USOO887 1941B2

(12) United States Patent (10) Patent No.: US 8,871,941 B2 Lahm et al. (45) Date of Patent: Oct. 28, 2014

(54) 8-BROMO-5-QUINOLINECARBOXALDEHYDE 8,138,213 B2 3/2012 Mita et al. OXME 8,217,180 B2 7/2012 Annis et al. 8,231,888 B2 7/2012 Lahm et al. 8.410,153 B2 4/2013 Lahm et al. (71) Applicant: E.I. du Pont de Nemours and 8,513,431 B2 8/2013 Annis et al. Company, Wilmington, DE (US) 2003/0114501 A1 6/2003 Braun et al. 2005, O250822 A1 11/2005 Mita et al. (72) Inventors: George Philip Lahm, Wilmington, DE 2007/00666.17 A1 3, 2007 Mita et al. (US); Wesley Lawrence Shoop 2009/0023923 A1 1/2009 Mizukoshi et al. H11illsborough, b NJ (US); MingMi Xu,k 2009,2009.0143410 O133319 A1 6,5/2009 2009 LahmPatel et al. Newark, DE (US) 2010.0137612 A1 6, 2010 Yaosaka et al. 2010/0173948 A1 7, 2010 Lahm et al. (73) Assignee: E.I. du Pont de Nemours and (Continued) Company, Wilmington, DE (US) (*) Notice: Subject to any disclaimer, the term of this FOREIGN PATENT DOCUMENTS patent is extended or adjusted under 35 CA 2252543 11, 1997 U.S.C. 154(b) by 0 days. CA 2558848 9, 2005 (21) Appl. No.: 14/275,664 (Continued)Continued OTHER PUBLICATIONS (22) Filed: May 12, 2014 Sato, et al., Science of Synthesis, 18:821 (2005) pp. IV and 924).* (65) Prior Publication Data (Continued) US 2014/0249314 A1 Sep. 4, 2014 Primary Examiner — Michael Barker Related U.S. Application Data (74) Attorney, Agent, or Firm — Pepper Hamilton LLP (63) Continuation of application No. 14/047,500, filed on (57) ABSTRACT Oct. 7, 2013, now abandoned, which is a continuation Disclosed are compounds of Formula 1, including all geo of application No. 13/561,546, filed on Jul. 30, 2012, mp s g all g now Pat. No. 8,552,218, which is a continuation of metric and Stereoisomers, N-oxides, and salts thereof, application No. 13/156,653, filed on Jun. 9, 2011, now Pat. No. 8,231,888, which is a continuation of 1 application No. 12/086,935, filed as application No. PCT/US2006/049459 on Dec. 28, 2006, now Pat. No. 7,964,204. (60) Provisional application No. 60/857,307, filed on Nov. 7, 2006, provisional application No. 60/839,988, filed on Aug. 23, 2006, provisional application No. 60/755,247, filed on Dec. 30, 2005. (51) Int. Cl. C07D 215/12 (2006.01) wherein AOIN 43/42 2006.O1 (52) U.S. Cl ( ) A', A, A, A, A and Aare independently selected from CPC A0IN 43/42 (2013.01); C07D 215/12 the group consisting of CR and N: provided that at most ------s (2013.01) 3 of A', A, A, A, A. and A is N: USPC 54.6/176 B', B and B are independently selected from the group ------2 (58) NoneField of Classification Search each consistingR is independently of CR and H,N: halogen, C-C alkyl, C-C, See application file for complete search history. haloalkyl, C-C cycloalkyl, C-C halocycloalkyl, C-C, alkoxy, C-C haloalkoxy, C-C alkylthio, C-C haloalky (56) References Cited lthio, C-C alkyl sulfinyl, C-C haloalkylsulfinyl, C-C, alkylsulfonyl, C-C haloalkylsulfonyl, C-C alkylamino, U.S. PATENT DOCUMENTS C-C dialkylamino, CN or - NO; and R', R. R. R. W. 3,879,532 A 4, 1975 Hasset al. and n are as defined in the disclosure. 4,129,568 A 12, 1978 Howe Also disclosed are compositions containing the compounds 6,645,984 B2 11/2003 Braun et al. of Formula 1 and methods for controlling an invertebrate pest 7,662.972 B2 2/2010 Mita et al. comprising contacting the invertebrate pest or its environ 7,897,630 B2 3/2011 Lahm et al. 7,947,715 B2 5, 2011 Mita et al. ment with a biologically effective amount of a compound or 7,951,828 B1 5, 2011 Mita et al. a composition of the invention. 7,964,204 B2 6/2011 Lahm et al. 8,022,089 B2 9, 2011 Mita et al. 1 Claim, No Drawings US 8,871,941 B2 Page 2

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(56) References Cited Notice of Allowance received in copending U.S. Appl.No. 13/561,546 dated Jun. 7, 2013. OTHER PUBLICATIONS Notice of Allowance received in copending U.S. Appl. No. 13/544,113 dated Apr. 15, 2013. Office Action dated Jun. 8, 2012 received in copending U.S. Appl. Notice of Allowance received in copending U.S. Appl. No. No. 12/663,751. 12/933,493 dated May 14, 2013. Office Action dated Jul. 2, 2012 received in copending U.S. Appl. No. Final Office Action received in copending U.S. Appl. No. 12/663,848 12/677,927. dated Jan. 28, 2013. Office Action dated Aug. 14, 2012 received in copending U.S. Appl. Final Office Action received in copending U.S. Appl. No. 12/602,821 No. 12/933,493. dated Mar. 13, 2013. Notice of Allowance datedMar. 21, 2012 received in copending U.S. Notice of Allowance received in counterpart U.S. Appl. No. Appl. No. 13/156,653. 12/663,751 dated Nov. 14, 2012. Office Action dated Sep. 21, 2011 received in counterpart U.S. Appl. No. 13/156,653. * cited by examiner US 8,871,941 B2 1. 8-BROMO-5-QUINOLINECARBOXALDEHYDE

OXIME

CROSS-REFERENCE TO RELATED APPLICATIONS 5 This application is a Continuation application filing of U.S. patent application Ser. No. 14/047,500 filed Oct. 7, 2013, which is a Continuation application filing of U.S. patent application Ser. No. 13/561,546, filed Jul. 30, 2012, which is 10 a Continuation application filing of U.S. patent application Ser. No. 12/086,935, filed Jun. 20, 2008 which is a U.S. wherein National Stage Application of International Application No. A, A, A, A, A and Aare independently selected from PCT/US2006/049459, filed Dec. 28, 2006, which claims pri the group consisting of CR and N, provided that at most ority to U.S. Provisional Application No. 60/857,307, filed 15 3 of A, A, A, A, A and Aare N: Nov. 7, 2006, U.S. Provisional Application No. 60/839,988, B', B and B are independently selected from the group filed Aug. 23, 2006, and U.S. Provisional Application No. consisting of CR and N: 60/755.247, filed Dec. 30, 2005, each of which is incorpo W is O or S; rated herein by reference in its entirety. R" is C-C alkyl, C-C alkenyl, C-C alkynyl, C-C, FIELD OF THE INVENTION cycloalkyl, C-C, alkylcycloalkyl or C-C cycloalkyla lkyl, each optionally substituted with one or more sub This invention relates to certain isoxazolines, their N-ox stituents independently selected from R: ides, salts and compositions suitable for agronomic and nona each R is independently H, halogen, C-C alkyl, C-C, gronomic uses, including those uses listed below, and meth 25 haloalkyl, C-C alkoxy, C-Chaloalkoxy, C-C alkylthio. ods of their use for controlling invertebrate pests such as C-C haloalkylthio, C-C alkylsulfinyl, C-C haloalkyl arthropods in both agronomic and nonagronomic environ Sulfinyl, C-C alkylsulfonyl, C-Chaloalkylsulfonyl, C-C, mentS. alkylamino, C-C dialkylamino, C-C alkoxycarbonyl, —CN or - NO; BACKGROUND OF THE INVENTION 30 each R is independently H, halogen, C-C alkyl, C-C, haloalkyl, C-C cycloalkyl, C-C halocycloalkyl, C-C, The control of invertebrate pests is extremely important in alkoxy, C-C haloalkoxy, C-C alkylthio, C-C haloalky achieving high crop efficiency. Damage by invertebrate pests lthio, C-C alkylsulfinyl, C-C haloalkylsulfinyl, C-C, to growing and stored agronomic crops can cause significant alkylsulfonyl, C-C haloalkylsulfonyl, C-C alkylamino, reduction in productivity and thereby resultin increased costs 35 C-C dialkylamino, —CN or - NO; to the consumer. The control of invertebrate pests in forestry, R" is H. C-C alkyl, C-C alkenyl, C-C alkynyl, C-C, greenhouse crops, ornamentals, nursery crops, stored food cycloalkyl, Ca-C, alkylcycloalkyl, Ca-C7 cycloalkyla and fiber products, livestock, household, turf, wood products, lkyl, C-C, alkylcarbonyl or C-C, alkoxycarbonyl: and public and animal health is also important. Many prod R is H, OR', NR'R' or Q'; or C-C alkyl, C-C, ucts are commercially available for these purposes, but the 40 alkenyl, C-C alkynyl, C-C cycloalkyl, C-C, alkyl need continues for new compounds that are more effective, cycloalkyl or C-C cycloalkylalkyl, each optionally less costly, less toxic, environmentally safer or have different substituted with one or more substituents independently modes of action. selected from R'; or PCT Patent Publication WO 05/085216 discloses isoxazo R" and Rare taken together with the nitrogen to which line derivatives of Formula i as insecticides 45 they are attached to form a ring containing 2 to 6 atoms of carbon and optionally one additional atom selected from the group consisting of N, S and O, said ring optionally substituted with 1 to 4 substituents indepen R 9NN dently selected from the group consisting of C-C alkyl, 50 halogen, —CN. —NO and C-C alkoxy; (X), (Y), each R is independently halogen, C-C alkyl, C-C alkoxy, SASA2 R2 C-C alkylthio, C-C alkylsulfinyl, C-C alkylsulfonyl, 3 —CN or - NO; A n% N RI each R" is independently halogen, C-C alkyl, C-C, 55 cycloalkyl, C-C alkoxy, C-C alkylthio, C-C alkylsulfi W nyl, C-C alkylsulfonyl, C-C alkylamino, C-C dialky lamino, C-C cycloalkylamino, C-C, alkylcarbonyl, C-C, wherein, interalia, each of A', A and Aare independently C alkoxycarbonyl, C-C, alkylaminocarbonyl, C-Co dialky or N; G is a benzene ring; W is O or S; and X is halogen or laminocarbonyl, C-C, haloalkylcarbonyl, C-C, C-Chaloalkyl. 60 haloalkoxycarbonyl, C-C, haloalkylaminocarbonyl, C-Co halodialkylaminocarbonyl, hydroxy, NH, —CN or SUMMARY OF THE INVENTION - NO; or Q: each R is independently halogen, C-C alkoxy, C-C, This invention is directed to compounds of Formula 1 haloalkoxy, C-C alkylthio, C-C haloalkylthio, C-C, including all geometric and stereoisomers, N-oxides, and 65 alkylsulfinyl, C-C haloalkylsulfinyl, C-C alkylsulfonyl, salts thereof, and compositions containing them and their use C-C haloalkylsulfonyl, C-C alkylamino, C-C dialky for controlling invertebrate pests: lamino, C-C alkoxycarbonyl, —CN or —NO; US 8,871,941 B2 3 4 each R is independently halogen, C-C alkyl, C-C, adapted to be placed in or near a locus of potential or known haloalkyl, C-C cycloalkyl, C-C halocycloalkyl, C-C, activity for the invertebrate pest. alkoxy, C-C haloalkoxy, C-C alkylthio, C-C haloalky This invention also provides a method for controlling an lthio, C-C alkylsulfinyl, C-C haloalkylsulfinyl, C-C, invertebrate pest comprising contacting the invertebrate pest alkylsulfonyl, C-C haloalkylsulfonyl, C-C alkylamino, or its environment with a biologically effective amount of a C-C dialkylamino. —CN. —NO phenyl or pyridinyl: compound of Formula 1, an N-oxide or a salt thereof (e.g., as R" is H; or C-C alkyl, C-C alkenyl, C-C alkynyl, a composition described herein). This invention also relates to C-C cycloalkyl, Ca-C, alkylcycloalkyl or C-C, such method wherein the invertebrate pest or its environment cycloalkylalkyl, each optionally substituted with one or is contacted with a composition comprising a biologically more halogen; 10 effective amount of a compound of Formula 1, an N-oxide or a salt thereof, and at least one additional component selected R'' is H. C-C alkyl, C-C alkenyl, C-C alkynyl, C-C, from the group consisting of a Surfactant, a Solid diluent and cycloalkyl, C-C, alkylcycloalkyl, Ca-C7 cycloalkyla a liquid diluent, said composition optionally further compris lkyl, C-C, alkylcarbonyl or C-C, alkoxycarbonyl: ing a biologically effective amount of at least one additional R’ is H; Q; or C-C alkyl, C-C alkenyl, C-C alkynyl, 15 biologically active compound or agent. C-C cycloalkyl, C-C, alkylcycloalkyl or C-C, cycloalkylalkyl, each optionally substituted with one or DETAILS OF THE INVENTION more substituents independently selected from R”; or R'' and R'' are taken together with the nitrogen to which As used herein, the terms “comprises.” “comprising.” they are attached to form a ring containing 2 to 6 atoms “includes.” “including.” “has.” “having.” “contains” or “con of carbon and optionally one additional atom selected taining.” or any other variation thereof, are intended to cover from the group consisting of N, S and O, said ring a non-exclusive inclusion. For example, a composition, a optionally substituted with 1 to 4 substituents indepen mixture, process, method, article, or apparatus that comprises dently selected from the group consisting of C-C alkyl, a list of elements is not necessarily limited to only those halogen, —CN. —NO and C-C alkoxy; 25 elements but may include other elements not expressly listed Q" is a phenyl ring, a 5- or 6-membered heterocyclic ring, or inherent to Such composition, mixture, process, method, or an 8-, 9- or 10-membered fused bicyclic ring system article, or apparatus. Further, unless expressly stated to the optionally containing one to three heteroatoms selected contrary, “or” refers to an inclusive or and not to an exclusive from up to 1 O. up to 1 S and up to 3 N, each ring or ring or. For example, a condition A or B is satisfied by any one of system optionally substituted with one or more substitu 30 the following: A is true (or present) and B is false (or not ents independently selected from R: present), A is false (or not present) and B is true (or present), each Q is independently a phenyl ring or a 5- or 6-membered and both A and B are true (or present). heterocyclic ring, each ring optionally substituted with one or Also, the indefinite articles “a” and “an preceding an more substituents independently selected from R: element or component of the invention are intended to be Q is a phenyl ring or a 5- or 6-membered heterocyclic ring, 35 nonrestrictive regarding the number of instances (i.e. occur each ring optionally Substituted with one or more Sub rences) of the element or component. Therefore “a” or “an stituents independently selected from R. and should be read to include one or at least one, and the singular n is 0, 1 or 2. word form of the element or component also includes the This invention also provides a composition comprising a plural unless the number is obviously meant to be singular. compound of Formula 1, an N-oxide or a salt thereof, and at 40 As referred to in this disclosure, the term “invertebrate least one additional component selected from the group con pest” includes arthropods, gastropods and nematodes of eco sisting of a surfactant, a solid diluent and a liquid diluent. In nomic importance as pests. The term "arthropod' includes one embodiment, this invention also provides a composition insects, mites, spiders, Scorpions, centipedes, millipedes, pill for controlling an invertebrate pest comprising a biologically bugs and Symphylans. The term 'gastropod' includes Snails, effective amount of a compound of Formula 1, an N-oxide or 45 slugs and other Stylommatophora. The term “helminths’ a salt thereof, and at least one additional component selected includes worms in the phylum of Nemathelminth, Platyhel from the group consisting of a Surfactant, a Solid diluent and minth and Acanthocephala Such as: round worms, heart a liquid diluent, said composition optionally further compris worms, and phytophagous nematodes (Nematoda), flukes ing a biologically effective amount of at least one additional (Trematoda), tape worms (Cestoda) and throny-headed biologically active compound or agent. 50 WOS. This invention further provides a spray composition for In the context of this disclosure “invertebrate pest control controlling an invertebrate pest comprising a biologically means inhibition of invertebrate pest development (including effective amount of a compound of Formula 1, an N-oxide or mortality, feeding reduction, and/or mating disruption), and a salt thereof, or the composition described above and a related expressions are defined analogously. propellant. This invention also provides a bait composition 55 The term "agronomic’ refers to the production of field for controlling an invertebrate pest comprising a biologically crops such as for food and fiber and includes the growth of effective amount of a compound of Formula 1, an N-oxide or corn, soybeans and other legumes, rice, cereal (e.g., wheat, a salt thereof, or the composition described in the embodi oats, barley, rye, rice, maize), leafy vegetables (e.g., lettuce, ment above, one or more food materials, optionally an attrac cabbage, and other cole crops), fruiting vegetables (e.g., tant, and optionally a humectant. 60 tomatoes, pepper, eggplant, crucifers and cucurbits), pota This invention further provides a trap device for controlling toes, Sweet potatoes, grapes, cotton, tree fruits (e.g., pome, an invertebrate pest comprising said bait composition and a stone and citrus), small fruit (berries, cherries) and other housing adapted to receive said bait composition, wherein the specialty crops (e.g., canola, Sunflower, olives). The term housing has at least one opening sized to permit the inverte “nonagronomic' refers to other horticultural crops (e.g., brate pest to pass through the opening so the invertebrate pest 65 greenhouse, nursery or ornamental plants not grown in a can gain access to said bait composition from a location field), residential and commercial structures in urban and outside the housing, and wherein the housing is further industrial settings, turf (e.g., sod farm, pasture, golf course, US 8,871,941 B2 5 6 residential lawn, recreational sports field, etc.), wood prod The total number of carbon atoms in a Substituent group is ucts, stored product, agro-forestry and vegetation manage indicated by the "C-C prefix wherei andjare numbers from ment, public health (human) and animal health (e.g., domes 1 to 8. For example, C-C alkylsulfonyl designates methyl ticated animals such as pets, livestock and poultry, Sulfonyl through butylsulfonyl: C alkoxyalkyl designates undomesticated animals such as wildlife) applications. CHOCH, C, alkoxyalkyl designates, for example, CHCH In the above recitations, the term “alkyl, used either alone (OCH), CHOCH2CH2 or CHCHOCH; and C alkoxy or in compound words such as “alkylthio’ or “haloalkyl alkyl designates the various isomers of an alkyl group Substi includes straight-chain or branched alkyl, such as, methyl, tuted with an alkoxy group containing a total of four carbon ethyl, n-propyl, i-propyl, or the different butyl, pentyl or atoms, examples including CHCH2CH2OCH and hexyl isomers. “Alkenyl' includes straight-chain or branched 10 alkenes such as ethenyl, 1-propenyl, 2-propenyl, and the dif CHCHOCHCH. ferent butenyl, pentenyl and hexenyl isomers. “Alkenyl also When a compound is substituted with a substituent bearing includes polyenes such as 1,2-propadienyl and 2.4-hexadi a Subscript that indicates the number of said Substituents can enyl. “Alkynyl' includes straight-chain or branched alkynes exceed 1, said substituents (when they exceed 1) are indepen Such as ethynyl, 1-propynyl, 2-propynyl and the different 15 dently selected from the group of defined Substituents, e.g., butynyl, pentynyl and hexynyl isomers. “Alkynyl can also (R), n is 1,2,3,4 or 5. When a group contains a substituent include moieties comprised of multiple triple bonds such as which can be hydrogen, for example R, then when this 2.5-hexadiynyl. Substituent is taken as hydrogen, it is recognized that this is "Alkoxy' includes, for example, methoxy, ethoxy, n-pro equivalent to said group being unsubstituted. pyloxy, isopropyloxy and the different butoxy, pentoxy and The term "heterocyclic ring, "heterocycle' or "heterocy hexyloxy isomers. “Alkylthio' includes branched or straight clic ring system' denotes rings or ring systems in which at chain alkylthio moieties such as methylthio, ethylthio, and least one ring atom is not carbon, e.g., nitrogen, oxygen or the different propylthio, butylthio, pentylthio and hexylthio Sulfur. Typically a heterocyclic ring contains no more than 4 isomers. “Alkylsulfinyl' includes both enantiomers of an nitrogens, no more than 2 oxygens and no more than 2 Sulfurs. alkylsulfinyl group. Examples of “alkylsulfinyl' include 25 The heterocyclic ring can be attached through any available CHS(O) , CHCHS(O) , CHCHCHS(O) , (CH), carbon or nitrogen by replacement of hydrogen on said car CHS(O)—and the different butylsulfinyl, pentylsulfinyl and bon or nitrogen. The heterocyclic ring can be a saturated, hexylsulfinyl isomers. Examples of “alkylsulfonyl include partially unsaturated, or fully unsatuturated ring. When a CHS(O) . CHCHS(O) . CHCHCHS(O) , fully unsaturated heterocyclic ring satifies the Bickel rule, (CH),CHS(O) , and the different butylsulfonyl, pentyl 30 then said ring is also called a "heteroaromatic ring or "aro sulfonyl and hexylsulfonyl isomers. “Alkylamino”, “dialky matic heterocyclic ring. lamino', and the like, are defined analogously to the above The term 'aromatic ring or 'aromatic ring system” examples. "Cycloalkyl includes, for example, cyclopropyl. denotes fully unsaturated carbocycles and heterocycles in cyclobutyl, cyclopenty1 and cyclohexyl. The term “alkylcy which at least one ring of the polycyclic ring system is aro cloalkyl denotes alkyl substitution on a cycloalkyl moiety 35 matic (where aromatic indicates that the Bickel rule is satis and includes, for example, ethylcyclopropyl, i-propylcy fied for the ring system). The term “fused bicyclic ring sys clobutyl, 3-methylcyclopenty1 and 4-methylcyclohexyl. The tem’ includes a ring system comprised of two fused rings in term “cycloalkylalkyl denotes cycloalkyl substitution on an which either ring can be saturated, partially unsaturated, or alkyl moiety. Examples of “cycloalkylalkyl include cyclo fully unsatuturated. The term “fused heterobicyclic ring sys propylmethyl, cyclopentylethyl, and other cycloalkyl moi 40 tem’ includes a ring system comprised of two fused rings in eties bonded to straight-chain or branched alkyl groups. which at least one ring atom is not carbon and can be aromatic The term “halogen, either alone or in compound words or non aromatic, as defined above. Such as "haloalkyl, or when used in descriptions such as The term “optionally substituted in connection with the “alkyl substituted with halogen includes fluorine, chlorine, heterocyclic rings refers to groups which are unsubstituted or bromine or iodine. Further, when used in compound words 45 have at least one non-hydrogen Substituent that does not Such as "haloalkyl, or when used in descriptions such as extinguish the biological activity possessed by the unsubsti “alkyl substituted with halogen said alkyl may be partially or tuted analog. As used herein, the following definitions shall fully substituted with halogen atoms which may be the same apply unless otherwise indicated. The term “optionally sub or different. Examples of “haloalkyl or “alkyl substituted stituted” is used interchangeably with the phrase “substituted with halogen include FC , CICH CFCH and 50 or unsubstituted” or with the term “(un)substituted. Unless CFCC1 . The terms “halocycloalkyl”, “haloalkoxy’, otherwise indicated, an optionally substituted group may “haloalkylthio', and the like, are defined analogously to the have a Substituent at each Substitutable position of the group, term “haloalkyl. Examples of “haloalkoxy” include and each substitution is independent of the other. CFO , CC1, CHO , HCFCHCHO and When Q is a 5- or 6-membered nitrogen-containing het CFCHO—. Examples of “haloalkylthio' include CC1-S 55 erocyclic ring, it may be attached to the remainder of Formula CFS , CC1-CHS and CICHCHCHS . Examples of 1 though any available carbon or nitrogen ring atom, unless “haloalkylsulfinyl' include CFS(O)—, CC1-S(O)— otherwise described. Similarly, when Q or Q is a 5- or CFCHS(O)— and CFCFS(O)—. Examples of 6-membered nitrogen-containing heterocycle, it may be “haloalkylsulfonyl include CFS(O) , CC1-S(O) , attached through any available carbon or nitrogen ring atom, CFCHS(O) and CFCFS(O) . 60 unless otherwise described. Alkylcarbonyl denotes a straight-chain or branched alkyl As noted above, Q, Q or Q can be (among others) phenyl moieties bonded to a C(=O) moiety. Examples of “alkylcar optionally substituted with one or more substituents selected bonyl' include CHC(=O)—, CHCHCHC(=O) and from a group of Substituents as defined in the Summary of (CH)2CHC(=O)—. Examples of “alkoxycarbonyl include Invention. An example of phenyl optionally substituted with CHC(=O)—, CHCHOC(=O), CHCHCHC(=O) , 65 one to five substituents is the ring illustrated as U-1 in Exhibit (CH)2CHOC(=O)—and the different butoxy- or pentoxy 1, wherein R' is R or R as defined in the Summary of the carbonyl isomers. Invention for Q', Q’or Q and r is an integer from 0 to 5. US 8,871,941 B2 7 8 As noted above, Q', Q’or Q can be (among others)5- or -continued 6-membered heterocyclic ring, which may be saturated or U-11 unsaturated, optionally Substituted with one or more substitu 4 (R), ents selected from a group of Substituents as defined in the Summary of Invention. Examples of a 5- or 6-membered 5 unsaturated aromatic heterocyclic ring optionally substituted with from one or more substituents include the rings U-2 U-12 through U-61 illustrated in Exhibit 1 wherein R is any sub stituent as defined in the Summary of the Invention for Q', Q’ or Q (i.e. R or R) and r is an integer from 0 to 4. 10

U-13 Exhibit 1

U-1 15 (R), 2A U-14 N U-2 3 (R), Y. U-15 / 25 U-3 4 (R), U-16

2 S 30 U-4 3 (R), U-17 1. 35 U-5 U-18

4 ^ax S. 5 Sr., 40 U-19 U-6 (R), Sr. 45 U-7 U-20 (R), Y. 50 U-8 U-21

sx"NS r 55 (R) U-9 U-22

yO / 60 (R) U-10 U-23 N.' " 4 S 7 65

US 8,871,941 B2 11 12 -continued -continued U-49 U-60 4 (R),

U-50

10

15 Note that when Q', Q or Q is a 5- or 6-membered satu rated or unsaturated non-aromatic heterocyclic ring option ally substituted with one or more substituents selected from the group of substituents as defined in the Summary of Inven tion for Q, Q or Q, one or two carbon ring members of the U-52 heterocycle can optionally be in the oxidized form of a car bonyl moiety. Examples of a 5- or 6-membered saturated or non-aromatic unsaturated heterocyclic ring include the rings G-1 through 25 G-35 as illustrated in Exhibit 2. Note that when the attach U-53 ment point on the G group is illustrated as floating, the G group can be attached to the remainder of Formula 1 through any available carbon or nitrogen of the G group by replace ment of a hydrogen atom. The optional Substituents can be 30 attached to any available carbon or nitrogen by replacing a hydrogen atom. U-54 Note that when Q, Q or Q comprises a ring selected from G-28 through G-35, G is selected from O, S or N. Note that 35 when G is N, the nitrogenatom can complete its valence by substitution with either Hor the substituents as defined in the Summary of Invention for Q, Q or Q (i.e. R or R). U-55

40 Exhibit 2

U-56 45 NC y- (R). G-2 Q2 U-57 50

55 U-58 NC 3-(R'). G-4 Q2

60 NC 3-(R'). G-5 U-59 Q9

65

US 8,871,941 B2 15 16 -continued -continued G-33 U-89 (R), 9, 21 SAS ŽS. 5. U-90 G-34 21 O 10 SAS . U-91 G-35 21 S 15 Ás 2.MYR), U-92 21 N As noted above, Q' can be (among others) an 8-, 9- or IX 10-membered fused bicyclic ring system optionally substi Ás MYR), tuted with one or more substituents selected from a group of U-93 substituents as defined in the Summary of Invention (i.e. R). 21 N Examples of 8-, 9- or 10-membered fused bicyclic ring sys tem optionally substituted with from one or more substituents 25 2. include the rings U-81 through U-123 illustrated in Exhibit 3 Ás SY(R), wherein R is any substituent as defined in the Summary of the U-94 Invention for Q" (i.e. R) and r is an integer from 0 to 4. 21 N 30 Ás d5Y(R),2. Exhibit 3 U-95 ) U-81 21 N 35 2. sIX. Ás NY(R), U-96 ) U-82 21 NY 40

) U-83 U-97

sIX. 45 ) U-84 SOC Še. U-98 ) U-85 50 U-99

) U-86 55 SAS S(R)

U-100 SOC Še. 21 N

( ) U-87 60 OC.Ás (R), OC Še. U-101 U-88 21

65 OC) (R), US 8,871,941 B2 17 18 -continued -continued U-102 U-115 ys ŽSR). S.Äs 8. U-103 U-116 21 21 y (R), Ás GSR). 10 ya U-104 N U-117 21 nle. A S(R) 15 Ás 2 U-105 U-118 21 N 21 NN | H(R), | --(R), Ás 21 SAS 21 U-106 N U-119 21 n (R), h-ce. A-N-2n-1\ 25 SAS 2 U-107 N U-120 21 21 n | - H(R'), Ás - 30 OC ne. U-121 U-108 21 | - H(R'), - 35 Ás O U-109 U-122 21 NN 21 | - H(R'), | --(R), and 40 N - Ás U-123 U-110 21

S. | --(R),N Á 45 U-111 21 Although R' groups are shown in the structures U-1 through U-123, it is noted that they do not need to be present S. S 50 since they are optional substituents. Note that when R is H Ás when attached to an atom, this is the same as if said atom is U-112 unsubstituted. The nitrogenatoms that require Substitution to fill their valence are substituted with Hor R. Note that when --(R), the attachment point between (R), and the Ugroup is illus 55 trated as floating, (R), can be attached to any available car A-N-2n-1N bonatom or nitrogenatom of the Ugroup. Note that when the U-113 O attachment point on the Ugroup is illustrated as floating, the 21 U group can be attached to the remainder of Formula 1 N- (R), through any available carbon or nitrogen of the U group by 60 replacement of a hydrogen atom. Note that some U groups can only be substituted with less than 4 R' groups (e.g., U-2 U-114 through U-5, U-7 through U-48, and U-52 through U-61). Compounds of this invention can exist as one or more -- (R), Stereoisomers. The various Stereoisomers include enanti 65 omers, diastereomers, atropisomers and geometric isomers. One skilled in the art will appreciate that one stereoisomer may be more active and/or may exhibit beneficial effects US 8,871,941 B2 19 20 when enriched relative to the other stereoisomer(s) or when Embodiment 4 separated from the other stereoisomer(s). Additionally, the skilled artisan knows how to separate, enrich, and/or to selec A compound of Embodiment 3 wherein R' is C-C alkyl tively prepare said stereoisomers. The compounds of the substituted with F. invention may be present as a mixture of stereoisomers, indi vidual stereoisomers or as an optically active form. Embodiment 5 One skilled in the art will appreciate that not all nitrogen containing heterocyclic rings can form N-oxides since the A compound of Embodiment 4 wherein R' is C-C alkyl nitrogen requires an available lone pair for oxidation to the fully substituted with F. oxide; one skilled in the art will recognize those nitrogen 10 containing heterocyclic rings which can form N-oxides. One Embodiment 6 skilled in the art will also recognize that tertiary amines can form N-oxides. Synthetic methods for the preparation of A compound of Embodiment 5 wherein R' is CF. N-oxides of heterocycles and tertiary amines are very well 15 known by one skilled in the art including the oxidation of Embodiment 7 heterocycles and tertiary amines with peroxy acids such as peracetic and m-chloroperbenzoic acid (MCPBA), hydrogen A compound of Formula 1 wherein each R is indepen peroxide, alkyl hydroperoxides such as t-butyl hydroperoX dently H, halogen, C-C haloalkyl, C-C haloalkoxy or ide, Sodium perborate, and dioxiranes such as dimethyldiox CN. irane. These methods for the preparation of N-oxides have Embodiment 8 been extensively described and reviewed in the literature, see for example: T. L. Gilchrist in Comprehensive Organic Syn A compound of Embodiment 7 wherein each R is inde thesis, Vol. 7, pp 748-750, S.V. Ley, Ed., Pergamon Press: M. pendently H, CF. OCF, halogen or —CN. Tisler and B. Stanovnik in Comprehensive Heterocyclic 25 Chemistry, vol. 3, pp 18-20, A. J. Boulton and A. McKillop, Embodiment 9 Eds. Pergamon Press; M. R. Grimmett and B. R. T. Keene in Advances in Heterocyclic Chemistry, vol.43, pp 149-161, A. A compound of Embodiment 7 wherein each R is inde R. Katritzky, Ed., Academic Press; M. Tisler and B. pendently halogen or C-C haloalkyl. Stanovnik in Advances in Heterocyclic Chemistry, vol. 9, pp 30 285-291, A. R. Katritzky and A. J. Boulton, Eds. Academic Embodiment 10 Press; and G. W. H. Cheeseman and E. S. G. Werstiuk in Advances in Heterocyclic Chemistry, vol. 22, pp. 390-392, A. A compound of Formula 1 wherein each R is indepen R. Katritzky and A. J. Boulton, Eds. Academic Press. 35 dently H, halogen, C-C alkyl, C-C haloalkyl, C-C, The salts of the compounds of the invention include acid cycloalkyl, C-C halocycloalkyl, C-C alkoxy, C-C, addition salts with inorganic or organic acids such as hydro haloalkoxy, —CN or - NO. bromic, hydrochloric, nitric, phosphoric, Sulfuric, acetic, butyric, fumaric, lactic, maleic, malonic, oxalic, propionic, Embodiment 11 salicylic, tartaric, 4-toluenesulfonic or Valeric acids. The salts 40 of the compounds of the invention also include those formed A compound of Embodiment 10 wherein each R is inde with organic bases (e.g., pyridine or triethylamine) or inor pendently H, C-C alkyl, C-Chaloalkyl, C-C cycloalkyl, ganic bases (e.g., hydrides, hydroxides, or carbonates of C-C alkoxy or —CN. Sodium, potassium, lithium, calcium, magnesium or barium) when the compound contains an acidic moiety Such as when 45 Embodiment 12 R" is alkylcarbonyl and R is H. Accordingly, the present invention comprises compounds A compound of Embodiment 11 wherein each R is inde selected from Formula 1, N-oxides and agriculturally suitable pendently H, C-C alkyl or —CN. salts thereof. Embodiments of the present invention as described in the 50 Embodiment 13 Summary of the Invention include: A compound of Embodiment 12 wherein each R is H. Embodiment 1 Embodiment 14 A compound of Formula 1 wherein R' is C-C alkyl 55 optionally substituted with one or more substituents indepen A compound of Formula 1 wherein R is H, C-C alkyl, dently selected from R. C-C, alkylcarbonyl or C-C, alkoxycarbonyl. Embodiment 2 Embodiment 15 60 A compound of Embodiment 1 wherein R' is C-C alkyl A compound of Embodiment 14 wherein R is H. optionally substituted with halogen. Embodiment 16 Embodiment 3 65 A compound of Formula 1 wherein R is H, OR', A compound of Embodiment 2 wherein R' is C-C alkyl NR'R' or Q"; or C-C alkyl, C-C alkenyl, C-C alkynyl, substituted with halogen. C-C cycloalkyl, Ca-C, alkylcycloalkyl or C-C, cycloalky US 8,871,941 B2 21 22 lalkyl, each optionally substituted with one or more substitu Embodiment 29 ents independently selected from R7. A compound of Embodiment 28 wherein each R" is inde Embodiment 17 pendently halogen or Q'. 5 A compound of Embodiment 16 wherein R is H; or C-C, Embodiment 30 alkyl, C-C alkenyl, C-C alkynyl, C-C cycloalkyl, C-C, alkylcycloalkyl or C-C-7 cycloalkylalkyl, each optionally A compound of Embodiment 29 wherein each R" is inde substituted with one or more substituents independently O pendently F, C1 or Br. selected from R7. Embodiment 31 Embodiment 18 A compound of Embodiment 17 wherein R is H; or C-C, A compound of Embodiment 30 wherein each R" is F. alkyl optionally substituted with one or more substituents 15 independently selected from R7. Embodiment 32 Embodiment 19 A compound of Embodiment 29 wherein each R" is Q'. A compound of Embodiment 18 wherein R is C-C alkyl Embodiment 33 optionally substituted with one or more substituents indepen dently selected from R. A compound of Formula 1 wherein each R is indepen dently halogen, C-C alkyl, C-C haloalkyl or —CN. Embodiment 20 25 Embodiment 34 A compound of Embodiment 19 wherein R is CHCF. A compound of Formula 1 wherein each R is halogen, Embodiment 21 C-C alkyl, C-C haloalkyl, -CN. phenyl or pyridinyl. A compound of Embodiment 19 wherein R is CH-2- 30 pyridinyl. Embodiment 35 Embodiment 22 A compound of Formula 1 wherein R' is H; or C-C alkyl optionally substituted with one or more halogen. 35 A compound of Embodiment 16 wherein R is OR". NR'R'2 or Q'. Embodiment 36 Embodiment 24 A compound of Formula 1 wherein R'' is H. C-C alkyl, 40 C-C, alkylcarbonyl or C-C, alkoxycarbonyl. A compound of Embodiment 22 wherein R is Q'. Embodiment 37 Embodiment 25 A compound of Embodiment 34 wherein R'' is H. A compound of Formula 1 wherein R is halogen. 45 Embodiment 38 Embodiment 26 A compound of Formula 1 wherein each R" is indepen A compound of Formula 1 wherein R' is Hor Q; or C-C, dently halogen, C-C alkyl, C-C alkoxy, C-C alkylthio. 50 alkyl optionally substituted with one or more substituents C-C alkylsulfinyl, C-C alkylsulfonyl, C-C alkylcarbo independently selected from R. nyl, C-C alkoxycarbonyl, C-C alkylaminocarbonyl, C-Cs haloalkylcarbonyl, C-Cs haloalkoxycarbonyl, C-Cs Embodiment 39 haloalkylaminocarbonyl, -NH2, —CN or - NO.; or Q'. 55 A compound of Formula 1 wherein Q'is phenyl, pyridinyl, Embodiment 27 thiazolyl, A compound of Embodiment 26 wherein each R" is inde pendently halogen, C-C alkoxycarbonyl, C-C alkylami nocarbonyl, C-Cs haloalkoxycarbonyl, C-Cs haloalkylami 60 nocarbonyl, NH, CN or - NO; or Q. Embodiment 28 O s

A compound of Embodiment 27 wherein each R" is inde 65 pendently halogen, C-C alkylaminocarbonyl, C-Cs haloalkylaminocarbonyl or Q'. US 8,871,941 B2 23 24 each optionally substituted with one or more substituents Embodiment 52 independently selected from R. A compound of Formula 1 wherein B is CR; and B and Embodiment 40 B are N. A compound of Formula 1 wherein each Q is indepen Embodiment 53 dently phenyl, pyridinyl or thiazolyl, each optionally Substi tuted with one or more substituents independently selected A compound of Formula 1 wherein W is O. from R. Embodiment 54 10 Embodiment 41 A compound of Formula 1 wherein n is O. Embodiments of this invention, including Embodiments A compound of Embodiment 34 wherein each Q is inde 1-54 above as well as any other embodiments described pendently phenyl, pyridinyl or thiazolyl. herein, can be combined in any manner, and the descriptions 15 of variables in the embodiments pertain not only to the com pounds of Formula 1 but also to the starting compounds and Embodiment 42 intermediate compounds. In addition, embodiments of this invention, including Embodiments 1-54 above as well as any A compound of Formula 1 wherein Q is phenyl, pyridinyl other embodiments described herein, and any combination or thiazolyl, each optionally substituted with one or more thereof, pertain to the compositions and methods of the substituents independently selected from R. present invention. Combinations of Embodiments 1-54 are illustrated by: Embodiment 43 Embodiment A A compound of Formula 1 wherein A' A' and Aare A, 25 A compound of Formula 1 wherein A, A, A, A, A and Aare each CR. R" is C-C alkyl optionally substituted with one or more substituents independently selected from R: Embodiment 44 each R is independently H, halogen, C-Chaloalkyl, C-C, haloalkoxy or —CN; and A compound of Formula 1 wherein A' is N; and A, A, A, 30 each R is independently H, halogen, C-C alkyl, C-C, A and Aare each CR. haloalkyl, C-C cycloalkyl, C-C halocycloalkyl, C-C, alkoxy, C-Chaloalkoxy, —CN or - NO. Embodiment 45 Embodiment B 35 A compound of Formula 1 wherein A is N; and A', A.A. A compound of Embodiment A wherein A and Aare each CR. B', B and Bare independently CR; W is O: Embodiment 46 R" is H. C-C alkyl, C-C, alkylcarbonyl or C-C, alkoxy carbonyl; and A compound of Formula 1 wherein A' is N; and A', A.A. 40 R is H, NR'R' or Q'; or C-C alkyl, C-C alkenyl, A and Aare each CR. C-C alkynyl, C-C cycloalkyl, C-C, alkylcycloalkyl or C-C, cycloalkylalkyl, each optionally substituted Embodiment 47 with one or more substituents independently selected from R7. 45 A compound of Formula 1 wherein A is N; and A', A.A. A and Aare each CR. Embodiment C A compound of Embodiment B wherein Embodiment 48 R" is C-C alkyl optionally substituted with halogen; 50 each R is independently H, CF. OCF, halogen or —CN: A compound of Formula 1 wherein B, B and B are each R is independently H, C-C alkyl, C-C haloalkyl, independently CR. C-C cyclopropyl, C-C alkoxy or —CN; and each R" is independently halogen, C-C alkyl, C-C alkoxy, Embodiment 49 C-C alkylthio, C-C alkylsulfinyl, C-C alkylsulfonyl, 55 C-C alkylcarbonyl, C-C alkoxycarbonyl, C-C alkylami A compound of Embodiment 48 wherein B is CH. nocarbonyl, C-Cs haloalkylcarbonyl, C-Cs haloalkoxycar bonyl, C-Cs haloalkylaminocarbonyl, -NH2, —CN or Embodiment 50 - NO; or Q. A compound of Formula 1 wherein B is N; and B and B 60 Embodiment D are independently CR. A compound of Embodiment C wherein R is H: Embodiment 51 R is C-C alkyl optionally substituted with one or more 65 substituents independently selected from R: A compound of Formula 1 wherein B is N; and B and B each R" is independently halogen or Q; and are independently CR. each Q is independently phenyl, pyridinyl orthiazolyl. US 8,871,941 B2 25 26 Embodiment E Embodiments of the present invention further include: A compound of Embodiment D wherein Embodiment AA R" is CF; A, A, A, A, A and Aare each CR; 5 A compound of Formula Iq, an N-oxide, or a salt thereof, B is CR; and each R is independently H, C-C alkyl or —CN.

Embodiment F 10 A compound of Embodiment E wherein B? is CH: each R is independently halogen or C-C haloalkyl; R is H: R is CHCF, or CH-2-pyridinyl; and 15 n is 0, Specific embodiments include compounds of Formula 1 selected from the group consisting of: 4-5-(3,5-dichlorophenyl)-4,5-dihydro-5-(trifluoromethyl)- wherein 3-isoxazolyl-N-(2.2.2-trifluoroethyl)-1-naphthalenecar- 20 A', A, A, A, A and Aare independently selected from boxamide, the group consisting of CR and N, provided that at most 4-5-(3,5-dichlorophenyl)-4,5-dihydro-5-(trifluoromethyl)- 3 of A, A, A, A, A and A are N: 3-isoxazolyl-N-(2-pyridinylmethyl)-1-naphthalenecar W is O or S; boxamide, R" is C-C alkyl, C-C alkenyl, C-C alkynyl, C-C, 4-5-(3,5-dichlorophenyl)-4,5-dihydro-5-(trifluoromethyl)- 25 cycloalkyl, C-C, alkylcycloalkyl or C-C cycloalkyla 3-isoxazolyl-N-(2-pyridinylmethyl)-1-naphthalenecar lkyl, each optionally substituted with one or more sub bothioamide, stituents independently selected from R: 4-5-(3,5-dichlorophenyl)-4,5-dihydro-5-(trifluoromethyl)- each R is independently H, halogen, C-C alkyl, C-C, 3-isoxazolyl-N-ethyl-1-naphthalenecarboxamide, haloalkyl, C-C alkoxy, C-Chaloalkoxy, C-C alkylthio. 4-5-(3,5-dichlorophenyl)-4,5-dihydro-5-(trifluoromethyl)- 30 C-C haloalkylthio. C-C alkylsulfinyl, C-C haloalkyl 3-isoxazolyl-N-(2-methoxyethyl)-1-naphthalenecar Sulfinyl, C-C alkylsulfonyl, C-Chaloalkylsulfonyl, C-C, boxamide, alkylamino, C-C dialkylamino, C-C alkoxycarbonyl, 4-5-(3,5-dichlorophenyl)-4,5-dihydro-5-(trifluoromethyl)- —CN or - NO; 3-isoxazolyl-N-2-(2.2.2-trifluoroethyl)-2-oxoethyl)-1- each R is independently H, halogen, C-C alkyl, C-C, naphthalenecarboxamide, 35 haloalkyl, C-C cycloalkyl, C-C halocycloalkyl, C-C, 5-5-(3,5-dichlorophenyl)-4,5-dihydro-5-(trifluoromethyl)- alkoxy, C-C haloalkoxy, C-C alkylthio, C-C haloalky 3-isoxazolyl-N-(2-pyridinylmethyl)-8-quinolinecar lthio, C-C alkylsulfinyl, C-C haloalkylsulfinyl, C-C, boxamide, alkylsulfonyl, C-C haloalkylsulfonyl, C-C alkylamino, 5-5-(3,5-dichlorophenyl)-4,5-dihydro-5-(trifluoromethyl)- C-C dialkylamino, —CN or - NO; 3-isoxazolyl-N-(2-pyridinylmethyl)-8-isoquinolinecar- 40 R" is H, C-C alkyl, C-C alkenyl, C-C alkynyl, C-C, boxamide, and cycloalkyl, Ca-C, alkylcycloalkyl, Ca-C7 cycloalkyla 1-5-(3,5-dichlorophenyl)-4,5-dihydro-5-(trifluoromethyl)- lkyl, C-C, alkylcarbonyl or C-C, alkoxycarbonyl: 3-isoxazolyl-N-(2-pyridinylmethyl)-4-isoquinolinecar R is H, OR', NR'R' or Q'; or C-C alkyl, C-C, boxamide. alkenyl, C-C alkynyl, C-C cycloalkyl, Ca-C, alkyl Of note are specific embodiments include compounds of 45 cycloalkyl or C-C cycloalkylalkyl, each optionally Formula 1 selected from the group consisting of: substituted with one or more substituents independently 4-5-(3,5-dichlorophenyl)-4,5-dihydro-5-(trifluoromethyl)- selected from R”; or 3-isoxazolyl-N-(2.2.2-trifluoroethyl)-1-naphthalenecar R" and Rare taken together with the nitrogen to which boxamide, they are attached to form a ring containing 2 to 6 atoms 4-5-(3,5-dichlorophenyl)-4,5-dihydro-5-(trifluoromethyl)- 50 of carbon and optionally one additional atom selected 3-isoxazolyl-N-(2-pyridinylmethyl)-1-naphthalenecar from the group consisting of N, S and O, said ring boxamide, optionally substituted with 1 to 4 substituents indepen 4-5-(3,5-dichlorophenyl)-4,5-dihydro-5-(trifluoromethyl)- dently selected from the group consisting of C-C alkyl, 3-isoxazolyl-N-(2-pyridinylmethyl)-1-naphthalenecar halogen, —CN. —NO and C-C alkoxy: bothioamide, 55 each R is independently halogen, C-C alkyl, C-C alkoxy, 5-5-(3,5-dichlorophenyl)-4,5-dihydro-5-(trifluoromethyl)- C-C alkylthio, C-C alkylsulfinyl, C-C alkylsulfonyl, 3-isoxazolyl-N-(2-pyridinylmethyl)-8-quinolinecar —CN or - NO; boxamide, each R" is independently halogen, C-C alkyl, C-C alkoxy, 5-5-(3,5-dichlorophenyl)-4,5-dihydro-5-(trifluoromethyl)- C-C alkylthio, C-C alkylsulfinyl, C-C alkylsulfonyl, 3-isoxazolyl-N-(2-pyridinylmethyl)-8-isoquinolinecar- 60 C-C alkylamino, C-C dialkylamino, C-C cycloalky boxamide, and lamino, C-C, alkylcarbonyl, C-C, alkoxycarbonyl, C-C, 1-5-(3,5-dichlorophenyl)-4,5-dihydro-5-(trifluoromethyl)- alkylaminocarbonyl, C-C dialkylaminocarbonyl, C-C, 3-isoxazolyl-N-(2-pyridinylmethyl)-4-isoquinolinecar haloalkylcarbonyl, C-C, haloalkoxycarbonyl, C-C, boxamide. haloalkylaminocarbonyl, C-C halodialkylaminocarbonyl, Further specific embodiments include any combination of 65 hydroxy, NH, —CN or - NO.; or Q’; the compounds of Formula 1 selected from the group imme each R is independently halogen, C-C alkoxy, C-C, diately above. haloalkoxy, C-C alkylthio, C-C haloalkylthio, C-C, US 8,871,941 B2 27 28 alkylsulfinyl, C-C haloalkylsulfinyl, C-C alkylsulfonyl, the group consisting of a surfactant, a solid diluent and a C-C haloalkylsulfonyl, C-C alkylamino, C-C dialky liquid diluent, said compositions optionally further compris lamino, C-C alkoxycarbonyl, —CN or —NO; ing a biologically effective amount of at least one additional each R is independently halogen, C-C alkyl, C-C, biologically active compound or agent. Embodiments of the haloalkyl, C-C cycloalkyl, C-C halocycloalkyl, C-C, invention further include methods for controlling an inverte alkoxy, C-C haloalkoxy, C-C alkylthio, C-C haloalky brate pest comprising contacting the invertebrate pest or its lthio, C-C alkylsulfinyl, C-C haloalkylsulfinyl, C-C, environment with a biologically effective amount of a com alkylsulfonyl, C-C haloalkylsulfonyl, C-C alkylamino, pound of any of the preceding Embodiments (e.g., as a com C-C dialkylamino. —CN, - NO phenyl or pyridinyl: position described herein). R" is H; or C-C alkyl, C-C alkenyl, C-C alkynyl, 10 C-C cycloalkyl, C-C, alkylcycloalkyl or C-C, Embodiments of the invention also include a composition cycloalkylalkyl, each optionally substituted with one or comprising a compound of any of the preceding Embodi more halogen; ments, in the form of a soil drench liquid formulation. R'' is H. C-C alkyl, C-C alkenyl, C-C alkynyl, C-C, Embodiments of the invention further include methods for cycloalkyl, C-C, alkylcycloalkyl, Ca-C7 cycloalkyla 15 controlling an invertebrate pest comprising contacting the lkyl, C-C, alkylcarbonyl or C-C, alkoxycarbonyl: soil with a liquid composition as a soil drench comprising a R" is H; Q; or C-C alkyl, C-C alkenyl, C-C alkynyl, biologically effective amount of a compound of any of the C-C cycloalkyl, C-C, alkylcycloalkyl or C-C, preceding Embodiments. cycloalkylalkyl, each optionally substituted with one or more substituents independently selected from R"; or Embodiments of the invention also include a spray com R'' and R'' are taken together with the nitrogen to which position for controlling an invertebrate pest comprising a they are attached to form a ring containing 2 to 6 atoms biologically effective amount of a compound of any of the of carbon and optionally one additional atom selected preceding Embodiments and a propellant. Embodiments of from the group consisting of N, S and O, said ring the invention further include a bait composition for control optionally substituted with 1 to 4 substituents indepen 25 ling an invertebrate pest comprising a biologically effective dently selected from the group consisting of C-C alkyl, amount of a compound of any of the preceding Embodiments, halogen, —CN. —NO and C-C alkoxy; one or more food materials, optionally an attractant, and Q" is a phenyl ring, a 5- or 6-membered heterocyclic ring, optionally a humectant. Embodiments of the invention also or an 8-, 9- or 10-membered fused bicyclic ring system include a device for controlling an invertebrate pest compris optionally containing one to three heteroatoms selected 30 ing said bait composition and a housing adapted to receive from up to 1 O. up to 1 S and up to 3 N, each ring or ring said bait composition, wherein the housing has at least one system optionally substituted with one or more substitu opening sized to permit the invertebrate pest to pass through ents independently selected from R: the opening so the invertebrate pest can gain access to said each Q is independently a phenyl ring or a 5- or 6-membered bait composition from a location outside the housing, and heterocyclic ring, each ring optionally substituted with one or 35 wherein the housing is further adapted to be placed in or near more substituents independently selected from R: Q is a phenyl ring or a 5- or 6-membered heterocyclic ring, a locus of potential or known activity for the invertebrate pest. each ring optionally Substituted with one or more Sub One or more of the following methods and variations as stituents independently selected from R. and described in Schemes 1-12 can be used to prepare the com n" is 1, 2, 3, 4 or 5. 40 pounds of Formula 1. The definitions of R', R. R. R. A", Of note is that compounds of this invention are character A, A, A, A, A, B, B, B, n and W in the compounds of ized by favorable metabolic and/or soil residual patterns and Formulae 1-15 below areas defined above in the Summary of exhibit activity controlling a spectrum of agronomic and the Invention unless indicated otherwise. Compounds of For nonagronomic invertebrate pests. mulae Ia and Ib are subsets of the compounds of Formula 1, Of particular note, for reasons of invertebrate pest control 45 compounds of Formulae 12a-12c are Subsets of the com spectrum and economic importance, protection of agronomic pounds of Formula 12, and the compound of Formula 15a is crops from damage or injury caused by invertebrate pests by a compound of Formula 15. controlling invertebrate pests are embodiments of the inven Compounds of Formula Ia (Formula 1 wherein W is O) can tion. Compounds of this invention because of their favorable be prepared by aminocarbonylation of aryl bromides or translocation properties or systemicity in plants also protect 50 iodides of Formula 2 wherein X is Br or I, with appropriately foliar or other plant parts which are not directly contacted Substituted amino compounds of Formula 3 as shown in with a compound of Formula 1 or a composition comprising Scheme 1. the compound. Also noteworthy as embodiments of the present invention are compositions comprising a compound of any of the pre 55 Scheme 1 ceding Embodiments, as well as any other embodiments

described herein, and any combinations thereof, and at least one additional component selected from the group consisting of a Surfactant, a Solid diluent and a liquid diluent, said com positions optionally further comprising at least one additional 60 biologically active compound or agent. Further noteworthy as embodiments of the present inven tion are compositions for controlling an invertebrate pest comprising a biologically effective amount of a compound of any of the preceding Embodiments, as well as any other 65 embodiments described herein, and any combinations X is halides thereof, and at least one additional component selected from US 8,871,941 B2 29 30 -continued -continued

10 la

This reaction is typically carried out with an aryl bromide The method of Scheme 2 can be conducted over a wide of Formula 2 wherein X is Br in the presence of a palladium range oftemperatures, including from about 50 to about 150° catalyst under CO atmosphere. The palladium catalysts used 15 for the present method typically comprises palladium in a C. Of note are temperatures from about 70 and about 120°C., formal oxidation state of either 0 (i.e. Pd(0)) or 2 (i.e. Pd(II)). which typically provide fast reaction rates and high product A wide variety of such palladium-containing compounds and yields. The method of Scheme 2 is illustrated in Example 3. complexes are useful as catalysts for the present method. Examples of palladium-containing compounds and com Compounds of Formula Ia can also be prepared by cou plexes useful as catalysts in the method of Scheme 1 include pling carboxylic acids of Formula 4 with appropriately Sub PdCl2(PPh) (bis(triphenylphosphine)palladium (II) dichlo stituted amino compounds of Formula 3 as shown in Scheme ride), Pd(PPh) (tetrakis(triphenylphosphine)palladium(0)), 3. Pd(CHO) (palladium(II) acetylacetonate), Pd(dba) (tris (dibenzylideneacetone)dipalladium(0)), and 1,1'-bis(diphe 25 nylphosphino) ferrocenedichloropalladium(II). The method Scheme 3 of Scheme 1 is generally conducted in a liquid phase, and therefore to be most effective the palladium catalyst prefer ably has good solubility in the liquid phase. Useful solvents include, for example, ethers such as 1,2-dimethoxyethane, 30 amides Such as N,N-dimethylacetamide, and non-haloge nated aromatic hydrocarbons such as toluene. The method of Scheme 1 can be conducted over a wide range of temperatures, ranging from about 25 to about 150° C. Of note are temperatures from about 60 and about 110°C., 35 which typically provide fast reaction rates and high product yields. The general methods and procedures foraminocarbo nylation with an aryl bromide and an amine are well known in the literature; see, for example, H. Horino et al., Synthesis 1989, 715; and J. J. Li, G. W. Gribble, editors, Palladium in 40 Heterocyclic Chemistry: A Guide for the Synthetic Chemist, 2000. The method of Scheme 1 is illustrated in Step C of Example 2 and Step E of Example 4. As shown in Scheme 2, compounds of Formula Ib (For mula 1 wherein W is S) can be prepared by treatment of 45 corresponding amide compounds of Formula Ia with a thio transfer reagent, such as PSs (see for example, E. Klingsberg et al., J. Am. Chem. Soc. 1951, 72,4988: E. C. Taylor Jr. et al., J. Am. Chem. Soc. 1953, 75, 1904; R. Crossley et al., J. Chem. Soc. Perkin Trans. 1 1976, 977) or Lawesson’s reagent (2.5- 50 la bis(4-methoxyphenyl)-1,3-dithia-2,4-diphosphetane-2,4- disulfide; see, for example, S. Prabhakar et al. Synthesis, 1984, 829). This reaction is generally carried out in the presence of a dehydrating coupling reagent Such as dicyclohexylcarbodi 55

imide, 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide, 1-propanephosphonic acid cyclic anhydride or carbonyl diimidazole in the presence of a base Such as triethylamine, PSs or pyridine, 4-(dimethylamino)pyridine or N,N-diisopropyl Lawesson's reagent 60 ethylamine in an anhydrous aprotic solvent Such as dichlo He romethane or tetrahydrofuran at a temperature typically between room temperature and 70° C. The method of Scheme 3 is illustrated in Step E of Example 1.

65 Compounds of Formula 4 can be prepared by hydrolysis of la the ester of Formula 5, wherein R is methyl or ethyl, as shown in Scheme 4. US 8,871,941 B2 32 or chloramine-T is combined with the oxime in the presence of the styrene. Depending on the conditions, amine bases Such as pyridine or triethylamine may be necessary to facili tate the dehydrochlorination reaction. The reaction can be run in a wide variety of Solvents including tetrahydrofuran, diethyl ether, methylene chloride, dioxane, and toluene with temperatures ranging from room temperature to the reflux temperature of the solvent. General procedures for cycload dition of nitrile oxides with olefins are well documented in the 10 chemical literature; for example, see Lee, Synthesis, 1982, 6, 508-509: Kanemasa et al., Tetrahedron, 2000, 56, 1057-1064; EP 1,538,138-A1, as well as references cited within. The method of Scheme 4 is illustrated in Step C of Example 1. Compounds of Formula 2 can also be prepared by the 15 1,3-dipolar cycloaddition of styrenes of Formula 7 with nitrile oxides derived from oximes of Formula 8 as shown in Scheme 6.

Scheme 6 R1 HON H

In this method, the ester compound of Formula 5 is con R A. verted to the corresponding carboxylic acid of Formula 4 by (R2) NS A121 Na NAS general procedures well known in the art. For example, treat 25 \ + | -- ment of a methyl or ethyl ester of Formula 5 with aqueous B-B; A. s N A lithium hydroxide in tetrahydrofuran, followed by acidifica tion yields the corresponding carboxylic acid of Formula 4. 7 X The method of Scheme 4 is illustrated in Step D of Example 30 1. Compounds of Formula 5 can be prepared by the 1,3- dipolar cycloaddition of styrenes of Formula 7 with nitrile oxides derived from oximes of Formula 6 as shown in Scheme 5. 35

H NOH

A. cholorinating A51S NA reagent 40 In the method of Scheme 6, the compounds of Formula 2 e wherein X is a halogenatom are generated by contacting the 4 2 compound of Formula 8 with a chlorinating reagent followed AS4 2^ by adding a compound of Formula 7. The method of Scheme 6 is conducted analogously to the method of Scheme 5 R 45 already described. The method of Scheme 6 is illustrated in O O1 Step B of Example 2, Step D of Example 4 and Step C of 6 Example 5. RI An especially useful group of styrenes for the synthesis of compounds of Formula 1 are represented by Formula 7a as -- O R 2 50 shown in Scheme 7. These intermediates can be prepared by N1 (R) NN the palladium-catalyzed coupling of an arylboronic acids of \, 2 Formula 9 with the commercially available 2-bromo-3,3,3- BSB; trifluoropropene (Formula 10). General procedures for this A. reaction are documented in the chemical literature; see Panet A51'N1 NA 7 al., J. Fluorine Chemistry, 1999, 95, 167-170. The method of | | | —- 5 Scheme 7 is illustrated in Step B of Example 1. AS2 2^

R O O1 Scheme 7 60 B(OH)2 (R), s This reaction typically proceeds through the intermediacy N -- -e- of an in situ generated hydroxamyl chloride, which is dehy drochlorinated to the nitrile oxide, which then undergoes \ NB3\ FC Br 1,3-dipolar cycloaddition with the styrene 7 to afford com 65 pounds of Formula 5. In a typical procedure, a chlorinating 9 10 reagent such as Sodium hypochlorite, N-chlorosuccinimide, US 8,871,941 B2 33 34 -continued aryl esters, see references P. R. Bernstein et al. Bioorg. Med. FC Chem. Lett. 2001, 2769 and L. W. Deady et al. Aust. J. Chem.

2 1989, 42, 1029. s NS For a specific example, as shown in Scheme 10, aldehydes B\, 2 of Formula 12 can be prepared from the corresponding B2NB3 methyl-substituted compounds of Formula 13 (wherein X is 7a. halogen) by reacting with N-bromosuccinimide (NBS) in the presence of 2,2'-azobis(2-methylpropionitrile) (AIBN) and 10 Sodium acetate to give acetates of Formula 14, which are then The oximes of Formula 6 can be prepared by the reaction of converted to the aldehydes of Formula 12 by esterification aldehydes 11 with hydroxylamine as shown in Scheme 8. For and oxidation. The method of Scheme 10 is illustrated in example, see, H. K. Jung et al. Bioorg. Med. Chem. 2004, 12, Example 4, Steps A and B. 3965. 15 The aldehydes of Formula 1 1 can be prepared by a wide variety of methods known in the art; some of the aldehydes Scheme 10 are known compounds or commercially available. For CH3 example, preparation of the compound of Formula 11 A. wherein A, A, A, A, A, and Aare CH and R is Me, is Y n s NBS disclosed by P. Madenson et al.J.Med. Chem. 2002, 45,5755. A. A2 NaOAc The method of Scheme 8 is illustrated in Step A of Example N% 2 1. 25 X 13 Scheme 8 H O H NOH

30 A. A. A51'N1 NA A51 N1 NA s" As O | -- l, 51 N. NA AS2 2^ AS4 2^ h HerMeOH 4 2 35 R R AS% 2^ O O1 O O1 X 11 6 14 H O As shown in Scheme 9, the oximes of Formula 8, wherein 40 X is a halogen atom, can be prepared from the corresponding A. aldehydes of Formula 12 analogous to the method of Scheme A51 N1 NA

8. The method of Scheme 9 is illustrated in Step A of Example 4 2 2, Step C of Example 4 and Step B of Example 5. 45 AS4 2 A.

X Scheme 9 12 H O H NOH 50 A. A. The compounds of Formula 13 are commercially available Srs N-> or known compounds, or they can be prepared by a wide AS44 2^2 AS44 2^2 variety of methods known in the art. For example, a com 55 pound of Formula 13, wherein A is N, A, A, A, A and A X X are CH, can be prepared as disclosed in Molecules, 2004, 9, 178. 12 8 An alternative method for preparing aldehydes of Formula 60 12 (wherein X is a halogenatom) is shown in Scheme 11. The Compounds of Formula 12 are commercially available or formyl group of Formula 12 can be introduced to the known compounds, or they can be prepared by a wide variety 10-membered aromatic ring system by displacing the bromo of methods known in the art. For example, a compound of substituent of a compound of Formula 15. For references of Formula 12 can be prepared by direct formylation of the 65 this general method, see Synthesis, 2006, 293 and Bioorg. corresponding aryl halides, see G. E. Boswell et al. J. Org. Med. Chem. 2004, 12, 715. The method of Scheme 11 is Chem. 1995, 65, 6592; or by reduction of the corresponding illustrated in Step A of Example 5. US 8,871,941 B2 35 36 skilled in the art will recognize that, in some cases, after the Scheme 11 introduction of a given reagent as it is depicted in any indi vidual scheme, it may be necessary to perform additional Br routine synthetic steps not described in detail to complete the A. O synthesis of compounds of Formula 1. One skilled in the art A51'N1 NA n-BuLi will also recognize that it may be necessary to perform a | + -CH3 rate - combination of the steps illustrated in the above schemes in A.n^ne 2 A. H N an order other than that implied by the particular sequence CH3 presented to prepare the compounds of Formula 1. X One skilled in the art will also recognize that compounds of 10 Formula 1 and the intermediates described herein can be 15 Subjected to various electrophilic, nucleophilic, radical, orga nometallic, oxidation, and reduction reactions to add Sub stituents or modify existing Substituents Without further elaboration, it is believed that one skilled 15 in the art using the preceding description can utilize the NYS present invention to its fullest extent. The following 4 2 Examples are, therefore, to be construed as merely illustra AS4 2^ tive, and not limiting of the disclosure in any way whatsoever. "H NMR spectra are reported in ppm downfield from tetram X ethylsilane: “s' means singlet, “d means doublet, “t’ means 12 triplet, “m” means multiplet, “dd” means doublet of doublets, and “brs’ means broad singlet. As shown in Scheme 12, aldehydes of Formulae 12b and Example 1 12c can be prepared from 5,8-dibromoisoquinoline (Formula 25 15a) by treating the compound of Formula 15a with n-Bulliat Preparation of 4-5-(3,5-dichlorophenyl)-4,5-dihy -78°C. and quenching with N,N-dimethylformamide. dro-5-(trifluoromethyl)-3-isoxazolyl-N-(2.2.2-trif luoroethyl)-1-naphthalenecarboxamide Scheme 12 30 Step A: Preparation of methyl Br 4-(hydroxyimino)methyl-1-naphthalenecarboxylate

N n-BuLi To a stirred solution of methyl 4-formyl-1-naphthalenecar O boxylate (2.2g, 10.3 mmol) in methanol (50 mL) was added 35 a solution of hydroxylamine (1.33 mL, 50% in water). After 4 J stirring at room temperature for 2 h, the reaction mixture was Br H N(CH(CH3)2 concentrated under reduced pressure to provide the title com 15a pound as a pale yellow solid (2.55 g). O H Br H NMR (CDC1): 8.93 (d. 1H), 8.86 (s, 1H), 8.41 (d. 1H), 40 8.14 (d. 1H), 7.82 (d. 1H), 7.63 (m, 2H), 4.02 (s, 3H). N N Step B: Preparation of 1,3-dichloro-5-1-(trimeth -- 2N ylfluoromethyl)ethenylbenzene 2 N 45 To a mixture of tetrahydrofuran (33 mL), 1,2-dimethoxy Br H O ethane (33 mL), and 4 Naqueous potassium hydroxide (33 12b mL) in a 200 mL Fisher-Porter sealed tube was added 3.5- dichlorophenylboronic acid (8.72 g, 45.7 mmol) and 2-bromo-3,3,3-trifluoropropene (10.0 g, 57.2 mmol), fol The compound of Formula 15a can be prepared by the 50 lowed by the addition of tetrakis(triphenylphosphine)palla method disclosed in Synthesis, 2002, 83; see, for example, or dium(0) (264 mg., 0.229 mmol). Then the mixture was heated by the method of G. E. Boswell et al. J. Org. Chem. 1995, 65, to 75° C. for 3 h. The reaction mixture was partitioned 6592. Alternatively, aryl aldehydes of Formula 12 can be between diethyl ether and water. The aqueous extract was prepared by a wide variety of other methods known in the art, washed with diethyl ether (2x20 mL). The organic extracts e.g., by reduction of the corresponding aryl esters, see refer 55 were combined, dried (MgSO), and concentrated under ences P. R. Bernstein et al. Bioorg. Med. Chem. Lett. 2001, reduced pressure. The residue was purified by silica gel chro 2769 and L. W. Deady et al. Aust. J. Chem. 1989, 42, 1029. matography using hexanes/ethyl acetate as eluent to afford It is recognized that some reagents and reaction conditions the title compound as a clear oil (4.421 g). described above for preparing compounds of Formula 1 may "H NMR (CDC1): 8 7.41 (s, 2H), 7.33 (s, 1H), 6.04 (d. not be compatible with certain functionalities present in the 60 1H), 5.82 (d. 1H). intermediates. In these instances, the incorporation of protec tion/deprotection sequences or functional group interconver Step C: Preparation of methyl 4-5-(3,5-dichlorophe sions into the synthesis will aid in obtaining the desired prod nyl)-4,5-dihydro-5-(trifluoromethyl)-3-isoxazolyl)-1- ucts. The use and choice of the protecting groups will be naphthalenecarboxylate apparent to one skilled in chemical synthesis (see, for 65 example, Greene, T. W.; Wuts, P. G. M. Protective Groups in To a stirred solution of methyl 4-(hydroxyimino)methyl Organic Synthesis, 2nd ed.: Wiley: New York, 1991). One 1-naphthalenecarboxylate (i.e. the product from Step A) (1.0 US 8,871,941 B2 37 38 g, 4.36 mmol) in N,N-dimethylformamide (5.0 mL) was aqueous solution of hydroxylamine (1.25 mL, 50% in water). added N-chlorosuccinimide (1.16 g, 8.72 mmol). This mix After stirring at room temperature for 3 h, the reaction mix ture was stirred for 1.5 h at room temperature, and then a ture was concentrated under reduced pressure to provide the solution of 1,3-dichloro-5-1-(trifluoromethyl)ethenylben title compound as a pale yellow solid (3.8 g). Zene (i.e. the product from Step B) (3.20 g, 13.1 mmol) and triethylamine (6.1 mL, 43.6 mmol) in N,N-dimethylforma "H NMR (DMSO-d): 11.60 (s, 1H), 8.81 (s, 1H), 8.71 (d. mide (4.0 mL) was added. After stirring for additional 2 hat 1H), 8.24 (d. 1H), 7.95 (d. 1H), 7.74 (m, 3H). room temperature, the reaction mixture was diluted with water and extracted with ethyl acetate. The organic layer was Step B: Preparation of 3-(4-bromo-1-naphthalenyl)- washed with brine, dried (NaSO), and concentrated under 5-(3,5-dichlorophenyl)-4,5-dihydro-5-(trifluorom reduced pressure. The residue was purified by silica gel chro 10 ethyl)isoxazole matography using hexanes/ethyl acetate as eluent to afford the title compound as a pale yellow oil (700 mg, 34% yield). To a stirred solution of 4-bromo-1-naphthalenecarboxylate "H NMR (CDC1): 8.88 (d. 1H), 8.80 (d. 1H),8.10 (d. 1H), oxime (i.e. the product from Step A) (2.33 g, 9.3 mmol) in 7.68 (m, 2H), 7.55 (m, 3H), 7.46 (dd. 1H), 4.27 (d. 1H), 4.03 N,N-dimethylformamide (6.0 mL) was added N-chlorosuc (s, 3H), 3.91 (d. 1H). 15 cinimide (1.70 g, 12.7 mmol). The reaction mixture was stirred for 1 h at room temperature, and then a solution of Step D: Preparation of 4-5-(3,5-dichlorophenyl)-4, 1,3-dichloro-5-1-(trifluoromethyl)ethenylbenzene (i.e. the 5-dihydro-5-(trifluoromethyl)-3-isoxazolyl)-1-naph product from Step B of Example 1) (2.70 g, 11.2 mmol) and thalenecarboxylic acid triethylamine (4.5 mL, 32.0 mmol) in N,N-dimethylforma mide (9.0 mL) was added. After stirring for additional 2 hat To a stirred solution of methyl 4-5-(3,5-dichlorophenyl)- room temperature, the reaction mixture was diluted with 4,5-dihydro-5-(trifluoromethyl)-3-isoxazolyl)-1-naphthale water and extracted with ethyl acetate. The organic layer was necarboxylate (i.e. the product from Step C) (650 mg, 1.39 washed with brine, dried (NaSO), and concentrated under mmol) in tetrahydrofuran (10 mL) was added a solution of reduced pressure. The residue was purified by silica gel col lithium hydroxide monohydrate (350 mg, 8.34 mmol) in 25 umn chromatography using hexanes/ethyl acetate as eluent to water (10 mL), followed by methanol (10 mL). The resulting afford the title compound as a white solid (2.9 g, 64% yield). mixture was stirred overnight at room temperature. The reac H NMR (CDC1): 8.87 (n, 1H), 8.32 (m, 1H), 7.77 (d. tion mixture was partitioned between water and diethyl ether. 1H), 7.66 (m, 2H), 7.55 (s. 2H), 7.46 (dd. 1H), 7.32 (d. 1H), Then the aqueous layer was acidified with 6 Naqueous hydro 4.24 (d. 1H), 3.88 (d. 3H). chloric acid to pH 2 and extracted with ethyl acetate. The 30 combined organic layers were washed with brine, dried and Step C: Preparation of 4-5-(3,5-dichlorophenyl)-4, concentrated to provide the title compound as a white solid 5-dihydro-5-(trifluoromethyl)-3-isoxazolyl-N-(2- (450 mg). pyridinylmethyl)-1-naphthalenecarboxamide H NMR (CDC1):9.08 (d. 1H), 8.80 (d. 1H), 8.31 (d. 1H), 7.71 (m, 2H), 7.57 (m, 3H), 7.46 (dd. 1H), 4.28 (d. 1H), 3.91 35 A mixture of 3-(4-bromo-1-naphthalenyl)-5-(3,5-dichlo (d. 1H). rophenyl)-4,5-dihydro-5-(trifluoromethyl)isoxazole (i.e. the product from Step B) (1.0 g, 2.04 mmol), 1,1'-bis(diphe Step E: Preparation of 4-5-(3,5-dichlorophenyl)-4,5- nylphosphino) ferrocenedichloropalladium(II) (PdC1, dihydro-5-(trifluoromethyl)-3-isoxazolyl-N-(2.2.2- (dppf)) (0.22 g, 0.30 mmol), 2-(aminomethyl)pyridine (0.86 trifluoroethyl)-1-naphthalenecarboxamide 40 g, 7.96 mmol) and triethylamine (5.6 mL, 40 mmol) in tolu ene (15 mL) was purged with carbon monoxide for 15 min A mixture of 4-5-(3,5-dichlorophenyl)-4,5-dihydro-5- utes. Then the reaction vial was maintained with carbon mon (bifluoromethyl)-3-isoxazolyl)-1-naphthalenecarboxylic oxide using a balloon. The reaction mixture was stirred at 70° acid (i.e. the product from Step C) (190 mg, 0.42 mmol), C. under carbon monoxide atmosphere overnight. The mix 4-(dimethylamino)pyridine (77 mg, 0.63 mmol), propylphos 45 ture was cooled to room temperature, filtered through a short phonic anhydride (0.38 mL, 0.63 mmol. 50% in ethyl acetate) pad of Celite R diatomaceous filter aid and rinsed with small and 2.2.2-trifluoroethylamine (0.033 mL, 0.42 mL) in dichlo amount of ethyl acetate. The filtrate was concentrated, and the romethane (5 mL) was stirred at room temperature overnight. residue was purified by column chromatography on silica gel The reaction mixture was concentrated, and the residue was using hexanes/ethyl acetate as eluent to provide the title prod purified by column chromatography on silica gel using hex 50 uct, a compound of the present invention, as a white solid anes/ethyl acetate as eluent to give the title product, a com (0.72g, 65% yield). pound of the present invention, as a white solid (71 mg). "H NMR (CDC1): 8.81 (d. 1H),8.55 (d. 1H), 8.38 (d. 1H), "H NMR (CDC1): 8.78 (d. 1H), 8.18 (d. 1H), 7.63 (m, 2H), 7.80-7.27 (m. 10H), 4.89 (d. 2H), 4.22 (d. 1H), 3.86 (d. 1H). 7.56 (m, 2H), 7.52 (d. 1H), 7.46 (m, 1H), 7.44 (d. 1H), 6.41 (t, 1H), 4.23 (d. 1H), 4.20 (m, 2H), 3.87 (d. 1H). 55 Example 3 Example 2 Preparation of 4-5-(3,5-dichlorophenyl)-4,5-dihy dro-5-(trifluoromethyl)-3-isoxazolyl-N-(2-pyridi Preparation of 4-5-(3,5-dichlorophenyl)-4,5-dihy nylmethyl)-1-naphthalenecarbothioamide dro-5-(trifluoromethyl)-3-isoxazolyl-N-(2-pyridi 60 nylmethyl)-1-naphthalenecarboxamide A mixture of 4-5-(3,5-dichlorophenyl)-4,5-dihydro-5- (trifluoromethyl)-3-isoxazolyl-N-(2-pyridinylmethyl)-1- Step A: Preparation of naphthalenecarboxamide (i.e. the product from Example 2) 4-bromo-1-naphthalenecarboxylate oxime (40 mg, 0.073 mmol) and 2.5-bis(4-methoxyphenyl)-1,3- 65 dithia-2,4-diphosphetane-2,4-disulfide (Lawesson’s reagent) To a stirred solution of 4-bromo-1-naphthalenecarboxal (18 mg, 0.044 mmol) in toluene (2 mL) was heated at reflux dehyde (3.7g, 15.7 mmol) in ethanol (30 mL) was added an for 2h. The reaction mixture was cooled to room temperature, US 8,871,941 B2 39 40 and directly purified by silica gel column chromatography perature for 2 h, the reaction mixture was concentrated under using hexanes/ethyl acetate as eluent to provide the title prod reduced pressure to provide the title compound as a pale uct, a compound of the present invention, as a yellow solid (29 yellow solid (1.8 g). mg, 71% yield). "H NMR (DMSO-d): 11.61 (s, 1H), 9.16 (dd. 1H), 9.07 "H NMR (CDC1): 9.41 (bris 1H), 8.91 (dd. 1H), 8.70 (dd, (dd. 1H), 8.79 (s, 1H), 8.20 (d. 1H), 7.79 (d. 1H), 7.72 (dd, 1H), 8.46 (d. 1H), 8.21 (d. 1H), 7.75 (dt, 1H), 7.64 (d. 1H), 1H). 7.57 (s. 2H), 7.47 (dd. 1H), 7.43 (t, 1H), 7.38 (d. 1H), 7.24 (dd, Step D: Preparation of 8-bromo-5-5-(3,5-dichlo 1H), 5.14 (d. 2H), 4.68 (d. 1H), 4.39 (d. 1H). rophenyl)-4,5-dihydro-5-(trifluoromethyl)-3-isox azolylquinoline Example 4 10 To a stirred solution of 8-bromo-5-quinolinecarboxalde Preparation of 5-5-(3,5-dichlorophenyl)-4,5-dihy hyde oxime (i.e. the product from Step C) (1.7 g. 6.8 mmol) in dro-5-(trifluoromethyl)-3-isoxazolyl-N-(2-pyridi N,N-dimethylformamide (13.0 mL) was added N-chlorosuc nylmethyl)-8-quinolinecarboxamide cinimide (1.24g, 9.3 mmol). The reaction mixture was stirred 15 for 1 h at room temperature, and then a solution of 1,3- Step A: Preparation of (8-bromo-5-quinolinyl)methyl dichloro-5-1-(trifluoromethyl)ethenylbenzene (i.e. the acetate product from Example 1, Step B) (1.96 g, 8.1 mmol) and triethylamine (2.86 mL. 20.4 mmol) in N,N-dimethylforma A mixture of 8-bromo-5-methylduinoline (5.4 g. 24.3 mide (7.0 mL) was added. After stirring for additional 12 hat mmol), N-bromosuccinimide (5.2 g, 29.2 mmol), and 2,2'- room temperature, the reaction mixture was diluted with azobis(2-methylpropionitrile) (AIBN) (0.40g, 24.3 mmol) in water and extracted with ethyl acetate. The organic layer was washed with brine, dried (NaSO), and concentrated under carbon tetrachloride (80 mL) was heated at reflux for 3 h reduced pressure. The residue was purified by column chro under nitrogen atmosphere. The reaction mixture was cooled matography on silica gel using hexanes/ethyl acetate as eluent to room temperature and filtered, using hexane for rinsing. to afford the title compound as a white solid (2.0 g. 61% The filtrate was concentrated under reduced pressure. The 25 yield). residue was dissolved in N,N-dimethylformamide (50 mL), H NMR (CDC1): 9.39 (dd. 1H), 9.08 (dd. 1H), 8.05 (d. and then sodium acetate (4.0 g, 48.8 mmol) was added. The 1H), 7.59 (dd. 1H), 7.55 (s. 2H), 7.44 (t, 1H), 7.40 (d. 1H), resulting mixture was stirred at 100° C. for 2 hunder nitrogen 4.27 (d. 1H), 3.92 (d. 1H). atmosphere. The reaction mixture was cooled to room tem perature, diluted with water and extracted with a mixture of 30 Step E: Preparation of 5-5-(3,5-dichlorophenyl)-4,5- ethyl acetate and hexane (3:7). The organic layer was washed dihydro-5-(trifluoromethyl)-3-isoxazolyl-N-(2-py with brine, dried (NaSO), and concentrated under reduced ridinylmethyl)-8-quinolinecarboxamide pressure. The crude product was purified by column chroma tography on silica gel using hexanes/ethyl acetate as eluent to A mixture of 8-bromo-5-5-(3,5-dichlorophenyl)-4,5-di afford the title product as a pale yellow solid (4.8 g). 35 hydro-5-(trifluoromethyl)-3-isoxazolylquinoline (i.e. the product from Step D) (500 mg, 1.0 mmol), 1,1'-bis(diphe Step B: Preparation of nylphosphino) ferrocenedichloropalladium(II) (PdC1, 8-bromo-5-quinolinecarboxaldehyde (dppf)) (75 mg, 0.10 mmol), 2-(aminomethyl)pyridine (0.43 mL, 4.0 mmol) and triethylamine (2.8 mL. 20 mmol) in A mixture of the (8-bromo-5-quinolinyl)methyl acetate 40 toluene (10 mL) was purged with carbon monoxide for 15 (i.e. the product from Step A) and methanol (50 mL) was minutes. Then the reaction vial was maintained with carbon heated at reflux for 1 h in the presence of trace amount of monoxide using a balloon. The reaction mixture was stirred at potassium carbonate (10 mg). Then the reaction mixture was 70° C. under carbon monoxide atmosphere overnight. The cooled to room temperature and concentrated under reduced mixture was cooled to room temperature, filtered through a pressure to provide the corresponding alcohol in quantitative 45 short pad of Celite(R) diatomaceous filter aid and rinsed with yield as a pale yellow solid. small amount of ethyl acetate. The filtrate was concentrated, To a stirred solution of the crude alcohol (2.0 g, 8.3 mmol) and the residue was purified by column chromatography on in dichloromethane (60 mL) was added slowly 1,1,1-tris(ac silica gel using hexanes/ethyl acetate as eluent to provide the etoxy)-1,1-dihydro-1,2-benziodoxol-3(1H)-one (Dess-Mar title product, a compound of the present invention, as a brown tin periodinane) (4.0g, 9.4 mmol) at room temperature. After 50 foamy solid (60 mg, 11% yield). stirring for 0.5 h, the reaction mixture was diluted with H NMR (CDC1): 12.02 (bris 1H), 9.52 (d. 1H), 9.01 (s, dichloromethane, washed with Saturated aqueous sodium 1H), 8.88 (d. 1H), 8.62 (d. 1H), 7.60-7.74 (m, 3H), 7.56 (s, bicarbonate and brine, dried (NaSO), and concentrated 2H), 7.45 (brs 2H), 7.20 (dd. 1H), 4.96 (d. 2H), 4.32 (d. 1H), under reduced pressure. The crude product was purified by 3.98 (d. 1H). column chromatography on silica gel using hexanes/ethyl 55 acetate as eluent to afford the title product as a white solid (1.8 Example 5 g). "H NMR (CDC1): 10.31 (s, 1H), 9.65 (dd. 1H), 9.12 (dd, Preparation of 5-5-(3,5-dichlorophenyl)-4,5-dihy 1H), 8.26 (d. 1H), 7.88 (d. 1H), 7.66 (dd. 1H). dro-5-(trifluoromethyl)-3-isoxazolyl-N-(2-pyridi 60 nylmethyl)-8-isoquinolinecarboxamide Step C: Preparation of 8-bromo-5-quinolinecarboxaldehyde oxime Step A: Preparation of 8-bromo-5-isoquinolinecarboxaldehyde and To a stirred solution of 8-bromo-5-quinolinecarboxalde 5-bromo-8-isoquinolinecarboxaldehyde hyde (i.e. the product from Step B) (1.7 g 7.1 mmol) in 65 ethanol (30 mL) was added an aqueous Solution of hydroxy To a stirred mixture of 5,8-dibromoisoquinoline (4.0 g. lamine (0.7 mL, 50% in water). After stirring at room tem 13.9 mmol) in tetrahydrofuran (120 mL) at -78°C. under US 8,871,941 B2 41 42 nitrogen atmosphere was added dropwise a solution of n-bu solution of 1,3-dichloro-5-1-(trifluoromethyl)ethenylben tyllithium (2.3 M in hexane, 7.3 mL, 16.8 mmol). The reac Zene (135 mg, 0.56 mmol) (i.e. the product from Example 1, tion mixture turned dark. After stirring for 15 minutes, the Step B) and triethylamine (0.12 mL, 0.86 mmol) in N.N- reaction mixture was quenched by adding N,N-dimethylfor dimethylformamide (1.5 mL) was added. After stirring for an mamide (4.0 mL). After stirring at -78°C. for an additional 1 additional 12hat room temperature, the reaction mixture was h, the reaction mixture was quenched with water, extracted diluted with water and extracted with ethyl acetate. The with mixture of ethyl acetate/hexane (2:8), washed with water organic layer was washed with brine, dried (Na2SO4), and and brine, dried (NaSO), and concentrated under reduced concentrated under reduced pressure. The residue was puri pressure. The residue was purified by column chromatogra fied by silica gel column chromatography using hexanes/ phy on silica gel using hexanes/ethyl acetate as eluent to 10 ethyl acetate as eluent to afford the title compound (20 mg) afford the 8-bromo-5-isoquinolinecarboxaldehyde (0.10 g). contaminated with Some impurity. followed by 5-bromo-8-isoquinolinecarboxaldehyde (1.0 g) as white solids. Step D: Preparation of 5-5-(3,5-dichlorophenyl)-4, H NMR (CDC1) of 8-bromo-5-isoquinolinecarboxalde 5-dihydro-5-(trifluoromethyl)-3-isoxazolyl-N-(2- hyde: 10.36 (s, 1H), 9.72 (s, 1H), 9.00 (d. 1H), 8.79 (d. 1H), 15 pyridinylmethyl)-8-isoquinolinecarboxamide 8.04 (d. 1H), 8.01 (dd. 1H); and "H NMR (CDC1) of 5-bromo-8-isoquinolinecarboxalde A mixture of 8-bromo-5-5-(3,5-dichlorophenyl)-4,5-di hyde: 10.57 (s, 1H), 10.41 (s, 1H), 8.81 (d. 1H), 8.18 (d. 1H), hydro-5-(trifluoromethyl)-3-isoxazolylisoquinoline (i.e. the 8.11 (d. 1H), 7.94 (d. 1H). product from Step C) (20 mg 0.04 mmol), 1,1'-bis(diphe nylphosphino) ferrocenedichloropalladium(II) (PdC1, Step B: Preparation of (dppf)) (6 mg, 0.008 mmol), 2-(aminomethyl)pyridine (17 8-bromo-5-isoquinolinecarboxaldehyde oxime mg, 0.16 mmol) and triethylamine (0.1 mL, 0.7 mmol) in toluene (2 mL) was purged with carbon monoxide for 15 To a stirred solution of 8-bromo-5-isoquinolinecarboxal minutes. Then the reaction vial was maintained with carbon dehyde (i.e. a product from Step A) (75 mg, 0.3 mmol) in 25 monoxide using a balloon. The reaction mixture was stirred at ethanol (7 mL) was added an aqueous solution of hydroxy 70° C. under carbon monoxide atmosphere overnight. The lamine (0.5 mL, 50% in water). After stirring at room tem mixture was cooled to room temperature, filtered through a perature overnight, the reaction mixture was concentrated short pad of Celite R diatomaceous filter and rinsed with small under reduced pressure to provide the title compound as a amount of ethyl acetate. The filtrate was concentrated and the yellow solid (70 mg). 30 residue was purified by column chromatography on silica gel "H NMR (DMSO-d): 11.75 (s, 1H), 9.55 (s, 1H), 8.78 (s, using hexanes/ethyl acetate as eluent to provide the title prod 1H), 8.71 (d. 1H), 8.59 (d. 1H), 8.07 (d. 1H), 7.96 (d. 1H). uct, a compound of the present invention, as a pale white solid (15 mg). Step C: Preparation of 8-bromo-5-5-(3,5-dichlo H NMR (CDC1): 9.77 (s, 1H), 8.80 (d. 1H), 8.70 (d. 1H), rophenyl)-4,5-dihydro-5-(trifluoromethyl)-3-isox 35 8.52 (s, 1H), 7.81-7.23 (m, 9H), 4.88 (d. 2H), 4.28 (d. 1H), azolylisoquinoline 3.92 (d. 1H). By the procedures described herein together with methods To a stirred solution of 8-bromo-5-isoquinolinecarboxal known in the art, the following compounds of Tables 1 to 9 dehyde oxime (i.e. the product from Step B) (70 mg, 0.28 can be prepared. The following abbreviations are used in the mmol) in N,N-dimethylformamide (2.0 mL) was added 40 Tables which follow:—CN means cyano, Ph means phenyl, N-chlorosuccinimide (64g, 0.48 mmol). The reaction mix Py means pyridinyl, Me means methyl, Et means ethyl and ture was stirred for 0.5 h at room temperature, and then a i-Pr means isopropyl. TABLE 1

wherein m is 1, 2, 3, 4, or 5. R (R), CF H H H CHCF, CF H Me H CHCF CF 2-CI H H CHCF, CF 2-CI Me H CHCF, CF 3-CI H H CHCF, CF 3-CI Me H CHCF CF 4-CI H H CHCF, CF 4-CI Me H CHCF CF 2-Cl, 4-Cl H H CHCF, CF 2-Cl, 4-CI Me H CHCF CF 3-Cl, 4-Cl H H CHCF, CF 3-Cl, 4-CI Me H CHCF, CF 3-Cl, 5-Cl H H CHCF, CF 3-Cl, 5-Cl Me H CHCF CF 2-F H H CHCF, CF 2-F Me H CHCF CF 3-F H H CHCF, CF 3-F Me H CHCF H H CHCF, CF 4-F Me H CHCF, CF 2-F, 4-F H H CHCF, CF 2-F, 4-F Me H CHCF CF 3-F, 4-F H H CHCF, CF 3-F, 4-F Me H CHCF

US 8,871,941 B2 83 84 TABLE 9-continued

wherein m is 1, 2, 3, 4, or 5. wherein m is 1, 2, 3 or 4.

RI (R), R3 R4 R RI (R), R3 R4 R

CFCF 3-OMe H CHCF CFCF 3-OMe Me H CH-2-Py CFCF 3-OCF H CHCF CFCF 3-OCF. Me H CH-2-Py CF(CF). H H CHCF CF(CF). H Me H CH-2-Py CF(CF) 2-Cl H CHCF CF(CF) 2-Cl Me H CH-2-Py CF(CF), 3-Cl H CHCF CF(CF), 3-Cl Me H CH-2-Py CF(CF), 3-Cl, 5-Cl H CHCF CF(CF), 3-Cl, 5-Cl Me H CH-2-Py CF(CF) 2-F H CHCF CF(CF) 2-F Me H CH-2-Py CF(CF) 3-F H CHCF CF(CF) 3-F Me H CH-2-Py CF(CF) 3-F, 5-F H CHCF CF(CF) 3-F, 5-F Me H CH-2-Py CF(CF) 3-CF H CHCF CF(CF) 3-CF Me H CH-2-Py CF(CF), 3-CF, 5-CF. H. H CHCF CF(CF), 3-CF.s. 5-CF Me H CH-2-Py CF(CF) 3-Cl, 5-CF H CHCF CF(CF) 3-Cl, 5-CF Me H CH-2-Py CF(CF) 3-Br, 5-Br H CHCF CF(CF) 3-Br, 5-Br Me H CH-2-Py CF(CF) 3-Br H CHCF CF(CF) 3-Br Me H CH-2-Py CF(CF) 3-I H CHCF CF (CF) 3-I Me H CH-2-Py CF(CF), 3-CN H CHCF CF(CF), 3-CN Me H CH-2-Py CF(CF) 3-Me H CHCF CF(CF) 3-Me Me H CH-2-Py CF(CF) 3-OMe H CHCF CF(CF) 3-OMe Me H CH-2-Py CF(CF) 3-OCF H CHCF CF(CF) 3-OCF. Me H CH-2-Py

Formulation/Utility Weight Percent Compounds of this invention will generally be used as a 40 formulation or composition with a Suitable carrier comprising Active Ingredient Diluent Surfactant at least one of a liquid diluent, a solid diluent or a Surfactant. Water-Dispersible and O.OO1-90 O-99.999 O-15 The formulation or composition ingredients are selected to be Water-soluble Granules, consistent with the physical properties of the active ingredi Tablets and Powders. ent, mode of application and environmental factors such as Suspensions, Emulsions, 1-SO 40-99 O-SO 45 Solutions (including soil type, moisture and temperature. Useful formulations Emulsifiable Concentrates) include liquids such as solutions (including emulsifiable con Dusts 1-2S 70-99 O-5 centrates), Suspensions, emulsions (including microemul Granules and Pellets O.OO1-99 S-99.999 O-15 sions and/or Suspoemulsions) and the like which optionally High Strength Compositions 90-99 O-10 O-2 can be thickened into gels. Useful formulations further 50 include solids such as dusts, powders, granules, pellets, tab Typical solid diluents are described in Watkins, et al., lets, films (including seed coatings), and the like which can be Handbook of Insecticide Dust Diluents and Carriers, 2nd water-dispersible (“wettable') or water-soluble. Active ingre Ed., Dorland Books, Caldwell, N.J. Typical liquid diluents dient can be (micro)encapsulated and further formed into a are described in Marsden, Solvents Guide, 2nd Ed., Inter suspension or solid formulation; alternatively the entire for 55 science, New York, 1950. McCutcheon's Detergents and mulation of active ingredient can be encapsulated (or "over Emulsifiers Annual. Allured Publ. Corp., Ridgewood, N.J., as coated'). Encapsulation can control or delay release of the well as Sisely and Wood, Encyclopedia of Surface Active active ingredient. Sprayable formulations can be extended in Agents, Chemical Publ. Co., Inc., New York, 1964, list sur Suitable media and used at spray Volumes from about one to factants and recommended uses. All formulations can contain 60 minor amounts of additives to reduce foam, caking, corro several hundred liters per hectare. High-strength composi Sion, microbiological growth and the like, or thickeners to tions are primarily used as intermediates for further formula increase viscosity. tion. Surfactants include, for example, polyethoxylated alco The formulations will typically contain effective amounts hols, polyethoxylated alkylphenols, polyethoxylated sorbitan of active ingredient, diluent and surfactant within the follow 65 fatty acid esters, dialkyl SulfoSuccinates, alkylsulfates, alky ing approximate ranges which add up to 100 percent by Ibenzene Sulfonates, organosilicones, N,N-dialkyltaurates, weight. lignin Sulfonates, naphthalene Sulfonate formaldehyde con US 8,871,941 B2 85 86 densates, polycarboxylates, glycerol esters, polyoxyethyl Wiley and Sons, Inc., New York, 1961, pp 81–96: Hance et al., ene/polyoxypropylene block copolymers, and alkylpolygly Weed Control Handbook, 8th Ed., Blackwell Scientific Pub cosides where the number of glucose units, referred to as lications, Oxford, 1989; and Developments in formulation degree of polymerization (D.P.), can range from 1 to 3 and the technology, PJB Publications, Richmond, UK, 2000. alkyl units can range from C to C (see Pure and Applied 5 In the following Examples, all percentages are by weight Chemistry 72, 1255-1264). Solid diluents include, for and all formulations are prepared in conventional ways. Com example, clays Such as bentonite, montmorillonite, attapulg pound numbers refer to compounds in Index Tables A-C. ite and kaolin, starch, Sugar, silica, talc, diatomaceous earth, Without further elaboration, it is believed that one skilled in urea, calcium carbonate, sodium carbonate and bicarbonate, the art using the preceding description can utilize the present and Sodium sulfate. Liquid diluents include, for example, 10 water, N,N-dimethylformamide, dimethylsulfoxide, N-alky invention to its fullest extent. The following Examples are, lpyrrolidone, ethylene glycol, polypropylene glycol, propy therefore, to be constructed as merely illustrative, and not lene carbonate, dibasic esters, paraffins, alkylbenzenes, alky limiting of the disclosure in any way whatsoever. Percentages lnaphthalenes, glycerine, triacetine, oils of olive, castor, are by weight except where otherwise indicated. linseed, tung, Sesame, corn, peanut, cotton-seed, soybean, 15 rape-seed and coconut, fatty acid esters, ketones such as cyclohexanone, 2-heptanone, isophorone and 4-hydroxy-4- Example A methyl-2-pentanone, acetates Such as hexyl acetate, heptyl Wettable Powder acetate and octyl acetate, and alcohols such as methanol, Compound 1 65.0% cyclohexanol, decanol, benzyl and tetrahydrofurfuryl alco dodecylphenol polyethylene glycol ether 2.0% hol. Sodium ligninsulfonate 4.0% Useful formulations of this invention may also contain Sodium silicoaluminate 6.0% materials well knownto those skilled in the art as formulation montmorillonite (calcined) 23.0% aids such as antifoams, film formers and dyes. Antifoams can Example B include water dispersible liquids comprising polyorganosi 25 Granule loxanes like Rhodorsil R. 416. The film formers can include polyvinyl acetates, polyvinyl acetate copolymers, polyvi Compound 2 10.0% attapulgite granules (low volatile matter, 0.71/0.30 mm: 90.0% nylpyrrolidone-vinyl acetate copolymer, polyvinyl alcohols, U.S.S. No. 25-50 sieves) polyvinyl alcohol copolymers and waxes. Dyes can include Example C water dispersible liquid colorant compositions like Pro 30 1zed(R) Colorant Red. One skilled in the art will appreciate that Extruded Pellet this is a non-exhaustive list of formulation aids. Suitable Compound 8 25.0% examples of formulation aids include those listed herein and anhydrous sodium sulfate 10.0% those listed in McCutcheon's 2001, Volume 2: Functional crude calcium ligninsulfonate S.O% Materials published by MC Publishing Company and PCT 35 Sodium alkylnaphthalenesulfonate 1.0% calcium/magnesium bentonite 59.0% Publication WO 03/024222. Example D Solutions, including emulsifiable concentrates, can be pre pared by simply mixing the ingredients. Dusts and powders Emulsifiable Concentrate can be prepared by blending and, usually, grinding as in a Compound 20 20.0% hammer mill or fluid-energy mill Suspensions are usually 40 blend of oil soluble Sulfonates and polyoxyethylene ethers 10.0% prepared by wet-milling; see, for example, U.S. Pat. No. isophorone 70.0% 3,060,084. Granules and pellets can be prepared by spraying Example E the active material upon preformed granular carriers or by agglomeration techniques. See Browning, "Agglomeration'. Microemulsion Chemical Engineering, Dec. 4, 1967, pp 147-48, Perry's 45 Compound 21 S.O% Chemical Engineer's Handbook, 4th Ed., McGraw-Hill, New polyvinylpyrrollidone-vinyl acetate copolymer 30.0% York, 1963, pages 8-57 and following, and WO 91/13546. alkylpolyglycoside 30.0% glyceryl monooleate 15.0% Pellets can be prepared as described in U.S. Pat. No. 4,172, Water 20.0% 714. Water-dispersible and water-soluble granules can be pre Example F pared as taught in U.S. Pat. No. 4,144,050, U.S. Pat. No. 50 3,920,442 and DE 3.246,493. Tablets can be prepared as Seed Treatment taught in U.S. Pat. No. 5,180,587, U.S. Pat. No. 5.232,701 and Compound 101 20.00% U.S. Pat. No. 5,208,030. Films can be prepared as taught in polyvinylpyrrollidone-vinyl acetate copolymer S.OO% GB 2,095,558 and U.S. Pat. No. 3,299,566. montan acid wax S.OO% 55 calcium ligninsulfonate 1.00% For further information regarding the art of formulation, polyoxyethylene polyoxypropylene block copolymers 1.00% see T. S. Woods, “The Formulator's Toolbox Product stearyl alcohol (POE 20) 2.00% Forms for Modern Agriculture' in Pesticide Chemistry and poly organosilane O.20% Bioscience, The Food-Environment Challenge, T. Brooks and colorant red dye O.05% Water 65.75% T. R. Roberts, Eds. Proceedings of the 9th International Con Example G gress on Pesticide Chemistry. The Royal Society of Chemis 60 try, Cambridge, 1999, pp. 120-133. See also U.S. Pat. No. Fertilizer Stick 3.235,361, Col. 6, line 16 through Col. 7, line 19 and Compound 201 2.50% Examples 10-41; U.S. Pat. No. 3,309,192, Col. 5, line 43 pyrrollidone-styrene copolymer 4.80% through Col. 7, line 62 and Examples 8, 12, 15, 39, 41, 52, 53. tristyrylphenyl 16-ethoxylate 2.30% 58, 132, 138-140, 162-164, 166, 167 and 169-182: U.S. Pat. 65 talc O.80% No. 2,891,855, Col. 3, line 66 through Col. 5, line 17 and corn starch S.OO% Examples 1-4. Klingman, Weed Control as a Science, John US 8,871,941 B2 88 -continued uses of the present compounds and compositions also include invertebrate pest control in ornamental plants, forests, in Nitrophoska (R) Permanent 15-9-15 36.00% yards, along roadsides and railroad rights of way, and on turf slow-release fertilizer (BASF) kaolin 38.00% Such as lawns, golf courses and pastures. Nonagronomic uses Water 10.60% of the present compounds and compositions also include invertebrate pest control in houses and other buildings which may be occupied by humans and/or companion, farm, ranch, Compounds of this invention exhibit activity against a wide Zoo or other animals. Nonagronomic uses of the present com spectrum of invertebrate pests. These pests include inverte pounds and compositions also include the control of pests brates inhabiting a variety of environments such as, for 10 Such as termites that can damage wood or other structural example, plant foliage, roots, soil, harvested crops or other materials used in buildings. foodstuffs, building structures or animal integuments. These Nonagronomic uses of the present compounds and com pests include, for example, invertebrates feeding on foliage positions also include protecting human and animal health by (including leaves, stems, flowers and fruits), seeds, wood, controlling invertebrate pests that are parasitic or transmit textile fibers or animal blood or tissues, and thereby causing 15 infectious diseases. The controlling of animal parasites injury or damage to, for example, growing or stored agro includes controlling external parasites that are parasitic to the nomic crops, forests, greenhouse crops, ornamentals, nursery Surface of the body of the host animal (e.g., shoulders, arm crops, stored foodstuffs or fiber products, or houses or other pits, abdomen, inner part of the thighs) and internal parasites structures or their contents, or being harmful to animal health that are parasitic to the inside of the body of the host animal or public health. Those skilled in the art will appreciate that (e.g., stomach, intestine, lung, veins, under the skin, lym not all compounds are equally effective against all growth phatic tissue). External parasitic or disease transmitting pests stages of all pests. include, for example, chiggers, ticks, lice, mosquitoes, flies, These present compounds and compositions are thus use mites and fleas. Internal parasites include heartworms, hook ful agronomically for protecting field crops from phytopha worms and helminths. Compounds and compositions of the gous invertebrate pests, and also nonagronomically for pro 25 present invention are suitable for systemic and/or non-sys tecting other horticultural crops and plants from temic control of infestation or infection by parasites on ani phytophagous invertebrate pests. This utility includes pro mals. Compounds and compositions of the present invention tecting crops and other plants (i.e. both agronomic and nona are particularly suitable for combating external parasitic or gronomic) that contain genetic material introduced by genetic disease transmitting pests. Compounds and compositions of engineering (i.e. transgenic) or modified by mutagenesis to 30 the present invention are Suitable for combating parasites that provide advantageous traits. Examples of Such traits include infest agricultural working animals, such as cattle, sheep, tolerance to herbicides, resistance to phytophagous pests goats, horses, pigs, donkeys, camels, buffalos, rabbits, hens, (e.g., insects, mites, aphids, spiders, nematodes, Snails, plant turkeys, ducks, geese and bees; pet animals and domestic pathogenic fungi, bacteria and viruses), improved plant animals such as dogs, cats, pet birds and aquarium fish; as growth, increased tolerance of adverse growing conditions 35 well as so-called experimental animals, such as hamsters, Such as high or low temperatures, low or high soil moisture, guinea pigs, rats and mice. By combating these parasites, and high Salinity, increased flowering or fruiting, greater har fatalities and performance reduction (in term of meat, milk, Vest yields, more rapid maturation, higher quality and/or wool, skins, eggs, honey, etc.) are reduced, so that applying a nutritional value of the harvested product, or improved stor composition comprising a compound of the present invention age or process properties of the harvested products. Trans 40 allows more economic and simple husbandry of animals. genic plants can be modified to express multiple traits. Examples of agronomic or nonagronomic invertebrate Examples of plants containing traits provided by genetic pests include eggs, larvae and adults of the order Lepidoptera, engineering or mutagenesis include varieties of corn, cotton, Such as armyworms, cutworms, loopers, and heliothines in Soybean and potato expressing an insecticidal Bacillus thur the family Noctuidae (e.g., pink stem borer (Sesamia inferens ingiensis toxin such as YIELD GARDR, KNOCKOUTR), 45 Walker), corn stalk borer (Sesamia nonagrioides Lefebvre), STARLINK(R), BOLLGARDR), NCOTNOR) and Southern armyworm (Spodoptera eridania Cramer), fall NEWLEAF(R), and herbicide-tolerant varieties of corn, cot armyworm (Spodopterafiugiperda J. E. Smith), beet army ton, soybean and rapeseed such as ROUNDUP READYR, worm (Spodoptera exigua Hübner), cotton leafworm LIBERTY LINK(R), IMIR), STS(R) and CLEARFIELDR), as (Spodoptera littoralis Boisduval), yellowstriped armyworm well as crops expressing N-acetyltransferase (GAT) to pro 50 (Spodoptera Ornithogalli Guenée), black cutworm (Agrotis vide resistance to glyphosate herbicide, or crops containing ipsilon Hufnagel), Velvetbean caterpillar (Anticarsia gem the HRA gene providing resistance to herbicides inhibiting matalis Hübner), green fruitworm (Lithophane antennata acetolactate synthase (ALS). The present compounds and Walker), cabbage armyworm (Barathra brassicae Linnaeus), compositions may interact synergistically with traits intro Soybean looper (Pseudoplusia includens Walker), cabbage duced by genetic engineering or modified by mutagenesis, 55 looper (Trichoplusia ni Hübner), tobacco budworm (Helio thus enhancing phenotypic expression or effectiveness of the this virescens Fabricius)); borers, casebearers, webworms, traits or increasing the invertebrate pest control effectiveness coneworms, cabbageworms and skeletonizers from the fam of the present compounds and compositions. In particular, the ily Pyralidae (e.g., European corn borer (Ostrinia nubilalis present compounds and compositions may interact synergis Hübner), navel orangeworm (Amyelois transitella Walker), tically with the phenotypic expression of proteins or other 60 corn root webworm (Crambus caliginosellus Clemens), Sod natural products toxic to invertebrate pests to provide greater webworms (Pyralidae: Crambinae) such as sod worm (Her than-additive control of these pests. petogramma licarsisalis Walker), Sugarcane stem borer Nonagronomic uses refer to invertebrate pest control in the (Chilo infiscatellus Snellen), tomato small borer (Neoleuci areas other than fields of crop plants. Nonagronomic uses of nodes elegantalis Guenée), green leafroller (Cnaphalocerus the present compounds and compositions include control of 65 medinalis), grape leaffolder (Desmia funeralis Hübner), invertebrate pests in stored grains, beans and other foodstuffs, melon worm (Diaphania initidalis Stoll), cabbage centergrub and in textiles such as clothing and carpets. Nonagronomic (Helluala hydralis Guenée), yellow stem borer (Scirpophaga US 8,871,941 B2 89 90 incertulas Walker), early shoot borer (Scirpophaga infisca family Elateridae; bark beetles from the family Scolytidae tellus Snellen), white stem borer (Scirpophaga innotata and flour beetles from the family Tenebrionidae. In addition, Walker), top shoot borer (Scirpophaga nivella Fabricius), agronomic and nonagronomic pests include: eggs, adults and dark-headed rice borer (Chilopolychrysus Meyrick), cabbage larvae of the order Dermaptera including earwigs from the cluster caterpillar (Crocidolomia binotalis English)); leafrol family Forficulidae (e.g., European earwig (Forficula auricu lers, budworms, seed worms, and fruit worms in the family laria Linnaeus), black earwig (Chelisoches mono Fabricius)); Tortricidae (e.g., codling moth (Cydia pomonella Linnaeus), eggs, immatures, adults and nymphs of the orders Hemiptera grape berry moth (Endopiza viteana Clemens), oriental fruit and Homoptera Such as, plant bugs from the family Miridae, moth (Grapholita molesta Busck), citrus false codling moth cicadas from the family Cicadidae, leafhoppers (e.g. (Cryptophlebia leucotreta Meyrick), citrus borer (Ecdytolo 10 Empoasca spp.) from the family Cicadellidae, bed bugs pha aurantiana Lima), redbanded leafroller (Argyrotaenia (e.g., Cimex lectularius Linnaeus) from the family Cimi velutinana Walker), obliquebanded leafroller (Choristoneura cidae, planthoppers from the families Fulgoroidae and Del rosaceana Harris), light brown apple moth (Epiphyas postvit phacidae, treehoppers from the family Membracidae, psyllids tana Walker), European grape berry moth (Eupoecilia ambig from the family Psyllidae, whiteflies from the family Aley uella Hübner), apple bud moth (Pandemis pyrusana Kear 15 rodidae, aphids from the family Aphididae, phylloxera from fott), omnivorous leafroller (Platynota Stultana the family Phylloxeridae, mealybugs from the family Pseudo Walsingham), barred fruit-tree tortrix (Pandemis cerasana coccidae, scales from the families Coccidae, Diaspididae and Hübner), apple brown tortrix (Pandemis heparana Denis & Margarodidae, lace bugs from the family Tingidae, Stink bugs Schiffermüller)); and many other economically important from the family Pentatomidae, chinchbugs (e.g., hairy chinch lepidoptera (e.g., diamondback moth (Plutella xylostella Lin bug (Blissus leucopterus hiritus Montandon) and Southern naeus), pink bollworm (Pectinophora gossypiella Saunders), chinch bug (Blissus insularis Barber)) and other seed bugs gypsy moth (Lymantria dispar Linnaeus), peach fruit borer from the family Lygaeidae, spittlebugs from the family Cer (Carposina niponensis Walsingham), peach twig borer copidae squash bugs from the family Coreidae, and redbugs (Anarsia lineatella Zeller), potato tuberworm (Phthorimaea and cotton stainers from the family Pyrrhocoridae. Also operculella Zeller), spotted teniform leafminer (Lithocolletis 25 included are eggs, larvae, nymphs and adults of the order blancardella Fabricius), Asiatic apple leafminer (Lithocolle Acari (mites) Such as spidermites and red mites in the family tis ringoniella Matsumura), rice leaffolder (Lerodea eufala Tetranychidae (e.g., European red mite (Panonychus ulmi Edwards), apple leafminer (Leucoptera scitella Zeller)); Koch), two spotted spider mite (Tetranychus urticae Koch), eggs, nymphs and adults of the order Blattodea including McDaniel mite (Tetranychus mcdanieli McGregor)); flat cockroaches from the families Blattellidae and Blattidae 30 mites in the family Tenuipalpidae (e.g., citrus flat mite (Brevi (e.g., oriental cockroach (Blatta Orientalis Linnaeus), Asian palpus lewisi McGregor)); rust and bud mites in the family cockroach (Blatella asahinai Mizukubo), German cockroach Eriophyidae and other foliar feeding mites and mites impor (Blattella germanica Linnaeus), brownbanded cockroach tant in human and animal health, i.e. dust mites in the family (Supella longipalpa Fabricius), American cockroach Epidermoptidae, follicle mites in the family Demodicidae, (Periplaneta americana Linnaeus), brown cockroach 35 grain mites in the family Glycyphagidae, ticks in the order (Periplaneta brunnea Burmeister), Madeira cockroach (Leu Ixodidae (e.g., deer tick (Ixodes scapularis Say), Australian cophaea maderae Fabricius)). Smoky brown cockroach paralysis tick (Ixodes holocyclus Neumann), American dog (Periplaneta fuliginosa Service), Australian Cockroach tick (Dermacentor variabilis Say), lone star tick (Amblvo (Periplaneta australasiae Fabr.), lobster cockroach (Naupho mma americanum Linnaeus)) and scab and itch mites in the eta cinerea Olivier) and Smooth cockroach (Symplocepallens 40 families Psoroptidae, Pyemotidae, and Sarcoptidae; eggs, Stephens)); eggs, foliar feeding, fruit feeding, root feeding, adults and immatures of the order Orthoptera including grass seed feeding and vesicular tissue feeding larvae and adults of hoppers, locusts and crickets (e.g., migratory grasshoppers the order Coleoptera including weevils from the families (e.g., Melanoplus sanguinipes Fabricius, M. differentialis Anthribidae, Bruchidae, and Curculionidae (e.g., boll weevil Thomas), American grasshoppers (e.g., Schistocerca ameri (Anthonomus grandis Boheman), rice water weevil (Lissor 45 cana Drury), desert locust (Schistocerca gregaria Forskal), hoptrus Oryzophilus Kuschel), granary weevil (Sitophilus migratory locust (Locusta migratoria Linnaeus), bush locust granarius Linnaeus), rice weevil (Sitophilus Oryzae Lin (Zonocerus spp.), house cricket (Acheta domesticus Lin naeus)), annual bluegrass weevil (Listronotus maculicollis naeus), mole crickets (e.g., tawny mole cricket (Scapteriscus Dietz), bluegrass billbug (Sphenophorus parvulus Gyllen vicinus Scudder) and Southern mole cricket (Scapteriscus hal), hunting billbug (Sphenophorus venatus Vestitus), Den 50 borelli Giglio-Tos)); eggs, adults and immatures of the order ver billbug (Sphenophorus cicatristriatus Fahraeus); flea Diptera including leafminers (e.g., Liriomyza spp. Such as beetles, cucumber beetles, rootworms, leaf beetles, potato serpentine vegetable leafminer (Liriomyza sativae Blan beetles, and leafminers in the family Chrysomelidae (e.g., chard)), midges, fruit flies (Tephritidae), frit flies (e.g., Colorado potato beetle (Leptinotarsa decemlineata Say), Oscinella frit Linnaeus), Soil maggots, house flies (e.g., western corn rootworm (Diabrotica virgifera virgifera 55 Musca domestica Linnaeus), lesser house flies (e.g., Fannia LeConte)); chafers and other beetles from the family Scara canicularis Linnaeus, F, femoralis Stein), stable flies (e.g., baeidae (e.g., Japanese beetle (Popillia japonica Newman), Stomoxys calcitrans Linnaeus), face flies, horn flies, blow oriental beetle (Anomala Orientalis Waterhouse, Exomala flies (e.g., Chrysomya spp., Phormia spp.), and other muscoid orientalis (Waterhouse) Baraud), northern masked chafer fly pests, horse flies (e.g., Tabanus spp.), bot flies (e.g., Gas (Cyclocephala borealis Arrow), Southern masked chafer (Cy 60 trophilus spp., Oestrus spp.), cattle grubs (e.g., Hypoderma clocephala immaculata Olivier or C. lurida Bland) dung spp.), deer flies (e.g., Chrysops spp.), keds (e.g., Mellophagus beetle and white grub (Aphodius spp.), black turfgrass atae ovinus Linnaeus) and other Brachycera, mosquitoes (e.g., nius (Ataenius spretulus Haldeman), green June beetle (Coti Aedes spp., Anopheles spp., Culex spp.), black flies (e.g., nis initida Linnaeus), Asiatic garden beetle (Maladera casta Prosimulium spp., Simulium spp.), biting midges, sand flies, nea Arrow), May/June beetles (Phyllophaga spp.) and 65 Sciarids, and other Nematocera; eggs, adults and immatures European chafer (Rhizotrogus maialis Razoumowsky)); car of the order Thysanoptera including onion thrips (Thrips pet beetles from the family Dermestidae; wireworms from the tabaci Lindeman), flower thrips (Frankliniella spp.), and US 8,871,941 B2 91 92 other foliar feeding thrips; insect pests of the order Compounds of the invention show particularly high activ Hymenoptera including ants of the Family Formicidae ity against pests in the order Lepidoptera (e.g., Alabama including the Florida carpenter ant (Camponotus floridanus argillacea Hübner (cotton leaf worm), Archips argyrospilla Buckley), red carpenterant (Camponotus ferrugineus Fabri Walker (fruit tree leaf roller), A. rosana Linnaeus (European cius), black carpenter ant (Camponotus pennsylvanicus De leaf roller) and other Archips species, Chilo suppressalis Geer), white-footed ant (Technomyrmex albipes fr. Smith), Walker (rice stem borer), Cnaphalocrosis medinalis Guenee big headed ants (Pheidole sp.), ghostant (Tapinoma melano (rice leafroller), Crambus caliginosellus Clemens (corn root cephalum Fabricius); Pharaoh ant (Monomorium pharaonis webworm), Crambus teterrellus Zincken (bluegrass web Linnaeus), little fire ant (Wasmannia auropunctata Roger), worm), Cydia pomonella Linnaeus (codling moth), Earias fireant (Solenopsis geminata Fabricius), red imported fireant 10 (Solenopsis invicta Buren), Argentine ant (Iridomyrmex insulana Boisduval (spiny bollworm), Earias vittella Fabri humilis Mayr), crazy ant (Paratrechina longicornis cius (spotted bollworm), Helicoverpa armigera Hübner Latreille), pavementant (Tetramorium caespitum Linnaeus), (American bollworm), Helicoverpa zea Boddie (corn ear cornfield ant (Lasius alienus Forster) and odorous house ant worm), Heliothis virescens Fabricius (tobacco budworm), (Tapinoma sessile Say). Other Hymenoptera including bees 15 Herpetogramma licarsisalis Walker (sod webworm), Lobe (including carpenter bees), hornets, yellow jackets, wasps, sia botrana Denis & Schiffermiller (grape berry moth), Pec and sawflies (Neodiprion spp.; Cephus spp.); insect pests of tinophora gossypiella Saunders (pink bollworm), Phyllocnis the order Isoptera including termites in the Termitidae (e.g., tis citrella Stainton (citrus leafminer), Pieris brassicae Macrotermes sp., Odontotermes obesus Rambur), Kaloter Linnaeus (large white butterfly), Pieris rapae Linnaeus mitidae (e.g., Cryptotermes sp.), and Rhinotermitidae (e.g., (small white butterfly), Plutella xylostella Linnaeus (dia Reticulitermes sp., Coptotermes sp., Heterotermes tenuis mondback moth), Spodoptera exigua Hübner (beet army Hagen) families, the eastern Subterranean termite (Reticuli worm), Spodoptera litura Fabricius (tobacco cutworm, clus termes flavipes Kollar), western subterranean termite (Reti ter caterpillar), Spodoptera frugiperda J. E. Smith (fall culitermes hesperus Banks). Formosan Subterranean termite armyworm), Trichoplusia ni Hübner (cabbage looper) and (Coptotermes formosanus Shiraki), West Indian drywood ter 25 Tuta absoluta Meyrick (tomato leafminer)). mite (Incisitermes immigrans Snyder), powder post termite Compounds of the invention also have significant activity (Cryptotermes brevis Walker), drywood termite (Incisitermes on members from the order Homoptera including: Acyrthisi Snyderi Light), Southeastern Subterranean termite (Reticuli phon pisum Harris (pea aphid), Aphis craccivora Koch (cow termes virginicus Banks), western drywood termite (In pea aphid), Aphis fabae Scopoli (black bean aphid), Aphis cisitermes minor Hagen), arboreal termites such as Nasuti 30 gossypii Glover (cotton aphid, melon aphid), Aphis pomi De termes sp. and other termites of economic importance; insect pests of the order Thysanura such as silverfish (Lepisma sac Geer (apple aphid), Aphis spiraecola Patch (spirea aphid), charina Linnaeus) and firebrat (Thermobia domestica Pack Aulacorthum Solani Kaltenbach (foxglove aphid), Chaetosi ard); insect pests of the order Mallophaga and including the phon fragaefolii Cockerell (strawberry aphid), Diuraphis headlouse (Pediculus humanus capitis De Geer), body louse 35 noxia Kurdumov/Mordvilko (Russian wheat aphid), Dysa (Pediculus humanus Linnaeus), chicken body louse (Mena phis plantaginea Paaserini (rosy apple aphid), Eriosoma lani canthus Stramineus NitsZch), dog biting louse (Trichodectes gerum Hausmann (woolly apple aphid), Hvalopterus pruni canis De Geer), fluff louse (Goniocotes gallinae De Geer), Geoffroy (mealy plum aphid), Lipaphis erysimi Kaltenbach sheep body louse (Bovicola ovis Schrank), short-nosed cattle (turnip aphid), Metopolophium dirrhodium Walker (cereal louse (Haematopinus eurysternus Nitzsch), long-nosed cattle 40 aphid), Macrosipum euphorbiae Thomas (potato aphid), louse (Linognathus vituli Linnaeus) and other Sucking and Myzus persicae Sulzer (peach-potato aphid, green peach chewing parasitic lice that attack man and animals; insect aphid), Nasonovia ribisnigri Mosley (lettuce aphid), Pemphi pests of the order Siphonoptera including the oriental rat flea gus spp. (root aphids and gallaphids), Rhopalosiphum maidis (Xenopsylla cheopis Rothschild), cat flea (Ctenocephalides Fitch (corn leaf aphid), Rhopalosiphum padi Linnaeus (bird felis Bouche), dog flea (Ctenocephalides canis Curtis), hen 45 cherry-oat aphid), Schizaphis graminum Rondani (green flea (Ceratophyllus gallinae Schrank), Sticktight flea (Echid bug), Sitobion avenae Fabricius (English grain aphid), The nophaga gallinacea Westwood), human flea (Pulex irritans rioaphis maculata Buckton (spotted alfalfa aphid), Toxoptera Linnaeus) and other fleasafflicting mammals and birds. Addi aurantii Boyer de Fonscolombe (black citrus aphid), and tional arthropod pests covered include: spiders in the order Toxoptera citricida Kirkaldy (brown citrus aphid); Adelges Araneae such as the brown recluse spider (Loxosceles reclusa 50 spp. (adelgids); Phylloxera devastatrix Pergande (pecan Gertsch & Mulaik) and the black widow spider (Latrodectus phylloxera); Bemisia tabaci Gennadius (tobacco whitefly, mactans Fabricius), and centipedes in the order Scutigero sweetpotato whitefly), Bemisia argentifolii Bellows & Per morpha Such as the house centipede (Scutigera Coleoptrata ring (silverleaf whitefly), Dialeurodes citri Ashmead (citrus Linnaeus). Compounds of the present invention also have whitefly) and Trialeurodes vaporariorum Westwood (green activity on members of the Classes Nematoda, Cestoda, 55 house whitefly); Empoasca fabae Harris (potato leafhopper), Trematoda, and Acanthocephala including economically Laodelphax striatellus Fallen (Smaller brown planthopper), important members of the orders Strongylida, Ascaridida, Macrolestes quadrilineatus Forbes (aster leafhopper), Oxyurida, Rhabditida, Spirurida, and Enoplida such as but Nephotettix cinticeps Uhler (green leafhopper), Nephotettix not limited to economically important agricultural pests (i.e. nigropictus Stål (rice leafhopper), Nilaparvata lugens Stål root knot nematodes in the genus Meloidogyne, lesion nema 60 (brown planthopper), Peregrinus maidis Ashmead (corn todes in the genus Pratylenchus, Stubby root nematodes in the planthopper), Sogatella fircifera Horvath (white-backed genus Trichodorus, etc.) and animal and human health pests planthopper), Sogatodes Orizicola Muir (rice delphacid), (i.e. all economically important flukes, tapeworms, and Tiphlocyba pomaria McAtee white apple leafhopper, Eryth roundworms, such as Strongylus vulgaris in horses, Toxocara roneoura spp. (grape leafhoppers); Magicidada Septendecim canis in dogs, Haemonchus contortus in sheep, Dirofilaria 65 Linnaeus (periodical cicada); Icerya purchasi Maskell (cot immitis Leidy in dogs, Anoplocephala perfoliata in horses, tony cushion scale), Ouadraspidiotus perniciosus Comstock Fasciola hepatica Linnaeus in ruminants, etc.). (San Jose scale); Planococcus citri Risso (citrus mealybug); US 8,871,941 B2 93 94 Pseudococcus spp. (other mealybug complex); Cacopsylla and the two formulations combined together before applica pyricola Foerster (pear psylla), Trioza diospyri Ashmead tion (e.g., in a spray tank) or, alternatively, applied in Succes (persimmon psylla). Sion. Compounds of this invention also have activity on mem Other biologically active compounds or agents useful in bers from the order Hemiptera including: Acrosternum hilare the compositions of the present invention can be selected Say (green Stink bug), Anasa tristis De Geer (squash bug), from invertebrate pest control agents having a different mode Blissus leucopterus leucopterus Say (chinch bug), Cimex of action or a different chemical class Sodium channel modu lectularius Linnaeus (bedbug) Corythuca gossypii Fabricius lators, cholinesterase inhibitors, neonicotinoids, insecticidal (cotton lace bug), Cyrtopeltis modesta Distant (tomato bug), macrocyclic lactones, GABA (y-aminobutyric acid)-regu 10 lated chloride channel blockers, chitin synthesis inhibitors, Dysdercus suturellus Henich-Schäffer (cotton stainer), juvenile hormone mimics, octopamine receptor ligands, Euchistus servus Say (brown Stink bug), Euchistus vari ecdysone agonists, ryanodine receptor ligands, nereistoxin Olarius Palisot de Beauvois (one-spotted Stink bug), Grap analogs, mitochondrial electron transport inhibitors, lipid tosthetus spp. (complex of seedbugs), Leptoglossus Corculus biosynthesis inhibitors, cyclodiene insecticides, molting Say (leaf-footed pine seed bug), Lygus lineolaris Palisot de 15 inhibitors and biological agents including nucleopolyhe Beauvois (tarnished plant bug), Nezara viridula Linnaeus drovirus (NPV), a member of Bacillus thuringiensis, an (Southern green Stink bug), Oebalus pugnax Fabricius (rice encapsulated delta-endotoxin of Bacillus thuringiensis and a Stink bug). Oncopeltus fasciatus Dallas (large milkweed naturally occurring or a genetically modified viral insecti bug), Pseudatomoscelis seriatus Reuter (cotton fleahopper). cide. Other insect orders controlled by compounds of the invention Of note is a composition of the present invention wherein at include Thysanoptera (e.g., Frankliniella Occidentalis Per least one additional biologically active compound or agent is gande (western flower thrip), Scirthothrips citri Moulton (cit selected from insecticides of the group consisting of sodium rus thrip), Sericothrips variabilis Beach (soybean thrip), and channel modulators, cholinesterase inhibitors, neonicoti Thrips tabaci Lindeman (onion thrip); and the order noids, insecticidal macrocyclic lactones, GABA-regulated Coleoptera (e.g., Leptinotarsa decemlineata Say (Colorado 25 chloride channel blockers, chitin synthesis inhibitors, juve potato beetle), Epilachna varivestis Mulsant (Mexican bean nile hormone mimics, octopamine receptor ligands, ecdysone beetle) and wireworms of the genera Agriotes, Althous or agonists, ryanodine receptor ligands, nereistoxin analogs, Limonius). mitochondrial electron transport inhibitors, lipid biosynthesis Note that some contemporary classification systems place inhibitors, cyclodiene insecticides, molting inhibitors and Homoptera as a suborder within the order Hemiptera. 30 biological agents including nucleopolyhedrovirus, a member Of note is use of compounds of this invention for control of Bacillus thuringiensis, an encapsulated delta-endotoxin of ling silverleaf whitefly (Bemisia argentifolii). Of note is use Bacillus thuringiensis and a naturally occurring or a geneti of compounds of this invention for controlling western flower cally modified viral insecticide. thrip (Frankliniella occidentalis). Of note is use of com Of particular note are additional biologically active com pounds of this invention for controlling potato leafhopper 35 pounds or agents selected from insecticides of the group (Empoasca fabae). Of note is use of compounds of this inven consisting of sodium channel modulators, cholinesterase tion for controlling corn planthopper (Peregrinus maidis). Of inhibitors, neonicotinoids, insecticidal macrocyclic lactones, note is use of compounds of this invention for controlling GABA-regulated chloride channel blockers, chitin synthesis cotton melon aphid (Aphis gossypii). Of note is use of com inhibitors, juvenile hormone mimics, octopamine receptor pounds of this invention for controlling green peach aphid 40 ligands, ecdysone agonists, ryanodine receptor ligands, nere (Myzus persicae). Of note is use of compounds of this inven istoxin analogs, mitochondrial electron transport inhibitors, tion for controlling diamondback moth (Plutella xylostella). lipid biosynthesis inhibitors, cyclodiene insecticides, nucle Of note is use of compounds of this invention for controlling opolyhedrovirus; a member of Bacillus thuringiensis, an fall armyworm (Spodoptera frugiperda). encapsulated delta-endotoxin of Bacillus thuringiensis; and a Compounds of this invention can also be mixed with one or 45 naturally occurring or a genetically modified viral insecti more other biologically active compounds or agents includ cide. ing insecticides, fungicides, nematicides, bactericides, acari Of further note are additional biologically active com cides, herbicides, growth regulators such as rooting stimu pounds or agents selected from insecticides of the group lants, chemosterilants, semiochemicals, repellents, consisting of pyrethroids, carbamates, neonicotinoids, neu attractants, pheromones, feeding stimulants, other biologi 50 ronal sodium channel blockers, insecticidal macrocyclic lac cally active compounds or entomopathogenic bacteria, virus tones, y-aminobutyric acid antagonists, insecticidal ureas and or fungi to form a multi-component pesticide giving an even juvenile hormone mimics, a member of Bacillus thuringien broader spectrum of agronomic and nonagronomic utility. sis, a Bacillus thuringiensis delta-endotoxin, and a naturally Thus the present invention also pertains to a composition occurring or a genetically modified viral insecticide. comprising a biologically effective amount of a compound of 55 Examples of such biologically active compounds or agents Formula 1, an N-oxide or salt thereof, and an effective amount with which compounds of this invention can be formulated of at least one additional biologically active compound or are: insecticides Such as abamectin, acephate, acetamiprid, agent and can further comprise at least one of a surfactant, a acetoprole, amidoflumet (S-1955), avermectin, azadirachtin, solid diluent or a liquid diluent. The other biologically active azinphos-methyl, bifenthrin, bifenazate, buprofezin, bistrif compounds or agents can be formulated in compositions 60 luoron, buprofezin, carbofuran, cartap, chlorfenapyr, chlor comprising at least one of a Surfactant, Solid or liquid diluent. fluaZuron, chlorantraniliprole (DPX-E2Y45), chlorpyrifos, For mixtures of the present invention, the other biologically chlorpyrifos-methyl, chromafenozide, clothianidin, cyflu active compounds or agents can be formulated together with metofen, cyfluthrin, beta-cyfluthrin, cyhalothrin, gamma-cy the present compounds, including the compounds of Formula halothrin lambda-cyhalothrin, cypermethrin, cyromazine, 1, to form a premix, or the other biologically active com 65 deltamethrin, diafenthiuron, diazinon, dieldrin, diflubenzu pounds or agents can be formulated separately from the ron, dimefluthrin, dimethoate, dinotefuran, diofenolan, ema present compounds, including the compounds of Formula 1, mectin, endosulfan, esfenvalerate, ethiprole, fenothiocarb, US 8,871,941 B2 95 96 fenoxycarb, fenpropathrin, fenvalerate, fipronil, flonicamid, fenaZaquin, fenbutatin oxide, fenpropathrin, fenpyroximate, flubendiamide, flucythrinate, tau-fluvalinate, flufenerim hexythiazox, propargite, pyridaben and tebufenpyrad; and (UR-50701), flufenoxuron, fonophos, halofenozide, hexaflu biological agents including entomopathogenic bacteria, Such muron, hydramethylnon, imidacloprid, indoxacarb, isofen as Bacillus thuringiensis Subsp. aizawai, Bacillus thuringien phos, lufenuron, malathion, metaflumizone, metaldehyde, sis Subsp. kurstaki, and the encapsulated delta-endotoxins of methamidophos, methidathion, methomyl, methoprene, Bacillus thuringiensis (e.g., Cellcap, MPV. MPVII); ento methoxychlor, metofluthrin, monocrotophos, methoxy mopathogenic fungi, such as green muscardine fungus; and fenozide, monocrotophos, nitenpyram, nithiazine, novalu entomopathogenic virus including baculovirus, nucleopoly ron, noviflumuron (XDE-007), oxamyl, parathion, parathion hedrovirus (NPV) such as Helicoverpa zea nucleopolyhe methyl, permethrin, phorate, phosalone, phosmet, 10 drovirus (HZNPV), Anagrapha falcifera nucleopolyhedrovi phosphamidon, pirimicarb, profenofos, profluthrin, prot rus (AfNPV); and granulosis virus (GV) such as Cydia rifenbute, pymetrozine, pyrafluprole, pyrethrin, pyridalyl, pomonella granulosis virus (CpGV). pyrifluquinazon, pyriprole, pyriproxyfen, rotenone, ryanod Compounds of this invention and compositions thereof can ine, spinetoram, spinosad, spirodiclofen, spiromesifen (BSN be applied to plants genetically transformed to express pro 2060), spirotetramat, sulprofos, tebufenozide, teflubenzuron, 15 teins toxic to invertebrate pests (such as Bacillus thuringien tefluthrin, terbufos, tetrachlorvinphos, thiacloprid, thia sis delta-endotoxins). The effect of the exogenously applied methoxam, thiodicarb, thiosultap-sodium, tolfenpyrad, tral invertebrate pest control compounds of this invention may be omethrin, triazamate, trichlorfon and triflumuron; fungicides synergistic with the expressed toxin proteins. Such as acibenzolar, aldimorph, amisulbrom, azaconazole, General references for these agricultural protectants (i.e. azoxystrobin, benalaxyl, benomyl, benthiavalicarb, benthia insecticides, fungicides, nematicides, acaricides, herbicides valicarb-isopropyl, binomial, biphenyl, bitertanol, blastici and biological agents) include The Pesticide Manual, 13th din-S, Bordeaux mixture (Tribasic copper sulfate), boscalid/ Edition, C. D. S. Tomlin, Ed., British Crop Protection Coun nicobifen, bromuconazole, bupirimate, buthiobate, carboxin, cil, Farnham, Surrey, U.K., 2003 and The BioPesticide carpropamid, captafol, captan, carbendazim, chloroneb, Manual, 2" Edition, L. G. Copping, Ed., British Crop Pro chlorothalonil, chloZolinate, clotrimazole, copper oxychlo 25 tection Council, Farnham, Surrey, U.K., 2001. ride, copper salts such as copper Sulfate and copper hydrox Of note is a composition of the present invention wherein at ide, cyaZofamid, cyflunamid, cymoxanil, cyproconazole, least one additional biologically active compound or agent is cyprodinil, dichlofluanid, diclocymet, diclomeZine, dicloran, selected from the group consisting of abamectin, acephate, diethofencarb, difenoconazole, dimethomorph, dimox acetamiprid, acetoprole, aldicarb, amidoflumet, amitraz, yStrobin, diniconazole, diniconazole-M, dinocap, discos 30 avermectin, azadirachtin, azinphos-methyl, bifenthrin, trobin, dithianon, dodemorph, dodine, econazole, etacona bifenazate, bistrifluoron, buprofezin, carbofuran, cartap, chi Zole, edifenphos, epoxiconazole, ethaboxam, ethirimol, nomethionat, chlorfenapyr, chlorfluaZuron, chlorantranilip ethridiazole, famoxadone, fenamidone, fenarimol, fen role, chlorpyrifos, chlorpyrifos-methyl, chlorobenzilate, buconazole, fencaramid, fenfuram, fenhexamide, fenoxaniil, chromafenozide, clothianidin, cyflumetofen, cyfluthrin, beta fenpiclonil, fenpropidin, fenpropimorph, fentin acetate, fen 35 cyfluthrin, cyhalothrin, gamma-cyhalothrin, lambda-cyhalo tin hydroxide, ferbam, ferfurazoate, ferim Zone, fluazinam, thrin, cyhexatin, cypermethrin, cyromazine, deltamethrin, fludioxonil, flumetover, fluopicolide, fluoxastrobin, fluguin diafenthiuron, diazinon, dicofol, dieldrin, dienochlor, conazole, fluguinconazole, flusilaZole, flusulfamide, flutola diflubenzuron, dimefluthrin, dimethoate, dinotefuran, nil, flutriafol, folpet, fosetyl-aluminum, fuberidazole, fural diofenolan, emamectin, endosulfan, esfenvalerate, ethiprole, axyl, furametapyr, hexaconazole, hymexazole, guazatline, 40 etoxazole, fenamiphos, fenaZaquin, fenbutatin oxide, imazalil, imibenconazole, iminoctadine, iodicarb, ipcona fenothiocarb, fenoxycarb, fempropathrin, fenpyroximate, Zole, iprobenfos, iprodione, iprovalicarb, isoconazole, iso fenvalerate, fipronil, flonicamid, flubendiamide, flucythri prothiolane, kasugamycin, kresoxim-methyl, mancoZeb, nate, tau-fluvalinate, flufenerim, flufenoXuron, fonophos, mandipropamid, maneb, mapanipyrin, mefenoxam, halofenozide, hexaflumuron, hexythiazox, hydramethylnon, mepronil, metalaxyl, metconazole, methasulfocarb, metiram, 45 imicyafos, imidacloprid, indoxacarb, isofenphos, lufenuron, metominostrobin/fenominostrobin, mepanipyrim, malathion, metaflumizone, metaldehyde, methamidophos, metrafenone, miconazole, myclobutanil, neo-asozin (ferric methidathion, methomyl, methoprene, methoxychlor, meth methanearsonate), nuarimol, octhillinone, ofurace, orysas oxyfenozide, metofluthrin, monocrotophos, nitenpyram, trobin, oxadixyl, oxolinic acid, oxpoconazole, oxycarboxin, nithiazine, novaluron, noviflumuron, oxamyl, parathion, par paclobutraZol, penconazole, pencycuron, penthiopyriad, per 50 athion-methyl, permethrin, phorate, phosalone, phosmet, furazoate, phosphonic acid, phthalide, picobenzamid, picox phosphamidon, pirimicarb, profenofos, profluthrin, proparg yStrobin, polyoxin, probenazole, prochloraz, procymidone, ite, protrifenbute, pymetrozine, pyrafluprole, pyrethrin, propamocarb, propamocarb-hydrochloride, propiconazole, pyridaben, pyridalyl pyrifluquinazon, pyriprole, pyriproxy propineb, produinazid, prothioconazole, pyraclostrobin, fen, rotenone, ryanodine, spinetoram, spinosad, spiridi pryaZophos, pyrifenox, pyrimethanil, pyrifenox, pyrolni 55 clofen, spiromesifen, spirotetramat, Sulprofos, tebufenozide, trine, pyroquilon, quinconazole, quinoxyfen, quintoZene, tebufenpyrad, teflubenZuron, tefluthrin, terbufos, tetrachlor silthiofam, Simeconazole, spiroxamine, Streptomycin, Sulfur, Vinphos, thiacloprid, thiamethoxam, thiodicarb, thiosultap tebuconazole, techraZene, tecloftalam, tecnaZene, tetracona Sodium, tolfenpyrad, tralomethrin, triaZamate, trichlorfon, Zole, thiabendazole, thifluZamide, thiophanate, thiophanate triflumuron, Bacillus thuringiensis Subsp. aizawai, Bacillus methyl, thiram, tiadinil, tolclofos-methyl, tolyfluanid, tri 60 thuringiensis Subsp. kurstaki, nucleopolyhedrovirus, an adimefon, triadimenol, triarimol, triaZOxide, tridemorph, encapsulated delta-endotoxin of Bacillus thuringiensis, bacu trimoprhamide tricyclazole, trifloxystrobin, triforine, triti lovirus, entomopathogenic bacteria, entomopathogenic virus conazole, uniconazole, validamycin, VincloZolin, Zineb, and entomopathogenic fungi. Ziram, and Zoxamide; nematicides Such as aldicarb, imi Also of note is a composition of the present invention cyafos, oxamyl and fenamiphos; bactericides such as Strep 65 wherein at least one additional biologically active compound tomycin; acaricides such as amitraz, chinomethionat, chlo or agent is selected from the group consisting of abamectin, robenzilate, cyhexatin, dicofol, dienochlor, etoxazole, acetamiprid, amitraz, avermectin, azadirachtin, bifenthrin, US 8,871,941 B2 97 98 buprofezin, cartap, chlorantraniliprole, chlorfenapyr, chlo control agent can be applied relative to a compound of For rpyrifos, clothianidin, cyfluthrin, beta-cyfluthrin, cyhalo mula 1, an N-oxide, or a salt thereof, (e.g., “50:1 to 1:50 of thrin, lambda-cyhalothrin, cypermethrin, cyromazine, delta abamectin relative to a compound of Formula 1 by weight). methrin, dieldrin, dinotefuran, diofenolan, emamectin, Thus, for example, the first line of Table A specifically dis endosulfan, esfenvalerate, ethiprole, fenothiocarb, fenoxy closes the combination of a compound of Formula 1 with carb, fenvalerate, fipronil, flonicamid, flubendiamide, abamectin can be applied in a weight ratio between 50:1 to flufenoXuron, hexaflumuron, hydramethylnon, imidacloprid, 1:50. The remaining lines of Table A are to be construed indoxacarb, lufenuron, metaflumizone, methomyl, methop similarly. Of further note Table A lists specific combinations rene, methoxyfenozide, nitenpyram, nithiazine, novaluron, of a compound of Formula 1 with other invertebrate pest oxamyl, pymetrozine, pyrethrin, pyridaben, pyridalyl, 10 control agents illustrative of the mixtures, compositions and pyriproxyfen, ryanodine, spinetoram, spinosad, spirodi methods of the present invention and includes additional clofen, Spiromesifen, tebufenozide, thiacloprid, thia embodiments of weight ratio ranges for application rates. methoxam, thiodicarb, thiosultap-sodium, tralomethrin, tri aZamate, triflumuron, Bacillus thuringiensis Subsp. aizawai, TABLE A Bacillus thuringiensis Subsp. kurstaki, nucleopolyhedrovirus 15 Invertebrate Pest Mode of Action Typical and an encapsulated delta-endotoxin of Bacillus thuringien Control Agent or Chemical Class Weight Ratio Sis. For embodiments where one or more of these various mix Abamectin macrocyclic lactones SO:1 to 1:SO Acetamiprid neonicotinoids SO:1 to 1:200 ing partners are used, the weight ratio of these various mixing Amitraz Octopamine receptor ligands 2OO:1 to 1:100 partners (in total) to the compound of Formula 1 is typically Avermectin macrocyclic lactones SO:1 to 1:SO between about 1:3000 and about 3000:1. Of note are weight Azadirachtin ecclysone agonists OO:1 to 1:120 ratios between about 1:300 and about 300:1 (for example Beta-cyfluthrin Sodium channel modulators SO:1 to 1:200 Bifenthrin Sodium channel modulators OO:1 to 1:10 ratios between about 1:30 and about 30:1). One skilled in the Buprofezin chitin synthesis inhibitors SOO:1 to 1:SO art can easily determine through simple experimentation the Cartap nereistoxin analogs OO:1 to 1:200 biologically effective amounts of active ingredients neces 25 Chlorantraniliprole ryanodine receptor ligands OO:1 to 1:120 sary for the desired spectrum of biological activity. It will be Chlorfeinapyr mitochondrial electron 3OO:1 to 1:200 evident that including these additional components may transport inhibitors Chlorpyrifos cholinesterase inhibitors SOO:1 to 1:200 expand the spectrum of invertebrate pests controlled beyond Clothianidin neonicotinoids OO:1 to 1:400 the spectrum controlled by the compound of Formula 1 alone. Cyfluthrin Sodium channel modulators SO:1 to 1:200 In certain instances, combinations of a compound of this 30 Cyhalothrin Sodium channel modulators SO:1 to 1:200 invention with other biologically active (particularly inverte Cypermethrin Sodium channel modulators SO:1 to 1:200 Cyromazine chitin synthesis inhibitors 400:1 to 1:50 brate pest control) compounds or agents (i.e. active ingredi Deltamethrin Sodium channel modulators 50:1 to 1:400 ents) can result in a greater-than-additive (i.e. synergistic) Dieldrin cyclodiene insecticides 2OO:1 to 1:100 effect. Reducing the quantity of active ingredients released in Dinotefuran neonicotinoids SO:1 to 1:200 35 Diofenolan molting inhibitor SO:1 to 1:200 the environment while ensuring effective pest control is Emamectin macrocyclic lactones 50:1 to 1:10 always desirable. When synergism of invertebrate pest con Endosulfan cyclodiene insecticides 2OO:1 to 1:100 trol active ingredients occurs at application rates giving agro Esfenvalerate Sodium channel modulators OO:1 to 1:400 nomically satisfactory levels of invertebrate pest control, Ethiprole GABA-regulated chloride 2OO:1 to 1:100 Such combinations can be advantageous for reducing crop channel blockers Fenothiocarb SO:1 to 1:200 production cost and decreasing environmental load. 40 Fenoxycarb juvenile hormone mimics SOO:1 to 1:100 Of note is a combination of a compound of Formula 1 with Fenvalerate Sodium channel modulators SO:1 to 1:200 at least one other invertebrate pest control active ingredient. Fipronil GABA-regulated chloride SO:1 to 1:100 channel blockers Of particular note is such a combination where the other Flonicamid 2OO:1 to 1:100 invertebrate pest control active ingredient has different site of Flubendiamide ryanodine receptor ligands OO:1 to 1:120 action from the compound of Formula 1. In certain instances, 45 Fufenoxuron chitin synthesis inhibitors 2OO:1 to 1:100 a combination with at least one other invertebrate pest control Hexaflumuron chitin synthesis inhibitors 300:1 to 1:SO active ingredient having a similar spectrum of control but a Hydramethylnon mitochondrial electron SO:1 to 1:250 transport inhibitors different site of action will be particularly advantageous for midacloprid neonicotinoids 1OOO:1 to 1:1000 resistance management. Thus, a composition of the present indoxacarb Sodium channel modulators 2001 to 1:SO invention can further comprise a biologically effective 50 Lambda-cyhaloduin Sodium channel modulators SO:1 to 1:250 Lufenuron chitin synthesis inhibitors SOO:1 to 1:250 amount of at least one additional invertebrate pest control Metaflumizone 2OO:1 to 1:200 active ingredient having a similar spectrum of control but a Methomyl cholinesterase inhibitors SOO:1 to 1:100 different site of action. Contacting a plant genetically modi Methoprene juvenile hormone mimics SOO:1 to 1:100 fied to express an invertebrate pest compound (e.g., protein) Methoxyfenozide ecclysone agonists SO:1 to 1:SO 55 Nitenpyram neonicotinoids 1SO:1 to 1:200 or the locus of the plant with a biologically effective amount Nithiazine neonicotinoids 1SO:1 to 1:200 of a compound of this invention can also provide a broader Novaluron chitin synthesis inhibitors SOO:1 to 1:150 spectrum of plant protection and be advantageous for resis Oxamyl cholinesterase inhibitors 2OO:1 to 1:200 tance management. Pymetrozine 2OO:1 to 1:100 Pyrethrin Sodium channel modulators 100:1 to 1:10 Table A lists specific combinations of a compound of For Pyridaben mitochondrial electron 2OO:1 to 1:100 mula 1 with other invertebrate pest control agents illustrative 60 transport inhibitors of the mixtures, compositions and methods of the present Pyridalyl 2OO:1 to 1:100 invention. The first column of Table A lists the specific inver Pyriproxyfen juvenile hormone mimics SOO:1 to 1:100 Ryanodine ryanodine receptor ligands 100:1 to 1:120 tebrate pest control agents (e.g., "Abamectin’ in the first line). Spinetoram macrocyclic lactones 150:1 to 1:100 The second column of Table A lists the mode of action (if Spinosad macrocyclic lactones SOO:1 to 1:10 known) or chemical class of the invertebrate pest control 65 Spirodiclofen lipid biosynthesis inhibitors 2OO:1 to 1:200 agents. The third column of Table A lists embodiment(s) of Spiromesifen lipid biosynthesis inhibitors 2OO:1 to 1:200 ranges of weight ratios for rates at which the invertebrate pest US 8,871,941 B2 99 100 TABLE A-continued pymetrozine, amitraz, Bacillus thuringiensis aisawai, Bacil lus thuringiensis kurstaki, Bacillus thuringiensis delta endot Invertebrate Pest Mode of Action Typical oxin and entomophagous fungi. Control Agent or Chemical Class Weight Ratio The weight ratios of a compound, including a compound of Tebufenozide ecclysone agonists SOO:1 to 1:250 Formula 1, an N-oxide or a salt thereof, to the additional Thiacloprid neonicotinoids 100:1 to 1:200 Thiamethoxam neonicotinoids 12SO:1 to 1:1000 invertebrate pest control agent typically are between 1000:1 Thiodicarb cholinesterase inhibitors SOO:1 to 1:400 and 1:1000, with one embodiment being between 500:1 and ThiOSultap-sodium 150:1 to 1:100 1:500, another embodiment being between 250:1 and 1:200 Trailomethrin Sodium channel modulators 1SO:1 to 1:200 Triazamate cholinesterase inhibitors 2SO:1 to 1:100 10 and another embodiment being between 100:1 and 1:50. Trifumuron chitin synthesis inhibitors 2OO:1 to 1:100 Listed below in Table B are embodiments of specific com Bacilius biological agents 50:1 to 1:10 positions comprising a compound of Formula 1 (compound thiringiensis Bacilius biological agents 50:1 to 1:10 numbers refer to compounds in Index Tables A-C) and an thiringiensis additional invertebrate pest control agent. delta-endotoxin 15 NPV (e.g., Gemstar) biological agents 50:1 to 1:10 TABLE B Mixture Comp. Invertebrate Pest One embodiment of invertebrate pest control agents (e.g., No. No. 8 Control Agent insecticides and acaricides) for mixing with compounds of A-1 8 Abamectin this invention include Sodium channel modulators such as A-2 8 Acetamiprid bifenthrin, cypermethrin, cyhalothrin, lambda-cyhalothrin, A-3 8 Amitraz cyfluthrin, beta-cyfluthrin, deltamethrin, dimefluthrin, esfen A-4 8 Avermectin A-5 8 Azadirachtin Valerate, fenvalerate, indoxacarb, metofluthrin, profluthrin, A-6 8 Beta-cyfluthrin pyrethrin and tralomethrin; cholinesterase inhibitors such as A-7 8 Bifenthrin chlorpyrifos, methomyl, oxamyl, thiodicarb and triazamate; 25 A-8 8 Buprofezin neonicotinoids Such as acetamiprid, clothianidin, dinotefu A-9 8 Cartap ran, imidacloprid, nitenpyram, nithiazine, thiacloprid and A-10 8 Chlorantraniliprole A-11 8 Chlorfeinapyr thiamethoxam; insecticidal macrocyclic lactones such as A-12 8 Chlorpyrifos spinetoram, spinosad, abamectin, avermectin and emamec A-13 8 Clothianidin tin; GABA (y-aminobutyric acid)-regulated chloride channel 30 A-14 8 Cyfluthrin blockers such as endosulfan, ethiprole and fipronil; chitin A-15 8 Cyhalothrin A-16 8 Cypermethrin synthesis inhibitors such as buprofezin, cyromazine, A-17 8 Cyromazine flufenoXuron, hexaflumuron, lufenuron, novaluron, noviflu A-18 8 Deltamethrin muron and triflumuron; juvenile hormone mimics Such as A-19 8 Dieldrin diofenolan, fenoxycarb, methoprene and pyriproxyfen; octo 35 A-20 8 Dinotefuran A-21 8 Diofenolan pamine receptor ligands such as amitraz: ecdysone agonists A-22 8 Emamectin Such as azadirachtin, methoxyfenozide and tebufenozide; A-23 8 Endosulfan ryanodine receptor ligands such as ryanodine, anthranilic A-24 8 Esfenvalerate diamides such as chlorantraniliprole (see U.S. Pat. No. 6,747, A-25 8 Ethiprole A-26 8 Fenothiocarb 40 047, PCT Publications WO 2003/015518 and WO 2004/ A-27 8 Fenoxycarb 067528) and flubendiamide (see U.S. Pat. No. 6,603,044); A-28 8 Fenvalerate nereistoxin analogs such as cartap; mitochondrial electron A-29 8 Fipronil transport inhibitors such as chlorfeinapyr, hydramethylnon A-30 8 Flonicamid A-31 8 Flubendiamide and pyridaben; lipid biosynthesis inhibitors such as spirodi A-32 8 Fufenoxuron clofen and Spiromesi?en; cyclodiene insecticides such as 45 A-33 8 Hexaflumuron dieldrin: cyflumetofen; fenothiocarb; flonicamid; metaflumi A-34 8 Hydramethylnon Zone; pyrafluprole; pyridalyl; pyriprole; pymetrozine; A-35 8 midacloprid A-36 8 indoxacarb spirotetramat; and thiosultap-sodium. One embodiment of A-37 8 Lambda-cyhalothrin biological agents for mixing with compounds of this inven A-38 8 Lufenuron tion include nucleopolyhedrovirus such as HZNPV and 50 A-39 8 Metaflumizone AfNPV; Bacillus thuringiensis and encapsulated delta-endot A-40 8 Methomyl A-41 8 Methoprene oxins of Bacillus thuringiensis such as Cellcap. MPV and A-42 8 Methoxyfenozide MPVII; as well as naturally occurring and genetically modi A-43 8 Nitenpyram fied viral insecticides including members of the family Bacu A-44. 8 Nithiazine loviridae as well as entomophagous fungi. Of note is the 55 A-45 8 Novaluron A-46 8 Oxamyl composition of the present invention wherein the at least one A-47 8 Pymetrozine additional biologically active compound or agent is selected A-48 8 Pyrethrin from the Invertebrate Pest Control Agents listed in Table A A-49 8 Pyridaben above. Also of note is the composition of the present invention A-50 8 Pyridalyl A-51 8 Pyriproxyfen wherein the at least one additional biologically active com 60 A-52 8 Ryanodine pound or agent is selected from the group consisting of cyper A-53 8 Spinetoram methrin, cyhalothrin, cyfluthrin, beta-cyfluthrin, esfenvaler A-54 8 Spinosad A-SS 8 Spirodiclofen ate, fenvalerate, tralomethrin, fenothiocarb, methomyl. A-56 8 Spiromesifen oxamyl, thiodicarb, acetamiprid, clothianidin, imidacloprid, A-57 8 Tebufenozide thiamethoxam, thiacloprid, indoxacarb, Spinosad, abamectin, 65 A-58 8 Thiacloprid avermectin, emamectin, endosulfan, ethiprole, fipronil. A-59 8 Thiamethoxam flufenoXuron, triflumuron, diofenolan, pyriproxyfen, US 8,871,941 B2 101 102 TABLE B-continued TABLE B-continued

Mixture Comp. Invertebrate Pest Mixture Comp. Invertebrate Pest No. No. 8 Control Agent No. No. 8 Control Agent A-60 Thiodicarb C-1 Abamectin A-61 Thiosultap-sodium C-2 Acetamiprid A-62 Trailomethrin Amitraz A-63 Triazamate C-4 Avermectin A-64 Trifumuron C-5 Azadirachtin A-65 Bacillus thuringiensis C-6 Beta-cyfluthrin A-66 Bacillus thuringiensis 10 C-7 Bifenthrin delta-endotoxin C-8 Buprofezin A-67 NPV (e.g., Gemstar) C-9 Cartap B-1 Abamectin C-10 Chlorantraniliprole B-2 Acetamiprid C-11 Chlorfeinapyr B-3 Amitraz C-12 Chlorpyrifos B-4 Avermectin 15 C-13 Clothianidin B-5 Azadirachtin C-14 Cyfluthrin B-6 Beta-cyfluthrin C-15 Cyhalothrin Bifenthrin C-16 Cypermethrin Buprofezin C-17 Cyromazine Cartap C-18 Deltamethrin B-10 Chlorantraniliprole C-19 Dieldrin B-11 Chlorfeinapyr C-2O Dinotefuran B-12 Chlorpyrifos C-21 Diofenolan B-13 Clothianidin C-22 Emamectin B-14 Cyfluthrin C-23 Endosulfan B-1S Cyhalothrin C-24 Esfenvalerate B-16 Cypermethrin C-2S Ethiprole B-17 Cyromazine 25 C-26 Fenothiocarb B-18 Deltamethrin C-27 Fenoxycarb B-19 Dieldrin C-28 Fenvalerate B-2O Dinotefuran C-29 Fipronil B-21 Diofenolan C-30 Flonicamid B-22 Emamectin C-31 Flubendiamide B-23 Endosulfan 30 C-32 Fufenoxuron B-24 Esfenvalerate C-33 Hexaflumuron B-2S Ethiprole C-34 Hydramethylnon B-26 Fenothiocarb C-3S midacloprid B-27 Fenoxycarb C-36 indoxacarb B-28 Fenvalerate C-37 Lambda-cyhalothrin B-29 Fipronil 35 C-38 Lufenuron B-30 Flonicamid C-39 Metaflumizone B-31 Flubendiamide C-40 Methomyl B-32 Fufenoxuron C-41 Methoprene B-33 Hexaflumuron C-42 Methoxyfenozide B-34 Hydramethylnon C-43 Nitenpyram B-3S midacloprid C-44 Nithiazine B-36 indoxacarb 40 C-45 Novaluron B-37 Lambda-cyhalothrin C-46 Oxamyl B-38 Lufenuron C-47 Pymetrozine B-39 Metaflumizone C-48 Pyrethrin B-40 Methomyl C-49 Pyridaben B-41 Methoprene C-SO Pyridalyl B-42 Methoxyfenozide 45 C-S1 Pyriproxyfen B-43 Nitenpyram C-52 Ryanodine B-44 Nithiazine C-53 Spinetoram B-45 Novaluron C-54 Spinosad B-46 Oxamyl C-55 Spirodiclofen B-47 Pymetrozine C-56 Spiromesifen B-48 Pyrethrin 50 C-57 Tebufenozide B-49 Pyridaben C-58 Thiacloprid B-SO Pyridalyl C-59 Thiamethoxam B-51 Pyriproxyfen C-60 Thiodicarb B-52 Ryanodine C-61 Thiosultap-sodium B-53 Spinetoram C-62 Trailomethrin B-54 Spinosad 55 C-63 Triazamate B-55 Spirodiclofen C-64 Trifumuron B-56 Spiromesifen C-65 Bacilius thuringiensis B-57 Tebufenozide C-66 Bacilius thuringiensis B-58 Thiacloprid delta-endotoxin B-59 Thiamethoxam C-67 O NPV (e.g., Gemstar) B-60 Thiodicarb D-1 Abamectin B-61 Thiosultap-sodium 60 D-2 Acetamiprid B-62 Trailomethrin D-3 Amitraz B-63 Triazamate D-4 Avermectin B-64 Trifumuron Azadirachtin B-6S Bacillus thuringiensis D-6 Beta-cyfluthrin B-66 Bacillus thuringiensis D-7 Bifenthrin delta-endotoxin 65 D-8 Buprofezin B-67 8 NPV (e.g., Gemstar) D-9 Cartap US 8,871,941 B2 103 104 TABLE B-continued TABLE B-continued

Mixture Comp. Invertebrate Pest Comp. nvertebrate Pest No. No. 8 Control Agent No. 8 Control Agent D-10 Chlorantraniliprole Dieldrin D-11 Chlorfeinapyr Dinotefuran D-12 Chlorpyrifos Diofenolan D-13 Clothianidin Emamectin D-14 Cyfluthrin Endosulfan D-1S Cyhalothrin Esfenvalerate D-16 Cypermethrin 10 Ethiprole D-17 Cyromazine Fenothiocarb D-18 Deltamethrin Fenoxycarb D-19 Dieldrin Fenvalerate D-2O Dinotefuran Fipronil D-21 Diofenolan Flonicamid D-22 Emamectin 15 Flubendiamide D-23 Endosulfan Fufenoxuron D-24 Esfenvalerate Hexaflumuron D-2S Ethiprole Hydramethylnon D-26 Fenothiocarb midacloprid D-27 Fenoxycarb indoxacarb D-28 Fenvalerate Lambda-cyhalothrin D-29 Fipronil Lufenuron D-30 Flonicamid Metaflumizone D-31 Flubendiamide Methomyl D-32 Fufenoxuron Methoprene D-33 Hexaflumuron Methoxyfenozide D-34 Hydramethylnon Nitenpyram D-35 midacloprid 25 Nithiazine D-36 indoxacarb Novaluron D-37 Lambda-cyhalothrin Oxamyl D-38 Lufenuron Pymetrozine D-39 Metaflumizone Pyrethrin D-40 Methomyl Pyridaben D-41 Methoprene 30 Pyridalyl D-42 Methoxyfenozide Pyriproxyfen D-43 Nitenpyram Ryanodine D-44 Nithiazine Spinetoram D-45 Novaluron Spinosad D-46 Oxamyl Spirodiclofen D-47 Pymetrozine 35 Spiromesifen D-48 Pyrethrin Tebufenozide D-49 Pyridaben Thiacloprid D-SO Pyridalyl Thiamethoxam D-51 Pyriproxyfen Thiodicarb D-52 Ryanodine Thiosultap-sodium D-53 Spinetoram Trailomethrin D-54 Spinosad 40 Triazamate D-55 Spirodiclofen Trifumuron D-56 Spiromesifen Bacilius thuringiensis D-57 Tebufenozide Bacilius thuringiensis D-58 Thiacloprid delta-endotoxin D-59 Thiamethoxam E-67 NPV (e.g., Gemstar) D-60 Thiodicarb 45 Abamectin D-61 Thiosultap-sodium Acetamiprid D-62 Trailomethrin Amitraz D-63 Triazamate Avermectin D-64 Trifumuron Azadirachtin D-6S Bacillus thuringiensis Beta-cyfluthrin D-66 Bacillus thuringiensis 50 Bifenthrin delta-endotoxin Buprofezin O4 NPV (e.g., Gemstar) Cartap Abamectin F-10 Chlorantraniliprole Acetamiprid F-11 Chlorfeinapyr Amitraz F-12 Chlorpyrifos Avermectin 55 F-13 Clothianidin Azadirachtin F-14 Cyfluthrin Beta-cyfluthrin F-15 Cyhalothrin Bifenthrin F-16 Cypermethrin Buprofezin F-17 Cyromazine Cartap F-18 Deltamethrin Chlorantraniliprole F-19 Dieldrin Chlorfeinapyr 60 F-2O Dinotefuran Chlorpyrifos F-21 Diofenolan Clothianidin F-22 Emamectin Cyfluthrin F-23 Endosulfan Cyhalothrin F-24 Esfenvalerate Cypermethrin F-25 Ethiprole Cyromazine 65 F-26 Fenothiocarb Deltamethrin F-27 Fenoxycarb US 8,871,941 B2 105 106 TABLE B-continued TABLE B-continued

Mixture Comp. Invertebrate Pest Mixture Comp. Invertebrate Pest No. O. 8 Control Agent No. No. 8 Control Agent F-28 Fenvalerate G-37 Lambda-cyhalothrin F-29 Fipronil G-38 Lufenuron F-30 Flonicamid G-39 Metaflumizone F-31 Flubendiamide G-40 Methomyl F-32 Flufenoxuron G-41 Methoprene F-33 Hexaflumuron G-42 Methoxyfenozide F-34 Hydramethylnon 10 G-43 Nitenpyram F-35 Imidacloprid G-44 Nithiazine F-36 Indoxacarb G-45 Novaluron F-37 Lambda-cyhalothrin G-46 Oxamyl F-38 Lufenuron G-47 Pymetrozine F-39 Metaflumizone G-48 Pyrethrin F-40 Methomyl 15 G-49 Pyridaben F-41 Methoprene G-SO Pyridalyl F-42 Methoxyfenozide G-51 Pyriproxyfen F-43 Nitenpyram G-52 Ryanodine F-44 Nithiazine G-53 Spinetoram F-45 Novaluron G-54 Spinosad F-46 Oxamyl G-55 Spirodiclofen F-47 Pymetrozine G-56 Spiromesifen F-48 Pyrethrin G-57 Tebufenozide F-49 Pyridaben G-58 Thiacloprid F-50 Pyridalyl G-59 Thiamethoxam F-51 Pyriproxyfen G-60 Thiodicarb F-52 Ryanodine G-61 Thiosultap-sodium F-53 Spinetoram 25 G-62 Trailomethrin F-54 Spinosad G-63 Triazamate F-55 Spirodiclofen G-64 Trifumuron F-56 Spiromesifen G-65 Bacilius thuringiensis F-57 Tebufenozide G-66 Bacilius thuringiensis F-58 Thiacloprid delta-endotoxin F-59 Thiamethoxam 30 NPV (e.g., Gemstar) F-60 Thiodicarb Abamectin F-61 Thiosultap-sodium Acetamiprid F-62 Trailomethrin Amitraz F-63 Triazamate Avermectin F-64 Trifumuron Azadirachtin F-65 Bacillus thuringiensis 35 Beta-cyfluthrin F-66 Bacillus thuringiensis Bifenthrin delta-endotoxin Buprofezin O NPV (e.g., Gemstar) Cartap Abamectin Chlorantraniliprole Acetamiprid Chlorfeinapyr Amitraz Chlorpyrifos Avermectin 40 Clothianidin Azadirachtin Cyfluthrin Beta-cyfluthrin Cyhalothrin Bifenthrin Cypermethrin Buprofezin Cyromazine Cartap Deltamethrin G-10 Chlorantraniliprole 45 Dieldrin G-11 Chlorfeinapyr Dinotefuran G-12 Chlorpyrifos Diofenolan G-13 Clothianidin Emamectin G-14 Cyfluthrin Endosulfan G-15 Cyhalothrin Esfenvalerate G-16 Cypermethrin 50 Ethiprole G-17 Cyromazine Fenothiocarb G-18 Deltamethrin Fenoxycarb G-19 Dieldrin Fenvalerate G-2O Dinotefuran Fipronil G-21 Diofenolan Flonicamid G-22 Emamectin 55 Flubendiamide G-23 Endosulfan Fufenoxuron C-24 Esfenvalerate Hexaflumuron G-25 Ethiprole Hydramethylnon G-26 Fenothiocarb midacloprid C-27 Fenoxycarb indoxacarb G-28 Fenvalerate Lambda-cyhalothrin G-29 Fipronil 60 Lufenuron G-30 Flonicamid Metaflumizone G-31 Flubendiamide Methomyl G-32 Fufenoxuron Methoprene G-33 Hexaflumuron Methoxyfenozide G-34 Hydramethylnon Nitenpyram G-35 midacloprid 65 Nithiazine G-36 indoxacarb Novaluron US 8,871,941 B2 107 108 TABLE B-continued tacting the invertebrate pest or its environment with a biologi cally effective amount of a compound of the present invention Mixture Comp. Invertebrate Pest or with a composition comprising a biologically effective No. No. 8 Control Agent amount of a compound of the present invention. Of further H-46 5 8 Oxamyl 5 note is this method wherein the environment is soil and the H-47 5 8 Pymetrozine composition is applied to the Soil as a soildrench formulation. H-48 5 8 Pyrethrin H-49 5 8 Pyridaben Of further note is that compounds of this invention are also H-SO 5 8 Pyridalyl effective by localized application to the locus of infestation. H-51 5 8 Pyriproxyfen Other methods of contact include application of a compound H-52 5 8 Ryanodine 10 or a composition of the invention by direct and residual H-53 5 8 Spinetoram H-54 5 8 Spinosad sprays, aerial sprays, gels, seed coatings, microencapsula H-5S 5 8 Spirodiclofen tions, systemic uptake, baits, ear tags, boluses, foggers, fumi H-56 5 8 Spiromesifen gants, aerosols, dusts and many others. One embodiment of a H-57 5 8 Tebufenozide method of contact is a dimensionally stable fertilizer granule, H-58 5 8 Thiacloprid 15 H-59 5 8 Thiamethoxam Stick or tablet comprising a compound or composition of the H-60 5 8 Thiodicarb invention. The compounds of this invention can also be H-61 5 8 Thiosultap-sodium impregnated into materials for fabricating invertebrate con H-62 5 8 Trailomethrin trol devices (e.g., insect netting). H-63 5 8 Triazamate H-64 5 8 Trifumuron Compounds of this invention are also useful in seed treat H-65 5 8 Bacillus thuringiensis ments for protecting seeds from invertebrate pests. In the H-66 5 8 Bacillus thuringiensis context of the present disclosure and claims, treating a seed delta-endotoxin means contacting the seed with a biologically effective H-67 5 8 NPV (e.g., Gemstar) amount of a compound of this invention, which is typically formulated as a composition of the invention. This seed treat The specific mixtures listed in Table B typically combinea 25 ment protects the seed from invertebrate soil pests and gen compound of Formula 1 with the other invertebrate pest agent erally can also protect roots and other plant parts in contact in the ratios specified in Table A. with the Soil of the seedling developing from the germinating Invertebrate pests are controlled in agronomic and nona seed. The seed treatment may also provide protection of foli gronomic applications by applying one or more compounds age by translocation of the compound of this invention or a of this invention, typically in the form of a composition, in a 30 second active ingredient within the developing plant. Seed biologically effective amount, to the environment of the pests, treatments can be applied to all types of seeds, including those including the agronomic and/or nonagronomic locus of infes from which plants genetically transformed to express special tation, to the area to be protected, or directly on the pests to be ized traits will germinate. Representative examples include controlled. those expressing proteins toxic to invertebrate pests, such as 35 Bacillus thuringiensis toxin or those expressing herbicide Thus the present invention comprises a method for control resistance Such as glyphosate acetyltransferase, which pro ling an invertebrate pest in agronomic and/or nonagronomic vides resistance to glyphosate. applications, comprising contacting the invertebrate pest or One method of seed treatment is by spraying or dusting the its environment with a biologically effective amount of one or seed with a compound of the invention (i.e. as a formulated more of the compounds of the invention, or with a composi 40 composition) before sowing the seeds. Compositions formu tion comprising at least one such compound or a composition lated for seed treatment generally comprise a film former or comprising at least one such compound and a biologically adhesive agent. Therefore typically a seed coating composi effective amount of at least one additional biologically active tion of the present invention comprises a biologically effec compound or agent. Examples of suitable compositions com tive amount of a compound of Formula 1, an N-oxide or salt prising a compound of the invention and a biologically effec 45 thereof, and a film former or adhesive agent. Seed can be tive amount of at least one additional biologically active coated by spraying a flowable Suspension concentrate compound or agent include granular compositions wherein directly into a tumbling bed of seeds and then drying the the additional active compound is present on the same granule seeds. Alternatively, other formulation types such as wetted as the compound of the invention or on granules separate from powders, Solutions, Suspoemulsions, emulsifiable concen those of the compound of the invention. 50 trates and emulsions in water can be sprayed on the seed. This To achieve contact with a compound or composition of the process is particularly useful for applying film coatings on invention to protect a field crop from invertebrate pests, the seeds. Various coating machines and processes are available compound or composition is typically applied to the seed of to one skilled in the art. Suitable processes include those the crop before planting, to the foliage (e.g., leaves, stems, listed in P. Kosters et al., Seed Treatment Progress and Pros flowers, fruits) of crop plants, or to the soil or other growth 55 pects, 1994 BCPC Mongraph No. 57, and references listed medium before or after the crop is planted. therein. One embodiment of a method of contact is by spraying. The treated seed typically comprises a compound of the Alternatively, a granular composition comprising a com present invention in an amount from about 0.1 g to 1 kg per pound of the invention can be applied to the plant foliage or 100 kg of seed (i.e. from about 0.0001 to 1% by weight of the the soil. Compounds of this invention can also be effectively 60 seed before treatment). A flowable suspension formulated for delivered through plant uptake by contacting the plant with a seed treatment typically comprises from about 0.5 to about composition comprising a compound of this invention 70% of the active ingredient, from about 0.5 to about 30% of applied as a soil drench of a liquid formulation, a granular a film-forming adhesive, from about 0.5 to about 20% of a formulation to the soil, a nursery box treatment or a dip of dispersing agent, from 0 to about 5% of a thickener, from 0 to transplants. Of note is a composition of the present invention 65 about 5% of a pigment and/or dye, from 0 to about 2% of an in the form of a soil drench liquid formulation. Also of note is antifoaming agent, from 0 to about 1% of a preservative, and a method for controlling an invertebrate pest comprising con from 0 to about 75% of a volatile liquid diluent. US 8,871,941 B2 109 110 The compounds of this invention can be incorporated into wasps, yellowjackets, hornets, ticks, spiders, ants, gnats, and a bait composition that is consumed by an invertebrate pest or the like, including individually or in combinations. used within a device Such as a trap, bait station, and the like. Nonagronomic applications include protecting an animal, Such a bait composition can be in the form of granules which particularly a vertebrate, more particularly a homeothermic comprise (a) active ingredients, namely a biologically effec Vertebrate (e.g., mammal or bird) and most particularly a tive amount of a compound of Formula 1, an N-oxide, or salt mammal, from an invertebrate parasitic pest by administering thereof; (b) one or more food materials; optionally (c) an a parasiticidally effective (i.e. biologically effective) amount attractant, and optionally (d) one or more humectants. Of note of a compound of the invention, typically in the form of a are granules or bait compositions which comprise between composition formulated for veterinary use, to the animal to be 10 protected. Therefore of note is a method for protecting an about 0.001-5% active ingredients, about 40-99% food mate animal comprising administering to the animal a parasiticid rial and/or attractant; and optionally about 0.05-10% humec ally effective amount of a compound of the invention. As tants, which are effective in controlling soil invertebrate pests referred to in the present disclosure and claims, the terms at very low application rates, particularly at doses of active “parasiticidal and “parasiticidally” refers to observable ingredient that are lethal by ingestion rather than by direct 15 effects on an invertebrate parasite pest to provide protection contact. Some food materials can function both as a food of an animal from the pest. Parasiticidal effects typically Source and an attractant. Food materials include carbohy relate to diminishing the occurrence or activity of the target drates, proteins and lipids. Examples of food materials are invertebrate parasitic pest. Such effects on the pest include Vegetable flour, Sugar, starches, animal fat, vegetable oil, necrosis, death, retarded growth, diminished mobility or less yeast extracts and milk Solids. Examples of attractants are ened ability to remain on or in the host animal, reduced odorants and flavorants, such as fruit or plant extracts, per feeding and inhibition of reproduction. These effects on fume, or other animal or plant component, pheromones or invertebrate parasite pests provide control (including preven other agents known to attract a target invertebrate pest. tion, reduction or elimination) of parasitic infestation or Examples of humectants, i.e. moisture retaining agents, are infection of the animal. Examples of invertebrate parasitic glycols and other polyols, glycerine and Sorbitol. Of note is a 25 pests controlled by administering a parasiticidally effective bait composition (and a method utilizing Such a bait compo amount of a compound of the invention to an animal to be sition) used to control at least one invertebrate pest selected protected include ectoparasites (arthropods, acarines, etc) from the group consisting of ants, termites and cockroaches. and endoparasites (helminths, e.g., nematodes, trematodes, A device for controlling an invertebrate pest can comprise the cestodes, acanthocephalans, etc.). In particular, the com present bait composition and a housing adapted to receive the 30 pounds of this invention are effective against ectoparasites bait composition, wherein the housing has at least one open including: flies such as Haematobia (Lyperosia) irritans ing sized to permit the invertebrate pest to pass through the (horn fly), Stomoxys calcitrans (stable fly), Simulium spp. opening so the invertebrate pest can gain access to the bait (blackfly), Glossina spp. (tsetse flies), Hydrotaea irritans composition from a location outside the housing, and wherein (head fly), Musca autumnalis (face fly), Musca domestica the housing is further adapted to be placed in or near a locus 35 (house fly), Morelia simplex (Sweat fly), Tabanus spp. of potential or known activity for the invertebrate pest. (horese fly), Hypoderma bovis, Hypoderma lineatum, Lucilia The compounds of this invention can be applied without sericata, Lucilia Cuprina (green blowfly), Caliphora spp. other adjuvants, but most often application will be of a for (blowfly), Protophormia spp., Oestrus ovis (nasal botfly), mulation comprising one or more active ingredients with Culicoides spp. (midges), Hippobosca equine, Gastrophilus Suitable carriers, diluents, and Surfactants and possibly in 40 instestinalis, Gastrophilus haemorrhoidalis and Gastrophi combination with a food depending on the contemplated end lus nasilis; lices such as Bovicola (Damalinia) bovis, Bovicola use. One method of application involves spraying a water equi, Haematopinus asini, Felicola subrostratus, Hetero dispersion or refined oil solution of a compound of the present doxus spiniger; Lignonathus setosus and Trichodectes canis; invention. Combinations with spray oils, spray oil concentra keds Such as Mellophagus Ovinus; mites such as Psoroptes tions, spreader Stickers, adjuvants, other solvents, and Syner 45 spp., Sarcoptes scabei, Chorioptes bovis, Demodex equi, gists Such as piperonyl butoxide often enhance compound Cheyletiella spp., Notoedres cati, Trombicula spp. and Oto efficacy. For nonagronomic uses such sprays can be applied dectes cyanotis (ear mites); ticks such as Ixodes spp., Boo from spray containers such as a can, a bottle or other con philus spp., Rhipicephalus spp., Amblyomma spp., Derma tainer, either by means of a pump or by releasing it from a centor spp., Hyalomma spp. and Haemaphysalis spp., fleas pressurized container, e.g., a pressurized aerosol spray can. 50 Such as Ctenocephalides felis (cat flea) and Ctenocephalides Such spray compositions can take various forms, for canis (dog flea). example, sprays, mists, foams, fumes or fog. Such spray Nonagronomic applications in the veterinary sector are by compositions thus can further comprise propellants, foaming conventional means such as by enteral administration in the agents, etc. as the case may be. Of note is a spray composition form of, for example, tablets, capsules, drinks, drenching comprising a biologically effective amount of a compound or 55 preparations, granulates, pastes, boli, feed-through proce a composition of the present invention and a carrier. One dures, Suppositories; or by parenteral administration, such as embodiment of Such a spray composition comprises a bio by injection (including intramuscular, Subcutaneous, intrave logically effective amount of a compound or a composition of nous, intraperitoneal), implants; by nasal administration; by the present invention and a propellant. Representative propel topical administration, for example, in the form of immersion lants include, but are not limited to, methane, ethane, pro 60 or dipping, spraying, washing, coating with powder, or appli pane, butane, isobutane, butene, pentane, isopentane, neopen cation to a small area of the animal, and through articles Such tane, pentene, hydrofluorocarbons, chlorofluorocarbons, as neck collars, ear tags, tail bands, limb bands or halters dimethyl ether, and mixtures of the foregoing. Of note is a which comprise compounds or compositions of the present spray composition (and a method utilizing such a spray com invention. position dispensed from a spray container) used to control at 65 Typically a parasiticidal composition according to the least one invertebrate pest selected from the group consisting present invention comprises a mixture of a compound of of mosquitoes, black flies, stable flies, deer flies, horse flies, Formula 1, an N-oxide or a salt thereof, with one or more US 8,871,941 B2 111 112 pharmaceutically or veterinarily acceptable carriers compris paste, aerosol, ointment, Salve or gel. More typically a topical ing excipients and auxiliaries selected with regard to the formulation is a water-soluble solution, which can be in the intended route of administration (e.g., oral, topical or form of a concentrate that is diluted before use. Parasiticidal parenteral administration Such as injection) and in accor compositions suitable for topical administration typically dance with standard practice. In addition, a Suitable carrier is comprise a compound of the present invention and one or selected on the basis of compatibility with the one or more more topically suitable carriers. In applications of a parasiti active ingredients in the composition, including Such consid cidal composition topically to the exterior of an animal as a erations as stability relative to pH and moisture content. line or spot (i.e. 'spot-on' treatment), the active ingredient is Therefore of note is a composition for protecting an animal expected to migrate over the surface of the active to cover from an invertebrate parasitic pest comprising a parasitically 10 effective amount of a compound of the invention and at least most or all of its external Surface area. As a result, the treated one carrier. animal is particularly protected from invertebrate pests that For parenteral administration including intravenous, intra feed off the epidermis of the animal such as ticks, fleas and muscular and Subcutaneous injection, a compound of the lice. Therefore formulations for topical localized administra present invention can beformulated in Suspension, Solution or 15 tion often comprise at least one organic solvent to facilitate emulsion in oily or aqueous vehicles, and may contain transport of the active ingredient over the skin and/or penetra adjuncts Such as Suspending, stabilizing and/or dispersing tion into the epidermis of the animal. Solvents commonly agents. Pharmaceutical compositions for injection include used as carriers in Such formulations include propylene gly aqueous solutions of water-soluble forms of active ingredi col, paraffins, aromatics, esters such as isopropyl myristate, ents (e.g., a salt of an active compound), preferably in physi glycol ethers, and alcohols such as ethanol and n-propanol. ologically compatible buffers containing other excipients or The rate of application required for effective control (i.e. auxiliaries as are known in the art of pharmaceutical formu “biologically effective amount') will depend on such factors lation. as the species of invertebrate to be controlled, the pest’s life For oral administration including Solutions (the most cycle, life stage, its size, location, time of year, host crop or readily available form for absorption), emulsions, Suspen 25 animal, feeding behavior, mating behavior, ambient moisture, sions, pastes, gels, capsules, tablets, boluses powders, gran temperature, and the like. Under normal circumstances, ules, rumen-retention and feed/water/lick blocks, a com application rates of about 0.01 to 2 kg of active ingredients per pound of the present invention can be formulated with hectare are sufficient to control pests in agronomic ecosys binders/fillers known in the art to be suitable for oral admin tems, but as little as 0.0001 kg/hectare may be sufficient or as istration compositions, such as Sugars (e.g., lactose, Sucrose, 30 much as 8 kg/hectare may be required. For nonagronomic mannitol, Sorbitol), starch (e.g., maize starch, wheat starch, rice starch, potato starch), cellulose and derivatives (e.g., applications, effective use rates will range from about 1.0 to methylcellulose, carboxymethylcellulose, ethylhydroxycel 50 mg/square meter but as little as 0.1 mg/square meter may lulose), protein derivatives (e.g., Zein, gelatin), and synthetic be sufficient or as much as 150 mg/square meter may be polymers (e.g., polyvinyl alcohol, polyvinylpyrrolidone). If 35 required. One skilled in the art can easily determine the bio desired, lubricants (e.g., magnesium Stearate), disintegrating logically effective amount necessary for the desired level of agents (e.g., cross-linked polyvinylpyrrolidinone, agar, alg invertebrate pest control. inic acid) and dyes or pigments can be added. Pastes and gels In general for veterinary use, a compound of Formula 1, an often also contain adhesives (e.g., acacia, alginic acid, ben N-oxide or a salt thereof, is administered in a parasiticidally tonite, cellulose, Xanthangum, colloidal magnesium alumi 40 effective amount to an animal to be protected from inverte num silicate) to aid in keeping the composition in contact with brate parasite pests. A parasiticidally effective amount is the the oral cavity and not being easily ejected. amount of active ingredient needed to achieve an observable If the parasiticidal compositions are in the form of feed effect diminishing the occurrence or activity of the target concentrates, the carrier is typically selected from high-per invertebrate parasite pest. One skilled in the art will appreci formance feed, feed cereals or protein concentrates. Such 45 ate that the parasitically effective dose can vary for the various feed concentrate-containing compositions can, in addition to compounds and compositions of the present invention, the the parasiticidal active ingredients, comprise additives pro desired parasitical effect and duration, the target invertebrate moting animal health or growth, improving quality of meat pest species, the animal to be protected, the mode of applica from animals for slaughter or otherwise useful to animal tion and the like, and the amount needed to achieve a particu husbandry. These additives can include, for example, Vita 50 lar result can be determined through simple experimentation. mins, antibiotics, chemotherapeutics, bacteriostats, fung For oral administration to homeothermic animals, the daily istats, coccidiostats and hormones. dosage of a compound of the present invention typically Compounds of the present invention have been discovered ranges from about 0.01 mg/kg to about 100 mg/kg, more to have favorable pharmacokinetic and pharmacodynamic typically from about 0.5 mg/kg to about 100 mg/kg, of animal properties providing systemic availability from oral adminis 55 body weight. For topical (e.g., dermal) administration, dips tration and ingestion. Therefore after ingestion by the animal and sprays typically contain from about 0.5 ppm to about to be protected, parasiticidally effective concentrations of 5000 ppm, more typically from about 1 ppm to about 3000 compounds of the invention in the bloodstream protect the ppm, of a compound of the present invention. treated animal from blood-sucking pests such as fleas, ticks The following abbreviations are used in the Index Tables and lice. Therefore of note is a composition for protecting an 60 A-C which follow: i is iso, tis tert, c is cyclo, Me is methyl, Et animal from an invertebrate parasite pest in a form for oral is ethyl, c-Pr is cyclopropyl and t-Bu is tert-butyl. Naphthyl administration (i.e. comprising, in addition to a parasiticid means naphthalenyl. (R) or (S) denotes the absolute chirality ally effective amount of a compound of the invention, one or of the asymmetric carbon center. The abbreviation “Ex.’ more carriers selected from binders and fillers suitable for stands for “Example' and is followed by a number indicating oral administration and feed concentrate carriers). 65 in which example the compound is prepared. In Index Table Formulations for topical administration are typically in the A, (R), refers to the combination of (R), with instances of form of a powder, cream, Suspension, spray, emulsion, foam, CR for B, B and B.

US 8,871,941 B2 119 120 INDEX TABLE D-continued mental compounds in these tests were sprayed at 250 and/or 50 ppm, and the test was replicated three times. After spraying Compd. of the formulated test compound, each test unit was allowed "H NMR Data (CDCls solution unless indicated otherwise)" to dry for 1 hand then a black, Screened cap was placed on top. 53 88.83 (d. 1H), 8.42 (d. 1H), 8.18 (d. 1H), 7.73 (d. 1H), The test units were held for 6 days in a growth chamber at 25° 7.70-7.55 (m, 7H), 7.50 (d. 1H), 7.46(dd, 1H), 6.84 (dd, 1H), 6.80 (d. 1H)4.26 (d. 1H), 3.90 (d. 1H). C. and 70% relative humidity. Plant feeding damage was then 89.24 (d. 1H), 8.75 (s, 1H), 8.52 (d. 1H), 8.45 (d. 1H), visually assessed based on foliage consumed and a pest mor 7.82-7.70 (m, 3H), 7.64 (brs, 1H), 7.58 (s, 2H), 7.44 (t, 1H), tality rating was also counted and calculated for each test unit. 7.37 (d. 1H).7.24 (dd, 1H), 4.87 (d. 2H), Of the compounds of Formula 1 tested the following pro O2 89.63 (d. 1H), 9.04 (brt, 1H), 8.93 (d. 1H), 8.60 (d. 1H), 8.52 10 (s, 1H), 7.86 (dd, 1H), 7.74 (dd.1H), 7.69 (dd. 1H), 7.57 (s, 2H), vided very good to excellent levels of control efficacy (20% or 7.46 (dd, 1H), 7.40 (d. 1H), 7.23 (dd, 1H), 4.85 (d. 2H), 4.31 less feeding damage or 80% or more mortality): 1, 2, 4, 5, 6, (d. 1H), 3.94 (d. 1H). 7,8,9, 10, 11, 12, 13, 14, 15, 16, 18, 19, 20, 21, 22, 23, 26, 27, 05 8 10.17 (s, 1H), 8.64 (d. 1H), 8.53 (d. 1H), 8.22 (d. 1H), 28, 29, 30, 31, 32,33, 34,35, 36,38, 39, 41,42, 43, 45,46, 47, 7.90 (d. 1H), 7.73 (dt, 1H), 7.68 (brt, 1H), 7.59 (d. 1H), 7.56 48, 49, 50, 51, 101, 102, 103, 104, 105, 106, 107*, 108*, (s. 2H), 7.46 (t, 1H).7.37 (d. 1H), 7.24 (dd, 1H), 4.85 (d. 2H), 15 4.27 (d.1H), 3.92 (d. 1H). 109*, 110, 111, 201 and 202. 88.95 (dd. 1H), 8.88 (dd, 1H), 8.55 (d. 1H), 8.26 (d. 1H), 7.83 * means very good to excellent levels of control efficacy (d. 1H), 7.72 (dt, 1H), 7.60-7.50 (m, 4H), 7.43 (t, 1H), 7.36 observed only at 250 ppm. (d. 1H).7.24 (dd, 1H), 4.85 (d. 2H), 4.72 (d. 1H), 4.42 (d. 1H). 88.89 (dd. 1H), 8.61 (d. 1H), 7.99 (d. 1H), 7.59 (d. 1H), 7.55 (s, 2H), 7.45 (m, 2H), 6.89 (brt, 1H), 4.68 (d. 1H), Test B 4.32 (d. 1H), 4.18 (m, 2H). 89.41 (brs, 1H), 8.91 (dd. 1H), 8.70 (dd, 1H), 8.46 (d. 1H), 8.21 For evaluating control of fall armyworm (Spodoptera fru (d. 1H), 7.75 (dt, 1H), 7.64 (d. 1H), 7.57 (s. 2H), 7.47 (dd. 1H), 7.43(t, 1H), 7.38 (d. 1H), 7.24 (dd, 1H), 5.14 (d. 2H), giperda) the test unit consisted of a small open container with 4.68 (d. 1H), 4.39 (d. 1H). a 4-5-day-old corn (maize) plant inside. This was pre-infested 09 88.88 (d. 1H), 8.47 (dd, 1H), 8.12 (brs, 1H), 7.97 (d. 1H), 7.53 (using a core sampler) with 10-151-day-old larvae on a piece (s, 2H), 7.47 (m, 3H), 4.74 (m, 2H), 4.59 (d. 1H), 4.25 (d. 1H). 25 of insect diet. Test compounds were formulated and sprayed 10 88.75 (d. 1H), 8.42 (d. 1H), 7.86 (d. 1H), 7.68 (dt, 1H), 7.57 (s. 2H), 7.55-7.35 (m, 5H), 7.31(s, 1H), 7.18 (dd, 1H), 4.82 at 250 and/or 50 ppm as described for Test A and replicated (d. 2H), 4.25(d. 1H), 3.90 (d. 1H), 2.44 (s.3H). three times. After spraying, the test units were maintained in 11 8 8.59 (d. 1H), 7.58 (s. 2H), 7.54 (d. 1H), 7.47 (t, 1H), a growth chamber and then the control efficacy was rated for 7.36-7.44(m, 2H), 7.10 (s, 1H), 6.80 (brt, 1H), 4.20 (d. 1H), each test unit as described for Test A. 4.08(m, 2H), 3.86 (d. 1H), 2.23 (s, 3H). 30 88.71 (d. 1H), 8.48 (m, 1H), 8.13 (d. 1H), 7.55-7.64 (m, 3H), Of the compounds of Formula 1 tested the following pro 7.49 (d. 1H), 7.44 (d. 1H), 7.35 (dd, 1H), 6.74 (t, 1H), vided very good to excellent levels of control efficacy (20% or 4.24 (d. 1H), 4.17 (m, 2H), 3.83 (d. 1H). less feeding damage or 80% or more mortality): 1, 2, 5, 6, 7, 88.79 (d. 1H), 8.50 (m, 2H), 8.35 (d. 1H), 7.50-7.72 (m, 7H), 8, 9, 10, 11, 12, 13, 14, 15, 16, 18, 19, 20, 21, 22, 23, 25, 26, 7.47 (d. 1H), 7.36 (d. 1H), 7.22 (dd. 1H), 4.83 (d. 2H), 28, 29, 30, 31, 32, 33, 34,35, 36, 39, 41, 42,46, 49, 51, 101, 4.28 (d. 1H), 3.89 (d. 1H). 35 102, 103, 104,106*, 107*, 110*, 111*, 201 and 202. H NMR data are in ppm downfield from tetramethylsilane. * means very good to excellent levels of control efficacy Couplings are designated by (s)-singlet, (d)-doublet, (t)-triplet, (q)-quartet, (m)-multiplet, (dd)-doublet of doublets, (dt)-doublet of triplets, (bris)-broad singlet, (brt)-broad triplet, observed only at 250 ppm. Test C BIOLOGICAL, EXAMPLES OF THE INVENTION 40 For evaluating control of potato leafhopper (Empoasca The following Tests demonstrate the control efficacy of fabae Harris) through contact and/or systemic means, the test compounds of this invention on specific pests. “Control effi unit consisted of a small open container with a 5-6 day old cacy” represents inhibition of invertebrate pest development Soleil bean plant (primary leaves emerged) inside. White (including mortality) that causes significantly reduced feed 45 sand was added to the top of the soil and one of the primary ing. The pest control protection afforded by the compounds is leaves was excised prior to application. Test compounds were not limited, however, to these species. See Index Tables A-C formulated and sprayed at 250 and/or 50 ppm, and the test was for compound descriptions. replicated three times as described for Test A. After spraying, the test units were allowed to dry for 1 hour before they were Test A 50 post-infested with 5 potato leafhoppers (18- to 21-day old adults). A black, Screened cap was placed on the top of the For evaluating control of diamondback moth (Plutella cylinder. The test units were held for 6 days in a growth xylostella) the test unit consisted of a small open container chamber at 19-21 C. and 50-70% relative humidity. The with a 12-14-day-old radish plant inside. This was pre-in control efficacy of each test unit was then visually assessed by fested with about 50 neonate larvae that were dispensed into 55 the insect mortality. the test unit via corn cob grits using a bazooka inoculator. The Of the compounds of Formula 1 tested the following pro larvae moved onto the test plant after being dispensed into the vided very good to excellent levels of control efficacy (80% or test unit. more mortality): 1, 2, 8, 10, 11, 14*, 15, 16, 18*, 19, 20, 21, Test compounds were formulated using a solution contain 26, 28, 31, 32*, 34, 36,38, 46*, 101, 102* and 106*. ing 10% acetone, 90% water and 300 ppm X-77TM Spreader 60 * means very good to excellent levels of control efficacy Lo-Foam Formula non-ionic Surfactant containing alky observed only at 250 ppm. larylpolyoxyethylene, free fatty acids, glycols and isopro panol (Loveland Industries, Inc. Greeley, Colo., USA). The Test D formulated compounds were applied in 1 mL of liquid through a SUJ2 atomizer nozzle with 1/8 JJ custom body 65 For evaluating control of the western flower thrips (Fran (Spraying Systems Co. Wheaton, Ill., USA) positioned 1.27 kliniella occidentalis) through contact and/or systemic cm (0.5 inches) above the top of each test unit. All experi means, the test unit consisted of a small open container with US 8,871,941 B2 121 122 a 5-7 day old Soleil Bean plant inside. Test compounds were formulated and sprayed at 250 and/or 50 ppm, and the test was replicated three times as described for Test A. After spraying, the test units were allowed to dry for 1 hour and then 22-27 adult thrips were added to each unit and then a black, screened cap was placed on top. The test units were held for 6 days at 25°C. and 45-55% relative humidity. A mortality rating was assessed along with a plant damage rating for each test unit. Of the compounds of Formula 1 tested the following pro vided very good to excellent levels of control efficacy (20% or 10 less feeding damage or 80% or more mortality): 1, 2, 8, 10, 11, 13*, 14*, 15*, 16, 18, 19, 20*, 21, 26, 32,33*, 34*, 35, 39*, 41, 42, 45*, 46*, 47*, 48*, 49, 51, 101 and 104. * means very good to excellent levels of control efficacy observed only at 250 ppm. 15 Test E For evaluating control of the cat flea (Ctenocephalides felis Bouche), a CD-1(R) mouse (about 30 g. male, obtained from Charles River Laboratories, Wilmington, Mass.) was orally dosed with a test compound in an amount of 10 mg/kg Solu bilized in propylene glycol/glycerol formal (60:40). Two hours after oral administration of the test compound, approxi mately 8 to 16 adult fleas were applied to each mouse. The 25 fleas were then evaluated for mortality 48 hours after flea application to the mouse. Of the compounds tested, the following compounds caused 30% or more mortality: 1*, 2, 10*, 41* and 51*. * means the compound caused 50% or more mortality. 30 What is claimed is: 1.8-bromo-5-quinolinecarboxaldehyde oxime.

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