USOO7754738B2

(12) United States Patent (10) Patent No.: US 7,754,738 B2 Lahm et al. (45) Date of Patent: Jul. 13, 2010

(54) PYRAZOLE AND PYRROLE CARBOXAMIDE 7,241,767 B2 7/2007 Clarket al. INSECTICDES 7,288,554 B2 * 10/2007 Finkelstein et al...... 514,341 2004.0102324 A1 5/2004 Annis et al.

(75) Inventors: George Philip Lahm, Wilmington, DE 2.8. 8. A. 183. Rerger et al. Strans' TE: Marti 2004/0242645 A1 12/2004 Clarket al...... 514,340 1Im1ngton, ; nomas IV artin 2005.0075372 A1 4, 2005 Lahm et al. Stevenson, Newark, DE (US) 2006/0205748 A1* 9, 2006 Annis et al...... 514,275 (73) Assignee: E.I. du Pont de Nemours and FOREIGN PATENT DOCUMENTS Company, Wilmington, DE (US) EP O 946 508 A1 10, 1999 EP O991 625 B1 6, 2005 (*) Notice: Subject to any disclaimer, the term of this JP 2129.171 5, 1990 patent is extended or adjusted under 35 WO WO98.28269 7, 1998 U.S.C. 154(b) by 0 days. WO WO98,57937 12/1998 WO WOO 170671 9, 2001 (21) Appl. No.: 10/514, 183 WO WOO3016300 2, 2003 WO WOO3016304 2, 2003 (22) PCT Filed: Jun. 10, 2003 WO WOO3O26415 4/2003 WO WOO3O27099 4/2003 (86). PCT No.: PCT/USO3A18609 OTHER PUBLICATIONS S371 (c)(1), Kordiketal, Pyrazolecarboxamide human neuropeptideY5 receptor (2),2). (4) Date: Nov. 10,9 2004 ligands with in vivo antifeedant activity, Bioorganic & Medicinal Chemistry Letters, 2001, 11(17), 2287-2290.* (87) PCT Pub. No.: WO03/106427 XPO02275434 Order Nos. 5K-0011, SK-014, 2H-016, SK-020, 5K026 and “Interchim Intermediates' Jul. 9, 2002, Interchim, 231 PCT Pub. Date: Dec. 24, 2003 Avenue. * cited by examiner (65) Prior Publication Data y US 2006/0167060A1 Jul 27, 2006 Pririmary ExaminerExaminer—Allon Alton NPIN Pryor Related U.S. Application Data (57)57 ABSTRACT (60) Provisional application No. 60/388,244, filed on Jun. This invention provides compounds of Formula (I), N-oxides 13, 2002. and salts thereof wherein: A is O or S: B is a phenyl ring or a s pyridine ring, each ring optionally substituted with 1 to 5 R; (51) Int. Cl. J is a pyrazole or a pyrrole heterocyclic ring system as defined AOIN 43/40 (2006.01) herein; and; R is H; or C-C alkyl, C-C alkenyl, C-C, A6 IK 3/44 (2006.01) alkynyl or C-C cycloalkyl each optionally Substituted with (52) U.S. Cl...... 514/332, 514/333, 514/341, one or more Substituents selected from the group consisting s s 514,406 of halogen, CN, NO, hydroxy, C-C alkoxy, C-C alky (58) Field of Classification Search ...... 51434. Ithio. C-C alkylsulfinyl, C1-C4 alkylsulfonyl, C2-C alkoxy 5147406. 332 333 carbonyl, C-C alkylamino, C-C dialkylamino and C-C, See application file for complete search histo s cycloalkylamino. Also disclosed are methods for controlling pp p ry. at least one invertebrate pest comprising contacting the inver (56) References Cited tebrate pest or its environment with a biologically effective amount of at least one compound of Formula I, an N-oxide or U.S. PATENT DOCUMENTS a salt thereof (e.g., as a composition described herein). This 5.998.424. A 12/1999 Galemmo, Jr. et al. invention also pertains to a composition comprising at least 6,020,357 A 2/2000 Pinto et al. one compound of Formula I, an N-oxide or a salt thereof; and 6,403,620 B1 6/2002 Galemmo, Jr. et al. at least one additional component selected from the group 6,548,512 B1 4/2003 Pinto et al. consisting of a Surfactant, a solid diluent and a liquid diluent. 6,602,895 B2 8/2003 Galemmo, Jr. et al. 6,747,047 B2 6, 2004 Lahm et al. 6,965,032 B2 11/2005 Freudenberger (I) 6,995, 178 B2 2/2006 Lahm et al. 7,038,057 B2 5, 2006 Annis et al. 7,087,598 B2 8, 2006 Clark 7,148,217 B2 12/2006 Selby 7,157,475 B2 1, 2007 Clark 7,179,824 B2 2/2007 Zimmerman 7,199,138 B2 4/2007 Finkelstein et al. 7,232,836 B2 6, 2007 Lahm et al. 8 Claims, No Drawings US 7,754,738 B2 1. PYRAZOLE AND PYRROLE CARBOXAMIDE INSECTICDES -continued

J-2 BACKGROUND OF THE INVENTION 5 This invention relates to certain heterocyclic amides, their N-oxides, salts and compositions Suitable for agronomic and nonagronomic uses, including those uses listed below, and a J-3 method of their use for controlling invertebrate pests in both R8, agronomic and nonagronomic environments. 10 The control of invertebrate pests is extremely important in -N achieving high crop efficiency. Damage by invertebrate pests to growing and stored agronomic crops can cause significant / - reduction in productivity and thereby resultin increased costs 3 to the consumer. The control of invertebrate pests in forestry, 15 R5 J-4 greenhouse crops, ornamentals, nursery crops, stored food 3 4 and fiber products, livestock, household, and public and ani W A-R7 mal health is also important. Many products are commer 2 y cially available for these purposes, but the need continues for new compounds that are more effective, less costly, less toxic, N environmentally safer or have different modes of action. R5 J-5 JP02129171 discloses pyrazolecarboxanilide derivatives 4 5 of Formula i as insecticides N 25 N NRs and 2 R5 J-6 R8. NH X3 A 30 N

wherein, R' through R and X' through R are as defined 35 therein. R" is H; or C-C alkyl, C-C alkenyl, C-C alkynyl or C-C cycloalkyl each optionally substituted with one or SUMMARY OF THE INVENTION more Substituents selected from the group consisting of halogen, CN, NO, hydroxy, C-C alkoxy, C-C alky This invention pertains to compounds of Formula I, and 40 lthio, C-C alkylsulfinyl, C-C alkylsulfonyl, C-C N-oxides or salts thereof alkoxycarbonyl, C-C alkylamino, C-C dialkylamino and C-C cycloalkylamino; or R" is C-C alkylcarbonyl, C-C alkoxycarbonyl, C-C, 45 alkylaminocarbonyl, or C-C dialkylaminocarbonyl: each R is independently selected from the group consist ing of H. C-C alkyl, C-C alkenyl, C-C alkynyl, C-C cycloalkyl, C-C haloalkyl, C-C haloalkenyl, C-C haloalkynyl, C-C halocycloalkyl, C-C 50 cyanoalkyl, halogen, CN, NO, piperidine, C-C wherein alkoxy, C-Chaloalkoxy, C-C alkylthio, C-C alkyl A is O or S: Sulfinyl, C-C alkylsulfonyl, C-C haloalkylthio. B is a phenyl ring or a pyridine ring, each ring Substituted C-C haloalkylsulfinyl, C-C haloalkylsulfonyl, with 1 to 5 R: C-C alkylamino, C-C dialkylamino, and C-C, J is a pyrazole or a pyrrole heterocyclic ring system 55 cycloalkylamino; or Selected from the group consisting of J-1, J-2, J-3, J-4. each R is independently selected from the group consist J-5 and J-6: ing of a phenyl, benzyl or phenoxy ring, each ring optionally substituted with one or more substituents Selected from the group consisting of C-C alkyl, C-C J-1 60 alkenyl, C-C alkynyl, C-C cycloalkyl, C-C haloalkyl, C-Chaloalkenyl, C-Chaloalkynyl, C-C, halocycloalkyl, halogen, CN, NO, C-C alkoxy, C-C, haloalkoxy, C-C alkylthio, C-C alkylsulfinyl, C-C, alkylsulfonyl, C-C alkylamino, C-Cs dialkylamino, 65 C-C cycloalkylamino, Ca-C, (alkyl)cycloalkylamino, C-C alkoxycarbonyl, C-C alkylaminocarbonyl, and C-Cs dialkylaminocarbonyl: US 7,754,738 B2 4 R is mers. “Cyanoalkyl denotes an alkyl group substituted with one cyano group. Examples of “cyanoalkyl” include NCCH NCCHCH and CHCH(CN)CH. “Alkylamio”, “dialky lamino', and the like, are defined analogously to the above examples. "Cycloalkyl includes, for example, cyclopropyl. cyclobutyl, cyclopentyl, and cyclohexyl. The term “cycloalkylamino' includes the same groups linked through a nitrogen atom Such as cyclopentylamino and cyclohexy lamino. 10 The term "hetero” in connection with rings or ring systems refers to a ring or ring system in which at least one ring atom is not carbon and which can contain 1 to 4 heteroatoms independently selected from the group consisting of nitrogen, each R. R* and R7 is independently selected from the oxygen and Sulfur, provided that each ring contains no more group consisting of H. C-C alkyl, C-C cycloalkyl, 15 than 4 nitrogens, no more than 2 oxygens and no more than 2 C-C haloalkyl, halogen, CN, C-C alkoxy, C-C, Sulfurs. The terms "heteroaromatic ring or ring system” and alkylthio, C-C haloalkoxy and C-C haloalkylthio; “aromatic fused heterobicyclic ring system’ includes fully and aromatic heterocycles and heterocycles in which at least one R is H. C-C alkyl, C-C haloalkyl, C-C alkenyl, ring of a polycyclic ring system is aromatic (where aromatic C-C haloalkenyl, C-C alkynyl, C-C haloalkynyl, indicates that the Hickel rule is satisfied). The heterocyclic or C-Chaloalkoxy. ring or ring system can be attached through any available This invention also pertains to a method for controlling at carbon or nitrogen by replacement of a hydrogen on said least one invertebrate pest comprising contacting the inverte carbon or nitrogen. brate pest or its environment with a biologically effective The term “halogen, either alone or in compound words amount of at least one compound of Formula I, an N-oxide or 25 such as “haloalkyl, includes fluorine, chlorine, bromine or a salt thereof (e.g., as a composition described herein). This iodine. Further, when used in compound words such as invention also relates to such a method wherein the inverte “haloalkyl or “halocycloalkyl, said alkyl or cycloalkyl may brate pest or its environment is contacted with a biologically be partially or fully substituted with halogen atoms which effective amount of at least one compound of Formula I, an may be the same or different. Examples of “haloalkyl N-oxide or a salt thereof, or with a biologically effective 30 include FC, CICH, CFCH and CFCC1. The terms amount of a composition comprising at least one compound “haloalkenyl', “haloalkynyl', “haloalkoxy”, “haloalky of Formula I, an N-oxide or a salt thereof; and a biologically lthio', and the like, are defined analogously to the term effective amount of at least one other biologically active “haloalkyl. Examples of “haloalkenyl' include (Cl), compound or agent for controlling invertebrate pests. C=CHCH, and CFCH-CH=CHCH. Examples of This invention also pertains to a composition comprising at 35 “haloalkynyl' include HC=CCHC1, CFC=C, CC1-C=C least one compound of Formula I, an N-oxide or a salt thereof; and FCHC=CCH. Examples of “haloalkoxy' include and at least one additional component selected from the group CFO, CC1-CHO, HCFCHCHO and CFCH.O. consisting of a Surfactant, a Solid diluent and a liquid diluent. Examples of “haloalkylthio' include CCIS, CFS, This invention also pertains to a composition comprising at CCCHS and CICHCHCHS. Examples of “haloalkyl least one compound of Formula I, an N-oxide or a salt thereof; 40 sulfinyl' include CFS(O), CC1-S(O), CFCHS(O) and and at least one other biologically active compound or agent. CFCFS(O). Examples of "haloalkylsulfonyl' include CFS DETAILS OF THE INVENTION (O), CC1-S(O), CFCHS(O) and CFCFS(O). Examples of “alkylcarbonyl' include C(O)CH, C(O) In the above recitations, the term “alkyl, used either alone 45 CHCHCH and C(O)CH(CH). Examples of “alkoxycar or in compound words such as “alkylthio’ or “haloalkyl bonyl include CHC(=O), CHCHC(=O), includes straight-chain or branched alkyl, such as, methyl, CHCHCHC(=O), (CH)CHOC(=O) and the different ethyl, n-propyl, i-propyl, or the different butyl, pentyl or butoxy- or pentoxycarbonyl isomers. Examples of 'alkylami hexyl isomers. “Alkenyl' includes straight-chain or branched nocarbonyl' include CH-NHC(=O), CHCH-NHC(=O), alkenes such as ethenyl, 1-propenyl, 2-propenyl, and the dif 50 CHCHCH-NHC(=O), (CH),CHNHC(=O) and the dif ferent butenyl, pentenyl and hexenyl isomers. “Alkenyl also ferent butylamino- or pentylaminocarbonyl isomers. includes polyenes such as 1,2-propadienyl and 2.4-hexadi Examples of “dialkylaminocarbonyl' include (CH)NC enyl. “Alkynyl' includes straight-chain or branched alkynes (=O), (CHCH)NC(=O), CHCH (CH)NC(=O), Such as ethynyl, 1-propynyl, 2-propynyl and the different CHCHCH (CH)NC(=O) and (CH),CHN(CH3)C butynyl, pentynyl and hexynyl isomers. “Alkynyl can also 55 (=O). include moieties comprised of multiple triple bonds such as The total number of carbon atoms in a Substituent group is 2.5-hexadiynyl. "Alkoxy' includes, for example, methoxy, indicated by the "C-C, prefix wherei andjare numbers from ethoxy, n-propyloxy, isopropyloxy and the different butoxy, 1 to 8. For example, C-C alkylsulfonyl designates methyl pentoxy and hexyloxy isomers. “Alkylthio' includes Sulfonyl through propylsulfonyl: C alkoxyalkyl designates branched or straight-chain alkylthio moieties such as meth 60 CHOCH, C, alkoxyalkyl designates, for example, CHCH ylthio, ethylthio, and the different propylthio and butylthio (OCH), CHOCH2CH2 or CHCHOCH; and C alkoxy isomers. “Alkylsulfinyl' includes both enantiomers of an alkyl designates the various isomers of an alkyl group Substi alkylsulfinyl group. Examples of “alkylsulfinyl' include tuted with an alkoxy group containing a total of four carbon CHS(O), CHCHS(O), CHCHCHS(O), (CH),CHS(O) atoms, examples including CHCH2CH2OCH and and the different butylsulfinyl isomers. Examples of “alkyl 65 CHCHOCHCH. sulfonyl include CHS(O), CHCHS(O), CHCHCHS In the above recitations, when a compound of Formula I is (O) (CH). CHS(O) and the different butylsulfonyl iso comprised of one or more heterocyclic rings, all Substituents US 7,754,738 B2 5 6 are attached to these rings through any available carbon or Such as a carboxylic acid or phenol. In the compositions and nitrogen by replacement of a hydrogen on said carbon or methods of this invention, the salts of the compounds of the nitrogen. invention are preferably suitable for the agronomic and/or When a compound is substituted with a substituent bearing non-agronomic uses described herein. a Subscript that indicates the number of said Substituents can As noted above, B is a phenyl ring or a pyridine ring, each exceed 1, said substituents (when they exceed 1) are indepen ring substituted with 1 to 5 R. Examples of said B rings dently selected from the group of defined substituents. Fur wherein said rings are substituted with 1 to 5 R include the ther, when the subscript indicates a range, e.g. (R), then the ring systems illustrated as B-1 to B-4 in Exhibit 1 below, number of substituents may be selected from the integers whereinn is an integer from 1 to 5 and R is as defined above. between i and j inclusive. 10 Note that some B groups can only be substituted with less The term “optionally substituted with one to three substitu than 5R groups (e.g. B-2through B-4 can only be substituted ents' and the like indicates that one to three of the available with 4 R). positions on the group may be substituted. When a group contains a substituent which can behydrogen, for example R' Exhibit 1 or R, then, when this substituent is taken as hydrogen, it is 15 recognized that this is equivalent to said group being unsub stituted. Compounds of this invention can exist as one or more B-1 Stereoisomers. The various Stereoisomers include enanti 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 B-2 when enriched relative to the other stereoisomer(s) or when separated from the other stereoisomer(s). Additionally, the skilled artisan knows how to separate, enrich, and/or to selec 25 tively prepare said stereoisomers. Accordingly, the present invention comprises compounds selected from Formula I, B-3 N-oxides and salts thereof. The compounds of the invention can be present as a mixture of stereoisomers, individual Ste and reoisomers, or as an optically active form. 30 One skilled in the art will appreciate that not all nitrogen B-4 containing heterocycles can form N-oxides since the nitrogen requires an available lone pair for oxidation to the oxide; one skilled in the art will recognize those nitrogen containing heterocycles which can form N-oxides. One skilled in the art 35 will also recognize that tertiary amines can form N-oxides. Synthetic methods for the preparation of N-oxides of hetero A preferred Bring is optionally substituted phenyl. cycles and tertiary amines are very well known by one skilled Of note are compounds of Formula I wherein in the art including the oxidation of heterocycles and tertiary A is O or S: amines with peroxy acids such as peracetic and m-chlorop 40 B is a phenyl ring or a pyridine ring, each ring Substituted erbenzoic acid (MCPBA), hydrogen peroxide, alkyl hydrop with 1 to 5 R: eroxides Such as t-butyl hydroperoxide, Sodium perborate, J is a pyrazole or a pyrrole heterocyclic ring system and dioxiranes such as dimethydioxirane. These methods for Selected from the group consisting of J-1, J-2, J-3, J-4. the preparation of N-oxides have been extensively described J-5 and J-6: and reviewed in the literature, see for example: T. L. Gilchrist 45 in Comprehensive Organic Synthesis, vol. 7, pp 748-750, S. V. Ley, Ed., Pergamon Press: M. Tisler and B. Stanovnik in J-1 Comprehensive Heterocyclic Chemistry, vol. 3, pp 18-20, A. R7, J. Boulton and A. McKillop, Eds. Pergamon Press: M. R. 4 3 Grimmett and B. R. T. Keene in Advances in Heterocyclic 50 / \, Chemistry, Vol. 43, pp 149-161, A. R. Katritzky, Ed., Aca N demic Press: M. Tisler and B. Stanovnik in Advances in N Heterocyclic Chemistry, vol. 9, pp. 285-291, A. R. Katritzky R5 and A. J. Boulton, Eds. Academic Press; and G. W. H. J-2 Cheeseman and E. S. G. Werstiuk in Advances in Heterocy 55 clic Chemistry, vol. 22, pp.390-392, A. R. Katritzky and A. J. Boulton, Eds., Academic Press. The salts of the compounds of the invention include acid addition salts with inorganic or organic acids such as hydro J-3 bromic, hydrochloric, nitric, phosphoric, Sulfuric, acetic, 60 R8, butyric, fumaric, lactic, maleic, malonic, oxalic, propionic, M salicylic, tartaric, 4-toluenesulfonic or Valeric acids. The salts 5 NI of the compounds of the invention also include those formed with organic bases (e.g., pyridine, ammonia, or triethy 4 W - 3 lamine) or inorganic bases (e.g., hydrides, hydroxides, or 65 carbonates of sodium, potassium, lithium, calcium, magne R5 sium or barium) when the compound contains an acidic group US 7,754,738 B2 7 8 haloalkyl, halogen, CN, C-C alkoxy, C-C alkylthio. -continued C-Chaloalkoxy and C-Chaloalkylthio; and J-4 R is H. C-C alkyl, C-C haloalkyl, C-C alkenyl, C-C haloalkenyl, C-C alkynyl, C-C haloalkynyl, 5 or C-Chaloalkoxy. Preferred compounds for reasons of better activity and/or ease of synthesis are: Preferred 1. Compounds of Formula I above, and N-oxides and salts thereof, wherein 10 J is J-1, J-2, J-3, or J-6. Preferred 2. Compounds Preferred 1 wherein A is O: R" is H: from 1 to 3 R' groups are other than H and are indepen 15 dently selected from the group consisting of C-C alkyl, C-C haloalkyl, C-C cyanoalkyl, halogen, CN, NO, piperidine, C-C alkoxy, C-C haloalkoxy, C-C, alkoxycarbonyl, C-C alkylthio, C-C alkylsulfinyl, C-C alkylsulfonyl, C-C haloalkylthio, C-C haloalkylsulfinyl and C-Chaloalkylsulfonyl; and at least one Ras defined immediately above is ortho to the NR'C(=A).J. moiety. R" is H; or C-C alkyl, C-C alkenyl, C-C alkynyl or Preferred 3. Compounds of Preferred 2 wherein C-C cycloalkyl each optionally Substituted with one or two Rare ortho to the NRC(A).J. moiety. more Substituents selected from the group consisting of Preferred 4. Compounds of Preferred 2 wherein halogen, CN, NO, hydroxy, C-C alkoxy, C-C alky R is H. C-C alkyl, C-Chaloalkyl, halogen or CN; and lthio, C-C alkylsulfinyl, C-C alkylsulfonyl, C-C R’ is H, CH, CF, CHCF, CHF, OCHCF, OCHF, or alkoxycarbonyl, C-C alkylamino, C-C dialkylamino halogen. and C-C cycloalkylamino; or Preferred 5. Compounds of Preferred 4 wherein 30 J is J-1; R" is C-C alkylcarbonyl, C-C alkoxycarbonyl, C-C, R is C1 or Br; and alkylaminocarbonyl, or C-C dialkylaminocarbonyl: R’ is halogen, OCHCF, OCHF, or CF. each R is independently selected from the group consist Preferred 6. Compounds of Preferred 4 wherein ing of H, C-C alkyl, C-C alkenyl, C-C alkynyl, J is J-2: C-C cycloalkyl, C-C haloalkyl, C-C haloalkenyl, 35 R is C1 or Br; and C-C haloalkynyl, C-C halocycloalkyl, C-C, R is CHCF, or CHF. cyanoalkyl, halogen, CN, NO, piperidine, C-C Preferred 7. Compounds of Preferred 4 wherein alkoxy, C-Chaloalkoxy, C-C alkoxycarbonyl, C-C J is J-3: alkylthio, C-C alkylsulfinyl, C-C alkylsulfonyl, R is C1 or Br; and C-C haloalkylthio, C-C haloalkylsulfinyl, C-C 40 R is CHCF, or CHF. haloalkylsulfonyl, C-C alkylamino, C-C dialky Preferred 8. Compounds of Preferred 4 wherein lamino, and C-C cycloalkylamino; or J is J-5; each R is independently selected from the group consist R is C1 or Br; and ing of a phenyl, benzyl or phenoxy ring, each ring R is CHCF, or CHF. optionally substituted with one or more substituents 45 Preferred 9. Compounds of Preferred 4 wherein selected from the group consisting of C-C alkyl, C-C, J is J-6: alkenyl, C-C alkynyl, C-C cycloalkyl, C-C R is C1 or Br; and haloalkyl, C-Chaloalkenyl, C-Chaloalkynyl, C-C, R is CHCF, or CHF. halocycloalkyl, halogen, CN, NO, C-C alkoxy, C-C, This invention also pertains to a composition comprising at haloalkoxy, C-C alkylthio, C-C alkylsulfinyl, C-C, 50 least one compound of Formula I, an N-oxide or a salt thereof; alkylsulfonyl, C-C alkylamino, C-Cs dialkylamino, and at least one additional component selected from the group C-C cycloalkylamino, Ca-C, (alkyl)cycloalkylamino, consisting of a Surfactant, a Solid diluent, and a liquid diluent. C-C alkoxycarbonyl, C-C alkylaminocarbonyl, and This invention also pertains to a composition comprising at C-Cs dialkylaminocarbonyl: least one compound of Formula I, an N-oxide or a salt thereof; R is 55 and at least one other biologically active compound or agent. The preferred compositions of the present invention are those which comprise the above preferred compounds. This invention also pertains to a method for controlling at least one invertebrate pest comprising contacting the inverte 60 brate pest or its environment with a biologically effective amount of at least one compound of Formula I, an N-oxide or a salt thereof (e.g., as a composition described herein). This invention also relates to such a method wherein the inverte brate pest or its environment is contacted with a biologically 65 effective amount of at least one compound of Formula I, an each Rand R7 is independently selected from the group N-oxide or a salt thereof, or with a biologically effective consisting of H. C-C alkyl, C-C cycloalkyl, C-C, amount of a composition comprising at least one compound US 7,754,738 B2 9 10 of Formula I, an N-oxide or a salt thereof; and a biologically Heterocyclic acids 4, where J is equal to an optionally effective amount of at least one other biologically active substituted pyrazole or an optionally substituted pyrrole compound or agent for controlling invertebrate pests. The include those of Formula J-1 through J-6. More preferred preferred methods of use are those involving the above pre analogs include the pyrazole and pyrrole acids that are Sub ferred compounds and compositions. 5 The compounds of Formula I can be prepared by one or stituted with Ras an optionally substituted phenylorpyridyl. more of the following methods and variations as described in Procedures for the synthesis of representative examples of Schemes 1-10. The definitions of A, B, J. R. R. R. R7 and each are detailed in Schemes 3-9. R in the compounds of Formulae I and 2-32 below are as The synthesis of representative pyrazole carboxylic acids defined above in the Summary of the Invention unless other 10 of Formula 5, which are related to Formula J-1 wherein R is wise indicated. Compounds of Formulae Ia-c are subsets of 2-pyridyl and attached to the nitrogen, is depicted in Scheme the compounds of Formula I. 3. Reaction of a pyrazole 6 with 2,3-dihalopyridines of For A typical procedure is detailed in Scheme 1 and involves mula 7 affords good yields of the 1-pyridylpyrazole 8 with coupling of an aniline oraminopyridine of Formula 2 with an good specificity for the desired regiochemistry. Metallation acid chloride of Formula 3 in the presence of a base to provide 15 the compound of Formula Ia. Typical bases include amines of a compound of Formula 8 with lithium diisopropylamide Such as triethylamine, diisopropylethylamine and pyridine; (LDA) followed by quenching of the lithium salt with carbon other bases includehydroxides such as sodium and potassium dioxide affords the pyrazole acids of Formula 5. Additional hydroxide and carbonates such as sodium carbonate and details for these procedures are also described in Examples 1 potassium carbonate. In certain instances it is useful to use 2O and 2. polymer-Supported acid scavengers such as polymer-bound equivalent of diisopropylethylamine and dimethylaminopy ridine, such as PS CHN(iPr), wherein PS is the polysty Scheme 3 rene backbone. In a Subsequent step, amides of Formula Ia X can be converted to thioamides of Formula Ibusing a variety 25 6 R7 of standard thio transfer reagents including phosphorus pen N21 R tasulfide and Lawesson’s reagent (i.e. 2,4-bis(4-methoxyphe R7 nyl)-1,3-dithia-2,4-diphosphetane-2,4-disulfide). S } \ ? \ 7 N N 1) LDA YN K2CO3, DMF R6 2) CO2 N1 N A J H On J N 6 2 --base - Na C solvent B 35 8 Ia (A is O) Ib (A is S)

As shown in Scheme 2, an alternate procedure for the 40 preparation of compounds of Formula Ia involves coupling of an aniline or aminopyridine of Formula 2 with an acid of Formula 4 in the presence of a dehydrating agent such as dicyclohexylcarbodiimide (DCC). Polymer supported reagents are again useful here, such as polymer-bound 45 equivalent of cyclohexylcarbodiimide (PS CH-N=C=N- cyclohexyl). Synthetic procedures of Schemes 1 and 2 are only representative examples of useful methods for the prepa ration of Formula I compounds, as the synthetic literature is The starting pyrazoles 6 wherein R is CF, C1 or Br are extensive for this type of reaction. 50 known compounds. Pyrazole 6 wherein R7 is CF can be prepared by literature procedures (J. Fluorine Chem. 1991, 53(1), 61-70). Pyrazoles 6 wherein R is C1 or Br can also be prepared by literature procedures (H. Reimlinger and A. Van O J Overstraeten, Chem. Ber: 1966, 99(10), 3350-7). A useful 1 NH n N couplingdehydrative reagent alternative method for the preparation of 6 wherein R is Clor B R -- Br is depicted in Scheme 4. OH B 2 4 Ia Scheme 4 60 One skilled in the art will also realize that acid chlorides of Formula 3 may be prepared from acids of Formula 4 by ( \ numerous well-known methods, for example but not limited YN 1. n-BuLi to, reaction of the acid with chlorinating reagents such as 2. RCC1-CC1R oxalyl chloride and thionyl chloride. Anilines and aminopy 65 S(O)NMe2 ridines of Formula 2 are commercially available or are readily prepared by numerous well known methods. US 7,754,738 B2 12 separated by chromatographic methods and converted to the -continued corresponding acids. Preferred R substituents include alkyl and haloalkyl groups.

N R TFA 6 (R 7 is C or Br) 5 S(O)NMe2 10

10 Metallation of the sulfamoyl pyrazole 9 with n-butyllithium followed by direct halogenation of the anion with either hexachloroethane (for R being Cl) or 1,2-dibromotetrachlo roethane (for R being Br) affords the halogenated derivatives 10. Removal of the sulfamoyl group with trifluoroacetic acid 15 (TFA) at room temperature proceeds cleanly and in good yield to afford the pyrazoles 6 wherein R is C1 or Brrespec tively. Further experimental details for this method are described in Example 2. The synthesis of representative pyrazole acids of Formula 14, which are related to Formula J-2 wherein R is 2-pyridyl and attached to the 5 position of the pyrazole ring, is depicted in Scheme 5. Reaction of the dimethylaminoylidene ketoester of Formula 12 with substituted hydrazines affords the pyridylpyrazoles 13. Preferred R substituents include alkyl 25 and haloalkyl, with trifluoroethyl especially preferred. The esters 13 are converted to the acids of Formula 14 by standard hydrolysis.

30 Scheme 5 R6 O O

21 OEt (MeO)2CHNMe2 35 He N-N

The synthesis of pyrrole acids of Formula 22, which are related to Formula J-4 wherein R is 2-pyridyland attached to the nitrogen of the pyrrole ring, is depicted in Scheme 7. 3-Chloro-2-aminopyridine 19 is a known compound (see J. Heterocycl. Chem. 1987, 24(5), 1313-16). A convenient preparation of 19 from 2-aminopyridine 18 involves protec tion, ortho-metallation, chlorination and Subsequent depro The synthesis of representative pyrazole acids of Formula tection. Treatment of a compound of Formula 19 with 2.5- 17, which are related to Formula J-3 wherein R is 2-pyridyl dimethoxytetrahydrofuran affords pyrrole 20. Formylation of and attached to the 3 position of the pyrazole ring as well as an pyrrole 20 to the aldehyde of Formula 21 can be accom alternative synthesis of Formula 14, is depicted in Scheme 6. 60 Reaction of the dimethylaminoylidene ketoester of Formula plished by using standard Vilsmeier-Haack formylation con 12 with hydrazine affords the pyrazole 15. Reaction of the ditions. Halogenation of a compound of Formula 21 with pyrazole 15 with alkylating agents R-LG (wherein LG is a N-halosuccinimides (NXS) occurs preferentially at the 4 leaving group Such as halogen (e.g., Br, I), OS(O)CH position of the pyrrole ring. Oxidation of the halogenated (methanesulfonate), OS(O)CF, OS(O). Ph-p-CH (p-tolu 65 aldehyde affords the pyridylpyrrole acids of Formula 22. The enesulfonate), and the like) affords a mixture of pyridylpyra oxidation can be accomplished by using a variety of standard Zoles 13 and 16. This mixture of pyrazole isomers is readily oxidation conditions. US 7,754,738 B2 13 14

-continued Scheme 7 C

21 1) t-BuCOCI 5 soph

2) 2 eq. n-BuLi N 3) CCl6 TBAF N NH2 4sic 18 C EtOC 21 MeO O OMe 10 26 C N N NH2 -e-r 21 19 HOAc N 8 1) R-LG 21 C 1s N NH t NaOH / 3) HCI N DMF EtOC N N \ pool, 27 S. 2O The synthesis of pyrrole acids of Formula 32, which are 21 related to Formula J-6 wherein R is 2-chlorophenyl or 2-py CHO ridyl, is depicted in Scheme 9. Reaction of a cinnamic ester of s N 1) NXS Formula 29 with tosylmethyl isocyanide 30 (TosMIC) pro N 2) oxidation vides a pyrrole of Formula 31. For a leading reference to this S. X is halogen method see, Xu, Z. et al.J. Org. Chem. 1998, 63, 5031-5041. 21 Reaction of a compound of Formula 31 with an alkylating 21 C agent of Formula R-LG (wherein LG is a leaving group as COOH 30 defined above) followed by hydrolysis of the ester affords a N pyrrole acid of Formula 32. N N N S. Scheme 9 7 35 R C 22 21 wherein R is Clor Br ToSMIC N 30 N 21 COEt - - 40 The synthesis of pyrrole acids of Formula 28, which are 29 related to Formula J-5 wherein R is phenyl or 2-pyridyl and 21 C attached to the 2 position of the pyrrole ring, is depicted in Scheme 8. Cycloaddition of an allene of Formula 25 with an S. 1) R8-LG arylsulfonamide of Formula 24 (see Pavri, N. P.; Trudell, M. as N e 2. No L.J. Org. Chem. 1997, 62,2649-2651) affords the pyroline of NH i. Formula 26. Treatment of a pyrroline of Formula 26 with EtOC S. tetrabutylammonium fluoride (TBAF) gives a pyrrole of For- 2 mula 27. Reaction of a pyrrole 27 with alkylating agents 31 R-LG (wherein LG is a leaving group as defined above) 50 21 C followed by hydrolysis affords a pyrrole acid of Formula 28.

N e Scheme 8 N-R C 55 S. 21 HOC N PhSONH2 32 N CHO 23 The synthesis of pyrazole amide analogs of Formula Ic is 21 C 60 depicted in Scheme 10. This procedure takes advantage of the O 4 NeoE lithiated derivative of Formula 8. Treatment of a compound of N 2NSA 21 Formula 8 with lithium diisopropylamide (LDA) followed by N 7Np, 25 quenching of the lithium salt with aryl isocyanate affords O PPh 65 compounds of Formula Ic, a subset of the compounds of 24 Formula I. Additional details for this procedure are described in Example 1. US 7,754,738 B2 15 16 remove solids. N,N-Dimethylformamide and excess dichlo ropyridine were removed by distillation at atmospheric pres Scheme 1() sure. Distillation of the product at reduced pressure (b.p. 139-141° C., 7 mm) afforded the title compound as a clear R7 R7 yellow oil (113.4 g). H NMR (CDC1) & 6.78 (s, 1H), 7.36 (t, 1H), 7.93 (d. 1H), { y { \ NH 8.15 (s, 1H), 8.45 (d. 1H). N 1) LDA N B Step B: Preparation of 1-(3-chloro-2-pyridinyl)-3-(trifluo R6 2) B-NCO O 10 romethyl)-1H-pyrazole-5-carboxylic acid N N N R6 To a solution of 3-chloro-2-3-(trifluoromethyl)-1H-pyra Zol-1-ylpyridine (i.e. the pyrazole product from Step A) 2 2 (105.0 g, 425 mmol) in dry tetrahydrofuran (700 mL) at -75° 8 Ic C. was added via cannula a -30°C. solution of lithium diiso 15 propylamide (425 mmol) in dry tetrahydrofuran (300 mL). The deep red solution was stirred for 15 minutes, after which It is recognized that some reagents and reaction conditions time carbon dioxide was bubbled through at 63°C. until the described above for preparing compounds of Formula I may Solution became pale yellow and the exothermicity ceased. not be compatible with certain functionalities present in the The reaction was stirred for an additional 20 minutes and then intermediates. In these instances, the incorporation of protec quenched with water (20 mL). The solvent was removed tion/deprotection sequences or functional group interconver under reduced pressure, and the reaction mixture was parti sions into the synthesis will aid in obtaining the desired prod tioned between ether and 0.5 N aqueous sodium hydroxide ucts. The use and choice of the protecting groups will be solution. The aqueous extracts were washed with ether (3x), apparent to one skilled in chemical synthesis (see, for filtered through Celite(R) diatomaceous filter aid to remove example, Greene, T. W.; Wuts, P. G. M. Protective Groups in residual solids, and then acidified to a pH of approximately 4, Organic Synthesis, 2nd ed.: Wiley: New York, 1991). One 25 at which point an orange oil formed. The aqueous mixture skilled in the art will recognize that, in some cases, after the was stirred vigorously and additional acid was added to lower introduction of a given reagent as it is depicted in any indi the pH to 2.5-3. The orange oil congealed into a granular vidual scheme, it may be necessary to perform additional solid, which was filtered, washed successively with water and routine synthetic steps not described in detail to complete the 30 1 N hydrochloric acid, and dried under vacuum at 50° C. to synthesis of compounds of Formula I. One skilled in the art afford the title product as an off-white solid (130 g). (Product will also recognize that it may be necessary to perform a from another run following similar procedure melted at 175 combination of the steps illustrated in the above schemes in 176° C.) an order other than that implied by the particular sequence 'HNMR (DMSO-d) & 7.61 (s, 1H), 7.76 (dd. 1H),8.31 (d. presented to prepare the compounds of Formula I. 1H), 8.60 (d. 1H). One skilled in the art will also recognize that compounds of Formula I and the intermediates described herein can be Step C: Preparation of Preparation of N-(2-chloro-6-meth Subjected to various electrophilic, nucleophilic, radical, orga ylphenyl-1-(3-chloro-2-pyridinyl)-3-(trifluoromethyl)-1H nometallic, oxidation, and reduction reactions to add Sub pyrazole-5-carboxamide stituents or modify existing Substituents. A solution of 3-chloro-2-3-(trifluoromethyl)-1H-pyrazol Without further elaboration, it is believed that one skilled 40 1-ylpyridine (i.e. the pyrazole product from Step A) (2.72 g, in the art using the preceding description can utilize the 11.14 mmol) intetrahydrofuran (50 ml) was cooled to -70° C. present invention to its fullest extent. The following Lithium diisopropylamine (2M in THF/Heptane, 5.5 mL, Examples are, therefore, to be construed as merely illustra 11.0 mmol) was added over 2 minutes and the mixture was tive, and not limiting of the disclosure in any way whatsoever. stirred for 15 minutes. 2-Chloro-6-methylphenyl isocyanate Percentages are by weight except for chromatographic Sol 45 (1.90 g, 11.33 mmol) was added via syringe. The mixture was vent mixtures or where otherwise indicated. Parts and per allowed to warm to 20° C. and quenched with a saturated centages for chromatographic solvent mixtures are by Vol aqueous Solution of ammonium chloride (50 mL). The reac ume unless otherwise indicated. "HNMR spectra are reported tion mass was extracted with ethyl acetate (100 mL), dried in ppm downfield from tetramethylsilane; S is singlet, d is over magnesium sulfate and concentrated. Chromatography doublet, t is triplet, q is quartet, m is multiplet, dd is doublet of 50 on silica gel with a gradient of 3:1 hexanes/ethylacetate to 1:1 doublets, dt is doublet of triplets, brs is broad singlet. hexanes/ethyl acetate afforded the title compound, a com pound of the present invention as a solid (3.0 g) melting at Example 1 212-213° C. H NMR (CDC1) & 2.24 (3H), 7.1 (1H), 7.2 (1H), 7.25 Preparation of N-(2-chloro-6-methylphenyl)-1-(3- 55 (1H), 7.4 (1H), 7.6 (1H), 7.9 (1H), 8.5 (1H). chloro-2-pyridinyl)-3-(trifluoromethyl)-1H-pyrazole 5-carboxamide Example 2 Preparation of N-(2-bromo-4,6-difluorophenyl)-1-(3- Step A: Preparation of 3-chloro-2-3-(trifluoromethyl)-1H 60 pyrazol-1-ylpyridine chloro-2-pyridinyl)-3-bromo-1H-pyrazole-5-car To a mixture of 2,3-dichloropyridine (99.0g, 0.67 mol) and boxamide 3-(trifluoromethyl)-pyrazole (83 g, 0.61 mol) in dry N.N- dimethylformamide (300 mL) was added potassium carbon Step A: Preparation of 3-bromo-N,N-dimethyl-1H-pyrazole ate (166.0 g, 1.2 mol) and the reaction was then heated to 65 1-sulfonamide 10-125° C. over 48 hours. The reaction was cooled to 100° C. To a solution of N-dimethylsulfamoylpyrazole (44.0 g, and filtered through Celite R diatomaceous filter aid to 0.251 mol) in dry tetrahydrofuran (500 mL) at -78°C. was US 7,754,738 B2 17 18 added dropwise a solution of n-butyllithium (2.5M in hexane, -76°C., and carbon dioxide was then bubbled through for 10 105.5 mL, 0.264 mol) while maintaining the temperature minutes, causing warming to -57°C. The reaction mixture below 60°C. A thick solid formed during the addition. Upon was warmed to -20° C. and quenched with water. The reac completion of the addition the reaction mixture was main tion mixture was concentrated and then taken up in water (1 tained for an additional 15 minutes, after which time a solu 5 L) and ether (500 mL), and then aqueous sodium hydroxide tion of 1,2-dibromotetrachloroethane (90 g, 0.276 mol) in solution (1 N. 20 mL) was added. The aqueous extracts were tetrahydrofuran (150 mL) was added dropwise while main washed with ether and acidified with hydrochloric acid. The taining the temperature below -70° C. The reaction mixture precipitated solids were filtered, washed with water and dried turned a clear orange; stirring was continued for an additional to afford the title product as a tan solid (27.7g). (Product from 15 minutes. The -78°C. bath was removed and the reaction 10 another run following similar procedure melted at 200-201 was quenched with water (600 mL). The reaction mixture was C.) extracted with methylene chloride (4x), and the organic 'HNMR (DMSO-d) & 7.25 (s, 1H), 7.68 (dd. 1H),8.24 (d. extracts were dried over magnesium Sulfate and concentrated. 1H), 8.56 (d. 1H). The crude product was further purified by chromatography on silica gel using methylene chloride-hexane (50:50) as eluent 15 Step E: Preparation of N-(2-bromo-4,6-difluorophenyl)-1- to afford the title product as a clear colorless oil (57.04 g). (3-chloro-2-pyridinyl)-3-bromo-1H-pyrazole-5-carboxam "H NMR (CDC1) & 3.07 (d. 6H), 6.44 (m, 1H), 7.62 (m, ide 1H). Oxalyl chloride (0.043 mL, 0.5 mmol) was added to a mixture of 3-bromo-1-(3-chloro-2-pyridinyl)-1H-pyrazole Step B: Preparation of 3-bromopyrazole 5-carboxylic acid (i.e. the product of Step D) (200 mg. 0.66 To trifluoroacetic acid (70 mL) was slowly added 3-bromo mmol) and two drops of N,N-dimethylformamide (DMF) in N,N-dimethyl-1H-pyrazole-1-sulfonamide (i.e. the bro 30 mL of methylene chloride at room temperature and the mopyrazole product of Step A) (57.04 g). The reaction mix reaction was stirred for 10 minutes. After this time a catalytic ture was stirred at room temperature for 30 minutes and then amount of 4-(dimethylamino)pyridine was added, followed concentrated at reduced pressure. The residue was taken up in 25 by dropwise addition of a mixture of triethylamine (184 mL, hexane, insoluble solids were filtered off, and the hexane was 1.4 mmol) and 2-bromo-4,6-difluoroaniline in 10 mL of evaporated to afford the crude product as an oil. The crude methylene chloride. The reaction was stirred overnight and product was further purified by chromatography on silica gel then concentrated to near dryness. Chromatography on silica using ethyl acetate/dichloromethane (10:90) as eluent to gel with hexane/ethyl acetate gradient as eluent (9:1 to 1:1) afford an oil. The oil was taken up in dichloromethane, neu 30 afforded an oil. The oil was then cooled in dry ice and tritu tralized with aqueous sodium bicarbonate solution, extracted rated with ether/hexane to provide the title compound (0.22 with methylene chloride (3x), dried over magnesium sulfate g), a compound of the present invention, as a solid melting at and concentrated to afford the title product as a white solid 138-1399 C. (25.9 g), m.p. 61-4°C. "H NMR (CDC1) & 6.90 (m, 1H), 6.98 (s, 1H), 7.18 (m, "H NMR (CDC1) & 6.37 (d. 1H), 7.59 (d. 1H), 12.4 (brs, 35 1H). 1H), 7.40 (dd. 1H), 7.55 (brs, 1H), 7.90 (d. 1H), 8.47 (d. 1H). Step C: Preparation of 2-(3-bromo-1H-pyrazol-1-yl)-3-chlo Example 3 ropyridine To a mixture of 2,3-dichloropyridine (27.4g, 185 mmol) Preparation of 1-(3-chloro-2-pyridinyl)-N-(2,4- and 3-bromopyrazole (i.e. the product of Step B) (25.4g, 176 40 dichlorophenyl)-3-(trifluoromethyl)-1H-pyrazole-5- mmol) in dry N,N-dimethylformamide (88 mL) was added carboxamide potassium carbonate (48.6 g., 352 mmol), and the reaction mixture was heated to 125° C. for 18 hours. The reaction To a solution of 1-(3-chloro-2-pyridinyl)-3-(trifluorom mixture was cooled to room temperature and poured into ice ethyl)-1H-pyrazole-5-carboxylic acid (i.e. the product from water (800 mL). A precipitate formed. The precipitated solids 45 Step B in Example 1) (6.0 g, 20.76 mmol) in 60 mL of were stirred for 1.5 hours, filtered and washed with water methylene chloride was added oxalyl chloride (5.7g, 44.88 (2x100 mL). The solid filter cake was taken up in methylene mmol) followed by two drops of DMF. The mixture was chloride and washed sequentially with water, 1N hydrochlo stirred for two hours after which time the reaction was con ric acid, Saturated aqueous Sodium bicarbonate Solution, and 50 centrated on a rotary evaporator at reduced pressure, taken up brine. The organic extracts were then dried over magnesium in chloroform, and concentrated a second time to remove sulfate and concentrated to afford 39.9 g of a pink solid. The residual oxalyl chloride. The resultant acid chloride was used crude Solid was suspended in hexane and stirred vigorously directly in the next step. for 1 hour. The solids were filtered, washed with hexane and dried to afford the title product as an off-white powder (30.4 To a solution of 2,4-dichloroaniline (382 mg, 2.35 mmol) 55 in 3 mL of dry tetrahydrofuran was added a solution of the g) determined to be >94% pure by NMR. This material was acid chloride (307 mg, 1.0 mmol) in 3 mL of chloroform, and used without further purification in Step D. the mixture was stirred at room temperature for four hours. "H NMR (CDC1) & 6.52 (s, 1H), 7.30 (dd. 1H), 7.92 (d. After this time the reaction was partitioned between chloro 1H), 8.05 (s, 1H), 8.43 (d. 1H). form and Saturated aqueous sodium bicarbonate. The chloro Step D: Preparation of 3-bromo-1-(3-chloro-2-pyridinyl)- 60 form extracts were dried over magnesium sulfate, filtered and 1H-pyrazole-5-carboxylic acid concentrated under reduced pressure. Chromatography on To a solution of 2-(3-bromo-1H-pyrazol-1-yl)-3-chloropy silica gel with hexane/ethyl acetate as eluent (8:1) afforded 67 ridine (i.e. the product of Step C) (30.4g, 118 mmol) in dry mg of the title compound, a compound of the present inven tetrahydrofuran (250 mL) at -76°C. was added dropwise a tion, as a colorless oil. solution of lithium diisopropylamide (118 mmol) in tetrahy 65 H NMR (CDC1) & 7.16 (s, 1H), 7.2 (m, 1H), 7.42 (s, 1H), drofuran at Such a rate as to maintain the temperature below 7.48 (dd. 1H), 7.94 (dd. 1H), 8.17 (dd. 1H), 8.38 (brs, 1H), -71° C. The reaction mixture was stirred for 15 minutes at 8.52 (dd. 1H). US 7,754,738 B2 19 20 Example 4 added to a Whatman(R) MBPP filter plate that had previously been prepared by charging each well with 200 mg of Hydro Preparation of the Amide Library of Index Table B matrix (plus-calcined diatomaceous earth) (Varian, Inc. Wal nut Creek, Calif., USA) and then hydrating with 200LL of 0.1 To a solution of 1-(3-chloro-2-pyridinyl)-3-(trifluorom 5 M sodium hydroxide. The plate was gravity filtered into a ethyl)-1H-pyrazole-5-carboxylic acid (i.e. the product from pre-tared micronics plate and the Hydromatrix was washed Step B in Example 1) (1.467 g. 6.3 mmol) in 25 mL of with 300 uL of methylene chloride into the same plate. A methylene chloride was added oxalyl chloride (2.6 mL, 37.8 sample was removed for LCMS (Liquid Chromatography mmol). After the initial gas evolution ceased, the Solution was Mass Spectrometry) analysis and the solvent was then heated to reflux for 2.5 h. The mixture was then cooled to 10 removed under reduced pressure. The prepared library is room temperature and concentrated. The resultant yellow oil reported in Index Table B. Product analysis was done by using residue was triturated with methylene chloride (3x25 mL) to LCMS on a Micromass LCTTM TOF (time of flight) mass remove traces of oxalyl chloride. A 0.1 M stock solution of spectrometer (Macromass Inc. Manchester, UK) operating in this acid chloride was prepared by diluting the residue to a electrospray ionization mode and collecting data from 100 volume of 63 mL with methylene chloride. The stock solution 15 1200 Daltons for 9 minutes. The LC system was a Waters was used immediately in the next step. A 0.1 M stock solution Alliance 2790 with a 2.1x30 mm Zorbax SB-C18 Rapid in methylene chloride of each of the anilines used in the Resolution column (Waters Co. Milford, Mass., USA). A six library was prepared. A 0.83 M stock solution of triethy minute linear gradient of 10% acetonitrile in water with 0.1% lamine in methylene chloride containing 0.5 mg/mL of formic acid to 100% acetonitrile with 0.1% formic acid fol 4-(dimethylamino)pyridine was prepared. In the drybox, the lowed by a three minute hold was used to elute the com aniline stock solutions (250LL) were distributed to individual pounds. Each injection was 3 uI of an approximately 0.5 wells of a 96 well block via pipette. To each well was added mg/mL solution. The observed M+H (protonated molecular the acid chloride stock solution (300 LL) followed by the ion) is reported in Index Table B. triethylamine stock solution 1 (50 uL). The block was then By the procedures described herein together with methods sealed, removed from the drybox and placed in a modified 25 known in the art, the following compounds of Tables 1 to 7 FlexchemR) oven (Robbins Scientific Co. Sunnyvale, Calif., can be prepared. The following abbreviations are used in the USA) to agitate at room temperature overnight under nitrogen Tables: t is tertiary, S is secondary, n is normal, i is iso, c is atmosphere. The top of the block was then removed and cyclo, Me is methyl, Et is ethyl, Pr is propyl, i-Pris isopropyl. trisamine resin (75 mg) was added to each well. The block t-Bu is tertiary butyl, Ph is phenyl, OMe is methoxy, OEt is was resealed and agitated overnight. The contents of the block 30 ethoxy, SMe is methylthio, SEt is ethylthio, CN is cyano, NO. were filtered into a 96 well microtiter plate and washed with is nitro, TMS is trimethylsilyl, S(O)Me is methylsulfinyl, and 200 uL of methylene chloride. The combined filtrates were S(O)Me is methylsulfonyl.

TABLE 1. | N-Cl N2 N1 NN R7 O S.

R2a 2x^-N H R2b l S. ySa. R2& R2c R7 R2a R2b R2c R7

H C H H Br H C 2-F H Br H C 2-C H Br H C 2-Br H Br H C 2- H Br H C 2-Me H Br H C 2-E H Br H C 2-CF H Br H C 2-OCFH H Br 4-F C 2-F 4-F Br 4-F C 2-C 4-F Br 4-F C 2-Br 4-F H Br 4-F C 2- 4-F Br 4-F C 2-Me 4-F H Br 4-F C 2-Et 4-F H Br 4-F C 2-CF 4-F Br 4-F C 2-OCFH 4-F Br 4-CI C 2-F 4-CI Br 4-CI C 2-C 4-CI Br 4-CI C 2-Br 4-CI Br

US 7,754,738 B2 31 32

TABLE 2-continued

3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3

3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3

US 7,754,738 B2 37 38

TABLE 2-continued

US 7,754,738 B2 41 42

TABLE 3-continued US 7,754,738 B2 43 44

TABLE 3-continued

R2e

Me Me Me Me Me Me Me Me Me Me Me Me Me Me Me Me Me Me Me Me Me Me Me Me Me Me Me Me Me Me Me Me Me Me Me C C C C C C C 2 C C C C C C C C C C C C C C

US 7,754,738 B2 57 58

TABLE 4-continued

N YN1Q R7 M 4 O S 3

N n H

R" is attached to the 5 position R" is attached to the 4 position

R2 i R2a R2& R2e R7

4-Br Br 2-Me 4-Br 6-F Br 4-Br Br 2-Et 4-Br 6-F Br 4-Br Br 2-CF 4-Br 6-F Br 4-Br Br 2-OCF2H 4-Br 6-F Br

TABLE 5

OCH OCH OCH OCH OCH OCH OCH OCH OCH OCH OCH OCH OCH OCH eF3e OCH 3 OCH OCH OCH OCH OCH OCH OCH OCH OCH OCH OCH OCH OCH OCH OCH OCH

US 7,754,738 B2 63 64

TABLE 5-continued

US 7,754,738 B2 75 76 carrier comprising at least one of a liquid diluent, a solid TABLE 7-continued diluent or a Surfactant. The formulation or composition ingre dients are selected to be consistent with the physical proper ties of the active ingredient, mode of application and environ mental factors such as soil type, moisture and temperature. Useful formulations include liquids Such as Solutions (includ ing emulsifiable concentrates), Suspensions, emulsions (in cluding microemulsions and/or Suspoemulsions) and the like which optionally can be thickened into gels. Useful formula 10 tions further include solids such as dusts, powders, granules, pellets, tablets, films, and the like which can be water-dis persible (“wettable') or water-soluble. Active ingredient can be (micro)encapsulated and further formed into a suspension or solid formulation; alternatively the entire formulation of 15 active ingredient can be encapsulated (or "overcoated'). Encapsulation can control or delay release of the active ingre dient. Sprayable formulations can be extended in suitable W media and used at spray Volumes from about one to several hundred liters per hectare. High-strength compositions are primarily used as intermediates for further formulation. The formulations will typically contain effective amounts of active ingredient, diluent and surfactant within the follow ing approximate ranges that add up to 100 percent by weight.

25

Weight Percent Active Ingredient Diluent Surfactant 30 Water-Dispersible and S-90 O-94 1-15 Water-soluble Granules, Tablets and Powders. Suspensions, Emulsions, 5-50 40-95 O-15 Solutions (including 35 Emulsifiable Concentrates) Dusts 1-2S 70-99 O-5 Granules and Pellets O.O1-99 S-99.99 O-15 High Strength Compositions 90-99 O-10 O-2 -Me

40 Typical solid diluents are described in Watkins, et al., Handbook of Insecticide Dust Diluents and Carriers, 2nd Ed., Dorland Books, Caldwell, N.J. Typical liquid diluents are described in Marsden, Solvents Guide, 2nd Ed., Inter science, New York, 1950. McCutcheon's Detergents and 45 Emulsifiers Annual. Allured Publ. Corp., Ridgewood, N.J., as s well as Sisely and Wood, Encyclopedia of Surface Active -Me Agents, Chemical Publ. Co., Inc., New York, 1964, list sur factants and recommended uses. All formulations can contain 3 minor amounts of additives to reduce foam, caking, corro 50 Sion, microbiological growth and the like, or thickeners to increase viscosity. Surfactants include, for example, polyethoxylated alco s hols, polyethoxylated alkylphenols, polyethoxylated sorbitan fatty acid esters, dialkyl SulfoSuccinates, alkylsulfates, alky 3 55 Ibenzene Sulfonates, organosilicones, N,N-dialkyltaurates, lignin Sulfonates, naphthalene Sulfonate formaldehyde con densates, polycarboxylates, and polyoxyethylenelpolyox t ypropylene block copolymers. Solid diluents include, for example, clays such as bentonite, montnorillonite, attapulgite h3 60 and kaolin, starch, Sugar, silica, talc, diatomaceous earth, urea, calcium carbonate, Sodium carbonate and bicarbonate, and sodium sulfate. Liquid diluents include, for example, water, N,N-dimethylformamide, dimethylsulfoxide, N-alky FFFF lpyrrolidone, ethylene glycol, polypropylene glycol, paraf Formulation/Utility 65 fins, alkylbenzenes, alkylnaphthalenes, oils of olive, castor, Compounds of this invention will generally be used as a linseed, tung, Sesame, corn, peanut, cotton-seed, soybean, formulation or composition with an agriculturally suitable rape-seed and coconut, fatty acid esters, ketones such as US 7,754,738 B2 77 78 cyclohexanone, 2-heptanone, isophorone and 4-hydroxy-4- Example C methyl-2-pentanone, and alcohols such as methanol, cyclo hexanol, decanol and tetrahydrofurfuryl alcohol. Solutions, including emulsifiable concentrates, can be pre pared by simply mixing the ingredients. Dusts and powders Extruded Pellet can be prepared by blending and, usually, grinding as in a Compound 1 25.0% hammer mill or fluid-energy mill. Suspensions are usually anhydrous sodium sulfate 10.0% prepared by wet-milling; see, for example, U.S. Pat. No. crude calcium ligninsulfonate S.0% 3,060,084. Granules and pellets can be prepared by spraying sodium alkylnaphthalenesulfonate 1.0% the active material upon preformed granular carriers or by 10 calcium magnesium bentonite 59.0%. agglomeration techniques. See Browning, "Agglomeration'. Chemical Engineering, Dec. 4, 1967, pp 147-48, Perry's Chemical Engineer's Handbook, 4th Ed., McGraw-Hill, New Example D York, 1963, pages 8-57 and following, and PCT Publication 15 WO 91/13546. Pellets can be prepared as described in U.S. Pat. No. 4,172,714. Water-dispersible and water-soluble granules can be prepared as taught in U.S. Pat. No. 4,144,050, Emulsifiable Concentrate U.S. Pat. No. 3,920,442 and DE 3,246,493. Tablets can be Compound 1 20.0% prepared as taught in U.S. Pat. No. 5,180,587, U.S. Pat. No. blend of oil soluble Sulfonates and polyoxyethylene ethers 10.0% 5,232,701 and U.S. Pat. No. 5,208,030. Films can be prepared isophorone 70.0%. as taught in GB 2,095,558 and U.S. Pat. No. 3.299,566. For further information regarding the art of formulation, see T. S. Woods, “The Formulator's Toolbox Product Example E Forms for Modern Agriculture' in Pesticide Chemistry and 25 Bioscience, The Food-Environment Challenge, T. Brooks and T. R. Roberts, Eds. Proceedings of the 9th International Con gress on Pesticide Chemistry. The Royal Society of Chemis Granule try, Cambridge, 1999, pp. 120-133. See also U.S. Pat. No. 30 3.235,361, Col. 6, line 16 through Col. 7, line 19 and Compound 1 O.S9/o cellulose 2.5% Examples 10-41; U.S. Pat. No. 3,309,192, Col. 5, line 43 lactose 4.0% through Col. 7, line 62 and Examples 8, 12, 15, 39, 41, 52, 53. cornmeal 93.0%. 58, 132, 138-140, 162-164, 166, 167 and 169-182: U.S. Pat. No. 2,891,855, Col. 3, line 66 through Col. 5, line 17 and 35 Compounds of this invention are characterized by favor Examples 14, Klingman, Weed Control as a Science, John able metabolic and/or soil residual patterns and exhibit activ Wiley and Sons, Inc., New York, 1961, pp 81-96; and Hance ity controlling a spectrum of agronomic and non-agronomic et al., Weed Control Handbook, 8th Ed., Blackwell Scientific invertebrate pests. (In the context of this disclosure “inverte Publications, Oxford, 1989. brate pest control’ means inhibition of invertebrate pest In the following Examples, all percentages are by weight 40 development (including mortality) that causes significant and all formulations are prepared in conventional ways. Com reduction in feeding or other injury or damage caused by the pound numbers refer to compounds in Index Table A. pest, related expressions are defined analogously.) As referred to in this disclosure, the term “invertebrate pest' Example A includes arthropods, gastropods and nematodes of economic 45 importance as pests. The term “arthropod' includes insects, mites, spiders, Scorpions, centipedes, millipedes, pill bugs and Symphylans. The term 'gastropod' includes Snails, slugs and other Stylommatophora. The term “nematode' includes Wettable Powder all of the helminths, such as: roundworms, heartworms, and 50 phytophagous nematodes (Nematoda), flukes (Tematoda), Compound 1 65.0% Acanthocephala, and tapeworms (Cestoda). Those skilled in dodecylphenol polyethylene-glycol ether 2.0% the art will recognize that not all compounds are equally sodium ligninsulfonate 4.0% effective against all pests. Compounds of this invention dis sodium silicoaluminate 6.0% play activity against economically important agronomic and montmorillonite (calcined) 23.0%. nonagronomic pests. The term 'agronomic' refers to the pro 55 duction of field crops such as for food and fiber and includes the growth of cereal crops (e.g., wheat, oats, barley, rye, rice, Example B maize), soybeans, vegetable crops (e.g., lettuce, cabbage, tomatoes, beans), potatoes, Sweet potatoes, grapes, cotton, and tree fruits (e.g., pome fruits, stone fruits and citrus fruits). 60 The term “nonagronomic’ refers to other horticultural (e.g., forest, greenhouse, nursery or ornamental plants not grown in Granule a field), public (human) and animal health, domestic and Compound 1 10.0% commercial structure, household, and stored product appli attapulgite granules (low volatile matter, 0.71/0.30 mm; U.S.S. 90.0%. cations or pests. For reason of invertebrate pest control spec No. 25-50 sieves) 65 trum and economic importance, protection (from damage or injury caused by invertebrate pests) of agronomic crops of cotton, maize, soybeans, rice, vegetable crops, potato, Sweet US 7,754,738 B2 79 80 potato, grapes and tree fruit by controlling invertebrate pests McGregor)), rustandbud mites in the family Eriophyidae and are preferred embodiments of the invention. Agronomic or other foliar feeding mites and mites important in human and nonagronomic pests include larvae of the order Lepidoptera, animal health, i.e. dust mites in the family Epidermoptidae, Such as armyworms, cutworms, loopers, and heliothines in follicle mites in the family Demodicidae, grain mites in the the family Noctuidae (e.g., fall armyworm (Spodoptera family Glycyphagidae, ticks in the order Ixodidae (e.g., deer fiugiperda J. E. Smith), beet armyworm (Spodoptera exigua tick (Ixodes scapularis Say), Australian paralysis tick (Ixodes Hübner), black cutworm (Agrotis ipsilon Hufnagel), cabbage holocyclus Neumann), American dog tick (Dermacentor looper (Trichoplusia ni Hübner), tobacco budworm (Helio variabilis Say), lone startick (Amblyomma americanum Lin this virescens Fabricius); borers, casebearers, webworms, naeus) and scab and itch mites in the families Psoroptidae, coneworms, cabbageworms and skeletonizers from the fam 10 Pyemotidae, and Sarcoptidae; adults and immatures of the ily Pyralidae (e.g., European corn borer (Ostrinia nubilalis order Orthoptera including grasshoppers, locusts and crickets Hübner), navel orangeworm (Amyelois transitella Walker), (e.g., migratory grasshoppers (e.g., Melanoplus Sanguinipes corn root webworm (Crambus caliginosellus Clemens), Sod Fabricius, M. differentialis Thomas), American grasshoppers webworm (Herpetogrammalicarsisalis Walker)); leafrollers, (e.g., Schistocerca americana Drury), desert locust (Schisto budworms, seed worms, and fruit worms in the family Tor 15 cerca gregaria Forskal), migratory locust (Locusta migrato tricidae (e.g., codling moth (Cydia pomonella Linnaeus), ria Linnaeus), house cricket (Acheta domesticus Linnaeus), grape berry moth (Endopiza viteana Clemens), oriental fruit mole crickets (Givllotalpa spp.); adults and immatures of the moth (Grapholita molesta Busck)); and many other economi order Diptera including leafminers, midges, fruit flies (Te cally important lepidoptera (e.g., diamondback moth (Plu phritidae), frit flies (e.g., Oscinella frit Linnaeus), soil mag tella xylostella Linnaeus), pink bollworm (Pectinophora gos gots, house flies (e.g., Musca domestica Linnaeus), lesser sypiella Saunders), gypsy moth (Lymantria dispar house flies (e.g., Fannia canicularis Linnaeus, F, femoralis Linnaeus)): nymphs and adults of the order Blattodea includ Stein), stable flies (e.g., Stomoxys calcitrans Linnaeus), face ing cockroaches from the families Blattellidae and Blattidae flies, horn flies, blow flies (e.g., Chrysomya spp., Phormia (e.g., oriental cockroach (Blatta Orientalis Linnaeus), Asian spp.), and other muscoid fly pests, horse flies (e.g., Tabanus cockroach (Blatella asahinai Mizukubo), German cockroach spp.), bot flies (e.g., Gastrophilus spp., Oestrus spp.), cattle (Blattella germanica Linnaeus), brownbanded cockroach 25 grubs (e.g., Hypoderma spp.), deer flies (e.g., Chrysops spp.), (Supella longipalpa Fabricius), American cockroach keds (e.g., Mellophagus Ovinus Linnaeus) and other Brachyc (Periplaneta americana Linnaeus), brown cockroach era, mosquitoes (e.g., Aedes spp., Anopheles spp., Culex (Periplaneta brunnea Burmeister), Madeira cockroach (Leu spp.), black flies (e.g., Prosimulium spp., Simulium spp.), cophaea maderae Fabricius)); foliar feeding larvae and adults biting midges, sand flies, Sciarids, and other Nematocera; of the order Coleoptera including weevils from the families 30 adults and immatures of the order Thysanoptera including Anthribidae, Bruchidae, and Curculionidae (e.g., boll weevil onion thrips (Thrips tabaci Lindeman) and other foliar feed (Anthononus grandis Boheman), rice water weevil (Lissor ing thrips; insect pests of the order Hymenoptera including hoptrus Oryzophilus Kuschel), granary weevil (Sitophilus ants (e.g., red carpenterant (Camponotus ferrugineus Fabri granarius Linnaeus), rice weevil (Sitophilus Oryzae Lin cius), black carpenter ant (Camponotus pennsylvanicus De naeus)); flea beetles, cucumber beetles, rootworms, leaf Geer), Pharaoh ant (Monomorium pharaonis Linnaeus), little beetles, potato beetles, and leafminers in the family Chry 35 fire ant (Wasmannia auropunctata Roger), fire ant (Solenop somelidae (e.g., Colorado potato beetle (Leptinotarsa decem sis geminata Fabricius), red imported fire ant (Solenopsis lineata Say), western corn rootworm (Diabrotica virgifera invicta Buren), Argentine ant (Iridomyrmex humilis Mayr), virgifera LeConte); chafers and other beetles from the family crazy ant (Paratrechina longicornis Latreille), pavementant Scaribaeidae (e.g., Japanese beetle (Popillia japonica New (Tetramorium caespitum Linnaeus), cornfield ant (Lasius man) and European chafer (Rhizotrogus maialis Razou 40 alienus Förster), odorous house ant (Tapinoma sessile Say)). mowsky)); carpet beetles from the family Dermestidae; wire bees (including carpenter bees), hornets, yellow jackets and worms from the family Elateridae: bark beetles from the wasps; insect pests of the order Isoptera including the eastern family Scolytidae and flour beetles from the family Tenebri subterranean termite (Reticulitermes flavipes Kollar), west onidae. In addition agronomic and nonagronomic pests ern Subterranean termite (Reticulitermes hesperus Banks), include: adults and larvae of the order Dermaptera including 45 Formosan Subterranean termite (Coptotermes formosanus earwigs from the family Forficulidae (e.g., European earwig Shiraki), West Indian drywood termite (Incisitermes immi (Forficula auricularia Linnaeus), black earwig (Chelisoches grams Snyder) and other termites of economic importance; morio Fabricius)); adults and nymphs of the orders Hemiptera insect pests of the order Thysanura Such as silverfish (Lepi and Homoptera Such as, plant bugs from the family Miridae, sma saccharina Linnaeus) and firebrat (Thermobia domes cicadas from the family Cicadidae, leafhoppers (e.g. 50 tica Packard); insect pests of the order Mallophaga and Empoasca spp.) from the family Cicadellidae, planthoppers including the head louse (Pediculus humanus capitis De from the families Fulgoroidae and Delphacidae, treehoppers Geer), body louse (Pediculus humanus humanus Linnaeus), from the family Membracidae, psyllids from the family Psyl chicken body louse (Menacanthus stramineus NitsZch), dog lidae, whiteflies from the family Aleyrodidae, aphids from the biting louse (Trichodectes canis De Geer), flufflouse (Gonio family Aphididae, phylloxera from the family Phylloxeridae, cotes gallinae De Geer), sheep body louse (Bovicola Ovis mealybugs from the family Pseudococcidae, Scales from the 55 Schrank), short-nosed cattle louse (Haematopinus euryster families Coccidae, Diaspididae and Margarodidae, lace bugs nus Nitzsch), long-nosed cattle louse (Linognathus vituli Lin from the family Tingidae, stink bugs from the family Pentato naeus) and other Sucking and chewing parasitic lice that midae, cinch bugs (e.g., Blissus spp.) and other seed bugs attack man and animals; insect pests of the order from the family Lygaeidae, spittlebugs from the family Cer Siphonoptera including the oriental rat flea (Xenopsylla cheo copidae squash bugs from the family Coreidae, and redbugs 60 pis Rothschild), cat flea (Ctenocephalides felis Bouche), dog and cotton stainers from the family Pyrrhocoridae. Also flea (Ctenocephalides canis Curtis), hen flea (Ceratophyllus included are adults and larvae of the order Acari (mites) such gallinae Schrank), Sticktight flea (Echidnophaga gallinacea as spider mites and red mites in the family Tetranychidae Westwood), human flea (Pulex irritans Linnaeus) and other (e.g., European red mite (Panonychus ulmi Koch), two spot fleas afflicting mammals and birds. Additional arthropod ted spider mite (Teiranychus urticae Koch), McDaniel mite 65 pests covered include: spiders in the order Araneae such as the (Tetranychus mcdanieli McGregor)), flat mites in the family brown recluse spider (Loxosceles reclusa Gertsch & Mulaik) Tenuipalpidae (e.g., citrus flat mite (Brevipalpus lewisi and the black widow spider (Latrodectus mactans Fabricius), US 7,754,738 B2 81 82 and centipedes in the order Scutigeromorpha Such as the Macrolestes quadrilineatus Forbes (aster leafhopper), house centipede (Scutigera Coleoptrata Linnaeus). Com Nephotettix cinticeps Uhler (green leafhopper), Nephotettix pounds of the present invention also have activity on mem nigropictus Stal (rice leafhopper), Nilaparvata lugens Stal bers of the Classes Nematoda, Cestoda, Trematoda, and (brown planthopper), Peregrinus maidis Ashmead (corn Acanthocephala including economically important members planthopper), Sogatella fircifera Horvath (white-backed of the orders Strongylida, Ascaridida, Oxyurida, Rhabditida, planthopper), Sogatodes Orizicola Muir (rice delphacid), Spirurida, and Enoplida Such as but not limited to economi Typhlocybapomaria McAtee white apple leafhopper, Eryth cally important agricultural pests (i.e. root knot nematodes in roneoura spp. (grape leafhoppers); Magicidada Septendecim the genus Meloidogyne, lesion nematodes in the genus Praty Linnaeus (periodical cicada); Icerya purchasi Maskell (cot lenchus, stubby root nematodes in the genus Trichodorus, 10 tony cushion scale), Ouadraspidiotus perniciosus Comstock etc.) and animal and human health pests (i.e. all economically (San Jose scale); Planococcus citri Risso (citrus mealybug); important flukes, tapeworms, and roundworms. Such as Pseudococcus spp. (other mealybug complex); Cacopsylla Strongylus vulgaris in horses, Toxocara canis in dogs, Hae pyricola Foerster (pear psylla), Trioza diospyri Ashmead monchus contortus in sheep, Dirofilaria immitis Leidy in (persimmon psylla). These compounds also have activity on dogs, Anoplocephala perfoliata in horses, Fasciola hepatica members from the order Hemiptera including: Acrosternum Linnaeus in ruminants, etc.). 15 hilare Say (green Stink bug), Anasa tristis De Geer (squash Compounds of the invention show particularly high activ bug), Blissus leucopterus leucopterus Say (chinch bug), ity against pests in the order Lepidoptera (e.g., Alabama Corythuca gossypii Fabricius (cotton lace bug), Cyrtopeltis argillacea Hübner (cotton leaf worm), Archips argyrospilla modesta Distant (tomato bug), Dysdercus suturellus Herrich Walker (fruit tree leafroller), A. rosana Linnaeus (European Schäffer (cotton stainer), Euchistus servus Say (brown stink leaf roller) and other Archips species, Chilo suppressalis bug), Euchistus variolarius Palisot de Beauvois (one-spotted Walker (rice stem borer), Cnaphalocrosis medinalis Guenee Stink bug), Graptosthetus spp. (complex of seed bugs), Lep (rice leafroller), Crambus caliginosellus Clemens (corn root toglossus Corculus Say (leaf-footed pine seed bug), Lygus webworm), Crambus teterrellus Zincken (bluegrass web lineolaris Palisot de Beauvois (tarnished plant bug), Nezara worm), Cydia pomonella Linnaeus (codling moth), Earias viridula Linnaeus (Southern green Stink bug), Oebalus pug 25 nax Fabricius (rice Stink bug). Oncopeltus fasciatus Dallas insulana Boisduval (spiny bollworm), Earias vittella Fabri (large milkweed bug), Pseudatomoscelis seriatus Reuter cius (spotted bollworm), Helicoverpa armigera Hübner (cotton fleahopper). Other insect orders controlled by com (American bollworm), Helicoverpa zea Boddie (corn ear pounds of the invention include Thysanoptera (e.g., Franklin worm), Heliothis virescens Fabricius (tobacco budworm), iella occidentalis Pergande (western flower thrip), Scirtho Herpetogramma licarsisalis Walker (sod webworm), Lobe thrips citri Moulton (citrus thrip), Sericothrips variabilis sia botrana Denis & Schiffermüller (grape berry moth), Pec 30 Beach (soybean thrip), and Thrips tabaci Lindeman (onion tinophora gossypiella Saunders (pink bollworm), Phyllocnis thrip); and the order Coleoptera (e.g., Leptinotarsa decemlin tis citrella Stainton (citrus leafminer), Pieris brassicae eata Say (Colorado potato beetle), Epilachna varivestis Mul Linnaeus (large white butterfly), Pieris rapae Linnaeus sant (Mexican bean beetle) and wireworms of the genera (small white butterfly), Plutella xylostella Linnaeus (dia Agriotes, Athous or Limonius). mondback moth), Spodoptera exigua Hübner (beet army 35 worm), Spodoptera litura Fabricius (tobacco cutworm, clus Compounds of this invention can also be mixed with one or ter caterpillar), Spodoptera frugiperda J. E. Smith (fall more other biologically active compounds or agents, e.g. a armyworm), Trichoplusia ni Hübner (cabbage looper) and compound different from a compound of Formula I, an N-ox Tuta absoluta Meyrick (tomato leafminer)). Compounds of ide or a salt thereof, including insecticides, fungicides, nema the invention also have commercially significant activity on tocides, bactericides, acaricides, growth regulators such as members from the order Homoptera including: Acyrthiisi 40 rooting stimulants, chemosterilants, semiochemicals, repel phon pisum Harris (pea aphid), Aphis Craccivora Koch (cow lents, attractants, pheromones, feeding stimulants, other bio pea aphid), Aphis fabae Scopoli (black bean aphid), Aphis logically active compounds or entomopathogenic bacteria, gossypii Glover (cotton aphid, melon aphid), Aphis pomi De virus or fungi to form a multi-component pesticide giving an Geer (apple aphid), Aphis spiraecola Patch (spirea aphid), even broader spectrum of agricultural utility. Thus, composi Aulacorthum Solani Kaltenbach (foxglove aphid), Chaetosi 45 tions of the present invention can also comprise at least one phon fragaefolii Cockerell (strawberry aphid), Diuraphis other biologically active compound or agent selected from the noxia Kurdumov/Mordvilko (Russian wheat aphid), Dysa group consisting of an other insecticide, a fungicide, a nema phis plantaginea Paaserini (rosy apple aphid), Eriosoma lani tocide, a bactericide, an acaricide, a growth regulator, a root gerum Hausmann (woolly apple aphid), Hvalopterus pruni ing stimulant, a chemosterilant, a semiochemical, a repellent, Geoffroy (mealy plum aphid), Lipaphis erysimi Kaltenbach 50 an attractant, a pheromone, a feeding stimulant, and an ento (turnip aphid), Metopolophium dirrhodium Walker (cereal mopathogenic bacterium, virus or fungus. Such compositions aphid), Macrosipum euphorbiae Thomas (potato aphid), preferably further comprise at least one additional component Myzus persicae Sulzer (peach-potato aphid, green peach selected from the group consisting of a Surfactant, a solid aphid), Nasonovia ribisnigri Mosley (lettuce aphid), Pemphi diluent, and a liquid diluent. gus spp. (root aphids and gallaphids), Rhopalosiphum maidis Examples of other biologically active compounds or Fitch (corn leaf aphid), Rhopalosiphum padi Linnaeus (bird 55 agents with which compounds of this invention can be for cherry-oat aphid), Schizaphis graminum Rondani (green mulated are: insecticides such as abamectin, acephate, bug), Sitobion avenae Fabricius (English grain aphid), The acetamiprid, avermectin, azadirachtin, azinphos-methyl, rioaphis maculata Buckton (spotted alfalfa aphid), Toxoptera bifenthrin, binfenazate, buprofezin, carbofuran, chlor aurantii Boyer de Fonscolombe (black citrus aphid), and fenapyr, chlorfluaZuron, chlorpyrifos, chlorpyrifos-methyl, Toxoptera citricida Kirkaldy (brown citrus aphid); Adelges 60 chromafenozide, clothianidin, cyfluthrin, beta-cyfluthrin, spp. (adelgids); Phlylloxera devastatrix Pergande (pecan cyhalothrin, lambda-cyhalothrin, cypermethrin, cyromazine, phylloxera); Bemisia tabaci Gennadius (tobacco whitefly, deltamethrin, diafenthiuron, diazinon, diflubenzuron, sweetpotato whitefly), Bemisia argentifoli Bellows & Perring dimethoate, diofenolan, emamectin, endosulfan, esfenvaler (silverleaf whitefly), Dialeurodes citri Ashmead (citrus ate, ethiprole, fenothicarb, fenoxycarb, fenpropathrin, fen whitefly) and Trialeurodes vaporariorum Westwood (green 65 proximate, fenvalerate, fipronil, flonicamid, flucythrinate, house whitefly); Empoasca fabae Harris (potato leafhopper), tau-fluvalinate, flufenoXuron, fonophos, halofenozide, Laodelphax striatellus Fallen (Smaller brown planthopper), hexaflumuron, imidacloprid, indoxacarb, isofenphos, lufenu US 7,754,738 B2 83 84 ron, malathion, metaldehyde, methamidophos, methidathion, and genetically modified viral insecticides including mem methomyl, methoprene, methoxychlor, monocrotophos, bers of the family Baculoviridae as well as entomophagous methoxyfenozide, nithiazin, novaluron, oxamyl, parathion, fungi. parathion-methyl, permethrin, phorate, phosalone, phosmet, Most preferred mixtures useful in the compositions and phosphamidon, pirimicarb, profenofos, pymetrozine, pyrida methods of this invention include a mixture of a compound of lyl pyriproxyfen, rotenone, spinosad, Sulprofos, this invention with cyhalothrin; a mixture of a compound of tebufenozide, teflubenZuron, tefluthrin, terbufos, tetrachlorv this invention with beta-cyfluthrin; a mixture of a compound inphos, thiacloprid, thiamethoxam, thiodicarb, thiosultap-so of this invention with esfenvalerate; a mixture of a compound dium, tralomethrin, trichlorfon and triflumuron; fungicides of this invention with methomyl; a mixture of a compound of Such as acibenzolar, azoxystrobin, benomyl, blasticidin-S, this invention with imidacloprid; a mixture of a compound of Bordeaux mixture (tribasic copper Sulfate), bromuconazole, 10 this invention with thiacloprid; a mixture of a compound of carpropamid, captafol, captan, carbendazim, chloroneb, this invention with indoxacarb; a mixture of a compound of chlorothalonil, copper oxychloride, copper salts, cyflufena this invention with abamectin; a mixture of a compound of mid, cymoxanil, cyproconazole, cyprodinil, (S)-3.5- this invention with endosulfan; a mixture of a compound of dichloro-N-(3-chloro-1-ethyl-1-methyl-2-oxopropyl)-4-me this invention with ethiprole; a mixture of a compound of this thylbenzamide (RH 7281), diclocymet (S-2900), 15 invention with fipronil; a mixture of a compound of this diclomezine, dicloran, difenoconazole, (S)-3,5-dihydro-5- invention with flufenoxuron; a mixture of a compound of this methyl-2-(methylthio)-5-phenyl-3-(phenylamino)-4H-imi invention with pyriproxyfen; a mixture of a compound of this dazol-4-one (RP 407213), dimethomorph, dimoxystrobin, invention with pymetrozine; a mixture of a compound of this diniconazole, diniconazole-M, dodine, edifenphos, epoxi invention with amitraz: a mixture of a compound of this conazole, famoxadone, fenamidone, fenarimol, fenbucona invention with Bacillus thuringiensis and a mixture of a com Zole, fencaramid (SZX0722), fenpiclonil, fempropidin, fen pound of this invention with Bacillus thuringiensis delta propimorph, fentin acetate, fentin hydroxide, fluazinam, endotoxin. fludioxonil, flumetover (RPA 403397), fluguinconazole, In certain instances, combinations with other invertebrate flusilazole, flutolanil, flutriafol, folpet, fosetyl-aluminum, pest control compounds or agents having a similar spectrum furalaxyl, furametapyr (S-82658), hexaconazole, ipconazole, 25 of control but a different mode of action will be particularly iprobenfos, iprodione, isoprothiolane, kasugamycin, advantageous for resistance management. Thus, composi kresoxim-methyl, mancoZeb, maneb, mefenoxam, mepronil. tions and methods of the present invention can further com metalaxyl, metconazole, metomino-strobin/fenominostrobin prise a biologically effective amount of at least one other (SSF-126), myclobutanil, neo-asozin (ferric methanearson invertebrate pest control compound or agent having a similar ate), oxadixyl, penconazole, pencycuron, probenazole, spectrum of control but a different mode of action from the prochloraz, propamocarb, propiconazole, pyrifenox, pyra 30 compounds of the invention. Contacting a plant genetically clostrobin, pyrimethanil, pyroquilon, quinoxyfen, spiroxam modified to express a plant protection compound (e.g., pro ine, Sulfur, tebuconazole, tetraconazole, thiabendazole, thi tein) or the locus of the plant with a biologically effective fluZamide, thiophanate-methyl, thiram, tiadinil, triadimefon, amount of a compound of this invention can also provide a triadimenol, tricyclazole, trifloxystrobin, triticonazole, val broader spectrum of plant protection and be advantageous for idamycin and VincloZolin; nematocides such as aldicarb, 35 resistance management. oxamyl and fenamiphos; bactericides Such as streptomycin; At least one invertebrate pest is controlled in agronomic acaricides such as amitraz, chinomethionat, chlorobenzilate, and/or nonagronomic applications by applying one or more cyhexatin, dicofol, dienochlor, etoxazole, fenazaquin, fenb of the compounds or compositions of this invention, in a utatin oxide, fempropathrin, fenpyroximate, hexythiazox, biologically effective amount, to the environment of the pest propargite, pyridaben and tebufenpyrad; and biological 40 including the agronomic and/or nonagronomic locus of infes agents such as Bacillus thuringiensis including ssp. aizawai tation, to the area to be protected, or directly on the pest to be and kurstaki, Bacillus thuringiensis delta endotoxin, bacu controlled. Thus, the present invention further comprises a lovirus, and entomopathogenic bacteria, virus and fungi. method for the control of at least one invertebrate pest in an Compounds of this invention and compositions thereof may agronomic and/or a nonagronomic environment, comprising be applied to plants genetically transformed to express pro 45 contacting the invertebrate pest or its environment with a teins toxic to invertebrate pests (such as Bacillus thuringien biologically effective amount of one or more of the com sis toxin). The effect of the exogenous invertebrate pest con pounds of the invention; or with a biologically effective trol compounds and compositions may be synergistic with the amount of a composition comprising at least one Such com expressed toxin proteins. pound; or with a biologically effective amount of composi A general reference for these agricultural protectants is The 50 tion comprising at least one such compound and a biologi Pesticide Manual, 12th Edition, C. D. S. Tomlin, Ed., British cally effective amount of at least one other biologically active Crop Protection Council, Farnham, Surrey, U.K., 2000. compound or agent. Examples of Suitable compositions com Preferred compositions of this invention include as an prising at least one compound of the invention and at least one other biologically active compound or agent insecticides and other biologically active compound or agent include granular acaricides including pyrethroids such as cypermethrin, cyha compositions wherein the other biologically active com lothrin, cyfluthrin, beta-cyfluthrin, esfenvalerate, fenvalerate 55 pound is present on the same granule as the compound of the and tralomethrin; carbamates Such as fenothicarb, methomyl. invention or on a granule separate from the granule where the oxamyl and thiodicarb; neonicotinoids such as clothianidin, compound of this invention is present. imidacloprid and thiacloprid; neuronal sodium channel A preferred method of contact is by spraying. Alterna blockers such as indoxacarb; insecticidal macrocyclic lac tively, a granular composition comprising a compound of the tones Such as spinosad, abamectin, avermectin and emamec 60 invention can be applied to the plant foliage or the soil. tin, y-aminobutyric acid (GABA) antagonists such as Compounds of this invention are also effectively delivered endosulfan, ethiprole and fipronil; insecticidal ureas Such as through plant uptake by contacting the plant with a compo flufenoXuron and trifumuron; juvenile hormone mimics Such sition comprising a compound of this invention applied as a as diofenolan and pyriproxyfen; pymetrozine; and amitraz. soil drench of a liquid formulation, a granular formulation to Preferred biological agents for mixing with compounds of 65 the soil, a nursery box treatment or a dip of transplants. this invention include Bacillus thuringiensis and Bacillus Compounds are also effective by topical application of a thuringiensis delta endotoxin as well as naturally occurring composition comprising a compound of this invention to the US 7,754,738 B2 85 86 locus of infestation. Other methods of contact include appli cacy” represents inhibition of invertebrate pest development cation of a compound or a composition of the invention by (including mortality) that causes significantly reduced feed direct and residual sprays, aerial sprays, gels, seed coatings, ing. The pest control protection afforded by the compounds is microencapsulations, systemic uptake, baits, eartags, not limited, however, to these species. See Index Tables A and boluses, foggers, fumigants, aerosols, dusts and many others. B for compound descriptions. The following abbreviations The compounds of this invention may also be impregnated are used in the Index Tables which follow t is tertiary, n is into materials for fabricating invertebrate control devices normal, i is iso, c is cyclo, S is secondary, Me is methyl, Et is (e.g. insect netting). ethyl, Pr is propyl, i-Pr is isopropyl, Bu is butyl, n-butyl is The compounds of this invention can be incorporated into butyl, t-Buis tertiary butyl, Hex is hexyl, c-Hex is cyclohexyl, baits that are consumed by the invertebrates or within devices OMe is methoxy, OEt is ethoxy, SMe is methylthio, SEt is Such as traps and the like. Granules or baits comprising 10 ethylthio, CN is cyano, and NO is nitro. The abbreviation between 0.01-5% active ingredient, 0.05-10% moisture “Ex. stands for “Example” and is followed by a number retaining agent(s) and 40-99% vegetable flour are effective in indicating in which example the compound is prepared. controlling soil insects at very low application rates, particu larly at doses of active ingredient that are lethal by ingestion rather than by direct contact. 15 The compounds of this invention can be applied in their - INDEXTABLE A pure state, but most often application will be of a formulation comprising one or more compounds with Suitable carriers, | N C diluents, and Surfactants and possibly in combination with a food depending on the contemplated end use. A preferred 20 N2. method of application involves spraying a water dispersion or N-N refined oil solution of the compounds. Combinations with N R7 spray oils, spray oil concentrations, spreader Stickers, adju- O S. vants, other solvents, and synergists such as piperonylbutox ide often enhance compound efficacy. 25 R2a N The rate of application required for effective control (i.e. e NH “biologically effective amount') will depend on such factors R2b-- as the species of invertebrate to be controlled, the pest’s life S cycle, life stage, its size, location, time of year, host crop or R3c animal, feeding behavior, mating behavior, ambient moisture, 30 temperature, and the like. Under normal circumstances, Compound R' R2& R2e R7 U. mp C. application rates of about 0.01 to 2 kg of active ingredient per hectare are Sufficient to control pests in agronomic ecosys- 1 (Ex. 1) 2-Me 6-Cl H CF, CH 212. 213 tems, but as little as 0.0001 kg/hectare may be sufficient or as : ii. Bye E. 8 kg/hectare may be required. For nonagronomic applica- 4 2-Me H 6-i-Pr CF, CH 145-15S tions, effective use rates will range from about 1.0 to 50 35 5 2-Me 4-Me H CF, CH 110-120 mg/square meter but as little as 0.1 mg/square meter may be 6 2-Me H H Bir CH 180–181 Sufficient or as much as 150 mg/square meter may be 7 (Ex. 2) 2-F 4-F 6-Br Bir CH 138139 required. One skilled in the art can easily determine the bio- 8 E.6 3) : 2. C F. t 19. i 94 logically effective amount necessary for the desired level of 127 2-F 4-F 6-Br CI CH 147-148 invertebrate pest control. 40 128 2-Me H H CF, N 145-147 The following TESTS demonstrate the control efficacy of compounds of this invention on specific pets. “Control effi

INDEXTABLEB (Ex. 4) | Y-Cl N2 NV CF O S. R2aean-Yi R'tSa. a Compound R' R2a R2& R2e M+H Observed

9 H 2-NO- H 6-NO, 457.00 10 H 2-Br 4-NO- 6-Br 569.96 11 H 2-Br 4-Me 6-Br 538.95 12 H 2-F 4-F 6-F 421.06 13 H 2-F H 6-F 403.03

US 7,754,738 B2 91 92 Biological Examples Of The Invention Test D Test A For evaluating control of beet armyworm (Spodoptera exigua) the test unit consisted of a small open container with a 4-5-day-old corn plant inside. This was pre-infested (using For evaluating control of diamondback moth (Plutella a core sampler) with 10-15 1-day-old larvae on a piece of xylostella) the test unit consisted of a small open container insect diet. with a 12-14-day-old radish plant inside. This was pre-in Test compounds were formulated and sprayed at 250 ppm fested with 10-15 neonate larvae on a piece of insect diet by (or lower) as described for Test A. The applications were use of a core sampler to remove a plug from a sheet of replicated three times. After spraying, the test units were hardened insect diet having many larvae growing on it and 10 maintained in a growth chamber and then visually rated as transfer the plug containing larvae and diet to the test unit. described for Test A. The larvae moved onto the test plant as the diet plug dried out. Of the compounds tested, the following provided very good to excellent levels of plant protection (20% or less Test compounds were formulated using a solution containing feeding damage): 7***. 10% acetone, 90% water and 300 ppm X-77(R) Spreader Lo 15 Foam Formula non-ionic Surfactant containing alky larylpolyoxyethylene, free fatty acids, glycols and isopro Test E panol (Loveland Industries, Inc., Greely, Colo. USA), unless As an alternative to evaluate control of fall armyworm otherwise indicated. The formulated compounds were (Spodoptera frugiperda) the test unit consisted of a microtiter applied in 1 mL of liquid through a SUJ2 atomizer nozzle plate filled with 175uL of lepidopteran soy wheat germ diet. with /& JJ custom body (Spraying Systems Co. Wheaton, Ill., Each well was treated with 25uL of a 1050 uM (or lower) USA) positioned 1.27 cm (0.5 inches) above the top of each experimental compound, formulated in 75/25 acetone/water. test unit. All experimental compounds in these tests were Following chemical application, the plates were dried in a sprayed at 250 ppm (or lower) and replicated three times. ventilated enclosure for 24 hours. Following the 24 hour After spraying of the formulated test compound, each test unit 25 drying period, the plates were infested with fall armyworm was allowed to dry for 1 hour and then a black, screened cap egg and then sealed. Test units were then stored for 6 days at was placed on top. The test units were held for 6 days in a 27°C. (day) 70% relative humidity. Activity was assessed growth chamber at 25°C. and 70% relative humidity. Plant based on insect kill. feeding damage was then visually assessed based on foliage Of the compounds tested, the following provided very consumed. 30 good to excellent levels of fall armyworm control (90% or Of the compounds tested the following provided very more of live insect killed): 10, 11, 12, 13, 14, 15, 17, 19, 20, good to excellent levels of plant protection (ratings of 0-1, 22, 26, 27, 28, 29, 31, 32, 34, 44, 64, 69,91, 94, 99, 100, 114, 10% or less feeding damage): 1*, 7***, 8*** 126***, 115, 120 and 121. 127*** and 128***. *Compounds 9 through 125 of Index Table B were not evalu 35 ated in this test. Test B ** Tested at 250 ppm. For evaluating control of fall armyworm (Spodoptera fru Tested at 50 ppm giperda) the test unit consisted of a small open container with What is claimed is: a 4-5-day-old corn (maize) plant inside. This was pre-infested 40 1. A compound of Formula I, an N-oxide or a salt thereof (using a core sampler) with 10-151-day-old larvae on a piece of insect diet. Test compounds were formulated and sprayed at 250 ppm (or lower) as described for Test A. The applications were replicated three times. After spraying, the test units were 45 maintained in a growth chamber and then visually rated as described for Test A. Of the compounds tested, the following provided excel lent levels of plant protection (10% or less feeding damage): wherein: 188, 6:38, 788, 8 * * * and 127* * * 50 A is O: B is a phenyl ring orapyridinering, each ring Substituted Test C with 1 to 5 R: J is J-1; For evaluating control of tobacco budworm (Heliothis vire 55 scens) the test unit consisted of a small open container with a 6-7 day old cotton plant inside. This was pre-infested (using a core sampler) with 82-day-old larvae on a piece of insect diet. Test compounds were formulated and sprayed at 250 ppm 60 (or lower) as described for Test A. The applications were replicated three times. After spraying, the test units were maintained in a growth chamber and then visually rated as described for Test A. Of the compounds tested, the following provided very 65 R" is H or C-C alkyl: good to excellent levels of plant protection (20% or less from 1 to 3 R' groups are other than Hand are indepen feeding damage): 7*** and 8***. dently selected from the group consisting of C-C, US 7,754,738 B2 93 94 alkyl, C-C haloalkyl, C-C cyanoalkyl, halogen, haloalkyl, halogen, CN, C-C alkoxy, C-C alkylthio. CN, NO, C-C alkoxy, C-C haloalkoxy, C-C, C-Chaloalkoxy, and C-Chaloalkylthio. alkylthio, C-C alkylsulfinyl, C-C alkylsulfonyl, 2. The compound of claim 1 whereintwo Rare ortho to the C-C haloalkylthio, C-C haloalkylsulfinyl and NR'C(=A).J. moiety. C-C haloalkylsulfonyl; and 5 3. The compound of claim 1 wherein at least one R is ortho to the NR'C(A).J. moiety and is R is C-C alkyl, C-C haloalkyl, halogen or CN; and other than H: R7 is H, CH, CF, CHCF, CHF, OCHCF, OCHF, or R is halogen. 4. The compound of claim 3 wherein: 10 R is C1 or Br; and R’ is halogen, OCHCF, OCHF, or CF. 5. A composition comprising: at least one compound of claim 1; and at least one additional component selected from R6; the group consisting of a surfactant, a solid diluent and a N 15 liquid diluent. 6. The composition of claim 5 further comprising at least 2 one other biologically active compound or agent. 7. A method for controlling at least one invertebrate pest R6a comprising: contacting the invertebrate pest or its environ 2O ment with a biologically effective amount of at least one R is selected from the group consisting of C-C alkyl, compound of claim 1. C-C cycloalkyl, C-C haloalkyl, halogen, CN, 8. The method of claim 7 wherein the composition further C-C alkoxy, C-C alkylthio, C-Chaloalkoxy, and comprises a biologically effective amount of at least one other C-C haloalkylthio; and biologically active compound or agent for controlling inver each R" and Rare independently selected from the group 25 tebrate pests. consisting of H. C-C alkyl, C-C cycloalkyl, C-C, UNITED STATES PATENT AND TRADEMARK OFFICE CERTIFICATE OF CORRECTION PATENT NO. : 7,754,738 B2 Page 1 of 3 APPLICATIONNO. : 10/514183 DATED : July 13, 2010 INVENTOR(S) : George Philip Lahm et al. It is certified that error appears in the above-identified patent and that said Letters Patent is hereby corrected as shown below:

Column 17, line 34, “61-4°C. should read --61-64°C.-- Columns 20, 21, 23, 25, 27, 29, Table 1, in the formula structure “R” should read --R- Table 1 N 2 N-N O SS Y-7R R2a N R2 R2c Columns 29, 31, 33,35, 37, Table 2, in the formula structure “R” should read --R-

Signed and Sealed this Seventh Day of August, 2012

David J. Kappos Director of the United States Patent and Trademark Office CERTIFICATE OF CORRECTION (continued) Page 2 of 3 U.S. Pat. No. 7,754,738 B2 Columns 29, 31, 33,35, 37, Table 2, in the headings in the 4" and 8" columns “R” should read --R- Columns 39, 41, 43, 45, Table 3, in the formula structure “R” should read --R*-

Columns 39, 41, 43, 45, Table 3, in the headings in the 4" and 8" columns “R” should read --R'-- Columns 47,49, 51,53,55, 57, Table 4, in the formula structure “R” should read --R- Table 4

I N Cl 2 5 R7 4. () Sa R2a N R2b R2c

Table S

CERTIFICATE OF CORRECTION (continued) Page 3 of 3 U.S. Pat. No. 7,754,738 B2 Columns 65, 67, 69, 71, 73, Table 6, in the formula structure “R” should read --R- Table 6

N-d

-8 O S. N-R

Column 86, Index Table A, in the formula structure “R” should read --R- INDEX TABLE A

C N N W 7 O S. R R2a N R2 U R2c Columns 86, 87,89, Index Table B (Ex. 4), in the formula structure “R” should read --R'-- INDEXTABLEB (Ex. 4)

N

N-- N W CF S. 3

R2a N YR R2b R2c

Column 92, line 37 “Tested at 50 ppm should read -***Tested at 50 ppm--