WO2013158422A1

WO2013158422A1 - Heterocyclic compounds for controlling invertebrate pests

Info

Publication number: WO2013158422A1
Application number: PCT/US2013/035873
Authority: WO
Inventors: Ming Xu; Stephen Frederick Mccann; Ramakrishnan VALLINAYAGAM
Original assignee: E. I. Du Pont De Nemours And Company
Priority date: 2012-04-17
Filing date: 2013-04-10
Publication date: 2013-10-24

Abstract

Disclosed are compounds of Formula 1, N-oxides, and salts thereof, wherein R², R⁴, R⁵, R⁶, A, L, Q and n are as defined in the disclosure. Also disclosed are compositions containing the compounds of Formula 1 and methods for controlling an invertebrate pest comprising contacting the invertebrate pest or its environment with a biologically effective amount of a compound or a composition of the invention.

Description

TITLE

HETEROCYCLIC COMPOUNDS FOR CONTROLLING INVERTEBRATE PESTS

FIELD OF THE INVENTION

This invention relates to certain substituted pyridine compounds, their N-oxides, salts and their compositions suitable for agronomic, nonagronomic and animal health uses, methods of their use for controlling invertebrate pests such as arthropods in both agronomic and nonagronomic environments, and for treatment of parasite infections in animals or infestations in the general environment.

BACKGROUND OF THE INVENTION

The control of invertebrate pests is extremely important in achieving high crop efficiency. Damage by invertebrate pests to growing and stored agronomic crops can cause significant reduction in productivity and thereby result in increased costs to the consumer. The control of invertebrate pests in forestry, greenhouse crops, ornamentals, nursery crops, stored food and fiber products, livestock, household, turf, wood products, and public health is also important. Many products are commercially available for these purposes, but the need continues for new compounds that are more effective, less costly, less toxic, environmentally safer or have different sites of action.

The control of animal parasites in animal health is essential, especially in the areas of food production and companion animals. Existing methods of treatment and parasite control are being compromised due to growing resistance to many current commercial parasiticides. The discovery of more effective ways to control animal parasites is therefore imperative.

SUMMARY OF THE INVENTION

This invention is directed to compounds of Formula 1 (including all stereoisomers), N- oxides, and salts thereof, and compositions containing them and their use for controlling invertebrate pests:

1

wherein

L is a group selected from

-l L-2 L-3 L-4

L-5 L-6 L-7 L-8

L-9 L-10 L-11 L-12

wherein the bond projecting to the left is bonded to the aromatic ring containing A and the bond projecting to the right is bonded to the aromatic ring containing Q; or L is O, S(0)_m or NR⁷;

A is N or CR³;

Q is N, CH or CR⁶;

R^{l a} and R^lb are each independently selected from hydrogen, halogen and C1-C2 alkyl;

R² and R⁵ are each independently selected from hydrogen and fluorine;

R³and R⁴ are each independently selected from hydrogen, halogen, cyano, amino, nitro, SF₅, -CHO, -Cg alkyl, C₂-C₆ alkenyl, C₂-C₆ alkynyl, -Cg haloalkyl, C₂-C6 haloalkenyl, C2~Cg haloalkynyl, C3-C6 cycloalkyl, C3-C6 halocycloalkyl, C4-C8 alkylcycloalkyl, Cz Cg cycloalkylalkyl, C3-C6 cycloalkenyl, C2~Cg alkoxyalkyl, C2~Cg alkylthioalkyl, C2~Cg alkylcarbonyl, C2~Cg

haloalkylcarbonyl, C2~Cg alkoxycarbonyl, C2~Cg alkylaminocarbonyl, C3-C8 dialkylaminocarbonyl, C2~Cg cyanoalkyl, C^-Cg alkoxy, C^-Cg haloalkoxy, C2- Cg alkoxyalkoxy, C^-Cg alkylthio, C^-Cg haloalkylthio, C^-Cg alkylsulfinyl, C^-Cg haloalkylsulfinyl, C^-Cg alkylsulfonyl, C^-Cg haloalkylsulfonyl, C3-C9 trialkylsilyl, C^-Cg alkylamino, C2~Cg dialkylamino, C2~Cg haloalkylamino, C2~Cg halodialkylamino and C2~Cg alkylcarbonylamino; or Q¹, OQ¹ or SQ¹; each R⁶ is independently halogen, hydroxy, amino, cyano, nitro, SF₅, C^-Cg alkyl, C2~Cg alkenyl, C2~Cg alkynyl, C3~Cg cycloalkyl, C4-C10 cycloalkylalkyl, C4- C Q alkylcycloalkyl, C5-C10 alkylcycloalkylalkyl, Cg-C^ cycloalkylcycloalkyl, C^-Cg haloalkyl, C2~Cg haloalkenyl, C2~Cg haloalkynyl, C3~Cg halocycloalkyl, C1-C4 alkoxy, C1-C4 haloalkoxy, C2-C4 alkoxyalkoxy, C1-C4 alkylthio, C1-C4 alkylsulfmyl, C1-C4 alkylsulfonyl, C1-C4 haloalkylthio, C1-C4

haloalkylsulfinyl, C1-C4 haloalkylsulfonyl, C1-C4 alkylamino, C2~Cg dialkylamino, C3-C6 cycloalkylamino, C2-C4 alkoxyalkyl, C1-C4 hydroxyalkyl, C2-C4 alkylcarbonyl, C2~Cg alkoxycarbonyl, C2~Cg alkylcarbonyloxy, C2~Cg alkylcarbonylthio, C2~Cg alkylaminocarbonyl, C3-C8 dialkylaminocarbonyl, C3- Cg haloalkylcarbonylamino, C3-C6 haloalkylcarbonyl(alkyl)amino or C3-C6 trialkylsilyl; or phenyl, phenoxy or naphthalenyl optionally substituted with up to 3 substituents independently selected from halogen, cyano, C1-C2 alkyl, C1-C2 haloalkyl, C1-C2 alkoxy and C1-C2 haloalkoxy; or a 5- to 6-membered heteroaromatic ring containing ring members selected from carbon atoms and up to 4 heteroatoms independently selected from up to 2 O, up to 2 S and up to 4 N atoms, and optionally substituted with up to 3 substituents independently selected from halogen, cyano, C1-C2 alkyl, C1-C2 haloalkyl, C1-C2 alkoxy and C1-C2 haloalkoxy on carbon atom ring members and cyano, C1-C2 alkyl and C1-C2 alkoxy on nitrogen atom ring members; or a 3- to 7-membered nonaromatic ring containing ring members selected from carbon atoms and up to 4 heteroatoms independently selected from up to 2 O, up to 2 S and up to 4 N atoms, wherein up to 3 carbon atom ring members are independently selected from C(=0) and C(=S), the sulfur atom ring members are independently selected from

S(=O)_s(=NR¹⁰)f and the ring optionally substituted with up to 3 substituents independently selected from halogen, cyano, C1-C2 alkyl, C1-C2 haloalkyl, C - C2 alkoxy and C1-C2 haloalkoxy on carbon atom ring members and cyano, C^- C2 alkyl and C1-C2 alkoxy on nitrogen atom ring members;

R⁷ is hydrogen, cyano, C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy, C2-C3

alkylcarbonyl, C2-C3 alkoxycarbonyl or C3-C6 cycloalkyl;

R¹⁰ is independently hydrogen, cyano, C^-Cg alkyl, C^-Cg haloalkyl, C3-C8

cycloalkyl, C3-C8 halocycloalkyl, C^-Cg alkoxy, C^-Cg haloalkoxy, C^-Cg alkylamino, C2~Cg dialkylamino, C^-Cg haloalkylamino or phenyl;

Q¹ is phenyl or naphthalenyl optionally substituted with up to 3 substituents

independently selected from halogen, cyano, C1-C2 alkyl, -C2 haloalkyl, C - C2 alkoxy and C1-C2 haloalkoxy; or a 5- to 6-membered heteroaromatic ring containing ring members selected from carbon atoms and up to 4 heteroatoms independently selected from up to 2 O, up to 2 S and up to 4 N atoms, and optionally substituted with up to 3 substituents independently selected from halogen, cyano, C1-C2 alkyl, C1-C2 haloalkyl, C1-C2 alkoxy and C1-C2 haloalkoxy on carbon atom ring members and cyano, C1-C2 alkyl and C1-C2 alkoxy on nitrogen atom ring members; or a 3- to 7-membered nonaromatic ring containing ring members selected from carbon atoms and up to 4 heteroatoms independently selected from up to 2 O, up to 2 S and up to 4 N atoms, wherein up to 3 carbon atom ring members are independently selected from C(=0) and

C(=S), the sulfur atom ring members are independently selected from S(=O)_s(=NR¹⁰)f and the ring optionally substituted with up to 3 substituents independently selected from halogen, cyano, C1-C2 alkyl, C1-C2 haloalkyl, C - C2 alkoxy and C1-C2 haloalkoxy on carbon atom ring members and cyano, C^- C2 alkyl and C1-C2 alkoxy on nitrogen atom ring members;

m is 0, 1 or 2;

n is 0, 1, 2, 3, 4 or 5; and

s and f are independently 0, 1 or 2 in each instance of S(=O)_s(=NR¹⁰)f, provided that the sum of s and f is 0, 1 or 2;

provided that

when L is O, S(0)_m or NR⁷, then A is CR³ and both R³ and R⁴ are other than

hydrogen.

This invention is also directed to such compounds of Formula 1 (including all stereoisomers), N-oxides, and salts thereof, and compositions containing them and their use for controlling invertebrate pests.

This invention also provides a composition comprising a compound of Formula 1, an N-oxide, or a salt thereof, and at least one additional component selected from the group consisting of surfactants, solid diluents and liquid diluents. In one embodiment, this invention also provides a composition for controlling an invertebrate pest comprising a compound of Formula 1, an N-oxide, or a salt thereof, and at least one additional component selected from the group consisting of surfactants, solid diluents and liquid diluents, said composition further comprising at least one additional biologically active compound or agent.

This invention provides a method for controlling an invertebrate pest comprising contacting the invertebrate pest or its environment with a biologically effective amount of a compound of Formula 1, an N-oxide, or a salt thereof (e.g., as a composition described herein). This invention also relates to such method wherein the invertebrate pest or its environment is contacted with a composition comprising a biologically effective amount of a compound of Formula 1, an N-oxide, or a salt thereof, and at least one additional component selected from the group consisting of surfactants, solid diluents and liquid diluents, said composition optionally further comprising a biologically effective amount of at least one additional biologically active compound or agent.

This invention also provides a method for controlling an invertebrate pest comprising contacting the invertebrate pest or its environment with a biologically effective amount of any of the aforesaid compositions wherein the environment is a plant.

This invention also provides a method for controlling an invertebrate pest comprising contacting the invertebrate pest or its environment with a biologically effective amount of any of the aforesaid compositions wherein the environment is an animal.

This invention also provides a method for controlling an invertebrate pest comprising contacting the invertebrate pest or its environment with a biologically effective amount of any of the aforesaid compositions wherein the environment is a seed.

This invention also provides a method for protecting a seed from an invertebrate pest comprising contacting the seed with a biologically effective amount of a compound of Formula 1, an N-oxide, or a salt thereof (e.g., as a composition described herein). This invention also relates to the treated seed.

This invention further provides a composition for protecting an animal from an invertebrate parasitic pest comprising a parasiticidally effective amount of a compound of Formula 1, an N-oxide, or a salt thereof, and at least one carrier.

This invention further provides a method for treating, preventing, inhibiting and/or killing ecto and/or endoparasites comprising administering to and/or on an animal a parasiticidally effective amount of a compound of Formula 1, an N-oxide, or a salt thereof (e.g., as a composition described herein). This invention also relates to such method wherein a parasiticidally effective amount of a compound of Formula 1, an N-oxide, or a salt thereof, (e.g., as a composition described herein) is administered to an environment (e.g., a stall or blanket) in which an animal resides.

DETAILS OF THE INVENTION

As used herein, the terms "comprises", "comprising", "includes", "including", "has", "having", "contains", "containing", "characterized by" or any other variation thereof, are intended to cover a non-exclusive inclusion, subject to any limitation explicitly indicated. For example, a composition, mixture, process or method that comprises a list of elements is not necessarily limited to only those elements but may include other elements not expressly listed or inherent to such composition, mixture, process or method.

The transitional phrase "consisting of excludes any element, step or ingredient not specified. If in the claim, such would close the claim to the inclusion of materials other than those recited except for impurities ordinarily associated therewith. When the phrase "consisting of appears in a clause of the body of a claim, rather than immediately following the preamble, it limits only the element set forth in that clause; other elements are not excluded from the claim as a whole.

The transitional phrase "consisting essentially of is used to define a composition or method that includes materials, steps, features, components or elements, in addition to those literally disclosed, provided that these additional materials, steps, features, components or elements do not materially affect the basic and novel characteristic(s) of the claimed invention. The term "consisting essentially of occupies a middle ground between

"comprising" and "consisting of.

Where applicants have defined an invention or a portion thereof with an open-ended term such as "comprising", it should be readily understood that (unless otherwise stated) the description should be interpreted to also describe such an invention using the terms

"consisting essentially of or "consisting of.

Further, unless expressly stated to the contrary, "or" refers to an inclusive or and not to an exclusive or. For example, a condition A or B is satisfied by any one of the following: A is true (or present) and B is false (or not present), A is false (or not present) and B is true (or present), and both A and B are true (or present).

Also, the indefinite articles "a" and "an" preceding an element or component of the invention are intended to be nonrestrictive regarding the number of instances (i.e. occurrences) of the element or component. Therefore "a" or "an" should be read to include one or at least one, and the singular word form of the element or component also includes the plural unless the number is obviously meant to be singular.

As referred to in this disclosure, the term "invertebrate pest" includes arthropods, gastropods, nematodes and helminths of economic importance as pests. The term

"arthropod" includes insects, mites, spiders, scorpions, centipedes, millipedes, pill bugs and symphylans. The term "gastropod" includes snails, slugs and other Stylommatophora. The term "nematode" includes members of the phylum Nematoda, such as phytophagous nematodes and helminth nematodes parasitizing animals. The term "helminth" includes all of the parasitic worms, such as roundworms (phylum Nematoda), heartworms (phylum

Nematoda, class Secernentea), flukes (phylum Platyhelminthes, class Tematoda), acanthocephalans (phylum Acanthocephala), and tapeworms (phylum Platyhelminthes, class

Cestoda).

In the context of this disclosure "invertebrate pest control" means inhibition of invertebrate pest development (including mortality, feeding reduction, and/or mating disruption), and related expressions are defined analogously.

The term "agronomic" refers to the production of field crops such as for food and fiber and includes the growth of corn, soybeans and other legumes, rice, cereal (e.g., wheat, oats, barley, rye, rice, maize), leafy vegetables (e.g., lettuce, cabbage, and other cole crops), fruiting vegetables (e.g., tomatoes, pepper, eggplant, crucifers and cucurbits), potatoes, sweet potatoes, grapes, cotton, tree fruits (e.g., pome, stone and citrus), small fruit (berries, cherries) and other specialty crops (e.g., canola, sunflower, olives).

The term "nonagronomic" refers to other than field crops, such as horticultural crops

(e.g., greenhouse, nursery or ornamental plants not grown in a field), residential, agricultural, commercial and industrial structures, turf (e.g., sod farm, pasture, golf course, lawn, sports field, etc.), wood products, stored product, agro-forestry and vegetation management, public health (i.e. human) and animal health (e.g., domesticated animals such as pets, livestock and poultry, undomesticated animals such as wildlife) applications.

Nonagronomic applications include protecting an animal from an invertebrate parasitic pest by administering a parasiticidally effective (i.e. biologically effective) amount of a compound of the invention, typically in the form of a composition formulated for veterinary use, to the animal to be protected. As referred to in the present disclosure and claims, the terms "parasiticidal" and "parasiticidally" refers to observable effects on an invertebrate parasite pest to provide protection of an animal from the pest. Parasiticidal effects typically relate to diminishing the occurrence or activity of the target invertebrate parasitic pest. Such effects on the pest include necrosis, death, retarded growth, diminished mobility or lessened ability to remain on or in the host animal, reduced feeding and inhibition of reproduction. These effects on invertebrate parasite pests provide control (including prevention, reduction or elimination) of parasitic infestation or infection of the animal.

In the above recitations, the term "alkyl", used either alone or in compound words such as "haloalkyl" includes straight-chain or branched alkyl, such as, methyl, ethyl, n-propyl, /-propyl, or the different butyl, pentyl or hexyl isomers. "Alkenyl" includes straight-chain or branched alkenes such as ethenyl, 1-propenyl, 2-propenyl, and the different butenyl, pentenyl and hexenyl isomers. "Alkenyl" also includes polyenes such as 1 ,2-propadienyl and 2,4-hexadienyl. "Alkynyl" includes straight-chain or branched alkynes such as ethynyl, 1-propynyl, 2-propynyl and the different butynyl, pentynyl and hexynyl isomers. "Alkynyl" can also include moieties comprised of multiple triple bonds such as 2,5-hexadiynyl.

"Cycloalkyl" includes, for example, cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl. The term "cycloalkylalkyl" denotes cycloalkyl substitution on an alkyl moiety. Examples of "cycloalkylalkyl" include cyclopropylmethyl, cyclopentylethyl, and other cycloalkyl moieties bonded to straight-chain or branched alkyl groups. "Cycloalkenyl" includes groups such as cyclopentenyl and cyclohexenyl as well as groups with more than one double bond such as 1,3- and 1,4-cyclohexadienyl. The term "cycloalkoxy" denotes cycloalkyl attached to and linked through an oxygen atom such as cyclopentyloxy and cyclohexyloxy. "Alkylcycloalkylalkyl" denotes an alkyl group substituted with alkylcycloalkyl. Examples of "alkylcycloalkylalkyl" include 1-, 2-, 3- or 4-methyl or -ethyl cyclohexylmethyl. The term "cycloalkylcycloalkyl" denotes cycloalkyl substitution on another cycloalkyl ring, wherein each cycloalkyl ring independently has from 3 to 7 carbon atom ring members. Examples of cycloalkylcycloalkyl include cyclopropylcyclopropyl (such as Ι,Γ-bicyclopropyl-l-yl, l,l'-bicyclopropyl-2-yl), cyclohexylcyclopentyl (such as 4- cyclopentylcyclohexyl) and cyclohexylcyclohexyl (such as Ι,Γ-bicyclohexyl-l-yl), and the different cis- and trans-cycloalkylcycloalkyl isomers, (such as (li?,25)-l,l'-bicyclopropyl-2- yl and (li?,2i?)-l,l'-bicyclopropyl-2-yl). "Cycloalkylamino" denotes an NH radical substituted with cycloalkyl. Examples of "cycloalkylamino" include cyclopropylamino and cyclohexylamino. The term "cycloalkylaminoalkyl" denotes cycloalkylamino substitution on an alkyl group. Examples of "cycloalkylaminoalkyl" include cyclopropylaminomethyl, cyclopentylaminoethyl, and other cycloalkylamino moieties bonded to straight-chain or branched alkyl groups.

The term "halogen", either alone or in compound words such as "haloalkyl", or when used in descriptions such as "alkyl substituted with halogen" includes fluorine, chlorine, bromine or iodine. Further, when used in compound words such as "haloalkyl", or when used in descriptions such as "alkyl substituted with halogen" said alkyl may be partially or fully substituted with halogen atoms which may be the same or different. Examples of "haloalkyl" or "alkyl substituted with halogen" include CF₃, CH₂C1, CH₂CF₃ and CC1₂CF₃. The terms "haloalkenyl", "haloalkynyl" "haloalkoxy", "haloalkylthio", "haloalkylamino", "haloalkylsulfinyl", "haloalkylsulfonyl", "halocycloalkyl", and the like, are defined analogously to the term "haloalkyl". Examples of "haloalkenyl" include (C1)2C=CHCH2 and CF₃CH₂CH=CHCH₂. Examples of "haloalkynyl" include HC≡CCHC1, CF₃C≡C, CC1₃C≡C and FCH₂C≡CCH₂. Examples of "haloalkoxy" include CF₃0, CC1₃CH₂0, HCF₂CH₂CH₂0 and CF₃CH₂0. Examples of "haloalkylthio" include CC1₃S, CF₃S, CC1₃CH₂S and C1CH₂CH₂CH₂S. Examples of "haloalkylamino" include CF₃(CH₃)CHNH, (CF₃)₂CHNH and CH₂C1CH₂NH. Examples of "haloalkylsulfinyl" include CF₃S(=0), CC1₃S(=0), CF₃CH₂S(=0) and CF₃CF₂S(=0). Examples of "haloalkylsulfonyl" include CF₃S(=0)₂, CC1₃S(=0)₂, CF₃CH₂S(=0)₂ and CF₃CF₂S(=0)₂. Examples of "halocycloalkyl" include 2-chlorocyclopropyl, 2-fluorocyclobutyl, 3-bromocyclopentyl and 4-chlorocyclohexyl. The term "halodialkyl", either alone or in compound words such as "halodialkylamino", means at least one of the two alkyl groups is substituted with at least one halogen atom, and independently each halogenated alkyl group may be partially or fully substituted with halogen atoms which may be the same or different. Examples of "halodialkylamino" include (BrCH₂CH₂)₂N and BrCH₂CH₂(ClCH₂CH₂)N. "Alkoxy" includes, for example, methoxy, ethoxy, n-propoxy, isopropoxy and the different butoxy, pentoxy and hexyloxy isomers. "Alkoxyalkyl" denotes alkoxy substitution on alkyl. Examples of "alkoxyalkyl" include CH₂OCH₃, CH₂CH₂OCH₃, CH₂OCH₂CH₃, CH₂OCH₂CH₂CH₂CH₃ and CH₂CH₂OCH₂CH₃. "Alkenyloxy" includes straight-chain or branched alkenyl attached to and linked through an oxygen atom. Examples of "alkenyloxy" include H₂C=CHCH₂0, (CH₃)₂C=CHCH₂0, (CH₃)CH=CHCH₂0,

(CH₃)CH=C(CH₃)CH₂0 and CH₂=CHCH₂CH₂0. "Alkynyloxy" includes straight-chain or branched alkynyloxy moieties. Examples of "alkynyloxy" include HC≡CCH₂0, CH₃C≡CCH₂0 and CH₃C≡CCH₂CH₂0.

The term "alkylthio" includes straight-chain or branched alkylthio moieties such as methylthio, ethylthio, and the different propylthio, butylthio, pentylthio and hexylthio isomers. "Alkylsulfmyl" includes both enantiomers of an alkylsulfinyl group. Examples of "alkylsulfmyl" include CH₃S(=0), CH₃CH₂S(=0), CH₃CH₂CH₂S(=0), (CH₃)₂CHS(=0) and the different butylsulfinyl, pentylsulfinyl and hexylsulfinyl isomers. Examples of "alkylsulfonyl" include CH₃S(=0)₂, CH₃CH₂S(=0)₂, CH₃CH₂CH₂S(=0)₂, (CH₃)₂CHS(=0)₂, and the different butylsulfonyl, pentylsulfonyl and hexylsulfonyl isomers. The chemical abbreviations S(O) and S(=0) as used herein represent a sulfmyl moiety. The chemical abbreviations S0₂, S(0)₂ and S(=0)₂ as used herein represent a sulfonyl moiety.

"Alkylamino" denotes an NH radical substituted with straight-chain or branched alkyl. Examples of "alkylamino" include NHCH₂CH₃, NHCH₂CH₂CH₃, and NHCH₂CH(CH₃)₂. "Dialkylamino" denotes an N radical substituted independently with two straight-chain or branched alkyl groups. Examples of "dialkylamino" include N(CH₃)₂, N(CH₃CH₂CH₂)₂ and N(CH₃)CH₂CH₃. "Halodialkylamino" denotes one straight-chain or branched alkyl moiety and one straight-chain or branched haloalkyl moiety bonded to an N radical, or two independent straight-chain or branched haloalkyl moieties bonded to an N radical, wherein "haloalkyl" is as defined above. Examples of "halodialkylamino" include N(CH₂CH₃)(CH₂CH₂C1) and N(CF₂CF₃)₂. An example of haloalkylcarbonylamino is NHC(0)CF₃ and an example of haloalkylcarbonyl(alkyl)amino is N(CH₃)C(0)CF₃.

"Alkylcarbonyl" denotes a straight-chain or branched alkyl moiety bonded to a C(O) moiety. The chemical abbreviations C(O) and C(=0) as used herein represent a carbonyl moiety. Examples of "alkylcarbonyl" include C(0)CH₃, C(0)CH₂CH₂CH₃ and C(0)CH(CH₃)₂. Examples of "haloalkylcarbonyl" include C(0)CF₃, C(0)CC1₃, C(0)CH₂CF₃ and C(0)CF₂CF₃.

"Alkoxycarbonyl" denotes a straight-chain or branched alkyl moiety bonded to a C0₂ moiety. The chemical abbreviations C0₂, C(0)0 and C(=0)0 as used herein represent an oxycarbonyl moiety. Examples of "alkoxycarbonyl" include C(0)OCH₃, C(0)OCH₂CH₃, C(0)OCH₂CH₂CH₃ and C(0)OCH(CH₃)₂.

"Alkylaminocarbonyl" denotes a straight-chain or branched alkyl moiety bonded to a C(0)NH moiety. The chemical abbreviations C(0)NH, and C(0)N as used herein represent an amide moiety (i.e. an aminocarbonyl group). Examples of "alkylaminocarbonyl" include C(0)NHCH₃, C(0)NHCH₂CH₂CH₃ and C(0)NHCH(CH₃)₂. "Dialkylaminocarbonyl" denotes two independent straight-chain or branched alkyl moieties bonded to a C(0)N moiety. Examples of "dialkylaminocarbonyl" include C(0)N(CH₃)₂ and C(0)N(CH₃)(CH₂CH₃).

"Trialkylsilyl" includes 3 branched and/or straight-chain alkyl radicals attached to and linked through a silicon atom, such as trimethylsilyl, triethylsilyl and tert-butyldimethylsilyl.

"-CHO" means formyl.

The total number of carbon atoms in a substituent group is indicated by the "C -Cj" prefix where i and j are numbers from 1 to 14. For example, C1-C4 alkyl designates methyl through butyl; C₂ alkoxyalkyl designates CH₂OCH₃; C₃ alkoxyalkyl designates, for example, CH₃CH(OCH₃), CH₂CH₂OCH₃ or CH₂OCH₂CH₃; and C₄ alkoxyalkyl designates the various isomers of an alkyl group substituted with an alkoxy group containing a total of four carbon atoms, examples including CH₂OCH₂CH₂CH₃ and CH₂CH₂OCH₂CH₃.

When a group contains a substituent which can be hydrogen, for example R², then when this substituent is taken as hydrogen, it is recognized that this is equivalent to said group being unsubstituted. When a variable group is shown to be optionally attached to a position, for example (R⁶)_n in Formula 1 wherein n may be 0, then hydrogen can be at the position even if not recited in the variable group definition. When one or more positions on a group are said to be "not substituted" or "unsubstituted", then hydrogen atoms are attached to take up any free valency.

Unless otherwise indicated, a "ring" or "ring system" as a component of Formula 1 is carbocyclic or heterocyclic. The term "ring system" denotes two or more connected rings. The term "bicyclic ring system" denotes a ring system consisting of two rings sharing two or more common atoms.

A ring or a bicyclic ring system can be part of an extended ring system containing more than two rings wherein substituents on the ring or bicyclic ring system are taken together to form the additional rings, which may be in bicyclic relationships with other rings in the extended ring system.

The term "ring member" refers to an atom (e.g., C, O, N or S) or other moiety (e.g., C(=0) or C(=S) or S(=O)_s(=NR¹⁰)f)) forming the backbone of a ring or ring system. The term "aromatic" indicates that each of the ring atoms is essentially in the same plane and has a /^-orbital perpendicular to the ring plane, and that (4n + 2) π electrons, where n is a positive integer, are associated with the ring or ring system to comply with Huckel's rule.

"Partially saturated" and "partially unsaturated" with reference to a ring or ring system means that the ring or ring system contains at least one double bond but the ring or ring system is not aromatic. A ring system is aromatic if at least one component ring is aromatic.

The term "carbocyclic ring" denotes a ring wherein the atoms forming the ring backbone are selected only from carbon. Unless otherwise indicated, a carbocyclic ring can be a saturated, partially unsaturated, or fully unsaturated ring. When a fully unsaturated carbocyclic ring satisfies Huckel's rule, then said ring is also called an "aromatic ring". "Saturated carbocyclic ring" refers to a ring having a backbone consisting of carbon atoms linked to one another by single bonds; unless otherwise specified, the remaining carbon valences are occupied by hydrogen atoms.

The terms "heterocyclic ring" or "heterocycle" denotes a ring wherein at least one of the atoms forming the ring backbone is other than carbon. Unless otherwise indicated, a heterocyclic ring can be a saturated, partially unsaturated, or fully unsaturated ring. "Saturated heterocyclic ring" refers to a heterocyclic ring containing only single bonds between ring members. "Partially saturated heterocyclic ring" refers a heterocyclic ring containing at least one double bond but which is not aromatic. The term "heteroaromatic ring" denotes a fully unsaturated aromatic ring in which at least one atom forming the ring backbone is not carbon. Typically a heteroaromatic ring contains no more than 4 nitrogens, no more than 1 oxygen and no more than 1 sulfur. Unless otherwise indicated, heteroaromatic rings can be attached through any available carbon or nitrogen by replacement of a hydrogen on said carbon or nitrogen. The term "heteroaromatic bicyclic ring system" denotes a ring system consisting of two fused rings, in which at least one of the two rings is a heteroaromatic ring as defined above.

When a radical (e.g., a 5- to 6-membered heteroaromatic ring in the definition of R⁶) is optionally substituted with listed substituents with the number of substituents stated (e.g., "up to 3"), then the radical may be unsubstituted or substituted with a number of substituents ranging up to the high number stated (e.g., "3"), and the attached substituents are independently selected from the substituents listed.

When a substituent (e.g., Q¹) is a ring or ring system, it can be attached to the remainder of Formula 1 through any available ring member, unless otherwise described.

As noted above, R⁶ is, among others, a 3- to 7-membered nonaromatic ring, each ring containing ring members selected from carbon atoms and up to 4 heteroatoms independently selected from up to 2 O, up to 2 S and up to 4 N wherein up to 3 carbon atom ring members are independently selected from C(=0) and C(=S) and the sulfur atom ring members are independently selected from S(=O)_s(=NR¹⁰)f. In this definition the ring members selected from up to 2 O, up to 2 S and up to 4 N are optional, because the number of heteroatom ring members may be zero. When no heteroatom ring members are present, the ring or ring system is carbocyclic. If at least one heteroatom ring member is present, the ring or ring system is heterocyclic. The definition of S(=O)_s(=NR¹⁰)f allows up to 2 sulfur ring members, which can be oxidized sulfur moieties (e.g., S(=0) or S(=0)2) or unoxidized sulfur atoms (i.e. when s and f are both zero). The nitrogen atom ring members may be oxidized as N-oxides, because compounds relating to Formula 1 also include N-oxide derivatives. The up to 3 carbon atom ring members selected from C(=0) and C(=S) are in addition to the up to 4 heteroatoms selected from up to 2 O, up to 2 S and up to 4 N atoms. As the ring substituents are optional, 0 to 3 substituents may be present, limited only by the number of available points of attachment.

The term "unsubstituted" in connection with a group such as a ring or ring system means the group does not have any substituents other than its one or more attachments to the remainder of Formula 1. The term "optionally substituted" means that the number of substituents can be zero. Unless otherwise indicated, optionally substituted groups may be substituted with as many optional substituents as can be accommodated by replacing a hydrogen atom with a non-hydrogen substituent on any available carbon or nitrogen atom. Commonly, the number of optional substituents (when present) ranges from 1 to 3.

The number of optional substituents may be restricted by an expressed limitation. For example, the phrase "optionally substituted with up to 3 substituents independently selected from halogen, cyano, C1-C2 alkyl, C1-C2 haloalkyl, C1-C2 alkoxy and C1-C2 haloalkoxy on carbon atom ring members and cyano, C1-C2 alkyl and C1-C2 alkoxy on nitrogen atom ring members" means that 0, 1, 2 or 3 substituents can be present (if the number of potential connection points allows). When a range specified for the number of substituents exceeds the number of positions available for substituents on a ring, the actual higher end of the range is recognized to be the number of available positions.

When the number of optional substituents is not restricted by an expressed limitation (e.g., the phrases "optionally substituted with halogen" or "unsubstituted or substituted with at least one substituent independently selected from"), it is understood to mean that the number of optional substituents can range from 0 up to the number of positions available. One skilled in the art will appreciate that while some substituents such as halogen can be present at every available position (for example, the C2F5 substituent is a C2 alkyl group substituted with the maximum number of 5 fluorine atoms), practical factors such as cost and synthetic accessibility can limit the number of occurences of other substituents. These limitations are part of the general synthetic knowledge known to those skilled in the art. Of note are embodiments wherein in the absence of expressed limitation of number of optional substituents, the number of optional substituents is up to 3 (i.e. 0, 1, 2 or 3) if accommodated by the number of available positions.

As noted above, substituents such as R⁶ can be (among others) a 5- or 6-membered heteroaromatic ring optionally substituted with up to 3 substituents selected from a group of substituents as defined in the Summary of Invention. Examples of a 5- or 6-membered heteroaromatic ring optionally substituted with one or more substituents include the rings U-2 through U-61 illustrated in Exhibit 1 wherein R^v is any substituent as defined in the Summary of the Invention for R⁶ (halogen, cyano, C1-C2 alkyl, C1-C2 haloalkyl, C1-C2 alkoxy and C1-C2 haloalkoxy on carbon atom ring members and cyano, C1-C2 alkyl and C1-C2 alkoxy on nitrogen atom ring members) and r is an integer from 0 to 3, limited by the number of available positions on each U group. As U-29, U-30, U-36, U-37, U-38, U-39, U-40, U-41, U-42 and U-43 have only one available position, for these U groups r is limited to the integers 0 or 1 , and r being 0 means that the U group is unsubstituted and a hydrogen is present at the position indicated by (R^v)_r.

Exhibit 1

U-l U-2 U-3 U-4 U-5

U-16 U-17 U-l U-19 U-20

U-21 U-22 U-23 -24 U-25

-26 U-27 U-28 U-29 U-30

U-31 U-32 U-33 U-34 U-35

-36 U-37 -38 -39 U-40

U-41 U-42 U-43 U-44 U-45

U-46 U-47 U-48 U-49 U-50

U-51 U-52 U-53 U-54 U-55

U-56 U-57 U-58 U-59 U-60

U-61

Note that when R⁶ is a 3- to 7-membered saturated or unsaturated non-aromatic heterocyclic ring optionally substituted with up to 3 substituents selected from the group of substituents as defined in the Summary of Invention for R⁶, one or two carbon ring members of the heterocycle can optionally be in the oxidized form of a carbonyl moiety.

Examples of a 3- to 7-membered saturated or non-aromatic unsaturated heterocyclic ring include the rings G-1 through G-40 as illustrated in Exhibit 2. Note that when the attachment point on the G group is illustrated as floating, the G group can be attached to the remainder of Formula 1 through any available carbon or nitrogen of the G group by replacement of a hydrogen atom. The optional substituents corresponding to R^v can be attached to any available carbon or nitrogen by replacing a hydrogen atom. For these G rings, r is typically an integer from 0 to 4, limited by the number of available positions on each G group.

Note that when R⁶ comprises a ring selected from G-33 through G-40, G² is selected from O, S or N. Note that when G² is N, the nitrogen atom can complete its valence by substitution with either H or the substituents corresponding to R^v as defined in the Summary of Invention for R⁶ (i.e. halogen, cyano, C1-C2 alkyl, C1-C2 haloalkyl, C1-C2 alkoxy and C1-C2 haloalkoxy on carbon atom ring members and cyano, C1-C2 alkyl and C1-C2 alkoxy on nitrogen atom ring members).

Exhibit 2

G-l l G-12 G-13 G-14 G-15

G-36 G-37 G-38 G-39 G-40

Although R^v groups are shown in the structures of Exhibits 1 and 2, it is noted that they do not need to be present since they are optional substituents. Note that when R^v is H when attached to an atom, this is the same as if said atom is unsubstituted. The nitrogen atoms that require substitution to fill their valence are substituted with H or R^v. Note that when the attachment point between (R^v)_r and the ring is illustrated as floating, (R^v)_r can be attached to any available carbon atom or nitrogen atom of the ring. Note that when the attachment point on the ring is illustrated as floating, the ring can be attached to the remainder of Formula 1 through any available carbon or nitrogen of the ring by replacement of a hydrogen atom.

A wide variety of synthetic methods are known in the art to enable preparation of aromatic and nonaromatic heterocyclic rings and ring systems; for extensive reviews see the eight volume set of Comprehensive Heterocyclic Chemistry, A. R. Katritzky and C. W. Rees editors-in-chief, Pergamon Press, Oxford, 1984 and the twelve volume set of Comprehensive Heterocyclic Chemistry II, A. R. Katritzky, C. W. Rees and E. F. V. Scriven editors-in-chief, Pergamon Press, Oxford, 1996.

Compounds of this invention can exist as one or more stereoisomers. The various stereoisomers include enantiomers, diastereomers and atropisomers. One skilled in the art will appreciate that one stereoisomer may be more active and/or may exhibit beneficial effects when enriched relative to the other stereoisomer(s) or when separated from the other stereoisomer(s). Additionally, the skilled artisan knows how to separate, enrich, and/or to selectively prepare said stereoisomers. The compounds of the invention may be present as a mixture of stereoisomers, individual stereoisomers or as an optically active form. For example, two possible enantiomers of Formula 1 are depicted as Formula la and Formula lb involving the chiral center identified with an asterisk (*). Analogously, other chiral centers are possible in other roups, for example in R⁴ or R⁶.

la lb

Molecular depictions drawn herein follow standard conventions for depicting stereochemistry. To indicate stereoconfiguration, bonds rising from the plane of the drawing and towards the viewer are denoted by solid wedges wherein the broad end of the wedge is attached to the atom rising from the plane of the drawing towards the viewer. Bonds going below the plane of the drawing and away from the viewer are denoted by dashed wedges wherein the narrow end of the wedge is attached to the atom further away from the viewer. Constant width lines indicate bonds with a direction opposite or neutral relative to bonds shown with solid or dashed wedges; constant width lines also depict bonds in molecules or parts of molecules in which no particular stereoconfiguration is intended to be specified. This invention comprises racemic mixtures, for example, equal amounts of the enantiomers of Formulae la and lb. In addition, this invention includes compounds that are enriched compared to the racemic mixture in an enantiomer of Formula 1. Also included are the essentially pure enantiomers of compounds of Formula 1, for example, Formula la and Formula lb.

When enantiomerically enriched, one enantiomer is present in greater amounts than the other, and the extent of enrichment can be defined by an expression of enantiomeric excess ("ee"), which is defined as (2χ-1)· 100 %, where x is the mole fraction of the dominant enantiomer in the mixture (e.g., an ee of 20 % corresponds to a 60:40 ratio of enantiomers).

Preferably the compositions of this invention have at least a 50 % enantiomeric excess; more preferably at least a 75 % enantiomeric excess; still more preferably at least a 90 % enantiomeric excess; and the most preferably at least a 94 % enantiomeric excess of the more active isomer. Of particular note are enantiomerically pure embodiments of the more active isomer.

Compounds of Formula 1 can comprise additional chiral centers. For example, substituents and other molecular constituents such as R⁴ may themselves contain chiral centers. This invention comprises racemic mixtures as well as enriched and essentially pure stereoconfigurations at these additional chiral centers.

Compounds selected from Formula 1 (including all stereoisomers, N-oxides, and salts thereof) typically exist in more than one form, and Formula 1 thus includes all crystalline and non-crystalline forms of the compounds that Formula 1 represents. Non-crystalline forms include embodiments which are solids such as waxes and gums as well as embodiments which are liquids such as solutions and melts. Crystalline forms include embodiments which represent essentially a single crystal type and embodiments which represent a mixture of polymorphs (i.e. different crystalline types). The term "polymorph" refers to a particular crystalline form of a chemical compound that can crystallize in different crystalline forms, these forms having different arrangements and/or conformations of the molecules in the crystal lattice. Although polymorphs can have the same chemical composition, they can also differ in composition due to the presence or absence of co- crystallized water or other molecules, which can be weakly or strongly bound in the lattice. Polymorphs can differ in such chemical, physical and biological properties as crystal shape, density, hardness, color, chemical stability, melting point, hygroscopicity, suspensibility, dissolution rate and biological availability. One skilled in the art will appreciate that a polymorph of a compound represented by Formula 1 can exhibit beneficial effects (e.g., suitability for preparation of useful formulations, improved biological performance) relative to another polymorph or a mixture of polymorphs of the same compound represented by Formula 1. Preparation and isolation of a particular polymorph of a compound represented by Formula 1 can be achieved by methods known to those skilled in the art including, for example, crystallization using selected solvents and temperatures.

One skilled in the art will appreciate that not all nitrogen-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 will also recognize that tertiary amines can form N-oxides. Synthetic methods for the preparation of N-oxides of heterocycles and tertiary amines are very well known by one skilled in the art including the oxidation of heterocycles and tertiary amines with peroxy acids such as peracetic and 3-chloroperbenzoic acid (MCPBA), hydrogen peroxide, alkyl hydroperoxides such as t-butyl hydroperoxide, sodium perborate, and dioxiranes such as dimethyldioxirane. These methods for the preparation of N-oxides have been extensively described and reviewed in the literature, see for example: T. L. Gilchrist in Comprehensive Organic Synthesis, vol. 7, pp 748-750, S. V. Ley, Ed., Pergamon Press; M. Tisler and B. Stanovnik in Comprehensive Heterocyclic Chemistry, vol. 3, pp 18-20, A. J. Boulton and A. McKillop, Eds., Pergamon Press; M. R. Grimmett and B. R. T. Keene in Advances in Heterocyclic Chemistry, vol. 43, pp 149-161, A. R. Katritzky, Ed., Academic Press; M. Tisler and B. Stanovnik in Advances in Heterocyclic Chemistry, vol. 9, pp 285-291, A. R. Katritzky and A. J. Boulton, Eds., Academic Press; and G. W. H. Cheeseman and E. S. G. Werstiuk in Advances in Heterocyclic Chemistry, vol. 22, pp 390-392, A. R. Katritzky and A. J. Boulton, Eds., Academic Press.

One skilled in the art recognizes that because in the environment and under physiological conditions salts of chemical compounds are in equilibrium with their corresponding nonsalt forms, salts share the biological utility of the nonsalt forms. Thus a wide variety of salts of the compounds of Formula 1 are useful for control of invertebrate pests and animal parasites (i.e. are suitable for animal health use). The salts of the compounds of Formula 1 include acid-addition salts with inorganic or organic acids such as hydrobromic, hydrochloric, nitric, phosphoric, sulfuric, acetic, butyric, fumaric, lactic, maleic, malonic, oxalic, propionic, salicylic, tartaric, 4-toluenesulfonic or valeric acids. When a compound of Formula 1 contains an acidic moiety such as a carboxylic acid or phenol, salts also include those formed with organic or inorganic bases such as pyridine, triethylamine or ammonia, or amides, hydrides, hydroxides or carbonates of sodium, potassium, lithium, calcium, magnesium or barium. Accordingly, the present invention comprises compounds selected from Formula 1, N-oxides, and salts thereof.

Embodiments of the present invention as described in the Summary of the Invention include those described below. In the following Embodiments Formula 1 includes stereoisomers, N-oxides, and salts thereof, and reference to "a compound of Formula 1" includes the definitions of substituents specified in the Summary of the Invention unless further defined in the Embodiments.

Embodiment 1. A compound of Formula 1 wherein L is L-l, L-2, L-3, L-4 or L-5. Embodiment la. A compound of Embodiment 1 wherein L is L-l, L-2 or L-3.

Embodiment lb. A compound of Embodiment la wherein L is L-l or L-2.

Embodiment lc. A compound of Formula 1 wherein L is O, S(0)_m or NR⁷ provided that A is CR³ and both R³ and R⁴ are other than hydrogen.

Embodiment 2. A compound of Formula 1 or any one of Embodiments 1 through lc wherein A is N.

Embodiment 2a. A compound of Formula 1 or any one of Embodiments 1 through lc wherein A is CR³.

Embodiment 3. A compound of Formula 1 or any one of Embodiments 1 through 2a either alone or in combination, wherein Q is N.

Embodiment 3 a. A compound of Formula 1 or any one of Embodiments 1 through 2a either alone or in combination, wherein Q is CH or CR⁶.

Embodiment 3b. A compound Embodiment 3a wherein Q is CH.

Embodiment 3c. A compound of Embodiment 3a wherein Q is CR⁶.

Embodiment 4. A compound of Formula 1 or any one of Embodiments 1 through 3 c either alone or in combination, wherein R^la and R¹^ are each independently selected from hydrogen, fluorine, chlorine and C1-C2 alkyl.

Embodiment 4a. A compound of Embodiment 4 wherein R^la and R¹^ are each

independently selected from hydrogen, fluorine and methyl.

Embodiment 4b. A compound of Embodiment 4a wherein R^la and R¹^ are each

independently selected from hydrogen and fluorine.

Embodiment 4c. A compound of Embodiment 4b wherein at least one of R^la or R¹^ is fluorine.

Embodiment 4d. A compound of Embodiment 4b wherein R^la and R¹^ are each

hydrogen.

Embodiment 5. A compound of Formula 1 or any one of Embodiments 1 through 4d, either alone or in combination, wherein at least one of R² and R⁵ is fluorine. Embodiment 5 a. A compound of Formula 1 or any one of Embodiments 1 through 4d, either alone or in combination, wherein R² and R⁵ are each hydrogen. Embodiment 6. A compound of Formula 1 or any one of Embodiments 1 through 5 a, either alone or in combination, wherein R³ and R⁴ are each independently selected from hydrogen, halogen, cyano, amino, nitro, SF₅, -CHO, C^-Cg alkyl, C2-C6 alkenyl, C2~Cg alkynyl, C^-Cg haloalkyl, C2~Cg haloalkenyl, C2~Cg haloalkynyl, C3-C6 cycloalkyl, C3-C6 halocycloalkyl, C4-C8 alkylcycloalkyl, C4-C8 cycloalkylalkyl, C3-C6 cycloalkenyl, C2~Cg alkoxyalkyl, C2~Cg alkylthioalkyl, C2~Cg alkylcarbonyl, C2~Cg haloalkylcarbonyl, C2~Cg alkoxycarbonyl, C2~Cg alkylaminocarbonyl, C3-C8 dialkylaminocarbonyl, C2- Cg cyanoalkyl, C^-Cg alkoxy, C^-Cg haloalkoxy, C2~Cg alkoxyalkoxy, C^-Cg alkylthio, C^-Cg haloalkylthio, C^-Cg alkylsulfinyl, C^-Cg haloalkylsulfinyl, C^-Cg alkylsulfonyl, C^-Cg haloalkylsulfonyl, C3-C9 trialkylsilyl, C^-Cg alkylamino, C2~Cg dialkylamino, C2~Cg haloalkylamino, C2~Cg

halodialkylamino and C2~Cg alkylcarbonylamino; or Q¹.

Embodiment 6a. A compound of Embodiment 6 wherein R³ and R⁴ are each

independently selected from hydrogen, halogen, C^-Cg alkyl, C^-Cg haloalkyl, C_j-Cg alkoxy, C^-Cg haloalkoxy, C^-Cg alkylthio, C^-Cg alkylsulfinyl and C - Cg alkylsulfonyl; or Q¹.

Embodiment 6b. A compound of Embodiment 6a wherein R³ and R⁴ are each

independently selected from hydrogen, halogen, C^-Cg alkyl, C^-Cg alkoxy, C^-Cg alkylthio, C^-Cg alkylsulfinyl, C^-Cg alkylsulfonyl, pyrazole, imidazole, 1 ,2,3-triazole and 1 ,2,4-triazole.

Embodiment 6c. A compound of Embodiment 6b wherein R³ and R⁴ are each

independently selected from hydrogen, fluoro, chloro, methoxy, methylthio, methylsulfmyl, methylsulfonyl and pyrazole.

Embodiment 6d. A compound of Embodiment 6c wherein R³ and R⁴ are each

independently selected from hydrogen, fluoro, chloro, methoxy and methylthio.

Embodiment 6e. A compound of Embodiments 6 through 6d wherein R³ and R⁴ are other than hydrogen.

Embodiment 7. A compound of Formula 1 or any one of Embodiments 1 through 6e, either alone or in combination, wherein each R⁶ is independently halogen, hydroxy, amino, cyano, nitro, SF₅, C^-Cg alkyl, C2~Cg alkenyl, C2~Cg alkynyl, C3~Cg cycloalkyl, C4-C10 cycloalkylalkyl, C4-C10 alkylcycloalkyl, C5-C10 alkylcycloalkylalkyl, Cg-C^ cycloalkylcycloalkyl, C^-Cg haloalkyl, C2~Cg haloalkenyl, C2~Cg haloalkynyl, C3~Cg halocycloalkyl, C1-C4 alkoxy, C1-C4 haloalkoxy, C2-C4 alkoxyalkoxy, C1-C4 alkylthio, C1-C4 alkylsulfinyl, C1-C4 alkylsulfonyl, -C4 haloalkylthio, C1-C4 haloalkylsulfinyl, C1-C4

haloalkylsulfonyl, C1-C4 alkylamino, C2~Cg dialkylamino, C3~Cg

cycloalkylamino, C2-C4 alkoxyalkyl, C1-C4 hydroxyalkyl, C2-C4

alkylcarbonyl, C2~Cg alkoxycarbonyl, C2~Cg alkylcarbonyloxy, C2~Cg alkylcarbonylthio, C2~Cg alkylaminocarbonyl, C3-C8 dialkylaminocarbonyl, C3-C6 haloalkylcarbonylamino, C3-C6 haloalkylcarbonyl(alkyl)amino or C3-C6 trialkylsilyl; or phenyl.

Embodiment 7a. A compound of Embodiment 7 wherein R⁶ is halogen, hydroxy,

amino, cyano, nitro, SF₅, C^-Cg alkyl, C2~Cg alkenyl, C2~Cg alkynyl, C3-C6 cycloalkyl, C4-C10 cycloalkylalkyl, C4-C10 alkylcycloalkyl, C5-C10

alkylcycloalkylalkyl, Cg-C^ cycloalkylcycloalkyl, C^-Cg haloalkyl, C2~Cg haloalkenyl, C2~Cg haloalkynyl, C3-C6 halocycloalkyl, C1-C4 alkoxy, C1-C4 haloalkoxy, C1-C4 alkylthio, C1-C4 alkylsulfinyl, C1-C4 alkylsulfonyl, C1-C4 haloalkylthio, C1-C4 haloalkylsulfinyl, C1-C4 haloalkylsulfonyl, C1-C4 alkylamino, C2~Cg dialkylamino, C3-C6 cycloalkylamino, C2-C4 alkoxyalkyl, C1-C4 hydroxyalkyl, C2-C4 alkylcarbonyl, C2~Cg alkylcarbonyloxy, C2~Cg alkylcarbonylthio, or C3-C6 trialkylsilyl; or phenyl.

Embodiment 7b. A compound of Embodiment 7a wherein each R⁶ is independently halogen, SF₅, C^-Cg alkyl, C^-Cg haloalkyl, C1-C4 alkoxy, C1-C4 haloalkoxy,

C1-C4 alkylthio, C1-C4 alkylsulfinyl, C1-C4 alkylsulfonyl, C1-C4 haloalkylthio, C1-C4 haloalkylsulfinyl, C1-C4 haloalkylsulfonyl or C3~Cg trialkylsilyl.

Embodiment 7c. A compound of Embodiment 7b wherein each R⁶ is independently halogen, SF₅, C^-Cg alkyl, C^-Cg haloalkyl, C1-C4 alkoxy, C1-C4 haloalkoxy -C4 alkylthio or C!-C₄ haloalkylthio.

Embodiment 7d. A compound of Embodiment 7c wherein each R⁶ is independently halogen, SF₅, ieri-butyl, CF₃, OCF₃, CF₂CF₃, CF(CF₃)₂ or SCF₃.

Embodiment 8. A compound of Formula 1 or any one of Embodiments 1 through 7d, either alone or in combination, wherein n is 0, 1 or 2.

Embodiment 8a. A compound of Embodiment 8 wherein n is 0 or 1.

Embodiment 8b. A compound of Embodiment 8 wherein n is 1.

Embodiment 9. A compound of Formula 1 or any one of Embodiments 1 through 8b, either alone or in combination, wherein R⁷ is hydrogen or C1-C3 alkyl.

Embodiment 10. A compound of Formula 1 or any one of Embodiments 1 through 9, either alone or in combination, wherein Q¹ is phenyl optionally substituted with up to 3 substituents independently selected from halogen, cyano, C1-C2 alkyl, C1-C2 haloalkyl, C1-C2 alkoxy and C1-C2 haloalkoxy; or a 5- to 6-membered heteroaromatic ring containing ring members selected from carbon atoms and up to 4 heteroatoms independently selected from up to 2 O, up to 2 S and up to 4 N atoms, and optionally substituted with up to 3 substituents independently selected from halogen, cyano, C1-C2 alkyl, C1-C2 haloalkyl, C1-C2 alkoxy and C1-C2 haloalkoxy on carbon atom ring members and cyano, C1-C2 alkyl and C1-C2 alkoxy on nitrogen atom ring members; or a 3- to 7-membered nonaromatic ring containing ring members selected from carbon atoms and up to 4 heteroatoms independently selected from up to 2 O, up to 2 S and up to 4 N atoms, wherein up to 3 carbon atom ring members are independently selected from C(=0) and C(=S), the sulfur atom ring members are independently selected from S(=O)_s(=NR¹⁰)f and the ring optionally substituted with up to 3 substituents independently selected from halogen, cyano, C1-C2 alkyl, C1-C2 haloalkyl, C1-C2 alkoxy and C1-C2 haloalkoxy on carbon atom ring members and cyano, C1-C2 alkyl and C1-C2 alkoxy on nitrogen atom ring members

Embodiment 10a. A compound of Embodiment 10 wherein Q¹ is phenyl optionally substituted with up to 3 substituents independently selected from halogen, cyano, C1-C2 alkyl, C1-C2 haloalkyl, C1-C2 alkoxy and C1-C2 haloalkoxy. Embodiment 10b. A compound of Embodiment 10 wherein Q¹ is a 5- to 6-membered heteroaromatic ring containing ring members selected from carbon atoms and up to 4 heteroatoms independently selected from up to 2 O, up to 2 S and up to 4 N atoms, and optionally substituted with up to 3 substituents independently selected from halogen, cyano, C1-C2 alkyl, C1-C2 haloalkyl, C1-C2 alkoxy and C1-C2 haloalkoxy on carbon atom ring members and cyano, C1-C2 alkyl and 1-C2 alkoxy on nitrogen atom ring members; or a 3- to 7-membered nonaromatic ring containing ring members selected from carbon atoms and up to 4 heteroatoms independently selected from up to 2 O, up to 2 S and up to 4 N atoms, wherein up to 3 carbon atom ring members are independently selected from C(=0) and C(=S), the sulfur atom ring members are independently selected from S(=O)_s(=NR¹⁰)f and the ring optionally substituted with up to 3 substituents independently selected from halogen, cyano, C1-C2 alkyl, C1-C2 haloalkyl, C1-C2 alkoxy and C1-C2 haloalkoxy on carbon atom ring members and cyano, C1-C2 alkyl and C1-C2 alkoxy on nitrogen atom ring members; Embodiment 10c. A compound of Embodiment 10b wherein Q¹ is pyrazole, imidazole, 1,2,3-triazole, 1,2,4-triazole, pyrrolidine, piperidine or morpholine,

Embodiment lOd. A compound of Embodiment 10c wherein Q¹ is pyrazole, imidazole,

1,2,3-triazole or 1,2,4-triazole.

Embodiment lOe. A compound of Embodiment lOd wherein Q¹ is pyrazole. Embodiments of this invention, including Embodiments 1-1 Oe above, as well as any other embodiments described herein, can be combined in any manner, and the descriptions of variables in the embodiments pertain not only to the compounds of Formula 1 but also to the starting compounds and intermediate compounds useful for preparing the compounds of Formula 1. In addition, embodiments of this invention, including Embodiments 1-1 Oe above as well as any other embodiments described herein, and any combination thereof, pertain to the compositions and methods of the present invention.

Combinations of Embodiments 1-1 Oe are illustrated by:

Embodiment A. A compound of Formula 1 wherein

L is L-l, L-2, L-3, L-4 or L-5;

A is CR³;

R^la and R¹^ are each independently selected from hydrogen, fluorine and methyl;

R² and R⁵ are each hydrogen;

R³ and R⁴ are each independently selected from hydrogen, halogen, C^-Cg alkyl, C^-C^ haloalkyl, C^-C^ alkoxy, C^-C^ haloalkoxy, C^-C^ alkylthio, C^-Cg alkylsulfmyl and C^-Cg alkylsulfonyl; or Q¹;

Q is CH or CR⁶; and

each R⁶ is independently halogen, SF₅, C^-Cg alkyl, C^-Cg haloalkyl, C1-C4 alkoxy, C1-C4 haloalkoxy, C1-C4 alkylthio, C1-C4 alkylsulfmyl, Cj- C4 alkylsulfonyl, C1-C4 haloalkylthio, C1-C4 haloalkylsulfinyl, C1-C4 haloalkylsulfonyl or C₃-C6 trialkylsilyl.

Embodiment Al . A compound of Formula 1 wherein

L is O, S(0)_m or NR⁷;

A is CR³;

R² and R⁵ are each hydrogen;

R³ and R⁴ are each independently selected from halogen, C^-Cg alkyl, C^-Cg haloalkyl, C^-Cg alkoxy, C^-Cg haloalkoxy, C^-Cg alkylthio, C^-Cg alkylsulfmyl and C^-Cg alkylsulfonyl; or Q¹;

Q is CH or CR⁶;

each R⁶ is independently halogen, SF₅, C^-Cg alkyl, C^-Cg haloalkyl, C1-C4 alkoxy, C1-C4 haloalkoxy, C1-C4 alkylthio, C1-C4 alkylsulfinyl, C^-

C4 alkylsulfonyl, C1-C4 haloalkylthio, C1-C4 haloalkylsulfinyl, C1-C4 haloalkylsulfonyl or C₃-C6 trialkylsilyl; and

R⁷ is hydrogen or C1-C₃ alkyl.

Embodiment B. A compound of Embodiment A wherein

L is L-l or L-2;

R^la and R^lb are each independently selected from hydrogen and fluorine; Q is CH;

n is 0, 1 or 2; and

R⁶ is independently halogen, SF₅, C^-Cg alkyl, C^-Cg haloalkyl, C1-C4 alkoxy, C1-C4 haloalkoxy C1-C4 alkylthio or C1-C4 haloalkylthio. Embodiment B 1. A compound of Embodiment Al wherein

Q is CH;

n is 0, 1 or 2; and

R⁶ is independently halogen, SF₅, C^-Cg alkyl, C^-Cg haloalkyl, -C4 alkoxy, C1-C4 haloalkoxy C1-C4 alkylthio or C1-C4 haloalkylthio. Embodiment C. A compound of Embodiment B wherein

R³ and R⁴ are each independently selected from hydrogen, fluoro, chloro, methoxy, methylthio, methylsulfmyl, methylsulfonyl and pyrazole; and each R⁶ is independently halogen, SF₅, tert-butyl, CF₃, OCF₃, CF₂CF₃,

CF(CF₃)₂ or SCF₃.

Embodiment CI . A compound of Embodiment Bl wherein

R³ and R⁴ are each independently selected from fluoro, chloro, methoxy, methylthio, methylsulfmyl, methylsulfonyl and pyrazole; and each R⁶ is independently halogen, SF₅, tert-butyl, CF₃, OCF₃, CF₂CF₃,

CF(CF₃)₂ or SCF₃.

Specific embodiments include compounds of Formula 1 selected from the group consisting of:

3,5-difluoro-4-[2-[4-(l,l-dimethylethyl)]phenyl]-2-oxiranyl]pyridine;

3,5-difluoro-4-[ 1 -[4-(l , 1 -dimethylethyl)]phenyl]ethenyl]pyridine;

3,5-difluoro-4-[2-[4-[(trifluoromethyl)thio]phenyl]-2-oxiranyl]pyridine;

3,5-difluoro-4-[l-[4-[(trifluoromethyl)thio]phenyl]cyclopropyl]pyridine;

3-chloro-4-[(lZ)-2-fluoro-2-[4-(trifluoromethoxy)phenyl]ethenyl]pyridine; and

3,5-dichloro-4-[4-(l,l-dimethylethyl)phenoxy]pyridine.

Of note is that compounds of this invention are characterized by favorable metabolic and/or soil residual patterns and exhibit activity controlling a spectrum of agronomic and nonagronomic invertebrate pests.

Of particular note, for reasons of invertebrate pest control spectrum and economic importance, protection of agronomic crops from damage or injury caused by invertebrate pests by controlling invertebrate pests are embodiments of the invention. Compounds of this invention because of their favorable translocation properties or systemicity in plants also protect foliar or other plant parts which are not directly contacted with a compound of Formula 1 or a composition comprising the compound.

Also noteworthy as embodiments of the present invention are compositions comprising a compound of any of the preceding Embodiments, as well as any other embodiments described herein, and any combinations thereof, and at least one additional component selected from the group consisting of a surfactant, a solid diluent and a liquid diluent, said compositions optionally further comprising at least one additional biologically active compound or agent.

Further noteworthy as embodiments of the present invention are compositions for controlling an invertebrate pest comprising a compound (i.e. in a biologically effective amount) of any of the preceding Embodiments, as well as any other embodiments described herein, and any combinations thereof, and at least one additional component selected from the group consisting of a surfactant, a solid diluent and a liquid diluent, said compositions optionally further comprising at least one additional biologically active compound or agent (i.e. in a biologically effective amount).

Embodiments of the invention also include a composition for protecting an animal comprising a compound (i.e. in a parasiticidally effective amount) of any of the preceding Embodiments, either alone or in combination, and a carrier.

Embodiments of the invention further include methods for controlling an invertebrate pest comprising contacting the invertebrate pest or its environment with a biologically effective amount of a compound of any of the preceding Embodiments, either alone or in combination, (e.g., as a composition described herein). Of particular note is a method for protecting an animal comprising administering to the animal a parasiticidally effective amount of a compound of any of the preceding Embodiments, either alone or in combination, (e.g., as a composition described herein).

Embodiments of the invention also include a composition comprising a compound of any of the preceding Embodiments, either alone or in combination, in the form of a soil drench liquid formulation. Embodiments of the invention further include methods for controlling an invertebrate pest comprising contacting the soil with a liquid composition as a soil drench comprising a biologically effective amount of a compound of any of the preceding Embodiments, either alone or in combination.

Embodiments of the invention also include a spray composition for controlling an invertebrate pest comprising a compound (i.e. in a biologically effective amount) of any of the preceding Embodiments, either alone or in combination, and a propellant. Embodiments of the invention further include a bait composition for controlling an invertebrate pest comprising a compound (i.e. in a biologically effective amount) of any of the preceding Embodiments, either alone or in combination, one or more food materials, optionally an attractant, and optionally a humectant. Embodiments of the invention also include a device for controlling an invertebrate pest comprising said bait composition and a housing adapted to receive said bait composition, wherein the housing has at least one opening sized to permit the invertebrate pest to pass through the opening so the invertebrate pest can gain access to said bait composition from a location outside the housing, and wherein the housing is further adapted to be placed in or near a locus of potential or known activity for the invertebrate pest.

Embodiments of the invention also include a method for protecting a seed from an invertebrate pest comprising contacting the seed with a biologically effective amount of a compound of any of the preceding Embodiments, either alone or in combination, (e.g., as a composition described herein).

Embodiments of the invention also include methods for protecting an animal from an invertebrate parasitic pest comprising administering to the animal a parasiticidally effective amount of a compound of any of the preceding Embodiments, either alone or in combination.

Embodiments of the invention also include methods for controlling an invertebrate pest comprising contacting the invertebrate pest or its environment with a biologically effective amount of a compound of Formula 1, an N-oxide, or a salt thereof, (e.g., as a composition described herein), provided that the methods are not methods of medical treatment of a human or animal body by therapy.

Embodiments of the invention also include any of the preceding embodiments, either alone or in combination, wherein the invertebrate pest is an arthropod. Embodiments of the invention also include any of the preceding embodiments, either alone or in combination, wherein the arthropod is selected from the group consisting of insects, mites, spiders, scorpions, centipedes, millipedes, pill bugs and symphylans. Embodiments of the invention also include any of the preceding embodiments, either alone or in combination, wherein the arthropod is an insect.

Embodiments of the invention also include any of the preceding embodiments, either alone or in combination, wherein the invertebrate pest is a gastropod. Embodiments of the invention also include any of the preceding embodiments, either alone or in combination, wherein the gastropod is selected from the group consisting of snails, slugs and other Stylommatophora.

Embodiments of the invention also include any of the preceding embodiments, either alone or in combination, wherein the invertebrate pest is a nematode. Embodiments of the invention also include any of the preceding embodiments, either alone or in combination, wherein the nematode is selected from phytophagous nematodes.

Embodiments of the invention also include any of the preceding embodiments, either alone or in combination, wherein the invertebrate pest is a helminth. Embodiments of the invention also include any of the preceding embodiments, either alone or in combination, wherein the helminth is selected from the group consisting of roundworms, heartworms, flukes, acanthocephalans and tapeworms.

This invention also relates to such methods wherein the invertebrate pest or its environment is contacted with a composition comprising a biologically effective amount of a compound of Formula 1, an N-oxide, or a salt thereof, and at least one additional component selected from the group consisting of surfactants, solid diluents and liquid diluents, said composition optionally further comprising a biologically effective amount of at least one additional biologically active compound or agent, provided that the methods are not methods of medical treatment of a human or animal body by therapy.

One or more of the following methods and variations as described in Schemes 1-25 can be used to prepare the compounds of Formula 1. The definitions of R^la, R^lb, R², R³, R⁴, R⁵, R⁶, L, Q, A and n in the compounds of Formulae 1-25 below are as defined above in the Summary of the Invention unless otherwise noted. Formulae la-ln are various subsets of Formula 1, and all substituents for Formulae la-ln are as defined above for Formula 1 unless otherwise indicated. Ambient or room temperature is defined as about 20-25 °C.

As shown in Scheme 1, compounds of Formula la (compounds of Formula 1 wherein L is L-1) can be prepared by treatment of the corresponding olefin compounds of Formula lb (compounds of Formula 1 wherein L is L-3) with Me3SI/t-BuOK or CH2l2 ZnEt3 in various solvents, such as diethyl ether, tetrahydrofuran or dichloromethane. The formation of cyclopropyl derivatives are well known in the literature, for example, see V. J. Cee, et al. WO2009/154775 and B. Lv, et al. Bio. & Med. Chem. Lett. 2009, 19, 6877. The method of Scheme 1 is illustrated by synthesis Example 1, Step E.

Scheme 1

lb la

As shown in Scheme 2, compounds of Formula lc (compounds of Formula 1 wherein L is L-2) can be prepared by treatment of the corresponding olefin compounds of Formula lb (compounds of Formula 1 wherein L is L-3) with oxidant reagents, such as mCPBA (meto-chloroperbenzoic acid) or methyl(trifluoromethyl)dioxirane in various solvents, such as dichloromethane or acetonitrile/water. The synthesis of epoxides via olefins is well known in the chemical literature, for example, see M. W. C. Robinson, et al. Tetrahedron 2010, 66, 8377; J. L. Peglion, et al. WO2006/106241 and D. Yang, et al. J. Org. Chem. 1995, 60, 3887-9. The method of Scheme 2 is illustrated by synthesis Example 2.

Scheme 2

lb lc

As shown in Scheme 3, compounds of Formula lc (compounds of Formula 1 wherein L is L-2 and both R^la and R¹^ are H) can be prepared by treatment of corresponding carbonyl compounds of Formula 2 with Me3SI in the presence of base such as t-BuOK or NaH in solvents like dimethylsulfoxide or tetrahydrofuran. This method of epoxide synthesis via ketones is well known in the chemical literature, for example, see K. Varazo, et al. Tetrahedron Lett. 2008, 49, 5293. The method of Scheme 3 is illustrated by synthesis Example 3. Scheme 3

2 lc

wherein R^^a and R^ are H

As shown in Scheme 4, compounds of Formula lb (compounds of Formula 1 wherein L is L-3) can be prepared by elimination of corresponding alcohol compounds of Formula 3 with acids, such as H₂S0₄, HC1, HBr, acetic acid or /?-toluenesulfonic acid in solvents like toluene, xylene, acetic acid or water in a temperature range from 50 to 150 °C. This method of olefin synthesis via elimination of water from an alcohol is well known in the art, for example, see Q. Hu, et al. J. Med. Chem. 2010, 53, 5049. The method of Scheme 4 is illustrated by synthesis Example 1, Step D.

Scheme 4

As shown in Scheme 5, compounds of Formula 3 can be prepared by reaction of the corresponding carbonyl compounds of Formula 2 with commercially available Grinard reagents or lithium reagents, such as methylmagnesium bromide or methyl lithium in ethereal solvents like diethyl ether or tetrahydrofuran at a temperature range from -78 °C to room temperature. This method of alcohol formation from carbonyl compounds is well known in the chemical literature. The method of Scheme 5 is illustrated by synthesis Example 1, Step C. Scheme 5

As shown in Scheme 6, compounds of Formula 2 can be prepared by oxidation reaction of the corresponding alcohol compounds of Formula 4 with oxidants, such as manganese dioxide or Dess-Martin periodiane in solvents like dichloromethane or chloroform at a temperature range from room temperature to the reflux temperature of the solvent. This oxidation reaction is well known in the chemical literature. The method of Scheme 6 is illustrated by synthesis Example 1, Step B.

Scheme 6

As shown in Scheme 7, compounds of Formula 4 can be prepared by reaction of nucleophiles generated from compounds of Formula 5 with aldehydes of Formula 6. For example, metal-halogen exchange of compounds of Formula 5 (wherein X is Br or I) with n-butyllithium or z^'-propylmagnesium bromide in ether solvents, such as THF, diethyl ether or dioxanes at temperatures between -100 °C to -40 °C will generate the desired anions. The compounds of Formula 4 can be prepared by trapping those anions with various aldehydes of Formula 6. This method is well known in the chemical literature, see for example, T. Francois, et al. Tetrahedron, 2000, 56, 1349.

Compounds of Formula 4 can also be prepared by treating compounds of Formula 5 (wherein X is H) with bases, such as lithium diisopropylamide or 2,2,6,6- tetramethylpiperidinyl magnesium chloride - lithium chloride complex in ether solvents, such as tetrahydrofuran, diethyl ether or dioxanes at temperatures between -100 °C to - 10 °C. The resulting anion is treated with aldehydes of Formula 6 to give compounds of Formula 4. This method is well known in the chemical literature, see for example, R. J. Mattson, et al. J. Org. Chem., 1990, 55, 3410. The method of Scheme 7 is illustrated by synthesis Example 1 , Step A.

Scheme 7

wherein X is Br, I or H

Compounds of Formula Id (compounds of Formula 1 wherein R^la is F) can be prepared using the procedure shown in Scheme 8. Compounds of Formula 7 react with aryllithium reagents of Formula 8 to form products of Formula Id. Aryllithiums of Formula 8 are typically generated in tetrahydrofuran or diethyl ether solvent at a temperature ranging from -78 °C to 0 °C, followed by treatment with a compound of Formula 7 at temperatures ranging from -78 °C to ambient temperatures. The aryllithium reagents of Formula 8 are typically used in stoichiometric excess, typically 1.1 to 3.0 molar equivalents. An example of an analogous reaction may be found in J. Fluorine Chem. 1984, 25, 169-193. The method of Scheme 8 is illustrated by Synthesis Example 5.

Scheme 8

wherein R is F

Compounds of Formula 7 can be prepared by the method shown in Scheme 9. An aryl bromide or and aryl iodide of Formula 9 reacts with iodo(trifluoroethenyl)zinc in the presence of a palladium catalyst in a solvent to form trifluorovinyl compounds of Formula 7. Typical palladium catalysts include, but are not limited to, Pd(PPh₃)₄, Pd(o-tolyl)₄ and PdCl2(PPh₃)₂. Typical solvents include, but are not limited to, N,N-dimethylforamide or tetrahydrofuran. Typical reaction temperatures range from 0 °C to the reflux temperature of the solvent. The amount of catalyst can range from 0.02 to 1.0 equivalents, with 0.1 equivalents being the amount typically used. The amount of iodo(trifluoroethenyl)zinc used is typically 1 to 3 molar equivalents. An example of an analogous reaction may be found in J. Fluorine Chem. 2001, 111, 247-252.

Scheme 9

wherein X is Br or I

Compounds of Formula le (compounds of Formula 1 wherein R^la is H or C1 -C2 alkyl) can be prepared using the procedure illustrated in Scheme 10. Fluoro-phosphonates of Formula 10 react aldehydes or ketones of Formula 11 in the presence between 1 and 3 molar equivalents of a base to form fluoro-olefins of Formula le (where R^la is H or C1 -C2 alkyl). Typical bases used in these reactions include cesium carbonate, sodium hydride and lithium diisopropylamide. Ether solvents such as tetrahydrofuran or diethyl ether are typically used, and reaction temperatures range from -78 °C to ambient temperature. An example of an analogous reaction may be found in Tetrahedron Lett. 1996, 37, 629-632. The method of Scheme 10 is illustrated by Synthesis Example 6.

Scheme 10

Compounds of Formula 10 can be prepared using the procedure illustrated in Scheme 11. An aromatic aldehyde of Formula 6 can be treated with 1 to 3 molar equivalents of diethylphosphite in the presence of a base to produce hydroxyl-phosphonates of Formula 12. Typical bases for this reaction include, but are not limited to, alkoxides such as potassium tert-butoxide, carbonates such as potassium carbonate and amines such as triethylamine. Between 1.1 and 3.0 molar equivalents of base are typically used. Typical solvents include N,N-dimethylforamide or tetrahydrofuran. The reactions are typically performed at temperatures ranging from 0 °C up to the reflux temperature of the solvent. An example of an analogous reaction may be found in J. Fluorine Chem. 2011, 132, 636-640.

The hydroxyl-phosphonates of Formula 12 can be treated with a fluorinating reagent such as (diethylamino)sulfur trifluoride (DAST) or bis(2-methoxyethyl)aminosulfur trifluoride (Deoxo-Fluor ®) in a solvent such as dichloromethane at temperatures ranging from -78 °C to ambient temperature to form the fluoro-phosphonates of Formula 10. The fluorinating reagents are used in stoichiometric excess, typically 1.1 to 3.0 molar equivalents. An example of an analogous reaction may be found in Synlett 2009, 2180-2182.

Scheme 11

As shown in Scheme 12, compounds of Formula If (compounds of Formula 1 wherein L is L-6) can be prepared by the treatment of corresponding hydroxy compounds of Formula 13 with fluorinating reagents such as (diethylamino)sulfur trifluoride (DAST) or bis(2- methoxyethyl)aminosulfur trifluoride (Deoxo-Fluor ®) in solvents, such as diethyl ether, tetrahydrofuran or dichloromethane. The preparation of hydroxy compounds of Formula 13 are well known in the chemical literature, for example, see J. Yuan, et al. WO 2006/113704 (example 52). The method of Scheme 12 is illustrated by Synthesis Example 4. Scheme 12

Compounds of Formula lg (compounds of Formula 1 wherein Rib is Br) can be prepared using the procedure illustrated in Scheme 13. Olefins of Formula 14 react with a solution of N-bromosuccinamide and pyridine-hydrogen fluoride complex in diethyl ether and dichloromethane solvent to give compounds of Formula lg. Representative examples of reactions analogous to that shown in Scheme 13 can be found in J. Medicinal Chem. 2008, 51, 2708. The method of Scheme 13 is illustrated by Synthesis Example 7.

As shown in Scheme 14, olefins of Formula 14 can be prepared by reaction of an aldehyde or ketone of Formula 11 with a phophonate of Formula 15 in the presence of a base. Suitable bases for the reaction include alkoxide bases such as potassium tert-butoxide in an ethereal solvent such as diethyl ether or tetrahydrofuran, a hydride base such as sodium hydride in an aprotic solvent such as N,N-dimethylforamide or tetrahydrofuran, or an amide base such as lithium diisopropylamide in an aprotic solvent such as tetrahydrofuran. Typical reaction conditions employ the use of one to five molar equivalents of the base at temperatures ranging from -78 °C up to the reflux temperature of the solvent. Scheme 14

Compounds of Formula lh (compounds of Formula 1 wherein Rib is F) can be prepared using the procedure illustrated in Scheme 15. Compounds of Formula lh can be formed by the reaction diols of Formula 16 with an excess of two molar equivalents of fluorinating reagents such as (diethylamino)sulfur trifluoride (DAST) or bis(2- methoxyethyl)aminosulfur trifluoride (Deoxo-Fluor ®) in haloalkane solvents, such as dichloromethane or 1 ,2-dichloroethane at temperatures ranging from -78 °C to ambient temperature. The method of Scheme 15 is illustrated by Synthesis Example 8.

Scheme 15

As shown in Scheme 16 Compounds of Formula 14 are converted to diols of Formula 16 by treatment with dihydroxylation reagents such as osmium tetroxide used either stoichiometrically or catalytically (when used with a stoichiometric co-oxidant such as N- methyl morpholine-N-oxide, hydrogen peroxide, or potassium ferrocyanide). A analogous example can be found in J. Am. Chem. Soc. 2001, 123, 1365-1371. One skilled in the art will recognize that the use of Sharpless's AD-mix reagents can provide enantiomerically- enriched forms of diols of Formula 16. A representative example can be found in Tetrahedron Lett. 1996, 37, 5609-5612. These reactions are typically conducted in polar solvents such as acetone, tert-butanol, dioxane, tetrahydrofuran and/or water. Reaction temperatures typically range from 0 °C up to ambient temperatures. Scheme 16

As shown in Scheme 17, compounds of Formula li (compounds of Formula 1 wherein L is L-10) can be prepared by ring expanding reaction of corresponding epoxide compounds of Formula lc (wherein R^la and R¹^ are hydrogen). The reagents typically used for this transformation are IV^SOI in the presence of t-BuOK. This method is known in the chemical literature, for example see, K. Okuma, et al. J. Org. Chem. 1983, 48, 5133.

Scheme 17

lc li

wherein R and R are H

As shown in Scheme 18, compounds of Formula lj (compounds of Formula 1 wherein L is L-8, L-9, L-10, L-l l, L12) can be prepared by contacting compounds of Formula 17 wherein X² is a good leaving group, such as CI, Br, I or OTf, with a compound of Formula 18 (a boronic acid or ester) in the presence of a palladium catalyst. A wide variety of palladium-containing compounds and complexes are useful as catalysts for the present method. Examples of palladium-containing compounds and complexes useful as catalysts in the method of Scheme 18 include Pd(OAc)₂ (palladium(II) acetate), PdCl₂ (palladium(II) chloride), PdCl2(PPh₃)₂ bis(triphenylphosphine)palladium(II) dichloride, Pd(PPh₃)₄ (tetrakis(triphenylphosphine)palladium(O), Pd(C₅H₇0₂)2 (palladium(II) acetylacetonate) and Pd₂(dba)₃ tris (dibenzylideneacetone)dipalladium(O). Coupling reactions with boronic acids or derivatives in the presence of palladium catalysts can be conducted over a wide range of temperatures, including from about 25 to about 150 °C. Of note are temperatures from about 80 and about 110 °C, which typically provide fast reaction rates and high product yields. Useful solvents include, for example, ethers such as 1 ,2-dimethoxyethane, amides such as N,N-dimethylacetamide, and nonhalogenated aromatic hydrocarbons such as toluene. A wide variety of known general procedures are reasonably believed to be readily adaptable by one skilled in the art to the method of Scheme 18. For recent review articles and books about this type of functional group transformation; see, for example, F. Bellina et al., Synthesis 2004, 15, 2419-2440; P. Espinet and A. M. Echavarren, Angewandte Chemie, International Edition 2004, 43, 4704-4734; and J. J. Li, G. W. Gribble, editors, Palladium in Heterocyclic Chemistry: A Guide for the Synthetic Chemist. 2000.

Scheme 18

wherein X² is Br, I, OS0₂CF₃;

G^G² is CH₂CH₂, CH₂0, OCH₂, CH₂S or SCH₂;

and R 20 is H or Me

As shown in Scheme 19, compounds of Formula 17 (wherein G^l-G² is CH₂CH₂, CH₂0, OCH₂, CH₂S orSCH₂ and X² is a good leaving group like Br, I orOS0₂CF₃) can be prepared by converting the corresponding alcohol of Formula 19 to a bromide, iodide or trifluoromethanesulfonate derivative. By treating compounds of Formula 19 with, for example, PBr3, CBr4 or MeS0₂Cl in solvents like dichloromethane or chloroform will provide compounds of Formula 17. This conversion is known in the chemical literature, for example see, M. Meroni, et al. J. Med. Chem. 1979, 22, 183. Scheme 19

19 17

wherein X² is Br, I, OS0₂CF₃; and

G^G² is CH₂CH₂, CH₂0, OCH₂, CH₂S or SCH₂

As shown in Scheme 20, compounds of Formula 19 (wherein wherein G^l-G² is CH₂CH₂, CH₂0, OCH₂, CH₂S orSCH₂) can be prepared by adding anions generated from compounds of Formula 5 to carbonyl compounds of Formula 20. The anions of Formula 5 can be generated according to the procedures described for Scheme 7. The anions of generated from compounds of Formula 5 can be treated with commercially available or known carbonyl compounds of Formula 20 in solvents, such as tetrahydrofuran, diethyl ether or dioxanes at temperatures in the range of -78 °C to room temperature to generate the desired alcohol compounds of Formula 19. This method is known in the chemical literature, for example see J. Che, et al. WO2011/014515, and M. S. Chambers, et al. WO2006/059149.

Scheme 20

wherein X is H or Br, I; and

G^G² is CH₂CH₂, CH₂0, OCH₂, CH₂S or SCH₂

As shown in Scheme 21, compounds of Formula lk (wherein A is CR³ and L is O) can be formed by contacting pyridines of Formula 21 (wherein X³ is a leaving group such as F, CI, Br, I or a sulfonate such as methanesulfonate) with a hydroxy aryl compound of Formula 22 in the presence of base such as potassium carbonate or cesium carbonate in a solvent such as, but not limited to, N,N-dimethylformamide, tetrahydrofuran or acetone or a hydride base such as sodium hydride in a solvent such as N,N-dimethylformamide or tetrahydrofuran. Typical Scheme 21 reactions employ the use of an excess of base, usually 1.1 to 5.0 molar equivalents and reaction temperatures typically range from 0 °C up to the reflux temperature of the solvent. In certain cases, microwave radiation is used to achieve reaction temperatures that exceed the atmospheric pressure reflux temperatures of the solvent. In certain cases, additives such as copper (0) or copper(I)iodide are added in catalytic amounts to increase the rate of formation of compounds of Formula lk. A related synthesis example may be found in Tetrahedron Lett. 2006, 47, 5045-5048. The method of Scheme 21 is illustrated in Synthesis Example 9.

Scheme 21

21 22 lk

wherein X^J is F, CI, Br, I or OS0₂CF₃

As shown in Scheme 22, compounds of Formula 11 (wherein A is CR³ and L is S) may be prepared by contacting a pyridine of Formula 21 with a aryl thiol of Formula 23 using conditions that are analogous to those described for Scheme 21 reactions. The method of Scheme 22 is illustrated in Synthesis Example 10.

Scheme 22

21 23 11

wherein is F, CI, Br, I or OS0₂CF₃

As shown in Scheme 23, compounds of Formula lm (wherein A is CR³, L is S(0)_m and m=l) can be formed by contacting compounds of Formula 11 with an oxidant such as, but not limited to, sodium periodate or Oxone ® in solvents such as tetrahydrofuran, acetonitrile, methanol, ethanol or water (or mixtures of solvents) at temperatures ranging from 0 °C to ambient temperature. Alternatively, peracids such as m-chloroperbenzoic acid or peracetic acid may be used in solvents such as dichloromethane or ethyl acetate at temperatures ranging from 0 °C to ambient temperature. In cases where peracids are used in Scheme 23 reactions, it may be necessary to avoid the use of excess oxidant in order to minimize formation of sulfones of Formula lm (wherein m=2) or to minimize oxidation on the pyridine nitrogen atom. An analgous literature example to Scheme 23 reactions may be found in J. Org. Chem. 1993, 58, 6996-7000.

Scheme 23

11 lm

wherein m is 1

As shown in Scheme 24, compounds of Formula lm (wherein A is CR³, L is S(0)_m and m=2) may be formed by contacting pyridines of Formula 21 with sodium aryl sulfuric acid salts of Formula 24 using procedures described in Org. Lett. 2011, 13, 102-105.

Scheme 24

As shown in Scheme 25, compounds of Formula In (wherein L is NR⁷) can be prepared by contacting pyridines of Formula 21 with an arylamine of Formula 25 in the presence of an amine base such as triethylamine in a solvent such as l-methyl-2- pyrrolidinone. Typical reaction temperatures range from 100 °C to 250 °C with heating most conveniently supplied by microwave radiation. Analogous reaction procedures may be found in the chemical literature, see for example, Tetrahedron 2010, 66, 2398-2403. The method of Scheme 25 is illustrated in Synthesis Example 11.

Scheme 25

wherein X^J is F, CI, Br, I or OS0₂CF₃

It is recognized that some reagents and reaction conditions described above for preparing compounds of Formula 1 may not be compatible with certain functionalities present in the intermediates. In these instances, the incorporation of protection/deprotection sequences or functional group interconversions into the synthesis will aid in obtaining the desired products. The use and choice of the protecting groups will be apparent to one skilled in chemical synthesis (see, for example, Greene, T. W.; Wuts, P. G. M. Protective Groups in Organic Synthesis, 2nd ed.; Wiley: New York, 1991). One skilled in the art will recognize that, in some cases, after the introduction of a given reagent as it is depicted in any individual scheme, it may be necessary to perform additional routine synthetic steps not described in detail to complete the synthesis of compounds of Formula 1. One skilled in the art will also recognize that it may be necessary to perform a combination of the steps illustrated in the above schemes in an order other than that implied by the particular sequence presented to prepare the compounds of Formula 1.

One skilled in the art will also recognize that compounds of Formula 1 and the intermediates described herein can be subjected to various electrophilic, nucleophilic, radical, organometallic, oxidation, and reduction reactions to add substituents or modify existing substituents.

Without further elaboration, it is believed that one skilled in the art using the preceding description can utilize the present invention to its fullest extent. The following Synthesis Examples are, therefore, to be construed as merely illustrative, and not limiting of the disclosure in any way whatsoever. Steps in the following Synthesis Examples illustrate a procedure for each step in an overall synthetic transformation, and the starting material for each step may not have necessarily been prepared by a particular preparative run whose procedure is described in other Examples or Steps. Ambient or room temperature is defined as about 20-25 °C. Percentages are by weight except for chromatographic solvent mixtures or where otherwise indicated. Parts and percentages for chromatographic solvent mixtures are by volume unless otherwise indicated. MPLC refers to medium pressure liquid chromatography on silica gel. !pi NMR spectra are reported in ppm downfield from tetramethylsilane; "s" means singlet, "d" means doublet, "dd" means doublet of doublets, "ddd" means doublet of doublet of doublets, "t" means triplet, "m" means multiplet, and "br s" means broad singlet. For mass spectral data, the numerical value reported is the molecular weight of the parent molecular ion (M) formed by addition of H⁺ (molecular weight of 1) to the molecule to give a M+l peak observed by mass spectrometry using atmospheric pressure chemical ionization (AP⁺).

SYNTHESIS EXAMPLE 1

Preparation of 3 ,5 -difluoro-4- [ 1 - [4-[(trifluoromethyl)thio]phenyl] ethenyljpyridine

(compound number 25) and 3,5-difluoro-4-[l-[4-[(trifluoromethyl)thio]phenyl]- cyclopropyl]pyridine (compound number 18)

Step A: Preparation of 3,5-difluoro-a-[4-[(trifluoromethyl)thio]phenyl]-4- pyridinemethanol

A solution of 2,2,6,6-tetramethylpiperidinyl magnesium chloride lithium chloride complex solution (25 mL, 1.0 M in toluene/tetrahydrofuran) was slowly added to a stirred solution of 3,5-difluoropyridine (2.4 g, 20.9 mmol) in tetrahydrofuran (60 mL) at -78 °C. After stirring at -40 °C to -20 °C for 1 hr, the reaction mixture was treated with 4-(trifluoromethylthio)benzyaldehyde (4.3 g, 20.9 mmol) in tetrahydrofuran (10 mL) at - 78 °C. After stirring for another 1 hr at -78 °C, the reaction mixture was diluted with water and extracted with ethyl acetate. The combined organic phases were washed with water and saturated aqueous NaCl solution, dried with anhydrous sodium sulfate and concentrated. The residue was purified by column chromatography on silica gel using hexanes/ethyl acetate (70:30 to 20:80) as eluent to afford the title product as a colorless oil (6.0 g, 18.7 mmol).

!H NMR (CDCI3) δ 8.35 (s, 2H), 7.66 (d, 2H), 7.48 (d, 2H), 6.29 (s, 1H), 3.00 (s, br. 1H). Step B: Preparation of (3,5-difluoro-4-pyridinyl)[4-[(trifluoromethyl)thio]phenyl]- methanone

To a stirred solution of 3,5-difluoro-a-[4-[(trifluoromethyl)thio]phenyl]-4- pyridinemethanol (i.e. the product of Step A) (1.22 g, 3.79 mmol) in dichloromethane (20 mL) was added Dess-Martin periodiane (1.93 g, 4.55 mmol) at room temperature. After stirring at room temperature for 0.5 h, the reaction mixture was treated with saturated NaHCC"3 aqueous solution and extracted with dichloromethane. The combined organic phases were washed with water and saturated aqueous NaCl solution, dried with anhydrous sodium sulfate and concentrated. The residue was purified by column chromatography on silica gel using hexanes/ethyl acetate (90: 10 to 50:50) as eluent to afford the title compound as a pale yellow oil (1.20 g, 3.76 mmol).

!H NMR (CDCI3) δ 8.53 (s, 2H), 7.88 (d, 2H), 7.79 (d, 2H).

Step C: Preparation of 3,5-difluoro-a-methyl-a-[4-[(trifluoromethyl)thio]phenyl]-4- pyridinemethanol

To a stirred solution of (3,5-difluoro-4-pyridinyl)[4-[(trifluoromethyl)thio]phenyl]- methanone (i.e. the product of Step B) (0.50 g, 1.57 mmol) in tetrahydrofuran (5 mL) was added Methylmagnesium bromide solution (1.40 mL, 1.96 mmol, 1.4 M in toluene/THF) at 0 °C. The reaction mixture was allowed to warm to room temperature and stir for 2 h. Then the reaction mixture was treated with saturated NH₄C1 aqueous solution and extracted with EtOAc. The combined organic phases were washed with water and saturated aqueous NaCl solution, dried with anhydrous sodium sulfate and concentrated. The residue was purified by column chromatography on silica gel using hexanes/ethyl acetate (80:20 to 50:50) as eluent to afford the title compound as a pale yellow oil (0.29 g, 0.87 mmol).

!H NMR (CDCI3) δ 8.34 (d, 2H), 7.64 (d, 2H), 7.41 (d, 2H), 3.22 (s, br. 1H), 2.02 (s, 3H).

Step D: Preparation of 3,5-difluoro-4-[l-[4-[(trifluoromethyl)thio]phenyl]ethenyl]- pyridine

A mixture of 3,5-difluoro-a-methyl-a-[4-[(trifluoromethyl)thio]phenyl]-4- pyridinemethanol (i.e. the product of Step C) (290 mg, 0.86 mmol) and p-toluenesulfonic acid (197 mg, 1.04 mmol) in xylenee (5 mL) was refluxed under N2 atmosphere overnight. The reaction mixture was then partitioned between saturated NaHCC^ aqueous solution and EtOAc. The organic phase separated, washed with water and saturated aqueous NaCl solution, dried with anhydrous sodium sulfate and concentrated. The residue was purified by column chromatography on silica gel using hexanes/ethyl acetate (90: 10 to 70:30) as eluent to afford the title compound, a compound of the present invention, as a yellow oil (270 mg, 0.85 mmol).

!H NMR (CDCI3) δ 8.42 (s, 2H), 7.62 (d, 2H), 7.33 (d, 2H), 6.14 (s, 1H), 5.62 (s, 1H).

Step E: Preparation of 3,5-difluoro-4-[l-[4-[(trifluoromethyl)thio]phenyl]- cyclopropyl]pyridine

To a stirred solution of potassium tert-butoxide (170 mg, 1.51 mmol) in DMSO (5 mL) was added 3,5-difluoro-4-[l-[4-[(trifluoromethyl)thio]phenyl]ethenyl]pyridine (i.e. the product of Step D) (240 mg, 0.75 mmol) in tetrahydrofuran (8 mL) at room temperature. The reaction mixture was stirred under N2 atmosphere at room temperature for 18 h, then poured to an ice/water mixture and extracted with EtOAc. The combined organic phases were washed with water and saturated aqueous NaCl solution, dried with anhydrous sodium sulfate and concentrated. The residue was purified by column chromatography on silica gel using hexanes/ethyl acetate (90: 10 to 50:50) as eluent to afford the title compound, a compound of the present invention, as a pale yellow oil (1.20 g, 3.76 mmol).

!H NMR (CDCI3) δ 8.32 (s, 2H), 7.56 (d, 2H), 7.34 (d, 2H), 1.48-1.40 (m, 3H), 0.88 (m, 1H).

SYNTHESIS EXAMPLE 2

Preparation of 3,5-difluoro-4-[2-[4-(l,l-dimethylethyl)phenyl]-2-oxiranyl]pyridine

(compound number 1) and 3,5-difluoro-4-[l-[4-(l,l- dimethylethyl)phenyl]ethenyl]pyridine 1 -oxide (compound number 65) To a stirred solution of 3,5-difluoro-4-[l-[4-(l,l-dimethylethyl)phenyl]ethenyl]- pyridine (prepared in a similar manner as Synthesis Example 1, Steps A through D) (120 mg, 0.44 mmol), in dichloromethane (5 mL) was added 3-chloroperbenzoic acid (150 mg, 77%) at room temperature. The reaction mixture was stirred at room temperature for 4 hrs, then treated with sodium sulfite aqueous solution and extracted with EtOAc. The combined organic phases were washed with water and saturated aqueous NaCl solution, dried with anhydrous sodium sulfate and concentrated. The residue was purified by column chromatography on silica gel using hexanes/ethyl acetate (90: 10 to 70:30) as eluent to afford the title epoxide compound, a compound of the present invention, as a colorless solid (14 mg, 0.05 mmol) and the N-oxide compound, a compound of the present invention,as a yellow oil (50 mg, 0.17 mmol).

!H NMR (CDCI3) epoxide: δ 8.36 (s, 2H), 7.34 (d, 2H), 7.19 (d, 2H), 3.32 (d, 1H), 3.19 (d, 1H), 1.27 (s, 9H); N-oxide: δ 8.04 (s, 2H), 7.34 (d, 2H), 7.19 (d, 2H), 6.01 (s, 1H), 5.42 (s, 1H), 1.28 (s, 9H).

SYNTHESIS EXAMPLE 3

Preparation of 3 ,5 -difluoro-4- [2- [4-[(trifluoromethyl)thio]phenyl] -2-oxiranyl]pyridine

(compound number 7)

To a stirred mixture of (3,5-difluoro-4-pyridinyl)[4-[(trifluoromethyl)thio]phenyl]- methanone (i.e. the product of Example 1, Step B) (200 mg, 0.62 mmol) and trimethylsulfonium iodide (256 mg, 1.25 mmol) in DMSO (2 mL) was added potassium tert- butoxide (119 mg, 1.06 mmol) slowly at room temperature. After stirring at room temperature for 40 min, the reaction mixture was partitioned between water and chloroform. The combined organic phases were washed with water and saturated aqueous NaCl solution, dried with anhydrous sodium sulfate and concentrated. The residue was purified by column chromatography on silica gel using hexanes/ethyl acetate (90: 10 to 60:40) as eluent to afford the title compound, a compound of the present invention, as a colorless oil (54 mg, 0.16 mmol).

lH NMR (CDCI3) δ 8.43 (s, 2H), 7.64 (d, 2H), 7.37 (d, 2H), 3.43 (d, 1H), 3.20 (d, 1H).

SYNTHESIS EXAMPLE 4

Preparation of 3 -chloro-4- [ 1 -fluoro-2- [4-(trifluoromethoxy)phenyl] ethyl]-5 -(methylthio)- pyridine (compound number 34)

Step A: Preparation of 3-chloro-5-(methylthio)-a-[[4-(trifluoromethoxy)phenyl]- methyl] -4-pyridinemethanol

Zinc (360 mg, 5.46 mmol) in anhydrous THF (5 mL) was treated with 0.4 mL of 1,2- dibromoethane, and the reaction mixture is heated to 66 °C. A solution of 4- trifluoromethoxybenzyl bromide (956 mg, 3.75 mmol) and 1 ,2-dibromoethane (0.4mL) in THF (5 mL) was added slowly via cannula. After stirring for 1 h at 66 °C, the reaction mixture is cooled to room temperature and then is added into a solution of 3-chloro-6- thiomethyl-4-pyridinecarboxaldehyde (563 mg, 3.0 mmole) in THF (10 mL) at 0 °C. The reaction mixture was allowed to warm to room temperature and stir for 5 h. The reaction mixture was then treated with saturated aqueous ammonium chloride. The organic phase was separated and the aqueous phase extracted with EtOAc. The combined organic phases were washed with saturated aqueous NaCl solution, dried over sodium sulfate and concentrated. The residue was purified by column chromatography on silica gel using 15 % hexanes/ethyl acetate to afford the title compound as a yellow solid (141 mg, 0.39 mmol). !H NMR (CDCI3) δ 8.38 (s, 1H), 8.30 (s, 1H), 7.19-7.16 (m, 2H), 7.09-7.07 (m, 2H), 5.48 (q, 1H), 3.24 (dd, 1H), 3.04 (dd, 1H), 2.46 (s, 3H).

Step B: Preparation of 3-chloro-4-[l-fluoro-2-[4-(trifluoromethoxy)phenyl]ethyl]-5-

(methylthio)-pyridine

To a stirred mixture of 3-chloro-5-(methylthio)-a-[[4-(trifluoromethoxy)phenyl]- methyl] -4-pyridinemethanol (i.e. the product of Step A) (43.5 mg, 0.12 mmol) in dichloromethane (5 mL) was added (diethylamino)sulfur trifluoride (DAST) (25 mg, 0.156 mmol) at 0 °C slowly via syringe. The reaction mixture was allowed to warm to room temperature and stir for 2 h. The reaction mixture was then treated with water, the phases separated and the aqueous phase extracted with dichloromethane. The combined organic phases were washed with water and saturated aqueous NaCl solution, dried with anhydrous sodium sulfate and concentrated. The residue was purified by column chromatography on silica gel using 25 % hexanes/ethyl acetate as eluent to afford the title compound, a compound of the present invention, as a yellow oil (11 mg, 0.03 mmol).

!H NMR (CD₃C(0)CD₃) δ 8.38 (s, 2H), 7.29-7.27 (m, 2H), 7.17-7.15 (m, 2H), 6.24 - 6.12 (m, 1H), 3.65 - 3.57 (m, 1H), 3.18 - 3.09 (m, 1H), 2.53 (s, 3H).

SYNTHESIS EXAMPLE 5

Preparation of 3,5-dichloro-4-[(lE)-2-[4-(l,l-dimethylethyl)phenyl]-l,2-difluoroethenyl]- pyridine (compound number 37)

Step A: Preparation of 1 -( 1 , 1 -dimethylethyl)-4-( 1 ,2,2-trifluoroethenyl)benzene

Using a procedure analogous to that found in J. Fluorine Chem. 2001, 111, 247-252, iodotrifluoroethylene (1.1 mL, 12.1 mmol, condensed in a gas-addition funnel) was added dropwise to a stirred suspension of zinc powder (1.58 g, 24.2 mmol, acid washed and dried before use) and anhydrous DMF (12 mL) while keeping temperature of the exothermic reaction below 30 °C with an ice-water bath. The resulting dark brown suspension of iodo(trifluoroethenyl)zinc (ca. 1.0 molar) was stirred at ambient temperature for 2 h. To a solution of 4-tert-butyl-iodobenzene (1.30 g, 5.0 mmol) in anhydrous DMF (5.0 mL) was added tris(dibenzylideneacetone)dipalladium(0) (229 mg, 0.25 mmol) and triphenylphosphine (262 mg, 1.0 mmol) at 25 °C. The palladium containing solution was further treated with 10 mL of the supernatant from crude solution of iodo(trifluoroethenyl)zinc (ca. 10.0 mmol) prepared above and the resulting mixture was heated at 60 °C for 15 h. The resulting mixture was cooled to ambient temperature and partitioned between diethyl ether and water. The organic phase was washed with water, dried over anhydrous magnesium sulfate, and concentrated. The crude residue was dissolved in dichloromethane and concentrated onto 2.5 g silica gel. The residue was purified by column chromatography on silica gel using a gradient of 0% to 50% ethyl acetate in hexanes as eluent to afford the title compound as a colorless oil (540 mg).

!H NMR (CDC1₃) δ 7.44 (d, 2H), 7.39 (d, 2H), 1.33 (s, 9H).

!9F NMR (CDC1₃) δ -100.8 (q, IF), -115.7 (q, IF), -176.7 (q, IF).

Step B: Preparation of 3,5-dichloro-4-[(lE)-2-[4-(l,l-dimethylethyl)phenyl]-l,2- difluoroethenyljpyridine

A solution of n-BuLi in hexanes (0.22 mL of a 2.5 M, 0.56 mmol) was added to a solution of diisopropylamine (0.085 mL, 0.61 mmol) in anhydrous THF (2.8 mL) at -70 °C. The resulting solution was stirred at 0 °C for 15 min, re-cooled to -70 °C and then treated with 3,5-dichloropyridine (83 mg, 0.56 mmol) in a single portion. After stirring at -70 °C for 1 h the resulting solution was treated with a solution of l-(l,l-dimethylethyl)-4-( 1,2,2- trifluoroethenyl)benzene (i.e. the product of Step A) (100 mg, 0.47 mmol) in anhydrous THF (0.5 mL) at -70 °C. After stirring 1 h at -70 °C, the reaction mixture was treated with saturated aqueous ammonium chloride solution (2 mL) and warmed to ambient temperature. The mixture was partitioned between ethyl acetate and saturated aqueous ammonium chloride solution and the organic phase was dried over anhydrous magnesium sulfate and concentrated onto silica gel (1 g). The residue was purified by column chromatography on silica gel using a gradient of 0% to 50% ethyl acetate in hexanes as eluent to afford the title compound, a compound of the present invention, (42 mg) as a 55:45 mixture of E and Z stereoisomers, respectively, as estimated by integration of signals in the ¹⁹F NMR spectrum. MS (APCI) m/e 342 and 344 (M+l, CI isotopes)

¹⁹F NMR (CDC1₃) δ -126.66 (d, J= 19Hz, 0.45F, Z-isomer), -132.63 (d, J= 19Hz, 0.45F, Z- isomer), -146.71 (d, J= 131Hz, 0.55F, E-isomer), -147.89 (d, J= 131Hz, 0.55F, E-isomer).

SYNTHESIS EXAMPLE 6

Preparation of 3,5-dichloro-4-[(lZ)-2-[4-(l,l-dimethylethyl)phenyl]-2-fluoroethenyl]- pyridine (compound number 38)

Step A: Preparation of diethyl -[[4-(l , 1 -dimethylethyl)phenyl]hydroxymethyl]- phosphonate

Potassium tert-butoxide (50 mg, 0.44 mmol) was added to a solution of 4-tert-butyl benzaldehyde (1.53 g, 9.4 mmol) and diethylphosphite (1.40 mL, 10.8 mmol) at 25 °C. After stirring for 2 h, triethylamine (2.6 mL, 18.9 mmol) was added. After stirring for 15 h at 25 °C, the reaction mixture was partitioned between dichloromethane and saturated aqueous ammonium chloride solution. The organic phase was concentrated onto silica gel (6 g) and the residue was purified by medium pressure liquid chromatography on a silica column eluting with a gradient of 0% to 100% ethyl acetate in hexanes to give the title compound as a pale yellow viscous oil (1.65 g).

!H NMR (CDCI3) δ 7.40 (q, 4H), 4.97 (dd, 1H), 4.15-3.90 (m, 4H), 2.95 (br s, 1H), 1.35- 1.20 (m, 6H).

Step B : Preparation of diethyl -[[4-(l , 1 -dimethylethyl)phenyl]fluoromethyl]- phosphonate

A solution of (diethylamino)sulfur trifluoride (DAST) (0.74 mL, 5.6 mmol) and dichloromethane (1 mL) was added to a solution of diethyl -[[4-(l,l- dimethylethyl)phenyl]hydroxymethyl]phosphonate (i.e. the product of Step A) (1.40 g, 4.7 mmol) in dichloromethane (8.3 mL) at -78 °C. The solution was stirred a -78 °C for 1 h, at 0 °C for 1 h, and the resulting solution was treated with saturated aqueous sodium bicarbonate solution (3 mL). The mixture was partitioned between dichloromethane and saturated aqueous sodium bicarbonate solution, the organic phase was washed with saturated aqueous ammonium chloride solution, dried over anhydrous magnesium sulfate, and concentrated onto 3 g of silica gel. Purification by medium pressure liquid chromatography on a silica column eluting with a gradient of 0% to 100% ethyl acetate in hexane gave the title compound as a colorless oil (726 mg).

lH NMR (CDCI3) δ 7.42 (q, 4H), 5.62 (dd, 1H), 4.18-4.00 (m, 4H), 1.35-1.22 (m, 6H).

1⁹F NMR (CDC13) δ -199.02 (q).

Step C: Preparation of 3,5-dichloro-4-[(lZ)-2-[4-(l,l-dimethylethyl)phenyl]-2- fluoroethenyljpyridine

n-Butyllithium (0.32 mL of a 2.5 M solution in hexanes, 0.80 mmol) was added to a solution of diisopropylamine (0.12 mL, 0.86 mmol) and anhydrous THF (2.6 mL) at -70 °C. The resulting solution was stirred at 0 °C for 15 min, re-cooled to -70 °C, and treated with a solution of diethyl -[[4-(l,l-dimethylethyl)phenyl]fluoromethyl]phosphonate (i.e. the product of Step B) (200 mg, 0.66 mmol) and anhydrous THF. After stirring at -70 °C for 1 h, the resulting solution was treated with 3,5-dichloro-4-pyridine carboxaldehyde (105 mg, 0.60 mmol) at -70 °C, stirred at -70 °C for 1 h, stirred at 25 °C for 1 h, and the resulting solution was quenched with saturated aqueous ammonium chloride solution at 0 °C. The resulting mixture was partitioned between diethyl ether and saturated aqueous ammonium chloride solution, the organic phase was washed with saturated aqueous ammonium chloride solution, dried over anhydrous magnesium sulfate, and concentrated onto 1 g of silica gel. Purification by medium pressure liquid chromatography on a silica column eluting with a gradient of 0% to 30% ethyl acetate in hexanes gave the title compound, a compound of the present invention, as a colorless oil (145 mg). ¹⁹F NMR analysis showed a 58:42 mixture of E to Z isomers, respectively.

1⁹F NMR (CDCI3) δ -94.00 (d, J=18.8Hz, 0.42F, Z-isomer), -101.00 (d, J=37.6Hz, 0.58F, E- isomer).

SYNTHESIS EXAMPLE 7

Preparation of 4-[ 1 -bromo-2-[4-(l , 1 -dimethylethyl)phenyl]-2-fluoroethyl]-3,5- dichloropyridine (compound number 60)

Step A: Preparation of 3,5-dichloro-4-[(lE)-2-[4-(l,l-dimethylethyl)phenyl]ethenyl]- pyridine

Potassium tert-butoxide (434 mg, 3.9 mmol) was added to a solution of diethyl (4-tert- butylbenzyl)phosphonate (1.00 g, 3.5 mmol), 3,5-dichloro-4-pyridine carboxylate (310 mg, 1.76 mmol) and anhydrous THF (9 mL) at 0 °C. There was a slight exotherm to 10 °C. The resulting mixture was stirred at 25 °C for 15 h, cooled to 0 °C and treated with saturated aqueous ammonium chloride solution. The mixture was partitioned between diethyl ether and saturated aqueous ammonium chloride solution and the organic phase was dried over anhydrous magnesium sulfate and concentrated onto 3 g silica gel. Purification by medium pressure liquid chromatography on a silica column eluting with a gradient of 0% to 50% ethyl acetate in hexanes gave the title compound, a compound of the present invention, as a light yellow semi-solid (220 mg).

!H NMR (CDCI3) δ 8.48 (s, 2H), 7.52 (d, 2H), 7.46 (d, J= 16Hz, 1H), 7.44 (d, 2H), 7.08 (d, 1H), 1.34 (s, 9H). Consistent for E isomer.

Step B: Preparation of 4-[l-bromo-2-[4-(l,l-dimethylethyl)phenyl]-2-fluoroethyl]- 3,5-dichloropyridine

N-Bromosuccinimide (166 mg, 0.93 mmol) was added to a solution of 3,5-dichloro-4- [(lE)-2-[4-(l,l-dimethylethyl)phenyl]ethenyl]pyridine (i.e. the product of Step A) (190 mg, 0.62 mmol), hydrogen fluoride-pyridine complex (70% HF, 6.2 mL) and diethyl ether (6.2 mL) at 0 °C in a teflon round-bottom flask. The reaction mixture was stirred at 0 °C for 1 h, 25 °C for 2 h and the resulting mixture was poured into 100 g of ice. The resulting mixture was diluted with diethyl ether and basified to pH=8 with solid KOH (added with stirring and ice-bath cooling). The organic phase was separated, washed with saturated aqueous sodium bicarbonate solution, dried over anhydrous magnesium sulfate and concentrated to afford the title compound, a compound of the present invention, as a yellow oil (232 mg). Mass spectral analysis (APCI) m/e 404 and 406 (M+l , Br isotopes).

!H NMR (CDCI3) δ 8.57 (s, 1H), 8.54 (s, 1H), 7.48 (q, 4H), 6.38 (dd, J= 48, 8 Hz, 1H), 5.88 (J= 3, 8Hz, 1H), 1.33 (s, 9H). Minor amounts of isomeric impurities present.

SYNTHESIS EXAMPLE 8

Preparation of 4-[2-[4-(l,l -dimethylethyl)pheny 1] - 1 ,2-difluoroethyl] -3 ,5 -dichloropyridine (compound number 31)

Step A: Preparation of l-(3,5-dichloro-4-pyridinyl)-2-[4-(l,l-dimethylethyl)phenyl]-

1 ,2-ethanediol

A solution of 3,5-dichloro-4-[(lE)-2-[4-(l,l-dimethylethyl)phenyl]ethenyl]-pyridine (i.e. the product of Synthesis Example 7, Step A) (360 mg, 1.2 mmol) and tert-butanol (6 mL) was added to a mixture of AD-mix-a (1.65 g, Aldrich) and water 6 mL at 0 °C. The mixture was stirred at 0 °C for 3 h and then at ambient temperature for 18 h. Methanesulfonamide (0.3 g, 3.2 mmol) was added and the resulting mixture was stirred for 24 h at ambient temperature, diluted with acetonitrile (100 mL) and concentrated onto silica gel. Purification by medium pressure liquid chromatography on a silica column eluting with a gradient of 0% to 100% ethyl acetate in hexanes gave an off-white glassy solid (120 mg). in NMR (CDCI3) δ 8.33 (s, 2H), 7.24 (d, 2H), 7.14 (d, 2H), 5.39 (t, 1H), 5.29 (dd, 1H), 3.43-3.35 (m, 1H), 2.98-2.90 (m, 1H), 1.26 (s, 9H).

Step B: Preparation of 4-[2-[4-(l,l-dimethylethyl)phenyl]-l,2-difluoroethyl]-3,5- dichloropyridine

Bis(2-methoxyethyl)aminosulfur trifluoride (Deoxo-Fluor ®) (0.15 mL, 0.79 mmol) was added to a solution of l-(3,5-dichloro-4-pyridinyl)-2-[4-(l,l-dimethylethyl)phenyl]-l,2- ethanediol (i.e. the product of Step A) (108 mg, 0.32 mmol) and dichloromethane (3.2 mL) at -70 °C. The reaction mixture was stirred at -70 °C for 1 h and at 25 °C for 2 h, and the resulting mixture was partitioned between ethyl acetate and saturated aqueous ammonium chloride solution. The organic phase was washed with saturated aqueous ammonium chloride solution, dried over anhydrous magnesium sulfate and concentrated onto 1 g of silica gel. Purification by medium pressure liquid chromatography on a silica column eluting with a gradient of 0% to 50% ethyl acetate in hexanes gave the title compound, a compound of the present invention, as a mixure of isomers by ¾ NMR and ¹⁹F NMR analysis (55 mg).

MS (APCI) m/e 344 and 346 (M+l, two CI isotopes).

SYNTHESIS EXAMPLE 9

Preparation of 3,5-difluoro-4-[4-(trifluoromethoxy)phenoxy]pyridine (compound number

50)

A mixture of 3,4,5-trifluoropyridine (135 mg, 1.0 mmol), 4-trifluoromethoxy phenol

(200 mg, 1.1 mmol), anhydrous potassium carbonate (210 mg, 1.5 mmol) and anhydrous DMF (2 mL) was stirred at 25 °C for 18 h. The resulting mixture was partitioned between ethyl acetate and water, the organic phase was washed with water, dried (celite column) and concentrated. Purification of the crude product by medium pressure liquid chromatography on a silica column eluting with a gradient of 0% to 50% ethyl acetate in hexanes gave the title compound, a compound of the present invention, as a colorless oil (129 mg).

!9F NMR (CDCI3) δ -58.33 (s, 3F), -140.27.

SYNTHESIS EXAMPLE 10

Preparation of 3,5-dichloro-4-[[4-(trifluoromethoxy)phenyl]thio]pyridine (compound

number 53)

A mixture of 3,4,5-trichloropyridine (566 mg, 3.1 mmol), 4-trifluoromethoxy benzenethiol (662 mg, 3.4 mmol), anhydrous potassium carbonate (643 mg, 4.7 mmol) and anhydrous DMF (6 mL) was stirred at 25 °C for 18 h. The resulting mixture was partitioned between ethyl acetate and water, the organic phase was washed with water and saturated aqueous sodium chloride solution. The organic phase was dried over anhydrous magnesium sulfate and concentrated to give the title compound, a compound of the present invention, as a yellow oil (1.03 g).

!H NMR (CDCI3) δ 8.55 (s, 2H), 7.28 (d, 2H), 7.14 (d, 2H).

1⁹F NMR (CDC1₃) 5 -58.01.

SYNTHESIS EXAMPLE 11

Preparation of 3,5-dichloro-N-[4-(l,l-dimethylethyl)phenyl]-4-pyridinamine (compound number 58)

A solution of 3,4,5-trichloropyridine (400 mg, 2.2 mmol), 4-fert-butylaniline (0.71 mL, 4.5 mmol), triethylamine (0.61 mL, 4.4 mmol), and anhydrous l-methyl-2- pyrrolidinone (12 mL) was heated at 250 °C in a microwave reactor (C.E.M. Discover) for 1 h. The resulting mixture was partitioned between ethyl acetate and saturated aqueous sodium bicarbonate solution, the organic phase was washed with water, saturated aqueous sodium chloride solution, dried over anhydrous magnesium sulfate and concentrated onto silica gel. Purification by medium pressure liquid chromatography on a silica column eluting with a gradient of 0% to 50% ethyl acetate in hexanes gave the title compound, a compound of the current invention, as an orange solid (180 mg).

!H NMR (CDCI3) δ 8.34 (s, 2H), 7.33 (d, 2H), 6.89 (d, 2H), 6.37 (br s, 1H), 1.32 (s, 9H).

By the procedures described herein together with methods known in the art, the following compounds of Tables 1A to 121 can be prepared. The following abbreviations are used in Tables 1A to 121 which follow: / is tertiary, s is secondary, n is normal, is iso, Me is methyl, Et is ethyl, Pr is propyl, Bu is butyl, Ph is phenyl, OMe is methoxy, OEt is ethoxy, SMe is methylthio, S(0)Me is methylsulfmyl and SC^Me is methylsulfonyl.

In the tables below, the fragment B is defined to mean the following substructure of Formula 1:

Tables 1A-201A pertain to the structure shown below.

TABLE 1A

R³ is H and R⁴ is H

B B B

4-chlorophenyl 3-(CF₃)phenyl 3-F, 4-(CF₃)phenyl

4-bromophenyl 3-(OCF₃)phenyl 3 -CI, 4-(CF₃)phenyl

4-iodophenyl 3-(s-Bu)phenyl 3 -Br, 4-(CF₃)phenyl

4-nitrophenyl 3-(i-Bu)phenyl 3 -Me, 4-(CF₃)phenyl

4-cyanophenyl 3-(CMe₂CH₂CH₃)phenyl 2,6-diF, 4-(CF₃)phenyl

4-(C0₂CH₃)phenyl 3-(SiMe3)phenyl 2,6-diCl, 4-(CF₃)phenyl

4-(CF₃)phenyl 3-(0-;^'-Pr))phenyl 2-F, 4-(OCF₃)phenyl

4-(OCF₃)phenyl 3-(Oi-Bu)phenyl 2-Cl, 4-(OCF₃)phenyl

4-(s-Bu)phenyl 3-(OCH₂OCH₃)phenyl 2-Me, 4-(OCF₃)phenyl

4-(i-Bu)phenyl 3 -(OCMe₂C0₂Et)phenyl 3-F, 4-(OCF₃)phenyl

4-(CMe₂CH₂CH3)phenyl 3-(S-z-Pr)phenyl 3 -CI, 4-(OCF₃)phenyl

4-(SiMe3)phenyl 3-(SCH₂CF₃)phenyl 3-Br, 4-(OCF₃)phenyl

4-(0-z-Pr))phenyl 3-(NMeCOCF₃)phenyl 3 -Me, 4-(OCF₃)phenyl

4-(0-i-Bu)phenyl 3-(CF(CF₃)₂)phenyl 2,6-diF, 4-(OCF₃)phenyl

4-(OCH₂OCH₃)phenyl 3-(0-Ph)phenyl 2,6-diCl, 4-(OCF₃)phenyl

4-(OCMe₂C0₂Et)phenyl 2-F, 4-(i-Bu)phenyl 2,6-diMe, 4-(CF(CF₃)₂)phenyl

4-(S- -Pr)phenyl 2-Cl, 4-(f-Bu)phenyl 2,6-diF, 4-(CF(CF₃)₂)phenyl

4-((SCH₂CF₃)phenyl 2-Me, 4-(i-Bu)phenyl 2,6-diCl, 4-(CF(CF₃)₂)phenyl

4-(NMeCOCF₃)phenyl 3-F, 4-(i-Bu)phenyl 2-F, 4-(CF₂CF₃)phenyl

4-(CF(CF₃)₂)phenyl 3 -CI, 4-(/-Bu)phenyl 2-Cl, 4-(CF₂CF₃)phenyl

4-(0-Ph)phenyl 3 -Br, 4-(i-Bu)phenyl 2-Me, 4-(CF₂CF₃)phenyl

3-chlorophenyl 3 -Me, 4-(f-Bu)phenyl 3-F, 4-(CF₂CF₃)phenyl

3-bromophenyl 2,6-diF, 4-(7-Bu)phenyl 3 -CI, 4-(CF₂CF₃)phenyl

3-iodophenyl 2,6-diCl, 4-(i-Bu)phenyl 3-Br, 4-(CF₂CF₃)phenyl

3-nitrophenyl 2-F, 4-(CF₃)phenyl 3-Me, 4-(CF₂CF₃)phenyl

3-cyanoplienyl 2-Cl, 4-(CF₃)phenyl 2,6-diF, 4-(CF₂CF₃)phenyl

3-(C0₂CH₃)phenyl 2-Me, 4-(CF₃)phenyl 2,6-diCl, 4-(CF₂CF₃)phenyl

4-(SCF₃)phenyl 3-(SCF₃)phenyl 2-CF3-5-pyridyl B B B

4-(S(0)CF₃)phenyl 3-(S(0)CF₃)phenyl 2-CF₂CF₃-5-pyridyl

4-(S0₂CF₃)phenyl 3-(S0₂CF₃)phenyl 2-COCF₃-5-pyridyl

4-(CF₂CF₃)phenyl 3-(CF₂CF₃)phenyl 2-OCF₃-5-pyridyl

4-(CF₂CF₂CF3)phenyl 3-(CF₂CF₂CF₃)phenyl 2-SCF₃-5-pyridyl

4-(SF₅)phenyl 3-(SF₅)phenyl 2-CH₂CF₃-5-pyridyl

4-(OCF₂CF₃)phenyl 3-(OCF₂CF₃)phenyl 2-CF₃-4-pyridyl

2-F, 4-(SCF₃)phenyl 2-F, 4-(OCF₂CF₃)phenyl 2-CF₂CF₃-4-pyridyl

2-Cl, 4-(SCF₃)phenyl 2-Cl, 4-(OCF₂CF₃)phenyl 2-COCF₃-4-pyridyl

2-Me, 4-(SCF₃)phenyl 2-Me, 4-(OCF₂CF₃)phenyl 2-OCF₃4-pyridyl

3-F, 4-(SCF₃)phenyl 3-F, 4-(OCF₂CF₃)phenyl 2-SCF₃-4-pyridyl

3 -CI, 4-(SCF₃)phenyl 3 -CI, 4-(OCF₂CF₃)phenyl 2-CH₂CF₃-4-pyridyl

3 -Br, 4-(SCF₃)phenyl 3 -Br, 4-(OCF₂CF₃)phenyl 5-CF₃-2-pyridyl

3-Me, 4-(SCF₃)phenyl 3-Me, 4-(OCF₂CF₃)phenyl 5-CF₂CF₃-2-pyridyl

2,6-diF, 4-(SCF₃)phenyl 2,6-diF, 4-(OCF₂CF₃)phenyl 5-OCF₃-2-pyridyl

2,6-diCl, 4-(SCF₃)phenyl 2,6-diCl, 4-(OCF₂CF₃)phenyl 5-SCF₃-2-pyridyl

The present disclosure also includes Tables 2A through 201 A, each of which is constructed the same as Table 1 A above except that the row heading in Table 1 A (i.e. "R³ is H and R⁴ is H.") below the Markush structure is replaced with the respective row heading shown below. For example, in Table 2A the row heading is "R³ is H and R⁴ is F, and B is as defined in Table 1 A above. Thus, the first entry in Table 2 A specifically discloses 3-fluoro- 4-[ 1 -(4-chlorophenyl)cyclopropyl]pyridine.

Table Table Headings

2A R³ is F and R⁴ is F

3A R³ is F and R⁴ is CI

4A R³ is F and R⁴ is Br

5A R³ is F and R⁴ is I

6A R³ is F and R⁴ is Me

7A R³ is F and R⁴ is Et

8A R³ is F and R⁴ is n-Pr

9A R³ is F and R⁴ is z^'-Pr

10A R³ is F and R⁴ is «-Bu

11A R³ is F and R⁴ is z^'-Bu

Table

12A

13A

14A

15A

16A

17A

18A

19A

20A

21A

22A

23A

24A

25A

26A

27A

28A

29A

3 OA

31A

32A

33A

34A

35A

36A

37A

38A

39A

40A

41A

42A

43A

44A

45A

46A

Table

47A

48A

49A

50A

51A

52A

53A

54A

55A

56A

57A

58A

59A

60A

61A

62A

63A

64A

65A

66A

67A

68A

69A

70A

71A

72A

73A

74A

75A

76A

77A

78A

79A

80A

81A

Table Table Headings Table Table Headings

82A R³ is CI and R⁴ is SEt 182A R³ is Me and R⁴ is SEt

83A R³ is CI and R⁴ is S(0)Et 183A R³ is Me and R⁴ is S(0)Et

84A R³ is CI and R⁴ is S0₂Et 184A R³ is Me and R⁴ is S0₂Et

85A R³ is CI and R⁴ is S-«-Pr 185 A R³ is Me and R⁴ is S-n-Pr

86A R³ is CI and R⁴ is S(0)-«-Pr 186A R³ is Me and R⁴ is S(0)-«-Pr

87A R³ is CI and R⁴ is S0₂-«-Pr 187 A R³ is Me and R⁴ is S0₂-»-Pr

88A R³ is CI and R⁴ is S-z^'-Pr 188A R³ is Me and R⁴ is S-/-Pr

89A R³ is CI and R⁴ is S(0)-z-Pr 189 A R³ is Me and R⁴ is S(0)-z-Pr

90A R³ is CI and R⁴ is S0₂-z-Pr 190 A R³ is Me and R⁴ is S0 -z-Pr

91A R³ is CI and R⁴ is is SCH₂CF₃ 191A R³ is Me and R⁴ is is SCH₂CF₃

92A R³ is CI and R⁴ is S(0)CH₂CF₃ 192 A R³ is Me and R⁴ is S(0)CH₂CF₃

93A R³ is CI and R⁴ is S0₂CH₂CF₃ 193A R³ is Me and R⁴ is S0₂CH₂CF₃

94A R³ is CI and R⁴ is Ph 194 A R³ is Me and R⁴ is Ph

95A R³ is CI and R⁴ is 2-Pyridinyl 195A R³ is Me and R⁴ is 2-Pyridinyl

96A R³ is CI and R⁴ is 3-Pyridinyl 196A R³ is Me and R⁴ is 3-Pyridinyl

97A R³ is CI and R⁴ is 4-Pyridinyl 197A R³ is Me and R⁴ is 4-Pyridinyl

98A R³ is CI and R⁴ is 1 -pyrazole 198A R³ is Me and R⁴ is 1 -pyrazole

99A R³ is CI and R⁴ is 1- imidazole 199 A R³ is Me and R⁴ is 1 -imidazole

100 A R³ is CI and R⁴ is 1- 1,2,3-triazole 200A R^J is Me and R⁴ is 1-1,2,3-triazole

101A R³ is CI and R⁴ is 2- 1,2,3-triazole 201A R³ is Me and R⁴ is 2-1,2,3-triazole

TABLE IB

Table IB is identical to Table 1A, except that the chemical structure in the Table IB heading is replaced with the following structure:

For example, the first compound in Table IB is the structure shown immediately above wherein R³ is H, R⁴ is H and B is 4-chlorophenyl.

TABLES 2B-201B

Tables 2B through 20 IB are constructed in a similar manner as Tables 2 A through 201A. TABLE 1C

Table 1C is identical to Table 1A, except that the chemical structure in the Table 1C heading is replaced with the following structure:

For example, the first compound in Table 1C is the structure shown immediately above wherein R³ is H, R⁴ is H and B is 4-chlorophenyl.

TABLES 2C-201C

Tables 2C through 201C are constructed in a similar manner as Tables 2A through 201A.

TABLE ID

Table ID is identical to Table 1A, except that the chemical structure in the Table ID heading is replaced with the foll ing structure:

For example, the first compound in Table ID is the structure shown immediately above wherein R³ is H, R⁴ is H and B is 4-chlorophenyl.

TABLES 2D-201D

Tables 2D through 20 ID are constructed in a similar manner as Tables 2 A through 201A.

TABLE IE

Table IE is identical to Table 1A, except that the chemical structure in the Table IE heading is replaced with the following structure:

For example, the first compound in Table IE is the structure shown immediately above wherein R³ is H, R⁴ is H and B is 4-chlorophenyl.

TABLES 2E-201E

Tables 2E through 20 IE are constructed in a similar manner as Tables 2 A through

201A.

TABLE IF

Table IF is identical to Table 1A, except that the chemical structure in the Table IF heading is replaced with the foll ing structure:

For example, the first compound in Table IF is the structure shown immediately above wherein R³ is H, R⁴ is H and B is 4-chlorophenyl.

TABLES 2F-201F

Tables 2F through 20 IF are constructed in a similar manner as Tables 2 A through 201A.

TABLE IG

Table IG is identical to Table 1A, except that the chemical structure in the Table IG heading is replaced with the following structure:

For example, the first compound in Table IG is the structure shown immediately above wherein R³ is H, R⁴ is H and B is 4-chlorophenyl. TABLES 2G-201G

Tables 2G through 201G are constructed in a similar manner as Tables 2A through 201A.

TABLE 1H

Table 1H is identical to Table 1A, except that the chemical structure in the Table 1H heading is replaced with the followin structure:

For example, the first compound in Table 1H is the structure shown immediately above wherein R³ is H, R⁴ is H and B is 4-chlorophenyl.

TABLES 2H-201H

Tables 2H through 201H are constructed in a similar manner as Tables 2 A through 201A.

TABLE II

Table II is identical to Table 1A, except that the chemical structure in the Table II heading is replaced with the followin structure:

For example, the first compound in Table II is the structure shown immediately above wherein R³ is H, R⁴ is H and B is 4-chlorophenyl.

TABLES 21-2011

Tables 21 through 2011 are constructed in a similar manner as Tables 2 A through 201A.

TABLE 1J

Table 1J is identical to Table 1A, except that the chemical structure in the Table 1J heading is replaced with the following structure:

For example, the first compound in Table 1J is the structure shown immediately above wherein R³ is H, R⁴ is H and B is 4-chlorophenyl.

TABLES 2J-201J

Tables 2 J through 201J are constructed in a similar manner as Tables 2 A through 201A.

TABLE IK

Table IK is identical to Table 1A, except that the chemical structure in the Table IK heading is replaced with the followin structure:

For example, the first compound in Table IK is the structure shown immediately above wherein R³ is H, R⁴ is H and B is 4-chlorophenyl.

TABLES 2K-201K

Tables 2K through 20 IK are constructed in a similar manner as Tables 2 A through 201A.

TABLE 1L

Table 1L is identical to Table 1A, except that the chemical structure in the Table 1L heading is replaced with the following structure:

For example, the first compound in Table 1L is the structure shown immediately above wherein R³ is H, R⁴ is H and B is 4-chlorophenyl. TABLES 2L-201L

Tables 2L through 201L are constructed in a similar manner as Tables 2A through 201A.

TABLE 1M

Table 1M is identical to Table 1A, except that the chemical structure in the Table 1M heading is replaced with the following structure:

For example, the first compound in Table 1M is the structure shown immediately above wherein R³ is H, R⁴ is H and B is 4-chlorophenyl.

TABLES 2M-201M

Tables 2M through 201M are constructed in a similar manner as Tables 2 A through 201A.

TABLE IN

Table IN is identical to Table 1A, except that the chemical structure in the Table IN heading is replaced with the following structure:

For example, the first compound in Table IN is the structure shown immediately above wherein R³ is H, R⁴ is H and B is 4-chlorophenyl.

TABLES 2N-201N

Tables 2N through 20 IN are constructed in a similar manner as Tables 2A through 201A.

TABLE 10

Table 10 is identical to Table 1A, except that the chemical structure in the Table 10 heading is replaced with the following structure:

For example, the first compound in Table 10 is the structure shown immediately above wherein R³ is H, R⁴ is H and B is 4-chlorophenyl.

TABLES 2O-201O

Tables 20 through 2010 are constructed in a similar manner as Tables 2A through

201A.

TABLE IP

Table IP is identical to Table 1A, except that the chemical structure in the Table IP heading is replaced with the following structure:

For example, the first compound in Table IP is the structure shown immediately above wherein R³ is H, R⁴ is H and B is 4-chlorophenyl.

TABLES 2P-201P

Tables 2P through 20 IP are constructed in a similar manner as Tables 2 A through 201A.

TABLE 10

Table 1Q is identical to Table 1A, except that the chemical structure in the Table 1Q heading is replaced with the following structure:

For example, the first compound in Table 1Q is the structure shown immediately above wherein R³ is H, R⁴ is H and B is 4-chlorophenyl. TABLES 2Q-201Q

Tables 2Q through 201Q are constructed in a similar manner as Tables 2A through 201A.

TABLE IR

Table IR is identical to Table 1A, except that the chemical structure in the Table IR heading is replaced with the followin structure:

For example, the first compound in Table IR is the structure shown immediately above wherein R³ is H, R⁴ is H and B is 4-chlorophenyl.

TABLES 2R-201R

Tables 2R through 20 IR are constructed in a similar manner as Tables 2 A through 201A.

TABLE IS

Table IS is identical to Table 1A, except that the chemical structure in the Table IS heading is replaced with the following structure:

For example, the first compound in Table IS is the structure shown immediately above wherein R³ is H, R⁴ is H and B is 4-chlorophenyl.

TABLES 2S-201S

Tables 2S through 20 IS are constructed in a similar manner as Tables 2A through 201A.

Tables 1T-147T pertain to the structure shown below.

TABLE IT

R³ is F and R⁴ is F

B B B

4-chlorophenyl 3-(CF₃)phenyl 3-F, 4-(CF₃)phenyl

4-bromophenyl 3-(OCF₃)phenyl 3 -CI, 4-(CF₃)phenyl

4-iodophenyl 3-(s-Bu)phenyl 3 -Br, 4-(CF₃)phenyl

4-nitrophenyl 3-(/-Bu)phenyl 3 -Me, 4-(CF₃)phenyl

4-cyanophenyl 3-(CMe₂CH₂CH₃)phenyl 2,6-diF, 4-(CF₃)phenyl

4-(C0₂CH₃)phenyl 3-(SiMe₃)phenyl 2,6-diCl, 4-(CF₃)phenyl

4-(CF₃)phenyl 3-(0-z-Pr))phenyl 2-F, 4-(OCF₃)phenyl

4-(OCF₃)phenyl 3-(Oi-Bu)phenyl 2-Cl, 4-(OCF₃)phenyl

4-(s-Bu)phenyl 3-(OCH₂OCH₃)phenyl 2-Me, 4-(OCF₃)phenyl

4-(i-Bu)phenyl 3 -(OCMe₂C0₂Et)phenyl 3-F, 4-(OCF₃)phenyl

4-(CMe₂CH₂CH₃)phenyl 3-(S-/^'-Pr)phenyl 3 -CI, 4-(OCF₃)phenyl

4-(SiMe₃)phenyl 3-(SCH₂CF₃)phenyl 3 -Br, 4-(OCF₃)phenyl

4-(0-z-Pr))phenyl 3-(NMeCOCF₃)phenyl 3 -Me, 4-(OCF₃)phenyl

4-(0-f-Bu)phenyl 3-(CF(CF₃)₂)phenyl 2,6-diF, 4-(OCF₃)phenyl

4-(OCH₂OCH₃)phenyl 3-(0-Ph)phenyl 2,6-diCl, 4-(OCF₃)phenyl

4-(OCMe₂C0₂Et)phenyl 2-F, 4-(i-Bu)phenyl 2,6-diMe, 4-(CF(CF₃)₂)phenyl

4-(S-/-Pr)phenyl 2-Cl, 4-(7-Bu)phenyl 2,6-diF, 4-(CF(CF₃)₂)phenyl

4-((SCH₂CF₃)phenyl 2-Me, 4-(i-Bu)phenyl 2,6-diCl, 4-(CF(CF₃)₂)phenyl

4-(NMeCOCF₃)phenyl 3-F, 4-(i-Bu)phenyl 2-F, 4-(CF₂CF₃)phenyl

4-(CF(CF₃)₂)phenyl 3 -CI, 4-(i-Bu)phenyl 2-Cl, 4-(CF₂CF₃)phenyl

4-(0-Ph)phenyl 3 -Br, 4-(/-Bu)phenyl 2-Me, 4-(CF₂CF₃)phenyl

3-chlorophenyl 3 -Me, 4-(i-Bu)phenyl 3-F, 4-(CF₂CF₃)phenyl

3-bromophenyl 2,6-diF, 4-(i-Bu)phenyl 3 -CI, 4-(CF₂CF₃)phenyl

3-iodophenyl 2,6-diCl, 4-((-Bu)phenyl 3-Br, 4-(CF₂CF₃)phenyl B B B

3-nitrophenyl 2-F, 4-(CF₃)phenyl 3-Me, 4-(CF₂CF₃)phenyl

3-cyanophenyl 2-Cl, 4-(CF₃)phenyl 2,6-diF, 4-(CF₂CF₃)phenyl

3-(C0₂CH₃)phenyl 2-Me, 4-(CF₃)phenyl 2,6-diCl, 4-(CF₂CF₃)phenyl

4-(SCF₃)phenyl 3-(SCF₃)phenyl 2-CF₃-5-pyridyl

4-(S(0)CF₃)phenyl 3-(S(0)CF₃)phenyl 2-CF₂CF₃-5-pyridyl

4-(S0₂CF₃)phenyl 3-(S0₂CF₃)phenyl 2-COCF₃-5-pyridyl

4-(CF₂CF₃)phenyl 3-(CF₂CF₃)phenyl 2-OCF₃-5-pyridyl

4-(CF₂CF₂CF₃)phenyl 3-(CF₂CF₂CF₃)phenyl 2-SCF₃-5-pyridyl

4-(SF₅)phenyl 3-(SF₅)phenyl 2-CH₂CF₃-5-pyridyl

4-(OCF₂CF₃)phenyl 3-(OCF₂CF₃)phenyl 2-CF₃-4-pyridyl

2-F, 4-(SCF₃)phenyl 2-F, 4-(OCF₂CF₃)phenyl 2-CF₂CF₃-4-pyridyl

2-Cl, 4-(SCF₃)phenyl 2-Cl, 4-(OCF₂CF₃)phenyl 2-COCF₃-4-pyridyl

2-Me, 4-(SCF₃)phenyl 2-Me, 4-(OCF₂CF₃)phenyl 2-OCF₃4-pyridyl

3-F, 4-(SCF₃)phenyl 3-F, 4-(OCF₂CF₃)phenyl 2-SCF₃-4-pyridyl

3 -CI, 4-(SCF₃)phenyl 3 -CI, 4-(OCF₂CF₃)phenyl 2-CH₂CF₃-4-pyridyl

3 -Br, 4-(SCF₃)phenyl 3 -Br, 4-(OCF₂CF₃)phenyl 5-CF₃-2-pyridyl

3-Me, 4-(SCF₃)phenyl 3-Me, 4-(OCF₂CF₃)phenyl 5-CF₂CF₃-2-pyridyl

2,6-diF, 4-(SCF₃)phenyl 2,6-diF, 4-(OCF₂CF₃)phenyl 5-OCF₃-2-pyridyl

2,6-diCl, 4-(SCF₃)phenyl 2,6-diCl, 4-(OCF₂CF₃)phenyl 5-SCF₃-2-pyridyl

The present disclosure also includes Tables 2T through 147T, each of which is constructed the same as Table IT above except that the row heading in Table IT (i.e. "R³ is F and R⁴ is F.") below the Markush structure is replaced with the respective row heading shown below. For example, in Table 2T the row heading is "R³ is F and R⁴ is CI, and B is as defined in Table IT above. Thus, the first entry in Table 2T specifically discloses 3- chloro-4-(4-chlorophenoxy)-5-fluoropyridine.

Table Table Headings Table Table Headings

2T R³ is F and R⁴ is CI 51T R³ is CI and R⁴ is CI

3T R is F and R⁴ is Br 52T R³ is CI and R⁴ is Br

4T R³ is F and R⁴ is I 53T R³ is CI and R⁴ is I

5T R³ is F and R⁴ is Me 54T R³ is CI and R⁴ is Me

6T R³ is F and R⁴ is Et 55T R³ is CI and R⁴ is Et

7T R is F and R⁴ is n-Pr 56T R³ is CI and R⁴ is n-Pr

8T R is F and R⁴ is z^'-Pr 57T R³ is CI and R⁴ is z^'-Pr Table Table Headings Table Table Headings

9T R³ is F and R⁴ is «-Bu 58T R³ is CI and R⁴ is «-Bu

10T R³ is F and R⁴ is z^'-Bu 59T R³ is CI and R⁴ is z-Bu

11T R³ is F and R⁴ is i-Bu 60T R³ is CI and R⁴ is t-B

12T R³ is F and R⁴ is C≡CH 61T R³ is CI and R⁴ is C≡CH

13T R³ is F and R⁴ is CH=CH₂ 62T R³ is CI and R⁴ is CH=CH₂

14T R³ is F and R⁴ is CF₃ 63T R³ is CI and R⁴ is CF₃

15T R³ is F and R⁴ is CF₂CF₃ 64T R³ is CI and R⁴ is CF₂CF₃

16T R³ is F and R⁴ is OMe 65T R³ is CI and R⁴ is OMe

17T R³ is F and R⁴ is OEt 66T R³ is CI and R⁴ is OEt

18T R³ is F and R⁴ is O-w-Pr 67T R³ is CI and R⁴ is Ο-κ-Pr

19T R³ is F and R⁴ is O-z-Pr 68T R³ is CI and R⁴ is O-z^'-Pr

20T R³ is F and R⁴ is O-i-Bu 69T R³ is CI and R⁴ is O-t-B

21T R³ is F and R⁴ is OCH₂CF₃ 70T R³ is CI and R⁴ is OCH₂CF₃

22T R³ is F and R⁴ is OCH₂CHF₂ 71T R³ is CI and R⁴ is OCH₂CHF₂

23T R³ is F and R⁴ is OCH₂CH₂F 72T R³ is CI and R⁴ is OCH₂CH₂F

24T R³ is F and R⁴ is CH₂OMe 73T R³ is CI and R⁴ is CH₂OMe

25T R³ is F and R⁴ is CH₂OEt 74T R³ is CI and R⁴ is CH₂OEt

26T R³ is F and R⁴ is OCH₂CH₂OMe 75T R³ is CI and R⁴ is OCH₂CH₂OMe

27T R³ is F and R⁴ is OCH₂CH₂OEt 76T R³ is CI and R⁴ is OCH₂CH₂OEt

28T R³ is F and R⁴ is SMe 77T R³ is CI and R⁴ is SMe

29T R³ is F and R⁴ is S(0)Me 78T R³ is CI and R⁴ is S(0)Me

30T R³ is F and R⁴ is S0₂Me 79T R³ is CI and R⁴ is S0₂Me

31T R³ is F and R⁴ is SEt SOT R³ is CI and R⁴ is SEt

32T R³ is F and R⁴ is S(0)Et 81T R³ is CI and R⁴ is S(0)Et

33T R³ is F and R⁴ is S0₂Et 82T R³ is CI and R⁴ is S0₂Et

34T R³ is F and R⁴ is S-«-Pr 83T R³ is CI and R⁴ is S-«-Pr

35T R³ is F and R⁴ is S(0)-«-Pr 84T R³ is CI and R⁴ is S(0)-«-Pr

36T R³ is F and R⁴ is S0₂-«-Pr 85T R³ is CI and R⁴ is S0₂-«-Pr

37T R³ is F and R⁴ is S-z-Pr 86T R³ is CI and R⁴ is S-z-Pr

38T R³ is F and R⁴ is S(0)-z-Pr 87T R³ is CI and R⁴ is S(0)-z-Pr

39T R³ is F and R⁴ is S0₂- -Pr 88T R³ is CI and R⁴ is S0₂-z-Pr

40T R³ is F and R⁴ is SCH₂CF₃ 89T R³ is CI and R⁴ is is SCH₂CF₃

41T R³ is F and R⁴ is S(0)CH₂CF₃ 90T R³ is CI and R⁴ is S(0)CH₂CF₃

42T R³ is F and R⁴ is S0₂CH₂CF₃ 91T R³ is CI and R⁴ is S0₂CH₂CF₃

43T R³ is F and R⁴ is Ph 92T R³ is CI and R⁴ is Ph Table Table Headings Table Table Headings

44T R³ is F and R⁴ is 2-Pyridinyl 93T R³ is CI and R⁴ is 2-Pyridinyl

45T R³ is F and R⁴ is 3-Pyridinyl 94T R³ is CI and R⁴ is 3-Pyridinyl

46T R³ is F and R⁴ is 4-Pyridinyl 95T R³ is CI and R⁴ is 4-Pyridinyl

47T R³ is F and R⁴ is 1-pyrazole 96T R³ is CI and R⁴ is 1-pyrazole

48T R³ is F and R⁴ is 1 -imidazole 97T R³ is CI and R⁴ is 1 -imidazole

49T R³ is F and R⁴ is 1 -1 ,2,3-triazole 98T R³ is CI and R⁴ is 1-1,2,3-triazole

50T R³ is F and R⁴ is 2-1,2,3-triazole 99T R³ is CI and R⁴ is 2-1,2,3-triazole

100T R³ is Me and R⁴ is Br 124T R³ is Me and R⁴ is OCH₂CH₂OEt

101T R³ is Me and R⁴ is I 125T R³ is Me and R⁴ is SMe

102T R³ is Me and R⁴ is Me 126T R³ is Me and R⁴ is S(0)Me

103T R³ is Me and R⁴ is Et 127T R³ is Me and R⁴ is S0₂Me

104T R³ is Me and R⁴ is «-Pr 128T R³ is Me and R⁴ is SEt

105T R³ is Me and R⁴ is z^'-Pr 129T R³ is Me and R⁴ is S(0)Et

106T R³ is Me and R⁴ is «-Bu 130T R³ is Me and R⁴ is S0₂Et

107T R³ is Me and R⁴ is ;^'-Bu 131T R³ is Me and R⁴ is S-«-Pr

108T R³ is Me and R⁴ is t-B 132T R³ is Me and R⁴ is S(0)-«-Pr

109T R³ is Me and R⁴ is C≡CH 133T R³ is Me and R⁴ is S0₂-«-Pr

HOT R³ is Me and R⁴ is CH=CH₂ 134T R³ is Me and R⁴ is S- -Pr

H IT R³ is Me and R⁴ is CF₃ 135T R³ is Me and R⁴ is S(0)-/-Pr

112T R³ is Me and R⁴ is CF₂CF₃ 136T R³ is Me and R⁴ is S0₂-;^'-Pr

113T R³ is Me and R⁴ is OMe 137T R³ is Me and R⁴ is is SCH₂CF₃

114T R³ is Me and R⁴ is OEt 138T R³ is Me and R⁴ is S(0)CH₂CF₃

115T R³ is Me and R⁴ is O-w-Pr 139T R³ is Me and R⁴ is S0₂CH₂CF₃

116T R³ is Me and R⁴ is O-z-Pr 140T R³ is Me and R⁴ is Ph

117T R³ is Me and R⁴ is O-i-Bu 141T R³ is Me and R⁴ is 2-Pyridinyl

118T R³ is Me and R⁴ is OCH₂CF₃ 142T R³ is Me and R⁴ is 3-Pyridinyl

119T R³ is Me and R⁴ is OCH₂CHF₂ 143T R³ is Me and R⁴ is 4-Pyridinyl

120T R³ is Me and R⁴ is OCH₂CH₂F 144T R³ is Me and R⁴ is 1-pyrazole

121T R³ is Me and R⁴ is CH₂OMe 145T R³ is Me and R⁴ is 1 -imidazole

122T R³ is Me and R⁴ is CH₂OEt 146T R³ is Me and R⁴ is 1-1,2,3-triazole

123T R³ is Me and R⁴ is OCH₂CH₂OMe 147T R³ is Me and R⁴ is 2-1,2,3-triazole

TABLE 1U

Table 1U is identical to Table IT, except that the chemical structure in the Table 1U heading is replaced with the following structure:

For example, the first compound in Table 1U is the structure shown immediately above wherein R³ is H, R⁴ is H and B is 4-chlorophenyl.

TABLES 2U-147U

Tables 2U through 147U are constructed in a similar manner as Tables 2T through

147T.

TABLE IV

Table IV is identical to Table IT, except that the chemical structure in the Table IV heading is replaced with the followin structure:

For example, the first compound in Table IV is the structure shown immediately above wherein R³ is H, R⁴ is H and B is 4-chlorophenyl.

TABLES 2V-147V

Tables 2V through 147V are constructed in a similar manner as Tables 2T through

147T.

TABLE IW

Table IW is identical to Table IT, except that the chemical structure in the Table IW heading is replaced with the followin structure:

For example, the first compound in Table IW is the structure shown immediately above wherein R³ is H, R⁴ is H and B is 4-chlorophenyl. TABLES 2W-147W

Tables 2W through 147W are constructed in a similar manner as Tables 2T through

147T.

Examples of intermediates useful in the preparation of compounds of this invention are shown in Tables II through 121. In the tables below, the fragment B is defined to mean the following substructure of Formul

Tables 11-121 pertain to the structure shown below.

is SMe and R⁴ is H

B B B

4-(i-Bu)phenyl 4-(OCF₃)phenyl 4-(OCF₂CF₃)phenyl

4-(SCF₃)phenyl 4-(SF₅)phenyl 4-(CF₃)phenyl

4-(CF₂CF₃)phenyl 3-F, 4-(7-Bu)phenyl 3 -CI, 4-(i-Bu)phenyl

3-F, 4-(OCF₃)phenyl 3 -CI, 4-(OCF₃)phenyl 3-F, 4-(OCF₂CF₃)phenyl 3 -CI, 4-(OCF₂CF₃)phenyl 3-F, 4-(SCF₃)phenyl 3 -CI, 4-(SCF₃)phenyl

3-F, 4-(SF₅)phenyl 3 -CI, 4-(SF₅)phenyl 3-F, 4-(CF₃)phenyl

3 -CI, 4-(CF₃)phenyl 3-F, 4-(CF₂CF₃)phenyl 3 -CI, 4-(CF₂CF₃)phenyl

The present disclosure also includes Tables 12 through 121, each of which is constructed the same as Table II above except that the row heading in Table II (i.e. "R³ is SMe and R⁴ is H.") below the Markush structure is replaced with the respective row heading shown below. For example, in Table 12 the row heading is "R³ is SMe and R⁴ is F, and B is as defined in Table II above. Thus, the first entry in Table 12 specifically discloses 3-fluoro- a- [4-( 1 , 1 -dimethylethyl)phenyl] -a-methyl-5 -(methylthio)-4-pyridinemethanol. Table Table Headings

12 R³ is SEt and R⁴ is CI

13 R³ is S(0)Et and R⁴ is H

14 R³ is S(0)Et and R⁴ is F

15 R³ is S(0)Et and R⁴ is CI

16 R³ is S0₂Et and R⁴ is H

17 R³ is S0₂Et and R⁴ is F

18 R³ is S0₂Et and R⁴ is CI

19 R³ is OMe and R⁴ is H

110 R³ is OMe and R⁴ is F

111 R³ is OMe and R⁴ is CI

A compound of this invention will generally be used as an invertebrate pest control active ingredient in a composition, i.e. formulation, with at least one additional component selected from the group consisting of surfactants, solid diluents and liquid diluents, which serves as a carrier. The formulation or composition ingredients are selected to be consistent with the physical properties of the active ingredient, mode of application and environmental factors such as soil type, moisture and temperature.

Useful formulations include both liquid and solid compositions. Liquid compositions include solutions (including emulsifiable concentrates), suspensions, emulsions (including microemulsions and/or suspoemulsions) and the like, which optionally can be thickened into gels. The general types of aqueous liquid compositions are soluble concentrate, suspension concentrate, capsule suspension, concentrated emulsion, microemulsion and suspo-emulsion. The general types of nonaqueous liquid compositions are emulsifiable concentrate, microemulsifiable concentrate, dispersible concentrate and oil dispersion.

The general types of solid compositions are dusts, powders, granules, pellets, prills, pastilles, tablets, filled films (including seed coatings) and the like, which can be water-dispersible ("wettable") or water-soluble. Films and coatings formed from film- forming solutions or flowable suspensions are particularly useful for seed treatment. Active ingredient can be (micro)encapsulated and further formed into a suspension or solid formulation; alternatively the entire formulation of active ingredient can be encapsulated (or "overcoated"). Encapsulation can control or delay release of the active ingredient. An emulsifiable granule combines the advantages of both an emulsifiable concentrate formulation and a dry granular formulation. High-strength compositions are primarily used as intermediates for further formulation. Sprayable formulations are typically extended in a suitable medium before spraying. Such liquid and solid formulations are formulated to be readily diluted in the spray medium, usually water. Spray volumes can range from about one to several thousand liters per hectare, but more typically are in the range from about ten to several hundred liters per hectare. Sprayable formulations can be tank mixed with water or another suitable medium for foliar treatment by aerial or ground application, or for application to the growing medium of the plant. Liquid and dry formulations can be metered directly into drip irrigation systems or metered into the furrow during planting. Liquid and solid formulations can be applied onto seeds of crops and other desirable vegetation as seed treatments before planting to protect developing roots and other subterranean plant parts and/or foliage through systemic uptake.

The formulations will typically contain effective amounts of active ingredient, diluent and surfactant within the following approximate ranges which add up to 100 percent by weight.

Weight Percent

Active

Ingredient Diluent Surfactant

Water-Dispersible and Water- 0.001-90 0-99.999 0-15

soluble Granules, Tablets and

Powders

Oil Dispersions, Suspensions, 1-50 40-99 0-50

Emulsions, Solutions

(including Emulsifiable

Concentrates)

Dusts 1-25 70-99 0-5

Granules and Pellets 0.001-95 5-99.999 0-15

High Strength Compositions 90-99 0-10 0-2

Solid diluents include, for example, clays such as bentonite, montmorillonite, attapulgite and kaolin, gypsum, cellulose, titanium dioxide, zinc oxide, starch, dextrin, sugars (e.g., lactose, sucrose), silica, talc, mica, diatomaceous earth, urea, calcium carbonate, sodium carbonate and bicarbonate, and sodium sulfate. Typical solid diluents are described in Watkins et al., Handbook of Insecticide Dust Diluents and Carriers, 2nd Ed., Dorland Books, Caldwell, New Jersey.

Liquid diluents include, for example, water, N,N-dimethylalkanamides (e.g., N,N-dimethylformamide), limonene, dimethyl sulfoxide, N-alkylpyrrolidones (e.g., N-methylpyrrolidinone), ethylene glycol, triethylene glycol, propylene glycol, dipropylene glycol, polypropylene glycol, propylene carbonate, butylene carbonate, paraffins (e.g., white mineral oils, normal paraffins, isoparaffins), alkylbenzenes, alkylnaphthalenes, glycerine, glycerol triacetate, sorbitol, triacetin, aromatic hydrocarbons, dearomatized aliphatics, alkylbenzenes, alkylnaphthalenes, ketones such as cyclohexanone, 2-heptanone, isophorone and 4-hydroxy-4-methyl-2-pentanone, acetates such as isoamyl acetate, hexyl acetate, heptyl acetate, octyl acetate, nonyl acetate, tridecyl acetate and isobornyl acetate, other esters such as alkylated lactate esters, dibasic esters and γ-butyrolactone, and alcohols, which can be linear, branched, saturated or unsaturated, such as methanol, ethanol, n-propanol, isopropyl alcohol, n-butanol, isobutyl alcohol, n-hexanol, 2-ethylhexanol, n-octanol, decanol, isodecyl alcohol, isooctadecanol, cetyl alcohol, lauryl alcohol, tridecyl alcohol, oleyl alcohol, cyclohexanol, tetrahydrofurfuryl alcohol, diacetone alcohol and benzyl alcohol. Liquid diluents also include glycerol esters of saturated and unsaturated fatty acids (typically C6-C22), such as plant seed and fruit oils (e.g, oils of olive, castor, linseed, sesame, corn (maize), peanut, sunflower, grapeseed, safflower, cottonseed, soybean, rapeseed, coconut and palm kernel), animal-sourced fats (e.g., beef tallow, pork tallow, lard, cod liver oil, fish oil), and mixtures thereof. Liquid diluents also include alkylated fatty acids (e.g., methylated, ethylated, butylated) wherein the fatty acids can be obtained by hydrolysis of glycerol esters from plant and animal sources, and can be purified by distillation. Typical liquid diluents are described in Marsden, Solvents Guide, 2nd Ed., Interscience, New York, 1950.

The solid and liquid compositions of the present invention often include one or more surfactants. When added to a liquid, surfactants (also known as "surface-active agents") generally modify, most often reduce, the surface tension of the liquid. Depending on the nature of the hydrophilic and lipophilic groups in a surfactant molecule, surfactants can be useful as wetting agents, dispersants, emulsifiers or defoaming agents.

Surfactants can be classified as nonionic, anionic or cationic. Nonionic surfactants useful for the present compositions include, but are not limited to: alcohol alkoxylates such as alcohol alkoxylates based on natural and synthetic alcohols (which are branched or linear) and prepared from the alcohols and ethylene oxide, propylene oxide, butylene oxide or mixtures thereof; amine ethoxylates, alkanolamides and ethoxylated alkanolamides; alkoxylated triglycerides such as ethoxylated soybean, castor and rapeseed oils; alkylphenol alkoxylates such as octylphenol ethoxylates, nonylphenol ethoxylates, dinonyl phenol ethoxylates and dodecyl phenol ethoxylates (prepared from the phenols and ethylene oxide, propylene oxide, butylene oxide or mixtures thereof); block polymers prepared from ethylene oxide or propylene oxide and reverse block polymers where the terminal blocks are prepared from propylene oxide; ethoxylated fatty acids; ethoxylated fatty esters and oils; ethoxylated methyl esters; ethoxylated tristyrylphenol (including those prepared from ethylene oxide, propylene oxide, butylene oxide or mixtures thereof); fatty acid esters, glycerol esters, lanolin-based derivatives, polyethoxylate esters such as polyethoxylated sorbitan fatty acid esters, polyethoxylated sorbitol fatty acid esters and polyethoxylated glycerol fatty acid esters; other sorbitan derivatives such as sorbitan esters; polymeric surfactants such as random copolymers, block copolymers, alkyd peg (polyethylene glycol) resins, graft or comb polymers and star polymers; polyethylene glycols (pegs); polyethylene glycol fatty acid esters; silicone-based surfactants; and sugar-derivatives such as sucrose esters, alkyl polyglycosides and alkyl polysaccharides.

Useful anionic surfactants include, but are not limited to: alkylaryl sulfonic acids and their salts; carboxylated alcohol or alkylphenol ethoxylates; diphenyl sulfonate derivatives; lignin and lignin derivatives such as lignosulfonates; maleic or succinic acids or their anhydrides; olefin sulfonates; phosphate esters such as phosphate esters of alcohol alkoxylates, phosphate esters of alkylphenol alkoxylates and phosphate esters of styryl phenol ethoxylates; protein-based surfactants; sarcosine derivatives; styryl phenol ether sulfate; sulfates and sulfonates of oils and fatty acids; sulfates and sulfonates of ethoxylated alkylphenols; sulfates of alcohols; sulfates of ethoxylated alcohols; sulfonates of amines and amides such as N,N-alkyltaurates; sulfonates of benzene, cumene, toluene, xylene, and dodecyl and tridecylbenzenes; sulfonates of condensed naphthalenes; sulfonates of naphthalene and alkyl naphthalene; sulfonates of fractionated petroleum; sulfosuccinamates; and sulfosuccinates and their derivatives such as dialkyl sulfosuccinate salts.

Useful cationic surfactants include, but are not limited to: amides and ethoxylated amides; amines such as N-alkyl propanediamines, tripropylenetriamines and dipropylenetetramines, and ethoxylated amines, ethoxylated diamines and propoxylated amines (prepared from the amines and ethylene oxide, propylene oxide, butylene oxide or mixtures thereof); amine salts such as amine acetates and diamine salts; quaternary ammonium salts such as quaternary salts, ethoxylated quaternary salts and diquaternary salts; and amine oxides such as alkyldimethylamine oxides and bis-(2-hydroxyethyl)-alkylamine oxides.

Also useful for the present compositions are mixtures of nonionic and anionic surfactants or mixtures of nonionic and cationic surfactants. Nonionic, anionic and cationic surfactants and their recommended uses are disclosed in a variety of published references including McCutcheon 's Emulsifiers and Detergents, annual American and International Editions published by McCutcheon's Division, The Manufacturing Confectioner Publishing Co.; Sisely and Wood, Encyclopedia of Surface Active Agents, Chemical Publ. Co., Inc., New York, 1964; and A. S. Davidson and B. Milwidsky, Synthetic Detergents, Seventh Edition, John Wiley and Sons, New York, 1987.

Compositions of this invention can also contain formulation auxiliaries and additives, known to those skilled in the art as formulation aids (some of which can be considered to also function as solid diluents, liquid diluents or surfactants). Such formulation auxiliaries and additives can control: pH (buffers), foaming during processing (antifoams such polyorganosiloxanes), sedimentation of active ingredients (suspending agents), viscosity (thixotropic thickeners), in-container microbial growth (antimicrobials), product freezing (antifreezes), color (dyes/pigment dispersions), wash-off (film formers or stickers), evaporation (evaporation retardants), and other formulation attributes. Film formers include, for example, polyvinyl acetates, polyvinyl acetate copolymers, polyvinylpyrrolidone-vinyl acetate copolymer, polyvinyl alcohols, polyvinyl alcohol copolymers and waxes. Examples of formulation auxiliaries and additives include those listed in McCutcheon 's Volume 2: Functional Materials, annual International and North American editions published by McCutcheon's Division, The Manufacturing Confectioner Publishing Co.; and PCT Publication WO 03/024222.

The compound of Formula 1 and any other active ingredients are typically incorporated into the present compositions by dissolving the active ingredient in a solvent or by grinding in a liquid or dry diluent. Solutions, including emulsifiable concentrates, can be prepared by simply mixing the ingredients. If the solvent of a liquid composition intended for use as an emulsifiable concentrate is water-immiscible, an emulsifier is typically added to emulsify the active-containing solvent upon dilution with water. Active ingredient slurries, with particle diameters of up to 2,000 μιη can be wet milled using media mills to obtain particles with average diameters below 3 μιη. Aqueous slurries can be made into finished suspension concentrates (see, for example, U.S. 3,060,084) or further processed by spray drying to form water-dispersible granules. Dry formulations usually require dry milling processes, which produce average particle diameters in the 2 to 10 um range. Dusts and powders can be prepared by blending and usually grinding (such as with a hammer mill or fluid-energy mill). Granules and pellets can be prepared by spraying the active material upon preformed granular carriers or by agglomeration techniques. See Browning, "Agglomeration", Chemical Engineering, December 4, 1967, pp 147-48, Perry 's Chemical Engineer's Handbook, 4th Ed., McGraw-Hill, New York, 1963, pages 8-57 and following, and WO 91/13546. Pellets can be prepared as described in U.S. 4,172,714. Water-dispersible and water-soluble granules can be prepared as taught in U.S. 4,144,050, U.S. 3,920,442 and DE 3,246,493. Tablets can be prepared as taught in U.S. 5,180,587, U.S. 5,232,701 and U.S. 5,208,030. Films can be prepared as taught in GB 2,095,558 and U.S. 3,299,566.

For further information regarding the art of formulation, see T. S. Woods, "The Formulator's Toolbox - Product Forms for Modern Agriculture" in Pesticide Chemistry and Bioscience, The Food-Environment Challenge, T. Brooks and T. R. Roberts, Eds., Proceedings of the 9th International Congress on Pesticide Chemistry, The Royal Society of Chemistry, Cambridge, 1999, pp. 120-133. See also U.S. 3,235,361, Col. 6, line 16 through Col. 7, line 19 and Examples 10-41; U.S. 3,309,192, Col. 5, line 43 through Col. 7, line 62 and Examples 8, 12, 15, 39, 41, 52, 53, 58, 132, 138-140, 162-164, 166, 167 and 169-182; U.S. 2,891,855, Col. 3, line 66 through Col. 5, line 17 and Examples 1-4; Klmgman, Weed Control as a Science, John Wiley and Sons, Inc., New York, 1961, pp 81-96; Hance et al, Weed Control Handbook, 8th Ed., Blackwell Scientific Publications, Oxford, 1989; and Developments in formulation technology, PJB Publications, Richmond, UK, 2000.

In the following Examples, all formulations are prepared in conventional ways. Compound numbers refer to compounds in Index Tables A-E. Without further elaboration, it is believed that one skilled in the art using the preceding description can utilize the present invention to its fullest extent. The following Examples are, therefore, to be construed as merely illustrative, and not limiting of the disclosure in any way whatsoever. Percentages are by weight except where otherwise indicated.

Example A

High Strength Concentrate

compound 1 98.5% silica aerogel 0.5% synthetic amorphous fine silica 1.0%

Example B

Wettable Powder

compound 7 65.0% dodecylphenol polyethylene glycol ether 2.0% sodium ligninsulfonate 4.0% sodium silicoaluminate 6.0% montmorillonite (calcined) 23.0%

Example C

Granule

compound 18 10.0% attapulgite granules (low volatile matter, 0.71/0.30 mm; 90.0% U.S.S. No. 25-50 sieves)

Example D

Extruded Pellet

compound 21 25.0% anhydrous sodium sulfate 10.0% crude calcium ligninsulfonate 5.0% sodium alkylnaphthalenesulfonate 1.0% calcium/magnesium bentonite 59.0%

Example E

Emulsifiable Concentrate

compound 40 10.0% polyoxyethylene sorbitol hexoleate 20.0%

C6~Cio fatty acid methyl ester 70.0%>

Example F

Microemulsion

compound 46 5.0% polyvinylpyrrolidone -vinyl acetate copolymer 30.0% alkylpolyglycoside 30.0%> glyceryl monooleate 15.0% water 20.0%

Example G

Seed Treatment

compound 1 20.00%) polyvinylpyrrolidone -vinyl acetate copolymer 5.00% montan acid wax 5.00% calcium ligninsulfonate 1.00% polyoxyethylene/polyoxypropylene block copolymers 1.00%) stearyl alcohol (POE 20) 2.00% polyorganosilane 0.20%> colorant red dye 0.05%> water 65.75% Example H

Fertilizer Stick

compound 7 2.50% pyrrolidone-styrene copolymer 4.80% tristyrylphenyl 16-ethoxylate 2.30% talc 0.80% corn starch 5.00% slow-release fertilizer 36.00%> kaolin 38.00% water 10.60%

Example I

Suspension Concentrate

compound 18 35% butyl polyoxyethylene/polypropylene block copolymer 4.0% stearic acid/polyethylene glycol copolymer 1.0%) styrene acrylic polymer 1.0% xanthan gum 0.1% propylene glycol 5.0%> silicone based defoamer 0.1 % l,2-benzisothiazolin-3-one 0.1% water 53.7%

Example J

Emulsion in Water

compound 21 10.0% butyl polyoxyethylene/polypropylene block copolymer 4.0%> stearic acid/polyethylene glycol copolymer 1.0%) styrene acrylic polymer 1.0% xanthan gum 0.1% propylene glycol 5.0%> silicone based defoamer 0.1 % l,2-benzisothiazolin-3-one 0.1% aromatic petroleum based hydrocarbon 20.0 water 58.7% Example

Oil Dispersion

compound 40 25% polyoxy ethylene sorbitol hexaoleate 15% organically modified bentonite clay 2.5% fatty acid methyl ester 57.5%

Example L

Suspoemulsion

compound 46 10.0% imidacloprid 5.0% butyl polyoxyethylene/polypropylene block copolymer 4.0% stearic acid/polyethylene glycol copolymer 1.0%) styrene acrylic polymer 1.0% xanthan gum 0.1% propylene glycol 5.0%> silicone based defoamer 0.1 % l,2-benzisothiazolin-3-one 0.1% aromatic petroleum based hydrocarbon 20.0% water 53.7%

Compounds of this invention exhibit activity against a wide spectrum of invertebrate pests. These pests include invertebrates inhabiting a variety of environments such as, for example, plant foliage, roots, soil, harvested crops or other foodstuffs, building structures or animal integuments. These pests include, for example, invertebrates feeding on foliage (including leaves, stems, flowers and fruits), seeds, wood, textile fibers or animal blood or tissues, and thereby causing injury or damage to, for example, growing or stored agronomic crops, forests, greenhouse crops, ornamentals, nursery crops, stored foodstuffs or fiber products, or houses or other structures or their contents, or being harmful to animal health or public health. Those skilled in the art will appreciate that not all compounds are equally effective against all growth stages of all pests.

These present compounds and compositions are thus useful agronomically for protecting field crops from phytophagous invertebrate pests, and also nonagronomically for protecting other horticultural crops and plants from phytophagous invertebrate pests. This utility includes protecting crops and other plants (i.e. both agronomic and nonagronomic) that contain genetic material introduced by genetic engineering (i.e. transgenic) or modified by mutagenesis to provide advantageous traits. Examples of such traits include tolerance to herbicides, resistance to phytophagous pests (e.g., insects, mites, aphids, spiders, nematodes, snails, plant-pathogenic fungi, bacteria and viruses), improved plant growth, increased tolerance of adverse growing conditions such as high or low temperatures, low or high soil moisture, and high salinity, increased flowering or fruiting, greater harvest yields, more rapid maturation, higher quality and/or nutritional value of the harvested product, or improved storage or process properties of the harvested products. Transgenic plants can be modified to express multiple traits. Examples of plants containing traits provided by genetic engineering or mutagenesis include varieties of corn, cotton, soybean and potato expressing an insecticidal Bacillus thuringiensis toxin such as YIELD GARD^®, KNOCKOUT^®, STARLINK^® , BOLLGARD^®, NuCOTN^® and NEWLEAF^®, and herbicide-tolerant varieties of corn, cotton, soybean and rapeseed such as ROUNDUP READY^®, LIBERTY LINK^®,

ΊΜΓ, STS and CLEARFIELD , as well as crops expressing N-acetyltransferase (GAT) to provide resistance to glyphosate herbicide, or crops containing the HRA gene providing resistance to herbicides inhibiting acetolactate synthase (ALS). The present compounds and compositions may interact synergistically with traits introduced by genetic engineering or modified by mutagenesis, thus enhancing phenotypic expression or effectiveness of the traits or increasing the invertebrate pest control effectiveness of the present compounds and compositions. In particular, the present compounds and compositions may interact synergistically with the phenotypic expression of proteins or other natural products toxic to invertebrate pests to provide greater-than-additive control of these pests.

Compositions of this invention can also optionally comprise plant nutrients, e.g., a fertilizer composition comprising at least one plant nutrient selected from nitrogen, phosphorus, potassium, sulfur, calcium, magnesium, iron, copper, boron, manganese, zinc, and molybdenum. Of note are compositions comprising at least one fertilizer composition comprising at least one plant nutrient selected from nitrogen, phosphorus, potassium, sulfur, calcium and magnesium. Compositions of the present invention which further comprise at least one plant nutrient can be in the form of liquids or solids. Of note are solid formulations in the form of granules, small sticks or tablets. Solid formulations comprising a fertilizer composition can be prepared by mixing the compound or composition of the present invention with the fertilizer composition together with formulating ingredients and then preparing the formulation by methods such as granulation or extrusion. Alternatively solid formulations can be prepared by spraying a solution or suspension of a compound or composition of the present invention in a volatile solvent onto a previous prepared fertilizer composition in the form of dimensionally stable mixtures, e.g., granules, small sticks or tablets, and then evaporating the solvent. Examples of agronomic or nonagronomic invertebrate pests include eggs, larvae and adults of the order Lepidoptera, such as armyworms, cutworms, loopers, and heliothines in the family Noctuidae (e.g., pink stem borer (Sesamia inferens Walker), corn stalk borer (Sesamia nonagrioides Lefebvre), southern armyworm (Spodoptera eridania Cramer), fall armyworm (Spodoptera fugiperda J. E. Smith), beet armyworm (Spodoptera exigua Hiibner), cotton leafworm (Spodoptera littoralis Boisduval), yellowstriped armyworm (Spodoptera ornithogaUi Guenee), black cutworm (Agrotis ipsilon Hufnagel), velvetbean caterpillar (Anticarsia gemmatalis Hiibner), green fruitworm (Lithophane antennata Walker), cabbage armyworm (Barathra brassicae Linnaeus), soybean looper (Pseudoplusia includens Walker), cabbage looper (Trichoplusia ni Hiibner), tobacco budworm (Heliothis virescens Fabricius)); borers, casebearers, webworms, coneworms, cabbageworms and skeletonizers from the family Pyralidae (e.g., European corn borer (Ostrinia nubilalis Hiibner), navel orangeworm (Amyelois transitella Walker), corn root webworm (Crambus caliginosellus Clemens), sod webworms (Pyralidae: Crambinae) such as sod worm (Herpetogramma licarsisalis Walker), sugarcane stem borer (Chilo infuscatellus Snellen), tomato small borer (Neoleucinodes elegantalis Guenee), green leafroller (Cnaphalocerus medinalis), grape leaffolder (Desmia funeralis Hiibner), melon worm (Diaphania nitidalis Stoll), cabbage center grub (Helluala hydralis Guenee), yellow stem borer (Scirpophaga incertulas Walker), early shoot borer (Scirpophaga infuscatellus Snellen), white stem borer (Scirpophaga innotata Walker), top shoot borer (Scirpophaga nivella Fabricius), dark- headed rice borer (Chilo polychrysus Meyrick), cabbage cluster caterpillar (Crocidolomia binotalis English)); leafrollers, budworms, seed worms, and fruit worms in the family Tortricidae (e.g., codling moth (Cydia pomonella Linnaeus), grape berry moth (Endopiza viteana Clemens), oriental fruit moth (Grapholita molesta Busck), citrus false codling moth (Cryptophlebia leucotreta Meyrick), citrus borer (Ecdytolopha aurantiana Lima), redbanded leafroller (Argyrotaenia velutinana Walker), obliquebanded leafroller (Choristoneura rosaceana Harris), light brown apple moth (Epiphyas postvittana Walker), European grape berry moth (Eupoecilia ambiguella Hiibner), apple bud moth (Pandemis pyrusana Kearfott), omnivorous leafroller (Platynota stultana Walsingham), barred fruit-tree tortrix (Pandemis cerasana Hiibner), apple brown tortrix (Pandemis heparana Denis & Schiffermuller)); and many other economically important lepidoptera (e.g., diamondback moth (Plutella xylostella Linnaeus), pink bollworm (Pectinophora gossypiella Saunders), gypsy moth (Lymantria dispar Linnaeus), peach fruit borer (Carposina niponensis Walsingham), peach twig borer (Anarsia lineatella Zeller), potato tuberworm (Phthorimaea operculella Zeller), spotted teniform leafminer (Lithocolletis blancardella Fabricius), Asiatic apple leafminer (Lithocolletis ringoniella Matsumura), rice leaffolder (Lerodea eufala Edwards), apple leafminer (Leucoptera scitella Zeller)); eggs, nymphs and adults of the order Blattodea including cockroaches from the families Blattellidae and Blattidae (e.g., oriental cockroach (Blatta orientalis Linnaeus), Asian cockroach (Blatella asahinai Mizukubo), German cockroach (Blattella germanica Linnaeus), brownbanded cockroach (Supella longipalpa Fabricius), American cockroach (Periplaneta americana Linnaeus), brown cockroach (Periplaneta brunnea Burmeister), Madeira cockroach (Leucophaea maderae Fabricius)), smoky brown cockroach (Periplaneta fuliginosa Service), Australian Cockroach (Periplaneta australasiae Fabr.), lobster cockroach (Nauphoeta cinerea Olivier) and smooth cockroach (Symploce pallens Stephens)); eggs, foliar feeding, fruit feeding, root feeding, seed feeding and vesicular tissue feeding larvae and adults of the order Coleoptera including weevils from the families Anthribidae, Bruchidae, and Curculionidae (e.g., boll weevil (Anthonomus grandis Boheman), rice water weevil (Lissorhoptrus oryzophilus Kuschel), granary weevil (Sitophilus granarius Linnaeus), rice weevil (Sitophilus oryzae Linnaeus)), annual bluegrass weevil (Listronotus maculicollis Dietz), bluegrass billbug (Sphenophorus parvulus Gyllenhal), hunting billbug (Sphenophorus venatus vestitus), Denver billbug (Sphenophorus cicatristriatus Fahraeus)); flea beetles, cucumber beetles, rootworms, leaf beetles, potato beetles, and leafminers in the family Chrysomelidae (e.g., Colorado potato beetle (Leptinotarsa decemlineata Say), western corn rootworm (Diabrotica virgifera virgifera LeConte)); chafers and other beetles from the family Scarabaeidae (e.g., Japanese beetle (Popillia japonica Newman), oriental beetle (Anomala orientalis Waterhouse, Exomala orientalis (Waterhouse) Baraud), northern masked chafer (Cyclocephala borealis Arrow), southern masked chafer (Cyclocephala immaculata Olivier or C lurida Bland), dung beetle and white grub (Aphodius spp.), black turfgrass ataenius (Ataenius spretulus Haldeman), green June beetle (Cotinis nitida Linnaeus), Asiatic garden beetle (Maladera castanea Arrow), May/June beetles (Phyllophaga spp.) and European chafer (Rhizotrogus majalis Razoumowsky)); carpet beetles from the family Dermestidae; wireworms from the family Elateridae; bark beetles from the family Scolytidae and flour beetles from the family Tenebrionidae.

In addition, agronomic and nonagronomic pests include: eggs, adults and larvae of the order Dermaptera including earwigs from the family Forficulidae (e.g., European earwig (Forficula auricularia Linnaeus), black earwig (Chelisoches morio Fabricius)); eggs, immatures, adults and nymphs of the orders Hemiptera and Homoptera such as, plant bugs from the family Miridae, cicadas from the family Cicadidae, leafhoppers (e.g. Empoasca spp.) from the family Cicadellidae, bed bugs (e.g., Cimex lectularius Linnaeus) from the family Cimicidae, planthoppers from the families Fulgoroidae and Delphacidae, treehoppers from the family Membracidae, psyllids from the family Psyllidae, whiteflies from the family Aleyrodidae, aphids from the family Aphididae, phylloxera from the family Phylloxeridae, mealybugs from the family Pseudococcidae, scales from the families Coccidae, Diaspididae and Margarodidae, lace bugs from the family Tingidae, stink bugs from the family Pentatomidae, chinch bugs (e.g., hairy chinch bug (Blissus leucopterus hirtus Montandon) and southern chinch bug {Blissus insularis Barber)) and other seed bugs from the family Lygaeidae, spittlebugs from the family Cercopidae squash bugs from the family Coreidae, and red bugs and cotton stainers from the family Pyrrhocoridae.

Agronomic and nonagronomic pests also include: eggs, larvae, nymphs and adults of the order Acari (mites) such as spider mites and red mites in the family Tetranychidae (e.g., European red mite {Panonychus ulmi Koch), two spotted spider mite (Tetranychus urticae Koch), McDaniel mite {Tetranychus mcdanieli McGregor)); flat mites in the family Tenuipalpidae (e.g., citrus flat mite {Brevipalpus lewisi McGregor)); rust and bud mites in the family Eriophyidae and other foliar feeding mites and mites important in human and animal health, i.e. dust mites in the family Epidermoptidae, follicle mites in the family Demodicidae, grain mites in the family Glycyphagidae; ticks in the family Ixodidae, commonly known as hard ticks (e.g., deer tick {Ixodes scapularis Say), Australian paralysis tick {Ixodes holocyclus Neumann), American dog tick {Dermacentor variabilis Say), lone star tick {Amblyomma americanum Linnaeus)) and ticks in the family Argasidae, commonly known as soft ticks (e.g., relapsing fever tick {Ornithodoros turicata), common fowl tick {Argas radiatus)); scab and itch mites in the families Psoroptidae, Pyemotidae, and Sarcoptidae; eggs, adults and immatures of the order Orthoptera including grasshoppers, locusts and crickets (e.g., migratory grasshoppers (e.g., Melanoplus sanguinipes Fabricius, M. differ entialis Thomas), American grasshoppers (e.g., Schistocerca americana Drury), desert locust {Schistocerca gregaria Forskal), migratory locust {Locusta migratoria Linnaeus), bush locust {Zonocerus spp.), house cricket {Acheta domesticus Linnaeus), mole crickets (e.g., tawny mole cricket {Scapteriscus vicinus Scudder) and southern mole cricket {Scapteriscus borellii Giglio-Tos)); eggs, adults and immatures of the order Diptera including leafminers (e.g., Liriomyza spp. such as serpentine vegetable leafminer {Liriomyza sativae Blanchard)), midges, fruit flies (Tephritidae), frit flies (e.g., Oscinella frit Linnaeus), soil maggots, house flies (e.g., Musca domestica Linnaeus), lesser house flies (e.g., Fannia canicularis Linnaeus, F. femoralis Stein), stable flies (e.g., Stomoxys calcitrans Linnaeus), face flies, horn flies, blow flies (e.g., Chrysomya spp., Phormia spp.), and other muscoid fly pests, horse flies (e.g., Tabanus spp.), bot flies (e.g., Gastrophilus spp., Oestrus spp.), cattle grubs (e.g., Hypoderma spp.), deer flies (e.g., Chrysops spp.), keds (e.g., Melophagus ovinus Linnaeus) and other Brachycera, mosquitoes (e.g., Aedes spp., Anopheles spp., Culex spp.), black flies (e.g., Prosimulium spp., Simulium spp.), biting midges, sand flies, sciarids, and other Nematocera; eggs, adults and immatures of the order Thysanoptera including onion thrips (Thrips tabaci Lindeman), flower thrips {Frankliniella spp.), and other foliar feeding thrips; insect pests of the order Hymenoptera including ants of the Family Formicidae including the Florida carpenter ant (Camponotus floridanus Buckley), red carpenter ant (Camponotus ferrugineus Fabricius), black carpenter ant (Camponotus pennsylvanicus De Geer), white-footed ant (Technomyrmex albipes fr. Smith), big headed ants (Pheidole sp.), ghost ant (Tapinoma melanocephalum Fabricius); Pharaoh ant (Monomorium pharaonis Linnaeus), little fire ant (Wasmannia auropunctata Roger), fire ant (Solenopsis geminata Fabricius), red imported fire ant (Solenopsis invicta Buren), Argentine ant (Iridomyrmex humilis Mayr), crazy ant (Paratrechina longicornis Latreille), pavement ant (Tetramorium caespitum Linnaeus), cornfield ant (Lasius alienus Forster) and odorous house ant (Tapinoma sessile Say). Other Hymenoptera including bees (including carpenter bees), hornets, yellow jackets, wasps, and sawflies (Neodiprion spp.; Cephus spp.); insect pests of the order Isoptera including termites in the Termitidae (e.g., Macrotermes sp., Odontotermes obesus Rambur), Kalotermitidae (e.g., Cryptotermes sp.), and Rhinotermitidae (e.g., Reticulitermes sp., Coptotermes sp., Heterotermes tenuis Hagen) families, the eastern subterranean termite (Reticulitermes flavipes Kollar), western subterranean termite (Reticulitermes hesperus Banks), Formosan subterranean termite (Coptotermes formosanus Shiraki), West Indian drywood termite (Incisitermes immigrans Snyder), powder post termite (Cryptotermes brevis Walker), drywood termite (Incisitermes snyderi Light), southeastern subterranean termite (Reticulitermes virginicus Banks), western drywood termite (Incisitermes minor Hagen), arboreal termites such as Nasutitermes sp. and other termites of economic importance; insect pests of the order Thysanura such as silverfish (Lepisma saccharina Linnaeus) and firebrat (Thermobia domestica Packard); insect pests of the order Mallophaga and including the head louse (Pediculus humanus capitis De Geer), body louse (Pediculus humanus Linnaeus), chicken body louse (Menacanthus stramineus Nitszch), dog biting louse (Trichodectes canis De Geer), fluff louse (Goniocotes gallinae De Geer), sheep body louse (Bovicola ovis Schrank), short-nosed cattle louse (Haematopinus eurysternus Nitzsch), long-nosed cattle louse (Linognathus vituli Linnaeus) and other sucking and chewing parasitic lice that attack man and animals; insect pests of the order Siphonoptera including the oriental rat flea (Xenopsylla cheopis Rothschild), cat flea (Ctenocephalides felis Bouche), dog flea (Ctenocephalides canis Curtis), hen flea (Ceratophyllus gallinae Schrank), sticktight flea (Echidnophaga gallinacea Westwood), human flea (Pulex irritans Linnaeus) and other fleas afflicting mammals and birds. Additional arthropod pests covered include: spiders in the order Araneae such as the brown recluse spider (Loxosceles reclusa Gertsch & Mulaik) and the black widow spider {Latrodectus mactans Fabricius), and centipedes in the order Scutigeromorpha such as the house centipede (Scutigera coleoptrata Linnaeus).

Examples of invertebrate pests of stored grain include larger grain borer (Prostephanus truncatus), lesser grain borer (Rhyzopertha dominica), rice weevil (Stiophilus oryzae), maize weevil (Stiophilus zeamais), cowpea weevil (Callosobruchus maculatus), red flour beetle (Tribolium castaneum), granary weevil (Stiophilus granarius), Indian meal moth (Plodia interpunctella), Mediterranean flour beetle (Ephestia kuhniella) and fiat or rusty grain beetle (Cryptolestis ferrugineus).

Compounds of the invention show particularly high activity against pests in the order Lepidoptera (e.g., Alabama argillacea Hiibner (cotton leaf worm), Archips argyrospila Walker (fruit tree leaf roller), A. rosana Linnaeus (European leaf roller) and other Archips species, Chilo suppressalis Walker (rice stem borer), Cnaphalocrosis medinalis Guenee (rice leaf roller), Crambus caliginosellus Clemens (corn root webworm), Crambus teterrellus Zincken (bluegrass webworm), Cydia pomonella Linnaeus (codling moth), Earias insulana Boisduval (spiny bollworm), Earias vittella Fabricius (spotted bollworm), Helicoverpa armigera Hiibner (American bollworm), Helicoverpa zea Boddie (corn earworm), Heliothis virescens Fabricius (tobacco budworm), Herpetogramma licarsisalis Walker (sod webworm), Lobesia botrana Denis & Schiffermuller (grape berry moth), Pectinophora gossypiella Saunders (pink bollworm), Phyllocnistis citrella Stainton (citrus leafminer), Pieris brassicae Linnaeus (large white butterfly), Pieris rapae Linnaeus (small white butterfly), Plutella xylostella Linnaeus (diamondback moth), Spodoptera exigua Hiibner (beet armyworm), Spodoptera litura Fabricius (tobacco cutworm, cluster caterpillar), Spodoptera frugiperda J. E. Smith (fall armyworm), Trichoplusia ni Hiibner (cabbage looper) and Tuta absoluta Meyrick (tomato leafminer)).

Compounds of the invention also have significant activity on members from the order

Homoptera including: Acyrthosiphon pisum Harris (pea aphid), Aphis craccivora Koch (cowpea aphid), Aphis fabae Scopoli (black bean aphid), Aphis gossypii Glover (cotton aphid, melon aphid), Aphis pomi De Geer (apple aphid), Aphis spiraecola Patch (spirea aphid), Aulacorthum solani Kaltenbach (foxglove aphid), Chaetosiphon fragaefolii Cockerell (strawberry aphid), Diuraphis noxia Kurdjumov/Mordvilko (Russian wheat aphid), Dysaphis plantaginea Paaserini (rosy apple aphid), Eriosoma lanigerum Hausmann (woolly apple aphid), Hyalopterus pruni Geoffroy (mealy plum aphid), Lipaphis erysimi Kaltenbach (turnip aphid), Metopolophium dirrhodum Walker (cereal aphid), Macrosiphum euphorbiae Thomas (potato aphid), Myzus persicae Sulzer (peach-potato aphid, green peach aphid), Nasonovia ribisnigri Mosley (lettuce aphid), Pemphigus spp. (root aphids and gall aphids), Rhopalosiphum maidis Fitch (corn leaf aphid), Rhopalosiphum padi Linnaeus (bird cherry-oat aphid), Schizaphis graminum Rondani (greenbug), Sitobion avenae Fabricius (English grain aphid), Therioaphis maculata Buckton (spotted alfalfa aphid), Toxoptera aurantii Boyer de Fonscolombe (black citrus aphid), and Toxoptera citricida Kirkaldy (brown citrus aphid); Adelges spp. (adelgids); Phylloxera devastatrix Pergande (pecan phylloxera); Bemisia tabaci Gennadius (tobacco whitefiy, sweetpotato whitefly), Bemisia argentifolii Bellows & Perring (silverleaf whitefly), Dialeurodes citri Ashmead (citrus whitefly) and Trialeurodes vaporariorum Westwood (greenhouse whitefly); Empoasca fabae Harris (potato leafhopper), Laodelphax striatellus Fallen (smaller brown planthopper), Macrolestes quadrilineatus Forbes (aster leafhopper), Nephotettix cinticeps Uhler (green leafhopper), Nephotettix nigropictus Stal (rice leafhopper), Nilaparvata lugens Stal (brown planthopper), Peregrinus maidis Ashmead (corn planthopper), Sogatella furcifera Horvath (white-backed planthopper), Sogatodes orizicola Muir (rice delphacid), Typhlocyba pomaria McAtee white apple leafhopper, Erythroneoura spp. (grape leafhoppers); Magicidada septendecim Linnaeus (periodical cicada); Icerya purchasi Maskell (cottony cushion scale), Quadraspidiotus perniciosus Comstock (San Jose scale); Planococcus citri Risso (citrus mealybug); Pseudococcus spp. (other mealybug complex); Cacopsylla pyricola Foerster (pear psylla), Trioza diospyri Ashmead (persimmon psylla).

Compounds of this invention may also have activity on members from the order Hemiptera including: Acrosternum hilare Say (green stink bug), Anasa tristis De Geer (squash bug), Blissus leucopterus leucopterus Say (chinch bug), Cimex lectularius Linnaeus (bed bug) Corythuca gossypii Fabricius (cotton lace bug), Cyrtopeltis modesta Distant (tomato bug), Dysdercus suturellus Herrich-Schaffer (cotton stainer), Euchistus servus Say (brown stink bug), Euchistus variolarius Palisot de Beauvois (one-spotted stink bug), Graptosthetus spp. (complex of seed bugs), Leptoglossus corculus Say (leaf- footed pine seed bug), Lygus lineolaris Palisot de Beauvois (tarnished plant bug), Nezara viridula Linnaeus (southern green stink bug), Oebalus pugnax Fabricius (rice stink bug), Oncopeltus fasciatus Dallas (large milkweed bug), Pseudatomoscelis seriatus Reuter (cotton fieahopper). Other insect orders controlled by compounds of the invention include Thysanoptera (e.g., Frankliniella occidentalis Pergande (western flower thrips), Scirthothrips citri Moulton (citrus thrips), Sericothrips variabilis Beach (soybean thrips), and Thrips tabaci Lindeman (onion thrips); and the order Coleoptera (e.g., Leptinotarsa decemlineata Say (Colorado potato beetle), Epilachna varivestis Mulsant (Mexican bean beetle) and wireworms of the genera Agriotes, Athous or Limonius).

Compounds of the present invention also have activity on members of the Classes Nematoda, Cestoda, Trematoda, and Acanthocephala including economically important members of the orders Strongylida, Ascaridida, Oxyurida, Rhabditida, Spirurida, and Enoplida such as but not limited to economically important agricultural pests (i.e. root knot nematodes in the genus Meloidogyne, lesion nematodes in the genus Pratylenchus, stubby root nematodes in the genus Trichodorus, etc.) and animal and human health pests (i.e. all economically important flukes, tapeworms, and roundworms, such as Strongylus vulgaris in horses, Toxocara canis in dogs, Haemonchus contortus in sheep, Dirofilaria immitis Leidy in dogs, Anoplocephala perfoliata in horses, Fasciola hepatica Linnaeus in ruminants, etc.).

Note that some contemporary classification systems place Homoptera as a suborder within the order Hemiptera.

Of note is use of compounds of this invention for controlling potato leafhopper (Empoasca fabae). Of note is use of compounds of this invention for controlling corn planthopper (Peregrinus maidis). Of note is use of compounds of this invention for controlling cotton melon aphid {Aphis gossypii). Of note is use of compounds of this invention for controlling green peach aphid {Myzus persicae). Of note is use of compounds of this invention for controlling diamondback moth {Plutella xylostella). Of note is use of compounds of this invention for controlling fall armyworm {Spodoptera frugiperda).

Of note is use of compounds of this invention for controlling southern green stink bug {Nezara viridula), western tarnished plant bug {Lygus hesperus), rice water weevil {Lissorhoptrus oryzophilus), rice brown planthopper {Nilaparvata lugens), rice green leafhopper {Nephotettix virescens) and striped rice borer {Chilo suppress alls).

Compounds of this invention can also be mixed with one or more other biologically active compounds or agents including insecticides, fungicides, nematocides, bactericides, acaricides, herbicides, herbicide safeners, growth regulators such as insect molting inhibitors and rooting stimulants, chemosterilants, semiochemicals, repellents, attractants, pheromones, feeding stimulants, other biologically active compounds or entomopathogenic bacteria, virus or fungi to form a multi-component pesticide giving an even broader spectrum of agronomic and nonagronomic utility. Thus the present invention also pertains to a composition comprising a biologically effective amount of a compound of Formula 1, an N-oxide, or salt thereof, at least one additional component selected from the group consisting of surfactants, solid diluents and liquid diluents, and at least one additional biologically active compound or agent. For mixtures of the present invention, the other biologically active compounds or agents can be formulated together with the present compounds, including the compounds of Formula 1, to form a premix, or the other biologically active compounds or agents can be formulated separately from the present compounds, including the compounds of Formula 1, and the two formulations combined together before application (e.g., in a spray tank) or, alternatively, applied in succession. Examples of such biologically active compounds or agents with which compounds of this invention can be formulated are insecticides such as abamectin, acephate, acequinocyl, acetamiprid, acrinathrin, amidoflumet, amitraz, avermectin, azadirachtin, azinphos-methyl, bensultap, bifenthrin, bifenazate, bistrifluron, borate, buprofezin, cadusafos, carbaryl, carbofuran, cartap, carzol, chlorantraniliprole, chlorfenapyr, chlorfluazuron, chlorpyrifos, chlorpyrifos-methyl, chromafenozide, clofentezin, clothianidin, cyantraniliprole, cyflumetofen, cyfluthrin, beta-cyfluthrin, cyhalothrin, gamma-cyhalothrin, lambda- cyhalothrin, cypermethrin, alpha-cypermethrin, zeta-cypermethrin, cyromazine, deltamethrin, diafenthiuron, diazinon, dieldrin, diflubenzuron, dimefluthrin, dimehypo, dimethoate, dinotefuran, diofenolan, emamectin, endosulfan, esfenvalerate, ethiprole, etofenprox, etoxazole, fenbutatin oxide, fenothiocarb, fenoxycarb, fenpropathrin, fenvalerate, fipronil, flonicamid, flubendiamide, flucythrinate, flufenerim, flufenoxuron, fluvalinate, tau-fluvalinate, fonophos, formetanate, fosthiazate, halofenozide, hexaflumuron, hexythiazox, hydramethylnon, imidacloprid, indoxacarb, insecticidal soaps, isofenphos, lufenuron, malathion, meperfluthrin, metaflumizone, metaldehyde, methamidophos, methidathion, methiodicarb, methomyl, methoprene, methoxychlor, metofluthrin, monocrotophos, methoxyfenozide, nitenpyram, nithiazine, novaluron, noviflumuron, oxamyl, parathion, parathion-methyl, permethrin, phorate, phosalone, phosmet, phosphamidon, pirimicarb, profenofos, profluthrin, propargite, protrifenbute, pymetrozine, pyrafluprole, pyrethrin, pyridaben, pyridalyl, pyrifluquinazon, pyriprole, pyriproxyfen, rotenone, ryanodine, spinetoram, spinosad, spirodiclofen, spiromesifen, spirotetramat, sulprofos, sulfoxaflor, tebufenozide, tebufenpyrad, teflubenzuron, tefluthrin, terbufos, tetrachlorvinphos, tetramethrin, tetramethylfluthrin, thiacloprid, thiamethoxam, thiodicarb, thiosultap-sodium, tolfenpyrad, tralomethrin, triazamate, trichlorfon, triflumuron, Bacillus thuringiensis delta-endotoxins, entomopathogenic bacteria, entomopathogenic viruses and entomopathogenic fungi.

Of note are insecticides such as abamectin, acetamiprid, acrinathrin, amitraz, avermectin, azadirachtin, bensultap, bifenthrin, buprofezin, cadusafos, carbaryl, cartap, chlorantraniliprole, chlorfenapyr, chlorpyrifos, clothianidin, cyantraniliprole, cyfluthrin, beta-cyfluthrin, cyhalothrin, gamma-cyhalothrin, lambda-cyhalothrin, cypermethrin, alpha- cypermethrin, zeta-cypermethrin, cyromazine, deltamethrin, dieldrin, dinotefuran, diofenolan, emamectin, endosulfan, esfenvalerate, ethiprole, etofenprox, etoxazole, fenothiocarb, fenoxycarb, fenvalerate, fipronil, flonicamid, flubendiamide, flufenoxuron, fluvalinate, formetanate, fosthiazate, hexaflumuron, hydramethylnon, imidacloprid, indoxacarb, lufenuron, metaflumizone, methiodicarb, methomyl, methoprene, methoxyfenozide, nitenpyram, nithiazine, novaluron, oxamyl, pymetrozine, pyrethrin, pyridaben, pyridalyl, pyriproxyfen, ryanodine, spinetoram, spinosad, spirodiclofen, spiromesifen, spirotetramat, tebufenozide, tetramethrin, thiacloprid, thiamethoxam, thiodicarb, thiosultap-sodium, tralomethrin, triazamate, triflumuron, Bacillus thuringiensis delta-endotoxins, all strains of Bacillus thuringiensis and all strains of Nucleo polyhydrosis viruses.

One embodiment of biological agents for mixing with compounds of this invention include entomopathogenic bacteria such as Bacillus thuringiensis, and the encapsulated delta-endotoxins of Bacillus thuringiensis such as MVP® and MVPII® bioinsecticides prepared by the CellCap® process (CellCap®, MVP® and MVPII® are trademarks of Mycogen Corporation, Indianapolis, Indiana, USA); entomopathogenic fungi such as green muscardine fungus; and entomopathogenic (both naturally occurring and genetically modified) viruses including baculovirus, nucleopolyhedro virus (NPV) such as Helicoverpa zea nucleopolyhedrovirus (HzNPV), Anagrapha falcifera nucleopolyhedrovirus (AfNPV); and granulosis virus (GV) such as Cydia pomonella granulosis virus (CpGV).

Of particular note is such a combination where the other invertebrate pest control active ingredient belongs to a different chemical class or has a different site of action than the compound of Formula 1. In certain instances, a combination with at least one other invertebrate pest control active ingredient having a similar spectrum of control but a different site of action will be particularly advantageous for resistance management. Thus, a composition of the present invention can further comprise a biologically effective amount of at least one additional invertebrate pest control active ingredient having a similar spectrum of control but belonging to a different chemical class or having a different site of action. These additional biologically active compounds or agents include, but are not limited to, sodium channel modulators such as bifenthrin, cypermethrin, cyhalothrin, lambda- cyhalothrin, cyfluthrin, beta-cyfluthrin, deltamethrin, dimefluthrin, esfenvalerate, fenvalerate, indoxacarb, metofluthrin, profluthrin, pyrethrin and tralomethrin; cholinesterase inhibitors such as chlorpyrifos, methomyl, oxamyl, thiodicarb and triazamate; neonicotinoids such as acetamiprid, clothianidin, dinotefuran, imidacloprid, nitenpyram, nithiazine, thiacloprid and thiamethoxam; insecticidal macrocyclic lactones such as spinetoram, spinosad, abamectin, avermectin and emamectin; GAB A (γ-aminobutyric acid)-gated chloride channel antagonists such as avermectin or blockers such as ethiprole and fipronil; chitin synthesis inhibitors such as buprofezin, cyromazine, flufenoxuron, hexaflumuron, lufenuron, novaluron, noviflumuron and triflumuron; juvenile hormone mimics such as diofenolan, fenoxycarb, methoprene and pyriproxyfen; octopamine receptor ligands such as amitraz; molting inhibitors and ecdysone agonists such as azadirachtin, methoxyfenozide and tebufenozide; ryanodine receptor ligands such as ryanodine, anthranilic diamides such as chlorantraniliprole, cyantraniliprole and flubendiamide; nereistoxin analogs such as cartap; mitochondrial electron transport inhibitors such as chlorfenapyr, hydramethylnon and pyridaben; lipid biosynthesis inhibitors such as spirodiclofen and spiromesifen; cyclodiene insecticides such as dieldrin or endosulfan; pyrethroids; carbamates; insecticidal ureas; and biological agents including nucleopolyhedro viruses (NPV), members of Bacillus thuringiensis, encapsulated delta-endotoxins of Bacillus thuringiensis, and other naturally occurring or genetically modified insecticidal viruses.

Further examples of biologically active compounds or agents with which compounds of this invention can be formulated are: fungicides such as l-[4-[4-[5-(2,6-difluorophenyl)- 4,5 -dihydro-3 -isoxazolyl] -2-thiazolyl] - 1 -piperidinyl]-2- [5 -methyl-3 -(trifluoromethyl)- 1H- pyrazol-l-yl]ethanone, acibenzolar, aldimorph, amisulbrom, azaconazole, azoxystrobin, benalaxyl, benomyl, benthiavalicarb, benthiavalicarb-isopropyl, binomial, biphenyl, bitertanol, blasticidin-S, Bordeaux mixture (Tribasic copper sulfate), boscalid/nicobifen, bromuconazole, bupirimate, buthiobate, carboxin, carpropamid, captafol, captan, carbendazim, chloroneb, chlorothalonil, chlozolinate, clotrimazole, copper oxychloride, copper salts such as copper sulfate and copper hydroxide, cyazofamid, cyflunamid, cymoxanil, cyproconazole, cyprodinil, dichlofluanid, diclocymet, diclomezine, dicloran, diethofencarb, difenoconazole, dimethomorph, dimoxystrobin, diniconazole, diniconazole-M, dinocap, discostrobin, dithianon, dodemorph, dodine, econazole, etaconazole, edifenphos, epoxiconazole, ethaboxam, ethirimol, ethridiazole, famoxadone, fenamidone, fenarimol, fenbuconazole, fencaramid, fenfuram, fenhexamide, fenoxanil, fenpiclonil, fenpropidin, fenpropimorph, fentin acetate, fentin hydroxide, ferbam, ferfurazoate, ferimzone, fluazinam, fludioxonil, flumetover, fluopicolide, fluoxastrobin, fluquinconazole, fluquinconazole, flusilazole, flusulfamide, flutolanil, flutriafol, fluxapyroxad, folpet, fosetyl-aluminum, fthalide, fuberidazole, furalaxyl, furametpyr, hexaconazole, hymexazole, guazatine, imazalil, imibenconazole, iminoctadine, iodicarb, ipconazole, iprobenfos, iprodione, iprovalicarb, isoconazole, isoprothiolane, isotianil, kasugamycin, kresoxim-methyl, mancozeb, mandipropamid, maneb, mapanipyrin, mefenoxam, mepronil, metalaxyl, metconazole, methasulfocarb, metiram, metominostrobin/fenominostrobin, mepanipyrim, metrafenone, miconazole, myclobutanil, neo-asozin (ferric methanearsonate), nuarimol, octhilinone, ofurace, orysastrobin, oxadixyl, oxolinic acid, oxpoconazole, oxycarboxin, paclobutrazol, penconazole, pencycuron, penflufen, penthiopyrad, perfurazoate, phosphonic acid, phthalide, picobenzamid, picoxystrobin, polyoxin, probenazole, prochloraz, procymidone, propamocarb, propamocarb-hydrochloride, propiconazole, propineb, proquinazid, prothioconazole, pyraclostrobin, pyrametostrobin, pyraoxystrobin, pryazophos, pyrifenox, pyrimethanil, pyrifenox, pyriofenone, pyrolnitrine, pyroquilon, quinconazole, quinoxyfen, quintozene, silthiofam, simeconazole, spiroxamine, streptomycin, sulfur, tebuconazole, tebufloquin, techrazene, tecloftalam, tecnazene, tetraconazole, thiabendazole, thifluzamide, thiophanate, thiophanate-methyl, thiram, tiadinil, tolclofos-methyl, tolyfluanid, triadimefon, triadimenol, triarimol, triazoxide, tridemorph, trimorphamide, tricyclazole, trifloxystrobin, triforine, triticonazole, uniconazole, validamycin, valifenalate, vinclozolin, zineb, ziram, and zoxamide; nematocides such as aldicarb, imicyafos, oxamyl and fenamiphos; bactericides such as streptomycin; acaricides such as amitraz, chinomethionat, chlorobenzilate, cyhexatin, dicofol, dienochlor, etoxazole, fenazaquin, fenbutatin oxide, fenpropathrin, fenpyroximate, hexythiazox, propargite, pyridaben and tebufenpyrad.

Of note are fungicides and compositions comprising fungicides such as l-[4-[4-[5- (2,6-difluorophenyl)-4,5-dihydro-3-isoxazolyl]-2-thiazolyl]-l-piperidinyl]-2-[5-methyl-3- (trifluoromethyl)-lH-pyrazol-l-yl]ethanone, azoxystrobin, copper hydroxide, cymoxanil, cyproconazole, difenoconazole, famoxadone, fenoxanil, ferimzone, flusilazole, flutolanil, fthalide, furametpyr, hexaconazole, isoprothiolane, isotianil, kasugamycin, mancozeb, metominostrobin, orysastrobin, pencycuron, penthiopyrad, picoxystrobin, probenazole, propiconazole, proquinazid, pyroquilon, simeconazole, tiadinil, tricyclazole, trifloxystrobin and validamycin.

In certain instances, combinations of a compound of this invention with other biologically active (particularly invertebrate pest control) compounds or agents (i.e. active ingredients) can result in a greater-than-additive (i.e. synergistic) effect. Reducing the quantity of active ingredients released in the environment while ensuring effective pest control is always desirable. When synergism of invertebrate pest control active ingredients occurs at application rates giving agronomically satisfactory levels of invertebrate pest control, such combinations can be advantageous for reducing crop production cost and decreasing environmental load.

Compounds of this invention and compositions thereof can be applied to plants genetically transformed to express proteins toxic to invertebrate pests (such as Bacillus thuringiensis delta-endotoxins). Such an application may provide a broader spectrum of plant protection and be advantageous for resistance management. The effect of the exogenously applied invertebrate pest control compounds of this invention may be synergistic with the expressed toxin proteins.

General references for these agricultural protectants (i.e. insecticides, fungicides, nematocides, acaricides, herbicides and biological agents) include The Pesticide Manual, 13th Edition, C. D. S. Tomlin, Ed., British Crop Protection Council, Farnham, Surrey, U.K., 2003 and The BioPesticide Manual, 2ⁿ Edition, L. G. Copping, Ed., British Crop Protection Council, Farnham, Surrey, U.K., 2001.

For embodiments where one or more of these various mixing partners are used, the weight ratio of these various mixing partners (in total) to the compound of Formula 1, an N- oxide, or salt thereof, is typically between about 1 :3000 and about 3000: 1. Of note are weight ratios between about 1 :300 and about 300: 1 (for example ratios between about 1 :30 and about 30: 1). One skilled in the art can easily determine through simple experimentation the biologically effective amounts of active ingredients necessary for the desired spectrum of biological activity. It will be evident that including these additional components can expand the spectrum of invertebrate pests controlled beyond the spectrum controlled by the compound of Formula 1 alone.

Table A lists specific combinations of a compound of Formula 1 with other invertebrate pest control agents illustrative of the mixtures, compositions and methods of the present invention. The first column of Table A lists the specific invertebrate pest control agents (e.g., "Abamectin" in the first line). The second column of Table A lists the mode of action (if known) or chemical class of the invertebrate pest control agents. The third column of Table A lists embodiment(s) of ranges of weight ratios for rates at which a compound of Formula 1 can be applied relative to an invertebrate pest control agent (e.g., "50:1 to 1 :50" of a compound of Formula 1 relative to abamectin by weight). Thus, for example, the first line of Table A specifically discloses the combination of a compound of Formula 1 with abamectin can be applied in a weight ratio between 50: 1 to 1 :50. The remaining lines of Table A are to be construed similarly. Of further note Table A lists specific combinations of a compound of Formula 1 with other invertebrate pest control agents illustrative of the mixtures, compositions and methods of the present invention and includes additional embodiments of weight ratio ranges for application rates.

Table A

Invertebrate Pest Mode of Action or Chemical Class Typical Control Agent Weight Ratio

Abamectin macrocyclic lactones 50 1 to 1 50

Acetamiprid neonicotinoids 150 1 to 1 200

Amitraz octopamine receptor ligands 200 1 to 1 100

Avermectin macrocyclic lactones 50 1 to 1 50

Azadirachtin ecdysone agonists 100 1 to 1 120

Beta-cyfluthrin sodium channel modulators 150 1 to 1 200

Bifenthrin sodium channel modulators 100: 1 to 1 : 10

Buprofezin chitin synthesis inhibitors 500: 1 to 1 :50 Invertebrate Pest Mode of Action or Chemical Class Typical Control Agent Weight Ratio

Cartap nereistoxin analogs 100:1 to 1:200

Chlorantraniliprole ryanodine receptor ligands 100:1 to 1:120

Chlorfenapyr mitochondrial electron transport inhibitors 300:1 to 1:200

Chlorpyrifos cholinesterase inhibitors 500:1 to 1:200

Clothianidin neonicotinoids 100:1 to 1:400

Cyantraniliprole ryanodine receptor ligands 100:1 to 1:120

Cyfluthrin sodium channel modulators 150:1 to 1:200

Cyhalothrin sodium channel modulators 150:1 to 1:200

Cypermethrin sodium channel modulators 150:1 to 1:200

Cyromazine chitin synthesis inhibitors 400:1 to 1:50

Deltamethrin sodium channel modulators 50:1 to 1:400

Dieldrin cyclodiene insecticides 200:1 to 1:100

Dinotefuran neonicotinoids 150:1 to 1:200

Diofenolan molting inhibitor 150:1 to 1:200

Emamectin macrocyclic lactones 50:1 to 1:10

Endosulfan cyclodiene insecticides 200:1 to 1:100

Esfenvalerate sodium channel modulators 100:1 to 1:400

Ethiprole GABA-regulated chloride channel 200:1 to 1:100 blockers

Fenothiocarb 150:1 to 1:200

Fenoxycarb juvenile hormone mimics 500:1 to 1:100

Fenvalerate sodium channel modulators 150:1 to 1:200

Fipronil GABA-regulated chloride channel 150:1 to 1:100 blockers

Flonicamid 200:1 to 1:100

Flubendiamide ryanodine receptor ligands 100:1 to 1:120

Flufenoxuron chitin synthesis inhibitors 200:1 to 1:100

Hexaflumuron chitin synthesis inhibitors 300:1 to 1:50

Hydramethylnon mitochondrial electron transport inhibitors 150:1 to 1:250

Imidacloprid neonicotinoids 1000:1 to 1:1000

Indoxacarb sodium channel modulators 200:1 to 1:50

Lambda-cyhalothrin sodium channel modulators 50:1 to 1:250

Lufenuron chitin synthesis inhibitors 500:1 to 1:250 Invertebrate Pest Mode of Action or Chemical Class Typical Control Agent Weight Ratio

Metaflumizone 200 1 to 1 200

Methomyl cholinesterase inhibitors 500 1 to 1 100

Methoprene juvenile hormone mimics 500 1 to 1 100

Methoxyfenozide ecdysone agonists 50 1 to 1 50

Nitenpyram neonicotinoids 150 1 to 1 200

Nithiazine neonicotinoids 150 1 to 1 200

Novaluron chitin synthesis inhibitors 500 1 to 1 150

Oxamyl cholinesterase inhibitors 200 1 to 1 200

Pymetrozine 200 1 to 1 100

Pyrethrin sodium channel modulators 100: 1 to 1 : 10

Pyridaben mitochondrial electron transport inhibitors 200 1 to 1 100

Pyridalyl 200 1 to 1 100

Pyriproxyfen juvenile hormone mimics 500 1 to 1 100

Ryanodine ryanodine receptor ligands 100 1 to 1 120

Spinetoram macrocyclic lactones 150 1 to 1 100

Spinosad macrocyclic lactones 500: 1 to 1 :10

Spirodiclofen lipid biosynthesis inhibitors 200 1 to 1 200

Spiromesifen lipid biosynthesis inhibitors 200 1 to 1 200

Tebufenozide ecdysone agonists 500 1 to 1 250

Thiacloprid neonicotinoids 100 1 to 1 200

Thiamethoxam neonicotinoids 1250 1 to 1 1000

Thiodicarb cholinesterase inhibitors 500 1 to 1 400

Thiosultap-sodium 150 1 to 1 100

Tralomethrin sodium channel modulators 150 1 to 1 200

Triazamate cholinesterase inhibitors 250 1 to 1 100

Triflumuron chitin synthesis inhibitors 200 1 to 1 100

Bacillus thuringiensis biological agents 50 1 to 1 10

Bacillus thuringiensis biological agents 50 1 to 1 10 delta-endotoxin

NPV (e.g., Gemstar) biological agents 50: 1 to 1 : 10

Of note is the composition of the present invention wherein the at least one additional biologically active compound or agent is selected from the Invertebrate Pest Control Agents listed in Table A above. The weight ratios of a compound, including a compound of Formula 1, an N-oxide, or salt thereof, to the additional invertebrate pest control agent typically are between 1000:1 and 1 : 1000, with one embodiment being between 500: 1 and 1 :500, another embodiment being between 250:1 and 1 :200 and another embodiment being between 100:1 and 1 :50.

Listed below in Tables Bl to B12 are embodiments of specific compositions comprising a compound of Formula 1 (compound numbers (Cmpd. No.) refer to compounds in Index Tables A-D) and an additional invertebrate pest control agent.

Table Bl

Mixture Cmpd. and Invertebrate Pest Control Mixture Cmpd. and Invertebrate Pest No. No. Agent No. No. Control Agent

Bl-1 1 and Abamectin Bl-36 1 and Imidacloprid

Bl-2 1 and Acetamiprid Bl-37 1 and Indoxacarb

Bl-3 1 and Amitraz Bl-38 1 and Lambda- cyhalothrin

Bl-4 1 and Avermectin Bl-39 1 and Lufenuron

Bl-5 1 and Azadirachtin Bl-40 1 and Metaflumizone

Bl-5a 1 and Bensultap Bl-41 1 and Methomyl

Bl-6 1 and Beta-cyfluthrin Bl-42 1 and Methoprene

Bl-7 1 and Bifenthrin Bl-43 1 and Methoxyfenozide

Bl-8 1 and Buprofezin Bl-44 1 and Nitenpyram

Bl-9 1 and Cartap Bl-45 1 and Nithiazine

Bl-10 1 and Chlorantraniliprole Bl-46 1 and Novaluron

Bl-11 1 and Chlorfenapyr Bl-47 1 and Oxamyl

Bl-12 1 and Chlorpyrifos Bl-48 1 and Phosmet

Bl-13 1 and Clothianidin Bl-49 1 and Pymetrozine

Bl-14 1 and Cyantraniliprole Bl-50 1 and Pyrethrin

Bl-15 1 and Cyfluthrin Bl-51 1 and Pyridaben

Bl-16 1 and Cyhalothrin Bl-52 1 and Pyridalyl

Bl-17 1 and Cypermethrin Bl-53 1 and Pyriproxyfen

Bl-18 1 and Cyromazine Bl-54 1 and Ryanodine

Bl-19 1 and Deltamethrin Bl-55 1 and Spinetoram

Bl-20 1 and Dieldrin Bl-56 1 and Spinosad

Bl-21 1 and Dinotefuran Bl-57 1 and Spirodiclofen

Bl-22 1 and Diofenolan Bl-58 1 and Spiromesifen

Bl-23 1 and Emamectin Bl-59 1 and Spirotetramat

Bl-24 1 and Endosulfan Bl-60 1 and Tebufenozide

Bl-25 1 and Esfenvalerate Bl-61 1 and Thiacloprid Mixture Cmpd. and Invertebrate Pest Control Mixture Cmpd. and Invertebrate Pest No. No. Agent No. No. Control Agent

Bl-26 1 and Ethiprole Bl-62 1 and Thiamethoxam

Bl-27 1 and Fenothiocarb Bl-63 1 and Thiodicarb

Bl-28 1 and Fenoxycarb Bl-64 1 and Thiosultap-sodium

Bl-29 1 and Fenvalerate Bl-65 1 and Tolfenpyrad

Bl-30 1 and Fipronil Bl-66 1 and Tralomethrin

Bl-31 1 and Flonicamid Bl-67 1 and Triazamate

Bl-32 1 and Flubendiamide Bl-68 1 and Triflumuron

Bl-33 1 and Flufenoxuron Bl-69 1 and Bacillus thuringiensis

Bacillus thuringiensis

Bl-34 ¹ and Hexaflumuron Bl-70 ¹ and

delta- endotoxin

Bl-35 1 and Hydramethylnon Bl-71 1 and NPV (e.g., Gemstar)

Table B2

Table B2 is identical to Table B 1 , except that each reference to compound 1 in the column headed "Cmpd. No." is replaced by a reference to compound 7. For example, the first mixture in Table B2 is designated B2-1 and is a mixture of compound 7 and the additional invertebrate pest control agent abamectin.

Table B3

Table B3 is identical to Table B 1 , except that each reference to compound 1 in the column headed "Cmpd. No." is replaced by a reference to compound 18. For example, the first mixture in Table B3 is designated B3-1 and is a mixture of compound 18 and the additional invertebrate pest control agent abamectin.

Table B4

Table B4 is identical to Table B 1 , except that each reference to compound 1 in the column headed "Cmpd. No." is replaced by a reference to compound 21. For example, the first mixture in Table B4 is designated B4-1 and is a mixture of compound 21 and the additional invertebrate pest control agent abamectin.

Table B5

Table B5 is identical to Table B 1 , except that each reference to compound 1 in the column headed "Cmpd. No." is replaced by a reference to compound 40. For example, the first mixture in Table B5 is designated B5-1 and is a mixture of compound 40 and the additional invertebrate pest control agent abamectin. Table B6

Table B6 is identical to Table B 1 , except that each reference to compound 1 in the column headed "Cmpd. No." is replaced by a reference to compound 46. For example, the first mixture in Table B6 is designated B6-1 and is a mixture of compound 46 and the additional invertebrate pest control agent abamectin.

Listed below in Tables CI to C12 are embodiments of specific compositions comprising a compound of Formula 1 (compound numbers (Cmpd. No.) refer to compounds in Index Tables A-D) and an additional fungicide.

Table CI

Mixture Cmpd. and Mixture No. Cmpd. and

Fungicide Fungicide

No. No. No.

Cl-1 1 and Probenazole Cl-17 1 and Difenoconazole

Cl-2 1 and Tiadinil Cl-18 1 and Cyproconazole

Cl-3 1 and Isotianil Cl-19 1 and Propiconazole

Cl-4 1 and Pyroquilon Cl-20 1 and Fenoxanil

Cl-5 1 and Metominostrobin Cl-21 1 and Ferimzone

Cl-6 1 and Flutolanil CI -22 1 and Fthalide

Cl-7 1 and Validamycin Cl-23 1 and Kasugamycin

Cl-8 1 and Furametpyr CI -24 1 and Picoxystrobin

Cl-9 1 and Pencycuron CI -25 1 and Penthiopyrad

Cl-10 1 and Simeconazole Cl-26 1 and Famoxadone

Cl-11 1 and Orysastrobin CI -27 1 and Cymoxanil

Cl-12 1 and Trifloxystrobin Cl-28 1 and Proquinazid

Cl-13 1 and Isoprothiolane CI -29 1 and Flusilazole

Cl-14 1 and Azoxystrobin Cl-30 1 and Mancozeb

Cl-15 1 and Tricyclazole Cl-31 1 and Copper hydroxide

Cl-16 1 and Hexaconazole Cl-32 1 and (a)

(a) l-[4-[4-[5-(2,6-difluorophenyl)-4,5-dihydro-3-isoxazolyl]-2-thiazolyl]-l-piperidinyl]-2-[5-methyl-3- (trifluoromethyl)- l /-pyrazol- 1 -yljethanone

Table C2

Table C2 is identical to Table C 1 , except that each reference to compound 1 in the column headed "Cmpd. No." is replaced by a reference to compound 7. For example, the first mixture in Table C2 is designated C2-1 and is a mixture of compound 7 and the additional fungicide probenazole. Table C3

Table C3 is identical to Table C 1 , except that each reference to compound 1 in the column headed "Cmpd. No." is replaced by a reference to compound 18. For example, the first mixture in Table C3 is designated C3-1 and is a mixture of compound 18 and the additional fungicide probenazole.

Table C4

Table C4 is identical to Table C 1 , except that each reference to compound 1 in the column headed "Cmpd. No." is replaced by a reference to compound 21. For example, the first mixture in Table C4 is designated C4-1 and is a mixture of compound 21 and the additional fungicide probenazole.

Table C5

Table C5 is identical to Table C 1 , except that each reference to compound 1 in the column headed "Cmpd. No." is replaced by a reference to compound 40. For example, the first mixture in Table C5 is designated C5-1 and is a mixture of compound 40 and the additional fungicide probenazole.

Table C6

Table C6 is identical to Table C 1 , except that each reference to compound 1 in the column headed "Cmpd. No." is replaced by a reference to compound 46. For example, the first mixture in Table C6 is designated C6-1 and is a mixture of compound 46 and the additional fungicide probenazole.

Invertebrate pests are controlled in agronomic and nonagronomic applications by applying one or more compounds of this invention, typically in the form of a composition, in a biologically effective amount, to the environment of the pests, including the agronomic and/or nonagronomic locus of infestation, to the area to be protected, or directly on the pests to be controlled.

Thus the present invention comprises a method for controlling an invertebrate pest in agronomic and/or nonagronomic applications, comprising contacting the invertebrate pest or its environment with a biologically effective amount of one or more of the compounds of the invention, or with a composition comprising at least one such compound or a composition comprising at least one such compound and a biologically effective amount of at least one additional biologically active compound or agent. Examples of suitable compositions comprising a compound of the invention and a biologically effective amount of at least one additional biologically active compound or agent include granular compositions wherein the additional active compound is present on the same granule as the compound of the invention or on granules separate from those of the compound of the invention.

Embodiments of the method of this invention include contacting the environment. Of note is the method wherein the environment is a plant. Also of note is the method wherein the environment is an animal. Also of note is the method wherein the environment is a seed.

To achieve contact with a compound or composition of the invention to protect a field crop from invertebrate pests, the compound or composition is typically applied to the seed of the crop before planting, to the foliage (e.g., leaves, stems, flowers, fruits) of crop plants, or to the soil or other growth medium before or after the crop is planted.

One embodiment of a method of contact is by spraying. Alternatively, a granular composition comprising a compound of the invention can be applied to the plant foliage or the soil. Compounds of this invention can also be effectively delivered through plant uptake by contacting the plant with a composition comprising a compound of this invention applied as a soil drench of a liquid formulation, a granular formulation to the soil, a nursery box treatment or a dip of transplants. Of note is a composition of the present invention in the form of a soil drench liquid formulation. Also of note is a method for controlling an invertebrate pest comprising contacting the invertebrate pest or its environment with a biologically effective amount of a compound of the present invention or with a composition comprising a biologically effective amount of a compound of the present invention. Of further note is this method wherein the environment is soil and the composition is applied to the soil as a soil drench formulation. Of further note is that compounds of this invention are also effective by localized application to the locus of infestation. Other methods of contact include application of a compound or a composition of the invention by direct and residual sprays, aerial sprays, gels, seed coatings, microencapsulations, systemic uptake, baits, ear tags, boluses, foggers, fumigants, aerosols, dusts and many others. One embodiment of a method of contact is a dimensionally stable fertilizer granule, stick or tablet comprising a compound or composition of the invention. The compounds of this invention can also be impregnated into materials for fabricating invertebrate control devices (e.g., insect netting).

Compounds of this invention are also useful in seed treatments for protecting seeds from invertebrate pests. In the context of the present disclosure and claims, treating a seed means contacting the seed with a biologically effective amount of a compound of this invention, which is typically formulated as a composition of the invention. This seed treatment protects the seed from invertebrate soil pests and generally can also protect roots and other plant parts in contact with the soil of the seedling developing from the germinating seed. The seed treatment may also provide protection of foliage by translocation of the compound of this invention or a second active ingredient within the developing plant. Seed treatments can be applied to all types of seeds, including those from which plants genetically transformed to express specialized traits will germinate. Representative examples include those expressing proteins toxic to invertebrate pests, such as Bacillus thuringiensis toxin or those expressing herbicide resistance such as glyphosate acetyltransferase, which provides resistance to glyphosate.

One method of seed treatment is by spraying or dusting the seed with a compound of the invention (i.e. as a formulated composition) before sowing the seeds. Compositions formulated for seed treatment generally comprise a film former or adhesive agent. Therefore typically a seed coating composition of the present invention comprises a biologically effective amount of a compound of Formula 1, an N-oxide, or salt thereof, and a film former or adhesive agent. Seed can be coated by spraying a flowable suspension concentrate directly into a tumbling bed of seeds and then drying the seeds. Alternatively, other formulation types such as wetted powders, solutions, suspoemulsions, emulsifiable concentrates and emulsions in water can be sprayed on the seed. This process is particularly useful for applying film coatings on seeds. Various coating machines and processes are available to one skilled in the art. Suitable processes include those listed in P. Kosters et al, Seed Treatment: Progress and Prospects, 1994 BCPC Mongraph No. 57, and references listed therein.

Compounds of Formula 1 and their compositions, both alone and in combination with other insecticides, nematicides, and fungicides, are particularly useful in seed treatment for crops including, but not limited to, maize or corn, soybeans, cotton, cereal (e.g., wheat, oats, barley, rye and rice), potatoes, vegetables and oilseed rape.

Other insecticides or nematicides with which compounds of Formula 1 can be formulated to provide mixtures useful in seed treatment include but are not limited to abamectin, acetamiprid, acrinathrin, amitraz, avermectin, azadirachtin, bensultap, bifenthrin, buprofezin, cadusafos, carbaryl, carbofuran, cartap, chlorantraniliprole, chlorfenapyr, chlorpyrifos, clothianidin, cyantraniliprole, cyfluthrin, beta-cyf uthrin, cyhalothrin, gamma- cyhalothrin, lambda-cyhalothrin, cypermethrin, alpha-cypermethrin, zeta-cypermethrin, cyromazine, deltamethrin, dieldrin, dinotefuran, diofenolan, emamectin, endosulfan, esfenvalerate, ethiprole, etofenprox, etoxazole, fenothiocarb, fenoxycarb, fenvalerate, fipronil, f onicamid, flubendiamide, f ufenoxuron, fluvalinate, formetanate, fosthiazate, hexaf umuron, hydramethylnon, imidacloprid, indoxacarb, lufenuron, metaflumizone, methiocarb, methomyl, methoprene, methoxyfenozide, nitenpyram, nithiazine, novaluron, oxamyl, pymetrozine, pyrethrin, pyridaben, pyridalyl, pyriproxyfen, ryanodine, spinetoram, spinosad, spirodiclofen, spiromesifen, spirotetramat, sulfoxaf or, tebufenozide, tetramethrin, thiacloprid, thiamethoxam, thiodicarb, thiosultap-sodium, tralomethrin, triazamate, triflumuron, Bacillus thuringiensis delta-endotoxins, all strains of Bacillus thuringiensis and all strains of Nucleo polyhydrosis viruses.

Fungicides with which compounds of Formula 1 can be formulated to provide mixtures useful in seed treatment include but are not limited to amisulbrom, azoxystrobin, boscalid, carbendazim, carboxin, cymoxanil, cyproconazole, difenoconazole, dimethomorph, fluazinam, fludioxonil, fluquinconazole, fluopicolide, fluoxastrobin, flutriafol, fluxapyroxad, ipconazole, iprodione, metalaxyl, mefenoxam, metconazole, myclobutanil, paclobutrazole, penflufen, picoxystrobin, prothioconazole, pyraclostrobin, sedaxane, silthiofam, tebuconazole, thiabendazole, thiophanate -methyl, thiram, trifloxystrobin and triticonazole.

Compositions comprising compounds of Formula 1 useful for seed treatment can further comprise bacteria and fungi that have the ability to provide protection from the harmful effects of plant pathogenic fungi or bacteria and/or soil born animals such as nematodes. Bacteria exhibiting nematicidal properties may include but are not limited to Bacillus firmus, Bacillus cereus, Bacillius subtiliis and Pasteuria penetrans. A suitable Bacillus firmus strain is strain CNCM 1-1582 (GB-126) which is commercially available as BioNem™. A suitable Bacillus cereus strain is strain NCMM 1-1592. Both Bacillus strains are disclosed in US 6,406,690. Other suitable bacteria exhibiting nematicidal activity are B. amyloliquefaciens IN937a and B. subtilis strain GB03. Bacteria exhibiting fungicidal properties may include but are not limited to B. pumilus strain GB34. Fungal species exhibiting nematicidal properties may include but are not limited to Myrothecium verrucaria, Paecilomyces lilacinus and Purpureocillium lilacinum.

Seed treatments can also include one or more nematicidal agents of natural origin such as the elicitor protein called harpin which is isolated from certain bacterial plant pathogens such as Erwinia amylovora. An example is the Harpin-N-Tek seed treatment technology available as N-Hibit™ Gold CST.

Seed treatments can also include one or more species of legume-root nodulating bacteria such as the microsymbiotic nitrogen- fixing bacteria Bradyrhizobium japonicum. These inocculants can optionally include one or more lipo-chitooligosaccharides (LCOs), which are nodulation (Nod) factors produced by rhizobia bacteria during the initiation of nodule formation on the roots of legumes. For example, the Optimize® brand seed treatment technology incorporates LCO Promoter Technology™ in combination with an inocculant.

Seed treatments can also include one or more isoflavones which can increase the level of root colonization by mycorrhizal fungi. Mycorrhizal fungi improve plant growth by enhancing the root uptake of nutrients such as water, sulfates, nitrates, phosphates and metals. Examples of isoflavones include, but are not limited to, genistein, biochanin A, formononetin, daidzein, glycitein, hesperetin, naringenin and pratensein. Formononetin is available as an active ingredient in mycorrhizal inocculant products such as PHC Colonize® AG.

Seed treatments can also include one or more plant activators that induce systemic acquired resistance in plants following contact by a pathogen. An example of a plant activator which induces such protective mechanisms is acibenzolar-S-methyl.

The treated seed typically comprises a compound of the present invention in an amount from about 0.1 g to 1 kg per 100 kg of seed (i.e. from about 0.0001 to 1% by weight of the seed before treatment). A flowable suspension formulated for seed treatment typically comprises from about 0.5 to about 70% of the active ingredient, from about 0.5 to about 30% of a film- forming adhesive, from about 0.5 to about 20% of a dispersing agent, from 0 to about 5% of a thickener, from 0 to about 5% of a pigment and/or dye, from 0 to about 2% of an antifoaming agent, from 0 to about 1% of a preservative, and from 0 to about 75% of a volatile liquid diluent.

The compounds of this invention can be incorporated into a bait composition that is consumed by an invertebrate pest or used within a device such as a trap, bait station, and the like. Such a bait composition can be in the form of granules which comprise (a) active ingredients, namely a biologically effective amount of a compound of Formula 1 an N-oxide, or salt thereof; (b) one or more food materials; optionally (c) an attractant, and optionally (d) one or more humectants. Of note are granules or bait compositions which comprise between about 0.001-5% active ingredients, about 40-99% food material and/or attractant; and optionally about 0.05-10% humectants, which are effective in controlling soil invertebrate pests at very low application rates, particularly at doses of active ingredient that are lethal by ingestion rather than by direct contact. Some food materials can function both as a food source and an attractant. Food materials include carbohydrates, proteins and lipids. Examples of food materials are vegetable flour, sugar, starches, animal fat, vegetable oil, yeast extracts and milk solids. Examples of attractants are odorants and flavorants, such as fruit or plant extracts, perfume, or other animal or plant component, pheromones or other agents known to attract a target invertebrate pest. Examples of humectants, i.e. moisture retaining agents, are glycols and other polyols, glycerine and sorbitol. Of note is a bait composition (and a method utilizing such a bait composition) used to control at least one invertebrate pest selected from the group consisting of ants, termites and cockroaches. A device for controlling an invertebrate pest can comprise the present bait composition and a housing adapted to receive the bait composition, wherein the housing has at least one opening sized to permit the invertebrate pest to pass through the opening so the invertebrate pest can gain access to the bait composition from a location outside the housing, and wherein the housing is further adapted to be placed in or near a locus of potential or known activity for the invertebrate pest.

The compounds of this invention can be applied without other adjuvants, but most often application will be of a formulation comprising one or more active ingredients with suitable carriers, diluents, and surfactants and possibly in combination with a food depending on the contemplated end use. One method of application involves spraying a water dispersion or refined oil solution of a compound of the present invention. Combinations with spray oils, spray oil concentrations, spreader stickers, adjuvants, other solvents, and synergists such as piperonyl butoxide often enhance compound efficacy. For nonagronomic uses such sprays can be applied from spray containers such as a can, a bottle or other container, either by means of a pump or by releasing it from a pressurized container, e.g., a pressurized aerosol spray can. Such spray compositions can take various forms, for example, sprays, mists, foams, fumes or fog. Such spray compositions thus can further comprise propellants, foaming agents, etc. as needed for application. Of note is a spray composition comprising a biologically effective amount of a compound or a composition of the present invention and a carrier. One embodiment of such a spray composition comprises a biologically effective amount of a compound or a composition of the present invention and a propellant. Representative propellants include, but are not limited to, methane, ethane, propane, butane, isobutane, butene, pentane, isopentane, neopentane, pentene, hydrofluorocarbons, chlorofluorocarbons, dimethyl ether, and mixtures of the foregoing. Of note is a spray composition (and a method utilizing such a spray composition dispensed from a spray container) used to control at least one invertebrate pest selected from the group consisting of mosquitoes, black flies, stable flies, deer flies, horse flies, wasps, yellow jackets, hornets, ticks, spiders, ants, gnats, and the like, including individually or in combinations.

Nonagronomic uses refer to invertebrate pest control in the areas other than fields of crop plants. Nonagronomic uses of the present compounds and compositions include control of invertebrate pests in stored grains, beans and other foodstuffs, and in textiles such as clothing and carpets. Nonagronomic uses of the present compounds and compositions also include invertebrate pest control in ornamental plants, forests, in yards, along roadsides and railroad rights of way, and on turf such as lawns, golf courses and pastures. Nonagronomic uses of the present compounds and compositions also include invertebrate pest control in houses and other buildings which may be occupied by humans and/or companion, farm, ranch, zoo or other animals. Nonagronomic uses of the present compounds and compositions also include the control of pests such as termites that can damage wood or other structural materials used in buildings. Nonagronomic uses of the present compounds and compositions also include protecting human and animal health by controlling invertebrate pests that are parasitic or transmit infectious diseases. The controlling of animal parasites includes controlling external parasites that are parasitic to the surface of the body of the host animal (e.g., shoulders, armpits, abdomen, inner part of the thighs) and internal parasites that are parasitic to the inside of the body of the host animal (e.g., stomach, intestine, lung, veins, under the skin, lymphatic tissue). External parasitic or disease transmitting pests include, for example, chiggers, ticks, lice, mosquitoes, flies, mites and fleas. Internal parasites include heartworms, hookworms and helminths. Compounds and compositions of the present invention are particularly suitable for combating external parasitic or disease transmitting pests. Compounds and compositions of the present invention are suitable for systemic and/or non-systemic control of infestation or infection by parasites on animals.

Compounds and compositions of the present invention are suitable for combating parasites that infest animal subjects including those in the wild, livestock and agricultural working animals such as cattle, sheep, goats, horses, pigs, donkeys, camels, bison, buffalos, rabbits, hens, turkeys, ducks, geese and bees (e.g., raised for meat, milk, butter, eggs, fur, leather, feathers and/or wool). By combating parasites, fatalities and performance reduction (in terms of meat, milk, wool, skins, eggs, honey, etc.) are reduced, so that applying a composition comprising a compound of the present invention allows more economic and simple husbandry of animals.

Compounds and compositions of the present invention are especially suitable for combating parasites that infest companion animals and pets (e.g., dogs, cats, pet birds and aquarium fish), research and experimental animals (e.g., hamsters, guinea pigs, rats and mice), as well as animals raised for/in zoos, wild habitats and/or circuses.

In an embodiment of this invention, the animal is preferably a vertebrate, and more preferably a mammal, avian or fish. In a particular embodiment, the animal subject is a mammal (including great apes, such as humans). Other mammalian subjects include primates (e.g., monkeys), bovine (e.g., cattle or dairy cows), porcine (e.g., hogs or pigs), ovine (e.g., goats or sheep), equine (e.g., horses), canine (e.g., dogs), feline (e.g., house cats), camels, deer, donkeys, bison, buffalos, antelopes, rabbits, and rodents (e.g., guinea pigs, squirrels, rats, mice, gerbils, and hamsters). Avians include Anatidae (swans, ducks and geese), Columbidae (e.g., doves and pigeons), Phasianidae (e.g., partridges, grouse and turkeys), Thesienidae (e.g., domestic chickens), Psittacines (e.g., parakeets, macaws, and parrots), game birds, and ratites (e.g., ostriches).

Birds treated or protected by the inventive compounds can be associated with either commercial or noncommercial aviculture. These include Anatidae, such as swans, geese, and ducks, Columbidae, such as doves and domestic pigeons, Phasianidae, such as partridge, grouse and turkeys, Thesienidae, such as domestic chickens, and Psittacines, such as parakeets, macaws, and parrots raised for the pet or collector market, among others.

For purposes of the present invention, the term "fish" shall be understood to include without limitation, the Teleosti grouping of fish, i.e., teleosts. Both the Salmoniformes order (which includes the Salmonidae family) and the Perciformes order (which includes the Centrarchidae family) are contained within the Teleosti grouping. Examples of potential fish recipients include the Salmonidae, Serranidae, Sparidae, Cichlidae, and Centrarchidae, among others.

Other animals are also contemplated to benefit from the inventive methods, including marsupials (such as kangaroos), reptiles (such as farmed turtles), and other economically important domestic animals for which the inventive methods are safe and effective in treating or preventing parasite infection or infestation.

Examples of invertebrate parasitic pests controlled by administering a parasiticidally effective amount of a compound of this invention to an animal to be protected include ectoparasites (arthropods, acarines, etc) and endoparasites (helminths, e.g., nematodes, trematodes, cestodes, acanthocephalans, etc.).

The disease or group of diseases described generally as helminthiasis is due to infection of an animal host with parasitic worms known as helminths. The term 'helminths' is meant to include nematodes, trematodes, cestodes and acanthocephalans. Helminthiasis is a prevalent and serious economic problem with domesticated animals such as swine, sheep, horses, cattle, goats, dogs, cats and poultry.

Among the Helminths, the group of worms described as nematodes causes widespread and at times serious infection in various species of animals. Nematodes that are contemplated to be treated by the compounds of this invention and by the inventive methods include, without limitation, the following genera: Acanthocheilonema, Aelurostrongylus, Ancylo stoma, Angiostrongylus, Ascaridia, Ascaris, Brugia, Bunostomum, Capillaria, Chabertia, Cooperia, Crenosoma, Dictyocaulus, Dioctophyme, Dipetalonema, Diphyllobothrium, Dirofilaria, Dracunculus, Enterobius, Filaroides, Haemonchus, Heterakis, Lagochilascaris, Loa, Mansonella, Muellerius, Necator, Nematodirus, Oesophagostomum, Ostertagia, Oxyuris, Parafilaria, Parascaris, Physaloptera, Protostrongylus, Setaria, Spirocerca, Stephanofilaria, Strongyloides, Strongylus, Thelazia, Toxascaris, Toxocara, Trichinella, Trichonema, Tricho strongylus, Trichuris, Uncinaria and Wuchereria.

Of the above, the most common genera of nematodes infecting the animals referred to above are Haemonchus, Tricho strongylus, Ostertagia, Nematodirus, Cooperia, Ascaris, Bunostomum, Oesophagostomum, Chabertia, Trichuris, Strongylus, Trichonema, Dictyocaulus, Capillaria, Heterakis, Toxocara, Ascaridia, Oxyuris, Ancylo stoma, Uncinaria, Toxascaris and Parascaris. Certain of these, such as Nematodirus, Cooperia and Oesophagostomum attack primarily the intestinal tract while others, such as Haemonchus and Ostertagia, are more prevalent in the stomach while others such as Dictyocaulus are found in the lungs. Still other parasites may be located in other tissues such as the heart and blood vessels, subcutaneous and lymphatic tissue and the like.

Trematodes that are contemplated to be treated by the compounds of this invention and by the inventive methods include, without limitation, the following genera: Alaria, Fasciola, Nanophyetus, Opisthorchis, Paragonimus and Schistosoma.

Cestodes that are contemplated to be treated by the compounds of this invention and by the inventive methods include, without limitation, the following genera: Diphyllobothrium, Diplydium, Spirometra and Taenia.

The most common genera of parasites of the gastrointestinal tract of humans are Ancylostoma, Necator, Ascaris, Strongy hides, Trichinella, Capillaria, Trichuris and Enterobius. Other medically important genera of parasites which are found in the blood or other tissues and organs outside the gastrointestinal tract are the filarial worms such as Wuchereria, Brugia, Onchocerca and Loa, as well as Dracunculus and extra intestinal stages of the intestinal worms Strongyloides and Trichinella.

Numerous other Helminth genera and species are known to the art, and are also contemplated to be treated by the compounds of the invention. These are enumerated in great detail in Textbook of Veterinary Clinical Parasitology, Volume 1, Helminths, E. J. L. Soulsby, F. A. Davis Co., Philadelphia, Pa.; Helminths, Arthropods and Protozoa, (6^th Edition of Monnig's Veterinary Helminthology and Entomology), E. J. L. Soulsby, The Williams and Wilkins Co., Baltimore, Md.

It is also contemplated that the inventive compounds are effective against a number of ectoparasites of animals, e.g., arthropod ectoparasites of mammals and birds although it is also recognized that some arthropods can be endoparasites as well.

Thus, insect and acarine pests include, e.g., biting insects, such as flies and mosquitoes, mites, ticks, lice, fleas, true bugs, parasitic maggots, and the like.

Adult flies include, e.g., the horn fly or Haematobia irritans, the horse fly or Tabanus spp., the stable fly or Stomoxys calcitrans, the black fly or Simulium spp., the deer fly or Chrysops spp., the louse fly or Melophagus ovinus, the tsetse fly or Glossina spp. Parasitic fly maggots include, e.g., the bot fly {Oestrus ovis and Cuterebra spp.), the blow fly or Phaenicia spp., the screwworm or Cochliomyia hominivorax, the cattle grub or Hypoderma spp., the fleeceworm and the Gastrophilus of horses. Mosquitoes include, for example, Culex spp., Anopheles spp., and Aedes spp.

Mites include Mesostigmata spp. e.g., mesostigmatids such as the chicken mite, Dermanyssus gallinae; itch or scab mites such as Sarcoptidae spp. for example, Sarcoptes scabiei; mange mites such as Psoroptidae spp. including Chorioptes bovis and Psoroptes ovis; chiggers e.g., Trombiculidae spp. for example the North American chigger, Trombicula alfreddugesi.

Ticks include, e.g., soft-bodied ticks including Argasidae spp. for example Argas spp. and Ornithodoros spp.; hard-bodied ticks including Ixodidae spp., for example Rhipicephalus sanguineus, Dermacentor variabilis, Dermacentor andersoni, Amblyomma americanum, Ixodes scapularis and Boophilus spp.

Lice include, e.g., sucking lice, e.g., Menopon spp. and Bovicola spp.; biting lice, e.g., Haematopinus spp., Linognathus spp. and Solenopotes spp.

Fleas include, e.g., Ctenocephalides spp., such as dog flea (Ctenocephalides canis) and cat flea {Ctenocephalides felis); Xenopsylla spp. such as oriental rat flea (Xenopsylla cheopis); and Pulex spp. such as human flea (Pulex irritans).

True bugs include, e.g., Cimicidae or e.g., the common bed bug (Cimex lectularius); Triatominae spp. including triatomid bugs also known as kissing bugs; for example Rhodnius prolixus and Triatoma spp.

Generally, flies, fleas, lice, mosquitoes, gnats, mites, ticks and helminths cause tremendous losses to the livestock and companion animal sectors. Arthropod parasites also are a nuisance to humans and can vector disease-causing organisms in humans and animals.

Numerous other arthropod pests and ectoparasites are known to the art, and are also contemplated to be treated by the compounds of the invention. These are enumerated in great detail in Medical and Veterinary Entomology, D. S. Kettle, John Wiley & Sons, New York and Toronto; Control of Arthropod Pests of Livestock: A Review of Technology, R. O. Drummand, J. E. George, and S. E. Kunz, CRC Press, Boca Raton, Fla.

The compounds and compositions of this invention may also be effective against a number of protozoa endoparasites of animals, such as those summarized by Table 1, as follows.

Table 1

Exemplary Parasitic Protozoa and Associated Human Diseases

Human Disease or

Phylum Subphvlum Representative Genera Disorder

S arcomastigophora Mastigophora Leishmania Visceral, cutaneous Table 1

Exemplary Parasitic Protozoa and Associated Human Diseases

Human Disease or

Phylum Subphylum Representative Genera Disorder

(with flagella, (Flagella) and mucocutaneous pseudopodia, or Infection

both)

Trypansoma Sleeping sickness

Chagas' disease

Giardia Diarrhea

Trichomonas Vaginitis

Sarcodina Entamoeba Dysentery, liver (pseudopodia) Abscess

Dientamoeba Colitis

Naegleria and Central nervous

Acanthamoeba system and corneal ulcers

Babesia Babesiesis

Apicomplexa Plasmodium Malaria

(apical complex)

Isospora Diarrhea

Sarcocystis Diarrhea

Crypto sporidum Diarrhea

Toxoplasma Toxoplasmosis

Eimeria Chicken coccidiosis

Microspora Enterocytozoon Diarrhea

Ciliaphora (with Balantidium Dysentery

cilia)

Unclassified Pneumocystis Pneumonia

In particular, the compounds of this invention are effective against ectoparasites including fleas such as Ctenocephalides felis (cat flea) and Ctenocephalides canis (dog flea).

The compounds of this invention may also be effective against other ectoparasites including flies such as Haematobia (Lyperosia) irritans (horn fly), Stomoxys calcitrans (stable fly), Simulium spp. (blackfly), Glossina spp. (tsetse flies), Hydrotaea irritans (head fly), Musca autumnalis (face fly), Musca domestica (house fly), Morellia simplex (sweat fly), Tabanus spp. (horse fly), Hypoderma bovis, Hypoderma lineatum, Lucilia sericata, Lucilia cuprina (green blowfly), Calliphora spp. (blowfly), Protophormia spp., Oestrus ovis (nasal botfly), Culicoides spp. (midges), Hippobosca equine, Gastrophilus instestinalis, Gastrophilus haemorrhoidalis and Gastrophilus naslis; lice such as Bovicola (Damalinia) bovis, Bovicola equi, Haematopinus asini, Felicola subrostratus, Heterodoxus spiniger, Lignonathus setosus and Trichodectes canis; keds such as Melophagus ovinus; mites such as Psoroptes spp., Sarcoptes scabei, Chorioptes bovis, Demodex equi, Cheyletiella spp., Notoedres cati, Trombicula spp. and Otodectes cyanotis (ear mites); and ticks such as Ixodes spp., Boophilus spp., Rhipicephalus spp., Amblyomma spp., Dermacentor spp., Hyalomma spp. and Haemaphysalis spp.

Biologically active compounds or agents useful in the compositions of the present invention include the organophosphate pesticides. This class of pesticides has very broad activity as insecticides and, in certain instances, anthelminitic activity. Organophosphate pesticides include, e.g., dicrotophos, terbufos, dimethoate, diazinon, disulfoton, trichlorfon, azinphos-methyl, chlorpyrifos, malathion, oxydemeton-methyl, methamidophos, acephate, ethyl parathion, methyl parathion, mevinphos, phorate, carbofenthion and phosalone. It is also contemplated to include combinations of the inventive methods and compounds with carbamate type pesticides, including, e.g., carbaryl, carbofuran, aldicarb, molinate, methomyl, carbofuran, etc., as well as combinations with the organochlorine type pesticides. It is further contemplated to include combinations with biological pesticides, including repellents, the pyrethrins (as well as synthetic variations thereof, e.g., allethrin, resmethrin, permethrin, tralomethrin), and nicotine, that is often employed as an acaricide. Other contemplated combinations are with miscellaneous pesticides including: bacillus thuringensis, chlorobenzilate, formamidines (e.g., amitraz), copper compounds (e.g., copper hydroxide and cupric oxychloride sulfate), cyfluthrin, cypermethrin, dicofol, endosulfan, esenfenvalerate, fenvalerate, lambda-cyhalothrin, methoxychlor and sulfur.

Of note are additional biologically active compounds or agents selected from art- known anthelmintics, such as, for example, avermectins (e.g., ivermectin, moxidectin, milbemycin), benzimidazoles (e.g., albendazole, triclabendazole), salicylanilides (e.g., closantel, oxyclozanide), substituted phenols (e.g., nitroxynil), pyrimidines (e.g., pyrantel), imidazothiazoles (e.g., levamisole) and praziquantel.

Other biologically active compounds or agents useful in the compositions of the present invention can be selected from Insect Growth Regulators (IGRs) and Juvenile Hormone Analogues (JHAs) such as diflubenzuron, triflumuron, fluazuron, cyromazine, methoprene, etc., thereby providing both initial and sustained control of parasites (at all stages of insect development, including eggs) on the animal subject, as well as within the environment of the animal subject.

Of note are biologically active compounds or agents useful in the compositions of the present invention selected from the antiparasitic class of avermectin compounds. As stated above, the avermectin family of compounds is a series of very potent antiparasitic agents known to be useful against a broad spectrum of endoparasites and ectoparasites in mammals.

A notable compound for use within the scope of the present invention is ivermectin. Ivermectin is a semi-synthetic derivative of avermectin and is generally produced as a mixture of at least 80% 22,23-dihydroavermectin B^_a and less than 20% 22,23- dihydroavermectin B^. Ivermectin is disclosed in U.S. 4,199,569.

Abamectin is an avermectin that is disclosed as Avermectin B^_a/B^ in U.S. 4,310,519. Abamectin contains at least 80% of avermectin B^_a and not more than 20% of avermectin

^Blb-

Another notable avermectin is Doramectin, also known as 25-cyclohexyl-avermectin Bj. The structure and preparation of Doramectin is disclosed in U.S. 5,089,480.

Another notable avermectin is Moxidectin. Moxidectin, also known as LL-F28249 alpha, is known from U.S. 4,916,154.

Another notable avermectin is Selamectin. Selamectin is 25-cyclohexyl-25-de(l- methylpropyl)-5-deoxy-22,23-dihydro-5-(hydroxyimino)-avermectin B^ monosaccharide.

Milbemycin, or B41, is a substance which is isolated from the fermentation broth of a

Milbemycin producing strain of Streptomyces. The microorganism, the fermentation conditions and the isolation procedures are more fully described in U.S. 3,950,360 and U.S. 3,984,564.

Emamectin (4"-deoxy-4"-epi-methylaminoavermectin B^), which can be prepared as described in U.S. 5,288,710 or U.S. 5,399,717, is a mixture of two homologues, 4"-deoxy- 4"-epi-methylaminoavermectin B^_a and 4"-deoxy-4"-epi-methylaminoavermectin B^. Preferably, a salt of Emamectin is used. Non- limiting examples of salts of Emamectin which can be used in the present invention include the salts described in U.S. 5,288,710, e.g., salts derived from benzoic acid, substituted benzoic acid, benzenesulfonic acid, citric acid, phosphoric acid, tartaric acid, maleic acid, and the like. Most preferably, the Emamectin salt used in the present invention is Emamectin benzoate.

Eprinomectin is chemically known as 4"-epi-acetylamino-4"-deoxy-avermectin B^. Eprinomectin was specifically developed to be used in all cattle classes and age groups. It was the first avermectin to show broad-spectrum activity against both endo- and ecto- parasites while also leaving minimal residues in meat and milk. It has the additional advantage of being highly potent when delivered topically. The composition of the present invention optionally comprises combinations of one or more of the following antiparasite compounds: imidazo[l,2-b]pyridazine compounds as described by U.S. application Ser. No. 11/019,597, filed on Dec. 22, 2004, and published on Aug. 18, 2005 as US 2005-0182059A1; l-(4-mono and di-halomethylsulphonylphenyl)-2- acylamino-3-fluoropropanol compounds, as described by U.S. application Ser. No. 11/018,156, filed on Dec. 21, 2004, now US Patent 7,361,689; trifiuoromethanesulfonanilide oxime ether derivatives, as described by U.S. application Ser. No. 11/231,423, filed on Sep. 21, 2005, now US Patent 7,312,248; and n- [(phenyloxy)phenyl]- 1,1,1 - trif uoromethanesulfonamide and n-[(phenylsulfanyl)phenyl]- 1,1,1 - trifluoromethanesulfonamide derivatives, as described by U.S. Provisional Application Ser. No. 60/688,898, filed on Jun. 9, 2005, and published as US 2006-0281695A1 on Dec. 14, 2006.

The compositions of the present invention can also further comprise a flukicide. Suitable flukicides include, for example, triclabendazole, fenbendazole, albendazole, Clorsulon and oxibendazole. It will be appreciated that the above combinations can further include combinations of antibiotic, antiparasitic and anti-fluke active compounds.

In addition to the above combinations, it is also contemplated to provide combinations of the inventive methods and compounds, as described herein, with other animal health remedies such as trace elements, anti-inflammatories, anti-infectives, hormones, dermatological preparations, including antiseptics and disinfectants, and immunobiologicals such as vaccines and antisera for the prevention of disease.

For example, such antinfectives include one or more antibiotics that are optionally coadministered during treatment using the inventive compounds or methods, e.g., in a combined composition and/or in separate dosage forms. Art-known antibiotics suitable for this purpose include, for example, those listed herein below.

One useful antibiotic is Florfenicol, also known as D-(threo)-l-(4- methylsulfonylphenyl)-2-dichloroacetamido-3-fluoro-l-propanol. Another notable antibiotic compound is D-(threo)- 1 -(4-methylsulfonyphenyl)-2-difluoroacetamido-3-fluoro- 1 - propanol. Another useful antibiotic is Thiamphenicol. Processes for the manufacture of these antibiotic compounds, and intermediates useful in such processes, are described in U.S. 4,311,857; U.S. 4,582,918; U.S. 4,973,750; U.S. 4,876,352; U.S. 5,227,494; U.S. 4,743,700; U.S. 5,567,844; U.S. 5,105,009; U.S. 5,382,673; U.S. 5,352,832; and U.S. 5,663,361. Other florfenicol analogs and/or prodrugs have been disclosed and such analogs also can be used in the compositions and methods of the present invention (see e.g., U.S. Patent Application Publication No: 2004/0082553, now US Patent 7,041,670, and U.S. patent application Ser. No. 11/016,794, now US Patent 7,153,842). Another useful antibiotic compound is Tilmicosin. Tilmicosin is a macrolide antibiotic that is chemically defined as 20-dihydro-20-deoxy-20-(cz^'5-3,5-dimethylpiperidin-l-yl)- desmycosin and which is reportedly disclosed in U.S. 4,820,695.

Another useful antibiotic for use in the present invention is tulathromycin. Tulathromycin is also identified as (2R,3S,4R,5R,8R,10R,11R,12S,13S,14R) 13-[(2,6- dideoxy-3-C-methyl-3-0-methyl-4-C-[(propylamino)methyl]-alpha-L-ribo-hexopyranosyl]- oxy]-2-ethyl-3 ,4, 10-trihydroxy-3 ,5,8,10,12,14-hexamethyl- 11 -[[3 ,4,6-trideoxy-3-(dimethyl- amino)-beta-D-xylo-hexopyranosyl]oxy]-l-oxa-6-azacyclopentadecan-15-one.

Tulathromycin can be prepared in accordance with the procedures set forth in U.S. Patent Publication No. 2003/0064939 Al .

Further antibiotics for use in the present invention include the cephalosporins such as, for example, ceftiofur, cefquinome, etc. The concentration of the cephalosporin in the formulation of the present invention optionally varies between about 1 mg/mL to 500 mg/mL.

Another useful antibiotic includes the fluoroquinolones, such as, for example, enrofloxacin, danofloxacin, difloxacin, orbifloxacin and marbofloxacin. Enrofloxacin is typically administered in a concentration of about 100 mg/mL. Danofloxacin is typically administered at a concentration of about 180 mg/mL.

Other useful macrolide antibiotics include compounds from the class of ketolides, or, more specifically, the azalides. Such compounds are described in, for example, U.S.

6,514,945, U.S. 6,472,371, U.S. 6,270,768, U.S. 6,437,151, U.S. 6,271,255, U.S. 6,239,112,

U.S. 5,958,888, U.S. 6,339,063 and U.S. 6,054,434.

Other useful antibiotics include the tetracyclines, particularly chlortetracycline and oxytetracycline. Other antibiotics may include β-lactams such as penicillins, e.g., penicillin, ampicillin, amoxicillin, or a combination of amoxicillin with clavulanic acid or other beta lactamase inhibitors.

Nonagronomic applications in the veterinary sector are by conventional means such as by enteral administration in the form of, for example, tablets, capsules, drinks, drenching preparations, granulates, pastes, boli, feed-through procedures, or suppositories; or by parenteral administration, such as by injection (including intramuscular, subcutaneous, intravenous, intraperitoneal) or implants; by nasal administration; by topical administration, for example, in the form of immersion or dipping, spraying, washing, coating with powder, or application to a small area of the animal, and through articles such as neck collars, ear tags, tail bands, limb bands or halters which comprise compounds or compositions of the present invention. Any of the compounds of the present invention, or a suitable combination of such compounds, may be administered directly to the animal subject and/or indirectly by applying it to the local environment in which the animal dwells (such as bedding, enclosures, or the like). Direct administration includes contacting the skin, fur or feathers of a subject animal with the compounds, or by feeding or injecting the compounds into the animal.

The compounds of the present invention may be administered in a controlled release form, e.g., in a subcutaneous slow release formulation, or in the form of a controlled release device affixed to an animal such as a fleacollar. Collars for the controlled release of an insecticide agent for long term protection against flea infestation in a companion animal are art-known, and are described, for example, by U.S. 3,852,416, U.S. 4,224,901, U.S. 5,555,848 and U.S. 5,184,573.

Typically a parasiticidal composition according to the present invention comprises a mixture of a compound of Formula 1, an N-oxide, or salt thereof, with one or more pharmaceutically or veterinarily acceptable carriers comprising excipients and auxiliaries selected with regard to the intended route of administration (e.g., oral, topical or parenteral administration such as injection) and in accordance with standard practice. In addition, a suitable carrier is selected on the basis of compatibility with the one or more active ingredients in the composition, including such considerations as stability relative to pH and moisture content. Therefore of note is a composition for protecting an animal from an invertebrate parasitic pest comprising a parasitically effective amount of a compound of the invention and at least one carrier.

For parenteral administration including intravenous, intramuscular and subcutaneous injection, a compound of the present invention can be formulated in suspension, solution or emulsion in oily or aqueous vehicles, and may contain adjuncts such as suspending, stabilizing and/or dispersing agents. The compounds of the present invention may also be formulated for bolus injection or continuous infusion. Pharmaceutical compositions for injection include aqueous solutions of water-soluble forms of active ingredients (e.g., a salt of an active compound), preferably in physiologically compatible buffers containing other excipients or auxiliaries as are known in the art of pharmaceutical formulation. Additionally, suspensions of the active compounds may be prepared in a lipophilic vehicle. Suitable lipophilic vehicles include fatty oils such as sesame oil, synthetic fatty acid esters such as ethyl oleate and triglycerides, or materials such as liposomes. Aqueous injection suspensions may contain substances that increase the viscosity of the suspension, such as sodium carboxymethyl cellulose, sorbitol, or dextran. Formulations for injection may be presented in unit dosage form, e.g., in ampoules or in multi-dose containers. Alternatively, the active ingredient may be in powder form for constitution with a suitable vehicle, e.g., sterile, pyrogen- free water, before use.

In addition to the formulations described supra, the compounds of the present invention may also be formulated as a depot preparation. Such long acting formulations may be administered by implantation (for example, subcutaneously or intramuscularly) or by intramuscular or subcutaneous injection. The compounds of the present invention may be formulated for this route of administration with suitable polymeric or hydrophobic materials (for instance, in an emulsion with a pharmacologically acceptable oil), with ion exchange resins, or as a sparingly soluble derivative such as, without limitation, a sparingly soluble salt.

For administration by inhalation, the compounds of the present invention can be delivered in the form of an aerosol spray using a pressurized pack or a nebulizer and a suitable propellant, e.g., without limitation, dichlorodifluoromethane, trichlorofluoromethane, dichlorotetrafluoroethane or carbon dioxide. In the case of a pressurized aerosol, the dosage unit may be controlled by providing a valve to deliver a metered amount. Capsules and cartridges of, for example, gelatin for use in an inhaler or insufflator may be formulated containing a powder mix of the compound and a suitable powder base such as lactose or starch.

Compounds of the present invention have been discovered to have favorable pharmacokinetic and pharmacodynamic properties providing systemic availability from oral administration and ingestion. Therefore after ingestion by the animal to be protected, parasiticidally effective concentrations of compounds of the invention in the bloodstream protect the treated animal from blood-sucking pests such as fleas, ticks and lice. Therefore of note is a composition for protecting an animal from an invertebrate parasite pest in a form for oral administration (i.e. comprising, in addition to a parasiticidally effective amount of a compound of the invention, one or more carriers selected from binders and fillers suitable for oral administration and feed concentrate carriers).

For oral administration in the form of solutions (the most readily available form for absorption), emulsions, suspensions, pastes, gels, capsules, tablets, boluses, powders, granules, rumen-retention and feed/water/lick blocks, a compound of the present invention can be formulated with binders/fillers known in the art to be suitable for oral administration compositions, such as sugars and sugar derivatives (e.g., lactose, sucrose, mannitol, sorbitol), starch (e.g., maize starch, wheat starch, rice starch, potato starch), cellulose and derivatives (e.g., methylcellulose, carboxymethylcellulose, ethylhydroxycellulose), protein derivatives (e.g., zein, gelatin), and synthetic polymers (e.g., polyvinyl alcohol, polyvinylpyrrolidone). If desired, lubricants (e.g., magnesium stearate), disintegrating agents (e.g., cross-linked polyvinylpyrrolidinone, agar, alginic acid) and dyes or pigments can be added. Pastes and gels often also contain adhesives (e.g., acacia, alginic acid, bentonite, cellulose, xanthan gum, colloidal magnesium aluminum silicate) to aid in keeping the composition in contact with the oral cavity and not being easily ejected.

If the parasiticidal compositions are in the form of feed concentrates, the carrier is typically selected from high-performance feed, feed cereals or protein concentrates. Such feed concentrate-containing compositions can, in addition to the parasiticidal active ingredients, comprise additives promoting animal health or growth, improving quality of meat from animals for slaughter or otherwise useful to animal husbandry. These additives can include, for example, vitamins, antibiotics, chemotherapeutics, bacteriostats, fungistats, coccidiostats and hormones.

The compounds of Formula 1 may also be formulated in rectal compositions such as suppositories or retention enemas, using, e.g., conventional suppository bases such as cocoa butter or other glycerides.

Formulations for topical administration are typically in the form of a powder, cream, suspension, spray, emulsion, foam, paste, aerosol, ointment, salve or gel. More typically a topical formulation is a water-soluble solution, which can be in the form of a concentrate that is diluted before use. Parasiticidal compositions suitable for topical administration typically comprise a compound of the present invention and one or more topically suitable carriers. In applications of a parasiticidal composition topically to the exterior of an animal as a line or spot (i.e. "spot-on" treatment), the active ingredient migrates over the surface of the animal to cover most or all of its external surface area. As a result, the treated animal is particularly protected from invertebrate pests that feed off the epidermis of the animal such as ticks, fleas and lice. Therefore formulations for topical localized administration often comprise at least one organic solvent to facilitate transport of the active ingredient over the skin and/or penetration into the epidermis of the animal. Carriers in such formulations include propylene glycol, paraffins, aromatics, esters such as isopropyl myristate, glycol ethers, alcohols such as ethanol, n-propanol, 2-octyl dodecanol or oleyl alcohol; solutions in esters of monocarboxylic acids, such as isopropyl myristate, isopropyl palmitate, lauric acid oxalic ester, oleic acid oleyl ester, oleic acid decyl ester, hexyl laurate, oleyl oleate, decyl oleate, caproic acid esters of saturated fatty alcohols of chain length C i 2-Ci ; solutions of esters of dicarboxylic acids, such as dibutyl phthalate, diisopropyl isophthalate, adipic acid diisopropyl ester, di-n-butyl adipate or solutions of esters of aliphatic acids, e.g., glycols. It may be advantageous for a crystallization inhibitor or a dispersant known from the pharmaceutical or cosmetic industry also to be present. A pour-on formulation may also be prepared for control of parasites in an animal of agricultural worth. The pour-on formulations of this invention can be in the form of a liquid, powder, emulsion, foam, paste, aerosol, ointment, salve or gel. Typically, the pour-on formulation is liquid. These pour-on formulations can be effectively applied to sheep, cattle, goats, other ruminants, camelids, pigs and horses. The pour-on formulation is typically applied by pouring in one or several lines or in a spot-on the dorsal midline (back) or shoulder of an animal. More typically, the formulation is applied by pouring it along the back of the animal, following the spine. The formulation can also be applied to the animal by other conventional methods, including wiping an impregnated material over at least a small area of the animal, or applying it using a commercially available applicator, by means of a syringe, by spraying or by using a spray race. The pour-on formulations include a carrier and can also include one or more additional ingredients. Examples of suitable additional ingredients are stabilizers such as antioxidants, spreading agents, preservatives, adhesion promoters, active solubilisers such as oleic acid, viscosity modifiers, UV blockers or absorbers, and colourants. Surface active agents, including anionic, cationic, non-ionic and ampholytic surface active agents, can also be included in these formulations.

The formulations of this invention typically include an antioxidant, such as BHT (butylated hydroxytoluene). The antioxidant is generally present in amounts of at 0.1-5% (wt/vol). Some of the formulations require a solubilizer, such as oleic acid, to dissolve the active agent, particularly if spinosad is used. Common spreading agents used in these pour- on formulations are: IPM, IPP, caprylic/capric acid esters of saturated C^-C^g fatty alcohols, oleic acid, oleyl ester, ethyl oleate, triglycerides, silicone oils and DPM. The pour- on formulations of this invention are prepared according to known techniques. Where the pour-on is a solution, the parasiticide/insecticide is mixed with the carrier or vehicle, using heat and stirring where required. Auxiliary or additional ingredients can be added to the mixture of active agent and carrier, or they can be mixed with the active agent prior to the addition of the carrier. If the pour-on is an emulsion or suspension, these formulations are similarly prepared using known techniques.

Other delivery systems for relatively hydrophobic pharmaceutical compounds may be employed. Liposomes and emulsions are well-known examples of delivery vehicles or carriers for hydrophobic drugs. In addition, organic solvents such as dimethylsulfoxide may be used, if needed.

For agronomic applications, the rate of application required for effective control (i.e. "biologically effective amount") will depend on such factors as the species of invertebrate to be controlled, the pest's life cycle, life stage, its size, location, time of year, host crop or animal, feeding behavior, mating behavior, ambient moisture, temperature, and the like. Under normal circumstances, application rates of about 0.01 to 2 kg of active ingredients per hectare are sufficient to control pests in agronomic ecosystems, but as little as 0.0001 kg/hectare may be sufficient or as much as 8 kg/hectare may be required. For nonagronomic applications, effective use rates will range from about 1.0 to 50 mg/square meter but as little as 0.1 mg/square meter may be sufficient or as much as 150 mg/square meter may be required. One skilled in the art can easily determine the biologically effective amount necessary for the desired level of invertebrate pest control.

In general for veterinary use, a compound of Formula 1, an N-oxide, or salt thereof, is administered in a parasiticidally effective amount to an animal to be protected from invertebrate parasite pests. A parasiticidally effective amount is the amount of active ingredient needed to achieve an observable effect diminishing the occurrence or activity of the target invertebrate parasite pest. One skilled in the art will appreciate that the parasitically effective dose can vary for the various compounds and compositions of the present invention, the desired parasitical effect and duration, the target invertebrate pest species, the animal to be protected, the mode of application and the like, and the amount needed to achieve a particular result can be determined through simple experimentation.

For oral administration to homeothermic animals, the daily dosage of a compound of the present invention typically ranges from about 0.01 mg/kg to about 100 mg/kg, more typically from about 0.5 mg/kg to about 100 mg/kg, of animal body weight. For topical (e.g., dermal) administration, dips and sprays typically contain from about 0.5 ppm to about 5000 ppm, more typically from about 1 ppm to about 3000 ppm, of a compound of the present invention.

Representative compounds of this invention prepared by the methods described herein are shown in Index Tables A-C. See Index Table D for 1H NMR data. For mass spectral data (AP⁺ (M+l)), the numerical value reported is the molecular weight of the parent molecular ion (M) formed by addition of H⁺ (molecular weight of 1) to the molecule to give a M+l peak observed by mass spectrometry using atmospheric pressure chemical ionization (AP⁺). The alternate molecular ion peaks (e.g., M+2 or M+4) that occur with compounds containing multiple halogens are not reported.

The following abbreviations are used in the Index Tables which follow: Cmpd means

Compound, Me is methyl, Et is ethyl, z^'-Pr is isopropyl, n-Pr is normal-propyl, c-Pr is cyclo- propyl, n-Bu is normal-butyl, t-Bu is tertiary-butyl, z^'-Pn is z^'so-pentyl, Ph is phenyl, SMe is methylthio, S(0)Me is methylsulfmyl and S02Me is methylsulfonyl.

Fragments L-la through L-7a shown below are referred to in the Index Tables. The letter "p" denotes the point of attachment of the fragment to the pyridine ring and the letter "b" denotes the point of attachment to the benzene ring.

INDEX TABLE A

AP+

1 F F L-2a 4-C(CH₃)₃ 290

2 CI CI L-2a 4-OCF₃ 350

3 F SMe L-2a 4-C(CH₃)₃ 318

4 F F L-2a 4-OCF3 318

5 F SMe L-2a 4-OCF3 346

6 F SMe L-2a 4-SCF3 362

7 F F L-2a 4-SCF3 334

8 CI SMe L-2a 4-OCF3 362

9 H H L-2a 4-C(CH₃)₃ 254

10 CI SMe L-2a 4-SCF3 378

11 F SMe L-2a 4-CF3 330 AP+

Cmpd R£ L (M+l)

12 F F L-2a 4-CF₃ 302

13 CI SMe L-2a 4-CF3 346

14 CI SMe L-2a 3-F, 4-OCF3 380

15 H F L-2a 4-SCF3 316

16 H CI L-2a 4-CF3 300

17 H H L-la 4-C(CH₃)₃ 252

18 F F L-la 4-SCF3 332

19 F F L-la 4-C(CH₃)₃ 288

20 F F L-la 4-OCF3 316

21 F F L-3a 4-C(CH₃)₃ 274

22 F SM e L-3a 4-OCF3 330

23 H H L-3a 4-C(CH₃)₃ 238

24 H F L-3a 4-SCF3 300

25 F F L-3a 4-SCF3 318

26 F SMe L-3b 4-CF3 328

27 F SMe L-3a 4-C(CH₃)₃ 302

28 F F L-3b 4-CF3 300

29 H CI L-6a 4-C(CH₃)₃ 292

30 H CI L-6a 4-OCF3 320

31 CI CI L-6b 4-C(CH₃)₃ 344

32 H CI L-6c 4-C(CH₃)₃ 310

33 H CI L-6c 4-OCF3 338

34 CI SMe L-6a 4-OCF3 365

35 CI SMe L-6a 4-C(CH₃)₃ 338

36 CI SMe L-4a 4-C(CH₃)₃ *

37 CI CI L-4a 4-C(CH₃)₃ 342

38 CI CI L-5a 4-C(CH₃)₃ *

39 H CI L-5a 4-C(CH₃)₃ *

40 H CI L-5a 4-OCF3 318

41 H CI L-5a 4-CF3 302

42 H CI L-5a 4-CF3 302

43 H SMe L-5a 4-CF3 314

44 H SMe L-5a 4-OCF3 330

45 H SMe L-5a 4-OCF3 302 AP+

Cmpd R£ L (M+l)

46 Cl Cl O 4-C(CH₃)₃ 296

47 CI Cl O 4-CF₃ 308

48 Cl Cl O 4-OCF3 324

49 F F O 4-C(CH₃)₃ 264

50 F F O 4-OCF3 292

51 F F O 4-CF3 276

52 Cl Cl s 4-CF3 324

53 Cl Cl s 4-OCF3 340

54 Cl Cl s 4-C(CH₃)₃ 312

55 F F s 4-C(CH₃)₃ 380

56 F F s 4-OCF3 308

57 F F s 4-CF3 292

58 Cl Cl NH 4-C(CH₃)₃ 295

59 Cl Cl NH 4-OCF3 323

60 Cl Cl L-7a 4-C(CH₃)₃ 404

69 H F L-10 4-OCF3 314

70 F F L-10 4-CF3 316

* See Index Table C for ¹ H NMR data.

INDEX TABLE B

AP+ (M+l)

335

INDEX TABLE C

Cmpd No. ¹⁹F NMR Data ^a

36 δ -128.42 (d, J=19Hz, Z-isomer), -132.24 (d, J=19Hz, Z-isomer), -146.38 (d, J=131Hz, E- isomer), -147.47 (d, J=131Hz, E-isomer).

38 δ -94.00 (d, J=18.8Hz, 0.42F, Z-isomer), -101.00 (d, J=37.6Hz, 0.58F, E-isomer).

39 δ -87.6 (d, J= 20Hz, E-isomer, -105.90 (d, J= 40Hz, Z-isomer).

a 19p d_a a are in ppm up field from CFCI3. CDCI3 solution unless indicated otherwise. Couplings are designated by (s)-singlet, (d)-doublet, (t)-triplet, (m)-multiplet, (dd)-doublet of doublets, (br s)-broad singlet.

The following Tests demonstrate the control efficacy of compounds of this invention on specific pests. "Control efficacy" represents inhibition of invertebrate pest development (including mortality) that causes significantly reduced feeding. The pest control protection afforded by the compounds is not limited, however, to these species. Compound numbers refer to compounds in Index Tables A-C. BIOLOGICAL EXAMPLES OF THE INVENTION

TEST A

For evaluating control of diamondback moth (Plutella xylostella) the test unit consisted of a small open container with a 12-14-day-old radish plant inside. This was pre-infested with ~50 neonate larvae that were dispensed into the test unit via corn cob grits using a bazooka inoculator. The larvae moved onto the test plant after being dispensed into the test unit.

Test compounds were formulated using a solution containing 10% acetone, 90% water and 300 ppm X-77® Spreader Lo-Foam Formula non-ionic surfactant containing alkylarylpolyoxyethylene, free fatty acids, glycols and isopropanol (Loveland Industries, Inc. Greeley, Colorado, USA). The formulated compounds were applied in 1 mL of liquid through a SUJ2 atomizer nozzle with 1/8 JJ custom body (Spraying Systems Co., Wheaton, Illinois, USA) positioned 1.27 cm (0.5 inches) above the top of each test unit. Test compounds were sprayed at 50 ppm and/or 10 ppm, and replicated three times. After spraying of the formulated test compound, each test unit was allowed to dry for 1 h and then a black, screened cap was placed on top. The test units were held for 6 days in a growth chamber at 25 °C and 70% relative humidity. Plant feeding damage was then visually assessed based on foliage consumed.

Of the compounds of Formula 1 tested at 250 ppm, the following provided very good to excellent levels of control efficacy (40% or less feeding damage and/or 100% mortality): 1, 2, 5, 7, 8, 10, 12, 13, 14, 18, 19, 21, 22, 23, 24, 25, 26, 27, 39, 40, 41, 42, 46, 47, 48, 49, 52, 53, 54, 55, and 62.

TEST B

For evaluating control of green peach aphid (Myzus persicae) through contact and/or systemic means, the test unit consisted of a small open container with a 12- 15 -day-old radish plant inside. This was pre-infested by placing on a leaf of the test plant 30-40 aphids on a piece of leaf excised from a culture plant (cut-leaf method). The aphids moved onto the test plant as the leaf piece desiccated. After pre-infestation, the soil of the test unit was covered with a layer of sand.

Test compounds were formulated and sprayed at 50 ppm and/or 10 ppm as described for Test A. The applications were replicated three times. After spraying of the formulated test compound, each test unit was allowed to dry for 1 h and then a black, screened cap was placed on top. The test units were held for 6 days in a growth chamber at 19-21 °C and 50- 70% relative humidity. Each test unit was then visually assessed for insect mortality. Of the compounds of Formula 1 tested at 250 ppm, the following resulted in at least 80% mortality: 1, 2, 5, 6, 7, 8, 10, 13, 14, 16, 18, 19, 22, 25, 26, 27, 34, 39, 40, 41, 42, 43, 44, 46, 52, 53, and 55.

TEST C

For evaluating control of cotton melon aphid {Aphis gossypii) through contact and/or systemic means, the test unit consisted of a small open container with a 6-7-day-old cotton plant inside. This was pre-infested with 30-40 insects on a piece of leaf according to the cut- leaf method described for Test C, and the soil of the test unit was covered with a layer of sand.

Test compounds were formulated and sprayed at 50 ppm and/or 10 ppm as described for Test C. 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 C.

Of the compounds of Formula 1 tested at 250 ppm, the following resulted in at least 80% mortality: 1, 2, 4, 5, 6, 7, 14, 16, 18, 19, 20, 22, 23, 24, 25, 26, 33, 34, 40, 41, 42, 43, 44, 47, 48, 49, 52, 55, and 56.

TEST D

For evaluating control of corn planthopper (Peregrinus maidis) through contact and/or systemic means, the test unit consisted of a small open container with a 3-4-day-old maize plant (spike) inside. White sand was added to the top of the soil prior to application. Test compounds were formulated and sprayed at 50 ppm and/or 10 ppm, and replicated three times as described for Test A. After spraying, the test units were allowed to dry for 1 h before they were post-infested with -15-20 nymphs (18 to 21 day old) by sprinkling them onto the sand with a salt shaker. A black, screened cap was placed on the top of each test unit, and the test units were held for 6 days in a growth chamber at 22-24 °C and 50-70% relative humidity. Each test unit was then visually assessed for insect mortality.

Of the compounds of Formula 1 tested at 250 ppm the following provided very good to excellent levels of control efficacy (80%> or more mortality): 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 29, 31, 32, 33, 34, 35, 36, 37, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, and 65.

TEST E

For evaluating control of potato leafhopper (Empoasca fabae) through contact and/or systemic means, the test unit consisted of a small open container with a 5-6-day-old Soleil bean plant (primary leaves emerged) inside. White sand was added to the top of the soil and one of the primary leaves was excised prior to application. Test compounds were formulated and sprayed at 50 ppm and/or 10 ppm, and the tests were replicated three times as described for Test A. After spraying, the test units were allowed to dry for 1 h before they were post-infested with 5 potato leafhoppers (18-21 -day- old adults). A black, screened cap was placed on the top of each test unit, and the test units were held for 6 days in a growth chamber at 24 °C and 70% relative humidity. Each test unit was then visually assessed for insect mortality.

Of the compounds of Formula 1 tested at 250 ppm the following provided very good to excellent levels of control efficacy (80%> or more mortality): 1, 2, 5, 7, 16, 18, 21, 22, 34, 46, and 48.

TEST F

For evaluating control of the western flower thrips {Frankliniella occidentalis) through contact and/or systemic means, the test unit consisted of a small open container with a 5-7- day-old Soleil bean plant inside.

Test compounds were formulated and sprayed at 250 ppm and replicated three times as described for Test A. After spraying, the test units were allowed to dry for 1 hour and then 22-27 adult thrips were added to the unit and then a black, screened cap was placed on top. The test units were held for 7 days at 25 °C and 45-55% relative humidity.

Of the compounds of Formula 1 tested the following provided very good to excellent levels of control efficacy (30% or less plant damage and/or 100% mortality) at 250 ppm: compounds 1, 2, 4, 5, 6, 7, 8, 12, 18, 18, 20, 21, 22, 25, 26, 28, 41, 47, 48, 52, and 53.

TEST G

For evaluating control of the silverleaf whitefly (Bemisia tabaci) through contact and/or systemic means, the test unit consists of a small open container with a 12-14 day old cotton plant inside. Prior to the spray application, both cotyledons are removed from the plant, leaving one true leaf for the assay. Adult whiteflies are allowed to lay eggs on the plant and then are removed from the test unit. Cotton plants infested with at least 15 eggs are submitted to the test for spraying.

Test compounds were formulated and sprayed at 250 ppm and replicated three times as described for Test A. After spraying, the test units are allowed to dry for 1 hour. The cylinders are then removed and the units are taken to a growth chamber and held for 13 days at 28 °C and 50-70%) relative humidity. Each test unit is then visually assessed for insect mortality.

Of the compounds of Formula 1 tested the following provided very good to excellent levels of control efficacy (50%> or more mortality) at 250 ppm: compounds 1, 3, 21, 24, 35, and 49.

Claims

126 CLAIMS What is claimed is:

1. A compound of Formula 1, an N-oxide, or salt thereof,

wherein

L is a group selected from

-6 -7

L-9 L-10 L-l l L-12 wherein the bond projecting to the left is bonded to the aromatic ring containing A and the bond projecting to the right is bonded to the aromatic ring containing Q; or L is O, S(0)_m or NR⁷;

A is N or CR³;

Q is N, CH or CR⁶;

R^la and R^lb are each independently selected from hydrogen, halogen and C₁-C₂ alkyl; R² and R⁵ are each independently selected from hydrogen and fluorine; R³and R⁴ are each independently selected from hydrogen, halogen, cyano, amino, nitro, SF₅, -CHO, -Q, alkyl, C₂-C₆ alkenyl, C₂-C₆ alkynyl, -Q, haloalkyl, C2-C6 haloalkenyl, C2-C6 haloalkynyl, C3-C6 cycloalkyl, C3-C6 halocycloalkyl, C4-C8 alkylcycloalkyl, C4-C8 cycloalkylalkyl, C3-C6 cycloalkenyl, C2-C6 alkoxyalkyl, C2-C6 alkylthioalkyl, C2-C6 alkylcarbonyl, C2-C6

haloalkylcarbonyl, C2-C6 alkoxycarbonyl, C2-C6 alkylaminocarbonyl, C3-C8 dialkylaminocarbonyl, C2-C6 cyanoalkyl, C^-C6 alkoxy, C^-C6 haloalkoxy, C2- Cft alkoxyalkoxy, C^-C6 alkylthio, C^-C6 haloalkylthio, C^-C6 alkylsulfinyl, Ci-Cft haloalkylsulfinyl, Ci~C₍, alkylsulfonyl, Ci~C₍, haloalkylsulfonyl, C3-C9 trialkylsilyl, C^-C6 alkylamino, C2-C6 dialkylamino, C2-C6 haloalkylamino,

C2-C6 halodialkylamino and C2-C6 alkylcarbonylamino; or Q¹, OQ¹ or SQ¹; each R⁶ is independently halogen, hydroxy, amino, cyano, nitro, SF₅, Ci~C₍, alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C4-C10 cycloalkylalkyl, C4- C Q alkylcycloalkyl, C5-C10 alkylcycloalkylalkyl, CQ-CI^ cycloalkylcycloalkyl, C -C^ haloalkyl, C2-C6 haloalkenyl, C2-C6 haloalkynyl, C3-C6 halocycloalkyl,

C1-C4 alkoxy, C1-C4 haloalkoxy, C2-C4 alkoxyalkoxy, C1-C4 alkylthio, C1-C4 alkylsulfinyl, C1-C4 alkylsulfonyl, C1-C4 haloalkylthio, C1-C4

haloalkylsulfinyl, C1-C4 haloalkylsulfonyl, C1-C4 alkylamino, C2~Cg dialkylamino, C3-C6 cycloalkylamino, C2-C4 alkoxyalkyl, C1-C4 hydroxyalkyl, C2-C4 alkylcarbonyl, C2-C6 alkoxycarbonyl, C2-C6 alkylcarbonyloxy, C2-C6 alkylcarbonylthio, C2-C6 alkylaminocarbonyl, C3-C8 dialkylaminocarbonyl, C3- Cft haloalkylcarbonylamino, C3-C6 haloalkylcarbonyl(alkyl)amino or C3-C6 trialkylsilyl; or phenyl, phenoxy or naphthalenyl optionally substituted with up to 3 substituents independently selected from halogen, cyano, C1-C2 alkyl, C1-C2 haloalkyl, C1-C2 alkoxy and C1-C2 haloalkoxy; or a 5- to 6-membered heteroaromatic ring containing ring members selected from carbon atoms and up to 4 heteroatoms independently selected from up to 2 O, up to 2 S and up to 4 N atoms, and optionally substituted with up to 3 substituents independently selected from halogen, cyano, C1-C2 alkyl, C1-C2 haloalkyl, C1-C2 alkoxy and C1-C2 haloalkoxy on carbon atom ring members and cyano, C1-C2 alkyl and C1-C2 alkoxy on nitrogen atom ring members; or a 3- to 7-membered nonaromatic ring containing ring members selected from carbon atoms and up to 4 heteroatoms independently selected from up to 2 O, up to 2 S and up to 4 N atoms, wherein up to 3 carbon atom ring members are independently selected from C(=0) and C(=S), the sulfur atom ring members are independently selected from

S(=O)_s(=NR¹⁰)f and the ring optionally substituted with up to 3 substituents independently selected from halogen, cyano, C1-C2 alkyl, C1-C2 haloalkyl, C - C2 alkoxy and Ci-C haloalkoxy on carbon atom ring members and cyano, C^- C2 alkyl and C1-C2 alkoxy on nitrogen atom ring members;

R⁷ is hydrogen, cyano, C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy, C2-C3

alkylcarbonyl, C2-C3 alkoxycarbonyl or C3-C6 cycloalkyl;

R¹⁰ is independently hydrogen, cyano, C_}-C6 alkyl, Ci~C^ haloalkyl, C3-C8

cycloalkyl, C3-C8 halocycloalkyl, Ci~C^ alkoxy, C_}-C6 haloalkoxy, Ci~C^ alkylamino, C2~Cg dialkylamino, C -C^ haloalkylamino or phenyl;

Q¹ is phenyl or naphthalenyl optionally substituted with up to 3 substituents

independently selected from halogen, cyano, C1-C2 alkyl, -C2 haloalkyl, C -

C2 alkoxy and C1-C2 haloalkoxy; or a 5- to 6-membered heteroaromatic ring containing ring members selected from carbon atoms and up to 4 heteroatoms independently selected from up to 2 O, up to 2 S and up to 4 N atoms, and optionally substituted with up to 3 substituents independently selected from halogen, cyano, C1-C2 alkyl, C1-C2 haloalkyl, C1-C2 alkoxy and C1-C2 haloalkoxy on carbon atom ring members and cyano, C1-C2 alkyl and C1-C2 alkoxy on nitrogen atom ring members; or a 3- to 7-membered nonaromatic ring containing ring members selected from carbon atoms and up to 4 heteroatoms independently selected from up to 2 O, up to 2 S and up to 4 N atoms, wherein up to 3 carbon atom ring members are independently selected from C(=0) and

C(=S), the sulfur atom ring members are independently selected from

m is 0, 1 or 2;

n is 0, 1, 2, 3, 4 or 5; and

provided that

hydrogen.

2. A compound of Claim 1 wherein

L is L-l, L-2, L-3, L-4 or L-5;

A is CR³;

R^la and R^lb are each independently selected from hydrogen, fluorine and methyl; R² and R⁵ are each hydrogen;

R³ and R⁴ are each independently selected from hydrogen, halogen, C_}-C6 alkyl, C - C(, haloalkyl, Ci~C(, alkoxy, Ci~C(, haloalkoxy, Ci~C(, alkylthio, Ci~C(, alkylsulfinyl and Ci~C₍, alkylsulfonyl; or Q¹;

Q is CH or CR⁶; and

each R⁶ is independently halogen, SF₅, Ci~C₍, alkyl, Ci~C₍, haloalkyl, C1-C4 alkoxy, C1-C4 haloalkoxy, C1-C4 alkylthio, C1-C4 alkylsulfinyl, C1-C4 alkylsulfonyl, C1-C4 haloalkylthio, C1-C4 haloalkylsulfinyl, C1-C4 haloalkylsulfonyl or C3- Cft trialkylsilyl.

3. A compound of Claim 2 wherein

L is L-l or L-2;

R^la and R^lb are each independently selected from hydrogen and fluorine;

Q is CH;

n is 0, 1 or 2; and

R⁶ is independently halogen, SF₅, Ci~C₍, alkyl, Ci~C₍, haloalkyl, C1-C4 alkoxy, C - C4 haloalkoxy C1-C4 alkylthio or C1-C4 haloalkylthio.

4. A compound of Claim 3 wherein

R³ and R⁴ are each independently selected from hydrogen, fluoro, chloro, methoxy, methylthio, methylsulfinyl, methylsulfonyl and pyrazole; and

each R⁶ is independently halogen, SF₅, tert-butyl, CF₃, OCF₃, CF₂CF₃, CF(CF₃)₂ or SCF₃.

5. A compound of Claim 1 wherein

L is O, S(0)_m or NR⁷;

A is CR³;

R² and R⁵ are each hydrogen;

R³ and R⁴ are each independently selected from halogen, Ci~C₍, alkyl, Ci~C₍,

haloalkyl, Ci~C(, alkoxy, Ci~C(, haloalkoxy, Ci~C(, alkylthio, Ci~C(, alkylsulfinyl and Ci~C₍, alkylsulfonyl; or Q¹;

Q is CH or CR⁶;

each R⁶ is independently halogen, SF₅, Ci~C₍, alkyl, Ci~C₍, haloalkyl, C1-C4 alkoxy, C1-C4 haloalkoxy, C1-C4 alkylthio, C1-C4 alkylsulfinyl, C1-C4 alkylsulfonyl, C1-C4 haloalkylthio, C1-C4 haloalkylsulfinyl, C1-C4 haloalkylsulfonyl or C3- C(, trialkylsilyl; and

R⁷ is hydrogen or C1-C3 alkyl.

6. A compound of Claim 5 wherein Q is CH;

n is 0, 1 or 2; and

R⁶ is independently halogen, SF₅, C_}-C6 alkyl, C_}-C6 haloalkyl, C1-C4 alkoxy, C - C4 haloalkoxy C1-C4 alkylthio or C1-C4 haloalkylthio.

7. A compound of Claim 6 wherein

R³ and R⁴ are each independently selected from fluoro, chloro, methoxy, methylthio, methylsulfmyl, methylsulfonyl and pyrazole; and

each R⁶ is independently halogen, SF₅, tert-butyl, CF₃, OCF₃, CF₂CF₃, CF(CF₃)₂ or

SCF₃.

8. A compound of Claim 1 that is selected from the group consisting of:

3,5-difluoro-4-[2-[4-(l,l-dimethylethyl)]phenyl]-2-oxiranyl]pyridine;

3,5-difluoro-4-[ 1 -[4-(l , 1 -dimethylethyl)]phenyl]ethenyl]pyridine;

3,5-difluoro-4-[2-[4-[(trifluoromethyl)thio]phenyl]-2-oxiranyl]pyridine;

3,5-difluoro-4-[l-[4-[(trifluoromethyl)thio]phenyl]cyclopropyl]pyridine;

3-chloro-4-[(lZ)-2-fluoro-2-[4-(trifluoromethoxy)phenyl]ethenyl]pyridine; and

3,5-dichloro-4-[4-(l,l-dimethylethyl)phenoxy]pyridine.

9. A composition comprising a compound of Claim 1 and at least one additional component selected from the group consisting of surfactants, solid diluents and liquid diluents.

10. The composition of Claim 9 further comprising at least one additional biologically active compound or agent.

11. The composition of Claim 10 wherein the at least one additional biologically active compound or agent is selected from the group consisting of abamectin, acephate, acequinocyl, acetamiprid, acrinathrin, amidoflumet, amitraz, avermectin, azadirachtin, azinphos-methyl, bensultap, bifenthrin, bifenazate, bistrifluron, borate, buprofezin, cadusafos, carbaryl, carbofuran, cartap, carzol, chlorantraniliprole, chlorfenapyr,

chlorfluazuron, chlorpyrifos, chlorpyrifos-methyl, chromafenozide, clofentezin, clothianidin, cyantraniliprole, cyflumetofen, cyfluthrin, beta-cyfluthrin, cyhalothrin, gamma-cyhalothrin, lambda-cyhalothrin, cypermethrin, alpha-cypermethrin, zeta-cypermethrin, cyromazine, deltamethrin, diafenthiuron, diazinon, dieldrin, diflubenzuron, dimef uthrin, dimehypo, dimethoate, dinotefuran, diofenolan, emamectin, endosulfan, esfenvalerate, ethiprole, etofenprox, etoxazole, fenbutatin oxide, fenothiocarb, fenoxycarb, fenpropathrin, fenvalerate, fipronil, flonicamid, flubendiamide, flucythrinate, flufenerim, flufenoxuron, fluvalmate, tau-fluvalinate, fonophos, formetanate, fosthiazate, halofenozide, hexaflumuron, hexythiazox, hydramethylnon, imidacloprid, indoxacarb, insecticidal soaps, isofenphos, lufenuron, malathion, metaflumizone, metaldehyde, methamidophos, methidathion, methiodicarb, methomyl, methoprene, methoxychlor, metofluthrin, monocrotophos, methoxyfenozide, nitenpyram, nithiazine, novaluron, noviflumuron, oxamyl, parathion, parathion-methyl, permethrin, phorate, phosalone, phosmet, phosphamidon, pirimicarb, profenofos, profluthrin, propargite, protrifenbute, pymetrozine, pyrafluprole, pyrethrin, pyridaben, pyridalyl, pyrifluquinazon, pyriprole, pyriproxyfen, rotenone, ryanodine, spinetoram, spinosad, spirodiclofen, spiromesifen, spirotetramat, sulprofos, sulfoxaflor, tebufenozide, tebufenpyrad, teflubenzuron, tefluthrin, terbufos, tetrachlorvinphos, tetramethrin, thiacloprid, thiamethoxam, thiodicarb, thiosultap-sodium, tolfenpyrad, tralomethrin, triazamate, trichlorfon, triflumuron, Bacillus thuringiensis delta-endotoxins, entomopathogenic bacteria, entomopathogenic viruses and entomopathogenic fungi.

12. A composition for protecting an animal from an invertebrate parasitic pest comprising a parasiticidally effective amount of a compound of Claim 1 and at least one carrier.

13. A method for controlling an invertebrate pest comprising contacting the invertebrate pest or its environment with a biologically effective amount of a compound of Claim 1.

14. A treated seed comprising a compound of Claim 1 in an amount of from about 0.0001 to 1 % by weight of the seed before treatment.