aphid (Aphis gossypii) on cotton plant leaf discs when compared to like populations of untreated cotton aphid on cotton plant leaf discs. These tests were conducted in the following manner:
  • Three week to one month-old cotton plants (Gossypium hirsutium) were prepared for infesting by cutting off the cotyledons and new true leaf growth, leaving the oldest two true leaves.
  • the prepared test plant was infested with cotton aphids by translocation from cotton plants grown in a cotton aphid colony.
  • the wells of clear 128-well trays (CD-International, Pittman, New Jersey) were filled with 1 mL of a warm, aqueous 3% agar solution and allowed to cool to ambient temperature.
  • the aphid infested cotton leaves were removed from the plants and placed bottom side up on a cutting platform.
  • Circular discs were cut from the infested leaves and placed bottom side up onto the cooled agar gel, one disc per well. Each leaf disc was visually inspected to assure that a minimum of 10 live aphids were present.
  • a 50 mM stock solution of the test compound was prepared by dissolving the appropriate amount of the test compound in DMSO.
  • a solution comprising 1000 part per million (ppm) of each test compound was prepared by dissolving 10 ⁇ l of the stock solution in 140 ⁇ l of an aqueous 0.003% Kinetic® (a nonionic wetter/spreader/penetrant adjuvant, Helena Chemical Company, Collierville, Tennessee) solution.
  • Kinetic® a nonionic wetter/spreader/penetrant adjuvant, Helena Chemical Company, Collierville, Tennessee
  • test compound was serially diluted with a solution consisting of 66mL of DMSO and 30 ⁇ l of Kinetic® in 934 mL of water (diluting solution) to provide solutions of each test compound for lower rates of application, for example, 300 ppm, 100 ppm, 30 ppm, or 10 ppm.
  • a solution consisting of 66mL of DMSO and 30 ⁇ l of Kinetic® in 934 mL of water (diluting solution) to provide solutions of each test compound for lower rates of application, for example, 300 ppm, 100 ppm, 30 ppm, or 10 ppm.
  • Each replicate infested test plant disc was sprayed with 10 ⁇ l of the test solution at about 8 psi for 1 second.
  • a solution of a standard, such as bifenthrin, prepared in a manner analogous to that set forth above, as well as an aqueous solution of 0.003% Kinetic® containing no test compound and the diluting solution containing no test compound were also sprayed onto infested test plant discs.
  • a solution of a standard such as bifenthrin
  • Kinetic® aqueous solution of 0.003% Kinetic® containing no test compound and the diluting solution containing no test compound
  • the plant discs were allowed to dry.
  • the test trays were covered with a plastic film. Three slits were made in the film over each well to allow air into each well.
  • the test trays were placed in a biochamber (25 0 C, 16 hours light, 8 hours of dark and 35-40% relative humidity) for three days.
  • each plant disc was assessed for percent mortality caused by the test compound when compared to the population of aphids that was infested onto the test plant discs containing no test compound.
  • a test compound was designated as possessing insecticidal activity (SA) if there was 40% to 75% mortality of cotton aphid on plant discs sprayed with that compound. If there was 75% mortality or greater of the cotton aphid, a test compound was designated as being more insecticidally active (A). If there was 40% mortality or less of the cotton aphid, the test compound was termed as inactive (I).
  • test compounds of formula I are identified by numbers that correspond to those in Table 1.
  • Candidate insecticides were evaluated for insecticidal activity by observing mortality in a population of cotton aphid (Aphis gossvpii ) on treated cotton plants when compared to like populations of cotton aphid on untreated plants. These tests were conducted in the following manner: For each rate of application of test compound, two seven-to-ten days old cotton seedlings (Gossvpium hirsutium) grown in 7.6 cm diameter pots were selected for the test. Each test plant was infested with about 120 adult cotton aphids by placing onto each test plant cuttings of leaves from cotton plants grown in a cotton aphid colony.
  • test plants were maintained for up to about 12 hours to allow complete translocation of the aphids onto the test plant.
  • a solution comprising 1000 part per million (ppm) of each test compound was prepared by dissolving 10 milligrams of the test compound in 1 mL of acetone. Each solution was then diluted with 9 mL of a solution of 0.03 mL of polyoxyethylene(l ⁇ ) isooctylphenyl ether in 100 mL of water. About 2.5 mL of solution of each test compound was needed to spray each replicate of test plant (5 mL total for each test compound).
  • test compound was serially diluted with a solution of 10% acetone and 300 ppm of polyoxyethylene(l ⁇ ) isooctylphenyl ether in water to provide solutions of each test compound for lower rates of application, for example, 300 ppm, 100 ppm, 30 ppm, or 10 ppm.
  • 300 ppm, 100 ppm, 30 ppm, or 10 ppm were sprayed with the solutions of test compound until run-off on both the upper and lower surfaces of the leaves. All the test plants were sprayed using a DeVilbus Atomizer Model 152 (Sunrise Medical, Carlsbad, CA) at a pressure of about 0.63-0.74 kilogram per square centimeter from a distance of about 30.5 centimeters from the test plants.
  • a solution of 10% acetone and 300 ppm of polyoxyethylene(l ⁇ ) isooctylphenyl ether in water containing no test compound was also sprayed onto control test plants.
  • the plants were allowed to dry.
  • the test and control plants were placed in a tray containing about 2.5 centimeters of water, where they were maintained in a growth chamber for 72 hours. After this time, each plant was assessed for percent mortality caused by the test compound when compared to the population of aphids that was infested onto the test plants prior to treatment with test compound.
  • test compound was designated as possessing insecticidal activity (SA) if there was 40% to 75% mortality of cotton aphid on plants sprayed with that compound. If there was 75% mortality or greater of the cotton aphid, a test compound was designated as being more insecticidally active (A). If there was 40% mortality or less of the cotton aphid, the test compound was termed as inactive (I).
  • test compounds of formula I are identified by numbers that correspond to those in Table 1.
  • Cotton Aphid (Aphis gossypii) Between 40% and 100% When Applied At An Application Rate Of 1 OOOppm Or Less On Infested Cotton Plants
  • the tested compounds of the present invention reduced the aphid population by at least 40% at an application rate of lOOOppm or less.
  • Candidate insecticides were evaluated for insecticidal activity by observing mortality in a population of silverleaf whitefly (Bemisia argentifolii) on treated cotton plant cotyledons when compared to like populations of silverleaf whitefly on untreated plant cotyledons. These tests were conducted in the following manner:
  • test compound For each rate of application of test compound, two four to six days old cotton seedlings (Gossypium hirsutium) grown in 3-inch diameter pots were selected for the test. Each test plant was sprayed with a test solution comprising 300 part per million (ppm), or less, of each test compound prepared by dissolving 12 milligrams of the test compound in 4 mL of acetone. Each solution was then diluted with 36 mL of a surfactant and water solution prepared by dissolving 0.03 gm of Triton X-100 ® surfactant in 100 mL of distilled water, providing a stock test solution of 300 ppm.
  • ppm part per million
  • test plants were sprayed using a DeVilbus Atomizer Model 152 (Sunrise Medical, Carlsbad, CA) at a pressure of about 0.63-0.74 kilogram per square centimeter from a distance of about 30.5 centimeters from the test plants.
  • a DeVilbus Atomizer Model 152 Silicon-based Atomizer Model 152 (Sunrise Medical, Carlsbad, CA) at a pressure of about 0.63-0.74 kilogram per square centimeter from a distance of about 30.5 centimeters from the test plants.
  • the test plants were allowed to dry.
  • the test plants were excised at the soil surface and placed in a 1 ounce plastic cup containing a 2.5 cm filter paper moistened with 50 microliters of distilled water.
  • Whiteflies 25-50 were added to each cup and a lid was placed on each.
  • the test cups were maintained in a growth chamber for 72 hours at 70% relative humidity (light 12 hours/day).
  • test compound was assessed for percent mortality caused by the test compound when compared to the population of whiteflies that were infested onto the test plants.
  • a test compound was designated as possessing insecticidal activity (SA) if there was 40% to 75% mortality of whiteflies on plants sprayed with that compound. If there was 75% mortality or greater of whiteflies, a test compound was designated as being more insecticidally active (A). If there was 40% mortality or less of the cotton aphid, the test compound was termed as inactive (I).
  • SA insecticidal activity
  • A insecticidally active
  • I inactive
  • Table 5 An assessment of the insecticidal activity at selected rates of application from this test is provided in Table 5.
  • the test compounds of formula >I are identified by numbers that correspond to those in Table 1.
  • Silverleaf Whitefly (Bemisia argentifoHi) by 40% to 100% When Applied at an Application Rate of 300ppm or Less
  • Candidate insecticides were evaluated for insecticidal activity by observing mortality in a population of tarnished plant bug nymphs (Lygus lineolaris) on treated broccoli plant leaves when compared to like populations of tarnished plant bug on untreated plant leaves. These tests were conducted in the following manner: For each rate of application of test compound, four ten to fifteen days old broccoli seedlings ⁇ Brassica oleraced) grown in 3 -inch diameter pots were selected for the test.
  • test solution comprising 300 part per million (ppm), or less, of each test compound prepared by dissolving 12 milligrams of the test compound in 4 mL of acetone.
  • Each solution was then diluted with 36 mL of a surfactant and water solution prepared by dissolving 0.03 gm of Triton X- 100 ® surfactant in 100 mL of distilled water, providing a stock test solution of 300 ppm.
  • About 2.5 mL of solution of each test compound was needed to spray each replicate of test plant (10 mL total for each test compound).
  • the solution of 300 ppm of test compound was diluted with a solution of 10% acetone and 300 ppm of Triton X- 100 ® surfactant in water to provide solutions of each test compound for lower rates of application, for example, 100 ppm, 30 ppm, or 10 ppm.
  • Each replicate of test plant was sprayed with the solutions of test compound until run-off on both the upper and lower surfaces of the leaves. All the test plants were sprayed using a DeVilbus Atomizer Model 152 (Sunrise Medical, Carlsbad, CA) at a pressure of about 0.63-0.74 kilogram per square centimeter from a distance of about 30.5 centimeters from the test plants.
  • test compound was designated as possessing insecticidal activity (SA) if there was 40% to 75% mortality of cotton aphid on plants sprayed with that compound. If there was 75% mortality or greater of the cotton aphid, a test compound was designated as being more insecticidally active (A). If there was less than 40% mortality of the cotton aphid, the test compound was termed as inactive (I).
  • test compounds of formula I are identified by numbers that correspond to those in Table 1.
  • the initial test solution was serially diluted with acetone to provide solutions of each test compound for lower rates of application onto 30 grams of sandy clay loam top soil, for example, 100 ppm, 30 ppm, 10 ppm, 3 ppm, 1 ppm, 0.3 ppm or 0.1 ppm.
  • test solution 3 mL was added to 30 grams of unsterilized sandy clay loam top soil in a container and mixed well. The treated soil was allowed to dry at ambient temperature in a hood for 30 minutes. Three mL of distilled water was added to the treated soil providing a soil moisture of 10%. The treated soil was distributed equally into three 60 x 15 mm Petri dishes. The soil in each Petri dish was infested with 10 adult Formosan termites after residual periods of 0 days.
  • soil samples containing 10% moisture as described above were prepared from an untreated sandy clay loam top soil sample (untreated check). Upon completion of infestation the tops were placed on the Petri dishes and the Petri dishes were placed in a growth chamber where they were maintained in the dark for 7 days at 80% relative humidity.
  • each test was assessed daily up to 7 days after infestation (DAI) for percent mortality caused by the test compound when compared to the population of termites that were infested onto the control soil tests containing no test compound. Termites are classified as dead if they fail to show movement when probed.
  • DAI daily up to 7 days after infestation
  • test compounds of formula I are identified by numbers that correspond to those in Table 1.
  • Candidate insecticides were evaluated for mammalian toxicity in a GABA receptor test. Rat brains were homogenized with physiological saline (same pH as in the rat plasma). A portion of this suspension (0.1 mL) was mixed with a radioligand [4'-ethynyl-4-n- ⁇ ropyl bicycloorthobenzoate (EBOB)]. Tubes containing this mixture and a test compound were compared with a reference (tubes with this mixture but without test compound).
  • EBOB radioligand
  • the radioligand binds to a site within the known GABA receptor channel. If there is no test compound, the radioligand does bind; if there is a toxic compound effective on the same site, the amount of radioligand is reduced because the test compound replaces the radioligand.

Abstract

Certain novel 5-di-(substituted)aminopyrazole derivatives have unexpecte activity in controlling insects, general household pests and animal parasites. Thes compounds are represented by formula I: where A, B, W, X, Y and R through R6, inclusively, are fully described herein, h addition, compositions comprising a pesticidally effective amount of at least one compound of formula I, and optionally, an effective amount of at least one of an additional 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.

Description

PESTICIDAL 5-DI-(SUBSTITUTEDUMINOPYRAZOLE DERIVATIVES
This application claims the benefit of U.S. Provisional Application No. 60/690,014 filed June 13, 2005, and U.S. Provisional Application No. 60/763,071, filed January 27, 2006.
FIELD OF THE INVENTION
The present invention relates to novel compounds and their use in controlling pests such as insects, acarids, general household pests and animal pests. In particular, it pertains to 5-di-(substituted)aminopyrazole derivatives, insecticidally acceptable salts thereof, compositions containing them and methods for their use in controlling agricultural pests. The invention also relates to 5-di- (substituted)aminopyrazole derivatives, pesticidally acceptable salts thereof, compositions containing them and methods for their use in controlling general household pests. The invention also relates to 5-di-(substituted)aminopyrazole derivatives, veterinarily acceptable salts thereof, compositions containing them and methods for their use in controlling parasites in or on domestic and non-domestic animals.
BACKGROUND OF THE INVENTION It is well known that insects in general can cause significant damage, not only to crops grown in agriculture, but also, for example, to structures and turf where the damage is caused by soil-borne insects, such as termites and white grubs. Such damage may result in the loss of millions of dollars of value associated with a given crop, turf or structures. Insecticides and acaricides are useful for controlling insects and acarids which may otherwise cause significant damage to crops such as wheat, corn, soybeans, potatoes, and cotton to name a few. For crop protection, insecticides and acaricides are desired which can control the insects and acarids without damaging the crops, and which have no deleterious effects to mammals and other living organisms. It is generally a goal of veterinarians to possess sufficient means to control parasites, particularly arthropods or helminths, when they attempt to invade or attack animals, particularly domestic animals and/or livestock. A classical method of controlling such parasites has been the use of topical and/or systemic pesticides on or in the animal which is being attacked. Generally effective treatments include the oral administration of insect growth regulators, such as lufenuron, antihelminth compounds such as an ivermectin or avermectin or the topical application of the insecticide fipronil. The control of insects, arachnids and helminths with 1-arylpyrazole compounds has been described in, for example, patent publication numbers WO 98/28277, WO 98/282278, EP 500209, EP 295117, U.S. 5,814,652 and U.S. 5,232,940. The control of parasites in animals with 1-arylpyrazole compounds has been described in, for example, patent publication numbers WO 03/074492, WO 03/074493, WO 00/35884, WO 97/28126, U.S. 6,069,157, and U.S. 6,531,501.
SUMMARY OF THE INVENTION
In accordance with the present invention, it has now been found that certain novel 5- di-(substituted)aminopyrazole derivatives are surprisingly active in the control of insects, acarids, general household pests and domestic and non-domestic animal parasites when used in the pesticidal compositions and methods of this invention. The novel derivatives are represented by the following general formula I:
Figure imgf000003_0001
I wherein
W is C-halogen, C-CH3, C-CH2F, C-CHF2, C-CF3, C-NO2 or N;
R1 is selected from halogen, cyano, (Ci-C4)alkyl, (CrC4)haloalkyl, (C3-
C6)cycloalkyl, -S(O)nR10, formyl, acetyl, nitro, -C(S)NH2, -C(=NNH2)NH2; or R1 is -CR^N-O-Y1, wherein R7 is hydrogen, alkyl or R7 and Y1 are taken together to form a 5 or 6 member ring or R7 is -NR8R9, wherein R8 and R9 are independently hydrogen or alkyl and Y1 is hydrogen, alkenyl, alkynyl, formyl, alkylcarbonyl, cycloalkylcarbonyl, haloalkylcarbonyl, aroyl, arylalkylcarbonyl, alkylsulfonyl, arylsulfonyl, haloalkylcarbonyl, aminoalkylcarbonyl, alkylaminoalkylcarbonyl, dialkylaminocarbonyl, alkoxyalkylcarbonyl, arylalkoxycarbonyl, alkylthioalkylcarbonyl, alkylsulfonylalkylcarbonyl, arylthioalkoxycarbonyl, N-alkylcarbamoyl, N-arylcarbamoyl, N- alkylthiocarbamoyl, N-arylthiocarbamoyl, alpha-hydroxyarylalkylcarbonyl, hydroxyalkylcarbonyl, carboxyalkylcarbonyl, alkoxycarbonylalkylcarbonyl, -
P(=O)(O-alkyl)2, -P(=S)(O-alkyl)2, -P(=O)(S-alkyl)2, trialkylsilyl, alkylcarbonylaminoalkylcarbonyl, alkylcarbonyloxyalkylcarbonyl, aryl, pyridinyl, pyrimidinyl, -C(=O)S-alkyl, -C(=O)S-aryl, -C(=O)S-alkylaryl, alkoxyalkoxycarbonyl, alkylthioalkoxycarbonyl, alkylsulfonylalkyxoycarbonyl, arylthioalkoxycarbonyl, alkoxycarbonyl, aryloxycarbonyl and aryloxycarbonylalkylcarbonyl; or alkyl or haloalkyl, optionally substituted by alkoxy, alkoxycarbonyl, carboxy, cyano, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, alkylthio, nitro, alkylsulfinyl, alkylsulfonyl, alkylcarbonyl, amino, alkylamino, dialkylamino, hydroxy, alkylcarbonylamino or alkylcarbonyloxy;
R2 is selected from hydrogen, halogen, -S(O)nR10, (Q-C^alkyl, (CrC^haloalkyl, (C3-C5)alkenyl, (C3-C5)haloalkenyl, (C3-C6)cycloalkyl, (C3-C6)halocycloalkyl, (C3-C5)alkynyl, aryl, heteroaryl, -NR8R9, -CO2R15,
Figure imgf000004_0001
nitro or cyano; n is an integer selected from 0,1 and 2;
R is hydrogen, halogen, cyano, formyl, acetyl, alkyl, haloalkyl or nitro;
R4 is halogen, (CrC4)alkyl, (CrC4)haloalkyl, (C3-C5)alkenyl, (C3-C5)alkynyl, (C1-
C4)alkoxy, (Q-GOhaloalkoxy, -S(O)nhaloalkyl or -SF5; A and B are independently selected from alkylene and haloalkylene; X and Y are independently selected from O, N-R11, N(O)-R13, SiR10R10, and S(O)n; R5 and R6 are independently selected from hydrogen, (C3-C5)alkenyl, (C3- C5)haloalkenyl, (C3-C5)alkynyl, (C3-C5)haloalkynyl, (C3-C6)cycloalkyl, - (CH2)qR12, -(CH2)qR13 and -NR15R16; or is (Q-C^alkyl unsubstituted or substituted by one or more radicals selected from the group consisting of halogen, alkoxy, haloalkoxy, alkenyloxy, haloalkenyloxy, alkynyloxy, haloalkynyloxy, trialkylsilyl, cycloalkyl, -S(O)nR13, -CN, -NO2, -OH, -OR12, -OR14, -COR15, -NR15COR16, -P(=O)(O-alkyl)2, -P(=S)(O-alkyl)2, - NR15SO2R13, -CONR15R16, -NR15R16, -S(O)nR12, -S(O)nR14, and -CO2R15; or R5 and R6 are taken together to form a ring selected from the following:
Figure imgf000005_0002
Figure imgf000005_0003
Figure imgf000005_0001
p is an integer selected from O or 1 ; q is an integer selected from O, 1 , 2 and 3; t is an integer selected from 0,1 and 2;
R10 is alkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, cycloalkyl or halocycloalkyl ;
R11 hydrogen, alkyl and haloalkyl;
R12 is phenyl unsubstituted or substituted by one or more radicals selected from the group consisting of halogen, alkyl, haloalkyl, alkoxy, haloalkoxy, -CN, -NO2, -
S(O)nR13, -COR16, -COR18, -CONR15R16, -SO2NR15R16, -NR15R16, -OH, - SO3H and alkylideneimino;
R13 is haloalkyl, alkylcarbonyl or alkoxycarbonyl;
R is heterocyclyl unsubstituted or substituted by one or more radicals selected from the group consisting of halogen, alkyl, haloalkyl, alkoxy, haloalkoxy, -CN,
-NO2, -S(O)nR13, -OH and -CO2alkyl; R15 and R17 are each independently hydrogen, alkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, cycloalkyl, cycloalkylalkyl, -(CH2)qR18 or -(CH2)qR14; R16 and R19 are each independently hydrogen, alkyl, haloalkyl, cycloalkyl or cycloalkylalkyl; R18 is phenyl unsubstituted or substituted by one or more radicals selected from the group consisting of halogen, alkyl, haloalkyl, alkoxy, haloalkoxy,-CN, -NO2, -
S(O)nR13 and -NR16R19; R20 and R21 are independently selected from hydrogen, alkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, cycloalkyl, cycloalkylalkyl, -(CH2)qR18, - (CH2)qR14, -COalkyl, -S(O)nalkyl or
Figure imgf000006_0001
(13);
R22 is hydrogen, alkyl, alkoxy, alkoxyalkyl, alkylthioalkyl or alkylsulfmylalkyl; and each heterocyclyl in the above-mentioned radicals is independently a heterocyclic radical having 3 to 7 ring atoms and 1 , 2 or 3 hetero atoms in the ring selected from the group consisting of N, O and S; and pesticidally acceptable salts thereof; provided that when R1 is cyano and R2 is -S(O)nR10, then A and B are other than methylene, X and Y are other than O and R5 and R6 are other than methyl.
The present invention also includes compositions containing a pesticidally effective amount of at least one compound of formula I, and optionally, an effective amount of at least one additional compound, with at least one pesticidally compatible carrier. The present invention also includes methods of controlling insects, general household pests and animal parasites in an area where control is desired, which comprise applying a pesticidally effective amount of the above composition to the locus of crops, buildings, soil, animals or other areas where insects, general house hold pests or animal parasites are present or are expected to be present.
DETAILED DESCRIPTION OF THE INVENTION The present invention generally relates to pesticidal compositions of 5-di-
(substituted)aminopyrazole derivatives and to certain new and useful compounds, namely certain 5-di-(substituted)aminopyrazole derivatives that are surprisingly active in the control of insects, acarids, general household pests and domestic and non-domestic animal parasites when used in the pesticidal compositions and methods of this invention. The pesticidal compositions of the present invention are comprised of 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:
Figure imgf000007_0001
I wherein
W is C-halogen, C-CH3, C-CH2F, C-CHF2, C-CF3, C-NO2 or N;
R1 is selected from halogen, cyano, (Ci-C4)alkyl, (Q-G^haloalkyl, (C3- C6)cycloalkyl, -S(O)nR10, formyl, acetyl, nitro, -C(S)NH2, -C(=NNH2)NH2; or
R1 is -CR^N-O-Y1, wherein R7 is hydrogen, alkyl or R7 and Y1 are taken together to form a 5 or 6 member ring or R7 is -NR8R9, wherein R8 and R9 are independently hydrogen or alkyl and Y1 is hydrogen, alkenyl, alkynyl, formyl, alkylcarbonyl, cycloalkylcarbonyl, haloalkylcarbonyl, aroyl, arylalkylcarbonyl, alkylsulfonyl, arylsulfonyl, haloalkylcarbonyl, aminoalkylcarbonyl, alkylaminoalkylcarbonyl, dialkylaminocarbonyl, alkoxyalkylcarbonyl, arylalkoxycarbonyl, alkylthioalkylcarbonyl, alkylsulfonylalkylcarbonyl, arylthioalkoxycarbonyl, N-alkylcarbamoyl, N-arylcarbamoyl, N- alkylthiocarbamoyl, N-arylthiocarbamoyl, alpha-hydroxyarylalkylcarbonyl, hydroxyalkylcarbonyl, carboxyalkylcarbonyl, alkoxycarbonylalkylcarbonyl, - P(=O)(O-alkyl)2, -P(=S)(O-alkyl)2, -P(=O)(S-alkyl)2, trialkylsilyl, alkylcarbonylaminoalkylcarbonyl, alkylcarbonyloxyalkylcarbonyl, aryl, pyridinyl, pyrimidinyl, -C(=O)S-alkyl, -C(=O)S-aryl, -C(=O)S-alkylaryl, alkoxyalkoxycarbonyl, alkylthioalkoxycarbonyl, alkylsulfonylalkyxoycarbonyl, arylthioalkoxycarbonyl, alkoxycarbonyl, aryloxycarbonyl and aryloxycarbonylalkylcarbonyl; or alkyl or haloalkyl, optionally substituted by alkoxy, alkoxycarbonyl, carboxy, cyano, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, alkylthio, nitro, alkylsulfinyl, alkylsulfonyl, alkylcarbonyl, amino, alkylamino, dialkylamino, hydroxy, alkylcarbonylamino or alkylcarbonyloxy;
R2 is selected from hydrogen, halogen, -S(O)nR10, (Q-GOalkyl, (Ci-C4)haloalkyl, (C3-C5)alkenyl, (C3-C5)haloalkenyl, (C3-C6)cycloalkyl, (C3-C6)halocycloalkyl, (C3-C5)alkynyl, aryl, heteroaryl, -NR8R9, -CO2R15, -CR^N-O-Y1 , nitro or cyano; n is an integer selected from 0,1 and 2;
R3 is hydrogen, halogen, cyano, formyl, acetyl, alkyl, haloalkyl or nitro;
R4 is halogen,
Figure imgf000008_0001
(C3-C5)alkenyl, (C3-C5)alkynyl, (C1-
C4)alkoxy, (d-C^haloalkoxy, -S(0)nhaloalkyl or -SF5; A and B are independently selected from (C2-C7)alkylene and haloalkylene;
X and Y are independently selected from O, N-R11, N(O)-R13, SiR10R10, and S(O)n;
R5 and R6 are independently selected from hydrogen, (C3-C5)alkenyl, (C3- C5)haloalkenyl, (C3-C5)alkynyl, (C3-C5)haloalkynyl, (C3-C6)cycloalkyl, - (CH2)qR12, -(CH2)qR13 and -NR15R16; or is (Q-C^alkyl unsubstituted or substituted by one or more radicals selected from the group consisting of halogen, alkoxy, haloalkoxy, alkenyloxy, haloalkenyloxy, alkynyloxy, haloalkynyloxy, trialkylsilyl, cycloalkyl, -S(O)nR13, -CN, -NO2, -OH, -OR12, -OR14, -COR15, -NR15COR16, -P(=O)(O-alkyl)2, -P(=S)(O-alkyl)2, -NR15SO2R13, -CONR15R16, -NR15R16, -S(O)nR12, -S(O)nR14, and -CO2R15; or R5 and R6 are taken together to form a ring selected from the following:
Figure imgf000009_0002
Figure imgf000009_0003
Figure imgf000009_0001
p is an integer selected from O or 1 ; q is an integer selected from 0, 1, 2 and 3; t is an integer selected from 0,1 and 2;
R10 is alkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, cycloalkyl or halocycloalkyl;
R11 hydrogen, alkyl and haloalkyl; R12 is phenyl unsubstiruted or substituted by one or more radicals selected from the group consisting of halogen, alkyl, haloalkyl, alkoxy, haloalkoxy, -CN, -NO2, -
S(O)nR13, -COR16, -COR18, -CONR15R16, -SO2NR15R16, -NR15R16, -OH, -
SO3H and alkylideneimino; R13 is haloalkyl, alkylcarbonyl or alkoxycarbonyl; R14 is heterocyclyl unsubstituted or substituted by one or more radicals selected from the group consisting of halogen, alkyl, haloalkyl, alkoxy, haloalkoxy, -CN,
-NO2, -S(O)nR13, -OH and -CO2alkyl;
R15 and R17 are each independently hydrogen, alkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, cycloalkyl, cycloalkylalkyl, -(CH2)qR 1i8δ or -(CH2)qR , 1144.; R16 and R19 are each independently hydrogen, alkyl, haloalkyl, cycloalkyl or cycloalkylalkyl; R is phenyl unsubstituted or substituted by one or more radicals selected from the group consisting of halogen, alkyl, haloalkyl, alkoxy, haloalkoxy,-CN, -NO2, -
S(O)nR13 and -NR16R19; R and R are independently selected from hydrogen, alkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, cycloalkyl, cycloalkylalkyl, -(CH2)qR18, -
(CH2)qR14, -COalkyl, -S(O)nalkyl or
Figure imgf000010_0001
(13) ;
R22 is hydrogen, alkyl, alkoxy, alkoxyalkyl, alkylthioalkyl or alkylsulfmylalkyl; and each heterocyclyl in the above-mentioned radicals is independently a heterocyclic radical having 3 to 7 ring atoms and 1, 2 or 3 hetero atoms in the ring selected from the group consisting of N, O and S; and pesticidally acceptable salts thereof; provided that when R1 is cyano and R2 is -S(O)nR10, then A and B are other than methylene, X and Y are other than O and R5 and R6 are other than methyl.
Preferred 5-di-(substituted)aminopyrazole derivatives from the group set forth above are those where: W is C-halogen; R1 is cyano;
R2 is, -S(O)nR10 or haloalkyl; R3 is halogen; R4 is haloalkyl;
A and B are each -CH2-;
X and Y are each O or S(O)n; and R5 and R6 are each (Q-C^alkyl or are taken together to form a ring of formula (9), formula (11) or formula (12).
More preferred 5-di-(substituted)aminopyrazole derivatives of the group set forth above are those where: W is C-Cl;
R2 is, -S(O)CF3 or CF3; R3 is chlorine; R4 is CF3;
X and Y are each O or S(O)n where n is 0; and R5 and R6 are each methyl or ethyl.
The compounds of the present invention may exist as tautomers, in which migration of a hydrogen atom within the molecule results in two or more structures, which are in equilibrium. For example, compounds of formula I wherein R1 is - CR^N-O-Y1, in which R7 represents -NR8R9, in which R8 represents hydrogen and R represents hydrogen or alkyl may exist in tautomeric forms as shown in formulae Ia and Ib. Such tautomerism is well known as is described in S. Patai (The Chemistry of Functional Groups: Amidines and Imidates, VoI 2, 1991, pages 276- 277). It will be understood that all such tautomeric forms are embraced by the present invention.
Figure imgf000011_0001
In addition, in certain cases the compounds of the present invention may possess asymmetric centers, which can give rise to optical enantiomorphs and diastereomers. The compounds may exist in two or more forms, i.e., polymorphs, which are significantly different in physical and chemical properties. The compounds of the present invention may also possess acidic or basic moieties, which may allow for the formation of agriculturally acceptable salts or agriculturally acceptable metal complexes. This invention includes the use of such enantiomorphs, polymorphs, tautomers, salts and metal complexes. Insecticidally 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 comprise causing an insecticidally effective amount of a compound of formula I to be administered to insects in order to kill or control the insects. Preferred insecticidally effective amounts are those that are sufficient to kill the insect. It is within the scope of the present invention to cause a compound of formula I to be present within insects by contacting the insects with a derivative of that compound, which derivative is converted within the insect to a compound of formula I. This invention includes the use of such compounds, which are referred to as pro-insecticides.
Another aspect of the present invention relates to compositions containing an insecticidally effective amount of at least one compound of formula I.
Another aspect of the present invention relates to compositions containing an insecticidally effective amount of at least one compound of formula I, and an effective amount of at least one additional compound.
Another aspect of the present invention relates to methods of controlling insects by applying an insecticidally effective amount of a composition as set forth above to a locus of crops such as, without limitation, cereals, cotton, vegetables, and fruits, or other areas where insects are present or are expected to be present. The present invention also includes the use of the compounds and compositions set forth herein for control of non-agricultural insect species, for example, dry wood termites and subterranean termites; as well as for use as pharmaceutical agents. In the field of veterinary medicine, the compounds of the present invention are expected to be effective, orally, parenterally and topically, against certain endo- and ecfo-parasites, such as insects and worms, which prey on animals. Examples of such animal parasites include, without limitation, Gastrophilus spp., Stomoxys spp., Trichodectes spp., Rhodnius spp., Ctenocephalides cards, and other species.
The compounds of the present invention are generally more efficacious or have a reduced insect resistance factor or have a broader spectrum of activity or are safer (e.g. less toxic to mammals) or have other more advantageous properties than the compounds of the prior art. 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 "alkylene" is to be understood as meaning a straight or branched saturated carbon chain having from 1 to 12 atoms. The term "haloalkylene" is to be understood as meaning a straight or branched saturated carbon chain having from 1 to 12 atoms, in which one or more hydrogen atoms are replaced by the same number of halogen atoms. The terms "haloalkyl" and "haloalkoxy" 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, wherein one or more hydrogen atoms have been replaced with halogen atoms, for example, trifluoromethyl or 2,2,2- trifiuoroethoxy. 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 "aroyl" designates a carbonyl aromatic radical, that is, aryl- C(O)-, which is preferably a benzoyl optionally substituted by one or more alkyl, alkoxy or halogen groups. The term "aryl" refers to an aromatic ring structure, including fused rings, having six to ten carbon atoms, for example, phenyl, indanyl, indenyl, naphthyl or 5,6,7,8-tetrahydronaphthyl. 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. Heteroaryl rings include, without limitation, for example, oxazolyl, thiazolyl, imidazolyl, pyrazolyl, triazolyl or thiadiazolyl. The term "DMF" refers to N5N- dimethylformamide. The term "THF" refers to tetrahydrofuran. The term "halogen" or "halo" refers to fluorine, bromine, iodine, or chlorine. The term "ambient temperature", for example, in reference to a chemical reaction mixture temperature, refers to a temperature in the range of 20 0C to 30 °C. The term "insecticidal" or "acaricidal", "insecticide" or "acaricide" refers to a compound of the present invention, either alone or in admixture with at least one additional compound, or with at least one compatible carrier, which causes the destruction or the inhibition of action of insects or acarids. The term "independently selected from" as set forth above and in the claims section of the present specification refers to the possibility that moieties, for example the R5 and R6, may be the same or they may be different within the group that the selection is made. The term "general household pest" refers to any insect or pest, such as German cockroach, American cockroach, Smokey-Brown cockroach, Oriental cockroach, house fly, biting fly, filth fly, red imported fire ant (RIFA), odorous house ant, carpenter ant, pharaoh ant, termite, Argentine ant, mosquito, tick, flea, sowbug, pillbug, centipede, spider, silverfish, scorpion and bed bug, that cause harm or nuisance to person or property. The 5-di-(substituted)aminopyrazole derivatives of formula I can be synthesized by methods that are individually known to one skilled in the art from available intermediate compounds. A number of the compounds of the present invention were prepared in the manner shown in Scheme 1.
Scheme 1
base, solvent
Figure imgf000014_0002
(SMl) where R1 is cyano, R2is SOCF3, R3 is Cl, (a) W is C-Cl, R4 is CF3
Figure imgf000015_0001
A Compound of formula I
As depicted in Scheme 1, the reaction of an appropriately substituted l-arylpyrazole(SMl) (known compound) and an excess of a halogenated alkyl alkyl ether, for example, bromomethyl methyl ether (SM2) yielded the appropriate di(substituted-alkyl)aminopyrazole intermediate (a), for example, 3-cyano-l-(2,6- dichloro-4-trifluoromethyl)phenyl-5-bis(methoxymethyl)amino-4- (trifluoromethylsulfinyl)pyrazole. The reaction of intermediate (a) with an appropriately substituted alcohol, for example, ethylene glycol, yielded the correspondingly substituted pyrazole, for example, l-(2,6-dichloro-4- trifluoromethylphenyl)-5-(l,5,3-dioxazaperhydroepin-3-yl)-4- (trifluoromethylsulfinyl)pyrazole-3-carbonitrile, a compound of formula I, described in detail in Example 1 set forth below. Another method for the production of compounds of formula I is shown in
Scheme 2.
Scheme 2
Figure imgf000016_0001
A Compound of
Acid, solvent formula I
(a) + HO AND
Figure imgf000016_0002
A Compound of formula I
The reaction of intermediate (a) with an appropriately substituted alcohol, for example, 3-hydroxypropionitrile, yielded the substituted pyrazole compounds where I) R5 and R6 are both cyanoethyl and 2) R5 is methyl and R6 is cyanoethyl, for example, 1) l-(2,6-dichloro-4-trifluoromethylphenyl)-5-{bis[(2- cyanoethoxy)methyl] amino } -4-(trifluoromethylsulfϊnyl)pyrazole-3 -carbonitrile and 2) 1 -(2,6-dichloro-4-trifluoromethylphenyl)-5- { [(2- cyanoethoxy)methyl](methoxymethyl)amino}-4-(trifluoromethylsulrinyl)pyrazole- 3-carbonitrile, compounds of formula I, described in detail in Example 2 set forth below.
A general method for the preparation of compounds of the present invention where the R1 group is other than cyano is shown in Scheme 3.
Scheme 3
Figure imgf000017_0001
A Compound of formula I
The reaction of intermediate (a) with hydroxylamine hydrochloride under basic conditions yielded 3-(amino(hydroxyimino)methyl)-l-(2,6-dichloro-4- trifluoromethylphenyl)-5-[bis(methoxymethyl)amino]-4-
(trifluoromethylsulfinyl)pyrazole, a compound of formula I described in detail in Example 3 set forth below.
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 and general household pest use the present insecticidal 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 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 insecticidal 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 insecticides, 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 insecticidal applications are emulsifiable concentrates (ECs) which are homogeneous liquid compositions dispersible in water or other dispersant, and may consist entirely of the insecticidal compound and a liquid or solid emulsifying agent, or may also contain a liquid carrier, such as xylene, heavy aromatic naphthas, isophorone, or other non-volatile organic solvents. For insecticidal 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 insecticidal 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 agricultural 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 insecticidal 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 insecticidal compounds of this invention may be formulated and/or applied with one or more additional compound. Such combinations may provide certain advantages, such as, without limitation, exhibiting synergistic effects for greater control of insect pests, reducing rates of application of insecticide thereby minimizing any impact to the environment and to worker safety, controlling a broader spectrum of insect pests, safening of crop plants to phytotoxicity, and improving tolerance by non-pest species, such as mammals and fish.
Additional compounds include, without limitation, 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 insecticidal compounds of the present invention are used in combination with at least one additional compound, e.g., with other pesticides such as herbicides, the herbicides include, without limitation, for example: N- (phosphonomethyl)glycines such as glyphosate; aryloxyalkanoic acids such as 2,4- D, MCPA, and MCPP; ureas such as isoproturon; imidazolinones such as imazapyr, imazamethabenz, imazethapyr, and imazaquin; diphenyl ethers such as acifluorfen, bifenox, and fomasafen; hydroxybenzonitriles such as ioxynil and bromoxynil; sulfonylureas such as chlorimuron, achlorsulfuron, bensulfuron, pyrazosulfuron, thifensulfuron, and triasulfuron; 2-(4-aryloxyphenoxy)alkanoic acids such as fenoxaprop, fluazifop, quizalofop, and diclofop; benzothiadiazinones such as bentazone; 2-chloroacetanilides such as butachlor, metolachlor, acetochlor, and dimethenamide; arenecarboxylic acids such as dicamba; pyridyloxyacetic acids such as fluroxypyr, aryl triazolinones such as sulfentrazone and carfentrazone-ethyl; isoxazolidinones such as clomazone; and other herbicides. When the active insecticidal compounds of the present invention are used in combination with at least one additional compound, 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, αfø/zα-cypermethrin, δetα-cypermethrin, zetα-cypermethrin, bifenthrin, cypermethrin, permethrin, 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, spinosad, imidacloprid, and other insecticides. When the active insecticidal compounds of the present invention are used in combination with one or more of an additional compound, 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, simeconazole, 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 insecticidal compounds of the present invention are used in combination with at least one additional compound, e.g., with other pesticides such as nematicides, the nematicides include, for example: carbofuran, carbosulfan, terbufos, aldecarb, ethoprop, fenamphos, oxamyl, isazofos, cadusafos, and other nematicides.
When the active insecticidal compounds of the present invention are used in combination with one or more of an additional compound, 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 insecticidal 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 insecticidal 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.
For veterinary use of the compounds of the present invention in domestic and non-domestic animals, the compounds may be administered alone or in a formulation appropriate to the specific use envisaged and to the particular species of host animal being treated and the parasite involved. The methods by which the compounds may be administered include oral administration by capsule, bolus, tablet or drench, or as a pour-on or spot-on formulation, or alternatively, they can be administered by injection (e.g. subcutaneously, intramuscularly or intravenously), dip, spray, mousse, shampoo, powder, or as an implant.
Such formulations are prepared in a conventional manner in accordance with standard veterinary practice. Thus capsules, boluses or tablets may be prepared by mixing the active ingredient with a suitable finely divided diluent or carrier additionally containing a disintegrating agent and/or binder such as starch, lactose, talc, magnesium stearate etc. Oral drenches are prepared by dissolving or suspending the active ingredient in a suitable medium. Injectable formulations may be prepared in the form of a sterile solution which may contain other substances, for example, enough salts or glucose to make the solution isotonic with blood. Acceptable liquid carriers include the vegetable oils such as sesame oil and the like, glycerides such as triacetin and the like, esters such as benzyl benzoate, isopropyl myristate and fatty acid derivatives of propylene glycol and the like, as well as organic solvents such as pyrrolidone, glycerol formal and the like. The formulations are prepared by dissolving or suspending the active ingredient in the liquid carrier such that the final formulation contains from 0.01 to 10% by weight of the active ingredient.
These formulations will vary with regard to the weight of active compound contained therein depending on the species of host animal to be treated, the severity and type of infection and the body weight of the host. For parenteral, topical (e.g. using pour-on or spot-on, dip, spray, mousse, shampoo or powder to deliver the compound) and oral administration, typical dose ranges of the active ingredient are 0.01-100 mg per kg of body weight of the animal. Preferably the range is 0.1 to 10 mg per kg.
As an alternative the compounds may be administered with the animal feedstuff and for this purpose a concentrated feed additive or premix may be prepared for mixing with the normal animal feed.
The compounds of the invention may, in particular, be used in the field of veterinary medicine and livestock husbandry against arthropods, helminths or protozoa which are parasitic internally or externally upon vertebrates, particularly warm-blooded vertebrates, for example domestic and non-domestic animals, e.g. cattle, sheep, goats, equines, swine, poultry, dogs, and cats. The compounds of the invention are particularly useful in controlling arthropods, helminths or protozoa which are present inside the host animals or which feed in or on the skin or suck the blood of the animal, for which purpose they may be administered orally, parenterally, percutaneously or topically. According to a further aspect of the invention, there is provided a pesticidal formulation comprising a compound of the invention, in admixture with a compatible adjuvant, diluent or carrier. Preferably, the formulation is adapted for topical administration.
The invention further provides a compound of the invention for use as a pesticide; and a method of treating a pest infestation at a locus, which comprises treatment of the locus with an effective amount of a compound of the invention. Preferably, the locus is the skin or fur of an animal. 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 l-(2,6-dichloro-4- trifluoromethylphenyl)-5-(l,5,3-dioxazaperhydroepin-3-yl)-4- (ttfluoromethylsulfinyl)-pyrazole-3-carbonitrile
(Compound 3-10) Step A 3-cyano-l-(2,6-dichloro-4-trifluoromethyl)phenyl-5- bis(methoxymethyl)amino-4-(trifluoromethylsulfinyl)pyrazole as an intermediate Under a dry nitrogen atmosphere a solution of 1.0 gram (0.0023 mole) of 5-amino-3- cyano-l-(2,6-dichloro-4-trifluoromethyl)phenyl-4-(trifluoromethylsulfinyl)pyrazole (known compound, U.S. Patent 5,232,940) in 10 mL of THF was added to a stirred, cold (0°C) mixture of 0.2 gram (0.005 mole) of a 60% sodium hydride suspension in mineral oil in 10 mL of THF. The cold reaction mixture was stirred for 10 minutes and 0.61 gram (0.005 mole) of bromomethyl methyl ether was added. The cold reaction mixture was stirred for 3 hours. The reaction mixture was diluted with ethyl acetate, washed in succession with an aqueous saturated ammonium chloride solution, an aqueous saturated sodium bicarbonate solution and an aqueous saturated sodium chloride solution, and then dried with magnesium sulfate. The solution was filtered and the filtrate was concentrated under reduced pressure leaving an oil. The oil was dissolved in aboutlO mL of diethyl ether to which n-heptane was added slowly, forming a white solid. The solid was isolated and dried under reduced pressure, yielding 0.81 gram of the subject compound. The NMR spectrum was consistent with the proposed structure.
Step B 1 -(2,6-dichloro-4-trifluoromethylρhenyl)-5-(l ,5,3- dioxazaρerhydroepin-3-yl)-4-(trifluoromethylsulfinyl)-pyrazole-3- carbonitrile (Compound 3-10) Under a dry nitrogen atmosphere a mixture of 0.28 gram (0.00053 mole) of 3-cyano- l-(2,6-dicWoro-4-Mfluoromethyl)phenyl-5-bis(methoxymethyl)arnino-4- (trifluoromethylsulflnyl)pyrazole, 0.34 gram (0.0054 mole) of ethylene glycol and 0.1 mL of a 4M solution of hydrochloric acid in 1,4-dioxane was stirred in 10 mL of acetonitrile at ambient temperature for about 18 hours. The reaction mixture was concentrated under reduced pressure leaving a residue. The residue was purified by column chromatography on silica gel, eluting with mixtures of ethyl acetate in hexanes. The appropriate fractions were combined and concentrated under reduced pressure, yielding 0.09 gram of the title compound as a solid. The NMR spectrum was consistent with the proposed structure.
EXAMPLE 2
This example illustrates one protocol for the preparation of l-(2,6-dichloro-4- trifluoromethylphenyl)-5-{[(2-cyanoethoxy)methyl](methoxymethyl)amino}-4- (trifluoromethylsulfinyl)pyrazole-3-carbonitrile (Compound 1-58) and l-(2,6- dichloro-4-trifluoromethylphenyl)-5-{bis[(2-cyanoethoxy)methyl]amino}-4-
(trifluoromethylsulfinyl)pyrazole-3-carbonitrile (Compound 1-47) Under a dry nitrogen atmosphere a mixture of 0.2 gram (0.00038 mole) of 3-cyano- l-(2,6-dichloro-4-trifluoromethyl)phenyl-5-bis(methoxymethyl)amino-4- (Irifluoromethylsulfinyl)pyrazole, 0.27 gram (0.00038 mole) of 3- hydroxypropionitrile and 0.1 mL of a 4M solution of hydrochloric acid in 1,4- dioxane was stirred in 10 mL of acetonitrile at ambient temperature for about 18 hours. The reaction mixture was concentrated under reduced pressure leaving a residue. The residue was purified by column chromatography on silica gel, eluting with mixtures of ethyl acetate in hexanes, providing two products. The appropriate fractions of the first product to elute were combined and concentrated under reduced pressure, yielding 0.34 gram of a residue. Analysis of the residue by NMR indicated a quantity of 3-hydroxyρropionitrile was present. The residue was dissolved in methylene chloride, washed with two portions of water then concentrated under reduced pressure to yield 0.1 gram of l-(2,6-dichloro-4-trifluoromethylphenyl)-5- {[(2-cyanoethoxy)methyl](methoxymethyl)amino}-4-
(trifluoromethylsulfinyl)ρyrazole-3-carbonitrile (Compound 1-58) as an oil. The appropriate fractions of the second product to elute were combined and concentrated under reduced pressure yielding 0.045 gram of l-(2,6-dichloro-4- trifluoromethylphenyl)-5- {bis[(2-cyanoethoxy)methyl]amino} -4- (trifluoromethylsulrlnyl)pyrazole-3-carbonitrile (Compound 1-47) as an oil. The NMR spectra were consistent with the proposed structures.
EXAMPLE 3
This example illustrates one protocol for the preparation of 3- (amino(hydroxyimino)methyl)-l-(2,6-dichloro-4-trifluoromethylphenyl)-5- [bis(methoxymethyl) amino] -4-(trifluoromethylsulfϊnyl)pyrazole (Compound 1 -5) A mixture of 0.21 gram (0.0004 mole) of 3-cyano-l-(2,6-dichloro-4- trifluoromethyl)phenyl-5-bis(methoxymethyl)amino-4- (trifluoromethylsulfinyl)pyrazole, 0.028 gram (0.0004 mole) of hydroxylamine hydrochloride and 0.05 gram (0.00046 mole) of triethylamine in 10.0 mL of methanol was stirred at ambient temperature in a sealed reaction vial for about 18 hours. The reaction mixture was concentrated under reduced pressure leaving a residue. The residue was partitioned between ethyl acetate and water. The organic phase was washed with an aqueous saturated sodium chloride solution, dried with magnesium sulfate and filtered. The filtrate was concentrated under reduced pressure to a residue. The residue was purified by column chromatography on silica gel, eluting with mixtures of ethyl acetate and hexanes. The appropriate fractions were combined and concentrated under reduced pressure to yield 0.1 gram of the title compound as a solid. 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 compounds of formula I: Table 1 5-Di-(substituted-alkyl)aminopyrazole derivatives
Figure imgf000027_0001
compounds of formula I where R3 is chlorine, R4 is -CF3, W is C-Cl providing the following compounds:
Figure imgf000027_0002
Cmpd.
No R1 R2 -A-X-R5 -B-Y-R6
1-1 -CN -SOCF3 -CH2SCH2CH2OH -CH2SCH2CH2OH
1-2 -CN -SOCF3 -CH2OC2H5 -CH2OC2H5
1-3 -CN -CF3 -CH2OCH3 -CH2OCH3
1-4 -CN -SOCF3 -CH2SOC2H5 -CH2SOC2H5
1-5 -C(NOH)NH2 -SOCF3 -CH2OCH3 -CH2OCH3
1-6 -CN -SOCF3 -CH2SCH2Ph -CH2SCH2Ph
1-7 -CN -SOCF3 -CH2OCH2Ph -CH2OCH2Ph
1-8 -CN -SOCF3 -CH2OCH2CH=CH2 -CH2OCH2CH=CH2
1-9 -CHO -SOCF3 -CH2OCH3 -CH2OCH3
1-10 -COCH3 -SOCF3 -CH2OCH3 -CH2OCH3
1-11 -Cl -SOCF3 -CH2OCH3 -CH2OCH3
1-12 -C(NOCH3)H -SOCF3 -CH2OCH3 -CH2OCH3
1-13 -CSNH2 -SOCF3 -CH2OCH3 -CH2OCH3
1-14 -CHO -SOCHF2 -CH2OCH3 -CH2OCH3
1-15 -COCH3 -SOCHF2 -CH2OCH3 -CH2OCH3
1-16 -C(NOCH3)H -SOCHF2 -CH2OCH3 -CH2OCH3
1-17 -CSNH2 -SOCH2F -CH2OCH3 -CH2OCH3
1-18 -CHO -SOCH2F -CH2OCH3 -CH2OCH3
1-19 -CSNH2 -SOCH2F -CH2OCH3 -CH2OCH3
1-20 -CHO -SOCH3 -CH2OCH3 -CH2OCH3
1-21 -COCH3 -SOCH3 -CH2OCH3 -CH2OCH3
1-22 -C(NOCH3)H -SOCH3 -CH2OCH3 -CH2OCH3
1-23 -NO2 -SOCF3 -CH2OCH3 -CH2OCH3
1-24 -CN -SOCF3 -C2H4OCH3 -CH2OCH3
1-25 -CN -SOCH3 -C2H4OCH3 -CH2OCH3 Cmpd.
No R1 R2 -A-X-R5 -B-Y-R6
1-26 -CN -SOC2H5 -C2H4OCH3 -CH2OCH3
1-27 -CN -SOCF3 -C2H4OCH3 -C2H4OCH3
1-28 -CN -SOCF3 -C2H4OCH3 -CH2OCH3
1-29 -CN -SOCH3 -C2H4OCH3 -CH2OCH3
1-30 -CN -SOC2H5 -C2H4OCH3 -CH2OCH3
1-31 -CN -SOCHF2 -C2H4OCH3 -C2H4OCH3
1-32 -CN -SOCF3 -C2H4NHCH3 -CH2OCH3
1-33 -CN -SOCF3 -C2H4NHCH3 -CH2SCH3
1-34 -CN -SOCF3 -C2H4SO2CH3 -CH2OCH3
1-35 -CN -SOCF3 -C2H4NO(CHs)2 -CH2OCH3
1-36 -CN -SOCF3 -CH2SCH3 -CH2SCH3
1-37 -CN -SOCF3 -CH2OSOCH3 -CH2OSOCH3
1-38 -CN -SOCF3 -CH2SCH3 -CH2OCH3
1-39 -CN -SOCF3 -CH2N(CH3)2 -CH2OCH3
1-40 -CN -SOCF3 -CH2N(CH3)2 -CH2N(CHj)2
1-41 -CN -SOCF3 -CH2OCOCH3 -CH2OCOCH3
1-42 -CN -SOCF3 -CH2NCOCH3 -CH2NCOCH3
1-43 -CN -SOCF3 -CH2OSO2CH3 -CH2OSO2CH3
1-44 -CN -SOCF3 -CH2NSO2CH3 -CH2NSO2CH3
1-45 -CN -SOCF3 -CH2OC2H4OCH3 -CH2OC2H4OCH3
1-46 -CN -SOCF3 -CH2OC2H4Si(CH3)S -CH2OC2H4Si(CH3)J
1-47 -CN -SOCF3 -CH2OC2H4CN -CH2OC2H4CN
1-48 -CN *-SOCF3 -CH2OCH3 -CH2OCH3
1-49 -CN **-SOCF3 -CH2OCH3 -CH2OCH3
1-50 -CN *-SOCF3 -CH2SCH3 -CH2SCH3
1-51 -CN **-SOCF3 -CH2SCH3 -CH2SCH3
1-52 -CN -SOCF3 -CH2OPO(OCH3)2 -CH2OPO(OCH3)2
1-53 -CN -SOCF3 -C2H4N(CH3)2 -CH2OCH3
1-54 -CN -SOCF3 -CH2SC2H4OPh -CH2SC2H4OPh
1-55 -CN -SOCF3 -CH2OC2H4SCH3 -CH2OC2H4SCH3
1-56 -CN -SOCF3 -CH2OCH2C=CH -CH2OCH2OCH
1-57 -CN -SOCF3 -CH2OC2H4SO2Ph -CH2OCH3
1-58 -CN -SOCF3 -CH2OC2H4CN -CH2OCH3
1-59 -CN -SOCF3 -CH2OCH2CH=CH2 -CH2OCH3
1-60 -CN -SOCF3 -CH2SOC2H5 -CH2SO2C2H5
1-61 -CN -SOCF3 -CH2OCH2PO(C2Hs)2 -CH2OCH2PO(C2H5);,
1-62 -CN -SOCF3 -CH2OCHCH3CN -CH2OCHCH3CN
1-63 -CN -SOCF3 -CH2OC2H4CH≡CH -CH2OC2H4CH=CH
1-64 -CN -SOCH3 -CH2OCH2CH=CH2 -CH2OCH2CH=CH2
1-65 -CN -SOCH3 -CH2OCH2CH=CH -CH2OCH2CH=CH
1-66 -CN -SOCF3 -CH2OC2H4CH=CH2 -CH2SCH3
1-67 -CN -SOCF3 -CH2OC2H4CH=CH2 -CH2OC2H4CH=CH2
1-68 -CN -SOCF3 -CH2OCH2CHOHCH2SCH3 -CH2SCH3
1-69 -CN -SOCF3 -CH2OC2H4OCH(CH3);. -CH2OC2H4θCH(CH3)2
1-70 -CN -SOCF3 -CH2OCH2COCH3 -CH2SCH3
1-71 -CN -SOCF3 -CH2OCH2COCH3 -CH2OCH2COCH3
1-72 -CN -SOCF3 -CH2OCH2CO2CH3 -CH2OCH2CO2CH3
1-73 -CN -SOCH2F -CH2OCH2C=CH -CH2OCH2C=CH
1-74 -CN -SOCF3 -CH2OC7H15 -CH2OCH3
1-75 -CN -SOCHF2 -CH2OCH2OCH -CH2OCH2C=CH
1-76 -CN -SOCF3
Figure imgf000028_0001
-CH2SC2H5
* Sulfoxide is i the (R) enantiomer.
** Sulfoxide is the (S) enantiomer. compounds of formula I where R1 is -CN, and W is C-Cl providing the following compounds:
Figure imgf000029_0001
Cmpd.
No R2 RJ R4 -A-X-R5 -B-Y-R6
2-1 -CF3 -Cl -Cl -CH2OCH3 -CH2OCH3
2-2 -CHF2 -Cl -Cl -CH2OCH3 -CH2OCH3
2-3 -CH2F -Cl -Cl -CH2OCH3 -CH2OCH3
2-4 -CH3 -Cl -Cl -CH2OCH3 -CH2OCH3
2-5 -Br -Cl -Cl -CH2OCH3 -CH2OCH3
2-6 -Cl -Cl -Cl -CH2OCH3 -CH2OCH3
2-7 -NO2 -Cl -Cl -CH2OCH3 -CH2OCH3
2-8 -C(CH3)3 -Cl -Cl -CH2OCH3 -CH2OCH3
2-9 -Ph -Cl -Cl -CH2OCH3 -CH2OCH3
2-10 -NHC3H7 -Cl -Cl -CH2OCH3 -CH2OCH3
2-11 -Cl -Cl -CH2OCH3 -CH2OCH3
-<
2-12 -CO2C2H5 -Cl -Cl -CH2OCH3 -CH2OCH3
2-13 -CHF2 -Cl -OCF3 -CH2OCH3 -CH2OCH3
2-14 -CH2F -Cl -OCF3 -CH2OCH3 -CH2OCH3
2-15 -CH3 -Cl -OCF3 -CH2OCH3 -CH2OCH3
2-16 -SOC2H5 -Cl -OCF3 -CH2OCH3 -CH2OCH3
2-17 -SOCF3 -Cl -OCF3 -C2H4OCH3 -CH2OCH3
2-18 -SOCF3 -Br -CF3 -C2H4OCH3 -CH2OCH3
2-19 -SOCF3 -CH3 -CF3 -C2H4OCH3 -CH2OCH3
2-20 -SOCH3 -Cl OCF3 -CH2OCH3 -CH2OCH3
compounds of formula I where R1 is -CN, R2 is SOCF3, W is C-Cl, R3 is Cl, R4 is CF3 , R5 and R6 are taken together to form a ring selected from (1) - (12), R20 is hydrogen and p is O providing the following compounds:
Figure imgf000030_0001
Cmpd. Ring
R- 21 R- 22
No Formula
3-1 (1)
3-2 (7)
3-3 (2)
3-4 (6)
Figure imgf000030_0002
3-8 (8) 0
3-9 (1) -
3-10 (9) - H
3-11 (10) - H
3-12 (H) 0
3-13 (12) 0
3-14 (12) 2
3-15 (9) - -CH2OCH3
3-16 (H) 2
3-17 (12) 1
3-18* (9) - -CH2SCH3
3-19** (9) - -CH2SCH3
3-20 (9) - -CH2SCH3
* 5-[(6R)-6-(methylthiomethyl)(l,5,3-dioxazaρerhydroeρin-3-yl)]-l-(2,6-dichloro-4- trifluoromethylphenyl)-4-trifluoroiiiethylsulfinyl)pyrazole-3-carboDitrile ** 5-[(6S)-6-(methylthiomethyl)(l,5,3-dioxazaperhydroepin-3-yl)]-l~(2,6-dichloro-4- trifluoromethylphenyl)-4-trifluoroinethylsulfinyl)pyrazole-3-carbonitrile
compounds of formula I where R1 is -CN, and W is C-CH3, R3 is Cl, and R4 is CF3 providing the following compounds:
Figure imgf000031_0001
Cmpd.
No R2 -A-X-R5 -B-Y-R6
4-1 -SOCF3 -CH2SCH3 -CH2SCH3
4-2 -SOCF3 -CH2OC2H5 -CH2OC2H5
4-3 -CF3 -CH2OCH3 -CH2OCH3
4-4 -SOCH3 -CH2SCH3 -CH2SCH3
4-5 -SOC2H5 -CE1SCH3 -CH2SCH3
The following table sets forth physical characterizing data for certain compounds of formula I of the present invention. The test compounds of formula I are identified by numbers that correspond to those in Table 1 :
Table 2
5-Di-(substituted)aminopyrazole Derivatives Compound Characterization
Characterizing Data
Melting point Melting point
(0C) of solids (0C) of solids or
Cmpd. Emperical or Physical Cmpd. Emperical Physical
No. Formulae State No. Formulae State
1-1 C18H16Cl2F6N4O3S3 OIL 1-3 C16H12Cl2F6N4O2 78-79
1-4 C18H16Cl2F6N4O3S3 OIL 1-5 C16H15Cl2F6N5O4S 143
1-6 C28H20Cl2F6N4OS3 OIL 1-7 C28H20Cl2F6N4O3S 118-120
1-8 C20H16Cl2F6N4O3S 99-101 1-36 C16H12Cl2F6N4OS3 120-123
1-45 C20H20Cl2F6N4O5S OIL 1-46 C24H32Cl2F6N4O3SSi2 SOLID
1-47 C20H14Cl2F6N6O3S OIL 1-54 C30H24Cl2F6N4O3S3 OIL 1-55 C20H20Cl2F6N4O3S3 63-65 1-56 C20H12Cl2F6N4O3S 120-122
1-57 C23H18Cl2F6N4O5S2 120-125 1-58 C18H13Cl2F6N5O3S OIL
1-59 C18H14Cl2F6N4O3S 80-82 1-60 C18H16Cl2F6N4O4S3 90-100
1-61 C24H30Cl2F6N4O9P2S OIL 1-62 C20H14Cl2F6N6O3S OIL
1-63 C22H16Cl2F6N4O3S OIL 1-64 C20H19Cl2F3N4O3S 71-72
1-65 C20H15Cl2F3N4O3S 124-126 1-66 C20H18Cl2F6N4O2S2 OIL
1-67 C22H20Cl2F6N4O3S OIL 1-68 C20H20Cl2F6N4O3S3 OIL
1-69 C24H28Cl2F6N4O5S OIL 1-70 C19H16Cl2F6N4O3S2 OIL
1-71 C20H16Cl2F6N4O5S OIL 1-72 C20H16Cl2F6N4O7S OIL
1-73 C20H14Cl2F4N4O3S 110-111 1-74 C22H24Cl2F6N4O3S OIL
1-75 C20Hi3Cl2F5N4O3S 122-124 1-76 C18H16Cl2F6N4OS3 OIL
3-9 C15H8Cl2F6N4O3S OIL 3-10 C16H10Cl2F6N4O3S 200-209
3-12 C16HI0CI2F6N4OS3 151-155 3-13 C16Hi0Cl2F6N4O2S2 192-197
3-14 C16H10Cl2F6N4O4S2 200 3-15 C18H14Cl2F6N4O4S FOAM
3-16 C16H10Cl2F6N4O3S3 130-134 3-17 C16H10Cl2F6N4O3S2 100-160
3-18 C18H14Cl2F6N4O3S2 160-162 3-19 Ci8Hi4Cl2F6N4O3S2 OIL
3-20 C18H14Cl2F6N4O4S2 FOAM
Figure imgf000032_0001
Candidate insecticides were evaluated for activity against the tobacco budworm (Heliothis virescens [Fabricius]) in a surface-treated diet test. In this test one mL of molten (65-7O0C) 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 diameter 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 the 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 the candidate insecticide with a 1 :1 water/acetone solution (VTV) in a ratio of 1 :7 stock solution to water/acetone. The robot subsequently pipetted 40 microliters 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. 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 were 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 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 a second instar tobacco budworm larvae, 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. 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 relative to the weight of insects from untreated controls, and percent mortality when compared to the total number of insects infested.
Insecticidal activity data at selected rates of application from this test are provided in Table 3. The test compounds of formula I are identified by numbers that correspond to those in Table 1.
Table 3 Insecticidal Activity of Certain 5-Di-(substituted)aminopyrazole Derivatives When
Applied to the Surface of the Diet of Tobacco Budworm (Heliothis virescens [Fabricius])
Percent Percent
Cmpd. Percent Growth Cmpd. Percent Growth
No. Mortality Inhibition No. Mortality Inhibition
1-1 100 100 1-2 100 100
1-3 100 100 1-5 100 100
1-6 100 100 1-7 100 100
1-8 100 100 1-36 83 100
1-57 100 100 1-58 100 100
1-60 100 100 1-61 100 100
1-62 100 100 1-63 100 100
1-76 100 100 3-10 50 94
3-12 100 100 3-13 100 100 3-14 100 100 3-15 100 100
3-16 100 100 3-17 100 100
Concentration of the candidate insecticide on the surface of the diet is 0.25 millimolar
As set forth in Table 3, all of the tested compounds of the present invention provided insecticidal activity against the tobacco budworm, with many of the compounds providing 100% mortality and/or 100% growth inhibition.
Candidate insecticides were evaluated for insecticidal activity by observing mortality in a population of treated cotton aphid (Aphis gossypii) on cotton plant leaf discs when compared to like populations of untreated cotton aphid on cotton plant leaf discs. These tests were conducted in the following manner:
Three week to one month-old cotton plants (Gossypium hirsutium) were prepared for infesting by cutting off the cotyledons and new true leaf growth, leaving the oldest two true leaves. The prepared test plant was infested with cotton aphids by translocation from cotton plants grown in a cotton aphid colony. The wells of clear 128-well trays (CD-International, Pittman, New Jersey) were filled with 1 mL of a warm, aqueous 3% agar solution and allowed to cool to ambient temperature. The aphid infested cotton leaves were removed from the plants and placed bottom side up on a cutting platform. Circular discs were cut from the infested leaves and placed bottom side up onto the cooled agar gel, one disc per well. Each leaf disc was visually inspected to assure that a minimum of 10 live aphids were present. A 50 mM stock solution of the test compound was prepared by dissolving the appropriate amount of the test compound in DMSO. A solution comprising 1000 part per million (ppm) of each test compound was prepared by dissolving 10 μl of the stock solution in 140 μl of an aqueous 0.003% Kinetic® (a nonionic wetter/spreader/penetrant adjuvant, Helena Chemical Company, Collierville, Tennessee) solution. If needed, the solution of 1000 ppm of test compound was serially diluted with a solution consisting of 66mL of DMSO and 30 μl of Kinetic® in 934 mL of water (diluting solution) to provide solutions of each test compound for lower rates of application, for example, 300 ppm, 100 ppm, 30 ppm, or 10 ppm. Each replicate infested test plant disc was sprayed with 10 μl of the test solution at about 8 psi for 1 second. For comparison purposes, a solution of a standard, such as bifenthrin, prepared in a manner analogous to that set forth above, as well as an aqueous solution of 0.003% Kinetic® containing no test compound and the diluting solution containing no test compound were also sprayed onto infested test plant discs. Upon completion of spraying the solutions of test compound, the solution of standard, and the solutions containing no test compound, the plant discs were allowed to dry. Upon completion of drying, the test trays were covered with a plastic film. Three slits were made in the film over each well to allow air into each well. The test trays were placed in a biochamber (250C, 16 hours light, 8 hours of dark and 35-40% relative humidity) for three days. After this time, each plant disc was assessed for percent mortality caused by the test compound when compared to the population of aphids that was infested onto the test plant discs containing no test compound. A test compound was designated as possessing insecticidal activity (SA) if there was 40% to 75% mortality of cotton aphid on plant discs sprayed with that compound. If there was 75% mortality or greater of the cotton aphid, a test compound was designated as being more insecticidally active (A). If there was 40% mortality or less of the cotton aphid, the test compound was termed as inactive (I).
An assessment of the insecticidal activity at selected rates of application from this test is provided in Table 4. The test compounds of formula I are identified by numbers that correspond to those in Table 1.
Table 4
The Following Compounds Of The Present Invention Reduced The Population Of Cotton Aphid By 40 to 100% When Applied At An Application Rate Of lOOOppm
Or Less To Infested Cotton Leaf Discs ,
Cmpd. Cmpd. Cmpd. Cmpd. Cmpd. Cmpd. Cmpd. Cmpd. Cmpd. Cmpd.
No. No. No. No. No. No. No. No. No. No.
1-2 1-3 1-4 1-6 1-7 1-54 1-57 1-58 1-61 1-62 1-76 3-10 3-12 3-13 3-14 3-15 3-16 3-17
Candidate insecticides were evaluated for insecticidal activity by observing mortality in a population of cotton aphid (Aphis gossvpii ) on treated cotton plants when compared to like populations of cotton aphid on untreated plants. These tests were conducted in the following manner: For each rate of application of test compound, two seven-to-ten days old cotton seedlings (Gossvpium hirsutium) grown in 7.6 cm diameter pots were selected for the test. Each test plant was infested with about 120 adult cotton aphids by placing onto each test plant cuttings of leaves from cotton plants grown in a cotton aphid colony. Once infested, the test plants were maintained for up to about 12 hours to allow complete translocation of the aphids onto the test plant. A solution comprising 1000 part per million (ppm) of each test compound was prepared by dissolving 10 milligrams of the test compound in 1 mL of acetone. Each solution was then diluted with 9 mL of a solution of 0.03 mL of polyoxyethylene(lθ) isooctylphenyl ether in 100 mL of water. About 2.5 mL of solution of each test compound was needed to spray each replicate of test plant (5 mL total for each test compound). If needed, the solution of 1000 ppm of test compound was serially diluted with a solution of 10% acetone and 300 ppm of polyoxyethylene(lθ) isooctylphenyl ether in water to provide solutions of each test compound for lower rates of application, for example, 300 ppm, 100 ppm, 30 ppm, or 10 ppm. Each replicate of test plant was sprayed with the solutions of test compound until run-off on both the upper and lower surfaces of the leaves. All the test plants were sprayed using a DeVilbus Atomizer Model 152 (Sunrise Medical, Carlsbad, CA) at a pressure of about 0.63-0.74 kilogram per square centimeter from a distance of about 30.5 centimeters from the test plants. For comparison purposes, a solution of 10% acetone and 300 ppm of polyoxyethylene(lθ) isooctylphenyl ether in water containing no test compound was also sprayed onto control test plants. Upon completion of spraying the solutions of test compound and the solution containing no test compound, the plants were allowed to dry. Upon completion of drying, the test and control plants were placed in a tray containing about 2.5 centimeters of water, where they were maintained in a growth chamber for 72 hours. After this time, each plant was assessed for percent mortality caused by the test compound when compared to the population of aphids that was infested onto the test plants prior to treatment with test compound. A test compound was designated as possessing insecticidal activity (SA) if there was 40% to 75% mortality of cotton aphid on plants sprayed with that compound. If there was 75% mortality or greater of the cotton aphid, a test compound was designated as being more insecticidally active (A). If there was 40% mortality or less of the cotton aphid, the test compound was termed as inactive (I).
An assessment of the insecticidal activity at selected rates of application from this test is provided in Table 4A. The test compounds of formula I are identified by numbers that correspond to those in Table 1.
Table 4A The Following Compounds Of The Present Invention Reduced The Population Of
Cotton Aphid (Aphis gossypii) Between 40% and 100% When Applied At An Application Rate Of 1 OOOppm Or Less On Infested Cotton Plants
Cmpd. Cmpd. Cmpd. Cmpd. Cmpd. Cmpd. Cmpd. Cmpd. Cmpd. Cmpd.
No. No. No. No. No. No. No. No. No. No.
1-1 1-2 1-5 1-36 1-46 1-55 1-57 1-60 1-62 1-63
1-64 1-65 1-66 1-67 1-68 1-69 1-70 1-71 1-72 1-73
1-74 1-76 3-10 3-17 3-19 3-20
As set forth in Tables 4 and 4A, the tested compounds of the present invention reduced the aphid population by at least 40% at an application rate of lOOOppm or less.
Candidate insecticides were evaluated for insecticidal activity by observing mortality in a population of silverleaf whitefly (Bemisia argentifolii) on treated cotton plant cotyledons when compared to like populations of silverleaf whitefly on untreated plant cotyledons. These tests were conducted in the following manner:
For each rate of application of test compound, two four to six days old cotton seedlings (Gossypium hirsutium) grown in 3-inch diameter pots were selected for the test. Each test plant was sprayed with a test solution comprising 300 part per million (ppm), or less, of each test compound prepared by dissolving 12 milligrams of the test compound in 4 mL of acetone. Each solution was then diluted with 36 mL of a surfactant and water solution prepared by dissolving 0.03 gm of Triton X-100® surfactant in 100 mL of distilled water, providing a stock test solution of 300 ppm. About 2.5 mL of solution of each test compound was needed to spray each replicate of test plant (5 mL total for each test compound). If needed, the solution of 300 ppm of test compound was diluted with a solution of 10% acetone and 300 ppm of Triton X-100® surfactant in water to provide solutions of each test compound for lower rates of application, for example, 100 ppm, 30 ppm, or 10 ppm. Each replicate of test plant was sprayed with the solutions of test compound until run-off on both the upper and lower surfaces of the leaves. All the test plants were sprayed using a DeVilbus Atomizer Model 152 (Sunrise Medical, Carlsbad, CA) at a pressure of about 0.63-0.74 kilogram per square centimeter from a distance of about 30.5 centimeters from the test plants. Upon completion of spraying the solutions of test compound and the solution containing no test compound, the plants were allowed to dry. Upon completion of drying, the test plants were excised at the soil surface and placed in a 1 ounce plastic cup containing a 2.5 cm filter paper moistened with 50 microliters of distilled water. Whiteflies (25-50) were added to each cup and a lid was placed on each. The test cups were maintained in a growth chamber for 72 hours at 70% relative humidity (light 12 hours/day). After this time, each test was assessed for percent mortality caused by the test compound when compared to the population of whiteflies that were infested onto the test plants. A test compound was designated as possessing insecticidal activity (SA) if there was 40% to 75% mortality of whiteflies on plants sprayed with that compound. If there was 75% mortality or greater of whiteflies, a test compound was designated as being more insecticidally active (A). If there was 40% mortality or less of the cotton aphid, the test compound was termed as inactive (I). An assessment of the insecticidal activity at selected rates of application from this test is provided in Table 5. The test compounds of formula >I are identified by numbers that correspond to those in Table 1.
Table 5 The following Compounds of The Present Invention Reduced the Population of
Silverleaf Whitefly (Bemisia argentifoHi) by 40% to 100% When Applied at an Application Rate of 300ppm or Less
Cmpd. Cmpd. Cmpd. Cmpd. Cmpd. Cmpd. Cmpd. Cmpd. Cmpd. Cmpd.
No. No. No. No. No. No. No. No. No. No.
1-1 1-2 1-3 1-5 1-6 1-7 1-8 1-36 1-45 1-47
1-55 1-56 1-58 1-59 1-66 1-67 1-68 1-69 1-70 1-71
1-74 1-76 3-9 3-10 1-12 3-14 3-15 3-17 3-19 3-20 Candidate insecticides were evaluated for insecticidal activity by observing mortality in a population of tarnished plant bug nymphs (Lygus lineolaris) on treated broccoli plant leaves when compared to like populations of tarnished plant bug on untreated plant leaves. These tests were conducted in the following manner: For each rate of application of test compound, four ten to fifteen days old broccoli seedlings {Brassica oleraced) grown in 3 -inch diameter pots were selected for the test. Each test plant was sprayed with a test solution comprising 300 part per million (ppm), or less, of each test compound prepared by dissolving 12 milligrams of the test compound in 4 mL of acetone. Each solution was then diluted with 36 mL of a surfactant and water solution prepared by dissolving 0.03 gm of Triton X- 100® surfactant in 100 mL of distilled water, providing a stock test solution of 300 ppm. About 2.5 mL of solution of each test compound was needed to spray each replicate of test plant (10 mL total for each test compound). If needed, the solution of 300 ppm of test compound was diluted with a solution of 10% acetone and 300 ppm of Triton X- 100® surfactant in water to provide solutions of each test compound for lower rates of application, for example, 100 ppm, 30 ppm, or 10 ppm. Each replicate of test plant was sprayed with the solutions of test compound until run-off on both the upper and lower surfaces of the leaves. All the test plants were sprayed using a DeVilbus Atomizer Model 152 (Sunrise Medical, Carlsbad, CA) at a pressure of about 0.63-0.74 kilogram per square centimeter from a distance of about 30.5 centimeters from the test plants. Upon completion of spraying the solutions of test compound and the solution containing no test compound, the plants were allowed to dry. Upon completion of drying, the treated foliage was removed and two leaves were placed into an 8 ounce unwaxed paper cup which contained a one inch piece of cut cotton wick, moistened by soaking for five seconds with distilled water. Four late second to early third instar tarnished plant bug nymphs were placed into each cup and a lid was placed on each. The test cups were maintained in a growth chamber for 72 hours at 70% relative humidity (light 12 hours/day). After this time, each test was assessed for percent mortality caused by the test compound when compared to the population of tarnished plant bug nymphs that were infested onto the test plant leaves. A test compound was designated as possessing insecticidal activity (SA) if there was 40% to 75% mortality of cotton aphid on plants sprayed with that compound. If there was 75% mortality or greater of the cotton aphid, a test compound was designated as being more insecticidally active (A). If there was less than 40% mortality of the cotton aphid, the test compound was termed as inactive (I).
An assessment of the insecticidal activity at selected rates of application from this test is provided in Table 6. The test compounds of formula I are identified by numbers that correspond to those in Table 1.
Table 6
The Following Compounds of The Present Invention Reduced the Population of Tarnished Leaf Bug Nymphs (Lygus lineolaris) By 40% to 100 % When Applied at an Application Rate of 300ppm or Less
Cmpd. Cmpd. Cmpd. Cmpd. Cmpd. Cmpd. Cmpd. Cmpd. Cmpd. Cmpd.
No. No. No. No. No. No. No. No. No. No.
1-1 1-2 1-3 1-4 1-6 1-8 1-36 1-45 1-46 1-55
1-56 1-57 1-58 1-59 1-60 1-61 1-62 1-63 1-66 1-70
1-72 1-73 1-76 3-9 3-12 3-13 3-14 3-15 3-17 3-18
3-19 3-20
Candidate insecticides were evaluated for insecticidal activity by observing mortality in a population of Formosan termite (Coptotermes formosanus) on treated sandy clay loam top soil when compared to like populations of Formosan termite on untreated sandy clay loam top soil. These tests were conducted in the following manner: For a test rate of application of 300 parts per million (ppm), a test solution was prepared by dissolving 9 mg of the test compound in 3 mL of acetone. Application of this solution to 30 grams of sandy clay loam top soil provided a concentration of 300 ppm of the test compound in the soil (300 ppm = 0.3mg/g x 30 gm of top soil= 9.0 mg of test compound). If needed, the initial test solution was serially diluted with acetone to provide solutions of each test compound for lower rates of application onto 30 grams of sandy clay loam top soil, for example, 100 ppm, 30 ppm, 10 ppm, 3 ppm, 1 ppm, 0.3 ppm or 0.1 ppm.
For each test rate, 3 mL of the test solution was added to 30 grams of unsterilized sandy clay loam top soil in a container and mixed well. The treated soil was allowed to dry at ambient temperature in a hood for 30 minutes. Three mL of distilled water was added to the treated soil providing a soil moisture of 10%. The treated soil was distributed equally into three 60 x 15 mm Petri dishes. The soil in each Petri dish was infested with 10 adult Formosan termites after residual periods of 0 days.
For comparison purposes, soil samples containing 10% moisture as described above were prepared from an untreated sandy clay loam top soil sample (untreated check). Upon completion of infestation the tops were placed on the Petri dishes and the Petri dishes were placed in a growth chamber where they were maintained in the dark for 7 days at 80% relative humidity.
During this time, each test was assessed daily up to 7 days after infestation (DAI) for percent mortality caused by the test compound when compared to the population of termites that were infested onto the control soil tests containing no test compound. Termites are classified as dead if they fail to show movement when probed.
An assessment of the insecticidal activity at selected rates of application from this test is provided in Table 7 below. The test compounds of formula I are identified by numbers that correspond to those in Table 1.
Table 7
Termiticidal Activity of The Following Compounds of The Present Invention when Applied at an Application Rate of 30ppm Infesting at Day Zero After Treatment
Figure imgf000041_0001
Candidate insecticides were evaluated for mammalian toxicity in a GABA receptor test. Rat brains were homogenized with physiological saline (same pH as in the rat plasma). A portion of this suspension (0.1 mL) was mixed with a radioligand [4'-ethynyl-4-n-ρropyl bicycloorthobenzoate (EBOB)]. Tubes containing this mixture and a test compound were compared with a reference (tubes with this mixture but without test compound).
All tubes were incubated (90 minutes, 2O0C). The content was filtered and the radioactivity remaining on the filter was determined. The concentration of the test compound that inhibited 50% of the controlled binding was the IC-50 of the compound.
The radioligand binds to a site within the known GABA receptor channel. If there is no test compound, the radioligand does bind; if there is a toxic compound effective on the same site, the amount of radioligand is reduced because the test compound replaces the radioligand.
In the above in vivo test on the GABA receptor channel, representative compounds of the invention were inactive or weakly active at a very high concentration (high IC-50), which shows that the compounds are still safe for mammals even when toxic to pests.
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 compound of formula I
Figure imgf000043_0001
wherein
W is C-halogen, C-CH3, C-CH2F, C-CHF2, C-CF3, C-NO2 or N;
R1 is selected from halogen, cyano,
Figure imgf000043_0002
(d-C4)haloalkyl, -S(O)nR10, formyl, acetyl, nitro, -C(S)NH2, -C(=NNH2)NH2; or R1 is -CR7=N-0-Y!, wherein R7 is hydrogen, alkyl or R7 and Y1 may be taken together to form a 5 or 6 member ring or R7 is -NR8R9, wherein R8 and R9 are independently hydrogen or alkyl and Y1 is hydrogen, alkenyl, alkynyl, formyl, alkylcarbonyl, cycloalkylcarbonyl, haloalkylcarbonyl, aroyl, arylalkylcarbonyl, alkylsulfonyl, arylsulfonyl, haloalkylcarbonyl, aminoalkylcarbonyl, alkylaminoalkylcarbonyl, dialkylaminocarbonyl, alkoxyalkylcarbonyl, arylalkoxycarbonyl, alkylthioalkylcarbonyl, alkylsulfonylalkylcarbonyl, arylthioalkoxycarbonyl, N- alkylcarbamoyl, N-arylcarbamoyl, N-alkylthiocarbamoyl, N-arylthiocarbamoyl, alpha-hydroxyarylalkylcarbonyl, hydroxyalkylcarbonyl, carboxyalkylcarbonyl, alkoxycarbonylalkylcarbonyl, -P(=O)(O-alkyl)2, -P(=S)(O-alkyl)2, -P(-O)(S- alkyl)2, trialkylsilyl, alkylcarbonylaminoalkylcarbonyl, alkylcarbonyloxyalkylcarbonyl, aryl, pyridinyl, pyrimidinyl, -C(=O)S-alkyl, - C(=O)S-aryl, -C(=O)S-alkylaryl, alkoxyalkoxycarbonyl, alkylthioalkoxycarbonyl, alkylsulfonylalkyxoycarbonyl, arylthioalkoxycarbonyl, alkoxycarbonyl, aryloxycarbonyl and aryloxycarbonylalkylcarbonyl; or alkyl or haloalkyl, optionally substituted by alkoxy, alkoxycarbonyl, carboxy, cyano, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, alkylthio, nitro, alkylsulfinyl, alkylsulfonyl, alkylcarbonyl, amino, alkylamino, dialkylamino, hydroxy, alkylcarbonylamino or alkylcarbonyloxy; R2 is selected from hydrogen, halogen, -S(O)nR10, (Ci-C4)alkyl, (Q-GOhaloalkyl, (C3-C5)alkenyl, (C3-C5)haloalkenyl, (C3-C6)cycloalkyl, (C3-C6)halocycloalkyl, (C3-C5)alkynyl, aryl, heteroaryl, -NR8R9, -CO2R15, -CR^N-O-Y1, nitro or cyano; n is an integer selected from 0,1 and 2;
R3 is hydrogen, halogen, cyano, formyl, acetyl, alkyl, haloalkyl or nitro;
R4 is halogen, (C1-C4)alkyl,
Figure imgf000044_0001
(C3-C5)alkenyl, (C3-C5)alkynyl, (C1- C4)alkoxy, (d-C4)haloalkoxy, -S(O)πhaloalkyl or -SF5;
A and B are independently selected from alkylene and haloalkylene;
X and Y are independently selected from O, N-R11, N(O)-R13, SiR10R10, and S(O)n;
R5 and R6 are independently selected from hydrogen(C3-C5)alkenyl, (C3- C5)haloalkenyl, (C3-C5)alkynyl, (C3-C5)haloalkynyl, (C3-C6)cycloalkyl, - (CH2)qR12, -(CH2)qR13 and -NR15R16; or is (Q-C^alkyl unsubstituted or substituted by one or more radicals selected from the group consisting of halogen, alkoxy, haloalkoxy, alkenyloxy, haloalkenyloxy, alkynyloxy, haloalkynyloxy, trialkylsilyl, cycloalkyl, -S(O)nR13, -CN, -NO2, -OH, -OR 12 -OR14, -COR15, -NR15COR16, -P(=O)(O-alkyl)2, -P(=S)(O-alkyl)2, -NR15SO2R13, -CONR15R16, -NR15R16, -S(O)nR12, -S(O)nR14, and -CO2R15; or R5 and R6 may be taken together to form a ring selected from the following:
Figure imgf000044_0003
Figure imgf000044_0002
Figure imgf000045_0001
p is an integer selected from O or 1; q is an integer selected from 0, 1, 2 and 3; t is an integer selected from 0,1 and 2;
R10 is alkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, cycloalkyl or halocycloalkyl;
R11 hydrogen, alkyl and haloalkyl; R12 is phenyl unsubstituted or substituted by one or more radicals selected from the group consisting of halogen, alkyl, haloalkyl, alkoxy, haloalkoxy, -CN, -NO2, -
S(O)nR13, -COR16, -COR18, -CONR15R16, -SO2NR15R16, -NR15R16, -OH, -
SO3H and alkylideneimino; R13 is haloalkyl, alkylcarbonyl or alkoxycarbonyl; R14 is heterocyclyl unsubstituted or substituted by one or more radicals selected from the group consisting of halogen, alkyl, haloalkyl, alkoxy, haloalkoxy, -CN,
-NO2, -S(O)nR13, -OH and -CO2alkyl;
R15 and R17 are each independently hydrogen, alkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, cycloalkyl, cycloalkylalkyl, -(CH2)qR18 or -(CH2)qR14; R16 and R19 are each independently hydrogen, alkyl, haloalkyl, cycloalkyl or cycloalkylalkyl; R18 is phenyl unsubstituted or substituted by one or more radicals selected from the group consisting of halogen, alkyl, haloalkyl, alkoxy, haloalkoxy,-CN, -NO2, -
S(O)nR13 and -NR16R19; R20 and R21 are independently selected from hydrogen, alkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, cycloalkyl, cycloalkylalkyl, -(CH2)qR18, -
(CH2)qR14, -COalkyl, -S(O)nalkyl or
Figure imgf000046_0001
(13);
R22 is hydrogen, alkyl, alkoxy, alkoxyalkyl, alkylthioalkyl or alkylsulfϊnylalkyl; and each heterocyclyl in the above-mentioned radicals is independently a heterocyclic radical having 3 to 7 ring atoms and 1 ,
2 or 3 hetero atoms in the ring selected from the group consisting of N, O and S; and pesticidally acceptable salts thereof; provided that when R1 is cyano and R2 is -S(O)nR10, then A and B are other than methylene, X and Y are other than O and R5 and R6 are other than methyl.
Claim 2 A compound of claim 1 , wherein
W is C-halogen; R1 is cyano;
R2 is, -S(O)nR10 or haloalkyl; R3 is halogen; R4 is haloalkyl; and A and B are each -CH2-; X and Y are each O or S(O)n; and
R5 and R6 are each alkyl or are taken together to form a ring of formula (9), formula (11) or formula (12).
Claim 3. A compound of claim 2, wherein
W is C-Cl;
R2 is. , -S(O)CF 3 or CF3;
R3 is chlorine;
R4 is CF3;
X and Y are each O or S(O)n where n is O; and R5 and R6 are each methyl or ethyl.
Claim 4. A composition comprising an insecticidally effective amount of a compound of claim 1 and at least one agriculturally acceptable extender or adjuvant.
Claim 5. The insecticidal composition of claim 4, further comprising one or more additional compounds selected from the group consisting of pesticides, plant growth regulators, fertilizers and soil conditioners.
Claim 6. A method of controlling insects, comprising applying an insecticidally effective amount of a composition of claim 4 to a locus where insects are present or are expected to be present.
Claim 7. A method of controlling insects, comprising applying an insecticidally effective amount of a composition of claim 5 to a locus where insects are present or are expected to be present.
Claim 8. A composition comprising a general household pesticidally effective amount of a compound of claim 1 and at least one acceptable extender or adjuvant.
Claim 9. The pesticidal composition of claim 8, further comprising one or more additional compounds selected from the group consisting of insecticides.
Claim 10. A method of controlling general household pests, comprising applying a pesticidally effective amount of a composition of claim 8 to a locus where general household pests are present or are expected to be present.
Claim 11. A method of controlling general household pests, comprising applying a pesticidally effective amount of a composition of claim 9 to a locus where general household pests are present or are expected to be present.
Claim 12. A composition comprising a parasitically effective amount of a compound of claim 1 and at least one acceptable extender or adjuvant.
Claim 13. The parasitic composition of claim 12, further comprising one or more additional compounds selected from the group consisting of insecticides.
Claim 14. A method of controlling animal parasites, comprising applying a parasitically effective amount of a composition of claim 12 to a locus where animal parasites are present or are expected to be present.
Claim 15. A method of controlling animal parasites, comprising applying a parasitically effective amount of a composition of claim 13 to a locus where animal parasites are present or are expected to be present.
PCT/US2006/022356 2005-06-13 2006-06-07 Pesticidal 5-di-(substituted)aminopyrazole derivatives WO2006138147A1 (en)

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US60/763,071 2006-01-27

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Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20130165482A1 (en) * 2010-08-31 2013-06-27 Meiji Seika Pharma Co., Ltd. Pest control agent
US20150203660A1 (en) * 2012-03-28 2015-07-23 Lanxess Deutschland Gmbh Fungicide formulations for plasticized pvc
CN105541821A (en) * 2016-01-28 2016-05-04 中南民族大学 Oxazine ketonization arylpyrazole compound as well as ultrasonic radiation synthesis method and application thereof
WO2018011673A3 (en) * 2016-07-09 2018-04-19 Kishor Prabhakar Kumbhar 1, 3, 5-dioxazine derivatives, method of preparation and application thereof as sulfide scavenger
WO2023275116A1 (en) * 2021-07-02 2023-01-05 Syngenta Crop Protection Ag Use of fluazifop-p-butyl for insect control

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6812347B2 (en) * 2000-06-09 2004-11-02 Bayer Cropscience S.A. Processes for the preparation of pesticidal compounds and novel intermediates thereof

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6812347B2 (en) * 2000-06-09 2004-11-02 Bayer Cropscience S.A. Processes for the preparation of pesticidal compounds and novel intermediates thereof

Cited By (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20130165482A1 (en) * 2010-08-31 2013-06-27 Meiji Seika Pharma Co., Ltd. Pest control agent
US8957214B2 (en) * 2010-08-31 2015-02-17 Meiji Seika Pharma Co., Ltd. Pest control agent
US9328068B2 (en) 2010-08-31 2016-05-03 Meiji Seika Pharma Co., Ltd. N-[1-((6-chloropyridin-3-yl) methyl)pyridin-2(1H)-ylidene]-2,2,2-trifluoroacetamide for control of animal parasitic pests and agricultural/horticultural pests
US9717242B2 (en) 2010-08-31 2017-08-01 Meiji Seika Pharma Co., Ltd. N-[1-((6-chloropyridin-3-yl)methyl)pyridin-2(1H)-ylidene]-2,2,2-trifluoroacetamide for control of agricultural/horticultural pests
US10085449B2 (en) 2010-08-31 2018-10-02 Meiji Seika Pharma Co., Ltd. N-[1-((6-chloropyridin-3-yl)methyl)pyridin-2(1H)-ylidene]-2,2,2- trifluoroacetamide for control of agricultural/horticultural pests
US20150203660A1 (en) * 2012-03-28 2015-07-23 Lanxess Deutschland Gmbh Fungicide formulations for plasticized pvc
US9296878B2 (en) * 2012-03-28 2016-03-29 Lanxess Deutschland Gmbh Fungicide formulations for plasticized PVC
CN105541821A (en) * 2016-01-28 2016-05-04 中南民族大学 Oxazine ketonization arylpyrazole compound as well as ultrasonic radiation synthesis method and application thereof
CN105541821B (en) * 2016-01-28 2018-05-18 中南民族大学 Oxazine assimilation arylpyrazole type compound and its Ultrasonic Radiation synthetic method and application
WO2018011673A3 (en) * 2016-07-09 2018-04-19 Kishor Prabhakar Kumbhar 1, 3, 5-dioxazine derivatives, method of preparation and application thereof as sulfide scavenger
US11053232B2 (en) 2016-07-09 2021-07-06 Kishor Prabhakar Kumbhar 1,3,5-dioxazine derivatives, method of preparation and application thereof as sulfide scavenger
WO2023275116A1 (en) * 2021-07-02 2023-01-05 Syngenta Crop Protection Ag Use of fluazifop-p-butyl for insect control

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